Home About us Contact
|
Home About us Contact | ||
|
|
||
Established Methods (established + methods)
Selected AbstractsAn efficient real-time method of analysis for non-coherent fault treesQUALITY AND RELIABILITY ENGINEERING INTERNATIONAL, Issue 2 2009Rasa Remenyte-Prescott Abstract Fault tree analysis is commonly used to assess the reliability of potentially hazardous industrial systems. The type of logic is usually restricted to AND and OR gates, which makes the fault tree structure coherent. In non-coherent structures not only components' failures but also components' working states contribute to the failure of the system. The qualitative and quantitative analyses of such fault trees can present additional difficulties when compared with the coherent versions. It is shown that the binary decision diagram (BDD) method can overcome some of the difficulties in the analysis of non-coherent fault trees. This paper presents the conversion process of non-coherent fault trees to BDDs. A fault tree is converted to a BDD that represents the system structure function (SFBDD). An SFBDD can then be used to quantify the system failure parameters but is not suitable for the qualitative analysis. Established methods, such as the meta-products BDD method, the zero-suppressed BDD (ZBDD) method and the labelled BDD (L-BDD) method, require an additional BDD that contains all prime implicant sets. The process using some of the methods can be time consuming and is not very efficient. In addition, in real-time applications the conversion process is less important and the requirement is to provide an efficient analysis. Recent uses of the BDD method are for real-time system prognosis. In such situations as events happen, or failures occur, the prediction of mission success is updated and used in the decision-making process. Both qualitative and quantitative assessments are required for the decision making. Under these conditions fast processing and small storage requirements are essential. Fast processing is a feature of the BDD method. It would be advantageous if a single BDD structure could be used for both the qualitative and quantitative analyses. Therefore, a new method, the ternary decision diagram (TDD) method, is presented in this paper, where a fault tree is converted to a TDD that allows both qualitative and quantitative analyses and no additional BDDs are required. The efficiency of the four methods is compared using an example fault tree library. Copyright © 2008 John Wiley & Sons, Ltd. [source] Glycaemic control in relation to xanthine oxidase and antioxidant indices in Malaysian Type 2 diabetes patientsDIABETIC MEDICINE, Issue 10 2005U. R. Kuppusamy Abstract Aims Increased oxidative stress and oxidative damage are present in Type 2 diabetes mellitus (DM). The aim of this study was to assess the oxidative stress levels in the three major ethnic groups in Malaysia and to study the association between glycaemic control and oxidant,antioxidant levels in these patients. Methods Oxidative indices and glycaemic control were assessed in 650 Type 2 DM patients and 280 healthy age-matched controls by known established methods. Results Type 2 DM patients had significantly lower levels of antioxidant enzymes and non-enzymatic antioxidant (FRAP) and increased levels of HbA1c, fasting blood glucose (FBG), malondialdehyde (MDA) and xanthine oxidase (XO) when compared with control subjects. Markers of oxidative stress were more apparent in Indian patients compared with Malay and Chinese patients. Correlation analysis of oxidant,antioxidant parameters as a function of HbA1c in each ethnic group revealed a strong association of HbA1c with oxidative indices. Conclusions The present study provides evidence for the possible contribution of XO to oxidative stress and the pathophysiology of diabetes. HbA1c remains an important marker of glycaemic control for the management of Type 2 DM, but other confounding factors that predispose or lead to oxidative stress should also be taken into consideration. [source] Annual Banned-Substance ReviewDRUG TESTING AND ANALYSIS, Issue 4 2010You have free access to this content The annual update of the list of prohibited substances and doping methods as issued by the World Anti-Doping Agency (WADA) allows the implementation of most recent considerations of performance manipulation and emerging therapeutics into human sports doping control programmes. The annual banned-substance review for human doping controls critically summarizes recent innovations in analytical approaches that support the efforts of convicting cheating athletes by improved or newly established methods that focus on known as well as newly outlawed substances and doping methods. In the current review, literature published between October 2008 and September 2009 reporting on new and/or enhanced procedures and techniques for doping analysis, as well as aspects relevant to the doping control arena, was considered to complement the 2009 annual banned-substance review. Copyright © 2010 John Wiley & Sons, Ltd. [source] DIASTOLIC DYSFUNCTION IN HYPERTENSIVES AS ASSESSED BY TISSUE DOPPLER; RELATION TO MATRIX METALLOPROTEINASESECHOCARDIOGRAPHY, Issue 5 2004S. Nadar Objectives: To assess the severity of diastolic dysfunction in hypertensive patients as compared to normal controls and correlate it with plasma matrix metalloproteinases (MMPs). Methods: 52 patients with controlled hypertension (HT) (38 male, age 57+ 11 yrs) and 24 normotensive controls 15 male, mean age 53+ 12 years) had tissue doppler echocardiography to assess diastolic dysfunction (e, and e,/e ratios). They also had plasma MMP-9 and TIMP-1 measured. Results: The HT patients had significantly lower e, and higher e,/e ratios as compared to normotensive controls. They also had higher MMP-9 and TIMP-1 values. There was a significant inverese correlation between MMP-9 and TIMP-1 with e, and a significant positive correlation between the MMPs and e,/e ratio. THe e/a ratios as assessed by pulse wave doppler were also higher in the controls than the hypertensive patients suggesting abnormal diastolic function. Conclusions: There is significant diastolic dysfunction even in controlled hypertensives which can be assessed by tissue doppler. This newer technique compares favourably with established methods such as e/a ratio. The tissue doppler indices also correlate well with abnormalities in the matrix metalloproteinases suggesting that abnormal matrix turnover is responsible for the diastolic dysfunction. [source] Novel methods improve prediction of species' distributions from occurrence dataECOGRAPHY, Issue 2 2006Jane Elith Prediction of species' distributions is central to diverse applications in ecology, evolution and conservation science. There is increasing electronic access to vast sets of occurrence records in museums and herbaria, yet little effective guidance on how best to use this information in the context of numerous approaches for modelling distributions. To meet this need, we compared 16 modelling methods over 226 species from 6 regions of the world, creating the most comprehensive set of model comparisons to date. We used presence-only data to fit models, and independent presence-absence data to evaluate the predictions. Along with well-established modelling methods such as generalised additive models and GARP and BIOCLIM, we explored methods that either have been developed recently or have rarely been applied to modelling species' distributions. These include machine-learning methods and community models, both of which have features that may make them particularly well suited to noisy or sparse information, as is typical of species' occurrence data. Presence-only data were effective for modelling species' distributions for many species and regions. The novel methods consistently outperformed more established methods. The results of our analysis are promising for the use of data from museums and herbaria, especially as methods suited to the noise inherent in such data improve. [source] Characterization of Hprt mutations in cDNA and genomic DNA of T-cell mutants from control and 1,3-butadiene-exposed male B6C3F1 mice and F344 ratsENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 2 2004Quanxin Meng Abstract A multiplex PCR procedure for analysis of genomic DNA mutations in the mouse hypoxanthine-guanine phosphoribosyltransferase (Hprt) gene was developed and then used with other established methods for the coincident identification of large- and small-scale genetic alterations in the Hprt gene of mutant T-cell isolates propagated from sham- and 1,3-butadiene (BD)-exposed mice and rats. The spectra data for RT-PCR/cDNA analysis and multiplex PCR of genomic DNA from Hprt mutants were combined, and statistical analyses of the mutant fractions for the classes of mutations identified in control versus exposed animals were conducted. Under the assumption that the mutant fractions are distributed as Poisson variates, BD exposure of mice significantly increased the frequencies of (1) nearly all types of base substitutions; (2) single-base deletions and insertions; and (3) all subcategories of deletions. Significantly elevated fractions of G:C,C:G and A:T,T:A transversions in the Hprt gene of BD-exposed mice were consistent with the occurrence of these substitutions as the predominant ras gene mutations in multiple tumor types increased in incidence in carcinogenicity studies of BD in mice. BD exposure of rats produced significant increases in (1) base substitutions only at A:T base pairs; (2) single-base insertions; (3) complex mutations; and (4) deletions (mainly 5, partial and complete gene deletions). Future coincident analyses of large- and small-scale mutations in rodents exposed to specific BD metabolites should help identify species differences in the sources of deletion mutations and other types of mutations induced by BD exposures in mice versus rats. Environ. Mol. Mutagen. 43:75,92, 2004. © 2004 Wiley-Liss, Inc. [source] A protocol to estimate the release of anthropogenic hydrocarbons from contaminated soilsENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 9 2003Raymond C. Loehr Abstract An operational protocol, appropriate for a tier 1 or tier 2 type relative risk evaluation of a site that has polycyclic aromatic hydrocarbon (PAH) or petroleum hydrocarbon impacted soils, was developed to estimate the fraction of anthropogenic hydrophobic hydrocarbons that will be released rapidly from such soils. The development of this protocol used over 400 datasets from 40 different field samples to establish and verify the operational protocol. The datasets resulted from four-month kinetic desorption studies of these field samples. Based on the chemicals evaluated, the protocol has greatest application to two, three, and four ring-PAH and to diesel range aliphatic hydrocarbons. The protocol is a simple batch desorption analysis that uses established methods and is conducted for 7 d. The protocol results were verified with specific correlation relationships (r2 = 0.81 to 0.96) to estimate the rapidly releasing fraction (F value) that is obtained in a full, four-month chemical release evaluation. [source] A Genetic Approach to Detecting Clusters in Point Data SetsGEOGRAPHICAL ANALYSIS, Issue 3 2005Jamison Conley Spatial analysis techniques are widely used throughout geography. However, as the size of geographic data sets increases exponentially, limitations to the traditional methods of spatial analysis become apparent. To overcome some of these limitations, many algorithms for exploratory spatial analysis have been developed. This article presents both a new cluster detection method based on a genetic algorithm, and Programs for Cluster Detection, a toolkit application containing the new method as well as implementations of three established methods: Openshaw's Geographical Analysis Machine (GAM), case point-centered searching (proposed by Besag and Newell), and randomized GAM (proposed by Fotheringham and Zhan). We compare the effectiveness of cluster detection and the runtime performance of these four methods and Kulldorf's spatial scan statistic on a synthetic point data set simulating incidence of a rare disease among a spatially variable background population. The proposed method has faster average running times than the other methods and significantly reduces overreporting of the underlying clusters, thus reducing the user's postprocessing burden. Therefore, the proposed method improves upon previous methods for automated cluster detection. The results of our method are also compared with those of Map Explorer (MAPEX), a previous attempt to develop a genetic algorithm for cluster detection. The results of these comparisons indicate that our method overcomes many of the problems faced by MAPEX, thus, we believe, establishing that genetic algorithms can indeed offer a viable approach to cluster detection. [source] Using focus groups to seek the views of patients dying from cancer about the care they receiveHEALTH EXPECTATIONS, Issue 3 2000Norma V. Raynes Purpose The prime purpose of the study was to investigate whether focus groups were a practical way of seeking the views of dying people and whether the information collected added to that collected by more established methods. Design A sample frame of Macmillan nurse patients was collated from which three cluster samples were randomly selected to participate in focus groups. The focus groups were structured with an experienced facilitator and recorder to answer three key questions. Setting and participants Patients of Macmillan nurses in three NHS Trusts in West Yorkshire who were living at home with incurable cancer. They were aware of their condition and were willing to participate. Main variables studied The three key questions were; what kind of help are you currently receiving? What sort of help do you want? Of the kind of help you are receiving what kind is most important to you? Results 17 patients participated in three focus groups. Participants were generally fairly able and living with spouses or relatives. They were of varying age with different types and duration of cancer. They were receiving a range of health and social services of varying importance to them. More help was particularly wanted with support for daily living, support from specialist cancer nurses, help getting out and with housework. Macmillan nurses and general practice services were highly rated in some but not all three trust areas. Conclusions We propose that focus groups are a practical way of collecting information about dying patients that can complement other sources of information in planning and auditing the provision of care. [source] Optimal Thermal Unit Commitment Integrated with Renewable Energy Sources Using Advanced Particle Swarm OptimizationIEEJ TRANSACTIONS ON ELECTRICAL AND ELECTRONIC ENGINEERING, Issue 5 2009Shantanu Chakraborty Student member Abstract This paper presents a methodology for solving generation planning problem for thermal units integrated with wind and solar energy systems. The renewable energy sources are included in this model due to their low electricity cost and positive effect on environment. The generation planning problem also known by unit commitment problem is solved by a genetic algorithm operated improved binary particle swarm optimization (PSO) algorithm. Unlike trivial PSO, this algorithm runs the refinement process through the solutions within multiple populations. Some genetic algorithm operators such as crossover, elitism, and mutation are stochastically applied within the higher potential solutions to generate new solutions for next population. The PSO includes a new variable for updating velocity in accordance with population best along with conventional particle best and global best. The algorithm performs effectively in various sized thermal power system with equivalent solar and wind energy system and is able to produce high quality (minimized production cost) solutions. The solution model is also beneficial for reconstructed deregulated power system. The simulation results show the effectiveness of this algorithm by comparing the outcome with several established methods. Copyright © 2009 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc. [source] Matched interface and boundary (MIB) method for the vibration analysis of platesINTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN BIOMEDICAL ENGINEERING, Issue 9 2009S. N. Yu Abstract This paper proposes a novel approach, the matched interface and boundary (MIB) method, for the vibration analysis of rectangular plates with simply supported, clamped and free edges, and their arbitrary combinations. In previous work, the MIB method was developed for three-dimensional elliptic equations with arbitrarily complex material interfaces and geometric shapes. The present work generalizes the MIB method for eigenvalue problems in structural analysis with complex boundary conditions. The MIB method utilizes both uniform and non-uniform Cartesian grids. Fictitious values are utilized to facilitate the central finite difference schemes throughout the entire computational domain. Boundary conditions are enforced with fictitious values,a common practice used in the previous discrete singular convolution algorithm. An essential idea of the MIB method is to repeatedly use the boundary conditions to achieve arbitrarily high-order accuracy. A new feature in the proposed approach is the implementation of the cross derivatives in the free boundary conditions. The proposed method has a banded matrix. Nine different plates, particularly those with free edges and free corners, are employed to validate the proposed method. The performance of the proposed method is compared with that of other established methods. Convergence and comparison studies indicate that the proposed MIB method works very well for the vibration analysis of plates. In particular, modal bending moments and shear forces predicted by the proposed method vanish at boundaries for free edges. Copyright © 2008 John Wiley & Sons, Ltd. [source] Polyphenolic profile and antioxidant activity of five apple cultivars grown under organic and conventional agricultural practicesINTERNATIONAL JOURNAL OF FOOD SCIENCE & TECHNOLOGY, Issue 6 2009Athanasios Valavanidis Summary The polyphenols and total antioxidant activities of five apple cultivars, grown by organic and conventional agricultural methods in neighbouring farms, were determined and compared. Total polyphenols in the whole fruit and in the peel were determined by the Folin-Ciocalteu method, and the total antioxidant activity was determined by three established methods, diphenyl picrylhydrazyl (DPPH), azinobis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) and ferric reducing/antioxidant power (FRAP). Polyphenolic content for the whole fruit was in the range of 80,196 and for the peel 165,400 (mg Gallic Acid Equivalent (GAE)/100 g fresh weight) for both types of agricultural practices. Antioxidant activities of fruit extracts were also relatively similar and well correlated to their polyphenolic content. High-performance liquid chromatography (HPLC) analysis of the most important polyphenolics (chlorogenic acid, catechin, epicatechin, procyanidin B1 and B2, cyaniding 3-galactoside, phloridzin, quercetin 3-galactoside and quercetin 3-arabinoside) also showed that concentrations do not differentiate significantly between the organic and conventional apples. Statistical significance of differences in antioxidant activities among the same cultivars was relatively small (flesh + peel or peel only) for both types of apples. These results indicate that organic apples do not present higher antioxidant or nutritional value compared with conventionally grown ones, as far as polyphenolic content and total antioxidant activities are concerned. [source] Real-time Visualization and Quantification of Retrograde Cardioplegia Delivery using Near Infrared Fluorescent ImagingJOURNAL OF CARDIAC SURGERY, Issue 6 2008Aravind T. Rangaraj M.D. Presently, there exist no established methods to quantitatively assess cardioplegia distribution intraoperatively and determine when retrograde cardioplegia is required. In this study, we evaluate the feasibility of near infrared (NIR) imaging for real-time visualization of cardioplegia distribution in a porcine model. Methods: A portable, intraoperative, real-time NIR imaging system was utilized. NIR fluorescent cardioplegia solution was developed by incorporating indocyanine green (ICG) into crystalloid cardioplegia solution. Real-time NIR imaging was performed while the fluorescent cardioplegia solution was infused via the retrograde route in five ex vivo normal porcine hearts and in five ex vivo porcine hearts status post left anterior descending (LAD) coronary artery ligation. Horizontal cross-sections of the hearts were obtained at proximal, middle, and distal LAD levels. Videodensitometry was performed to quantify distribution of fluorophore content. Results: The progressive distribution of cardioplegia was clearly visualized with NIR imaging. Complete visualization of retrograde distribution occurred within 4 minutes of infusion. Videodensitometry revealed retrograde cardioplegia, primarily distributed to the left ventricle (LV) and anterior septum. In hearts with LAD ligation, antegrade cardioplegia did not distribute to the anterior LV. This deficiency was compensated for with retrograde cardioplegia supplementation. Conclusions: Incorporation of ICG into cardioplegia allows real-time visualization of cardioplegia delivery via NIR imaging. This technology may prove useful in guiding intraoperative decisions pertaining to when retrograde cardioplegia is mandated. [source] One-pot synthesis of [11C]ureas via triphenylphosphiniminesJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 4 2006Erica W. van Tilburg Abstract A series of 11C-labeled ureas was prepared using a rapid and efficient one-pot procedure. First, the intermediate [11C]phenylisocyanate was formed with phenyltriphenylphosphinimine and [11C]CO2. A range of amines was then reacted with the [11C]phenylisocyanate yielding the [11C]urea derivatives in short synthesis times. This easy-to-handle method circumvents disadvantages of known procedures and generates the possibility to prepare other kinds of 11C-labeled compounds using a variety of phenylphosphinimines in combination with different nucleophiles. The presented approach is an alternative to the use of established methods in 11C-labeling chemistry. Copyright © 2006 John Wiley & Sons, Ltd. [source] In-gel deglycosylation of sodiumdodecyl sulfate polyacrylamide gel electrophoresis-separated glycoproteins for carbohydrate estimation by matrix-assisted laser desorption/ionization time-of-flight mass spectrometryJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 3 2002S. Kilz Abstract Mass determination by mass spectrometric methods (electrospray ionization mass spectrometry (ESI-MS), matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS)) of sodiumdodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE)-separated proteins is a well known procedure and reliable protocols are available. In our efforts to use the established methods to determine the molecular mass of the disulfide brigded, heterodimeric glycoprotein GP3 and to determine the carbohydrate content of each protein subunit we developed an in-gel chemical deglycosylation method. For this purpose we established experimental conditions that allow maximum extraction of the high molecular mass protein subunits and developed a routine method to apply the HF,pyridine deglycosylation protocol to proteins isolated from polyacrylamide gel pieces. The novel protocol and extraction procedure described can be used to analyze O -glycosylated proteins up to 150 kDa after SDS-PAGE separation. Copyright © 2002 John Wiley & Sons, Ltd. [source] Atlas-Based Anatomic Labeling in Neurodegenerative Disease via Structure-Driven Atlas WarpingJOURNAL OF NEUROIMAGING, Issue 1 2005Dominik S. Meier PhD ABSTRACT A new method is presented for the automated anatomic labeling and comparative morphometric analysis of brain magnetic reso nance imaging, warping a prelabeled atlas into congruence with the subject anatomy. The strategy emphasizes anatomically meaningful atlas deformations in the presence of strong degen eration and substantial morphologic differences, for example, cases with high levels of atrophy. The atlas deformation is not driven by image intensity similarities but by continuous anatomic correspondence maps, derived from individual presegmented brain structures. Automatically generated correspondence maps provide large sets of fiducials, driving a warp with many thousand degrees of freedom. Validation included a scan-rescan study and anatomically relevant self-validation in multiple sclerosis patients with substantial cortical and subcortical degeneration. The mean coefficient of variation in the scan-rescan study was 1.4%, with no significant difference in preci sion between normal and neurodegenerative anatomies. The self-validation demonstrated good structural overlap, with substantial improvement over established methods, such as Talairach spatial normalization. [source] X-ray birefringence and dichroism obtained from magnetic materialsJOURNAL OF SYNCHROTRON RADIATION, Issue 4 2001S. W. Lovesey In the past decade, synchrotron radiation has triggered a surge in studies of the polarization dependence of X-ray beams passing through non-isotropic materials. A vast range of experimental results concerning polarization-dependent absorption (dichroism) and dispersion (birefringence, for example) are available from materials which are either magnetic or exhibit preferred directions due to the local atomic environment. This article aims to bring together the diversity of modern experiments in this field with established methods of optical calculus, in a way that highlights the simplicity of the underlying physics. A useful framework is formed when observable quantities, in the X-ray case, are related to atomic variables of the sample material. Atomic descriptions of absorption spectra with various levels of complexity are considered, and some well documented sum-rules are encountered. The framework is the most general allowed within the electric dipole approximation. By way of illustration, dichroic X-ray absorption by two materials with highly anisotropic properties and magnetic ions with different valence shells are considered; namely, a 3d -transition ion in ferrous niobate, and a lanthanide ion in dysprosium borocarbide. Both materials display interesting magnetic properties that are challenging to interpret at an atomic level of detail, and it is shown how absorption experiments can contribute to resolving some issues. [source] A practical guide to methods of parentage analysisMOLECULAR ECOLOGY RESOURCES, Issue 1 2010ADAM G. JONES Abstract The use of molecular techniques for parentage analysis has been a booming science for over a decade. The most important technological breakthrough was the introduction of microsatellite markers to molecular ecology, an advance that was accompanied by a proliferation and refinement of statistical techniques for the analysis of parentage data. Over the last several years, we have seen steady progress in a number of areas related to parentage analysis, and the prospects for successful studies continue to improve. Here, we provide an updated guide for scientists interested in embarking on parentage analysis in natural or artificial populations of organisms, with a particular focus on computer software packages that implement various methods of analysis. Our survey of the literature shows that there are a few established methods that perform extremely well in the analysis of most types of parentage studies. However, particular experimental designs or study systems can benefit from some of the less well-known computer packages available. Overall, we find that parentage analysis is feasible and satisfying in most systems, and we try to provide a simple roadmap to help other scientists navigate the confusing topography of statistical techniques. [source] A comparison of manual and automated methods of measuring conjunctival vessel widths from photographic and digital imagesOPHTHALMIC AND PHYSIOLOGICAL OPTICS, Issue 2 2004Christopher G. Owen Abstract We investigated the application of a fully automated computer algorithm for identifying vessels of the conjunctiva from their scleral surround, and compared measures of vessel width with established methods. Vessel widths at 101 locations (ranging from 20 to 140 ,m), from 12 patients, were measured from film and digital images, using a variety of methods, and compared. Widths were measured manually, by semi-automated methods using grey level (densitometric) profiles taken from digital images, and by automated techniques set at different operating levels. Good intra-session repeatibility was obtained using the automated method with an operating sigma value of 3 pixels (16 ,m) (mean difference 0.5 ,m, 95% CI ,8.5 to 9.4 ,m) and manual calliper measurements from digitally created photographic slides (mean difference 0.4 ,m, ,9.3 to 10.1 ,m). For comparison with other measures of width, the latter was used as the gold standard. Widths measured from film were slightly larger than those measured directly from digital images, although this effect was small (5 ,m) for most vessels. Overall widths measured using the automated method, with a sigma value of 3 pixels, agreed best with the gold standard (inter-method repeatibility; mean difference 1.4 ,m, ,32.5 to 35.2 ,m) although the automated method overestimated small widths (<40 ,m) and underestimated larger vessel widths (>40 ,m). Automated detection of vessels of the conjunctiva from digital images avoids manual and operator involved measures which are time consuming, and which preclude large patient studies. The resulting data may help in monitoring the vascular response of the conjunctiva to surgical or pharmacological intervention, and in describing vascular changes in response to ocular or systemic disease. The application of this algorithm to the study of retinal vessels is yet to be realised. [source] A quantitative strategy to detect changes in accessibility of protein regions to chemical modification on heterodimerizationPROTEIN SCIENCE, Issue 7 2009Mathias Dreger Abstract We describe a method for studying quantitative changes in accessibility of surface lysine residues of the PB1 subunit of the influenza RNA polymerase as a result of association with the PA subunit to form a PB1-PA heterodimer. Our method combines two established methods: (i) the chemical modification of surface lysine residues of native proteins by N -hydroxysuccinimidobiotin (NHS-biotin) and (ii) the stable isotope labeling of amino acids in cell culture (SILAC) followed by tryptic digestion and mass spectrometry. By linking the chemical modification with the SILAC methodology for the first time, we obtain quantitative data on chemical modification allowing subtle changes in accessibility to be described. Five regions in the PB1 monomer showed altered reactivity to NHS-biotin when compared with the [PB1-PA] heterodimer. Mutational analysis of residues in two such regions,at K265 and K481 of PB1, which were about three- and twofold, respectively, less accessible to biotinylation in the PB1-PA heterodimer compared with the PB1 monomer, demonstrated that both K265 and K481 were crucial for polymerase function. This novel assay of quantitative profiling of biotinylation patterns (Q-POP assay) highlights likely conformational changes at important functional sites, as observed here for PB1, and may provide information on protein,protein interaction interfaces. The Q-POP assay should be a generally applicable approach and may detect novel functional sites suitable for targeting by drugs. [source] Social Identity and the Yup'ik Eskimo Village Tunnel System in Precolonial and Colonial Western Coastal AlaskaARCHEOLOGICAL PAPERS OF THE AMERICAN ANTHROPOLOGICAL ASSOCIATION, Issue 1 2006Lisa Frink Some western Alaskan coastal prehistoric and protohistoric village sites had intrasite semisubterranean passageways that connected the village men's house(s) and the smaller family houses. These tunnels acted as an interstitial and negotiated space that connected the gendered spatial spheres of Yup'ik Eskimo women and men. Instead of examining a newly constructed space that may have transformed relationships, this work examines the historically contingent consequence of the loss of these tunnels as a built medium, both between women and men and among women. It is my contention that the dismantling of the multipurpose village tunnels insulated women from one another, from their established methods for learning and means for building influence and authority, and from intimate engagement with the expanding mercantilist economy and equitable access to social and economic resources. [source] Postmarketing surveillance for human teratogenicity: A model approach,BIRTH DEFECTS RESEARCH, Issue 5 2001Christina D. Chambers Background Most congenital defects associated with prenatal exposures are notable for a pattern of major and minor malformations, rather than for a single major malformation. Thus, traditional epidemiological methods are not universally effective in identifying new teratogens. The purpose of this report is to outline a complementary approach that can be used in addition to other more established methods to provide the most comprehensive evaluation of prenatal exposures with respect to teratogenicity. Methods We describe a multicenter prospective cohort study design involving dysmorphological assessment of liveborn infants. This design uses the Organization of Teratology Information Services, a North American network of information providers who also collaborate for research purposes. Procedures for subject selection, methods for data collection, standard criteria for outcome classification, and the approach to analysis are detailed. Results The focused cohort study design allows for evaluation of a spectrum of adverse pregnancy outcomes ranging from spontaneous abortion to functional deficit. While sample sizes are typically inadequate to identify increased risks for single major malformations, the use of dysmorphological examinations to classify structural anomalies provides the unique advantage of screening for a pattern of malformation among exposed infants. Conclusions As the known human teratogens are generally associated with patterns of structural defects, it is only when studies of this type are used in combination with more traditional methods that we can achieve an acceptable level of confidence regarding the risk or safety of specific exposures during pregnancy. Teratology 64:252,261, 2001. © 2001 Wiley-Liss, Inc. [source] More to teamwork than knowledge, skill and attitudeBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 10 2010D Siassakos Please cite this paper as: Siassakos D, Draycott T, Crofts J, Hunt L, Winter C, Fox R. More to teamwork than knowledge, skill and attitude. BJOG 2010;117:1262,1269. Objective, To assess whether team performance in simulated eclampsia is related to the knowledge, skills and attitudes of individual team members. Design, Cross-sectional analysis of data from the Simulation and Fire Drill Evaluation randomised controlled trial. Setting, Six secondary and tertiary maternity units in south-west England. Participants, One hundred and fourteen maternity professionals in 19 teams of six members; one senior and one junior obstetrician; two senior and two junior midwives. Methods, We validated a team performance ranking scheme with respect to magnesium administration (Magnesium Administration Rank, MAR) by expert consensus (face validity) and correlation with clinical measures (construct validity). We tested for correlation between MAR and measures of knowledge, skills and attitudes. Main outcome measures, Correlation between team performance (MAR) and scores in validated multiple-choice questionnaires (MCQs) (knowledge), a measure of individual manual skill to manage an obstetric emergency (skill) and scores in a widely used teamwork/safety attitude questionnaire (attitude). Results, There was no relationship between team performance and cumulative individual MCQs, skill or teamwork/safety attitude scores. Conclusions, The knowledge, manual skills and attitudes of the individuals comprising each team, measured by established methods, did not correlate in this study with the team's clinical efficiency in the management of simulated eclampsia. The inference is that unidentified characteristic(s) play a crucial part in the efficiency of teams managing emergencies. Any emphasis of training programmes to promote individual knowledge, skills and attitudes alone may have to be re-examined. This highlights a need to understand what makes a team efficient in dealing with clinical emergencies. [source] Prospective comparison of [18F]fluorodeoxyglucose positron emission tomography with conventional assessment by computed tomography scans and serum tumor markers for the evaluation of residual masses in patients with nonseminomatous germ cell carcinomaCANCER, Issue 9 2002Christian Kollmannsberger M.D. Abstract BACKGROUND To assess the ability of [18F]fluorodeoxyglucose (F-18 FDG) positron emission tomography (PET) to predict the viability of residual masses after chemotherapy in patients with metastatic nonseminomatous germ cell tumors (GCT), PET results were compared in a blinded analysis with computed tomography (CT) scans and serum tumor marker changes (TUM) as established methods of assessment. METHODS Independent reviewers who were blinded to each other's results evaluated the PET results and corresponding CT scan and TUM results in 85 residual lesions from 45 patients. All patients were treated within prospective clinical trials and received primary/salvage, high-dose chemotherapy with autologous blood stem cell support for primary poor prognosis disease or recurrent disease. PET results were assessed both visually and by quantifying glucose uptake (standardized uptake values). Results were validated either by histologic examination of a resected mass and/or biopsy (n = 28 lesions) or by a 6-month clinical follow-up after evaluation (n = 57 lesions). RESULTS F-18 FDG PET showed increased tracer uptake in 32 of 85 residual lesions, with 29 true positive (TP) lesions and three false positive (FP) lesions. Fifty-three lesions were classified by PET as negative (no viable GCT), 33 lesions were classified by PET as true negative (TN), and 20 lesions were classified by PET as false negative (FN). In the blinded reading of the corresponding CT scan and TUM results, 38 residual lesions were assessed correctly as containing viable carcinoma and/or teratoma. Forty-six lesions were classified as nonsuspicious by CT scan/TUM (33 TN lesions and 14 falsely classified lesions). PET correctly predicted the presence of viable carcinoma in 5 of these 14 and the absence of viable carcinoma in 3 of these 14 lesions. Resulting sensitivities and specificities for the prediction of residual mass viability were as follows: PET, 59% sensitivity and 92% specificity; radiologic monitoring, 55% sensitivity and 86% specificity; and TUM, 42% sensitivity and 100% specificity. The positive and negative predictive values for PET were 91% and 62%, respectively. The diagnostic efficacy of PET did not improve when patients with teratomatous elements in the primary tumor were excluded from the analysis. In patients with multiple residual masses, a uniformly increased residual F-18 FDG uptake in all lesions was a strong predictor for the presence of viable carcinoma. CONCLUSIONS F-18 FDG PET imaging performed in conjunction with conventional staging methods offers additional information for the prediction of residual mass histology in patients with nonseminomatous GCT. A positive PET is highly predictive for the presence of viable carcinoma. Other useful indications for a PET examination include patients with multiple residual masses and patients with marker negative disease. Cancer 2002;94:2353,62. © 2002 American Cancer Society. DOI 10.1002/cncr.10494 [source] Autocatalytic Enantiomerisation at the Crystal Surface in Deracemisation of Scalemic ConglomeratesCHEMISTRY - A EUROPEAN JOURNAL, Issue 39 2009Shengwei Wei Dr. Abstract Deracemisation of racemic or scalemic conglomerates of intrinsically chiral compounds appears to be a promising method of chiral resolution. By combining the established methods of asymmetric synthesis and the physical process of crystal growth, we were able to achieve a complete deracemisation (with 100,%,ee) of an asymmetric Mannich product conglomerate,vigorously stirred in its saturated solution,from a starting enantiomeric excess value of 15.8,% in the presence of pyrrolidine (8,mol,%) as an achiral catalyst for the CC bond-forming reaction. Strong activation of this deracemisation process was observed on mild isothermal heating to only 40,°C, resulting in dramatic acceleration by a factor of about 20 with respect to the results obtained at room temperature. Despite the fact that the racemisation half-life time of the nearly enantiopure Mannich product (with 99,%,ee) in the homogenous solution at the reaction temperature is eight days, the deracemisation process took only hours in a small-scale experiment. This apparent paradox is explained by a proposed rapid enantiomerisation at the crystal/solution interface, which was corroborated by a 13C labelling experiment that confirmed the involvement of rapid enantiomerisation. Frequent monitoring of the solution-phase ee of the slowly racemising compound further revealed that the minor enantiomer dominated in solution, supporting an explanation based on a kinetic model. A generalisation of the process of "aymmetric autocatalysis" (resulting in automultiplication of chiral products in homogenous media) to encompass heterogeneous systems is also suggested. [source] A luminescent bioassay for thyroid blocking antibodiesCLINICAL ENDOCRINOLOGY, Issue 3 2001N. J. Jordan Thyroid blocking antibodies (TBAb) have a role in the development of hypothyroidism and in the neonate are responsible for transient hypothyroidism. Specific measurement of TBAb requires a bioassay, but current methods are lengthy and cumbersome. We describe a rapid luciferase-based method for the detection of TBAb using the lulu* cell line which is suitable for the provision of a clinical service Chinese hamster ovary (CHO) cells were transfected with human TSH-R together with G418 resistance and a cAMP responsive luciferase construct. Stable pools of transfected cells were selected and clones identified by limiting dilution. Clone lulu* gave the best response to stimulation by TSH and was used to develop a bioassay for TBAb. The luminescent bioassay conditions have been optimized and validated using 12 serum samples from patients found to be TBAb positive in a bioassay using an established method quantifying cAMP by radioimmunoassay (RIA). The effect of thyroid stimulating antibodies (TSAb) on the calculation of Inhibition Index (InI) using two previously described formulae have been investigated and we have used serum containing both TSAb and TBAb to investigate detection of TBAb in samples containing more than one type of activity. Lulu* displays a dose dependent increase in luciferase expression in response to stimulation with bovine (b) TSH which is more effective in serum free medium than in salt free buffer. TSH stimulated luciferase expression can be inhibited by TBAb in either serum or an immunoglobulin preparation. Using optimized assay conditions, challenging 10% serum against 1 U/l bTSH in culture medium, we have tested 31 euthyroid sera to determine a reference range: InI values >23% were considered positive. Twelve samples previously shown to contain TBAb by an established method quantifying cAMP by RIA were positive by the luciferase-based assay. Of control sera, 20/20 systemic lupus erythematosus, 13/14 rheumatoid arthritis, 12/12 multinodular goitre were negative. We demonstrated that if more complex formulae are used to calculate InI, false positive TBAb results can be obtained in samples containing only TSAb. Finally, when sera contain both TSAb and TBAb, the net activity of stimulating and blocking antibodies is detected in the bioassay. Where TSAb are also present, analysis of serum may be required at several dilutions to detect TBAb. We describe the production of a new cell line, lulu*, and its use to develop a luminescent bioassay for TBAb suitable for clinical use. Comparing two established methods of calculating TBAb, we found that they do not give identical results. In light of this, the high prevalence reported for TBAb in some studies has to be considered with caution. [source] Legendre polynomial kernel estimation of a density function with censored observations and an application to clinical trialsCOMMUNICATIONS ON PURE & APPLIED MATHEMATICS, Issue 8 2007Simeon M. Berman Let f(x), x , ,M, M , 1, be a density function on ,M, and X1, ,., Xn a sample of independent random vectors with this common density. For a rectangle B in ,M, suppose that the X's are censored outside B, that is, the value Xk is observed only if Xk , B. The restriction of f(x) to x , B is clearly estimable by established methods on the basis of the censored observations. The purpose of this paper is to show how to extrapolate a particular estimator, based on the censored sample, from the rectangle B to a specified rectangle C containing B. The results are stated explicitly for M = 1, 2, and are directly extendible to M , 3. For M = 2, the extrapolation from the rectangle B to the rectangle C is extended to the case where B and C are triangles. This is done by means of an elementary mapping of the positive quarter-plane onto the strip {(u, v): 0 , u , 1, v > 0}. This particular extrapolation is applied to the estimation of the survival distribution based on censored observations in clinical trials. It represents a generalization of a method proposed in 2001 by the author [2]. The extrapolator has the following form: For m , 1 and n , 1, let Km, n(x) be the classical kernel estimator of f(x), x , B, based on the orthonormal Legendre polynomial kernel of degree m and a sample of n observed vectors censored outside B. The main result, stated in the cases M = 1, 2, is an explicit bound for E|Km, n(x) , f(x)| for x , C, which represents the expected absolute error of extrapolation to C. It is shown that the extrapolator is a consistent estimator of f(x), x , C, if f is sufficiently smooth and if m and n both tend to , in a way that n increases sufficiently rapidly relative to m. © 2006 Wiley Periodicals, Inc. [source] | ||||||||||||||||||||||