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Selected AbstractsApproaches to identify genes for complex human diseases: Lessons from Mendelian disorders,,HUMAN MUTATION, Issue 4 2003Michael Dean Abstract The focus of most molecular genetics research is the identification of genes involved in human disease. In the 20th century, genetics progressed from the rediscovery of Mendel's Laws to the identification of nearly every Mendelian genetic disease. At this pace, the genetic component of all complex human diseases could be identified by the end of the 21st century, and rational therapies could be developed. However, it is clear that no one approach will identify the genes for all diseases with a genetic component, because multiple mechanisms are involved in altering human phenotypes, including common alleles with small to moderate effects, rare alleles with moderate to large effects, complex gene,gene and gene,environment interactions, genomic alterations, and noninherited genetic effects. The knowledge gained from the study of Mendelian diseases may be applied to future research that combines linkage-based, association-based, and sequence-based approaches to detect most disease alleles. The technology to complete these studies is at hand and requires that modest improvements be applied on a wide scale. Improved analytical tools, phenotypic characterizations, and functional analyses will enable complete understanding of the genetic basis of complex diseases. Hum Mutat 22:261,274, 2003. Published © 2003 Wiley-Liss, Inc. [source] Highly accurate solutions of the bifurcation structure of mixed-convection heat transfer using spectral methodINTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN FLUIDS, Issue 5 2002M. Selmi Abstract This paper is concerned with producing highly accurate solution and bifurcation structure using the pseudo-spectral method for the two-dimensional pressure-driven flow through a horizontal duct of a square cross-section that is heated by a uniform flux in the axial direction with a uniform temperature on the periphery. Two approaches are presented. In one approach, the streamwise vorticity, streamwise momentum and energy equations are solved for the stream function, axial velocity, and temperature. In the second approach, the streamwise vorticity and a combination of the energy and momentum equations are solved for stream function and temperature only. While the second approach solves less number of equations than the first approach, a grid sensitivity analysis has shown no distinct advantage of one method over the other. The overall solution structure composed of two symmetric and four asymmetric branches in the range of Grashof number (Gr) of 0,2 × 106 for a Prandtl number (Pr) of 0.73 has been computed using the first approach. The computed structure is comparable to that found by Nandakumar and Weinitschke (1991) using a finite difference scheme for Grashof numbers in the range of 0,1×106. The stability properties of some solution branches; however, are different. In particular, the two-cell structure of the isolated symmetric branch that has been found to be unstable by the study of Nandakumar and Weinitschke is found to be stable by the current study. Copyright © 2002 John Wiley & Sons, Ltd. [source] Identifying Rivals and Rivalries in World PoliticsINTERNATIONAL STUDIES QUARTERLY, Issue 4 2001William R. Thompson Instead of assuming that all actors are equally likely to clash, and that they do so independently of previous clashes, rivalry analysis can focus on the small number of feuding dyads that cause much of the trouble in the international system. But the value added of this approach will hinge in part on how rivalries are identified. Rivalry dyads are usually identified by satisfying thresholds in the frequency of militarized disputes occurring within some prespecified interval of time. But this approach implies a number of analytical problems including the possibility that rivalry analyses are simply being restricted to a device for distinguishing between states that engage in frequent and infrequent conflict. An alternative approach defines rivalry as a perceptual categorizing process in which actors identify which states are sufficiently threatening competitors to qualify as enemies. A systematic approach to identifying these strategic rivalries is elaborated. The outcome, 174 rivalries in existence between 1816 and 1999 are named and compared to the rivalry identification lists produced by three dispute density approaches. The point of the comparison is not necessarily to assert the superiority of one approach over others as it is to highlight the very real costs and benefits associated with different operational assumptions. The question must also be raised whether all approaches are equally focused on what we customarily mean by rivalries. Moreover, in the absence of a consensus on basic concepts and measures, rivalry findings will be anything but additive even if the subfield continues to be monopolized by largely divergent dispute density approaches. [source] Teaching nature of science within a controversial topic: Integrated versus nonintegratedJOURNAL OF RESEARCH IN SCIENCE TEACHING, Issue 4 2006Rola Khishfe This study investigated the influence of two different explicit instructional approaches in promoting more informed understandings of nature of science (NOS) among students. Participants, a total of 42 students, comprised two groups in two intact sections of ninth grade. Participants in the two groups were taught environmental science by their regular classroom teacher, with the difference being the context in which NOS was explicitly taught. For the "integrated" group, NOS instruction was related to the science content about global warming. For the "nonintegrated" group, NOS was taught through a set of activities that specifically addressed NOS issues and were dispersed across the content about global warming. The treatment for both groups spanned 6 weeks and addressed a unit about global warming and NOS. An open-ended questionnaire, in conjunction with semistructured interviews, was used to assess students' views before and after instruction. Results showed improvements in participants' views of NOS regardless of whether NOS was integrated within the regular content about global warming. Comparison of differences between the two groups showed "slightly" greater improvement in the informed views of the integrated group participants. On the other hand, there was greater improvement in the transitional views of the nonintegrated group participants. Therefore, the overall results did not provide any conclusive evidence in favor of one approach over the other. Implications on the teaching and learning of NOS are discussed. © 2006 Wiley Periodicals, Inc. J Res Sci Teach 43: 395,418, 2006 [source] Cardioversion for Atrial Fibrillation: Treatment Options and AdvancesPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 8 2009JAMES A. REIFFEL M.D. Atrial fibrillation (AF) is associated with significant morbidity and mortality. There are two basic approaches to managing AF: slowing the ventricular rate, while allowing the arrhythmia to continue (the rate-control approach), and restoring and maintaining sinus rhythm (the rhythm-control approach) with antiarrhythmic drugs (AADs) and/or ablation, electrical cardioversion (CV), if needed, or both. Strategy trials comparing rate and rhythm control have found no survival advantage of one approach over the other, but other considerations, such as symptom reduction, often necessitate pursuit of rhythm control. Electrical, or direct current, CV is a widely used and effective method for termination of nonparoxysmal AF, although its success can be affected by patient- and technique-related variables. Pharmacological CV options also exist and are preferable in specific circumstances. Both pharmacological and electrical CV are associated with the risk of proarrhythmia. Many AADs are under development for both CV and maintenance of sinus rhythm. Some are atrioselective, such as vernakalant, and target ion channels in the atria, with little or no effects in the ventricle. Vernakalant, currently under Food and Drug Administration review, appears to offer a safer profile than current CV agents and is likely to expand the role of pharmacological CV. Other new AADs that provide increased efficacy or safety while maintaining normal sinus rhythm may also be better than current drugs; if so, rate-rhythm comparisons will differ from those of previous studies. In conclusion, further trials should clarify the long-term safety profiles of new atrioselective agents and other investigational drugs and define their role in the treatment of AF. [source] Optimal portion control using variable cutter-blade spacing in can-fillingPACKAGING TECHNOLOGY AND SCIENCE, Issue 4 2001F. Omar Abstract In the present context, optimal portion control refers to the process of preparing can-filling portions so that the deviation of the portion weight from a specified target weight is minimized. An approach has been developed for achieving this where a batch of objects is placed in a linearly overlapped optimal arrangement and then cut into portions using a series of parallel blades. The parameters of optimization are the arrangement order, orientation and degree of overlap of the objects. The approach has been demonstrated to produce impressive improvements in the application of fish canning. For this application, two approaches of optimal cutting are compared in the present paper. In one approach, the blade spacing is kept fixed and constant at a predetermined value. In the second approach, the blade spacing is varied for each portion after the objects are placed according to the optimal arrangement, where the target weight distribution is allowed to vary within a tolerance interval. The results presented in this paper indicate that the second approach produces a significantly higher percentage of acceptable portions than the first approach. What is presented are results from computer simulations, utilizing true data as measured from actual batches of fish. The paper demonstrates the potential benefit of the optimal portion control approach when applied in an industrial fish-canning process. Copyright © 2001 John Wiley & Sons, Ltd. [source] Is there an elephant in the room?AMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 5 2007Addressing rival approaches to the interpretation of growth perturbations, small size Two interpretations of growth perturbation and small size are commonly applied in human biology: an adaptationist approach in which small size is considered to be an a relatively beneficial adjustment to environmental stressors, and a biomedical approach in which small size is considered nonadaptive, a sign of dysfunction or pathology. These two interpretations conflict, but are used without acknowledging or addressing the conflict. This article reviews the strengths and weaknesses of the two. This exercise does not prove the indisputable superiority of either approach. Considerations of epistemology show that biologists will never be faced with a decisive test of either, much as they might like such clear cut evidence. Nevertheless, it is possible that a gradual decrease in the productivity of one approach will become a sufficient reason to abandon it. Alternatively, if specific areas of application can be distinguished, each approach might continue to be productive in its own domain. Am. J. Hum. Biol., 2007. © 2007 Wiley-Liss, Inc. [source] Public Management Reform: Competing Drivers of ChangePUBLIC ADMINISTRATION REVIEW, Issue 5 2002Lois Recascino Wise Public management reforms often are portrayed as part of a global wave of change, and all organizational change is interpreted within a single reform paradigm that is rooted in economics and market,based principles. Reforms outside this paradigm go unnoticed. This article examines the assertion that different drivers of change competing with the dominant focus of management discourse remain present and influence the direction of reform. It presents three alternative drivers of change rooted in normative values and provides evidence of their relevance from three national cases. Normative influences are reflected in a stream of activities occurring within the same time period in different civil service systems. The direction of public management practice cannot be seen as fully determined by any one approach to government reform or as traveling in only one direction. Understanding the balance among competing drivers of change is a key to interpreting both contemporary and future administrative reform. [source] Local dynamic partial least squares approaches for the modelling of batch processesTHE CANADIAN JOURNAL OF CHEMICAL ENGINEERING, Issue 5 2008N. M. Fletcher Abstract The application of multivariate statistical projection based techniques has been recognized as one approach to contributing to an increased understanding of process behaviour. The key methodologies have included multi-way principal component analysis (PCA), multi-way partial least squares (PLS) and batch observation level analysis. Batch processes typically exhibit nonlinear, time variant behaviour and these characteristics challenge the aforementioned techniques. To address these challenges, dynamic PLS has been proposed to capture the process dynamics. Likewise approaches to removing the process nonlinearities have included the removal of the mean trajectory and the application of nonlinear PLS. An alternative approach is described whereby the batch trajectories are sub-divided into operating regions with a linear/linear dynamic model being fitted to each region. These individual models are spliced together to provide an overall nonlinear global model. Such a structure provides the potential for an alternative approach to batch process performance monitoring. In the paper a number of techniques are considered for developing the local model, including multi-way PLS and dynamic multi-way PLS. Utilising the most promising set of results from a simulation study of a batch process, the local model comprising individual linear dynamic PLS models was benchmarked against global nonlinear dynamic PLS using data from an industrial batch fermentation process. In conclusion the results for the local operating region techniques were comparable to the global model in terms of the residual sum of squares but for the global model structure was evident in the residuals. Consequently, the local modelling approach is statistically more robust. L'application de techniques basées sur la projection statistique multivariée est reconnue comme étant une approche qui contribue à une meilleure compréhension du comportement des procédés. Les méthodologies clés incluent l'analyse des composantes principales (PCA) à plusieurs critères de classification, les moindres carrés partiels (PLS) à plusieurs critères de classification et l'analyse des niveaux d'observation discontinus. Les procédés discontinus présentent typiquement un comportement non linéaire et variable dans le temps et ces caractéristiques mettent au défi les techniques mentionnées ci-dessus. Devant ces défis, la méthode PLS dynamique est proposée pour saisir la dynamique des procédés. Des approches semblables pour supprimer la non linéarité des procédés incluent le retrait de la trajectoire principale et l'application des PLS non linéaires. On décrit une autre approche où les trajectoires discontinues sont subdivisées en régions opératoires avec un modèle dynamique linéaire/linéaire adapté à chaque région. Ces modèles individuels sont raccordés pour obtenir un modèle non linéaire global. Une telle structure présente un potentiel pour une approche différente du suivi des performances des procédés discontinus. Dans cet article, plusieurs techniques sont considérées pour la mise au point du modèle local, incluant les PLS à plusieurs critères de classification et les PLS à plusieurs critères de classification dynamique. En utilisant la série de résultats les plus prometteurs d'une étude de simulation d'un procédé discontinu, le modèle local comprenant les modèles de PLS dynamiques linéaires individuels a été comparé à la méthode de PLS non linéaires dynamique globale utilisant des données d'un procédé de fermentation discontinu industriel. En conclusion, les résultats pour les techniques des régions opératoires locales sont comparables au modèle global en termes de somme des carrés des résidus mais pour le modèle global, la présence d'une structure dans les résidus est évidente. En conséquence, l'approche de modélisation locale est statistiquement plus robuste. [source] Stylar glycoproteins bind to S-RNase in vitroTHE PLANT JOURNAL, Issue 3 2005Felipe Cruz-Garcia Summary S-RNases determine the specificity of S -specific pollen rejection in self-incompatible plants of the Solanaceae, Rosaceae, and Scrophulariaceae. They are also implicated in at least two distinct types of unilateral interspecific incompatibility in Nicotiana. However, S-RNase itself is not sufficient for most types of pollen rejection, and evidence for its direct interaction with pollen tubes is limited. Thus, non-S-RNase factors also are required for pollen rejection. As one approach to identifying such factors, we tested whether SC10 -RNase from Nicotiana alata would bind to other stylar proteins in vitro. SC10 -RNase was immobilized on Affi-gel, and binding proteins were analyzed by SDS-PAGE and immunoblotting. In addition to SC10 -RNase and a small protein similar to lily chemocyanin, the most prominent binding proteins include NaTTS, 120K, and NaPELPIII, these latter three being arabinogalactan proteins previously shown to interact directly with pollen tubes. We also show that SC10 -RNase and these glycoproteins migrate as a complex in a native PAGE system. Our hypothesis is that S-RNase forms a complex with these glycoproteins in the stylar ECM, that the glycoproteins interact directly with the pollen tubes and thus that the initial interaction between the pollen tube and S-RNase is indirect. [source] Genetical genomics in livestock: potentials and pitfallsANIMAL GENETICS, Issue 2006C. Haley Summary Genetical genomics combines gene mapping and gene expression approaches to identify loci controlling gene expression (eQTLs) that may underlie functional trait variation. The combination of genomic tools has great potential to facilitate dissection of complex traits, but studies need careful design and interpretation. Here we explore both the potential and the pitfalls of this approach with illustrations from actual studies. There are now an appreciable number of studies in model species and even humans demonstrating the feasibility of genetical genomics. However, most studies are too limited in size and design to unlock the full potential of the approach. Limited statistical power of studies exacerbates the problem of detection of false-positive eQTL and some reported results should be interpreted with caution. As one approach to more successful implementation of genetical genomics, we propose to combine expression studies with fine mapping of functional trait loci. This synergistic approach facilitates the implementation of genetical genomics for species without inbred resources but is equally applicable to model species. These properties make it particularly suitable for livestock populations where many QTL are already in the public domain and potentially very large pedigreed populations can be accessed. [source] Prediction of Operating Cash Flows: Further Evidence from AustraliaAUSTRALIAN ACCOUNTING REVIEW, Issue 2 2010Ahsan Habib This paper examines empirically the relative abilities of current operating cash flows (hereafter OCF) and earnings in predicting future operating cash flows in Australia. It extends prior Australian research on cash flow prediction (Percy and Stokes 1992; Clinch, Sidhu and Sing 2002; Farshadfar, Ng and Brimble 2009) by examining future cash flow predictions for one-, two- and three-year-ahead forecast horizons; incorporating additional contextual variables likely to affect the predictive association between current cash flows or earnings and future cash flows; and comparing cross-sectional versus time series-based prediction models to ascertain the relative superiority of one approach over the other. Regression results reveal that the cash flow-based models are more accurate in predicting future operating cash flows than earnings-based models. This result, however, is moderated by firm-specific contextual factors like firm size, negative versus positive cash flow pattern, cash flow variability and firm operating cycle. Finally, a comparison between cross-sectional and time series approaches reveals that the cross-sectional model outperforms the time series model for both the operating cash flows and earnings models in most of the forecast years. [source] Isolation of Caenorhabditis elegans genomic DNA and detection of deletions in the unc-93 gene using PCRBIOCHEMISTRY AND MOLECULAR BIOLOGY EDUCATION, Issue 3 2005James L. Lissemore Abstract PCR, genomic DNA isolation, and agarose gel electrophoresis are common molecular biology techniques with a wide range of applications. Therefore, we have developed a series of exercises employing these techniques for an intermediate level undergraduate molecular biology laboratory course. In these exercises, students isolate genomic DNA from the nematode Caenorhabditis elegans and use PCR to detect deletions in the C. elegans unc-93 gene. In advance of the exercises, wild-type and three different unc-93 deletion mutant strains are grown, harvested, and frozen by the instructor. In one approach, students isolate genomic DNA from each strain using a genomic DNA isolation kit and use agarose gel electrophoresis to analyze the DNA and to estimate its concentration. PCRs using primers directed to two different regions of the unc-93 gene are carried out on the genomic DNA from wild-type and mutant strains, and the PCR products are analyzed by agarose gel electrophoresis. Students analyze the gel to determine the approximate location and size of deletions in the three mutant strains. Alternatively, students may lyse single nematodes and carry out PCR in one laboratory session. These exercises should be easily adaptable to detection of well characterized deletions in any organism. [source] Making use of the primary tumourBIOESSAYS, Issue 1 2003Arnold Baars Surgical resection of a primary tumour is often not sufficient to cure a patient. Even when no residual cancer can be detected at time of surgery, metastases may appear in the following years, which indicates that the primary tumour had apparently spread before surgery. Following surgery, systemic chemotherapy may be used to eradicate micro-metastatic disease. Here we present two unconventional strategies that implement new insights into tumour biology and tumour immunology in the treatment of patients with cancer. Both experimental strategies use the individual characteristics of the patient's primary tumour to optimise the control of life-threatening micro-metastases. We aim to modulate the patient's adaptive immune system, targeting it towards the patient's own tumour cells to eradicate residual disease following local treatment. In one approach, this is done by autologous tumour cell vaccinations as adjuvant treatment for colon cancer patients and, in a second approach, by giving chemo-imunotherapy before local treatment to women with locally advanced breast cancer. BioEssays 25:79,86, 2003. © 2002 Wiley Periodicals, Inc. [source] Data linkage using probabilistic decision rules: A primer,BIRTH DEFECTS RESEARCH, Issue 11 2008Craig Alan Mason Abstract Electronic data linkage is increasingly being used by researchers and health professionals in the birth defects field as a tool for enhancing both research and service/care. However, in many cases, a common pre-existing ID number does not exist across different datasets, and common identifiers, such as names or dates of birth, which could be used to match records, may be known to contain errors or even legitimate differences over time. In such situations, probabilistic matching, which does not require that all identifying fields exactly agree in order for one to conclude that two records belong to the same individual, can be a valuable tool for improving data linkage. However, probabilistic matching is computationally complex and demanding, and not well understood by many who may wish to apply it in their work. Therefore, the purpose of this article is to provide an overview of one approach to probabilistic matching, including the step-by-step procedures involved in the calculation of indices corresponding to the likelihood that two records are a correct match. In addition, the use of multiple iterative protocols, in which several different matching strategies are used in order to maximize the number of linked records, is discussed. Finally, issues related to deduplication and verification of internal-consistency in the linked data set are also reviewed. Birth Defects Research (Part A), 2008. © 2008 Wiley-Liss, Inc. [source] The effectiveness of Nurture Groups: preliminary research findingsBRITISH JOURNAL OF SPECIAL EDUCATION, Issue 4 2001Paul Cooper Interest in Nurture Groups continues to grow. As Rebecca Doyle's article in the previous issue of this journal demonstrated, practitioners are enthusiastically exploring nurture-based practice as one approach to the inclusion of pupils with social, emotional and behavioural difficulties. In this article, Paul Cooper, Professor of Education at the University of Leicester, Ray Arnold and Eve Boyd, both researchers with the Nurture Groups project, provide a report on their research to date. This interim report raises some important questions for policy makers and practitioners as well as indicating ways forward into further enquiry. [source] Does avian species richness in natural patch mosaics follow the forest fragmentation paradigm?ANIMAL CONSERVATION, Issue 1 2007D. C. Pavlacky Jr. Abstract As one approaches the north-eastern limit of pinyon (Pinus spp.) juniper (Juniperus spp.) vegetation on the Colorado Plateau, USA, woodland patches become increasingly disjunct, grading into sagebrush (Artemisia spp.)-dominated landscapes. Patterns of avian species richness in naturally heterogeneous forests may or may not respond to patch discontinuity in the same manner as bird assemblages in fragmented agricultural systems. We used observational data from naturally patchy woodlands and predictions derived from studies of human-modified agricultural forests to estimate the effects of patch area, shape, isolation and distance to contiguous woodland on avian species richness. We predicted that patterns of species richness in naturally patchy juniper woodlands would differ from those observed in fragmented agricultural systems. Our objectives were to (1) estimate the effect of naturally occurring patch structure on avian species richness with respect to habitat affinity and migratory strategy and (2) assess the concordance of the effects to predictions from agricultural forest systems. We used the analogy between populations and communities to estimate species richness, where species are treated as individuals in the application of traditional capture,recapture theory. Information-theoretic model selection showed that overall species richness was explained primarily by the species area relationship. There was some support for a model with greater complexity than the equilibrium theory of island biogeography where the isolation of large patches resulted in greater species richness. Species richness of woodland-dwelling birds was best explained by the equilibrium hypothesis with partial landscape complementation by open-country species in isolated patches. Species richness within specific migratory strategies showed concomitant increases and no shifts in species composition along the patch area gradient. Our results indicate that many patterns of species richness considered to be fragmentation effects may be general consequences of patch discontinuity and are ubiquitous in naturally heterogeneous systems. There was no evidence for the effects of patch shape and distance to contiguous woodland in juniper woodland, suggesting edge effects and dependence upon regional species pools are characteristics of fragmented agricultural systems. Natural patch mosaics may provide benchmarks for evaluating fragmentation effects and managing forests by mimicking natural landscape patterns. [source] |