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Selected AbstractsEvaluation of in silico splice tools for decision-making in molecular diagnosis,HUMAN MUTATION, Issue 7 2008Claude Houdayer Abstract It appears that all types of genomic nucleotide variations can be deleterious by affecting normal pre-mRNA splicing via disruption/creation of splice site consensus sequences. As it is neither pertinent nor realistic to perform functional testing for all of these variants, it is important to identify those that could lead to a splice defect in order to restrict transcript analyses to the most appropriate cases. Web-based tools designed to provide such predictions are available. We evaluated the performance of six of these tools (Splice Site Prediction by Neural Network [NNSplice], Splice-Site Finder [SSF], MaxEntScan [MES], Automated Splice-Site Analyses [ASSA], Exonic Splicing Enhancer [ESE] Finder, and Relative Enhancer and Silencer Classification by Unanimous Enrichment [RESCUE]-ESE) using 39 unrelated retinoblastoma patients carrying different RB1 variants (31 intronic and eight exonic). These 39 patients were screened for abnormal splicing using puromycin-treated cell lines and the results were compared to the predictions. As expected, 17 variants impacting canonical AG/GT splice sites were correctly predicted as deleterious. A total of 22 variations occurring at loosely defined positions (±60 nucleotides from an AG/GT site) led to a splice defect in 19 cases and 16 of them were classified as deleterious by at least one tool (84% sensitivity). In other words, three variants escaped in silico detection and the remaining three were correctly predicted as neutral. Overall our results suggest that a combination of complementary in silico tools is necessary to guide molecular geneticists (balance between the time and cost required by RNA analysis and the risk of missing a deleterious mutation) because the weaknesses of one in silico tool may be overcome by the results of another tool. Hum Mutat 29(7), 975,982, 2008. © 2008 Wiley-Liss, Inc. [source] Interpreting missense variants: comparing computational methods in human disease genes CDKN2A, MLH1, MSH2, MECP2, and tyrosinase (TYR),,HUMAN MUTATION, Issue 7 2007Philip A. Chan Abstract The human genome contains frequent single-basepair variants that may or may not cause genetic disease. To characterize benign vs. pathogenic missense variants, numerous computational algorithms have been developed based on comparative sequence and/or protein structure analysis. We compared computational methods that use evolutionary conservation alone, amino acid (AA) change alone, and a combination of conservation and AA change in predicting the consequences of 254 missense variants in the CDKN2A (n = 92), MLH1 (n = 28), MSH2 (n = 14), MECP2 (n = 30), and tyrosinase (TYR) (n = 90) genes. Variants were validated as either neutral or deleterious by curated locus-specific mutation databases and published functional data. All methods that use evolutionary sequence analysis have comparable overall prediction accuracy (72.9,82.0%). Mutations at codons where the AA is absolutely conserved over a sufficient evolutionary distance (about one-third of variants) had a 91.6 to 96.8% likelihood of being deleterious. Three algorithms (SIFT, PolyPhen, and A-GVGD) that differentiate one variant from another at a given codon did not significantly improve predictive value over conservation score alone using the BLOSUM62 matrix. However, when all four methods were in agreement (62.7% of variants), predictive value improved to 88.1%. These results confirm a high predictive value for methods that use evolutionary sequence conservation, with or without considering protein structural change, to predict the clinical consequences of missense variants. The methods can be generalized across genes that cause different types of genetic disease. The results support the clinical use of computational methods as one tool to help interpret missense variants in genes associated with human genetic disease. Hum Mutat 28(7), 683,693, 2007. Published 2007 Wiley-Liss, Inc. [source] Wild coffee management and plant diversity in the montane rainforest of southwestern EthiopiaAFRICAN JOURNAL OF ECOLOGY, Issue 1 2010Christine B. Schmitt Abstract Coffea arabica occurs naturally in the montane rainforests of Ethiopia, but large areas of these unique forests have been converted to other land-uses. In the remaining forest, wild coffee is managed and harvested with increasing intensity because of rising coffee prices in the world market. This study evaluated the impact of coffee management on wild coffee populations and the forest vegetation as a basis for conservation planning in southwestern Ethiopia. Vegetation surveys and yield assessments were carried out in unmanaged natural forest and in managed semi-forest coffee (SFC) systems. Analyses show that wild coffee density and coffee yields were low in natural forest (max. 15 kg ha,1 year,1). In SFC systems, 30% of the canopy trees and most undergrowth vegetation were removed. This stimulated wild coffee growth and strongly enhanced yields (max. 54 kg ha,1 year,1), but severely disturbed forest structure. Species richness increased by 26% because of an increase in species of ruderal and secondary vegetation; however, species richness and abundance of typical forest species declined. Conservation of the natural forest therefore requires the control of wild coffee management. Wild coffee certification is discussed as one tool to reconcile conservation measures and the interests of local farmers. Résumé Coffea arabica pousse naturellement dans les forêts pluviales de montagne en Ethiopie, mais de grandes superficies de ces forêts uniques ont été transformées pour d'autres usages. Dans la forêt restante, le café sauvage est géré et récolté de façon de plus en plus intense en raison de l'augmentation du prix du café au niveau mondial. Cette étude a évalué l'impact de la gestion des populations sauvages de café, ainsi que la végétation forestière, afin d'établir une base pour la planification de la conservation dans le sud-ouest de l'Ethiopie. Des études de végétation et des évaluations des récoltes ont été réalisées dans une forêt naturelle non gérée et dans des systèmes semi forestiers où les caféiers sont gérés. Les analyses révèlent que la densité des caféiers sauvages et les récoltes de café sont faibles dans la forêt naturelle (max 15 kg ha,1an,1). Dans les systèmes semi forestiers, 30% des arbres de la canopée et la plus grande partie de la végétation en sous-bois ont été enlevés. Cela stimule la croissance des caféiers et augmente fortement les récoltes (max 54 kg ha,1an,1), mais cela perturbe gravement la structure forestière. La richesse en espèces a augmenté de 26%à cause de l'augmentation des espèces dans la végétation rudérale et secondaire; cependant, la richesse et l'abondance des espèces typiquement forestières ont décliné. La conservation de la forêt naturelle exige dès lors le contrôle de la gestion du café sauvage. On discute de la certification du café sauvage comme moyen de réconcilier les mesures de conservation et les intérêts des fermiers locaux. [source] Toward implementing distributed scaffolding: Helping students learn science from designJOURNAL OF RESEARCH IN SCIENCE TEACHING, Issue 2 2005Sadhana Puntambekar In this article, we present two studies that helped us understand the kinds of support that students need to learn science successfully from design activities. Both were enacted in the context of an approach to learning science from design called learning by design (LBD). In our first study, we designed and integrated a paper-and-pencil scaffolding tool, the design diary, into an LBD unit to support students' design-related activities. We learned two important lessons from the first study. First, we refined our understanding of the processes involved in designing and the ways we might present those processes to students. Second, and more important, we observed that in the dynamic, complex environment of the classroom, not all of the scaffolding could be provided with any one tool or agent. We found that students need multiple forms of support and multiple learning opportunities to learn science successfully from design activities. In our next study, we provided additional support through an organized system of tools and agents. Our analysis of data from the second study leads us to believe that supporting multiple students in a classroom requires us to rethink the notion of scaffolding as it applied to groups of learners in a classroom. We put forth the notion of distributed scaffolding as an approach to supporting hands-on inquiry learning in a classroom. © 2005 Wiley Periodicals, Inc. J Res Sci Teach 42: 185,217, 2005 [source] Off-gas treatment carbon footprint calculator: Form and functionREMEDIATION, Issue 1 2008Lowell Kessel The quantification of greenhouse gas (GHG) emissions can be a powerful sustainability measurement indicator for assessing environmental impacts of various operations, which can include remediation of chemically impacted media or construction projects. A carbon footprint calculator was developed and is presented in this article as one tool for applying sustainable practices to environmental remediation,specifically to assess the GHG footprint for remediation projects. The calculator is constructed from a compilation of published metrics and "standards." © 2008 Wiley Periodicals, Inc. [source] Comparing Parameter Manipulation with Mouse, Pen, and Slider User InterfacesCOMPUTER GRAPHICS FORUM, Issue 3 2009Colin Swindells Abstract Visual fixation on one's tool(s) takes much attention away from one's primary task. Following the belief that the best tools ,disappear' and become invisible to the user, we present a study comparing visual fixations (eye gaze within locations on a graphical display) and performance for mouse, pen, and physical slider user interfaces. Participants conducted a controlled, yet representative, color matching task that required user interaction representative of many data exploration tasks such as parameter exploration of medical or fuel cell data. We demonstrate that users may spend up to 95% fewer visual fixations on physical sliders versus standard mouse and pen tools without any loss in performance for a generalized visual performance task. [source] | ||||||||||