Home About us Contact
|
Home About us Contact | ||
|
|
||
Highly Accurate (highly + accurate)
Selected AbstractsSuccessful amplification of degraded DNA for use with high-throughput SNP genotyping platforms,HUMAN MUTATION, Issue 12 2008Simon Mead Abstract Highly accurate and high-throughput SNP genotyping platforms are increasingly popular but the performance of suboptimal DNA samples remains unclear. The aim of our study was to determine the best platform, amplification technique, and loading concentration to maximize genotype accuracy and call rate using degraded samples. We amplified high-molecular weight genomic DNA samples recently extracted from whole blood and degraded DNA samples extracted from 50-year-old patient sera. Two whole-genome amplification (WGA) methodologies were used: an isothermal multiple displacement amplification method (MDA) and a fragmentation-PCR,based method (GenomePlex® [GPLEX]; Sigma-Aldrich, St. Louis, MO). Duplicate runs were performed on genome-wide dense SNP arrays (Nsp-Mendel; Affymetrix) and custom SNP platforms based on molecular inversion probes (Targeted Genotyping [TG]; Affymetrix) and BeadArray technology (Golden Gate [GG]; Illumina). Miscalls and no-calls on Mendel arrays were correlated with each other, with confidence scores from the Bayesian calling algorithm, and with average probe intensity. Degraded DNA amplified with MDA gave low call rates and concordance across all platforms at standard loading concentrations. The call rate with MDA on GG was improved when a 5,×,concentration of amplified DNA was used. The GPLEX amplification gave high call rate and concordance for degraded DNA at standard and higher loading concentrations on both TG and GG platforms. Based on these analyses, after standard filtering for SNP and sample performance, we were able to achieve a mean call rate of 99.7% and concordance 99.7% using degraded samples amplified by GPLEX on GG technology at 2,×,loading concentration. These findings may be useful for investigators planning case-control association studies with patient samples of suboptimal quality. Hum Mutat 0, 1,7, 2008. © 2008 Wiley-Liss, Inc. [source] Study of a highly accurate and fast protein,ligand docking method based on molecular dynamicsCONCURRENCY AND COMPUTATION: PRACTICE & EXPERIENCE, Issue 14 2005M. Taufer Abstract Few methods use molecular dynamics simulations in concert with atomically detailed force fields to perform protein,ligand docking calculations because they are considered too time demanding, despite their accuracy. In this paper we present a docking algorithm based on molecular dynamics which has a highly flexible computational granularity. We compare the accuracy and the time required with well-known, commonly used docking methods such as AutoDock, DOCK, FlexX, ICM, and GOLD. We show that our algorithm is accurate, fast and, because of its flexibility, applicable even to loosely coupled distributed systems such as desktop Grids for docking. Copyright © 2005 John Wiley & Sons, Ltd. [source] Integrating modelling and experiments to assess dynamic musculoskeletal function in humansEXPERIMENTAL PHYSIOLOGY, Issue 2 2006J. W. Fernandez Magnetic resonance imaging, bi-plane X-ray fluoroscopy and biomechanical modelling are enabling technologies for the non-invasive evaluation of muscle, ligament and joint function during dynamic activity. This paper reviews these various technologies in the context of their application to the study of human movement. We describe how three-dimensional, subject-specific computer models of the muscles, ligaments, cartilage and bones can be developed from high-resolution magnetic resonance images; how X-ray fluoroscopy can be used to measure the relative movements of the bones at a joint in three dimensions with submillimetre accuracy; how complex 3-D dynamic simulations of movement can be performed using new computational methods based on non-linear control theory; and how musculoskeletal forces derived from such simulations can be used as inputs to elaborate finite-element models of a joint to calculate contact stress distributions on a subject-specific basis. A hierarchical modelling approach is highlighted that links rigid-body models of limb segments with detailed finite-element models of the joints. A framework is proposed that integrates subject-specific musculoskeletal computer models with highly accurate in vivo experimental data. [source] Krylov precise time-step integration methodINTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN ENGINEERING, Issue 11 2006T. C. Fung Abstract An efficient precise time-step integration (PTI) algorithm to solve large-scale transient problems is presented in this paper. The Krylov subspace method and the Padé approximations are applied to modify the original PTI algorithm in order to improve the computational efficiency. Both the stability and accuracy characteristics of the resultant algorithms are investigated. The efficiency can be further improved by expanding the dimension to avoid the computation of the particular solutions. The present algorithm can also be extended to tackle nonlinear problems without difficulty. Two numerical examples are given to illustrate the highly accurate and efficient algorithm. Copyright © 2006 John Wiley & Sons, Ltd. [source] Single Laboratory Method Performance Evaluation for the Analysis of Total Food Folate by Trienzyme Extraction and Microplate AssayJOURNAL OF FOOD SCIENCE, Issue 5 2007L. Chen ABSTRACT:, Single laboratory method performance parameters, including the calibration curve, accuracy, recovery, precision, limit of detection (LOD), and limit of quantification (LOQ), were evaluated for the analysis of total food folate by the trienzyme extraction and microplate assay with Lactobacillus casei subsp. rhamnosus. Standard Reference Material (SRM) 1546 (meat homogenate), SRM 2383 (baby food composite), SRM 1846 (infant formula), Certified Reference Material (CRM) 121 (wholemeal flour), and CRM 485 (mixed vegetables), representing a broad selection of food matrices, were used to evaluate the performance of the method. A generated 4-parameter logistic equation of the calibration curve was y= (0.0705 , 1.0396)/(1 + (x/0.0165) 1.3072) + 1.0396 (P < 0.0001). The test of parallelism demonstrated that matrix components in the food extracts did not affect the accuracy. Measured values of the SRMs and CRMs were within their certified or reference values. Recoveries for all reference materials met the requirements of the AOAC guidelines for single laboratory validation. Precision measured as repeatability, including simultaneous and consecutive replicates for each SRM and CRM, met the Horwitz criterion. LOD and LOQ values were 0.3 and 0.6 ,g/100 g, respectively. The results showed that trienzyme digestion using ,-amylase, PronaseR, and conjugase from chicken pancreas coupled with a 96-well microplate assay provided a highly accurate, reproducible, and sensitive method for the determination of folate in a variety of foods. [source] Data and Graph Mining in Chemical Space for ADME and Activity Data SetsMOLECULAR INFORMATICS, Issue 3 2006Abstract We present a classification method, which is based on a coordinate-free chemical space. Thus, it does not depend on descriptor values commonly used by coordinate-based chemical space methods. In our method the molecular similarity of chemical structures is evaluated by a generalized maximum common graph isomorphism, which supports the usage of numerical physicochemical atom property labels in addition to discrete-atom-type labels. The Maximum Common Substructure (MCS) algorithm applies the Highest Scoring Common Substructure (HSCS) ranking of Sheridan and co-workers, which penalizes discontinuous fragments. For all compared classification algorithms used in this work we analyze their usefulness based on two objectives. First, we are interested in highly accurate and general hypotheses and second, the interpretation ability is highly important to increase our structural knowledge for the ADME data sets and the activity data set investigated in this work. [source] Optimisation of surface passivation for highly reliable angular AMR sensorsPHYSICA STATUS SOLIDI (C) - CURRENT TOPICS IN SOLID STATE PHYSICS, Issue 2 2010M. Isler Abstract For state-of-the-art angular sensors based on the anisotropic magnetoresistive (AMR) effect in NiFe layers, the angular accuracy over time is limited by a drift of the offset voltage of the Wheatstone bridge configuration. It is shown that the interaction of the passivation layer and the magnetic permalloy is crucial for the drift of the offset voltage. By investigating the time and temperature dependence, the offset drift is attributed to stress relief of the PECVD passivation layer due to microstructural changes. Hydrogen outdiffusion from the passivation layer is involved in the observed stress evolution. It is demonstrated that optimising the passivation layer composition as well as the time of the subsequent annealing is beneficial for stress stabilisation of the permalloy-passivation layer system. With this optimised passivation layer a significant offset drift reduction of the NiFe Wheatstone bridge has been achieved resulting in highly accurate and long-term stable angular AMR sensors. (© 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] A de Novo PABPN1 Germline Mutation in a Patient with Oculopharyngeal Muscular Dystrophy,THE LARYNGOSCOPE, Issue 1 2006Nicolas Gürtler Abstract Background: Oculopharyngeal muscular dystrophy (OPMD) is a late-onset autosomal dominantly inherited disorder characterized by dysphagia, ptosis, and proximal limb weakness and is caused by germline mutations (triplet repeat expansions) in the polyadenylate binding protein nuclear 1 (PABPN1) gene. Objective: To describe a 70-year-old female patient with OPMD on the clinical and molecular genetic level and to develop a rapid and efficient molecular genetic screening method to study large patient groups. Methods: Detailed family history and clinical assessment of the OPMD patient were followed by mutation analysis of the PABPN1 gene by direct DNA sequencing and by our newly developed method, fluorescent PABPN1 polymerase chain reaction (PCR) product (flPPP) method. A cohort of 50 healthy Swiss probands was screened using the flPPP to assess the frequency of the (GCG)7 allele in the Swiss population. Cricopharyngeal myotomy was performed as treatment for dysphagia. Results: A heterozygous (GCG)9 triplet repeat expansion in PABPN1 was identified. Since the family history proved to be negative, the mutation is likely to have occurred de novo. The frequency of the (GCG)7 allele among healthy Swiss controls amounted to 1%. The flPPP method showed a sensitivity and specificity of 100%. Two years after cricopharyngeal myotomy, the patient is still relieved of dysphagia. Conclusions: An otolaryngologist should include OPMD in the differential diagnosis of a patient presenting with dysphagia, as this symptom can be the first sign of the disease and family history can be negative. Molecular genetic testing represents a highly accurate and rapid way to confirm the clinical diagnosis of OPMD. Cricopharyngeal myotomy relieves the patient of dysphagia in the majority of cases. [source] Circulating tumour-associated plasma DNA represents an independent and informative predictor of prostate cancerBJU INTERNATIONAL, Issue 3 2006FELIX K.-H. OBJECTIVE To investigate whether preoperative plasma levels of free DNA can discriminate between men with localized prostate cancer and benign prostatic hyperplasia (BPH). PATIENTS AND METHODS In all, 161 referred patients suspicious for prostate cancer either by an elevated prostate-specific antigen (PSA) level and/or abnormal digital rectal examination (DRE) were included in this prospective study. Peripheral plasma was taken before prostate biopsy and genomic DNA was extracted from the plasma using the a commercial kit and a vacuum chamber. After controlling for age, PSA level, the percentage free/total (f/t) PSA and prostate volume, the median prostate cancer plasma DNA concentration served as diagnostic threshold in uni- and multivariate logistic regression models. Multivariate models were subjected to 200 bootstraps for internal validation and to reduce over-fit bias. RESULTS Subgroups consisted of 142 men with clinically localized prostate cancer and 19 with BPH. The median plasma concentration of cell-free DNA was 267 ng/mL in men with BPH vs 709 ng/mL in men with prostate cancer. In univariate analyses, plasma DNA concentration was a statistically significant and informative predictor (P = 0.032 and predictive accuracy 0.643). In multivariate analyses, it remained statistically significant after controlling for age, tPSA, f/tPSA and prostate volume, increasing the predictive accuracy by 5.6%. CONCLUSIONS Our data suggest that plasma DNA level is a highly accurate and informative predictor in uni- and multivariate models for the presence of prostate cancer on needle biopsy. The predictive accuracy was substantially increased by adding plasma DNA level. However, larger-scale studies are needed to further confirm its clinical impact on prostate cancer detection. [source] | ||||||||||||||||