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Search Results: 1 - 10 of 520 matches for " Clive Woolfe "
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Comparative genomics using Fugu reveals insights into regulatory subfunctionalization
Adam Woolfe, Greg Elgar
Genome Biology , 2007, DOI: 10.1186/gb-2007-8-4-r53
Abstract: Using the abundance of duplicated genes within the Fugu genome, we selected seven pairs of teleost-specific paralogs involved in early vertebrate development, each containing clusters of CNEs in their vicinity. CNEs present around each Fugu duplicated gene were identified using multiple alignments of orthologous regions between single-copy mammalian orthologs (representing the ancestral locus) and each fish duplicated region in turn. Comparative analysis reveals a pattern of element retention and loss between paralogs indicative of subfunctionalization, the extent of which differs between duplicate pairs. In addition to complete loss of specific regulatory elements, a number of CNEs have been retained in both regions but may be responsible for more subtle levels of subfunctionalization through sequence divergence.Comparative analysis of conserved elements between duplicated genes provides a powerful approach for studying regulatory subfunctionalization at the level of the regulatory elements involved.Gene duplication is thought to be a major driving force in evolutionary innovation by providing material from which novel gene functions and expression patterns may arise. Duplicated genes have been shown to be present in all eukaryotic genomes currently sequenced [1] and are thought to arise by tandem, chromosomal or whole genome duplication events. Unless the duplication event is immediately advantageous (for example, by gene dosage increasing evolutionary fitness), the gene pair will exhibit functional redundancy, allowing one of the pair to accumulate mutations without affecting key functions. Because deleterious mutations are thought to occur much more commonly than neutral or advantageous ones, the classic model for the evolutionary fate of duplicated genes [2,3] predicts the degeneration of one of the copies to a pseudogene as the most likely outcome (a process known as non-functionalization). Less commonly, a mutation will be advantageous, allowing one of the ge
Genomic features defining exonic variants that modulate splicing
Adam Woolfe, James C Mullikin, Laura Elnitski
Genome Biology , 2010, DOI: 10.1186/gb-2010-11-2-r20
Abstract: We assessed the features of single-nucleotide genomic variants verified to cause exon skipping and compared them to a large set of coding SNPs common in the human population, which are likely to have no effect on splicing. Our findings implicate a number of features important for their ability to discriminate splice-affecting variants, including the naturally occurring density of exonic splicing enhancers and exonic splicing silencers of the exon and intronic environment, extensive changes in the number of predicted exonic splicing enhancers and exonic splicing silencers, proximity to the splice junctions and evolutionary constraint of the region surrounding the variant. By extending this approach to additional datasets, we also identified relevant features of variants that cause increased exon inclusion and ectopic splice site activation.We identified a number of features that have statistically significant representation among exonic variants that modulate splicing. These analyses highlight putative mechanisms responsible for splicing outcome and emphasize the role of features important for exon definition. We developed a web-tool, Skippy, to score coding variants for these relevant splice-modulating features.The majority of genes in mammalian genomes are made up of multiple exons separated by much longer introns. To create a mature mRNA, exons must be identified accurately from within the transcript and then spliced together by removing the intervening introns. This process is carried out by a large complex of small nuclear RNAs and polypeptides known as the spliceosome. Disruption to the fidelity of splicing, particularly of exons that are constitutively spliced, can effectively inactivate a gene by creating unstable mRNAs and defective protein structure, or cause disease by disrupting the balance of expression of different splice isoforms [1]. The most important features for exon recognition are the splice junctions that define the boundaries of the exons, at w
Organisational Creativity: Building a Business Ba-Haus?  [PDF]
Andy Wilkins, Clive Holtham
Creative Education (CE) , 2012, DOI: 10.4236/ce.2012.326110
Abstract: Our focus is on the systemic nature of creativity and the role of business schools in stimulating and enhancing organisational creativity, across all sectors of the economy, particularly those which are not conventionally regarded as ‘creative’ industries. After defining creativity and reviewing a number of frequently occurring ‘creativity clichés’ that are potentially keeping organisational creativity in a rut, we go on to explore some of the key challenges with creativity that need particular focus, including: taking a systemic approach, as well as more attention on ‘difficult’ aspects such as the climate for creativity or creativity ‘ba’. We propose a Systemic Innovation Maturity Framework as a way to conceptualise and organise a way forward in organisations and in business schools. We believe that in a similar way to the Bauhaus of the early 20th century, there needs to be a step change in the way creativity is researched, taught and applied that encompasses a more ecological approach. We believe a more comprehensive, inclusive and useful conception of creativity may result from the consideration of the four dimensions of the framework and their interactions. We wonder; is it time for a new Business Ba-Haus?
Co-enrollment of critically ill patients into multiple studies: patterns, predictors and consequences
Deborah Cook, Ellen McDonald, Orla Smith, Nicole Zytaruk, Diane Heels-Ansdell, Irene Watpool, Tracy McArdle, Andrea Matte, France Clarke, Shirley Vallance, Simon Finfer, Pauline Galt, Tim Crozier, Rob Fowler, Yaseen Arabi, Clive Woolfe, Neil Orford, Richard Hall, Neill KJ Adhikari, Marie-Clauide Ferland, John Marshall, Maureen Meade, The PROTECT Research Coordinators, PROTECT Investigators, Canadian Critical Care Trials Group and the Australian and New Zealand Intensive Care Society Clinical Trials Group
Critical Care , 2013, DOI: 10.1186/cc11917
Abstract: In an observational analysis of an international thromboprophylaxis trial in 67 ICUs, we examined the co-enrollment of critically ill medical-surgical patients into more than one study, and examined the clinical and trial outcomes among co-enrolled and non-co-enrolled patients.Among 3,746 patients enrolled in PROTECT (Prophylaxis for ThromboEmbolism in Critical Care Trial), 713 (19.0%) were co-enrolled in at least one other study (53.6% in a randomized trial, 37.0% in an observational study and 9.4% in both). Six factors independently associated with co-enrollment (all P < 0.001) were illness severity (odds ratio (OR) 1.35, 95% confidence interval (CI) 1.19 to 1.53 for each 10-point Acute Physiology and Chronic Health Evaluation (APACHE) II score increase), substitute decision-makers providing consent, rather than patients (OR 3.31, 2.03 to 5.41), experience of persons inviting consent (OR 2.67, 1.74 to 4.11 for persons with > 10 years' experience compared to persons with none), center size (all ORs > 10 for ICUs with > 15 beds), affiliation with trials groups (OR 5.59, 3.49 to 8.95), and main trial rather than pilot phase (all ORs > 8 for recruitment year beyond the pilot). Co-enrollment did not influence clinical or trial outcomes or risk of adverse events.Co-enrollment was strongly associated with features of the patients, research personnel, setting and study. Co-enrollment had no impact on trial results, and appeared safe, acceptable and feasible. Transparent reporting, scholarly discourse, ethical analysis and further research are needed on the complex topic of co-enrollment during critical illness.Clinical trials are essential to improve care and reduce morbidity and mortality in the intensive care unit (ICU). Some critically ill patients are eligible for more than one study. Restricting enrollment to only one study when patients are eligible for more than one is a potentially modifiable barrier to recruitment [1]. Testing two interventions concurrently can b
The Importance of Definitive Diagnosis in Chronic Schistosomiasis, with Reference to Schistosoma haematobium
Clive Shiff
Journal of Parasitology Research , 2012, DOI: 10.1155/2012/761269
Abstract: Schistosomes are long-lived parasites, hence schistosomiasis is a chronic disease with severe long-term implications. However, definitive diagnosis of active infection has been difficult because demonstration of infection has depended on detecting parasite eggs in urine and/or stool. In the case of Schistosoma haematobium which parasitizes the urinogenital system, this method has low sensitivity in adults. Detection of parasite-specific DNA in urine has been demonstrated and this has similar specificity but improved sensitivity. The implications of this new procedure and the impact on diagnosis are discussed. 1. Background and Introduction In Africa, the health impact of schistosomiasis, whether caused by Schistosoma haematobium or by S. mansoni, is a well-known public health problem, one that is now receiving well-deserved attention [1]. This attention is focused primarily on the most vulnerable part of the community, that part of the population that is heavily debilitated by the disease and will benefit from mass drug administration. For the purpose of control and local elimination of the parasites, a quick sensitive test that may be low in specificity is acceptable but there is need to improve the detection of infection in chronic stages of disease or when parasitaemia is low. The detection of infection among adults with long standing chronic infections is important particularly in the hospital environment when sequelae of the infection are suspected. Bladder damage and even bladder cancer are common problems in endemic areas [2] and a definitive diagnosis which has high sensitivity, specificity, and can be carried out in a diagnostic laboratory with adequate facilities is needed. Definitive diagnosis of schistosomiasis is dependent on the demonstration of parasite eggs in urine or stool, and more recently the detection of circulating antigens [3]; however, these tests have not been assessed in adults. Detection of parasite-specific DNA is an option that is being used with several infections for example, malaria [4], and it presents an opportunity with Schistosoma haematobium [5] and perhaps with S. mansoni [6]. The importance of this has been shown in a recent study involving S. haematobium, it was evaluated using latent class modeling and was shown to detect parasite-specific DNA fragments in adults both when eggs were present in urine and in 10% of cases, where eggs were not present [7]. Gelfand [8] in a very careful clinical analysis of mainly adults infected with bilharzia (schistosomiasis) concluded that “In Rhodesia (now Zimbabwe)
Reviewer acknowledgement 2012
Clive Grattan
Clinical and Translational Allergy , 2013, DOI: 10.1186/2045-7022-3-4
Abstract: Werner AbererAustriaIoana AgacheRomaniaIgnacio AnsoteguiSpainRiccardo AseroItalyMalin AxelssonSwedenSami BahnaUnited States of AmericaJoan BartraSpainSevim BavbekTurkeyMehmet BayramTurkeyBlanca Bazan-PerkinsMexicoCarlos BlancoSpainSergio BoniniItalyJean BousquetFranceHelen A BroughUnited KingdomMoises A CalderonUnited KingdomTomás ChivatoSpainCemal CingiTurkeyLuis DelgadoPortugalPascal DemolyFranceThomas EiweggerAustriaEsben EllerDenmarkWytske FokkensNetherlandsGabriele GadermaierAustriaRoy Gerth van WijkNetherlandsPhilippe GevaertBelgiumM Hazel GowlandUnited KingdomPeter HellingsBelgiumKarin Hoffmann-SommergruberAustriaThomas HolzhauserGermanyBogdan JakielaPolandTuomas JarttiFinlandOmer KalayciTurkeyAllen KaplanUnited States of AmericaRebecca KnibbUnited KingdomGeorge KonstantinouUnited States of AmericaMarcin KurowskiPolandAntti LauermaFinlandOlga LuengoSpainParaskevi MagginaGreeceSoili M?kinen-KiljunenFinlandNadine MarroucheUnited KingdomGiovanni MelioliItalyJoaquim MullolSpainRobert NivenUnited KingdomPedro OjedaSpainOliver PfaarGermanyRoland E PomsAustriaTodor A PopovBulgariaRisto RenkonenFinlandClaudio RhynerSwitzerlandGraham RobertsUnited KingdomFranziska RueffGermanyAnna Sala-CunillSpainPeter Schmid-GrendelmeierSwitzerlandSvetlana SergejevaEstoniaMasahiro ShojiJapanChrysanthi SkevakiGreeceChristian TaubeNetherlandsSanna Toppila-SalmiFinlandMassimo TriggianiItalyJohann C VirchowSwitzerlandCornelis van DrunenNetherlandsCarina VenterUnited KingdomBarbara YawnUnited States of America
Animals, Quo Vadis? Welcome to a New, Multidisciplinary, Integrated, Open Access Journal: Animals
Clive Phillips
Animals , 2011, DOI: 10.3390/ani1010001
Abstract: Without animals this planet would be a very different place, indeed many of the remaining life forms could not exist. As animals ourselves we are linked to a vast network of moving, living, reproducing organisms that form an essential part of the various ecosystems that are themselves competing for survival. By virtue of our large cognitive capacity and complex societal living structures, we manage and influence many of these ecosystems, in the most extreme way by keeping animals captive for our own benefit. [...]
Electrodeposited gold composites
Clive Larson
Gold Bulletin , 1975, DOI: 10.1007/BF03215086
Abstract: Co-deposited refractory carbide particles in gold electroplates have been shown to enhance the hardness, the tensile strength and the sliding wear resistance of the gold. The low electrical contact resistance of gold is not significantly impaired by the presence of the carbide particles.
Electrodeposited gold composite coatings
Clive Larson
Gold Bulletin , 1984, DOI: 10.1007/BF03216574
Abstract: The special properties exhibited by electrodeposited composite coatings have ensured industrial applications for them as a result of the high specification demands of modern technology. Recent advances in the understanding of the mechanism of formation of such coatings, including those involving gold matrices, and awareness of the properties of the latter, justify interest in their potential applications.
中国生物工程杂志 , 2009,
Abstract: 本文介绍了2008年转基因作物的主要情况。由于采用转基因作物取得了巨大经济、环境和社会效益,2008年(转基因作物商业化的第十三个年头),全世界上百万小型和资源匮乏型农户继续种植转基因作物,种植面积有了较大增长(图1)。2008年在其它几个重要的方面也取得了进步:全球种植转基因作物的面积、国家数量和农户数量明显增多,在最具挑战性的非洲取得了实质性进展,更多地采用复合性状作物,引进新的转基因作物。转基因作物能够对全球社会面临的主要挑战做出贡献,包括:食品安全、高价食品、可持续发展、减轻贫穷和饥饿的压力、缓解气候变化带来的挑战等。
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