133,695 research outputs found
Revisiting the Coyne Affair: A Singular Event That Changed the Course of Canadian Monetary History
No full textThe Coyne affair is the greatest institutional crisis faced by the Bank of Canada in its history. The crisis took place in 1959-1961 and led to the resignation of the Governor, once he was cleared of any wrongdoing. The crisis eventually resulted in a major reform of the Bank of Canada. The paper highlights the critical role played by the directive in central banking legislation. Archival and empirical evidence is used to assess the performance of monetary policy throughout the 1950s. In doing so, a real-time dataset is constructed for both Canada and the US that permits estimation of reaction functions. I find that the case against James Coyne is \'not proven\'.Coyne Affair; monetary policy stance; Taylor rules; real-time data
Vitamin D receptor activator selectivity in the treatment of secondary hyperparathyroidism : understanding the differences among therapies
No full textSecondary hyperparathyroidism (SHPT) is a common and serious consequence of chronic kidney disease (CKD). SHPT is a complex condition characterised by a decline in 1,25-dihydroxyvitamin D and consequent vitamin D receptor (VDR) activation, abnormalities in serum calcium and phosphorus levels, parathyroid gland hyperplasia, elevated parathyroid hormone (PTH) secretion, and systemic mineral and bone abnormalities. There are three classes of drugs used for treatment of SHPT: (i) nonselective VDR activators or agonists (VDRAs); (ii) selective VDRAs; and (iii) calcimimetics. The VDRAs act on the VDR, whereas the calcimimetics act on the calcium-sensing receptor. Calcimimetics are commonly used in conjunction with VDRA therapy. By virtue of the differences in their chemical structure, the nonselective and selective VDRAs differ in their effects on gene expression, and ultimately parathyroid gland, bone and intestine function. Medications in all three classes are effective in suppression of PTH; however, clinical studies show that calcimimetics are associated with an unfavourable tolerability profile and hypocalcaemia, whereas nonselective VDRAs, and to a lesser extent selective VDRAs, are associated with dose-limiting hypercalcaemia and hyperphosphataemia. Selective VDRAs also have minimal undesirable effects on calcium absorption in the intestine, and calcium and phosphorus mobilisation in the bone compared with nonselective VDRAs. Calcium load in patients with CKD can lead to vascular calcification, accelerated progression of cardiovascular disease and increased mortality. High serum phosphorus levels are also associated with adverse effects on cardiorenal function and survival. Recent evidence suggests that VDRAs are associated with a survival benefit in CKD patients, with a more favourable effect with selective VDRAs than nonselective VDRAs. Paricalcitol, a selective VDRA, is reported to exert specific effects on gene expression in various cell types that are involved in vascular calcification and the development of coronary artery disease. This article examines the molecular mechanisms that determine selectivity of VDRAs, and reviews the evidence for clinical efficacy, safety and survival associated with the three drug classes used for treatment of SHPT in CKD patient
Investigation of the role of the extracellular β-agarase, produced by the bacterial epiphyte Pseudoalteromonas sp. LS2i, in the virulence response towards the agarophyte Gracilaria gracilis
No full textIncludes abstractIncludes bibliographical referencesGracilaria gracilis that grows naturally at Saldanha Bay, South Africa is economically important as a source of agar. The Gracilaria yields from natural beds at Saldanha Bay are however unreliable, and consequently the South African Gracilaria industry has experienced a number of setbacks over the years. The only way a consistent supply can be assured is by mariculture to supplement the natural harvests. In 1993 the Seaweed Research Institute (SRU) found that mariculture of G. gracilis in Saldanha Bay is feasible but that there is potential to improve yields by technical research and development (Anderson et al.1996a). Jaffray and Coyne (1996) developed a pathogenicity assay that demonstrated that agarolytic bacteria isolated from Saldanha Bay Gracilaria induced disease symptoms such as thallus bleaching, while non-agarolytic isolates did not. It is thought that unfavorable environmental conditions such as elevated water temperature and nutrient depletion, which occur during the summer months in the surface layers of the water column in Saldanha Bay, induce the onset of agarase production or result in changes in the bacterial community structure in which agarase-producers become more dominant. By using the pathogenicity assay, Jaffray and Coyne (1996) identified the highly agarolytic Gracilaria gracilis pathogen, Pseudoalteromonas sp. LS2i. The aim of this study was to characterize the bacterial pathogen, Pseudoalteromonas sp. LS2i to further our understanding of virulence regulation and specifically, the role of the agarase enzymes in the process of seaweed-pathogen interaction. Two agarolytic clones, pEB1 and pJB1, were obtained after constructing and screening a Pseudoalteromonas sp. LS2i genomic library in Esherichia coli. Restriction enzyme mapping suggested that both clones contain the same agarase gene. Southern hybridization studies confirmed the origin of the cloned DNA and sequencing studies revealed the 1062 bp ORF, putative promoter region, putative ribosome binding site and putative transcriptional start point of the cloned agarase gene. The ORF showed sequence identity to several other β-agarases and was identified as a member of the GH-16 family of glycoside hydrolases. The agarase was purified from the E. coli JM109 (pEB3) transformant. The molecular weight was estimated to be 39 kDa by SDS-PAGE. Zymogram analysis confirmed that the purified protein is agarolytic and TLC analysis revealed that the predominant end-products of agar hydrolysis are neoagarohexaose and neoagarobiose, which indicates the same mode of action as that observed for the agarase produced extracellularly by Pseudoalteromonas sp. LS2i
Registration of Great Northern Common Bean Cultivar ‘Coyne’ with Enhanced Disease Resistance to Common Bacterial Blight and Bean Rust
No full textGreat northern common bean (Phaseolus vulgaris L.) ‘Coyne’ (Reg. No. CV-287, PI 655574) was developed by the dry bean breeding program at the University of Nebraska Agricultural Research Division and released in 2008. It was bred specifically for adaptation to Nebraska growing conditions and for enhanced resistance to common bacterial blight (CBB), a major disease of common bean caused by the seed-borne bacterium Xanthomonas campestris pv. phaseoli (Smith) Dye, and bean common rust Uromyces appendiculatus (Pers.:Pers) Unger. Coyne is a great northern F7:8 line derived from a three-way cross (G95023/Weihing//BelMiNeb-RMR-11). The first cross was made in winter 2003. The F7:8 was tested in advanced yield trials at Scottsbluff and Mitchell, NE, and in growers’ fields in Nebraska. Yield of Coyne was only 47 kg ha–1 lower than ‘Marquis’ in Morrill and Scotts Bluff, NE, counties. Reaction of Coyne to CBB under field conditions was consistent across 3 yr at the West Central Research and Extension Center, North Platte, NE, where fi eld disease ratings of 3.2, 3.5, and 4.4 were recorded in 2005, 2006, and 2007, respectively. Coyne has the Ur-3 and Ur-6 genes for resistance to common bean rust and carries the single dominant hypersensitive I gene that provides resistance to all non-necrotic strains of Bean common mosaic virus. Coyne has bright white seed, blooms 44 d after planting, and is a midseason bean, maturing 91 d after planting
Beyond performance: productive and counterproductive workplace behaviours.Simposio al XIIIth European Congress of Work and Organisational Psychology, Sustainable work: Promoting Human and Organisational Vitality, Stockholm. Pubbl. in The XIIIth European Congress of Work and Organisational Psychology, Sustainable work: Promoting Human and Organisational Vitality. Stockholm, May 9-12 2007
No full textWhy the HADS is still important: Reply to Coyne & van Sonderen
No full textWhy the HADS is still important: Reply to Coyne & van Sondere
Why the HADS is still important: Reply to Coyne & van Sonderen
No full textWhy the HADS is still important: Reply to Coyne & van Sondere
The Development of Physiologically Relevant Cell Culture Models for Intestinal Enterovirus Infection
No full textEnteroviruses are small, single stranded RNA viruses that are spread via the fecal-oral route and encounter the small intestinal epithelium as their primary site of infection. This family of pathogens, including poliovirus, coxsackieviruses, and echoviruses, is responsible for pediatric and neonatal infections with severe and often fatal outcomes. Echovirus 11 can cause particularly devastating neonatal infections, resulting in enteroviral sepsis, meningitis, and hepatic failure. In order to gain access to sites where severe virally-induced disease occurs, enteroviruses must first overcome the defenses of the epithelial barrier of the small intestine. The human small intestine is a complex organ made up of a variety of specialized, differentiated sub-cell types. Research of enterovirus infection at this important primary barrier to infection is limited by the fact that no accurate in vitro model of infection exists, nor does an animal model that recapitulates the natural gastrointestinal (GI) route of infection.
Here, I utilize two recently developed cell culture models designed to better represent the human small intestinal epithelium as it exists in vivo, in order to characterize enterovirus infection at this important entry portal. First, I describe the use of a bioreactor and microscaffold beads for culturing intestinal cell lines 3-dimensions (3-D). The resulting polarized cell cultures, with enhanced brush borders and upregulated expression of intestinal genes, were used to model coxsackievirus B (CVB) infection. Secondly, human intestinal enteroid cultures, derived from primary intestinal crypts, were used as an ex-vivo cell model. These cells proliferate and differentiate into the repertoire of epithelial cell sub-types found in the human small intestine in-vivo. Human enteroids were used to study epithelial infection by different enteroviruses. In differentiated cultures, we find that the absorptive enterocyte and enteroendocrine cell lineages are highly permissive to echovirus 11 infection, while goblet cells were restrictive to infection. Contrary to infection in traditional cultures of immortalized intestinal cell lines, we find that enteroids derived from the primary intestinal stem cells produce robust antiviral signaling in response to echovirus 11 challenge. In summary, the models for intestinal infection presented in this dissertation will allow for novel enterovirus studies not previously possible in undifferentiated cell lines
MeSH term explosion and author rank improve expert recommendations
No full textInformation overload is an often-cited phenomenon that reduces the productivity, efficiency and efficacy of scientists. One challenge for scientists is to find appropriate collaborators in their research. The literature describes various solutions to the problem of expertise location, but most current approaches do not appear to be very suitable for expert recommendations in biomedical research. In this study, we present the development and initial evaluation of a vector space model-based algorithm to calculate researcher similarity using four inputs: 1) MeSH terms of publications; 2) MeSH terms and author rank; 3) exploded MeSH terms; and 4) exploded MeSH terms and author rank. We developed and evaluated the algorithm using a data set of 17,525 authors and their 22,542 papers. On average, our algorithms correctly predicted 2.5 of the top 5/10 coauthors of individual scientists. Exploded MeSH and author rank outperformed all other algorithms in accuracy, followed closely by MeSH and author rank. Our results show that the accuracy of MeSH term-based matching can be enhanced with other metadata such as author rank
The Persistence of the R.A. Fisher-Sewall Wright Controversy
No full textThis paper considers recent heated debates led by Jerry A. Coyne and Michael J. Wade on issues stemming from the 1929-1962 R. A. Fisher-Sewall Wright controversy in population genetics. William B. Provine once remarked that the Fisher-Wright controversy is central, fundamental, and very influential. Indeed, it is also persistent. The argumentative structure of the recent (1997-2000) debates is analyzed with the aim of eliminating a logical conflict in them, viz., that the two “sides” in the debates have different aims and that, as such, they are talking past each other. Given a philosophical analysis of the argumentative structure of the debates, suggestions supportive of Wade’s work on the debate are made that are aimed, modestly, at putting the persistent Fisher-Wright controversy on the course to resolution
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