Development and Validation of GC-ECD Method for the Determination of Metamitron in Soil
Tandon, Shishir; Kumar, Satyendra; Sand, N. K.
2015-01-01
This paper aims at developing and validating a convenient, rapid, and sensitive method for estimation of metamitron from soil samples.Determination andquantification was carried out by Gas Chromatography on microcapillary column with an Electron Capture Detector source. The compound was extracted from soil using methanol and cleanup by C-18 SPE. After optimization, the method was validated by evaluating the analytical curves, linearity, limits of detection, and quantification, precision (repeatability and intermediate precision), and accuracy (recovery). Recovery values ranged from 89 to 93.5% within 0.05- 2.0 µg L−1 with average RSD 1.80%. The precision (repeatability) ranged from 1.7034 to 1.9144% and intermediate precision from 1.5685 to 2.1323%. Retention time was 6.3 minutes, and minimum detectable and quantifiable limits were 0.02 ng mL−1 and 0.05 ng g−1, respectively. Good linearity (R 2 = 0.998) of the calibration curves was obtained over the range from 0.05 to 2.0 µg L−1. Results indicated that the developed method is rapid and easy to perform, making it applicable for analysis in large pesticide monitoring programmes. PMID:25733978
Watanabe, Jun; Oki, Tomoyuki; Takebayashi, Jun; Yamasaki, Koji; Takano-Ishikawa, Yuko; Hino, Akihiro; Yasui, Akemi
2013-01-01
We improved the procedure for lipophilic-oxygen radical absorbance capacity (L-ORAC) measurement for better repeatability and intermediate precision. A sealing film was placed on the assay plate, and glass vials and microdispensers equipped with glass capillaries were used. The antioxidant capacities of food extracts can be evaluated by this method with nearly the same precision as antioxidant solutions.
de Andrade, Jucimara Kulek; de Andrade, Camila Kulek; Komatsu, Emy; Perreault, Hélène; Torres, Yohandra Reyes; da Rosa, Marcos Roberto; Felsner, Maria Lurdes
2017-08-01
Corn syrups, important ingredients used in food and beverage industries, often contain high levels of 5-hydroxymethyl-2-furfural (HMF), a toxic contaminant. In this work, an in house validation of a difference spectrophotometric method for HMF analysis in corn syrups was developed using sophisticated statistical tools by the first time. The methodology showed excellent analytical performance with good selectivity, linearity (R 2 =99.9%, r>0.99), accuracy and low limits (LOD=0.10mgL -1 and LOQ=0.34mgL -1 ). An excellent precision was confirmed by repeatability (RSD (%)=0.30) and intermediate precision (RSD (%)=0.36) estimates and by Horrat value (0.07). A detailed study of method precision using a nested design demonstrated that variation sources such as instruments, operators and time did not interfere in the variability of results within laboratory and consequently in its intermediate precision. The developed method is environmentally friendly, fast, cheap and easy to implement resulting in an attractive alternative for corn syrups quality control in industries and official laboratories. Copyright © 2017 Elsevier Ltd. All rights reserved.
Leaner and greener analysis of cannabinoids.
Mudge, Elizabeth M; Murch, Susan J; Brown, Paula N
2017-05-01
There is an explosion in the number of labs analyzing cannabinoids in marijuana (Cannabis sativa L., Cannabaceae) but existing methods are inefficient, require expert analysts, and use large volumes of potentially environmentally damaging solvents. The objective of this work was to develop and validate an accurate method for analyzing cannabinoids in cannabis raw materials and finished products that is more efficient and uses fewer toxic solvents. An HPLC-DAD method was developed for eight cannabinoids in cannabis flowers and oils using a statistically guided optimization plan based on the principles of green chemistry. A single-laboratory validation determined the linearity, selectivity, accuracy, repeatability, intermediate precision, limit of detection, and limit of quantitation of the method. Amounts of individual cannabinoids above the limit of quantitation in the flowers ranged from 0.02 to 14.9% w/w, with repeatability ranging from 0.78 to 10.08% relative standard deviation. The intermediate precision determined using HorRat ratios ranged from 0.3 to 2.0. The LOQs for individual cannabinoids in flowers ranged from 0.02 to 0.17% w/w. This is a significant improvement over previous methods and is suitable for a wide range of applications including regulatory compliance, clinical studies, direct patient medical services, and commercial suppliers.
Sánchez, Raquel; Snell, James; Held, Andrea; Emons, Hendrik
2015-08-01
A simple, robust and reliable method for mercury determination in seawater matrices based on the combination of cold vapour generation and inductively coupled plasma mass spectrometry (CV-ICP-MS) and its complete in-house validation are described. The method validation covers parameters such as linearity, limit of detection (LOD), limit of quantification (LOQ), trueness, repeatability, intermediate precision and robustness. A calibration curve covering the whole working range was achieved with coefficients of determination typically higher than 0.9992. The repeatability of the method (RSDrep) was 0.5 %, and the intermediate precision was 2.3 % at the target mass fraction of 20 ng/kg. Moreover, the method was robust with respect to the salinity of the seawater. The limit of quantification was 2.7 ng/kg, which corresponds to 13.5 % of the target mass fraction in the future certified reference material (20 ng/kg). An uncertainty budget for the measurement of mercury in seawater has been established. The relative expanded (k = 2) combined uncertainty is 6 %. The performance of the validated method was demonstrated by generating results for process control and a homogeneity study for the production of a candidate certified reference material.
Chung, Y L; Liu, J T; Lin, C H
2001-08-15
The analytical profiles for 3,4-methylenedioxymethamphetamine (3,4-MDMA) and related amphetamines in urine samples are described for non-aqueous capillary electrophoresis-fluorescence spectroscopy. 3,4-MDMA was detected and identified on-line, using a cryogenic molecular fluorescence technique at 77 K. Under optimized conditions, baseline separation of the selected compounds was achieved in less than 12 min. Precision was evaluated by measuring the repeatability and intermediate precision of the migration times and corrected peak areas. The non-aqueous CE separation conditions and the spectral characteristics of 3,4-MDMA with respect to solvent and temperature effects are also discussed.
de Toffoli, Ana L; da Mata, Kamilla; Bisinoti, Márcia C; Moreira, Altair B
2015-01-01
A method for the identification and quantification of pesticide residues in water, soil, and sediment samples has been developed, validated, and applied for the analysis of real samples. The specificity was determined by the retention time and the confirmation and quantification of analyte ions. Linearity was demonstrated over the concentration range of 20 to 120 µg L(-1), and the correlation coefficients varied between 0.979 and 0.996, depending on the analytes. The recovery rates for all analytes in the studied matrix were between 86% and 112%. The intermediate precision and repeatability were determined at three concentration levels (40, 80, and 120 µg L(-1)), with the relative standard deviation for the intermediate precision between 1% and 5.3% and the repeatability varying between 2% and 13.4% for individual analytes. The limits of detection and quantification for fipronil, fipronil sulfide, fipronil-sulfone, and fipronil-desulfinyl were 6.2, 3.0, 6.6, and 4.0 ng L(-1) and 20.4, 9.0, 21.6, and 13.0 ng L(-1), respectively. The method developed was used in water, soil, and sediment samples containing 2.1 mg L(-1) and 1.2% and 5.3% of carbon, respectively. The recovery of pesticides in the environmental matrices varied from 88.26 to 109.63% for the lowest fortification level (40 and 100 µg kg(-1)), from 91.17 to 110.18% for the intermediate level (80 and 200 µg kg(-1)), and from 89.09 to 109.82% for the highest fortification level (120 and 300 µg kg(-1)). The relative standard deviation for the recovery of pesticides was under 15%.
Xie, Wei-Qi; Chai, Xin-Sheng
2016-10-14
This work reports on a novel method for the determination of isocyanate groups in the related organic intermediates by a reaction-based headspace gas chromatography. The method is based on measuring the CO 2 formed from the reaction between the isocyanate groups in the organic intermediates and water in a closed headspace sample vial at 45°C for 20min. The results showed that the method has a good precision and accuracy, in which the relative standard deviation in the repeatability measurement was 5.26%, and the relative differences between the data obtained by the HS-GC method and the reference back-titration method were within 9.42%. The present method is simple and efficient and is particularly suitable to be used for determining the isocyanate groups in the batch sample analysis. Copyright © 2016 Elsevier B.V. All rights reserved.
Ansermot, Nicolas; Rudaz, Serge; Brawand-Amey, Marlyse; Fleury-Souverain, Sandrine; Veuthey, Jean-Luc; Eap, Chin B
2009-08-01
Matrix effects, which represent an important issue in liquid chromatography coupled to mass spectrometry or tandem mass spectrometry detection, should be closely assessed during method development. In the case of quantitative analysis, the use of stable isotope-labelled internal standard with physico-chemical properties and ionization behaviour similar to the analyte is recommended. In this paper, an example of the choice of a co-eluting deuterated internal standard to compensate for short-term and long-term matrix effect in the case of chiral (R,S)-methadone plasma quantification is reported. The method was fully validated over a concentration range of 5-800 ng/mL for each methadone enantiomer with satisfactory relative bias (-1.0 to 1.0%), repeatability (0.9-4.9%) and intermediate precision (1.4-12.0%). From the results obtained during validation, a control chart process during 52 series of routine analysis was established using both intermediate precision standard deviation and FDA acceptance criteria. The results of routine quality control samples were generally included in the +/-15% variability around the target value and mainly in the two standard deviation interval illustrating the long-term stability of the method. The intermediate precision variability estimated in method validation was found to be coherent with the routine use of the method. During this period, 257 trough concentration and 54 peak concentration plasma samples of patients undergoing (R,S)-methadone treatment were successfully analysed for routine therapeutic drug monitoring.
Estimate of the uncertainty in measurement for the determination of mercury in seafood by TDA AAS.
Torres, Daiane Placido; Olivares, Igor R B; Queiroz, Helena Müller
2015-01-01
An approach for the estimate of the uncertainty in measurement considering the individual sources related to the different steps of the method under evaluation as well as the uncertainties estimated from the validation data for the determination of mercury in seafood by using thermal decomposition/amalgamation atomic absorption spectrometry (TDA AAS) is proposed. The considered method has been fully optimized and validated in an official laboratory of the Ministry of Agriculture, Livestock and Food Supply of Brazil, in order to comply with national and international food regulations and quality assurance. The referred method has been accredited under the ISO/IEC 17025 norm since 2010. The approach of the present work in order to reach the aim of estimating of the uncertainty in measurement was based on six sources of uncertainty for mercury determination in seafood by TDA AAS, following the validation process, which were: Linear least square regression, Repeatability, Intermediate precision, Correction factor of the analytical curve, Sample mass, and Standard reference solution. Those that most influenced the uncertainty in measurement were sample weight, repeatability, intermediate precision and calibration curve. The obtained result for the estimate of uncertainty in measurement in the present work reached a value of 13.39%, which complies with the European Regulation EC 836/2011. This figure represents a very realistic estimate of the routine conditions, since it fairly encompasses the dispersion obtained from the value attributed to the sample and the value measured by the laboratory analysts. From this outcome, it is possible to infer that the validation data (based on calibration curve, recovery and precision), together with the variation on sample mass, can offer a proper estimate of uncertainty in measurement.
Pathways and intermediates in forced unfolding of spectrin repeats.
Altmann, Stephan M; Grünberg, Raik G; Lenne, Pierre-François; Ylänne, Jari; Raae, Arnt; Herbert, Kristina; Saraste, Matti; Nilges, Michael; Hörber, J K Heinrich
2002-08-01
Spectrin repeats are triple-helical coiled-coil domains found in many proteins that are regularly subjected to mechanical stress. We used atomic force microscopy technique and steered molecular dynamics simulations to study the behavior of a wild-type spectrin repeat and two mutants. The experiments indicate that spectrin repeats can form stable unfolding intermediates when subjected to external forces. In the simulations the unfolding proceeded via a variety of pathways. Stable intermediates were associated to kinking of the central helix close to a proline residue. A mutant stabilizing the central helix showed no intermediates in experiments, in agreement with simulation. Spectrin repeats may thus function as elastic elements, extendable to intermediate states at various lengths.
Automation of ⁹⁹Tc extraction by LOV prior ICP-MS detection: application to environmental samples.
Rodríguez, Rogelio; Leal, Luz; Miranda, Silvia; Ferrer, Laura; Avivar, Jessica; García, Ariel; Cerdà, Víctor
2015-02-01
A new, fast, automated and inexpensive sample pre-treatment method for (99)Tc determination by inductively coupled plasma-mass spectrometry (ICP-MS) detection is presented. The miniaturized approach is based on a lab-on-valve (LOV) system, allowing automatic separation and preconcentration of (99)Tc. Selectivity is provided by the solid phase extraction system used (TEVA resin) which retains selectively pertechnetate ion in diluted nitric acid solution. The proposed system has some advantages such as minimization of sample handling, reduction of reagents volume, improvement of intermediate precision and sample throughput, offering a significant decrease of both time and cost per analysis in comparison to other flow techniques and batch methods. The proposed LOV system has been successfully applied to different samples of environmental interest (water and soil) with satisfactory recoveries, between 94% and 98%. The detection limit (LOD) of the developed method is 0.005 ng. The high durability of the resin and its low amount (32 mg), its good intermediate precision (RSD 3.8%) and repeatability (RSD 2%) and its high extraction frequency (up to 5 h(-1)) makes this method an inexpensive, high precision and fast tool for monitoring (99)Tc in environmental samples. Copyright © 2014 Elsevier B.V. All rights reserved.
Nechansky, A; Szolar, O H J; Siegl, P; Zinoecker, I; Halanek, N; Wiederkum, S; Kircheis, R
2009-05-01
The fully humanized Lewis-Y carbohydrate specific monoclonal antibody (mAb) IGN311 is currently tested in a passive immunotherapy approach in a clinical phase I trail and therefore regulatory requirements demand qualified assays for product analysis. To demonstrate the functionality of its Fc-region, the capacity of IGN311 to mediate complement dependent cytotoxicity (CDC) against human breast cancer cells was evaluated. The "classical" radioactive method using chromium-51 and a FACS-based assay were established and qualified according to ICH guidelines. Parameters evaluated were specificity, response function, bias, repeatability (intra-day precision), intermediate precision (operator-time different), and linearity (assay range). In the course of a fully nested design, a four-parameter logistic equation was identified as appropriate calibration model for both methods. For the radioactive assay, the bias ranged from -6.1% to -3.6%. The intermediate precision for future means of duplicate measurements revealed values from 12.5% to 15.9% and the total error (beta-expectation tolerance interval) of the method was found to be <40%. For the FACS-based assay, the bias ranged from -8.3% to 0.6% and the intermediate precision for future means of duplicate measurements revealed values from 4.2% to 8.0%. The total error of the method was found to be <25%. The presented data demonstrate that the FACS-based CDC is more accurate than the radioactive assay. Also, the elimination of radioactivity and the 'real-time' counting of apoptotic cells further justifies the implementation of this method which was subsequently applied for testing the influence of storage at 4 degrees C and 25 degrees C ('stability testing') on the potency of IGN311 drug product. The obtained results demonstrate that the qualified functional assay represents a stability indicating test method.
ATXN2 trinucleotide repeat length correlates with risk of ALS.
Sproviero, William; Shatunov, Aleksey; Stahl, Daniel; Shoai, Maryam; van Rheenen, Wouter; Jones, Ashley R; Al-Sarraj, Safa; Andersen, Peter M; Bonini, Nancy M; Conforti, Francesca L; Van Damme, Philip; Daoud, Hussein; Del Mar Amador, Maria; Fogh, Isabella; Forzan, Monica; Gaastra, Ben; Gellera, Cinzia; Gitler, Aaron D; Hardy, John; Fratta, Pietro; La Bella, Vincenzo; Le Ber, Isabelle; Van Langenhove, Tim; Lattante, Serena; Lee, Yi-Chung; Malaspina, Andrea; Meininger, Vincent; Millecamps, Stéphanie; Orrell, Richard; Rademakers, Rosa; Robberecht, Wim; Rouleau, Guy; Ross, Owen A; Salachas, Francois; Sidle, Katie; Smith, Bradley N; Soong, Bing-Wen; Sorarù, Gianni; Stevanin, Giovanni; Kabashi, Edor; Troakes, Claire; van Broeckhoven, Christine; Veldink, Jan H; van den Berg, Leonard H; Shaw, Christopher E; Powell, John F; Al-Chalabi, Ammar
2017-03-01
We investigated a CAG trinucleotide repeat expansion in the ATXN2 gene in amyotrophic lateral sclerosis (ALS). Two new case-control studies, a British dataset of 1474 ALS cases and 567 controls, and a Dutch dataset of 1328 ALS cases and 691 controls were analyzed. In addition, to increase power, we systematically searched PubMed for case-control studies published after 1 August 2010 that investigated the association between ATXN2 intermediate repeats and ALS. We conducted a meta-analysis of the new and existing studies for the relative risks of ATXN2 intermediate repeat alleles of between 24 and 34 CAG trinucleotide repeats and ALS. There was an overall increased risk of ALS for those carrying intermediate sized trinucleotide repeat alleles (odds ratio 3.06 [95% confidence interval 2.37-3.94]; p = 6 × 10 -18 ), with an exponential relationship between repeat length and ALS risk for alleles of 29-32 repeats (R 2 = 0.91, p = 0.0002). No relationship was seen for repeat length and age of onset or survival. In contrast to trinucleotide repeat diseases, intermediate ATXN2 trinucleotide repeat expansion in ALS does not predict age of onset but does predict disease risk. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.
Bianchi, F; Careri, M; Maffini, M; Mangia, A; Mucchino, C
2003-01-01
A sensitive method for the simultaneous determination of (7)Li, (27)Al and (56)Fe by cold plasma ICP-MS was developed and validated. Experimental design was used to investigate the effects of torch position, torch power, lens 2 voltage, and coolant flow. Regression models and desirability functions were applied to find the experimental conditions providing the highest global sensitivity in a multi-elemental analysis. Validation was performed in terms of limits of detection (LOD), limits of quantitation (LOQ), linearity and precision. LODs were 1.4 and 159 ng L(-1) for (7)Li and (56)Fe, respectively; the highest LOD found being that for (27)Al (425 ng L(-1)). Linear ranges of 5 orders of magnitude for Li and 3 orders for Fe were statistically verified for each compound. Precision was evaluated by testing two concentration levels, and good results in terms of both intra-day repeatability and intermediate precision were obtained. RSD values lower than 4.8% at the lowest concentration level were calculated for intra-day repeatability. Commercially available soft drinks and alcoholic beverages contained in different packaging materials (TetraPack, polyethylene terephthalate (PET), commercial cans and glass) were analysed, and all the analytes were detected and quantitated. Copyright 2002 John Wiley & Sons, Ltd.
Precision and repeatability of the Optotrak 3020 motion measurement system.
States, R A; Pappas, E
2006-01-01
Several motion analysis systems are used by researchers to quantify human motion and to perform accurate surgical procedures. The Optotrak 3020 is one of these systems and despite its widespread use there is not any published information on its precision and repeatability. We used a repeated measures design study to evaluate the precision and repeatability of the Optotrak 3020 by measuring distance and angle in three sessions, four distances and three conditions (motion, static vertical, and static tilted). Precision and repeatability were found to be excellent for both angle and distance although they decreased with increasing distance from the sensors and with tilt from the plane of the sensors. Motion did not have a significant effect on the precision of the measurements. In conclusion, the measurement error of the Optotrak is minimal. Further studies are needed to evaluate its precision and repeatability under human motion conditions.
NASA Astrophysics Data System (ADS)
Wang, Xiufang; Nie, Xinyi; Liang, Yilang; Lu, Falong; Yan, Zhongming; Wang, Yu
2017-01-01
Intermediate resonator (repeater) between transmitter and receiver can significantly increase the distance of wireless power transfer (WPT) and the efficiency of wireless power transfer. The wireless power transfer via strongly coupled magnetic resonances with an high temperature superconducting (HTS) coil and copper coil as intermediate resonators was presented in this paper. The electromagnetic experiment system under different conditions with different repeating coils were simulated by finite element software. The spatial distribution patterns of magnetic induction intensity at different distances were plotted. In this paper, we examined transfer characteristics with HTS repeating coil and copper repeating coil at 77 K and 300 K, respectively. Simulation and experimental results show that HTS and copper repeating coil can effectively enhance the space magnetic induction intensity, which has significant effect on improving the transmission efficiency and lengthening transmission distance. We found that the efficiency and the distance of wireless power transfer system with an HTS coil as repeater is much higher by using of copper coil as repeater.
Li, Danhui; Martini, Nataly; Wu, Zimei; Wen, Jingyuan
2012-10-01
The aim of this study was to develop a simple, rapid and accurate isocratic HPLC analytical method to qualify and quantify five catechin derivatives, namely (+)-catechin (C), (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECG), (-)-epicatechin (EC) and (-)-epigallocatechin gallate (EGCG). To validate the analytical method, linearity, repeatability, intermediate precision, sensitivity, selectivity and recovery were investigated. The five catechin derivatives were completely separated by HPLC using a mobile phase containing 0.1% TFA in Milli-Q water (pH 2.0) mixed with methanol at the volume ratio of 75:25 at a flow rate of 0.8 ml/min. The method was shown to be linear (r²>0.99), repeatable with instrumental precision<2.0 and intra-assay precision<2.5 (%CV, percent coefficient of variation), precise with intra-day variation<1 and inter-day variation<2.5 (%CV, percent coefficient of variation) and sensitive (LOD<1 μg/mL and LOQ<3 μg/mL) over the calibration range for all five derivatives. Derivatives could be fully recovered in the presence of niosomal formulation (recovery rates>91%). Selectivity of the method was proven by the forced degradation studies, which showed that under acidic, basic, oxidation temperature and photolysis stresses, the parent drug can be separated from the degradation products by means of this analytical method. The described method was successfully applied in the in vitro release studies of catechin-loaded niosomes to manifest its utility in formulation characterization. Obtained results indicated that the drug release from niosomal formulations was a biphasic process and a diffusion mechanism regulated the permeation of catechin niosomes. Copyright © 2012 Elsevier B.V. All rights reserved.
Chekri, Rachida; Noël, Laurent; Vastel, Christelle; Millour, Sandrine; Kadar, Ali; Guérin, Thierry
2010-01-01
This paper describes a validation process in compliance with the NFIEN ISO/IEC 17025 standard for the determination of the macrominerals calcium, magnesium, sodium, and potassium in foodstuffs by microsampling with flame atomic absorption spectrometry after closed-vessel microwave digestion. The French Standards Commission (Agence Francaise de Normalisation) standards NF V03-110, NF EN V03-115, and XP T-90-210 were used to evaluate this method. The method was validated in the context of an analysis of the 1322 food samples of the second French Total Diet Study (TDS). Several performance criteria (linearity, LOQ, specificity, trueness, precision under repeatability conditions, and intermediate precision reproducibility) were evaluated. Furthermore, the method was monitored by several internal quality controls. The LOQ values obtained (25, 5, 8.3, and 8.3 mg/kg for Ca, Mg, Na, and K, respectively) were in compliance with the needs of the TDS. The method provided accurate results as demonstrated by a repeatability CV (CVr) of < 7% and a reproducibility CV (CVR) of < 12% for all the elements. Therefore, the results indicated that this method could be used in the laboratory for the routine determination of these four elements in foodstuffs with acceptable analytical performance.
Chen, Qingshan; Lazennec, Jean Yves; Guyen, Olivier; Kinbrum, Amy; Berry, Daniel J; An, Kai-Nan
2005-07-01
Tripolar total hip arthroplasty (THA) prosthesis had been suggested as a method to reduce the occurrence of hip dislocation and microseparation. Precisely measuring the motion of the intermediate component in vitro would provide fundamental knowledge for understanding its mechanism. The present study validates the accuracy and repeatability of a three-dimensional motion analysis system to quantitatively measure the relative motion of the intermediate component of tripolar total hip arthroplasty prostheses. Static and dynamic validations of the system were made by comparing the measurement to that of a potentiometer. Differences between the mean system-calculated angle and the angle measured by the potentiometer were within +/-1 degrees . The mean within-trial variability was less than 1 degrees . The mean slope was 0.9-1.02 for different angular velocities. The dynamic noise was within 1 degrees . The system was then applied to measure the relative motion of an eccentric THA prosthesis. The study shows that this motion analysis system provides an accurate and practical method for measuring the relative motion of the tripolar THA prosthesis in vitro, a necessary first step towards the understanding of its in vivo kinematics.
Multiple intermediates on the energy landscape of a 15-HEAT-repeat protein
Tsytlonok, Maksym; Craig, Patricio O.; Sivertsson, Elin; Serquera, David; Perrett, Sarah; Best, Robert B.; Wolynes, Peter G.; Itzhaki, Laura S.
2014-01-01
Repeat proteins are a special class of modular, non-globular proteins composed of small structural motifs arrayed to form elongated architectures and stabilised solely by short-range contacts. We find a remarkable complexity in the unfolding of the large HEAT repeat protein PR65/A. In contrast to what has been seen for small repeat proteins in which unfolding propagates from one end, the HEAT array of PR65/A ruptures at multiple distant sites, leading to intermediate states with non-contiguous folded subdomains. Kinetic analysis allows us to define a network of intermediates and to delineate the pathways that connect them. There is a dominant sequence of unfolding, reflecting a non-uniform distribution of stability across the repeat array; however the unfolding of certain intermediates is competitive, leading to parallel pathways. Theoretical models accounting for the heterogeneous contact density in the folded structure are able to rationalize the variation in stability across the array. This variation in stability also suggests how folding may direct function in a large repeat protein: The stability distribution enables certain regions to present rigid motifs for molecular recognition while affording others flexibility to broaden the search area as in a fly-casting mechanism. Thus PR65/A uses the two ends of the repeat array to bind diverse partners and thereby coordinate the dephosphorylation of many different substrates and of multiple sites within hyperphosphorylated substrates. PMID:24120762
Tan, Rachel H; Kril, Jillian J; McGinley, Ciara; Hassani, Mohammad; Masuda-Suzukake, Masami; Hasegawa, Masato; Mito, Remika; Kiernan, Matthew C; Halliday, Glenda M
2016-02-01
Despite evidence suggesting that the cerebellum may be targeted in amyotrophic lateral sclerosis (ALS), particularly in cases with repeat expansions in the ATXN2 and C9ORF72 genes, the integrity of cerebellar neurons has yet to be examined. The present study undertakes a histopathological analysis to assess the impact of these repeat expansions on cerebellar neurons and determine whether similar cerebellar pathology occurs in sporadic disease. Purkinje and granule cells were quantified in the vermis and lateral cerebellar hemispheres of ALS cases with repeat expansions in the ATXN2 and C9ORF72 genes, sporadic disease, and sporadic progressive muscular atrophy with only lower motor neuron degeneration. ALS cases with intermediate repeat expansions in the ATXN2 gene demonstrate a significant loss in Purkinje cells in the cerebellar vermis only. Despite ALS cases with expansions in the C9ORF72 gene having the highest burden of inclusion pathology, no neuronal loss was observed in this group. Neuronal numbers were also unchanged in sporadic ALS and sporadic PMA cases. The present study has established a selective loss of Purkinje cells in the cerebellar vermis of ALS cases with intermediate repeat expansions in the ATXN2 gene, suggesting a divergent pathogenic mechanism independent of upper and lower motor neuron degeneration in ALS. We discuss these findings in the context of large repeat expansions in ATXN2 and spinocerebellar ataxia type 2, providing evidence that intermediate repeats in ATXN2 cause significant, albeit less substantial, spinocerebellar damage compared with longer repeats in ATXN2. © 2016 American Neurological Association.
Storms, S M; Feltus, A; Barker, A R; Joly, M-A; Girard, M
2009-03-01
Measurement of somatropin charged variants by isoelectric focusing was replaced with capillary zone electrophoresis in the January 2006 European Pharmacopoeia Supplement 5.3, based on results from an interlaboratory collaborative study. Due to incompatibilities and method-robustness issues encountered prior to verification, a number of method parameters required optimisation. As the use of a diode array detector at 195 nm or 200 nm led to a loss of resolution, a variable wavelength detector using a 200 nm filter was employed. Improved injection repeatability was obtained by increasing the injection time and pressure, and changing the sample diluent from water to running buffer. Finally, definition of capillary pre-treatment and rinse procedures resulted in more consistent separations over time. Method verification data are presented demonstrating linearity, specificity, repeatability, intermediate precision, limit of quantitation, sample stability, solution stability, and robustness. Based on these experiments, several modifications to the current method have been recommended and incorporated into the European Pharmacopoeia to help improve method performance across laboratories globally.
EL-Houssini, Ola M.; Zawilla, Nagwan H.; Mohammad, Mohammad A.
2013-01-01
Specific stability indicating reverse-phase liquid chromatography (RP-LC) assay method (SIAM) was developed for the determination of cinnarizine (Cinn)/piracetam (Pira) and cinnarizine (Cinn)/heptaminol acefyllinate (Hept) in the presence of the reported degradation products of Cinn. A C18 column and gradient mobile phase was applied for good resolution of all peaks. The detection was achieved at 210 nm and 254 nm for Cinn/Pira and Cinn/Hept, respectively. The responses were linear over concentration ranges of 20–200, 20–1000 and 25–1000 μgmL−1 for Cinn, Pira, and Hept respectively. The proposed method was validated for linearity, accuracy, repeatability, intermediate precision, and robustness via statistical analysis of the data. The method was shown to be precise, accurate, reproducible, sensitive, and selective for the analysis of Cinn/Pira and Cinn/Hept in laboratory prepared mixtures and in pharmaceutical formulations. PMID:24137049
Rezende, Patrícia Sueli; Carmo, Geraldo Paulo do; Esteves, Eduardo Gonçalves
2015-06-01
We report the use of a method to determine the refractive index of copper(II) serum (RICS) in milk as a tool to detect the fraudulent addition of water. This practice is highly profitable, unlawful, and difficult to deter. The method was optimized and validated and is simple, fast and robust. The optimized method yielded statistically equivalent results compared to the reference method with an accuracy of 0.4% and quadrupled analytical throughput. Trueness, precision (repeatability and intermediate precision) and ruggedness are determined to be satisfactory at a 95.45% confidence level. The expanded uncertainty of the measurement was ±0.38°Zeiss at the 95.45% confidence level (k=3.30), corresponding to 1.03% of the minimum measurement expected in adequate samples (>37.00°Zeiss). Copyright © 2015 Elsevier B.V. All rights reserved.
Fang, Ching; Chung, Yu-Lin; Liu, Ju-Tsung; Lin, Cheng-Huang
2002-02-18
Because of the increasing use of 3,4-methylenedioxymethamphetamine (3,4-MDMA), a rapid and sensitive analytical technique is required for its detection and determination. Using nonaqueous capillary electrophoresis/fluorescence spectroscopy (NACE/FS) detection, it is possible to determine this drug at the level 0.5 ppm without any pre-treatment in less than 5 min. After liquid-liquid extraction, the sample can be condensed and a detection limit of 3,4-MDMA in urine of 50 ppb (S/N = 3) can be achieved. The precision of the method was evaluated by measuring the repeatability and intermediate precision of migration time and the corrected peak height by comparison with a 3,4-MDMA-D5 internal standard. With the conventional GC/MS method, it is necessary to derivatize the 3,4-MDMA before injection and the GC migration time also is in excess of 20 min. Therefore, NACE/FS represents a good complementary method to GC/MS for use in forensic analysis.
Hatoum-Aslan, Asma; Maniv, Inbal; Marraffini, Luciano A
2011-12-27
Precise RNA processing is fundamental to all small RNA-mediated interference pathways. In prokaryotes, clustered, regularly interspaced, short palindromic repeats (CRISPR) loci encode small CRISPR RNAs (crRNAs) that protect against invasive genetic elements by antisense targeting. CRISPR loci are transcribed as a long precursor that is cleaved within repeat sequences by CRISPR-associated (Cas) proteins. In many organisms, this primary processing generates crRNA intermediates that are subject to additional nucleolytic trimming to render mature crRNAs of specific lengths. The molecular mechanisms underlying this maturation event remain poorly understood. Here, we defined the genetic requirements for crRNA primary processing and maturation in Staphylococcus epidermidis. We show that changes in the position of the primary processing site result in extended or diminished maturation to generate mature crRNAs of constant length. These results indicate that crRNA maturation occurs by a ruler mechanism anchored at the primary processing site. We also show that maturation is mediated by specific cas genes distinct from those genes involved in primary processing, showing that this event is directed by CRISPR/Cas loci.
Zeleny, Reinhard; Harbeck, Stefan; Schimmel, Heinz
2009-01-09
A liquid chromatography-electrospray ionisation tandem mass spectrometry method for the simultaneous detection and quantitation of 5-nitroimidazole veterinary drugs in lyophilised pork meat, the chosen format of a candidate certified reference material, has been developed and validated. Six analytes have been included in the scope of validation, i.e. dimetridazole (DMZ), metronidazole (MNZ), ronidazole (RNZ), hydroxymetronidazole (MNZOH), hydroxyipronidazole (IPZOH), and 2-hydroxymethyl-1-methyl-5-nitroimidazole (HMMNI). The analytes were extracted from the sample with ethyl acetate, chromatographically separated on a C(18) column, and finally identified and quantified by tandem mass spectrometry in the multiple reaction monitoring mode (MRM) using matrix-matched calibration and (2)H(3)-labelled analogues of the analytes (except for MNZOH, where [(2)H(3)]MNZ was used). The method was validated in accordance with Commission Decision 2002/657/EC, by determining selectivity, linearity, matrix effect, apparent recovery, repeatability and intermediate precision, decision limits and detection capabilities, robustness of sample preparation method, and stability of extracts. Recovery at 1 microg/kg level was at 100% (estimates in the range of 101-107%) for all analytes, repeatabilities and intermediate precisions at this level were in the range of 4-12% and 2-9%, respectively. Linearity of calibration curves in the working range 0.5-10 microg/kg was confirmed, with r values typically >0.99. Decision limits (CCalpha) and detection capabilities (CCbeta) according to ISO 11843-2 (calibration curve approach) were 0.29-0.44 and 0.36-0.54 microg/kg, respectively. The method reliably identifies and quantifies the selected nitroimidazoles in the reconstituted pork meat in the low and sub-microg/kg range and will be applied in an interlaboratory comparison for determining the mass fraction of the selected nitroimidazoles in the candidate reference material currently developed at IRMM.
Fernandes, Ana Josane Dantas; Ferreira, Magda Rhayanny Assunção; Randau, Karina Perrelli; de Souza, Tatiane Pereira; Soares, Luiz Alberto Lira
2012-01-01
The aim of this work was to evaluate the spectrophotometric methodology for determining the total flavonoid content (TFC) in herbal drug and derived products from Bauhinia monandra Kurz. Several analytical parameters from this method grounded on the complex formed between flavonoids and AlCl₃ were evaluated such as herbal amount (0.25 to 1.25 g); solvent composition (ethanol 40 to 80%, v/v); as well as the reaction time and AlCl₃ concentration (2 to 9%, w/v). The method was adjusted to aqueous extractives and its performance studied through precision, linearity and preliminary robustness. The results showed an important dependence of the method response from reaction time, AlCl₃ concentration, sample amount, and solvent mixture. After choosing the optimized condition, the method was applied for the matrixes (herbal material and extractives), showing precision lower than 5% (for both parameters repeatability and intermediate precision), coefficient of determination higher than 0.99, and no important influence could be observed for slight variations from wavelength or AlCl₃ concentration. Thus, it could be concluded that the evaluated analytical procedure was suitable to quantify the total flavonoid content in raw material and aqueous extractives from leaves of B. monandra.
Mechanical Interferometry Imaging for Creep Modeling of the Cornea
Yoo, Lawrence; Reed, Jason; Gimzewski, James K.
2011-01-01
Purpose. A novel nanoindentation technique was used to biomechanically characterize each of three main layers of the cornea by using Hertzian viscoelastic formulation of creep, the deformation resulting from sustained-force application. Methods. The nanoindentation method known as mechanical interferometry imaging (MII) with <1-nm displacement precision was used to observe indentation of bovine corneal epithelium, endothelium, and stroma by a spherical ferrous probe in a calibrated magnetic field. For each specimen, creep testing was performed using two different forces for 200 seconds. Measurements for single force were used to build a quantitative Hertzian model that was then used to predict creep behavior for another imposed force. Results. For all three layers, displacement measurements were highly repeatable and were well predicted by Hertzian models. Although short- and long-term stiffnesses of the endothelium were highest of the three layers at 339.2 and 20.2 kPa, respectively, both stromal stiffnesses were lowest at 100.4 and 3.6 kPa, respectively. Stiffnesses for the epithelium were intermediate at 264.6 and 12.2 kPa, respectively. Conclusions. Precise, repeatable measurements of corneal creep behavior can be conveniently obtained using MII at mechanical scale as small as one cell thickness. When interpreted in analytical context of Hertzian viscoelasticity, MII technique proved to be a powerful tool for biomechanical characterization of time-dependent biomechanics of corneal regions. PMID:21969299
Yang, Pinfen; Sale, Winfield S.
1998-01-01
Previous structural and biochemical studies have revealed that the inner arm dynein I1 is targeted and anchored to a unique site located proximal to the first radial spoke in each 96-nm axoneme repeat on flagellar doublet microtubules. To determine whether intermediate chains mediate the positioning and docking of dynein complexes, we cloned and characterized the 140-kDa intermediate chain (IC140) of the I1 complex. Sequence and secondary structural analysis, with particular emphasis on β-sheet organization, predicted that IC140 contains seven WD repeats. Reexamination of other members of the dynein intermediate chain family of WD proteins indicated that these polypeptides also bear seven WD/β-sheet repeats arranged in the same pattern along each intermediate chain protein. A polyclonal antibody was raised against a 53-kDa fusion protein derived from the C-terminal third of IC140. The antibody is highly specific for IC140 and does not bind to other dynein intermediate chains or proteins in Chlamydomonas flagella. Immunofluorescent microscopy of Chlamydomonas cells confirmed that IC140 is distributed along the length of both flagellar axonemes. In vitro reconstitution experiments demonstrated that the 53-kDa C-terminal fusion protein binds specifically to axonemes lacking the I1 complex. Chemical cross-linking indicated that IC140 is closely associated with a second intermediate chain in the I1 complex. These data suggest that IC140 contains domains responsible for the assembly and docking of the I1 complex to the doublet microtubule cargo. PMID:9843573
Multicenter performance evaluation of a second generation cortisol assay.
Vogeser, Michael; Kratzsch, Jürgen; Ju Bae, Yoon; Bruegel, Mathias; Ceglarek, Uta; Fiers, Tom; Gaudl, Alexander; Kurka, Hedwig; Milczynski, Christoph; Prat Knoll, Cristina; Suhr, Anna C; Teupser, Daniel; Zahn, Ingrid; Ostlund, Richard E
2017-05-01
Untreated disorders of the adrenocortical system, such as Cushing's or Addison's disease, can be fatal, and accurate quantification of a patient's cortisol levels is vital for diagnosis. The objective of this study was to assess the analytical performance of a new fully-automated Elecsys® Cortisol II assay (second generation) to measure cortisol levels in serum and saliva. Four European investigational sites assessed the intermediate precision and reproducibility of the Cortisol II assay (Roche Diagnostics) under routine conditions. Method comparisons of the Cortisol II assay vs. liquid chromatography-tandem mass spectrometry (LC-MS/MS), the gold standard for cortisol measurement, were performed. Cortisol reference ranges from three US sites were determined using samples from self-reported healthy individuals. The coefficients of variation (CVs) for repeatability, intermediate precision, and reproducibility for serum samples were ≤2.6%, ≤5.8%, and ≤9.5%, respectively, and for saliva were ≤4.4% and ≤10.9%, and ≤11.4%, respectively. Agreement between the Cortisol II assay and LC-MS/MS in serum samples was close, with a slope of 1.02 and an intercept of 4.473 nmol/L. Reference range samples were collected from healthy individuals (n=300) and serum morning cortisol concentrations (5-95th percentile) were 166.1-507 nmol/L and afternoon concentrations were 73.8-291 nmol/L. Morning, afternoon, and midnight saliva concentrations (95th percentile) were 20.3, 6.94, and 7.56 nmol/L, respectively. The Cortisol II assay had good precision over the entire measuring range and had excellent agreement with LC-MS/MS. This test was found suitable for routine diagnostic application and will be valuable for the diagnosis of adrenocortical diseases.
Improving Aquatic Warbler Population Assessments by Accounting for Imperfect Detection
Oppel, Steffen; Marczakiewicz, Piotr; Lachmann, Lars; Grzywaczewski, Grzegorz
2014-01-01
Monitoring programs designed to assess changes in population size over time need to account for imperfect detection and provide estimates of precision around annual abundance estimates. Especially for species dependent on conservation management, robust monitoring is essential to evaluate the effectiveness of management. Many bird species of temperate grasslands depend on specific conservation management to maintain suitable breeding habitat. One such species is the Aquatic Warbler (Acrocephalus paludicola), which breeds in open fen mires in Central Europe. Aquatic Warbler populations have so far been assessed using a complete survey that aims to enumerate all singing males over a large area. Because this approach provides no estimate of precision and does not account for observation error, detecting moderate population changes is challenging. From 2011 to 2013 we trialled a new line transect sampling monitoring design in the Biebrza valley, Poland, to estimate abundance of singing male Aquatic Warblers. We surveyed Aquatic Warblers repeatedly along 50 randomly placed 1-km transects, and used binomial mixture models to estimate abundances per transect. The repeated line transect sampling required 150 observer days, and thus less effort than the traditional ‘full count’ approach (175 observer days). Aquatic Warbler abundance was highest at intermediate water levels, and detection probability varied between years and was influenced by vegetation height. A power analysis indicated that our line transect sampling design had a power of 68% to detect a 20% population change over 10 years, whereas raw count data had a 9% power to detect the same trend. Thus, by accounting for imperfect detection we increased the power to detect population changes. We recommend to adopt the repeated line transect sampling approach for monitoring Aquatic Warblers in Poland and in other important breeding areas to monitor changes in population size and the effects of habitat management. PMID:24713994
2012-01-01
Background Several pre-erythrocytic malaria vaccines based on the circumsporozoite protein (CSP) antigen of Plasmodium falciparum are in clinical development. Vaccine immunogenicity is commonly evaluated by the determination of anti-CSP antibody levels using IgG-based assays, but no standard assay is available to allow comparison of the different vaccines. Methods The validation of an anti-CSP repeat region enzyme-linked immunosorbent assay (ELISA) is described. This assay is based on the binding of serum antibodies to R32LR, a recombinant protein composed of the repeat region of P. falciparum CSP. In addition to the original recombinant R32LR, an easy to purify recombinant His-tagged R32LR protein has been constructed to be used as solid phase antigen in the assay. Also, hybridoma cell lines have been generated producing human anti-R32LR monoclonal antibodies to be used as a potential inexhaustible source of anti-CSP repeats standard, instead of a reference serum. Results The anti-CSP repeats ELISA was shown to be robust, specific and linear within the analytical range, and adequately fulfilled all validation criteria as defined in the ICH guidelines. Furthermore, the coefficient of variation for repeatability and intermediate precision did not exceed 23%. Non-interference was demonstrated for R32LR-binding sera, and the assay was shown to be stable over time. Conclusions This ELISA, specific for antibodies directed against the CSP repeat region, can be used as a standard assay for the determination of humoral immunogenicity in the development of any CSP-based P. falciparum malaria vaccine. PMID:23173602
Dubey, Anju; Sonker, Atul; Chaudhary, Rajendra K
2015-01-01
Antibody titration is traditionally performed using a conventional test tube (CTT) method, which is subjected to interlaboratory variations because of a lack of standardization and reproducibility. The aim of this study is to compare newer methods such as get column technology (GCT) and erythrocyte magnetized technology (EMT) for antibody titration in terms of accuracy and precision. Patient serum samples that contained immunoglobin G (IgG) red blood cell (RBC) alloantibodies of a single specificity for Rh or K anitgens were identified during routine transfusion service testing and stored. Titration and scoring were performed separately by and stored. Titration and scoring were performed separately by different laboratory personnel on CTT, GCT, and EMT. Testing was performed a total of three times on each sample. Results were analyzed for accuracy and precision. A total of 50 samples were tested. Only 20 percent of samples tested with GCT shoed titers identical to CTT, whereas 48 percent of samples tested with EMT showed titers identical to CTT. Overall, the mean of th titer difference from CTT was higher using GCT (+0.31) compared with that using EMT (+0.13). Precision shown by CTT was 30 percent, EMT was 76 percent, and GCT was 92 percent on repeat testing. GCT showed higher titer values in comparison with CTT but was found to be the most precise. EMT titers were comparable to CTT, and its precision was intermediate. Further studies to validate this method are required.
Pauwels, Jochen; D'Autry, Ward; Van den Bossche, Larissa; Dewever, Cédric; Forier, Michel; Vandenwaeyenberg, Stephanie; Wolfs, Kris; Hoogmartens, Jos; Van Schepdael, Ann; Adams, Erwin
2012-02-23
Capsaicinoids, salicylic acid, methyl and ethyl salicylate, glycol monosalicylate, camphor and l-menthol are widely used in topical formulations to relieve local pain. For each separate compound or simple mixtures, quantitative analysis methods are reported. However, for a mixture containing all above mentioned active compounds, no assay methods were found. Due to the differing physicochemical characteristics, two methods were developed and optimized simultaneously. The non-volatile capsaicinoids, salicylic acid and glycol monosalicylate were analyzed with liquid chromatography following liquid-liquid extraction, whereas the volatile compounds were analyzed with static headspace-gas chromatography. For the latter method, liquid paraffin was selected as compatible dilution solvent. The optimized methods were validated in terms of specificity, linearity, accuracy and precision in a range of 80% to 120% of the expected concentrations. For both methods, peaks were well separated without interference of other compounds. Linear relationships were demonstrated with R² values higher than 0.996 for all compounds. Accuracy was assessed by performing replicate recovery experiments with spiked blank samples. Mean recovery values were all between 98% and 102%. Precision was checked at three levels: system repeatability, method precision and intermediate precision. Both methods were found to be acceptably precise at all three levels. Finally, the method was successfully applied to the analysis of some real samples (cutaneous sticks). Copyright © 2011 Elsevier B.V. All rights reserved.
Validation of the Filovirus Plaque Assay for Use in Preclinical Studies
Shurtleff, Amy C.; Bloomfield, Holly A.; Mort, Shannon; Orr, Steven A.; Audet, Brian; Whitaker, Thomas; Richards, Michelle J.; Bavari, Sina
2016-01-01
A plaque assay for quantitating filoviruses in virus stocks, prepared viral challenge inocula and samples from research animals has recently been fully characterized and standardized for use across multiple institutions performing Biosafety Level 4 (BSL-4) studies. After standardization studies were completed, Good Laboratory Practices (GLP)-compliant plaque assay method validation studies to demonstrate suitability for reliable and reproducible measurement of the Marburg Virus Angola (MARV) variant and Ebola Virus Kikwit (EBOV) variant commenced at the United States Army Medical Research Institute of Infectious Diseases (USAMRIID). The validation parameters tested included accuracy, precision, linearity, robustness, stability of the virus stocks and system suitability. The MARV and EBOV assays were confirmed to be accurate to ±0.5 log10 PFU/mL. Repeatability precision, intermediate precision and reproducibility precision were sufficient to return viral titers with a coefficient of variation (%CV) of ≤30%, deemed acceptable variation for a cell-based bioassay. Intraclass correlation statistical techniques for the evaluation of the assay’s precision when the same plaques were quantitated by two analysts returned values passing the acceptance criteria, indicating high agreement between analysts. The assay was shown to be accurate and specific when run on Nonhuman Primates (NHP) serum and plasma samples diluted in plaque assay medium, with negligible matrix effects. Virus stocks demonstrated stability for freeze-thaw cycles typical of normal usage during assay retests. The results demonstrated that the EBOV and MARV plaque assays are accurate, precise and robust for filovirus titration in samples associated with the performance of GLP animal model studies. PMID:27110807
Is There Convincing Evidence that Intermediate Repeats in the HTT Gene Cause Huntington's Disease?
Oosterloo, Mayke; Van Belzen, Martine J; Bijlsma, Emilia K; Roos, Raymund A C
2015-01-01
Huntington's disease (HD) is a neurodegenerative disease associated with a CAG repeat expansion in the Huntingtin (HTT) gene. A trinucleotide size between 27 and 35 is considered 'intermediate' and not to cause symptoms and signs of HD. There are articles claiming otherwise, however publishing only the cases that have a HD phenotype introduces a significant publication bias. Our objective is to determine if there is convincing evidence that intermediate repeats (IA) cause HD. Previously published case reports on HTT intermediate repeat sizes and all cases from the Netherlands with an IA were reviewed for clinical symptoms and signs. Four patients had a clinical presentation of Huntington's disease and an IA out of ten reported cases in literature. Between 2001 and 2012, 1,690 patients were tested for HD in the Netherlands. One case out of 60 with an IA had a phenotype resembling HD, but had already been published in a case report. Given the high background frequency of intermediate alleles in several populations, the possibility of developing HD would have huge implications for 1-7% of the normal population. It is possible that IAs present as an endophenotype with the potential of subsequent clinical manifestations. However, given the scarcity of convincing cases, the lack of convincing biological evidence for pathogenicity of intermediate alleles, and many genes still to be discovered for HD mimics, we find that it is premature to claim that IAs can cause HD. We recommend systematic follow up of this group of individuals and if possible brain pathology for confirmation or exclusion of HD.
He, Yufei; Li, Qing; Bi, Kaishun
2015-04-01
To control the quality of Rhizoma Chuanxiong, a method based on high-performance liquid chromatography method coupled with diode array detection was developed for the quantitative analysis of six active ingredients using a single standard to determine multi-components and chemical fingerprint analysis for the first time. The separation was performed on an Agilent Zorbax SB-C18 column by gradient elution with methanol and aqueous phase (containing 0.5% glacial acetic acid) at a flow rate of 1.0 mL/min. The UV wavelength was set at 274 nm. This assay was fully validated with respect to precision, repeatability, and accuracy. All calibration curves showed good linearity (R(2) > 0.9994) within test ranges. The limit of detection and limit of quantification were lower than 0.01 and 0.03 μg/mL, respectively. The relative standard deviation for repeatability and the intermediate precision of six analytes were less than 1.6 and 2.5%, respectively, the overall recovery was 96.1-103.1%. In addition, fingerprint chromatography using hierarchical clustering analysis and similarity analysis was performed to differentiate and classify the samples. The method described here could provide a more comprehensive and reasonable scientific assessment of the quality of Rhizoma Chuanxiong. Therefore, the strategy is feasible, credible, and is easily and effectively adapted for evaluating the quality control of Rhizoma Chuanxiong. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Fast and direct analysis of Cr, Cd and Pb in brown sugar by GF AAS.
Dos Santos, Jeferson M; Quináia, Sueli P; Felsner, Maria L
2018-09-15
A simple and fast analytical method for the determination of Cr, Pb and Cd in brown sugar by GF AAS using slurry sampling was developed and in house validated for the first time. Analytical curves were prepared by external standardization for Cr, and by matrix simulation for Pb and Cd and they were linear. Low limits of quantification for Cr (32.8 ng g -1 ), Pb (49.3 ng g -1 ) and Cd (4.5 ng g -1 ) were found. Repeatability and intermediate precision estimates (<10% and <15%, respectively) and recovery rates (95-103%) demonstrated a good precision and accuracy. The levels in brown sugar samples ranged from <32.8 to 160 ng g -1 for Cr, from <49.3 to 211.0 ng g -1 for Pb and from <4.5 to 7.0 ng g -1 for Cd and they may be assigned to anthropogenic activities and the adoption of inadequate practices of production and processing. Copyright © 2018 Elsevier Ltd. All rights reserved.
Setyaningsih, W; Saputro, I E; Palma, M; Barroso, C G
2015-02-15
A new microwave-assisted extraction (MAE) method has been investigated for the extraction of phenolic compounds from rice grains. The experimental conditions studied included temperature (125-175°C), microwave power (500-1000W), time (5-15min), solvent (10-90% EtOAc in MeOH) and solvent-to-sample ratio (10:1 to 20:1). The extraction variables were optimised by the response surface methodology. Extraction temperature and solvent were found to have a highly significant effect on the response value (p<0.0005) and the extraction time also had a significant effect (p<0.05). The optimised MAE conditions were as follows: extraction temperature 185°C, microwave power 1000W, extraction time 20min, solvent 100% MeOH, and solvent-to-sample ratio 10:1. The developed method had a high precision (in terms of CV: 5.3% for repeatability and 5.5% for intermediate precision). Finally, the new method was applied to real samples in order to investigate the presence of phenolic compounds in a wide variety of rice grains. Copyright © 2014 Elsevier Ltd. All rights reserved.
Fernandes, Ana Josane Dantas; Ferreira, Magda Rhayanny Assunção; Randau, Karina Perrelli; de Souza, Tatiane Pereira; Soares, Luiz Alberto Lira
2012-01-01
The aim of this work was to evaluate the spectrophotometric methodology for determining the total flavonoid content (TFC) in herbal drug and derived products from Bauhinia monandra Kurz. Several analytical parameters from this method grounded on the complex formed between flavonoids and AlCl3 were evaluated such as herbal amount (0.25 to 1.25 g); solvent composition (ethanol 40 to 80%, v/v); as well as the reaction time and AlCl3 concentration (2 to 9%, w/v). The method was adjusted to aqueous extractives and its performance studied through precision, linearity and preliminary robustness. The results showed an important dependence of the method response from reaction time, AlCl3 concentration, sample amount, and solvent mixture. After choosing the optimized condition, the method was applied for the matrixes (herbal material and extractives), showing precision lower than 5% (for both parameters repeatability and intermediate precision), coefficient of determination higher than 0.99, and no important influence could be observed for slight variations from wavelength or AlCl3 concentration. Thus, it could be concluded that the evaluated analytical procedure was suitable to quantify the total flavonoid content in raw material and aqueous extractives from leaves of B. monandra. PMID:22701375
Large-scale assessment of polyglutamine repeat expansions in Parkinson disease
Wang, Lisa; Aasly, Jan O.; Annesi, Grazia; Bardien, Soraya; Bozi, Maria; Brice, Alexis; Carr, Jonathan; Chung, Sun J.; Clarke, Carl; Crosiers, David; Deutschländer, Angela; Eckstein, Gertrud; Farrer, Matthew J.; Goldwurm, Stefano; Garraux, Gaetan; Hadjigeorgiou, Georgios M.; Hicks, Andrew A.; Hattori, Nobutaka; Klein, Christine; Jeon, Beom; Kim, Yun J.; Lesage, Suzanne; Lin, Juei-Jueng; Lynch, Timothy; Lichtner, Peter; Lang, Anthony E.; Mok, Vincent; Jasinska-Myga, Barbara; Mellick, George D.; Morrison, Karen E.; Opala, Grzegorz; Pihlstrøm, Lasse; Pramstaller, Peter P.; Park, Sung S.; Quattrone, Aldo; Rogaeva, Ekaterina; Ross, Owen A.; Stefanis, Leonidas; Stockton, Joanne D.; Silburn, Peter A.; Theuns, Jessie; Tan, Eng K.; Tomiyama, Hiroyuki; Toft, Mathias; Van Broeckhoven, Christine; Uitti, Ryan J.; Wirdefeldt, Karin; Wszolek, Zbigniew; Xiromerisiou, Georgia; Yueh, Kuo-Chu; Zhao, Yi; Gasser, Thomas; Maraganore, Demetrius M.; Krüger, Rejko
2015-01-01
Objectives: We aim to clarify the pathogenic role of intermediate size repeat expansions of SCA2, SCA3, SCA6, and SCA17 as risk factors for idiopathic Parkinson disease (PD). Methods: We invited researchers from the Genetic Epidemiology of Parkinson's Disease Consortium to participate in the study. There were 12,346 cases and 8,164 controls genotyped, for a total of 4 repeats within the SCA2, SCA3, SCA6, and SCA17 genes. Fixed- and random-effects models were used to estimate the summary risk estimates for the genes. We investigated between-study heterogeneity and heterogeneity between different ethnic populations. Results: We did not observe any definite pathogenic repeat expansions for SCA2, SCA3, SCA6, and SCA17 genes in patients with idiopathic PD from Caucasian and Asian populations. Furthermore, overall analysis did not reveal any significant association between intermediate repeats and PD. The effect estimates (odds ratio) ranged from 0.93 to 1.01 in the overall cohort for the SCA2, SCA3, SCA6, and SCA17 loci. Conclusions: Our study did not support a major role for definite pathogenic repeat expansions in SCA2, SCA3, SCA6, and SCA17 genes for idiopathic PD. Thus, results of this large study do not support diagnostic screening of SCA2, SCA3, SCA6, and SCA17 gene repeats in the common idiopathic form of PD. Likewise, this largest multicentered study performed to date excludes the role of intermediate repeats of these genes as a risk factor for PD. PMID:26354989
Panda, Sagar Suman; Patanaik, Debasis; Ravi Kumar, Bera V. V.
2012-01-01
A simple, precise and accurate isocratic RP-HPLC stability-indicating assay method has been developed to determine diclofenac potassium and metaxalone in their combined dosage forms. Isocratic separation was achieved on a Hibar-C18, Lichrosphere-100® (250 mm × 4.6 mm i.d., particle size 5 μm) column at room temperature in isocratic mode, the mobile phase consists of methanol: water (80:20, v/v) at a flow rate of 1.0 ml/min, the injection volume was 20 μl and UV detection was carried out at 280nm. The drug was subjected to acid and alkali hydrolysis, oxidation, photolysis and heat as stress conditions. The method was validated for specificity, linearity, precision, accuracy, robustness and system suitability. The method was linear in the drug concentration range of 2.5–30 μg/ml and 20–240 μg/ml for diclofenac potassium and metaxalone, respectively. The precision (RSD) of six samples was 0.83 and 0.93% for repeatability, and the intermediate precision (RSD) among six-sample preparation was 1.63 and 0.49% for diclofenac potassium and metaxalone, respectively. The mean recoveries were between 100.99–102.58% and 99.97–100.01% for diclofenac potassium and metaxalone, respectively. The proposed method can be used successfully for routine analysis of the drug in bulk and combined pharmaceutical dosage forms. PMID:22396909
Coran, Silvia A; Mulas, Stefano
2012-11-01
A novel HPTLC-densitometric method was developed for separation and quantitation of primulasaponin I and II in different matrices. HPTLC silica gel 60 F254(S), 20 cm × 10 cm, plates with ethyl acetate:water:formic acid (5:1:1 v/v) as the mobile phase were used. Densitometric determinations were performed in reflectance mode at 540 nm after derivatization with vanillin reagent. The method was validated giving rise to a dependable and high throughput procedure well suited to routine applications. Primulasaponins were quantified in the range of 150-450 ng with RSD of repeatability and intermediate precision between 0.8 and 1.4% and accuracy within the acceptance limits. The method was tested on commercial herbal medicinal preparations claiming to contain primula root extract. Copyright © 2012 Elsevier B.V. All rights reserved.
Nielsen, Troels Tolstrup; Svenstrup, Kirsten; Budtz-Jørgensen, Esben; Eiberg, Hans; Hasholt, Lis; Nielsen, Jørgen E
2012-10-15
Hereditary spastic paraplegia (HSP) confines a group of heterogeneous neurodegenerative disorders characterized by progressive spasticity and lower limb weakness. Age of onset is highly variable even in familial cases with known mutations suggesting that the disease is modulated by other yet unknown parameters. Although progressive gait disturbances, lower limb spasticity and extensor plantar responses are hallmarks of HSP these characteristics are also found in other neurodegenerative disorders, e.g. amytrophic lateral sclerosis (ALS). HSP has been linked to ALS and frontotemporal degeneration with motor neuron disease (FTD-MND), since TDP-43 positive inclusions have recently been found in an HSP subtype, and TDP-43 are found in abundance in pathological inclusions of both ALS and FTD-MND. Furthermore, ataxin-2 (encoded by the gene ATXN2), a polyglutamine containing protein elongated in spinocerebellar ataxia type 2, has been shown to be a modulator of TDP-43 induced toxicity in ALS animal and cell models. Finally, it has been shown that ATXN2 with non-pathogenic intermediate-length CAG/CAA repeat elongations (encoding the polyglutamine tract) is a genetic risk factor of ALS. Considering the similarities in the disease phenotype and the neuropathological link between ALS and HSP we hypothesized that intermediate-length CAG/CAA repeats in ATXN2 could be a modulator of HSP. We show that in a cohort of 181 HSP patients 4.9 % of the patients had intermediate-length CAG/CAA repeats in ATXN2 which was not significantly different from the frequencies in a Danish control cohort or in American and European control populations. However, the mean age of onset was significantly lower in HSP patients with intermediate-length CAG/CAA repeats in ATXN2 compared to patients with normal length repeats. Based on these results we conclude that ATXN2 is most likely not a risk factor of HSP, whereas it might serve as a modulator of age of onset. Copyright © 2012 Elsevier B.V. All rights reserved.
Pastore, Lisa M; Young, Steven L; Manichaikul, Ani; Baker, Valerie L; Wang, Xin Q; Finkelstein, Joel S
2017-01-01
To study whether reported, but inconsistent, associations between the FMR1 CGG repeat lengths in the intermediate, high normal, or low normal range differentiate women diagnosed with diminished ovarian reserve (DOR) from population controls and whether associations vary by race/ethnic group. Case-control study. Academic and private fertility clinics. DOR cases (n = 129; 95 Whites, 22 Asian, 12 other) from five U.S. fertility clinics were clinically diagnosed, with regular menses and no fragile X syndrome family history. Normal fertility controls (n = 803; 386 Whites, 219 African-Americans, 102 Japanese, 96 Chinese) from the United States-based SWAN Study had one or more menstrual period in the 3 months pre-enrollment, one or more pregnancy, no history of infertility or hormone therapy, and menopause ≥46 years. Previously, the SWAN Chinese and Japanese groups had similar FMR1 CGG repeat lengths, thus they were combined. None. FMR1 CGG repeat lengths. Median CGG repeats were nearly identical by case/control group. DOR cases had fewer CGG repeats in the shorter FMR1 allele than controls among Whites, but this was not significant among Asians. White cases had fewer CGG repeats in the shorter allele than Asian cases. No significant differences were found in the high normal/intermediate range between cases and controls or by race/ethnic group within cases in the longer allele. This study refutes prior reports of an association between DOR and high normal/intermediate repeats and confirms an association between DOR and low normal repeats in Whites. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Lopez-Gazpio, Josu; Garcia-Arrona, Rosa; Millán, Esmeralda
2015-04-01
In this work, a simple and reliable micellar electrokinetic chromatography method for the separation and quantification of 14 preservatives, including isothiazolinones, and two benzophenone-type UV filters in household, cosmetic and personal care products was developed. The selected priority compounds are widely used as ingredients in many personal care products, and are included in the European Regulation concerning cosmetic products. The electrophoretic separation parameters were optimized by means of a modified chromatographic response function in combination with an experimental design, namely a central composite design. After optimization of experimental conditions, the BGE selected for the separation of the targets consisted of 60 mM SDS, 18 mM sodium tetraborate, pH 9.4 and 10% v/v methanol. The MEKC method was checked in terms of linearity, LODs and quantification, repeatability, intermediate precision, and accuracy, providing appropriate values (i.e. R(2) ≥ 0.992, repeatability RSD values ˂9%, and accuracy 90-115%). Applicability of the validated method was successfully assessed by quantifying preservatives and UV filters in commercial consumer products. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Pascale, Raffaella; Caivano, Marianna; Buchicchio, Alessandro; Mancini, Ignazio M; Bianco, Giuliana; Caniani, Donatella
2017-01-13
Wastewater treatment plants (WWTPs) emit CO 2 and N 2 O, which may lead to climate change and global warming. Over the last few years, awareness of greenhouse gas (GHG) emissions from WWTPs has increased. Moreover, the development of valid, reliable, and high-throughput analytical methods for simultaneous gas analysis is an essential requirement for environmental applications. In the present study, an analytical method based on a gas chromatograph (GC) equipped with a barrier ionization discharge (BID) detector was developed for the first time. This new method simultaneously analyses CO 2 and N 2 O and has a precision, measured in terms of relative standard of variation RSD%, equal to or less than 6.6% and 5.1%, respectively. The method's detection limits are 5.3ppm v for CO 2 and 62.0ppb v for N 2 O. The method's selectivity, linearity, accuracy, repeatability, intermediate precision, limit of detection and limit of quantification were good at trace concentration levels. After validation, the method was applied to a real case of N 2 O and CO 2 emissions from a WWTP, confirming its suitability as a standard procedure for simultaneous GHG analysis in environmental samples containing CO 2 levels less than 12,000mg/L. Copyright © 2016 Elsevier B.V. All rights reserved.
NASA Astrophysics Data System (ADS)
Fogl, Claudia; Mohammed, Fiyaz; Al-Jassar, Caezar; Jeeves, Mark; Knowles, Timothy J.; Rodriguez-Zamora, Penelope; White, Scott A.; Odintsova, Elena; Overduin, Michael; Chidgey, Martyn
2016-03-01
Plakin proteins form critical connections between cell junctions and the cytoskeleton; their disruption within epithelial and cardiac muscle cells cause skin-blistering diseases and cardiomyopathies. Envoplakin has a single plakin repeat domain (PRD) which recognizes intermediate filaments through an unresolved mechanism. Herein we report the crystal structure of envoplakin's complete PRD fold, revealing binding determinants within its electropositive binding groove. Four of its five internal repeats recognize negatively charged patches within vimentin via five basic determinants that are identified by nuclear magnetic resonance spectroscopy. Mutations of the Lys1901 or Arg1914 binding determinants delocalize heterodimeric envoplakin from intracellular vimentin and keratin filaments in cultured cells. Recognition of vimentin is abolished when its residues Asp112 or Asp119 are mutated. The latter slot intermediate filament rods into basic PRD domain grooves through electrosteric complementarity in a widely applicable mechanism. Together this reveals how plakin family members form dynamic linkages with cytoskeletal frameworks.
Ciura, Sorana; Sellier, Chantal; Campanari, Maria-Letizia; Charlet-Berguerand, Nicolas; Kabashi, Edor
2016-01-01
ABSTRACT The most common genetic cause for amyotrophic lateral sclerosis and frontotemporal dementia (ALS-FTD) is repeat expansion of a hexanucleotide sequence (GGGGCC) within the C9orf72 genomic sequence. To elucidate the functional role of C9orf72 in disease pathogenesis, we identified certain molecular interactors of this factor. We determined that C9orf72 exists in a complex with SMCR8 and WDR41 and that this complex acts as a GDP/GTP exchange factor for RAB8 and RAB39, 2 RAB GTPases involved in macroautophagy/autophagy. Consequently, C9orf72 depletion in neuronal cultures leads to accumulation of unresolved aggregates of SQSTM1/p62 and phosphorylated TARDBP/TDP-43. However, C9orf72 reduction does not lead to major neuronal toxicity, suggesting that a second stress may be required to induce neuronal cell death. An intermediate size of polyglutamine repeats within ATXN2 is an important genetic modifier of ALS-FTD. We found that coexpression of intermediate polyglutamine repeats (30Q) of ATXN2 combined with C9orf72 depletion increases the aggregation of ATXN2 and neuronal toxicity. These results were confirmed in zebrafish embryos where partial C9orf72 knockdown along with intermediate (but not normal) repeat expansions in ATXN2 causes locomotion deficits and abnormal axonal projections from spinal motor neurons. These results demonstrate that C9orf72 plays an important role in the autophagy pathway while genetically interacting with another major genetic risk factor, ATXN2, to contribute to ALS-FTD pathogenesis. PMID:27245636
Ciura, Sorana; Sellier, Chantal; Campanari, Maria-Letizia; Charlet-Berguerand, Nicolas; Kabashi, Edor
2016-08-02
The most common genetic cause for amyotrophic lateral sclerosis and frontotemporal dementia (ALS-FTD) is repeat expansion of a hexanucleotide sequence (GGGGCC) within the C9orf72 genomic sequence. To elucidate the functional role of C9orf72 in disease pathogenesis, we identified certain molecular interactors of this factor. We determined that C9orf72 exists in a complex with SMCR8 and WDR41 and that this complex acts as a GDP/GTP exchange factor for RAB8 and RAB39, 2 RAB GTPases involved in macroautophagy/autophagy. Consequently, C9orf72 depletion in neuronal cultures leads to accumulation of unresolved aggregates of SQSTM1/p62 and phosphorylated TARDBP/TDP-43. However, C9orf72 reduction does not lead to major neuronal toxicity, suggesting that a second stress may be required to induce neuronal cell death. An intermediate size of polyglutamine repeats within ATXN2 is an important genetic modifier of ALS-FTD. We found that coexpression of intermediate polyglutamine repeats (30Q) of ATXN2 combined with C9orf72 depletion increases the aggregation of ATXN2 and neuronal toxicity. These results were confirmed in zebrafish embryos where partial C9orf72 knockdown along with intermediate (but not normal) repeat expansions in ATXN2 causes locomotion deficits and abnormal axonal projections from spinal motor neurons. These results demonstrate that C9orf72 plays an important role in the autophagy pathway while genetically interacting with another major genetic risk factor, ATXN2, to contribute to ALS-FTD pathogenesis.
Francisco, Fabiane Lacerda; Saviano, Alessandro Morais; Pinto, Terezinha de Jesus Andreoli; Lourenço, Felipe Rebello
2014-08-01
Microbiological assays have been used to evaluate antimicrobial activity since the discovery of the first antibiotics. Despite their limitations, microbiological assays are widely employed to determine antibiotic potency of pharmaceutical dosage forms, since they provide a measure of biological activity. The aim of this work is to develop, optimize and validate a rapid colorimetric microplate bioassay for the potency of neomycin in pharmaceutical drug products. Factorial and response surface methodologies were used in the development and optimization of the choice of microorganism, culture medium composition, amount of inoculum, triphenyltetrazolium chloride (TTC) concentration and neomycin concentration. The optimized bioassay method was validated by the assessment of linearity (range 3.0 to 5.0μg/mL, r=0.998 and 0.994 for standard and sample curves, respectively), precision (relative standard deviation (RSD) of 2.8% and 4.0 for repeatability and intermediate precision, respectively), accuracy (mean recovery=100.2%) and robustness. Statistical analysis showed equivalency between agar diffusion microbiological assay and rapid colorimetric microplate bioassay. In addition, microplate bioassay had advantages concerning the sensitivity of response, time of incubation, and amount of culture medium and solutions required. Copyright © 2014 Elsevier B.V. All rights reserved.
Evidence for Long-Timescale Patterns of Synaptic Inputs in CA1 of Awake Behaving Mice.
Kolb, Ilya; Talei Franzesi, Giovanni; Wang, Michael; Kodandaramaiah, Suhasa B; Forest, Craig R; Boyden, Edward S; Singer, Annabelle C
2018-02-14
Repeated sequences of neural activity are a pervasive feature of neural networks in vivo and in vitro In the hippocampus, sequential firing of many neurons over periods of 100-300 ms reoccurs during behavior and during periods of quiescence. However, it is not known whether the hippocampus produces longer sequences of activity or whether such sequences are restricted to specific network states. Furthermore, whether long repeated patterns of activity are transmitted to single cells downstream is unclear. To answer these questions, we recorded intracellularly from hippocampal CA1 of awake, behaving male mice to examine both subthreshold activity and spiking output in single neurons. In eight of nine recordings, we discovered long (900 ms) reoccurring subthreshold fluctuations or "repeats." Repeats generally were high-amplitude, nonoscillatory events reoccurring with 10 ms precision. Using statistical controls, we determined that repeats occurred more often than would be expected from unstructured network activity (e.g., by chance). Most spikes occurred during a repeat, and when a repeat contained a spike, the spike reoccurred with precision on the order of ≤20 ms, showing that long repeated patterns of subthreshold activity are strongly connected to spike output. Unexpectedly, we found that repeats occurred independently of classic hippocampal network states like theta oscillations or sharp-wave ripples. Together, these results reveal surprisingly long patterns of repeated activity in the hippocampal network that occur nonstochastically, are transmitted to single downstream neurons, and strongly shape their output. This suggests that the timescale of information transmission in the hippocampal network is much longer than previously thought. SIGNIFICANCE STATEMENT We found long (≥900 ms), repeated, subthreshold patterns of activity in CA1 of awake, behaving mice. These repeated patterns ("repeats") occurred more often than expected by chance and with 10 ms precision. Most spikes occurred within repeats and reoccurred with a precision on the order of 20 ms. Surprisingly, there was no correlation between repeat occurrence and classical network states such as theta oscillations and sharp-wave ripples. These results provide strong evidence that long patterns of activity are repeated and transmitted to downstream neurons, suggesting that the hippocampus can generate longer sequences of repeated activity than previously thought. Copyright © 2018 the authors 0270-6474/18/381822-14$15.00/0.
High-precision radius automatic measurement using laser differential confocal technology
NASA Astrophysics Data System (ADS)
Jiang, Hongwei; Zhao, Weiqian; Yang, Jiamiao; Guo, Yongkui; Xiao, Yang
2015-02-01
A high precision radius automatic measurement method using laser differential confocal technology is proposed. Based on the property of an axial intensity curve that the null point precisely corresponds to the focus of the objective and the bipolar property, the method uses the composite PID (proportional-integral-derivative) control to ensure the steady movement of the motor for process of quick-trigger scanning, and uses least-squares linear fitting to obtain the position of the cat-eye and confocal positions, then calculates the radius of curvature of lens. By setting the number of measure times, precision auto-repeat measurement of the radius of curvature is achieved. The experiment indicates that the method has the measurement accuracy of better than 2 ppm, and the measuring repeatability is better than 0.05 μm. In comparison with the existing manual-single measurement, this method has a high measurement precision, a strong environment anti-interference capability, a better measuring repeatability which is only tenth of former's.
Chernyatina, Anastasia A; Nicolet, Stefan; Aebi, Ueli; Herrmann, Harald; Strelkov, Sergei V
2012-08-21
Together with actin filaments and microtubules, intermediate filaments (IFs) are the basic cytoskeletal components of metazoan cells. Over 80 human diseases have been linked to mutations in various IF proteins to date. However, the filament structure is far from being resolved at the atomic level, which hampers rational understanding of IF pathologies. The elementary building block of all IF proteins is a dimer consisting of an α-helical coiled-coil (CC) "rod" domain flanked by the flexible head and tail domains. Here we present three crystal structures of overlapping human vimentin fragments that comprise the first half of its rod domain. Given the previously solved fragments, a nearly complete atomic structure of the vimentin rod has become available. It consists of three α-helical segments (coils 1A, 1B, and 2) interconnected by linkers (L1 and L12). Most of the CC structure has a left-handed twist with heptad repeats, but both coil 1B and coil 2 also exhibit untwisted, parallel stretches with hendecad repeats. In the crystal structure, linker L1 was found to be α-helical without being involved in the CC formation. The available data allow us to construct an atomic model of the antiparallel tetramer representing the second level of vimentin assembly. Although the presence of the nonhelical head domains is essential for proper tetramer stabilization, the precise alignment of the dimers forming the tetramer appears to depend on the complementarity of their surface charge distribution patterns, while the structural plasticity of linker L1 and coil 1A plays a role in the subsequent IF assembly process.
Information encoded in non-native states drives substrate-chaperone pairing.
Mapa, Koyeli; Tiwari, Satyam; Kumar, Vignesh; Jayaraj, Gopal Gunanathan; Maiti, Souvik
2012-09-05
Many proteins refold in vitro through kinetic folding intermediates that are believed to be by-products of native-state centric evolution. These intermediates are postulated to play only minor roles, if any, in vivo because they lack any information related to translation-associated vectorial folding. We demonstrate that refolding intermediate of a test protein, generated in vitro, is able to find its cognate chaperone, from the whole complement of Escherichia coli soluble chaperones. Cognate chaperone-binding uniquely alters the conformation of non-native substrate. Importantly, precise chaperone targeting of substrates are maintained as long as physiological molar ratios of chaperones remain unaltered. Using a library of different chaperone substrates, we demonstrate that kinetically trapped refolding intermediates contain sufficient structural features for precise targeting to cognate chaperones. We posit that evolution favors sequences that, in addition to coding for a functional native state, encode folding intermediates with higher affinity for cognate chaperones than noncognate ones. Copyright © 2012 Elsevier Ltd. All rights reserved.
Contribution of ATXN2 intermediary polyQ expansions in a spectrum of neurodegenerative disorders.
Lattante, Serena; Millecamps, Stéphanie; Stevanin, Giovanni; Rivaud-Péchoux, Sophie; Moigneu, Carine; Camuzat, Agnès; Da Barroca, Sandra; Mundwiller, Emeline; Couarch, Philippe; Salachas, François; Hannequin, Didier; Meininger, Vincent; Pasquier, Florence; Seilhean, Danielle; Couratier, Philippe; Danel-Brunaud, Véronique; Bonnet, Anne-Marie; Tranchant, Christine; LeGuern, Eric; Brice, Alexis; Le Ber, Isabelle; Kabashi, Edor
2014-09-09
The aim of this study was to establish the frequency of ATXN2 polyglutamine (polyQ) expansion in large cohorts of patients with amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and progressive supranuclear palsy (PSP), and to evaluate whether ATXN2 could act as a modifier gene in patients carrying the C9orf72 expansion. We screened a large cohort of French patients (1,144 ALS, 203 FTD, 168 FTD-ALS, and 109 PSP) for ATXN2 CAG repeat length. We included in our cohort 322 carriers of the C9orf72 expansion (202 ALS, 63 FTD, and 57 FTD-ALS). We found a significant association with intermediate repeat size (≥29 CAG) in patients with ALS (both familial and sporadic) and, for the first time, in patients with familial FTD-ALS. Of interest, we found the co-occurrence of pathogenic C9orf72 expansion in 23.2% of ATXN2 intermediate-repeat carriers, all in the FTD-ALS and familial ALS subgroups. In the cohort of C9orf72 carriers, 3.1% of patients also carried an intermediate ATXN2 repeat length. ATXN2 repeat lengths in patients with PSP and FTD were found to be similar to the controls. ATXN2 intermediary repeat length is a strong risk factor for ALS and FTD-ALS. Furthermore, we propose that ATXN2 polyQ expansions could act as a strong modifier of the FTD phenotype in the presence of a C9orf72 repeat expansion, leading to the development of clinical signs featuring both FTD and ALS. © 2014 American Academy of Neurology.
Contribution of ATXN2 intermediary polyQ expansions in a spectrum of neurodegenerative disorders
Lattante, Serena; Millecamps, Stéphanie; Stevanin, Giovanni; Rivaud-Péchoux, Sophie; Moigneu, Carine; Camuzat, Agnès; Da Barroca, Sandra; Mundwiller, Emeline; Couarch, Philippe; Salachas, François; Hannequin, Didier; Meininger, Vincent; Pasquier, Florence; Seilhean, Danielle; Couratier, Philippe; Danel-Brunaud, Véronique; Bonnet, Anne-Marie; Tranchant, Christine; LeGuern, Eric; Brice, Alexis; Le Ber, Isabelle
2014-01-01
Objective: The aim of this study was to establish the frequency of ATXN2 polyglutamine (polyQ) expansion in large cohorts of patients with amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and progressive supranuclear palsy (PSP), and to evaluate whether ATXN2 could act as a modifier gene in patients carrying the C9orf72 expansion. Methods: We screened a large cohort of French patients (1,144 ALS, 203 FTD, 168 FTD-ALS, and 109 PSP) for ATXN2 CAG repeat length. We included in our cohort 322 carriers of the C9orf72 expansion (202 ALS, 63 FTD, and 57 FTD-ALS). Results: We found a significant association with intermediate repeat size (≥29 CAG) in patients with ALS (both familial and sporadic) and, for the first time, in patients with familial FTD-ALS. Of interest, we found the co-occurrence of pathogenic C9orf72 expansion in 23.2% of ATXN2 intermediate-repeat carriers, all in the FTD-ALS and familial ALS subgroups. In the cohort of C9orf72 carriers, 3.1% of patients also carried an intermediate ATXN2 repeat length. ATXN2 repeat lengths in patients with PSP and FTD were found to be similar to the controls. Conclusions: ATXN2 intermediary repeat length is a strong risk factor for ALS and FTD-ALS. Furthermore, we propose that ATXN2 polyQ expansions could act as a strong modifier of the FTD phenotype in the presence of a C9orf72 repeat expansion, leading to the development of clinical signs featuring both FTD and ALS. PMID:25098532
Direct evaluation of fault trees using object-oriented programming techniques
NASA Technical Reports Server (NTRS)
Patterson-Hine, F. A.; Koen, B. V.
1989-01-01
Object-oriented programming techniques are used in an algorithm for the direct evaluation of fault trees. The algorithm combines a simple bottom-up procedure for trees without repeated events with a top-down recursive procedure for trees with repeated events. The object-oriented approach results in a dynamic modularization of the tree at each step in the reduction process. The algorithm reduces the number of recursive calls required to solve trees with repeated events and calculates intermediate results as well as the solution of the top event. The intermediate results can be reused if part of the tree is modified. An example is presented in which the results of the algorithm implemented with conventional techniques are compared to those of the object-oriented approach.
Development and application of a method for Cr(III) determination in dairy products by HPLC-ICP-MS.
Hernandez, Fanny; Jitaru, Petru; Cormant, Florence; Noël, Laurent; Guérin, Thierry
2018-02-01
This study describes the development of an analytical approach for the determination of Cr(III) in dairy products by microwave assisted extraction, complexation in situ by ethylenediaminetetraacetate (EDTA) and high performance liquid chromatography hyphenated to inductively coupled plasma-mass spectrometry (HPLC-ICP-MS). The extraction step was optimised by using an experimental design. A limit of quantification of 38µgkg -1 dry weight (d.w.) was obtained whereas the bias (%) measured ranged from 10 to 18%. The repeatability and intermediate precision varied between 1.2-5.0% and 7.5-13.5%, respectively. The method was applied to the analysis of several dairy samples beforehand characterized in terms of Cr(VI) and total chromium (Cr total ). Cr(III) concentrations ranged from <13 to 255µgkg -1 d.w. The results showed a good agreement between Cr(III) and Cr total concentration levels. Copyright © 2017 Elsevier Ltd. All rights reserved.
NASA Astrophysics Data System (ADS)
Ivanova, V.; Surleva, A.; Koleva, B.
2018-06-01
An ion chromatographic method for determination of fluoride, chloride, nitrate and sulphate in untreated and treated drinking waters was described. An automated 850 IC Professional, Metrohm system equipped with conductivity detector and Metrosep A Supp 7-250 (250 x 4 mm) column was used. The validation of the method was performed for simultaneous determination of all studied analytes and the results have showed that the validated method fits the requirements of the current water legislation. The main analytical characteristics were estimated for each of studied analytes: limits of detection, limits of quantification, working and linear ranges, repeatability and intermediate precision, recovery. The trueness of the method was estimated by analysis of certified reference material for soft drinking water. Recovery test was performed on spiked drinking water samples. An uncertainty was estimated. The method was applied for analysis of drinking waters before and after chlorination.
Coran, Silvia A; Mulas, Stefano; Mulinacci, Nadia
2012-01-13
A new HPTLC method was envisaged to determine rosmarinic acid (RA) in different matrices with the aim of testing the influence of optimizing the main HPTLC operative parameters in view of a more stringent validation process. HPTLC LiChrospher silica gel 60 F254s, 20 cm × 10 cm, plates with toluene:ethyl formate:formic acid (6:4:1, v/v) as the mobile phase were used. Densitometric determinations were performed in reflectance mode at 330 nm. The method was validated giving rise to a dependable and high throughput procedure well suited to routine applications. RA was quantified in the range of 132-660 ng with RSD of repeatability and intermediate precision not exceeding 2.0% and accuracy within the acceptance limits. The method was tested on several commercial preparations containing RA in different amounts. Copyright © 2011 Elsevier B.V. All rights reserved.
Selective determination of aloin in different matrices by HPTLC densitometry in fluorescence mode.
Coran, Silvia A; Bartolucci, Gianluca; Bambagiotti-Alberti, Massimo
2011-01-25
A novel method based on the fluorescence excited solely on aloin by a H₃BO₃ derivatizing procedure, allowed its rapid and selective determination among the co-occurring components in a variety of complex matrices as several Aloes dried extracts and related commercial products. HPTLC LiChrospher silica gel 60 F254S, 20 cm x 10 cm, plates with ethyl formate: CH₃OH:H₂O (100:14.5:10, v/v) as the mobile phase were used. Densitometric determinations were performed in fluorescence mode, exciting wavelength 365 nm, optical filter K540 after derivatization with H₃BO₃. The method was validated giving rise to a dependable and high throughput procedure well suited to routine application. Aloin was quantified in the range of 110-330 ng with RSD of repeatability and intermediate precision not exceeding 2.3% and accuracy inside the acceptance limits. Copyright © 2010 Elsevier B.V. All rights reserved.
Analysis of eight glycols in serum using LC-ESI-MS-MS.
Imbert, Laurent; Saussereau, Elodie; Lacroix, Christian
2014-01-01
A liquid chromatography coupled with electrospray tandem mass spectrometry method was developed for the analysis of ethylene glycol, diethylene glycol, triethylene glycol, 1,4-butanediol, 1,2-butanediol, 2,3-butanediol, 1,2-propanediol and 1,3-propanediol, in serum after a Schotten-Baumann derivatization by benzoyl chloride. Usual validation parameters were tested: linearity, repeatability and intermediate precision, limits of detection and quantification, carry over and ion suppression. Limits of detection were between 0.18 and 1.1 mg/L, and limits of quantification were between 0.4 and 2.3 mg/L. Separation of isomers was possible either chromatographically or by selecting specific multiple reaction monitoring transitions. This method could be a useful tool in case of suspected intoxication with antifreeze agents, solvents, dietary supplements or some medical drug compounds. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Norambuena, Luis; Gras, Nuri; Contreras, Sergio
2013-08-15
A simple and rapid method for the detection and extraction of oxolinic acid, flumequine, florfenicol and oxytetracycline from marine sediments was developed and validated. The analytes were extracted from the marine sediment using a solution of oxalic acid diluted in methanol with sonication before detection by HPLC using a diode-array detector (florfenicol and oxytetracycline) and fluorescence (oxolinic acid and flumequine). The quantification limits (QL) were 100 ng/g for oxytetracycline and florfenicol and 5 ng/g for oxolinic acid and flumequine. The coefficients of variation of the repeatability and intermediate precision were less than 10% in all of the analytes. The calibration curves were linear between 50 and 500 ng/ml for oxytetracycline and florfenicol and 1 and 20 ng/ml for oxolinic acid and flumequine. The recuperation rate for the analytes was above 86%. Copyright © 2013 Elsevier Ltd. All rights reserved.
ATXN2 is a modifier of phenotype in ALS patients of Sardinian ancestry
Borghero, Giuseppe; Pugliatti, Maura; Marrosu, Francesco; Marrosu, Maria Giovanna; Murru, Maria Rita; Floris, Gianluca; Cannas, Antonino; Parish, Leslie D.; Cau, Tea B.; Loi, Daniela; Ticca, Anna; Traccis, Sebastiano; Manera, Umberto; Canosa, Antonio; Moglia, Cristina; Calvo, Andrea; Barberis, Marco; Brunetti, Maura; Renton, Alan E.; Nalls, Mike A.; Traynor, Bryan J.; Restagno, Gabriella; Chiò, Adriano
2016-01-01
Intermediate-length CAG expansions (encoding 27–33 glutamines, polyQ) of the Ataxin2 (ATXN2) gene represent a risk factor for amyotrophic lateral sclerosis (ALS). Recently, it has been proposed that ≥31 CAG expansions may influence ALS phenotype. We assessed whether ATXN2 intermediate-length polyQ expansions influence ALS phenotype in a series of 375 patients of Sardinian ancestry. Controls were 247 neurologically healthy subjects, resident in the study area, age- and gender-matched to cases. The frequency of ≥31 polyQ ATNX2 repeats was significantly more common in ALS cases (4 patients vs. no control, p = 0.0001). All patients with ≥31 polyQ repeats had a spinal onset versus 73.3% of patients with <31 polyQ repeats. Patients with an increased number of polyQ repeats have a shorter survival than those with <31 repeats (1.2 vs. 4.2 years, p = 0.035). In this large series of ALS patients of Sardinian ancestry, we have found that ≥31 polyQ repeats of the ATXN2 gene influenced patients' phenotype, being associated to a spinal onset and a significantly shorter survival. PMID:26208502
Satpathy, Gouri; Tyagi, Yogesh Kumar; Gupta, Rajinder Kumar
2011-08-01
A rapid, effective and ecofriendly method for sensitive screening and quantification of 72 pesticides residue in fruits and vegetables, by microwave-assisted extraction (MAE) followed by dispersive solid-phase extraction (d-SPE), retention time locked (RTL) capillary gas-chromatographic separation in trace ion mode mass spectrometric determination has been validated as per ISO/IEC: 17025:2005. Identification and reporting with total and extracted ion chromatograms were facilitated to a great extent by Deconvolution reporting software (DRS). For all compounds LOD were 0.002-0.02mg/kg and LOQ were 0.025-0.100mg/kg. Correlation coefficients of the calibration curves in the range of 0.025-0.50mg/kg were >0.993. To validate matrix effects repeatability, reproducibility, recovery and overall uncertainty were calculated for the 35 matrices at 0.025, 0.050 and 0.100mg/kg. Recovery ranged between 72% and 114% with RSD of <20% for repeatability and intermediate precision. The reproducibility of the method was evaluated by an inter laboratory participation and Z score obtained within ±2. Copyright © 2011 Elsevier Ltd. All rights reserved.
NASA Astrophysics Data System (ADS)
Hahn, Gitte Holst; Christensen, Karl Bang; Leung, Terence S.; Greisen, Gorm
2010-05-01
Coherence between spontaneous fluctuations in arterial blood pressure (ABP) and the cerebral near-infrared spectroscopy signal can detect cerebral autoregulation. Because reliable measurement depends on signals with high signal-to-noise ratio, we hypothesized that coherence is more precisely determined when fluctuations in ABP are large rather than small. Therefore, we investigated whether adjusting for variability in ABP (variabilityABP) improves precision. We examined the impact of variabilityABP within the power spectrum in each measurement and between repeated measurements in preterm infants. We also examined total monitoring time required to discriminate among infants with a simulation study. We studied 22 preterm infants (GA<30) yielding 215 10-min measurements. Surprisingly, adjusting for variabilityABP within the power spectrum did not improve the precision. However, adjusting for the variabilityABP among repeated measurements (i.e., weighting measurements with high variabilityABP in favor of those with low) improved the precision. The evidence of drift in individual infants was weak. Minimum monitoring time needed to discriminate among infants was 1.3-3.7 h. Coherence analysis in low frequencies (0.04-0.1 Hz) had higher precision and statistically more power than in very low frequencies (0.003-0.04 Hz). In conclusion, a reliable detection of cerebral autoregulation takes hours and the precision is improved by adjusting for variabilityABP between repeated measurements.
Brenhouse, Heather C; Montalto, Stefanie; Stellar, James R
2006-06-30
Repeated exposure to cocaine leads to behavioral sensitization, which is the augmentation of the locomotor response to a subsequent exposure to the drug. The nucleus accumbens (NAc), a major termination site of dopaminergic neurons, is believed to be involved in behavioral sensitization and studies have demonstrated that the NAc shell can be split into five zones of analysis; the vertex, arch, cone, intermediate and ventrolateral zones [Todtenkopf MS, Stellar JR. Assessment of tyrosine hydroxylase immunoreactive innervation in five subregions of the nucleus accumbens shell in rats treated with repeated cocaine. Synapse 2000;38:261-70]. Several reports show cocaine-induced c-fos expression particularly in the intermediate zone after 14, but not 2, drug-free days following repeated cocaine administration, suggesting that this region may be involved in sensitization and particularly in the later phase of expression, versus the earlier phase of sensitization. Bilateral electrolytic lesions of the intermediate zone were made in two groups of rats, which were then repeatedly exposed to cocaine (15 mg/kg, twice/day for 5 days). One group was subsequently given a single cocaine challenge injection (15 mg/kg) after 14 drug-free days, while the other group was challenged after only 2 drug-free days. Two sham surgery groups in which an electrode was lowered but no current was passed served as controls. Results show that lesioned animals as well as sham controls exhibited behavioral sensitization to the drug. However, following a 14-day drug-free period, the lesioned animals showed significant reduction in sensitization, compared to sham controls. Together these findings suggest that the intermediate zone of the NAc shell is indeed involved in the expression phase of behavioral sensitization to cocaine.
Bianchi, Sara E; Teixeira, Helder F; Kaiser, Samuel; Ortega, George G; Schneider, Paulo Henrique; Bassani, Valquiria L
2016-05-01
Coumestrol is present in several species of the Fabaceae family widely distributed in plants. The estrogenic and antioxidant activities of this molecule show its potential as skin anti-aging agent. These characteristics reveal the interest in developing analytical methodology for permeation studies, as well as to know the stability of coumestrol identifying the major degradation products. Thus, the present study was designed, first, to develop and validate a versatile liquid chromatography (HPLC) method to quantify coumestrol in a hydrogel formulation in different porcine skin layers (stratum corneum, epidermis, and dermis) in permeation tests. In the stability-indicating test coumestrol samples were exposed to stress conditions: temperature, UVC light, oxidative, acid and alkaline media. The degradation products, as well as the constituents extracted from the hydrogel, adhesive tape or skin were not eluted in the retention time of the coumestrol. Hence, the HPLC method showed to be versatile, specific, accurate, precise and robust showing excellent performance for quantifying coumestrol in complex matrices involving skin permeation studies. Coumestrol recovery from porcine ear skin was found to be in the range of 97.07-107.28 μg/mL; the intra-day precision (repeatability) and intermediate precision (inter-day precision), respectively lower than 4.71% and 2.09%. The analysis using ultra-performance liquid chromatography coupled to a quadrupole time-of-flight high definition mass spectrometry detector (UPLC-QTOF/HDMS) suggest the MS fragmentation patterns and the chemical structure of the main degradation products. These results represent new and relevant findings for the development of coumestrol pharmaceutical and cosmetic products. Copyright © 2016 Elsevier B.V. All rights reserved.
Azougagh, M; Elkarbane, M; Bakhous, K; Issmaili, S; Skalli, A; Iben Moussad, S; Benaji, B
2016-09-01
An innovative simple, fast, precise and accurate ultra-high performance liquid chromatography (UPLC) method was developed for the determination of diclofenac (Dic) along with its impurities including the new dimer impurity in various pharmaceutical dosage forms. An Acquity HSS T3 (C18, 100×2.1mm, 1.8μm) column in gradient mode was used with mobile phase comprising of phosphoric acid, which has a pH value of 2.3 and methanol. The flow rate and the injection volume were set at 0.35ml·min(-1) and 1μl, respectively, and the UV detection was carried out at 254nm by using photodiode array detector. Dic was subjected to stress conditions from acid, base, hydrolytic, thermal, oxidative and photolytic degradation. The new developed method was successfully validated in accordance to the International Conference on Harmonization (ICH) guidelines with respect to specificity, limit of detection, limit of quantitation, precision, linearity, accuracy and robustness. The degradation products were well resolved from main peak and its seven impurities, proving the specificity power of the method. The method showed good linearity with consistent recoveries for Dic content and its impurities. The relative percentage of standard deviation obtained for the repeatability and intermediate precision experiments was less than 3% and LOQ was less than 0.5μg·ml(-1) for all compounds. The new proposed method was found to be accurate, precise, specific, linear and robust. In addition, the method was successfully applied for the assay determination of Dic and its impurities in the several pharmaceutical dosage forms. Copyright © 2016 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.
da Silva, Layzon Antonio Lemos; Pezzini, Bianca Ramos; Soares, Luciano
2015-01-01
Background: The chemical characterization is essential to validate the pharmaceutical use of vegetable raw materials. Ultraviolet spectroscopy is an important technique to determine flavonoids, which are important active compounds from Ocimum basilicum. Objective: The objective of this work was to optimize a spectrophotometric method, based on flavonoid-aluminum chloride (AlCl3) complexation to determine the total flavonoid content (TFC) in leaves of O. basilicum (herbal material), using response surface methodology. Materials and Methods: The effects of (1) the herbal material: Solvent ratio (0.02, 0.03, 0.05, 0.07, and 0.08 g/mL), (2) stock solution volume (0.8, 2.3, 4.4, 6.5, and 8.0 mL) and (3) AlCl3 volume (0.8, 1.0, 1.2, 1.4, and 1.6 mL) on the TFC were evaluated. The analytical performance parameters precision, linearity and robustness of the method were tested. Results: The herbal material: Solvent ratio and stock solution volume showed an important influence on the method response. After choosing the optimized conditions, the method exhibited a precision (RSD%) lower than 6% for repeatability (RSD%) and lower than 8% for intermediate precision (on the order of literature values for biotechnological methods), coefficient of correlation of 0.9984, and no important influence could be observed for variations of the time of complexation with AlCl3. However, the time and temperature of extraction were critical for TFC method and must be carefully controlled during the analysis. Conclusion: Thus, this study allowed the optimization of a simple, fast and precise method for the determination of the TFC in leaves of O. basilicum, which can be used to support the quality assessment of this herbal material. PMID:25709217
Kalmár, Eva; Gyuricza, Anett; Kunos-Tóth, Erika; Szakonyi, Gerda; Dombi, György
2014-01-01
Combined drug products have the advantages of better patient compliance and possible synergic effects. The simultaneous application of several active ingredients at a time is therefore frequently chosen. However, the quantitative analysis of such medicines can be challenging. The aim of this study is to provide a validated method for the investigation of a multidose packed oral powder that contained acetylsalicylic acid, paracetamol and papaverine-HCl. Reversed-phase high-pressure liquid chromatography was used. The Agilent Zorbax SB-C18 column was found to be the most suitable of the three different stationary phases tested for the separation of the components of this sample. The key parameters in the method development (apart from the nature of the column) were the pH of the aqueous phase (set to 3.4) and the ratio of the organic (acetonitrile) and the aqueous (25 mM phosphate buffer) phases, which was varied from 7:93 (v/v) to 25:75 (v/v) in a linear gradient, preceded by an initial hold. The method was validated: linearity, precision (repeatability and intermediate precision), accuracy, specificity and robustness were all tested, and the results met the ICH guidelines. © The Author [2013]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
N-nitrosamines as "special case" leachables in a metered dose inhaler drug product.
Norwood, Daniel L; Mullis, James O; Feinberg, Thomas N; Davis, Letha K
2009-01-01
N-nitrosamines are chemical entities, some of which are considered to be possible human carcinogens, which can be found at trace levels in some types of foods, tobacco smoke, certain cosmetics, and certain types of rubber. N-nitrosamines are of regulatory concern as leachables in inhalation drug products, particularly metered dose inhalers, which incorporate rubber seals into their container closure systems. The United States Food and Drug Administration considers N-nitrosamines (along with polycyclic aromatic hydrocarbons and 2-mercaptobenzothiazole) to be "special case" leachables in inhalation drug products, meaning that there are no recognized safety or analytical thresholds and these compounds must therefore be identified and quantitated at the lowest practical level. This report presents the development of a quantitative analytical method for target volatile N-nitrosamines in a metered dose inhaler drug product, Atrovent HFA. The method incorporates a target analyte recovery procedure from the drug product matrix with analysis by gas chromatography/thermal energy analysis detection. The capability of the method was investigated with respect to specificity, linearity/range, accuracy (linearity of recovery), precision (repeatability, intermediate precision), limits of quantitation, standard/sample stability, and system suitability. Sample analyses showed that Atrovent HFA contains no target N-nitrosamines at the trace level of 1 ng/canister.
Physiological and metabolic responses of gestating Brahaman cows to repeated transportation
USDA-ARS?s Scientific Manuscript database
The purpose of this study was to examine physiological and metabolic responses to repeated transportation of gestating Brahman cows, previously classified as mature cows into temperament groups of Calm, Intermediate, or Temperamental. Brahman cows (n = 48) were subjected to 2 hours of transport (TRA...
Hoffmann, K; Kesners, P; Bader, A; Avermaete, A; Altmeyer, P; Gambichler, T
2001-11-01
Spectrophotometric assessment (in vitro) is the most established method for determining the ultraviolet protection factor (UPF) of textiles. Apart from stringent requirements for measurement precision, practical methods are required for the routine determination of the UPF. We report here spectrophotometric measurements of textiles using a newly developed autosampler. Measurement precision was evaluated under repeatable conditions. Fifteen different textiles were spectrophotometrically assessed for the determination of the UPF. Sample handling inside the spectrophotometer was performed with a computer-controlled sampling device, capable of loading and unloading a textile sample from a magazine as well as rotating the sample perpendicular to the spectrometer beam. In order to evaluate the repeatability of measurements, one sample of each textile was assessed eight times under the same conditions in the same laboratory. A mean percentage of the standard error of 1% [E(UPF)] was calculated for the UPF measurements. For UPFs >30, a significantly higher E(UPF) was found (r=0.78; P<0.001). E(UV) (3.9%) of ultraviolet A (UVA) transmission differed significantly from E(UV) (1.1 %) of ultraviolet B (UVB) transmission (P<0.05). Though a slight decrease of repeatability was observed for UVA transmission measurements and UPFs higher than 30, our data indicate a high measurement precision under repeatable conditions. In conclusion, spectrophotometric measurements of textiles with the aid of the autosampler presented have been shown to be highly practical, time saving and precise.
Indexing system for optical beam steering
NASA Technical Reports Server (NTRS)
Sullivan, Mark T.; Cannon, David M.; Debra, Daniel B.; Young, Jeffrey A.; Mansfield, Joseph A.; Carmichael, Roger E.; Lissol, Peter S.; Pryor, G. M.; Miklosy, Les G.; Lee, Jeffrey H.
1990-01-01
This paper describes the design and testing of an indexing system for optical-beam steering. The cryogenic beam-steering mechanism is a 360-degree rotation device capable of discrete, high-precision alignment positions. It uses low-precision components for its rough alignment and kinematic design to meet its stringent repeatability and stability requirements (of about 5 arcsec). The principal advantages of this design include a decoupling of the low-precision, large angular motion from the high-precision alignment, and a power-off alignment position that potentially extends the life or hold time of cryogenic systems. An alternate design, which takes advantage of these attributes while reducing overall motion, is also presented. Preliminary test results show the kinematic mount capable of sub-arc second repeatability.
"Repeating Events" as Estimator of Location Precision: The China National Seismograph Network
NASA Astrophysics Data System (ADS)
Jiang, Changsheng; Wu, Zhongliang; Li, Yutong; Ma, Tengfei
2014-03-01
"Repeating earthquakes" identified by waveform cross-correlation, with inter-event separation of no more than 1 km, can be used for assessment of location precision. Assuming that the network-measured apparent inter-epicenter distance X of the "repeating doublets" indicates the location precision, we estimated the regionalized location quality of the China National Seismograph Network by comparing the "repeating events" in and around China by S chaff and R ichards (Science 303: 1176-1178, 2004; J Geophys Res 116: B03309, 2011) and the monthly catalogue of the China Earthquake Networks Center. The comparison shows that the average X value of the China National Seismograph Network is approximately 10 km. The mis-location is larger for the Tibetan Plateau, west and north of Xinjiang, and east of Inner Mongolia, as indicated by larger X values. Mis-location is correlated with the completeness magnitude of the earthquake catalogue. Using the data from the Beijing Capital Circle Region, the dependence of the mis-location on the distribution of seismic stations can be further confirmed.
NASA Astrophysics Data System (ADS)
Tivey, M. K.; Evans, G. N.; Ferrini, V. L.; Spierer, H.
2016-12-01
High-resolution bathymetric mapping and recovery and study of samples from precisely known locations relative to local tectonic and volcanic features provide insight into the formation of seafloor massive sulfide deposits. Additional insight comes from repeat mapping efforts in 2005 and 2016 that provide details of relations and changes that may have occurred over time. Located 21 km apart on the Valu Fa Ridge, the Tui Malila and Mariner vent fields exhibit contrasting vent fluid chemistry, mineral deposit composition, deposit morphology, and seafloor morphology. At the Tui Malila vent field, near-neutral pH fluids with low metal contents vent from Zn- and Ba-rich, but Cu-poor deposits. The highest temperature fluids are found near the intersection of two faults and between volcanic domes. In contrast, acidic, metal-rich hydrothermal fluids at the Mariner vent field vent from Cu-rich, Zn-poor deposits. No discernable faults are present. At both the Tui Malila and Mariner vent fields, intermediate temperature fluids were sampled emanating from barite-rich deposits. At the Tui Malila vent field, intermediate fluids vent from flange-dominated edifices that are located on brecciated lava flow that overlays one of the two faults. Intermediate fluids at the Mariner vent field vent from squat terrace-like edifices located peripheral (10-15 m) to high-temperature chimney edifices, and seafloor morphology is dominated by brecciated lava flows. Thermodynamic models of mixing between high-temperature hydrothermal fluids and seawater that consider subsurface deposition of sulfide minerals and iron oxyhydroxide were used to reproduce the chemistry of intermediate fluids. This study suggests that the porous, brecciated lavas characteristic of these two vent fields provide sites for subsurface mixing and contribute to mineral deposition, with the faults at the Tui Malila vent field providing a pathway for subsurface fluid flow.
Adler, Paul; Scally, Andrew J; Barrett, Brendan T
2012-05-01
To determine the test-retest reliability of the Randot stereoacuity test when used as part of vision screening in schools. Randot stereoacuity (graded-circles) and logMAR visual acuity measures were gathered in an unselected sample of 139 children (aged 4-12, mean 8.1±2.1 years) in two schools. Randot testing was repeated on two occasions (average interval between successive tests 8 days, range: 1-21 days). Three Randot scores were obtained in 97.8% of children. Randot stereoacuity improved by an average of one plate (ie, one test level) on repeat testing but was little changed when tested on the third occasion. Within-subject variability was up to three test levels on repeat testing. When stereoacuity was categorised as 'fine', 'intermediate' or 'coarse', the greatest variability was found among younger children who exhibited 'intermediate' or 'coarse'/nil stereopsis on initial testing. Whereas 90.8% of children with 'fine' stereopsis (≤50 arc-seconds) on the first test exhibited 'fine' stereopsis on both subsequent tests, only ∼16% of children with 'intermediate' (>50 but ≤140 arc-seconds) or 'coarse'/nil (≥200 arc-seconds) stereoacuity on initial testing exhibited stable test results on repeat testing. Children exhibiting abnormal stereoacuity on initial testing are very likely to exhibit a normal result when retested. The value of a single, abnormal Randot graded-circles stereoacuity measure from school screening is therefore questionable.
Timms, Mark; Hall, Nikki; Levina, Vita; Vine, John; Steel, Rohan
2014-10-01
The growth hormone releasing peptides (GHRPs) hexarelin, ipamorelin, alexamorelin, GHRP-1, GHRP-2, GHRP-4, GHRP-5, and GHRP-6 are all synthetic met-enkephalin analogues that include unnatural D-amino acids. They were designed specifically for their ability to stimulate growth hormone release and may serve as performance enhancing drugs. To regulate the use of these peptides within the horse racing industry and by human athletes, a method is presented for the extraction, derivatization, and detection of GHRPs from equine and human urine. This method takes advantage of a highly specific solid-phase extraction combined with a novel derivatization method to improve the chromatography of basic peptides. The method was validated with respect to linearity, repeatability, intermediate precision, specificity, limits of detection, limits of confirmation, ion suppression, and stability. As proof of principle, all eight GHRPs or their metabolites could be detected in urine collected from rats after intravenous administration. Copyright © 2014 John Wiley & Sons, Ltd.
Hasegawa, Takashi; Takahashi, Kazunaga; Fukiwake, Tomohide; Saijo, Masaaki; Motoki, Yuji
2013-01-01
We developed a simple and rapid liquid chromatography/mass spectrometry (LC/MS) method for the enantiomeric determination of DOPA in dietary supplements containing Mucuna pruriens. L- and D-DOPA were ultrasonically extracted with 1% formic acid aqueous solution. The isolated extracts were analyzed by LC/MS using a Crownpak CR (-) column at 30℃. The mass spectrometer was operated in the positive mode of electrospray ionization, and the mobile phase was aqueous formic acid (pH 2.0). L-DOPA-ring-d3 was used as an internal standard. The method was validated for a dietary supplement spiked with L- and D-DOPA at 50 and 500 μg/g, respectively, and the recoveries of the DOPA enantiomers were between 97.5% and 101.3%. Relative standard deviation values of repeatability and intermediate precision were less than 7%. The method was applied to 14 dietary supplements. L-DOPA was detected in these supplements in the range of 0.88-12.8 mg/unit. D-DOPA was not detected.
Vigna, Camila R M; Morais, Lais S R; Collins, Carol H; Jardim, Isabel C S F
2006-05-12
A laboratory-made sorbent for solid-phase extraction (SPE) was obtained by thermal immobilization of poly(methyloctylsiloxane) (PMOS) onto silica. Cartridges packed with the new sorbent were used for the simultaneous determination of imazethapyr, nicosulfuron, diuron, linuron and chlorimuron-ethyl in water. These pesticides were separated and quantified using high-performance liquid chromatography with diode array detection (HPLC-DAD). The recoveries achieved with the laboratory-made PMOS cartridges were compared with those of some commercially available silica-based and polymer-based cartridges having C18, C8 and NH(2) pendant groups. Method validation using the laboratory-made sorbent was performed for the five pesticides at three fortifications levels (1x, 2x and 10x the limit of quantification of each pesticide). The laboratory-made PMOS cartridge has low cost preparation and showed good recoveries (72-111%) for all pesticides. Repeatability and intermediate precision were lower than 15%. Its performance was similar or even better, in some cases, than those of the commercial cartridges.
Development of HPLC-ELSD method for determination of maltodextrin in raw milk.
Moraes, Flávia Santana; da Costa, Marion Pereira; de Melo Silva, Vitor Luiz; de Barros Pinto Moreira, Rodrigo Vilela; de Barros, Raphael Ferreira; Mársico, Eliane Teixeira; Conte-Junior, Carlos Adam; de Oliveira Silva, Adriana Cristina
2017-02-15
An analytical method was developed and validated for the determination of maltodextrin in raw milk, using high-performance liquid chromatography with evaporative light scattering detection. Maltodextrin content was evaluated in adulterated raw milk using a Supelcosil LC-NH2 (25cm×4.6mm) column and isocratic elution (68% of acetonitrile). Validation parameters exhibited adequate linearity, with relative standard deviation values between 0.74 and 2.16% (n=10) for repeatability and 0.11-19.39% (n=5) for intermediate precision. Limits of detection and quantification were 0.78 and 1.56mg.mL(-1), respectively, and recovery rates were between 91 and 93% for three levels. The application of this method shows that maltodextrin concentrations found in adulterated samples are lower than expected, which may be related to the quality of the commercial maltodextrin used. The method proposed proved to be simple and appropriate for the determination of maltodextrin in raw milk, with detection down to adulteration levels of 1%. Copyright © 2016 Elsevier Ltd. All rights reserved.
Coran, Silvia A; Bartolucci, Gianluca; Bambagiotti-Alberti, Massimo
2008-10-17
The validation of a HPTLC-densitometric method for the determination of secoisolariciresinol diglucoside (SDG) in flaxseed was performed improving the reproducibility of a previously reported HPTLC densitometric procedure by the use of fully wettable reversed phase plates (silica gel 60 RP18W F(254S), 10cmx10cm) with MeOH:HCOOH 0.1% (40:60, v/v) mobile phase. The analysis required only the alkaline hydrolysis in aqueous medium of undefatted samples and densitometry at 282nm of HPTLC runs. The method was validated following the protocol proposed by the Société Francaise des Sciences et Techniques Pharmaceutiques (SFSTP) giving rise to a dependable and high throughput procedure well suited to routine application. SDG was quantified in the range of 321-1071ng with RSD of repeatability and intermediate precision not exceeding 3.61% and accuracy inside the acceptance limits. Flaxseed of five cultivars of different origin was elected as test-bed.
Labat, L; Dehon, B; Lhermitte, M
2003-05-01
An inductively coupled plasma mass spectrometer (ICP-MS) with a rapid sample-preparative procedure was used for the determination of selenium in blood serum. Blood serum was prepared by dilution in an acidic solution consisting of nitric acid (1%), X-triton (0.1%) and 1-butanol (0.8%). A calibration curve was established for 1-40 microg mL(-1) (r(2)>0.99). The limit of detection was 0.5 microg mL(-1). Repeatability and intermediate precision were satisfactory with relative standard deviations (RSD) of 2.0% and 3.2%, respectively. This method was easily applied to reference materials with satisfactory accuracy. Good correlation (r(2)=0.96) was observed between ICP-MS and atomic absorption spectrometry (AAS) for the determination of (82)Se in blood serum from 23 patients. These results suggest that the sample preparative procedure coupled with ICP-MS can be used for the routine determination of (82)Se in human blood serum.
A demonstration of high precision GPS orbit determination for geodetic applications
NASA Technical Reports Server (NTRS)
Lichten, S. M.; Border, J. S.
1987-01-01
High precision orbit determination of Global Positioning System (GPS) satellites is a key requirement for GPS-based precise geodetic measurements and precise low-earth orbiter tracking, currently under study at JPL. Different strategies for orbit determination have been explored at JPL with data from a 1985 GPS field experiment. The most successful strategy uses multi-day arcs for orbit determination and includes fine tuning of spacecraft solar pressure coefficients and station zenith tropospheric delays using the GPS data. Average rms orbit repeatability values for 5 of the GPS satellites are 1.0, 1.2, and 1.7 m in altitude, cross-track, and down-track componenets when two independent 5-day fits are compared. Orbit predictions up to 24 hours outside the multi-day arcs agree within 4 m of independent solutions obtained with well tracked satellites in the prediction interval. Baseline repeatability improves with multi-day as compared to single-day arc orbit solutions. When tropospheric delay fluctuations are modeled with process noise, significant additional improvement in baseline repeatability is achieved. For a 246-km baseline, with 6-day arc solutions for GPS orbits, baseline repeatability is 2 parts in 100 million (0.4-0.6 cm) for east, north, and length components and 8 parts in 100 million for the vertical component. For 1314 and 1509 km baselines with the same orbits, baseline repeatability is 2 parts in 100 million for the north components (2-3 cm) and 4 parts in 100 million or better for east, length, and vertical components.
Rasmussen, Sebastian R; Konge, Lars; Mikkelsen, Peter T; Sørensen, Mads S; Andersen, Steven A W
2016-03-01
Cognitive load (CL) theory suggests that working memory can be overloaded in complex learning tasks such as surgical technical skills training, which can impair learning. Valid and feasible methods for estimating the CL in specific learning contexts are necessary before the efficacy of CL-lowering instructional interventions can be established. This study aims to explore secondary task precision for the estimation of CL in virtual reality (VR) surgical simulation and also investigate the effects of CL-modifying factors such as simulator-integrated tutoring and repeated practice. Twenty-four participants were randomized for visual assistance by a simulator-integrated tutor function during the first 5 of 12 repeated mastoidectomy procedures on a VR temporal bone simulator. Secondary task precision was found to be significantly lower during simulation compared with nonsimulation baseline, p < .001. Contrary to expectations, simulator-integrated tutoring and repeated practice did not have an impact on secondary task precision. This finding suggests that even though considerable changes in CL are reflected in secondary task precision, it lacks sensitivity. In contrast, secondary task reaction time could be more sensitive, but requires substantial postprocessing of data. Therefore, future studies on the effect of CL modifying interventions should weigh the pros and cons of the various secondary task measurements. © The Author(s) 2015.
Real-time and high accuracy frequency measurements for intermediate frequency narrowband signals
NASA Astrophysics Data System (ADS)
Tian, Jing; Meng, Xiaofeng; Nie, Jing; Lin, Liwei
2018-01-01
Real-time and accurate measurements of intermediate frequency signals based on microprocessors are difficult due to the computational complexity and limited time constraints. In this paper, a fast and precise methodology based on the sigma-delta modulator is designed and implemented by first generating the twiddle factors using the designed recursive scheme. This scheme requires zero times of multiplications and only half amounts of addition operations by using the discrete Fourier transform (DFT) and the combination of the Rife algorithm and Fourier coefficient interpolation as compared with conventional methods such as DFT and Fast Fourier Transform. Experimentally, when the sampling frequency is 10 MHz, the real-time frequency measurements with intermediate frequency and narrowband signals have a measurement mean squared error of ±2.4 Hz. Furthermore, a single measurement of the whole system only requires approximately 0.3 s to achieve fast iteration, high precision, and less calculation time.
Clamping characteristics study on different types of clamping unit
DOE Office of Scientific and Technical Information (OSTI.GOV)
Jiao, Zhiwei; Liu, Haichao; Xie, Pengcheng
2015-05-22
Plastic products are becoming more and more widely used in aerospace, IT, digital electronics and many other fields. With the development of technology, the requirement of product precision is getting higher and higher. However, type and working performance of clamping unit play a decisive role in product precision. Clamping characteristics of different types of clamping unit are discussed in this article, which use finite element numerical analysis method through the software ABAQUS to study the clamping uniformity, and detect the clamping force repeatability precision. The result shows that compared with toggled three-platen clamping unit, clamping characteristics of internal circulation two-platenmore » clamping unit are better, for instance, its mold cavity deformation and force that bars and mold parting surface suffered are more uniform, and its clamping uniformity and repeatability precision is also better.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Goode, P.R.; Barrett, B.R.; Portilho, O.
1979-02-01
The earlier calculations of Goode and Barrett are repeated using the super-soft-core potential of Gogny, Pires, and de Tourreil. The particular third-order folded diagram which they calculated now converges in its intermediate-state energy summation, because of the suppression of the strong short-range repulsive effects present in earlier calculations.
ERIC Educational Resources Information Center
Crossley, Scott A.; Yang, Hae Sung; McNamara, Danielle S.
2014-01-01
This study uses a moving windows self-paced reading task to assess both text comprehension and processing time of authentic texts and these same texts simplified to beginning and intermediate levels. Forty-eight second language learners each read 9 texts (3 different authentic, beginning, and intermediate level texts). Repeated measures ANOVAs…
Precise through-space control of an abiotic electrophilic aromatic substitution reaction
NASA Astrophysics Data System (ADS)
Murphy, Kyle E.; Bocanegra, Jessica L.; Liu, Xiaoxi; Chau, H.-Y. Katharine; Lee, Patrick C.; Li, Jianing; Schneebeli, Severin T.
2017-04-01
Nature has evolved selective enzymes for the efficient biosynthesis of complex products. This exceptional ability stems from adapted enzymatic pockets, which geometrically constrain reactants and stabilize specific reactive intermediates by placing electron-donating/accepting residues nearby. Here we perform an abiotic electrophilic aromatic substitution reaction, which is directed precisely through space. Ester arms--positioned above the planes of aromatic rings--enable it to distinguish between nearly identical, neighbouring reactive positions. Quantum mechanical calculations show that, in two competing reaction pathways, both [C-H...O]-hydrogen bonding and electrophile preorganization by coordination to a carbonyl group likely play a role in controlling the reaction. These through-space-directed mechanisms are inspired by dimethylallyl tryptophan synthases, which direct biological electrophilic aromatic substitutions by preorganizing dimethylallyl cations and by stabilizing reactive intermediates with [C-H...N]-hydrogen bonding. Our results demonstrate how the third dimension above and underneath aromatic rings can be exploited to precisely control electrophilic aromatic substitutions.
Escuder-Gilabert, Laura; Martín-Biosca, Yolanda; Perez-Baeza, Mireia; Sagrado, Salvador; Medina-Hernández, María José
2018-05-09
A great number of available pharmaceuticals are chiral compounds. Although they are usually manufactured as racemic mixtures, they can be enantioselectively biodegraded as a result of microbial processes. In this paper, a biodegradability assay in similar conditions to those recommended in OECD tests of enantiomers of trimeprazine (a phenothiazine employed as a racemate) is carried out. Experiments were performed in batch mode using a minimal salts medium inoculated with an activated sludge (collected from a Valencian Waste Water Treatment Plant, WWTP) and supplemented with the racemate. The concentration of the enantiomers of trimeprazine were monitored by means of a chiral HPLC method using a cellulose-based chiral stationary phase and 0.5 M NaClO 4 /acetonitrile (60:40, v/v) mobile phases. Experiments were performed at three concentration levels of the racemate. In parallel, the optical density at 600 nm (OD600) was measured to control the biomass growth and to connect it with enantioselectivity. The calculated enantiomeric fractions (EF) offer the first evidence of enantioselective biodegradation of trimeprazine. A simplified Monod equation was used as a curve fitting approach for concentration (S), biodegradation (BD), and for the first time, EF experimental data in order to expand the usefulness of the results. Precision studies on S (repeatability conditions) and, for the first time, EF (intermediate precision conditions) were also performed. Copyright © 2018 Elsevier Ltd. All rights reserved.
Guan, Jin; Min, Jie; Yan, Feng; Xu, Wen-Ya; Shi, Shuang; Wang, Si-Lin
2017-04-01
A new gas chromatographic method for the simultaneous determination of six organic residual solvents (acetonitrile, tetrahydrofuran, ethanol, acetone, 2-propanol and ethyl acetate) in azilsartan bulk drug is described. The chromatographic determination was achieved on an OV-624 capillary column employing programmed temperature within 21 min. The validation was carried out according to International Conference on Harmonization validation guidelines. The method was shown to be specific (no interference in the blank solution), sensitive (Limit of detection can achieve 1.5 μg/mL), precise (relative standard deviation of repeatability and intermediate precision ≤5.0%), linear (r≥ 0.999), accurate (recoveries range from 98.8% to 107.8%) and robust (carrier gas flow from 2.7 to 3.3 mL/min, initial oven temperature from 35°C to 45°C, temperature ramping rate from 19°C/min to 21°C/min, final oven temperature from 145°C to 155°C, injector temperature from 190°C to 210°C and detector temperature from 240°C to 260°C did not significantly affect the system suitability, test parameters and peak areas). This extensively validated method has been applied to the determination of residual solvents in real azilsartan bulk samples. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
How training citizen scientists affects the accuracy and precision of phenological data
NASA Astrophysics Data System (ADS)
Feldman, Richard E.; Žemaitė, Irma; Miller-Rushing, Abraham J.
2018-05-01
Monitoring plant and animal phenology is a critical step to anticipating and predicting changes in species interactions and biodiversity. Because phenology necessarily involves frequent and repeated observations over time, citizen scientists have become a vital part of collecting phenological data. However, there is still concern over the accuracy and precision of citizen science data. It is possible that training citizen scientists can improve data quality though there are few comparisons of trained and untrained citizen scientists in the ability of each to accurately and precisely measure phenology. We assessed how three types of observers—experts, trained citizen scientists that make repeated observations, and untrained citizen scientists making once-per-year observations—differ in quantifying temporal change in flower and fruit abundance of American mountain ash trees (Sorbus americana Marsh.) and arthropods in Acadia National Park, Maine, USA. We found that trained more so than untrained citizen science observers over- or under-estimated abundances leading to precise but inaccurate characterizations of phenological patterns. Our results suggest a new type of bias induced by repeated observations: A type of learning takes place that reduces the independence of observations taken on different trees or different dates. Thus, in this and many other cases, having individuals make one-off observations of marked plants may produce data as good if not better than individuals making repeated observations. For citizen science programs related to phenology, our results underscore the importance of (a) attracting the most number of observers possible even if they only make one observation, (b) producing easy-to-use and informative data sheets, and (c) carefully planning effective training programs that are, perhaps, repeated at different points during the data collection period.
How training citizen scientists affects the accuracy and precision of phenological data.
Feldman, Richard E; Žemaitė, Irma; Miller-Rushing, Abraham J
2018-05-07
Monitoring plant and animal phenology is a critical step to anticipating and predicting changes in species interactions and biodiversity. Because phenology necessarily involves frequent and repeated observations over time, citizen scientists have become a vital part of collecting phenological data. However, there is still concern over the accuracy and precision of citizen science data. It is possible that training citizen scientists can improve data quality though there are few comparisons of trained and untrained citizen scientists in the ability of each to accurately and precisely measure phenology. We assessed how three types of observers-experts, trained citizen scientists that make repeated observations, and untrained citizen scientists making once-per-year observations-differ in quantifying temporal change in flower and fruit abundance of American mountain ash trees (Sorbus americana Marsh.) and arthropods in Acadia National Park, Maine, USA. We found that trained more so than untrained citizen science observers over- or under-estimated abundances leading to precise but inaccurate characterizations of phenological patterns. Our results suggest a new type of bias induced by repeated observations: A type of learning takes place that reduces the independence of observations taken on different trees or different dates. Thus, in this and many other cases, having individuals make one-off observations of marked plants may produce data as good if not better than individuals making repeated observations. For citizen science programs related to phenology, our results underscore the importance of (a) attracting the most number of observers possible even if they only make one observation, (b) producing easy-to-use and informative data sheets, and (c) carefully planning effective training programs that are, perhaps, repeated at different points during the data collection period.
López-Miguel, Alberto; Martínez-Almeida, Loreto; González-García, María J; Coco-Martín, María B; Sobrado-Calvo, Paloma; Maldonado, Miguel J
2013-02-01
To assess the intrasession and intersession precision of ocular, corneal, and internal higher-order aberrations (HOAs) measured using an integrated topographer and Hartmann-Shack wavefront sensor (Topcon KR-1W) in refractive surgery candidates. IOBA-Eye Institute, Valladolid, Spain. Evaluation of diagnostic technology. To analyze intrasession repeatability, 1 experienced examiner measured eyes 9 times successively. To study intersession reproducibility, the same clinician obtained measurements from another set of eyes in 2 consecutive sessions 1 week apart. Ocular, corneal, and internal HOAs were obtained. Coma and spherical aberrations, 3rd- and 4th-order aberrations, and total HOAs were calculated for a 6.0 mm pupil diameter. For intrasession repeatability (75 eyes), excellent intraclass correlation coefficients (ICCs) were obtained (ICC >0.87), except for internal primary coma (ICC = 0.75) and 3rd-order (ICC = 0.72) HOAs. Repeatability precision (1.96 × S(w)) values ranged from 0.03 μm (corneal primary spherical) to 0.08 μm (ocular primary coma). For intersession reproducibility (50 eyes), ICCs were good (>0.8) for ocular primary spherical, 3rd-order, and total higher-order aberrations; reproducibility precision values ranged from 0.06 μm (corneal primary spherical) to 0.21 μm (internal 3rd order), with internal HOAs having the lowest precision (≥0.12 μm). No systematic bias was found between examinations on different days. The intrasession repeatability was high; therefore, the device's ability to measure HOAs in a reliable way was excellent. Under intersession reproducibility conditions, dependable corneal primary spherical aberrations were provided. No author has a financial or proprietary interest in any material or method mentioned. Copyright © 2012 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.
Seamless editing of the chloroplast genome in plants.
Martin Avila, Elena; Gisby, Martin F; Day, Anil
2016-07-29
Gene editing technologies enable the precise insertion of favourable mutations and performance enhancing trait genes into chromosomes whilst excluding all excess DNA from modified genomes. The technology gives rise to a new class of biotech crops which is likely to have widespread applications in agriculture. Despite progress in the nucleus, the seamless insertions of point mutations and non-selectable foreign genes into the organelle genomes of crops have not been described. The chloroplast genome is an attractive target to improve photosynthesis and crop performance. Current chloroplast genome engineering technologies for introducing point mutations into native chloroplast genes leave DNA scars, such as the target sites for recombination enzymes. Seamless editing methods to modify chloroplast genes need to address reversal of site-directed point mutations by template mediated repair with the vast excess of wild type chloroplast genomes that are present early in the transformation process. Using tobacco, we developed an efficient two-step method to edit a chloroplast gene by replacing the wild type sequence with a transient intermediate. This was resolved to the final edited gene by recombination between imperfect direct repeats. Six out of 11 transplastomic plants isolated contained the desired intermediate and at the second step this was resolved to the edited chloroplast gene in five of six plants tested. Maintenance of a single base deletion mutation in an imperfect direct repeat of the native chloroplast rbcL gene showed the limited influence of biased repair back to the wild type sequence. The deletion caused a frameshift, which replaced the five C-terminal amino acids of the Rubisco large subunit with 16 alternative residues resulting in a ~30-fold reduction in its accumulation. We monitored the process in vivo by engineering an overlapping gusA gene downstream of the edited rbcL gene. Translational coupling between the overlapping rbcL and gusA genes resulted in relatively high GUS accumulation (~0.5 % of leaf protein). Editing chloroplast genomes using transient imperfect direct repeats provides an efficient method for introducing point mutations into chloroplast genes. Moreover, we describe the first synthetic operon allowing expression of a downstream overlapping gene by translational coupling in chloroplasts. Overlapping genes provide a new mechanism for co-ordinating the translation of foreign proteins in chloroplasts.
Holman, Benjamin W B; Collins, Damian; Kilgannon, Ashleigh K; Hopkins, David L
2018-01-01
The Nix Pro Colour Sensor™ (NIX) can be potentially used to measure meat colour, but procedural guidelines that assure measurement reproducibility and repeatability (precision) must first be established. Technical replicate number (r) will minimise response variation, measureable as standard error of predicted mean (SEM), and contribute to improved precision. Consequently, we aimed to explore the effects of r on NIX precision when measuring aged beef colour (colorimetrics; L*, a*, b*, hue and chroma values). Each colorimetric SEM declined with increasing r to indicate improved precision and followed a diminishing rate of improvement that allowed us to recommend r=7 for meat colour studies using the NIX. This definition was based on practical limitations and a* variability, as additional r would be required if other colorimetrics or advanced levels of precision are necessary. Beef ageing and display period, holding temperature, loin and sampled portion were also found to contribute to colorimetric variation, but were incorporated within our definition of r. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.
Insights into the Aggregation Mechanism of PolyQ Proteins with Different Glutamine Repeat Lengths.
Yushchenko, Tetyana; Deuerling, Elke; Hauser, Karin
2018-04-24
Polyglutamine (polyQ) diseases, including Huntington's disease, result from the aggregation of an abnormally expanded polyQ repeat in the affected protein. The length of the polyQ repeat is essential for the disease's onset; however, the molecular mechanism of polyQ aggregation is still poorly understood. Controlled conditions and initiation of the aggregation process are prerequisites for the detection of transient intermediate states. We present an attenuated total reflection Fourier-transform infrared spectroscopic approach combined with protein immobilization to study polyQ aggregation dependent on the polyQ length. PolyQ proteins were engineered mimicking the mammalian N-terminus fragment of the Huntingtin protein and containing a polyQ sequence with the number of glutamines below (Q11), close to (Q38), and above (Q56) the disease threshold. A monolayer of the polyQ construct was chemically immobilized on the internal reflection element of the attenuated total reflection cell, and the aggregation was initiated via enzymatic cleavage. Structural changes of the polyQ sequence were monitored by time-resolved infrared difference spectroscopy. We observed faster aggregation kinetics for the longer sequences, and furthermore, we could distinguish β-structured intermediates for the different constructs, allowing us to propose aggregation mechanisms dependent on the repeat length. Q11 forms a β-structured aggregate by intermolecular interaction of stretched monomers, whereas Q38 and Q56 undergo conformational changes to various β-structured intermediates, including intramolecular β-sheets. Copyright © 2018 Biophysical Society. Published by Elsevier Inc. All rights reserved.
2017-01-01
The World Health Organization (WHO) enzyme-linked immunosorbent assay (ELISA) guideline is currently accepted as the gold standard for the evaluation of immunoglobulin G (IgG) antibodies specific to pneumococcal capsular polysaccharide. We conducted validation of the WHO ELISA for 7 pneumococcal serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F) by evaluating its specificity, precision (reproducibility and intermediate precision), accuracy, spiking recovery test, lower limit of quantification (LLOQ), and stability at the Ewha Center for Vaccine Evaluation and Study, Seoul, Korea. We found that the specificity, reproducibility, and intermediate precision were within acceptance ranges (reproducibility, coefficient of variability [CV] ≤ 15%; intermediate precision, CV ≤ 20%) for all serotypes. Comparisons between the provisional assignments of calibration sera and the results from this laboratory showed a high correlation > 94% for all 7 serotypes, supporting the accuracy of the ELISA. The spiking recovery test also fell within an acceptable range. The quantification limit, calculated using the LLOQ, for each of the serotypes was 0.05–0.093 μg/mL. The freeze-thaw stability and the short-term temperature stability were also within an acceptable range. In conclusion, we showed good performance using the standardized WHO ELISA for the evaluation of serotype-specific anti-pneumococcal IgG antibodies; the WHO ELISA can evaluate the immune response against pneumococcal vaccines with consistency and accuracy. PMID:28875600
Lee, Hyunju; Lim, Soo Young; Kim, Kyung Hyo
2017-10-01
The World Health Organization (WHO) enzyme-linked immunosorbent assay (ELISA) guideline is currently accepted as the gold standard for the evaluation of immunoglobulin G (IgG) antibodies specific to pneumococcal capsular polysaccharide. We conducted validation of the WHO ELISA for 7 pneumococcal serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F) by evaluating its specificity, precision (reproducibility and intermediate precision), accuracy, spiking recovery test, lower limit of quantification (LLOQ), and stability at the Ewha Center for Vaccine Evaluation and Study, Seoul, Korea. We found that the specificity, reproducibility, and intermediate precision were within acceptance ranges (reproducibility, coefficient of variability [CV] ≤ 15%; intermediate precision, CV ≤ 20%) for all serotypes. Comparisons between the provisional assignments of calibration sera and the results from this laboratory showed a high correlation > 94% for all 7 serotypes, supporting the accuracy of the ELISA. The spiking recovery test also fell within an acceptable range. The quantification limit, calculated using the LLOQ, for each of the serotypes was 0.05-0.093 μg/mL. The freeze-thaw stability and the short-term temperature stability were also within an acceptable range. In conclusion, we showed good performance using the standardized WHO ELISA for the evaluation of serotype-specific anti-pneumococcal IgG antibodies; the WHO ELISA can evaluate the immune response against pneumococcal vaccines with consistency and accuracy. © 2017 The Korean Academy of Medical Sciences.
Platform Precision Autopilot Overview and Mission Performance
NASA Technical Reports Server (NTRS)
Strovers, Brian K.; Lee, James A.
2009-01-01
The Platform Precision Autopilot is an instrument landing system-interfaced autopilot system, developed to enable an aircraft to repeatedly fly nearly the same trajectory hours, days, or weeks later. The Platform Precision Autopilot uses a novel design to interface with a NASA Gulfstream III jet by imitating the output of an instrument landing system approach. This technique minimizes, as much as possible, modifications to the baseline Gulfstream III jet and retains the safety features of the aircraft autopilot. The Platform Precision Autopilot requirement is to fly within a 5-m (16.4-ft) radius tube for distances to 200 km (108 nmi) in the presence of light turbulence for at least 90 percent of the time. This capability allows precise repeat-pass interferometry for the Unmanned Aerial Vehicle Synthetic Aperture Radar program, whose primary objective is to develop a miniaturized, polarimetric, L-band synthetic aperture radar. Precise navigation is achieved using an accurate differential global positioning system developed by the Jet Propulsion Laboratory. Flight-testing has demonstrated the ability of the Platform Precision Autopilot to control the aircraft within the specified tolerance greater than 90 percent of the time in the presence of aircraft system noise and nonlinearities, constant pilot throttle adjustments, and light turbulence.
Platform Precision Autopilot Overview and Flight Test Results
NASA Technical Reports Server (NTRS)
Lin, V.; Strovers, B.; Lee, J.; Beck, R.
2008-01-01
The Platform Precision Autopilot is an instrument landing system interfaced autopilot system, developed to enable an aircraft to repeatedly fly nearly the same trajectory hours, days, or weeks later. The Platform Precision Autopilot uses a novel design to interface with a NASA Gulfstream III jet by imitating the output of an instrument landing system approach. This technique minimizes, as much as possible, modifications to the baseline Gulfstream III jet and retains the safety features of the aircraft autopilot. The Platform Precision Autopilot requirement is to fly within a 5-m (16.4-ft) radius tube for distances to 200 km (108 nmi) in the presence of light turbulence for at least 90 percent of the time. This capability allows precise repeat-pass interferometry for the Uninhabited Aerial Vehicle Synthetic Aperture Radar program, whose primary objective is to develop a miniaturized, polarimetric, L-band synthetic aperture radar. Precise navigation is achieved using an accurate differential global positioning system developed by the Jet Propulsion Laboratory. Flight-testing has demonstrated the ability of the Platform Precision Autopilot to control the aircraft within the specified tolerance greater than 90 percent of the time in the presence of aircraft system noise and nonlinearities, constant pilot throttle adjustments, and light turbulence.
Precision GPS orbit determination strategies for an earth orbiter and geodetic tracking system
NASA Technical Reports Server (NTRS)
Lichten, Stephen M.; Bertiger, Willy I.; Border, James S.
1988-01-01
Data from two 1985 GPS field tests were processed and precise GPS orbits were determined. With a combined carrier phase and pseudorange, the 1314-km repeatability improves substantially to 5 parts in 10 to the 9th (0.6 cm) in the north and 2 parts in 10 to the 8th (2-3 cm) in the other components. To achieve these levels of repeatability and accuracy, it is necessary to fine-tune the GPS solar radiation coefficients and ground station zenith tropospheric delays.
Laser Cutting of Thin Nickel Bellows
NASA Technical Reports Server (NTRS)
Butler, C. L.
1986-01-01
Laser cutting technique produces narrow, precise, fast, and repeatable cuts in thin nickel-allow bellows material. Laser cutting operation uses intense focused beam to melt material and assisting gas to force melted material through part thickness, creating void. When part rotated or moved longitudinally, melting and material removal continuous and creates narrow, fast, precise, and repeatable cut. Technique used to produce cuts of specified depths less than material thickness. Avoids distortion, dents, and nicks produced in delicate materials during lathe trimming operations, which require high cutting-tool pressure and holding-fixture forces.
Sonoelastographic Features of the Patellar Ligament in Clinically Normal Dogs.
Piccionello, Angela P; Serrani, Daniele; Busoni, Valeria; Salvaggio, Alberto; Bonazzi, Mattia; Bergamino, Chiara; Volta, Antonella
2018-06-11
This article describes the sonoelastographic features of the patellar ligament of sound dogs and tests feasibility, reproducibility and repeatability. Clinically healthy medium-to-large breed dogs were enrolled. Sonoelastographic images of the patellar ligaments were obtained in lateral recumbency with the stifle flexed by an experienced operator and by a senior veterinary student. The elasticity colour map included red (soft), green (intermediate) and blue (hard). Tissue elasticity was measured by calculating the percentage of softness with dedicated software. Categorical, qualitative data analysis was performed using a weighted kappa statistic for repeatability and reproducibility. A categorical qualitative assessment was performed based on a grading scale of 1 to 5 (soft, mostly soft, intermediate, mostly hard and hard). Fourteen clinically normal dogs were considered. A total of 28 patellar ligaments were examined. Overall, 25 of the patellar ligaments were graded as soft or mostly soft and the remaining 3 as intermediate. Repeatability was 86.2%, with a weighted kappa of 0.64 (good), for the well-trained sonographer and 83.3%, with a weighted kappa of 0.53 (moderate), for the senior student. Reproducibility was 86.2%, with a weighed kappa of 0.65 (good). Sonoelastography of the canine patellar ligament is a feasible and reproducible technique. Patellar ligaments in clinically normal dogs showed highly elastic biomechanical properties. Schattauer GmbH Stuttgart.
Holzer, Ralf; Qureshi, Shakeel; Ghasemi, Abdolrahim; Vincent, Julie; Sievert, Horst; Gruenstein, Daniel; Weber, Howard; Alday, Luis; Peirone, Alejandro; Zellers, Thomas; Cheatham, John; Slack, Michael; Rome, Jonathan
2010-10-01
Since the 1980s, stent implantation has evolved as an important therapeutic strategy for coarctation of the aorta. However, available data is frequently flawed by short follow-up, lack of adequate follow-up imaging, and retrospective nature of data collection. Data was prospectively collected using a multicenter registry congenital cardiovascular interventional study consortium (CCISC). Between 2000 and 2009, 302 patients from 34 centers with a median weight of 58 kg underwent stent implantation for coarctation. Eligible patients (44%) completed intermediate follow-up (3-18 months) with integrated imaging (cath, CT, MRI), whereas 21% completed long-term follow-up (>18-60 months). Procedural success was defined as UL/LL systolic gradient of less than 20 mm Hg, lack of significant recurrent obstruction, and freedom from unplanned repeat intervention. Acute procedural success was 96%. Cumulative intermediate success was 86%, and cumulative long-term success was 77%. Unplanned repeat interventions were required in 4%, and aortic wall complications were seen in 1% of patients (dissection n = 1 and aneurysm n = 3). Other adverse events (n = 15) occurred mainly acutely and included technical complications such as stent malposition (n = 9). At long-term follow-up, 23% of patients continued to have systolic blood pressure above the 95th centile, 9% had an upper-to-lower limb blood pressure gradient in excess of 20 mm Hg, and 32% were taking antihypertensive medication. This study documented acute, intermediate, and long-term outcome data comparable or superior with other surgical or interventional series. However, even with successful initial stent therapy, patients continue to require long-term follow-up and have associated long-term morbidity, relating to aortic wall complications, systemic hypertension, recurrent obstruction as well as need for repeat intervention. © 2010 Wiley-Liss, Inc.
A comparison of computer-assisted and manual wound size measurement.
Thawer, Habiba A; Houghton, Pamela E; Woodbury, M Gail; Keast, David; Campbell, Karen
2002-10-01
Accurate and precise wound measurements are a critical component of every wound assessment. To examine the reliability and validity of a new computerized technique for measuring human and animal wounds, chronic human wounds (N = 45) and surgical animal wounds (N = 38) were assessed using manual and computerized techniques. Using intraclass correlation coefficients, intrarater and interrater reliability of surface area measurements obtained using the computerized technique were compared to those obtained using acetate tracings and planimetry. A single measurement of surface area using either technique produced excellent intrarater and interrater reliability for both human and animal wounds, but the computerized technique was more precise than the manual technique for measuring the surface area of animal wounds. For both types of wounds and measurement techniques, intrarater and interrater reliability improved when the average of three repeated measurements was obtained. The precision of each technique with human wounds and the precision of the manual technique with animal wounds also improved when three repeated measurement results were averaged. Concurrent validity between the two techniques was excellent for human wounds but poor for the smaller animal wounds, regardless of whether single or the average of three repeated surface area measurements was used. The computerized technique permits reliable and valid assessment of the surface area of both human and animal wounds.
Apolinário, T A; Paiva, C L A; Agostinho, L A
2017-04-05
Huntington's disease (HD) is an autosomal dominant progressive neurodegenerative disorder caused by a dynamic mutation due to the expansion of CAG repeats in the HTT gene (4p16.3). The considered normal alleles have less than 27 CAG repeats. Intermediate alleles (IAs) show 27 to 35 CAG repeats and expanded alleles have more than 35 repeats. The IAs apparently have shown a normal phenotype. However, there are some reported associations between individuals that bear an IA and clinical HD signs, such as behavioral disturbs. The association of IAs with the presence of clinical signs gives clinical relevance to these patients. We emphasized the importance of determining the frequency of IA alleles in the general population as well as in HD families. Therefore, the aim of this study was to conduct a systematic review, in order to investigate the frequency of IAs in the overall chromosomes of different ethnic groups and of families with HD history worldwide as well as the frequency of individuals who bear the intermediate alleles. We searched indexed articles from the following electronic databases: U.S. National Library of Medicine and the National Institutes of Health (PubMed), Pubmed Central (PMC) and Virtual Health Library (VHL). Therefore, 488 articles were obtained and, of these, 33 had been published in more than one database. We accepted the article of only one database and ended up with 455 articles for this review. The frequency of IAs within the chromosomes of the general population ranged from 0.45 to 8.7% and of individuals with family history of HD ranged from 0.05 to 5.1%. The higher frequency of IAs in the general population (8.7%) was found in one Brazilian cohort.
Collins, A L; Saunders, S; McCarthy, H D; Williams, J E; Fuller, N J
2004-01-01
To determine and compare the extent of within- and between-laboratory precision in body volume (BV) measurements using air displacement plethysmography (ADP), the BOD POD body composition system, and to interpret any such variability in terms of body composition estimates. Repeated test procedures of BV assessment using the BOD POD ADP were reproduced at two laboratories for the estimation of precision, both within and between laboratories. In total, 30 healthy adult volunteers, 14 men (age, 19-48 y; body mass index (BMI), 19.7-30.3 kg/m2) and 16 women (age, 19-40 y; BMI, 16.3-35.7 kg/m2), were each subjected to two test procedures at both laboratories. Two additional volunteers were independently subjected to 10 repeated test procedures at both laboratories. Repeated measurements of BV, uncorrected for the effects of isothermal air in the lungs and the surface area artifact, were obtained using the BOD POD ADP, with the identical protocol being faithfully applied at both laboratories. Uncorrected BV measurements were adjusted to give estimates of actual BV that were used to calculate body density (body weight (BWt)/actual BV) from which estimates of body composition were derived. The differences between repeated BV measurements or body composition estimates were used to assess within-laboratory precision (repeatability), as standard deviation (SD) and coefficient of variation; the differences between measurements reproduced at each laboratory were used to determine between-laboratory precision (reproducibility), as bias and 95% limits of agreement (from SD of the differences between laboratories). The extent of within-laboratory methodological precision for BV (uncorrected and actual) was variable according to subject, sample group and laboratory conditions (range of SD, 0.04-0.13 l), and was mostly due to within-individual biological variability (typically 78-99%) rather than to technical imprecision. There was a significant (P<0.05) bias between laboratories for the 10 repeats on the two independent subjects (up to 0.29 l). Although no significant bias (P=0.077) was evident for the sample group of 30 volunteers (-0.05 l), the 95% limits of agreement were considerable (-0.68 to 0.58 l). The effects of this variability in BV on body composition were relatively greater: for example, within-laboratory precision (SD) for body fat as % BWt was between 0.56 and 1.34% depending on the subject and laboratory; the bias (-0.59%) was not significant between laboratories, but there were large 95% limits of agreement (-3.67 to 2.50%). Within-laboratory precision for each BOD POD instrument was reasonably good, but was variable according to the prevailing conditions. Although the bias between the two instruments was not significant for the BV measurements, implying that they can be used interchangeably for groups of similar subjects, the relatively large 95% limits of agreement indicate that greater consideration may be needed for assessing individuals with different ADP instruments. Therefore, use of a single ADP instrument is apparently preferable when assessing individuals on a longitudinal basis.
Bouchard, P; Chomilier, J; Ravet, V; Mornon, J P; Viguès, B
2001-01-01
Epiplasmin C is the major protein component of the membrane skeleton in the ciliate Tetrahymena pyriformis. Cloning and analysis of the gene encoding epiplasmin C showed this protein to be a previously unrecognized protein. In particular, epiplasmin C was shown to lack the canonical features of already known epiplasmic proteins in ciliates and flagellates. By means of hydrophobic cluster analysis (HCA), it has been shown that epiplasmin C is constituted of a repeat of 25 domains of 40 residues each. These domains are related and can be grouped in two families called types I and types II. Connections between types I and types II present rules that can be evidenced in the sequence itself, thus enforcing the validity of the splitting of the domains. Using these repeated domains as queries, significant structural similarities were demonstrated with an extra six heptads shared by nuclear lamins and invertebrate cytoplasmic intermediate filament proteins and deleted in the cytoplasmic intermediate filament protein lineage at the protostome-deuterostome branching in the eukaryotic phylogenetic tree.
Molecular mechanism of ligand recognition by membrane transport protein, Mhp1
Simmons, Katie J; Jackson, Scott M; Brueckner, Florian; Patching, Simon G; Beckstein, Oliver; Ivanova, Ekaterina; Geng, Tian; Weyand, Simone; Drew, David; Lanigan, Joseph; Sharples, David J; Sansom, Mark SP; Iwata, So; Fishwick, Colin WG; Johnson, A Peter; Cameron, Alexander D; Henderson, Peter JF
2014-01-01
The hydantoin transporter Mhp1 is a sodium-coupled secondary active transport protein of the nucleobase-cation-symport family and a member of the widespread 5-helix inverted repeat superfamily of transporters. The structure of Mhp1 was previously solved in three different conformations providing insight into the molecular basis of the alternating access mechanism. Here, we elucidate detailed events of substrate binding, through a combination of crystallography, molecular dynamics, site-directed mutagenesis, biochemical/biophysical assays, and the design and synthesis of novel ligands. We show precisely where 5-substituted hydantoin substrates bind in an extended configuration at the interface of the bundle and hash domains. They are recognised through hydrogen bonds to the hydantoin moiety and the complementarity of the 5-substituent for a hydrophobic pocket in the protein. Furthermore, we describe a novel structure of an intermediate state of the protein with the external thin gate locked open by an inhibitor, 5-(2-naphthylmethyl)-L-hydantoin, which becomes a substrate when leucine 363 is changed to an alanine. We deduce the molecular events that underlie acquisition and transport of a ligand by Mhp1. PMID:24952894
Rienth, Markus; Romieu, Charles; Gregan, Rebecca; Walsh, Caroline; Torregrosa, Laurent; Kelly, Mary T
2014-04-16
A rapid and sensitive method is presented for the determination of proline in grape berries. Following acidification with formic acid, proline is derivatized by heating at 100 °C for 15 min with 3% ninhydrin in dimethyl sulfoxide, and the absorbance, which is stable for at least 60 min, is read at 520 nm. The method was statistically validated in the concentration range from 2.5 to 15 mg/L, giving a repeatability and intermediate precision of generally <3%; linearity was determined using the lack of fit test. Results obtained with this method concurred (r = 0.99) with those obtained for the same samples on an amino acid analyzer. In terms of sample preparation, a simple dilution (5-20-fold) is required, and sugars, primary amino acids, and anthocyanins were demonstrated not to interfere, as the latter are bleached by ninhydrin under the experimental conditions. The method was applied to the study of proline accumulation in the fruits of microvines grown in phytotrons, and it was established that proline accumulation and concentrations closely resemble those of field-grown macrovines.
Stipcovich, Tea; Barbero, Gerardo F; Ferreiro-González, Marta; Palma, Miguel; Barroso, Carmelo G
2018-01-15
A rapid high-performance liquid chromatography method with a C18 reverse-phase fused-core column has been developed for the determination and quantification of the main capsaicinoids (nornordihydrocapsaicin, nordihydrocapsaicin, capsaicin, dihydrocapsaicin, homocapsaicin and homodihydrocapsaicin) present in Naga Jolokia peppers. A fused-core Kinetex™ C18 column (50×2.1mm i.d.; 2.6μm) was used for the analysis. The chromatographic separation was obtained with a gradient method in which the mobile phase was water (0.1% acetic acid) as solvent A and acetonitrile (0.1% acetic acid) as solvent B. The separation of all compounds was achieved in less than 3min with a total analysis time (sample-to-sample) of 10min. The robustness of the method was evaluated. The method showed excellent repeatability and intermediate precision expressed as coefficient of variance of less than 2%. The developed method was employed for the quantification of the major capsaicinoids present in different peppers and commercial products containing chilli peppers. Copyright © 2017 Elsevier Ltd. All rights reserved.
Fanali, S; Pucci, V; Sabbioni, C; Raggi, M A
2000-07-01
In modern practice, the treatment of Parkinson's disease and syndrome is carried out using pharmaceutical formulations containing a combination of levodopa and a decarboxylation inhibitor (carbidopa or benserazide). Two pharmaceutical formulations were quantified by capillary zone electrophoresis using two procedures which differed only in the kind of background electrolyte used. One procedure used a 25 mM phosphate buffer, pH 2.5, while the second one used a 25 mM borate buffer, pH 8.5. The electrophoretic analysis was carried out using an uncoated fused- silica capillary, a separation voltage of 20 kV with currents typically less than 60 microA, and spectrophotometric detection at 205 nm. Calibration curves were performed for levodopa (concentration range 1-100 microg/mL), for carbidopa and benserazide (1-50 microg/mL), and the plots of the peak area versus concentration were found to be linear with a correlation coefficient better than 0.9990. Satisfactory results were obtained when commercial tablets were analyzed in terms of accuracy (98-102%), repeatability (0.6-2.0%), and intermediate precision (1.1-2.6%).
Coran, Silvia A; Mulas, Stefano; Vasconi, Alessio
2014-01-17
A novel method was set up with the aim to obtain a simultaneous cross comparative evaluation of different Gardenia Jasminoides Ellis fruits by the HPTLC fingerprint approach. The main components among the iridoid, hydroxycinnamic derivative and crocin classes were identified by TLC-MS ancillary techniques. The iridoids geniposide, gardenoside and genepin-1-β-d-gentiobioside were also quantitated by densitometric scanning at 240nm. LiChrospher HPTLC Silica gel 60 RP-18 W F254, 20cm×10cm plates with acetonitrile: formic acid 0.1% (40:60 v/v) as the mobile phase was used. The method was validated giving rise to a dependable and high throughput procedure well suited to routine applications. Iridoids were quantified in the range of 240-1140ng with RSD of repeatability and intermediate precision between 0.9-2.5% and accuracy with bias 1.6-2.6%. The method was tested on six commercial Gardenia Jasminoides fruit samples. Copyright © 2013 Elsevier B.V. All rights reserved.
Wang, Hanghang; Muehlbauer, Michael J.; O’Neal, Sara K.; Newgard, Christopher B.; Hauser, Elizabeth R.; Shah, Svati H.
2017-01-01
The field of metabolomics as applied to human disease and health is rapidly expanding. In recent efforts of metabolomics research, greater emphasis has been placed on quality control and method validation. In this study, we report an experience with quality control and a practical application of method validation. Specifically, we sought to identify and modify steps in gas chromatography-mass spectrometry (GC-MS)-based, non-targeted metabolomic profiling of human plasma that could influence metabolite identification and quantification. Our experimental design included two studies: (1) a limiting-dilution study, which investigated the effects of dilution on analyte identification and quantification; and (2) a concentration-specific study, which compared the optimal plasma extract volume established in the first study with the volume used in the current institutional protocol. We confirmed that contaminants, concentration, repeatability and intermediate precision are major factors influencing metabolite identification and quantification. In addition, we established methods for improved metabolite identification and quantification, which were summarized to provide recommendations for experimental design of GC-MS-based non-targeted profiling of human plasma. PMID:28841195
Choong, Eva; Rudaz, Serge; Kottelat, Astrid; Guillarme, Davy; Veuthey, Jean-Luc; Eap, Chin B
2009-12-05
A simple and sensitive LC-MS method was developed and validated for the simultaneous quantification of aripiprazole (ARI), atomoxetine (ATO), duloxetine (DUL), clozapine (CLO), olanzapine (OLA), sertindole (STN), venlafaxine (VEN) and their active metabolites dehydroaripiprazole (DARI), norclozapine (NCLO), dehydrosertindole (DSTN) and O-desmethylvenlafaxine (OVEN) in human plasma. The above mentioned compounds and the internal standard (remoxipride) were extracted from 0.5 mL plasma by solid-phase extraction (mix mode support). The analytical separation was carried out on a reverse phase liquid chromatography at basic pH (pH 8.1) in gradient mode. All analytes were monitored by MS detection in the single ion monitoring mode and the method was validated covering the corresponding therapeutic range: 2-200 ng/mL for DUL, OLA, and STN, 4-200 ng/mL for DSTN, 5-1000 ng/mL for ARI, DARI and finally 2-1000 ng/mL for ATO, CLO, NCLO, VEN, OVEN. For all investigated compounds, good performance in terms of recoveries, selectivity, stability, repeatability, intermediate precision, trueness and accuracy, was obtained. Real patient plasma samples were then successfully analysed.
Silva, Simone Alves da; Sampaio, Geni Rodrigues; Torres, Elizabeth Aparecida Ferraz da Silva
2017-04-15
Among the different food categories, the oils and fats are important sources of exposure to polycyclic aromatic hydrocarbons (PAHs), a group of organic chemical contaminants. The use of a validated method is essential to obtain reliable analytical results since the legislation establishes maximum limits in different foods. The objective of this study was to optimize and validate a method for the quantification of four PAHs [benzo(a)anthracene, chrysene, benzo(b)fluoranthene, benzo(a)pyrene] in vegetable oils. The samples were submitted to liquid-liquid extraction, followed by solid-phase extraction, and analyzed by ultra-high performance liquid chromatography. Under the optimized conditions, the validation parameters were evaluated according to the INMETRO Guidelines: linearity (r2 >0.99), selectivity (no matrix interference), limits of detection (0.08-0.30μgkg -1 ) and quantification (0.25-1.00μgkg -1 ), recovery (80.13-100.04%), repeatability and intermediate precision (<10% RSD). The method was found to be adequate for routine analysis of PAHs in the vegetable oils evaluated. Copyright © 2016. Published by Elsevier Ltd.
Bursts of retrotransposition reproduced in Arabidopsis.
Tsukahara, Sayuri; Kobayashi, Akie; Kawabe, Akira; Mathieu, Olivier; Miura, Asuka; Kakutani, Tetsuji
2009-09-17
Retrotransposons, which proliferate by reverse transcription of RNA intermediates, comprise a major portion of plant genomes. Plants often change the genome size and organization during evolution by rapid proliferation and deletion of long terminal repeat (LTR) retrotransposons. Precise transposon sequences throughout the Arabidopsis thaliana genome and the trans-acting mutations affecting epigenetic states make it an ideal model organism with which to study transposon dynamics. Here we report the mobilization of various families of endogenous A. thaliana LTR retrotransposons identified through genetic and genomic approaches with high-resolution genomic tiling arrays and mutants in the chromatin-remodelling gene DDM1 (DECREASE IN DNA METHYLATION 1). Using multiple lines of self-pollinated ddm1 mutant, we detected an increase in copy number, and verified this for various retrotransposons in a gypsy family (ATGP3) and copia families (ATCOPIA13, ATCOPIA21, ATCOPIA93), and also for a DNA transposon of a Mutator family, VANDAL21. A burst of retrotransposition occurred stochastically and independently for each element, suggesting an additional autocatalytic process. Furthermore, comparison of the identified LTR retrotransposons in related Arabidopsis species revealed that a lineage-specific burst of retrotransposition of these elements did indeed occur in natural Arabidopsis populations. The recent burst of retrotransposition in natural population is targeted to centromeric repeats, which is presumably less harmful than insertion into genes. The ddm1-induced retrotransposon proliferations and genome rearrangements mimic the transposon-mediated genome dynamics during evolution and provide experimental systems with which to investigate the controlling molecular factors directly.
Looking through the Zircon Kaleidoscope: Durations, Rates, and Fluxes in Silicic Magmatic System
NASA Astrophysics Data System (ADS)
Schaltegger, U.; Wotzlaw, J. F.
2014-12-01
The crystallization rate of zircon in a cooling magma depends on the cooling rate through the saturation interval in addition to compositional and kinetic factors. Repeated influx of hot magma over 10-20 ka leads to short-amplitude temperature oscillations, which are recorded by resorption/crystallization cycles of zircon. Plotting the number of dated zircons versus their high-precision U-Pb date results in curves that qualitatively relate to the evolution of magma temperature over time [1], [2]. The trace elemental, O and Hf isotopic composition of zircon gives indications about the degree of magma homogenization and thermal evolution. Zircons from systems with small volumes and magma fluxes record non-systematic chemical and Hf isotopic heterogeneity, suggesting crystallization in non-homogenized ephemeral magma batches. Such systems typically lead to small, mid-upper crustal plutons [3]. Zircons from large-volume crystal-poor rhyolites record initial heterogeneities and rapid amalgamation of smaller magma batches over 10 ka [4], while zircons from monotonous intermediates record magma evolution over several 100 ka with coherent fractionation trends suggesting homogenization and a coherent thermal evolution [2]. In both cases, volumes and flux rates were sufficient to produce large volumes of eruptible magma on very contrasting time scales. Zircon is therefore recording cyclic crystallization-rejuvenation processes during temperature fluctuations in intermediate to upper crustal magma reservoirs but may not relate to the physical pluton emplacement or eruption. We can quantify volumes, rates of magma influx, rates of cooling and crystallization, and the degree of convective homogenization from zircon data, and infer reservoir assembly and eruption trigger mechanisms. These parameters largely control the evolution of long-lived, low-flux silicic magmatic system typical for mid-to-upper crustal plutons, monotonous intermediates are characterized by intermediate durations and fluxes while short-lived, high-flux systems preferentially produce crystal-poor rhyolites. References: [1] Caricchi et al. (2014) Nature 511, 457-461; [2] Wotzlaw et al. (2013) Geology 41, 867-870; [3] Broderick (2013) PhD thesis, Univ. of Geneva; [3] Wotzlaw et al. (2014) Geology, doi:10.1130/G35979.1
Flow Cytometry: Evolution of Microbiological Methods for Probiotics Enumeration.
Pane, Marco; Allesina, Serena; Amoruso, Angela; Nicola, Stefania; Deidda, Francesca; Mogna, Luca
2018-05-14
The purpose of this trial was to verify that the analytical method ISO 19344:2015 (E)-IDF 232:2015 (E) is valid and reliable for quantifying the concentration of the probiotic Lactobacillus rhamnosus GG (ATCC 53103) in a finished product formulation. Flow cytometry assay is emerging as an alternative rapid method for microbial detection, enumeration, and population profiling. The use of flow cytometry not only permits the determination of viable cell counts but also allows for enumeration of damaged and dead cell subpopulations. Results are expressed as TFU (Total Fluorescent Units) and AFU (Active Fluorescent Units). In December 2015, the International Standard ISO 19344-IDF 232 "Milk and milk products-Starter cultures, probiotics and fermented products-Quantification of lactic acid bacteria by flow cytometry" was published. This particular ISO can be applied universally and regardless of the species of interest. Analytical method validation was conducted on 3 different industrial batches of L. rhamnosus GG according to USP39<1225>/ICH Q2R1 in term of: accuracy, precision (repeatability), intermediate precision (ruggedness), specificity, limit of quantification, linearity, range, robustness. The data obtained on the 3 batches of finished product have significantly demonstrated the validity and robustness of the cytofluorimetric analysis. On the basis of the results obtained, the ISO 19344:2015 (E)-IDF 232:2015 (E) "Quantification of lactic acid bacteria by flow cytometry" can be used for the enumeration of L. rhamnosus GG in a finished product formulation.
Lead Quantification in Urine Samples of Athletes by Coupling DLLME with UV-Vis Spectrophotometry.
Faraji, Hakim; Helalizadeh, Masoumeh
2017-04-01
Urine lead level is one of the most employed measures of lead exposure and risk. The urine samples used in this study were obtained from ten healthy male cyclists. Dispersive liquid-liquid microextraction combined with ultraviolet and visible spectrophotometry was utilized for preconcentration, extraction, and determination of lead in urine samples. Optimization of the independent variables was carried out based on chemometric methods in three steps. According to the screening and optimization study, 133 μL of CCl 4 (extracting solvent), 1.34 mL ethanol (dispersing solvent), pH 2.0, 0.00 % of salt, and 0.1 % O,O-diethyl dithiophosphoric (chelating agent) were used as the optimum independent variables for microextraction and determination of lead. Under the optimized conditions, R 2 was 0.9991, and linearity range was 0.01-100 μg L -1 . Precision was evaluated in terms of repeatability and intermediate precision, with relative standard deviations being <9.1 and <15.3 %, respectively. The accuracy was estimated using urine samples of cyclists as real samples and it was confirmed. The relative error of ≤5 % was considered significant in the method specificity study. The lead concentration mean for the cyclists was 3.79 μg L -1 in urine samples. As a result, the proposed method is a robust technique to quantify lead concentrations higher than 11.6 ng L -1 in urine samples.
Soares, Aline Rodrigues; Nascentes, Clésia Cristina
2013-02-15
A simple method was developed for determining the total lead content in lipstick samples by graphite furnace atomic absorption spectrometry (GFAAS) after treatment with tetramethylammonium hydroxide (TMAH). Multivariate optimization was used to establish the optimal conditions of sample preparation. The graphite furnace heating program was optimized through pyrolysis and atomization curves. An aliquot containing approximately 50mg of the sample was mixed with TMAH and heated in a water bath at 60°C for 60 min. Using Nb as the permanent modifier and Pd as the chemical modifier, the optimal temperatures were 900°C and 1800°C for pyrolysis and atomization, respectively. Under optimum conditions, the working range was from 1.73 to 50.0 μg L(-1), with detection and quantification limits of 0.20 and 0.34 μg g(-1), respectively. The precision was evaluated under conditions of repeatability and intermediate precision and showed standard deviations of 2.37%-4.61% and 4.93%-9.75%, respectively. The % recovery ranged from 96.2% to 109%, and no significant differences were found between the results obtained using the proposed method and the microwave decomposition method for real samples. Lead was detected in 21 tested lipstick samples; the lead content in these samples ranged from 0.27 to 4.54 μg g(-1). Copyright © 2012 Elsevier B.V. All rights reserved.
Non-invasive quantification of lower limb mechanical alignment in flexion
Deakin, Angela; Fogg, Quentin A.; Picard, Frederic
2014-01-01
Objective Non-invasive navigation techniques have recently been developed to determine mechanical femorotibial alignment (MFTA) in extension. The primary aim of this study was to evaluate the precision and accuracy of an image-free navigation system with new software designed to provide multiple kinematic measurements of the knee. The secondary aim was to test two types of strap material used to attach optical trackers to the lower limb. Methods Seventy-two registrations were carried out on 6 intact embalmed cadaveric specimens (mean age: 77.8 ± 12 years). A validated fabric strap, bone screws and novel rubber strap were used to secure the passive tracker baseplate for four full experiments with each knee. The MFTA angle was measured under the conditions of no applied stress, valgus stress, and varus stress. These measurements were carried out at full extension and at 30°, 40°, 50° and 60° of flexion. Intraclass correlation coefficients, repeatability coefficients, and limits of agreement (LOA) were used to convey precision and agreement in measuring MFTA with respect to each of the independent variables, i.e., degree of flexion, applied coronal stress, and method of tracker fixation. Based on the current literature, a repeatability coefficient and LOA of ≤3° were deemed acceptable. Results The mean fixed flexion for the 6 specimens was 12.8° (range: 6–20°). The mean repeatability coefficient measuring MFTA in extension with screws or fabric strapping of the baseplate was ≤2°, compared to 2.3° using rubber strapping. When flexing the knee, MFTA measurements taken using screws or fabric straps remained precise (repeatability coefficient ≤3°) throughout the tested range of flexion (12.8–60°); however, using rubber straps, the repeatability coefficient was >3° beyond 50° flexion. In general, applying a varus/valgus stress while measuring MFTA decreased precision beyond 40° flexion. Using fabric strapping, excellent repeatability (coefficient ≤2°) was observed until 40° flexion; however, beyond 50° flexion, the repeatability coefficient was >3°. As was the case with precision, agreement between the invasive and non-invasive systems was satisfactory in extension and worsened with flexion. Mean limits of agreement between the invasive and non-invasive system using fabric strapping to assess MFTA were 3° (range: 2.3–3.8°) with no stress applied and 3.9° (range: 2.8–5.2°) with varus and valgus stress. Using rubber strapping, the corresponding values were 4.4° (range: 2.8–8.5°) with no stress applied, 5.5° (range: 3.3–9.0°) with varus stress, and 5.6° (range: 3.3–11.9°) with valgus stress. Discussion Acceptable precision and accuracy may be possible when measuring knee kinematics in early flexion using a non-invasive system; however, we do not believe passive trackers should be mounted with rubber strapping such as was used in this study. Flexing the knee appears to decrease the precision and accuracy of the system. The functions of this new software using image-free navigation technology have many potential clinical applications, including assessment of bony and soft tissue deformity, pre-operative planning, and post-operative evaluation, as well as in further pure research comparing kinematics of the normal and pathological knee. PMID:24856249
Hapstack, M.; Talarek, T.R.; Zollinger, W.T.; Heckendorn, F.M. II; Park, L.R.
1994-02-15
An instrument carriage for inspection of piping comprises front and rear leg assemblies for engaging the interior of the piping and supporting and centering the carriage therein, and an instrumentation arm carried by a shaft system running from the front to rear leg assemblies. The shaft system has a screw shaft for moving the arm axially and a spline gear for moving the arm azimuthally. The arm has a pair of air cylinders that raise and lower a plate in the radial direction. On the plate are probes including an eddy current probe and an ultrasonic testing probe. The ultrasonic testing probe is capable of spinning 360[degree] about its axis. The instrument carriage uses servo motors and pressurized air cylinders for precise actuation of instrument components and precise, repeatable actuation of position control mechanisms. 8 figures.
Hapstack, Mark; Talarek, Ted R.; Zollinger, W. Thor; Heckendorn, II, Frank M.; Park, Larry R.
1994-01-01
An instrument carriage for inspection of piping comprises front and rear leg assemblies for engaging the interior of the piping and supporting and centering the carriage therein, and an instrumentation arm carried by a shaft system running from the front to rear leg assemblies. The shaft system has a screw shaft for moving the arm axially and a spline gear for moving the arm azimuthally. The arm has a pair of air cylinders that raise and lower a plate in the radial direction. On the plate are probes including an eddy current probe and an ultrasonic testing probe. The ultrasonic testing probe is capable of spinning 360.degree. about its axis. The instrument carriage uses servo motors and pressurized air cylinders for precise actuation of instrument components and precise, repeatable actuation of position control mechanisms.
Aldridge, Kristina; Boyadjiev, Simeon A.; Capone, George T.; DeLeon, Valerie B.; Richtsmeier, Joan T.
2015-01-01
The genetic basis for complex phenotypes is currently of great interest for both clinical investigators and basic scientists. In order to acquire a thorough understanding of the translation from genotype to phenotype, highly precise measures of phenotypic variation are required. New technologies, such as 3D photogrammetry are being implemented in phenotypic studies due to their ability to collect data rapidly and non-invasively. Before these systems can be broadly implemented the error associated with data collected from images acquired using these technologies must be assessed. This study investigates the precision, error, and repeatability associated with anthropometric landmark coordinate data collected from 3D digital photogrammetric images acquired with the 3dMDface System. Precision, error due to the imaging system, error due to digitization of the images, and repeatability are assessed in a sample of children and adults (N=15). Results show that data collected from images with the 3dMDface System are highly repeatable and precise. The average error associated with the placement of landmarks is sub-millimeter; both the error due to digitization and to the imaging system are very low. The few measures showing a higher degree of error include those crossing the labial fissure, which are influenced by even subtle movement of the mandible. These results suggest that 3D anthropometric data collected using the 3dMDface System are highly reliable and therefore useful for evaluation of clinical dysmorphology and surgery, analyses of genotype-phenotype correlations, and inheritance of complex phenotypes. PMID:16158436
NASA Technical Reports Server (NTRS)
Cunningham, William C. (Inventor)
1987-01-01
A remotely controlled spray gun is described in which a nozzle and orifice plate are held in precise axial alignment by an alignment member, which in turn is held in alignment with the general outlet of the spray gun by insert. By this arrangement, the precise repeatability of spray patterns is insured.
Precise Electrochemical Drilling of Repeated Deep Holes
NASA Technical Reports Server (NTRS)
Kincheloe, J. P.
1985-01-01
Tooling enables maintenance of close tolerances. Tooling includes guide that holds electrochemical drilling electrodes in proper relative alinement and guide-positioning fixture clamps directly on reference surfaces of strut. High precision achieved by positioning tooling anew on each strut before drilling: Tolerances of (0.008 mm) maintained in some details.
Iorgulescu, E; Voicu, V A; Sârbu, C; Tache, F; Albu, F; Medvedovici, A
2016-08-01
The influence of the experimental variability (instrumental repeatability, instrumental intermediate precision and sample preparation variability) and data pre-processing (normalization, peak alignment, background subtraction) on the discrimination power of multivariate data analysis methods (Principal Component Analysis -PCA- and Cluster Analysis -CA-) as well as a new algorithm based on linear regression was studied. Data used in the study were obtained through positive or negative ion monitoring electrospray mass spectrometry (+/-ESI/MS) and reversed phase liquid chromatography/UV spectrometric detection (RPLC/UV) applied to green tea extracts. Extractions in ethanol and heated water infusion were used as sample preparation procedures. The multivariate methods were directly applied to mass spectra and chromatograms, involving strictly a holistic comparison of shapes, without assignment of any structural identity to compounds. An alternative data interpretation based on linear regression analysis mutually applied to data series is also discussed. Slopes, intercepts and correlation coefficients produced by the linear regression analysis applied on pairs of very large experimental data series successfully retain information resulting from high frequency instrumental acquisition rates, obviously better defining the profiles being compared. Consequently, each type of sample or comparison between samples produces in the Cartesian space an ellipsoidal volume defined by the normal variation intervals of the slope, intercept and correlation coefficient. Distances between volumes graphically illustrates (dis)similarities between compared data. The instrumental intermediate precision had the major effect on the discrimination power of the multivariate data analysis methods. Mass spectra produced through ionization from liquid state in atmospheric pressure conditions of bulk complex mixtures resulting from extracted materials of natural origins provided an excellent data basis for multivariate analysis methods, equivalent to data resulting from chromatographic separations. The alternative evaluation of very large data series based on linear regression analysis produced information equivalent to results obtained through application of PCA an CA. Copyright © 2016 Elsevier B.V. All rights reserved.
Cescutti, Paola; Foschiatti, Michela; Furlanis, Linda; Lagatolla, Cristina; Rizzo, Roberto
2010-07-02
The repeating unit of cepacian, the exopolysaccharide produced by the majority of the microorganisms belonging to the Burkholderia cepacia complex, was isolated from inner bacterial membranes and investigated by mass spectrometry, with and without prior derivatisation. Interpretation of the mass spectra led to the determination of the biological repeating unit primary structure, thus disclosing the nature of the oligosaccharide produced in vivo. Moreover, mass spectra recorded on the native sample revealed that acetyl substitution was very variable, producing a mixture of repeating units containing zero to four acyl groups. At the same time, finding acetylated oligosaccharides showed that binding of these substituents occurred in the cellular periplasmic space, before the polymerisation process took place. In the chromatographic peak containing the repeating unit, oligosaccharides shorter than the repeating unit co-eluted. Mass spectrometric analysis showed that they were biosynthetic intermediates of the repeating unit and further investigation revealed the biosynthetic sequence of cepacian building block. Copyright 2010 Elsevier Ltd. All rights reserved.
Precision Attitude Determination for an Infrared Space Telescope
NASA Technical Reports Server (NTRS)
Benford, Dominic J.
2008-01-01
We have developed performance simulations for a precision attitude determination system using a focal plane star tracker on an infrared space telescope. The telescope is being designed for the Destiny mission to measure cosmologically distant supernovae as one of the candidate implementations for the Joint Dark Energy Mission. Repeat observations of the supernovae require attitude control at the level of 0.010 arcseconds (0.05 microradians) during integrations and at repeat intervals up to and over a year. While absolute accuracy is not required, the repoint precision is challenging. We have simulated the performance of a focal plane star tracker in a multidimensional parameter space, including pixel size, read noise, and readout rate. Systematic errors such as proper motion, velocity aberration, and parallax can be measured and compensated out. Our prediction is that a relative attitude determination accuracy of 0.001 to 0.002 arcseconds (0.005 to 0.010 microradians) will be achievable.
Validation of Fourier analysis of videokeratographic data.
Sideroudi, Haris; Labiris, Georgios; Ditzel, Fienke; Tsaragli, Efi; Georgatzoglou, Kimonas; Siganos, Haralampos; Kozobolis, Vassilios
2017-06-15
The aim was to assess the repeatability of Fourier transfom analysis of videokeratographic data using Pentacam in normal (CG), keratoconic (KC) and post-CXL (CXL) corneas. This was a prospective, clinic-based, observational study. One randomly selected eye from all study participants was included in the analysis: 62 normal eyes (CG group), 33 keratoconus eyes (KC group), while 34 eyes, which had already received CXL treatment, formed the CXL group. Fourier analysis of keratometric data were obtained using Pentacam, by two different operators within each of two sessions. Precision, repeatability and Intraclass Correlation Coefficient (ICC), were calculated for evaluating intrassesion and intersession repeatability for the following parameters: Spherical Component (SphRmin, SphEcc), Maximum Decentration (Max Dec), Regular Astigmatism, and Irregularitiy (Irr). Bland-Altman analysis was used for assessing interobserver repeatability. All parameters were presented to be repeatable, reliable and reproductible in all groups. Best intrasession and intersession repeatability and reliability were detected for parameters SphRmin, SphEcc and Max Dec parameters for both operators using ICC (intrasession: ICC > 98%, intersession: ICC > 94.7%) and within subject standard deviation. Best precision and lowest range of agreement was found for the SphRmin parameter (CG: 0.05, KC: 0.16, and CXL: 0.2) in all groups, while the lowest repeatability, reliability and reproducibility was detected for the Irr parameter. The Pentacam system provides accurate measurements of Fourier tranform keratometric data. A single Pentacam scan will be sufficient for most clinical applications.
Tejada, María-Isabel; Glover, Guillermo; Martínez, Francisco; Guitart, Miriam; de Diego-Otero, Yolanda; Fernández-Carvajal, Isabel; Ramos, Feliciano J.; Hernández-Chico, Concepción; Pintado, Elizabet; Rosell, Jordi; Calvo, María-Teresa; Ayuso, Carmen; Ramos-Arroyo, María-Antonia; Maortua, Hiart; Milà, Montserrat
2014-01-01
Fragile X syndrome is the most common inherited form of intellectual disability. Here we report on a study based on a collaborative registry, involving 12 Spanish centres, of molecular diagnostic tests in 1105 fragile X families comprising 5062 individuals, of whom, 1655 carried a full mutation or were mosaic, three cases had deletions, 1840 had a premutation, and 102 had intermediate alleles. Two patients with the full mutation also had Klinefelter syndrome. We have used this registry to assess the risk of expansion from parents to children. From mothers with premutation, the overall rate of allele expansion to full mutation is 52.5%, and we found that this rate is higher for male than female offspring (63.6% versus 45.6%; P < 0.001). Furthermore, in mothers with intermediate alleles (45–54 repeats), there were 10 cases of expansion to a premutation allele, and for the smallest premutation alleles (55–59 repeats), there was a 6.4% risk of expansion to a full mutation, with 56 repeats being the smallest allele that expanded to a full mutation allele in a single meiosis. Hence, in our series the risk for alleles of <59 repeats is somewhat higher than in other published series. These findings are important for genetic counselling. PMID:24987673
Repeatability precision of the falling number procedure under standard and modified methodologies
USDA-ARS?s Scientific Manuscript database
The falling number (FN) procedure is used worldwide to assess the integrity of the starch stored within wheat seed. As an indirect measurement of the activity level of alpha-amylase, FN relies on a dedicated viscometer that measures the amount of time needed for a metal stirring rod of precise geome...
Landau, Sabine; Emsley, Richard; Dunn, Graham
2018-06-01
Random allocation avoids confounding bias when estimating the average treatment effect. For continuous outcomes measured at post-treatment as well as prior to randomisation (baseline), analyses based on (A) post-treatment outcome alone, (B) change scores over the treatment phase or (C) conditioning on baseline values (analysis of covariance) provide unbiased estimators of the average treatment effect. The decision to include baseline values of the clinical outcome in the analysis is based on precision arguments, with analysis of covariance known to be most precise. Investigators increasingly carry out explanatory analyses to decompose total treatment effects into components that are mediated by an intermediate continuous outcome and a non-mediated part. Traditional mediation analysis might be performed based on (A) post-treatment values of the intermediate and clinical outcomes alone, (B) respective change scores or (C) conditioning on baseline measures of both intermediate and clinical outcomes. Using causal diagrams and Monte Carlo simulation, we investigated the performance of the three competing mediation approaches. We considered a data generating model that included three possible confounding processes involving baseline variables: The first two processes modelled baseline measures of the clinical variable or the intermediate variable as common causes of post-treatment measures of these two variables. The third process allowed the two baseline variables themselves to be correlated due to past common causes. We compared the analysis models implied by the competing mediation approaches with this data generating model to hypothesise likely biases in estimators, and tested these in a simulation study. We applied the methods to a randomised trial of pragmatic rehabilitation in patients with chronic fatigue syndrome, which examined the role of limiting activities as a mediator. Estimates of causal mediation effects derived by approach (A) will be biased if one of the three processes involving baseline measures of intermediate or clinical outcomes is operating. Necessary assumptions for the change score approach (B) to provide unbiased estimates under either process include the independence of baseline measures and change scores of the intermediate variable. Finally, estimates provided by the analysis of covariance approach (C) were found to be unbiased under all the three processes considered here. When applied to the example, there was evidence of mediation under all methods but the estimate of the indirect effect depended on the approach used with the proportion mediated varying from 57% to 86%. Trialists planning mediation analyses should measure baseline values of putative mediators as well as of continuous clinical outcomes. An analysis of covariance approach is recommended to avoid potential biases due to confounding processes involving baseline measures of intermediate or clinical outcomes, and not simply for increased precision.
Precision Pointing Control System (PPCS) star tracker test
NASA Technical Reports Server (NTRS)
1972-01-01
Tests performed on the TRW precision star tracker are described. The unit tested was a two-axis gimballed star tracker designed to provide star LOS data to an accuracy of 1 to 2 sec. The tracker features a unique bearing system and utilizes thermal and mechanical symmetry techniques to achieve high precision which can be demonstrated in a one g environment. The test program included a laboratory evaluation of tracker functional operation, sensitivity, repeatibility, and thermal stability.
Crowther, Caroline A; Aghajafari, Fariba; Askie, Lisa M; Asztalos, Elizabeth V; Brocklehurst, Peter; Bubner, Tanya K; Doyle, Lex W; Dutta, Sourabh; Garite, Thomas J; Guinn, Debra A; Hallman, Mikko; Hannah, Mary E; Hardy, Pollyanna; Maurel, Kimberly; Mazumder, Premasish; McEvoy, Cindy; Middleton, Philippa F; Murphy, Kellie E; Peltoniemi, Outi M; Peters, Dawn; Sullivan, Lisa; Thom, Elizabeth A; Voysey, Merryn; Wapner, Ronald J; Yelland, Lisa; Zhang, Sasha
2012-02-12
The aim of this individual participant data (IPD) meta-analysis is to assess whether the effects of repeat prenatal corticosteroid treatment given to women at risk of preterm birth to benefit their babies are modified in a clinically meaningful way by factors related to the women or the trial protocol. The Prenatal Repeat Corticosteroid International IPD Study Group: assessing the effects using the best level of Evidence (PRECISE) Group will conduct an IPD meta-analysis. The PRECISE International Collaborative Group was formed in 2010 and data collection commenced in 2011. Eleven trials with up to 5,000 women and 6,000 infants are eligible for the PRECISE IPD meta-analysis. The primary study outcomes for the infants will be serious neonatal outcome (defined by the PRECISE International IPD Study Group as one of death (foetal, neonatal or infant); severe respiratory disease; severe intraventricular haemorrhage (grade 3 and 4); chronic lung disease; necrotising enterocolitis; serious retinopathy of prematurity; and cystic periventricular leukomalacia); use of respiratory support (defined as mechanical ventilation or continuous positive airways pressure or other respiratory support); and birth weight (Z-scores). For the children, the primary study outcomes will be death or any neurological disability (however defined by trialists at childhood follow up and may include developmental delay or intellectual impairment (developmental quotient or intelligence quotient more than one standard deviation below the mean), cerebral palsy (abnormality of tone with motor dysfunction), blindness (for example, corrected visual acuity worse than 6/60 in the better eye) or deafness (for example, hearing loss requiring amplification or worse)). For the women, the primary outcome will be maternal sepsis (defined as chorioamnionitis; pyrexia after trial entry requiring the use of antibiotics; puerperal sepsis; intrapartum fever requiring the use of antibiotics; or postnatal pyrexia). Data analyses are expected to commence in 2011 with results publicly available in 2012.
CHROMOSPHERIC NANOFLARES AS A SOURCE OF CORONAL PLASMA. II. REPEATING NANOFLARES
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bradshaw, S. J.; Klimchuk, J. A., E-mail: stephen.bradshaw@rice.edu, E-mail: James.A.Klimchuk@nasa.gov
The million degree plasma of the solar corona must be supplied by the underlying layers of the atmosphere. The mechanism and location of energy release, and the precise source of coronal plasma, remain unresolved. In earlier work, we pursued the idea that warm plasma is supplied to the corona via direct heating of the chromosphere by nanoflares, contrary to the prevailing belief that the corona is heated in situ and the chromosphere is subsequently energized and ablated by thermal conduction. We found that single (low-frequency) chromospheric nanoflares could not explain the observed intensities, Doppler-shifts, and red/blue asymmetries in Fe xiimore » and xiv emission lines. In the present work, we follow up on another suggestion that the corona could be powered by chromospheric nanoflares that repeat on a timescale substantially shorter than the cooling/draining timescale. That is, a single magnetic strand is re-supplied with coronal plasma before the existing plasma has time to cool and drain. We perform a series of hydrodynamic experiments and predict the Fe xii and xiv line intensities, Doppler-shifts, and red/blue asymmetries. We find that our predicted quantities disagree dramatically with observations and fully developed loop structures cannot be created by intermediate- or high-frequency chromospheric nanoflares. We conclude that the mechanism ultimately responsible for producing coronal plasma operates above the chromosphere, but this does not preclude the possibility of a similar mechanism powering the chromosphere, extreme examples of which may be responsible for heating chromospheric plasma to transition region temperatures (e.g., type II spicules)« less
UAVSAR: An Airborne Window on Earth Surface Deformation
NASA Technical Reports Server (NTRS)
Hensley, Scott
2011-01-01
This study demonstrates that UAVSAR's precision autopilot and electronic steering have allowed for the reliable collection of airborne repeat pass radar interferometric data for deformation mapping. Deformation maps from temporal scales ranging from hours to months over a variety of signals of geophysical interest illustrate the utility of UAVSAR airborne repeat pass interferometry to these studies.
Data storage: Retrospective and prospective
NASA Technical Reports Server (NTRS)
Speliotis, Dennis E.
1993-01-01
We study history to learn from its lessons so we don't repeat the mistakes. Ironically, however, sometimes it seems that the lessons we learn from history is how to repeat the mistakes more precisely. A brief discussion about the history of magnetic recording is presented, and the lessons of the past are used to look into the future.
Kumar, Rishi; Maulik, Prakas R; Misra, Anup Kumar
2008-08-01
Concise chemical synthesis of a tetrasaccharide repeating unit of the O-antigen of Hafnia alvei 10457 is reported. Construction of the tetrasaccharide as its 4-methoxyphenyl glycoside was achieved by condensation of less abundant monosaccharide units such as, D-galactofuranose, N-acetyl-D-galactosamine and N-acetylneuraminic acid. The synthetic strategy consists of the preparation of suitably protected required monosaccharide intermediates from the commercially available reducing sugars and high yielding glycosylation reactions.
Development of a PD-L1 Complementary Diagnostic Immunohistochemistry Assay (SP142) for Atezolizumab.
Vennapusa, Bharathi; Baker, Brian; Kowanetz, Marcin; Boone, Jennifer; Menzl, Ina; Bruey, Jean-Marie; Fine, Gregg; Mariathasan, Sanjeev; McCaffery, Ian; Mocci, Simonetta; Rost, Sandra; Smith, Dustin; Dennis, Eslie; Tang, Szu-Yu; Damadzadeh, Bita; Walker, Espen; Hegde, Priti S; Williams, J Andrew; Koeppen, Hartmut; Boyd, Zachary
2018-01-16
Cancer immunotherapies, such as atezolizumab, are proving to be a valuable therapeutic strategy across indications, including non-small cell lung cancer (NSCLC) and urothelial cancer (UC). Here, we describe a diagnostic assay that measures programmed-death ligand 1 (PD-L1) expression, via immunohistochemistry, to identify patients who will derive the most benefit from treatment with atezolizumab, a humanized monoclonal anti-PD-L1 antibody. We describe the performance of the VENTANA PD-L1 (SP142) Assay in terms of specificity, sensitivity, and the ability to stain both tumor cells (TC) and tumor-infiltrating immune cells (IC), in NSCLC and UC tissues. The reader precision, repeatability and intermediate precision, interlaboratory reproducibility, and the effectiveness of pathologist training on the assessment of PD-L1 staining on both TC and IC were evaluated. We detail the analytical validation of the VENTANA PD-L1 (SP142) Assay for PD-L1 expression in NSCLC and UC tissues and show that the assay reliably evaluated staining on both TC and IC across multiple expression levels/clinical cut-offs. The reader precision showed high overall agreement when compared with consensus scores. In addition, pathologists met the predefined training criteria (≥85.0% overall percent agreement) for the assessment of PD-L1 expression in NSCLC and UC tissues with an average overall percent agreement ≥95.0%. The assay evaluates PD-L1 staining on both cell types and is robust and precise. In addition, it can help to identify those patients who may benefit the most from treatment with atezolizumab, although treatment benefit has been demonstrated in an all-comer NSCLC and UC patient population.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/.
Orthonectids Are Highly Degenerate Annelid Worms.
Schiffer, Philipp H; Robertson, Helen E; Telford, Maximilian J
2018-05-24
The animal groups of Orthonectida and Dicyemida are tiny, extremely simple, vermiform endoparasites of various marine animals and have been linked in the Mesozoa (Figure 1). The Orthonectida (Figures 1A and 1B) have a few hundred cells, including a nervous system of just ten cells [2], and the Dicyemida (Figure 1C) are even simpler, with ∼40 cells [3]. They are classic "Problematica" [4]-the name Mesozoa suggests an evolutionary position intermediate between Protozoa and Metazoa (animals) [5] and implies that their simplicity is a primitive state, but molecular data have shown they are members of Lophotrochozoa within Bilateria [6-9], which means that they derive from a more complex ancestor. Their precise affinities remain uncertain, however, and it is disputed whether they even constitute a clade. Ascertaining their affinities is complicated by the very fast evolution observed in their genes, potentially leading to the common systematic error of long-branch attraction (LBA) [10]. Here, we use mitochondrial and nuclear gene sequence data and show that both dicyemids and orthonectids are members of the Lophotrochozoa. Carefully addressing the effects of unequal rates of evolution, we show that the Mesozoa is polyphyletic. While the precise position of dicyemids remains unresolved within Lophotrochozoa, we identify orthonectids as members of the phylum Annelida. This result reveals one of the most extreme cases of body-plan simplification in the animal kingdom; our finding makes sense of an annelid-like cuticle in orthonectids [2] and suggests that the circular muscle cells repeated along their body [11] may be segmental in origin. Copyright © 2018 Elsevier Ltd. All rights reserved.
Ortega, Raquel; Navas, Natalia; Salmerón, Antonio; Cabeza, José; Capitán-Vallvey, Luís F
2011-01-01
A stability-indicating HPLC method with diode array detection for the determination of paricalcitol, a synthetic vitamin D2 analog, was developed. Analytical parameters were studied according to International Conference on Harmonization guidelines. A C18 column (250 x 4.6 mm, 5 microm particle size) maintained at 25 degrees C was used as the stationary phase, and acetonitrile-water (70 + 30, v/v) as the mobile phase. Chromatograms were recorded at 250 nm. In forced degradation studies, the effects of acid, base, oxidation, temperature, and UV light were investigated and showed no interference with the drug peak. The method was found to be linear (r = 0.9989) at concentrations ranging from 0.6 to 10.0 mg/L paricalcitol, precise (repeatability and intermediate precision estimated as RSD less than 3.5%), accurate (recoveries higher than 95%), specific, and robust. The LOD and LOQ were 0.6 and 0.2 mg/L, respectively. The validated method was used for paricalcitol determination in a formal stability study of its pharmaceutical dosage form in preloaded syringes. The stability of a diluted solution of its pharmaceutical form in Viaflo bags was also tested. The results showed that paricalcitol was stable in preloaded syringes during a period of 30 days from preparation in the different storage conditions tested (room temperature without protection from daylight and 4.4 degrees C with protection from daylight). On the contrary, paricalcitol was quickly lost when stored in Viaflo bags by adsorption onto the walls of the container.
Short-term memory in olfactory network dynamics
NASA Astrophysics Data System (ADS)
Stopfer, Mark; Laurent, Gilles
1999-12-01
Neural assemblies in a number of animal species display self-organized, synchronized oscillations in response to sensory stimuli in a variety of brain areas.. In the olfactory system of insects, odour-evoked oscillatory synchronization of antennal lobe projection neurons (PNs) is superimposed on slower and stimulus-specific temporal activity patterns. Hence, each odour activates a specific and dynamic projection neuron assembly whose evolution during a stimulus is locked to the oscillation clock. Here we examine, using locusts, the changes in population dynamics of projection-neuron assemblies over repeated odour stimulations, as would occur when an animal first encounters and then repeatedly samples an odour for identification or localization. We find that the responses of these assemblies rapidly decrease in intensity, while they show a marked increase in spike time precision and inter-neuronal oscillatory coherence. Once established, this enhanced precision in the representation endures for several minutes. This change is stimulus-specific, and depends on events within the antennal lobe circuits, independent of olfactory receptor adaptation: it may thus constitute a form of sensory memory. Our results suggest that this progressive change in olfactory network dynamics serves to converge, over repeated odour samplings, on a more precise and readily classifiable odour representation, using relational information contained across neural assemblies.
Structural Basis of Egg Coat-Sperm Recognition at Fertilization.
Raj, Isha; Sadat Al Hosseini, Hamed; Dioguardi, Elisa; Nishimura, Kaoru; Han, Ling; Villa, Alessandra; de Sanctis, Daniele; Jovine, Luca
2017-06-15
Recognition between sperm and the egg surface marks the beginning of life in all sexually reproducing organisms. This fundamental biological event depends on the species-specific interaction between rapidly evolving counterpart molecules on the gametes. We report biochemical, crystallographic, and mutational studies of domain repeats 1-3 of invertebrate egg coat protein VERL and their interaction with cognate sperm protein lysin. VERL repeats fold like the functionally essential N-terminal repeat of mammalian sperm receptor ZP2, whose structure is also described here. Whereas sequence-divergent repeat 1 does not bind lysin, repeat 3 binds it non-species specifically via a high-affinity, largely hydrophobic interface. Due to its intermediate binding affinity, repeat 2 selectively interacts with lysin from the same species. Exposure of a highly positively charged surface of VERL-bound lysin suggests that complex formation both disrupts the organization of egg coat filaments and triggers their electrostatic repulsion, thereby opening a hole for sperm penetration and fusion. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.
Huang, Jinhai; Savini, Giacomo; Wu, Fan; Yu, Xinxin; Yang, Jing; Yu, Ayong; Yu, Ye; Wang, Qinmei
2015-10-01
To assess the precision of ocular biometry with a new noncontact optical low-coherence interferometer (Aladdin) in healthy subjects and patients with cataracts. Eye Hospital of Wenzhou Medical University, Wenzhou, China. Observational cross-sectional study. Eyes from healthy subjects and eyes from patients with cataracts were examined with the new interferometer. Axial length (AL), anterior chamber depth (ACD), keratometry (K), and white-to-white (WTW) values were measured by 2 operators. The test-retest repeatability, coefficient of variation (CoV), and intraclass correlation coefficient (ICC) were calculated to evaluate intraoperator repeatability. Different-operator comparison was analyzed with paired t tests and Bland-Altman plots to assess interoperator reproducibility. Ninety-eight people were enrolled for this study, of which 52 eyes were from healthy subjects and 46 eyes were from patients with cataracts. The AL was the most repeatable and reproducible parameter. The ACD, K values, and WTW measurements were highly repeatable in healthy subjects with CoV less than 0.89% and ICC more than 0.94. However, in patients with cataracts, high repeatability could only be observed for AL, ACD, and K values, whereas WTW measurement had test-retest repeatability of 0.80 mm and an ICC of 0.795. Bland-Altman analysis also showed good agreement between the 2 operators for ocular component measurements, except that the WTW in patients with cataracts had wider 95% limits of agreement (range -0.88 to 0.95 mm). The new biometer showed excellent intraoperator repeatability and interoperator reproducibility for AL, ACD, and K values measurements in both groups. The precision of WTW measurements was lower in patients with cataracts. No author has a financial or proprietary interest in any material or method mentioned. Copyright © 2015 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.
Precision manufacturing for clinical-quality regenerative medicines.
Williams, David J; Thomas, Robert J; Hourd, Paul C; Chandra, Amit; Ratcliffe, Elizabeth; Liu, Yang; Rayment, Erin A; Archer, J Richard
2012-08-28
Innovations in engineering applied to healthcare make a significant difference to people's lives. Market growth is guaranteed by demographics. Regulation and requirements for good manufacturing practice-extreme levels of repeatability and reliability-demand high-precision process and measurement solutions. Emerging technologies using living biological materials add complexity. This paper presents some results of work demonstrating the precision automated manufacture of living materials, particularly the expansion of populations of human stem cells for therapeutic use as regenerative medicines. The paper also describes quality engineering techniques for precision process design and improvement, and identifies the requirements for manufacturing technology and measurement systems evolution for such therapies.
Gillian, Jeffrey K.; Karl, Jason W.; Elaksher, Ahmed; Duniway, Michael C.
2017-01-01
Structure-from-motion (SfM) photogrammetry from unmanned aerial system (UAS) imagery is an emerging tool for repeat topographic surveying of dryland erosion. These methods are particularly appealing due to the ability to cover large landscapes compared to field methods and at reduced costs and finer spatial resolution compared to airborne laser scanning. Accuracy and precision of high-resolution digital terrain models (DTMs) derived from UAS imagery have been explored in many studies, typically by comparing image coordinates to surveyed check points or LiDAR datasets. In addition to traditional check points, this study compared 5 cm resolution DTMs derived from fixed-wing UAS imagery with a traditional ground-based method of measuring soil surface change called erosion bridges. We assessed accuracy by comparing the elevation values between DTMs and erosion bridges along thirty topographic transects each 6.1 m long. Comparisons occurred at two points in time (June 2014, February 2015) which enabled us to assess vertical accuracy with 3314 data points and vertical precision (i.e., repeatability) with 1657 data points. We found strong vertical agreement (accuracy) between the methods (RMSE 2.9 and 3.2 cm in June 2014 and February 2015, respectively) and high vertical precision for the DTMs (RMSE 2.8 cm). Our results from comparing SfM-generated DTMs to check points, and strong agreement with erosion bridge measurements suggests repeat UAS imagery and SfM processing could replace erosion bridges for a more synoptic landscape assessment of shifting soil surfaces for some studies. However, while collecting the UAS imagery and generating the SfM DTMs for this study was faster than collecting erosion bridge measurements, technical challenges related to the need for ground control networks and image processing requirements must be addressed before this technique could be applied effectively to large landscapes.
Singh, Varoon; Garg, Prabhat; Chinthakindi, Sridhar; Tak, Vijay; Dubey, Devendra Kumar
2014-02-14
Analysis and identification of nitrogen containing aminoalcohols is an integral part of the verification analysis of chemical weapons convention (CWC). This study was aimed to develop extraction and derivatization of aminoalcohols of CWC relevance by using magnetic dispersive solid-phase extraction (MDSPE) in combination with on-resin derivatization (ORD). For this purpose, sulfonated magnetic cation-exchange resins (SMRs) were prepared using magnetite nanoparticles as core, styrene and divinylbenzene as polymer coat and sulfonic acid as acidic cation exchanger. SMRs were successfully employed as extractant for targeted basic analytes. Adsorbed analytes were derivatized with hexamethyldisilazane (HMDS) on the surface of extractant. Derivatized (silylated) compounds were analyzed by GC-MS in SIM and full scan mode. The linearity of the method ranged from 5 to 200ngmL(-1). The LOD and LOQ ranged from 2 to 6ngmL(-1) and 5 to 19ngmL(-1) respectively. The relative standard deviation for intra-day repeatability and inter-day intermediate precision ranged from 5.1% to 6.6% and 0.2% to 7.6% respectively. Recoveries of analytes from spiked water samples from different sources varied from 28.4% to 89.3%. Copyright © 2014 Elsevier B.V. All rights reserved.
Don, Elena; Farafonova, Olga; Pokhil, Suzanna; Barykina, Darya; Nikiforova, Marina; Shulga, Darya; Borshcheva, Alena; Tarasov, Sergey; Ermolaeva, Tatyana; Epstein, Oleg
2016-01-01
In preliminary ELISA studies where released-active forms (RAF) of antibodies (Abs) to interferon-gamma (IFNg) were added to the antigen-antibody system, a statistically significant difference in absorbance signals obtained in their presence in comparison to placebo was observed. A piezoelectric immunosensor assay was developed to support these data and investigate the effects of RAF Abs to IFNg on the specific interaction between Abs to IFNg and IFNg. The experimental conditions were designed and optimal electrode coating, detection circumstances and suitable chaotropic agents for electrode regeneration were selected. The developed technique was found to provide high repeatability, intermediate precision and specificity. The difference between the analytical signals of RAF Ab samples and those of the placebo was up to 50.8%, whereas the difference between non-specific controls and the placebo was within 5%–6%. Thus, the piezoelectric immunosensor as well as ELISA has the potential to be used for detecting the effects of RAF Abs to IFNg on the antigen-antibody interaction, which might be the result of RAF’s ability to modify the affinity of IFNg to specific/related Abs. PMID:26791304
Watson, Lynn; Potter, Ross; Murphy, Cory; Gibbs, Ryan
2015-01-01
Due to potential use in aquacultured fish products, the Canadian Food Inspection Agency has identified residue testing for steroids as a priority. These compounds are used in aquaculture primarily to direct sexual differentiation with both androgens and estrogens applied depending on the desired outcome. Published research is lacking with respect to steroid residue testing in fish; however, recent studies in other matrixes provided transferable cleanup techniques. A simple, rapid, and sensitive method was developed and validated for use in monitoring aquacultured fish products for the presence of methyltestosterone, nandrolone, epi-nandrolone, boldenone, and epi-boldenone residues. The developed method consists of solvent extraction followed by cleanup using hexane and dual cartridge SPE with analysis by ultra-HPLC-MS/MS. The method is capable of detecting and confirming steroid residue levels ranging from 0.05 to 25 ng/g in salmon and tilapia, depending on the analyte. Recoveries ranged from 88 to 130% for the analytes. Instrument repeatability was less than 13% for all compounds, while intermediate precision ranged from 5 to 25% RSD. HorRat values were within acceptable ranges.
Nussbaumer, Susanne; Fleury-Souverain, Sandrine; Rudaz, Serge; Bonnabry, Pascal; Veuthey, Jean-Luc
2009-02-20
A simple method based on capillary electrophoresis with a capacitively coupled contactless conductivity detector (CE-C(4)D) was developed for the determination of suxamethonium (SUX) in a pharmaceutical formulation. A hydro-organic mixture, consisting of 100mM Tris-acetate buffer at pH 4.2 and acetonitrile (90:10, v/v), was selected as background electrolyte (BGE). The applied voltage was 30kV, and the sample injection was performed in the hydrodynamic mode. All analyses were carried out in a fused silica capillary with an internal diameter of 50 microm and a total length of 64.5cm. Under these conditions, a complete separation between SUX, sodium ions and the main degradation products (choline) was achieved in less than 4min. The presence of acetonitrile in the BGE allowed a reduction of SUX adsorption on the capillary wall. The CE-C(4)D method was validated, and trueness values between 98.8% and 101.1% were obtained with repeatability and intermediate precision values of 0.7-1.3% and 1.2-1.6%, respectively. Therefore, this method was found appropriate for controlling pharmaceutical formulations containing suxamethonium and degradation products.
Salvati, Louis M; McClure, Sean C; Reddy, Todime M; Cellar, Nicholas A
2016-05-01
This method provides simultaneous determination of total vitamins B1, B2, B3, and B6 in infant formula and related nutritionals (adult and infant). The method was given First Action for vitamins B1, B2, and B6, but not B3, during the AOAC Annual Meeting in September 2015. The method uses acid phosphatase to dephosphorylate the phosphorylated vitamin forms. It then measures thiamine (vitamin B1); riboflavin (vitamin B2); nicotinamide and nicotinic acid (vitamin B3); and pyridoxine, pyridoxal, and pyridoxamine (vitamin B6) from digested sample extract by liquid chromatography-tandem mass spectrometry. A single-laboratory validation was performed on 14 matrixes provided by the AOAC Stakeholder Panel on Infant Formula and Adult Nutritionals (SPIFAN) to demonstrate method effectiveness. The method met requirements of the AOAC SPIFAN Standard Method Performance Requirement for each of the three vitamins, including average over-spike recovery of 99.6 ± 3.5%, average repeatability of 1.5 ± 0.8% relative standard deviation, and average intermediate precision of 3.9 ± 1.3% relative standard deviation.
Simón-Manso, Yamil; Lowenthal, Mark S; Kilpatrick, Lisa E; Sampson, Maureen L; Telu, Kelly H; Rudnick, Paul A; Mallard, W Gary; Bearden, Daniel W; Schock, Tracey B; Tchekhovskoi, Dmitrii V; Blonder, Niksa; Yan, Xinjian; Liang, Yuxue; Zheng, Yufang; Wallace, William E; Neta, Pedatsur; Phinney, Karen W; Remaley, Alan T; Stein, Stephen E
2013-12-17
Recent progress in metabolomics and the development of increasingly sensitive analytical techniques have renewed interest in global profiling, i.e., semiquantitative monitoring of all chemical constituents of biological fluids. In this work, we have performed global profiling of NIST SRM 1950, "Metabolites in Human Plasma", using GC-MS, LC-MS, and NMR. Metabolome coverage, difficulties, and reproducibility of the experiments on each platform are discussed. A total of 353 metabolites have been identified in this material. GC-MS provides 65 unique identifications, and most of the identifications from NMR overlap with the LC-MS identifications, except for some small sugars that are not directly found by LC-MS. Also, repeatability and intermediate precision analyses show that the SRM 1950 profiling is reproducible enough to consider this material as a good choice to distinguish between analytical and biological variability. Clinical laboratory data shows that most results are within the reference ranges for each assay. In-house computational tools have been developed or modified for MS data processing and interactive web display. All data and programs are freely available online at http://peptide.nist.gov/ and http://srmd.nist.gov/ .
Collapsing lattice animals and lattice trees in two dimensions
NASA Astrophysics Data System (ADS)
Hsu, Hsiao-Ping; Grassberger, Peter
2005-06-01
We present high statistics simulations of weighted lattice bond animals and lattice trees on the square lattice, with fugacities for each non-bonded contact and for each bond between two neighbouring monomers. The simulations are performed using a newly developed sequential sampling method with resampling, very similar to the pruned-enriched Rosenbluth method (PERM) used for linear chain polymers. We determine with high precision the line of second-order transitions from an extended to a collapsed phase in the resulting two-dimensional phase diagram. This line includes critical bond percolation as a multicritical point, and we verify that this point divides the line into different universality classes. One of them corresponds to the collapse driven by contacts and includes the collapse of (weakly embeddable) trees. There is some evidence that the other is subdivided again into two parts with different universality classes. One of these (at the far side from collapsing trees) is bond driven and is represented by the Derrida-Herrmann model of animals having bonds only (no contacts). Between the critical percolation point and this bond-driven collapse seems to be an intermediate regime, whose other end point is a multicritical point P* where a transition line between two collapsed phases (one bond driven and the other contact driven) sparks off. This point P* seems to be attractive (in the renormalization group sense) from the side of the intermediate regime, so there are four universality classes on the transition line (collapsing trees, critical percolation, intermediate regime, and Derrida-Herrmann). We obtain very precise estimates for all critical exponents for collapsing trees. It is already harder to estimate the critical exponents for the intermediate regime. Finally, it is very difficult to obtain with our method good estimates of the critical parameters of the Derrida-Herrmann universality class. As regards the bond-driven to contact-driven transition in the collapsed phase, we have some evidence for its existence and rough location, but no precise estimates of critical exponents.
Shehzadi, Naureen; Hussain, Khalid; Islam, Muhammad; Bukhari, Nadeem Irfan; Asif, Noman; Khan, Muhammad Tanveer; Salman, Muhammad; Qamar, Shaista; Parveen, Sajida; Zahid, Fakhra; Shah, Arshad Ali; Bilal, Abida; Abbasi, Muhammad Athar; Siddiqui, Sabahat Zahra; Rehman, Azizur
2018-03-01
The present study describes the development and validation of a simple high performance liquid chromatographic method for the determination of a novel drug candidate, 5-[(4-chlorophenoxy) methyl]-1, 3, 4-oxadiazole-2-thiol. The stability-indicating capacity of the method was evaluated by subjecting the compound's solution to hydrolytic, oxidative, photolytic, transition metal- and thermal- stress. The chromatographic separation was achieved over a C18 column (Promosil, 5 µm, 4.60 × 250 mm), maintained at 25°C, using an isocratic mobile phase comprising a mixture of acetonitrile and acidified water of pH 2.67 (1:1, v/v), at a flow rate of 1.00 mL/min and detection using a fluorescent light detector (excitation at 250 nm and emission at 410 nm). The Beer's law was followed over the concentration range 2.50-50.00 μg/ml. The recovery (98.56-100.19%, SD <5%), intraday accuracy and precision (97.31-100.81%, RSD <5%), inter-day accuracy and precision (97.50-100.75%, RSD <5%) and intermediate accuracy and precision (98.10-99.91%, RSD <5%) indicated that the method was reliable, repeatable, reproducible and rugged. The resolution and selectivity factors of the compound's peak from the nearest resolving peak, particularly in case of dry heat and copper metal stress, were found to be greater than 2 and 1, respectively, which indicated specificity and selectivity. The compound was extensively decomposed in alkaline-hydrolytic, oxidative, metal- and dry heat- stress. However, the compound in acidic and neutral conditions was resistant to photolysis. The results of the present study indicate that the developed method is specific, selective, sensitive and suitable, hence, may be used for quality control, stability testing and preformulation studies.
USDA-ARS?s Scientific Manuscript database
Structure-from-motion (SfM) photogrammetry from unmanned aircraft system (UAS) imagery is an emerging tool for repeat topographic surveying of dryland erosion. These methods are particularly appealing due to the ability to cover large landscapes compared to field methods and at reduced costs and hig...
Precise low cost chain gears for heliostats
NASA Astrophysics Data System (ADS)
Liedke, Phillip; Lewandowski, Arkadiusz; Pfahl, Andreas; Hölle, Erwin
2016-05-01
This work investigates the potential of chain gears as precise and low cost driving systems for rim drive heliostats. After explaining chain gear basics the polygon effect and chain lengthening are investigated. The polygon effect could be measured by a heliostat with chain rim gear and the chain lengthening with an accordant test set up. Two gear stages are scope of this work: a rim gear and an intermediate gear. Dimensioning, pretensioning and designing for both stages are explained.
Precise Relative Earthquake Depth Determination Using Array Processing Techniques
NASA Astrophysics Data System (ADS)
Florez, M. A.; Prieto, G. A.
2014-12-01
The mechanism for intermediate depth and deep earthquakes is still under debate. The temperatures and pressures are above the point where ordinary fractures ought to occur. Key to constraining this mechanism is the precise determination of hypocentral depth. It is well known that using depth phases allows for significant improvement in event depth determination, however routinely and systematically picking such phases for teleseismic or regional arrivals is problematic due to poor signal-to-noise ratios around the pP and sP phases. To overcome this limitation we have taken advantage of the additional information carried by seismic arrays. We have used beamforming and velocity spectral analysis techniques to precise measure pP-P and sP-P differential travel times. These techniques are further extended to achieve subsample accuracy and to allow for events where the signal-to-noise ratio is close to or even less than 1.0. The individual estimates obtained at different subarrays for a pair of earthquakes can be combined using a double-difference technique in order to precisely map seismicity in regions where it is tightly clustered. We illustrate these methods using data from the recent M 7.9 Alaska earthquake and its aftershocks, as well as data from the Bucaramanga nest in northern South America, arguably the densest and most active intermediate-depth earthquake nest in the world.
Motorization of a surgical microscope for intra-operative navigation and intuitive control.
Finke, M; Schweikard, A
2010-09-01
During surgical procedures, various medical systems, e.g. microscope or C-arm, are used. Their precise and repeatable manual positioning can be very cumbersome and interrupts the surgeon's work flow. Robotized systems can assist the surgeon but they require suitable kinematics and control. However, positioning must be fast, flexible and intuitive. We describe a fully motorized surgical microscope. Hardware components as well as implemented applications are specified. The kinematic equations are described and a novel control concept is proposed. Our microscope combines fast manual handling with accurate, automatic positioning. Intuitive control is provided by a small remote control mounted to one of the surgical instruments. Positioning accuracy and repeatability are < 1 mm and vibrations caused by automatic movements fade away in about 1 s. The robotic system assists the surgeon, so that he can position the microscope precisely and repeatedly without interrupting the clinical workflow. The combination of manual und automatic control guarantees fast and flexible positioning during surgical procedures. Copyright 2010 John Wiley & Sons, Ltd.
Precise regional baseline estimation using a priori orbital information
NASA Technical Reports Server (NTRS)
Lindqwister, Ulf J.; Lichten, Stephen M.; Blewitt, Geoffrey
1990-01-01
A solution using GPS measurements acquired during the CASA Uno campaign has resulted in 3-4 mm horizontal daily baseline repeatability and 13 mm vertical repeatability for a 729 km baseline, located in North America. The agreement with VLBI is at the level of 10-20 mm for all components. The results were obtained with the GIPSY orbit determination and baseline estimation software and are based on five single-day data arcs spanning the 20, 21, 25, 26, and 27 of January, 1988. The estimation strategy included resolving the carrier phase integer ambiguities, utilizing an optial set of fixed reference stations, and constraining GPS orbit parameters by applying a priori information. A multiday GPS orbit and baseline solution has yielded similar 2-4 mm horizontal daily repeatabilities for the same baseline, consistent with the constrained single-day arc solutions. The application of weak constraints to the orbital state for single-day data arcs produces solutions which approach the precise orbits obtained with unconstrained multiday arc solutions.
Jones, Sherri Lee; Germé, Katuschia; Graham, M Dean; Roy, Patrick; Gardner Gregory, James; Rosenbaum, Stephanie; Parada, Mayte; Pfaus, James G
2015-09-01
The acute administration of estradiol benzoate (EB) to the ovariectomized (OVX) rat induces low levels of lordosis while sexually appetitive behaviors (e.g., hops, darts, solicitations) are absent, yet the repeated administration of EB results in a behavioral sensitization in which lordosis is potentiated and sexually appetitive behaviors are induced. We have shown that repeated copulation attenuates the sensitization of appetitive sexual behaviors. Here, we assessed which component of male stimulation during copulation is involved in the attenuation. On 8 occasions, sexually experienced OVX Long-Evans rats were treated with 10μgEB and 48h later assigned to one of six groups that differed in their experience on intermediates tests (2-7). One was given repeated access to a male (EB/Male), and another was placed in the copulation chamber alone (EB/Alone) on intermediate tests. Three groups were given one of three somatosensory stimuli by the experimenter: manual flank stimulation (FLS), clitoral stimulation (CLS), or vaginocervical stimulation (VCS). Finally, the control group was left undisturbed in the animal care facility (ACF). Sexual behaviors were measured on Tests 1 and 8. VCS received from the experimenter (VCS) or from the male during copulation (EB/Male) attenuated the magnitude of the sensitization of appetitive sexual behaviors compared with those that were not brought to the testing rooms (ACF), and the effect was most pronounced on sexual solicitations. These results suggest that VCS received during penile intromission inhibits the sensitization of sexually appetitive behaviors by repeated administration of EB. As such, repeated administration of EB may oppose those mechanisms that induce estrous termination, perhaps by sensitizing inhibitory processes within the ventromedial hypothalamus that typically prevent the display of sexual behaviors (i.e., by facilitating disinhibition). Copyright © 2015 Elsevier Inc. All rights reserved.
NASA Astrophysics Data System (ADS)
Wray, J. D.
2003-05-01
The robotic observatory telescope must point precisely on the target object, and then track autonomously to a fraction of the FWHM of the system PSF for durations of ten to twenty minutes or more. It must retain this precision while continuing to function at rates approaching thousands of observations per night for all its years of useful life. These stringent requirements raise new challenges unique to robotic telescope systems design. Critical design considerations are driven by the applicability of the above requirements to all systems of the robotic observatory, including telescope and instrument systems, telescope-dome enclosure systems, combined electrical and electronics systems, environmental (e.g. seeing) control systems and integrated computer control software systems. Traditional telescope design considerations include the effects of differential thermal strain, elastic flexure, plastic flexure and slack or backlash with respect to focal stability, optical alignment and angular pointing and tracking precision. Robotic observatory design must holistically encapsulate these traditional considerations within the overall objective of maximized long-term sustainable precision performance. This overall objective is accomplished through combining appropriate mechanical and dynamical system characteristics with a full-time real-time telescope mount model feedback computer control system. Important design considerations include: identifying and reducing quasi-zero-backlash; increasing size to increase precision; directly encoding axis shaft rotation; pointing and tracking operation via real-time feedback between precision mount model and axis mounted encoders; use of monolithic construction whenever appropriate for sustainable mechanical integrity; accelerating dome motion to eliminate repetitive shock; ducting internal telescope air to outside dome; and the principal design criteria: maximizing elastic repeatability while minimizing slack, plastic deformation and hysteresis to facilitate long-term repeatably precise pointing and tracking performance.
Peifer, Susanne; Schneider, Konstantin; Nürenberg, Gudrun; Volmer, Dietrich A; Heinzle, Elmar
2012-11-01
Intermediates of the purine biosynthesis pathway play key roles in cellular metabolism including nucleic acid synthesis and signal mediation. In addition, they are also of major interest to the biotechnological industry as several intermediates either possess flavor-enhancing characteristics or are applied in medical therapy. In this study, we have developed an analytical method for quantitation of 12 intermediates from the purine biosynthesis pathway including important nucleotides and their corresponding nucleosides and nucleobases. The approach comprised a single-step acidic extraction/quenching procedure, followed by quantitative electrospray LC-MS/MS analysis. The assay was validated in terms of accuracy, precision, reproducibility, and applicability for complex biological matrices. The method was subsequently applied for determination of free intracellular pool sizes of purine biosynthetic pathway intermediates in the two Gram-positive bacteria Corynebacterium glutamicum and Corynebacterium ammoniagenes. Importantly, no ion pair reagents were applied in this approach as usually required for liquid chromatography analysis of large classes of diverse metabolites.
Image analysis software versus direct anthropometry for breast measurements.
Quieregatto, Paulo Rogério; Hochman, Bernardo; Furtado, Fabianne; Machado, Aline Fernanda Perez; Sabino Neto, Miguel; Ferreira, Lydia Masako
2014-10-01
To compare breast measurements performed using the software packages ImageTool(r), AutoCAD(r) and Adobe Photoshop(r) with direct anthropometric measurements. Points were marked on the breasts and arms of 40 volunteer women aged between 18 and 60 years. When connecting the points, seven linear segments and one angular measurement on each half of the body, and one medial segment common to both body halves were defined. The volunteers were photographed in a standardized manner. Photogrammetric measurements were performed by three independent observers using the three software packages and compared to direct anthropometric measurements made with calipers and a protractor. Measurements obtained with AutoCAD(r) were the most reproducible and those made with ImageTool(r) were the most similar to direct anthropometry, while measurements with Adobe Photoshop(r) showed the largest differences. Except for angular measurements, significant differences were found between measurements of line segments made using the three software packages and those obtained by direct anthropometry. AutoCAD(r) provided the highest precision and intermediate accuracy; ImageTool(r) had the highest accuracy and lowest precision; and Adobe Photoshop(r) showed intermediate precision and the worst accuracy among the three software packages.
McAlinden, Colm; Khadka, Jyoti; Pesudovs, Konrad
2011-07-01
The ever-expanding choice of ocular metrology and imaging equipment has driven research into the validity of their measurements. Consequently, studies of the agreement between two instruments or clinical tests have proliferated in the ophthalmic literature. It is important that researchers apply the appropriate statistical tests in agreement studies. Correlation coefficients are hazardous and should be avoided. The 'limits of agreement' method originally proposed by Altman and Bland in 1983 is the statistical procedure of choice. Its step-by-step use and practical considerations in relation to optometry and ophthalmology are detailed in addition to sample size considerations and statistical approaches to precision (repeatability or reproducibility) estimates. Ophthalmic & Physiological Optics © 2011 The College of Optometrists.
Accuracy and precision of two indirect methods for estimating canopy fuels
Abran Steele-Feldman; Elizabeth Reinhardt; Russell A. Parsons
2006-01-01
We compared the accuracy and precision of digital hemispherical photography and the LI-COR LAI-2000 plant canopy analyzer as predictors of canopy fuels. We collected data on 12 plots in western Montana under a variety of lighting and sky conditions, and used a variety of processing methods to compute estimates. Repeated measurements from each method displayed...
Accuracy of Digital Impressions and Fitness of Single Crowns Based on Digital Impressions
Yang, Xin; Lv, Pin; Liu, Yihong; Si, Wenjie; Feng, Hailan
2015-01-01
In this study, the accuracy (precision and trueness) of digital impressions and the fitness of single crowns manufactured based on digital impressions were evaluated. #14-17 epoxy resin dentitions were made, while full-crown preparations of extracted natural teeth were embedded at #16. (1) To assess precision, deviations among repeated scan models made by intraoral scanner TRIOS and MHT and model scanner D700 and inEos were calculated through best-fit algorithm and three-dimensional (3D) comparison. Root mean square (RMS) and color-coded difference images were offered. (2) To assess trueness, micro computed tomography (micro-CT) was used to get the reference model (REF). Deviations between REF and repeated scan models (from (1)) were calculated. (3) To assess fitness, single crowns were manufactured based on TRIOS, MHT, D700 and inEos scan models. The adhesive gaps were evaluated under stereomicroscope after cross-sectioned. Digital impressions showed lower precision and better trueness. Except for MHT, the means of RMS for precision were lower than 10 μm. Digital impressions showed better internal fitness. Fitness of single crowns based on digital impressions was up to clinical standard. Digital impressions could be an alternative method for single crowns manufacturing. PMID:28793417
A precision medicine approach for psychiatric disease based on repeated symptom scores.
Fojo, Anthony T; Musliner, Katherine L; Zandi, Peter P; Zeger, Scott L
2017-12-01
For psychiatric diseases, rich information exists in the serial measurement of mental health symptom scores. We present a precision medicine framework for using the trajectories of multiple symptoms to make personalized predictions about future symptoms and related psychiatric events. Our approach fits a Bayesian hierarchical model that estimates a population-average trajectory for all symptoms and individual deviations from the average trajectory, then fits a second model that uses individual symptom trajectories to estimate the risk of experiencing an event. The fitted models are used to make clinically relevant predictions for new individuals. We demonstrate this approach on data from a study of antipsychotic therapy for schizophrenia, predicting future scores for positive, negative, and general symptoms, and the risk of treatment failure in 522 schizophrenic patients with observations over 8 weeks. While precision medicine has focused largely on genetic and molecular data, the complementary approach we present illustrates that innovative analytic methods for existing data can extend its reach more broadly. The systematic use of repeated measurements of psychiatric symptoms offers the promise of precision medicine in the field of mental health. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
NASA Technical Reports Server (NTRS)
Agnes, Gregory S.; Waldman, Jeff; Hughes, Richard; Peterson, Lee D.
2015-01-01
NASA's proposed Surface Water Ocean Topography (SWOT) mission, scheduled to launch in 2020, would provide critical information about Earth's oceans, ocean circulation, fresh water storage, and river discharge. The mission concept calls for a dual-antenna Ka-band radar interferometer instrument, known as KaRIn, that would map the height of water globally along two 50 km wide swaths. The KaRIn antennas, which would be separated by 10 meters on either side of the spacecraft, would need to be precisely deployable in order to meet demanding pointing requirements. Consequently, an effort was undertaken to design build and prototype a precision deployable Mast for the KaRIn instrument. Each mast was 4.5-m long with a required dilitation stability of 2.5 microns over 3 minutes. It required a minimum first mode of 7 Hz. Deployment repeatability was less than +/- 7 arcsec in all three rotation directions. Overall mass could not exceed 41.5 Kg including any actuators and thermal blanketing. This set of requirements meant the boom had to be three times lighter and two orders of magnitude more precise than the existing state of the art for deployable booms.
Five critical elements to ensure the precision medicine.
Chen, Chengshui; He, Mingyan; Zhu, Yichun; Shi, Lin; Wang, Xiangdong
2015-06-01
The precision medicine as a new emerging area and therapeutic strategy has occurred and was practiced in the individual and brought unexpected successes, and gained high attentions from professional and social aspects as a new path to improve the treatment and prognosis of patients. There will be a number of new components to appear or be discovered, of which clinical bioinformatics integrates clinical phenotypes and informatics with bioinformatics, computational science, mathematics, and systems biology. In addition to those tools, precision medicine calls more accurate and repeatable methodologies for the identification and validation of gene discovery. Precision medicine will bring more new therapeutic strategies, drug discovery and development, and gene-oriented treatment. There is an urgent need to identify and validate disease-specific, mechanism-based, or epigenetics-dependent biomarkers to monitor precision medicine, and develop "precision" regulations to guard the application of precision medicine.
Weber, P.K.; Bacon, C.R.; Hutcheon, I.D.; Ingram, B.L.; Wooden, J.L.
2005-01-01
The ion microprobe has the capability to generate high resolution, high precision isotopic measurements, but analysis of the isotopic composition of strontium, as measured by the 87Sr/ 86Sr ratio, has been hindered by isobaric interferences. Here we report the first high precision measurements of 87Sr/ 86Sr by ion microprobe in calcium carbonate samples with moderate Sr concentrations. We use the high mass resolving power (7000 to 9000 M.R.P.) of the SHRIMP-RG ion microprobe in combination with its high transmission to reduce the number of interfering species while maintaining sufficiently high count rates for precise isotopic measurements. The isobaric interferences are characterized by peak modeling and repeated analyses of standards. We demonstrate that by sample-standard bracketing, 87Sr/86Sr ratios can be measured in inorganic and biogenic carbonates with Sr concentrations between 400 and 1500 ppm with ???2??? external precision (2??) for a single analysis, and subpermil external precision with repeated analyses. Explicit correction for isobaric interferences (peak-stripping) is found to be less accurate and precise than sample-standard bracketing. Spatial resolution is ???25 ??m laterally and 2 ??m deep for a single analysis, consuming on the order of 2 ng of material. The method is tested on otoliths from salmon to demonstrate its accuracy and utility. In these growth-banded aragonitic structures, one-week temporal resolution can be achieved. The analytical method should be applicable to other calcium carbonate samples with similar Sr concentrations. Copyright ?? 2005 Elsevier Ltd.
Using confidence intervals to evaluate the focus alignment of spectrograph detector arrays.
Sawyer, Travis W; Hawkins, Kyle S; Damento, Michael
2017-06-20
High-resolution spectrographs extract detailed spectral information of a sample and are frequently used in astronomy, laser-induced breakdown spectroscopy, and Raman spectroscopy. These instruments employ dispersive elements such as prisms and diffraction gratings to spatially separate different wavelengths of light, which are then detected by a charge-coupled device (CCD) or complementary metal-oxide-semiconductor (CMOS) detector array. Precise alignment along the optical axis (focus position) of the detector array is critical to maximize the instrumental resolution; however, traditional approaches of scanning the detector through focus lack a quantitative measure of precision, limiting the repeatability and relying on one's experience. Here we propose a method to evaluate the focus alignment of spectrograph detector arrays by establishing confidence intervals to measure the alignment precision. We show that propagation of uncertainty can be used to estimate the variance in an alignment, thus providing a quantitative and repeatable means to evaluate the precision and confidence of an alignment. We test the approach by aligning the detector array of a prototype miniature echelle spectrograph. The results indicate that the procedure effectively quantifies alignment precision, enabling one to objectively determine when an alignment has reached an acceptable level. This quantitative approach also provides a foundation for further optimization, including automated alignment. Furthermore, the procedure introduced here can be extended to other alignment techniques that rely on numerically fitting data to a model, providing a general framework for evaluating the precision of alignment methods.
RepeatsDB-lite: a web server for unit annotation of tandem repeat proteins.
Hirsh, Layla; Paladin, Lisanna; Piovesan, Damiano; Tosatto, Silvio C E
2018-05-09
RepeatsDB-lite (http://protein.bio.unipd.it/repeatsdb-lite) is a web server for the prediction of repetitive structural elements and units in tandem repeat (TR) proteins. TRs are a widespread but poorly annotated class of non-globular proteins carrying heterogeneous functions. RepeatsDB-lite extends the prediction to all TR types and strongly improves the performance both in terms of computational time and accuracy over previous methods, with precision above 95% for solenoid structures. The algorithm exploits an improved TR unit library derived from the RepeatsDB database to perform an iterative structural search and assignment. The web interface provides tools for analyzing the evolutionary relationships between units and manually refine the prediction by changing unit positions and protein classification. An all-against-all structure-based sequence similarity matrix is calculated and visualized in real-time for every user edit. Reviewed predictions can be submitted to RepeatsDB for review and inclusion.
SPM interferometer with large range for mirco-vibration measurement
NASA Astrophysics Data System (ADS)
Fu, Mingyi; Tang, Chaowei; He, Guotian; Hu, Jun; Wang, Li
2007-12-01
The measuring range and precision are two inconsistent parameters of traditional optical interferometry. In this paper, the interferometer measuring vibration with high precision and large range is proposed and its measuring principle is analyzed in detail. The interferometer obtains phase information by processing interference signals with two real-time phase discriminator and the vibration displacement could be gotten by expanding this phase. The measuring range was enlarged from half wavelength to millimeter. Meanwhile, the measuring precision was independent of external disturbance and vibration displacement measurement with high precision was realized. The measuring range of vibration displacement for 6000.5nm and the repeatable measuring precision was 5.72nm from experiment. The feasibility of the measuring method was validated by experiments.
High-Precision Coupling Mechanism Operable By Robots
NASA Technical Reports Server (NTRS)
Voellmer, George
1992-01-01
Coupling mechanism has features making it easily operable by hand and suitable for operation by robots: tolerates some initial misalignment, imposes precise final alignment, and protects itself against overtightening. Typically used to mount equipment module on structure. Mechanism includes kinematic mounts, which tolerate small initial misalignment and enforce precise final alignment as two assemblies brought together. Clamping force applied to kinematic mounts via two flexible plates. Bolt and nut tightened on flexible plates to impose spring clamping load. Repeatability of interface tested and found to be better than forty-millionths of inch.
Performance evaluation of the microINR® point-of-care INR-testing system.
Joubert, J; van Zyl, M C; Raubenheimer, J
2018-04-01
Point-of-care International Normalised Ratio (INR) testing is used frequently. We evaluated the microINR ® POC system for accuracy, precision and measurement repeatability, and investigated instrument and test chip variability and error rates. Venous blood INRs of 210 patients on warfarin were obtained with Thromborel ® S on the Sysmex CS-2100i ® analyser and compared with capillary blood microINR ® values. Precision was assessed using control materials. Measurement repeatability was calculated on 51 duplicate finger-prick INRs. Triplicate finger-prick INRs using three different instruments (30 patients) and three different test chip lots (29 patients) were used to evaluate instrument and test chip variability. Linear regression analysis of microINR ® and Sysmex CS2100i ® values showed a correlation coefficient of 0.96 (P < .0001) and a positive proportional bias of 4.4%. Dosage concordance was 93.8% and clinical agreement 95.7%. All acceptance criteria based on ISO standard 17593:2007 system accuracy requirements were met. Control material coefficients of variation (CV) varied from 6.2% to 16.7%. The capillary blood measurement repeatability CV was 7.5%. No significant instrument (P = .93) or test chip (P = .81) variability was found, and the error rate was low (2.8%). The microINR ® instrument is accurate and precise for monitoring warfarin therapy. © 2017 John Wiley & Sons Ltd.
Gómez-Ordóñez, Eva; Jiménez-Escrig, Antonio; Rupérez, Pilar
2012-05-15
Biological properties of polysaccharides from seaweeds are related to their composition and structure. Many factors such as the kind of sugar, type of linkage or sulfate content of algal biopolymers exert an influence in the relationship between structure and function. Besides, the molecular weight (MW) also plays an important role. Thus, a simple, reliable and fast HPSEC method with refractive index detection was developed and optimized for the MW estimation of soluble algal polysaccharides. Chromatogram shape and repeatability of retention time was considerably improved when sodium nitrate was used instead of ultrapure water as mobile phase. Pullulan and dextran standards of different MW were used for method calibration and validation. Also, main polysaccharide standards from brown (alginate, fucoidan, laminaran) and red seaweeds (kappa- and iota-carrageenan) were used for quantification and method precision and accuracy. Relative standard deviation (RSD) of repeatability for retention time, peak areas and inter-day precision was below 0.7%, 2.5% and 2.6%, respectively, which indicated good repeatability and precision. Recoveries (96.3-109.8%) also showed its fairly good accuracy. Regarding linearity, main polysaccharide standards from brown or red seaweeds showed a highly satisfactory correlation coefficient (r>0.999). Moreover, a good sensitivity was shown, with corresponding limits of detection and quantitation in mg/mL of 0.05-0.21 and 0.16-0.31, respectively. The method was applied to the MW estimation of standard algal polysaccharides, as well as to the soluble polysaccharide fractions from the brown seaweed Saccharina latissima and the red Mastocarpus stellatus, respectively. Although distribution of molecular weight was broad, the good repeatability for retention time provided a good precision in MW estimation of polysaccharides. Water- and alkali-soluble fractions from S. latissima ranged from very high (>2400 kDa) to low MW compounds (<6 kDa); this high heterogeneity could be attributable to the complex polysaccharide composition of brown algae. Regarding M. stellatus, sulfated galactans followed a descending order of MW (>1400 kDa to <10 kDa), related to the different solubility of carrageenans in red seaweeds. In summary, the method developed allows for the molecular weight analysis of seaweed polysaccharides with very good precision, accuracy, linearity and sensitivity within a short time. Copyright © 2012 Elsevier B.V. All rights reserved.
A Combined Hazard Index Fire Test Methodology for Aircraft Cabin Materials. Volume II.
1982-04-01
Technical Center. The report was divided into two parts: Part I described the improved technology investigated to upgrade existin methods for testing...proper implementation of the computerized data acquisition and reduction programs will improve materials hazards measurement precision. Thus, other...the hold chamber before and after injection of a sample, will improve precision and repeatability of measurement. The listed data acquisition and
Cagnoli, Claudia; Michielotto, Chiara; Matsuura, Tohru; Ashizawa, Tetsuo; Margolis, Russell L.; Holmes, Susan E.; Gellera, Cinzia; Migone, Nicola; Brusco, Alfredo
2004-01-01
At least 18 human genetic diseases are caused by expansion of short tandem repeats. Here we describe a successful application of a fluorescent PCR method for the detection of expanded repeats in FRDA1, SCA10, and SCA12 genes. Although this test cannot give a precise estimate of the size of the expansion, it is robust, reliable, and inexpensive, and can be used to screen large series of patients. It proved useful for confirming the presence of large expansions in the Friedreich ataxia gene following an ambiguous result of long-range PCR, as well as rapid pre-screening for large repeat expansions associated with Friedreich ataxia and SCA10 and the shorter repeat expansions associated with SCA12. PMID:15096564
Yılmaz, Pelin Köseoğlu; Ertaş, Abdulselam; Kolak, Ufuk
2014-08-01
A sensitive, rapid, and simple high-performance liquid chromatography with UV detection method was developed for the simultaneous determination of seven phthalic acid esters (dimethyl phthalate, dipropyl phthalate, di-n-butyl phthalate, benzyl butyl phthalate, dicyclohexyl phthalate, di-(2-ethylhexyl) phthalate, and di-n-octyl phthalate) in several kinds of beverage samples. Ultrasound and vortex-assisted dispersive liquid-liquid microextraction method was used. The separation was performed using an Intersil ODS-3 column (C18 , 250 × 4.6 mm, 5.0 μm) and a gradient elution with a mobile phase consisting of MeOH/ACN (50:50) and 0.2 M KH2 PO4 buffer. Analytes were detected by a UV detector at 230 nm. The developed method was validated in terms of linearity, limit of detection, limit of quantification, repeatability, accuracy, and recovery. Calibration equations and correlation coefficients (> 0.99) were calculated by least squares method with weighting factor. The limit of detection and quantification were in the range of 0.019-0.208 and 0.072-0.483 μg/L. The repeatability and intermediate precision were determined in terms of relative standard deviation to be within 0.03-3.93 and 0.02-4.74%, respectively. The accuracy was found to be in the range of -14.55 to 15.57% in terms of relative error. Seventeen different beverage samples in plastic bottles were successfully analyzed, and ten of them were found to be contaminated by different phthalic acid esters. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Lee, Yoojin; Callaghan, Martina F; Nagy, Zoltan
2017-01-01
In magnetic resonance imaging, precise measurements of longitudinal relaxation time ( T 1 ) is crucial to acquire useful information that is applicable to numerous clinical and neuroscience applications. In this work, we investigated the precision of T 1 relaxation time as measured using the variable flip angle method with emphasis on the noise propagated from radiofrequency transmit field ([Formula: see text]) measurements. The analytical solution for T 1 precision was derived by standard error propagation methods incorporating the noise from the three input sources: two spoiled gradient echo (SPGR) images and a [Formula: see text] map. Repeated in vivo experiments were performed to estimate the total variance in T 1 maps and we compared these experimentally obtained values with the theoretical predictions to validate the established theoretical framework. Both the analytical and experimental results showed that variance in the [Formula: see text] map propagated comparable noise levels into the T 1 maps as either of the two SPGR images. Improving precision of the [Formula: see text] measurements significantly reduced the variance in the estimated T 1 map. The variance estimated from the repeatedly measured in vivo T 1 maps agreed well with the theoretically-calculated variance in T 1 estimates, thus validating the analytical framework for realistic in vivo experiments. We concluded that for T 1 mapping experiments, the error propagated from the [Formula: see text] map must be considered. Optimizing the SPGR signals while neglecting to improve the precision of the [Formula: see text] map may result in grossly overestimating the precision of the estimated T 1 values.
A high-precision velocity measuring system design for projectiles based on S-shaped laser screen
NASA Astrophysics Data System (ADS)
Liu, Huayi; Qian, Zheng; Yu, Hao; Li, Yutao
2018-03-01
The high-precision measurement of the velocity of high-speed flying projectile is of great significance for the evaluation and development of modern weapons. The velocity of the high-speed flying projectile is usually measured by laser screen velocity measuring system. But this method cannot achieve the repeated measurements, so we cannot make an indepth evaluation of the uncertainty about the measuring system. This paper presents a design based on S-shaped laser screen velocity measuring system. This design can achieve repeated measurements. Therefore, it can effectively reduce the uncertainty of the velocity measuring system. In addition, we made a detailed analysis of the uncertainty of the measuring system. The measurement uncertainty is 0.2% when the velocity of the projectile is about 200m/s.
Development of a precision reverse offset printing system
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kim, Hyunchang; Lee, Eonseok; Choi, Young-Man
2016-01-15
In printed electronics technology, the overlay accuracy of printed patterns is a very important issue when applying printing technology to the production of electric devices. In order to achieve accurate positioning of the printed patterns, this study proposes a novel precision reverse offset printing system. Furthermore, the study evaluates the effects of synchronization and printing force on position errors of the printed patterns, and presents methods of controlling synchronization and printing force so as to eliminate positional errors caused by the above-mentioned reasons. Finally, the printing position repeatability of 0.40 μm and 0.32 μm (x and y direction, respectively) atmore » a sigma level is obtained over the dimension of 100 mm under repeated printing tests with identical printing conditions.« less
Small tandemly repeated DNA sequences of higher plants likely originate from a tRNA gene ancestor.
Benslimane, A A; Dron, M; Hartmann, C; Rode, A
1986-01-01
Several monomers (177 bp) of a tandemly arranged repetitive nuclear DNA sequence of Brassica oleracea have been cloned and sequenced. They share up to 95% homology between one another and up to 80% with other satellite DNA sequences of Cruciferae, suggesting a common ancestor. Both strands of these monomers show more than 50% homology with many tRNA genes; the best homologies have been obtained with Lys and His yeast mitochondrial tRNA genes (respectively 64% and 60%). These results suggest that small tandemly repeated DNA sequences of plants may have evolved from a tRNA gene ancestor. These tandem repeats have probably arisen via a process involving reverse transcription of polymerase III RNA intermediates, as is the case for interspersed DNA sequences of mammalians. A model is proposed to explain the formation of such small tandemly repeated DNA sequences. Images PMID:3774553
Concise CIO based precession-nutation formulations
NASA Astrophysics Data System (ADS)
Capitaine, N.; Wallace, P. T.
2008-01-01
Context: The IAU 2000/2006 precession-nutation models have precision goals measured in microarcseconds. To reach this level of performance has required series containing terms at over 1300 frequencies and involving several thousand amplitude coefficients. There are many astronomical applications for which such precision is not required and the associated heavy computations are wasteful. This justifies developing smaller models that achieve adequate precision with greatly reduced computing costs. Aims: We discuss strategies for developing simplified IAU 2000/2006 precession-nutation procedures that offer a range of compromises between accuracy and computing costs. Methods: The chain of transformations linking celestial and terrestrial coordinates comprises frame bias, precession-nutation, Earth rotation and polar motion. We address the bias and precession-nutation (NPB) portion of the chain, linking the Geocentric Celestial Reference System (GCRS) with the Celestial Intermediate Reference System (CIRS), the latter based on the Celestial Intermediate Pole (CIP) and Celestial Intermediate Origin (CIO). Starting from direct series that deliver the CIP coordinates X,Y and (via the quantity s + XY/2) the CIO locator s, we look at the opportunities for simplification. Results: The biggest reductions come from truncating the series, but some additional gains can be made in the areas of the matrix formulation, the expressions for the nutation arguments and by subsuming long period effects into the bias quantities. Three example models are demonstrated that approximate the IAU 2000/2006 CIP to accuracies of 1 mas, 16 mas and 0.4 arcsec throughout 1995-2050 but with computation costs reduced by 1, 2 and 3 orders of magnitude compared with the full model. Appendices A to G are only available in electronic form at http://www.aanda.org
NASA Astrophysics Data System (ADS)
Chen, Y.; Huang, X. J.; Kong, J. X.
2018-03-01
In this paper, the focused ion beam was used to study the subsurface deformed layer of single crystal copper caused by the nanoscale single-point diamond fly cutting, and the possibility of using nanometer ultra-precision cutting to remove the larger deformation layer caused by traditional rough cutting process was explored. The maximum cutting thickness of single-point diamond cutting was about 146 nm, and the surface of the single-crystal copper after cutting was etched and observed by using the focused ion beam method. It was found that the morphology of the near-surface layer and the intermediate layer of the copper material were larger differences: the near-surface of the material was smaller and more compact, and the intermediate material layer of the material was more coarse sparse. The results showed that the traditional precision cutting would residual significant subsurface deformed layer and the thickness was on micron level. Even more, the subsurface deformed layer was obviously removed from about 12μm to 5μm after single-point diamond fly cutting in this paper. This paper proved that the large-scale subsurface deformed layer caused by traditional cutting process could be removed by nanometer ultra-precision cutting. It was of great significance to further establish the method that control of the deformation of weak rigid components by reducing the depth of the subsurface deformed layers.
Returns to Scale and Economies of Scale: Further Observations.
ERIC Educational Resources Information Center
Gelles, Gregory M.; Mitchell, Douglas W.
1996-01-01
Maintains that most economics textbooks continue to repeat past mistakes concerning returns to scale and economies of scale under assumptions of constant and nonconstant input prices. Provides an adaptation for a calculus-based intermediate microeconomics class that demonstrates the pointwise relationship between returns to scale and economies of…
Mission design for NISAR repeat-pass Interferometric SAR
NASA Astrophysics Data System (ADS)
Alvarez-Salazar, Oscar; Hatch, Sara; Rocca, Jennifer; Rosen, Paul; Shaffer, Scott; Shen, Yuhsyen; Sweetser, Theodore; Xaypraseuth, Peter
2014-10-01
The proposed spaceborne NASA-ISRO SAR (NISAR) mission would use the repeat-pass interferometric Synthetic Aperture Radar (InSAR) technique to measure the changing shape of Earth's surface at the centimeter scale in support of investigations in solid Earth and cryospheric sciences. Repeat-pass InSAR relies on multiple SAR observations acquired from nearly identical positions of the spacecraft as seen from the ground. Consequently, there are tight constraints on the repeatability of the orbit, and given the narrow field of view of the radar antenna beam, on the repeatability of the beam pointing. The quality and accuracy of the InSAR data depend on highly precise control of both orbital position and observatory pointing throughout the science observation life of the mission. This paper describes preliminary NISAR requirements and rationale for orbit repeatability and attitude control in order to meet science requirements. A preliminary error budget allocation and an implementation approach to meet these allocations are also discussed.
Krishnaiah, Ch; Vishnu Murthy, M; Kumar, Ramesh; Mukkanti, K
2011-03-25
A simple, sensitive and reproducible ultra performance liquid chromatography (UPLC) coupled with a photodiode array detector method was developed for the quantitative determination of olanzapine (OLN) in API and pharmaceutical dosage forms. The method is applicable to the quantification of related substances and assays of drug substances. Chromatographic separation was achieved on Acquity UPLC BEH 100-mm, 2.1-mm, and 1.7-μm C-18 columns, and the gradient eluted within a short runtime, i.e., within 10.0 min. The eluted compounds were monitored at 250 nm, the flow rate was 0.3 mL/min, and the column oven temperature was maintained at 27°C. The resolution of OLN and eight (potential, bi-products and degradation) impurities was greater than 2.0 for all pairs of components. The high correlation coefficient (r(2)>0.9991) values indicated clear correlations between the investigated compound concentrations and their peak areas within the test ranges. The repeatability and intermediate precision, expressed by the RSD, were less than 2.4%. The accuracy and validity of the method were further ascertained by performing recovery studies via a spike method. The accuracy of the method expressed as relative error was satisfactory. No interference was observed from concomitant substances normally added to the tablets. The drug was subjected to the International Conference on Harmonization (ICH)-prescribed hydrolytic, oxidative, photolytic and thermal stress conditions. The performance of the method was validated according to the present ICH guidelines for specificity, limit of detection, limit of quantification, linearity, accuracy, precision, ruggedness and robustness. Copyright © 2010 Elsevier B.V. All rights reserved.
Saviano, Alessandro Morais; Francisco, Fabiane Lacerda; Ostronoff, Celina Silva; Lourenço, Felipe Rebello
2015-01-01
The aim of this study was to develop, optimize, and validate a microplate bioassay for relative potency determination of linezolid in pharmaceutical samples using quality-by-design and design space approaches. In addition, a procedure is described for estimating relative potency uncertainty based on microbiological response variability. The influence of culture media composition was studied using a factorial design and a central composite design was adopted to study the influence of inoculum proportion and triphenyltetrazolium chloride in microbial growth. The microplate bioassay was optimized regarding the responses of low, medium, and high doses of linezolid, negative and positive controls, and the slope, intercept, and correlation coefficient of dose-response curves. According to optimization results, design space ranges were established using: (a) low (1.0 μg/mL), medium (2.0 μg/mL), and high (4.0 μg/mL) doses of pharmaceutical samples and linezolid chemical reference substance; (b) Staphylococcus aureus ATCC 653 in an inoculum proportion of 10%; (c) antibiotic No. 3 culture medium pH 7.0±0.1; (d) 6 h incubation at 37.0±0.1ºC; and (e) addition of 50 μL of 0.5% (w/v) triphenyltetrazolium chloride solution. The microplate bioassay was linear (r2=0.992), specific, precise (repeatability RSD=2.3% and intermediate precision RSD=4.3%), accurate (mean recovery=101.4%), and robust. The overall measurement uncertainty was reasonable considering the increased variability inherent in microbiological response. Final uncertainty was comparable with those obtained with other microbiological assays, as well as chemical methods.
Trevisani, M; Cecchini, M; Taffetani, L; Vercellotti, L; Rosmini, R
2011-02-01
A square-wave anodic-stripping voltammetric method for the analysis of lead and cadmium in chicken muscle and liver was developed and validated, and the results of a monitoring study relative to chicken and pigeon meat are reported. The voltammetric method allows the analysis of lead and cadmium at the same time in samples after acid digestion. The use of perchloric acid for digestion and of acetate buffer in the supporting electrolyte are suitable to reduce matrix interferences and obtain limits of quantification which were below 10 ng g⁻¹ for meat and liver samples. The regression between the analytical signal and the concentration of the target analytes in spiked samples and Certified Reference Materials proved to be linear within the 10-100 ng g⁻¹ range for meat and within the 50-500 ng g⁻¹ range for liver. The analytical method was verified using available Certified Reference Materials BCR-184 (cattle meat) and BCR-185R (cattle liver) as well as with spiked chicken samples. Precision (i.e. repeatability and intermediate precision) and accuracy (percentage recovery and bias) were of the order of 0.3-4.5% for both lead and cadmium The level of lead in muscle was in the range between 6.4 and 59.8 ng g⁻¹ in chickens and between 7.9 and 63.6 ng g⁻¹ in farmed pigeons, whereas it was between 8.0 and 84.4 ng g⁻¹ in chicken liver. The cadmium concentration was 0.4-10.4 ng g⁻¹ in chicken muscle, 10.4-90.6 ng g⁻¹ in chicken liver and 2.2-8.0 ng g⁻¹ in farmed pigeons.
New primer for specific amplification of the CAG repeat in Huntington disease alleles
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bond, C.E.; Hodes, M.E.
1994-09-01
Huntington disease is an autosomal dominant neurodegenerative disorder caused by an expansion of a CAG trinucleotide repeat near the 5{prime} end of the gene for Huntington disease (IT15). The CAG repeat is flanked by a variable-length CCG repeat that is included in the amplification product obtained with most currently used primer sets and PCR protocols. Inclusion of this adjacent CCG repeat complicates the accurate assessment of CAG repeat length and interferes with the genotype determination of those individuals carrying alleles in the intermediate range between normal and expanded sized. Due to the GC-rich nature of this region, attempts at designingmore » a protocol for amplification of only the CAG repeat have proved unreliable and difficult to execute. We report here the development of a compatible primer set and PCR protocol that yields consistent amplification of the CAG-repeat region. PCR products can be visualized in ethidium bromide-stained agarose gels for rapid screening or in 6% polyacrylamide gels for determination of exact repeat length. This assay produces bands that can be sized accurately, while eliminating most nonspecific products. Fifty-five specimens examined showed consistency with another well-known method, but one that amplifies the CCG repeats as well. The results we obtained also matched the known carrier status of the donors.« less
ISO/IEC 17025 Sysmex R-500 hematology reticulocyte analyzer validation.
Dimopoulou, H A; Theodoridis, T; Galea, V; Christopoulou-Cokkinou, V; Spyridaki, M-H E; Georgakopoulos, C G
2007-01-01
The Sysmex R-500 (R-500) Hematology Analyzer is a bench-top system appropriate for the analysis of limited batches of blood samples. The R-500 provides percentage proportional (RET%), absolute reticulocyte (RET#), and absolute red blood cell (RBC#) counts. The system was validated at the Doping Control Laboratory of Athens, according to the International Committee for Standardization in Hematology, International Standards Organization (ISO/IEC) 17025, and World Antidoping Agency (WADA) specifications. The instrument calibration was performed according to the manufacturer and validation parameters comprised linearity, precision, uncertainty (intermediate and long-term precision), comparability, effect of drift, carryover, stability, and accuracy. The linearity and the comparability studies for RET#, RET%, and RBC# were expressed in regression factors (R2) and coefficients of correlation [r(x, y)], respectively. For the precision studies, the coefficients of variation for RET#, RET%, and RBC# were 9.49%, 9.83%, and <1.5%, respectively. For the intermediate precision studies, the coefficients of variation for RET#, RET%, and RBC# were 3.1%, 3.6%, and 0.6%, respectively. Carryover was found to be negligible. Sample stability was demonstrated at both room temperature and at 4 degrees C over a 24-hour period. Comparability studies for the R-500 were performed using a Sysmex SE-9500. The total evaluation led to the conclusion that the R-500 is an accurate and precise analyzer and because of to its relatively limited size, it can be considered a portable instrument, capable to be used in sports competition and training sites, where doping control and health tests are conducted. The analytical methodology of RET% measurement by the R-500 has been incorporated into the Doping Control Laboratory of Athens' Scope of Accreditation according to the ISO/IEC 17025 and WADA specifications.
Repeatability and oblique flow response characteristics of current meters
Fulford, Janice M.; Thibodeaux, Kirk G.; Kaehrle, William R.; ,
1993-01-01
Laboratory investigation into the precision and accuracy of various mechanical-current meters are presented. Horizontal-axis and vertical-axis meters that are used for the measurement of point velocities in streams and rivers were tested. Meters were tested for repeatability and response to oblique flows. Both horizontal- and vertical-axis meters were found to under- and over-register oblique flows with errors generally increasing as the velocity and angle of flow increased. For the oblique flow tests, magnitude of errors were smallest for horizontal-axis meters. Repeatability of all meters tested was good, with the horizontal- and vertical-axis meters performing similarly.
Webb, Robert H.; Boyer, Diane E.; Turner, Raymond M.; Bullock, Stephen H.
2007-01-01
The Desert Laboratory Repeat Photography Collection, the largest collection of its kind in the world, is housed at the U.S. Geological Survey (USGS) in Tucson, Arizona. The collection preserves thousands of photos taken precisely in the same places but at different times. This archive of 'repeat photographs' documents changes in the desert landscape and vegetation of the American Southwest, and also includes images from northwestern Mexico and Kenya. These images are an invaluable asset to help understand the effects of climate variation and land-use practices on arid and semiarid environments.
The flight test of Pi-SAR(L) for the repeat-pass interferometric SAR
NASA Astrophysics Data System (ADS)
Nohmi, Hitoshi; Shimada, Masanobu; Miyawaki, Masanori
2006-09-01
This paper describes the experiment of the repeat pass interferometric SAR using Pi-SAR(L). The air-borne repeat-pass interferometric SAR is expected as an effective method to detect landslide or predict a volcano eruption. To obtain a high-quality interferometric image, it is necessary to make two flights on the same flight pass. In addition, since the antenna of the Pi-SAR(L) is secured to the aircraft, it is necessary to fly at the same drift angle to keep the observation direction same. We built a flight control system using an auto pilot which has been installed in the airplane. This navigation system measures position and altitude precisely with using a differential GPS, and the PC Navigator outputs a difference from the desired course to the auto pilot. Since the air density is thinner and the speed is higher than the landing situation, the gain of the control system is required to be adjusted during the repeat pass flight. The observation direction could be controlled to some extent by adjusting a drift angle with using a flight speed control. The repeat-pass flight was conducted in Japan for three days in late November. The flight was stable and the deviation was within a few meters for both horizontal and vertical direction even in the gusty condition. The SAR data were processed in time domain based on range Doppler algorism to make the complete motion compensation. Thus, the interferometric image processed after precise phase compensation is shown.
Precision linear ramp function generator
Jatko, W.B.; McNeilly, D.R.; Thacker, L.H.
1984-08-01
A ramp function generator is provided which produces a precise linear ramp function which is repeatable and highly stable. A derivative feedback loop is used to stabilize the output of an integrator in the forward loop and control the ramp rate. The ramp may be started from a selected baseline voltage level and the desired ramp rate is selected by applying an appropriate constant voltage to the input of the integrator.
Precision linear ramp function generator
Jatko, W. Bruce; McNeilly, David R.; Thacker, Louis H.
1986-01-01
A ramp function generator is provided which produces a precise linear ramp unction which is repeatable and highly stable. A derivative feedback loop is used to stabilize the output of an integrator in the forward loop and control the ramp rate. The ramp may be started from a selected baseline voltage level and the desired ramp rate is selected by applying an appropriate constant voltage to the input of the integrator.
Low-cost precision rotary index calibration
NASA Astrophysics Data System (ADS)
Ng, T. W.; Lim, T. S.
2005-08-01
The traditional method for calibrating angular indexing repeatability of rotary axes on machine tools and measuring equipment is with a precision polygon (usually 12 sided) and an autocollimator or angular interferometer. Such a setup is typically expensive. Here, we propose a far more cost-effective approach that uses just a laser, diffractive optical element, and CCD camera. We show that significantly high accuracies can be achieved for angular index calibration.
Artacho, Paulina; Jouanneau, Isabelle; Le Galliard, Jean-François
2013-01-01
Studies of the relationship of performance and behavioral traits with environmental factors have tended to neglect interindividual variation even though quantification of this variation is fundamental to understanding how phenotypic traits can evolve. In ectotherms, functional integration of locomotor performance, thermal behavior, and energy metabolism is of special interest because of the potential for coadaptation among these traits. For this reason, we analyzed interindividual variation, covariation, and repeatability of the thermal sensitivity of maximal sprint speed, preferred body temperature, thermal precision, and resting metabolic rate measured in ca. 200 common lizards (Zootoca vivipara) that varied by sex, age, and body size. We found significant interindividual variation in selected body temperatures and in the thermal performance curve of maximal sprint speed for both the intercept (expected trait value at the average temperature) and the slope (measure of thermal sensitivity). Interindividual differences in maximal sprint speed across temperatures, preferred body temperature, and thermal precision were significantly repeatable. A positive relationship existed between preferred body temperature and thermal precision, implying that individuals selecting higher temperatures were more precise. The resting metabolic rate was highly variable but was not related to thermal sensitivity of maximal sprint speed or thermal behavior. Thus, locomotor performance, thermal behavior, and energy metabolism were not directly functionally linked in the common lizard.
Evaluation of the precision of contrast sensitivity function assessment on a tablet device
Dorr, Michael; Lesmes, Luis A.; Elze, Tobias; Wang, Hui; Lu, Zhong-Lin; Bex, Peter J.
2017-01-01
The contrast sensitivity function (CSF) relates the visibility of a spatial pattern to both its size and contrast, and is therefore a more comprehensive assessment of visual function than acuity, which only determines the smallest resolvable pattern size. Because of the additional dimension of contrast, estimating the CSF can be more time-consuming. Here, we compare two methods for rapid assessment of the CSF that were implemented on a tablet device. For a single-trial assessment, we asked 63 myopes and 38 emmetropes to tap the peak of a “sweep grating” on the tablet’s touch screen. For a more precise assessment, subjects performed 50 trials of the quick CSF method in a 10-AFC letter recognition task. Tests were performed with and without optical correction, and in monocular and binocular conditions; one condition was measured twice to assess repeatability. Results show that both methods are highly correlated; using both common and novel measures for test-retest repeatability, however, the quick CSF delivers more precision with testing times of under three minutes. Further analyses show how a population prior can improve convergence rate of the quick CSF, and how the multi-dimensional output of the quick CSF can provide greater precision than scalar outcome measures. PMID:28429773
Source Analysis of Bucaramanga Nest Intermediate-Depth Earthquakes
NASA Astrophysics Data System (ADS)
Prieto, G. A.; Pedraza, P.; Dionicio, V.; Levander, A.
2016-12-01
Intermediate-depth earthquakes are those that occur at depths of 50 to 300 km in subducting lithosphere and can occasionally be destructive. Despite their ubiquity in earthquake catalogs, their physical mechanism remains unclear because ambient temperatures and pressures at such depths are expected to lead to ductile flow, rather than brittle failure, as a response to stress. Intermediate-depth seismicity rates vary substantially worldwide, even within a single subduction zone having highly clustered seismicity in some cases (Vrancea, Hindu-Kush, etc.). One such places in known as the Bucaramanga Nest (BN), one of the highest concentration of intermediate-depth earthquakes in the world. Previous work on these earthquakes has shown 1) Focal mechanisms vary substantially within a very small volume. 2) Radiation efficiency is small for M<5 events. 3) repeating and reverse polarity events are present. 4) Larger events show a complex behavior with two distinct rupture stages. Due to on-going efforts by the Colombian Geological Survey (SGC) to densify the national seismic network, it is now possible to better constrain the rupture behavior of these events. In our work we will present results from focal mechanisms based on waveform inversion as well as polarity and S/P amplitude ratios. These results will be contrasted to the detection and classification of repeating families. For the larger events we will determine source parameters and radiation efficiencies. Preliminary results show that reverse polarity events are present and that two main focal mechanisms, with their corresponding reverse polarity events are dominant. Our results have significant implications in our understanding of intermedaite-depth earthquakes and the stress conditions that are responsible for this unusual cluster of seismicity.
De, Debojyoti; Dutta, Debajyoti; Kundu, Moloy; Mahato, Sourav; Schiavone, Marc T; Chaudhuri, Surabhi; Giri, Ashok; Gupta, Vidya; Bhattacharya, Sanjoy K
2005-01-01
Background Carbon dioxide fixation bioprocess in reactors necessitates recycling of D-ribulose1,5-bisphosphate (RuBP) for continuous operation. A radically new close loop of RuBP regenerating reactor design has been proposed that will harbor enzyme-complexes instead of purified enzymes. These reactors will need binders enabling selective capture and release of sugar and intermediate metabolites enabling specific conversions during regeneration. In the current manuscript we describe properties of proteins that will act as potential binders in RuBP regeneration reactors. Results We demonstrate specific binding of 3-phosphoglycerate (3PGA) and 3-phosphoglyceraldehyde (3PGAL) from sugar mixtures by inactive mutant of yeast enzymes phosphoglycerate mutase and enolase. The reversibility in binding with respect to pH and EDTA has also been shown. No chemical conversion of incubated sugars or sugar intermediate metabolites were found by the inactive enzymatic proteins. The dissociation constants for sugar metabolites are in the micromolar range, both proteins showed lower dissociation constant (Kd) for 3-phosphoglycerate (655–796 μM) compared to 3-phosphoglyceraldehyde (822–966 μM) indicating higher affinity for 3PGA. The proteins did not show binding to glucose, sucrose or fructose within the sensitivity limits of detection. Phosphoglycerate mutase showed slightly lower stability on repeated use than enolase mutants. Conclusions The sugar and their intermediate metabolite binders may have a useful role in RuBP regeneration reactors. The reversibility of binding with respect to changes in physicochemical factors and stability when subjected to repeated changes in these conditions are expected to make the mutant proteins candidates for in-situ removal of sugar intermediate metabolites for forward driving of specific reactions in enzyme-complex reactors. PMID:15689239
NASA Technical Reports Server (NTRS)
Potter, D. W.
1985-01-01
High time resolution particle data upstream of the bow shock during time intervals that have been identified as having intermediate ion distributions often show high amplitude oscillations in the ion fluxes of energy 2 and 6 keV. These ion oscillations, observed with the particle instruments of the University of California, Berkeley, on the ISEE 1 and 2 spacecraft, are at the same frequency (about 0.04 Hz) as the magnetic field oscillations. Typically, the 6-keV ion flux increases then the 2-keV flux increases followed by a decrease in the 2-keV flux and then the 6-keV flux decreases. This process repeats many times. Although there is no entirely satisfactory explanation, the presence of these ion flux oscillations suggests that distributions often are misidentified as intermediate ion distributions.
Time code dissemination experiment via the SIRIO-1 VHF transponder
NASA Technical Reports Server (NTRS)
Detoma, E.; Gobbo, G.; Leschiutta, S.; Pettiti, V.
1982-01-01
An experiment to evaluate the possibility of disseminating a time code via the SIRIO-1 satellite, by using the onboard VHF repeater is described. The precision in the synchronization of remote clocks was expected to be of the order of 0.1 to 1 ms. The RF carrier was in the VHF band, so that low cost receivers could be used and then a broader class of users could be served. An already existing repeater, even if not designed specifically for communications could be utilized; the operation of this repeater was not intended to affect any other function of the spacecraft (both the SHF repeater and the VHF telemetry link were active during the time code dissemination via the VHF transponder).
Mechanical unfolding of an ankyrin repeat protein.
Serquera, David; Lee, Whasil; Settanni, Giovanni; Marszalek, Piotr E; Paci, Emanuele; Itzhaki, Laura S
2010-04-07
Ankryin repeat proteins comprise tandem arrays of a 33-residue, predominantly alpha-helical motif that stacks roughly linearly to produce elongated and superhelical structures. They function as scaffolds mediating a diverse range of protein-protein interactions, and some have been proposed to play a role in mechanical signal transduction processes in the cell. Here we use atomic force microscopy and molecular-dynamics simulations to investigate the natural 7-ankyrin repeat protein gankyrin. We find that gankyrin unfolds under force via multiple distinct pathways. The reactions do not proceed in a cooperative manner, nor do they always involve fully stepwise unfolding of one repeat at a time. The peeling away of half an ankyrin repeat, or one or more ankyrin repeats, occurs at low forces; however, intermediate species are formed that are resistant to high forces, and the simulations indicate that in some instances they are stabilized by nonnative interactions. The unfolding of individual ankyrin repeats generates a refolding force, a feature that may be more easily detected in these proteins than in globular proteins because the refolding of a repeat involves a short contraction distance and incurs a low entropic cost. We discuss the origins of the differences between the force- and chemical-induced unfolding pathways of ankyrin repeat proteins, as well as the differences between the mechanics of natural occurring ankyrin repeat proteins and those of designed consensus ankyin repeat and globular proteins. Copyright (c) 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.
Liu, Jen-Pei; Lu, Li-Tien; Liao, C T
2009-09-01
Intermediate precision is one of the most important characteristics for evaluation of precision in assay validation. The current methods for evaluation of within-device precision recommended by the Clinical Laboratory Standard Institute (CLSI) guideline EP5-A2 are based on the point estimator. On the other hand, in addition to point estimators, confidence intervals can provide a range for the within-device precision with a probability statement. Therefore, we suggest a confidence interval approach for assessment of the within-device precision. Furthermore, under the two-stage nested random-effects model recommended by the approved CLSI guideline EP5-A2, in addition to the current Satterthwaite's approximation and the modified large sample (MLS) methods, we apply the technique of generalized pivotal quantities (GPQ) to derive the confidence interval for the within-device precision. The data from the approved CLSI guideline EP5-A2 illustrate the applications of the confidence interval approach and comparison of results between the three methods. Results of a simulation study on the coverage probability and expected length of the three methods are reported. The proposed method of the GPQ-based confidence intervals is also extended to consider the between-laboratories variation for precision assessment.
Productive Nanosystems: The Physics of Molecular Fabrication
ERIC Educational Resources Information Center
Drexler, K. Eric
2005-01-01
Fabrication techniques are the foundation of physical technology, and are thus of fundamental interest. Physical principles indicate that nanoscale systems will be able to fabricate a wide range of structures, operating with high productivity and precise molecular control. Advanced systems of this kind will require intermediate generations of…
Xu, Zhe; Peng, Mei; Jiang, Jun; Yang, Chun; Zhu, Weigen; Lu, Fan; Shen, Meixiao
2016-02-01
To measure the repeatability and reproducibility of Pentacam HR system thickness maps for the entire cornea in normal, post-laser in situ keratomileusis (post-LASIK), and keratoconus (KC) eyes. Reliability study. Sixty normal subjects (60 eyes), 30 post-LASIK subjects (60 eyes), and 14 KC patients (27 eyes) were imaged with the Pentacam HR system by 2 well-trained operators. For pachymetry the cornea was divided into 4 zones: a central zone (2-mm diameter) and concentric pericentral zone (2-5 mm), transitional zone (5-7 mm), and peripheral zone (7-10 mm). The 3 concentric zones were subdivided into 8 sectors. Intraobserver repeatability and interobserver reproducibility of entire corneal thickness maps were tested by the repeatability and reproducibility coefficients, intraclass correlation coefficients, coefficient of variation, and 95% limits of agreement. From central to peripheral zones, the precision of corneal thickness measurements became gradually smaller. Central zone repeatability and reproducibility were the best in the normal, post-LASIK, and KC groups. The peripheral superior sectors showed poorer repeatability and reproducibility for all subjects. The intraobserver repeatability and interobserver reproducibility for all zones were ≤19.3 μm, ≤22.1 μm, and ≤20.7 μm, in the normal, post-LASIK, and KC groups, respectively. The intraobserver and interobserver coefficients of variation for all zones were ≤1.3%, ≤1.6%, and ≤1.6% for all 3 groups. Pentacam HR system pachymetry of the entire cornea provided good precision in normal, post-LASIK, and KC corneas. Thickness measurements in the peripheral cornea should be interpreted with caution in abnormal corneas after surgery or with diseases. Copyright © 2016 Elsevier Inc. All rights reserved.
PolyQ repeat expansions in ATXN2 associated with ALS are CAA interrupted repeats.
Yu, Zhenming; Zhu, Yongqing; Chen-Plotkin, Alice S; Clay-Falcone, Dana; McCluskey, Leo; Elman, Lauren; Kalb, Robert G; Trojanowski, John Q; Lee, Virginia M-Y; Van Deerlin, Vivianna M; Gitler, Aaron D; Bonini, Nancy M
2011-03-29
Amyotrophic lateral sclerosis (ALS) is a devastating, rapidly progressive disease leading to paralysis and death. Recently, intermediate length polyglutamine (polyQ) repeats of 27-33 in ATAXIN-2 (ATXN2), encoding the ATXN2 protein, were found to increase risk for ALS. In ATXN2, polyQ expansions of ≥ 34, which are pure CAG repeat expansions, cause spinocerebellar ataxia type 2. However, similar length expansions that are interrupted with other codons, can present atypically with parkinsonism, suggesting that configuration of the repeat sequence plays an important role in disease manifestation in ATXN2 polyQ expansion diseases. Here we determined whether the expansions in ATXN2 associated with ALS were pure or interrupted CAG repeats, and defined single nucleotide polymorphisms (SNPs) rs695871 and rs695872 in exon 1 of the gene, to assess haplotype association. We found that the expanded repeat alleles of 40 ALS patients and 9 long-repeat length controls were all interrupted, bearing 1-3 CAA codons within the CAG repeat. 21/21 expanded ALS chromosomes with 3CAA interruptions arose from one haplotype (GT), while 18/19 expanded ALS chromosomes with <3CAA interruptions arose from a different haplotype (CC). Moreover, age of disease onset was significantly earlier in patients bearing 3 interruptions vs fewer, and was distinct between haplotypes. These results indicate that CAG repeat expansions in ATXN2 associated with ALS are uniformly interrupted repeats and that the nature of the repeat sequence and haplotype, as well as length of polyQ repeat, may play a role in the neurological effect conferred by expansions in ATXN2.
Modifying a numerical algorithm for solving the matrix equation X + AX T B = C
NASA Astrophysics Data System (ADS)
Vorontsov, Yu. O.
2013-06-01
Certain modifications are proposed for a numerical algorithm solving the matrix equation X + AX T B = C. By keeping the intermediate results in storage and repeatedly using them, it is possible to reduce the total complexity of the algorithm from O( n 4) to O( n 3) arithmetic operations.
The Effects of Computer Assisted Mediating Prompts on EFL Learners' Writing Ability
ERIC Educational Resources Information Center
Damavandi, Zahra Mousazadeh; Hassaskhah, Jaleh; Zafarghandi, Amir Mahdavi
2018-01-01
This study aims to examine the EFL learners' perception and process of writing development through using a digital storytelling tool, called "Storyjumper." To do so, 15 intermediate-level students were participants of the study. The participants' writing development was frequently assessed through a series of repeated writing tests…
Liu, Aifeng; Shen, Zhaoshuang; Tian, Yong; Shi, Rongguang; Liu, Yi; Zhao, Zongshan; Xian, Mo
2017-12-01
As brominated flame retardants (BFRs), tetrabromobisphenol A/S (TBBPA/S) and their derivatives have raised wide concerns owing to their widely usage, distributions and adverse effects on human health, thus monitoring these BFRs was urgently needed. In this study, a rapid and cost-effective method based on thin-layer chromatography (TLC) sample pre-treatment coupled with high performance liquid chromatography-diode array detector (HPLC-DAD) (UV=214nm) was developed for determining TBBPA/S and their derivatives in soils, including TBBPA, TBBPA bis(allyl ether) (TBBPA-BAE), TBBPA bis(2,3-dibromopropyl ether) (TBBPA-BDBPE), TBBPS bis(allyl ether) (TBBPS-BAE) and TBBPS bis(2,3-dibromopropyl ether) (TBBPS-BDBPE). The method detection limits (MDLs) and the method quantification limits (MQLs) for these BFRs ranged from 0.023 to 0.087μgg -1 dw and 0.076-0.29μgg -1 dw, respectively. The recoveries were 41-108% and both RSD of repeatability and intermediate precision were less than 11%. The developed method presented good performance for analyzing natural soil samples collected from BFRs industrial park, suggesting its great application potential for monitoring environmental TBBPA/S and their derivatives. Copyright © 2017 Elsevier B.V. All rights reserved.
Subunit mass analysis for monitoring antibody oxidation.
Sokolowska, Izabela; Mo, Jingjie; Dong, Jia; Lewis, Michael J; Hu, Ping
2017-04-01
Methionine oxidation is a common posttranslational modification (PTM) of monoclonal antibodies (mAbs). Oxidation can reduce the in-vivo half-life, efficacy and stability of the product. Peptide mapping is commonly used to monitor the levels of oxidation, but this is a relatively time-consuming method. A high-throughput, automated subunit mass analysis method was developed to monitor antibody methionine oxidation. In this method, samples were treated with IdeS, EndoS and dithiothreitol to generate three individual IgG subunits (light chain, Fd' and single chain Fc). These subunits were analyzed by reversed phase-ultra performance liquid chromatography coupled with an online quadrupole time-of-flight mass spectrometer and the levels of oxidation on each subunit were quantitated based on the deconvoluted mass spectra using the UNIFI software. The oxidation results obtained by subunit mass analysis correlated well with the results obtained by peptide mapping. Method qualification demonstrated that this subunit method had excellent repeatability and intermediate precision. In addition, UNIFI software used in this application allows automated data acquisition and processing, which makes this method suitable for high-throughput process monitoring and product characterization. Finally, subunit mass analysis revealed the different patterns of Fc methionine oxidation induced by chemical and photo stress, which makes it attractive for investigating the root cause of oxidation.
Kpaibe, André P S; Ben-Ameur, Randa; Coussot, Gaëlle; Ladner, Yoann; Montels, Jérôme; Ake, Michèle; Perrin, Catherine
2017-08-01
Snake venoms constitute a very promising resource for the development of new medicines. They are mainly composed of very complex peptide and protein mixtures, which composition may vary significantly from batch to batch. This latter consideration is a challenge for routine quality control (QC) in the pharmaceutical industry. In this paper, we report the use of capillary zone electrophoresis for the development of an analytical fingerprint methodology to assess the quality of snake venoms. The analytical fingerprint concept is being widely used for the QC of herbal drugs but rarely for venoms QC so far. CZE was chosen for its intrinsic efficiency in the separation of protein and peptide mixtures. The analytical fingerprint methodology was first developed and evaluated for a particular snake venom, Lachesis muta. Optimal analysis conditions required the use of PDADMAC capillary coating to avoid protein and peptide adsorption. Same analytical conditions were then applied to other snake venom species. Different electrophoretic profiles were obtained for each venom. Excellent repeatability and intermediate precision was observed for each batch. Analysis of different batches of the same species revealed inherent qualitative and quantitative composition variations of the venoms between individuals. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Multilocus Variable-Number Tandem Repeat Typing of Mycobacterium ulcerans
Ablordey, Anthony; Swings, Jean; Hubans, Christine; Chemlal, Karim; Locht, Camille; Portaels, Françoise; Supply, Philip
2005-01-01
The apparent genetic homogeneity of Mycobacterium ulcerans contributes to the poorly understood epidemiology of M. ulcerans infection. Here, we report the identification of variable number tandem repeat (VNTR) sequences as novel polymorphic elements in the genome of this species. A total of 19 potential VNTR loci identified in the closely related M. marinum genome sequence were screened in a collection of 23 M. ulcerans isolates, one Mycobacterium species referred to here as an intermediate species, and five M. marinum strains. Nine of the 19 loci were polymorphic in the three species (including the intermediate species) and revealed eight M. ulcerans and five M. marinum genotypes. The results from the VNTR analysis corroborated the genetic relationships of M. ulcerans isolates from various geographical origins, as defined by independent molecular markers. Although these results further highlight the extremely high clonal homogeneity within certain geographic regions, we report for the first time the discrimination of the two South American strains from Surinam and French Guyana. These findings support the potential of a VNTR-based genotyping method for strain discrimination within M. ulcerans and M. marinum. PMID:15814964
Distribution and Characteristics of Repeating Earthquakes in Northern California
NASA Astrophysics Data System (ADS)
Waldhauser, F.; Schaff, D. P.; Zechar, J. D.; Shaw, B. E.
2012-12-01
Repeating earthquakes are playing an increasingly important role in the study of fault processes and behavior, and have the potential to improve hazard assessment, earthquake forecast, and seismic monitoring capabilities. These events rupture the same fault patch repeatedly, generating virtually identical seismograms. In California, repeating earthquakes have been found predominately along the creeping section of the central San Andreas Fault, where they are believed to represent failing asperities on an otherwise creeping fault. Here, we use the northern California double-difference catalog of 450,000 precisely located events (1984-2009) and associated database of 2 billion waveform cross-correlation measurements to systematically search for repeating earthquakes across various tectonic regions. An initial search for pairs of earthquakes with high-correlation coefficients and similar magnitudes resulted in 4,610 clusters including a total of over 26,000 earthquakes. A subsequent double-difference re-analysis of these clusters resulted in 1,879 sequences (8,640 events) where a common rupture area can be resolved to the precision of a few tens of meters or less. These repeating earthquake sequences (RES) include between 3 and 24 events with magnitudes up to ML=4. We compute precise relative magnitudes between events in each sequence from differential amplitude measurements. Differences between these and standard coda-duration magnitudes have a standard deviation of 0.09. The RES occur throughout northern California, but RES with 10 or more events (6%) only occur along the central San Andreas and Calaveras faults. We are establishing baseline characteristics for each sequence, such as recurrence intervals and their coefficient of variation (CV), in order to compare them across tectonic regions. CVs for these clusters range from 0.002 to 2.6, indicating a range of behavior between periodic occurrence (CV~0), random occurrence, and temporal clustering. 10% of the RES show burst-like behavior with mean recurrence times smaller than one month. 5% of the RES have mean recurrence times greater than one year and include more than 10 earthquakes. Earthquakes in the 50 most periodic sequences (CV<0.2) do not appear to be predictable by either time- or slip-predictable models, consistent with previous findings. We demonstrate that changes in recurrence intervals of repeating earthquakes can be routinely monitored. This is especially important for sequences with CV~0, as they may indicate changes in the loading rate. We also present results from retrospective forecast experiments based on near-real time hazard functions.
Thomas, Freddy; Jamin, Eric
2009-09-01
An international collaborative study of isotopic methods applied to control the authenticity of vinegar was organized in order to support the recognition of these procedures as official methods. The determination of the 2H/1H ratio of the methyl site of acetic acid by SNIF-NMR (site-specific natural isotopic fractionation-nuclear magnetic resonance) and the determination of the 13C/12C ratio, by IRMS (isotope ratio mass spectrometry) provide complementary information to characterize the botanical origin of acetic acid and to detect adulterations of vinegar using synthetic acetic acid. Both methods use the same initial steps to recover pure acetic acid from vinegar. In the case of wine vinegar, the determination of the 18O/16O ratio of water by IRMS allows to differentiate wine vinegar from vinegars made from dried grapes. The same set of vinegar samples was used to validate these three determinations. The precision parameters of the method for measuring delta13C (carbon isotopic deviation) were found to be similar to the values previously obtained for similar methods applied to wine ethanol or sugars extracted from fruit juices: the average repeatability (r) was 0.45 per thousand, and the average reproducibility (R) was 0.91 per thousand. As expected from previous in-house study of the uncertainties, the precision parameters of the method for measuring the 2H/1H ratio of the methyl site were found to be slightly higher than the values previously obtained for similar methods applied to wine ethanol or fermentation ethanol in fruit juices: the average repeatability was 1.34 ppm, and the average reproducibility was 1.62 ppm. This precision is still significantly smaller than the differences between various acetic acid sources (delta13C and delta18O) and allows a satisfactory discrimination of vinegar types. The precision parameters of the method for measuring delta18O were found to be similar to the values previously obtained for other methods applied to wine and fruit juices: the average repeatability was 0.15 per thousand, and the average reproducibility was 0.59 per thousand. The above values are proposed as repeatability and reproducibility limits in the current state of the art. On the basis of this satisfactory inter-laboratory precision and on the accuracy demonstrated by a spiking experiment, the authors recommend the adoption of the three isotopic determinations included in this study as official methods for controlling the authenticity of vinegar.
Feehan, Lynne; Buie, Helen; Li, Linda; McKay, Heather
2013-12-24
High Resolution-Peripheral Quantitative Computed Tomography (HR-pQCT) is an emerging technology for evaluation of bone quality in Rheumatoid Arthritis (RA). However, there are limitations with standard HR-pQCT imaging protocols for examination of regions of bone commonly affected in RA. We developed a customized protocol for evaluation of volumetric bone mineral density (vBMD) and microstructure at the metacarpal head (MH), metacarpal shaft (MS) and ultra-ultra-distal (UUD) radius; three sites commonly affected in RA. The purpose was to evaluate short-term measurement precision for bone density and microstructure at these sites. 12 non-RA participants, individuals likely to have no pre-existing bone damage, consented to participate [8 females, aged 23 to 71 y [median (IQR): 44 (28) y]. The custom protocol includes more comfortable/stable positioning and adapted cortical segmentation and direct transformation analysis methods. Dominant arm MH, MS and UUD radius scans were completed on day one; repeated twice (with repositioning) three to seven days later. Short-term precision for repeated measures was explored using intraclass correlational coefficient (ICC), mean coefficient of variation (CV%), root mean square coefficient of variation (RMSCV%) and least significant change (LSC%95). Bone density and microstructure precision was excellent: ICCs varied from 0.88 (MH2 trabecular number) to .99 (MS3 polar moment of inertia); CV% varied from < 1 (MS2 vBMD) to 6 (MS3 marrow space diameter); RMSCV% varied from < 1 (MH2 full bone vBMD) to 7 (MS3 marrow space diameter); and LSC%95 varied from 2 (MS2 full bone vBMD to 21 (MS3 marrow space diameter). Cortical porosity measures were the exception; RMSCV% varying from 19 (MS3) to 42 (UUD). No scans were stopped for discomfort. 5% (5/104) were repeated due to motion during imaging. 8% (8/104) of final images had motion artifact graded > 3 on 5 point scale. In our facility, this custom protocol extends the potential for in vivo HR-pQCT imaging to assess, with high precision, regional differences in bone quality at three sites commonly affected in RA. Our methods are easy to adopt and we recommend other users of HR-pQCT consider this protocol for further evaluations of its precision and feasibility in their imaging facilities.
Nishimura, Chiaki; Dyson, H. Jane; Wright, Peter E.
2005-01-01
Hydrogen/deuterium exchange followed by trapping of the labeled species in the aprotic solvent DMSO has been used to elucidate structure in both the burst-phase molten globule-folding intermediate of apomyoglobin and in an equilibrium intermediate that models the kinetic intermediate. Precise estimates can be made of exchange times in an interrupted exchange-out experiment at pH 4 followed by analysis in DMSO solution, giving extensive sequence-specific information about the structure of the equilibrium intermediate. In addition, the use of DMSO as a solvent for NMR measurements after quench-flow pH-pulse labeling experiments gives a greatly increased data set for the elucidation of the kinetic folding pathway. Interestingly, differences are observed in some regions of apomyoglobin between the equilibrium and kinetic intermediates. These differences are quantitative rather than qualitative; that is, the overall patterns of labeling and secondary structure formation remain similar between the two species. However, local differences are observed, which probably reflect the difference in the solution conditions for the equilibrium experiment (pH 4) vs. the kinetic experiment (pH 6) and the change in the status of the stabilizing hydrogen bond between the side chains of His-24 and His-119. PMID:15769860
NASA Astrophysics Data System (ADS)
Besutiu, Lucian; Zlagnean, Luminita
2015-04-01
Background Located in the bending zone of East Carpathians, the so-called Vrancea zone is one of the most active seismic regions in Europe. Despite many years of international research, its intermediate-depth seismicity within full intra-continental environment still represents a challenge of the 21st century. Infrastructure In the attempt to join the above-mentioned efforts, the Solid Earth Dynamics Department (SEDD) in the Institute of Geodynamics of the Romanian Academy has developed a special research infrastructure, mainly devoted to gravity and space geodesy observations. A geodetic network covering the epicentre area of the intermediate-depth earthquakes has been designed and implemented for monitoring deep geodynamic processes and their surface echoes. Within each base-station of the above-mentioned network, a still-reinforced concrete pillar allows for high accuracy repeated gravity and GPS determinations. Results Starting from some results of the previously run CERGOP and UNIGRACE European programmes, to which additional SEDD repeated field campaigns were added, an unusual geodynamic behaviour has been revealed in the area. 1) Crust deformation: unlike the overall uprising of East Carpathians, as a result of denudation followed by erosion, their SE bending zone, with Vrancea epicentre area exhibits a slight subsidence. 2) Gravity change: more than 200 microgals non-tidal gravity decrease over a 20 years time-span has been noticed within the subsiding area. Extended observations showed the gravity lowering as a nowadays continuing process. Interpretation This strange combination of topography subsidence and gravity lowering has been interpreted in terms of crust stretching in the Vrancea epicentre zone due to the gravity pull created by densification of the lower crust as a result of phase-transform processes taking place in the lithospheric compartment sunken into the upper mantle. The occurrence of crust earthquakes with vertical-extension focal mechanism exclusively in the Vrancea seismic zone support the assumption. Recent studies on the Vrancea echoes of 2013 Galati-Izvoarele quake swarm have also confirmed our hypotheses. Based on numerical modelling of the geodynamic process, an estimate of the stretching rate has been obtained, fully consistent with results inferred from studies on the seismic energy released by the Vrancea intermediate earthquakes. Concluding remarks Looking further, the sinking of the Vrancea lithosphere into the upper mantle (and consequent crust stretching, appropriately reflected in the non-tidal gravity change) appears as an ongoing geodynamic process, tightly connected to the intermediate-depth seismicity generated within the lithosphere penetrating the upper mantle by thermo-baric accommodation phenomena. Time series provided by repeated gravity observations conducted on the above-mentioned infrastructure for about ten years have clearly revealed: (i) the persistence of the gravity lowering, and (ii) some apparent connection between the rate of the gravity change, and the amount of seismic energy released by intermediate-depth earthquakes. Acknowledgements. The research has been partly performed through CYBERDYNE project, funded through the EU structural programme (contract #184/2010).
Hills, Ronald D.; Kathuria, Sagar V.; Wallace, Louise A.; Day, Iain J.; Brooks, Charles L.; Matthews, C. Robert
2010-01-01
The thermodynamic hypothesis of Anfinsen postulates that structures and stabilities of globular proteins are determined by their amino acid sequences. Chain topology, however, is known to influence the folding reaction, in that motifs with a preponderance of local interactions typically fold more rapidly than those with a larger fraction of non-local interactions. Together, the topology and sequence can modulate the energy landscape and influence the rate at which the protein folds to the native conformation. To explore the relationship of sequence and topology in the folding of βα–repeat proteins, which are dominated by local interactions, a combined experimental and simulation analysis was performed on two members of the flavodoxin-like, α/β/α sandwich fold. Spo0F and the N-terminal receiver domain of NtrC (NT-NtrC) have similar topologies but low sequence identity, enabling a test of the effects of sequence on folding. Experimental results demonstrated that both response-regulator proteins fold via parallel channels through highly structured sub-millisecond intermediates before accessing their cis prolyl peptide bond-containing native conformations. Global analysis of the experimental results preferentially places these intermediates off the productive folding pathway. Sequence-sensitive Gō-model simulations conclude that frustration in the folding in Spo0F, corresponding to the appearance of the off-pathway intermediate, reflects competition for intra-subdomain van der Waals contacts between its N- and C-terminal subdomains. The extent of transient, premature structure appears to correlate with the number of isoleucine, leucine and valine (ILV) side-chains that form a large sequence-local cluster involving the central β-sheet and helices α2, α3 and α4. The failure to detect the off-pathway species in the simulations of NT-NtrC may reflect the reduced number of ILV side-chains in its corresponding hydrophobic cluster. The location of the hydrophobic clusters in the structure may also be related to the differing functional properties of these response regulators. Comparison with the results of previous experimental and simulation analyses on the homologous CheY argues that prematurely-folded unproductive intermediates are a common property of the βα-repeat motif. PMID:20226790
Establishment of National Gravity Base Network of Iran
NASA Astrophysics Data System (ADS)
Hatam Chavari, Y.; Bayer, R.; Hinderer, J.; Ghazavi, K.; Sedighi, M.; Luck, B.; Djamour, Y.; Le Moign, N.; Saadat, R.; Cheraghi, H.
2009-04-01
A gravity base network is supposed to be a set of benchmarks uniformly distributed across the country and the absolute gravity values at the benchmarks are known to the best accessible accuracy. The gravity at the benchmark stations are either measured directly with absolute devices or transferred by gravity difference measurements by gravimeters from known stations. To decrease the accumulation of random measuring errors arising from these transfers, the number of base stations distributed across the country should be as small as possible. This is feasible if the stations are selected near to the national airports long distances apart but faster accessible and measurable by a gravimeter carried in an airplane between the stations. To realize the importance of such a network, various applications of a gravity base network are firstly reviewed. A gravity base network is the required reference frame for establishing 1st , 2nd and 3rd order gravity networks. Such a gravity network is used for the following purposes: a. Mapping of the structure of upper crust in geology maps. The required accuracy for the measured gravity values is about 0.2 to 0.4 mGal. b. Oil and mineral explorations. The required accuracy for the measured gravity values is about 5 µGal. c. Geotechnical studies in mining areas for exploring the underground cavities as well as archeological studies. The required accuracy is about 5 µGal and better. d. Subsurface water resource explorations and mapping crustal layers which absorb it. An accuracy of the same level of previous applications is required here too. e. Studying the tectonics of the Earth's crust. Repeated precise gravity measurements at the gravity network stations can assist us in identifying systematic height changes. The accuracy of the order of 5 µGal and more is required. f. Studying volcanoes and their evolution. Repeated precise gravity measurements at the gravity network stations can provide valuable information on the gradual upward movement of lava. g. Producing precise mean gravity anomaly for precise geoid determination. Replacing precise spirit leveling by the GPS leveling using precise geoid model is one of the forth coming application of the precise geoid. A gravity base network of 28 stations established over Iran. The stations were built mainly at bedrocks. All stations were measured by an FG5 absolute gravimeter, at least 12 hours at each station, to obtain an accuracy of a few micro gals. Several stations were repeated several times during recent years to estimate the gravity changes.
Fong, Erika J.; Huang, Chao; Hamilton, Julie; ...
2015-11-23
Here, a major advantage of microfluidic devices is the ability to manipulate small sample volumes, thus reducing reagent waste and preserving precious sample. However, to achieve robust sample manipulation it is necessary to address device integration with the macroscale environment. To realize repeatable, sensitive particle separation with microfluidic devices, this protocol presents a complete automated and integrated microfluidic platform that enables precise processing of 0.15–1.5 ml samples using microfluidic devices. Important aspects of this system include modular device layout and robust fixtures resulting in reliable and flexible world to chip connections, and fully-automated fluid handling which accomplishes closed-loop sample collection,more » system cleaning and priming steps to ensure repeatable operation. Different microfluidic devices can be used interchangeably with this architecture. Here we incorporate an acoustofluidic device, detail its characterization, performance optimization, and demonstrate its use for size-separation of biological samples. By using real-time feedback during separation experiments, sample collection is optimized to conserve and concentrate sample. Although requiring the integration of multiple pieces of equipment, advantages of this architecture include the ability to process unknown samples with no additional system optimization, ease of device replacement, and precise, robust sample processing.« less
Underlying Changes in Repeated Reading: An Eye Movement Study
ERIC Educational Resources Information Center
Foster, Tori E.; Ardoin, Scott P.; Binder, Katherine S.
2013-01-01
conclusive evidence as to the mechanisms through which RR takes effect. Eye movement studies allow for precise examination of intervention effects. The current study examined underlying changes in elementary students' ("N" = 43) reading behavior…
Precise small molecule recognition of a toxic CUG RNA repeat expansion
Rzuczek, Suzanne G; Colgan, Lesley A; Nakai, Yoshio; Cameron, Michael D; Furling, Denis; Yasuda, Ryohei; Disney, Matthew D
2017-01-01
Excluding the ribosome and riboswitches, developing small molecules that selectively target RNA is a longstanding problem in chemical biology. A typical cellular RNA is difficult to target because it has little tertiary, but abundant secondary structure. We designed allele-selective compounds that target such an RNA, the toxic noncoding repeat expansion (r(CUG)exp) that causes myotonic dystrophy type 1 (DM1). We developed several strategies to generate allele-selective small molecules, including non-covalent binding, covalent binding, cleavage and on-site probe synthesis. Covalent binding and cleavage enabled target profiling in cells derived from individuals with DM1, showing precise recognition of r(CUG)exp. In the on-site probe synthesis approach, small molecules bound adjacent sites in r(CUG)exp and reacted to afford picomolar inhibitors via a proximity-based click reaction only in DM1-affected cells. We expanded this approach to image r(CUG)exp in its natural context. PMID:27941760
Precise small-molecule recognition of a toxic CUG RNA repeat expansion.
Rzuczek, Suzanne G; Colgan, Lesley A; Nakai, Yoshio; Cameron, Michael D; Furling, Denis; Yasuda, Ryohei; Disney, Matthew D
2017-02-01
Excluding the ribosome and riboswitches, developing small molecules that selectively target RNA is a longstanding problem in chemical biology. A typical cellular RNA is difficult to target because it has little tertiary, but abundant secondary structure. We designed allele-selective compounds that target such an RNA, the toxic noncoding repeat expansion (r(CUG) exp ) that causes myotonic dystrophy type 1 (DM1). We developed several strategies to generate allele-selective small molecules, including non-covalent binding, covalent binding, cleavage and on-site probe synthesis. Covalent binding and cleavage enabled target profiling in cells derived from individuals with DM1, showing precise recognition of r(CUG) exp . In the on-site probe synthesis approach, small molecules bound adjacent sites in r(CUG) exp and reacted to afford picomolar inhibitors via a proximity-based click reaction only in DM1-affected cells. We expanded this approach to image r(CUG) exp in its natural context.
Juárez, M; Polvillo, O; Contò, M; Ficco, A; Ballico, S; Failla, S
2008-05-09
Four different extraction-derivatization methods commonly used for fatty acid analysis in meat (in situ or one-step method, saponification method, classic method and a combination of classic extraction and saponification derivatization) were tested. The in situ method had low recovery and variation. The saponification method showed the best balance between recovery, precision, repeatability and reproducibility. The classic method had high recovery and acceptable variation values, except for the polyunsaturated fatty acids, showing higher variation than the former methods. The combination of extraction and methylation steps had great recovery values, but the precision, repeatability and reproducibility were not acceptable. Therefore the saponification method would be more convenient for polyunsaturated fatty acid analysis, whereas the in situ method would be an alternative for fast analysis. However the classic method would be the method of choice for the determination of the different lipid classes.
Effects of Immediate Repetition in L2 Speaking Tasks: A Focused Study
ERIC Educational Resources Information Center
Bei, Gavin Xiaoyue
2013-01-01
This paper reports on a focused investigation into the immediate effects of oral narrative task repetition by two adult EFL learners of intermediate and high proficiency. Two participants performed a narrative speaking task after watching a cartoon video clip and repeated their performance three times, followed by a retrospective report in an…
Novel Structure of Ty3 Reverse Transcriptase | Center for Cancer Research
Retrotransposons are mobile genetic elements that self amplify via a single-stranded RNA intermediate, which is converted to double-stranded DNA by an encoded reverse transcriptase (RT) with both DNA polymerase (pol) and ribonuclease H (RNase) activities. Categorized by whether they contain flanking long terminal repeat (LTR) sequences, retrotransposons play a critical role in
USDA-ARS?s Scientific Manuscript database
The Florida cooperative sugarcane cultivar development program conducts all of its early selection stages on muck (organic) soils at the USDA-ARS Sugarcane Field Station in Canal Point. About 25% of the locations in the final two stages (Stages 3 and 4) are conducted on sand soils, after a reduction...
Positioning accuracy in a registration-free CT-based navigation system
NASA Astrophysics Data System (ADS)
Brandenberger, D.; Birkfellner, W.; Baumann, B.; Messmer, P.; Huegli, R. W.; Regazzoni, P.; Jacob, A. L.
2007-12-01
In order to maintain overall navigation accuracy established by a calibration procedure in our CT-based registration-free navigation system, the CT scanner has to repeatedly generate identical volume images of a target at the same coordinates. We tested the positioning accuracy of the prototype of an advanced workplace for image-guided surgery (AWIGS) which features an operating table capable of direct patient transfer into a CT scanner. Volume images (N = 154) of a specialized phantom were analysed for translational shifting after various table translations. Variables included added weight and phantom position on the table. The navigation system's calibration accuracy was determined (bias 2.1 mm, precision ± 0.7 mm, N = 12). In repeated use, a bias of 3.0 mm and a precision of ± 0.9 mm (N = 10) were maintainable. Instances of translational image shifting were related to the table-to-CT scanner docking mechanism. A distance scaling error when altering the table's height was detected. Initial prototype problems visible in our study causing systematic errors were resolved by repeated system calibrations between interventions. We conclude that the accuracy achieved is sufficient for a wide range of clinical applications in surgery and interventional radiology.
Force Spectroscopy with 9-μs Resolution and Sub-pN Stability by Tailoring AFM Cantilever Geometry.
Edwards, Devin T; Faulk, Jaevyn K; LeBlanc, Marc-André; Perkins, Thomas T
2017-12-19
Atomic force microscopy (AFM)-based single-molecule force spectroscopy (SMFS) is a powerful yet accessible means to characterize the unfolding/refolding dynamics of individual molecules and resolve closely spaced, transiently occupied folding intermediates. On a modern commercial AFM, these applications and others are now limited by the mechanical properties of the cantilever. Specifically, AFM-based SMFS data quality is degraded by a commercial cantilever's limited combination of temporal resolution, force precision, and force stability. Recently, we modified commercial cantilevers with a focused ion beam to optimize their properties for SMFS. Here, we extend this capability by modifying a 40 × 18 μm 2 cantilever into one terminated with a gold-coated, 4 × 4 μm 2 reflective region connected to an uncoated 2-μm-wide central shaft. This "Warhammer" geometry achieved 8.5-μs resolution coupled with improved force precision and sub-pN stability over 100 s when measured on a commercial AFM. We highlighted this cantilever's biological utility by first resolving a calmodulin unfolding intermediate previously undetected by AFM and then measuring the stabilization of calmodulin by myosin light chain kinase at dramatically higher unfolding velocities than in previous AFM studies. More generally, enhancing data quality via an improved combination of time resolution, force precision, and force stability will broadly benefit biological applications of AFM. Published by Elsevier Inc.
Pre-Test Assessment of the Upper Bound of the Drag Coefficient Repeatability of a Wind Tunnel Model
NASA Technical Reports Server (NTRS)
Ulbrich, N.; L'Esperance, A.
2017-01-01
A new method is presented that computes a pre{test estimate of the upper bound of the drag coefficient repeatability of a wind tunnel model. This upper bound is a conservative estimate of the precision error of the drag coefficient. For clarity, precision error contributions associated with the measurement of the dynamic pressure are analyzed separately from those that are associated with the measurement of the aerodynamic loads. The upper bound is computed by using information about the model, the tunnel conditions, and the balance in combination with an estimate of the expected output variations as input. The model information consists of the reference area and an assumed angle of attack. The tunnel conditions are described by the Mach number and the total pressure or unit Reynolds number. The balance inputs are the partial derivatives of the axial and normal force with respect to all balance outputs. Finally, an empirical output variation of 1.0 microV/V is used to relate both random instrumentation and angle measurement errors to the precision error of the drag coefficient. Results of the analysis are reported by plotting the upper bound of the precision error versus the tunnel conditions. The analysis shows that the influence of the dynamic pressure measurement error on the precision error of the drag coefficient is often small when compared with the influence of errors that are associated with the load measurements. Consequently, the sensitivities of the axial and normal force gages of the balance have a significant influence on the overall magnitude of the drag coefficient's precision error. Therefore, results of the error analysis can be used for balance selection purposes as the drag prediction characteristics of balances of similar size and capacities can objectively be compared. Data from two wind tunnel models and three balances are used to illustrate the assessment of the precision error of the drag coefficient.
UAVSAR Instrument: Current Operations and Planned Upgrades
NASA Technical Reports Server (NTRS)
Lou, Yunling; Hensley, Scott; Chao, Roger; Chapin, Elaine; Heavy, Brandon; Jones, Cathleen; Miller, Timothy; Naftel, Chris; Fratello, David
2011-01-01
The Uninhabited Aerial Vehicle Synthetic Aperture Radar (UAVSAR) instrument is a pod-based Lband polarimetric synthetic aperture radar (SAR), specifically designed to acquire airborne repeat track SAR data for differential interferometric measurements. This instrument is currently installed on the NASA Gulfstream- III (G-III) aircraft with precision real-time Global Positioning System (GPS) and a sensor-controlled flight management system for precision repeat-pass data acquisitions. UAVSAR has conducted engineering and preliminary science data flights since October 2007 on the G-III. We are porting the radar to the Global Hawk Unmanned Airborne Vehicle (UAV) to enable long duration/long range data campaigns. We plan to install two radar pods (each with its own active array antenna) under the wings of the Global Hawk to enable the generation of precision topographic maps and single pass polarimetric-interferometry (SPI) providing vertical structure of ice and vegetation. Global Hawk's range of 8000 nm will enable regional surveys with far fewer sorties as well as measurements of remote locations without the need for long and complicated deployments. We are also developing P-band polarimetry and Ka-band single-pass interferometry capabilities on UAVSAR by replacing the radar antenna and front-end electronics to operate at these
UAV-based L-band SAR with precision flight path control
NASA Astrophysics Data System (ADS)
Madsen, Soren N.; Hensley, Scott; Wheeler, Kevin; Sadowy, Gregory A.; Miller, Tim; Muellerschoen, Ron; Lou, Yunling; Rosen, Paul A.
2005-01-01
NASA's Jet Propulsion Laboratory is currently implementing a reconfigurable polarimetric L-band synthetic aperture radar (SAR), specifically designed to acquire airborne repeat track interferometric (RTI) SAR data, also know as differential interferometric measurements. Differential interferometry can provide key displacement measurements, important for the scientific studies of Earthquakes and volcanoes1. Using precision real-time GPS and a sensor controlled flight management system, the system will be able to fly predefined paths with great precision. The radar will be designed to operate on a UAV (Unmanned Arial Vehicle) but will initially be demonstrated on a minimally piloted vehicle (MPV), such as the Proteus build by Scaled Composites. The application requires control of the flight path to within a 10 m tube to support repeat track and formation flying measurements. The design is fully polarimetric with an 80 MHz bandwidth (2 m range resolution) and 16 km range swath. The antenna is an electronically steered array to assure that the actual antenna pointing can be controlled independent of the wind direction and speed. The system will nominally operate at 45,000 ft. The program started out as a Instrument Incubator Project (IIP) funded by NASA Earth Science and Technology Office (ESTO).
Ballesteros Martín, M M; Casas López, J L; Oller, I; Malato, S; Sánchez Pérez, J A
2010-09-01
Four biodegradability tests (Pseudomonas putida bioassay, Zahn-Wellens test, BOD5/COD ratio and respirometry assay) have been used to determine the biodegradability enhancement during the treatment of wastewater containing 200 mg L(-1) of dissolved organic carbon (DOC) of a five commercial pesticides mixture (Vydate, Metomur, Couraze, Ditumur and Scala) by an advanced oxidation process (AOP). A comparative study was carried out taking into account repeatability and precision of each biodegradability test. Solar photo-Fenton was the AOP selected for pesticide degradation up to three levels of mineralization: 20%, 40% and 60% of initial DOC. Intra- and interday precisions were evaluated conducting each biodegradability test by triplicate and they were applied three times on different dates over a period of three months. Fisher's least significant difference method was applied to the means, P. putida and Zahn-Wellens tests giving higher repeatability and precision. The P. putida test requires a shorter time to obtain reliable results using a standardized inoculum and constitutes a worthwhile alternative to estimate biodegradability in contrast to other less accurate or more time consuming methods. Copyright (c) 2010 Elsevier Inc. All rights reserved.
UAV-Based L-Band SAR with Precision Flight Path Control
NASA Technical Reports Server (NTRS)
Madsen, Soren N.; Hensley, Scott; Wheeler, Kevin; Sadowy, Greg; Miller, Tim; Muellerschoen, Ron; Lou, Yunling; Rosen, Paul
2004-01-01
NASA's Jet Propulsion Laboratory is currently implementing a reconfigurable polarimetric L-band synthetic aperture radar (SAR), specifically designed to acquire airborne repeat track interferometric (RTI) SAR data, also know as differential interferometric measurements. Differential interferometry can provide key displacement measurements, important for the scientific studies of Earthquakes and volcanoes. Using precision real-time GPS and a sensor controlled flight management system, the system will be able to fly predefined paths with great precision. The radar will be designed to operate on a UAV (Unmanned Arial Vehicle) but will initially be demonstrated on a minimally piloted vehicle (MPV), such as the Proteus build by Scaled Composites. The application requires control of the flight path to within a 10 meter tube to support repeat track and formation flying measurements. The design is fully polarimetric with an 80 MHz bandwidth (2 meter range resolution) and 16 kilometer range swath. The antenna is an electronically steered array to assure that the actual antenna pointing can be controlled independent of the wind direction and speed. The system will nominally operate at 45,000 ft. The program started out as a Instrument Incubator Project (IIP) funded by NASA Earth Science and Technology Office (ESTO).
Precision Spectrophotometric Calibration System for Dark Energy Instruments
DOE Office of Scientific and Technical Information (OSTI.GOV)
Schubnell, Michael S.
2015-06-30
For this research we build a precision calibration system and carried out measurements to demonstrate the precision that can be achieved with a high precision spectrometric calibration system. It was shown that the system is capable of providing a complete spectrophotometric calibration at the sub-pixel level. The calibration system uses a fast, high precision monochromator that can quickly and efficiently scan over an instrument’s entire spectral range with a spectral line width of less than 0.01 nm corresponding to a fraction of a pixel on the CCD. The system was extensively evaluated in the laboratory. Our research showed that amore » complete spectrophotometric calibration standard for spectroscopic survey instruments such as DESI is possible. The monochromator precision and repeatability to a small fraction of the DESI spectrograph LSF was demonstrated with re-initialization on every scan and thermal drift compensation by locking to multiple external line sources. A projector system that mimics telescope aperture for point source at infinity was demonstrated.« less
LoPresti, Melissa; Daniels, Bradley; Buchanan, Edward P; Monson, Laura; Lam, Sandi
2017-04-01
Repeat surgery for restenosis after initial nonsyndromic craniosynostosis intervention is sometimes needed. Calvarial vault reconstruction through a healed surgical bed adds a level of intraoperative complexity and may benefit from preoperative and intraoperative definitions of biometric and aesthetic norms. Computer-assisted design and manufacturing using 3D imaging allows the precise formulation of operative plans in anticipation of surgical intervention. 3D printing turns virtual plans into anatomical replicas, templates, or customized implants by using a variety of materials. The authors present a technical note illustrating the use of this technology: a repeat calvarial vault reconstruction that was planned and executed using computer-assisted design and 3D printed intraoperative guides.
Junker; Reif; Steinhagen; Junker; Felli; Reggelin; Griesinger
2000-09-01
The structure of a catalytic intermediate with important implications for the interpretation of the stereochemical outcome of the palladium complex catalyzed allylic substitution with phosphino-oxazoline (PHOX) ligands is determined by liquid state NMR. The complex displays a novel structure that is highly distorted compared with other palladium eta2-olefin complexes known so far. The structure has been determined from nuclear overhauser data (NOE), scalar coupling constants, and long range projection angle restraints derived from dipole dipole cross-correlated relaxation of multiple quantum coherence. The latter restraints have been implemented into a distance geometry protocol. The projection angle restraints yield a higher precision in the determination of the relative orientation of the two molecular moieties and are essential to provide an exact structural definition of the olefinic part of the catalytic intermediate with respect to the ligand.
Cagnoli, Claudia; Stevanin, Giovanni; Michielotto, Chiara; Gerbino Promis, Giovanni; Brussino, Alessandro; Pappi, Patrizia; Durr, Alexandra; Dragone, Elisa; Viemont, Michelle; Gellera, Cinzia; Brice, Alexis; Migone, Nicola; Brusco, Alfredo
2006-02-01
Large expansions in the SCA2 and SCA7 genes (>100 CAG repeats) have been associated with juvenile and infantile forms of cerebellar ataxias that cannot be detected using standard polymerase chain reaction (PCR). Here, we describe a successful application of the fluorescent short tandem repeat-primed PCR method for accurate identification of these expanded repeats. The test is robust, reliable, and inexpensive and can be used to screen large series of patients, although it cannot give a precise evaluation of the size of the expansion. This test may be of practical value in prenatal diagnoses offered to affected or pre-symptomatic at-risk parents, in which a very large expansion inherited from one of the parents can be missed in the fetus by standard PCR.
Cagnoli, Claudia; Stevanin, Giovanni; Michielotto, Chiara; Gerbino Promis, Giovanni; Brussino, Alessandro; Pappi, Patrizia; Durr, Alexandra; Dragone, Elisa; Viemont, Michelle; Gellera, Cinzia; Brice, Alexis; Migone, Nicola; Brusco, Alfredo
2006-01-01
Large expansions in the SCA2 and SCA7 genes (>100 CAG repeats) have been associated with juvenile and infantile forms of cerebellar ataxias that cannot be detected using standard polymerase chain reaction (PCR). Here, we describe a successful application of the fluorescent short tandem repeat-primed PCR method for accurate identification of these expanded repeats. The test is robust, reliable, and inexpensive and can be used to screen large series of patients, although it cannot give a precise evaluation of the size of the expansion. This test may be of practical value in prenatal diagnoses offered to affected or pre-symptomatic at-risk parents, in which a very large expansion inherited from one of the parents can be missed in the fetus by standard PCR. PMID:16436644
Revolution of Alzheimer Precision Neurology Passageway of Systems Biology and Neurophysiology.
Hampel, Harald; Toschi, Nicola; Babiloni, Claudio; Baldacci, Filippo; Black, Keith L; Bokde, Arun L W; Bun, René S; Cacciola, Francesco; Cavedo, Enrica; Chiesa, Patrizia A; Colliot, Olivier; Coman, Cristina-Maria; Dubois, Bruno; Duggento, Andrea; Durrleman, Stanley; Ferretti, Maria-Teresa; George, Nathalie; Genthon, Remy; Habert, Marie-Odile; Herholz, Karl; Koronyo, Yosef; Koronyo-Hamaoui, Maya; Lamari, Foudil; Langevin, Todd; Lehéricy, Stéphane; Lorenceau, Jean; Neri, Christian; Nisticò, Robert; Nyasse-Messene, Francis; Ritchie, Craig; Rossi, Simone; Santarnecchi, Emiliano; Sporns, Olaf; Verdooner, Steven R; Vergallo, Andrea; Villain, Nicolas; Younesi, Erfan; Garaci, Francesco; Lista, Simone
2018-03-16
The Precision Neurology development process implements systems theory with system biology and neurophysiology in a parallel, bidirectional research path: a combined hypothesis-driven investigation of systems dysfunction within distinct molecular, cellular, and large-scale neural network systems in both animal models as well as through tests for the usefulness of these candidate dynamic systems biomarkers in different diseases and subgroups at different stages of pathophysiological progression. This translational research path is paralleled by an "omics"-based, hypothesis-free, exploratory research pathway, which will collect multimodal data from progressing asymptomatic, preclinical, and clinical neurodegenerative disease (ND) populations, within the wide continuous biological and clinical spectrum of ND, applying high-throughput and high-content technologies combined with powerful computational and statistical modeling tools, aimed at identifying novel dysfunctional systems and predictive marker signatures associated with ND. The goals are to identify common biological denominators or differentiating classifiers across the continuum of ND during detectable stages of pathophysiological progression, characterize systems-based intermediate endophenotypes, validate multi-modal novel diagnostic systems biomarkers, and advance clinical intervention trial designs by utilizing systems-based intermediate endophenotypes and candidate surrogate markers. Achieving these goals is key to the ultimate development of early and effective individualized treatment of ND, such as Alzheimer's disease. The Alzheimer Precision Medicine Initiative (APMI) and cohort program (APMI-CP), as well as the Paris based core of the Sorbonne University Clinical Research Group "Alzheimer Precision Medicine" (GRC-APM) were recently launched to facilitate the passageway from conventional clinical diagnostic and drug development toward breakthrough innovation based on the investigation of the comprehensive biological nature of aging individuals. The APMI movement is gaining momentum to systematically apply both systems neurophysiology and systems biology in exploratory translational neuroscience research on ND.
Revolution of Alzheimer Precision Neurology: Passageway of Systems Biology and Neurophysiology
Hampel, Harald; Toschi, Nicola; Babiloni, Claudio; Baldacci, Filippo; Black, Keith L.; Bokde, Arun L.W.; Bun, René S.; Cacciola, Francesco; Cavedo, Enrica; Chiesa, Patrizia A.; Colliot, Olivier; Coman, Cristina-Maria; Dubois, Bruno; Duggento, Andrea; Durrleman, Stanley; Ferretti, Maria-Teresa; George, Nathalie; Genthon, Remy; Habert, Marie-Odile; Herholz, Karl; Koronyo, Yosef; Koronyo-Hamaoui, Maya; Lamari, Foudil; Langevin, Todd; Lehéricy, Stéphane; Lorenceau, Jean; Neri, Christian; Nisticò, Robert; Nyasse-Messene, Francis; Ritchie, Craig; Rossi, Simone; Santarnecchi, Emiliano; Sporns, Olaf; Verdooner, Steven R.; Vergallo, Andrea; Villain, Nicolas; Younesi, Erfan; Garaci, Francesco; Lista, Simone
2018-01-01
The Precision Neurology development process implements systems theory with system biology and neurophysiology in a parallel, bidirectional research path: a combined hypothesis-driven investigation of systems dysfunction within distinct molecular, cellular and large-scale neural network systems in both animal models as well as through tests for the usefulness of these candidate dynamic systems biomarkers in different diseases and subgroups at different stages of pathophysiological progression. This translational research path is paralleled by an “omics”-based, hypothesis-free, exploratory research pathway, which will collect multimodal data from progressing asymptomatic, preclinical and clinical neurodegenerative disease (ND) populations, within the wide continuous biological and clinical spectrum of ND, applying high-throughput and high-content technologies combined with powerful computational and statistical modeling tools, aimed at identifying novel dysfunctional systems and predictive marker signatures associated with ND. The goals are to identify common biological denominators or differentiating classifiers across the continuum of ND during detectable stages of pathophysiological progression, characterize systems-based intermediate endophenotypes, validate multi-modal novel diagnostic systems biomarkers, and advance clinical intervention trial designs by utilizing systems-based intermediate endophenotypes and candidate surrogate markers. Achieving these goals is key to the ultimate development of early and effective individualized treatment of ND, such as Alzheimer’s disease (AD). The Alzheimer Precision Medicine Initiative (APMI) and cohort program (APMI-CP), as well as the Paris based core of the Sorbonne University Clinical Research Group “Alzheimer Precision Medicine” (GRC-APM) were recently launched to facilitate the passageway from conventional clinical diagnostic and drug development towards breakthrough innovation based on the investigation of the comprehensive biological nature of aging individuals. The APMI movement is gaining momentum to systematically apply both systems neurophysiology and systems biology in exploratory translational neuroscience research on ND. PMID:29562524
P.H. Cochran; K.W. Seidel
1999-01-01
Repeated thinning to five growing-stock levels resulted in widely differing tree sizes and volumes per acre after 30 years. Largest trees but the least cubic-volume yield per acre were produced in the heaviest thinning level, whereas highest board-foot yields were found in intermediate thinning levels. Partial defoliation by larch casebearer (Coleophora...
Ritterhoff, Tobias; Das, Hrishikesh; Hofhaus, Götz; Schröder, Rasmus R.; Flotho, Annette; Melchior, Frauke
2016-01-01
Continuous cycles of nucleocytoplasmic transport require disassembly of transport receptor/Ran-GTP complexes in the cytoplasm. A basic disassembly mechanism in all eukaryotes depends on soluble RanGAP and RanBP1. In vertebrates, a significant fraction of RanGAP1 stably interacts with the nucleoporin RanBP2 at a binding site that is flanked by FG-repeats and Ran-binding domains, and overlaps with RanBP2's SUMO E3 ligase region. Here, we show that the RanBP2/RanGAP1*SUMO1/Ubc9 complex functions as an autonomous disassembly machine with a preference for the export receptor Crm1. We describe three in vitro reconstituted disassembly intermediates, which show binding of a Crm1 export complex via two FG-repeat patches, cargo-release by RanBP2's Ran-binding domains and retention of free Crm1 at RanBP2 after Ran-GTP hydrolysis. Intriguingly, all intermediates are compatible with SUMO E3 ligase activity, suggesting that the RanBP2/RanGAP1*SUMO1/Ubc9 complex may link Crm1- and SUMO-dependent functions. PMID:27160050
Statistical evaluation of rainfall-simulator and erosion testing procedure : final report.
DOT National Transportation Integrated Search
1977-01-01
The specific aims of this study were (1) to supply documentation of statistical repeatability and precision of the rainfall-simulator and to document the statistical repeatabiity of the soil-loss data when using the previously recommended tentative l...
Identification of presumed ancestral DNA sequences of phaseolin in Phaseolus vulgaris.
Kami, J; Velásquez, V B; Debouck, D G; Gepts, P
1995-01-01
Common bean (Phaseolus vulgaris) consists of two major geographic gene pools, one distributed in Mexico, Central America, and Colombia and the other in the southern Andes (southern Peru, Bolivia, and Argentina). Amplification and sequencing of members of the multigene family coding for phaseolin, the major seed storage protein of the common bean, provide evidence for accumulation of tandem direct repeats in both introns and exons during evolution of the multigene family in this species. The presumed ancestral phaseolin sequences, without tandem repeats, were found in recently discovered but nearly extinct wild common bean populations of Ecuador and northern Peru that are intermediate between the two major gene pools of the species based on geographical and molecular arguments. Our results illustrate the usefulness of tandem direct repeats in establishing the polarity of DNA sequence divergence and therefore in proposing phylogenies. Images Fig. 1 Fig. 3 PMID:7862642
Wang, Jinjing Jenny; Odic, Darko; Halberda, Justin; Feigenson, Lisa
2016-07-01
From early in life, humans have access to an approximate number system (ANS) that supports an intuitive sense of numerical quantity. Previous work in both children and adults suggests that individual differences in the precision of ANS representations correlate with symbolic math performance. However, this work has been almost entirely correlational in nature. Here we tested for a causal link between ANS precision and symbolic math performance by asking whether a temporary modulation of ANS precision changes symbolic math performance. First, we replicated a recent finding that 5-year-old children make more precise ANS discriminations when starting with easier trials and gradually progressing to harder ones, compared with the reverse. Next, we show that this brief modulation of ANS precision influenced children's performance on a subsequent symbolic math task but not a vocabulary task. In a supplemental experiment, we present evidence that children who performed ANS discriminations in a random trial order showed intermediate performance on both the ANS task and the symbolic math task, compared with children who made ordered discriminations. Thus, our results point to a specific causal link from the ANS to symbolic math performance. Copyright © 2016 Elsevier Inc. All rights reserved.
Wang, Jinjing (Jenny); Odic, Darko; Halberda, Justin; Feigenson, Lisa
2016-01-01
From early in life, humans have access to an Approximate Number System (ANS) that supports an intuitive sense of numerical quantity. Previous work in both children and adults suggests that individual differences in the precision of ANS representations correlate with symbolic math performance. However, this work has been almost entirely correlational in nature. Here we tested for a causal link between ANS precision and symbolic math performance by asking whether a temporary modulation of ANS precision changes symbolic math performance. First we replicated a recent finding that 5-year-old children make more precise ANS discriminations when starting with easier trials and gradually progressing to harder ones, compared to the reverse. Next, we show that this brief modulation of ANS precision influenced children’s performance on a subsequent symbolic math task, but not a vocabulary task. In a supplemental experiment we present evidence that children who performed ANS discriminations in a random trial order showed intermediate performance both on the ANS task and the symbolic math task, compared to the children who made ordered discriminations. Thus, our results point to a specific causal link from the ANS to symbolic math performance. PMID:27061668
7075-T6 and 2024-T351 Aluminum Alloy Fatigue Crack Growth Rate Data
NASA Technical Reports Server (NTRS)
Forth, Scott C.; Wright, Christopher W.; Johnston, William M., Jr.
2005-01-01
Experimental test procedures for the development of fatigue crack growth rate data has been standardized by the American Society for Testing and Materials. Over the past 30 years several gradual changes have been made to the standard without rigorous assessment of the affect these changes have on the precision or variability of the data generated. Therefore, the ASTM committee on fatigue crack growth has initiated an international round robin test program to assess the precision and variability of test results generated using the standard E647-00. Crack growth rate data presented in this report, in support of the ASTM roundrobin, shows excellent precision and repeatability.
Human minisatellite alleles detectable only after PCR amplification.
Armour, J A; Crosier, M; Jeffreys, A J
1992-01-01
We present evidence that a proportion of alleles at two human minisatellite loci is undetected by standard Southern blot hybridization. In each case the missing allele(s) can be identified after PCR amplification and correspond to tandem arrays too short to detect by hybridization. At one locus, there is only one undetected allele (population frequency 0.3), which contains just three repeat units. At the second locus, there are at least five undetected alleles (total population frequency 0.9) containing 60-120 repeats; they are not detected because these tandem repeats give very poor signals when used as a probe in standard Southern blot hybridization, and also cross-hybridize with other sequences in the genome. Under these circumstances only signals from the longest tandemly repeated alleles are detectable above the nonspecific background. The structures of these loci have been compared in human and primate DNA, and at one locus the short human allele containing three repeat units is shown to be an intermediate state in the expansion of a monomeric precursor allele in primates to high copy number in the longer human arrays. We discuss the implications of such loci for studies of human populations, minisatellite isolation by cloning, and the evolution of highly variable tandem arrays.
NASA Astrophysics Data System (ADS)
Caress, D. W.; Clague, D. A.; Paduan, J. B.; Thomas, H. J.; Chadwick, W. W., Jr.; Nooner, S. L.; Yoerger, D.
2016-12-01
Axial Seamount is an intensely studied submarine hotspot volcano on the Juan de Fuca Ridge that erupted in 1998, 2011, and 2015. MBARI Mapping AUV surveys during 2006-2009 obtained nearly complete 1 m resolution topographic coverage of the Axial Seamount summit, including the caldera, the caldera rim, and the south rift zone. Surveys following both recent eruptions mapped new lava flows and extended coverage of the caldera rim and the north and south rifts. These include 2011 (post-eruption), 2014, and 2016 MBARI Mapping AUV surveys and 2015 (post-eruption) WHOI AUV Sentry surveys. These AUVs use 200 kHz or 400 kHz multibeam sonars operated from 50 m to 75 m altitudes to achieve 1 m lateral resolution and 0.1 m vertical precision. Differencing repeat surveys allows detection of topographic change > 0.2 m, a capability used to map the extent, morphology and volume of lava flows emplaced by the 2011 and 2015 eruptions. In situ pressure observations show the uplift and subsidence of the caldera center associated with pre-eruption inflation and co-eruption deflation of the sub-caldera magma chamber has a 2.5-3.5 m magnitude, and thus can be observed by repeat AUV surveys. A survey pattern crossing the caldera interior both E-W and N-S and extending 8 km down the south rift was established in 2011 that has been repeated in 2014, 2015, and 2016. The 2015 surveys established a larger, asterisk-shaped survey pattern extending about 4 km outside the caldera walls along seven lines that has now been repeated in 2016. Repeat survey comparison reveals the vertical deformation pattern of the eruption cycle. Between 2011 and 2014 the uplift has a maximum of 1.8 m near the caldera center, and diminishes steadily away from this site. Between 2014 and 2015 there is a 1.0 m subsidence of the caldera center associated with the April 2015 eruption. The comparison of the 2011 and 2015 surveys shows that the caldera floor is slightly uplifted four months after the 2015 eruption relative to four months after the 2011 eruption. Results incorporating the new 2016 surveys will be presented. These results are consistent with 1 cm precision pressure benchmark observations on the caldera and south rift by Chadwick and Nooner. Our AUV mapping method is less precise than pressure benchmark data but measures the deformation pattern over a larger, spatially continuous area.
Precision analysis of a quantitative CT liver surface nodularity score.
Smith, Andrew; Varney, Elliot; Zand, Kevin; Lewis, Tara; Sirous, Reza; York, James; Florez, Edward; Abou Elkassem, Asser; Howard-Claudio, Candace M; Roda, Manohar; Parker, Ellen; Scortegagna, Eduardo; Joyner, David; Sandlin, David; Newsome, Ashley; Brewster, Parker; Lirette, Seth T; Griswold, Michael
2018-04-26
To evaluate precision of a software-based liver surface nodularity (LSN) score derived from CT images. An anthropomorphic CT phantom was constructed with simulated liver containing smooth and nodular segments at the surface and simulated visceral and subcutaneous fat components. The phantom was scanned multiple times on a single CT scanner with adjustment of image acquisition and reconstruction parameters (N = 34) and on 22 different CT scanners from 4 manufacturers at 12 imaging centers. LSN scores were obtained using a software-based method. Repeatability and reproducibility were evaluated by intraclass correlation (ICC) and coefficient of variation. Using abdominal CT images from 68 patients with various stages of chronic liver disease, inter-observer agreement and test-retest repeatability among 12 readers assessing LSN by software- vs. visual-based scoring methods were evaluated by ICC. There was excellent repeatability of LSN scores (ICC:0.79-0.99) using the CT phantom and routine image acquisition and reconstruction parameters (kVp 100-140, mA 200-400, and auto-mA, section thickness 1.25-5.0 mm, field of view 35-50 cm, and smooth or standard kernels). There was excellent reproducibility (smooth ICC: 0.97; 95% CI 0.95, 0.99; CV: 7%; nodular ICC: 0.94; 95% CI 0.89, 0.97; CV: 8%) for LSN scores derived from CT images from 22 different scanners. Inter-observer agreement for the software-based LSN scoring method was excellent (ICC: 0.84; 95% CI 0.79, 0.88; CV: 28%) vs. good for the visual-based method (ICC: 0.61; 95% CI 0.51, 0.69; CV: 43%). Test-retest repeatability for the software-based LSN scoring method was excellent (ICC: 0.82; 95% CI 0.79, 0.84; CV: 12%). The software-based LSN score is a quantitative CT imaging biomarker with excellent repeatability, reproducibility, inter-observer agreement, and test-retest repeatability.
Object representation in the human auditory system
Winkler, István; van Zuijen, Titia L.; Sussman, Elyse; Horváth, János; Näätänen, Risto
2010-01-01
One important principle of object processing is exclusive allocation. Any part of the sensory input, including the border between two objects, can only belong to one object at a time. We tested whether tones forming a spectro-temporal border between two sound patterns can belong to both patterns at the same time. Sequences were composed of low-, intermediate- and high-pitched tones. Tones were delivered with short onset-to-onset intervals causing the high and low tones to automatically form separate low and high sound streams. The intermediate-pitch tones could be perceived as part of either one or the other stream, but not both streams at the same time. Thus these tones formed a pitch ’border’ between the two streams. The tones were presented in a fixed, cyclically repeating order. Linking the intermediate-pitch tones with the high or the low tones resulted in the perception of two different repeating tonal patterns. Participants were instructed to maintain perception of one of the two tone patterns throughout the stimulus sequences. Occasional changes violated either the selected or the alternative tone pattern, but not both at the same time. We found that only violations of the selected pattern elicited the mismatch negativity event-related potential, indicating that only this pattern was represented in the auditory system. This result suggests that individual sounds are processed as part of only one auditory pattern at a time. Thus tones forming a spectro-temporal border are exclusively assigned to one sound object at any given time, as are spatio-temporal borders in vision. PMID:16836636
High-Resolution Mapping of a Repeat Protein Folding Free Energy Landscape.
Fossat, Martin J; Dao, Thuy P; Jenkins, Kelly; Dellarole, Mariano; Yang, Yinshan; McCallum, Scott A; Garcia, Angel E; Barrick, Doug; Roumestand, Christian; Royer, Catherine A
2016-12-06
A complete description of the pathways and mechanisms of protein folding requires a detailed structural and energetic characterization of the conformational ensemble along the entire folding reaction coordinate. Simulations can provide this level of insight for small proteins. In contrast, with the exception of hydrogen exchange, which does not monitor folding directly, experimental studies of protein folding have not yielded such structural and energetic detail. NMR can provide residue specific atomic level structural information, but its implementation in protein folding studies using chemical or temperature perturbation is problematic. Here we present a highly detailed structural and energetic map of the entire folding landscape of the leucine-rich repeat protein, pp32 (Anp32), obtained by combining pressure-dependent site-specific 1 H- 15 N HSQC data with coarse-grained molecular dynamics simulations. The results obtained using this equilibrium approach demonstrate that the main barrier to folding of pp32 is quite broad and lies near the unfolded state, with structure apparent only in the C-terminal region. Significant deviation from two-state unfolding under pressure reveals an intermediate on the folded side of the main barrier in which the N-terminal region is disordered. A nonlinear temperature dependence of the population of this intermediate suggests a large heat capacity change associated with its formation. The combination of pressure, which favors the population of folding intermediates relative to chemical denaturants; NMR, which allows their observation; and constrained structure-based simulations yield unparalleled insight into protein folding mechanisms. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.
Software-defined microwave photonic filter with high reconfigurable resolution
Wei, Wei; Yi, Lilin; Jaouën, Yves; Hu, Weisheng
2016-01-01
Microwave photonic filters (MPFs) are of great interest in radio frequency systems since they provide prominent flexibility on microwave signal processing. Although filter reconfigurability and tunability have been demonstrated repeatedly, it is still difficult to control the filter shape with very high precision. Thus the MPF application is basically limited to signal selection. Here we present a polarization-insensitive single-passband arbitrary-shaped MPF with ~GHz bandwidth based on stimulated Brillouin scattering (SBS) in optical fibre. For the first time the filter shape, bandwidth and central frequency can all be precisely defined by software with ~MHz resolution. The unprecedented multi-dimensional filter flexibility offers new possibilities to process microwave signals directly in optical domain with high precision thus enhancing the MPF functionality. Nanosecond pulse shaping by implementing precisely defined filters is demonstrated to prove the filter superiority and practicability. PMID:27759062
Software-defined microwave photonic filter with high reconfigurable resolution.
Wei, Wei; Yi, Lilin; Jaouën, Yves; Hu, Weisheng
2016-10-19
Microwave photonic filters (MPFs) are of great interest in radio frequency systems since they provide prominent flexibility on microwave signal processing. Although filter reconfigurability and tunability have been demonstrated repeatedly, it is still difficult to control the filter shape with very high precision. Thus the MPF application is basically limited to signal selection. Here we present a polarization-insensitive single-passband arbitrary-shaped MPF with ~GHz bandwidth based on stimulated Brillouin scattering (SBS) in optical fibre. For the first time the filter shape, bandwidth and central frequency can all be precisely defined by software with ~MHz resolution. The unprecedented multi-dimensional filter flexibility offers new possibilities to process microwave signals directly in optical domain with high precision thus enhancing the MPF functionality. Nanosecond pulse shaping by implementing precisely defined filters is demonstrated to prove the filter superiority and practicability.
Flügge, Tabea V; Schlager, Stefan; Nelson, Katja; Nahles, Susanne; Metzger, Marc C
2013-09-01
Digital impression devices are used alternatively to conventional impression techniques and materials. The aims of this study were to evaluate the precision of digital intraoral scanning under clinical conditions (iTero; Align Technologies, San Jose, Calif) and to compare it with the precision of extraoral digitization. One patient received 10 full-arch intraoral scans with the iTero and conventional impressions with a polyether impression material (Impregum Penta; 3M ESPE, Seefeld, Germany). Stone cast models manufactured from the impressions were digitized 10 times with an extraoral scanner (D250; 3Shape, Copenhagen, Denmark) and 10 times with the iTero. Virtual models provided by each method were roughly aligned, and the model edges were trimmed with cutting planes to create common borders (Rapidform XOR; Inus Technologies, Seoul, Korea). A second model alignment was then performed along the closest distances of the surfaces (Artec Studio software; Artec Group, Luxembourg, Luxembourg). To assess precision, deviations between corresponding models were compared. Repeated intraoral scanning was evaluated in group 1, repeated extraoral model scanning with the iTero was assessed in group 2, and repeated model scanning with the D250 was assessed in group 3. Deviations between models were measured and expressed as maximums, means, medians, and root mean square errors for quantitative analysis. Color-coded displays of the deviations allowed qualitative visualization of the deviations. The greatest deviations and therefore the lowest precision were in group 1, with mean deviations of 50 μm, median deviations of 37 μm, and root mean square errors of 73 μm. Group 2 showed a higher precision, with mean deviations of 25 μm, median deviations of 18 μm, and root mean square errors of 51 μm. Scanning with the D250 had the highest precision, with mean deviations of 10 μm, median deviations of 5 μm, and root mean square errors of 20 μm. Intraoral and extraoral scanning with the iTero resulted in deviations at the facial surfaces of the anterior teeth and the buccal molar surfaces. Scanning with the iTero is less accurate than scanning with the D250. Intraoral scanning with the iTero is less accurate than model scanning with the iTero, suggesting that the intraoral conditions (saliva, limited spacing) contribute to the inaccuracy of a scan. For treatment planning and manufacturing of tooth-supported appliances, virtual models created with the iTero can be used. An extended scanning protocol could improve the scanning results in some regions. Copyright © 2013 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.
Nakamura, Shigeyoshi; Baba, Takayuki; Kidokoro, Shun-Ichi
2007-04-01
To understand the stabilization mechanism of the transient intermediate state in protein folding, it is very important to understand the structure and stability of the molten globule state under a native condition, in which the native state exists stably. The thermal transitions of horse cytochrome c were thermodynamically evaluated by highly precise differential scanning calorimetry (DSC) at pH 3.8-5.0. The heat capacity functions were analyzed using double deconvolution and the nonlinear least-squares method. An intermediate (I) state is clearly confirmed in the thermal native (N)-to-denatured (D) transition of horse cytochrome c. The mole fraction of the intermediate state shows the largest value, 0.4, at nearly 70 degrees C at pH 4.1. This intermediate state was also detected by the circular dichroism (CD) method and was found to have the properties of the molten globule-like structure by three-state analysis of the CD data. The Gibbs free-energy change between N and I, DeltaG(NI), and that between N and D, DeltaG(ND), were evaluated to be 9-22 kJ mol(-1) and 41-45 kJ mol(-1), respectively at 15( ) degrees C and pH 4.1.
Asymmetric cooperative catalysis of strong Brønsted acid-promoted reactions using chiral ureas.
Xu, Hao; Zuend, Stephan J; Woll, Matthew G; Tao, Ye; Jacobsen, Eric N
2010-02-19
Cationic organic intermediates participate in a wide variety of useful synthetic transformations, but their high reactivity can render selectivity in competing pathways difficult to control. Here, we describe a strategy for inducing enantioselectivity in reactions of protio-iminium ions, wherein a chiral catalyst interacts with the highly reactive intermediate through a network of noncovalent interactions. This interaction leads to an attenuation of the reactivity of the iminium ion and allows high enantioselectivity in cycloadditions with electron-rich alkenes (the Povarov reaction). A detailed experimental and computational analysis of this catalyst system has revealed the precise nature of the catalyst-substrate interactions and the likely basis for enantioinduction.
Asymmetric Cooperative Catalysis of Strong Brønsted Acid-Promoted Reactions Using Chiral Ureas
Xu, Hao; Zuend, Stephan J.; Woll, Matthew G.; Tao, Ye; Jacobsen, Eric N.
2010-01-01
Cationic organic intermediates participate in a wide variety of useful synthetic transformations, but their high reactivity can render selectivity in competing pathways difficult to control. We describe a strategy for inducing enantioselectivity in reactions of protio-iminium ions, wherein a chiral catalyst interacts with the highly reactive intermediate through a network of non-covalent interactions. This leads to an attenuation of the reactivity of the iminium ion, and allows high enantioselectivity in cycloadditions with electron-rich alkenes (the Povarov reaction). A detailed experimental and computational analysis of this catalyst system has revealed the precise nature of the catalyst-substrate interactions and the likely basis for enantioinduction. PMID:20167783
Belarouci, Ali; Benyattou, Taha; Letartre, Xavier; Viktorovitch, Pierre
2010-09-13
A new approach is proposed for the optimum addressing of a metallic nano-antenna (NA) with a free space optical beam. This approach relies on the use of an intermediate resonator structure that provides the appropriate modal conversion of the incoming beam. More precisely, the intermediate resonator consists in a Photonic Crystal (PC) membrane resonant structure that takes benefit of surface addressable slow Bloch modes. First, a phenomenological approach including a deep physical understanding of the NA-PC coupling and its optimization is presented. In a second step, the main features of this analysis are confirmed by numerical simulations (FDTD).
2004-03-01
probabilistic by design. Finally, as the fragments disperse, fragment density decreases, and the probability of a fragment strike drops rapidly. Given the...Any PPE subjected to such testing needs to be exposed repeatedly to several mines in order to obtain a sufficient number of strikes . This will allow...velocity of each fragment, and the location of fragment strikes cannot be controlled precisely. This means that the same test must be repeated a
Forteschi, Mauro; Zinellu, Angelo; Assaretti, Stefano; Mangoni, Arduino A; Pintus, Gianfranco; Carru, Ciriaco; Sotgia, Salvatore
2016-10-01
Plasma concentrations of choline, betaine, and dimethylglycine provide valuable information on the flow of methyl groups in key biological processes, particularly during folate deficiency states. We developed a new method to simultaneously measure these analytes in human plasma. Following sample deproteinization using acetonitrile, an aliquot was evaporated to dryness under vacuum to be then taken up by water. Finally, analytes were separated by capillary electrophoresis and detected by electrospray ionization triple-quadrupole mass spectrometry, in multiple reaction monitoring mode, using two stable isotope-labeled internal standards. Linearity of the calibration curves of each analyte was good (R(2) > 0.99). Average limits of detection (LODs) and limits of quantification (LOQs) for choline, betaine, and dimethylglycine were, respectively, 0.43, 0.62, and 0.31 μmol/L and 1.52, 2.11, and 0.97 μmol/L. Mean recovery of three replicates of two spiked concentrations levels was close to 100 % for all of the analytes. Repeatability and intermediate precision, expressed as %RSD of measurements, were <9 %. The method, applied to measure analytes in samples from 30 patients with chronic kidney disease and 30 age- and sex-matched healthy controls, was able to detect differences between groups and the sexes.
Bolzan, Cátia M; Caldas, Sergiane S; Guimarães, Bruno S; Primel, Ednei G
2016-09-01
A simple, rapid, and sensitive method for the determination of atrazine, simazine, cyproconazole, tebuconazole, and epoxiconazole in mineral water employing the dispersive liquid-liquid microextraction with solidification of a floating organic drop with determination by liquid chromatography tandem mass spectrometry has been developed. A mixed solution of 250 μL 1-dodecanol and 1250 μL methanol was injected rapidly into 10 mL aqueous solution (pH 7.0) with 2% w/v NaCl. After centrifugation for 5 min at 2000 rpm, the organic solvent droplets floated on the surface of the aqueous solution and the floating solvent solidified. The method limits of detection were between 3.75 and 37.5 ng/L and limits of quantification were between 12.5 and 125 ng/L. The recoveries ranged from 70 to 118% for repeatability and between 76 and 95% for intermediate precision with a relative standard deviation from 2 to 18% for all compounds. Low matrix effect was observed. The proposed method can be successfully applied in routine analysis for determination of pesticide residues in mineral water samples, allowing for monitoring of triazine and triazoles at levels below the regulatory limits set by international and national legislations. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Morlock, Gertrud E; Meyer, Stephanie; Zimmermann, Benno F; Roussel, Jean-Marc
2014-07-11
A high-performance TLC (HPTLC) method was newly developed and validated for analysis of 7 steviol glycosides in 6 different types of food and Stevia formulations. After a minimized one-step sample preparation, 21 samples were developed in parallel, allowing an effective food screening. Depending on the sample application volume, the method was suited to analyze food sample concentrations in the mg/kg range. LOQs of stevioside in natural yoghurt matrix spiked at 0.02, 0.13 and 0.2% were determined by the calibration curve method to be 12ng/band (peak height). ANOVA was successfully passed to prove data homogeneity in the working range (30-600ng/band). The accuracy (recovery tolerance limit, 92-120%), repeatability (3.1-5.4%) and intermediate precision (4.0-8.4%) were determined for stevioside in milk-based matrix including sample preparation and recovery rates at 3 different concentration levels. For the first time, the recording of HPTLC-ESI-MS spectra via the TLC-MS Interface was demonstrated for rebaudioside A. HPTLC contents for rebaudioside A were compared with results of two (U)HPLC methods. The running costs and analysis time of the three different methods were discussed in detail with regard to screening of food products. Copyright © 2014 Elsevier B.V. All rights reserved.
A new perspective on nonprescription statins: an opportunity for patient education and involvement.
Fuster, Valentin
2007-09-01
Education of the public and encouragement of patients' involvement in their own health care have been repeatedly proved effective means of increasing health awareness, promoting lifestyle modifications, and improving early disease detection in a variety of clinical scenarios. Despite substantial efforts from different public and private organizations to educate the population on cardiovascular risk, coronary heart disease remains the leading cause of death in the United States, and its prevalence continues to grow. Therefore, alternative approaches with the potential to elicit a meaningful impact in the community deserve consideration. A nonprescription statin program could provide consumers with a tool of proved benefit in cardiovascular risk prevention. The magnitude of the target population (millions of subjects with intermediate to high risk), as well as the safety and efficacy profile of lovastatin 20 mg, support the consideration of this drug for "over-the-counter" availability. Moreover, a nonprescription statin program could represent a unique opportunity not only to enhance patients' involvement in primary prevention but also to reinforce the education of the public and to encourage interaction with health care providers. The success of such a program will undoubtedly require precise labeling of the risks and benefits of the therapy, as well as active support and participation from major medical organizations. In conclusion, nonprescription statin availability, through enhanced unique patients' involvement, offers the potential for enormous public health benefit.
Quantifying low-frequency revertants in oral poliovirus vaccine using next generation sequencing.
Sarcey, Eric; Serres, Aurélie; Tindy, Fabrice; Chareyre, Audrey; Ng, Siemon; Nicolas, Marine; Vetter, Emmanuelle; Bonnevay, Thierry; Abachin, Eric; Mallet, Laurent
2017-08-01
Spontaneous reversion to neurovirulence of live attenuated oral poliovirus vaccine (OPV) serotype 3 (chiefly involving the n.472U>C mutation), must be monitored during production to ensure vaccine safety and consistency. Mutant analysis by polymerase chain reaction and restriction enzyme cleavage (MAPREC) has long been endorsed by the World Health Organization as the preferred in vitro test for this purpose; however, it requires radiolabeling, which is no longer supported by many laboratories. We evaluated the performance and suitability of next generation sequencing (NGS) as an alternative to MAPREC. The linearity of NGS was demonstrated at revertant concentrations equivalent to the study range of 0.25%-1.5%. NGS repeatability and intermediate precision were comparable across all tested samples, and NGS was highly reproducible, irrespective of sequencing platform or analysis software used. NGS was performed on OPV serotype 3 working seed lots and monovalent bulks (n=21) that were previously tested using MAPREC, and which covered the representative range of vaccine production. Percentages of 472-C revertants identified by NGS and MAPREC were comparable and highly correlated (r≥0.80), with a Pearson correlation coefficient of 0.95585 (p<0.0001). NGS demonstrated statistically equivalent performance to that of MAPREC for quantifying low-frequency OPV serotype 3 revertants, and offers a valid alternative to MAPREC. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.
Salgueiro-González, N; Turnes-Carou, I; Muniategui-Lorenzo, S; López-Mahía, P; Prada-Rodríguez, D
2015-02-27
A novel and Green analytical methodology for the determination of alkylphenols (4-tert-octylphenol, 4-n-octylphenol, 4-n-nonylphenol, nonylphenol) in sediments was developed and validated. The method was based on pressurized hot water extraction (PHWE) followed by miniaturized membrane assisted solvent extraction (MASE) and liquid chromatography-electrospray ionization tandem mass spectrometry detection (LC-ESI-MS/MS). The extraction conditions were optimized by a Plackett-Burman design in order to minimize the number of assays according to Green principles. Matrix effect was studied and compensated using deuterated labeled standards as surrogate standards for the quantitation of the target compounds. The analytical features of the method were satisfactory: relative recoveries varied between 92 and 103% and repeatability and intermediate precision were <9% for all compounds. Quantitation limits of the method (MQL) ranged from 0.061 (4-n-nonylphenol) to 1.7ngg(-1) dry weight (nonylphenol). Sensitivity, selectivity, automaticity and fastness are the main advantages of the exposed methodology. Reagent consumption, analysis time and waste generation were minimized. The "greenness" of the proposed method was evaluated using an analytical Eco-Scale approach and satisfactory results were obtained. The applicability of the proposed method was demonstrated analysing sediment samples of Galicia coast (NW of Spain) and the ubiquity of alkylphenols in the environment was demonstrated. Copyright © 2015 Elsevier B.V. All rights reserved.
Gil-Agustí, M; Carda-Broch, S; Monferrer-Pons, Ll; Esteve-Romero, J
2007-07-13
Two biogenic amines, tryptamine and tyramine, and their precursors, tryptophan and tyrosine, were determined by a liquid chromatographic procedure. A hybrid micellar mobile phase of sodium dodecyl sulphate (SDS) and 1-propanol, a C18 column and electrochemical detection were used. A pH study in the range of 3-9 was performed and pH 3 was finally selected in accordance with resolution and analysis time. Oxidation potential was also checked in the range 0.6-0.9V: the maximum area obtained in all those potentials was at 0.8V, which was selected to carry out the analysis using a sequence of pulsed amperometric detection waveform. The four compounds were resolved using a mobile phase of 0.15M SDS-5% 1-propanol with an analysis time of 16 min. Repeatabilities and intermediate precision were evaluated at three different concentrations for each compound with RSD values lower than 2.6 and 4.8%, respectively. Limits of detection and quantification were also obtained within the 10-40 and 33-135 ng/ml ranges, respectively. Finally, the applicability of the procedure was tested in several types of wine and no matrix effect was observed. The possibility of direct sample introduction simplifies and greatly expedites the treatments with reduced cost, improving the accuracy of the procedures.
Škereňová, Markéta; Mikulová, Veronika; Čapoun, Otakar; Zima, Tomáš
2016-01-01
Nowadays, on-a-chip capillary electrophoresis is a routine method for the detection of PCR fragments. The Agilent 2100 Bioanalyzer was one of the first commercial devices in this field. Our project was designed to study the characteristics of Agilent DNA 1000 kit in PCR fragment analysis as a part of circulating tumour cell (CTC) detection technique. Despite the common use of this kit a complex analysis of the results from a long-term project is still missing. A commercially available Agilent DNA 1000 kit was used as a final step in the CTC detection (AdnaTest) for the determination of the presence of PCR fragments generated by Multiplex PCR. Data from 30 prostate cancer patients obtained during two years of research were analyzed to determine the trueness and precision of the PCR fragment size determination. Additional experiments were performed to demonstrate the precision (repeatability, reproducibility) and robustness of PCR fragment concentration determination. The trueness and precision of the size determination was below 3% and 2% respectively. The repeatability of the concentration determination was below 15%. The difference in concentration determination increases when Multiplex-PCR/storage step is added between the two measurements of one sample. The characteristics established in our study are in concordance with the manufacturer's specifications established for a ladder as a sample. However, the concentration determination may vary depending on chip preparation, sample storage and concentration. The 15% variation of concentration determination repeatability was shown to be partly proportional and can be suppressed by proper normalization.
Superior accuracy of model-based radiostereometric analysis for measurement of polyethylene wear
Stilling, M.; Kold, S.; de Raedt, S.; Andersen, N. T.; Rahbek, O.; Søballe, K.
2012-01-01
Objectives The accuracy and precision of two new methods of model-based radiostereometric analysis (RSA) were hypothesised to be superior to a plain radiograph method in the assessment of polyethylene (PE) wear. Methods A phantom device was constructed to simulate three-dimensional (3D) PE wear. Images were obtained consecutively for each simulated wear position for each modality. Three commercially available packages were evaluated: model-based RSA using laser-scanned cup models (MB-RSA), model-based RSA using computer-generated elementary geometrical shape models (EGS-RSA), and PolyWare. Precision (95% repeatability limits) and accuracy (Root Mean Square Errors) for two-dimensional (2D) and 3D wear measurements were assessed. Results The precision for 2D wear measures was 0.078 mm, 0.102 mm, and 0.076 mm for EGS-RSA, MB-RSA, and PolyWare, respectively. For the 3D wear measures the precision was 0.185 mm, 0.189 mm, and 0.244 mm for EGS-RSA, MB-RSA, and PolyWare respectively. Repeatability was similar for all methods within the same dimension, when compared between 2D and 3D (all p > 0.28). For the 2D RSA methods, accuracy was below 0.055 mm and at least 0.335 mm for PolyWare. For 3D measurements, accuracy was 0.1 mm, 0.2 mm, and 0.3 mm for EGS-RSA, MB-RSA and PolyWare respectively. PolyWare was less accurate compared with RSA methods (p = 0.036). No difference was observed between the RSA methods (p = 0.10). Conclusions For all methods, precision and accuracy were better in 2D, with RSA methods being superior in accuracy. Although less accurate and precise, 3D RSA defines the clinically relevant wear pattern (multidirectional). PolyWare is a good and low-cost alternative to RSA, despite being less accurate and requiring a larger sample size. PMID:23610688
Few millimeter precision for baselines in the California Permanent GPS Geodetic Array
NASA Technical Reports Server (NTRS)
Lindqwister, Ulf J.; Zumberge, James F.; Webb, Frank H.; Blewitt, Geoffrey
1991-01-01
Geodetic measurements with Rogue GPS receivers from sites in the California Permanent GPS geodetic Array (PGGA) have been analyzed using the GIPSY orbit-determination and baseline-estimation software. Based on an unbiased selection of 23 daily measurements spanning 8 months, the LF contributions to the long-term repeatabilities of baseline measurements are approximately 5, 3, and 8 mm for the east, north, and vertical components. Short-term contributions to the long-term repeatabilities were evaluated by examining data from the week of October 21, 1990, which showed the lowest short-term scatter. For this week, daily repeatabilities of 2-3 mm in the horizontal and 4 mm in the vertical have been achieved for the 172-km JPL-Pinyon baseline, consistent with carrier phase date noise of about 6 mm. High quality (less than about 5 mm) repeatabilities have been achieved for all components of the other baselines as well.
Exploring the repeat protein universe through computational protein design
Brunette, TJ; Parmeggiani, Fabio; Huang, Po-Ssu; ...
2015-12-16
A central question in protein evolution is the extent to which naturally occurring proteins sample the space of folded structures accessible to the polypeptide chain. Repeat proteins composed of multiple tandem copies of a modular structure unit are widespread in nature and have critical roles in molecular recognition, signalling, and other essential biological processes. Naturally occurring repeat proteins have been re-engineered for molecular recognition and modular scaffolding applications. In this paper, we use computational protein design to investigate the space of folded structures that can be generated by tandem repeating a simple helix–loop–helix–loop structural motif. Eighty-three designs with sequences unrelatedmore » to known repeat proteins were experimentally characterized. Of these, 53 are monomeric and stable at 95 °C, and 43 have solution X-ray scattering spectra consistent with the design models. Crystal structures of 15 designs spanning a broad range of curvatures are in close agreement with the design models with root mean square deviations ranging from 0.7 to 2.5 Å. Finally, our results show that existing repeat proteins occupy only a small fraction of the possible repeat protein sequence and structure space and that it is possible to design novel repeat proteins with precisely specified geometries, opening up a wide array of new possibilities for biomolecular engineering.« less
Kay, Chris; Collins, Jennifer A; Wright, Galen E B; Baine, Fiona; Miedzybrodzka, Zosia; Aminkeng, Folefac; Semaka, Alicia J; McDonald, Cassandra; Davidson, Mark; Madore, Steven J; Gordon, Erynn S; Gerry, Norman P; Cornejo-Olivas, Mario; Squitieri, Ferdinando; Tishkoff, Sarah; Greenberg, Jacquie L; Krause, Amanda; Hayden, Michael R
2018-04-01
Huntington disease (HD) is the most common monogenic neurodegenerative disorder in populations of European ancestry, but occurs at lower prevalence in populations of East Asian or black African descent. New mutations for HD result from CAG repeat expansions of intermediate alleles (IAs), usually of paternal origin. The differing prevalence of HD may be related to the rate of new mutations in a population, but no comparative estimates of IA frequency or the HD new mutation rate are available. In this study, we characterize IA frequency and the CAG repeat distribution in fifteen populations of diverse ethnic origin. We estimate the HD new mutation rate in a series of populations using molecular IA expansion rates. The frequency of IAs was highest in Hispanic Americans and Northern Europeans, and lowest in black Africans and East Asians. The prevalence of HD correlated with the frequency of IAs by population and with the proportion of IAs found on the HD-associated A1 haplotype. The HD new mutation rate was estimated to be highest in populations with the highest frequency of IAs. In European ancestry populations, one in 5,372 individuals from the general population and 7.1% of individuals with an expanded CAG repeat in the HD range are estimated to have a molecular new mutation. Our data suggest that the new mutation rate for HD varies substantially between populations, and that IA frequency and haplotype are closely linked to observed epidemiological differences in the prevalence of HD across major ancestry groups in different countries. © 2018 Wiley Periodicals, Inc.
History, rare, and multiple events of mechanical unfolding of repeat proteins
NASA Astrophysics Data System (ADS)
Sumbul, Fidan; Marchesi, Arin; Rico, Felix
2018-03-01
Mechanical unfolding of proteins consisting of repeat domains is an excellent tool to obtain large statistics. Force spectroscopy experiments using atomic force microscopy on proteins presenting multiple domains have revealed that unfolding forces depend on the number of folded domains (history) and have reported intermediate states and rare events. However, the common use of unspecific attachment approaches to pull the protein of interest holds important limitations to study unfolding history and may lead to discarding rare and multiple probing events due to the presence of unspecific adhesion and uncertainty on the pulling site. Site-specific methods that have recently emerged minimize this uncertainty and would be excellent tools to probe unfolding history and rare events. However, detailed characterization of these approaches is required to identify their advantages and limitations. Here, we characterize a site-specific binding approach based on the ultrastable complex dockerin/cohesin III revealing its advantages and limitations to assess the unfolding history and to investigate rare and multiple events during the unfolding of repeated domains. We show that this approach is more robust, reproducible, and provides larger statistics than conventional unspecific methods. We show that the method is optimal to reveal the history of unfolding from the very first domain and to detect rare events, while being more limited to assess intermediate states. Finally, we quantify the forces required to unfold two molecules pulled in parallel, difficult when using unspecific approaches. The proposed method represents a step forward toward more reproducible measurements to probe protein unfolding history and opens the door to systematic probing of rare and multiple molecule unfolding mechanisms.
Aboud, Maurice J; Gassmann, Marcus; McCord, Bruce
2015-09-01
There are situations in which it is important to quickly and positively identify an individual. Examples include suspects detained in the neighborhood of a bombing or terrorist incident, individuals detained attempting to enter or leave the country, and victims of mass disasters. Systems utilized for these purposes must be fast, portable, and easy to maintain. DNA typing methods provide the best biometric information yielding identity, kinship, and geographical origin, but they are not portable and rapid. This study details the development of a portable short-channel microfluidic device based on a modified Agilent 2100 bioanalyzer for applications in forensic genomics. The system utilizes a denaturing polymer matrix with dual-channel laser-induced fluorescence and is capable of producing a genotype in 80 sec. The device was tested for precision and resolution using an allelic ladder created from 6 short tandem repeat (STR) loci and a sex marker (amelogenin). The results demonstrated a precision of 0.09-0.21 bp over the entire size range and resolution values from 2.5 to 4.1 bp. Overall, the results demonstrate the chip provides a portable, rapid, and precise method for screening amplified short tandem repeats and human identification screening. © 2015 American Academy of Forensic Sciences.
1993-04-01
return because the Regardless of how the remainder of the clean- package would have a higher franchise value up is funded, structured, or scheduled...estate assets); change in interest rates, reflect changing macroeconomic conditions. These events also 8. Changes in the tax law. may not be repeated... International Perspective," Bank of England Quarterly refers to funds being intermediated by financial institu- Bulletin, vol. 31, no. I tFebruary
Strategies for high-precision Global Positioning System orbit determination
NASA Technical Reports Server (NTRS)
Lichten, Stephen M.; Border, James S.
1987-01-01
Various strategies for the high-precision orbit determination of the GPS satellites are explored using data from the 1985 GPS field test. Several refinements to the orbit determination strategies were found to be crucial for achieving high levels of repeatability and accuracy. These include the fine tuning of the GPS solar radiation coefficients and the ground station zenith tropospheric delays. Multiday arcs of 3-6 days provided better orbits and baselines than the 8-hr arcs from single-day passes. Highest-quality orbits and baselines were obtained with combined carrier phase and pseudorange solutions.
Wang, Yongyi; Xu, Jinzhong; Qu, Haibin
2013-01-01
A simple and accurate analytical method was developed for simultaneous quantification of three steroidal saponins in the roots of Ophiopogon japonicus via high-performance liquid chromatography (HPLC) with mass spectrometry (MS) in this study. Separation was performed on a Tigerkin C(18) column and detection was performed by mass spectrometry. A mobile phase consisted of 0.02% formic acid in water (v/v) and 0.02% formic acid in acetonitrile (v/v) was used with a flow rate of 0.5 mL min(-1). The quantitative HPLC-MS method was validated for linearity, precision, repeatability, stability, recovery, limits of detection and quantification. This developed method provides good linearity (r >0.9993), intra- and inter-day precisions (RSD <4.18%), repeatability (RSD <5.05%), stability (RSD <2.08%) and recovery (93.82-102.84%) for three steroidal saponins. It could be considered as a suitable quality control method for O. japonicus.
NASA Astrophysics Data System (ADS)
Cabalín, L. M.; González, A.; Ruiz, J.; Laserna, J. J.
2010-08-01
Statistical uncertainty in the quantitative analysis of solid samples in motion by laser-induced breakdown spectroscopy (LIBS) has been assessed. For this purpose, a LIBS demonstrator was designed and constructed in our laboratory. The LIBS system consisted of a laboratory-scale conveyor belt, a compact optical module and a Nd:YAG laser operating at 532 nm. The speed of the conveyor belt was variable and could be adjusted up to a maximum speed of 2 m s - 1 . Statistical uncertainty in the analytical measurements was estimated in terms of precision (reproducibility and repeatability) and accuracy. The results obtained by LIBS on shredded scrap samples under real conditions have demonstrated that the analytical precision and accuracy of LIBS is dependent on the sample geometry, position on the conveyor belt and surface cleanliness. Flat, relatively clean scrap samples exhibited acceptable reproducibility and repeatability; by contrast, samples with an irregular shape or a dirty surface exhibited a poor relative standard deviation.
Muller, Lyle; Piantoni, Giovanni; Koller, Dominik; Cash, Sydney S; Halgren, Eric; Sejnowski, Terrence J
2016-01-01
During sleep, the thalamus generates a characteristic pattern of transient, 11-15 Hz sleep spindle oscillations, which synchronize the cortex through large-scale thalamocortical loops. Spindles have been increasingly demonstrated to be critical for sleep-dependent consolidation of memory, but the specific neural mechanism for this process remains unclear. We show here that cortical spindles are spatiotemporally organized into circular wave-like patterns, organizing neuronal activity over tens of milliseconds, within the timescale for storing memories in large-scale networks across the cortex via spike-time dependent plasticity. These circular patterns repeat over hours of sleep with millisecond temporal precision, allowing reinforcement of the activity patterns through hundreds of reverberations. These results provide a novel mechanistic account for how global sleep oscillations and synaptic plasticity could strengthen networks distributed across the cortex to store coherent and integrated memories. DOI: http://dx.doi.org/10.7554/eLife.17267.001 PMID:27855061
Origin-Dependent Inverted-Repeat Amplification: Tests of a Model for Inverted DNA Amplification
Brewer, Bonita J.; Payen, Celia; Di Rienzi, Sara C.; Higgins, Megan M.; Ong, Giang; Dunham, Maitreya J.; Raghuraman, M. K.
2015-01-01
DNA replication errors are a major driver of evolution—from single nucleotide polymorphisms to large-scale copy number variations (CNVs). Here we test a specific replication-based model to explain the generation of interstitial, inverted triplications. While no genetic information is lost, the novel inversion junctions and increased copy number of the included sequences create the potential for adaptive phenotypes. The model—Origin-Dependent Inverted-Repeat Amplification (ODIRA)—proposes that a replication error at pre-existing short, interrupted, inverted repeats in genomic sequences generates an extrachromosomal, inverted dimeric, autonomously replicating intermediate; subsequent genomic integration of the dimer yields this class of CNV without loss of distal chromosomal sequences. We used a combination of in vitro and in vivo approaches to test the feasibility of the proposed replication error and its downstream consequences on chromosome structure in the yeast Saccharomyces cerevisiae. We show that the proposed replication error—the ligation of leading and lagging nascent strands to create “closed” forks—can occur in vitro at short, interrupted inverted repeats. The removal of molecules with two closed forks results in a hairpin-capped linear duplex that we show replicates in vivo to create an inverted, dimeric plasmid that subsequently integrates into the genome by homologous recombination, creating an inverted triplication. While other models have been proposed to explain inverted triplications and their derivatives, our model can also explain the generation of human, de novo, inverted amplicons that have a 2:1 mixture of sequences from both homologues of a single parent—a feature readily explained by a plasmid intermediate that arises from one homologue and integrates into the other homologue prior to meiosis. Our tests of key features of ODIRA lend support to this mechanism and suggest further avenues of enquiry to unravel the origins of interstitial, inverted CNVs pivotal in human health and evolution. PMID:26700858
Origin-Dependent Inverted-Repeat Amplification: Tests of a Model for Inverted DNA Amplification.
Brewer, Bonita J; Payen, Celia; Di Rienzi, Sara C; Higgins, Megan M; Ong, Giang; Dunham, Maitreya J; Raghuraman, M K
2015-12-01
DNA replication errors are a major driver of evolution--from single nucleotide polymorphisms to large-scale copy number variations (CNVs). Here we test a specific replication-based model to explain the generation of interstitial, inverted triplications. While no genetic information is lost, the novel inversion junctions and increased copy number of the included sequences create the potential for adaptive phenotypes. The model--Origin-Dependent Inverted-Repeat Amplification (ODIRA)-proposes that a replication error at pre-existing short, interrupted, inverted repeats in genomic sequences generates an extrachromosomal, inverted dimeric, autonomously replicating intermediate; subsequent genomic integration of the dimer yields this class of CNV without loss of distal chromosomal sequences. We used a combination of in vitro and in vivo approaches to test the feasibility of the proposed replication error and its downstream consequences on chromosome structure in the yeast Saccharomyces cerevisiae. We show that the proposed replication error-the ligation of leading and lagging nascent strands to create "closed" forks-can occur in vitro at short, interrupted inverted repeats. The removal of molecules with two closed forks results in a hairpin-capped linear duplex that we show replicates in vivo to create an inverted, dimeric plasmid that subsequently integrates into the genome by homologous recombination, creating an inverted triplication. While other models have been proposed to explain inverted triplications and their derivatives, our model can also explain the generation of human, de novo, inverted amplicons that have a 2:1 mixture of sequences from both homologues of a single parent--a feature readily explained by a plasmid intermediate that arises from one homologue and integrates into the other homologue prior to meiosis. Our tests of key features of ODIRA lend support to this mechanism and suggest further avenues of enquiry to unravel the origins of interstitial, inverted CNVs pivotal in human health and evolution.
Yokoo, Takeshi; Serai, Suraj D; Pirasteh, Ali; Bashir, Mustafa R; Hamilton, Gavin; Hernando, Diego; Hu, Houchun H; Hetterich, Holger; Kühn, Jens-Peter; Kukuk, Guido M; Loomba, Rohit; Middleton, Michael S; Obuchowski, Nancy A; Song, Ji Soo; Tang, An; Wu, Xinhuai; Reeder, Scott B; Sirlin, Claude B
2018-02-01
Purpose To determine the linearity, bias, and precision of hepatic proton density fat fraction (PDFF) measurements by using magnetic resonance (MR) imaging across different field strengths, imager manufacturers, and reconstruction methods. Materials and Methods This meta-analysis was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A systematic literature search identified studies that evaluated the linearity and/or bias of hepatic PDFF measurements by using MR imaging (hereafter, MR imaging-PDFF) against PDFF measurements by using colocalized MR spectroscopy (hereafter, MR spectroscopy-PDFF) or the precision of MR imaging-PDFF. The quality of each study was evaluated by using the Quality Assessment of Studies of Diagnostic Accuracy 2 tool. De-identified original data sets from the selected studies were pooled. Linearity was evaluated by using linear regression between MR imaging-PDFF and MR spectroscopy-PDFF measurements. Bias, defined as the mean difference between MR imaging-PDFF and MR spectroscopy-PDFF measurements, was evaluated by using Bland-Altman analysis. Precision, defined as the agreement between repeated MR imaging-PDFF measurements, was evaluated by using a linear mixed-effects model, with field strength, imager manufacturer, reconstruction method, and region of interest as random effects. Results Twenty-three studies (1679 participants) were selected for linearity and bias analyses and 11 studies (425 participants) were selected for precision analyses. MR imaging-PDFF was linear with MR spectroscopy-PDFF (R 2 = 0.96). Regression slope (0.97; P < .001) and mean Bland-Altman bias (-0.13%; 95% limits of agreement: -3.95%, 3.40%) indicated minimal underestimation by using MR imaging-PDFF. MR imaging-PDFF was precise at the region-of-interest level, with repeatability and reproducibility coefficients of 2.99% and 4.12%, respectively. Field strength, imager manufacturer, and reconstruction method each had minimal effects on reproducibility. Conclusion MR imaging-PDFF has excellent linearity, bias, and precision across different field strengths, imager manufacturers, and reconstruction methods. © RSNA, 2017 Online supplemental material is available for this article. An earlier incorrect version of this article appeared online. This article was corrected on October 2, 2017.
Research of flaw image collecting and processing technology based on multi-baseline stereo imaging
NASA Astrophysics Data System (ADS)
Yao, Yong; Zhao, Jiguang; Pang, Xiaoyan
2008-03-01
Aiming at the practical situations such as accurate optimal design, complex algorithms and precise technical demands of gun bore flaw image collecting, the design frame of a 3-D image collecting and processing system based on multi-baseline stereo imaging was presented in this paper. This system mainly including computer, electrical control box, stepping motor and CCD camera and it can realize function of image collection, stereo matching, 3-D information reconstruction and after-treatments etc. Proved by theoretical analysis and experiment results, images collected by this system were precise and it can slake efficiently the uncertainty problem produced by universally veins or repeated veins. In the same time, this system has faster measure speed and upper measure precision.
Mizutani, Ken-Ichi
2018-01-01
Neurogenesis encompasses an entire set of events that leads to the generation of newborn neurons from neural stem cells and more committed progenitor cells, including cell division, the production of migratory precursors and their progeny, differentiation and integration into circuits. In particular, the precise control of neuronal migration and morphological changes is essential for the development of the neocortex. Postmitotic cells within the intermediate zone have been found to transiently assume a characteristic "multipolar" morphology, after which a multipolar-to-bipolar transition occurs before the cells enter the cortical plate; however, the importance of this multipolar phase in the establishment of mature cortical cytoarchitecture and the precise genetic control of this phase remains largely unknown. Thus, this review article focuses on the multipolar phase in the developing neocortex. It begins by summarizing the molecular mechanism that underlies multipolar migration for the regulation of each step in multipolar phase in intermediate zone. The physiological significance of this multipolar phase in the establishment of mature cortical lamination and neurodevelopmental disorders associated with migration defects is then described. © 2017 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.
NASA Astrophysics Data System (ADS)
Wysocka, Irena; Vassileva, Emilia
2017-02-01
Analytical procedure for the determination of fourteen rare earth elements (REEs) in the seawater samples has been developed and validated. The elements (La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu) at ultra-trace level were measured by high resolution sector field inductively coupled plasma mass spectrometry (HR ICP-SFMS) after off-line analytes pre-concentration and matrix separation. The sample pre-treatment was carried out by commercially available automated system seaFAST-pico™, which is a low-pressure ion chromatography technique, based on solid phase extraction principles. Efficient elimination of seawater matrix and up to 50-fold pre-concentration of REEs enabled their accurate and precise quantification at ng L- 1 level. A validation approach in line with the requirements of ISO/IEC 17025 standard and Eurachem guidelines were followed. With this in mind, selectivity, working range, linearity, recovery (from 92% to 102%), repeatability (1%-4%), intermediate precision (2%-6%), limits of detection (0.001-0.08 ng L- 1) were systematically assessed. The total uncertainty associated to each result was estimated and the main sources of uncertainty sorted out. All major contributions to the combined uncertainty of the obtained results were identified and propagated together, following the ISO/GUM guidelines. The relative expanded uncertainty was estimated at range from 10.4% to 11.6% (k = 2). Demonstration of traceability of measurement results was also presented. Due to the low limits of detection, this method enables the determination of ultra-low levels of REEs in the open seawater as well as small variations in their concentrations. The potential of the proposed analytical procedure, based on combination of seaFAST-pico™ for sample preparation and HR ICP-SFMS, was demonstrated by direct analysis of seawater form different regions of the world.
Teglia, Carla M; Cámara, María S; Goicoechea, Héctor C
2014-12-01
This paper reports the development of a method based on high-performance liquid chromatography (HPLC) coupled to second-order data modeling with multivariate curve resolution-alternating least-squares (MCR-ALS) for quantification of retinoic acid and its main isomers in plasma in only 5.5 min. The compounds retinoic acid (RA), 13-cis-retinoic acid, 9-cis-retinoic acid, and 9,13-di-cis-retinoic acid were partially separated by use of a Poroshell 120 EC-C18 (3.0 mm × 30 mm, 2.7 μm particle size) column. Overlapping not only among the target analytes but also with the plasma interferents was resolved by exploiting the second-order advantage of the multi-way calibration. A validation study led to the following results: trueness with recoveries of 98.5-105.9 % for RA, 95.7-110.1 % for 13-cis-RA, 97.1-110.8 % for 9-cis-RA, and 99.5-110.9 % for 9,13-di-cis-RA; repeatability with RSD of 3.5-3.1 % for RA, 3.5-1.5 % for 13-cis-RA, 4.6-2.7 % for 9-cis-RA, and 5.2-2.7 % for 9,13-di-cis-RA (low and high levels); and intermediate precision (inter-day precision) with RSD of 3.8-3.0 % for RA, 2.9-2.4 % for 13-cis-RA, 3.6-3.2 % for 9,13-di-cis-RA, and 3.2-2.9 % for 9-cis-RA (low and high levels). In addition, a robustness study revealed the method was suitable for monitoring patients with dermatological diseases treated with pharmaceutical products containing RA and 13-cis-RA.
Silva, Pedro; Silva, Catarina L; Perestrelo, Rosa; Nunes, Fernando M; Câmara, José S
2017-10-20
Sugarcane honey (SCH) is one of the Madeira Island products par excellence and it is now popular worldwide. Its sui generis and peculiar sensory properties, explained by a variety of volatile compounds including furanic derivatives (FDs), arise mainly from manufacturing and storage conditions. A simple high-throughput approach based on semi-automatic microextraction by packed sorbent (MEPS) combined with ultra-high performance liquid chromatography (UHPLC) was developed and validated for identification and quantification of target FDs in sugarcane honey. A Quality-by-Design (QbD) approach was used as a powerful strategy to optimize analytical conditions for high throughput analysis of FDs in complex sugar-rich food matrices. The optimum point into MEPS-Method Operable Design: Region (MODR) was obtained with R-CX sorbent, acetonitrile (ACN) as elution solvent, three loading cycles and 500μL of sample volume. The optimum point into UHPLC-MODR was obtained with a CORTECS column operating at a temperature of 50°C, ACN as eluent and a flow rate of 125μLmin -1 . The robustness was demonstrated by Monte Carlo simulation and capability analysis for estimation of residual errors. The concentration-response relationship for all FDs were described by polynomial function models, being confirmed by Fisher variance (F-test). The% recoveries were in a range of 91.9-112.1%. Good method precision was observed, yielding relative standard deviations (RSDs) less than 4.9% for repeatability and 8.8% for intermediate precision. The limits of quantitation for the analytes ranged from 30.6 to 737.7μgkg -1 . The MEPS R-CX /UHPLC CORTECS -PDA method revealed an effective and potential analytical tool for SCH authenticity control based on target analysis of FDs allowing a strict control and differentiation from other similar or adulterated products. Copyright © 2017 Elsevier B.V. All rights reserved.
The Spring 1985 high precision baseline test of the JPL GPS-based geodetic system
NASA Technical Reports Server (NTRS)
Davidson, John M.; Thornton, Catherine L.; Stephens, Scott A.; Blewitt, Geoffrey; Lichten, Stephen M.; Sovers, Ojars J.; Kroger, Peter M.; Skrumeda, Lisa L.; Border, James S.; Neilan, Ruth E.
1987-01-01
The Spring 1985 High Precision Baseline Test (HPBT) was conducted. The HPBT was designed to meet a number of objectives. Foremost among these was the demonstration of a level of accuracy of 1 to 2:10 to the 7th power, or better, for baselines ranging in length up to several hundred kilometers. These objectives were all met with a high degree of success, with respect to the demonstration of system accuracy in particular. The results from six baselines ranging in length from 70 to 729 km were examined for repeatability and, in the case of three baselines, were compared to results from colocated VLBI systems. Repeatability was found to be 5:10 to the 8th power (RMS) for the north baseline coordinate, independent of baseline length, while for the east coordinate RMS repeatability was found to be larger than this by factors of 2 to 4. The GPS-based results were found to be in agreement with those from colocated VLBI measurements, when corrected for the physical separations of the VLBI and CPG antennas, at the level of 1 to 2:10 to the 7th power in all coordinates, independent of baseline length. The results for baseline repeatability are consistent with the current GPA error budget, but the GPS-VLBI intercomparisons disagree at a somewhat larger level than expected. It is hypothesized that these differences may result from errors in the local survey measurements used to correct for the separations of the GPS and VLBI antenna reference centers.
Repeatability and Reproducibility of Virtual Subjective Refraction.
Perches, Sara; Collados, M Victoria; Ares, Jorge
2016-10-01
To establish the repeatability and reproducibility of a virtual refraction process using simulated retinal images. With simulation software, aberrated images corresponding with each step of the refraction process were calculated following the typical protocol of conventional subjective refraction. Fifty external examiners judged simulated retinal images until the best sphero-cylindrical refraction and the best visual acuity were achieved starting from the aberrometry data of three patients. Data analyses were performed to assess repeatability and reproducibility of the virtual refraction as a function of pupil size and aberrometric profile of different patients. SD values achieved in three components of refraction (M, J0, and J45) are lower than 0.25D in repeatability analysis. Regarding reproducibility, we found SD values lower than 0.25D in the most cases. When the results of virtual refraction with different pupil diameters (4 and 6 mm) were compared, the mean of differences (MoD) obtained were not clinically significant (less than 0.25D). Only one of the aberrometry profiles with high uncorrected astigmatism shows poor results for the M component in reproducibility and pupil size dependence analysis. In all cases, vision achieved was better than 0 logMAR. A comparison between the compensation obtained with virtual and conventional subjective refraction was made as an example of this application, showing good quality retinal images in both processes. The present study shows that virtual refraction has similar levels of precision as conventional subjective refraction. Moreover, virtual refraction has also shown that when high low order astigmatism is present, the refraction result is less precise and highly dependent on pupil size.
Methods for the Precise Locating and Forming of Arrays of Curved Features into a Workpiece
Gill, David Dennis; Keeler, Gordon A.; Serkland, Darwin K.; Mukherjee, Sayan D.
2008-10-14
Methods for manufacturing high precision arrays of curved features (e.g. lenses) in the surface of a workpiece are described utilizing orthogonal sets of inter-fitting locating grooves to mate a workpiece to a workpiece holder mounted to the spindle face of a rotating machine tool. The matching inter-fitting groove sets in the workpiece and the chuck allow precisely and non-kinematically indexing the workpiece to locations defined in two orthogonal directions perpendicular to the turning axis of the machine tool. At each location on the workpiece a curved feature can then be on-center machined to create arrays of curved features on the workpiece. The averaging effect of the corresponding sets of inter-fitting grooves provide for precise repeatability in determining, the relative locations of the centers of each of the curved features in an array of curved features.
Loat, C S; Craig, G; Plomin, R; Craig, I W
2006-09-01
The FMR1 gene contains a trinucleotide repeat tract which can expand from a normal size of around 30 repeats to over 200 repeats, causing mental retardation (Fragile X Syndrome). Evidence suggests that premutation males (55-200 repeats) are susceptible to a late-onset tremor/ataxia syndrome and females to premature ovarian failure, and that intermediate alleles ( approximately 41-55 repeats) and premutations may be in excess in samples with special educational needs. We explored the relationship between FMR1 allele length and cognitive ability in 621 low ability and control children assessed at 4 and 7 years, as well as 122 students with high IQ. The low and high ability and control samples showed no between-group differences in incidence of longer alleles. In males there was a significant negative correlation between allele length and non-verbal ability at 4 years (p = 0.048), academic achievement in maths (p = 0.003) and English (p = 0.011) at 7 years, and IQ in the high ability group (p = 0.018). There was a significant negative correlation between allele length and a standardised score for IQ and general cognitive ability at age 7 in the entire male sample (p = 0.002). This suggests that, within the normal spectrum of allele length, increased repeat numbers may have a limiting influence on cognitive performance.
Gan, Shi-Rui; Ni, Wang; Dong, Yi; Wang, Ning; Wu, Zhi-Ying
2015-01-01
Spinocerebellar ataxia type 3 (SCA3), also called Machado-Joseph disease (MJD), is one of the most common SCAs worldwide and caused by a CAG repeat expansion located in ATXN3 gene. Based on the CAG repeat numbers, alleles of ATXN3 can be divided into normal alleles (ANs), intermediate alleles (AIs) and expanded alleles (AEs). It was controversial whether the frequency of large normal alleles (large ANs) is related to the prevalence of SCA3 or not. And there were huge chaos in the comprehension of the specific numbers of the range of CAG repeats which is fundamental for genetic analysis of SCA3. To illustrate these issues, we made a novel CAG repeat ladder to detect CAG repeats of ATXN3 in 1003 unrelated Chinese normal individuals and studied haplotypes defined by three single nucleotide polymorphisms (SNPs) closed to ATXN3. We found that the number of CAG repeats ranged from 13 to 49, among them, 14 was the most common number. Positive skew, the highest frequency of large ANs and 4 AIs which had never been reported before were found. Also, AEs and large ANs shared the same haplotypes defined by the SNPs. Based on these data and other related studies, we presumed that de novo mutations of ATXN3 emerging from large ANs are at least one survival mechanisms of mutational ATXN3 and we can redefine the range of CAG repeats as: ANs≤44, 45 ≤AIs ≤49 and AEs≥50.
76 FR 69595 - Application of Third Party Testing Requirements; Reducing Third Party Testing Burdens
Federal Register 2010, 2011, 2012, 2013, 2014
2011-11-08
... subject to a third party testing requirement. Please identify specific technologies, except for those that... evaluate testing or screening technologies for consumer products (e.g., accuracy, precision, repeatability... than testing technologies? Should screening technologies be allowed only for third party conformity...
C9ORF72 repeat expansion in Australian and Spanish frontotemporal dementia patients.
Dobson-Stone, Carol; Hallupp, Marianne; Loy, Clement T; Thompson, Elizabeth M; Haan, Eric; Sue, Carolyn M; Panegyres, Peter K; Razquin, Cristina; Seijo-Martínez, Manuel; Rene, Ramon; Gascon, Jordi; Campdelacreu, Jaume; Schmoll, Birgit; Volk, Alexander E; Brooks, William S; Schofield, Peter R; Pastor, Pau; Kwok, John B J
2013-01-01
A hexanucleotide repeat expansion in C9ORF72 has been established as a common cause of frontotemporal dementia (FTD). However, the minimum repeat number necessary for disease pathogenesis is not known. The aims of our study were to determine the frequency of the C9ORF72 repeat expansion in two FTD patient collections (one Australian and one Spanish, combined n = 190), to examine C9ORF72 expansion allele length in a subset of FTD patients, and to examine C9ORF72 allele length in 'non-expansion' patients (those with <30 repeats). The C9ORF72 repeat expansion was detected in 5-17% of patients (21-41% of familial FTD patients). For one family, the expansion was present in the proband but absent in the mother, who was diagnosed with dementia at age 68. No association was found between C9ORF72 non-expanded allele length and age of onset and in the Spanish sample mean allele length was shorter in cases than in controls. Southern blotting analysis revealed that one of the nine 'expansion-positive' patients examined, who had neuropathologically confirmed frontotemporal lobar degeneration with TDP-43 pathology, harboured an 'intermediate' allele with a mean size of only ∼65 repeats. Our study indicates that the C9ORF72 repeat expansion accounts for a significant proportion of Australian and Spanish FTD cases. However, C9ORF72 allele length does not influence the age at onset of 'non-expansion' FTD patients in the series examined. Expansion of the C9ORF72 allele to as little as ∼65 repeats may be sufficient to cause disease.
Comparison of the carboxy-terminal DP-repeat region in the co-chaperones Hop and Hip
Nelson, Gregory M.; Huffman, Holly; Smith, David F.
2003-01-01
Functional steroid receptor complexes are assembled and maintained by an ordered pathway of interactions involving multiple components of the cellular chaperone machinery. Two of these components, Hop and Hip, serve as co-chaperones to the major heat shock proteins (Hsps), Hsp70 and Hsp90, and participate in intermediate stages of receptor assembly. In an effort to better understand the functions of Hop and Hip in the assembly process, we focused on a region of similarity located near the C-terminus of each co-chaperone. Contained within this region is a repeated sequence motif we have termed the DP repeat. Earlier mutagenesis studies implicated the DP repeat of either Hop or Hip in Hsp70 binding and in normal assembly of the co-chaperones with progesterone receptor (PR) complexes. We report here that the DP repeat lies within a protease-resistant domain that extends to or is near the C-terminus of both co-chaperones. Point mutations in the DP repeats render the C-terminal regions hypersensitive to proteolysis. In addition, a Hop DP mutant displays altered proteolytic digestion patterns, which suggest that the DP-repeat region influences the folding of other Hop domains. Although the respective DP regions of Hop and Hip share sequence and structural similarities, they are not functionally interchangeable. Moreover, a double-point mutation within the second DP-repeat unit of Hop that converts this to the sequence found in Hip disrupts Hop function; however, the corresponding mutation in Hip does not alter its function. We conclude that the DP repeats are important structural elements within a C-terminal domain, which is important for Hop and Hip function. PMID:14627198
Comparison of the carboxy-terminal DP-repeat region in the co-chaperones Hop and Hip.
Nelson, Gregory M; Huffman, Holly; Smith, David F
2003-01-01
Functional steroid receptor complexes are assembled and maintained by an ordered pathway of interactions involving multiple components of the cellular chaperone machinery. Two of these components, Hop and Hip, serve as co-chaperones to the major heat shock proteins (Hsps), Hsp70 and Hsp90, and participate in intermediate stages of receptor assembly. In an effort to better understand the functions of Hop and Hip in the assembly process, we focused on a region of similarity located near the C-terminus of each co-chaperone. Contained within this region is a repeated sequence motif we have termed the DP repeat. Earlier mutagenesis studies implicated the DP repeat of either Hop or Hip in Hsp70 binding and in normal assembly of the co-chaperones with progesterone receptor (PR) complexes. We report here that the DP repeat lies within a protease-resistant domain that extends to or is near the C-terminus of both co-chaperones. Point mutations in the DP repeats render the C-terminal regions hypersensitive to proteolysis. In addition, a Hop DP mutant displays altered proteolytic digestion patterns, which suggest that the DP-repeat region influences the folding of other Hop domains. Although the respective DP regions of Hop and Hip share sequence and structural similarities, they are not functionally interchangeable. Moreover, a double-point mutation within the second DP-repeat unit of Hop that converts this to the sequence found in Hip disrupts Hop function; however, the corresponding mutation in Hip does not alter its function. We conclude that the DP repeats are important structural elements within a C-terminal domain, which is important for Hop and Hip function.
Fuiko, R; Kotten, B; Zettl, R; Ritschl, P
2004-03-01
Cinematic and pointing procedures are used for non-image based navigated implantation during total knee replacement. Pointing procedures require an exact knowledge of the landmarks. In this anatomical study, landmarks are defined and repeatedly referenced. Precision and reproducibility are evaluated by means of an inter- and an intra-observer study. The axes of the femur and tibia are calculated using the landmarks. The specific landmarks of 30 femurs and 27 tibias were palpated by three surgeons and digitised by means of a photogrammetric system, as used intra-operatively. The recorded data were statistically evaluated. The specific landmarks can be referenced with great precision. The vectors that influence the implant position show a mean femoral deviation of 0.9 mm and a mean tibial deviation of 1.0 mm. The repeating accuracy of every observer was 1.5 mm femoral and 1.0 mm tibial. The calculated long axes at the femur and tibia thus reach a precision of 0.1 degrees (min.-max.: 0-0.9 degrees) at the femur and 0.2 degrees (.0-1.1 degrees) at the tibia. The short axes at the distal femur and proximal tibia exhibit an average deviation of from 0.7 degrees to 1.9 degrees (0-11.3 degrees). Long axes (mechanical axes) can be determined exactly but the precision of the short axes (rotational axes) is unsatisfactory, although palpation of landmarks was accurate. Therefore, palpation of more than one rotational axis at the femur and tibia is mandatory and should be visualized on the monitor during surgery.
De Vaugelade, S; Aime, M; Farcette, N; Maurel, E; Lacour, T; Thomas, C; Bouchonnet, S; Pirnay, S
2017-02-01
Compact Dry TC, a rapid method kit for determining aerobic colony counts, has been developed by Nissui Pharmaceutical Co. for food application. These plates are pre-sterilized and contain culture medium, a cold-soluble gelling agent and a colour redox indicator for rapid enumeration. In this study, the alternative method is compared with the standard method ISO 21149:2006 - Cosmetic - Microbiology - Enumeration and detection of aerobic mesophilic bacteria, for cosmetic emulsions application. An oil-in-water (o/w) cosmetic emulsion was contaminated with a pool of bacterial strains (Escherichia coli ATCC 8739, Staphylococcus aureus ATCC 6538 and Pseudomonas aeruginosa ATCC 9027). One millilitre of samples was spread on agar as described in ISO 21149. The colonies were enumerated after 3 days of incubation. At the same time, 1.2 mL samples were spread on Compact Dry TC kits. The kit was incubated at 35°C ± 1°C for 48 h, and the colonies were enumerated. Accuracy determination was carried out using six replicates at four levels of concentrations (10, 50, 100 and 250 CFU mL -1 ). The repeatability study was carried out using 12 replicates at four levels of concentrations (10, 50, 100 and 250 CFU mL -1 ). Variations relative to the analyst and to the batch of emulsion have been investigated. The linear correlation coefficients of Compact Dry TC Kit enumeration with standard method ISO 21149:2006 was 0.9999. In comparison study, no apparent differences were noted between the Compact Dry TC kit and the reference method ISO 21149, for the detection level of aerobic microorganisms. Relative accuracy, repeatability and intermediate precision studies were acceptable. In the repeatability study, the Shapiro-Wilk test has confirmed the normally distribution of the twelve assays. No significant variations in Compact Dry TC count results were observed with different analysts and different batches of emulsion. The results showed that the two compared methods 'Compact Dry TC' vs. 'conventional pour plate' performed equally well. Demonstration was achieved that the Compact Dry TC method may constitute a useful alternative tool for rapid enumeration of aerobic mesophilic bacteria in cosmetic emulsions. © 2016 Society of Cosmetic Scientists and the Société Française de Cosmétologie.
Biased distributions and decay of long interspersed nuclear elements in the chicken genome.
Abrusán, György; Krambeck, Hans-Jürgen; Junier, Thomas; Giordano, Joti; Warburton, Peter E
2008-01-01
The genomes of birds are much smaller than mammalian genomes, and transposable elements (TEs) make up only 10% of the chicken genome, compared with the 45% of the human genome. To study the mechanisms that constrain the copy numbers of TEs, and as a consequence the genome size of birds, we analyzed the distributions of LINEs (CR1's) and SINEs (MIRs) on the chicken autosomes and Z chromosome. We show that (1) CR1 repeats are longest on the Z chromosome and their length is negatively correlated with the local GC content; (2) the decay of CR1 elements is highly biased, and the 5'-ends of the insertions are lost much faster than their 3'-ends; (3) the GC distribution of CR1 repeats shows a bimodal pattern with repeats enriched in both AT-rich and GC-rich regions of the genome, but the CR1 families show large differences in their GC distribution; and (4) the few MIRs in the chicken are most abundant in regions with intermediate GC content. Our results indicate that the primary mechanism that removes repeats from the chicken genome is ectopic exchange and that the low abundance of repeats in avian genomes is likely to be the consequence of their high recombination rates.
Kayser, Jona; Haslbeck, Martin; Dempfle, Lisa; Krause, Maike; Grashoff, Carsten; Buchner, Johannes; Herrmann, Harald; Bausch, Andreas R
2013-10-15
The mechanical properties of living cells are essential for many processes. They are defined by the cytoskeleton, a composite network of protein fibers. Thus, the precise control of its architecture is of paramount importance. Our knowledge about the molecular and physical mechanisms defining the network structure remains scarce, especially for the intermediate filament cytoskeleton. Here, we investigate the effect of small heat shock proteins on the keratin 8/18 intermediate filament cytoskeleton using a well-controlled model system of reconstituted keratin networks. We demonstrate that Hsp27 severely alters the structure of such networks by changing their assembly dynamics. Furthermore, the C-terminal tail domain of keratin 8 is shown to be essential for this effect. Combining results from fluorescence and electron microscopy with data from analytical ultracentrifugation reveals the crucial role of kinetic trapping in keratin network formation. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.
Todd F. Hutchinson; Elaine Kennedy Sutherland; Daniel A. Yaussy
2005-01-01
This study quantifies prescribed fire effects at four sites in southern Ohio, from 1995 to 2002. Each site had three treatment units: an unburned control, a unit burned 2x (1996 and 1999), and a unit burned 4 x (1996-1999). Vegetation plots were stratified by an integrated moisture index (IMI) into xeric, intermediate, and mesic classes. Prior to treatments, oak (...
Kawalilak, C E; Johnston, J D; Cooper, D M L; Olszynski, W P; Kontulainen, S A
2016-02-01
Precision errors of cortical bone micro-architecture from high-resolution peripheral quantitative computed tomography (pQCT) ranged from 1 to 16 % and did not differ between automatic or manually modified endocortical contour methods in postmenopausal women or young adults. In postmenopausal women, manually modified contours led to generally higher cortical bone properties when compared to the automated method. First, the objective of the study was to define in vivo precision errors (coefficient of variation root mean square (CV%RMS)) and least significant change (LSC) for cortical bone micro-architecture using two endocortical contouring methods: automatic (AUTO) and manually modified (MOD) in two groups (postmenopausal women and young adults) from high-resolution pQCT (HR-pQCT) scans. Second, it was to compare precision errors and bone outcomes obtained with both methods within and between groups. Using HR-pQCT, we scanned twice the distal radius and tibia of 34 postmenopausal women (mean age ± SD 74 ± 7 years) and 30 young adults (27 ± 9 years). Cortical micro-architecture was determined using AUTO and MOD contour methods. CV%RMS and LSC were calculated. Repeated measures and multivariate ANOVA were used to compare mean CV% and bone outcomes between the methods within and between the groups. Significance was accepted at P < 0.05. CV%RMS ranged from 0.9 to 16.3 %. Within-group precision did not differ between evaluation methods. Compared to young adults, postmenopausal women had better precision for radial cortical porosity (precision difference 9.3 %) and pore volume (7.5 %) with MOD. Young adults had better precision for cortical thickness (0.8 %, MOD) and tibial cortical density (0.2 %, AUTO). In postmenopausal women, MOD resulted in 0.2-54 % higher values for most cortical outcomes, as well as 6-8 % lower radial and tibial cortical BMD and 2 % lower tibial cortical thickness. Results suggest that AUTO and MOD endocortical contour methods provide comparable repeatability. In postmenopausal women, manual modification of endocortical contours led to generally higher cortical bone properties when compared to the automated method, while no between-method differences were observed in young adults.
Klok, Frederikus A; Ageno, Walter; Barco, Stefano; Binder, Harald; Brenner, Benjamin; Duerschmied, Daniel; Empen, Klaus; Faggiano, Pompilio; Ficker, Joachim H; Galiè, Nazzareno; Ghuysen, Alexandre; Held, Matthias; Heydenreich, Nadine; Huisman, Menno V; Jiménez, David; Kozak, Matija; Lang, Irene M; Lankeit, Mareike; Münzel, Thomas; Petris, Antoniu; Pruszczyk, Piotr; Quitzau, Kurt; Schellong, Sebastian; Schmidt, Kai-Helge; Stefanovic, Branislav S; Verschuren, Franck; Wolf-Puetz, Anamaria; Meyer, Guy; Konstantinides, Stavros V
2017-12-01
Patients with intermediate-risk pulmonary embolism (PE) may, depending on the method and cut-off values used for definition, account for up to 60% of all patients with PE and have an 8% or higher risk of short-term adverse outcome. Although four non-vitamin K-dependent direct oral anticoagulants (NOACs) have been approved for the treatment of venous thromboembolism, their safety and efficacy as well as the optimal anticoagulation regimen using these drugs have not been systematically investigated in intermediate-risk PE. Moreover, it remains unknown how many patients with intermediate-high-risk and intermediate-low-risk PE were included in most of the phase III NOAC trials. The ongoing Pulmonary Embolism International Thrombolysis 2 (PEITHO-2) study is a prospective, multicentre, multinational, single-arm trial investigating whether treatment of acute intermediate-risk PE with parenteral heparin anticoagulation over the first 72 hours, followed by the direct oral thrombin inhibitor dabigatran over 6 months, is effective and safe. The primary efficacy outcome is recurrent symptomatic venous thromboembolism or death related to PE within the first 6 months. The primary safety outcome is major bleeding as defined by the International Society on Thrombosis and Haemostasis. Secondary outcomes include all-cause mortality, the overall duration of hospital stay (index event and repeated hospitalizations) and the temporal pattern of recovery of right ventricular function over the 6-month follow-up period. By applying and evaluating a contemporary risk-tailored treatment strategy for acute PE, PEITHO-2 will implement the recommendations of current guidelines and contribute to their further evolution.
An Accurate Co-registration Method for Airborne Repeat-pass InSAR
NASA Astrophysics Data System (ADS)
Dong, X. T.; Zhao, Y. H.; Yue, X. J.; Han, C. M.
2017-10-01
Interferometric Synthetic Aperture Radar (InSAR) technology plays a significant role in topographic mapping and surface deformation detection. Comparing with spaceborne repeat-pass InSAR, airborne repeat-pass InSAR solves the problems of long revisit time and low-resolution images. Due to the advantages of flexible, accurate, and fast obtaining abundant information, airborne repeat-pass InSAR is significant in deformation monitoring of shallow ground. In order to getting precise ground elevation information and interferometric coherence of deformation monitoring from master and slave images, accurate co-registration must be promised. Because of side looking, repeat observing path and long baseline, there are very different initial slant ranges and flight heights between repeat flight paths. The differences of initial slant ranges and flight height lead to the pixels, located identical coordinates on master and slave images, correspond to different size of ground resolution cells. The mismatching phenomenon performs very obvious on the long slant range parts of master image and slave image. In order to resolving the different sizes of pixels and getting accurate co-registration results, a new method is proposed based on Range-Doppler (RD) imaging model. VV-Polarization C-band airborne repeat-pass InSAR images were used in experiment. The experiment result shows that the proposed method leads to superior co-registration accuracy.
Superasymmetric fission of heavy nuclei induced by intermediate-energy protons
NASA Astrophysics Data System (ADS)
Deppman, A.; Andrade-II, E.; Guimarães, V.; Karapetyan, G. S.; Tavares, O. A. P.; Balabekyan, A. R.; Demekhina, N. A.; Adam, J.; Garcia, F.; Katovsky, K.
2013-12-01
In this work we present the results for the investigation of intermediate-mass fragment (IMF) production with the proton-induced reaction at 660 MeV on 238U and 237Np target. The data were obtained with the LNR Phasotron U-400M Cyclotron at Joint Institute for Nuclear Research (JINR), Dubna, Russia. A total of 93 isotopes, in the mass range of 30
Dynamic precision phenotyping reveals mechanism of crop tolerance to root herbivory
USDA-ARS?s Scientific Manuscript database
The western corn rootworm, Diabrotica virgifera virgifera (LeConte) is a major pest of maize, Zea mays L. Over the years, this pest has repeatedly shown its resilience and adaptability not only to traditional crop management strategies including chemical pesticides and crop rotation, but also to de...
NASA Technical Reports Server (NTRS)
Venkataraman, T. S.; Eidson, W. W.; Cohen, L. D.; Farina, J. D.; Acquista, C.
1983-01-01
The position and velocity of optically levitated glass spheres (radii 10-20 microns) movng in a gas are measured accurately, rapidly, and continuously using a high-speed rotating polygon mirror. The experimental technique developed here has repeatable position accuracies better than 20 microns. Each measurement takes less than 1 microsec and can be repeated every 100 microsec. The position of the levitated glass spheres can be manipulated accurately by modulating the laser power with an acoustic optic modulator. The technique provides a fast and accurate method to study general particle dynamics in a fluid.
Wong, Yu-Tung; Finley, Charles C; Giallo, Joseph F; Buckmire, Robert A
2011-08-01
To introduce a novel method of combining robotics and the CO(2) laser micromanipulator to provide excellent precision and performance repeatability designed for surgical applications. Pilot feasibility study. We developed a portable robotic controller that appends to a standard CO(2) laser micromanipulator. The robotic accuracy and laser beam path repeatability were compared to six experienced users of the industry standard micromanipulator performing the same simulated surgical tasks. Helium-neon laser beam video tracking techniques were employed. The robotic controller demonstrated superiority over experienced human manual micromanipulator control in accuracy (laser path within 1 mm of idealized centerline), 97.42% (standard deviation [SD] 2.65%), versus 85.11% (SD 14.51%), P = .018; and laser beam path repeatability (area of laser path divergence on successive trials), 21.42 mm(2) (SD 4.35 mm(2) ) versus 65.84 mm(2) (SD 11.93 mm(2) ), P = .006. Robotic micromanipulator control enhances accuracy and repeatability for specific laser tasks. Computerized control opens opportunity for alternative user interfaces and additional safety features. Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.
Di Fabio, Francesco; Alvarado, Carlos; Gologan, Adrian; Youssef, Emad; Voda, Linda; Mitmaker, Elliot; Beitel, Lenore K; Gordon, Philip H; Trifiro, Mark
2009-06-01
The X-linked human androgen receptor gene (AR) contains an exonic polymorphic trinucleotide CAG. The length of this encoded CAG tract inversely affects AR transcriptional activity. Colorectal carcinoma is known to express the androgen receptor, but data on somatic CAG repeat lengths variations in malignant and normal epithelial cells are still sporadic. Using laser capture microdissection (LCM), epithelial cells from colorectal carcinoma and normal-appearing mucosa were collected from the fresh tissue of eight consecutive male patients undergoing surgery (mean age, 70 y; range, 54-82). DNA isolated from each LCM sample underwent subsequent PCR and DNA sequencing to precisely determine AR CAG repeat lengths and the presence of microsatellite instability (MSI). Different AR CAG repeat lengths were observed in colorectal carcinoma (ranging from 0 to 36 CAG repeats), mainly in the form of multiple shorter repeat lengths. This genetic heterogeneity (somatic mosaicism) was also found in normal-appearing colorectal mucosa. Half of the carcinoma cases examined tended to have a higher number of AR CAG repeat lengths with a wider range of repeat size variation compared to normal mucosa. MSI carcinomas tended to have longer median AR CAG repeat lengths (n = 17) compared to microsatellite stable carcinomas (n = 14), although the difference was not significant (P = 0.31, Mann-Whitney test). Multiple unique somatic mutations of the AR CAG repeats occur in colorectal mucosa and in carcinoma, predominantly resulting in shorter alleles. Colorectal epithelial cells carrying AR alleles with shorter CAG repeat lengths may be more androgen-sensitive and therefore have a growth advantage.
Waye, J S; Willard, H F
1986-09-01
The centromeric regions of all human chromosomes are characterized by distinct subsets of a diverse tandemly repeated DNA family, alpha satellite. On human chromosome 17, the predominant form of alpha satellite is a 2.7-kilobase-pair higher-order repeat unit consisting of 16 alphoid monomers. We present the complete nucleotide sequence of the 16-monomer repeat, which is present in 500 to 1,000 copies per chromosome 17, as well as that of a less abundant 15-monomer repeat, also from chromosome 17. These repeat units were approximately 98% identical in sequence, differing by the exclusion of precisely 1 monomer from the 15-monomer repeat. Homologous unequal crossing-over is suggested as a probable mechanism by which the different repeat lengths on chromosome 17 were generated, and the putative site of such a recombination event is identified. The monomer organization of the chromosome 17 higher-order repeat unit is based, in part, on tandemly repeated pentamers. A similar pentameric suborganization has been previously demonstrated for alpha satellite of the human X chromosome. Despite the organizational similarities, substantial sequence divergence distinguishes these subsets. Hybridization experiments indicate that the chromosome 17 and X subsets are more similar to each other than to the subsets found on several other human chromosomes. We suggest that the chromosome 17 and X alpha satellite subsets may be related components of a larger alphoid subfamily which have evolved from a common ancestral repeat into the contemporary chromosome-specific subsets.
WDR62 Regulates Early Neural and Glial Progenitor Specification of Human Pluripotent Stem Cells
Alshawaf, Abdullah J.; Antonic, Ana; Skafidas, Efstratios
2017-01-01
Mutations in WD40-repeat protein 62 (WDR62) are commonly associated with primary microcephaly and other developmental cortical malformations. We used human pluripotent stem cells (hPSC) to examine WDR62 function during human neural differentiation and model early stages of human corticogenesis. Neurospheres lacking WDR62 expression showed decreased expression of intermediate progenitor marker, TBR2, and also glial marker, S100β. In contrast, inhibition of c-Jun N-terminal kinase (JNK) signalling during hPSC neural differentiation induced upregulation of WDR62 with a corresponding increase in neural and glial progenitor markers, PAX6 and EAAT1, respectively. These findings may signify a role of WDR62 in specifying intermediate neural and glial progenitors during human pluripotent stem cell differentiation. PMID:28690640
NASA Technical Reports Server (NTRS)
Shull, J. M.
1979-01-01
Copernicus UV data on interstellar lines toward Epsilon Ori and Pi-5 Ori are analyzed to study abundances and physical conditions in both low- and intermediate-velocity components. Clouds at -8 and +5 km/s (LSR) toward Epsilon Ori show typical depletions of Fe, Ti, Mg, and Si in dense (H number density about 100 per cu cm) gas. Low-column-density intermediate-velocity clouds toward both stars, with low densities (hydrogen number density less than 1 per cu cm) and near-cosmic Si abundances, are consistent with a widespread pattern of high-velocity gas over a 15-deg area surrounding the Orion region. Such activity may be attributed to the repeated action of supernovae in a patchy low-density region of interstellar gas.
NASA Astrophysics Data System (ADS)
Chen, C. T. A.
2015-12-01
It has been known that Kuroshio subsurface waters are the major source of nutrients to the East China Sea continental shelf, a major fishing ground. It has also been known that subsurface waters that upwell onto the shelf are heavily affected by the South China Sea (SCS) Tropical Water and the SCS Intermediate Water which contain more nutrients than the tropical (Smax) and intermediate (Smin) waters from the West Philippine Sea (WPS). A front has been found to separate the tropical and intermediate waters from the SCS and WPS. The reported front in the Okinawa Trough, however, was identified based only on one-time data from a single cross-section in the central Okinawa Trough. Here historical hydrographic data between Mar. 1950 and Dec. 2011 in the Okinawa Trough and its neighborhood are analyzed. A vertical front tilted toward the west is found in all seasons in all years across the World Ocean Circulation Repeated Lines PR 18 and 19 as well as at the PN cross-section in the central Okinawa Trough. The front at the Smax level (sigma theta=24.6-24.9) shows large seasonal and interannual variations. In winter during normal and La Niña periods the presence of the SCS Tropical Water is the most prominent. It is the weakest in autumn during normal periods and in spring during La Nina periods. Yet during El Niño periods the SCS Tropical Water is the most prominent in spring and it becomes the weakest in winter. As for intermediate waters (Smin at sigma theta= 26.7-26.9) the WPS Intermediate Water and SCS Intermediate Water show much weaker seasonality compared with tropical waters although during normal periods in winter the WPS Intermediate Water contribution is slightly larger than during other times. During El Niño periods the WPS Intermediate Water contribution is the smallest but in spring it is much strengthened. On the other hand, the WPS Intermediate Water contribution is the smallest in spring, and the largest in winter during La Niña periods.
Kotur, Nikola; Stankovic, Biljana; Kassela, Katerina; Georgitsi, Marianthi; Vicha, Anna; Leontari, Iliana; Dokmanovic, Lidija; Janic, Dragana; Krstovski, Nada; Klaassen, Kristel; Radmilovic, Milena; Stojiljkovic, Maja; Nikcevic, Gordana; Simeonidis, Argiris; Sivolapenko, Gregory; Pavlovic, Sonja; Patrinos, George P; Zukic, Branka
2012-02-01
TPMT activity is characterized by a trimodal distribution, namely low, intermediate and high methylator. TPMT gene promoter contains a variable number of GC-rich tandem repeats (VNTRs), namely A, B and C, ranging from three to nine repeats in length in an A(n)B(m)C architecture. We have previously shown that the VNTR architecture in the TPMT gene promoter affects TPMT gene transcription. MATERIALS, METHODS & RESULTS: Here we demonstrate, using reporter assays, that 6-mercaptopurine (6-MP) treatment results in a VNTR architecture-dependent decrease of TPMT gene transcription, mediated by the binding of newly recruited protein complexes to the TPMT gene promoter, upon 6-MP treatment. We also show that acute lymphoblastic leukemia patients undergoing 6-MP treatment display a VNTR architecture-dependent response to 6-MP. These data suggest that the TPMT gene promoter VNTR architecture can be potentially used as a pharmacogenomic marker to predict toxicity due to 6-MP treatment in acute lymphoblastic leukemia patients.
An SINS/GNSS Ground Vehicle Gravimetry Test Based on SGA-WZ02.
Yu, Ruihang; Cai, Shaokun; Wu, Meiping; Cao, Juliang; Zhang, Kaidong
2015-09-16
In March 2015, a ground vehicle gravimetry test was implemented in eastern Changsha to assess the repeatability and accuracy of ground vehicle SINS/GNSS gravimeter-SGA-WZ02. The gravity system developed by NUDT consisted of a Strapdown Inertial Navigation System (SINS), a Global Navigation Satellite System (GNSS) remote station on test vehicle, a GNSS static master station on the ground, and a data logging subsystem. A south-north profile of 35 km along the highway in eastern Changsha was chosen and four repeated available measure lines were obtained. The average speed of a vehicle is 40 km/h. To assess the external ground gravity disturbances, precise ground gravity data was built by CG-5 precise gravimeter as the reference. Under relative smooth conditions, internal accuracy among repeated lines shows an average agreement at the level of 1.86 mGal for half wavelengths about 1.1 km, and 1.22 mGal for 1.7 km. The root-mean-square (RMS) of difference between calculated gravity data and reference data is about 2.27 mGal/1.1 km, and 1.74 mGal/1.7 km. Not all of the noises caused by vehicle itself and experiments environments were eliminated in the primary results. By means of selecting reasonable filters and improving the GNSS observation conditions, further developments in ground vehicle gravimetry are promising.
Mosaheb, Sabrina; Thorpe, Julian R.; Hashemzadeh-Bonehi, Lida; Bigio, Eileen H.; Gearing, Marla; Cairns, Nigel J.
2006-01-01
Abnormal neuronal cytoplasmic inclusions (NCIs) containing aggregates of α-internexin and the neurofilament (NF) subunits, NF-H, NF-M, and NF-L, are the signature lesions of neuronal intermediate filament (IF) inclusion disease (NIFID). The disease has a clinically heterogeneous phenotype, including fronto-temporal dementia, pyramidal and extrapyramidal signs presenting at a young age. NCIs are variably ubiquitinated and about half of cases also have neuronal intranuclear inclusions (NIIs), which are also ubiquitinated. NIIs have been described in polyglutamine-repeat expansion diseases, where they are strongly ubiquitin immunoreactive. The fine structure of NIIs of NIFID has not previously been described. Therefore, to determine the ultrastructure of NIIs, immunoelectron microscopy was undertaken on NIFID cases and normal aged control brains. Our results indicate that the NIIs of NIFID are strongly ubiquitin immunoreactive. However, unlike NCIs which contain ubiquitin, α-internexin and NF epitopes, NIIs contain neither epitopes of α-internexin nor NF subunits. Neither NIIs nor NCIs were recognised by antibodies to expanded polyglutamine repeats. The NII of NIFID lacks a limiting membrane and contains straight filaments of 20 nm mean width (range 11–35 nm), while NCIs contain filaments with a mean width of 10 nm (range 5–18 nm; t-test, P<0.001). Biochemistry revealed no differences in neuronal IF protein mobilities between NIFID and normal brain tissue. Therefore, NIIs of NIFID contain filaments morphologically and immunologically distinct from those of NCIs, and both types of inclusion lack expanded polyglutamine tracts of the triplet-repeat expansion diseases. These observations indicate that abnormal protein aggregation follows separate pathways in different neuronal compartments of NIFID. PMID:16025283
Murray, Anna; Schoemaker, Minouk J; Bennett, Claire E; Ennis, Sarah; Macpherson, James N; Jones, Michael; Morris, Danielle H; Orr, Nick; Ashworth, Alan; Jacobs, Patricia A; Swerdlow, Anthony J
2014-01-01
Primary ovarian insufficiency before the age of 40 years affects 1% of the female population and is characterized by permanent cessation of menstruation. Genetic causes include FMR1 expansion mutations. Previous studies have estimated mutation prevalence in clinical referrals for primary ovarian insufficiency, but these are likely to be biased as compared with cases in the general population. The prevalence of FMR1 expansion mutations in early menopause (between the ages of 40 and 45 years) has not been published. We studied FMR1 CGG repeat number in more than 2,000 women from the Breakthrough Generations Study who underwent menopause before the age of 46 years. We determined the prevalence of premutation (55-200 CGG repeats) and intermediate (45-54 CGG repeats) alleles in women with primary ovarian insufficiency (n = 254) and early menopause (n = 1,881). The prevalence of the premutation was 2.0% in primary ovarian insufficiency, 0.7% in early menopause, and 0.4% in controls, corresponding to odds ratios of 5.4 (95% confidence interval = 1.7-17.4; P = 0.004) for primary ovarian insufficiency and 2.0 (95% confidence interval = 0.8-5.1; P = 0.12) for early menopause. Combining primary ovarian insufficiency and early menopause gave an odds ratio of 2.4 (95% confidence interval = 1.02-5.8; P = 0.04). Intermediate alleles were not significant risk factors for either early menopause or primary ovarian insufficiency. FMR1 premutations are not as prevalent in women with ovarian insufficiency as previous estimates have suggested, but they still represent a substantial cause of primary ovarian insufficiency and early menopause.
NASA Technical Reports Server (NTRS)
Lindensmith, Chris A.; Briggs, H. Clark; Beregovski, Yuri; Feria, V. Alfonso; Goullioud, Renaud; Gursel, Yekta; Hahn, Inseob; Kinsella, Gary; Orzewalla, Matthew; Phillips, Charles
2006-01-01
SIM Planetquest (SIM) is a large optical interferometer for making microarcsecond measurements of the positions of stars, and to detect Earth-sized planets around nearby stars. To achieve this precision, SIM requires stability of optical components to tens of picometers per hour. The combination of SIM s large size (9 meter baseline) and the high stability requirement makes it difficult and costly to measure all aspects of system performance on the ground. To reduce risks, costs and to allow for a design with fewer intermediate testing stages, the SIM project is developing an integrated thermal, mechanical and optical modeling process that will allow predictions of the system performance to be made at the required high precision. This modeling process uses commercial, off-the-shelf tools and has been validated against experimental results at the precision of the SIM performance requirements. This paper presents the description of the model development, some of the models, and their validation in the Thermo-Opto-Mechanical (TOM3) testbed which includes full scale brassboard optical components and the metrology to test them at the SIM performance requirement levels.
Alamidi, Daniel F; Smailagic, Amir; Bidar, Abdel W; Parker, Nicole S; Olsson, Marita; Hockings, Paul D; Lagerstrand, Kerstin M; Olsson, Lars E
2018-03-08
Lung T 1 is a potential translational biomarker of lung disease. The precision and repeatability of variable flip angle (VFA) T 1 mapping using modern 3D ultrashort echo time (UTE) imaging of the whole lung needs to be established before it can be used to assess response to disease and therapy. To evaluate the feasibility of regional lung T 1 quantification with VFA 3D-UTE and to investigate long- and short-term T 1 repeatability in the lungs of naive mice. Prospective preclinical animal study. Eight naive mice and phantoms. 3D free-breathing radial UTE (8 μs) at 4.7T. VFA 3D-UTE T 1 calculations were validated against T 1 values measured with inversion recovery (IR) in phantoms. Lung T 1 and proton density (S 0 ) measurements of whole lung and muscle were repeated five times over 1 month in free-breathing naive mice. Two consecutive T 1 measurements were performed during one of the imaging sessions. Agreement in T 1 between VFA 3D-UTE and IR in phantoms was assessed using Bland-Altman and Pearson 's correlation analysis. The T 1 repeatability in mice was evaluated using coefficient of variation (CV), repeated-measures analysis of variance (ANOVA), and paired t-test. Good T 1 agreement between the VFA 3D-UTE and IR methods was found in phantoms. T 1 in lung and muscle showed a 5% and 3% CV (1255 ± 63 msec and 1432 ± 42 msec, respectively, mean ± SD) with no changes in T 1 or S 0 over a month. Consecutive measurements resulted in an increase of 2% in both lung T 1 and S 0 . VFA 3D-UTE shows promise as a reliable T 1 mapping method that enables full lung coverage, high signal-to-noise ratio (∼25), and spatial resolution (300 μm) in freely breathing animals. The precision of the VFA 3D-UTE method will enable better design and powering of studies. 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018. © 2018 International Society for Magnetic Resonance in Medicine.
Simplified Summative Temporal Bone Dissection Scale Demonstrates Equivalence to Existing Measures.
Pisa, Justyn; Gousseau, Michael; Mowat, Stephanie; Westerberg, Brian; Unger, Bert; Hochman, Jordan B
2018-01-01
Emphasis on patient safety has created the need for quality assessment of fundamental surgical skills. Existing temporal bone rating scales are laborious, subject to evaluator fatigue, and contain inconsistencies when conferring points. To address these deficiencies, a novel binary assessment tool was designed and validated against a well-established rating scale. Residents completed a mastoidectomy with posterior tympanotomy on identical 3D-printed temporal bone models. Four neurotologists evaluated each specimen using a validated scale (Welling) and a newly developed "CanadaWest" scale, with scoring repeated after a 4-week interval. Nineteen participants were clustered into junior, intermediate, and senior cohorts. An ANOVA found significant differences between performance of the junior-intermediate and junior-senior cohorts for both Welling and CanadaWest scales ( P < .05). Neither scale found a significant difference between intermediate-senior resident performance ( P > .05). Cohen's kappa found strong intrarater reliability (0.711) with a high degree of interrater reliability of (0.858) for the CanadaWest scale, similar to scores on the Welling scale of (0.713) and (0.917), respectively. The CanadaWest scale was facile and delineated performance by experience level with strong intrarater reliability. Comparable to the validated Welling Scale, it distinguished junior from senior trainees but was challenged in differentiating intermediate and senior trainee performance.
A Review of Calibration Transfer Practices and Instrument Differences in Spectroscopy.
Workman, Jerome J
2018-03-01
Calibration transfer for use with spectroscopic instruments, particularly for near-infrared, infrared, and Raman analysis, has been the subject of multiple articles, research papers, book chapters, and technical reviews. There has been a myriad of approaches published and claims made for resolving the problems associated with transferring calibrations; however, the capability of attaining identical results over time from two or more instruments using an identical calibration still eludes technologists. Calibration transfer, in a precise definition, refers to a series of analytical approaches or chemometric techniques used to attempt to apply a single spectral database, and the calibration model developed using that database, for two or more instruments, with statistically retained accuracy and precision. Ideally, one would develop a single calibration for any particular application, and move it indiscriminately across instruments and achieve identical analysis or prediction results. There are many technical aspects involved in such precision calibration transfer, related to the measuring instrument reproducibility and repeatability, the reference chemical values used for the calibration, the multivariate mathematics used for calibration, and sample presentation repeatability and reproducibility. Ideally, a multivariate model developed on a single instrument would provide a statistically identical analysis when used on other instruments following transfer. This paper reviews common calibration transfer techniques, mostly related to instrument differences, and the mathematics of the uncertainty between instruments when making spectroscopic measurements of identical samples. It does not specifically address calibration maintenance or reference laboratory differences.
Baseline adjustments for binary data in repeated cross-sectional cluster randomized trials.
Nixon, R M; Thompson, S G
2003-09-15
Analysis of covariance models, which adjust for a baseline covariate, are often used to compare treatment groups in a controlled trial in which individuals are randomized. Such analysis adjusts for any baseline imbalance and usually increases the precision of the treatment effect estimate. We assess the value of such adjustments in the context of a cluster randomized trial with repeated cross-sectional design and a binary outcome. In such a design, a new sample of individuals is taken from the clusters at each measurement occasion, so that baseline adjustment has to be at the cluster level. Logistic regression models are used to analyse the data, with cluster level random effects to allow for different outcome probabilities in each cluster. We compare the estimated treatment effect and its precision in models that incorporate a covariate measuring the cluster level probabilities at baseline and those that do not. In two data sets, taken from a cluster randomized trial in the treatment of menorrhagia, the value of baseline adjustment is only evident when the number of subjects per cluster is large. We assess the generalizability of these findings by undertaking a simulation study, and find that increased precision of the treatment effect requires both large cluster sizes and substantial heterogeneity between clusters at baseline, but baseline imbalance arising by chance in a randomized study can always be effectively adjusted for. Copyright 2003 John Wiley & Sons, Ltd.
Characteristics of digital micromirror projection for 3D shape measurement at extreme speed
NASA Astrophysics Data System (ADS)
Höfling, Roland; Aswendt, Petra; Leischnig, Frank; Förster, Matthias
2015-03-01
3D shape measurement is one of the growing industrial applications of the Texas Instruments DLP® micro-mirror device. This paper presents investigations on precision and repeatability of that spatial light modulators output when it is driven up to its high-speed limit. The study concerns the basic switching behavior of the individual micro-mirror at different frame rates ranging over three orders of magnitude. The 3D shape measuring methodologies are focused on phase encoded triangulation, i.e. the projection of sinusoidal patterns. The DLP chip is a bi-stable device providing an on/off pattern at each certain moment in time, i.e. it has a native binary output. Sinusoidal patterns are the result of either a temporal integration of multiple on/off patterns or a spatial integration within one on/off pattern. Both approaches are studied experimentally with respect to precision and stability of the pattern output. The STAR-07 industrial projection unit, based upon the 0.7" DLP Discovery™4100 chipset, has been used for this work and the pattern frame rates cover the range from 225 frames per second (fps) to 50,000 fps. The STAR-07 output is detected by a photodiode, amplified, and analyzed in a Yokogawa digital storage oscilloscope. All results prove the very high precision and repeatability of the STAR-07 pattern projection, up to the extreme speed of 50,000 fps.
NASA Astrophysics Data System (ADS)
Titus, Jitto; Thakur, Mrinal
2002-03-01
Conjugation is not a prerequisite for electrical conductivity in polymers. Nonconjugated polymers having at least one double bond in the repeat can become conductive upon doping. Polyisoprene having one double bond repeating after three single bonds in the backbone becomes conductive upon doping with electron acceptors such as iodine.^1 The conductivity of doped polyisoprene is about 10-2 - 10-1 ohm-1cm-1. Poly(allocimene) has on the average one double bond repeating after two single bonds in the polymer backbone. The conductivity of poly(allocimene) is about 1 ohm-1cm-1 upon iodine doping. For polyacetylene, the conductivity upon iodine doping is about 100 ohm-1cm-1. There seems to be a power law dependence of conductivity on the fraction of double bonds in the repeat: σ ~ 10^5(f)^10, where σ is the conductivity in ohm-1cm-1, f is the number fraction of double bonds (e.g. 0.25 in polyisoprene, 0.33 in poly(allocimene) and 0.5 in polyacetylene). The conductivity depends partly on substituents and the morphology of the polymer as well. 1. M. Thakur, Macromolecules, 21 661 (1988); J. Macromol. Sci.-PAC, A38.12, Dec., (2001).
Gifford, Matthew E; Clay, Timothy A; Careau, Vincent
2014-01-01
Repeatability is an important concept in evolutionary analyses because it provides information regarding the benefit of repeated measurements and, in most cases, a putative upper limit to heritability estimates. Repeatability (R) of different aspects of energy metabolism and behavior has been demonstrated in a variety of organisms over short and long time intervals. Recent research suggests that consistent individual differences in behavior and energy metabolism might covary. Here we present new data on the repeatability of body mass, standard metabolic rate (SMR), voluntary exploratory behavior, and feeding rate in a semiaquatic salamander and ask whether individual variation in behavioral traits is correlated with individual variation in metabolism on a whole-animal basis and after conditioning on body mass. All measured traits were repeatable, but the repeatability estimates ranged from very high for body mass (R = 0.98), to intermediate for SMR (R = 0.39) and food intake (R = 0.58), to low for exploratory behavior (R = 0.25). Moreover, repeatability estimates for all traits except body mass declined over time (i.e., from 3 to 9 wk), although this pattern could be a consequence of the relatively low sample size used in this study. Despite significant repeatability in all traits, we find little evidence that behaviors are correlated with SMR at the phenotypic and among-individual levels when conditioned on body mass. Specifically, the phenotypic correlations between SMR and exploratory behavior were negative in all trials but significantly so in one trial only. Salamanders in this study showed individual variation in how their exploratory behavior changed across trials (but not body mass, SMR, and feed intake), which might have contributed to observed changing correlations across trials.
NASA Astrophysics Data System (ADS)
Huang, Bin; Wang, Xiaomeng; Li, Chengwei; Yi, Jiajing; Lu, Rongsheng; Tao, Jiayue
2016-09-01
This paper describes the design, working principle, as well as calibration of an air-floating six-axis force measurement platform, where the floating plate and nozzles were connected without contact, preventing inter-dimensional coupling and increasing precision significantly. The measurement repeatability error of the force size in the platform is less than 0.2% full scale (FS), which is significantly better than the precision of 1% FS in the six-axis force sensors on the current market. We overcame the difficulties of weight loading device in high-precision calibration by proposing a self-calibration method based on the floating plate gravity and met the calibration precision requirement of 0.02% FS. This study has general implications for the development and calibration of high-precision multi-axis force sensors. In particular, the air-floating six-axis force measurement platform could be applied to the calibration of some special sensors such as flexible tactile sensors and may be used as a micro-nano mechanical assembly platform for real-time assembly force testing.
Novel Structure of Ty3 Reverse Transcriptase | Center for Cancer Research
Retrotransposons are mobile genetic elements that self amplify via a single-stranded RNA intermediate, which is converted to double-stranded DNA by an encoded reverse transcriptase (RT) with both DNA polymerase (pol) and ribonuclease H (RNase) activities. Categorized by whether they contain flanking long terminal repeat (LTR) sequences, retrotransposons play a critical role in the architecture of eukaryotic genomes and are the evolutionary origin of retroviruses, including human immunodeficiency virus (HIV).
Multifunctional energy landscape for a DNA G-quadruplex: An evolved molecular switch
NASA Astrophysics Data System (ADS)
Cragnolini, Tristan; Chakraborty, Debayan; Šponer, Jiří; Derreumaux, Philippe; Pasquali, Samuela; Wales, David J.
2017-10-01
We explore the energy landscape for a four-fold telomere repeat, obtaining interconversion pathways between six experimentally characterised G-quadruplex topologies. The results reveal a multi-funnel system, with a variety of intermediate configurations and misfolded states. This organisation is identified with the intrinsically multi-functional nature of the system, suggesting a new paradigm for the classification of such biomolecules and clarifying issues regarding apparently conflicting experimental results.
Investigation of C9orf72 in 4 Neurodegenerative Disorders
Xi, Zhengrui; Zinman, Lorne; Grinberg, Yakov; Moreno, Danielle; Sato, Christine; Bilbao, Juan M.; Ghani, Mahdi; Hernández, Isabel; Ruiz, Agustín; Boada, Mercè; Morón, Francisco J.; Lang, Anthony E.; Marras, Connie; Bruni, Amalia; Colao, Rosanna; Maletta, Raffaele G.; Puccio, Gianfranco; Rainero, Innocenzo; Pinessi, Lorenzo; Galimberti, Daniela; Morrison, Karen E.; Moorby, Catriona; Stockton, Joanne D.; Masellis, Mario; Black, Sandra E.; Hazrati, Lili-Naz; Liang, Yan; van Haersma de With, Jan; Fornazzari, Luis; Villagra, Roque; Rojas-Garcia, Ricardo; Clarimón, Jordi; Mayeux, Richard; Robertson, Janice; St George-Hyslop, Peter; Rogaeva, Ekaterina
2014-01-01
Objective To estimate the allele frequency of C9orf72 (G4C2) repeats in amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), Alzheimer disease (AD), and Parkinson disease (PD). Design The number of repeats was estimated by a 2-step genotyping strategy. For expansion carriers, we sequenced the repeat flanking regions and obtained APOE genotypes and MAPT H1/H2 haplotypes. Setting Hospitals specializing in neurodegenerative disorders. Subjects We analyzed 520 patients with FTLD, 389 patients with ALS, 424 patients with AD, 289 patients with PD, 602 controls, 18 families, and 29 patients with PD with the LRRK2 G2019S mutation. Main Outcome Measure The expansion frequency. Results Based on a prior cutoff (>30 repeats), the expansion was detected in 9.3% of patients with ALS, 5.2% of patients with FTLD, and 0.7% of patients with PD but not in controls or patients with AD. It was significantly associated with family history of ALS or FTLD and age at onset of FTLD. Phenotype variation (ALS vs FTLD) was not associated with MAPT, APOE, or variability in the repeat flanking regions. Two patients with PD were carriers of 39 and 32 repeats with questionable pathological significance, since the 39-repeat allele does not segregate with PD. No expansion or intermediate alleles (20–29 repeats) were found among the G2019S carriers and AD cases with TAR DNA-binding protein 43–positive inclusions. Surprisingly, the frequency of the 10-repeat allele was marginally increased in all 4 neurodegenerative diseases compared with controls, indicating the presence of an unknown risk variation in the C9orf72 locus. Conclusions The C9orf72 expansion is a common cause of ALS and FTLD, but not of AD or PD. Our study raises concern about a reliable cutoff for the pathological repeat number, which is important in the utility of genetic screening. PMID:22964832
Furrer, Marc A; Vilaseca, Antoni; Corradi, Renato B; Boxler, Silvan; Thalmann, George N; Nguyen, Daniel P
2018-06-01
A growing number of men undergo repeat biopsies prior to radical prostatectomy for prostate cancer. However, the long-term impact of repeat biopsies on functional outcomes in this patient population remains unelucidated. Thus, we compared functional outcomes between patients who underwent single biopsy versus repeat biopsies before radical prostatectomy. From 1996 to 2015, 1015 consecutive patients underwent radical prostatectomy, and subsequently had urinary continence and erectile function assessed for >2 years follow-up. One-fourth of patients (275; 27%) had ≥2 biopsies before prostatectomy. Logistic regression models tested whether repeat biopsy before prostatectomy predicted continence or erectile function recovery. For the overall cohort, continence rates were 84%, 92%, 96%, and 98% at 3, 6, 12, and 24 months, respectively. Repeat biopsy before prostatectomy was associated with lower continence rate at 3 months compared to single biopsy (P = 0.03); however, no significant differences were observed at 6, 12, or 24 months. In multivariable analyses adjusting for age, body mass index and diabetes/cardiovascular disease/smoking, the association between repeat biopsy and lower likelihood of continence at 3 months remained (odds ratio 0.67, 95% confidence interval 0.47-0.97; P = 0.03). Overall erectile function recovery rates were 16%, 33%, 51%, and 55% at 3, 6, 12, and 24 months, respectively. No difference in erectile function recovery rates was seen at any time point for single biopsy versus repeat biopsy. In multivariable analyses, repeat biopsy was not predictive of erectile function recovery at any time point. Repeat biopsy before radical prostatectomy impairs early continence after surgery. However, erectile function recovery and mid-term to long-term continence are not affected. These data support the current trend towards active surveillance and delayed local treatment in patients with low- to intermediate-risk prostate cancer. © 2018 Wiley Periodicals, Inc.
Performance characteristics of a low-cost, field-deployable miniature CCD spectrometer
Coles, Simon; Nimmo, Malcolm; Worsfold, Paul J.
2000-01-01
Miniature spectrometers incorporating array detectors are becoming a viable, low-cost option for field and process deployments. The performance characteristics of one such instrument are reported and compared with those of a conventional benchtop instrument. The parameters investigated were wavelength repeatability, photometric linearity, instrumental noise (photometric precision) and instrumental drift. PMID:18924863
Keefe, Donald J.
1980-01-01
An automatically sweeping circuit for searching for an evoked response in an output signal in time with respect to a trigger input. Digital counters are used to activate a detector at precise intervals, and monitoring is repeated for statistical accuracy. If the response is not found then a different time window is examined until the signal is found.
ERIC Educational Resources Information Center
McSweeney, Frances K.
2004-01-01
Reinforcers lose their effectiveness when they are presented repeatedly. Early researchers labeled this loss of effectiveness as "satiation" without conducting an experimental analysis. When such an analysis is conducted, "habituation" provides a more precise and empirically accurate label for the changes in reinforcer effectiveness. This paper…
Radar Image Processing for the AFIT Anechoic Chamber
1990-12-01
analyzer is set up for data collection using the frequency list mode option. The frequency list mode, a variation of the step sweep mode, synthesizes each of...enhanced since the frequencies are precisely repeated. The frequency list option allows the operator to select any number of data samples from 1 to 401. This
NASA Technical Reports Server (NTRS)
1983-01-01
NASA-developed space shuttle technology is used in a laser wire stripper designed by Raytheon Company. Laser beams cut through insulation on a wire without damaging conductive metal, because laser radiation that melts plastic insulation is reflected by the metal. The laser process is fast, clean, precise and repeatable. It eliminates quality control problems and the expense of rejected wiring.
Speech task and timing considerations in MRI research
NASA Astrophysics Data System (ADS)
Epstein, Melissa A.; Stone, Maureen
2003-04-01
In order to create dynamic magnetic resonance images, subjects must repeat tokens as much as 30 times in a row, therefore, their precision is critical for image quality. Word repetition rate can be 1 or 1.5 s, and is matched to the rate of image recording. Unlike reciting tokens to the beat of a metronome, subjects must say each token during an extended period of noise that lasts about 75% of the repetition period. Furthermore, some tokens may be more difficult to say repetitively in these conditions. Therefore, this study simulated the acoustics of a MRI recording session to examine the effects of subject, token, and repetition rate on temporal precision. Subjects repeat up to ten mono- to trisyllabic words 30 times each at two repetition rates. Measurements are made of onsets and offsets of one or more phonemes within each word. Preliminary results (five subjects) indicate that there is an effect of subject and word. Further subjects are being measured to corroborate these results and to determine if one repetition rate is better than another and to test subject reliability.
A unique chromatin complex occupies young α-satellite arrays of human centromeres
Henikoff, Jorja G.; Thakur, Jitendra; Kasinathan, Sivakanthan; Henikoff, Steven
2015-01-01
The intractability of homogeneous α-satellite arrays has impeded understanding of human centromeres. Artificial centromeres are produced from higher-order repeats (HORs) present at centromere edges, although the exact sequences and chromatin conformations of centromere cores remain unknown. We use high-resolution chromatin immunoprecipitation (ChIP) of centromere components followed by clustering of sequence data as an unbiased approach to identify functional centromere sequences. We find that specific dimeric α-satellite units shared by multiple individuals dominate functional human centromeres. We identify two recently homogenized α-satellite dimers that are occupied by precisely positioned CENP-A (cenH3) nucleosomes with two ~100–base pair (bp) DNA wraps in tandem separated by a CENP-B/CENP-C–containing linker, whereas pericentromeric HORs show diffuse positioning. Precise positioning is largely maintained, whereas abundance decreases exponentially with divergence, which suggests that young α-satellite dimers with paired ~100-bp particles mediate evolution of functional human centromeres. Our unbiased strategy for identifying functional centromeric sequences should be generally applicable to tandem repeat arrays that dominate the centromeres of most eukaryotes. PMID:25927077
Dall'Ara, E; Barber, D; Viceconti, M
2014-09-22
The accurate measurement of local strain is necessary to study bone mechanics and to validate micro computed tomography (µCT) based finite element (FE) models at the tissue scale. Digital volume correlation (DVC) has been used to provide a volumetric estimation of local strain in trabecular bone sample with a reasonable accuracy. However, nothing has been reported so far for µCT based analysis of cortical bone. The goal of this study was to evaluate accuracy and precision of a deformable registration method for prediction of local zero-strains in bovine cortical and trabecular bone samples. The accuracy and precision were analyzed by comparing scans virtually displaced, repeated scans without any repositioning of the sample in the scanner and repeated scans with repositioning of the samples. The analysis showed that both precision and accuracy errors decrease with increasing the size of the region analyzed, by following power laws. The main source of error was found to be the intrinsic noise of the images compared to the others investigated. The results, once extrapolated for larger regions of interest that are typically used in the literature, were in most cases better than the ones previously reported. For a nodal spacing equal to 50 voxels (498 µm), the accuracy and precision ranges were 425-692 µε and 202-394 µε, respectively. In conclusion, it was shown that the proposed method can be used to study the local deformation of cortical and trabecular bone loaded beyond yield, if a sufficiently high nodal spacing is used. Copyright © 2014 Elsevier Ltd. All rights reserved.
Validation of a quantitative magnetic resonance method for measuring human body composition.
Napolitano, Antonella; Miller, Sam R; Murgatroyd, Peter R; Coward, W Andrew; Wright, Antony; Finer, Nick; De Bruin, Tjerk W; Bullmore, Edward T; Nunez, Derek J
2008-01-01
To evaluate a novel quantitative magnetic resonance (QMR) methodology (EchoMRI-AH, Echo Medical Systems) for measurement of whole-body fat and lean mass in humans. We have studied (i) the in vitro accuracy and precision by measuring 18 kg Canola oil with and without 9 kg water (ii) the accuracy and precision of measures of simulated fat mass changes in human subjects (n = 10) and (iii) QMR fat and lean mass measurements compared to those obtained using the established 4-compartment (4-C) model method (n = 30). (i) QMR represented 18 kg of oil at 40 degrees C as 17.1 kg fat and 1 kg lean while at 30 degrees C 15.8 kg fat and 4.7 kg lean were reported. The s.d. of repeated estimates was 0.13 kg for fat and 0.23 kg for lean mass. Adding 9 kg of water reduced the fat estimates, increased misrepresentation of fat as lean, and degraded the precision. (ii) the simulated change in the fat mass of human volunteers was accurately represented, independently of added water. (iii) compared to the 4-C model, QMR underestimated fat and over-estimated lean mass. The extent of difference increased with body mass. The s.d. of repeated measurements increased with adiposity, from 0.25 kg (fat) and 0.51 kg (lean) with BMI <25 kg/m(2) to 0.43 kg and 0.81 kg respectively with BMI >30 kg/m(2). EchoMRI-AH prototype showed shortcomings in absolute accuracy and specificity of fat mass measures, but detected simulated body composition change accurately and with precision roughly three times better than current best measures. This methodology should reduce the study duration and cohort number needed to evaluate anti-obesity interventions.
McCarthy, Troy; Lebeck, Mark G.; Capuano, Ana W.; Schnurr, David P.; Gray, Gregory C.
2009-01-01
Background Epidemiological data suggest that clinical outcomes of human adenovirus (HAdV) infection may be influenced by virus serotype, coinfection with multiple strains, or infection with novel intermediate strains. In this report, we propose a clinical algorithm for detecting HAdV coinfection and intermediate strains. Study Design We PCR amplified and sequenced subregions of the hexon and fiber genes of 342 HAdV positive clinical specimens obtained from 14 surveillance laboratories. Sequences were then compared with those from 52 HAdV prototypic strains. HAdV positive specimens that showed nucleotide sequence identity with a corresponding prototype strain were designated as being of that strain. When hexon and fiber gene sequences disagreed, or sequence identity was low, the specimens were further characterized by viral culture, plaque purification, repeat PCR with sequencing, and genome restriction enzyme digest analysis. Results Of the 342 HAdV-positive clinical specimens, 328 (95.9%) were single HAdV strain infections, 12 (3.5%) were coinfections, and 2 (0.6%) had intermediate strains. Coinfected specimens and intermediate HAdV strains considered together were more likely to be associated with severe illness compared to other HAdv-positive specimens (OR=3.8; 95% CI = 1.2–11.9). Conclusions The majority of severe cases of HAdV illness cases occurred among immunocompromised patients. The analytic algorithm we describe here can be used to screen clinical specimens for evidence of HAdV coinfection and novel intermediate HAdV strains. This algorithm may be especially useful in investigating HAdV outbreaks and clusters of unusually severe HAdV disease. PMID:19577957
[Design of low-intermediate frequency electrotherapy and pain assessment system].
Liang, Chunyan; Tian, Xuelong; Yu, Xuehong; Luo, Hongyan
2014-06-01
Aiming at the single treatment and the design separation between treatment and assessment in electrotherapy equipment, a kind of system including low-intermediate frequency treatment and efficacy evaluation was developed. With C8051F020 single-chip microcomputer as the core and the circuit design and software programming used, the system realized the random switch of therapeutic parameters, the collection, display and data storage of pressure pain threshold in the assessment. Experiment results showed that the stimulus waveform, current intensity, frequency, duty ratio of the system output were adjustable, accurate and reliable. The obtained pressure pain threshold had a higher accuracy (< 0.3 N) and better stability, guiding the parameter choice in the precise electrical stimulation. It, therefore, provides a reliable technical support for the treatment and curative effect assessment.
Ates, E; Mittendorf, K; Stroka, J; Senyuva, H
2013-01-01
An automated method involving on-line clean-up and analytical separation in a single run using TurboFlow™ reversed phase liquid chromatography coupled to a high resolution mass spectrometer has been developed for the simultaneous determination of deoxynivalenol, T2 toxin, HT2 toxin, zearalenone and fumonisins B1 and B2 in maize, wheat and animal feed. Detection was performed in full scan mode at a resolution of R = 100,000 full width at half maximum with high energy collision cell dissociation for the determination of fragment ions with a mass accuracy below 5 ppm. The extract from homogenised samples, after blending with a 0.1% aqueous mixture of 0.1% formic acid/acetonitrile (43:57) for 45 min, was injected directly onto the TurboFlow™ (TLX) column for automated on-line clean-up followed by analytical separation and accurate mass detection. The TurboFlow™ column enabled specific binding of target mycotoxins, whereas higher molecular weight compounds, like fats, proteins and other interferences with different chemical properties, were removed to waste. Single laboratory method validation was performed by spiking blank materials with mycotoxin standards. The recovery and repeatability was determined by spiking at three concentration levels (50, 100 and 200% of legislative limits) with six replicates. Average recovery, relative standard deviation and intermediate precision values were 71 to 120%, 1 to 19% and 4 to 19%, respectively. The method accuracy was confirmed with certified reference materials and participation in proficiency testing.
Kelly, Mary T; Blaise, Alain; Larroque, Michel
2010-11-19
This paper reports a new, simple, rapid and economical method for routine determination of 24 amino acids and biogenic amines in grapes and wine. No sample clean-up is required and total run time including column re-equilibration is less than 40min. Following automated in-loop automated pre-column derivatisation with an o-phthaldialdehyde, N-acetyl-l-cysteine reagent, compounds were separated on a 3mm×25cm C(18) column using a binary mobile phase. The method was validated in the range 0.25-10mg/l; repeatability was less than 3% RSD and the intermediate precision ranged from 2 to 7% RSD. The method was shown to be linear by the 'lack of fit' test and the accuracy was between 97 and 101%. The LLOQ varied between 10μg/l for aspartic and glutamic acids, ethanolamine and GABA, and 100μg/l for tyrosine, phenylalanine, putrescine and cadaverine. The method was applied to grapes, white wine, red wine, honey and three species of physalis fruit. Grapes and physalis fruit were crushed, sieved, centrifuged and diluted 1/20 and 1/100, respectively, for analysis; wines and honeys were simply diluted 10-fold. It was shown using this method that the amino acid content of grapes was strongly correlated with berry volume, moderately correlated with sugar concentration and inversely correlated with total acidity. Copyright © 2010 Elsevier B.V. All rights reserved.
Bicchi, Carlo; Cordero, Chiara; Liberto, Erica; Rubiolo, Patrizia; Sgorbini, Barbara
2004-01-23
High concentration capacity headspace techniques (headspace solid-phase microextraction (HS-SPME) and headspace sorptive extraction (HSSE)) are a bridge between static and dynamic headspace, since they give high concentration factors as does dynamic headspace (D-HS), and are as easy to apply and as reproducible as static headspace (S-HS). In 2000, Chromtech (Idstein, Germany) introduced an inside-needle technique for vapour and liquid sampling, solid-phase dynamic extraction (SPDE), also known as "the magic needle". In SPDE, analytes are concentrated on a 50 microm film of polydimethylsiloxane (PDMS) and activated carbon (10%) coated onto the inside wall of the stainless steel needle (5 cm) of a 2.5 ml gas tight syringe. When SPDE is used for headspace sampling (HS-SPDE), a fixed volume of the headspace of the sample under investigation is sucked up an appropriate number of times with the gas tight syringe and an analyte amount suitable for a reliable GC or GC-MS analysis accumulates in the polymer coating the needle wall. This article describes the preliminary results of both a study on the optimisation of sampling parameters conditioning HS-SPDE recovery, through the analysis of a standard mixture of highly volatile compounds (beta-pinene, isoamyl acetate and linalool) and of the HS-SPDE-GC-MS analyses of aromatic plants and food matrices. This study shows that HS-SPDE is a successful technique for HS-sampling with high concentration capability, good repeatability and intermediate precision, also when it is compared to HS-SPME.
Salgueiro-González, N; Turnes-Carou, I; Muniategui-Lorenzo, S; López-Mahía, P; Prada-Rodríguez, D
2014-12-10
A less time-, solvent- and sorbent-consuming analytical methodology for the determination of bisphenol A and alkylphenols (4-tert-octylphenol, 4-octylphenol, 4-n-nonylphenol, nonylphenol) in marine sediment was developed and validated. The method was based on selective pressurized liquid extraction (SPLE) with a simultaneous in cell clean up combined with liquid chromatography-electrospray ionization tandem mass spectrometry in negative mode (LC-ESI-MS/MS). The SPLE extraction conditions were optimized by a Plackett-Burman design followed by a central composite design. Quantitation was performed by standard addition curves in order to correct matrix effects. The analytical features of the method were satisfactory: relative recoveries varied between 94 and 100% and repeatability and intermediate precision were <6% for all compounds. Uncertainty assessment of measurement was estimated on the basis of an in-house validation according to EURACHEM/CITAC guide. Quantitation limits of the method (MQL) ranged between 0.17 (4-n-nonylphenol) and 4.01 ng g(-1) dry weight (nonylphenol). Sensitivity, selectivity, automaticity and fastness are the main advantages of this green methodology. As an application, marine sediment samples from Galicia coast (NW of Spain) were analysed. Nonylphenol and 4-tert-octylphenol were measured in all samples at concentrations between 20.1 and 1409 ng g(-1) dry weight, respectively. Sediment toxicity was estimated and no risk to aquatic biota was found. Copyright © 2014 Elsevier B.V. All rights reserved.
Lê, Laetitia Minh Mai; Eveleigh, Luc; Hasnaoui, Ikram; Prognon, Patrice; Baillet-Guffroy, Arlette; Caudron, Eric
2017-05-10
The aim of this study was to investigate near infrared spectroscopy (NIRS) combined to chemometric analysis to discriminate and quantify three antibiotics by direct measurement in plastic syringes.Solutions of benzylpenicillin (PENI), amoxicillin (AMOX) and amoxicillin/clavulanic acid (AMOX/CLAV) were analyzed at therapeutic concentrations in glass vials and plastic syringes with NIR spectrometer by direct measurement. Chemometric analysis using partial least squares regression and discriminative analysis was conducted to develop qualitative and quantitative calibration models. Discrimination of the three antibiotics was optimal for concentrated solutions with 100% of accuracy. For quantitative analysis, the three antibiotics furnished a linear response (R²>0.9994) for concentrations ranging from 0.05 to 0.2 g/mL for AMOX, 0.1 to 1.0 MUI/mL for PENI and 0.005 to 0.05 g/mL for AMOX/CLAV with excellent repeatability (maximum 1.3%) and intermediate precision (maximum of 3.2%). Based on proposed models, 94.4% of analyzed AMOX syringes, 80.0% of AMOX/CLAV syringes and 85.7% of PENI syringes were compliant with a relative error including the limit of ± 15%.NIRS as rapid, non-invasive and non-destructive analytical method represents a potentially powerful tool to further develop for securing the drug administration circuit of healthcare institutions to ensure that patients receive the correct product at the right dose. Copyright © 2017 Elsevier B.V. All rights reserved.
Salgueiro-González, N; Concha-Graña, E; Turnes-Carou, I; Muniategui-Lorenzo, S; López-Mahía, P; Prada-Rodríguez, D
2012-02-03
A fast, simple, sensitive and green analytical chemistry method for the simultaneous determination of alkylphenols (4-tert-octylphenol, 4-octylphenol, 4-n-nonylphenol, nonylphenol) and bisphenol A in seawater was developed and validated. The procedure was based on a dispersive liquid-liquid microextraction (DLLME) of a small volume of seawater sample (30 mL) using only 100 μL of 1-octanol, combined with liquid chromatography-electrospray ionization tandem mass spectrometry in negative mode (LC-ESI-MS/MS). The matrix effect was studied and compensated using deuterated labelled standards as surrogate standards for the quantitation of target compounds. The analytical features of the proposed method were satisfactory: repeatability and intermediate precision were <10% and recoveries were around 84-104% for all compounds. Uncertainty assessment of measurement was estimated on the basis of an in-house validation according to EURACHEM/CITAC guide. Quantitation limits of the method (MQL) ranged between 0.005 and 0.03 μg L⁻¹, therefore the levels established in the Directive 2008/105/EC were achieved. The applicability of the proposed method was demonstrated analyzing seawater samples from different sites of A Coruña (Northwest of Spain). The analyses showed the presence of all compounds at levels between 0.035 (bisphenol A) and 0.14 μg L⁻¹ (nonylphenol). Copyright © 2011 Elsevier B.V. All rights reserved.
Salgueiro-González, N; Turnes-Carou, I; Muniategui-Lorenzoa, S; López-Mahía, P; Prada-Rodríguez, D
2012-12-28
A novel and green analytical methodology for the determination of alkylphenols (4-tert-octylphenol, 4-n-octylphenol, 4-n-nonylphenol, nonylphenol technical mixture) and bisphenol A in bivalve mollusc samples was developed and validated. The method was based on selective pressurized liquid extraction (SPLE) with a simultaneous in cell clean up combined with liquid chromatography–electrospray ionization tandem mass spectrometry in negative mode (LC–ESI-MS/MS). Quantitation was performed by standard addition curves in order to correct matrix effects. The analytical features of the method were satisfactory: relative recoveries varied between 80 and 107% and repeatability and intermediate precision were <20% for all compounds. Uncertainty assessment of measurement was estimated on the basis of an in-house validation according to EURACHEM/CITAC guide. Quantitation limits of the method (MQL) ranged between 0.34 (4-n-octylphenol) and 3.6 ng g(−1) dry weight (nonylphenol). The main advantages of the method are sensitivity, selectivity, automaticity, low volumes of solvents required and low sample analysis time (according with the principles of Green Chemistry). The method was applied to the analysis of mussel samples of Galicia coast (NW of Spain). Nonylphenol and 4-tert-octylphenol were measured in all samples at concentrations between 9.3 and 372 ng g(−1) dw. As an approach, the human daily intake of these compounds was estimated and no risk for human health was found.
Otero, Raquel; Carrera, Guillem; Dulsat, Joan Francesc; Fábregas, José Luís; Claramunt, Juan
2004-11-19
A static headspace (HS) gas chromatographic method for quantitative determination of residual solvents in a drug substance has been developed according to European Pharmacopoeia general procedure. A water-dimethylformamide mixture is proposed as sample solvent to obtain good sensitivity and recovery. The standard addition technique with internal standard quantitation was used for ethanol, tetrahydrofuran and toluene determination. Validation was performed within the requirements of ICH validation guidelines Q2A and Q2B. Selectivity was tested for 36 solvents, and system suitability requirements described in the European Pharmacopoeia were checked. Limits of detection and quantitation, precision, linearity, accuracy, intermediate precision and robustness were determined, and excellent results were obtained.
Where in the world are my field plots? Using GPS effectively in environmental field studies
Johnson, Chris E.; Barton, Christopher C.
2004-01-01
Global positioning system (GPS) technology is rapidly replacing tape, compass, and traditional surveying instruments as the preferred tool for estimating the positions of environmental research sites. One important problem, however, is that it can be difficult to estimate the uncertainty of GPS-derived positions. Sources of error include various satellite- and site-related factors, such as forest canopy and topographic obstructions. In a case study from the Hubbard Brook Experimental Forest in New Hampshire, hand-held, mapping-grade GPS receivers generally estimated positions with 1–5 m precision in open, unobstructed settings, and 20–30 m precision under forest canopy. Surveying-grade receivers achieved precisions of 10 cm or less, even in challenging terrain. Users can maximize the quality of their GPS measurements by “mission planning” to take advantage of high-quality satellite conditions. Repeated measurements and simultaneous data collection at multiple points can be used to assess accuracy and precision.
Effects of Simple Leaching of Crushed and Powdered Materials on High-precision Pb Isotope Analyses
NASA Astrophysics Data System (ADS)
Todd, E.; Stracke, A.
2013-12-01
We present new results of simple leaching experiments on the Pb isotope composition of USGS standard reference material powders and on ocean island basalt whole rock splits and powders. Rock samples were leached with 6N HCl in two steps, first hot and then in an ultrasonic bath, and washed with ultrapure H2O before conventional sample digestion and chromatographic purification of Pb. Pb isotope analyses were determined with Tl-doped MC-ICP-MS. Intra- and inter-session analytical reproducibility of repeated analyses of both synthetic Pb solutions and Pb from single digests of chemically processed natural samples were generally < 100 ppm (2 S.D.). The comparison of leached and unleached samples shows that leaching reliably removes variable amounts of different contaminants for different starting materials. For repeated digests of a single sample, the leached samples reproduce better than the unleached ones, showing that leaching effectively removes heterogeneously distributed extraneous Pb. However, the reproducibility of repeated digests of variably contaminated natural samples is up to an order of magnitude worse than the analytical reproducibility of ca. 100 ppm. More complex leaching methods (e.g., Nobre Silva et al., 2009) yield Pb isotope ratios within error of and with similar reproducibility to our method, showing that the simple leaching method is reliable. The remaining Pb isotope heterogeneity of natural samples, which typically exceeds 100 ppm, is thus attributed to inherent isotopic sample heterogeneity. Tl-doped MC-ICP-MS Pb ratio determination is therefore a sufficiently precise method for Pb isotope analyses in natural rocks. More precise Pb double- or triple-spike methods (e.g., Galer, 1999; Thirlwall, 2000), may exploit their full potential only in cases where natural isotopic sample heterogeneity is demonstrably negligible. References: Galer, S., 1999, Chem. Geol. 157, 255-274. Nobre Silva, et al. 2009, Geochemistry Geophysics Geosystems 10, Q08012. Thirlwall, M.F., 2000, Chem. Geol. 163, 299-322.
Repeating aftershocks of the great 2004 Sumatra and 2005 Nias earthquakes
NASA Astrophysics Data System (ADS)
Yu, Wen-che; Song, Teh-Ru Alex; Silver, Paul G.
2013-05-01
We investigate repeating aftershocks associated with the great 2004 Sumatra-Andaman (Mw 9.2) and 2005 Nias-Simeulue (Mw 8.6) earthquakes by cross-correlating waveforms recorded by the regional seismographic station PSI and teleseismic stations. We identify 10 and 18 correlated aftershock sequences associated with the great 2004 Sumatra and 2005 Nias earthquakes, respectively. The majority of the correlated aftershock sequences are located near the down-dip end of a large afterslip patch. We determine the precise relative locations of event pairs among these sequences and estimate the source rupture areas. The correlated event pairs identified are appropriately referred to as repeating aftershocks, in that the source rupture areas are comparable and significantly overlap within a sequence. We use the repeating aftershocks to estimate afterslip based on the slip-seismic moment scaling relationship and to infer the temporal decay rate of the recurrence interval. The estimated afterslip resembles that measured from the near-field geodetic data to the first order. The decay rate of repeating aftershocks as a function of lapse time t follows a power-law decay 1/tp with the exponent p in the range 0.8-1.1. Both types of observations indicate that repeating aftershocks are governed by post-seismic afterslip.
The investigation of order–disorder transition process of ZSM-5 induced by spark plasma sintering
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wang, Liang; Wang, Lianjun, E-mail: wanglj@dhu.edu.cn; Jiang, Wan
2014-04-01
Based on the amorphization of zeolites, an order–disorder transition method was used to prepare silica glass via Spark Plasma Sintering (SPS). In order to get a better understanding about the mechanism of amorphization induced by SPS, the intermediate products in this process were prepared and characterized by different characterization techniques. X-ray diffraction and High-energy synchrotron X-ray scattering show a gradual transformation from ordered crystal to glass. Local structural changes in glass network including Si–O bond length, O–Si–O bond angle, size of rings, coordination were detected by Infrared spectroscopy and {sup 29}Si magic-angle spinning nuclear magnetic resonance (NMR) spectroscopy. Topologically ordered,more » amorphous material with a different intermediate-range structure can be obtained by precise control of intermediate process which can be expected to optimize and design material. - Graphical abstract: Low-density, ordered zeolites collapse to the rigid amorphous glass through spark plasma sintering. The intermediate-range structure formed in the process of order–disorder transition may give rise to specific property. - Highlights: • Order–disorder transition process of ZSM-5 induced by spark plasma sintering was investigated using several methods including XRD, High-energy synchrotron X-ray scattering, SAXS, IR, NMR, ect. • Order–disorder transition induced by SPS was compared with TIA and PIA. • Three stages has been divided during the whole process. • The collapse temperature range which may give rise to intermediate-range structure has been located.« less
A Gammaherpesviral Internal Repeat Contributes to Latency Amplification
Thakur, Nagendra N.; El-Gogo, Susanne; Steer, Beatrix; Freimüller, Klaus; Waha, Andreas; Adler, Heiko
2007-01-01
Background Gammaherpesviruses cause important infections of humans, in particular in immunocompromised patients. The genomes of gammaherpesviruses contain variable numbers of internal repeats whose precise role for in vivo pathogenesis is not well understood. Methodology/Principal Findings We used infection of laboratory mice with murine gammaherpesvirus 68 (MHV-68) to explore the biological role of the 40 bp internal repeat of MHV-68. We constructed several mutant viruses partially or completely lacking this repeat. Both in vitro and in vivo, the loss of the repeat did not substantially affect lytic replication of the mutant viruses. However, the extent of splenomegaly, which is associated with the establishment of latency, and the number of ex vivo reactivating and genome positive splenocytes were reduced. Since the 40 bp repeat is part of the hypothetical open reading frame (ORF) M6, it might function as part of M6 or as an independent structure. To differentiate between these two possibilities, we constructed an N-terminal M6STOP mutant, leaving the repeat structure intact but rendering ORF M6 unfunctional. Disruption of ORF M6 did neither affect lytic nor latent infection. In contrast to the situation in lytically infected NIH3T3 cells, the expression of the latency-associated genes K3 and ORF72 was reduced in the latently infected murine B cell line Ag8 in the absence of the 40 bp repeat. Conclusions/Significance These data suggest that the 40 bp repeat contributes to latency amplification and might be involved in the regulation of viral gene expression. PMID:17710133
NASA Astrophysics Data System (ADS)
Hwang, C.; Cheng, Y. S.
2015-12-01
In most cases, mountain glaciers are narrow and situated over steep slopes. A laser-based altimeter such as ICESat has a small illuminated footprint at about 70 m, thus allowing to measure precise elevations over narrow mountain glaciers. However, unlike a typical radar altimeter mission, ICESat does not have repeat ground tracks (except in its early phase) to measure heights of a specific point at different times. Within a time span, usually a reference digital elevation model is used to compute height anomalies at ICESat's measurement sites over a designated area, which are then averaged to produce a representative height change (anomaly) in this area. In contrast, a radar altimeter such as TOPEX/Poseidon (TP; its follow-on missions are Jason-1 and -2), repeats its ground tracks at an even time interval (10 days for TP), but has a larger illuminated footprint than ICESat's (about 1 km or larger), making it difficult to measure precise elevations over narrow mountain glaciers. Here we demonstrate the potential of TP and Jason-2 radar altimeters in detecting elevation changes over mountain glaciers that are sufficiently wide and smooth. We select several glacier-covered sites in Mt. Tanggula (Tibet) and the Himalayas to experiment with methods that can generate precise height measurements from the two altimeters. Over the same spot, ranging errors due to slope, volume scattering and radar penetration can be common between repeat cycles, and may be reduced by differencing successive heights. We retracked radar waveforms and classify the surfaces using the SRTM-derived elevations. The effects of terrain and slope are reduced by fitting a surface to the height measurements from repeat cycles. We remove outlier heights and apply a smoothing filter to form final time series of glacier elevation change at the selected sites, which are compared with the results from ICESat (note the different mission times). Because TP and Jason-2 measure height changes every 10 days, clear annual and inter-annual oscillations of glacier heights are present in the resulting time series, in comparison to the unevenly sampled height changes from ICESat that do not show such oscillations. The rates of glacier elevation change from T/P and Jason-2 are mostly negative, but vary with locations and heights.
Medical Device for Automated Prick Test Reading.
Justo, Xabier; Diaz, Inaki; Gil, Jorge Juan; Gastaminza, Gabriel
2018-05-01
Allergy tests are routinely performed in most hospitals everyday. However, measuring the outcomes of these tests is still a very laborious manual task. Current methods and systems lack of precision and repeatability. This paper presents a novel mechatronic system that is able to scan a patient's entire arm and provide allergists with precise measures of wheals for diagnosis. The device is based on 3-D laser technology and specific algorithms have been developed to process the information gathered. This system aims to automate the reading of skin prick tests and make gains in speed, accuracy, and reliability. Several experiments have been performed to evaluate the performance of the system.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Alfonso, Dominic R., E-mail: alfonso@netl.doe.gov; Kauffman, Douglas; Matranga, Christopher
2016-05-14
Recent experimental studies have reported the electrochemical reduction of carbon dioxide (CO{sub 2}) into CO at atomically precise negatively charged Au{sub 25}{sup −} nanoclusters. The studies showed CO{sub 2} conversion at remarkably low overpotentials, but the exact mechanisms and nature of the active sites remain unclear. We used first-principles density functional theory and continuum solvation models to examine the role of the cluster during electrochemical CO{sub 2} reduction and analyze the free energies of proposed intermediate species. Contrary to previous assumptions, our results show that the fully ligand protected cluster is not an active CO{sub 2} reduction catalyst because formationmore » of the crucial carboxyl intermediate required very high electrochemical potentials. Instead, our calculations suggest that the reduction process likely occurs on a dethiolated gold site, and adsorbed carboxyl intermediate formation was significantly stabilized at dethiolated gold sites. These findings point to the crucial role of exposed metal sites during electrochemical CO{sub 2} reduction at gold nanocluster catalysts.« less
Park, Chang-Ju; Yang, Dong-Seong; Cha, Jung-Joon; Lee, Jong-Hyun
2016-02-01
This paper presents the design, fabrication, and characterization of a polymeric micro check valve for a glaucoma drainage device (GDD) featuring the precise regulation of intraocular pressure (IOP) and effective aqueous humor turnover (AHT). The pedestal, slightly elevated by selective coating of a parylene C film, induces pre-stress in the thin valve membrane, which enhances the predictability of the cracking pressure of the GDD. The proposed GDD comprises a cannula and a normally closed polymeric micro check valve, which are made of PDMS, a biocompatible polymer, with three layers: top (cover), intermediate (thin valve membrane), and bottom (base plate). A feedback channel, located between the top and intermediate layers, prevents reverse flow by feeding the pressure of the outlet channel back to the thin valve membrane. To achieve a precise cracking pressure and sufficient drainage of humor for humans, the thicknesses of the valve membrane and parylene C film are designed to be 58 μm and 1 μm, respectively, which are confirmed using a COMSOL simulation. The experimental results show that the cracking pressure of the fabricated GDD lies within the range of normal IOP (1.33-2.67 kPa). The forward flow rate (drainage rate), 4.3 ± 0.9 μL/min at 2.5 kPa, is adequate to accommodate the rate of AHT in a normal human eye (2.4 ± 0.6 μL/min). The reverse flow was not observed when a hydrostatic pressure of up to 4 kPa was applied to the outlet and the feedback channel.
High Precision Rovibrational Spectroscopy of OH+
NASA Astrophysics Data System (ADS)
Markus, Charles R.; Hodges, James N.; Perry, Adam J.; Kocheril, G. Stephen; Müller, Holger S. P.; McCall, Benjamin J.
2016-02-01
The molecular ion OH+ has long been known to be an important component of the interstellar medium. Its relative abundance can be used to indirectly measure cosmic ray ionization rates of hydrogen, and it is the first intermediate in the interstellar formation of water. To date, only a limited number of pure rotational transitions have been observed in the laboratory making it necessary to indirectly calculate rotational levels from high-precision rovibrational spectroscopy. We have remeasured 30 transitions in the fundamental band with MHz-level precision, in order to enable the prediction of a THz spectrum of OH+. The ions were produced in a water cooled discharge of O2, H2, and He, and the rovibrational transitions were measured with the technique Noise Immune Cavity Enhanced Optical Heterodyne Velocity Modulation Spectroscopy. These values have been included in a global fit of field free data to a 3Σ- linear molecule effective Hamiltonian to determine improved spectroscopic parameters which were used to predict the pure rotational transition frequencies.
NASA Astrophysics Data System (ADS)
Pérez Lara, Carlos E.
2018-02-01
Our understanding of QCD under extreme conditions has advanced tremendously in the last 20 years with the discovery of the Quark Gluon Plasma and its characterisation in heavy ion collisions at RHIC and LHC. The sPHENIX detector planned at RHIC is designed to further study the microscopic nature of the QGP through precision measurements of jet, upsilon and open heavy flavor probes over a broad pT range. The multi-year sPHENIX physics program will commence in early 2023, using state-of-the art detector technologies to fully exploit the highest RHIC luminosities. The experiment incorporates the 1.4 T former BaBar solenoid magnet, and will feature high precision tracking and vertexing capabilities, provided by a compact TPC, Si-strip intermediate tracker and MAPS vertex detector. This is complemented by highly granular electromagnetic and hadronic calorimetry with full azimuthal coverage. In this document I describe the sPHENIX detector design and physics program, with particular emphasis on the comprehensive open heavy flavour program enabled by the experiment's large coverage, high rate capability and precision vertexing.
Trinh, T. Q.; Sinden, R. R.
1993-01-01
We describe a system to measure the frequency of both deletions and duplications between direct repeats. Short 17- and 18-bp palindromic and nonpalindromic DNA sequences were cloned into the EcoRI site within the chloramphenicol acetyltransferase gene of plasmids pBR325 and pJT7. This creates an insert between direct repeated EcoRI sites and results in a chloramphenicol-sensitive phenotype. Selection for chloramphenicol resistance was utilized to select chloramphenicol resistant revertants that included those with precise deletion of the insert from plasmid pBR325 and duplication of the insert in plasmid pJT7. The frequency of deletion or duplication varied more than 500-fold depending on the sequence of the short sequence inserted into the EcoRI site. For the nonpalindromic inserts, multiple internal direct repeats and the length of the direct repeats appear to influence the frequency of deletion. Certain palindromic DNA sequences with the potential to form DNA hairpin structures that might stabilize the misalignment of direct repeats had a high frequency of deletion. Other DNA sequences with the potential to form structures that might destabilize misalignment of direct repeats had a very low frequency of deletion. Duplication mutations occurred at the highest frequency when the DNA between the direct repeats contained no direct or inverted repeats. The presence of inverted repeats dramatically reduced the frequency of duplications. The results support the slippage-misalignment model, suggesting that misalignment occurring during DNA replication leads to deletion and duplication mutations. The results also support the idea that the formation of DNA secondary structures during DNA replication can facilitate and direct specific mutagenic events. PMID:8325478
Assessing disease stress and modeling yield losses in alfalfa
NASA Astrophysics Data System (ADS)
Guan, Jie
Alfalfa is the most important forage crop in the U.S. and worldwide. Fungal foliar diseases are believed to cause significant yield losses in alfalfa, yet, little quantitative information exists regarding the amount of crop loss. Different fungicides and application frequencies were used as tools to generate a range of foliar disease intensities in Ames and Nashua, IA. Visual disease assessments (disease incidence, disease severity, and percentage defoliation) were obtained weekly for each alfalfa growth cycle (two to three growing cycles per season). Remote sensing assessments were performed using a hand-held, multispectral radiometer to measure the amount and quality of sunlight reflected from alfalfa canopies. Factors such as incident radiation, sun angle, sensor height, and leaf wetness were all found to significantly affect the percentage reflectance of sunlight reflected from alfalfa canopies. The precision of visual and remote sensing assessment methods was quantified. Precision was defined as the intra-rater repeatability and inter-rater reliability of assessment methods. F-tests, slopes, intercepts, and coefficients of determination (R2) were used to compare assessment methods for precision. Results showed that among the three visual disease assessment methods (disease incidence, disease severity, and percentage defoliation), percentage defoliation had the highest intra-rater repeatability and inter-rater reliability. Remote sensing assessment method had better precision than the percentage defoliation assessment method based upon higher intra-rater repeatability and inter-rater reliability. Significant linear relationships between canopy reflectance (810 nm), percentage defoliation and yield were detected using linear regression and percentage reflectance (810 nm) assessments were found to have a stronger relationship with yield than percentage defoliation assessments. There were also significant linear relationships between percentage defoliation, dry weight, percentage reflectance (810 nm), and green leaf area index (GLAI). Percentage reflectance (810 nm) assessments had a stronger relationship with dry weight and green leaf area index than percentage defoliation assessments. Our research conclusively demonstrates that percentage reflectance measurements can be used to nondestructively assess green leaf area index which is a direct measure of plant health and an indirect measure of productivity. This research conclusively demonstrates that remote sensing is superior to visual assessment method to assess alfalfa stress and to model yield and GLAI in the alfalfa foliar disease pathosystem.
ERIC Educational Resources Information Center
Zuiker, Steven J.
2012-01-01
As a global cyberinfrastructure, the Internet makes authentic digital problem spaces like educational virtual environments (EVEs) available to a wide range of classrooms, schools and education systems operating under different circumstantial, practical, social and cultural conditions. And yet, if the makers and users of EVEs both have a hand in…
USDA-ARS?s Scientific Manuscript database
Plant disease resistance is often mediated by nucleotide binding-leucine rich repeat (NB-LRR or NLR) proteins, which trigger a hypersensitive response (HR), a rapid, localized cell death upon recognition of specific pathogens. The maize NLR-encoding Rp1-D21 gene is the result of an intergenic recomb...
ERIC Educational Resources Information Center
Montessori, Maria
2016-01-01
Montessori discusses the importance of the calm inner life (the soul) of the very young child. She stresses the importance of the soul's self-management, the child knowing what he needs to do, and of course, being allowed to do what he needs to do. The child can repeat the exercise or move ahead according to minimal clear and precise guidance from…
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kremer, B.; Theilmann, J.; Spence, N.
1995-08-01
A total of 254 affected parent-child pairs with Huntington disease (HD) and 440 parent-child pairs with CAG size in the normal range were assessed to determine the nature and frequency of intergenerational CAG changes in the HD gene. Intergenerational CAG changes are extremely rare (3/440 [0.68%]) on normal chromosomes. In contrast, on HD chromosomes, changes in CAG size occur in {approximately}70% of meioses on HD chromosomes, with expansions accounting for 73% of these changes. These intergenerational CAG changes make a significant but minor contribution to changes in age at onset (r{sup 2}=.19). The size of the CAG repeat influenced largermore » intergenerational expansions (>7 CAG repeats), but the likelihood of smaller expansions or contractions was not influenced by CAG size. Large expansions (>7 CAG repeats) occur almost exclusively through paternal transmission (0.96%; P<10{sub -7}), while offspring of affected mothers are more likely to show no change (P=.01) or contractions in CAG size (P=.002). This study demonstrates that sex of the transmitting parent is the major determinant for CAG intergenerational changes in the HD gene. Similar paternal sex effects are seen in the evolution of new mutations for HD from intermediate alleles and for large expansions on affected chromosomes. Affected mothers almost never transmit a significantly expanded CAG repeat, despite the fact that many have similar large-sized alleles, compared with affected fathers. The sex-dependent effects of major expansion and contractions of the CAG repeat in the HD gene implicate different effects of gametogenesis, in males versus females, on intergenerational CAG repeat stability. 22 refs., 4 figs., 3 tabs.« less
The DL1 repeats in the genome of Diphyllobothrium latum.
Usmanova, Nadezhda M; Kazakov, Vasiliy I
2010-07-01
Diphyllobothrium latum is a widespread intestinal parasite, which has a great clinical relevance, but there are no sequences of its nuclear genome. In this paper, a repetitive element in the D. latum genome is firstly described. The adult D. latum was obtained in the result of expulsion from intestinum of a patient suffering from diphyllobothriasis. Genomic DNA was isolated from several proglottids of this individual. PstI restriction products of D. latum genomic DNA were sequenced. Polymerase chain reaction (PCR) amplification of these products using genomic DNA and selected primers was carried out. Thereby a cluster of a repetitive element, called DL1, was discovered. For precise identification of a beginning and an end of the repeat, a product of PCR amplification of D. latum genomic DNA with one specific primer was sequenced. In discussion, several evidences that DL1 repeat is a member of the SINE family of retroposons were adduced.
[Standard sample preparation method for quick determination of trace elements in plastic].
Yao, Wen-Qing; Zong, Rui-Long; Zhu, Yong-Fa
2011-08-01
Reference sample was prepared by masterbatch method, containing heavy metals with known concentration of electronic information products (plastic), the repeatability and precision were determined, and reference sample preparation procedures were established. X-Ray fluorescence spectroscopy (XRF) analysis method was used to determine the repeatability and uncertainty in the analysis of the sample of heavy metals and bromine element. The working curve and the metrical methods for the reference sample were carried out. The results showed that the use of the method in the 200-2000 mg x kg(-1) concentration range for Hg, Pb, Cr and Br elements, and in the 20-200 mg x kg(-1) range for Cd elements, exhibited a very good linear relationship, and the repeatability of analysis methods for six times is good. In testing the circuit board ICB288G and ICB288 from the Mitsubishi Heavy Industry Company, results agreed with the recommended values.
Tan, Xinran; Zhu, Fan; Wang, Chao; Yu, Yang; Shi, Jian; Qi, Xue; Yuan, Feng; Tan, Jiubin
2017-11-19
This study presents a two-dimensional micro-/nanoradian angle generator (2D-MNAG) that achieves high angular displacement resolution and repeatability using a piezo-driven flexure hinge for two-dimensional deflections and three capacitive sensors for output angle monitoring and feedback control. The principal error of the capacitive sensor for precision microangle measurement is analyzed and compensated for; so as to achieve a high angle output resolution of 10 nrad (0.002 arcsec) and positioning repeatability of 120 nrad (0.024 arcsec) over a large angular range of ±4363 μrad (±900 arcsec) for the 2D-MNAG. The impact of each error component, together with the synthetic error of the 2D-MNAG after principal error compensation are determined using Monte Carlo simulation for further improvement of the 2D-MNAG.
Tan, Xinran; Zhu, Fan; Wang, Chao; Yu, Yang; Shi, Jian; Qi, Xue; Yuan, Feng; Tan, Jiubin
2017-01-01
This study presents a two-dimensional micro-/nanoradian angle generator (2D-MNAG) that achieves high angular displacement resolution and repeatability using a piezo-driven flexure hinge for two-dimensional deflections and three capacitive sensors for output angle monitoring and feedback control. The principal error of the capacitive sensor for precision microangle measurement is analyzed and compensated for; so as to achieve a high angle output resolution of 10 nrad (0.002 arcsec) and positioning repeatability of 120 nrad (0.024 arcsec) over a large angular range of ±4363 μrad (±900 arcsec) for the 2D-MNAG. The impact of each error component, together with the synthetic error of the 2D-MNAG after principal error compensation are determined using Monte Carlo simulation for further improvement of the 2D-MNAG. PMID:29156595
The Impact of Estimating High-Resolution Tropospheric Gradients on Multi-GNSS Precise Positioning
Zhou, Feng; Li, Xingxing; Li, Weiwei; Chen, Wen; Dong, Danan; Wickert, Jens; Schuh, Harald
2017-01-01
Benefits from the modernized US Global Positioning System (GPS), the revitalized Russian GLObal NAvigation Satellite System (GLONASS), and the newly-developed Chinese BeiDou Navigation Satellite System (BDS) and European Galileo, multi-constellation Global Navigation Satellite System (GNSS) has emerged as a powerful tool not only in positioning, navigation, and timing (PNT), but also in remote sensing of the atmosphere and ionosphere. Both precise positioning and the derivation of atmospheric parameters can benefit from multi-GNSS observations. In this contribution, extensive evaluations are conducted with multi-GNSS datasets collected from 134 globally-distributed ground stations of the International GNSS Service (IGS) Multi-GNSS Experiment (MGEX) network in July 2016. The datasets are processed in six different constellation combinations, i.e., GPS-, GLONASS-, BDS-only, GPS + GLONASS, GPS + BDS, and GPS + GLONASS + BDS + Galileo precise point positioning (PPP). Tropospheric gradients are estimated with eight different temporal resolutions, from 1 h to 24 h, to investigate the impact of estimating high-resolution gradients on position estimates. The standard deviation (STD) is used as an indicator of positioning repeatability. The results show that estimating tropospheric gradients with high temporal resolution can achieve better positioning performance than the traditional strategy in which tropospheric gradients are estimated on a daily basis. Moreover, the impact of estimating tropospheric gradients with different temporal resolutions at various elevation cutoff angles (from 3° to 20°) is investigated. It can be observed that with increasing elevation cutoff angles, the improvement in positioning repeatability is decreased. PMID:28368346
Independence of motor unit recruitment and rate modulation during precision force control.
Kamen, G; Du, D C
1999-01-01
The vertebrate motor system chiefly employs motor unit recruitment and rate coding to modulate muscle force output. In this paper, we studied how the recruitment of new motor units altered the firing rate of already-active motor units during precision force production in the first dorsal interosseous muscle. Six healthy adults performed linearly increasing isometric voluntary contractions while motor unit activity and force output were recorded. After motor unit discharges were identified, motor unit firing rates were calculated before and after the instances of new motor unit recruitment. Three procedures were applied to compute motor unit firing rate, including the mean of a fixed number of inter-spike intervals and the constant width weighted Hanning window filter method, as well as a modified boxcar technique. In contrast to previous reports, the analysis of the firing rates of over 200 motor units revealed that reduction of the active firing rates was not a common mechanism used to accommodate the twitch force produced by the recruitment of a new motor unit. Similarly, during de-recruitment there was no tendency for motor unit firing rates to increase immediately following the cessation of activity in other motor units. Considerable consistency in recruitment behavior was observed during repeated contractions. However, firing rates during repeated contractions demonstrated considerably more fluctuation. It is concluded that the neuromuscular system does not use short-term preferential motor unit disfacilitation to effect precise regulation of muscular force output.
The Impact of Estimating High-Resolution Tropospheric Gradients on Multi-GNSS Precise Positioning.
Zhou, Feng; Li, Xingxing; Li, Weiwei; Chen, Wen; Dong, Danan; Wickert, Jens; Schuh, Harald
2017-04-03
Benefits from the modernized US Global Positioning System (GPS), the revitalized Russian GLObal NAvigation Satellite System (GLONASS), and the newly-developed Chinese BeiDou Navigation Satellite System (BDS) and European Galileo, multi-constellation Global Navigation Satellite System (GNSS) has emerged as a powerful tool not only in positioning, navigation, and timing (PNT), but also in remote sensing of the atmosphere and ionosphere. Both precise positioning and the derivation of atmospheric parameters can benefit from multi-GNSS observations. In this contribution, extensive evaluations are conducted with multi-GNSS datasets collected from 134 globally-distributed ground stations of the International GNSS Service (IGS) Multi-GNSS Experiment (MGEX) network in July 2016. The datasets are processed in six different constellation combinations, i.e., GPS-, GLONASS-, BDS-only, GPS + GLONASS, GPS + BDS, and GPS + GLONASS + BDS + Galileo precise point positioning (PPP). Tropospheric gradients are estimated with eight different temporal resolutions, from 1 h to 24 h, to investigate the impact of estimating high-resolution gradients on position estimates. The standard deviation (STD) is used as an indicator of positioning repeatability. The results show that estimating tropospheric gradients with high temporal resolution can achieve better positioning performance than the traditional strategy in which tropospheric gradients are estimated on a daily basis. Moreover, the impact of estimating tropospheric gradients with different temporal resolutions at various elevation cutoff angles (from 3° to 20°) is investigated. It can be observed that with increasing elevation cutoff angles, the improvement in positioning repeatability is decreased.
A Functional Examination of Intermediate Cognitive Processes.
1986-01-01
memory ) and a body of accumulated information referred to as " semantic memory ". In contrast with episodic memory (which most psychological experiments...referents of input signals. (p. 386) But as Eysenck (1984) points out, there is "no precise dividing line" betveen episodic and semantic memory and although...involve), Tulving suggests that semantic memory is the more crucial to 5. .P, 31 performing everyday tasks: It is a mental thesaurus, the
Atomistic Picture for the Folding Pathway of a Hybrid-1 Type Human Telomeric DNA G-quadruplex
Bian, Yunqiang; Tan, Cheng; Wang, Jun; Sheng, Yuebiao; Zhang, Jian; Wang, Wei
2014-01-01
In this work we studied the folding process of the hybrid-1 type human telomeric DNA G-quadruplex with solvent and ions explicitly modeled. Enabled by the powerful bias-exchange metadynamics and large-scale conventional molecular dynamic simulations, the free energy landscape of this G-DNA was obtained for the first time and four folding intermediates were identified, including a triplex and a basically formed quadruplex. The simulations also provided atomistic pictures for the structures and cation binding patterns of the intermediates. The results showed that the structure formation and cation binding are cooperative and mutually supporting each other. The syn/anti reorientation dynamics of the intermediates was also investigated. It was found that the nucleotides usually take correct syn/anti configurations when they form native and stable hydrogen bonds with the others, while fluctuating between two configurations when they do not. Misfolded intermediates with wrong syn/anti configurations were observed in the early intermediates but not in the later ones. Based on the simulations, we also discussed the roles of the non-native interactions. Besides, the formation process of the parallel conformation in the first two G-repeats and the associated reversal loop were studied. Based on the above results, we proposed a folding pathway for the hybrid-1 type G-quadruplex with atomistic details, which is new and more complete compared with previous ones. The knowledge gained for this type of G-DNA may provide a general insight for the folding of the other G-quadruplexes. PMID:24722458
Ivnitsky, Jury Ju; Schäfer, Timur V; Malakhovsky, Vladimir N; Rejniuk, Vladimir L
2004-10-01
Rats poisoned with one LD50 of thiopental or amytal are shown to increase oxygen consumption when intraperitoneally given sucinate, malate, citrate, alpha-ketoglutarate, dimethylsuccinate or glutamate (the Krebs cycle intermediates or their precursors) but not when given glucose, pyruvate, acetate, benzoate or nicotinate (energy substrates of other metabolic stages etc). Survival was increased with succinate or malate from control groups, which ranged from 30-83% to 87-100%. These effects were unrelated to respiratory depression or hypoxia as judged by little or no effect of succinate on ventilation indices and by the lack of effect of oxygen administration. Body cooling of comatose rats at ambient temperature approximately 19 degrees C became slower with succinate, the rate of cooling correlated well with oxygen consumption decrease. Succinate had no potency to modify oxygen consumption and body temperature in intact rats. A condition for antidote effect of the Krebs intermediate was sufficiently high dosage (5 mmol/kg), further dose increase made no odds. Repeated dosing of succinate had more marked protective effect, than a single one, to oxygen consumption and tended to promote the attenuation of lethal effect of barbiturates. These data suggest that suppression of whole body oxygen consumption with barbiturate overdose could be an important contributor to both body cooling and mortality. Intermediates of Krebs cycle, not only succinate, may have a pronounced therapeutic effect under the proper treatment regimen. Availability of Krebs cycle intermediates may be a limiting factor for the whole body oxygen consumption in barbiturate coma, its role in brain needs further elucidation.
Optimization of deformation monitoring networks using finite element strain analysis
NASA Astrophysics Data System (ADS)
Alizadeh-Khameneh, M. Amin; Eshagh, Mehdi; Jensen, Anna B. O.
2018-04-01
An optimal design of a geodetic network can fulfill the requested precision and reliability of the network, and decrease the expenses of its execution by removing unnecessary observations. The role of an optimal design is highlighted in deformation monitoring network due to the repeatability of these networks. The core design problem is how to define precision and reliability criteria. This paper proposes a solution, where the precision criterion is defined based on the precision of deformation parameters, i. e. precision of strain and differential rotations. A strain analysis can be performed to obtain some information about the possible deformation of a deformable object. In this study, we split an area into a number of three-dimensional finite elements with the help of the Delaunay triangulation and performed the strain analysis on each element. According to the obtained precision of deformation parameters in each element, the precision criterion of displacement detection at each network point is then determined. The developed criterion is implemented to optimize the observations from the Global Positioning System (GPS) in Skåne monitoring network in Sweden. The network was established in 1989 and straddled the Tornquist zone, which is one of the most active faults in southern Sweden. The numerical results show that 17 out of all 21 possible GPS baseline observations are sufficient to detect minimum 3 mm displacement at each network point.
Street, Timothy O; Barrick, Doug
2009-01-01
The Notch ankyrin domain is a repeat protein whose folding has been characterized through equilibrium and kinetic measurements. In previous work, equilibrium folding free energies of truncated constructs were used to generate an experimentally determined folding energy landscape (Mello and Barrick, Proc Natl Acad Sci USA 2004;101:14102–14107). Here, this folding energy landscape is used to parameterize a kinetic model in which local transition probabilities between partly folded states are based on energy values from the landscape. The landscape-based model correctly predicts highly diverse experimentally determined folding kinetics of the Notch ankyrin domain and sequence variants. These predictions include monophasic folding and biphasic unfolding, curvature in the unfolding limb of the chevron plot, population of a transient unfolding intermediate, relative folding rates of 19 variants spanning three orders of magnitude, and a change in the folding pathway that results from C-terminal stabilization. These findings indicate that the folding pathway(s) of the Notch ankyrin domain are thermodynamically selected: the primary determinants of kinetic behavior can be simply deduced from the local stability of individual repeats. PMID:19177351
Mörlein, Daniel; Meier-Dinkel, Lisa; Moritz, Jasmin; Sharifi, Ahmad Reza; Knorr, Christoph
2013-08-01
This study aimed to assess whether repeated exposure affects subjects' ability to detect androstenone. Olfactory acuity of 77 female and 44 male subjects (age 37.5 ± 11.7 years) was assessed three times during six weeks. Replicate triangle tests using various dilutions of androstenone (0.5, 5.0, and 50.0 μg/g) on filter paper smell strips were applied. Subjects were either assigned to a test group (TRAIN) using androstenone for daily training, or to a control group (CONTR) using a placebo. For the low, the intermediate, and the high level of androstenone presented, detection rate increased from 14.1 to 30.6%, 40.5 to 62.8%, and 65.3 to 78.5% respectively within 6 weeks from the initial assessment. Results suggest that mere exposure during repeated olfactory testing increased subjects' ability to correctly discriminate androstenone. The olfactory improvement was, however, more pronounced in the TRAIN group. Androstenone detection appears to be associated with its individual appreciation. Copyright © 2013 Elsevier Ltd. All rights reserved.
Precision of measurement and body size in whole-body air-displacement plethysmography.
Wells, J C; Fuller, N J
2001-08-01
To investigate methodological and biological precision for air-displacement plethysmography (ADP) across a wide range of body size. Repeated measurements of body volume (BV) and body weight (WT), and derived estimates of density (BD) and indices of fat mass (FM) and fat-free mass (FFM). Sixteen men, aged 22--48 y; 12 women, aged 24--42 y; 13 boys, aged 5--14 y; 17 girls, aged 5--16 y. BV and WT were measured using the Bodpod ADP system from which estimates of BD, FM and FFM were derived. FM and FFM were further adjusted for height to give fat mass index (FMI) and fat-free mass index (FFMI). ADP is very precise for measuring both BV and BD (between 0.16 and 0.44% of the mean). After removing two outliers from the database, and converting BD to body composition, precision of FMI was <6% in adults and within 8% in children, while precision of FFMI was within 1.5% for both age groups. ADP shows good precision for BV and BD across a wide range of body size, subject to biological artefacts. If aberrant values can be identified and rejected, precision of body composition is also good. Aberrant values can be identified by using pairs of ADP procedures, allowing the rejection of data where successive BD values differed by >0.007 kg/l. Precision of FMI obtained using pairs of procedures improves to <4.5% in adults and <5.5% in children.
Error measuring system of rotary Inductosyn
NASA Astrophysics Data System (ADS)
Liu, Chengjun; Zou, Jibin; Fu, Xinghe
2008-10-01
The inductosyn is a kind of high-precision angle-position sensor. It has important applications in servo table, precision machine tool and other products. The precision of inductosyn is calibrated by its error. It's an important problem about the error measurement in the process of production and application of the inductosyn. At present, it mainly depends on the method of artificial measurement to obtain the error of inductosyn. Therefore, the disadvantages can't be ignored such as the high labour intensity of the operator, the occurrent error which is easy occurred and the poor repeatability, and so on. In order to solve these problems, a new automatic measurement method is put forward in this paper which based on a high precision optical dividing head. Error signal can be obtained by processing the output signal of inductosyn and optical dividing head precisely. When inductosyn rotating continuously, its zero position error can be measured dynamically, and zero error curves can be output automatically. The measuring and calculating errors caused by man-made factor can be overcome by this method, and it makes measuring process more quickly, exactly and reliably. Experiment proves that the accuracy of error measuring system is 1.1 arc-second (peak - peak value).
Precision controllability of the YF-17 airplane
NASA Technical Reports Server (NTRS)
Sisk, T. R.; Mataeny, N. W.
1980-01-01
A flying qualities evaluation conducted on the YF-17 airplane permitted assessment of its precision controllability in the transonic flight regime over the allowable angle of attack range. The precision controllability (tailchase tracking) study was conducted in constant-g and windup turn tracking maneuvers with the command augmentation system (CAS) on, automatic maneuver flaps, and the caged pipper gunsight depressed 70 mils. This study showed that the YF-17 airplane tracks essentially as well at 7 g's to 8 g's as earlier fighters did at 4 g's to 5 g's before they encountered wing rock. The pilots considered the YF-17 airplane one of the best tracking airplanes they had flown. Wing rock at the higher angles of attack degraded tracking precision, and lack of control harmony made precision controllability more difficult. The revised automatic maneuver flap schedule incorporated in the airplane at the time of the tests did not appear to be optimum. The largest tracking errors and greatest pilot workload occurred at high normal load factors at low angles of attack. The pilots reported that the high-g maneuvers caused some tunnel vision and that they found it difficult to think clearly after repeated maneuvers.
Agut, Christophe; Segalini, Audrey; Bauer, Michel; Boccardi, Giovanni
2006-05-03
The rounding of an analytical result is a process that should take into account the uncertainty of the result, which is in turn assessed during the validation exercise. Rounding rules are known in physical and analytical chemistry since a long time, but are often not used or misused in pharmaceutical analysis. The paper describes the theoretical background of the most common rules and their application to fix the rounding of results and specifications. The paper makes use of uncertainty values of impurity determination acquired during studies of reproducibility and intermediate precision with regards to 22 impurities of drug substances or drug products. As a general rule, authors propose the use of sound and well-established rounding rules to derive rounding from the results of the validation package.
Probing New Long-Range Interactions by Isotope Shift Spectroscopy
DOE Office of Scientific and Technical Information (OSTI.GOV)
Berengut, Julian C.; Budker, Dmitry; Delaunay, Cédric
We explore a method to probe new long- and intermediate-range interactions using precision atomic isotope shift spectroscopy. We develop a formalism to interpret linear King plots as bounds on new physics with minimal theory inputs. We focus only on bounding the new physics contributions that can be calculated independently of the standard model nuclear effects. We apply our method to existing Ca + data and project its sensitivity to conjectured new bosons with spin-independent couplings to the electron and the neutron using narrow transitions in other atoms and ions, specifically, Sr and Yb. Future measurements are expected to improve themore » relative precision by 5 orders of magnitude, and they can potentially lead to an unprecedented sensitivity for bosons within the 0.3 to 10 MeV mass range.« less
Probing New Long-Range Interactions by Isotope Shift Spectroscopy.
Berengut, Julian C; Budker, Dmitry; Delaunay, Cédric; Flambaum, Victor V; Frugiuele, Claudia; Fuchs, Elina; Grojean, Christophe; Harnik, Roni; Ozeri, Roee; Perez, Gilad; Soreq, Yotam
2018-03-02
We explore a method to probe new long- and intermediate-range interactions using precision atomic isotope shift spectroscopy. We develop a formalism to interpret linear King plots as bounds on new physics with minimal theory inputs. We focus only on bounding the new physics contributions that can be calculated independently of the standard model nuclear effects. We apply our method to existing Ca^{+} data and project its sensitivity to conjectured new bosons with spin-independent couplings to the electron and the neutron using narrow transitions in other atoms and ions, specifically, Sr and Yb. Future measurements are expected to improve the relative precision by 5 orders of magnitude, and they can potentially lead to an unprecedented sensitivity for bosons within the 0.3 to 10 MeV mass range.
Probing New Long-Range Interactions by Isotope Shift Spectroscopy
Berengut, Julian C.; Budker, Dmitry; Delaunay, Cédric; ...
2018-02-26
We explore a method to probe new long- and intermediate-range interactions using precision atomic isotope shift spectroscopy. We develop a formalism to interpret linear King plots as bounds on new physics with minimal theory inputs. We focus only on bounding the new physics contributions that can be calculated independently of the standard model nuclear effects. We apply our method to existing Ca + data and project its sensitivity to conjectured new bosons with spin-independent couplings to the electron and the neutron using narrow transitions in other atoms and ions, specifically, Sr and Yb. Future measurements are expected to improve themore » relative precision by 5 orders of magnitude, and they can potentially lead to an unprecedented sensitivity for bosons within the 0.3 to 10 MeV mass range.« less
Validation of a spectrophotometric assay method for bisoprolol using picric acid.
Panainte, Alina-Diana; Bibire, Nela; Tântaru, Gladiola; Apostu, M; Vieriu, Mădălina
2013-01-01
Bisoprolol is a drug belonging to beta blockers drugs used primarily for the treatment of cardiovascular diseases. A spectrophotometric method for quantitative determination of bisoprolol was developed based on the formation of a complex combination between bisoprolol and picric acid. The complex combination of bisoprolol and picric acid has a maximum absorbance peak at 420 nm. Optimum working conditions were established and the method was validated. The method presented a good linearity in the concentration range 5-120 microg/ml (regression coefficient r2 = 0.9992). The RSD for the precision of the method was 1.74 and for the intermediate precision 1.43, and recovery values ranged between 98.25-101.48%. The proposed and validated spectrophotometric method for the determination of bisoprolol is simple and cost effective.
Hung, Man; Nickisch, Florian; Beals, Timothy C; Greene, Tom; Clegg, Daniel O; Saltzman, Charles L
2012-08-01
Accurately measuring, reporting and comparing outcomes is essential for improving health care delivery. Current challenges with available health status scales include patient fatigue, floor/ceiling effects and validity/reliability. This study compared Patient Reported Outcomes Measurement Information System (PROMIS)-based Lower Extremity Physical Function Computerized Adaptive Test (LE CAT) and two legacy scales -the Foot and Function Index (FFI) and the sport module from the Foot and Ankle Ability Measure (spFAAM) -for 287 patients scheduled for elective foot and ankle surgery. We documented the time required by patients to complete the instrument, instrument precision, and the extent to which each instrument covered the full range of physical functioning across the patient sample. Average time of test administration: 66 seconds for LE CAT, 130 seconds for spFAAM and 239 seconds for FFI. All three instruments were fairly precise at intermediate physical functioning levels (i.e., Standard Error of Measurement < 0.35), were relatively less precise at the higher trait levels and the LE CAT maintained precision in the lower range while the spFAAM and FFI's had decreased precision. The LE CAT had less floor/ceiling effects than the FFI and the spFAAM. The LE CAT showed considerable advantage compared to legacy scales for measuring patient-reported outcomes in orthopaedic patients with foot and ankle problems. A paradigm shift to broader use of PROMIS-based CATs should be considered to improve precision and reduce patient burden with patient-reported outcome measuremen foot and ankle patients.
Schindler, B K; Bruns, S; Lach, G
2015-03-15
Mushrooms have, repeatedly, been shown to contain nicotine. Speculation about the source of contamination has been widespread, however the source of nicotine remains unknown. Previous studies indicate that putrescine, an intermediate in nicotine biosynthesis, can be formed in mushrooms, which might be metabolised to form nicotine. Thus, endogenous formation may be a possible cause for elevated nicotine levels in mushrooms. We present evidence from the literature that may support this hypothesis. Copyright © 2014 Elsevier Ltd. All rights reserved.
Process for preparing perfluorotriazine elastomers and precursors thereof
NASA Technical Reports Server (NTRS)
Rosser, R. W.; Chen, T. S.; Cheng, C. H. (Inventor)
1984-01-01
Perfluoroether triazine elastomers having improved properties and utility in seals, gaskets, sealing components and the like are prepared from oligomeric imidoylamidines that have, in turn, been prepared by the process of (1) reacting a perfluorodinitrile with liquid ammonia to yield a perfluorodiamidine, (2) isolating the perfluorodiamidine, (3) reacting the isolated diamidine with a perfluorodinitrile to yield a perfluoror(imidoylamidine) dinitrile, and then repeating step (1), (2), and (3) to sequentially grow an oligomer of desired molecular size. The isolated amidine and nitrile intermediates are also described.
Perfluoro (Imidoylamidine) diamidines
NASA Technical Reports Server (NTRS)
Rosser, R. W.; Chen, T. S.; Cheng, C. H. (Inventor)
1986-01-01
Perfluoroether triazine elastomers having improved properties are prepared from oligomeric imidoylamidines that were in turn, prepared by the process of: (1) reacting a perfluorodinitrile with liquid ammonia to yield a perfluorodiamidine, (2) isolating the perfluorodiamidine, (3) reacting the isolated diamidine with a perfluorodinitrile to yield a perfluoro(imidoylamidine) dinitrile, and then repeating the steps to sequentially grow an oligomer of desired molecular size. The isolated amidine and nitrile intermediates are also disclosed. The elastomers can be fashioned into seals, gaskets, and sealing components and the like.
New high-strength, high-conductivity Cu-Ag alloy sheets
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sakai, Y.; Inoue, K.; Maeda, H.
1995-04-01
A sheet-conductor fabrication method has been developed for Cu-Ag alloys containing 6--24 wt% Ag in which high-strength and high-conductivity are obtained by coldworking combined with intermediate heat treatments. The intermediate heat treatments were repeated three times at 400--450 C for 1--2 h at appropriate stages of cold-rolling. The optimized Cu-24 wt% Ag alloy sheet with a 96% reduction ratio shows an ultimate tensile strength of 1,050 MPa and an electrical conductivity of 75% IACS at room temperature. Anisotropy in the strength with respect to the rolling direction is less than 10%, and no anisotropy in the electrical conductivity occurs. Themore » authors demonstrated the ability to manufacture the Cu-Ag sheets for Bitter magnet on a commercial basis. The sheets fabricated by this method are promising as conductors for high-field Bitter magnet coils.« less
Foster, D H; Westland, S
1998-01-01
Visual search for an edge or line element differing in orientation from a background of other edge or line elements can be performed rapidly and effortlessly. In this study, based on psychophysical measurements with ten human observers, threshold values of the angle between a target and background line elements were obtained as functions of background-element orientation, in brief masked displays. A repeated-loess analysis of the threshold functions suggested the existence of several groups of orientation-selective mechanisms contributing to rapid orientated-line detection; specifically, coarse, intermediate and fine mechanisms with preferred orientations spaced at angles of approximately 90 degrees, 35 degrees, and 10 degrees-25 degrees, respectively. The preferred orientations of coarse and some intermediate mechanisms coincided with the vertical or horizontal of the frontoparallel plane, but the preferred orientations of fine mechanisms varied randomly from observer to observer, possibly reflecting individual variations in neuronal sampling characteristics. PMID:9753784
Correlation between fibroin amino acid sequence and physical silk properties.
Fedic, Robert; Zurovec, Michal; Sehnal, Frantisek
2003-09-12
The fiber properties of lepidopteran silk depend on the amino acid repeats that interact during H-fibroin polymerization. The aim of our research was to relate repeat composition to insect biology and fiber strength. Representative regions of the H-fibroin genes were sequenced and analyzed in three pyralid species: wax moth (Galleria mellonella), European flour moth (Ephestia kuehniella), and Indian meal moth (Plodia interpunctella). The amino acid repeats are species-specific, evidently a diversification of an ancestral region of 43 residues, and include three types of regularly dispersed motifs: modifications of GSSAASAA sequence, stretches of tripeptides GXZ where X and Z represent bulky residues, and sequences similar to PVIVIEE. No concatenations of GX dipeptide or alanine, which are typical for Bombyx silkworms and Antheraea silk moths, respectively, were found. Despite different repeat structure, the silks of G. mellonella and E. kuehniella exhibit similar tensile strength as the Bombyx and Antheraea silks. We suggest that in these latter two species, variations in the repeat length obstruct repeat alignment, but sufficiently long stretches of iterated residues get superposed to interact. In the pyralid H-fibroins, interactions of the widely separated and diverse motifs depend on the precision of repeat matching; silk is strong in G. mellonella and E. kuehniella, with 2-3 types of long homogeneous repeats, and nearly 10 times weaker in P. interpunctella, with seven types of shorter erratic repeats. The high proportion of large amino acids in the H-fibroin of pyralids has probably evolved in connection with the spinning habit of caterpillars that live in protective silk tubes and spin continuously, enlarging the tubes on one end and partly devouring the other one. The silk serves as a depot of energetically rich and essential amino acids that may be scarce in the diet.
Development and Characterization of a Low-Pressure Calibration System for Hypersonic Wind Tunnels
NASA Technical Reports Server (NTRS)
Green, Del L.; Everhart, Joel L.; Rhode, Matthew N.
2004-01-01
Minimization of uncertainty is essential for accurate ESP measurements at very low free-stream static pressures found in hypersonic wind tunnels. Statistical characterization of environmental error sources requires a well defined and controlled calibration method. A calibration system has been constructed and environmental control software developed to control experimentation to eliminate human induced error sources. The initial stability study of the calibration system shows a high degree of measurement accuracy and precision in temperature and pressure control. Control manometer drift and reference pressure instabilities induce uncertainty into the repeatability of voltage responses measured from the PSI System 8400 between calibrations. Methods of improving repeatability are possible through software programming and further experimentation.
Reflective coating for near-infrared immersion gratings
NASA Astrophysics Data System (ADS)
Kuzmenko, Paul J.; Ikeda, Yuji; Kobayashi, Naoto; Mirkarimi, Paul B.; Alameda, Jennifer B.
2012-09-01
Achieving high reflectivity from an immersed grating facet can be challenging in the near infrared. The reflectivity of metallic coatings in common use, such as Al and Cr/Au, decrease with decreasing wavelength in the near IR. A layer of copper on ZnSe or ZnS should have a high, immersed reflectivity based on tabulated values of refractive index, but in fact performs poorly. We attribute this to a chemical reaction between the copper and the selenium or sulfur. A non-reactive intermediate layer can prevent this problem. Since reflectivity at an interface increases with increasing difference in refractive index, it is beneficial to choose an intermediate layer of low index. A further improvement is gained by adjusting the layer thickness so that reflections from the two interfaces of the intermediate layer add constructively. We sputtered 130 nm of SiO2 onto ZnSe and ZnS substrates followed by 200 nm of Cu. The copper was then coated with 5 nm of SiC as a protective capping layer. Immersed reflectivity measured shortly after coating exceeded 95% between 1500 and 1100 nm and exceeded 90% down to 850 nm. A repeat measurement after long term exposure to high humidity conditions showed no changes.
Assessment of different methods to estimate bovine colostrum quality on farm.
Bartens, M-C; Drillich, M; Rychli, K; Iwersen, M; Arnholdt, T; Meyer, L; Klein-Jöbstl, D
2016-09-01
To evaluate two different hydrometers and an optical and a digital Brix refractometer for the assessment of bovine colostrum quality, in terms of accuracy and precision compared with the measurement of IgG concentrations using radial immunodiffusion (RID), and to evaluate the reliability and repeatability of the Brix refractometers. To determine reliability and repeatability, 145 colostrum samples were tested by two independent observers twice, using the optical and digital Brix refractometers. A further 193 colostrum samples from Holstein cows were collected on one commercial dairy farm at first milking and tested with two hydrometers and an optical and digital Brix refractometer. An aliquot of each sample was frozen for RID measurement of IgG concentrations and samples were classified as poor (≤50 g IgG/L) or good (>50 g IgG/L) quality colostrum. Intraclass correlation coefficients (ICC) were used to determine inter- and intra-observer reliability and repeatability. Optimised cut-off values for the four devices were determined using receiver operating characteristics (ROC) analysis with the RID results as the reference. Using these cut-offs, sensitivities and specificities for determining good quality colostrum were calculated. The ICC for inter-observer reliability was 0.98 for the optical Brix refractometer, and for intra-observer repeatability was 0.97 and 0.98 for the optical and the digital Brix refractometers, respectively. For the 193 colostrum samples, 67 (34.7%) had concentrations of IgG ≤50 g/L determined by RID. Optimised cut-off values evaluated by ROC analysis were higher for all devices compared with manufacturer reference or previously published values. Using these values, the sensitivities for the two hydrometers, and the optical and the digital Brix refractometers were 0.73, 0.71, 0.56 and 0.79, respectively; specificities were 0.72, 0.61, 0.90 and 0.69, respectively. The Brix refractometers provided the most accurate assessment of colostrum quality of the devices evaluated, and demonstrated excellent precision in terms of repeatability. To provide optimal health for newborn calves, a sufficient intake of good quality colostrum is essential. The Brix refractometers provide rapid, convenient tools for classification of colostrum quality.
NASA Astrophysics Data System (ADS)
Haller, John W.; Botteron, K.; Brunsden, Barry S.; Sheline, Yvette I.; Walkup, Ronald K.; Black, Kevin J.; Gado, Mokhtar; Vannier, Michael W.
1994-09-01
Goal: To estimate hippocampal volumes from in vivo 3D magnetic resonance (MR) brain images and determine inter-rater and intra- rater repeatability. Objective: The precision and repeatability of hippocampal volume estimates using stereologic measurement methods is sought. Design: Five normal control and five schizophrenic subjects were MR scanned using a MPRAGE protocol. Fixed grid stereologic methods were used to estimate hippocampal volumes on a graphics workstation. The images were preprocessed using histogram analysis to standardize 3D MR image scaling from 16 to 8 bits and image volumes were interpolated to 0.5 mm3 isotropic voxels. The following variables were constant for the repeated stereologic measures: grid size, inter-slice distance (1.5 mm), voxel dimensions (0.5 mm3), number of hippocampi measured (10), total number of measurements per rater (40), and number of raters (5). Two grid sizes were tested to determine the coefficient of error associated with the number of sampled 'hits' (approximately 140 and 280) on the hippocampus. Starting slice and grid position were randomly varied to assure unbiased volume estimates. Raters were blind to subject identity, diagnosis, and side of the brain from which the image volumes were extracted and the order of subject presentation was randomized for each of the raters. Inter- and intra-rater intraclass correlation coefficients (ICC) were determined. Results: The data indicate excellent repeatability of fixed grid stereologic hippocampal volume measures when using an inter-slice distance of 1.5 mm and a 6.25 mm2 grid (inter-rater ICCs equals 0.86 - 0.97, intra- rater ICCs equals 0.85 - 0.97). One major advantage of the current study was the use of 3D MR data which significantly improved visualization of hippocampal boundaries by providing the ability to access simultaneous orthogonal views while counting stereological marks within the hippocampus. Conclusion: Stereological estimates of 3D volumes from 2D MR sections provide an inexpensive, unbiased and efficient way of determining brain structural volumes. The high precision and repeatability demonstrated with stereological MR volumetry suggest that these methods may be efficiently used to measure small volume reductions associated with schizophrenia and other brain disorders.
Comparison of optical coherence tomography and fundus photography for measuring the optic disc size.
Neubauer, Aljoscha S; Krieglstein, Tina R; Chryssafis, Christos; Thiel, Martin; Kampik, Anselm
2006-01-01
To assess the agreement and repeatability of optic nerve head (ONH) size measurements by optical coherence tomography (OCT) as compared to conventional planimetry of fundus photographs in normal eyes. For comparison with planimetry the absolute size of the ONH of 25 eyes from 25 normal subjects were measured by both OCT and digital fundus photography (Zeiss FF camera 450). Repeatability of automated Stratus OCT measurements were investigated by repeatedly measuring the optic disc in five normal subjects. Mean disc size was 1763 +/- 186 vertically and 1632 +/- 160 microm horizontally on planimetry. On OCT, values of 1772 +/- 317 microm vertically (p = 0.82) and a significantly smaller horizontal diameter of 1492 +/- 302 microm (p = 0.04) were obtained. The 95% limits of agreement were (-546 microm; +527 microm) for vertical and (-502 microm; +782 microm) for horizontal planimetric compared to OCT measurements. In some cases large discrepancies existed. Repeatability of automatic measurements of the optic disc by OCT was moderately good with intra-class correlation coefficients (ICC) of 0.78 horizontally and 0.83 vertically. The coefficient of repeatability indicating instrument precision was 80 microm for horizontal and 168 microm for vertical measurements. OCT can be used to determine optic disc margins in moderate agreement with planimetry in normal subjects. However, in some cases significant disagreement with photographic assessment may occur making manual inspection advisable. Automatic disc detection by OCT is moderately repeatable.
Herishanu, Yuval O; Parvari, Ruti; Pollack, Yaakov; Shelef, Ilan; Marom, Batia; Martino, Tiziana; Cannella, Milena; Squitieri, Ferdinando
2009-02-15
We report a cluster of patients from a Karaite Jew community with a movement disorder suggestive of Huntington disease (HD), in some cases associated with repeat lengths below the edge of 36 CAG repeats. The study describes the clinical and genetic features of four patients who were followed over several years. Patients belonged to an inbred family in whom progressive chorea, manifesting predominantly with dystonia and cerebellar features, developed during middle age. Although severe psychiatric symptoms ultimately developed in two of the four patients, cognitive function remained reasonably well preserved in all of them even after several disease years. Moderate cognitive deficits were limited to the visuomotor organization and abstract thinking subtests in three of the four patients. Qualitative brain imaging showed atrophy of brain predominantly involving cortex and cerebellum. Genetic testing revealed a variable mutation penetrance among family members, some affected members showing an upper allele size ranging from 34 to 49, whereas others remained unaffected despite the presence of the full mutation beyond 40 CAG repeats. Co-morbidity with recessive hereditary inclusion body myopathy was found in two subjects from one family. Although the main diagnosis of HD remains to be confirmed by further neuropathological studies, these cases may suggest that HD could manifest with as few as 34 CAG repeats, in some geographic areas, the disease phenotype most probably being influenced by additional, as yet unidentified, genes.
ERIC Educational Resources Information Center
Buhr, Anthony P.; Jones, Robin M.; Conture, Edward G.; Kelly, Ellen M.
2016-01-01
Background: It is already known that preschool-age children who stutter (CWS) tend to stutter on function words at the beginning of sentences. It is also known that phonological errors potentially resulting in part-word repetitions tend to occur on content words. However, the precise relation between word class and repetition type in preschool-age…
DOE Office of Scientific and Technical Information (OSTI.GOV)
Fong, Erika J.; Huang, Chao; Hamilton, Julie
Here, a major advantage of microfluidic devices is the ability to manipulate small sample volumes, thus reducing reagent waste and preserving precious sample. However, to achieve robust sample manipulation it is necessary to address device integration with the macroscale environment. To realize repeatable, sensitive particle separation with microfluidic devices, this protocol presents a complete automated and integrated microfluidic platform that enables precise processing of 0.15–1.5 ml samples using microfluidic devices. Important aspects of this system include modular device layout and robust fixtures resulting in reliable and flexible world to chip connections, and fully-automated fluid handling which accomplishes closed-loop sample collection,more » system cleaning and priming steps to ensure repeatable operation. Different microfluidic devices can be used interchangeably with this architecture. Here we incorporate an acoustofluidic device, detail its characterization, performance optimization, and demonstrate its use for size-separation of biological samples. By using real-time feedback during separation experiments, sample collection is optimized to conserve and concentrate sample. Although requiring the integration of multiple pieces of equipment, advantages of this architecture include the ability to process unknown samples with no additional system optimization, ease of device replacement, and precise, robust sample processing.« less
Sample survey methods as a quality assurance tool in a general practice immunisation audit.
Cullen, R
1994-04-27
In a multidoctor family practice there are often just too many sets of patients records to make it practical to repeat an audit by census of even an age band of the practice on a regular basis. This paper attempts to demonstrate how sample survey methodology can be incorporated into the quality assurance cycle. A simple random sample (with replacement) of 120 from 580 children with permanent records who were aged between 6 weeks and 2 years old from an Auckland general practice was performed, with sample size selected to give a predetermined precision. The survey was then repeated after 4 weeks. Both surveys were able to be completed within the course of a normal working day. An unexpectedly low level of under 2 years olds that were recorded as not overdue for any immunisations was found (22.5%) with only a modest improvement after a standard telephone/letter catch up campaign. Seventy-two percent of the sample held a group one community services card. The advantages of properly conducted sample surveys in producing useful estimates of known precision without disrupting office routines excessively were demonstrated. Through some attention to methodology, the trauma of a practice census can be avoided.
New method for remote and repeatable monitoring of intraocular pressure variations.
Margalit, Israel; Beiderman, Yevgeny; Skaat, Alon; Rosenfeld, Elkanah; Belkin, Michael; Tornow, Ralf-Peter; Mico, Vicente; Garcia, Javier; Zalevsky, Zeev
2014-02-01
We present initial steps toward a new measurement device enabling high-precision, noncontact remote and repeatable monitoring of intraocular pressure (IOP)-based on an innovative measurement principle. Using only a camera and a laser source, the device measures IOP by tracking the secondary speckle pattern trajectories produced by the reflection of an illuminating laser beam from the iris or the sclera. The device was tested on rabbit eyes using two different methods to modify IOP: via an infusion bag and via mechanical pressure. In both cases, the eyes were stimulated with increasing and decreasing ramps of the IOP. As IOP variations changed the speckle distributions reflected back from the eye, data were recorded under various optical configurations to define and optimize the best experimental configuration for the IOP extraction. The association between the data provided by our proposed device and that resulting from controlled modification of the IOP was assessed, revealing high correlation (R2=0.98) and sensitivity and providing a high-precision measurement (5% estimated error) for the best experimental configuration. Future steps will be directed toward applying the proposed measurement principle in clinical trials for monitoring IOP with human subjects.
NASA Astrophysics Data System (ADS)
Clapuyt, Francois; Vanacker, Veerle; Van Oost, Kristof
2016-05-01
Combination of UAV-based aerial pictures and Structure-from-Motion (SfM) algorithm provides an efficient, low-cost and rapid framework for remote sensing and monitoring of dynamic natural environments. This methodology is particularly suitable for repeated topographic surveys in remote or poorly accessible areas. However, temporal analysis of landform topography requires high accuracy of measurements and reproducibility of the methodology as differencing of digital surface models leads to error propagation. In order to assess the repeatability of the SfM technique, we surveyed a study area characterized by gentle topography with an UAV platform equipped with a standard reflex camera, and varied the focal length of the camera and location of georeferencing targets between flights. Comparison of different SfM-derived topography datasets shows that precision of measurements is in the order of centimetres for identical replications which highlights the excellent performance of the SfM workflow, all parameters being equal. The precision is one order of magnitude higher for 3D topographic reconstructions involving independent sets of ground control points, which results from the fact that the accuracy of the localisation of ground control points strongly propagates into final results.
RRW: repeated random walks on genome-scale protein networks for local cluster discovery
Macropol, Kathy; Can, Tolga; Singh, Ambuj K
2009-01-01
Background We propose an efficient and biologically sensitive algorithm based on repeated random walks (RRW) for discovering functional modules, e.g., complexes and pathways, within large-scale protein networks. Compared to existing cluster identification techniques, RRW implicitly makes use of network topology, edge weights, and long range interactions between proteins. Results We apply the proposed technique on a functional network of yeast genes and accurately identify statistically significant clusters of proteins. We validate the biological significance of the results using known complexes in the MIPS complex catalogue database and well-characterized biological processes. We find that 90% of the created clusters have the majority of their catalogued proteins belonging to the same MIPS complex, and about 80% have the majority of their proteins involved in the same biological process. We compare our method to various other clustering techniques, such as the Markov Clustering Algorithm (MCL), and find a significant improvement in the RRW clusters' precision and accuracy values. Conclusion RRW, which is a technique that exploits the topology of the network, is more precise and robust in finding local clusters. In addition, it has the added flexibility of being able to find multi-functional proteins by allowing overlapping clusters. PMID:19740439
Precision Measurements of the B(E1) Strengths in 11Be
NASA Astrophysics Data System (ADS)
Kwan, E.; Wu, C. Y.; Summers, N. C.; Hackman, G.; Drake, T. E.; Andreoiu, C.; Ashley, R.; Ball, G. C.; Bender, P. C.; Boston, A. J.; Boston, H. C.; Chester, A.; Close, A.; Cline, D.; Cross, D. S.; Dunlop, R.; Finley, A.; Garnsworthy, A.; Hayes, A. B.; Laffoley, A. T.; Nano, T.; Navrátil, P.; Pearson, C. J.; Pore, J.; Starosta, K.; Thompson, I. J.; Voss, P.; Williams, S. J.; Wang, Z. M.
2014-09-01
The electromagnetic transition strength between the two bound states were measured in the one-neutron halo nucleus 11Be from Coulomb excitation on 196Pt at projectile energies of 1.727 and 2.086 MeV/nucleon at TRIUMF. A B(E1) strength of 0.102(2) e2fm2, deduced from the forward-scattering data, is consistent with previous Coulomb excitation measurements at intermediate projectile energies with a model-dependent analysis.
JPRS Report, Science and Technology, USSR: Science and Technology Policy.
1990-07-23
complex jobs, which are now "nobody’s." For precisely these intermediate directions are the most promising with respect to future discoveries. At the...34Of course! I work as an aircraft designer, while the invention applies to medical equipment. The coopera- tive is prepared to pay all the necessary...the introduction and practical appli - cation of useful technical innovations. The main principle is "from the idea to the finished product." We
Ringwald, Johanna; Wochnowski, Christina; Bosse, Kristin; Giel, Katrin Elisabeth; Schäffeler, Norbert; Zipfel, Stephan; Teufel, Martin
2016-10-01
Understanding the intermediate- and long-term psychological consequences of genetic testing for cancer patients has led to encouraging research, but a clear consensus of the psychosocial impact and clinical routine for cancer-affected BRCA1 and BRCA2 mutation carriers is still missing. We performed a systematic review of intermediate- and long-term studies investigating the psychological impact like psychological distress, anxiety, and depression in cancer-affected BRCA mutation carriers compared to unaffected mutation carriers. This review included the screening of 1243 studies. Eight intermediate- and long-term studies focusing on distress, anxiety, and depression symptoms among cancer-affected mutation carriers at least six months after the disclosure of genetic testing results were included. Studies reported a great variety of designs, methods, and patient outcomes. We found evidence indicating that cancer-affected mutation carriers experienced a negative effect in relation to psychological well-being in terms of an increase in symptoms of distress, anxiety, and depression in the first months after test disclosure. In the intermediate- and long-term, no significant clinical relevant symptoms occurred. However, none of the included studies used specific measurements, which can clearly identify psychological burdens of cancer-affected mutation carriers. We concluded that current well-implemented distress screening instruments are not sufficient for precisely identifying the psychological burden of genetic testing. Therefore, future studies should implement coping strategies, specific personality structures, the impact of genetic testing, supportive care needs and disease management behaviour to clearly screen for the possible intermediate- and long-term psychological impact of a positive test disclosure.
Classification of Tidal Disruption Events Based on Stellar Orbital Properties
NASA Astrophysics Data System (ADS)
Hayasaki, Kimitake; Zhong, Shiyan; Li, Shuo; Berczik, Peter; Spurzem, Rainer
2018-03-01
We study the rates of tidal disruption of stars on bound to unbound orbits by intermediate-mass to supermassive black holes using high-accuracy direct N-body experiments. Stars from the star cluster approaching the black hole can have three types of orbit: eccentric, parabolic, and hyperbolic. Since the mass fallback rate shows different variabilities depending on the orbital type, we can classify tidal disruption events (TDEs) into three main categories: eccentric, parabolic, and hyperbolic. The respective TDEs are characterized by two critical values of the orbital eccentricity: the lower critical eccentricity is the one below which stars on eccentric orbits cause finite, intense accretion, and the upper critical eccentricity is the one above which stars on hyperbolic orbits cause no accretion. Moreover, we find that parabolic TDEs can be divided into three subclasses: precisely parabolic, marginally eccentric, and marginally hyperbolic. We analytically derive that the mass fallback rate of marginally eccentric TDEs can be flatter and slightly higher than the standard fallback rate proportional to t ‑5/3, whereas it can be flatter and lower for marginally hyperbolic TDEs. We confirm using N-body experiments that only a few eccentric, precisely parabolic, and hyperbolic TDEs can occur in a spherical stellar system with a single intermediate-mass to supermassive black hole. A substantial fraction of the stars approaching the black hole would cause marginally eccentric or marginally hyperbolic TDEs.
An indicator gene to demonstrate intracellular transposition of defective retroviruses.
Heidmann, T; Heidmann, O; Nicolas, J F
1988-01-01
An indicator gene for detection and quantitation of RNA-mediated transposition was constructed (neoRT). It was inserted into a Moloney murine leukemia provirus (Mo-MLV) deleted for the envelope gene to test for intracellular transposition of defective retroviruses [Mo-MLV(neo)RT]. NeoRT contains the selectable neo gene (which confers resistance to the drug G418), inactivated by a polyadenylylation sequence inserted between the neo promotor and coding sequence. The polyadenylylation sequence is flanked (on the antisense strand of the DNA) by a donor and an acceptor splice site so as to be removed upon passage of the provirus through an RNA intermediate. 3T3 cells transfected with the defective Mo-MLV(neo)RT provirus are sensitive to G418. After trans-complementation with Mo-MLV, viral transcripts confer resistance to G418 upon infection of test cells. In the resistant cells, the polyadenylylation sequence has been removed, as a result in most cases of precise splicing of the intronic domain. Retrotransposition of the defective Mo-MLV(neo)RT provirus was demonstrated by submitting transfected G418-sensitive clones to selection. Between 1 and 10 G418-resistant clones were obtained per 10(7) cells. Several possess additional copies, with evidence for precise removal of the intronic domain. By using target test cells in coculture experiments, extracellular intermediates of retrotransposition could not be detected. Images PMID:2832848
Modi, Ketan Pravinbhai; Patel, Natvarlal Manilal; Goyal, Ramesh Kishorilal
2008-03-01
A selective, precise, and accurate high-performance thin-layer chromatographic (HPTLC) method has been developed for the analysis of L-dopa in Mucuna pruriens seed extract and its formulations. The method involves densitometric evaluation of L-dopa after resolving it by HPTLC on silica gel plates with n-butanol-acetic acid-water (4.0+1.0+1.0, v/v) as the mobile phase. Densitometric analysis of L-dopa was carried out in the absorbance mode at 280 nm. The relationship between the concentration of L-dopa and corresponding peak areas was found to be linear in the range of 100 to 1200 ng/spot. The method was validated for precision (inter and intraday), repeatability, and accuracy. Mean recovery was 100.30%. The relative standard deviation (RSD) values of the precision were found to be in the range 0.64-1.52%. In conclusion, the proposed TLC method was found to be precise, specific and accurate and can be used for identification and quantitative determination of L-dopa in herbal extract and its formulations.
Stability-indicating UPLC method for determining related substances and degradants in dronedarone.
Pydimarry, Surya Prakash Rao; Cholleti, Vijay Kumar; Vangala, Ranga Reddy
2014-08-01
A simple, sensitive and reproducible method was developed on ultra-performance liquid chromatography coupled with photodiode array detection for the quantitative determination of dronedarone hydrochloride (DRO) in drug substance and pharmaceutical dosage forms. The method is applicable for the quantification of related substances and assays of drug substances. Chromatographic separation was achieved on Acquity UPLC BEH C8 100 mm, 2.1 mm and 1.7 µm columns, using gradient elution within a short run time of 10.0 min. The eluted compounds were monitored at 288 nm, the flow rate was 0.5 mL/min and the column oven temperature was maintained at 40°C. The resolution of DRO and 11 impurities (potentials and by-products) was greater than 2.0 for all pairs of components. The high correlation coefficient value (>0.9995) indicates the clear correlations between the concentrations of investigated compound and their peak areas within the test ranges. The repeatability and intermediate precision, expressed by the relative standard deviation, were less than 2.5%. The accuracy and validity of the method were further ascertained by performing recovery studies via a spike method. The accuracy of the method, expressed as relative error, was satisfactory. No interference was observed from concomitant substances normally added to the tablets. DRO was subjected to the stress conditions of oxidative, acid, base, hydrolytic, thermal and photolytic degradation. DRO was found to degrade significantly in acid and base stress conditions and to remain stable in thermal, photolytic degradation, oxidative and hydrolytic conditions. The degradation products were well resolved from primary peak and its impurities, proving that the method is stability indicating. The developed method was validated as per International Conference on Harmonization guidelines with respect to specificity, limit of detection, limit of quantification, linearity, accuracy, precision, solution stability and robustness. This method is also suitable for the determination of DRO drug substance and pharmaceutical dosage forms. © The Author [2013]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Markiewicz, B; Sajnóg, A; Lorenc, W; Hanć, A; Komorowicz, I; Suliburska, J; Kocyłowski, R; Barałkiewicz, D
2017-11-01
Amniotic fluid is the substantial factor in the development of an embryo and fetus due to the fact that water and solutes contained in it penetrate the fetal membranes in an hydrostatic and osmotic way as well as being swallowed by the fetus. Elemental composition of amniotic fluid influences the growth and health of the fetus, therefore, an analysis of amniotic fluid is important because the results would indicate abnormal levels of minerals or toxic elements. Inductively coupled plasma mass spectroscopy (ICP-MS) is often used for determination of trace and ultra-trace level elements in a wide range of matrices including biological samples because of its unique analytical capabilities. In the case of trace and ultra-trace level analysis detailed characteristics of analytical procedure as well as properties of the analytical result are particularly important. The purpose of this study was to develop a new analytical procedure for multielemental analysis of 18 elements (Al, As, Ba, Ca, Cd, Co, Cr, Cu, Mg, Mn, Ni, Pb, Sb, Se, Sr, U, V and Zn) in amniotic fluid samples using ICP-MS. Dynamic reaction cell (DRC) with two reaction gases, ammonia and oxygen, was involved in the experiment to eliminate spectral interferences. Detailed validation was conducted using 3 certified reference mterials (CRMs) and real amniotic fluid samples collected from patients. Repeatability for all analyzed analytes was found to range from 0.70% to 8.0% and for intermediate precision results varied from 1.3% to 15%. Trueness expressed as recovery ranged from 80% to 125%. Traceability was assured through the analyses of CRMs. Uncertainty of the results was also evaluated using single-laboratory validation approach. The obtained expanded uncertainty (U) results for CRMs, expressed as a percentage of the concentration of an analyte, were found to be between 8.3% for V and 45% for Cd. Standard uncertainty of the precision was found to have a greater influence on the combined standard uncertainty than on trueness factor. Copyright © 2017 Elsevier B.V. All rights reserved.
Regueiro, Jorge; Wenzl, Thomas
2015-11-27
Facing growing restrictions on the use of bisphenol A in food contact materials, several bisphenol analogs are arising as major alternatives to replace this chemical in most of its applications. This work reports a simple and robust method based on mixed-mode solid-phase extraction and stable-isotope dilution liquid chromatography-tandem mass spectrometry for the analysis of bisphenol A and its main analogs - bisphenol S, 4,4'-sulfonylbis(2-methylphenol), bisphenol F, bisphenol E, bisphenol B, bisphenol Z, bisphenol AF, bisphenol AP, tetrabromobisphenol A and bisphenol P - in alcoholic and non-alcoholic beverages. Mixed-mode solid-phase extraction, combining cationic exchange and reversed-phase mechanisms, was optimized to provide a selective extraction and purification of the target analytes. Derivatization of bisphenols with pyridine-3-sulfonyl chloride allowed increasing their ionization efficiency by electrospray ionization. Validation of the proposed method was performed in terms of selectivity, matrix effects, linearity, precision, measurement uncertainty, trueness and limits of detection. Satisfactory repeatability and intermediate precision were obtained; the related relative standard deviations were ≤9% and ≤12%, respectively. The relative expanded uncertainty (k=2) was below 20% for all bisphenol analogs and the trueness of the method was demonstrated by recovery experiments. Limits of detection (LOD) ranged from 1.6ngL(-1) to 27.9ngL(-1) for all compounds. Finally, several canned and non-canned beverages were analyzed to demonstrate the applicability of the method. Only bisphenol A and three bisphenol F isomers were detected in any of the samples. Bisphenol A concentration ranged from
Ansermot, Nicolas; Brawand-Amey, Marlyse; Eap, Chin B
2012-02-15
A simple and sensitive liquid chromatography-electrospray ionization mass spectrometry method was developed for the simultaneous quantification in human plasma of all selective serotonin reuptake inhibitors (citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline) and their main active metabolites (desmethyl-citalopram and norfluoxetine). A stable isotope-labeled internal standard was used for each analyte to compensate for the global method variability, including extraction and ionization variations. After sample (250μl) pre-treatment with acetonitrile (500μl) to precipitate proteins, a fast solid-phase extraction procedure was performed using mixed mode Oasis MCX 96-well plate. Chromatographic separation was achieved in less than 9.0min on a XBridge C18 column (2.1×100mm; 3.5μm) using a gradient of ammonium acetate (pH 8.1; 50mM) and acetonitrile as mobile phase at a flow rate of 0.3ml/min. The method was fully validated according to Société Française des Sciences et Techniques Pharmaceutiques protocols and the latest Food and Drug Administration guidelines. Six point calibration curves were used to cover a large concentration range of 1-500ng/ml for citalopram, desmethyl-citalopram, paroxetine and sertraline, 1-1000ng/ml for fluoxetine and fluvoxamine, and 2-1000ng/ml for norfluoxetine. Good quantitative performances were achieved in terms of trueness (84.2-109.6%), repeatability (0.9-14.6%) and intermediate precision (1.8-18.0%) in the entire assay range including the lower limit of quantification. Internal standard-normalized matrix effects were lower than 13%. The accuracy profiles (total error) were mainly included in the acceptance limits of ±30% for biological samples. The method was successfully applied for routine therapeutic drug monitoring of more than 1600 patient plasma samples over 9 months. The β-expectation tolerance intervals determined during the validation phase were coherent with the results of quality control samples analyzed during routine use. This method is therefore precise and suitable both for therapeutic drug monitoring and pharmacokinetic studies in most clinical laboratories. Copyright © 2012 Elsevier B.V. All rights reserved.
NASA Astrophysics Data System (ADS)
Osada, Y.; Ohta, Y.; Demachi, T.; Kido, M.; Fujimoto, H.; Azuma, R.; Hino, R.
2013-12-01
Large interplate earthquake repeatedly occurred in Japan Trench. Recently, the detail crustal deformation revealed by the nation-wide inland GPS network called as GEONET by GSI. However, the maximum displacement region for interplate earthquake is mainly located offshore region. GPS/Acoustic seafloor geodetic observation (hereafter GPS/A) is quite important and useful for understanding of shallower part of the interplate coupling between subducting and overriding plates. We typically conduct GPS/A in specific ocean area based on repeated campaign style using research vessel or buoy. Therefore, we cannot monitor the temporal variation of seafloor crustal deformation in real time. The one of technical issue on real time observation is kinematic GPS analysis because kinematic GPS analysis based on reference and rover data. If the precise kinematic GPS analysis will be possible in the offshore region, it should be promising method for real time GPS/A with USV (Unmanned Surface Vehicle) and a moored buoy. We assessed stability, precision and accuracy of StarFireTM global satellites based augmentation system. We primarily tested for StarFire in the static condition. In order to assess coordinate precision and accuracy, we compared 1Hz StarFire time series and post-processed precise point positioning (PPP) 1Hz time series by GIPSY-OASIS II processing software Ver. 6.1.2 with three difference product types (ultra-rapid, rapid, and final orbits). We also used difference interval clock information (30 and 300 seconds) for the post-processed PPP processing. The standard deviation of real time StarFire time series is less than 30 mm (horizontal components) and 60 mm (vertical component) based on 1 month continuous processing. We also assessed noise spectrum of the estimated time series by StarFire and post-processed GIPSY PPP results. We found that the noise spectrum of StarFire time series is similar pattern with GIPSY-OASIS II processing result based on JPL rapid orbit products with 300 seconds interval clock information. And we report stability, precision and accuracy of StarFire in the moving conditon.
Surr, C A; Smith, S J; Crossland, J; Robins, J
2016-01-01
People with dementia occupy up to one quarter of acute hospital beds. However, the quality of care delivered to this patient group is of national concern. Staff working in acute hospitals report lack of knowledge, skills and confidence in caring for people with dementia. There is limited evidence about the most effective approaches to supporting acute hospital staff to deliver more person-centred care. This study aimed to evaluate the efficacy of a specialist training programme for acute hospital staff regarding improving attitudes, satisfaction and feelings of caring efficacy, in provision of care to people with dementia. A repeated measures design, with measures completed immediately prior to commencing training (T1), after completion of Foundation level training (T2: 4-6 weeks post-baseline), and following Intermediate level training (T3: 3-4 months post-baseline). One NHS Trust in the North of England, UK. 40 acute hospital staff working in clinical roles, the majority of whom (90%) were nurses. All participants received the 3.5 day Person-centred Care Training for Acute Hospitals (PCTAH) programme, comprised of two levels, Foundation (0.5 day) and Intermediate (3 days), delivered over a 3-4 months period. Staff demographics and previous exposure to dementia training were collected via a questionnaire. Staff attitudes were measured using the Approaches to Dementia Questionnaire (ADQ), satisfaction in caring for people with dementia was captured using the Staff Experiences of Working with Demented Residents questionnaire (SEWDR) and perceived caring efficacy was measured using the Caring Efficacy Scale (CES). The training programme was effective in producing a significant positive change on all three outcome measures following intermediate training compared to baseline. A significant positive effect was found on the ADQ between baseline and after completion of Foundation level training, but not for either of the other measures. Training acute hospital staff in Intermediate level person-centred dementia care is effective in producing significant improvements in attitudes towards and satisfaction in caring for people with dementia and feelings of caring efficacy. Foundation level training is effective in changing attitudes but does not seem to be sufficient to bring about change in satisfaction or caring efficacy. Copyright © 2015 Elsevier Ltd. All rights reserved.
Quantitative analysis of TALE-DNA interactions suggests polarity effects.
Meckler, Joshua F; Bhakta, Mital S; Kim, Moon-Soo; Ovadia, Robert; Habrian, Chris H; Zykovich, Artem; Yu, Abigail; Lockwood, Sarah H; Morbitzer, Robert; Elsäesser, Janett; Lahaye, Thomas; Segal, David J; Baldwin, Enoch P
2013-04-01
Transcription activator-like effectors (TALEs) have revolutionized the field of genome engineering. We present here a systematic assessment of TALE DNA recognition, using quantitative electrophoretic mobility shift assays and reporter gene activation assays. Within TALE proteins, tandem 34-amino acid repeats recognize one base pair each and direct sequence-specific DNA binding through repeat variable di-residues (RVDs). We found that RVD choice can affect affinity by four orders of magnitude, with the relative RVD contribution in the order NG > HD ≈ NN > NI > NK. The NN repeat preferred the base G over A, whereas the NK repeat bound G with 10(3)-fold lower affinity. We compared AvrBs3, a naturally occurring TALE that recognizes its target using some atypical RVD-base combinations, with a designed TALE that precisely matches 'standard' RVDs with the target bases. This comparison revealed unexpected differences in sensitivity to substitutions of the invariant 5'-T. Another surprising observation was that base mismatches at the 5' end of the target site had more disruptive effects on affinity than those at the 3' end, particularly in designed TALEs. These results provide evidence that TALE-DNA recognition exhibits a hitherto un-described polarity effect, in which the N-terminal repeats contribute more to affinity than C-terminal ones.
Apparatus for Precise Indium-Bump Bonding of Microchips
NASA Technical Reports Server (NTRS)
Wild, Larry; Mulder, Jerry; Alvarado, Nicholas
2005-01-01
An improved apparatus has been designed and built for use in precise positioning and pressing of a microchip onto a substrate (which could, optionally, be another microchip) for the purpose of indium-bump bonding. The apparatus (see figure) includes the following: A stereomicroscope, A stage for precise positioning of the microchip in rotation angle (theta) about the nominally vertical pressing axis and in translation along two nominally horizontal coordinate axes (x and y), and An actuator system that causes a bonding tip to press the microchip against the substrate with a precisely controlled force. In operation, the microscope and the stage are used to position the microchip under the bonding tip and to align the indium bumps on the chip and the substrate, then the actuator system is used to apply a prescribed bonding force for a prescribed time. The improved apparatus supplants a partly similar prior apparatus that operated with less precision and repeatability, producing inconsistent and unreliable bonds. Results of the use of the prior apparatus included broken microchips, uneven bonds, and bonds characterized, variously, by overcompression or undercompression. In that apparatus, the bonding force was generated and controlled by use of a micrometer head positioned over the center of a spring-loaded scale, and the force was applied to the microchip via the scale, which was equipped for digital readout of the force. The inconsistency of results was attributed to the following causes: It was not possible to control the bonding force with sufficient precision or repeatability. Particularly troublesome was the inability to control the force at levels less than the weight of 150 g. Excessive compliance in the spring-loaded scale, combined with deviations from parallelarity of the substrate and bonding-tip surfaces, gave rise to nonuniformity in the pressure applied to the microchip, thereby generating excessive stresses and deformations in the microchip. In the improved apparatus, the bonding tip and the components that hold the substrate and the microchip are more rigid and precise than in the prior apparatus, so as to ensure less deviation from parallelarity of the bonding-tip and substrate surfaces, thereby ensuring more nearly uniform distribution of bonding force over the area of the microchip. The bonding force is now applied through, and measured by, a load cell that makes it possible to exert finer control over the force. The force can be set at any value between 0 and the weight of 800 g in increments of 0.2 g.
Mansor, Syahir; Pfaehler, Elisabeth; Heijtel, Dennis; Lodge, Martin A; Boellaard, Ronald; Yaqub, Maqsood
2017-12-01
In longitudinal oncological and brain PET/CT studies, it is important to understand the repeatability of quantitative PET metrics in order to assess change in tracer uptake. The present studies were performed in order to assess precision as function of PET/CT system, reconstruction protocol, analysis method, scan duration (or image noise), and repositioning in the field of view. Multiple (repeated) scans have been performed using a NEMA image quality (IQ) phantom and a 3D Hoffman brain phantom filled with 18 F solutions on two systems. Studies were performed with and without randomly (< 2 cm) repositioning the phantom and all scans (12 replicates for IQ phantom and 10 replicates for Hoffman brain phantom) were performed at equal count statistics. For the NEMA IQ phantom, we studied the recovery coefficients (RC) of the maximum (SUV max ), peak (SUV peak ), and mean (SUV mean ) uptake in each sphere as a function of experimental conditions (noise level, reconstruction settings, and phantom repositioning). For the 3D Hoffman phantom, the mean activity concentration was determined within several volumes of interest and activity recovery and its precision was studied as function of experimental conditions. The impact of phantom repositioning on RC precision was mainly seen on the Philips Ingenuity PET/CT, especially in the case of smaller spheres (< 17 mm diameter, P < 0.05). This effect was much smaller for the Siemens Biograph system. When exploring SUV max , SUV peak , or SUV mean of the spheres in the NEMA IQ phantom, it was observed that precision depended on phantom repositioning, reconstruction algorithm, and scan duration, with SUV max being most and SUV peak least sensitive to phantom repositioning. For the brain phantom, regional averaged SUVs were only minimally affected by phantom repositioning (< 2 cm). The precision of quantitative PET metrics depends on the combination of reconstruction protocol, data analysis methods and scan duration (scan statistics). Moreover, precision was also affected by phantom repositioning but its impact depended on the data analysis method in combination with the reconstructed voxel size (tissue fraction effect). This study suggests that for oncological PET studies the use of SUV peak may be preferred over SUV max because SUV peak is less sensitive to patient repositioning/tumor sampling. © 2017 The Authors. Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.
Cis-acting factors modulate stability of intermediate alleles for Huntington disease
DOE Office of Scientific and Technical Information (OSTI.GOV)
Goldberg, Y.P.; Zeisler, J.; Thielmann, J.
1994-09-01
The genetic basis of Huntington disease (HD), a late-onset autosomal dominant neurodegenerative disorder, has recently been defined as a CAG trinucleotide expansion in a novel gene on 4p16.3. The CAG length in clinically normal people ranges from 9 to 37, with the vast majority of alleles (99%) containing less than 30 repeats. In contrast, HD patients have CAG lengths greater than 36 with the largest repeat reported to date being 121. Molecular analysis of sporadic cases of HD revealed that new mutations are not rare (3%), and arise from intermediate alleles (IAs). IAs are CAG alleles greater than that usuallymore » seen in the general population (>30), but less than that seen in patients with HD and occur with a frequency of approximately 1.5% of the general population (12/797). An important question is whether these IAs are also susceptible to expansion. In new mutation families, these IAs are unstable in passage through the male germline and in sporadic cases expand to the full mutation associated with the HD phenotype. On the 41 meioses analyzed in new mutation families, 61% were unstable. In contrast to IAs in the new mutation families, the IAs in the general population were predominately stable from one generation to the next. Comparison of the frequency of intergenerational stability between the general population and the new mutation families showed that IAs in the general population are considerably more stable than those in the new mutation families. In contrast to SCA 1 where sequence interruption is thought to play a role in CAG trinucleotide stability, sequence analysis of IAs both from the general population and the new mutation families failed to reveal any interruption of the CAG tracts. These findings suggest that while CAG size is an important factor, other cis-acting factors present in new mutation families but not in the general population are likely to be critical in conferring instability upon the CAG trinucleotide repeat.« less
Nagahashi, S; Endoh, H; Suzuki, Y; Okada, N
1991-11-20
A previous report from this laboratory showed that in vitro transcription of total genomic DNA of the newt Cynopus pyrrhogaster resulted in a discrete sized 8 S RNA, which represented highly repetitive and transcribable sequences with a glutamic acid tRNA-like structure in the newt genome. We isolated four independent clones from a newt genomic library and determined the complete sequences of three 2000 to 2400 base-pair PstI fragments spanning the 8 S RNA gene. The glutamic acid tRNA-related segment in the 8 S RNA gene contains the CCA sequence expected as the 3' terminus of a tRNA molecule. Further, the 11 nucleotides located 13 nucleotides upstream from one of the two transcription initiation sites of the 8 S RNA were found to be repeated in the region upstream from the termination site, suggesting that the original unit, which is shorter than the 8 S RNA, was retrotransposed via cDNA intermediates from the PolIII transcript. In the upstream region of the 8 S RNA gene, a 360 nucleotide unit containing the glutamic acid tRNA-related segment was found to be duplicated (clones NE1 and NE10) or triplicated (clone NE3). Except for the difference in the number of the 360 nucleotide unit, the three sequences of the 2000 to 2400 base-pair PstI fragment were essentially the same with only a few mutations and minor deletions. Inverse polymerase chain reaction and sequence determination of the products, together with a Southern hybridization experiment, demonstrated that the family consists of a tandemly repeated unit of 3300, 3700 or 4100 base-pairs. Thus during evolution, this family in the newt was created by retroposition via cDNA intermediates, followed by duplication or triplication of the 360 nucleotide unit and multiplication of the 3300 to 4100 base-pair region at the DNA level.
Inter-method Performance Study of Tumor Volumetry Assessment on Computed Tomography Test-retest Data
Buckler, Andrew J.; Danagoulian, Jovanna; Johnson, Kjell; Peskin, Adele; Gavrielides, Marios A.; Petrick, Nicholas; Obuchowski, Nancy A.; Beaumont, Hubert; Hadjiiski, Lubomir; Jarecha, Rudresh; Kuhnigk, Jan-Martin; Mantri, Ninad; McNitt-Gray, Michael; Moltz, Jan Hendrik; Nyiri, Gergely; Peterson, Sam; Tervé, Pierre; Tietjen, Christian; von Lavante, Etienne; Ma, Xiaonan; Pierre, Samantha St.; Athelogou, Maria
2015-01-01
Rationale and objectives Tumor volume change has potential as a biomarker for diagnosis, therapy planning, and treatment response. Precision was evaluated and compared among semi-automated lung tumor volume measurement algorithms from clinical thoracic CT datasets. The results inform approaches and testing requirements for establishing conformance with the Quantitative Imaging Biomarker Alliance (QIBA) CT Volumetry Profile. Materials and Methods Industry and academic groups participated in a challenge study. Intra-algorithm repeatability and inter-algorithm reproducibility were estimated. Relative magnitudes of various sources of variability were estimated using a linear mixed effects model. Segmentation boundaries were compared to provide a basis on which to optimize algorithm performance for developers. Results Intra-algorithm repeatability ranged from 13% (best performing) to 100% (least performing), with most algorithms demonstrating improved repeatability as the tumor size increased. Inter-algorithm reproducibility determined in three partitions and found to be 58% for the four best performing groups, 70% for the set of groups meeting repeatability requirements, and 84% when all groups but the least performer were included. The best performing partition performed markedly better on tumors with equivalent diameters above 40 mm. Larger tumors benefitted by human editing but smaller tumors did not. One-fifth to one-half of the total variability came from sources independent of the algorithms. Segmentation boundaries differed substantially, not just in overall volume but in detail. Conclusions Nine of the twelve participating algorithms pass precision requirements similar to what is indicated in the QIBA Profile, with the caveat that the current study was not designed to explicitly evaluate algorithm Profile conformance. Change in tumor volume can be measured with confidence to within ±14% using any of these nine algorithms on tumor sizes above 10 mm. No partition of the algorithms were able to meet the QIBA requirements for interchangeability down to 10 mm, though the partition comprised of the best performing algorithms did meet this requirement above a tumor size of approximately 40 mm. PMID:26376841
Sun, Ning; Critchley, David R; Paulin, Denise; Li, Zhenlin; Robson, Richard M
2008-05-01
The type VI intermediate filament (IF) protein synemin is a unique member of the IF protein superfamily. Synemin associates with the major type III IF protein desmin forming heteropolymeric intermediate filaments (IFs) within developed mammalian striated muscle cells. These IFs encircle and link all adjacent myofibrils together at their Z-lines, as well as link the Z-lines of the peripheral layer of cellular myofibrils to the costameres located periodically along and subjacent to the sarcolemma. Costameres are multi-protein assemblies enriched in the cytoskeletal proteins vinculin, alpha-actinin, and talin. We report herein a direct interaction of human alpha-synemin with the cytoskeletal protein talin by protein-protein interaction assays. The 312 amino acid insert (SNTIII) present only within alpha-synemin binds to the rod domain of talin in vitro and co-localizes with talin at focal adhesion sites within mammalian muscle cells. Confocal microscopy studies showed that synemin co-localizes with talin within the costameres of human skeletal muscle cells. Analysis of the primary sequences of human alpha- and beta-synemins revealed that SNTIII is composed of seven tandem repeats, each containing a specific Ser/Thr-X-Arg-His/Gln (S/T-X-R-H/Q) motif. Our results suggest human alpha-synemin plays an essential role in linking the heteropolymeric IFs to adherens-type junctions, such as the costameres within mammalian striated muscle cells, via its interaction with talin, thereby helping provide mechanical integration for the muscle cell cytoskeleton.
Roche, Julien; Louis, John M; Grishaev, Alexander; Ying, Jinfa; Bax, Adriaan
2014-03-04
The envelope glycoprotein gp41 mediates the process of membrane fusion that enables entry of the HIV-1 virus into the host cell. The actual fusion process involves a switch from a homotrimeric prehairpin intermediate conformation, consisting of parallel coiled-coil helices, to a postfusion state where the ectodomains are arranged as a trimer of helical hairpins, adopting a six-helix bundle (6HB) state. Here, we show by solution NMR spectroscopy that a water-soluble 6HB gp41 ectodomain binds to zwitterionic detergents that contain phosphocholine or phosphatidylcholine head groups and phospholipid vesicles that mimic T-cell membrane composition. Binding results in the dissociation of the 6HB and the formation of a monomeric state, where its two α-helices, N-terminal heptad repeat (NHR) and C-terminal heptad repeat (CHR), become embedded in the lipid-water interface of the virus and host cell. The atomic structure of the gp41 ectodomain monomer, based on NOE distance restraints and residual dipolar couplings, shows that the NHR and CHR helices remain mostly intact, but they completely lose interhelical contacts. The high affinity of the ectodomain helices for phospholipid surfaces suggests that unzippering of the prehairpin intermediate leads to a state where the NHR and CHR helices become embedded in the host cell and viral membranes, respectively, thereby providing a physical force for bringing these membranes into close juxtaposition before actual fusion.
Pastoris, O; Dossena, M; Gorini, A; Vercesi, L; Benzi, G
1985-03-01
Muscular glycolytic fuels, intermediates and end-products (glycogen, glucose, glucose-6-phosphate, pyruvate, lactate), Krebs cycle intermediates (citrate, alpha-ketoglutarate, succinate, malate), related free amino acids (glutamate, alanine), ammonia, energy store (creatine phosphate), energy mediators (ATP, ADP, AMP) and energy charge potential were evaluated. Furthermore the maximum rate (Vmax) of the following muscular enzyme activities was evaluated in the crude extract and/or mitochondrial fraction: for the anaerobic glycolytic pathway: hexokinase, phosphofructokinase, pyruvate kinase, lactate dehydrogenase; for the tricarboxylic acid cycle: citrate synthase, malate dehydrogenase; for the electron transfer chain: total NADH cytochrome c reductase, cytochrome oxidase. The rat gastrocnemius muscles were analyzed in normoxia and after repeated, alternate hypoxic and normoxic exposures (12 hours of hypoxia daily; for 5 days). Naftidrofuryl was administered daily at three different doses: 10, 15 and 22.5 mg/kg i.m., 30 min before the beginning of the experimental hypoxia. The biochemical adaptation to intermittent normobaric hypoxic-normoxic exposures was characterized by the decrease of the muscular contents of creatine phosphate, citrate, alpha-ketoglutarate and glutamate. This adaptation occurred in absence of significant changes in the Vmax of the muscle enzymes tested. By naftidrofuryl treatment, in gastrocnemius muscle from hypoxic rats both alpha-ketoglutarate and creatine phosphate contents maintained normal values, while glutamate concentration remained reduced to subnormal values. With the exception of hexokinase, naftidrofuryl treatment did not modify the Vmax of marker enzymes related to energy transduction.
Type 1 Does The Two-Step: Type 1 Secretion Substrates With A Functional Periplasmic Intermediate.
Smith, Timothy J; Sondermann, Holger; O'Toole, George A
2018-06-04
Bacteria have evolved several secretion strategies for polling and responding to environmental flux and insult. Of these, the type 1 secretion system (T1SS) is known to secrete an array of biologically diverse proteins - from small < 10 kDa bacteriocins to gigantic adhesins with a mass over 1 MDa. For the last several decades T1SS have been characterized as a one-step translocation strategy whereby the secreted substrate is transported directly into the extracellular environment from the cytoplasm with no periplasmic intermediate. Recent phylogenetic, biochemical, and genetic evidence point to a distinct sub-group of T1SS machinery linked with a bacterial transglutaminase-like cysteine proteinase (BTLCP), which uses a two-step secretion mechanism. BTLCP-linked T1SS transport a class of repeats-in-toxin (RTX) adhesins that are critical for biofilm formation. The prototype of this RTX adhesin group, LapA of Pseudomonas fluorescens Pf0-1, uses a novel N-terminal retention module to anchor the adhesin at the cell surface as a secretion intermediate threaded through the outer membrane-localized, TolC-like protein LapE. This secretion intermediate is post-translationally cleaved by the BTLCP family LapG protein to release LapA from its cognate T1SS pore. Thus, secretion of LapA and related RTX adhesins into the extracellular environment appears to be a T1SS-mediated, two-step process that involves a periplasmic intermediate. In this review, we contrast the T1SS machinery and substrates of the BLTCP-linked two-step secretion process with those of the classical one-step T1SS to better understand the newly recognized and expanded role of this secretion machinery. Copyright © 2018 American Society for Microbiology.
Sanders, Geoff; Sinclair, Kamila
2011-12-01
We report two Internet studies that investigated sex differences in the accuracy and precision of judging time to arrival. We used accuracy to mean the ability to match the actual time to arrival and precision to mean the consistency with which each participant made their judgments. Our task was presented as a computer game in which a toy UFO moved obliquely towards the participant through a virtual three-dimensional space on route to a docking station. The UFO disappeared before docking and participants pressed their space bar at the precise moment they thought the UFO would have docked. Study 1 showed it was possible to conduct quantitative studies of spatiotemporal judgments in virtual reality via the Internet and confirmed reports that men are more accurate because women underestimate, but found no difference in precision measured as intra-participant variation. Study 2 repeated Study 1 with five additional presentations of one condition to provide a better measure of precision. Again, men were more accurate than women but there were no sex differences in precision. However, within the coincidence-anticipation timing (CAT) literature, of those studies that report sex differences, a majority found that males are both more accurate and more precise than females. Noting that many CAT studies report no sex differences, we discuss appropriate interpretations of such null findings. While acknowledging that CAT performance may be influenced by experience we suggest that the sex difference may have originated among our ancestors with the evolutionary selection of men for hunting and women for gathering.
El-Amrawy, Fatema
2015-01-01
Objectives The new wave of wireless technologies, fitness trackers, and body sensor devices can have great impact on healthcare systems and the quality of life. However, there have not been enough studies to prove the accuracy and precision of these trackers. The objective of this study was to evaluate the accuracy, precision, and overall performance of seventeen wearable devices currently available compared with direct observation of step counts and heart rate monitoring. Methods Each participant in this study used three accelerometers at a time, running the three corresponding applications of each tracker on an Android or iOS device simultaneously. Each participant was instructed to walk 200, 500, and 1,000 steps. Each set was repeated 40 times. Data was recorded after each trial, and the mean step count, standard deviation, accuracy, and precision were estimated for each tracker. Heart rate was measured by all trackers (if applicable), which support heart rate monitoring, and compared to a positive control, the Onyx Vantage 9590 professional clinical pulse oximeter. Results The accuracy of the tested products ranged between 79.8% and 99.1%, while the coefficient of variation (precision) ranged between 4% and 17.5%. MisFit Shine showed the highest accuracy and precision (along with Qualcomm Toq), while Samsung Gear 2 showed the lowest accuracy, and Jawbone UP showed the lowest precision. However, Xiaomi Mi band showed the best package compared to its price. Conclusions The accuracy and precision of the selected fitness trackers are reasonable and can indicate the average level of activity and thus average energy expenditure. PMID:26618039
El-Amrawy, Fatema; Nounou, Mohamed Ismail
2015-10-01
The new wave of wireless technologies, fitness trackers, and body sensor devices can have great impact on healthcare systems and the quality of life. However, there have not been enough studies to prove the accuracy and precision of these trackers. The objective of this study was to evaluate the accuracy, precision, and overall performance of seventeen wearable devices currently available compared with direct observation of step counts and heart rate monitoring. Each participant in this study used three accelerometers at a time, running the three corresponding applications of each tracker on an Android or iOS device simultaneously. Each participant was instructed to walk 200, 500, and 1,000 steps. Each set was repeated 40 times. Data was recorded after each trial, and the mean step count, standard deviation, accuracy, and precision were estimated for each tracker. Heart rate was measured by all trackers (if applicable), which support heart rate monitoring, and compared to a positive control, the Onyx Vantage 9590 professional clinical pulse oximeter. The accuracy of the tested products ranged between 79.8% and 99.1%, while the coefficient of variation (precision) ranged between 4% and 17.5%. MisFit Shine showed the highest accuracy and precision (along with Qualcomm Toq), while Samsung Gear 2 showed the lowest accuracy, and Jawbone UP showed the lowest precision. However, Xiaomi Mi band showed the best package compared to its price. The accuracy and precision of the selected fitness trackers are reasonable and can indicate the average level of activity and thus average energy expenditure.
Large-scale quantum networks based on graphs
NASA Astrophysics Data System (ADS)
Epping, Michael; Kampermann, Hermann; Bruß, Dagmar
2016-05-01
Society relies and depends increasingly on information exchange and communication. In the quantum world, security and privacy is a built-in feature for information processing. The essential ingredient for exploiting these quantum advantages is the resource of entanglement, which can be shared between two or more parties. The distribution of entanglement over large distances constitutes a key challenge for current research and development. Due to losses of the transmitted quantum particles, which typically scale exponentially with the distance, intermediate quantum repeater stations are needed. Here we show how to generalise the quantum repeater concept to the multipartite case, by describing large-scale quantum networks, i.e. network nodes and their long-distance links, consistently in the language of graphs and graph states. This unifying approach comprises both the distribution of multipartite entanglement across the network, and the protection against errors via encoding. The correspondence to graph states also provides a tool for optimising the architecture of quantum networks.
Chuzhanova, Nadia; Abeysinghe, Shaun S; Krawczak, Michael; Cooper, David N
2003-09-01
Translocations and gross deletions are responsible for a significant proportion of both cancer and inherited disease. Although such gene rearrangements are nonuniformly distributed in the human genome, the underlying mutational mechanisms remain unclear. We have studied the potential involvement of various types of repetitive sequence elements in the formation of secondary structure intermediates between the single-stranded DNA ends that recombine during rearrangements. Complexity analysis was used to assess the potential of these ends to form secondary structures, the maximum decrease in complexity consequent to a gross rearrangement being used as an indicator of the type of repeat and the specific DNA ends involved. A total of 175 pairs of deletion/translocation breakpoint junction sequences available from the Gross Rearrangement Breakpoint Database [GRaBD; www.uwcm.ac.uk/uwcm/mg/grabd/grabd.html] were analyzed. Potential secondary structure was noted between the 5' flanking sequence of the first breakpoint and the 3' flanking sequence of the second breakpoint in 49% of rearrangements and between the 5' flanking sequence of the second breakpoint and the 3' flanking sequence of the first breakpoint in 36% of rearrangements. Inverted repeats, inversions of inverted repeats, and symmetric elements were found in association with gross rearrangements at approximately the same frequency. However, inverted repeats and inversions of inverted repeats accounted for the vast majority (83%) of deletions plus small insertions, symmetric elements for one-half of all antigen receptor-mediated translocations, while direct repeats appear only to be involved in mediating simple deletions. These findings extend our understanding of illegitimate recombination by highlighting the importance of secondary structure formation between single-stranded DNA ends at breakpoint junctions. Copyright 2003 Wiley-Liss, Inc.
NASA Astrophysics Data System (ADS)
Kim, Young-Rok; Park, Eunseo; Choi, Eun-Jung; Park, Sang-Young; Park, Chandeok; Lim, Hyung-Chul
2014-09-01
In this study, genetic resampling (GRS) approach is utilized for precise orbit determination (POD) using the batch filter based on particle filtering (PF). Two genetic operations, which are arithmetic crossover and residual mutation, are used for GRS of the batch filter based on PF (PF batch filter). For POD, Laser-ranging Precise Orbit Determination System (LPODS) and satellite laser ranging (SLR) observations of the CHAMP satellite are used. Monte Carlo trials for POD are performed by one hundred times. The characteristics of the POD results by PF batch filter with GRS are compared with those of a PF batch filter with minimum residual resampling (MRRS). The post-fit residual, 3D error by external orbit comparison, and POD repeatability are analyzed for orbit quality assessments. The POD results are externally checked by NASA JPL’s orbits using totally different software, measurements, and techniques. For post-fit residuals and 3D errors, both MRRS and GRS give accurate estimation results whose mean root mean square (RMS) values are at a level of 5 cm and 10-13 cm, respectively. The mean radial orbit errors of both methods are at a level of 5 cm. For POD repeatability represented as the standard deviations of post-fit residuals and 3D errors by repetitive PODs, however, GRS yields 25% and 13% more robust estimation results than MRRS for post-fit residual and 3D error, respectively. This study shows that PF batch filter with GRS approach using genetic operations is superior to PF batch filter with MRRS in terms of robustness in POD with SLR observations.
Diagnostic validation of three test methods for detection of cyprinid herpesvirus 3 (CyHV-3).
Clouthier, Sharon C; McClure, Carol; Schroeder, Tamara; Desai, Megan; Hawley, Laura; Khatkar, Sunita; Lindsay, Melissa; Lowe, Geoff; Richard, Jon; Anderson, Eric D
2017-03-06
Cyprinid herpesvirus 3 (CyHV-3) is the aetiological agent of koi herpesvirus disease in koi and common carp. The disease is notifiable to the World Organisation for Animal Health. Three tests-quantitative polymerase chain reaction (qPCR), conventional PCR (cPCR) and virus isolation by cell culture (VI)-were validated to assess their fitness as diagnostic tools for detection of CyHV-3. Test performance metrics of diagnostic accuracy were sensitivity (DSe) and specificity (DSp). Repeatability and reproducibility were measured to assess diagnostic precision. Estimates of test accuracy, in the absence of a gold standard reference test, were generated using latent class models. Test samples originated from wild common carp naturally exposed to CyHV-3 or domesticated koi either virus free or experimentally infected with the virus. Three laboratories in Canada participated in the precision study. Moderate to high repeatability (81 to 99%) and reproducibility (72 to 97%) were observed for the qPCR and cPCR tests. The lack of agreement observed between some of the PCR test pair results was attributed to cross-contamination of samples with CyHV-3 nucleic acid. Accuracy estimates for the PCR tests were 99% for DSe and 93% for DSp. Poor precision was observed for the VI test (4 to 95%). Accuracy estimates for VI/qPCR were 90% for DSe and 88% for DSp. Collectively, the results show that the CyHV-3 qPCR test is a suitable tool for surveillance, presumptive diagnosis and certification of individuals or populations as CyHV-3 free.
Reliability of the EchoMRI-Infant System for Water and Fat Measurements in Newborns
Toro-Ramos, Tatiana; Paley, Charles; Wong, William W.; Pi-Sunyer, F. Xavier; Yu, W.; Thornton, John; Gallagher, Dympna
2017-01-01
Objective The precision and accuracy of a quantitative magnetic resonance (EchoMRI-Infants™) system in newborn was determined. Methods: Canola oil and drinking water phantoms (increments of 10g to 1.9kg) were scanned four times. Instrument reproducibility was assessed from 3 scans (within 10-minutes) in 42 healthy term newborns (12–70 hours post-birth). Instrument precision was determined from the coefficient of variation (CV) of repeated scans for total water, lean, and fat measures for newborns and the mean difference between weight and measurement for phantoms. In newborns, the system accuracy for total body water (TBW) was tested against deuterium dilution (D2O). Results In phantoms, the repeatability and accuracy of fat and water measurements increased as the weight of oil and water increased. TBW was overestimated in amounts >200g. In newborns weighing 3.14kg, fat, lean and TBW were 0.52kg (16.48%), 2.28kg and 2.40kg, respectively. EchoMRI’s reproducibility (CV) was 3.27%, 1.83% and 1.34% for total body fat, lean, and TBW, respectively. EchoMRI-TBW values did not differ from D2O; mean difference − 1.95±6.76%, p=0.387; mean bias (limits of agreement) 0.046 kg (−0.30 to 0.39 kg). Conclusions EchoMRI infant system’s precision and accuracy for total body fat and lean are better than established techniques and equivalent to D2O for TBW in phantoms and newborns. PMID:28712143
Software-based evaluation of toric IOL orientation in a multicenter clinical study.
Kasthurirangan, Sanjeev; Feuchter, Lucas; Smith, Pamela; Nixon, Donald
2014-12-01
To evaluate the rotational stability of a new one-piece hydrophobic acrylic toric intraocular lens (IOL) using a custom-developed software for analysis of slit-lamp photographs. In a prospective, multicenter study, 174 eyes were implanted with the TECNIS Toric IOL (Abbott Medical Optics, Inc., Santa Ana, CA). A custom-developed software was used to analyze high-resolution slit-lamp photographs of 156 eyes taken at day 1 (baseline) and 1, 3, and 6 months postoperatively. The software uses iris and sclera landmarks to align the baseline image and later images for comparison. Validation of software was performed through repeated analyses of protractor images rotated from 0.1° to 10.0° and randomly selected photographs of 20 eyes. Software validation showed precision (repeatability plus reproducibility variation) of 0.02° using protractor images and 2.22° using slit-lamp photographs. Good quality slit-lamp images and clear landmarks were necessary for precise measurements. At 6 months, 94.2% of eyes had 5° or less change in IOL orientation versus baseline; only 2 eyes (1.4%) had axis shift greater than 30°. Most eyes were within 5° or less of rotation between 1 and 3 months (92.9%) and 3 and 6 months (94.1%). Mean absolute axis change (± standard deviation) from 1 day to 6 months was 2.70° ± 5.51°. The new custom software was precise and quick in analyzing slit-lamp photographs to determine postoperative toric IOL rotation. Copyright 2014, SLACK Incorporated.
Marmet, Cynthia; Actis-Goretta, Lucas; Renouf, Mathieu; Giuffrida, Francesca
2014-01-01
Chlorogenic acids and derivatives like phenolic acids are potentially bioactive phenolics, which are commonly found in many foods. Once absorbed, chlorogenic and phenolic acids are highly metabolized by the intestine and the liver, producing glucuronidated and/or sulphated compounds. These metabolites were analyzed in human plasma using a validated liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method. After protein precipitation, phenolic acids and their metabolites were extracted by using ethanol and chromatographic separation was achieved by reversed-phase using an Acquity UPLC BEH C18 column combined with a gradient elution system using 1% acetic acid aqueous solution and 1% acetic acid with 100% acetonitrile. The method was able to quantify 56 different compounds including 24 phenolic acids, 4 lactones, 15 sulfates and 13 glucuronides metabolites between 5 and 1000nM in plasma for most of them, except for m-dihydrocoumaric acid, 5-ferulloylquinic-glucuronide, 4-methoxycinnamic acid, 3-phenylpropionic acid, 3-(4-methoxyphenyl)propionic acid (25 to 1000nM) and p-dihydrocoumaric acid (50-1000nM). Values of repeatability and intermediate reproducibility were below 15% of deviation in general, and maximum 20% for the lowest concentrations. The validated method was successfully applied to quantify phenolic acids and their metabolites in plasma obtained after oral ingestion of soluble coffee. In conclusion, the developed and validated method is proved to be very sensitive, accurate and precise for the quantification of these possible dietary phenols. Copyright © 2013 Elsevier B.V. All rights reserved.
Telu, Kelly H.; Yan, Xinjian; Wallace, William E.; Stein, Stephen E.; Simón-Manso, Yamil
2016-01-01
RATIONALE The metabolite profiling of a NIST plasma Standard Reference Material (SRM 1950) on different LC-MS platforms showed significant differences. Although these findings suggest caution when interpreting metabolomics results, the degree of overlap of both profiles allowed us to use tandem mass spectral libraries of recurrent spectra to evaluate to what extent these results are transferable across platforms and to develop cross-platform chemical signatures. METHODS Non-targeted global metabolite profiles of SRM 1950 were obtained on different LC-MS platforms using reversed phase chromatography and different chromatographic scales (nano, conventional and UHPLC). The data processing and the metabolite differential analysis were carried out using publically available (XCMS), proprietary (Mass Profiler Professional) and in-house software (NIST pipeline). RESULTS Repeatability and intermediate precision showed that the non-targeted SRM 1950 profiling was highly reproducible when working on the same platform (RSD < 2%); however, substantial differences were found in the LC-MS patterns originating on different platforms or even using different chromatographic scales (conventional HPLC, UHPLC and nanoLC) on the same platform. A substantial degree of overlap (common molecular features) was also found. A procedure to generate consistent chemical signatures using tandem mass spectral libraries of recurrent spectra is proposed. CONLUSIONS Different platforms rendered significantly different metabolite profiles, but the results were highly reproducible when working within one platform. Tandem mass spectral libraries of recurrent spectra are proposed to evaluate the degree of transferability of chemical signatures generated on different platforms. Chemical signatures based on our procedure are most likely cross-platform transferable. PMID:26842580
Dutra, Lidiane S; Leite, Magda N; Brandão, Marcos A F; de Almeida, Priscila Aparecida; Vaz, Fernando A S; de Oliveira, Marcone A L
2013-01-01
Seeds of Aesculus hippocastanum L. are used in European phytotherapy to treat inflammatory and vascular problems, and also to help in the regulation of the microcirculation. Thus, the quality control of herbal medicines using this species is important. To develop and to optimise a capillary zone electrophoresis method to determine total β-escin in different extracts of A. hippocastanum L. The optimal condition found through chemometric approach was: 25 mmol/L of bicarbonate-carbonate buffer, pH 10.3; +20 kV of voltage; 20°C of cartridge temperature; direct ultraviolet detection at 226 nm; 13 mbar injection for 5 s and analysis time within 6 min. Repeatability, coefficient of variation (CV; %) = 3.19, 3.07 and 1.89 (n = 12), and intermediate precision, CV (%) = 3.05, 3.53 and 2.99 (n = 24) for dry, hydroalcoholic and hydroglycolic extracts, respectively were achieved. The accuracy was evaluated through recovery tests in concentration levels of 100, 150 and 200 g/L, ranging from 98.17 to 104.68%. The proposed method exhibited linearity (r = 0.9983) in the concentration range from 101.4 to 907.2 g/L and limits of detection and quantification equal to 11.63 and 38.76 g/L respectively. A fast and reliable methodology for determination of total β-escin was successfully validated and applied on extracts of A. hippocastanum L. demonstrating its usefulness to quality control of medicines containing this plant species. Copyright © 2013 John Wiley & Sons, Ltd.
Accuracy Profiles for Analyzing Residual Solvents in Textiles by GC-MS.
Bao, Qibei; Fu, Kejie; Ren, Qingqing; Zhong, Yingying; Qian, Dan
2017-10-01
Excess residual solvents (RSs) in clothes or other textiles could be toxic and pose risks to both humans and the environment. N,N-Dimethylformamide (DMF), N,N-dimethylacetamide (DMAc) and 1-methyl-2-pyrrolidinone (NMP) are important chemicals frequently used as solvents in the textile industry. Several organizations have proposed limiting DMF, DMAc and NMP in textiles, but an appropriate detection method has not been proposed. A sensitive GC-MS method for the quantification of DMF, DMAc and NMP in textiles was developed. After extraction with ethyl acetate, these RSs were separated on a DB-5MS capillary column. The oven temperature was increased from 50°C (held for 0.5 min) at 10°C/min to 120°C (held for 1 min). The method was fully validated according to the accuracy profile procedure, which is based on β-expectation tolerance intervals for the total measurement bias. Linearity was observed in the range of 0.5-10 mg/L for the solvents with limit of quantification values of 4.2, 3.5 and 2.5 mg/kg for DMF, DMAc and NMP, respectively. The repeatability and intermediate precision were <5.34% and 7.95% for DMF, 5.37% and 9.68% for DMAc, and 2.68% and 5.85% for NMP. The recoveries of DMF, DMAc and NMP were 91.2-106.3%, 89.5-97.7% and 85.6-101.3%, respectively. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Liao, Keren; Mei, Meng; Li, Haonan; Huang, Xiaojia; Wu, Cuiqin
2016-02-01
The development of a simple and sensitive analytical approach that combines multiple monolithic fiber solid-phase microextraction with liquid desorption followed by high-performance liquid chromatography with diode array detection is proposed for the determination of trace levels of seven steroid sex hormones (estriol, 17β-estradiol, testosterone, ethinylestradiol, estrone, progesterone and mestranol) in water and urine matrices. To extract the target analytes effectively, multiple monolithic fiber solid-phase microextraction based on a polymeric ionic liquid was used to concentrate hormones. Several key extraction parameters including desorption solvent, extraction and desorption time, pH value and ionic strength in sample matrix were investigated in detail. Under the optimal experimental conditions, the limits of detection were found to be in the range of 0.027-0.12 μg/L. The linear range was 0.10-200 μg/L for 17β-estradiol, 0.25-200 μg/L estriol, ethinylestradiol and estrone, and 0.50-200 μg/L for the other hormones. Satisfactory linearities were achieved for analytes with the correlation coefficients above 0.99. Acceptable method reproducibility was achieved by evaluating the repeatability and intermediate precision with relative standard deviations of both less than 8%. The enrichment factors ranged from 54- to 74-fold. Finally, the proposed method was successfully applied to the analysis of steroid sex hormones in environmental water samples and human urines with spiking recoveries ranged from 75.6 to 116%. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
The importance of position and path repeatability on force at the knee during six-DOF joint motion.
Darcy, Shon P; Gil, Jorge E; Woo, Savio L-Y; Debski, Richard E
2009-06-01
Mechanical devices, such as robotic manipulators have been designed to measure joint and ligament function because of their ability to position a diarthrodial joint in six degrees-of-freedom with fidelity. However, the precision and performance of these testing devices vary. Therefore, the objective of this study was to determine the effect of systematic errors in position and path repeatability of two high-payload robotic manipulators (Manipulators 1 and 2) on the resultant forces at the knee. Using a porcine knee, the position and path repeatability of these manipulators were determined during passive flexion-extension with a coordinate measuring machine. The position repeatability of Manipulator 1 was 0.3 mm in position and 0.2 degrees in orientation while Manipulator 2 had a better position repeatability of 0.1 mm in position and 0.1 degrees in orientation throughout the range of positions examined. The corresponding variability in the resultant force at the knee for these assigned positions was 32+/-33 N for Manipulator 1 and 4+/-1 N for Manipulator 2. Furthermore, the repeatability of the trajectory of each manipulator while moving between assigned positions (path repeatability) was 0.8 mm for Manipulator 1 while the path repeatability for Manipulator 2 was improved (0.1 mm). These path discrepancies produced variability in the resultant force at the knee of 44+/-24 and 21+/-8 N, respectively, for Manipulators 1 and 2 primarily due to contact between the articular surfaces of the tibia and femur. Therefore, improved position and path repeatability yields lower variability in the resultant forces at the knee. Although position repeatability has been the most common criteria for evaluating biomechanical testing devices, the current study has clearly demonstrated that path repeatability can have an even larger effect on the variability in resultant force at the knee. Consequently, the repeatability of the path followed by the joint throughout its prescribed trajectory is as important as the repeatability of the joint at reaching positions making up its trajectory, particularly when joint contact occurs.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Jiang, Linhua; Shen, Yue; McGreer, Ian D.
2016-02-20
We present a reverberation mapping (RM) experiment that combines broad- and intermediate-band photometry; it is the first such attempt targeting 13 quasars at 0.2 < z < 0.9. The quasars were selected to have strong Hα or Hβ emission lines that are located in one of three intermediate bands (with FWHM around 200 Å) centered at 8045, 8505, and 9171 Å. The imaging observations were carried out in the intermediate bands and the broad i and z bands using the prime-focus imager 90Prime on the 2.3 m Bok telescope. Because of the large (∼1 deg{sup 2}) field of view (FOV) of 90Prime, we includedmore » the 13 quasars within only five telescope pointings or fields. The five fields were repeatedly observed over 20–30 epochs that were unevenly distributed over a duration of 5–6 months. The combination of the broad- and intermediate-band photometry allows us to derive accurate light curves for both optical continuum emission (from the accretion disk) and line emission (from the broad-line region, or BLR). We detect Hα time lags between the continuum and line emission in six quasars. These quasars are at relatively low redshifts 0.2 < z < 0.4. The measured lags are consistent with the current BLR size–luminosity relation for Hβ at z < 0.3. While this experiment appears successful in detecting lags of the bright Hα line, further investigation is required to see if it can also be applied to the fainter Hβ line for quasars at higher redshifts. Finally we demonstrate that, by using a small telescope with a large FOV, intermediate-band photometric RM can be efficiently executed for a large sample of quasars at z > 0.2.« less
Digital antimicrobial susceptibility testing using the MilliDrop technology.
Jiang, L; Boitard, L; Broyer, P; Chareire, A-C; Bourne-Branchu, P; Mahé, P; Tournoud, M; Franceschi, C; Zambardi, G; Baudry, J; Bibette, J
2016-03-01
We present the MilliDrop Analyzer (MDA), a droplet-based millifluidic system for digital antimicrobial susceptibility testing (D-AST), which enables us to determine minimum inhibitory concentrations (MICs) precisely and accurately. The MilliDrop technology was validated by using resazurin for fluorescence readout, for comparison with standard methodology, and for conducting reproducibility studies. In this first assessment, the susceptibility of a reference Gram-negative strain Escherichia coli ATCC 25922 to gentamicin, chloramphenicol, and nalidixic acid were tested by the MDA, VITEK®2, and broth microdilution as a reference standard. We measured the susceptibility of clinically relevant Gram-positive strains of Staphylococcus aureus to vancomycin, including vancomycin-intermediate S. aureus (VISA), heterogeneous vancomycin-intermediate S. aureus (hVISA), and vancomycin-susceptible S. aureus (VSSA) strains. The MDA provided results which were much more accurate than those of VITEK®2 and standard broth microdilution. The enhanced accuracy enabled us to reliably discriminate between VSSA and hVISA strains.
Controlling the intermediate structure of an ionic liquid for f-block element separations
Abney, Carter W.; Do, Changwoo; Luo, Huimin; ...
2017-04-19
Recent research has revealed molecular structure beyond the inner coordination sphere is essential in defining the performance of separations processes, but nevertheless remains largely unexplored. Here we apply small angle neutron scattering (SANS) and x-ray absorption fine structure (XAFS) spectroscopy to investigate the structure of an ionic liquid system studied for f-block element separations. SANS data reveal dramatic changes in the ionic liquid microstructure (~150 Å) which we demonstrate can be controlled by judicious selection of counter ion. Mesoscale structural features (> 500 Å) are also observed as a function of metal concentration. XAFS analysis supports formation of extended aggregatemore » structures, similar to those observed in traditional solvent extraction processes, and suggest additional parallels may be drawn from further study. As a result, achieving precise tunability over the intermediate features is an important development in controlling mesoscale structure and realizing advanced new forms of soft matter.« less
Learning ability is a key outcome determinant of GSK-3 inhibition on visuospatial memory in rats.
Storozheva, Zinaida I; Gruden, Marina A; Proshin, Andrey T; Sewell, Robert D E
2015-07-01
Learning aptitude has never been a focus of visuospatial performance studies, particularly on memory consolidation and reconsolidation. The aim of this study was to determine the consequences of learning ability on memory consolidation/reconsolidation following inhibition of glucose synthase kinase-3 (GSK-3) by 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8). The anxiety-like nature of rats was characterized in the elevated plus maze. The rats were then trained for four days in the Morris water maze (MWM) and classified as 'superior', 'intermediate' or 'inferior' learners. There were no major differences between superior, intermediate or inferior learners with respect to anxiety which might have influenced learning. After training (day-5), TDZD-8 (2.0 mg/kg) was administered and half of the cohort were exposed to a MWM retrieval trial. Ten days later, animals were subjected to repeated MWM learning. TDZD-8 without a retrieval trial impaired subsequent reconsolidation in inferior learners, but enhanced it in superior learners. There was no modification of performance in intermediate learners. In TDZD-8-treated subjects exposed to retrieval, the pattern of outcomes was identical whereby impairment of reconsolidation occurred in inferior learners, enhancement occurred in superior learners but there was no modification of performance in intermediate learners. Thus, learning ability was a key determinant of the qualitative outcome from GSK-3 inhibition on visuospatial memory. © The Author(s) 2015.
NASA Astrophysics Data System (ADS)
Ford, Eric B.
2009-05-01
We present the results of a highly parallel Kepler equation solver using the Graphics Processing Unit (GPU) on a commercial nVidia GeForce 280GTX and the "Compute Unified Device Architecture" (CUDA) programming environment. We apply this to evaluate a goodness-of-fit statistic (e.g., χ2) for Doppler observations of stars potentially harboring multiple planetary companions (assuming negligible planet-planet interactions). Given the high-dimensionality of the model parameter space (at least five dimensions per planet), a global search is extremely computationally demanding. We expect that the underlying Kepler solver and model evaluator will be combined with a wide variety of more sophisticated algorithms to provide efficient global search, parameter estimation, model comparison, and adaptive experimental design for radial velocity and/or astrometric planet searches. We tested multiple implementations using single precision, double precision, pairs of single precision, and mixed precision arithmetic. We find that the vast majority of computations can be performed using single precision arithmetic, with selective use of compensated summation for increased precision. However, standard single precision is not adequate for calculating the mean anomaly from the time of observation and orbital period when evaluating the goodness-of-fit for real planetary systems and observational data sets. Using all double precision, our GPU code outperforms a similar code using a modern CPU by a factor of over 60. Using mixed precision, our GPU code provides a speed-up factor of over 600, when evaluating nsys > 1024 models planetary systems each containing npl = 4 planets and assuming nobs = 256 observations of each system. We conclude that modern GPUs also offer a powerful tool for repeatedly evaluating Kepler's equation and a goodness-of-fit statistic for orbital models when presented with a large parameter space.
Koyama, Masako; Hirano, Hidemi; Shirai, Natsuki; Matsuura, Yoshiyuki
2017-10-01
Xpo1p (yeast CRM1) is the major nuclear export receptor that carries a plethora of proteins and ribonucleoproteins from the nucleus to cytoplasm. The passage of the Xpo1p nuclear export complex through nuclear pore complexes (NPCs) is facilitated by interactions with nucleoporins (Nups) containing extensive repeats of phenylalanine-glycine (so-called FG repeats), although the precise role of each Nup in the nuclear export reaction remains incompletely understood. Here we report structural and biochemical characterization of the interactions between the Xpo1p nuclear export complex and the FG repeats of Nup42p, a nucleoporin localized at the cytoplasmic face of yeast NPCs and has characteristic SxFG/PxFG sequence repeat motif. The crystal structure of Xpo1p-PKI-Nup42p-Gsp1p-GTP complex identified three binding sites for the SxFG/PxFG repeats on HEAT repeats 14-20 of Xpo1p. Mutational analyses of Nup42p showed that the conserved serines and prolines in the SxFG/PxFG repeats contribute to Xpo1p-Nup42p binding. Our structural and biochemical data suggest that SxFG/PxFG-Nups such as Nup42p and Nup159p at the cytoplasmic face of NPCs provide high-affinity docking sites for the Xpo1p nuclear export complex in the terminal stage of NPC passage and that subsequent disassembly of the nuclear export complex facilitates recycling of free Xpo1p back to the nucleus. © 2017 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.
Sawja: Static Analysis Workshop for Java
NASA Astrophysics Data System (ADS)
Hubert, Laurent; Barré, Nicolas; Besson, Frédéric; Demange, Delphine; Jensen, Thomas; Monfort, Vincent; Pichardie, David; Turpin, Tiphaine
Static analysis is a powerful technique for automatic verification of programs but raises major engineering challenges when developing a full-fledged analyzer for a realistic language such as Java. Efficiency and precision of such a tool rely partly on low level components which only depend on the syntactic structure of the language and therefore should not be redesigned for each implementation of a new static analysis. This paper describes the Sawja library: a static analysis workshop fully compliant with Java 6 which provides OCaml modules for efficiently manipulating Java bytecode programs. We present the main features of the library, including i) efficient functional data-structures for representing a program with implicit sharing and lazy parsing, ii) an intermediate stack-less representation, and iii) fast computation and manipulation of complete programs. We provide experimental evaluations of the different features with respect to time, memory and precision.
Measurement uncertainty of liquid chromatographic analyses visualized by Ishikawa diagrams.
Meyer, Veronika R
2003-09-01
Ishikawa, or cause-and-effect diagrams, help to visualize the parameters that influence a chromatographic analysis. Therefore, they facilitate the set up of the uncertainty budget of the analysis, which can then be expressed in mathematical form. If the uncertainty is calculated as the Gaussian sum of all uncertainty parameters, it is necessary to quantitate them all, a task that is usually not practical. The other possible approach is to use the intermediate precision as a base for the uncertainty calculation. In this case, it is at least necessary to consider the uncertainty of the purity of the reference material in addition to the precision data. The Ishikawa diagram is then very simple, and so is the uncertainty calculation. This advantage is given by the loss of information about the parameters that influence the measurement uncertainty.
2008-06-01
Charlie Chaplin , in 1936, to make the aptly titled film Modern Times . Watch the movie to see what we mean. Postmodernism: The Humanist Reaction Along...PM, plus more. Further, because Pomo PMs do not insist on standardiza- tion to the degree Modern PMs do, they spend much less time producing the...voluminous, detailed documentation that Modern PMs require to ensure precise repeatability, and much more time on actually doing things (perhaps
NASA Astrophysics Data System (ADS)
Harding, D. J.; Miuller, J. R.
2005-12-01
Modeling the kinematics of the 2004 Great Sumatra-Andaman earthquake is limited in the northern two-thirds of the rupture zone by a scarcity of near-rupture geodetic deformation measurements. Precisely repeated Ice, Cloud, and Land Elevation Satellite (ICESat) profiles across the Andaman and Nicobar Islands provide a means to more fully document the spatial pattern of surface vertical displacements and thus better constrain geomechanical modeling of the slip distribution. ICESat profiles that total ~45 km in length cross Car Nicobar, Kamorta, and Katchall in the Nicobar chain. Within the Andamans, the coverage includes ~350 km on North, Central, and South Andaman Islands along two NNE and NNW-trending profiles that provide elevations on both the east and west coasts of the island chain. Two profiles totaling ~80 km in length cross South Sentinel Island, and one profile ~10 km long crosses North Sentinel Island. With an average laser footprint spacing of 175 m, the total coverage provides over 2700 georeferenced surface elevations measurements for each operations period. Laser backscatter waveforms recorded for each footprint enable detection of forest canopy top and underlying ground elevations with decimeter vertical precision. Surface elevation change is determined from elevation profiles, acquired before and after the earthquake, that are repeated with a cross-track separation of less than 100 m by precision pointing of the ICESat spacecraft. Apparent elevation changes associated with cross-track offsets are corrected according to local slopes calculated from multiple post-earthquake repeated profiles. The surface deformation measurements recorded by ICESat are generally consistent with the spatial distribution of uplift predicted by a preliminary slip distribution model. To predict co-seismic surface deformation, we apply a slip distribution, derived from the released energy distribution computed by Ishii et al. (2005), as the displacement discontinuity boundary condition on the Sumatra-Andaman subduction interface fault. The direction of slip on the fault surface is derived from the slip directions computed by Tsai et al. (in review) for centroid moment tensor focal mechanisms spatially distributed along the rupture. The slip model will be refined to better correspond to the observed surface deformation as additional results from the ICESat profiles become available.
Bland, Charles; Ramsey, Teresa L; Sabree, Fareedah; Lowe, Micheal; Brown, Kyndall; Kyrpides, Nikos C; Hugenholtz, Philip
2007-06-18
Clustered Regularly Interspaced Palindromic Repeats (CRISPRs) are a novel type of direct repeat found in a wide range of bacteria and archaea. CRISPRs are beginning to attract attention because of their proposed mechanism; that is, defending their hosts against invading extrachromosomal elements such as viruses. Existing repeat detection tools do a poor job of identifying CRISPRs due to the presence of unique spacer sequences separating the repeats. In this study, a new tool, CRT, is introduced that rapidly and accurately identifies CRISPRs in large DNA strings, such as genomes and metagenomes. CRT was compared to CRISPR detection tools, Patscan and Pilercr. In terms of correctness, CRT was shown to be very reliable, demonstrating significant improvements over Patscan for measures precision, recall and quality. When compared to Pilercr, CRT showed improved performance for recall and quality. In terms of speed, CRT proved to be a huge improvement over Patscan. Both CRT and Pilercr were comparable in speed, however CRT was faster for genomes containing large numbers of repeats. In this paper a new tool was introduced for the automatic detection of CRISPR elements. This tool, CRT, showed some important improvements over current techniques for CRISPR identification. CRT's approach to detecting repetitive sequences is straightforward. It uses a simple sequential scan of a DNA sequence and detects repeats directly without any major conversion or preprocessing of the input. This leads to a program that is easy to describe and understand; yet it is very accurate, fast and memory efficient, being O(n) in space and O(nm/l) in time.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bland, Charles; Ramsey, Teresa L.; Sabree, Fareedah
Clustered Regularly Interspaced Palindromic Repeats (CRISPRs) are a novel type of direct repeat found in a wide range of bacteria and archaea. CRISPRs are beginning to attract attention because of their proposed mechanism; that is, defending their hosts against invading extrachromosomal elements such as viruses. Existing repeat detection tools do a poor job of identifying CRISPRs due to the presence of unique spacer sequences separating the repeats. In this study, a new tool, CRT, is introduced that rapidly and accurately identifies CRISPRs in large DNA strings, such as genomes and metagenomes. CRT was compared to CRISPR detection tools, Patscan andmore » Pilercr. In terms of correctness, CRT was shown to be very reliable, demonstrating significant improvements over Patscan for measures precision, recall and quality. When compared to Pilercr, CRT showed improved performance for recall and quality. In terms of speed, CRT also demonstrated superior performance, especially for genomes containing large numbers of repeats. In this paper a new tool was introduced for the automatic detection of CRISPR elements. This tool, CRT, was shown to be a significant improvement over the current techniques for CRISPR identification. CRT's approach to detecting repetitive sequences is straightforward. It uses a simple sequential scan of a DNA sequence and detects repeats directly without any major conversion or preprocessing of the input. This leads to a program that is easy to describe and understand; yet it is very accurate, fast and memory efficient, being O(n) in space and O(nm/l) in time.« less
Optimally Repeatable Kinetic Model Variant for Myocardial Blood Flow Measurements with 82Rb PET.
Ocneanu, Adrian F; deKemp, Robert A; Renaud, Jennifer M; Adler, Andy; Beanlands, Rob S B; Klein, Ran
2017-01-01
Purpose. Myocardial blood flow (MBF) quantification with 82 Rb positron emission tomography (PET) is gaining clinical adoption, but improvements in precision are desired. This study aims to identify analysis variants producing the most repeatable MBF measures. Methods. 12 volunteers underwent same-day test-retest rest and dipyridamole stress imaging with dynamic 82 Rb PET, from which MBF was quantified using 1-tissue-compartment kinetic model variants: (1) blood-pool versus uptake region sampled input function (Blood/Uptake-ROI), (2) dual spillover correction (SOC-On/Off), (3) right blood correction (RBC-On/Off), (4) arterial blood transit delay (Delay-On/Off), and (5) distribution volume (DV) constraint (Global/Regional-DV). Repeatability of MBF, stress/rest myocardial flow reserve (MFR), and stress/rest MBF difference (ΔMBF) was assessed using nonparametric reproducibility coefficients (RPC np = 1.45 × interquartile range). Results. MBF using SOC-On, RVBC-Off, Blood-ROI, Global-DV, and Delay-Off was most repeatable for combined rest and stress: RPC np = 0.21 mL/min/g (15.8%). Corresponding MFR and ΔMBF RPC np were 0.42 (20.2%) and 0.24 mL/min/g (23.5%). MBF repeatability improved with SOC-On at stress ( p < 0.001) and tended to improve with RBC-Off at both rest and stress ( p < 0.08). DV and ROI did not significantly influence repeatability. The Delay-On model was overdetermined and did not reliably converge. Conclusion. MBF and MFR test-retest repeatability were the best with dual spillover correction, left atrium blood input function, and global DV.
Melanine value in the stria vascularis of pigmented guinea-pigs treated by kanamycin.
Attard, A; Gratacap, B; Charachon, R; Stoebner, P; Laurent, A
1988-01-01
In a previous report, kanamycin (400 mg/kg/d) seemed to increase the number of melanine granulations in intermediate cells of the stria vascularis, especially in the second and third turns. To precise these data, melanine was studied in those turns by ultrastructural morphometry in a control group with 12 animals. We observed a large intra-individual and inter-individual variation before intoxication. Thus, the meaning of melanine modifications by kanamycin must be carefully evaluated.
Bevel gear driver and method having torque limit selection
NASA Technical Reports Server (NTRS)
Cook, Joseph S., Jr. (Inventor)
1994-01-01
This invention comprises a torque drive mechanism utilizing axially translatable, mutually engageable transmission members having mating crown gears, driven and driving members with a three-element drive train being biased together by resilient means or by a fluid actuator system, the apparatus being operable to transmit a precisely controlled degree of torque to a driven member. The apparatus is applicable for use in hand tools and as a replacement for impact torque drivers, torque wrenches, motorized screw drivers, or the like, wherein the applied torque must be precisely controlled or limited. The bevel torque drive includes a drive gear which is axially displaceable and rotatable within cylindrical driver housing, a rotatable intermediate gear, and an output gear. Key rotationally secures displaceable gear with respect to input shaft but permits axial movement therebetween. A thrust bearing is preferably connected to the lower end of shaft for support to reduce play and friction between shaft and a transmission joint disc during rotation of the gear train. Coaxially mounted coiled spring is footed against displaceable gear for biasing the displaceable gear toward and into engagement with the intermediate gear for driving intermediate gear and output gear. Torque control is achieved by the use of straight or spiral beveled gears which are of configurations adapted to withdraw from mutual engagement upon the torque exceeding a predetermined limit. The novel, advantageous features of the invention include the configuration of the mating, crown gear sets and the axially translatable, slidable drive gear. The mechanism is capable of transmitting a high degree of torque within a narrow, compact transmission housing. The compact size and narrow, elongated configuration of the housing is particularly applicable for use in hand tools and in multiple torque driver mechanisms in which it is necessary to drive multiple fasteners which are located in close proximity. Prior torque drivers such as 'click-type' torque wrenches do not actually limit torque application but only provide an audible warning that the limit has been reached.
Mashimo, Tomoji
2014-01-01
The laboratory rat has been widely used as an animal model in biomedical science for more than 150 years. Applying zinc-finger nucleases or transcription activator-like effector nucleases to rat embryos via microinjection is an efficient genome editing tool for generating targeted knockout rats. Recently, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated endonucleases have been used as an effective tool for precise and multiplex genome editing in mice and rats. In this review, the advantages and disadvantages of these site-specific nuclease technologies for genetic analysis and manipulation in rats are discussed. © 2013 The Author Development, Growth & Differentiation © 2013 Japanese Society of Developmental Biologists.
Riedl, Verena; Agatz, Annika; Benstead, Rachel; Ashauer, Roman
2018-04-01
Chemical impacts on the environment are routinely assessed in single-species tests. They are employed to measure direct effects on nontarget organisms, but indirect effects on ecological interactions can only be detected in multispecies tests. Micro- and mesocosms are more complex and environmentally realistic, yet they are less frequently used for environmental risk assessment because resource demand is high, whereas repeatability and statistical power are often low. Test systems fulfilling regulatory needs (i.e., standardization, repeatability, and replication) and the assessment of impacts on species interactions and indirect effects are lacking. In the present study we describe the development of the TriCosm, a repeatable aquatic multispecies test with 3 trophic levels and increased statistical power. High repeatability of community dynamics of 3 interacting aquatic populations (algae, Ceriodaphnia, and Hydra) was found with an average coefficient of variation of 19.5% and the ability to determine small effect sizes. The TriCosm combines benefits of both single-species tests (fulfillment of regulatory requirements) and complex multispecies tests (ecological relevance) and can be used, for instance, at an intermediate tier in environmental risk assessment. Furthermore, comparatively quickly generated population and community toxicity data can be useful for the development and testing of mechanistic effect models. Environ Toxicol Chem 2018;37:1051-1060. © 2017 SETAC. © 2017 SETAC.
Jones, Kay H S; Ellis, Jason; von Schantz, Malcolm; Skene, Debra J; Dijk, Derk-Jan; Archer, Simon N
2007-03-01
The objective of this study was to investigate the effect of age on the association between preferred timing of sleep and waking activities and a coding-region variable number tandem repeat (VNTR) polymorphism in the clock gene PER3. We have previously reported this polymorphism to associate with diurnal preference and delayed sleep phase syndrome (DSPS). Participants (n = 1590; 707 males and 883 females) completed the Horne-Ostberg (HO) questionnaire for diurnal preference and provided a DNA sample. Overall HO scores were plotted against age. The 5% extremes and intermediates were selected for genotyping. Frequencies of the PER3 4- and 5-repeat alleles were examined in separate age groups (18-29, 30-39, 40-49 and 50+ years of age). The 4-repeat allele was significantly more frequent in evening types, and the 5-repeat allele more frequent in morning types (Fisher's exact test, P = 0.016). Analysis in the four age groupings revealed that the strength of this association attenuated with age and was significant only in the youngest group (18-29 years). These results extend our previous finding of an association between the PER3 VNTR and diurnal preference. They also demonstrate that diurnal preference in young people is more closely associated with this polymorphism than it is in other age groups.
Airborne Radar Interferometric Repeat-Pass Processing
NASA Technical Reports Server (NTRS)
Hensley, Scott; Michel, Thierry R.; Jones, Cathleen E.; Muellerschoen, Ronald J.; Chapman, Bruce D.; Fore, Alexander; Simard, Marc; Zebker, Howard A.
2011-01-01
Earth science research often requires crustal deformation measurements at a variety of time scales, from seconds to decades. Although satellites have been used for repeat-track interferometric (RTI) synthetic-aperture-radar (SAR) mapping for close to 20 years, RTI is much more difficult to implement from an airborne platform owing to the irregular trajectory of the aircraft compared with microwave imaging radar wavelengths. Two basic requirements for robust airborne repeat-pass radar interferometry include the ability to fly the platform to a desired trajectory within a narrow tube and the ability to have the radar beam pointed in a desired direction to a fraction of a beam width. Uninhabited Aerial Vehicle Synthetic Aperture Radar (UAVSAR) is equipped with a precision auto pilot developed by NASA Dryden that allows the platform, a Gulfstream III, to nominally fly within a 5 m diameter tube and with an electronically scanned antenna to position the radar beam to a fraction of a beam width based on INU (inertial navigation unit) attitude angle measurements.
Thermal denaturation of the BRCT tandem repeat region of human tumour suppressor gene product BRCA1.
Pyrpassopoulos, Serapion; Ladopoulou, Angela; Vlassi, Metaxia; Papanikolau, Yannis; Vorgias, Constantinos E; Yannoukakos, Drakoulis; Nounesis, George
2005-04-01
Reduced stability of the tandem BRCT domains of human BReast CAncer 1 (BRCA1) due to missense mutations may be critical for loss of function in DNA repair and damage-induced checkpoint control. In the present thermal denaturation study of the BRCA1 BRCT region, high-precision differential scanning calorimetry (DSC) and circular dichroism (CD) spectroscopy provide evidence for the existence of a denatured state that is structurally very similar to the native. Consistency between theoretical structure-based estimates of the enthalpy (DeltaH) and heat capacity change (DeltaCp) and the calorimetric results is obtained when considering partial thermal unfolding contained in the region of the conserved hydrophobic pocket formed at the interface of the two BRCT repeats. The structural integrity of this region has been shown to be crucial for the interaction of BRCA1 with phosphorylated peptides. In addition, cancer-causing missense mutations located at the inter-BRCT-repeat interface have been linked to the destabilization of the tandem BRCT structure.
Molecular and bioinformatic analysis of the FB-NOF transposable element.
Badal, Martí; Portela, Anna; Xamena, Noel; Cabré, Oriol
2006-04-12
The Drosophila melanogaster transposable element FB-NOF is known to play a role in genome plasticity through the generation of all sort of genomic rearrangements. Moreover, several insertional mutants due to FB mobilizations have been reported. Its structure and sequence, however, have been poorly studied mainly as a consequence of the long, complex and repetitive sequence of FB inverted repeats. This repetitive region is composed of several 154 bp blocks, each with five almost identical repeats. In this paper, we report the sequencing process of 2 kb long FB inverted repeats of a complete FB-NOF element, with high precision and reliability. This achievement has been possible using a new map of the FB repetitive region, which identifies unambiguously each repeat with new features that can be used as landmarks. With this new vision of the element, a list of FB-NOF in the D. melanogaster genomic clones has been done, improving previous works that used only bioinformatic algorithms. The availability of many FB and FB-NOF sequences allowed an analysis of the FB insertion sequences that showed no sequence specificity, but a preference for A/T rich sequences. The position of NOF into FB is also studied, revealing that it is always located after a second repeat in a random block. With the results of this analysis, we propose a model of transposition in which NOF jumps from FB to FB, using an unidentified transposase enzyme that should specifically recognize the second repeat end of the FB blocks.
Naveilhan, P; Baudet, C; Jabbour, W; Wion, D
1994-09-01
A model that may explain the limited division potential of certain cells such as human fibroblasts in culture is presented. The central postulate of this theory is that there exists, prior to certain key exons that code for materials needed for cell division, a unique sequence of specific repeating segments of DNA. One copy of such repeating segments is deleted during each cell cycle in cells that are not protected from such deletion through methylation of their cytosine residues. According to this theory, the means through which such repeated sequences are removed, one per cycle, is through the sequential action of enzymes that act much as bacterial restriction enzymes do--namely to produce scissions in both strands of DNA in areas that correspond to the DNA base sequence recognition specificities of such enzymes. After the first scission early in a replicative cycle, that enzyme becomes inhibited, but the cleavage of the first site exposes the closest site in the repetitive element to the action of a second restriction enzyme after which that enzyme also becomes inhibited. Then repair occurs, regenerating the original first site. Through this sequential activation and inhibition of two different restriction enzymes, only one copy of the repeating sequence is deleted during each cell cycle. In effect, the repeating sequence operates as a precise counter of the numbers of cell doubling that have occurred since the cells involved differentiated during development.
Platelet factor 4/heparin antibodies in blood bank donors.
Hursting, Marcie J; Pai, Poulomi J; McCracken, Julianna E; Hwang, Fred; Suvarna, Shayela; Lokhnygina, Yuliya; Bandarenko, Nicholas; Arepally, Gowthami M
2010-11-01
Platelet factor 4 (PF4)/heparin antibody, typically associated with heparin therapy, is reported in some heparin-naive people. Seroprevalence in the general population, however, remains unclear. We prospectively evaluated PF4/heparin antibody in approximately 4,000 blood bank donors using a commercial enzyme-linked immunosorbent assay for initial and then repeated (confirmatory) testing. Antibody was detected initially in 249 (6.6%; 95% confidence interval [CI], 5.8%-7.4%) of 3,795 donors and repeatedly in 163 (4.3%; 95% CI, 3.7%-5.0%) of 3,789 evaluable donors. "Unconfirmed" positives were mostly (93%) low positives (optical density [OD] = 0.40-0.59). Of 163 repeatedly positive samples, 116 (71.2%) were low positives, and 124 (76.1%) exhibited heparin-dependent binding. Predominant isotypes of intermediate to high seropositive samples (OD >0.6) were IgG (20/39 [51%]), IgM (9/39 [23%]), and indeterminate (10/39 [26%]). The marked background seroprevalence of PF4/heparin antibody (4.3%-6.6%) with the preponderance of low (and frequently nonreproducible) positives in blood donors suggests the need for further assay calibration, categorization of antibody level, and studies evaluating clinical relevance of "naturally occurring" PF4/heparin antibodies.
VES263: an intermediate mass YSO candidate as a new eruptive variable
NASA Astrophysics Data System (ADS)
Giannini, T.; Antoniucci, S.; Lorenzetti, D.; Harutyunyan, A.; Licchelli, D.; Munari, U.
2018-05-01
In the framework of our EXor monitoring programme dubbed EXORCISM (EXOR OptiCal and Infrared Systematic Monitoring - Antoniucci et al. 2013 PPVI, Lorenzetti et al. 2007 ApJ 665, 1182; Lorenzetti et al. 2009 ApJ 693, 1056), we observed the object VES263 signalled by a recent GAIA alert (http://gsaweb.ast.cam.ac.uk/alerts/alert/Gaia18azl) as "an emission line star undergoing repeat outbursts" having detected an alerting magnitude of 11.66 wrt a historic magnitude of 12.16.
NASA Technical Reports Server (NTRS)
1981-01-01
Progress in the development of processes for production of Celion/LARC-160 graphite-polyimide materials, quality control, and the fabrication of Space Shuttle composite structure components is reported. Liquid chromatographic analyses of three repeatibility batches were performed and are compared to previous Hexcel standard production and to variables study LARC-160 intermediate resins. Development of processes for chopped fiber molding are described and flexural strength, elastic modulus, and other physical and mechanical properties of the molding are presented.
Regional business cycle synchronization through expectations
NASA Astrophysics Data System (ADS)
Onozaki, Tamotsu; Yanagita, Tatsuo; Kaizoji, Taisei; Toyabe, Kazutaka
2007-09-01
This paper provides an example in which regional business cycles may synchronize via producers’ expectations, even though there is no interregional trade, by means of a system of globally coupled, noninvertible maps. We concentrate on the dependence of the dynamics on a parameter η which denotes the inverse of price elasticity of demand. Simulation results show that several phases (the short transient, the complete asynchronous, the long transient and the intermediate transient) appear one after another as η increases. In the long transient phase, the intermittent clustering process with a long chaotic transient appears repeatedly.
Jin, Lu; Xue, Ying; Zhang, Hui; Kim, Chan Kyung; Xie, Dai Qian; Yan, Guo Sen
2008-05-15
The possible mechanisms of the aminolysis of N-methyl-3-(methoxycarbonyl)-4-hydroxy-2-pyridone (beta-hydroxy-alpha,beta-unsaturated ester) with dimethylamine are investigated at the hybrid density functional theory B3LYP/6-31G(d,p) level in the gas phase. Single-point computations at the B3LYP/6-311++G(d,p) and the Becke88-Becke95 1-parameter model BB1K/6-311++G(d,p) levels are performed for more precise energy predictions. Solvent effects are also assessed by single-point calculations at the integral equation formalism polarized continuum model IEFPCM-B3LYP/6-311++G(d,p) and IEFPCM-BB1K/6-311++G(d,p) levels on the gas-phase optimized geometries. Three possible pathways, the concerted pathway (path A), the stepwise pathway involving tetrahedral intermediates (path B), and the stepwise pathway via alpha-oxo ketene intermediate due to the participation of beta-hydroxy (path C), are taken into account for the title reaction. Moreover, path C includes two sequential processes. The first process is to generate alpha-oxo ketene intermediate via the decomposition of N-methyl-3-(methoxycarbonyl)-4-hydroxy-2-pyridone; the second process is the addition of dimethylamine to alpha-oxo ketene intermediate. Our results indicate that path C is more favorable than paths A and B both in the gas phase and in solvent (heptane). In path C, the first process is the rate-determining step, and the second process is revealed to be a [4+2] pseudopericyclic reaction without the energy barrier. Being independent of the concentration of amine, the first process obeys the first-order rate law.
Theoretical study on the reaction mechanism of CH 4 with CaO
NASA Astrophysics Data System (ADS)
Yang, Hua-Qing; Hu, Chang-Wei; Qin, Song
2006-11-01
The reaction pathways and energetics for the reaction of methane with CaO are discussed on the singlet spin state potential energy surface at the B3LYP/6-311+G(2df,2p) and QCISD/6-311++G(3df,3pd)//B3LYP/6-311+G(2df,2p) levels of theory. The reaction of methane with CaO is proposed to proceed in the following reaction pathways: CaO + CH 4 → CaOCH 4 → [TS] → CaOH + CH 3, CaO + CH 4 → OCaCH 4 → [TS] → HOCaCH 3 → CaOH + CH 3 or [TS] → CaCH 3OH → Ca + CH 3OH, and OCaCH 4 → [TS] → HCaOCH 3 → CaOCH 3 + H or [TS] → CaCH 3OH → Ca + CH 3OH. The gas-phase methane-methanol conversion by CaO is suggested to proceed via two kinds of important reaction intermediates, HOCaCH 3 and HCaOCH 3, and the reaction pathway via the hydroxy intermediate (HOCaCH 3) is energetically more favorable than the other one via the methoxy intermediate (HCaOCH 3). The hydroxy intermediate HOCaCH 3 is predicted to be the energetically most preferred configuration in the reaction of CaO + CH 4. Meanwhile, these three product channels (CaOH + CH 3, CaOCH 3 + H and Ca + CH 3OH) are expected to compete with each other, and the formation of methyl radical is the most preferable pathway energetically. On the other hand, the intermediates HCaOCH 3 and HOCaCH 3 are predicted to be the energetically preferred configuration in the reaction of Ca + CH 3OH, which is precisely the reverse reaction of methane hydroxylation.
A new technique for radiographic measurement of acetabular cup orientation.
Derbyshire, Brian; Diggle, Peter J; Ingham, Christopher J; Macnair, Rory; Wimhurst, James; Jones, Henry Wynn
2014-02-01
Accurate radiographic measurement of acetabular cup orientation is required in order to assess susceptibility to impingement, dislocation, and edge loading wear. In this study, the accuracy and precision of a new radiographic cup orientation measurement system were assessed and compared to those of two commercially available systems. Two types of resurfacing hip prostheses and an uncemented prosthesis were assessed. Radiographic images of each prosthesis were created with the cup set at different, known angles of version and inclination in a measurement jig. The new system was the most accurate and precise and could repeatedly measure version and inclination to within a fraction of a degree. In addition it has a facility to distinguish cup retroversion from anteversion on anteroposterior radiographs. © 2013.
A 24 hr global campaign to assess precision timing of the millisecond pulsar J1713+0747
DOE Office of Scientific and Technical Information (OSTI.GOV)
Dolch, T.; Lam, M. T.; Cordes, J.
2014-10-10
The radio millisecond pulsar J1713+0747 is regarded as one of the highest-precision clocks in the sky and is regularly timed for the purpose of detecting gravitational waves. The International Pulsar Timing Array Collaboration undertook a 24 hr global observation of PSR J1713+0747 in an effort to better quantify sources of timing noise in this pulsar, particularly on intermediate (1-24 hr) timescales. We observed the pulsar continuously over 24 hr with the Arecibo, Effelsberg, GMRT, Green Bank, LOFAR, Lovell, Nançay, Parkes, and WSRT radio telescopes. The combined pulse times-of-arrival presented here provide an estimate of what sources of timing noise, excludingmore » DM variations, would be present as compared to an idealized √N improvement in timing precision, where N is the number of pulses analyzed. In the case of this particular pulsar, we find that intrinsic pulse phase jitter dominates arrival time precision when the signal-to-noise ratio of single pulses exceeds unity, as measured using the eight telescopes that observed at L band/1.4 GHz. We present first results of specific phenomena probed on the unusually long timescale (for a single continuous observing session) of tens of hours, in particular interstellar scintillation, and discuss the degree to which scintillation and profile evolution affect precision timing. This paper presents the data set as a basis for future, deeper studies.« less
Li, Chuanzhao; Chen, Li; Garland, Marc
2007-10-31
The combined application of two or more metals in homogeneous catalysis can lead to synergistic effects; however, the phenomenological basis for these observations often goes undetermined. The hetero-bimetallic catalytic binuclear elimination reaction, a system involving both mononuclear and dinuclear intermediates, has been repeatedly suggested as a possible mechanism. In the present contribution, the simultaneous application of Rh4(CO)12 and HRe(CO)5 as precursors in the hydroformylation reaction leads to a very strong synergistic rate effect. In situ spectroscopic measurements confirm the presence of both mononuclear and dinuclear intermediates such as RCORh(CO)4 and RhRe(CO)9 in the active system. Moreover, kinetic analysis confirms interconversion of these intermediates as well as their statistical correlation with organic product formation. Specifically, the rate of hydrogen activation by RhRe(CO)9 is exactly equal to the rate of aldehyde formation from binuclear elimination between HRe(CO)5 and RCORh(CO)4 at all reaction conditions studied. Thus the catalytic events involving mononuclear species and those involving dinuclear species are synchronized. In the present experiments, the new topology is orders of magnitude more efficient than the corresponding unicyclic rhodium system.
Reliability of the penetration aspiration scale with flexible endoscopic evaluation of swallowing.
Butler, Susan G; Markley, Lisa; Sanders, Brian; Stuart, Andrew
2015-06-01
The Penetration Aspiration Scale (PAS), although designed for videofluoroscopy, has been utilized with flexible endoscopic evaluation of swallowing (FEES) in both research and clinical practice. The purpose of this investigation was to determine inter- and intrarater reliability of the PAS with FEES as a function of clinician FEES experience and retest interval. Three groups of 3 clinicians (N=9) with varying FEES experience (beginning, intermediate, and advanced) assigned PAS scores to 35 swallows. Initial ratings were repeated following short-term (ie, 1 day) and long-term (ie, 1 week) retest intervals. Intraclass correlation coefficients were calculated to assess interrater reliability on the first rating for each group. The coefficients were .91, .82, and .89 for the beginning, intermediate, and advanced clinicians, respectively. Overall interrater reliability across all 9 clinicians, irrespective of experience, was .85. Intraclass correlation coefficients were also calculated to assess intrarater reliability. The intrarater reliability for short- and long-term ratings was .90, .94, and .96 and .96, .97, and .94 for the beginning, intermediate, and advanced clinicians, respectively. Overall intrarater reliability across all 9 clinicians and all 3 ratings was .94. Excellent inter- and intrarater reliability was evidenced with the application of the PAS for FEES regardless of clinician experience and retest interval. © The Author(s) 2015.
Auditory-motor entrainment and phonological skills: precise auditory timing hypothesis (PATH).
Tierney, Adam; Kraus, Nina
2014-01-01
Phonological skills are enhanced by music training, but the mechanisms enabling this cross-domain enhancement remain unknown. To explain this cross-domain transfer, we propose a precise auditory timing hypothesis (PATH) whereby entrainment practice is the core mechanism underlying enhanced phonological abilities in musicians. Both rhythmic synchronization and language skills such as consonant discrimination, detection of word and phrase boundaries, and conversational turn-taking rely on the perception of extremely fine-grained timing details in sound. Auditory-motor timing is an acoustic feature which meets all five of the pre-conditions necessary for cross-domain enhancement to occur (Patel, 2011, 2012, 2014). There is overlap between the neural networks that process timing in the context of both music and language. Entrainment to music demands more precise timing sensitivity than does language processing. Moreover, auditory-motor timing integration captures the emotion of the trainee, is repeatedly practiced, and demands focused attention. The PATH predicts that musical training emphasizing entrainment will be particularly effective in enhancing phonological skills.
Crowdsourcing as an Analytical Method: Metrology of Smartphone Measurements in Heritage Science.
Brigham, Rosie; Grau-Bové, Josep; Rudnicka, Anna; Cassar, May; Strlic, Matija
2018-06-18
This research assesses the precision, repeatability, and accuracy of crowdsourced scientific measurements, and whether their quality is sufficient to provide usable results. Measurements of colour and area were chosen because of the possibility of producing them with smartphone cameras. The quality of the measurements was estimated experimentally by comparing data contributed by anonymous participants in heritage sites with reference measurements of known accuracy and precision. Participants performed the measurements by taking photographs with their smartphones, from which colour and dimensional data could be extracted. The results indicate that smartphone measurements provided by citizen scientists can be used to measure changes in colour, but that the performance is strongly dependent on the measured colour coordinate. The same method can be used to measure areas when the difference in colour with the neighbouring areas is large enough. These results render the method useful in some heritage science contexts, but higher precision would be desirable. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Armour, M.; Ford, E.; Iordachita, I.; Wong, J.
2011-01-01
To study the effects of cranial irradiation, we have constructed an all-plastic mouse bed equipped with an immobilizing head holder. The bed integrates with our in-house Small Animal Radiation Research Platform (SARRP) for precision focal irradiation experiments and cone-beam CT. We assessed the reproducibility of our head holder to determine the need for CT based targeting in cranial irradiation studies. To measure the holder’s reproducibility, a C57BL/6 mouse was positioned and CT scanned nine times. Image sets were loaded into the Pinnacle3 radiation treatment planning system and were registered to one another by one investigator using rigid body alignment of the cranial regions. Rotational and translational offsets were measured. The average vector shift between scans was 0.80 ± 0.49 mm. Such a shift is too large to selectively treat subregions of the mouse brain. In response, we use onboard imaging to guide cranial irradiation applications that require sub-millimeter precision. PMID:20041766
Armour, M; Ford, E; Iordachita, I; Wong, J
2010-01-01
To study the effects of cranial irradiation, we have constructed an all-plastic mouse bed equipped with an immobilizing head holder. The bed integrates with our in-house Small Animal Radiation Research Platform (SARRP) for precision focal irradiation experiments and cone-beam CT. We assessed the reproducibility of our head holder to determine the need for CT-based targeting in cranial irradiation studies. To measure the holder's reproducibility, a C57BL/6 mouse was positioned and CT-scanned nine times. Image sets were loaded into the Pinnacle(3) radiation treatment planning system and were registered to one another by one investigator using rigid body alignment of the cranial regions. Rotational and translational offsets were measured. The average vector shift between scans was 0.80 +/- 0.49 mm. Such a shift is too large to selectively treat subregions of the mouse brain. In response, we use onboard imaging to guide cranial irradiation applications that require sub-millimeter precision.
NASA Astrophysics Data System (ADS)
Wang, Xiaodong; Zhang, Wei; Luo, Yi; Yang, Weimin; Chen, Liang
2013-01-01
In assembly of miniature devices, the position and orientation of the parts to be assembled should be guaranteed during or after assembly. In some cases, the relative position or orientation errors among the parts can not be measured from only one direction using visual method, because of visual occlusion or for the features of parts located in a three-dimensional way. An automatic assembly system for precise miniature devices is introduced. In the modular assembly system, two machine vision systems were employed for measurement of the three-dimensionally distributed assembly errors. High resolution CCD cameras and high position repeatability precision stages were integrated to realize high precision measurement in large work space. The two cameras worked in collaboration in measurement procedure to eliminate the influence of movement errors of the rotational or translational stages. A set of templates were designed for calibration of the vision systems and evaluation of the system's measurement accuracy.
An Externally Dispersed Interferometer for Sensitive Doppler Extrasolar Planet Searches
NASA Astrophysics Data System (ADS)
Ge, Jian; Erskine, David J.; Rushford, Mike
2002-09-01
A new kind of instrument for sensitive Doppler extrasolar planet searches, called an externally dispersed interferometer, is described in this paper. It is a combination of an optical Michelson-type interferometer and an intermediate-resolution grating spectrometer. The interferometer measures Doppler radial velocity (RV) variations of starlight through the phase shifts of moiré fringes, created by multiplication of the interferometer fringes with stellar absorption lines. The intermediate-resolution spectrograph disperses the moiré fringes into thousands of parallel-wavelength channels. This increases the instrument bandwidth and fringe visibility by preventing fringe cross-talk between neighboring spectral lines. This results in a net increase in the signal-to-noise ratio over an interferometer used alone with broadband light. Compared to current echelle spectrometers for extrasolar planet searches, this instrument offers two unique instrument properties: a simple, stable, well-defined sinusoidal instrument response function (point-spread function) and magnification of Doppler motion through moiré fringe techniques. Since instrument noise is chiefly limited by the ability to characterize the instrument response, this new technique provides unprecedented low instrumental noise in an economical compact apparatus, enabling higher precision for Doppler RV measurements. In practice, the moiré magnification can be 5-10 times depending on the interferometer comb angle. This instrument has better sensitivity for smaller Doppler shifts than echelle spectrometers. The instrument can be designed with much lower spectral resolving power without losing Doppler sensitivity and optimized for higher throughput than echelle spectrometers to allow a potential survey for planets around fainter stars than current magnitude limits. Lab-based experiments with a prototype instrument with a spectral resolution of R~20,000 demonstrated ~0.7 m s-1 precision for short-term RV measurements. A fiber-fed version of the prototype with R~5600 was tested with starlight at the Lick 1 m telescope and demonstrated ~7 m s-1 RV precision at 340 Å bandwidth. The increased velocity noise is attributed to the lower spectral resolution, lower fringe visibility, and uncontrolled instrument environment.
Nielsen, Troels Tolstrup; Mardosiene, Skirmante; Løkkegaard, Annemette; Stokholm, Jette; Ehrenfels, Susanne; Bech, Sara; Friberg, Lars; Nielsen, Jens Kellberg; Nielsen, Jørgen E
2012-08-13
The autosomal dominant spinocerebellar ataxias (SCAs) confine a group of rare and heterogeneous disorders, which present with progressive ataxia and numerous other features e.g. peripheral neuropathy, macular degeneration and cognitive impairment, and a subset of these disorders is caused by CAG-repeat expansions in their respective genes. The diagnosing of the SCAs is often difficult due to the phenotypic overlap among several of the subtypes and with other neurodegenerative disorders e.g. Huntington's disease. We report a family in which the proband had rapidly progressing cognitive decline and only subtle cerebellar symptoms from age 42. Sequencing of the TATA-box binding protein gene revealed a modest elongation of the CAG/CAA-repeat of only two repeats above the non-pathogenic threshold of 41, confirming a diagnosis of SCA17. Normally, repeats within this range show reduced penetrance and result in a milder disease course with slower progression and later age of onset. Thus, this case presented with an unusual phenotype. The current case highlights the diagnostic challenge of neurodegenerative disorders and the need for a thorough clinical and paraclinical examination of patients presenting with rapid cognitive decline to make a precise diagnosis on which further genetic counseling and initiation of treatment modalities can be based.
All-Printed Flexible and Stretchable Electronics.
Mohammed, Mohammed G; Kramer, Rebecca
2017-05-01
A fully automated additive manufacturing process that produces all-printed flexible and stretchable electronics is demonstrated. The printing process combines soft silicone elastomer printing and liquid metal processing on a single high-precision 3D stage. The platform is capable of fabricating extremely complex conductive circuits, strain and pressure sensors, stretchable wires, and wearable circuits with high yield and repeatability. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
MRI of bone marrow in the distal radius: in vivo precision of effective transverse relaxation times
NASA Technical Reports Server (NTRS)
Grampp, S.; Majumdar, S.; Jergas, M.; Lang, P.; Gies, A.; Genant, H. K.
1995-01-01
The effective transverse relaxation time T2* is influenced by the presence of trabecular bone, and can potentially provide a measure of bone density as well as bone structure. We determined the in vivo precision of T2* in repeated bone marrow measurements. The T2* measurements of the bone marrow of the distal radius were performed twice within 2 weeks in six healthy young volunteers using a modified water-presaturated 3D Gradient-Recalled Acquisition at Steady State (GRASS) sequence with TE 7, 10, 12, 20, and 30; TR 67; flip angle (FA) 90 degrees. An axial volume covering a length of 5.6 cm in the distal radius was measured. Regions of interest (ROIs) were determined manually and consisted of the entire trabecular bone cross-section extending proximally from the radial subchondral endplate. Reproducibility of T2* and area measurements was expressed as the absolute precision error (standard deviation [SD] in ms or mm2) or as the relative precision error (SD/mean x 100, or coefficient of variation [CV] in %) between the two-point measurements. Short-term precision of T2* and area measurements varied depending on section thickness and location of the ROI in the distal radius. Absolute precision errors for T2* times were between 1.3 and 2.9 ms (relative precision errors 3.8-9.5 %) and for area measurements between 20 and 55 mm2 (relative precision errors 5.1-16.4%). This MR technique for quantitative assessment of trabecular bone density showed reasonable reproducibility in vivo and is a promising future tool for the assessment of osteoporosis.
Sonic Estimation of Elasticity via Resonance: A New Method of Assessing Hemostasis
Corey, F. Scott; Walker, William F.
2015-01-01
Uncontrolled bleeding threatens patients undergoing major surgery and in care for traumatic injury. This paper describes a novel method of diagnosing coagulation dysfunction by repeatedly measuring the shear modulus of a blood sample as it clots in vitro. Each measurement applies a high-energy ultrasound pulse to induce a shear wave within a rigid walled chamber, and then uses low energy ultrasound pulses to measure displacements associated with the resonance of that shear wave. Measured displacements are correlated with predictions from Finite Difference Time Domain (FDTD) models, with the best fit corresponding to the modulus estimate. In our current implementation each measurement requires 62.4 ms. Experimental data was analyzed using a fixed-viscosity algorithm and a free-viscosity algorithm. In experiments utilizing human blood induced to clot by exposure to kaolin, the free-viscosity algorithm quantified the shear modulus of formed clots with a worst-case precision of 2.5%. Precision was improved to 1.8% by utilizing the fixed-viscosity algorithm. Repeated measurements showed a smooth evolution from liquid blood to a firm clot with a shear modulus between 1.4 kPa and 3.3 kPa. These results show the promise of this technique for rapid, point of care assessment of coagulation. PMID:26399992
Patil, Suyog S; Srivastava, Ashwini K
2013-01-01
A simple, precise, and rapid RPLC method has been developed without incorporation of any ion-pair reagent for the simultaneous determination of vitamin C (C) and seven B-complex vitamins, viz, thiamine hydrochloride (B1), pyridoxine hydrochloride (B6), nicotinamide (B3), cyanocobalamine (B12), folic acid, riboflavin (B2), and 4-aminobenzoic acid (Bx). Separations were achieved within 12.0 min at 30 degrees C by gradient elution on an RP C18 column using a mobile phase consisting of a mixture of 15 mM ammonium formate buffer and 0.1% triethylamine adjusted to pH 4.0 with formic acid and acetonitrile. Simultaneous UV detection was performed at 275 and 360 nm. The method was validated for system suitability, LOD, LOQ, linearity, precision, accuracy, specificity, and robustness in accordance with International Conference on Harmonization guidelines. The developed method was implemented successfully for determination of the aforementioned vitamins in pharmaceutical formulations containing an individual vitamin, in their multivitamin combinations, and in human urine samples. The calibration curves for all analytes showed good linearity, with coefficients of correlation higher than 0.9998. Accuracy, intraday repeatability (n = 6), and interday repeatability (n = 7) were found to be satisfactory.
Infrared Photometry for Automated Telescopes: Passband Selection
NASA Astrophysics Data System (ADS)
Milone, Gene; Young, Andrew T.
2011-03-01
The high precision that photometry in the near and intermediate infrared region can provide has not been achieved, partly because of technical challenges (including cryogenics, which most IR detectors require), and partly because the filters in common use are not optimized to avoid water-vapor absorptions, which are the principal impediment to precise ground-based IR photometry. We review the IRWG filters that achieve this goal, and the trials that were undertaken to demonstrate their superiority. We focus especially on the near IR set and, for high elevation sites, the passbands in the N window. We also discuss the price to be paid for the improved precision, in the form of lower throughput, and why it should be paid: to achieve not only higher precision (i.e., improved signal-to-noise ratio), but also lower extinction, thus producing higher accuracy in extra-atmospheric magnitudes. The edges of the IRWG passbands are not defined by the edges of the atmospheric windows: therefore, they admit no flux from these (constantly varying) edges. The throughput cost and the lack of a large body of data already obtained in these passbands are principal reasons why the IRWG filters are not in wide use at observatories around the world that currently do IR work. Yet a measure of the signal-to-noise ratio varies inversely with both extinction and with a measure of the Forbes effect. So, the small loss of raw throughput is recouped in signal-to-noise gain. We illustrate these points with passbands of both near and intermediate IR passbands. There is also the matter of cost for small production runs of these filters; reduced costs can be realized through bulk orders with uniform filter specifications. As a consequence, the near-IR IRWG passbands offer the prospect of being able to do photometry in those passbands at both high and low elevation sites that are capable of supporting precise photometry, thereby freeing infrared photometry from the need to access exclusively high and dry elevation sites, although photometry done at those sites can also benefit from improved accuracy and transformability. We suggest that if the IRWG passbands are made available, they will be used! New automated systems making use of these passbands have the advantage of establishing the system more widely, creating a larger body of data to which future observations will be fully transformable, and will be cheaper to purchase. This work has been supported in part by grants to EFM by the Canadian Natural Sciences and Engineering Research Council.
Evaluation of the EGNOS service for topographic profiling in field geosciences
NASA Astrophysics Data System (ADS)
Kromuszczyńska, Olga; Mège, Daniel; Castaldo, Luigi; Gurgurewicz, Joanna; Makowska, Magdalena; Dębniak, Krzysztof; Jelínek, Róbert
2016-09-01
Consumer grade Global Positioning System (GPS) receivers are commonly used as a tool for data collection in many fields, including geosciences. One of the methods for improving the GPS signal is provided by the Wide Area Differential GPS (WADGPS), which uses geostationary satellites to correct errors affecting the signal in real time. This study presents results of three experiments aiming at determining whether the precision of field measurements made by such a receiver (Garmin GPSMAP 62s) operating in either the non-differential and the WADGPS differential mode is suitable for characterizing geomorphological objects or landforms. It assumes in a typical field work situation, when time cannot be devoted in the field to long periods of stationary GPS measurements and the precision of topographic profile is at least as important as, if not more than, positioning of individual points. The results show that with maintaining some rules, the expected precision may meet the nominal precision. The repeatability (coherence) of topographic profiles conducted at low speed (0.5 m s- 1) in mountain terrain is good, and vertical precision is improved in the WADGPS mode. Horizontal precision is equivalent in both modes. The GPS receiver should be operating at least 30 min prior to measuring and should not be turned off between measurements that the user like to compare. If the GPS receiver needs to be reset between profiles to be compared, the measurement precision is higher in the non-differential GPS mode. Following these rules may result in improvement of measurement quality by 20% to 80%.