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Substantial Advantages (substantial + advantage)
Selected AbstractsEfficient Simulation of P Values for Linkage AnalysisGENETIC EPIDEMIOLOGY, Issue 2 2004Kyunghee K. Song Abstract In many genetic linkage analyses, the P value is obtained through simulation since the underlying distribution of the test statistic is complex and unknown. However, this can be very computationally intensive. A "bootstrap/replicate pool" approach has been suggested that generates P values more efficiently in terms of computation by resampling sums from a small set of simulated replicates for each pedigree. The replicate pool idea has been successfully applied, but, to our knowledge, has never been theoretically studied. An entirely different method for increasing the computational efficiency of P value simulation is Besag and Clifford's sequential sampling method. We propose an algorithm which combines Besag and Clifford's method with the replicate pool method to efficiently estimate P values for linkage studies. We derive variance expressions for the P value estimates from the replicate pool method and from our proposed hybrid method, and use these to show that the hybrid estimator has a substantial advantage over the other methods in most situations. Genet Epidemiol 26: 88,96, 2004. © 2004 Wiley-Liss, Inc. [source] Second-Generation Inhibitors for the Metalloprotease Neprilysin Based on Bicyclic Heteroaromatic Scaffolds: Synthesis, Biological Activity, and X-Ray Crystal-Structure AnalysisHELVETICA CHIMICA ACTA, Issue 4 2005Stefan Sahli A new class of nonpeptidic inhibitors of the ZnII -dependent metalloprotease neprilysin with IC50 values in the nanomolar activity range (0.034,0.30,,M) were developed based on structure-based de novo design (Figs.,1 and 2). The inhibitors feature benzimidazole and imidazo[4,5- c]pyridine moieties as central scaffolds to undergo H-bonding to Asn542 and Arg717 and to engage in favorable , - , stacking interactions with the imidazole ring of His711. The platform is decorated with a thiol vector to coordinate to the ZnII ion and an aryl residue to occupy the hydrophobic S1, pocket, but lack a substituent for binding in the S2, pocket, which remains closed by the side chains of Phe106 and Arg110 when not occupied. The enantioselective syntheses of the active compounds (+)- 1, (+)- 2, (+)- 25, and (+)- 26 were accomplished using Evans auxiliaries (Schemes,2, 4, and 5). The inhibitors (+)- 2 and (+)- 26 with an imidazo[4,5- c]pyridine core are ca. 8 times more active than those with a benzimidazole core ((+)- 1 and (+)- 25) (Table,1). The predicted binding mode was established by X-ray analysis of the complex of neprilysin with (+)- 2 at 2.25-Å resolution (Fig.,4 and Table,2). The ligand coordinates with its sulfanyl residue to the ZnII ion, and the benzyl residue occupies the S1, pocket. The 1H -imidazole moiety of the central scaffold forms the required H-bonds to the side chains of Asn542 and Arg717. The heterobicyclic platform additionally undergoes ,-, stacking with the side chain of His711 as well as edge-to-face-type interactions with the side chain of Trp693. According to the X-ray analysis, the substantial advantage in biological activity of the imidazo-pyridine inhibitors over the benzimidazole ligands arises from favorable interactions of the pyridine N-atom in the former with the side chain of Arg102. Unexpectedly, replacement of the phenyl group pointing into the deep S1, pocket by a biphenyl group does not enhance the binding affinity for this class of inhibitors. [source] Characterization of Pantoea dispersa UQ68J: producer of a highly efficient sucrose isomerase for isomaltulose biosynthesisJOURNAL OF APPLIED MICROBIOLOGY, Issue 1 2004L. Wu Abstract Aims:, Isolation, identification and characterization of a highly efficient isomaltulose producer. Methods and Results:, After an enrichment procedure for bacteria likely to metabolize isomaltulose in sucrose-rich environments, 578 isolates were screened for efficient isomaltulose biosynthesis using an aniline/diphenylamine assay and capillary electrophoresis. An isolate designated UQ68J was exceptionally efficient in sucrose isomerase activity. Conversion of sucrose into isomaltulose by UQ68J (enzyme activity of 90,100 U mg,1 DW) was much faster than the current industrial strain Protaminobacter rubrum CBS574.77 (41,66 U mg,1 DW) or a reference strain of Erwinia rhapontici (0·3,0·9 U mg,1 DW). Maximum yield of isomaltulose at 78,80% of supplied sucrose was achieved in less than half the reaction time needed by CBS574.77, and the amount of contaminating trehalulose (4%) was the lowest recorded from an isomaltulose-producing microbe. UQ68J is a Gram negative, facultatively anaerobic, motile, noncapsulate, straight rod-shaped bacterium producing acid but no gas from glucose. Based on 16S rDNA analysis UQ68J is closest to Klebsiella oxytoca, but it differs from Klebsiella in defining characteristics and most closely resembles Pantoea dispersa in phenotype. Significance and Impact of Study:, This organism is likely to have substantial advantage over previously characterized sucrose isomerase producers for the industrial production of isomaltulose. [source] Cellulose-Nanocomposites: Towards High Performance Composite MaterialsMACROMOLECULAR SYMPOSIA, Issue 1 2006Robert Kohler Abstract Summary: Strong cellulose fibres, e.g. flax and hemp, are increasingly used for composites. Despite substantial advantages, the tensile strength of these fibres is limited due to their complex structure and the unavoidable imperfections of the cell wall, inherent from growth or induced by processing. Essential improvements are possible by using highly crystalline cellulose fibrils ("whiskers") which can be isolated from the cell wall, thus eliminating the influence of adhesion and defects. Instead of complete fibrillation, which demands special time consuming processing, a partly fibrillation has been achieved by adapted textile finishing procedures which have the potential for mass production. By combining chemical and mechanical/hydro-mechanical treatments it is possible to produce finest fibrils with diameters from below 1 µm down to the nanometer range. The problem of fibril agglomeration during drying has been avoided by forming homogenous fibrous sheets in a wet-laid non-woven process. These sheets can be impregnated with thermosetting resins. Alternatively thermoplastic polymers can be directly integrated to form hybrid materials ready for moulding. The resulting composites show greatly enhanced mechanical properties. [source] Ultrasequencing of the meiofaunal biosphere: practice, pitfalls and promisesMOLECULAR ECOLOGY, Issue 2010S. CREER Abstract Biodiversity assessment is the key to understanding the relationship between biodiversity and ecosystem functioning, but there is a well-acknowledged biodiversity identification gap related to eukaryotic meiofaunal organisms. Meiofaunal identification is confounded by the small size of taxa, morphological convergence and intraspecific variation. However, the most important restricting factor in meiofaunal ecological research is the mismatch between diversity and the number of taxonomists that are able to simultaneously identify and catalogue meiofaunal diversity. Accordingly, a molecular operational taxonomic unit (MOTU)-based approach has been advocated for en mass meiofaunal biodiversity assessment, but it has been restricted by the lack of throughput afforded by chain termination sequencing. Contemporary pyrosequencing offers a solution to this problem in the form of environmental metagenetic analyses, but this represents a novel field of biodiversity assessment. Here, we provide an overview of meiofaunal metagenetic analyses, ranging from sample preservation and DNA extraction to PCR, sequencing and the bioinformatic interrogation of multiple, independent samples using 454 Roche sequencing platforms. We report two examples of environmental metagenetic nuclear small subunit 18S (nSSU) analyses of marine and tropical rainforest habitats and provide critical appraisals of the level of putative recombinant DNA molecules (chimeras) in metagenetic data sets. Following stringent quality control measures, environmental metagenetic analyses achieve MOTU formation across the eukaryote domain of life at a fraction of the time and cost of traditional approaches. The effectiveness of Roche 454 sequencing brings substantial advantages to studies aiming to elucidate the molecular genetic richness of not only meiofaunal, but also all complex eukaryotic communities. [source] Pilot study of the Human Proteome Organisation Brain Proteome Project: Applying different 2-DE techniques to monitor proteomic changes during murine brain developmentPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 18 2006Kai Stühler Dr. Abstract The Human Proteome Organisation Brain Proteome Project aims at coordinating neuroproteomic activities with respect to analysis of development, aging, and evolution in human and mice and at analysing normal aging processes as well as neurodegenerative diseases. Our group participated in the mouse pilot study of this project using two different 2-DE systems, to find out the optimal conditions for comprehensive gel-based differential proteome analysis. Besides the assessment of the best methodical conditions the question of "How many biological replicate analyses have to be performed to get reliable statistically validated results?" was addressed. In total 420 differences were detected in all analyses. Both 2-DE methods were found to be suitable for comprehensive differential proteome analysis. Nevertheless, each of the methods showed substantial advantages and disadvantages resulting in the fact that modification of both systems is essential. From our results we can draw the conclusions that for the future optimal quantitative differential gel-based brain proteome analyses the sample preparation has to be slightly changed, the resolution of the first as well as the second dimension has to be advanced, the number of experiments has to be increased and that the 2D-DIGE system should be applied. [source] Effective use of fluorides for the prevention of dental caries in the 21st century: the WHO approachCOMMUNITY DENTISTRY AND ORAL EPIDEMIOLOGY, Issue 5 2004Poul Erik Petersen Abstract , Despite great improvements in the oral health of populations across the world, problems still persist particularly among poor and disadvantaged groups in both developed and developing countries. According to the World Oral Health Report 2003, dental caries remains a major public health problem in most industrialized countries, affecting 60,90% of schoolchildren and the vast majority of adults. Although it appears that dental caries is less common and less severe in developing countries of Africa, it is anticipated that the incidence of caries will increase in several countries of that continent, due to changing living conditions and dietary habits, and inadequate exposure to fluorides. Research on the oral health effects of fluoride started around 100 years ago; the focus has been on the link between water and fluorides and dental caries and fluorosis, topical fluoride applications, fluoride toothpastes, and salt and milk fluoridation. Most recently, efforts have been made to summarize the extensive database through systematic reviews. Such reviews concluded that water fluoridation and use of fluoride toothpastes and mouthrinses significantly reduce the prevalence of dental caries. WHO recommends for public health that every effort must be made to develop affordable fluoridated toothpastes for use in developing countries. Water fluoridation, where technically feasible and culturally acceptable, has substantial advantages in public health; alternatively, fluoridation of salt and milk fluoridation schemes may be considered for prevention of dental caries. [source] | |||||||||||||