Two-photon exchange correction to the hyperfine splitting in muonic hydrogen

NASA Astrophysics Data System (ADS)

Tomalak, Oleksandr

2017-12-01

We reevaluate the Zemach, recoil and polarizability corrections to the hyperfine splitting in muonic hydrogen expressing them through the low-energy proton structure constants and obtain the precise values of the Zemach radius and two-photon exchange (TPE) contribution. The uncertainty of TPE correction to S energy levels in muonic hydrogen of 105 ppm exceeds the ppm accuracy level of the forthcoming 1S hyperfine splitting measurements at PSI, J-PARC and RIKEN-RAL.

Competing Visions of Aerospace Power: A Language for the 21st Century.

DTIC Science & Technology

1997-02-21

Power and the Ground War in Vietnam (Maxwell Air Force Base, Alabama: Air University Press, January 1988; Richard J. Overy, "Air Power and the... Richard the Lionhearted. These warriors studied carefully all five books of the De re militari, but they particularly valued the 26 chapters on...measure, or even to express in precise terms.ඇ 62 Beyerchen, "Clausewitz, Nonlinearity, and War," 63. Quoted in Andrew G. B. Vallance , "The

High precision pulsar timing and spin frequency second derivatives

NASA Astrophysics Data System (ADS)

Liu, X. J.; Bassa, C. G.; Stappers, B. W.

2018-05-01

We investigate the impact of intrinsic, kinematic and gravitational effects on high precision pulsar timing. We present an analytical derivation and a numerical computation of the impact of these effects on the first and second derivative of the pulsar spin frequency. In addition, in the presence of white noise, we derive an expression to determine the expected measurement uncertainty of a second derivative of the spin frequency for a given timing precision, observing cadence and timing baseline and find that it strongly depends on the latter (∝t-7/2). We show that for pulsars with significant proper motion, the spin frequency second derivative is dominated by a term dependent on the radial velocity of the pulsar. Considering the data sets from three Pulsar Timing Arrays, we find that for PSR J0437-4715 a detectable spin frequency second derivative will be present if the absolute value of the radial velocity exceeds 33 km s-1. Similarly, at the current timing precision and cadence, continued timing observations of PSR J1909-3744 for about another eleven years, will allow the measurement of its frequency second derivative and determine the radial velocity with an accuracy better than 14 km s-1. With the ever increasing timing precision and observing baselines, the impact of the, largely unknown, radial velocities of pulsars on high precision pulsar timing can not be neglected.

Determination of flavonoids from Orthosiphon stamineus in plasma using a simple HPLC method with ultraviolet detection.

PubMed

Loon, Yit Hong; Wong, Jia Woei; Yap, Siew Ping; Yuen, Kah Hay

2005-02-25

A simple liquid chromatographic method was developed for the simultaneous determination of flavonoids from Orthosiphon stamineus Benth, namely sinensitin, eupatorin and 3'-hydroxy-5,6,7,4'-tetramethoxyflavone, in plasma. Prior to analysis, the flavonoids and the internal standard (naproxen) were extracted from plasma samples using a 1:1 mixture of ethyl acetate and chloroform. The detection and quantification limits for the three flavonoids were similar being 3 and 5 ng/ml, respectively. The within-day and between-day accuracy values, expressed as percentage of true values, for the three flavonoids were between 95 and 107%, while the corresponding precision, expressed as coefficients of variation, for the three flavonoids were less than 14%. In addition, the mean recovery values of the extraction procedure for all the flavonoids were between 92 and 114%. The calibration curves were linear over a concentration range of 5-4000 ng/ml. The present method was applied to analyse plasma samples obtained from a pilot study using rats in which the mean absolute oral bioavailability values for sinensitin, eupatorin and 3'-hydroxy-5,6,7,4'-tetramethoxyflavone was 9.4, 1.0 and 1.5%, respectively.

A novel dual-marker expression panel for easy and accurate risk stratification of patients with gastric cancer.

PubMed

Kanda, Mitsuro; Murotani, Kenta; Tanaka, Haruyoshi; Miwa, Takashi; Umeda, Shinichi; Tanaka, Chie; Kobayashi, Daisuke; Hayashi, Masamichi; Hattori, Norifumi; Suenaga, Masaya; Yamada, Suguru; Nakayama, Goro; Fujiwara, Michitaka; Kodera, Yasuhiro

2018-05-07

Development of specific biomarkers is necessary for individualized management of patients with gastric cancer. The aim of this study was to design a simple expression panel comprising novel molecular markers for precise risk stratification. Patients (n = 200) who underwent gastrectomy for gastric cancer were randomly assigned into learning and validation sets. Tissue mRNA expression levels of 15 candidate molecular markers were determined using quantitative PCR analysis. A dual-marker expression panel was created according to concordance index (C-index) values of overall survival for all 105 combinations of two markers in the learning set. The reproducibility and clinical significance of the dual-marker expression panel were evaluated in the validation set. The patient characteristics of the learning and validation sets were well balanced. The C-index values of combinations were significantly higher compared with those of single markers. The panel with the highest C-index (0.718) of the learning set comprised SYT8 and MAGED2, which clearly stratified patients into low-, intermediate-, and high-risk groups. The reproducibility of the panel was demonstrated in the validation set. High expression scores were significantly associated with larger tumor size, vascular invasion, lymph node metastasis, peritoneal metastasis, and advanced disease. The dual-marker expression panel provides a simple tool that clearly stratifies patients with gastric cancer into low-, intermediate-, and high risk after gastrectomy. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Probabilistic seismic loss estimation via endurance time method

NASA Astrophysics Data System (ADS)

Tafakori, Ehsan; Pourzeynali, Saeid; Estekanchi, Homayoon E.

2017-01-01

Probabilistic Seismic Loss Estimation is a methodology used as a quantitative and explicit expression of the performance of buildings using terms that address the interests of both owners and insurance companies. Applying the ATC 58 approach for seismic loss assessment of buildings requires using Incremental Dynamic Analysis (IDA), which needs hundreds of time-consuming analyses, which in turn hinders its wide application. The Endurance Time Method (ETM) is proposed herein as part of a demand propagation prediction procedure and is shown to be an economical alternative to IDA. Various scenarios were considered to achieve this purpose and their appropriateness has been evaluated using statistical methods. The most precise and efficient scenario was validated through comparison against IDA driven response predictions of 34 code conforming benchmark structures and was proven to be sufficiently precise while offering a great deal of efficiency. The loss values were estimated by replacing IDA with the proposed ETM-based procedure in the ATC 58 procedure and it was found that these values suffer from varying inaccuracies, which were attributed to the discretized nature of damage and loss prediction functions provided by ATC 58.

Precision Effects for Solar Image Coordinates Within the FITS World Coordinate System

NASA Technical Reports Server (NTRS)

Thompson, W. T.

2010-01-01

The FITS world coordinate system (WCS) provides a number of tools for precisely specifying the spatial coordinates of an image. Many of the finer details that the WCS addresses have not historically been taken into account in solar image processing. This paper examines various effects which can affect the expression of coordinates in FITS headers, to determine under what conditions such effects need to be taken into account in data analysis, and under what conditions they can be safely ignored. Effects which are examined include perspective, parallax, spherical projection, optical axis determination, speed-of-light effects, stellar aberration, gravitational deflection, and scattering and refraction at radio wavelengths. Purely instrumental effects, such as misalignment or untreated optical aberrations, are not considered. Since the value of the solar radius is an experimental quantity, the effect of adopting a specific radius value is also examined. These effects are examined in the context of a previous paper outlining a WCS standard for encoding solar coordinates in FITS files. Aspects of that previous paper are clarified and extended in the present work.

Open source machine-learning algorithms for the prediction of optimal cancer drug therapies.

PubMed

Huang, Cai; Mezencev, Roman; McDonald, John F; Vannberg, Fredrik

2017-01-01

Precision medicine is a rapidly growing area of modern medical science and open source machine-learning codes promise to be a critical component for the successful development of standardized and automated analysis of patient data. One important goal of precision cancer medicine is the accurate prediction of optimal drug therapies from the genomic profiles of individual patient tumors. We introduce here an open source software platform that employs a highly versatile support vector machine (SVM) algorithm combined with a standard recursive feature elimination (RFE) approach to predict personalized drug responses from gene expression profiles. Drug specific models were built using gene expression and drug response data from the National Cancer Institute panel of 60 human cancer cell lines (NCI-60). The models are highly accurate in predicting the drug responsiveness of a variety of cancer cell lines including those comprising the recent NCI-DREAM Challenge. We demonstrate that predictive accuracy is optimized when the learning dataset utilizes all probe-set expression values from a diversity of cancer cell types without pre-filtering for genes generally considered to be "drivers" of cancer onset/progression. Application of our models to publically available ovarian cancer (OC) patient gene expression datasets generated predictions consistent with observed responses previously reported in the literature. By making our algorithm "open source", we hope to facilitate its testing in a variety of cancer types and contexts leading to community-driven improvements and refinements in subsequent applications.

Equity and Value in 'Precision Medicine'.

PubMed

Gray, Muir; Lagerberg, Tyra; Dombrádi, Viktor

2017-04-01

Precision medicine carries huge potential in the treatment of many diseases, particularly those with high-penetrance monogenic underpinnings. However, precision medicine through genomic technologies also has ethical implications. We will define allocative, personal, and technical value ('triple value') in healthcare and how this relates to equity. Equity is here taken to be implicit in the concept of triple value in countries that have publicly funded healthcare systems. It will be argued that precision medicine risks concentrating resources to those that already experience greater access to healthcare and power in society, nationally as well as globally. Healthcare payers, clinicians, and patients must all be involved in optimising the potential of precision medicine, without reducing equity. Throughout, the discussion will refer to the NHS RightCare Programme, which is a national initiative aiming to improve value and equity in the context of NHS England.

Modified expression for bulb-tracer depletion—Effect on argon dating standards

USGS Publications Warehouse

Fleck, Robert J.; Calvert, Andrew T.

2014-01-01

40Ar/39Ar geochronology depends critically on well-calibrated standards, often traceable to first-principles K-Ar age calibrations using bulb-tracer systems. Tracer systems also provide precise standards for noble-gas studies and interlaboratory calibration. The exponential expression long used for calculating isotope tracer concentrations in K-Ar age dating and calibration of 40Ar/39Ar age standards may provide a close approximation of those values, but is not correct. Appropriate equations are derived that accurately describe the depletion of tracer reservoirs and concentrations of sequential tracers. In the modified expression the depletion constant is not in the exponent, which only varies as integers by tracer-number. Evaluation of the expressions demonstrates that systematic error introduced through use of the original expression may be substantial where reservoir volumes are small and resulting depletion constants are large. Traditional use of large reservoir to tracer volumes and the resulting small depletion constants have kept errors well less than experimental uncertainties in most previous K-Ar and calibration studies. Use of the proper expression, however, permits use of volumes appropriate to the problems addressed.

Methods for the accurate estimation of confidence intervals on protein folding ϕ-values

PubMed Central

Ruczinski, Ingo; Sosnick, Tobin R.; Plaxco, Kevin W.

2006-01-01

ϕ-Values provide an important benchmark for the comparison of experimental protein folding studies to computer simulations and theories of the folding process. Despite the growing importance of ϕ measurements, however, formulas to quantify the precision with which ϕ is measured have seen little significant discussion. Moreover, a commonly employed method for the determination of standard errors on ϕ estimates assumes that estimates of the changes in free energy of the transition and folded states are independent. Here we demonstrate that this assumption is usually incorrect and that this typically leads to the underestimation of ϕ precision. We derive an analytical expression for the precision of ϕ estimates (assuming linear chevron behavior) that explicitly takes this dependence into account. We also describe an alternative method that implicitly corrects for the effect. By simulating experimental chevron data, we show that both methods accurately estimate ϕ confidence intervals. We also explore the effects of the commonly employed techniques of calculating ϕ from kinetics estimated at non-zero denaturant concentrations and via the assumption of parallel chevron arms. We find that these approaches can produce significantly different estimates for ϕ (again, even for truly linear chevron behavior), indicating that they are not equivalent, interchangeable measures of transition state structure. Lastly, we describe a Web-based implementation of the above algorithms for general use by the protein folding community. PMID:17008714

Differences in liver stiffness values obtained with new ultrasound elastography machines and Fibroscan: A comparative study.

PubMed

Piscaglia, Fabio; Salvatore, Veronica; Mulazzani, Lorenzo; Cantisani, Vito; Colecchia, Antonio; Di Donato, Roberto; Felicani, Cristina; Ferrarini, Alessia; Gamal, Nesrine; Grasso, Valentina; Marasco, Giovanni; Mazzotta, Elena; Ravaioli, Federico; Ruggieri, Giacomo; Serio, Ilaria; Sitouok Nkamgho, Joules Fabrice; Serra, Carla; Festi, Davide; Schiavone, Cosima; Bolondi, Luigi

2017-07-01

Whether Fibroscan thresholds can be immediately adopted for none, some or all other shear wave elastography techniques has not been tested. The aim of the present study was to test the concordance of the findings obtained from 7 of the most recent ultrasound elastography machines with respect to Fibroscan. Sixteen hepatitis C virus-related patients with fibrosis ≥2 and having reliable results at Fibroscan were investigated in two intercostal spaces using 7 different elastography machines. Coefficients of both precision (an index of data dispersion) and accuracy (an index of bias correction factors expressing different magnitudes of changes in comparison to the reference) were calculated. Median stiffness values differed among the different machines as did coefficients of both precision (range 0.54-0.72) and accuracy (range 0.28-0.87). When the average of the measurements of two intercostal spaces was considered, coefficients of precision significantly increased with all machines (range 0.72-0.90) whereas of accuracy improved more scatteredly and by a smaller degree (range 0.40-0.99). The present results showed only moderate concordance of the majority of elastography machines with the Fibroscan results, preventing the possibility of the immediate universal adoption of Fibroscan thresholds for defining liver fibrosis staging for all new machines. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

The Case for Personalized Medicine

PubMed Central

Abrahams, Edward; Silver, Mike

2009-01-01

Personalized medicine may be considered an extension of traditional approaches to understanding and treating disease, but with greater precision. Physicians may now use a patient's genetic variation or expression profile as well as protein and metabolic markers to guide the selection of certain drugs or treatments. In many cases, the information provided by molecular markers predicts susceptibility to conditions. The added precision introduces the possibility of a more preventive, effective approach to clinical care and reductions in the duration and cost of clinical trials. Here, we make the case, through real-world examples, that personalized medicine is delivering significant value to individuals, to industry, and to the health care system overall and that it will continue to grow in importance if we can lift the barriers that impede its adoption and build incentives to encourage its practice. PMID:20144313

Characterization and improvement of RNA-Seq precision in quantitative transcript expression profiling.

PubMed

Łabaj, Paweł P; Leparc, Germán G; Linggi, Bryan E; Markillie, Lye Meng; Wiley, H Steven; Kreil, David P

2011-07-01

Measurement precision determines the power of any analysis to reliably identify significant signals, such as in screens for differential expression, independent of whether the experimental design incorporates replicates or not. With the compilation of large-scale RNA-Seq datasets with technical replicate samples, however, we can now, for the first time, perform a systematic analysis of the precision of expression level estimates from massively parallel sequencing technology. This then allows considerations for its improvement by computational or experimental means. We report on a comprehensive study of target identification and measurement precision, including their dependence on transcript expression levels, read depth and other parameters. In particular, an impressive recall of 84% of the estimated true transcript population could be achieved with 331 million 50 bp reads, with diminishing returns from longer read lengths and even less gains from increased sequencing depths. Most of the measurement power (75%) is spent on only 7% of the known transcriptome, however, making less strongly expressed transcripts harder to measure. Consequently, <30% of all transcripts could be quantified reliably with a relative error<20%. Based on established tools, we then introduce a new approach for mapping and analysing sequencing reads that yields substantially improved performance in gene expression profiling, increasing the number of transcripts that can reliably be quantified to over 40%. Extrapolations to higher sequencing depths highlight the need for efficient complementary steps. In discussion we outline possible experimental and computational strategies for further improvements in quantification precision. rnaseq10@boku.ac.at

Reliable and efficient solution of genome-scale models of Metabolism and macromolecular Expression

DOE PAGES

Ma, Ding; Yang, Laurence; Fleming, Ronan M. T.; ...

2017-01-18

Currently, Constraint-Based Reconstruction and Analysis (COBRA) is the only methodology that permits integrated modeling of Metabolism and macromolecular Expression (ME) at genome-scale. Linear optimization computes steady-state flux solutions to ME models, but flux values are spread over many orders of magnitude. Data values also have greatly varying magnitudes. Furthermore, standard double-precision solvers may return inaccurate solutions or report that no solution exists. Exact simplex solvers based on rational arithmetic require a near-optimal warm start to be practical on large problems (current ME models have 70,000 constraints and variables and will grow larger). We also developed a quadrupleprecision version of ourmore » linear and nonlinear optimizer MINOS, and a solution procedure (DQQ) involving Double and Quad MINOS that achieves reliability and efficiency for ME models and other challenging problems tested here. DQQ will enable extensive use of large linear and nonlinear models in systems biology and other applications involving multiscale data.« less

Engineering xylose metabolism for production of polyhydroxybutyrate in the non-model bacterium Burkholderia sacchari.

PubMed

Guamán, Linda P; Barba-Ostria, Carlos; Zhang, Fuzhong; Oliveira-Filho, Edmar R; Gomez, José Gregório C; Silva, Luiziana F

2018-05-15

Despite its ability to grow and produce high-value molecules using renewable carbon sources, two main factors must be improved to use Burkholderia sacchari as a chassis for bioproduction at an industrial scale: first, the lack of molecular tools to engineer this organism and second, the inherently slow growth rate and poly-3-hydroxybutyrate [P(3HB)] production using xylose. In this work, we have addressed both factors. First, we adapted a set of BglBrick plasmids and showed tunable expression in B. sacchari. Finally, we assessed growth rate and P(3HB) production through overexpression of xylose transporters, catabolic or regulatory genes. Overexpression of xylR significantly improved growth rate (55.5% improvement), polymer yield (77.27% improvement), and resulted in 71% of cell dry weight as P(3HB). These values are unprecedented for P(3HB) accumulation using xylose as a sole carbon source and highlight the importance of precise expression control for improving utilization of hemicellulosic sugars in B. sacchari.

Reliable and efficient solution of genome-scale models of Metabolism and macromolecular Expression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma, Ding; Yang, Laurence; Fleming, Ronan M. T.

Currently, Constraint-Based Reconstruction and Analysis (COBRA) is the only methodology that permits integrated modeling of Metabolism and macromolecular Expression (ME) at genome-scale. Linear optimization computes steady-state flux solutions to ME models, but flux values are spread over many orders of magnitude. Data values also have greatly varying magnitudes. Furthermore, standard double-precision solvers may return inaccurate solutions or report that no solution exists. Exact simplex solvers based on rational arithmetic require a near-optimal warm start to be practical on large problems (current ME models have 70,000 constraints and variables and will grow larger). We also developed a quadrupleprecision version of ourmore » linear and nonlinear optimizer MINOS, and a solution procedure (DQQ) involving Double and Quad MINOS that achieves reliability and efficiency for ME models and other challenging problems tested here. DQQ will enable extensive use of large linear and nonlinear models in systems biology and other applications involving multiscale data.« less

Traditional and emerging molecular markers in neuroblastoma prognosis: the good, the bad and the ugly.

PubMed

Poremba, C; Hero, B; Goertz, H G; Scheel, C; Wai, D; Schaefer, K L; Christiansen, H; Berthold, F; Juergens, H; Boecker, W; Dockhorn-Dworniczak, B

2001-01-01

Neuroblastomas (NB) are a heterogeneous group of childhood tumours with a wide range of likelihood for tumour progression. As traditional parameters do not ensure completely accurate prognostic grouping, new molecular markers are needed for assessing the individual patient's prognosis more precisely. 133 NB of all stages were analysed in blind-trial fashion for telomerase activity (TA), expression of surviving, and MYCN status. These data were correlated with other traditional prognostic indicators and disease outcome. TA is a powerful independent prognostic marker for all stages and is capable of differentiating between good and poor outcome in putative "favourable" clinical or biological subgroups of NB patients. High surviving expression is associated with an adverse outcome, but is more difficult to interprete than TA because survivin expression needs to be accurately quantified to be of predictive value. We propose an extended progression model for NB including emerging prognostic markers, with emphasis on telomerase activity.

A discrete Markov metapopulation model for persistence and extinction of species.

PubMed

Thompson, Colin J; Shtilerman, Elad; Stone, Lewi

2016-09-07

A simple discrete generation Markov metapopulation model is formulated for studying the persistence and extinction dynamics of a species in a given region which is divided into a large number of sites or patches. Assuming a linear site occupancy probability from one generation to the next we obtain exact expressions for the time evolution of the expected number of occupied sites and the mean-time to extinction (MTE). Under quite general conditions we show that the MTE, to leading order, is proportional to the logarithm of the initial number of occupied sites and in precise agreement with similar expressions for continuous time-dependent stochastic models. Our key contribution is a novel application of generating function techniques and simple asymptotic methods to obtain a second order asymptotic expression for the MTE which is extremely accurate over the entire range of model parameter values. Copyright © 2016 Elsevier Ltd. All rights reserved.

Reexamination of the calculation of two-center, two-electron integrals over Slater-type orbitals. II. Neumann expansion of the exchange integrals

NASA Astrophysics Data System (ADS)

Lesiuk, Michał; Moszynski, Robert

2014-12-01

In this paper we consider the calculation of two-center exchange integrals over Slater-type orbitals (STOs). We apply the Neumann expansion of the Coulomb interaction potential and consider calculation of all basic quantities which appear in the resulting expression. Analytical closed-form equations for all auxiliary quantities have already been known but they suffer from large digital erosion when some of the parameters are large or small. We derive two differential equations which are obeyed by the most difficult basic integrals. Taking them as a starting point, useful series expansions for small parameter values or asymptotic expansions for large parameter values are systematically derived. The resulting expansions replace the corresponding analytical expressions when the latter introduce significant cancellations. Additionally, we reconsider numerical integration of some necessary quantities and present a new way to calculate the integrand with a controlled precision. All proposed methods are combined to lead to a general, stable algorithm. We perform extensive numerical tests of the introduced expressions to verify their validity and usefulness. Advances reported here provide methodology to compute two-electron exchange integrals over STOs for a broad range of the nonlinear parameters and large angular momenta.

The expression of the skeletal muscle force-length relationship in vivo: a simulation study.

PubMed

Winter, Samantha L; Challis, John H

2010-02-21

The force-length relationship is one of the most important mechanical characteristics of skeletal muscle in humans and animals. For a physiologically realistic joint range of motion and therefore range of muscle fibre lengths only part of the force-length curve may be used in vivo, i.e. only a section of the force-length curve is expressed. A generalised model of a mono-articular muscle-tendon complex was used to examine the effect of various muscle architecture parameters on the expressed section of the force-length relationship for a 90 degrees joint range of motion. The parameters investigated were: the ratio of tendon resting length to muscle fibre optimum length (L(TR):L(F.OPT)) (varied from 0.5 to 11.5), the ratio of muscle fibre optimum length to average moment arm (L(F.OPT):r) (varied from 0.5 to 5), the normalised tendon strain at maximum isometric force (c) (varied from 0 to 0.08), the muscle fibre pennation angle (theta) (varied from 0 degrees to 45 degrees) and the joint angle at which the optimum muscle fibre length occurred (phi). The range of values chosen for each parameter was based on values reported in the literature for five human mono-articular muscles with different functional roles. The ratios L(TR):L(F.OPT) and L(F.OPT):r were important in determining the amount of variability in the expressed section of the force-length relationship. The modelled muscle operated over only one limb at intermediate values of these two ratios (L(TR):L(F.OPT)=5; L(F.OPT):r=3), whether this was the ascending or descending limb was determined by the precise values of the other parameters. It was concluded that inter-individual variability in the expressed section of the force-length relationship is possible, particularly for muscles with intermediate values of L(TR):L(F.OPT) and L(F.OPT):r such as the brachialis and vastus lateralis. Understanding the potential for inter-individual variability in the expressed section is important when using muscle models to simulate movement. (c) 2009 Elsevier Ltd. All rights reserved.

Isotope dependence of the Zeeman effect in lithium-like calcium

PubMed Central

Köhler, Florian; Blaum, Klaus; Block, Michael; Chenmarev, Stanislav; Eliseev, Sergey; Glazov, Dmitry A.; Goncharov, Mikhail; Hou, Jiamin; Kracke, Anke; Nesterenko, Dmitri A.; Novikov, Yuri N.; Quint, Wolfgang; Minaya Ramirez, Enrique; Shabaev, Vladimir M.; Sturm, Sven; Volotka, Andrey V.; Werth, Günter

2016-01-01

The magnetic moment μ of a bound electron, generally expressed by the g-factor μ=−g μB s ħ−1 with μB the Bohr magneton and s the electron's spin, can be calculated by bound-state quantum electrodynamics (BS-QED) to very high precision. The recent ultra-precise experiment on hydrogen-like silicon determined this value to eleven significant digits, and thus allowed to rigorously probe the validity of BS-QED. Yet, the investigation of one of the most interesting contribution to the g-factor, the relativistic interaction between electron and nucleus, is limited by our knowledge of BS-QED effects. By comparing the g-factors of two isotopes, it is possible to cancel most of these contributions and sensitively probe nuclear effects. Here, we present calculations and experiments on the isotope dependence of the Zeeman effect in lithium-like calcium ions. The good agreement between the theoretical predicted recoil contribution and the high-precision g-factor measurements paves the way for a new generation of BS-QED tests. PMID:26776466

Plasticity Regulators Modulate Specific Root Traits in Discrete Nitrogen Environments

PubMed Central

Gifford, Miriam L.; Banta, Joshua A.; Katari, Manpreet S.; Hulsmans, Jo; Chen, Lisa; Ristova, Daniela; Tranchina, Daniel; Purugganan, Michael D.; Coruzzi, Gloria M.; Birnbaum, Kenneth D.

2013-01-01

Plant development is remarkably plastic but how precisely can the plant customize its form to specific environments? When the plant adjusts its development to different environments, related traits can change in a coordinated fashion, such that two traits co-vary across many genotypes. Alternatively, traits can vary independently, such that a change in one trait has little predictive value for the change in a second trait. To characterize such “tunability” in developmental plasticity, we carried out a detailed phenotypic characterization of complex root traits among 96 accessions of the model Arabidopsis thaliana in two nitrogen environments. The results revealed a surprising level of independence in the control of traits to environment – a highly tunable form of plasticity. We mapped genetic architecture of plasticity using genome-wide association studies and further used gene expression analysis to narrow down gene candidates in mapped regions. Mutants in genes implicated by association and expression analysis showed precise defects in the predicted traits in the predicted environment, corroborating the independent control of plasticity traits. The overall results suggest that there is a pool of genetic variability in plants that controls traits in specific environments, with opportunity to tune crop plants to a given environment. PMID:24039603

A Monte Carlo Simulation Comparing the Statistical Precision of Two High-Stakes Teacher Evaluation Methods: A Value-Added Model and a Composite Measure

ERIC Educational Resources Information Center

Spencer, Bryden

2016-01-01

Value-added models are a class of growth models used in education to assign responsibility for student growth to teachers or schools. For value-added models to be used fairly, sufficient statistical precision is necessary for accurate teacher classification. Previous research indicated precision below practical limits. An alternative approach has…

Use of Wilms Tumor 1 Gene Expression as a Reliable Marker for Prognosis and Minimal Residual Disease Monitoring in Acute Myeloid Leukemia With Normal Karyotype Patients.

PubMed

Marjanovic, Irena; Karan-Djurasevic, Teodora; Ugrin, Milena; Virijevic, Marijana; Vidovic, Ana; Tomin, Dragica; Suvajdzic Vukovic, Nada; Pavlovic, Sonja; Tosic, Natasa

2017-05-01

Acute myeloid leukemia with normal karyotype (AML-NK) represents the largest group of AML patients classified with an intermediate prognosis. A constant need exists to introduce new molecular markers for more precise risk stratification and for minimal residual disease (MRD) monitoring. Quantitative assessment of Wilms tumor 1 (WT1) gene transcripts was performed using real-time polymerase chain reaction. The bone marrow samples were collected at the diagnosis from 104 AML-NK patients and from 34 of these patients during follow-up or disease relapse. We found that overexpression of the WT1 gene (WT1 high status), present in 25.5% of patients, was an independent unfavorable factor for achieving complete remission. WT1 high status was also associated with resistance to therapy and shorter disease-free survival and overall survival. Assessment of the log reduction value of WT1 expression, measured in paired diagnosis/complete remission samples, revealed that patients with a log reduction of < 2 had a tendency toward shorter disease-free survival and overall survival and a greater incidence of disease relapse. Combining WT1 gene expression status with NPM1 and FLT3-ITD mutational status, we found that the tumor behavior of intermediate patients (FLT3-ITD - /NPM1 - double negative) with WT1 high status is almost the same as the tumor behavior of the adverse risk group. WT1 expression status represents a good molecular marker of prognosis, response to treatment, and MRD monitoring. Above all, the usage of the WT1 expression level as an additional marker for more precise risk stratification of AML-NK patients could lead to more adapted, personalized treatment protocols. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparison of central HER2 testing with quantitative total HER2 expression and HER2 homodimer measurements using a novel proximity-based assay.

PubMed

Huang, Weidong; Reinholz, Monica; Weidler, Jodi; Yolanda, Lie; Paquet, Agnes; Whitcomb, Jeannette; Lingle, Wilma; Jenkins, Robert B; Chen, Beiyun; Larson, Jeffrey S; Tan, Yuping; Sherwood, Thomas; Bates, Michael; Perez, Edith A

2010-08-01

The accuracy and reliability of immunohistochemical analysis and in situ hybridization for the assessment of HER2 status remains a subject of debate. We developed a novel assay (HERmark Breast Cancer Assay, Monogram Biosciences, South San Francisco, CA) that provides precise quantification of total HER2 protein expression (H2T) and HER2 homodimers (H2D) in formalin-fixed, paraffin-embedded tissue specimens. H2T and H2D results of 237 breast cancers were compared with those of immunohistochemical studies and fluorescence in situ hybridization (FISH) centrally performed at the Mayo Clinic, Rochester, MN. H2T described a continuum across a wide dynamic range ( approximately 2.5 log). Excluding the equivocal cases, HERmark showed 98% concordance with immunohistochemical studies for positive and negative assay values. For the 94 immunohistochemically equivocal cases, 67% and 39% concordance values were observed between HERmark and FISH for positive and negative assay values, respectively. Polysomy 17 in the absence of HER2 gene amplification did not result in HER2 overexpression as evaluated quantitatively using the HERmark assay.

Computing many-body wave functions with guaranteed precision: the first-order Møller-Plesset wave function for the ground state of helium atom.

PubMed

Bischoff, Florian A; Harrison, Robert J; Valeev, Edward F

2012-09-14

We present an approach to compute accurate correlation energies for atoms and molecules using an adaptive discontinuous spectral-element multiresolution representation for the two-electron wave function. Because of the exponential storage complexity of the spectral-element representation with the number of dimensions, a brute-force computation of two-electron (six-dimensional) wave functions with high precision was not practical. To overcome the key storage bottlenecks we utilized (1) a low-rank tensor approximation (specifically, the singular value decomposition) to compress the wave function, and (2) explicitly correlated R12-type terms in the wave function to regularize the Coulomb electron-electron singularities of the Hamiltonian. All operations necessary to solve the Schrödinger equation were expressed so that the reconstruction of the full-rank form of the wave function is never necessary. Numerical performance of the method was highlighted by computing the first-order Møller-Plesset wave function of a helium atom. The computed second-order Møller-Plesset energy is precise to ~2 microhartrees, which is at the precision limit of the existing general atomic-orbital-based approaches. Our approach does not assume special geometric symmetries, hence application to molecules is straightforward.

Automated analysis of flow cytometric data for measuring neutrophil CD64 expression using a multi-instrument compatible probability state model.

PubMed

Wong, Linda; Hill, Beth L; Hunsberger, Benjamin C; Bagwell, C Bruce; Curtis, Adam D; Davis, Bruce H

2015-01-01

Leuko64™ (Trillium Diagnostics) is a flow cytometric assay that measures neutrophil CD64 expression and serves as an in vitro indicator of infection/sepsis or the presence of a systemic acute inflammatory response. Leuko64 assay currently utilizes QuantiCALC, a semiautomated software that employs cluster algorithms to define cell populations. The software reduces subjective gating decisions, resulting in interanalyst variability of <5%. We evaluated a completely automated approach to measuring neutrophil CD64 expression using GemStone™ (Verity Software House) and probability state modeling (PSM). Four hundred and fifty-seven human blood samples were processed using the Leuko64 assay. Samples were analyzed on four different flow cytometer models: BD FACSCanto II, BD FACScan, BC Gallios/Navios, and BC FC500. A probability state model was designed to identify calibration beads and three leukocyte subpopulations based on differences in intensity levels of several parameters. PSM automatically calculates CD64 index values for each cell population using equations programmed into the model. GemStone software uses PSM that requires no operator intervention, thus totally automating data analysis and internal quality control flagging. Expert analysis with the predicate method (QuantiCALC) was performed. Interanalyst precision was evaluated for both methods of data analysis. PSM with GemStone correlates well with the expert manual analysis, r(2) = 0.99675 for the neutrophil CD64 index values with no intermethod bias detected. The average interanalyst imprecision for the QuantiCALC method was 1.06% (range 0.00-7.94%), which was reduced to 0.00% with the GemStone PSM. The operator-to-operator agreement in GemStone was a perfect correlation, r(2) = 1.000. Automated quantification of CD64 index values produced results that strongly correlate with expert analysis using a standard gate-based data analysis method. PSM successfully evaluated flow cytometric data generated by multiple instruments across multiple lots of the Leuko64 kit in all 457 cases. The probability-based method provides greater objectivity, higher data analysis speed, and allows for greater precision for in vitro diagnostic flow cytometric assays. © 2015 International Clinical Cytometry Society.

DETERMINING MOTOR INERTIA OF A STRESS-CONTROLLED RHEOMETER.

PubMed

Klemuk, Sarah A; Titze, Ingo R

2009-01-01

Viscoelastic measurements made with a stress-controlled rheometer are affected by system inertia. Of all contributors to system inertia, motor inertia is the largest. Its value is usually determined empirically and precision is rarely if ever specified. Inertia uncertainty has negligible effects on rheologic measurements below the coupled motor/plate/sample resonant frequency. But above the resonant frequency, G' values of soft viscoelastic materials such as dispersions, gels, biomaterials, and non-Newtonian polymers, err quadratically due to inertia uncertainty. In the present investigation, valid rheologic measurements were achieved near and above the coupled resonant frequency for a non-Newtonian reference material. At these elevated frequencies, accuracy in motor inertia is critical. Here we compare two methods for determining motor-inertia accurately. For the first (commercially-used) phase method, frequency responses of standard fluids were measured. Phase between G' and G" was analyzed at 5-70 Hz for motor inertia values of 50-150% of the manufacturer's nominal value. For a newly-devised two-plate method (10 mm and 60 mm parallel plates), dynamic measurements of a non-Newtonian standard were collected. Using a linear equation of motion with inertia, viscosity, and elasticity coefficients, G' expressions for both plates were equated and motor inertia was determined to be accurate (by comparison to the phase method) with a precision of ± 3%. The newly developed two-plate method had advantages of expressly eliminating dependence on gap, was explicitly derived from basic principles, quantified the error, and required fewer experiments than the commercially used phase method.

Hologic QDR 2000 whole-body scans: a comparison of three combinations of scan modes and analysis software

NASA Technical Reports Server (NTRS)

Spector, E.; LeBlanc, A.; Shackelford, L.

1995-01-01

This study reports on the short-term in vivo precision and absolute measurements of three combinations of whole-body scan modes and analysis software using a Hologic QDR 2000 dual-energy X-ray densitometer. A group of 21 normal, healthy volunteers (11 male and 10 female) were scanned six times, receiving one pencil-beam and one array whole-body scan on three occasions approximately 1 week apart. The following combinations of scan modes and analysis software were used: pencil-beam scans analyzed with Hologic's standard whole-body software (PB scans); the same pencil-beam analyzed with Hologic's newer "enhanced" software (EPB scans); and array scans analyzed with the enhanced software (EA scans). Precision values (% coefficient of variation, %CV) were calculated for whole-body and regional bone mineral content (BMC), bone mineral density (BMD), fat mass, lean mass, %fat and total mass. In general, there was no significant difference among the three scan types with respect to short-term precision of BMD and only slight differences in the precision of BMC. Precision of BMC and BMD for all three scan types was excellent: < 1% CV for whole-body values, with most regional values in the 1%-2% range. Pencil-beam scans demonstrated significantly better soft tissue precision than did array scans. Precision errors for whole-body lean mass were: 0.9% (PB), 1.1% (EPB) and 1.9% (EA). Precision errors for whole-body fat mass were: 1.7% (PB), 2.4% (EPB) and 5.6% (EA). EPB precision errors were slightly higher than PB precision errors for lean, fat and %fat measurements of all regions except the head, although these differences were significant only for the fat and % fat of the arms and legs. In addition EPB precision values exhibited greater individual variability than PB precision values. Finally, absolute values of bone and soft tissue were compared among the three combinations of scan and analysis modes. BMC, BMD, fat mass, %fat and lean mass were significantly different between PB scans and either of the EPB or EA scans. Differences were as large as 20%-25% for certain regional fat and BMD measurements. Additional work may be needed to examine the relative accuracy of the scan mode/software combinations and to identify reasons for the differences in soft tissue precision with the array whole-body scan mode.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matthias C. M. Troffaes; Gero Walter; Dana Kelly

In a standard Bayesian approach to the alpha-factor model for common-cause failure, a precise Dirichlet prior distribution models epistemic uncertainty in the alpha-factors. This Dirichlet prior is then updated with observed data to obtain a posterior distribution, which forms the basis for further inferences. In this paper, we adapt the imprecise Dirichlet model of Walley to represent epistemic uncertainty in the alpha-factors. In this approach, epistemic uncertainty is expressed more cautiously via lower and upper expectations for each alpha-factor, along with a learning parameter which determines how quickly the model learns from observed data. For this application, we focus onmore » elicitation of the learning parameter, and find that values in the range of 1 to 10 seem reasonable. The approach is compared with Kelly and Atwood's minimally informative Dirichlet prior for the alpha-factor model, which incorporated precise mean values for the alpha-factors, but which was otherwise quite diffuse. Next, we explore the use of a set of Gamma priors to model epistemic uncertainty in the marginal failure rate, expressed via a lower and upper expectation for this rate, again along with a learning parameter. As zero counts are generally less of an issue here, we find that the choice of this learning parameter is less crucial. Finally, we demonstrate how both epistemic uncertainty models can be combined to arrive at lower and upper expectations for all common-cause failure rates. Thereby, we effectively provide a full sensitivity analysis of common-cause failure rates, properly reflecting epistemic uncertainty of the analyst on all levels of the common-cause failure model.« less

Precise Analysis of Gallium Isotopic Composition by MC-ICP-MS.

PubMed

Yuan, Wei; Chen, Jiu Bin; Birck, Jean-Louis; Yin, Zuo Ying; Yuan, Sheng Liu; Cai, Hong Ming; Wang, Zhong Wei; Huang, Qiang; Wang, Zhu Hong

2016-10-04

Though an isotope approach could be beneficial for better understanding the biogeochemical cycle of gallium (Ga), an analogue of the monoisotopic element aluminum (Al), the geochemistry of Ga isotopes has not been widely elaborated. We developed a two-step method for purifying Ga from geological (biological) samples for precise measurement of Ga isotope ratio using multicollector inductively coupled plasma mass spectrometry (MC-ICP-MS). Ga was thoroughly separated from other matrix elements using two chromatographic columns loaded with AG 1-X4 and Ln-spec resin, respectively. The separation method was carefully calibrated using both synthetic and natural samples and validated by assessing the extraction yield (99.8 ± 0.8%, 2SD, n = 23) and the reproducibility (2SD uncertainty better than 0.05‰, n = 116) of the measured isotopic ratio (expressed as δ 71 Ga). The validation of the whole protocol, together with instrumental analysis, was confirmed by the investigation of the matrix effect, the result of a standard addition experiment, and the comparison of Ga isotope measurement on two mass spectrometers-Nu Plasma II and Neptune Plus. Although the measurements using the sample-standard bracketing (SSB) correction method on both instruments resulted in identical δ 71 Ga values for reference materials, the modified empirical external normalization (MEEN) method gave relatively better precision compared to SSB on Neptune. Our preliminary results showed large variation of δ 71 Ga (up to 1.83‰) for 10 standards, with higher values in industrially produced materials, implying potential application of Ga isotopes.

Exploiting position effects and the gypsy retrovirus insulator to engineer precisely expressed transgenes.

PubMed

Markstein, Michele; Pitsouli, Chrysoula; Villalta, Christians; Celniker, Susan E; Perrimon, Norbert

2008-04-01

A major obstacle to creating precisely expressed transgenes lies in the epigenetic effects of the host chromatin that surrounds them. Here we present a strategy to overcome this problem, employing a Gal4-inducible luciferase assay to systematically quantify position effects of host chromatin and the ability of insulators to counteract these effects at phiC31 integration loci randomly distributed throughout the Drosophila genome. We identify loci that can be exploited to deliver precise doses of transgene expression to specific tissues. Moreover, we uncover a previously unrecognized property of the gypsy retrovirus insulator to boost gene expression to levels severalfold greater than at most or possibly all un-insulated loci, in every tissue tested. These findings provide the first opportunity to create a battery of transgenes that can be reliably expressed at high levels in virtually any tissue by integration at a single locus, and conversely, to engineer a controlled phenotypic allelic series by exploiting several loci. The generality of our approach makes it adaptable to other model systems to identify and modify loci for optimal transgene expression.

Increased gene expression noise in human cancers is correlated with low p53 and immune activities as well as late stage cancer.

PubMed

Han, Rongfei; Huang, Guanqun; Wang, Yejun; Xu, Yafei; Hu, Yueming; Jiang, Wenqi; Wang, Tianfu; Xiao, Tian; Zheng, Duo

2016-11-01

Gene expression in metazoans is delicately organized. As genetic information transmits from DNA to RNA and protein, expression noise is inevitably generated. Recent studies begin to unveil the mechanisms of gene expression noise control, but the changes of gene expression precision in pathologic conditions like cancers are unknown. Here we analyzed the transcriptomic data of human breast, liver, lung and colon cancers, and found that the expression noise of more than 74.9% genes was increased in cancer tissues as compared to adjacent normal tissues. This suggested that gene expression precision controlling collapsed during cancer development. A set of 269 genes with noise increased more than 2-fold were identified across different cancer types. These genes were involved in cell adhesion, catalytic and metabolic functions, implying the vulnerability of deregulation of these processes in cancers. We also observed a tendency of increased expression noise in patients with low p53 and immune activity in breast, liver and lung caners but not in colon cancers, which indicated the contributions of p53 signaling and host immune surveillance to gene expression noise in cancers. Moreover, more than 53.7% genes had increased noise in patients with late stage than early stage cancers, suggesting that gene expression precision was associated with cancer outcome. Together, these results provided genomic scale explorations of gene expression noise control in human cancers.

[Influence of trabecular microstructure modeling on finite element analysis of dental implant].

PubMed

Shen, M J; Wang, G G; Zhu, X H; Ding, X

2016-09-01

To analyze the influence of trabecular microstructure modeling on the biomechanical distribution of implant-bone interface with a three-dimensional finite element mandible model of trabecular structure. Dental implants were embeded in the mandibles of a beagle dog. After three months of the implant installation, the mandibles with dental implants were harvested and scaned by micro-CT and cone-beam CT. Two three-dimensional finite element mandible models, trabecular microstructure(precise model) and macrostructure(simplified model), were built. The values of stress and strain of implant-bone interface were calculated using the software of Ansys 14.0. Compared with the simplified model, the precise models' average values of the implant bone interface stress increased obviously and its maximum values did not change greatly. The maximum values of quivalent stress of the precise models were 80% and 110% of the simplified model and the average values were 170% and 290% of simplified model. The maximum and average values of equivalent strain of precise models were obviously decreased, and the maximum values of the equivalent effect strain were 17% and 26% of simplified model and the average ones were 21% and 16% of simplified model respectively. Stress and strain concentrations at implant-bone interface were obvious in the simplified model. However, the distributions of stress and strain were uniform in the precise model. The precise model has significant effect on the distribution of stress and strain at implant-bone interface.

High-precision mass measurements for the rp-process at JYFLTRAP

NASA Astrophysics Data System (ADS)

Canete, Laetitia; Eronen, Tommi; Jokinen, Ari; Kankainen, Anu; Moore, Ian D.; Nesterenko, Dimitry; Rinta-Antila, Sami

2018-01-01

The double Penning trap JYFLTRAP at the University of Jyväskylä has been successfully used to achieve high-precision mass measurements of nuclei involved in the rapid proton-capture (rp) process. A precise mass measurement of 31Cl is essential to estimate the waiting point condition of 30S in the rp-process occurring in type I x-ray bursts (XRBs). The mass-excess of 31C1 measured at JYFLTRAP, -7034.7(3.4) keV, is 15 more precise than the value given in the Atomic Mass Evaluation 2012. The proton separation energy Sp determined from the new mass-excess value confirmed that 30S is a waiting point, with a lower-temperature limit of 0.44 GK. The mass of 52Co effects both 51Fe(p,γ)52Co and 52Co(p,γ)53Ni reactions. The mass-excess value measured, - 34 331.6(6.6) keV is 30 times more precise than the value given in AME2012. The Q values for the 51Fe(p,γ)52Co and 52Co(p,γ)53Ni reactions are now known with a high precision, 1418(11) keV and 2588(26) keV respectively. The results show that 52Co is more proton bound and 53Ni less proton bound than what was expected from the extrapolated value.

An Extended ADOP for Performance Evaluation of Single-Frequency Single-Epoch Positioning by BDS/GPS in Asia-Pacific Region

PubMed Central

Liu, Xin; Zhang, Shubi; Zhang, Qiuzhao; Yang, Wei

2017-01-01

Single-Frequency Single-Epoch (SFSE) high-precision positioning has always been the hot spot of Global Navigation Satellite System (GNSS), and ambiguity dilution of precision (ADOP) is a well-known scalar measure for success rate of ambiguity resolution. Traditional ADOP expression is complicated, thus the SFSE extended ADOP (E-ADOP), with the newly defined Summation-Multiplication Ratio of Weight (SMRW) and two theorems for short baseline, was developed. This simplifies the ADOP expression; gives a clearer insight into the influences of SMRW and number of satellites on E-ADOP; and makes theoretical analysis of E-ADOP more convenient than that of ADOP, and through that the E-ADOP value can be predicted more accurately than through the ADOP expression for ADOP value. E-ADOP reveals that number of satellites and SMRW or high-elevation satellite are important for ADOP and, through E-ADOP, we studied which factor is dominant to control ADOP in different conditions and make ADOP different between BeiDou Navigation Satellite System (BDS), Global Positioning System (GPS), and BDS/GPS. Based on experimental results of SFSE positioning with different baselines, some conclusions are made: (1) ADOP decreases when new satellites are added mainly because the number of satellites becomes larger; (2) when the number of satellites is constant, ADOP is mainly affected by SMRW; (3) in contrast to systems where the satellites with low-elevation are the majority or where low- and high-elevation satellites are equally distributed, in systems where the high-elevation satellites are the majority, the SMRW mainly makes ADOP smaller, even if there are fewer satellites than in the two previous cases, and the difference in numbers of satellites can be expanded as the proportion of high-elevation satellites becomes larger; and (4) ADOP of BDS is smaller than ADOP of GPS mainly because of its SMRW. PMID:28973977

Comprehensive Assessments of RNA-seq by the SEQC Consortium: FDA-Led Efforts Advance Precision Medicine.

PubMed

Xu, Joshua; Gong, Binsheng; Wu, Leihong; Thakkar, Shraddha; Hong, Huixiao; Tong, Weida

2016-03-15

Studies on gene expression in response to therapy have led to the discovery of pharmacogenomics biomarkers and advances in precision medicine. Whole transcriptome sequencing (RNA-seq) is an emerging tool for profiling gene expression and has received wide adoption in the biomedical research community. However, its value in regulatory decision making requires rigorous assessment and consensus between various stakeholders, including the research community, regulatory agencies, and industry. The FDA-led SEquencing Quality Control (SEQC) consortium has made considerable progress in this direction, and is the subject of this review. Specifically, three RNA-seq platforms (Illumina HiSeq, Life Technologies SOLiD, and Roche 454) were extensively evaluated at multiple sites to assess cross-site and cross-platform reproducibility. The results demonstrated that relative gene expression measurements were consistently comparable across labs and platforms, but not so for the measurement of absolute expression levels. As part of the quality evaluation several studies were included to evaluate the utility of RNA-seq in clinical settings and safety assessment. The neuroblastoma study profiled tumor samples from 498 pediatric neuroblastoma patients by both microarray and RNA-seq. RNA-seq offers more utilities than microarray in determining the transcriptomic characteristics of cancer. However, RNA-seq and microarray-based models were comparable in clinical endpoint prediction, even when including additional features unique to RNA-seq beyond gene expression. The toxicogenomics study compared microarray and RNA-seq profiles of the liver samples from rats exposed to 27 different chemicals representing multiple toxicity modes of action. Cross-platform concordance was dependent on chemical treatment and transcript abundance. Though both RNA-seq and microarray are suitable for developing gene expression based predictive models with comparable prediction performance, RNA-seq offers advantages over microarray in profiling genes with low expression. The rat BodyMap study provided a comprehensive rat transcriptomic body map by performing RNA-Seq on 320 samples from 11 organs in either sex of juvenile, adolescent, adult and aged Fischer 344 rats. Lastly, the transferability study demonstrated that signature genes of predictive models are reciprocally transferable between microarray and RNA-seq data for model development using a comprehensive approach with two large clinical data sets. This result suggests continued usefulness of legacy microarray data in the coming RNA-seq era. In conclusion, the SEQC project enhances our understanding of RNA-seq and provides valuable guidelines for RNA-seq based clinical application and safety evaluation to advance precision medicine.

Science and Art

NASA Astrophysics Data System (ADS)

Moore, John W.

2001-10-01

Science and art diverge in that art usually represents a single individual's conception and viewpoint, even when many others are involved in bringing a work to fruition, whereas science progresses by extending consensus among those knowledgeable in a field. Art usually communicates at an emotional level. It values individual expression and impact on the emotions at the expense of objectivity. Science, especially in its archival record, values objectivity and reproducibility and does not express the imagination and joy of discovery inherent in its practice. This is too bad, because it does not give a realistic picture of how science is really done and because individuality and emotion are inherently more interesting than consensus. Leaving out the personal, emotional side can make science seem boring and pedestrian, when exactly the opposite is true. In teaching science we need to remember that communication always benefits from imagination and esthetic sense. If we present science artistically and imaginatively, as well as objectively and precisely, students will develop a more complete understanding of what science and scientists are about--one that is likely to capture their imaginations, emotions, and best efforts.

Water vapor δ(2) H, δ(18) O and δ(17) O measurements using an off-axis integrated cavity output spectrometer - sensitivity to water vapor concentration, delta value and averaging-time.

PubMed

Tian, Chao; Wang, Lixin; Novick, Kimberly A

2016-10-15

High-precision analysis of atmospheric water vapor isotope compositions, especially δ(17) O values, can be used to improve our understanding of multiple hydrological and meteorological processes (e.g., differentiate equilibrium or kinetic fractionation). This study focused on assessing, for the first time, how the accuracy and precision of vapor δ(17) O laser spectroscopy measurements depend on vapor concentration, delta range, and averaging-time. A Triple Water Vapor Isotope Analyzer (T-WVIA) was used to evaluate the accuracy and precision of δ(2) H, δ(18) O and δ(17) O measurements. The sensitivity of accuracy and precision to water vapor concentration was evaluated using two international standards (GISP and SLAP2). The sensitivity of precision to delta value was evaluated using four working standards spanning a large delta range. The sensitivity of precision to averaging-time was assessed by measuring one standard continuously for 24 hours. Overall, the accuracy and precision of the δ(2) H, δ(18) O and δ(17) O measurements were high. Across all vapor concentrations, the accuracy of δ(2) H, δ(18) O and δ(17) O observations ranged from 0.10‰ to 1.84‰, 0.08‰ to 0.86‰ and 0.06‰ to 0.62‰, respectively, and the precision ranged from 0.099‰ to 0.430‰, 0.009‰ to 0.080‰ and 0.022‰ to 0.054‰, respectively. The accuracy and precision of all isotope measurements were sensitive to concentration, with the higher accuracy and precision generally observed under moderate vapor concentrations (i.e., 10000-15000 ppm) for all isotopes. The precision was also sensitive to the range of delta values, although the effect was not as large compared with the sensitivity to concentration. The precision was much less sensitive to averaging-time than the concentration and delta range effects. The accuracy and precision performance of the T-WVIA depend on concentration but depend less on the delta value and averaging-time. The instrument can simultaneously and continuously measure δ(2) H, δ(18) O and δ(17) O values in water vapor, opening a new window to better understand ecological, hydrological and meteorological processes. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Development of a LC-MS method for simultaneous determination of amoxicillin and metronidazole in human serum using hydrophilic interaction chromatography (HILIC).

PubMed

Kathriarachchi, Udani L; Vidhate, Sagar S; Al-Tannak, Naser; Thomson, Alison H; da Silva Neto, Michael J J; Watson, David G

2018-07-01

A method was developed for the determination of amoxicillin and metronidazole in human serum. The procedure used was hydrophilic interaction chromatography (HILIC) followed by mass spectrometric (MS) detection. Chromatographic separation was achieved on a ZIC-HILIC column and the mobile phase consisted of a mixture of 0.1% (v/v) formic acid in water and 0.1% (v/v) formic acid in acetonitrile. The method was validated with regard to selectivity, accuracy, precision, calibration, lower limit of quantification (LOQ), extraction recovery and matrix effect. The LOQs were 0.0138 and 0.008 μg/ml for amoxicillin and metronidazole respectively, while for quantification purposes linearity was achieved in the range of 0.1 μg/ml to 6.4 μg/ml for both drugs with correlation coefficients >0.9990. The intraday precision (expressed as %RSD) and the accuracy (expressed as the % deviation from the nominal value) was <15% for both antibiotics at all QC levels. Extraction recoveries for both drugs and internal standards were >80%, while a considerable matrix effect (<60%) was observed for amoxicillin. Finally, the method was applied to the determination of amoxicillin and metronidazole concentrations in serum for 20 patients. Copyright © 2018 Elsevier B.V. All rights reserved.

Precision half-life measurement of 11C: The most precise mirror transition F t value

NASA Astrophysics Data System (ADS)

Valverde, A. A.; Brodeur, M.; Ahn, T.; Allen, J.; Bardayan, D. W.; Becchetti, F. D.; Blankstein, D.; Brown, G.; Burdette, D. P.; Frentz, B.; Gilardy, G.; Hall, M. R.; King, S.; Kolata, J. J.; Long, J.; Macon, K. T.; Nelson, A.; O'Malley, P. D.; Skulski, M.; Strauss, S. Y.; Vande Kolk, B.

2018-03-01

Background: The precise determination of the F t value in T =1 /2 mixed mirror decays is an important avenue for testing the standard model of the electroweak interaction through the determination of Vu d in nuclear β decays. 11C is an interesting case, as its low mass and small QE C value make it particularly sensitive to violations of the conserved vector current hypothesis. The present dominant source of uncertainty in the 11CF t value is the half-life. Purpose: A high-precision measurement of the 11C half-life was performed, and a new world average half-life was calculated. Method: 11C was created by transfer reactions and separated using the TwinSol facility at the Nuclear Science Laboratory at the University of Notre Dame. It was then implanted into a tantalum foil, and β counting was used to determine the half-life. Results: The new half-life, t1 /2=1220.27 (26 ) s, is consistent with the previous values but significantly more precise. A new world average was calculated, t1/2 world=1220.41 (32 ) s, and a new estimate for the Gamow-Teller to Fermi mixing ratio ρ is presented along with standard model correlation parameters. Conclusions: The new 11C world average half-life allows the calculation of a F tmirror value that is now the most precise value for all superallowed mixed mirror transitions. This gives a strong impetus for an experimental determination of ρ , to allow for the determination of Vu d from this decay.

Black TiO2-based nanoprobes for T1-weighted MRI-guided photothermal therapy in CD133 high expressed pancreatic cancer stem-like cells.

PubMed

Wang, Siqi; Ren, Wenzhi; Wang, Jianhua; Jiang, Zhenqi; Saeed, Madiha; Zhang, Lili; Li, Aiguo; Wu, Aiguo

2018-06-27

At present, transmembrane glycoprotein CD133 highly expressed pancreatic cancer stem cells (PCSCs), with the features of chemotherapeutic/radiotherapeutic resistance and exclusive tumorigenic potential, are considered as the primary cause of metastasis and recurrence in pancreatic cancer, and therefore are an effective target in the disease treatment. Furthermore, with the launch of precision medicine, multifunctional nanoprobes have been applied as an efficient strategy for the magnetic resonance imaging (MRI)-guided photothermal therapy (PTT) of pancreatic cancer. In this research, with the aim of achieving precise MRI-guided PTT in CD133 highly expressed PCSCs, novel bTiO2-Gd-CD133mAb nanoprobes were designed and successfully prepared by loading Gd-DOTA and CD133 monoclonal antibodies on black TiO2 nanoparticles. It was very interesting to find that the r1 relaxivity value of the nanoprobes was 34.394 mM-1 s-1, about 7.5 times that of commercial Magnevist (4.5624 mM-1 s-1), which indicates that the nanoprobes have good potential as MRI T1 contrast agents with excellent performance. Herein, CD133 highly expressed PANC-1 cells were selected and verified as PCSCs model. In vitro experiments demonstrated that the nanoprobes exhibited active-targeting ability in PANC-1 cells, and consequently could specially enhance T1-weighted MR imaging and 808 nm near-infrared (NIR)-triggered PTT efficiency in the PCSCs model. Our study not only provides a new strategy for the effective treatment of pancreatic cancer and its' stem cells, but also further broadens the application of black TiO2 in the field of cancer theranostics.

CD147 overexpression may serve as a promising diagnostic and prognostic marker for gastric cancer: evidence from original research and literature.

PubMed

Hu, Chenghao; Dong, Xiaoxia; Wu, Junbo; Xiao, Feifan; Shang, Jun; Liu, Liang; Yang, Yuan; Luo, Dongmei; Li, Qiuting; Song, Qian; Yang, Jingcheng; Zhang, Chengdong; Shen, Li; Luo, Zhiguo

2017-05-09

Gastric cancer (GC) is one of the most common malignancies worldwide. The expression of CD147 protein is associated with GC. However, the clinical role of CD147 in GC has not been investigated extensively. Hence, we focused on studying the association between the expression of CD147 and clinicopathological features of GC patients in this study. Firstly, sixteen publications (1752 cases and 391 controls) and one from our own original research (143 cases) were included in the meta-analysis to obtain a more precise estimation of the diagnostic value of CD147. The results showed that expression rate of CD147 in the GC group is higher than that in control group. Moreover, gender, TNM stage, lymph node metastasis, and depth of invasion are all associated with CD147. Further, sections of gastric tissue from 143 cases underwent immunohistochemical staining for evaluation of CD147 protein expression. Our retrospective analysis demonstrated CD147 protein expression was significantly associated with clinical N stage, and tumor stage. Meanwhile, it can also serve as an independent prognosis biomarker. In conclusion, our results support the role of CD147 as a good indicator of diagnosis and prognosis.

High-precision branching ratio measurement for the superallowed β+ emitter Ga62

NASA Astrophysics Data System (ADS)

Finlay, P.; Ball, G. C.; Leslie, J. R.; Svensson, C. E.; Towner, I. S.; Austin, R. A. E.; Bandyopadhyay, D.; Chaffey, A.; Chakrawarthy, R. S.; Garrett, P. E.; Grinyer, G. F.; Hackman, G.; Hyland, B.; Kanungo, R.; Leach, K. G.; Mattoon, C. M.; Morton, A. C.; Pearson, C. J.; Phillips, A. A.; Ressler, J. J.; Sarazin, F.; Savajols, H.; Schumaker, M. A.; Wong, J.

2008-08-01

A high-precision branching ratio measurement for the superallowed β+ decay of Ga62 was performed at the Isotope Separator and Accelerator (ISAC) radioactive ion beam facility. The 8π spectrometer, an array of 20 high-purity germanium detectors, was employed to detect the γ rays emitted following Gamow-Teller and nonanalog Fermi β+ decays of Ga62, and the SCEPTAR plastic scintillator array was used to detect the emitted β particles. Thirty γ rays were identified following Ga62 decay, establishing the superallowed branching ratio to be 99.858(8)%. Combined with the world-average half-life and a recent high-precision Q-value measurement for Ga62, this branching ratio yields an ft value of 3074.3±1.1 s, making Ga62 among the most precisely determined superallowed ft values. Comparison between the superallowed ft value determined in this work and the world-average corrected F tmacr value allows the large nuclear-structure-dependent correction for Ga62 decay to be experimentally determined from the CVC hypothesis to better than 7% of its own value, the most precise experimental determination for any superallowed emitter. These results provide a benchmark for the refinement of the theoretical description of isospin-symmetry breaking in A⩾62 superallowed decays.

High-Precision Half-Life Measurement for the Superallowed β+ Emitter 22Mg

NASA Astrophysics Data System (ADS)

Dunlop, Michelle

2017-09-01

High precision measurements of the Ft values for superallowed Fermi beta transitions between 0+ isobaric analogue states allow for stringent tests of the electroweak interaction. These transitions provide an experimental probe of the Conserved-Vector-Current hypothesis, the most precise determination of the up-down element of the Cabibbo-Kobayashi-Maskawa matrix, and set stringent limits on the existence of scalar currents in the weak interaction. To calculate the Ft values several theoretical corrections must be applied to the experimental data, some of which have large model dependent variations. Precise experimental determinations of the ft values can be used to help constrain the different models. The uncertainty in the 22Mg superallowed Ft value is dominated by the uncertainty in the experimental ft value. The adopted half-life of 22Mg is determined from two measurements which disagree with one another, resulting in the inflation of the weighted-average half-life uncertainty by a factor of 2. The 22Mg half-life was measured with a precision of 0.02% via direct β counting at TRIUMF's ISAC facility, leading to an improvement in the world-average half-life by more than a factor of 3.

Clinical ethics and values: how do norms evolve from practice?

PubMed

Spranzi, Marta

2013-02-01

Bioethics laws in France have just undergone a revision process. The bioethics debate is often cast in terms of ethical principles and norms resisting emerging social and technological practices. This leads to the expression of confrontational attitudes based on widely differing interpretations of the same principles and values, and ultimately results in a deadlock. In this paper I would like to argue that focusing on values, as opposed to norms and principles, provides an interesting perspective on the evolution of norms. As Joseph Raz has convincingly argued, "life-building" values and practices are closely intertwined. Precisely because values have a more indeterminate meaning than norms, they can be cited as reasons for action by concerned stakeholders, and thus can help us understand how controversial practices, e.g. surrogate motherhood, can be justified. Finally, norms evolve when the interpretations of the relevant values shift and cause a change in the presumptions implicit in the norms. Thus, norms are not a prerequisite of the ethical solution of practical dilemmas, but rather the outcome of the decision-making process itself. Struggling to reach the right decision in controversial clinical ethics situations indirectly causes social and moral values to change and principles to be understood differently.

Dollar$ & $en$e. Part IV: Measuring the value of people, structural, and customer capital.

PubMed

Wilkinson, I

2001-01-01

In Part I of this series, I introduced the concept of memes (1). Memes are ideas or concepts, the information world equivalent of genes. The goal of this series of articles is to infect you with my memes, so that you will assimilate, translate, and express them. We discovered that no matter what our area of expertise or "-ology," we all are in the information business. Our goal is to be in the wisdom business. We saw that when we convert raw data into wisdom we are moving along a value chain. Each step in the chain adds a different amount of value to the final product: timely, relevant, accurate, and precise knowledge which can then be applied to create the ultimate product in the value chain: wisdom. In Part II of this series, I infected you with a set of memes for measuring the cost of adding value (2). In Part III of this series, I infected you with a new set of memes for measuring the added value of knowledge, i.e., intellectual capital (3). In Part IV of this series, I will infect you with memes for measuring the value of people, structural, and customer capital.

Call to Adopt a Nominal Set of Astrophysical Parameters and Constants to Improve the Accuracy of Fundamental Physical Properties of Stars

NASA Astrophysics Data System (ADS)

Harmanec, Petr; Prša, Andrej

2011-08-01

The increasing precision of astronomical observations of stars and stellar systems is gradually getting to a level where the use of slightly different values of the solar mass, radius, and luminosity, as well as different values of fundamental physical constants, can lead to measurable systematic differences in the determination of basic physical properties. An equivalent issue with an inconsistent value of the speed of light was resolved by adopting a nominal value that is constant and has no error associated with it. Analogously, we suggest that the systematic error in stellar parameters may be eliminated by (1) replacing the solar radius R⊙ and luminosity L⊙ by the nominal values that are by definition exact and expressed in SI units: and ; (2) computing stellar masses in terms of M⊙ by noting that the measurement error of the product GM⊙ is 5 orders of magnitude smaller than the error in G; (3) computing stellar masses and temperatures in SI units by using the derived values and ; and (4) clearly stating the reference for the values of the fundamental physical constants used. We discuss the need and demonstrate the advantages of such a paradigm shift.

Precision phase estimation based on weak-value amplification

NASA Astrophysics Data System (ADS)

Qiu, Xiaodong; Xie, Linguo; Liu, Xiong; Luo, Lan; Li, Zhaoxue; Zhang, Zhiyou; Du, Jinglei

2017-02-01

In this letter, we propose a precision method for phase estimation based on the weak-value amplification (WVA) technique using a monochromatic light source. The anomalous WVA significantly suppresses the technical noise with respect to the intensity difference signal induced by the phase delay when the post-selection procedure comes into play. The phase measured precision of this method is proportional to the weak-value of a polarization operator in the experimental range. Our results compete well with the wide spectrum light phase weak measurements and outperform the standard homodyne phase detection technique.

Diffusion theory of decision making in continuous report.

PubMed

Smith, Philip L

2016-07-01

I present a diffusion model for decision making in continuous report tasks, in which a continuous, circularly distributed, stimulus attribute in working memory is matched to a representation of the attribute in the stimulus display. Memory retrieval is modeled as a 2-dimensional diffusion process with vector-valued drift on a disk, whose bounding circle represents the decision criterion. The direction and magnitude of the drift vector describe the identity of the stimulus and the quality of its representation in memory, respectively. The point at which the diffusion exits the disk determines the reported value of the attribute and the time to exit the disk determines the decision time. Expressions for the joint distribution of decision times and report outcomes are obtained by means of the Girsanov change-of-measure theorem, which allows the properties of the nonzero-drift diffusion process to be characterized as a function of a Euclidian-distance Bessel process. Predicted report precision is equal to the product of the decision criterion and the drift magnitude and follows a von Mises distribution, in agreement with the treatment of precision in the working memory literature. Trial-to-trial variability in criterion and drift rate leads, respectively, to direct and inverse relationships between report accuracy and decision times, in agreement with, and generalizing, the standard diffusion model of 2-choice decisions. The 2-dimensional model provides a process account of working memory precision and its relationship with the diffusion model, and a new way to investigate the properties of working memory, via the distributions of decision times. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

High-Precision Half-Life and Branching Ratio Measurements for the Superallowed β+ Emitter 26Alm

NASA Astrophysics Data System (ADS)

Finlay, P.; Svensson, C. E.; Demand, G. A.; Garrett, P. E.; Green, K. L.; Leach, K. G.; Phillips, A. A.; Rand, E. T.; Ball, G.; Bandyopadhyay, D.; Djongolov, M.; Ettenauer, S.; Hackman, G.; Pearson, C. J.; Leslie, J. R.; Andreoiu, C.; Cross, D.; Austin, R. A. E.; Grinyer, G. F.; Sumithrarachchi, C. S.; Williams, S. J.; Triambak, S.

2013-03-01

High-precision half-life and branching-ratio measurements for the superallowed β+ emitter 26Alm were performed at the TRIUMF-ISAC radioactive ion beam facility. An upper limit of ≤ 15 ppm at 90% C.L. was determined for the sum of all possible non-analogue β+/EC decay branches of 26Alm, yielding a superallowed branching ratio of 100.0000+0-0.0015%. A value of T1/2 = 6:34654(76) s was determined for the 26Alm half-life which is consistent with, but 2.5 times more precise than, the previous world average. Combining these results with world-average measurements yields an ft value of 3037.58(60) s, the most precisely determined for any superallowed emitting nucleus to date. This high-precision ft value for 26Alm provides a new benchmark to refine theoretical models of isospin-symmetry-breaking effects in superallowed β decays.

Experimental Demonstration of Higher Precision Weak-Value-Based Metrology Using Power Recycling

NASA Astrophysics Data System (ADS)

Wang, Yi-Tao; Tang, Jian-Shun; Hu, Gang; Wang, Jian; Yu, Shang; Zhou, Zong-Quan; Cheng, Ze-Di; Xu, Jin-Shi; Fang, Sen-Zhi; Wu, Qing-Lin; Li, Chuan-Feng; Guo, Guang-Can

2016-12-01

The weak-value-based metrology is very promising and has attracted a lot of attention in recent years because of its remarkable ability in signal amplification. However, it is suggested that the upper limit of the precision of this metrology cannot exceed that of classical metrology because of the low sample size caused by the probe loss during postselection. Nevertheless, a recent proposal shows that this probe loss can be reduced by the power-recycling technique, and thus enhance the precision of weak-value-based metrology. Here we experimentally realize the power-recycled interferometric weak-value-based beam-deflection measurement and obtain the amplitude of the detected signal and white noise by discrete Fourier transform. Our results show that the detected signal can be strengthened by power recycling, and the power-recycled weak-value-based signal-to-noise ratio can surpass the upper limit of the classical scheme, corresponding to the shot-noise limit. This work sheds light on higher precision metrology and explores the real advantage of the weak-value-based metrology over classical metrology.

A new quantitative approach to measure perceived work-related stress in Italian employees.

PubMed

Cevenini, Gabriele; Fratini, Ilaria; Gambassi, Roberto

2012-09-01

We propose a method for a reliable quantitative measure of subjectively perceived occupational stress applicable in any company to enhance occupational safety and psychosocial health, to enable precise prevention policies and intervention and to improve work quality and efficiency. A suitable questionnaire was telephonically administered to a stratified sample of the whole Italian population of employees. Combined multivariate statistical methods, including principal component, cluster and discriminant analyses, were used to identify risk factors and to design a causal model for understanding work-related stress. The model explained the causal links of stress through employee perception of imbalance between job demands and resources for responding appropriately, by supplying a reliable U-shaped nonlinear stress index, expressed in terms of values of human systolic arterial pressure. Low, intermediate and high values indicated demotivation (or inefficiency), well-being and distress, respectively. Costs for stress-dependent productivity shortcomings were estimated to about 3.7% of national income from employment. The method identified useful structured information able to supply a simple and precise interpretation of employees' well-being and stress risk. Results could be compared with estimated national benchmarks to enable targeted intervention strategies to protect the health and safety of workers, and to reduce unproductive costs for firms.

Digital image analysis in pathology: benefits and obligation.

PubMed

Laurinavicius, Arvydas; Laurinaviciene, Aida; Dasevicius, Darius; Elie, Nicolas; Plancoulaine, Benoît; Bor, Catherine; Herlin, Paulette

2012-01-01

Pathology has recently entered the era of personalized medicine. This brings new expectations for the accuracy and precision of tissue-based diagnosis, in particular, when quantification of histologic features and biomarker expression is required. While for many years traditional pathologic diagnosis has been regarded as ground truth, this concept is no longer sufficient in contemporary tissue-based biomarker research and clinical use. Another major change in pathology is brought by the advancement of virtual microscopy technology enabling digitization of microscopy slides and presenting new opportunities for digital image analysis. Computerized vision provides an immediate benefit of increased capacity (automation) and precision (reproducibility), but not necessarily the accuracy of the analysis. To achieve the benefit of accuracy, pathologists will have to assume an obligation of validation and quality assurance of the image analysis algorithms. Reference values are needed to measure and control the accuracy. Although pathologists' consensus values are commonly used to validate these tools, we argue that the ground truth can be best achieved by stereology methods, estimating the same variable as an algorithm is intended to do. Proper adoption of the new technology will require a new quantitative mentality in pathology. In order to see a complete and sharp picture of a disease, pathologists will need to learn to use both their analogue and digital eyes.

A precise and accurate acupoint location obtained on the face using consistency matrix pointwise fusion method.

PubMed

Yanq, Xuming; Ye, Yijun; Xia, Yong; Wei, Xuanzhong; Wang, Zheyu; Ni, Hongmei; Zhu, Ying; Xu, Lingyu

2015-02-01

To develop a more precise and accurate method, and identified a procedure to measure whether an acupoint had been correctly located. On the face, we used an acupoint location from different acupuncture experts and obtained the most precise and accurate values of acupoint location based on the consistency information fusion algorithm, through a virtual simulation of the facial orientation coordinate system. Because of inconsistencies in each acupuncture expert's original data, the system error the general weight calculation. First, we corrected each expert of acupoint location system error itself, to obtain a rational quantification for each expert of acupuncture and moxibustion acupoint location consistent support degree, to obtain pointwise variable precision fusion results, to put every expert's acupuncture acupoint location fusion error enhanced to pointwise variable precision. Then, we more effectively used the measured characteristics of different acupuncture expert's acupoint location, to improve the measurement information utilization efficiency and acupuncture acupoint location precision and accuracy. Based on using the consistency matrix pointwise fusion method on the acupuncture experts' acupoint location values, each expert's acupoint location information could be calculated, and the most precise and accurate values of each expert's acupoint location could be obtained.

Effectiveness of Spectral Similarity Measures to Develop Precise Crop Spectra for Hyperspectral Data Analysis

NASA Astrophysics Data System (ADS)

Chauhan, H.; Krishna Mohan, B.

2014-11-01

The present study was undertaken with the objective to check effectiveness of spectral similarity measures to develop precise crop spectra from the collected hyperspectral field spectra. In Multispectral and Hyperspectral remote sensing, classification of pixels is obtained by statistical comparison (by means of spectral similarity) of known field or library spectra to unknown image spectra. Though these algorithms are readily used, little emphasis has been placed on use of various spectral similarity measures to select precise crop spectra from the set of field spectra. Conventionally crop spectra are developed after rejecting outliers based only on broad-spectrum analysis. Here a successful attempt has been made to develop precise crop spectra based on spectral similarity. As unevaluated data usage leads to uncertainty in the image classification, it is very crucial to evaluate the data. Hence, notwithstanding the conventional method, the data precision has been performed effectively to serve the purpose of the present research work. The effectiveness of developed precise field spectra was evaluated by spectral discrimination measures and found higher discrimination values compared to spectra developed conventionally. Overall classification accuracy for the image classified by field spectra selected conventionally is 51.89% and 75.47% for the image classified by field spectra selected precisely based on spectral similarity. KHAT values are 0.37, 0.62 and Z values are 2.77, 9.59 for image classified using conventional and precise field spectra respectively. Reasonable higher classification accuracy, KHAT and Z values shows the possibility of a new approach for field spectra selection based on spectral similarity measure.

High-precision measurement of phenylalanine δ15N values for environmental samples: a new approach coupling high-pressure liquid chromatography purification and elemental analyzer isotope ratio mass spectrometry.

PubMed

Broek, Taylor A B; Walker, Brett D; Andreasen, Dyke H; McCarthy, Matthew D

2013-11-15

Compound-specific isotope analysis of individual amino acids (CSI-AA) is a powerful new tool for tracing nitrogen (N) source and transformation in biogeochemical cycles. Specifically, the δ(15)N value of phenylalanine (δ(15)N(Phe)) represents an increasingly used proxy for source δ(15)N signatures, with particular promise for paleoceanographic applications. However, current derivatization/gas chromatography methods require expensive and relatively uncommon instrumentation, and have relatively low precision, making many potential applications impractical. A new offline approach has been developed for high-precision δ(15)N measurements of amino acids (δ(15)N(AA)), optimized for δ(15)N(Phe) values. Amino acids (AAs) are first purified via high-pressure liquid chromatography (HPLC), using a mixed-phase column and automated fraction collection. The δ(15)N values are determined via offline elemental analyzer-isotope ratio mass spectrometry (EA-IRMS). The combined HPLC/EA-IRMS method separated most protein AAs with sufficient resolution to obtain accurate δ(15)N values, despite significant intra-peak isotopic fractionation. For δ(15)N(Phe) values, the precision was ±0.16‰ for standards, 4× better than gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS; ±0.64‰). We also compared a δ(15)N(Phe) paleo-record from a deep-sea bamboo coral from Monterey Bay, CA, USA, using our method versus GC/C/IRMS. The two methods produced equivalent δ(15)N(Phe) values within error; however, the δ(15)N(Phe) values from HPLC/EA-IRMS had approximately twice the precision of GC/C/IRMS (average stdev of 0.27‰ ± 0.14‰ vs 0.60‰ ± 0.20‰, respectively). These results demonstrate that offline HPLC represents a viable alternative to traditional GC/C/IMRS for δ(15)N(AA) measurement. HPLC/EA-IRMS is more precise and widely available, and therefore useful in applications requiring increased precision for data interpretation (e.g. δ(15)N paleoproxies). Copyright © 2013 John Wiley & Sons, Ltd.

On the precision of experimentally determined protein folding rates and φ-values

PubMed Central

De Los Rios, Miguel A.; Muralidhara, B.K.; Wildes, David; Sosnick, Tobin R.; Marqusee, Susan; Wittung-Stafshede, Pernilla; Plaxco, Kevin W.; Ruczinski, Ingo

2006-01-01

φ-Values, a relatively direct probe of transition-state structure, are an important benchmark in both experimental and theoretical studies of protein folding. Recently, however, significant controversy has emerged regarding the reliability with which φ-values can be determined experimentally: Because φ is a ratio of differences between experimental observables it is extremely sensitive to errors in those observations when the differences are small. Here we address this issue directly by performing blind, replicate measurements in three laboratories. By monitoring within- and between-laboratory variability, we have determined the precision with which folding rates and φ-values are measured using generally accepted laboratory practices and under conditions typical of our laboratories. We find that, unless the change in free energy associated with the probing mutation is quite large, the precision of φ-values is relatively poor when determined using rates extrapolated to the absence of denaturant. In contrast, when we employ rates estimated at nonzero denaturant concentrations or assume that the slopes of the chevron arms (mf and mu) are invariant upon mutation, the precision of our estimates of φ is significantly improved. Nevertheless, the reproducibility we thus obtain still compares poorly with the confidence intervals typically reported in the literature. This discrepancy appears to arise due to differences in how precision is calculated, the dependence of precision on the number of data points employed in defining a chevron, and interlaboratory sources of variability that may have been largely ignored in the prior literature. PMID:16501226

The proposed terminology 'A(1c)-derived average glucose' is inherently imprecise and should not be adopted.

PubMed

Bloomgarden, Z T; Inzucchi, S E; Karnieli, E; Le Roith, D

2008-07-01

The proposed use of a more precise standard for glycated (A(1c)) and non-glycated haemoglobin would lead to an A(1c) value, when expressed as a percentage, that is lower than that currently in use. One approach advocated to address the potential confusion that would ensue is to replace 'HbA(1c)' with a new term, 'A(1c)-derived average glucose.' We review evidence from several sources suggesting that A(1c) is, in fact, inherently imprecise as a measure of average glucose, so that the proposed terminology should not be adopted.

Quantum interval-valued probability: Contextuality and the Born rule

NASA Astrophysics Data System (ADS)

Tai, Yu-Tsung; Hanson, Andrew J.; Ortiz, Gerardo; Sabry, Amr

2018-05-01

We present a mathematical framework based on quantum interval-valued probability measures to study the effect of experimental imperfections and finite precision measurements on defining aspects of quantum mechanics such as contextuality and the Born rule. While foundational results such as the Kochen-Specker and Gleason theorems are valid in the context of infinite precision, they fail to hold in general in a world with limited resources. Here we employ an interval-valued framework to establish bounds on the validity of those theorems in realistic experimental environments. In this way, not only can we quantify the idea of finite-precision measurement within our theory, but we can also suggest a possible resolution of the Meyer-Mermin debate on the impact of finite-precision measurement on the Kochen-Specker theorem.

Innovation, productivity, and pricing: Capturing value from precision medicine technology in Canada.

PubMed

Emery, J C Herbert; Zwicker, Jennifer D

2017-07-01

For new technology and innovation such as precision medicine to become part of the solution for the fiscal sustainability of Canadian Medicare, decision-makers need to change how services are priced rather than trying to restrain emerging technologies like precision medicine for short-term cost savings. If provincial public payers shift their thinking to be public purchasers, value considerations would direct reform of the reimbursement system to have prices that adjust with technologically driven productivity gains. This strategic shift in thinking is necessary if Canadians are to benefit from the promised benefits of innovations like precision medicine.

One- and two-photon states for quantum information

NASA Astrophysics Data System (ADS)

Peters, Nicholas A.

To find expression stability among transgenic lines, the Recombinase Mediated Transgene Integration (RMTI) technology using the Cre/ lox-mediated site-specific gene integration system was used. The objectives were to develop an efficient method of site-specific transgene integration and to test the effectiveness of this method by assaying transgene expression in the RMTI lines. The RMTI technology allows the precise integration of a transgene in a previously placed target genomic location containing a lox site. The efficiency of CRE-mediated site-specific integration in rice by particle bombardment was found to vary from 3 to 28% in nine different experiments. Some hemizygous site-specific integration plants that were derived from homozygous target locus were found to undergo CRE-mediated reversion of the integration locus. No reversion was observed in callus; however, reverting cells may have been excluded due to selection pressure. The expression of the transgene gus was studied in all 40 callus lines, 12 regenerated T0 plants and the T1 and T2 progenies of 5 lines. The isogenic SC lines had an average expression level based on the activity of beta-glucuronidase of 158 +/- 9 units/mg protein (mean +/- SEM; n=3; variance within SC lines are expressed as standard error of the mean SEM) indicating a significantly higher level of expression, as compared to MC lines that had a much lower expression level 44 +/- 8 units/mg protein (mean +/- SEM; n=3) and the imprecise lines that had 22 +/- 8 units/mg protein (mean +/- SEM; n=3). Transgene expression in the callus cells of precise single copy lines varied by ˜3 fold, whereas that in multi-copy lines varied by ˜30 fold. Furthermore, precise single copy lines, on an average, contained ˜3.5 fold higher expression than multi-copy lines. Transgene expression in the plants of precise single-copy lines was highly variable, which was found to be due to the loss of the integration because of CRE-mediated reversion in the locus. (Abstract shortened by UMI.)

High-precision QEC values of superallowed 0+ → 0+β-emitters 46Cr, 50Fe and 54Ni

NASA Astrophysics Data System (ADS)

Zhang, P.; Xu, X.; Shuai, P.; Chen, R. J.; Yan, X. L.; Zhang, Y. H.; Wang, M.; Litvinov, Yu. A.; Blaum, K.; Xu, H. S.; Bao, T.; Chen, X. C.; Chen, H.; Fu, C. Y.; He, J. J.; Kubono, S.; Lam, Y. H.; Liu, D. W.; Mao, R. S.; Ma, X. W.; Sun, M. Z.; Tu, X. L.; Xing, Y. M.; Yang, J. C.; Yuan, Y. J.; Zeng, Q.; Zhou, X.; Zhou, X. H.; Zhan, W. L.; Litvinov, S.; Audi, G.; Uesaka, T.; Yamaguchi, Y.; Yamaguchi, T.; Ozawa, A.; Sun, B. H.; Sun, Y.; Xu, F. R.

2017-04-01

Short-lived 46Cr, 50Fe and 54Ni were studied by isochronous mass spectrometry at the HIRFL-CSR facility in Lanzhou. The measured precision mass excesses (ME) of 46Cr, 50Fe and 54Ni are - 29471 (11) keV, - 34477 (6) keV and - 39278 (4) keV, respectively. The superallowed 0+ →0+β-decay Q values were derived to be QEC (46Cr) = 7604 (11) keV, QEC (50Fe) = 8150 (6) keV and QEC (54Ni) = 8731 (4) keV. The values for 50Fe and 54Ni are by one order of magnitude more precise than the adopted literature values. By combining the existing half-lives and branching ratios, we obtained the corrected Ft values to be Ft (50Fe) = 3103 (70) s and Ft (54Ni) = 3076 (50) s. The main contribution to the Ft uncertainties is now due to β-decay branching ratios, still, more high-precision measurements of the half-lives, the masses, and especially the branching ratios are needed in order to satisfy the requirements for a stringent CVC test.

Statistical analysis of an RNA titration series evaluates microarray precision and sensitivity on a whole-array basis

PubMed Central

Holloway, Andrew J; Oshlack, Alicia; Diyagama, Dileepa S; Bowtell, David DL; Smyth, Gordon K

2006-01-01

Background Concerns are often raised about the accuracy of microarray technologies and the degree of cross-platform agreement, but there are yet no methods which can unambiguously evaluate precision and sensitivity for these technologies on a whole-array basis. Results A methodology is described for evaluating the precision and sensitivity of whole-genome gene expression technologies such as microarrays. The method consists of an easy-to-construct titration series of RNA samples and an associated statistical analysis using non-linear regression. The method evaluates the precision and responsiveness of each microarray platform on a whole-array basis, i.e., using all the probes, without the need to match probes across platforms. An experiment is conducted to assess and compare four widely used microarray platforms. All four platforms are shown to have satisfactory precision but the commercial platforms are superior for resolving differential expression for genes at lower expression levels. The effective precision of the two-color platforms is improved by allowing for probe-specific dye-effects in the statistical model. The methodology is used to compare three data extraction algorithms for the Affymetrix platforms, demonstrating poor performance for the commonly used proprietary algorithm relative to the other algorithms. For probes which can be matched across platforms, the cross-platform variability is decomposed into within-platform and between-platform components, showing that platform disagreement is almost entirely systematic rather than due to measurement variability. Conclusion The results demonstrate good precision and sensitivity for all the platforms, but highlight the need for improved probe annotation. They quantify the extent to which cross-platform measures can be expected to be less accurate than within-platform comparisons for predicting disease progression or outcome. PMID:17118209

Determination of "net carbohydrates" using high-performance anion exchange chromatography.

PubMed

Lilla, Zach; Sullivan, Darryl; Ellefson, Wayne; Welton, Kevin; Crowley, Rick

2005-01-01

For labeling purposes, the carbohydrate content of foods has traditionally been determined by difference. This value includes sugars, starches, fiber, dextrins, sugar alcohols, polydextrose, and various other organic compounds. In some cases, the current method may lack sufficient specificity, precision, and accuracy. These are subsequently quantitated by high performance anion exchange chromatography with pulsed amperometric detection and expressed as total nonfiber saccharides or percent "net carbohydrates." In this research, a new method was developed to address this need. The method consists of enzyme digestions to convert starches, dextrins, sugars, and polysaccharides to their respective monosaccharide components. These are subsequently quantified by high-performance anion exchange chromatography with pulsed amperometric detector and expressed as total nonfiber saccharides or percent "net carbohydrates." Hydrolyzed end products of various novel fibers and similar carbohydrates have been evaluated to ensure that they do not register as false positives in the new test method. The data generated using the "net carbohydrate" method were, in many cases, significantly different than the values produced using the traditional methodology. The recoveries obtained in a fortified drink matrix ranged from 94.9 to 105%. The coefficient of variation was 3.3%.

Leadership = Communication? The Relations of Leaders' Communication Styles with Leadership Styles, Knowledge Sharing and Leadership Outcomes.

PubMed

de Vries, Reinout E; Bakker-Pieper, Angelique; Oostenveld, Wyneke

2010-09-01

PURPOSE: The purpose of this study was to investigate the relations between leaders' communication styles and charismatic leadership, human-oriented leadership (leader's consideration), task-oriented leadership (leader's initiating structure), and leadership outcomes. METHODOLOGY: A survey was conducted among 279 employees of a governmental organization. The following six main communication styles were operationalized: verbal aggressiveness, expressiveness, preciseness, assuredness, supportiveness, and argumentativeness. Regression analyses were employed to test three main hypotheses. FINDINGS: In line with expectations, the study showed that charismatic and human-oriented leadership are mainly communicative, while task-oriented leadership is significantly less communicative. The communication styles were strongly and differentially related to knowledge sharing behaviors, perceived leader performance, satisfaction with the leader, and subordinate's team commitment. Multiple regression analyses showed that the leadership styles mediated the relations between the communication styles and leadership outcomes. However, leader's preciseness explained variance in perceived leader performance and satisfaction with the leader above and beyond the leadership style variables. IMPLICATIONS: This study offers potentially invaluable input for leadership training programs by showing the importance of leader's supportiveness, assuredness, and preciseness when communicating with subordinates. ORIGINALITY/VALUE: Although one of the core elements of leadership is interpersonal communication, this study is one of the first to use a comprehensive communication styles instrument in the study of leadership.

S193 radiometer brightness temperature precision/accuracy for SL2 and SL3

NASA Technical Reports Server (NTRS)

Pounds, D. J.; Krishen, K.

1975-01-01

The precision and accuracy with which the S193 radiometer measured the brightness temperature of ground scenes is investigated. Estimates were derived from data collected during Skylab missions. Homogeneous ground sites were selected and S193 radiometer brightness temperature data analyzed. The precision was expressed as the standard deviation of the radiometer acquired brightness temperature. Precision was determined to be 2.40 K or better depending on mode and target temperature.

Discrepancies in describing pain: is there agreement between numeric rating scale scores and pain reduction percentage reported by patients with musculoskeletal pain after corticosteroid injection?

PubMed

Cushman, Daniel; McCormick, Zachary; Casey, Ellen; Plastaras, Christopher T

2015-05-01

Pain intensity is commonly rated on an 11-point Numerical Pain Rating Scale which can be expressed as a calculated percentage pain reduction (CPPR), or by patient-reported percentage pain reduction (PRPPR). We aimed to determine the agreement between CPPR and PRPPR in quantifying musculoskeletal pain improvement at short-term follow-up after a corticosteroid injection. Retrospective cohort study. Urban, academic, physical medicine, and rehabilitation outpatient interventional musculoskeletal and spine center. The agreement between CPPR and PRPPR was determined by concordance correlation coefficient (CCC) in subjects who had experienced improvement in musculoskeletal or radicular pain 3 weeks after a first-time injection at our clinic. Subjects who experienced unchanged pain (PRPPR = 0) were compared to CPPR with paired t-test. We examined 197 subjects with greater than 3/10 pain who underwent first-time fluoroscopic-guided corticosteroid injections. Ninety-three subjects reported higher PRPPR than CPPR values, and 41 subjects reported higher CPPR values. The CCC between CPPR and PRPPR was 0.44 (95% CI 0.35-0.54), with a precision of 0.54 and an accuracy of 0.81, and 95% limits of agreement ranging between -41% and +73%. Values for CCC, precision, and accuracy were higher for males compared to females and were highest in the youngest age group (18-40) and lowest in the middle age group (41-60). PRPPR may not agree with CPPR at 3 week follow-up, as these individuals tend to report a higher estimated percentage improvement compared to the value calculated from their pain scores. Wiley Periodicals, Inc.

Bit Grooming: statistically accurate precision-preserving quantization with compression, evaluated in the netCDF Operators (NCO, v4.4.8+)

NASA Astrophysics Data System (ADS)

Zender, Charles S.

2016-09-01

Geoscientific models and measurements generate false precision (scientifically meaningless data bits) that wastes storage space. False precision can mislead (by implying noise is signal) and be scientifically pointless, especially for measurements. By contrast, lossy compression can be both economical (save space) and heuristic (clarify data limitations) without compromising the scientific integrity of data. Data quantization can thus be appropriate regardless of whether space limitations are a concern. We introduce, implement, and characterize a new lossy compression scheme suitable for IEEE floating-point data. Our new Bit Grooming algorithm alternately shaves (to zero) and sets (to one) the least significant bits of consecutive values to preserve a desired precision. This is a symmetric, two-sided variant of an algorithm sometimes called Bit Shaving that quantizes values solely by zeroing bits. Our variation eliminates the artificial low bias produced by always zeroing bits, and makes Bit Grooming more suitable for arrays and multi-dimensional fields whose mean statistics are important. Bit Grooming relies on standard lossless compression to achieve the actual reduction in storage space, so we tested Bit Grooming by applying the DEFLATE compression algorithm to bit-groomed and full-precision climate data stored in netCDF3, netCDF4, HDF4, and HDF5 formats. Bit Grooming reduces the storage space required by initially uncompressed and compressed climate data by 25-80 and 5-65 %, respectively, for single-precision values (the most common case for climate data) quantized to retain 1-5 decimal digits of precision. The potential reduction is greater for double-precision datasets. When used aggressively (i.e., preserving only 1-2 digits), Bit Grooming produces storage reductions comparable to other quantization techniques such as Linear Packing. Unlike Linear Packing, whose guaranteed precision rapidly degrades within the relatively narrow dynamic range of values that it can compress, Bit Grooming guarantees the specified precision throughout the full floating-point range. Data quantization by Bit Grooming is irreversible (i.e., lossy) yet transparent, meaning that no extra processing is required by data users/readers. Hence Bit Grooming can easily reduce data storage volume without sacrificing scientific precision or imposing extra burdens on users.

Spotting and validation of a genome wide oligonucleotide chip with duplicate measurement of each gene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thomassen, Mads; Skov, Vibe; Eiriksdottir, Freyja

2006-06-16

The quality of DNA microarray based gene expression data relies on the reproducibility of several steps in a microarray experiment. We have developed a spotted genome wide microarray chip with oligonucleotides printed in duplicate in order to minimise undesirable biases, thereby optimising detection of true differential expression. The validation study design consisted of an assessment of the microarray chip performance using the MessageAmp and FairPlay labelling kits. Intraclass correlation coefficient (ICC) was used to demonstrate that MessageAmp was significantly more reproducible than FairPlay. Further examinations with MessageAmp revealed the applicability of the system. The linear range of the chips wasmore » three orders of magnitude, the precision was high, as 95% of measurements deviated less than 1.24-fold from the expected value, and the coefficient of variation for relative expression was 13.6%. Relative quantitation was more reproducible than absolute quantitation and substantial reduction of variance was attained with duplicate spotting. An analysis of variance (ANOVA) demonstrated no significant day-to-day variation.« less

'Innovation' in health care coverage decisions: all talk and no substance?

PubMed

Bryan, Stirling; Lee, Helen; Mitton, Craig

2013-01-01

There has been much discussion recently about 'innovation', or more precisely the lack of it, in pharmaceuticals and devices in health care. The concern has been expressed by national guideline bodies, such as the Common Drugs Review in Canada and the National Institute for Health & Clinical Excellence in the UK, applying strict cost-effectiveness criteria in their decision-making and, therefore, failing adequately to recognize the full benefits that come from innovation. In order to explore the legitimacy of such claims, we first define innovation, and second, explore the basis for assuming an independent and separable social value associated with innovation. We conclude that demands relating to innovation, such as relaxation of thresholds and premium prices for innovatory products, remain hollow until we have a compelling case on the demand side for a separable social value on 'innovation'. We see no such case currently.

High throughput estimation of functional cell activities reveals disease mechanisms and predicts relevant clinical outcomes

PubMed Central

Hidalgo, Marta R.; Cubuk, Cankut; Amadoz, Alicia; Salavert, Francisco; Carbonell-Caballero, José; Dopazo, Joaquin

2017-01-01

Understanding the aspects of the cell functionality that account for disease or drug action mechanisms is a main challenge for precision medicine. Here we propose a new method that models cell signaling using biological knowledge on signal transduction. The method recodes individual gene expression values (and/or gene mutations) into accurate measurements of changes in the activity of signaling circuits, which ultimately constitute high-throughput estimations of cell functionalities caused by gene activity within the pathway. Moreover, such estimations can be obtained either at cohort-level, in case/control comparisons, or personalized for individual patients. The accuracy of the method is demonstrated in an extensive analysis involving 5640 patients from 12 different cancer types. Circuit activity measurements not only have a high diagnostic value but also can be related to relevant disease outcomes such as survival, and can be used to assess therapeutic interventions. PMID:28042959

A comparison of Boolean-based retrieval to the WAIS system for retrieval of aeronautical information

NASA Technical Reports Server (NTRS)

Marchionini, Gary; Barlow, Diane

1994-01-01

An evaluation of an information retrieval system using a Boolean-based retrieval engine and inverted file architecture and WAIS, which uses a vector-based engine, was conducted. Four research questions in aeronautical engineering were used to retrieve sets of citations from the NASA Aerospace Database which was mounted on a WAIS server and available through Dialog File 108 which served as the Boolean-based system (BBS). High recall and high precision searches were done in the BBS and terse and verbose queries were used in the WAIS condition. Precision values for the WAIS searches were consistently above the precision values for high recall BBS searches and consistently below the precision values for high precision BBS searches. Terse WAIS queries gave somewhat better precision performance than verbose WAIS queries. In every case, a small number of relevant documents retrieved by one system were not retrieved by the other, indicating the incomplete nature of the results from either retrieval system. Relevant documents in the WAIS searches were found to be randomly distributed in the retrieved sets rather than distributed by ranks. Advantages and limitations of both types of systems are discussed.

High-precision half-life measurements of the T =1 /2 mirror β decays 17F and 33Cl

NASA Astrophysics Data System (ADS)

Grinyer, J.; Grinyer, G. F.; Babo, M.; Bouzomita, H.; Chauveau, P.; Delahaye, P.; Dubois, M.; Frigot, R.; Jardin, P.; Leboucher, C.; Maunoury, L.; Seiffert, C.; Thomas, J. C.; Traykov, E.

2015-10-01

Background: Measurements of the f t values for T =1 /2 mirror β+ decays offer a method to test the conserved vector current hypothesis and to determine Vud, the up-down matrix element of the Cabibbo-Kobayashi-Maskawa matrix. In most mirror decays used for these tests, uncertainties in the f t values are dominated by the uncertainties in the half-lives. Purpose: Two precision half-life measurements were performed for the T =1 /2 β+ emitters, 17F and 33Cl, in order to eliminate the half-life as the leading source of uncertainty in their f t values. Method: Half-lives of 17F and 33Cl were determined using β counting of implanted radioactive ion beam samples on a moving tape transport system at the Système de Production d'Ions Radioactifs Accélérés en Ligne low-energy identification station at the Grand Accélérateur National d'Ions Lourds. Results: The 17F half-life result, 64.347 (35) s, precise to ±0.05 % , is a factor of 5 times more precise than the previous world average. The half-life of 33Cl was determined to be 2.5038 (22) s. The current precision of ±0.09 % is nearly 2 times more precise compared to the previous world average. Conclusions: The precision achieved during the present measurements implies that the half-life no longer dominates the uncertainty of the f t values for both T =1 /2 mirror decays 17F and 33Cl.

Optimal Parameters to Determine the Apparent Diffusion Coefficient in Diffusion Weighted Imaging via Simulation

NASA Astrophysics Data System (ADS)

Perera, Dimuthu

Diffusion weighted (DW) Imaging is a non-invasive MR technique that provides information about the tissue microstructure using the diffusion of water molecules. The diffusion is generally characterized by the apparent diffusion coefficient (ADC) parametric map. The purpose of this study is to investigate in silico how the calculation of ADC is affected by image SNR, b-values, and the true tissue ADC. Also, to provide optimal parameter combination depending on the percentage accuracy and precision for prostate peripheral region cancer application. Moreover, to suggest parameter choices for any type of tissue, while providing the expected accuracy and precision. In this research DW images were generated assuming a mono-exponential signal model at two different b-values and for known true ADC values. Rician noise of different levels was added to the DWI images to adjust the image SNR. Using the two DWI images, ADC was calculated using a mono-exponential model for each set of b-values, SNR, and true ADC. 40,000 ADC data were collected for each parameter setting to determine the mean and the standard-deviation of the calculated ADC, as well as the percentage accuracy and precision with respect to the true ADC. The accuracy was calculated using the difference between known and calculated ADC. The precision was calculated using the standard-deviation of calculated ADC. The optimal parameters for a specific study was determined when both the percentage accuracy and precision were minimized. In our study, we simulated two true ADCs (ADC 0.00102 for tumor and 0.00180 mm2/s for normal prostate peripheral region tissue). Image SNR was varied from 2 to 100 and b-values were varied from 0 to 2000s/mm2. The results show that the percentage accuracy and percentage precision were minimized with image SNR. To increase SNR, 10 signal-averagings (NEX) were used considering the limitation in total scan time. The optimal NEX combination for tumor and normal tissue for prostate peripheral region was 1: 9. Also, the minimum percentage accuracy and percentage precision were obtained when low b-value is 0 and high b-value is 800 mm2/s for normal tissue and 1400 mm2/s for tumor tissue. Results also showed that for tissues with 1 x 10-3 < ADC < 2.1 x 10-3 mm 2/s the parameter combination at SNR = 20, b-value pair 0, 800 mm 2/s with NEX = 1:9 can calculate ADC with a percentage accuracy of less than 2% and percentage precision of 6-8%. Also, for tissues with 0.6 x 10-3 < ADC < 1.25 x 10-3 mm2 /s the parameter combination at SNR = 20, b-value pair 0, 1400 mm 2/s with NEX =1:9 can calculate ADC with a percentage accuracy of less than 2% and percentage precision of 6-8%.

Global differential expression of genes located in the Down Syndrome Critical Region in normal human brain

PubMed Central

Montoya, Julio Cesar; Fajardo, Dianora; Peña, Angela; Sánchez, Adalberto; Domínguez, Martha C; Satizábal, José María

2014-01-01

Background: The information of gene expression obtained from databases, have made possible the extraction and analysis of data related with several molecular processes involving not only in brain homeostasis but its disruption in some neuropathologies; principally in Down syndrome and the Alzheimer disease. Objective: To correlate the levels of transcription of 19 genes located in the Down Syndrome Critical Region (DSCR) with their expression in several substructures of normal human brain. Methods: There were obtained expression profiles of 19 DSCR genes in 42 brain substructures, from gene expression values available at the database of the human brain of the Brain Atlas of the Allen Institute for Brain Sciences", (http://human.brain-map.org/). The co-expression patterns of DSCR genes in brain were calculated by using multivariate statistical methods. Results: Highest levels of gene expression were registered at caudate nucleus, nucleus accumbens and putamen among central areas of cerebral cortex. Increased expression levels of RCAN1 that encode by a protein involved in signal transduction process of the CNS were recorded for PCP4 that participates in the binding to calmodulin and TTC3; a protein that is associated with differentiation of neurons. That previously identified brain structures play a crucial role in the learning process, in different class of memory and in motor skills. Conclusion: The precise regulation of DSCR gene expression is crucial to maintain the brain homeostasis, especially in those areas with high levels of gene expression associated with a remarkable process of learning and cognition. PMID:25767303

Precise determination of the 113Cd fourth-forbidden non-unique β -decay Q value

NASA Astrophysics Data System (ADS)

Gamage, N. D.; Bollen, G.; Eibach, M.; Gulyuz, K.; Izzo, C.; Kandegedara, R. M. E. B.; Redshaw, M.; Ringle, R.; Sandler, R.; Valverde, A. A.

2016-08-01

Using Penning trap mass spectrometry, we have performed a precise determination of the Q value for the highly forbidden β decay of 113Cd. An independent measurement of the Q value fixes the end-point energy in a fit to the 113Cdβ -decay spectrum. This provides a strong test of systematics for detectors that have observed this decay, such as those developed for β β -decay searches in cadmium and other isotopes. It will also aid in the theoretical description of the β -decay spectrum. The result, Qβ=323.89 (27 ) keV , agrees at the 1.3 σ level with the value obtained from the 2012 Atomic Mass Evaluation [Chin. Phys. C 36, 1603 (2012), 10.1088/1674-1137/36/12/003], but is a factor of almost four more precise. We also report improved values for the atomic masses of 113Cd,113In, and 112Cd.

High-Precision Half-Life Measurement for the Superallowed β+ Emitter Alm26

NASA Astrophysics Data System (ADS)

Finlay, P.; Ettenauer, S.; Ball, G. C.; Leslie, J. R.; Svensson, C. E.; Andreoiu, C.; Austin, R. A. E.; Bandyopadhyay, D.; Cross, D. S.; Demand, G.; Djongolov, M.; Garrett, P. E.; Green, K. L.; Grinyer, G. F.; Hackman, G.; Leach, K. G.; Pearson, C. J.; Phillips, A. A.; Sumithrarachchi, C. S.; Triambak, S.; Williams, S. J.

2011-01-01

A high-precision half-life measurement for the superallowed β+ emitter Alm26 was performed at the TRIUMF-ISAC radioactive ion beam facility yielding T1/2=6346.54±0.46stat±0.60systms, consistent with, but 2.5 times more precise than, the previous world average. The Alm26 half-life and ft value, 3037.53(61) s, are now the most precisely determined for any superallowed β decay. Combined with recent theoretical corrections for isospin-symmetry-breaking and radiative effects, the corrected Ft value for Alm26, 3073.0(12) s, sets a new benchmark for the high-precision superallowed Fermi β-decay studies used to test the conserved vector current hypothesis and determine the Vud element of the Cabibbo-Kobayashi-Maskawa quark mixing matrix.

Precision Medicine and PET/Computed Tomography: Challenges and Implementation.

PubMed

Subramaniam, Rathan M

2017-01-01

Precision Medicine is about selecting the right therapy for the right patient, at the right time, specific to the molecular targets expressed by disease or tumors, in the context of patient's environment and lifestyle. Some of the challenges for delivery of precision medicine in oncology include biomarkers for patient selection for enrichment-precision diagnostics, mapping out tumor heterogeneity that contributes to therapy failures, and early therapy assessment to identify resistance to therapies. PET/computed tomography offers solutions in these important areas of challenges and facilitates implementation of precision medicine. Copyright © 2016 Elsevier Inc. All rights reserved.

Measuring the apparent diffusion coefficient in primary rectal tumors: is there a benefit in performing histogram analyses?

PubMed

van Heeswijk, Miriam M; Lambregts, Doenja M J; Maas, Monique; Lahaye, Max J; Ayas, Z; Slenter, Jos M G M; Beets, Geerard L; Bakers, Frans C H; Beets-Tan, Regina G H

2017-06-01

The apparent diffusion coefficient (ADC) is a potential prognostic imaging marker in rectal cancer. Typically, mean ADC values are used, derived from precise manual whole-volume tumor delineations by experts. The aim was first to explore whether non-precise circular delineation combined with histogram analysis can be a less cumbersome alternative to acquire similar ADC measurements and second to explore whether histogram analyses provide additional prognostic information. Thirty-seven patients who underwent a primary staging MRI including diffusion-weighted imaging (DWI; b0, 25, 50, 100, 500, 1000; 1.5 T) were included. Volumes-of-interest (VOIs) were drawn on b1000-DWI: (a) precise delineation, manually tracing tumor boundaries (2 expert readers), and (b) non-precise delineation, drawing circular VOIs with a wide margin around the tumor (2 non-experts). Mean ADC and histogram metrics (mean, min, max, median, SD, skewness, kurtosis, 5th-95th percentiles) were derived from the VOIs and delineation time was recorded. Measurements were compared between the two methods and correlated with prognostic outcome parameters. Median delineation time reduced from 47-165 s (precise) to 21-43 s (non-precise). The 45th percentile of the non-precise delineation showed the best correlation with the mean ADC from the precise delineation as the reference standard (ICC 0.71-0.75). None of the mean ADC or histogram parameters showed significant prognostic value; only the total tumor volume (VOI) was significantly larger in patients with positive clinical N stage and mesorectal fascia involvement. When performing non-precise tumor delineation, histogram analysis (in specific 45th ADC percentile) may be used as an alternative to obtain similar ADC values as with precise whole tumor delineation. Histogram analyses are not beneficial to obtain additional prognostic information.

What to use to express the variability of data: Standard deviation or standard error of mean?

PubMed

Barde, Mohini P; Barde, Prajakt J

2012-07-01

Statistics plays a vital role in biomedical research. It helps present data precisely and draws the meaningful conclusions. While presenting data, one should be aware of using adequate statistical measures. In biomedical journals, Standard Error of Mean (SEM) and Standard Deviation (SD) are used interchangeably to express the variability; though they measure different parameters. SEM quantifies uncertainty in estimate of the mean whereas SD indicates dispersion of the data from mean. As readers are generally interested in knowing the variability within sample, descriptive data should be precisely summarized with SD. Use of SEM should be limited to compute CI which measures the precision of population estimate. Journals can avoid such errors by requiring authors to adhere to their guidelines.

Precision analysis for standard deviation measurements of immobile single fluorescent molecule images.

PubMed

DeSantis, Michael C; DeCenzo, Shawn H; Li, Je-Luen; Wang, Y M

2010-03-29

Standard deviation measurements of intensity profiles of stationary single fluorescent molecules are useful for studying axial localization, molecular orientation, and a fluorescence imaging system's spatial resolution. Here we report on the analysis of the precision of standard deviation measurements of intensity profiles of single fluorescent molecules imaged using an EMCCD camera.We have developed an analytical expression for the standard deviation measurement error of a single image which is a function of the total number of detected photons, the background photon noise, and the camera pixel size. The theoretical results agree well with the experimental, simulation, and numerical integration results. Using this expression, we show that single-molecule standard deviation measurements offer nanometer precision for a large range of experimental parameters.

Using hyperspectral data in precision farming applications

USDA-ARS?s Scientific Manuscript database

Precision farming practices such as variable rate applications of fertilizer and agricultural chemicals require accurate field variability mapping. This chapter investigated the value of hyperspectral remote sensing in providing useful information for five applications of precision farming: (a) Soil...

Precision of measurement and body size in whole-body air-displacement plethysmography.

PubMed

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.

High-precision Penning trap mass measurements of 9,10Be and the one-neutron halo nuclide 11Be

NASA Astrophysics Data System (ADS)

Ringle, R.; Brodeur, M.; Brunner, T.; Ettenauer, S.; Smith, M.; Lapierre, A.; Ryjkov, V. L.; Delheij, P.; Drake, G. W. F.; Lassen, J.; Lunney, D.; Dilling, J.

2009-05-01

Penning trap mass measurements of 9Be, 10Be (t1 / 2 = 1.51 My), and the one-neutron halo nuclide 11Be (t1 / 2 = 13.8 s) have been performed using TITAN at TRIUMF. The resulting 11Be mass excess (ME = 20 177.60 (58) keV) is in agreement with the current Atomic Mass Evaluation (AME03) [G. Audi, et al., Nucl. Phys. A 729 (2003) 337] value, but is over an order of magnitude more precise. The precision of the mass values of 9,10Be have been improved by about a factor of four and reveal a ≈ 2 σ deviation from the AME mass values. Results of new atomic physics calculations are presented for the isotope shift of 11Be relative to 9Be, and it is shown that the new mass values essentially remove atomic mass uncertainties as a contributing factor in determining the relative nuclear charge radius from the isotope shift. The new mass values of 10,11Be also allow for a more precise determination of the single-neutron binding energy of the halo neutron in 11Be.

High-precision Q EC values of superallowed 0 + → 0 + β-emitters 46Cr, 50Fe and 54Ni

DOE PAGES

Zhang, P.; Xu, X.; Shuai, P.; ...

2017-01-23

Short-lived 46Cr, 50Fe and 54Ni were studied by isochronous mass spectrometry at the HIRFL-CSR facility in Lanzhou. The measured precision mass excesses (ME) of 46Cr, 50Fe and 54Ni are -29471(11) keV, -34477(6) keV and -39278(4) keV, respectively. The superallowed 0 +→0+β-decay Q values were derived to be Q EC( 46Cr) =7604(11) keV, Q EC( 50Fe) =8150(6) keV and Q EC( 54Ni) =8731(4) keV. The values for 50Fe and 54Ni are by one order of magnitude more precise than the adopted literature values. By combining the existing half-lives and branching ratios, we obtained the corrected ℱt values to be ℱt(more » 50Fe) =3103(70) s and ℱt( 54Ni) =3076(50) s. The main contribution to the ℱt uncertainties is now due to β-decay branching ratios, still, more high-precision measurements of the half-lives, the masses, and especially the branching ratios are needed in order to satisfy the requirements for a stringent CVC test.« less

High-precision Q EC values of superallowed 0 + → 0 + β-emitters 46Cr, 50Fe and 54Ni

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, P.; Xu, X.; Shuai, P.

Short-lived 46Cr, 50Fe and 54Ni were studied by isochronous mass spectrometry at the HIRFL-CSR facility in Lanzhou. The measured precision mass excesses (ME) of 46Cr, 50Fe and 54Ni are -29471(11) keV, -34477(6) keV and -39278(4) keV, respectively. The superallowed 0 +→0+β-decay Q values were derived to be Q EC( 46Cr) =7604(11) keV, Q EC( 50Fe) =8150(6) keV and Q EC( 54Ni) =8731(4) keV. The values for 50Fe and 54Ni are by one order of magnitude more precise than the adopted literature values. By combining the existing half-lives and branching ratios, we obtained the corrected ℱt values to be ℱt(more » 50Fe) =3103(70) s and ℱt( 54Ni) =3076(50) s. The main contribution to the ℱt uncertainties is now due to β-decay branching ratios, still, more high-precision measurements of the half-lives, the masses, and especially the branching ratios are needed in order to satisfy the requirements for a stringent CVC test.« less

Extracting Date/Time Expressions in Super-Function Based Japanese-English Machine Translation

NASA Astrophysics Data System (ADS)

Sasayama, Manabu; Kuroiwa, Shingo; Ren, Fuji

Super-Function Based Machine Translation(SFBMT) which is a type of Example-Based Machine Translation has a feature which makes it possible to expand the coverage of examples by changing nouns into variables, however, there were problems extracting entire date/time expressions containing parts-of-speech other than nouns, because only nouns/numbers were changed into variables. We describe a method for extracting date/time expressions for SFBMT. SFBMT uses noun determination rules to extract nouns and a bilingual dictionary to obtain correspondence of the extracted nouns between the source and the target languages. In this method, we add a rule to extract date/time expressions and then extract date/time expressions from a Japanese-English bilingual corpus. The evaluation results shows that the precision of this method for Japanese sentences is 96.7%, with a recall of 98.2% and the precision for English sentences is 94.7%, with a recall of 92.7%.

a Permanent Magnet Hall Thruster for Orbit Control of Lunar Polar Satellites

NASA Astrophysics Data System (ADS)

Ferreira, Jose Leonardo; Silva Moraes, Bruno; Soares Ferreira, Ivan; Cardozo Mour, Decio; Winter, Othon

Future moon missions devoted to lunar surface remote sensing and to many others scientific exploration topics will require more fine and higher precision orbit control. It is well known that, lunar satellites in polar orbits will suffer a high increase on the eccentricity due to the gravitational perturbation of the Earth. Without proper orbit correction the satellite life time will decrease and end up in a collision with the moon surface. It is pointed out by many authors that this effect is a natural consequence of the Lidov-Kozai resonance. In the present work, we propose a precise method of orbit eccentricity control based on the use of a low thrust Hall plasma thruster. The proposed method is based on an approach intended to keep the orbital eccentricity of the satellite at low values. A previous work on this subject was made using numerical integration considering two systems: the 3-body problem, Moon-Earth-satellite and the 4-body problem, Moon-Earth-Sun-satellite (??). In such simulation it is possible to follow the evolution of the satellite's eccentricity and find empirical expressions for the length of time needed to occur the collision with the moon. In this work, a satellite orbit eccentricity control maneuvering is proposed. It is based on working parameters of a low thrust propulsion permanent magnet Hall plasma thruster (PMHT), which is been developed at University of Brasilia, Brazil. We studied different arcs of active lunar satellite propulsion in order to be able to introduce a correction of the eccentricity at each cycle. The calculations were made considering a set of different thrust values, from 0.1N up to 0.4N which can be obtained by using the PMHT. In each calculation procedure we measured the length of eccentricity correction provided by active propulsion. From these results we obtained empirical expressions of the time needed for the corrections as a function of the initial altitude and as a function of the thrust value. 1. Winter, O. C. et all in Controlling the Eccentricity of Polar Lunar Orbits with Low Thrust Propulsion, Mathematical Problems in Engineering, vol. on Space Dynamics, 2009.

Budget impact and cost-effectiveness: can we afford precision medicine in oncology?

PubMed

Doble, Brett

2016-01-01

Over the past decade there have been remarkable advancements in the understanding of the molecular underpinnings of malignancy. Methods of testing capable of elucidating patients' molecular profiles are now readily available and there is an increased desire to incorporate the information derived from such tests into treatment selection for cancer patients. This has led to more appropriate application of existing treatments as well as the development of a number of innovative and highly effective treatments or what is known collectively as precision medicine. The impact that precision medicine will have on health outcomes is uncertain, as are the costs it will incur. There is, therefore, a need to develop economic evidence and appropriate methods of evaluation to support its implementation to ensure the resources allocated to these approaches are affordable and offer value for money. The market for precision medicine in oncology continues to rapidly expand, placing an increased pressure on reimbursement decision-makers to consider the value and opportunity cost of funding such approaches to care. The benefits of molecular testing can be complex and difficult to evaluate given currently available economic methods, potentially causing a distorted appreciation of their value. Funding decisions of precision medicine will also have far-reaching implications, requiring the consideration of both patient and public perspectives in decision-making. Recommendations to improve the value proposition of precision medicine are, therefore, provided with the hopes of facilitating a better understanding of its impact on outcomes and the overall health budget.

Quantum-inspired algorithm for estimating the permanent of positive semidefinite matrices

NASA Astrophysics Data System (ADS)

Chakhmakhchyan, L.; Cerf, N. J.; Garcia-Patron, R.

2017-08-01

We construct a quantum-inspired classical algorithm for computing the permanent of Hermitian positive semidefinite matrices by exploiting a connection between these mathematical structures and the boson sampling model. Specifically, the permanent of a Hermitian positive semidefinite matrix can be expressed in terms of the expected value of a random variable, which stands for a specific photon-counting probability when measuring a linear-optically evolved random multimode coherent state. Our algorithm then approximates the matrix permanent from the corresponding sample mean and is shown to run in polynomial time for various sets of Hermitian positive semidefinite matrices, achieving a precision that improves over known techniques. This work illustrates how quantum optics may benefit algorithm development.

Nitrogen isotopic components in the early solar system

NASA Technical Reports Server (NTRS)

Kerridge, J. F.

1994-01-01

It is quite common to take the terrestrial atmospheric value of (15)N/(14)N (0.00366) as typical of nitrogen in the early solar system, but in fact there is little reason to suppose that this value had a nebula-wide significance. Indeed, it is not clear that there was a unique solar-system-wide (15)N/(14)N ratio, of whatever value. Here we review what is known about the distribution of the nitrogen isotopes among those solar-system objects that have been sampled so far and conclude that those isotopes reveal widespread inhomogeneity in the early solar system. Whether the isotopically distinct primordial components implied by this analysis were solid or gaseous or a mixture of both is not known. The isotopic composition of N in the Earth's mantle is controversial: estimates range from a 1.1 percent depletion in (15)N to a 1.4 percent enrichment. (Isotopic compositions will be expressed throughout as percent deviations from the terrestrial atmospheric value.) The present-day Martian atmosphere is characterized by a value of plus 62 percent but this enrichment in (15)N is attributed to selective loss of (14)N from the Martian exosphere. Modelling of this fractionation leads to an estimated primordial composition similar to the terrestrial atmospheric value, through the precision of this model-dependent result is unclear.

CSAX: Characterizing Systematic Anomalies in eXpression Data.

PubMed

Noto, Keith; Majidi, Saeed; Edlow, Andrea G; Wick, Heather C; Bianchi, Diana W; Slonim, Donna K

2015-05-01

Methods for translating gene expression signatures into clinically relevant information have typically relied upon having many samples from patients with similar molecular phenotypes. Here, we address the question of what can be done when it is relatively easy to obtain healthy patient samples, but when abnormalities corresponding to disease states may be rare and one-of-a-kind. The associated computational challenge, anomaly detection, is a well-studied machine-learning problem. However, due to the dimensionality and variability of expression data, existing methods based on feature space analysis or individual anomalously expressed genes are insufficient. We present a novel approach, CSAX, that identifies pathways in an individual sample in which the normal expression relationships are disrupted. To evaluate our approach, we have compiled and released a compendium of public expression data sets, reformulated to create a test bed for anomaly detection. We demonstrate the accuracy of CSAX on the data sets in our compendium, compare it to other leading methods, and show that CSAX aids in both identifying anomalies and explaining their underlying biology. We describe an approach to characterizing the difficulty of specific expression anomaly detection tasks. We then illustrate CSAX's value in two developmental case studies. Confirming prior hypotheses, CSAX highlights disruption of platelet activation pathways in a neonate with retinopathy of prematurity and identifies, for the first time, dysregulated oxidative stress response in second trimester amniotic fluid of fetuses with obese mothers. Our approach provides an important step toward identification of individual disease patterns in the era of precision medicine.

A Functional and Regulatory Network Associated with PIP Expression in Human Breast Cancer

PubMed Central

Debily, Marie-Anne; Marhomy, Sandrine El; Boulanger, Virginie; Eveno, Eric; Mariage-Samson, Régine; Camarca, Alessandra; Auffray, Charles; Piatier-Tonneau, Dominique; Imbeaud, Sandrine

2009-01-01

Background The PIP (prolactin-inducible protein) gene has been shown to be expressed in breast cancers, with contradictory results concerning its implication. As both the physiological role and the molecular pathways in which PIP is involved are poorly understood, we conducted combined gene expression profiling and network analysis studies on selected breast cancer cell lines presenting distinct PIP expression levels and hormonal receptor status, to explore the functional and regulatory network of PIP co-modulated genes. Principal Findings Microarray analysis allowed identification of genes co-modulated with PIP independently of modulations resulting from hormonal treatment or cell line heterogeneity. Relevant clusters of genes that can discriminate between [PIP+] and [PIP−] cells were identified. Functional and regulatory network analyses based on a knowledge database revealed a master network of PIP co-modulated genes, including many interconnecting oncogenes and tumor suppressor genes, half of which were detected as differentially expressed through high-precision measurements. The network identified appears associated with an inhibition of proliferation coupled with an increase of apoptosis and an enhancement of cell adhesion in breast cancer cell lines, and contains many genes with a STAT5 regulatory motif in their promoters. Conclusions Our global exploratory approach identified biological pathways modulated along with PIP expression, providing further support for its good prognostic value of disease-free survival in breast cancer. Moreover, our data pointed to the importance of a regulatory subnetwork associated with PIP expression in which STAT5 appears as a potential transcriptional regulator. PMID:19262752

Multifamily determination of pesticide residues in soya-based nutraceutical products by GC/MS-MS.

PubMed

Páleníková, Agneša; Martínez-Domínguez, Gerardo; Arrebola, Francisco Javier; Romero-González, Roberto; Hrouzková, Svetlana; Frenich, Antonia Garrido

2015-04-15

An analytical method based on a modified QuEChERS extraction coupled with gas chromatography-tandem mass spectrometry (GC-MS/MS) was evaluated for the determination of 177 pesticides in soya-based nutraceutical products. The QuEChERS method was optimised and different extraction solvents and clean-up approaches were tested, obtaining the most efficient conditions with a mixture of sorbents (PSA, C18, GBC and Zr-Sep(+)). Recoveries were evaluated at 10, 50 and 100 μg/kg and ranged between 70% and 120%. Precision was expressed as relative standard deviation (RSD), and it was evaluated for more than 160 pesticides as intra and inter-day precision, with values always below 20% and 25%, respectively. Limits of detection (LODs) ranged from 0.1 to 10 μg/kg, whereas limits of quantification (LOQs) from 0.5 to 20 μg/kg. The applicability of the method was proved by analysing soya-based nutraceuticals. Two pesticides were found in these samples, malathion and pyriproxyfen, at 11.1 and 1.5 μg/kg respectively. Copyright © 2014 Elsevier Ltd. All rights reserved.

A New Navigation Satellite Clock Bias Prediction Method Based on Modified Clock-bias Quadratic Polynomial Model

NASA Astrophysics Data System (ADS)

Wang, Y. P.; Lu, Z. P.; Sun, D. S.; Wang, N.

2016-01-01

In order to better express the characteristics of satellite clock bias (SCB) and improve SCB prediction precision, this paper proposed a new SCB prediction model which can take physical characteristics of space-borne atomic clock, the cyclic variation, and random part of SCB into consideration. First, the new model employs a quadratic polynomial model with periodic items to fit and extract the trend term and cyclic term of SCB; then based on the characteristics of fitting residuals, a time series ARIMA ~(Auto-Regressive Integrated Moving Average) model is used to model the residuals; eventually, the results from the two models are combined to obtain final SCB prediction values. At last, this paper uses precise SCB data from IGS (International GNSS Service) to conduct prediction tests, and the results show that the proposed model is effective and has better prediction performance compared with the quadratic polynomial model, grey model, and ARIMA model. In addition, the new method can also overcome the insufficiency of the ARIMA model in model recognition and order determination.

Influence of Ni on Martensitic Phase Transformations in NiTi Shape Memory Alloys

DOE Office of Scientific and Technical Information (OSTI.GOV)

Frenzel, J.; George, Easo P; Dlouhy, A.

High-precision data on phase transformation temperatures in NiTi, including numerical expressions for the effect of Ni on M{sub S}, M{sub F}, A{sub S}, A{sub F} and T{sub 0}, are obtained, and the reasons for the large experimental scatter observed in previous studies are discussed. Clear experimental evidence is provided confirming the predictions of Tang et al. 1999 regarding deviations from a linear relation between the thermodynamic equilibrium temperature and Ni concentration. In addition to affecting the phase transition temperatures, increasing Ni contents are found to decrease the width of thermal hysteresis and the heat of transformation. These findings are rationalizedmore » on the basis of the crystallographic data of Prokoshkin et al. 2004 and the theory of Ball and James. The results show that it is important to document carefully the details of the arc-melting procedure used to make shape memory alloys and that, if the effects of processing are properly accounted for, precise values for the Ni concentration of the NiTi matrix can be obtained.« less

[Mathematical model of micturition allowing a detailed analysis of free urine flowmetry].

PubMed

Valentini, F; Besson, G; Nelson, P

1999-04-01

A mathematical model of micturition allowing precise analysis of uroflowmetry curves (VBN method) is described together with some of its applications. The physiology of micturition and possible diagnostic hypotheses able to explain the shape of the uroflowmetry curve can be expressed by a series of differential equations. Integration of the system allows the validity of these hypotheses to be tested by simulation. A theoretical uroflowmetry is calculated in less than 1 second and analysis of a dysuric uroflowmetry takes about 5 minutes. The efficacy of the model is due to its rapidity and the precision of the comparisons between measured and predicted values. The method has been applied to almost one thousand curves. The uroflowmetries of normal subjects are restored without adjustment with a quadratic error of less than 1%, while those of dysuric patients require identification of one or two adaptive parameters characteristic of the underlying disease. These parameters remain constant during the same session, but vary with the disease and/or the treatment. This model could become a tool for noninvasive urodynamic studies.

Dollar$ & $en$e. Part V: What is your added value?

PubMed

Wilkinson, I

2001-01-01

In Part I of this series, I introduced the concept of memes (1). Memes are ideas or concepts--the information world equivalent of genes. The goal of this series of articles is to infect you with memes, so that you will assimilate, translate, and express them. No matter what our area of expertise or "-ology," we all are in the information business. Our goal is to be in the wisdom business. In the previous papers in this series, I showed that when we convert raw data into wisdom we are moving along a value chain. Each step in the chain adds a different amount of value to the final product: timely, relevant, accurate, and precise knowledge that can be applied to create the ultimate product in the value chain: wisdom. In Part II of this series, I introduced a set of memes for measuring the cost of adding value (2). In Part III of this series, I presented a new set of memes for measuring the added value of knowledge, i.e., intellectual capital (3). In Part IV of this series, I discussed practical knowledge management tools for measuring the value of people, structural, and customer capital (4). In Part V of this series, I will apply intellectual capital and knowledge management concepts at the individual level, to help answer a fundamental question: What is my added value?

Bit Grooming: Statistically accurate precision-preserving quantization with compression, evaluated in the netCDF operators (NCO, v4.4.8+)

DOE PAGES

Zender, Charles S.

2016-09-19

Geoscientific models and measurements generate false precision (scientifically meaningless data bits) that wastes storage space. False precision can mislead (by implying noise is signal) and be scientifically pointless, especially for measurements. By contrast, lossy compression can be both economical (save space) and heuristic (clarify data limitations) without compromising the scientific integrity of data. Data quantization can thus be appropriate regardless of whether space limitations are a concern. We introduce, implement, and characterize a new lossy compression scheme suitable for IEEE floating-point data. Our new Bit Grooming algorithm alternately shaves (to zero) and sets (to one) the least significant bits ofmore » consecutive values to preserve a desired precision. This is a symmetric, two-sided variant of an algorithm sometimes called Bit Shaving that quantizes values solely by zeroing bits. Our variation eliminates the artificial low bias produced by always zeroing bits, and makes Bit Grooming more suitable for arrays and multi-dimensional fields whose mean statistics are important. Bit Grooming relies on standard lossless compression to achieve the actual reduction in storage space, so we tested Bit Grooming by applying the DEFLATE compression algorithm to bit-groomed and full-precision climate data stored in netCDF3, netCDF4, HDF4, and HDF5 formats. Bit Grooming reduces the storage space required by initially uncompressed and compressed climate data by 25–80 and 5–65 %, respectively, for single-precision values (the most common case for climate data) quantized to retain 1–5 decimal digits of precision. The potential reduction is greater for double-precision datasets. When used aggressively (i.e., preserving only 1–2 digits), Bit Grooming produces storage reductions comparable to other quantization techniques such as Linear Packing. Unlike Linear Packing, whose guaranteed precision rapidly degrades within the relatively narrow dynamic range of values that it can compress, Bit Grooming guarantees the specified precision throughout the full floating-point range. Data quantization by Bit Grooming is irreversible (i.e., lossy) yet transparent, meaning that no extra processing is required by data users/readers. Hence Bit Grooming can easily reduce data storage volume without sacrificing scientific precision or imposing extra burdens on users.« less

Synthetic Gene Expression Circuits for Designing Precision Tools in Oncology

PubMed Central

Re, Angela

2017-01-01

Precision medicine in oncology needs to enhance its capabilities to match diagnostic and therapeutic technologies to individual patients. Synthetic biology streamlines the design and construction of functionalized devices through standardization and rational engineering of basic biological elements decoupled from their natural context. Remarkable improvements have opened the prospects for the availability of synthetic devices of enhanced mechanism clarity, robustness, sensitivity, as well as scalability and portability, which might bring new capabilities in precision cancer medicine implementations. In this review, we begin by presenting a brief overview of some of the major advances in the engineering of synthetic genetic circuits aimed to the control of gene expression and operating at the transcriptional, post-transcriptional/translational, and post-translational levels. We then focus on engineering synthetic circuits as an enabling methodology for the successful establishment of precision technologies in oncology. We describe significant advancements in our capabilities to tailor synthetic genetic circuits to specific applications in tumor diagnosis, tumor cell- and gene-based therapy, and drug delivery. PMID:28894736

Mapping the emotional face. How individual face parts contribute to successful emotion recognition.

PubMed

Wegrzyn, Martin; Vogt, Maria; Kireclioglu, Berna; Schneider, Julia; Kissler, Johanna

2017-01-01

Which facial features allow human observers to successfully recognize expressions of emotion? While the eyes and mouth have been frequently shown to be of high importance, research on facial action units has made more precise predictions about the areas involved in displaying each emotion. The present research investigated on a fine-grained level, which physical features are most relied on when decoding facial expressions. In the experiment, individual faces expressing the basic emotions according to Ekman were hidden behind a mask of 48 tiles, which was sequentially uncovered. Participants were instructed to stop the sequence as soon as they recognized the facial expression and assign it the correct label. For each part of the face, its contribution to successful recognition was computed, allowing to visualize the importance of different face areas for each expression. Overall, observers were mostly relying on the eye and mouth regions when successfully recognizing an emotion. Furthermore, the difference in the importance of eyes and mouth allowed to group the expressions in a continuous space, ranging from sadness and fear (reliance on the eyes) to disgust and happiness (mouth). The face parts with highest diagnostic value for expression identification were typically located in areas corresponding to action units from the facial action coding system. A similarity analysis of the usefulness of different face parts for expression recognition demonstrated that faces cluster according to the emotion they express, rather than by low-level physical features. Also, expressions relying more on the eyes or mouth region were in close proximity in the constructed similarity space. These analyses help to better understand how human observers process expressions of emotion, by delineating the mapping from facial features to psychological representation.

Mapping the emotional face. How individual face parts contribute to successful emotion recognition

PubMed Central

Wegrzyn, Martin; Vogt, Maria; Kireclioglu, Berna; Schneider, Julia; Kissler, Johanna

2017-01-01

Which facial features allow human observers to successfully recognize expressions of emotion? While the eyes and mouth have been frequently shown to be of high importance, research on facial action units has made more precise predictions about the areas involved in displaying each emotion. The present research investigated on a fine-grained level, which physical features are most relied on when decoding facial expressions. In the experiment, individual faces expressing the basic emotions according to Ekman were hidden behind a mask of 48 tiles, which was sequentially uncovered. Participants were instructed to stop the sequence as soon as they recognized the facial expression and assign it the correct label. For each part of the face, its contribution to successful recognition was computed, allowing to visualize the importance of different face areas for each expression. Overall, observers were mostly relying on the eye and mouth regions when successfully recognizing an emotion. Furthermore, the difference in the importance of eyes and mouth allowed to group the expressions in a continuous space, ranging from sadness and fear (reliance on the eyes) to disgust and happiness (mouth). The face parts with highest diagnostic value for expression identification were typically located in areas corresponding to action units from the facial action coding system. A similarity analysis of the usefulness of different face parts for expression recognition demonstrated that faces cluster according to the emotion they express, rather than by low-level physical features. Also, expressions relying more on the eyes or mouth region were in close proximity in the constructed similarity space. These analyses help to better understand how human observers process expressions of emotion, by delineating the mapping from facial features to psychological representation. PMID:28493921

[Some reflections on evidenced-based medicine, precision medicine, and big data-based research].

PubMed

Tang, J L; Li, L M

2018-01-10

Evidence-based medicine remains the best paradigm for medical practice. However, evidence alone is not decisions; decisions must also consider resources available and the values of people. Evidence shows that most of those treated with blood pressure-lowering, cholesterol-lowering, glucose-lowering and anti-cancer drugs do not benefit from preventing severe complications such as cardiovascular events and deaths. This implies that diagnosis and treatment in modern medicine in many circumstances is imprecise. It has become a dream to identify and treat only those few who can respond to the treatment. Precision medicine has thus come into being. Precision medicine is however not a new idea and cannot rely solely on gene sequencing as it was initially proposed. Neither is the large cohort and multi-factorial approach a new idea; in fact it has been used widely since 1950s. Since its very beginning, medicine has never stopped in searching for more precise diagnostic and therapeutic methods and already made achievements at various levels of our understanding and knowledge, such as vaccine, blood transfusion, imaging, and cataract surgery. Genetic biotechnology is not the only path to precision but merely a new method. Most genes are found only weakly associated with disease and are thus unlikely to lead to great improvement in diagnostic and therapeutic precision. The traditional multi-factorial approach by embracing big data and incorporating genetic factors is probably the most realistic way ahead for precision medicine. Big data boasts of possession of the total population and large sample size and claims correlation can displace causation. They are serious misleading concepts. Science has never had to observe the totality in order to draw a valid conclusion; a large sample size is required only when the anticipated effect is small and clinically less meaningful; emphasis on correlation over causation is equivalent to rejection of the scientific principles and methods in epidemiology and a call to give up the assurance for validity in scientific research, which will inevitably lead to futile interventions. Furthermore, in proving the effectiveness of intervention, analyses of real-world big data cannot displace the role of randomized controlled trial. We expressed doubts and critiques in this article on precision medicine and big data, merely hoping to stimulate discussing on the true potentials of precision medicine and big data.

Assessing the quality of life history information in publicly available databases.

PubMed

Thorson, James T; Cope, Jason M; Patrick, Wesley S

2014-01-01

Single-species life history parameters are central to ecological research and management, including the fields of macro-ecology, fisheries science, and ecosystem modeling. However, there has been little independent evaluation of the precision and accuracy of the life history values in global and publicly available databases. We therefore develop a novel method based on a Bayesian errors-in-variables model that compares database entries with estimates from local experts, and we illustrate this process by assessing the accuracy and precision of entries in FishBase, one of the largest and oldest life history databases. This model distinguishes biases among seven life history parameters, two types of information available in FishBase (i.e., published values and those estimated from other parameters), and two taxa (i.e., bony and cartilaginous fishes) relative to values from regional experts in the United States, while accounting for additional variance caused by sex- and region-specific life history traits. For published values in FishBase, the model identifies a small positive bias in natural mortality and negative bias in maximum age, perhaps caused by unacknowledged mortality caused by fishing. For life history values calculated by FishBase, the model identified large and inconsistent biases. The model also demonstrates greatest precision for body size parameters, decreased precision for values derived from geographically distant populations, and greatest between-sex differences in age at maturity. We recommend that our bias and precision estimates be used in future errors-in-variables models as a prior on measurement errors. This approach is broadly applicable to global databases of life history traits and, if used, will encourage further development and improvements in these databases.

Precision measurements of the RSA method using a phantom model of hip prosthesis.

PubMed

Mäkinen, Tatu J; Koort, Jyri K; Mattila, Kimmo T; Aro, Hannu T

2004-04-01

Radiostereometric analysis (RSA) has become one of the recommended techniques for pre-market evaluation of new joint implant designs. In this study we evaluated the effect of repositioning of X-ray tubes and phantom model on the precision of the RSA method. In precision measurements, we utilized mean error of rigid body fitting (ME) values as an internal control for examinations. ME value characterizes relative motion among the markers within each rigid body and is conventionally used to detect loosening of a bone marker. Three experiments, each consisting of 10 double examinations, were performed. In the first experiment, the X-ray tubes and the phantom model were not repositioned between one double examination. In experiments two and three, the X-ray tubes were repositioned between one double examination. In addition, the position of the phantom model was changed in experiment three. Results showed that significant differences could be found in 2 of 12 comparisons when evaluating the translation and rotation of the prosthetic components. Repositioning procedures increased ME values mimicking deformation of rigid body segments. Thus, ME value seemed to be a more sensitive parameter than migration values in this study design. These results confirmed the importance of standardized radiographic technique and accurate patient positioning for RSA measurements. Standardization and calibration procedures should be performed with phantom models in order to avoid unnecessary radiation dose of the patients. The present model gives the means to establish and to follow the intra-laboratory precision of the RSA method. The model is easily applicable in any research unit and allows the comparison of the precision values in different laboratories of multi-center trials.

Leadership = Communication? The Relations of Leaders’ Communication Styles with Leadership Styles, Knowledge Sharing and Leadership Outcomes

PubMed Central

Bakker-Pieper, Angelique; Oostenveld, Wyneke

2009-01-01

Purpose The purpose of this study was to investigate the relations between leaders’ communication styles and charismatic leadership, human-oriented leadership (leader’s consideration), task-oriented leadership (leader’s initiating structure), and leadership outcomes. Methodology A survey was conducted among 279 employees of a governmental organization. The following six main communication styles were operationalized: verbal aggressiveness, expressiveness, preciseness, assuredness, supportiveness, and argumentativeness. Regression analyses were employed to test three main hypotheses. Findings In line with expectations, the study showed that charismatic and human-oriented leadership are mainly communicative, while task-oriented leadership is significantly less communicative. The communication styles were strongly and differentially related to knowledge sharing behaviors, perceived leader performance, satisfaction with the leader, and subordinate’s team commitment. Multiple regression analyses showed that the leadership styles mediated the relations between the communication styles and leadership outcomes. However, leader’s preciseness explained variance in perceived leader performance and satisfaction with the leader above and beyond the leadership style variables. Implications This study offers potentially invaluable input for leadership training programs by showing the importance of leader’s supportiveness, assuredness, and preciseness when communicating with subordinates. Originality/value Although one of the core elements of leadership is interpersonal communication, this study is one of the first to use a comprehensive communication styles instrument in the study of leadership. PMID:20700375

Trans-10, cis-12-conjugated linoleic acid alters hepatic gene expression in a polygenic obese line of mice displaying hepatic lipidosis.

PubMed

Ashwell, Melissa S; Ceddia, Ryan P; House, Ralph L; Cassady, Joseph P; Eisen, Eugene J; Eling, Thomas E; Collins, Jennifer B; Grissom, Sherry F; Odle, Jack

2010-09-01

The trans-10, cis-12 isomer of conjugated linoleic acid (CLA) causes a rapid reduction of body and adipose mass in mice. In addition to changes in adipose tissue, numerous studies have reported alterations in hepatic lipid metabolism. Livers of CLA-fed mice gain mass, partly due to lipid accumulation; however, the precise molecular mechanisms are unknown. To elucidate these mechanisms, we examined fatty acid composition and gene expression profiles of livers from a polygenic obese line of mice fed 1% trans-10, cis-12-CLA for 14 days. Analysis of gene expression data led to the identification of 1393 genes differentially expressed in the liver of CLA-fed male mice at a nominal P value of .01, and 775 were considered significant using a false discovery rate (FDR) threshold of .05. While surprisingly few genes in lipid metabolism were impacted, pathway analysis found that protein kinase A (PKA) and cyclic adenosine monophosphate (cAMP) pathways signaling pathways were affected by CLA treatment and 98 of the 775 genes were found to be regulated by hepatocyte nuclear factor 4alpha, a transcription factor important in controlling liver metabolic status. Copyright 2010 Elsevier Inc. All rights reserved.

Half-life, branching-ratio, and Q-value measurement for the superallowed 0{sup +}{yields}0{sup +}{beta}{sup +} emitter {sup 42}Ti

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nieto, T. Kurtukian; Souin, J.; Audirac, L.

2009-09-15

The half-life, the branching ratio, and the decay Q value of the superallowed {beta} emitter {sup 42}Ti were measured in an experiment performed at the JYFLTRAP facility of the Accelerator Laboratory of the University of Jyvaeskylae. {sup 42}Ti is the heaviest T{sub z}=-1 nucleus for which high-precision measurements of these quantities have been tried. The half-life (T{sub 1/2}=208.14{+-}0.45 ms) and the Q value [Q{sub EC}=7016.83(25) keV] are close to or reach the required precision of about 0.1%. The branching ratio for the superallowed decay branch [BR=47.7(12)%], a by-product of the half-life measurement, does not reach the necessary precision yet. Nonetheless,more » these results allow one to determine the experimental ft value and the corrected Ft value to be 3114(79) and 3122(79) s, respectively.« less

Expression and Regulation of Drug Transporters and Metabolizing Enzymes in the Human Gastrointestinal Tract.

PubMed

Drozdzik, M; Oswald, S

2016-01-01

Orally administered drugs must pass through the intestinal wall and then through the liver before reaching systemic circulation. During this process drugs are subjected to different processes that may determine the therapeutic value. The intestinal barrier with active drug metabolizing enzymes and drug transporters in enterocytes plays an important role in the determination of drug bioavailability. Accumulating information demonstrates variable distribution of drug metabolizing enzymes and transporters along the human gastrointestinal tract (GI), that creates specific barrier characteristics in different segments of the GI. In this review, expression of drug metabolizing enzymes and transporters in the healthy and diseased human GI as well as their regulatory aspects: genetic, miRNA, DNA methylation are outlined. The knowledge of unique interplay between drug metabolizing enzymes and transporters in specific segments of the GI tract allows more precise definition of drug release sites within the GI in order to assure more complete bioavailability and prediction of drug interactions.

Precision matters for position decoding in the early fly embryo

NASA Astrophysics Data System (ADS)

Petkova, Mariela D.; Tkacik, Gasper; Wieschaus, Eric F.; Bialek, William; Gregor, Thomas

Genetic networks can determine cell fates in multicellular organisms with precision that often reaches the physical limits of the system. However, it is unclear how the organism uses this precision and whether it has biological content. Here we address this question in the developing fly embryo, in which a genetic network of patterning genes reaches 1% precision in positioning cells along the embryo axis. The network consists of three interconnected layers: an input layer of maternal gradients, a processing layer of gap genes, and an output layer of pair-rule genes with seven-striped patterns. From measurements of gap gene protein expression in hundreds of wild-type embryos we construct a ``decoder'', which is a look-up table that determines cellular positions from the concentration means, variances and co-variances. When we apply the decoder to measurements in mutant embryos lacking various combinations of the maternal inputs, we predict quantitative changes in the output layer such as missing, altered or displaced stripes. We confirm these predictions by measuring pair-rule expression in the mutant embryos. Our results thereby show that the precision of the patterning network is biologically meaningful and a necessary feature for decoding cell positions in the early fly embryo.

High-Precision Half-Life Measurement for the Superallowed {beta}{sup +} Emitter {sup 26}Al{sup m}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Finlay, P.; Svensson, C. E.; Green, K. L.

2011-01-21

A high-precision half-life measurement for the superallowed {beta}{sup +} emitter {sup 26}Al{sup m} was performed at the TRIUMF-ISAC radioactive ion beam facility yielding T{sub 1/2}=6346.54{+-}0.46{sub stat{+-}}0.60{sub syst} ms, consistent with, but 2.5 times more precise than, the previous world average. The {sup 26}Al{sup m} half-life and ft value, 3037.53(61) s, are now the most precisely determined for any superallowed {beta} decay. Combined with recent theoretical corrections for isospin-symmetry-breaking and radiative effects, the corrected Ft value for {sup 26}Al{sup m}, 3073.0(12) s, sets a new benchmark for the high-precision superallowed Fermi {beta}-decay studies used to test the conserved vector current hypothesismore » and determine the V{sub ud} element of the Cabibbo-Kobayashi-Maskawa quark mixing matrix.« less

Value Tools in Managed Care Decision Making: Current Hurdles and Future Opportunities.

PubMed

Schafer, Jeremy; Galante, Dominic; Shafrin, Jason

2017-06-01

Organizations such as the National Comprehensive Cancer Network, American Society of Clinical Oncology, Institute for Clinical and Economic Review, and Memorial Sloan Kettering have created distinct tools to help different stakeholders assess the value of oncology treatments. However, the oncology value tools were not necessarily created for payers, and it is unclear whether payers are using these tools as part of their drug management process. To understand what value tools payers are using in oncology management and what benefits and shortcomings the tools may have from the payer perspective. A survey targeting drug coverage decision makers at health plans was conducted in August 2016. Respondents attesting to using 2 or more value tools in drug management were eligible for an additional in-depth interview to understand the respondents' perceived benefits and shortcomings of current value tools. Respondents also were asked to describe desired attributes of a hypothetical payer-centric value tool. A total of 28 respondents representing approximately 160 million commercially insured medical lives completed the survey. Twenty respondents (71%) reported using at least 1 value tool in their drug management process. Twelve respondents (43%) used at least 2 tools, and 4 respondents (14%) used at least 3 tools. A total of 6 respondents were selected for in-depth interviews. Interviewees praised value tools for advancing the discussion on drug value and incorporating clinical evidence. However, interviewees felt available value tools varied on providing firm recommendations and relevant price benchmarks. Respondents most commonly recommended the following attributes of a proposed payer-centric value framework: taking a firm position on product value; product comparisons in lieu of comparative clinical trials; web-based tool access; and tool updates at least quarterly. Interview respondents also expressed some support for allowing manipulation of inputs and inclusion of quality-of-life and patient-reported outcome data. Although nearly half of payers surveyed use 2 or more value tools in the drug management process, payers identified a number of areas where the tools could be revised to increase their utility to payers. No outside funding or assistance of any kind was used for this research or in manuscript preparation. Schafer and Galante are employed by Precision for Value, a payer ad marketing agency that works exclusively with life science companies. Shafrin is employed by Precision Health Economics, a consulting company to insurance and life science industries. Shafer, along with Galante and Shafrin, contributed to study design, data collection, and manuscript preparation. The authors contributed equally to data analysis and interpretation and manuscript revision.

Selecting appropriate singular values of transmission matrix to improve precision of incident wavefront retrieval

NASA Astrophysics Data System (ADS)

Fang, Longjie; Zhang, Xicheng; Zuo, Haoyi; Pang, Lin; Yang, Zuogang; Du, Jinglei

2018-06-01

A method of selecting appropriate singular values of the transmission matrix to improve the precision of incident wavefront retrieval in focusing light through scattering media is proposed. The optimal singular values selected by this method can reduce the degree of ill-conditionedness of the transmission matrix effectively, which indicates that the incident wavefront retrieved from the optimal set of singular values is more accurate than the incident wavefront retrieved from other sets of singular values. The validity of this method is verified by numerical simulation and actual measurements of the incident wavefront of coherent light through ground glass.

Precision in the perception of direction of a moving pattern

NASA Technical Reports Server (NTRS)

Stone, Leland S.

1988-01-01

The precision of the model of pattern motion analysis put forth by Adelson and Movshon (1982) who proposed that humans determine the direction of a moving plaid (the sum of two sinusoidal gratings of different orientations) in two steps is qualitatively examined. The volocities of the grating components are first estimated, then combined using the intersection of constraints to determine the velocity of the plaid as a whole. Under the additional assumption that the noise sources for the component velocities are independent, an approximate expression can be derived for the precision in plaid direction as a function of the precision in the speed and direction of the components. Monte Carlo simulations verify that the expression is valid to within 5 percent over the natural range of the parameters. The expression is then used to predict human performance based on available estimates of human precision in the judgment of single component speed. Human performance is predicted to deteriorate by a factor of 3 as half the angle between the wavefronts (theta) decreases from 60 to 30 deg, but actual performance does not. The mean direction discrimination for three human observers was 4.3 plus or minus 0.9 deg (SD) for theta = 60 deg and 5.9 plus or minus 1.2 for theta = 30 deg. This discrepancy can be resolved in two ways. If the noises in the internal representations of the component speeds are smaller than the available estimates or if these noises are not independent, then the psychophysical results are consistent with the Adelson-Movshon hypothesis.

Predicting Document Retrieval System Performance: An Expected Precision Measure.

ERIC Educational Resources Information Center

Losee, Robert M., Jr.

1987-01-01

Describes an expected precision (EP) measure designed to predict document retrieval performance. Highlights include decision theoretic models; precision and recall as measures of system performance; EP graphs; relevance feedback; and computing the retrieval status value of a document for two models, the Binary Independent Model and the Two Poisson…

Thermospheric density and wind retrieval from Swarm observations

NASA Astrophysics Data System (ADS)

Visser, Pieter; Doornbos, Eelco; van den IJssel, Jose; Teixeira da Encarnação, João

2013-11-01

The three-satellite ESA Swarm mission aims at mapping the Earth's global geomagnetic field at unprecedented spatial and temporal resolution and precision. Swarm also aims at observing thermospheric density and possibly horizontal winds. Precise orbit determination (POD) and Thermospheric Density and Wind (TDW) chains form part of the Swarm Constellation and Application Facility (SCARF), which will provide the so-called Level 2 products. The POD and TDW chains generate the orbit, accelerometer calibration, and thermospheric density and wind Level 2 products. The POD and TDW chains have been tested with data from the CHAMP and GRACE missions, indicating that a 3D orbit precision of about 10 cm can be reached. In addition, POD allows to determine daily accelerometer bias and scale factor values with a precision of around 10-15 nm/s2 and 0.01-0.02, respectively, for the flight direction. With these accelerometer calibration parameter values, derived thermospheric density is consistent at the 9-11% level (standard deviation) with values predicted by models (taking into account that model values are 20-30% higher). The retrieval of crosswinds forms part of the processing chain, but will be challenging. The Swarm observations will be used for further developing and improving density and wind retrieval algorithms.

Precise measurement of energy of the first excited state of 115Sn (Eexc ≃ 497.3 keV)

NASA Astrophysics Data System (ADS)

Zheltonozhsky, V. A.; Savrasov, A. M.; Strilchuk, N. V.; Tretyak, V. I.

2018-01-01

Single beta decay of 115In to the first excited level of 115Sn (E\\text{exc}≃ 497.3 \\text{keV} ) is known as β-decay with the lowest Qβ value. To determine the Qβ precisely, one has to measure very accurately the E\\text{exc} value. A sample of tin enriched in 115Sn to 50.7% was irradiated by a proton beam at the U-120 accelerator of INR, Kyiv. The 115Sb radioactive isotope, created in the 115Sn(p,n)115Sb reaction, decays with T1/2 = 32 \\text{min} to 115Sn populating the 497 keV level with ≃ 96{%} probability. The total statistics of ˜105 counts collected in the 497 keV peak in a series of measurements, the exact description of the peak shape and the precisely known calibration points around the 497 keV peak allowed to obtain the value E\\text{exc}= 497.342(3) \\text{keV} , which is the most precise to-date. This leads to the following Qβ\\ast value for the decay 115In → 115Sn*: Qβ\\ast= 147 +/- 10 \\text{eV} .

BOKASUN: A fast and precise numerical program to calculate the Master Integrals of the two-loop sunrise diagrams

NASA Astrophysics Data System (ADS)

Caffo, Michele; Czyż, Henryk; Gunia, Michał; Remiddi, Ettore

2009-03-01

We present the program BOKASUN for fast and precise evaluation of the Master Integrals of the two-loop self-mass sunrise diagram for arbitrary values of the internal masses and the external four-momentum. We use a combination of two methods: a Bernoulli accelerated series expansion and a Runge-Kutta numerical solution of a system of linear differential equations. Program summaryProgram title: BOKASUN Catalogue identifier: AECG_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AECG_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 9404 No. of bytes in distributed program, including test data, etc.: 104 123 Distribution format: tar.gz Programming language: FORTRAN77 Computer: Any computer with a Fortran compiler accepting FORTRAN77 standard. Tested on various PC's with LINUX Operating system: LINUX RAM: 120 kbytes Classification: 4.4 Nature of problem: Any integral arising in the evaluation of the two-loop sunrise Feynman diagram can be expressed in terms of a given set of Master Integrals, which should be calculated numerically. The program provides a fast and precise evaluation method of the Master Integrals for arbitrary (but not vanishing) masses and arbitrary value of the external momentum. Solution method: The integrals depend on three internal masses and the external momentum squared p. The method is a combination of an accelerated expansion in 1/p in its (pretty large!) region of fast convergence and of a Runge-Kutta numerical solution of a system of linear differential equations. Running time: To obtain 4 Master Integrals on PC with 2 GHz processor it takes 3 μs for series expansion with pre-calculated coefficients, 80 μs for series expansion without pre-calculated coefficients, from a few seconds up to a few minutes for Runge-Kutta method (depending on the required accuracy and the values of the physical parameters).

The shortest path is not the one you know: application of biological network resources in precision oncology research.

PubMed

Kuperstein, Inna; Grieco, Luca; Cohen, David P A; Thieffry, Denis; Zinovyev, Andrei; Barillot, Emmanuel

2015-03-01

Several decades of molecular biology research have delivered a wealth of detailed descriptions of molecular interactions in normal and tumour cells. This knowledge has been functionally organised and assembled into dedicated biological pathway resources that serve as an invaluable tool, not only for structuring the information about molecular interactions but also for making it available for biological, clinical and computational studies. With the advent of high-throughput molecular profiling of tumours, close to complete molecular catalogues of mutations, gene expression and epigenetic modifications are available and require adequate interpretation. Taking into account the information about biological signalling machinery in cells may help to better interpret molecular profiles of tumours. Making sense out of these descriptions requires biological pathway resources for functional interpretation of the data. In this review, we describe the available biological pathway resources, their characteristics in terms of construction mode, focus, aims and paradigms of biological knowledge representation. We present a new resource that is focused on cancer-related signalling, the Atlas of Cancer Signalling Networks. We briefly discuss current approaches for data integration, visualisation and analysis, using biological networks, such as pathway scoring, guilt-by-association and network propagation. Finally, we illustrate with several examples the added value of data interpretation in the context of biological networks and demonstrate that it may help in analysis of high-throughput data like mutation, gene expression or small interfering RNA screening and can guide in patients stratification. Finally, we discuss perspectives for improving precision medicine using biological network resources and tools. Taking into account the information about biological signalling machinery in cells may help to better interpret molecular patterns of tumours and enable to put precision oncology into general clinical practice. © The Author 2015. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Blue light-mediated transcriptional activation and repression of gene expression in bacteria

PubMed Central

Jayaraman, Premkumar; Devarajan, Kavya; Chua, Tze Kwang; Zhang, Hanzhong; Gunawan, Erry; Poh, Chueh Loo

2016-01-01

Light-regulated modules offer unprecedented new ways to control cellular behavior in precise spatial and temporal resolution. The availability of such tools may dramatically accelerate the progression of synthetic biology applications. Nonetheless, current optogenetic toolbox of prokaryotes has potential issues such as lack of rapid and switchable control, less portable, low dynamic expression and limited parts. To address these shortcomings, we have engineered a novel bidirectional promoter system for Escherichia coli that can be induced or repressed rapidly and reversibly using the blue light dependent DNA-binding protein EL222. We demonstrated that by modulating the dosage of light pulses or intensity we could control the level of gene expression precisely. We show that both light-inducible and repressible system can function in parallel with high spatial precision in a single cell and can be switched stably between ON- and OFF-states by repetitive pulses of blue light. In addition, the light-inducible and repressible expression kinetics were quantitatively analysed using a mathematical model. We further apply the system, for the first time, to optogenetically synchronize two receiver cells performing different logic behaviors over time using blue light as a molecular clock signal. Overall, our modular approach layers a transformative platform for next-generation light-controllable synthetic biology systems in prokaryotes. PMID:27353329

A biological timer in the fat body comprising Blimp-1, βFtz-f1 and Shade regulates pupation timing in Drosophila melanogaster.

PubMed

Akagi, Kazutaka; Sarhan, Moustafa; Sultan, Abdel-Rahman S; Nishida, Haruka; Koie, Azusa; Nakayama, Takumi; Ueda, Hitoshi

2016-07-01

During the development of multicellular organisms, many events occur with precise timing. In Drosophila melanogaster, pupation occurs about 12 h after puparium formation and its timing is believed to be determined by the release of a steroid hormone, ecdysone (E), from the prothoracic gland. Here, we demonstrate that the ecdysone-20-monooxygenase Shade determines pupation timing by converting E to 20-hydroxyecdysone (20E) in the fat body, which is the organ that senses nutritional status. The timing of shade expression is determined by its transcriptional activator βFtz-f1. The βftz-f1 gene is activated after a decline in the expression of its transcriptional repressor Blimp-1, which is temporally expressed around puparium formation in response to a high titer of 20E. The expression level and stability of Blimp-1 is critical for the precise timing of pupation. Thus, we propose that Blimp-1 molecules function like sand in an hourglass in this precise developmental timer system. Furthermore, our data suggest that a biological advantage results from both the use of a transcriptional repressor for time determination and the association of developmental timing with nutritional status of the organism. © 2016. Published by The Company of Biologists Ltd.

Estimating the periodic components of a biomedical signal through inverse problem modelling and Bayesian inference with sparsity enforcing prior

NASA Astrophysics Data System (ADS)

Dumitru, Mircea; Djafari, Ali-Mohammad

2015-01-01

The recent developments in chronobiology need a periodic components variation analysis for the signals expressing the biological rhythms. A precise estimation of the periodic components vector is required. The classical approaches, based on FFT methods, are inefficient considering the particularities of the data (short length). In this paper we propose a new method, using the sparsity prior information (reduced number of non-zero values components). The considered law is the Student-t distribution, viewed as a marginal distribution of a Infinite Gaussian Scale Mixture (IGSM) defined via a hidden variable representing the inverse variances and modelled as a Gamma Distribution. The hyperparameters are modelled using the conjugate priors, i.e. using Inverse Gamma Distributions. The expression of the joint posterior law of the unknown periodic components vector, hidden variables and hyperparameters is obtained and then the unknowns are estimated via Joint Maximum A Posteriori (JMAP) and Posterior Mean (PM). For the PM estimator, the expression of the posterior law is approximated by a separable one, via the Bayesian Variational Approximation (BVA), using the Kullback-Leibler (KL) divergence. Finally we show the results on synthetic data in cancer treatment applications.

Capped antigenomic RNA transcript facilitates rescue of a plant rhabdovirus.

PubMed

Qian, Shasha; Chen, Xiaolan; Sun, Kai; Zhang, Yang; Li, Zhenghe

2017-06-13

Recovery of recombinant negative-stranded RNA viruses from cloned cDNAs is an inefficient process as multiple viral components need to be delivered into cells for reconstitution of infectious entities. Previously studies have shown that authentic viral RNA termini are essential for efficient virus rescue. However, little is known about the activity of viral RNAs processed by different strategies in supporting recovery of plant negative-stranded RNA virus. In this study, we used several versions of hammerhead ribozymes and a truncated cauliflower mosaic virus 35S promoter to generate precise 5' termini of sonchus yellow net rhabdovirus (SYNV) antigenomic RNA (agRNA) derivatives. These agRNAs were co-expressed with the SYNV core proteins in Nicotiana benthamiana leaves to evaluate their efficiency in supporting fluorescent reporter gene expression from an SYNV minireplicon (MR) and rescue of full-length virus. Optimization of hammerhead ribozyme cleavage activities led to improved SYNV MR reporter gene expression. Although the MR agRNA processed by the most active hammerhead variants is comparable to the capped, precisely transcribed agRNA in supporting MR activity, efficient recovery of recombinant SYNV was only achieved with capped agRNA. Further studies showed that the capped SYNV agRNA permitted transient expression of the nucleocapsid (N) protein, and an agRNA derivatives unable to express the N protein in cis exhibited dramatically reduced rescue efficiency. Our study reveals superior activity of precisely transcribed, capped SYNV agRNAs to uncapped, hammerhead ribozyme-processed agRNAs, and suggests a cis-acting function for the N protein expressed from the capped agRNA during recovery of SYNV from plasmids.

Quantitative Analyses of Core Promoters Enable Precise Engineering of Regulated Gene Expression in Mammalian Cells.

PubMed

Ede, Christopher; Chen, Ximin; Lin, Meng-Yin; Chen, Yvonne Y

2016-05-20

Inducible transcription systems play a crucial role in a wide array of synthetic biology circuits. However, the majority of inducible promoters are constructed from a limited set of tried-and-true promoter parts, which are susceptible to common shortcomings such as high basal expression levels (i.e., leakiness). To expand the toolbox for regulated mammalian gene expression and facilitate the construction of mammalian genetic circuits with precise functionality, we quantitatively characterized a panel of eight core promoters, including sequences with mammalian, viral, and synthetic origins. We demonstrate that this selection of core promoters can provide a wide range of basal gene expression levels and achieve a gradient of fold-inductions spanning 2 orders of magnitude. Furthermore, commonly used parts such as minimal CMV and minimal SV40 promoters were shown to achieve robust gene expression upon induction, but also suffer from high levels of leakiness. In contrast, a synthetic promoter, YB_TATA, was shown to combine low basal expression with high transcription rate in the induced state to achieve significantly higher fold-induction ratios compared to all other promoters tested. These behaviors remain consistent when the promoters are coupled to different genetic outputs and different response elements, as well as across different host-cell types and DNA copy numbers. We apply this quantitative understanding of core promoter properties to the successful engineering of human T cells that respond to antigen stimulation via chimeric antigen receptor signaling specifically under hypoxic environments. Results presented in this study can facilitate the design and calibration of future mammalian synthetic biology systems capable of precisely programmed functionality.

Using Public Data for Comparative Proteome Analysis in Precision Medicine Programs.

PubMed

Hughes, Christopher S; Morin, Gregg B

2018-03-01

Maximizing the clinical utility of information obtained in longitudinal precision medicine programs would benefit from robust comparative analyses to known information to assess biological features of patient material toward identifying the underlying features driving their disease phenotype. Herein, the potential for utilizing publically deposited mass-spectrometry-based proteomics data to perform inter-study comparisons of cell-line or tumor-tissue materials is investigated. To investigate the robustness of comparison between MS-based proteomics studies carried out with different methodologies, deposited data representative of label-free (MS1) and isobaric tagging (MS2 and MS3 quantification) are utilized. In-depth quantitative proteomics data acquired from analysis of ovarian cancer cell lines revealed the robust recapitulation of observable gene expression dynamics between individual studies carried out using significantly different methodologies. The observed signatures enable robust inter-study clustering of cell line samples. In addition, the ability to classify and cluster tumor samples based on observed gene expression trends when using a single patient sample is established. With this analysis, relevant gene expression dynamics are obtained from a single patient tumor, in the context of a precision medicine analysis, by leveraging a large cohort of repository data as a comparator. Together, these data establish the potential for state-of-the-art MS-based proteomics data to serve as resources for robust comparative analyses in precision medicine applications. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Precise measurement of a magnetic field generated by the electromagnetic flux compression technique.

PubMed

Nakamura, D; Sawabe, H; Matsuda, Y H; Takeyama, S

2013-04-01

The precision of the values of a magnetic field generated by electromagnetic flux compression was investigated in ultra-high magnetic fields of up to 700 T. In an attempt to calibrate the magnetic field measured by pickup coils, precise Faraday rotation (FR) measurements were conducted on optical (quartz and crown) glasses. A discernible "turn-around" phenomenon was observed in the FR signal as well as the pickup coils before the end of a liner implosion. We found that the magnetic field measured by pickup coils should be corrected by taking into account the high-frequency response of the signal transmission line. Near the peak magnetic field, however, the pickup coils failed to provide reliable values, leaving the FR measurement as the only method to precisely measure extremely high magnetic fields.

Comparison of gene expression microarray data with count-based RNA measurements informs microarray interpretation.

PubMed

Richard, Arianne C; Lyons, Paul A; Peters, James E; Biasci, Daniele; Flint, Shaun M; Lee, James C; McKinney, Eoin F; Siegel, Richard M; Smith, Kenneth G C

2014-08-04

Although numerous investigations have compared gene expression microarray platforms, preprocessing methods and batch correction algorithms using constructed spike-in or dilution datasets, there remains a paucity of studies examining the properties of microarray data using diverse biological samples. Most microarray experiments seek to identify subtle differences between samples with variable background noise, a scenario poorly represented by constructed datasets. Thus, microarray users lack important information regarding the complexities introduced in real-world experimental settings. The recent development of a multiplexed, digital technology for nucleic acid measurement enables counting of individual RNA molecules without amplification and, for the first time, permits such a study. Using a set of human leukocyte subset RNA samples, we compared previously acquired microarray expression values with RNA molecule counts determined by the nCounter Analysis System (NanoString Technologies) in selected genes. We found that gene measurements across samples correlated well between the two platforms, particularly for high-variance genes, while genes deemed unexpressed by the nCounter generally had both low expression and low variance on the microarray. Confirming previous findings from spike-in and dilution datasets, this "gold-standard" comparison demonstrated signal compression that varied dramatically by expression level and, to a lesser extent, by dataset. Most importantly, examination of three different cell types revealed that noise levels differed across tissues. Microarray measurements generally correlate with relative RNA molecule counts within optimal ranges but suffer from expression-dependent accuracy bias and precision that varies across datasets. We urge microarray users to consider expression-level effects in signal interpretation and to evaluate noise properties in each dataset independently.

CSAX: Characterizing Systematic Anomalies in eXpression Data

PubMed Central

Noto, Keith; Majidi, Saeed; Edlow, Andrea G.; Wick, Heather C.; Bianchi, Diana W.

2015-01-01

Abstract Methods for translating gene expression signatures into clinically relevant information have typically relied upon having many samples from patients with similar molecular phenotypes. Here, we address the question of what can be done when it is relatively easy to obtain healthy patient samples, but when abnormalities corresponding to disease states may be rare and one-of-a-kind. The associated computational challenge, anomaly detection, is a well-studied machine-learning problem. However, due to the dimensionality and variability of expression data, existing methods based on feature space analysis or individual anomalously expressed genes are insufficient. We present a novel approach, CSAX, that identifies pathways in an individual sample in which the normal expression relationships are disrupted. To evaluate our approach, we have compiled and released a compendium of public expression data sets, reformulated to create a test bed for anomaly detection. We demonstrate the accuracy of CSAX on the data sets in our compendium, compare it to other leading methods, and show that CSAX aids in both identifying anomalies and explaining their underlying biology. We describe an approach to characterizing the difficulty of specific expression anomaly detection tasks. We then illustrate CSAX's value in two developmental case studies. Confirming prior hypotheses, CSAX highlights disruption of platelet activation pathways in a neonate with retinopathy of prematurity and identifies, for the first time, dysregulated oxidative stress response in second trimester amniotic fluid of fetuses with obese mothers. Our approach provides an important step toward identification of individual disease patterns in the era of precision medicine. PMID:25651392

Becoming partners, retaining autonomy: ethical considerations on the development of precision medicine.

PubMed

Blasimme, Alessandro; Vayena, Effy

2016-11-04

Precision medicine promises to develop diagnoses and treatments that take individual variability into account. According to most specialists, turning this promise into reality will require adapting the established framework of clinical research ethics, and paying more attention to participants' attitudes towards sharing genotypic, phenotypic, lifestyle data and health records, and ultimately to their desire to be engaged as active partners in medical research.Notions such as participation, engagement and partnership have been introduced in bioethics debates concerning genetics and large-scale biobanking to broaden the focus of discussion beyond individual choice and individuals' moral interests. The uptake of those concepts in precision medicine is to be welcomed. However, as data and medical information from research participants in precision medicine cohorts will be collected on an individual basis, translating a participatory approach in this emerging area may prove cumbersome. Therefore, drawing on Joseph Raz's perfectionism, we propose a principle of respect for autonomous agents that, we reckon, can address many of the concerns driving recent scholarship on partnership and public participation, while avoiding some of the limitations these concept have in the context of precision medicine. Our approach offers a normative clarification to how becoming partners in precision is compatible with retaining autonomy.Realigning the value of autonomy with ideals of direct engagement, we show, can provide adequate normative orientation to precision medicine; it can do justice to the idea of moral pluralism by stressing the value of moral self-determination: and, finally, it can reconcile the notion of autonomy with other more communitarian values such as participation and solidarity.

Monte-Carlo Method Application for Precising Meteor Velocity from TV Observations

NASA Astrophysics Data System (ADS)

Kozak, P.

2014-12-01

Monte-Carlo method (method of statistical trials) as an application for meteor observations processing was developed in author's Ph.D. thesis in 2005 and first used in his works in 2008. The idea of using the method consists in that if we generate random values of input data - equatorial coordinates of the meteor head in a sequence of TV frames - in accordance with their statistical distributions we get a possibility to plot the probability density distributions for all its kinematical parameters, and to obtain their mean values and dispersions. At that the theoretical possibility appears to precise the most important parameter - geocentric velocity of a meteor - which has the highest influence onto precision of meteor heliocentric orbit elements calculation. In classical approach the velocity vector was calculated in two stages: first we calculate the vector direction as a vector multiplication of vectors of poles of meteor trajectory big circles, calculated from two observational points. Then we calculated the absolute value of velocity independently from each observational point selecting any of them from some reasons as a final parameter. In the given method we propose to obtain a statistical distribution of velocity absolute value as an intersection of two distributions corresponding to velocity values obtained from different points. We suppose that such an approach has to substantially increase the precision of meteor velocity calculation and remove any subjective inaccuracies.

S-193 scatterometer backscattering cross section precision/accuracy for Skylab 2 and 3 missions

NASA Technical Reports Server (NTRS)

Krishen, K.; Pounds, D. J.

1975-01-01

Procedures for measuring the precision and accuracy with which the S-193 scatterometer measured the background cross section of ground scenes are described. Homogeneous ground sites were selected, and data from Skylab missions were analyzed. The precision was expressed as the standard deviation of the scatterometer-acquired backscattering cross section. In special cases, inference of the precision of measurement was made by considering the total range from the maximum to minimum of the backscatter measurements within a data segment, rather than the standard deviation. For Skylab 2 and 3 missions a precision better than 1.5 dB is indicated. This procedure indicates an accuracy of better than 3 dB for the Skylab 2 and 3 missions. The estimates of precision and accuracy given in this report are for backscattering cross sections from -28 to 18 dB. Outside this range the precision and accuracy decrease significantly.

Why precision medicine is not the best route to a healthier world.

PubMed

Rey-López, Juan Pablo; Sá, Thiago Herick de; Rezende, Leandro Fórnias Machado de

2018-02-05

Precision medicine has been announced as a new health revolution. The term precision implies more accuracy in healthcare and prevention of diseases, which could yield substantial cost savings. However, scientific debate about precision medicine is needed to avoid wasting economic resources and hype. In this commentary, we express the reasons why precision medicine cannot be a health revolution for population health. Advocates of precision medicine neglect the limitations of individual-centred, high-risk strategies (reduced population health impact) and the current crisis of evidence-based medicine. Overrated "precision medicine" promises may be serving vested interests, by dictating priorities in the research agenda and justifying the exorbitant healthcare expenditure in our finance-based medicine. If societies aspire to address strong risk factors for non-communicable diseases (such as air pollution, smoking, poor diets, or physical inactivity), they need less medicine and more investment in population prevention strategies.

Determining Energy Expenditure during Some Household and Garden Tasks.

ERIC Educational Resources Information Center

Gunn, Simon M.; Brooks, Anthony G.; Withers, Robert T.; Gore, Christopher J.; Owen, Neville; Booth, Michael L.; Bauman, Adrian E.

2002-01-01

Calculated the reproducibility and precision for VO2 during moderate paced walking and four housework and gardening activities, examining which rated at least 3.0 when calculating exercise intensity in METs and multiples of measured resting metabolic rate (MRM). VO2 was measured with reproducibility and precision. Expressing energy expenditure in…

Uncertainty Analysis of Instrument Calibration and Application

NASA Technical Reports Server (NTRS)

Tripp, John S.; Tcheng, Ping

1999-01-01

Experimental aerodynamic researchers require estimated precision and bias uncertainties of measured physical quantities, typically at 95 percent confidence levels. Uncertainties of final computed aerodynamic parameters are obtained by propagation of individual measurement uncertainties through the defining functional expressions. In this paper, rigorous mathematical techniques are extended to determine precision and bias uncertainties of any instrument-sensor system. Through this analysis, instrument uncertainties determined through calibration are now expressed as functions of the corresponding measurement for linear and nonlinear univariate and multivariate processes. Treatment of correlated measurement precision error is developed. During laboratory calibration, calibration standard uncertainties are assumed to be an order of magnitude less than those of the instrument being calibrated. Often calibration standards do not satisfy this assumption. This paper applies rigorous statistical methods for inclusion of calibration standard uncertainty and covariance due to the order of their application. The effects of mathematical modeling error on calibration bias uncertainty are quantified. The effects of experimental design on uncertainty are analyzed. The importance of replication is emphasized, techniques for estimation of both bias and precision uncertainties using replication are developed. Statistical tests for stationarity of calibration parameters over time are obtained.

Msn2 Coordinates a Stoichiometric Gene Expression Program

PubMed Central

Stewart-Ornstein, Jacob; Nelson, Christopher; DeRisi, Joe; Weissman, Jonathan S.; El-Samad, Hana

2014-01-01

Summary Background Many cellular processes operate in an “analog” regime in which the magnitude of the response is precisely tailored to the intensity of the stimulus. In order to maintain the coherence of such responses, the cell must provide for proportional expression of multiple target genes across a wide dynamic range of induction states. Our understanding of the strategies used to achieve graded gene regulation is limited. Results In this work, we document a relationship between stress responsive gene expression and the transcription factor Msn2 that is graded over a large range of Msn2 cocnentrations. We use computational modeling, in vivo, and in vitro analysis to dissect the roots of this relationship. Our studies reveal a simple and general strategy based on non-cooperative low-affinity interactions between Msn2 and its cognate binding sites, as well as competition over a large number of Msn2 binding sites in the genome relative to the number of Msn2 molecules. Conclusions In addition to enabling precise tuning of gene expression to the state of the environment, this strategy ensures co-linear activation of target genes, allowing for stoichiometric expression of large groups of genes without extensive promoter tuning. Furthermore, such a strategy enables precise modulation of the activity of any given promoter by addition of binding sites without altering the qualitative relationship between different genes in a regulon. This feature renders a given regulon highly ‘evolvable’. PMID:24210615

CODATA recommended values of the fundamental constants

NASA Astrophysics Data System (ADS)

Mohr, Peter J.; Taylor, Barry N.

2000-11-01

A review is given of the latest Committee on Data for Science and Technology (CODATA) adjustment of the values of the fundamental constants. The new set of constants, referred to as the 1998 values, replaces the values recommended for international use by CODATA in 1986. The values of the constants, and particularly the Rydberg constant, are of relevance to the calculation of precise atomic spectra. The standard uncertainty (estimated standard deviation) of the new recommended value of the Rydberg constant, which is based on precision frequency metrology and a detailed analysis of the theory, is approximately 1/160 times the uncertainty of the 1986 value. The new set of recommended values as well as a searchable bibliographic database that gives citations to the relevant literature is available on the World Wide Web at physics.nist.gov/constants and physics.nist.gov/constantsbib, respectively. .

Effects of aspartame on hsp70, bcl-2 and bax expression in immune organs of Wistar albino rats

PubMed Central

Choudhary, Arbind Kumar; Devi, Rathinasamy Sheela

2016-01-01

Abstract Aspartame, a “first generation sweetener”, is widely used in a variety of foods, beverages, and medicine. The FDA has determined the acceptable daily intake (ADI) value of aspartame to be 50 mg/kg·day, while the JECFA (Joint FAO/WHO Expert Committee on Food Additives) has set this value at 40 mg/kg of body weight/day. Safety issues have been raised about aspartame due to its metabolites, specifically toxicity from methanol and/or its systemic metabolites formaldehyde and formic acid. The immune system is now recognized as a target organ for many xenobiotics, such as drugs and chemicals, which are able to trigger unwanted apoptosis or to alter the regulation of apoptosis. Our previous studies has shown that oral administration of aspartame [40 mg/(kg·day)] or its metabolites for 90 days increased oxidative stress in immune organs of Wistar albino rats. In this present study, we aimed to clarify whether aspartame consumption over a longer period (90-days) has any effect on the expression of hsp70, bcl-2 and bax at both mRNA transcript and protein expression levels in immune organs. We observed that oral administration of aspartame for 90 days did not cause any apparent DNA fragmentation in immune organs of aspartame treated animals; however, there was a significant increase in hsp70 expression, apart from significant alteration in bcl-2 and bax at both mRNA transcript and protein expression level in the immune organs of aspartame treated animals compared to controls. Hence, the results indicated that hsp70 levels increased in response to oxidative injury induced by aspartame metabolites; however, these metabolites did not induce apoptosis in the immune organs. Furthermore, detailed analyses are needed to elucidate the precise molecular mechanisms involved in these changes. PMID:27845306

Fundamental limits of scintillation detector timing precision

NASA Astrophysics Data System (ADS)

Derenzo, Stephen E.; Choong, Woon-Seng; Moses, William W.

2014-07-01

In this paper we review the primary factors that affect the timing precision of a scintillation detector. Monte Carlo calculations were performed to explore the dependence of the timing precision on the number of photoelectrons, the scintillator decay and rise times, the depth of interaction uncertainty, the time dispersion of the optical photons (modeled as an exponential decay), the photodetector rise time and transit time jitter, the leading-edge trigger level, and electronic noise. The Monte Carlo code was used to estimate the practical limits on the timing precision for an energy deposition of 511 keV in 3 mm × 3 mm × 30 mm Lu2SiO5:Ce and LaBr3:Ce crystals. The calculated timing precisions are consistent with the best experimental literature values. We then calculated the timing precision for 820 cases that sampled scintillator rise times from 0 to 1.0 ns, photon dispersion times from 0 to 0.2 ns, photodetector time jitters from 0 to 0.5 ns fwhm, and A from 10 to 10 000 photoelectrons per ns decay time. Since the timing precision R was found to depend on A-1/2 more than any other factor, we tabulated the parameter B, where R = BA-1/2. An empirical analytical formula was found that fit the tabulated values of B with an rms deviation of 2.2% of the value of B. The theoretical lower bound of the timing precision was calculated for the example of 0.5 ns rise time, 0.1 ns photon dispersion, and 0.2 ns fwhm photodetector time jitter. The lower bound was at most 15% lower than leading-edge timing discrimination for A from 10 to 10 000 photoelectrons ns-1. A timing precision of 8 ps fwhm should be possible for an energy deposition of 511 keV using currently available photodetectors if a theoretically possible scintillator were developed that could produce 10 000 photoelectrons ns-1.

Fundamental Limits of Scintillation Detector Timing Precision

PubMed Central

Derenzo, Stephen E.; Choong, Woon-Seng; Moses, William W.

2014-01-01

In this paper we review the primary factors that affect the timing precision of a scintillation detector. Monte Carlo calculations were performed to explore the dependence of the timing precision on the number of photoelectrons, the scintillator decay and rise times, the depth of interaction uncertainty, the time dispersion of the optical photons (modeled as an exponential decay), the photodetector rise time and transit time jitter, the leading-edge trigger level, and electronic noise. The Monte Carlo code was used to estimate the practical limits on the timing precision for an energy deposition of 511 keV in 3 mm × 3 mm × 30 mm Lu2SiO5:Ce and LaBr3:Ce crystals. The calculated timing precisions are consistent with the best experimental literature values. We then calculated the timing precision for 820 cases that sampled scintillator rise times from 0 to 1.0 ns, photon dispersion times from 0 to 0.2 ns, photodetector time jitters from 0 to 0.5 ns fwhm, and A from 10 to 10,000 photoelectrons per ns decay time. Since the timing precision R was found to depend on A−1/2 more than any other factor, we tabulated the parameter B, where R = BA−1/2. An empirical analytical formula was found that fit the tabulated values of B with an rms deviation of 2.2% of the value of B. The theoretical lower bound of the timing precision was calculated for the example of 0.5 ns rise time, 0.1 ns photon dispersion, and 0.2 ns fwhm photodetector time jitter. The lower bound was at most 15% lower than leading-edge timing discrimination for A from 10 to 10,000 photoelectrons/ns. A timing precision of 8 ps fwhm should be possible for an energy deposition of 511 keV using currently available photodetectors if a theoretically possible scintillator were developed that could produce 10,000 photoelectrons/ns. PMID:24874216

Precision of dual-energy X-ray absorptiometry of the knee and heel: methodology and implications for research to reduce bone mineral loss after spinal cord injury.

PubMed

Peppler, W T; Kim, W J; Ethans, K; Cowley, K C

2017-05-01

Methodological validation of dual-energy x-ray absorptiometry (DXA)-based measures of leg bone mineral density (BMD) based on the guidelines of the International Society for Clinical Densitometry. The primary objective of this study was to determine the precision of BMD estimates at the knee and heel using the manufacturer provided DXA acquisition algorithm. The secondary objective was to determine the smallest change in DXA-based measurement of BMD that should be surpassed (least significant change (LSC)) before suggesting that a biological change has occurred in the distal femur, proximal tibia and calcaneus. Academic Research Centre, Canada. Ten people with motor-complete SCI of at least 2 years duration and 10 people from the general population volunteered to have four DXA-based measurements taken of their femur, tibia and calcaneus. BMDs for seven regions of interest (RIs) were calculated, as were short-term precision (root-mean-square (RMS) standard deviation (g cm -2 ), RMS-coefficient of variation (RMS-CV, %)) and LSC. Overall, RMS-CV values were similar between SCI (3.63-10.20%, mean=5.3%) and able-bodied (1.85-5.73%, mean=4%) cohorts, despite lower absolute BMD values at each RIs in those with SCI (35%, heel to 54%, knee; P<0.0001). Precision was highest at the calcaneus and lowest at the femur. Except at the femur, RMS-CV values were under 6%. For DXA-based estimates of BMD at the distal femur, proximal tibia and calcaneus, these precision values suggest that LSC values >10% are needed to detect differences between treated and untreated groups in studies aimed at reducing bone mineral loss after SCI.

"Center punch" and "whole spot" bioanalysis of apixaban in human dried blood spot samples by UHPLC-MS/MS.

PubMed

Zheng, Naiyu; Yuan, Long; Ji, Qin C; Mangus, Heidi; Song, Yan; Frost, Charles; Zeng, Jianing; Aubry, Anne-Françoise; Arnold, Mark E

2015-04-15

Apixaban (Eliquis™) was developed by Bristol-Myers Squibb (BMS) and Pfizer to use as an antithrombotic/anticoagulant agent and has been recently approved for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. A clinical study of apixaban, sponsored by BMS and Pfizer, included a pilot exploratory portion to evaluate the potential for future drug concentration monitoring using dried blood spot (DBS) sample collection. For DBS sample collection, a fixed blood volume was dispensed onto a DBS card by either regular volumetric pipette (venous blood collection) or capillary dispenser (finger prick blood collection). A 96-well semi-automated liquid-liquid extraction sample preparation procedure was developed to provide clean extracts for UHPLC-MS/MS quantitation. Assays using both partial-spot center punch and whole spot punch were developed and validated. The linear dynamic ranges for all the analyses were from 0.5 to 500 ng/mL. The coefficient of determination (r(2)) values was >0.9944 for all the validation runs. For the center punch approach, the intra-assay precision (%CV) was within 4.4% and inter-assay precision was within 2.6%. The assay accuracy, expressed as %Dev., was within ± 5.4% of the nominal concentrations. One accuracy and precision run was performed using the whole spot approach, the intra-assay precision (%CV) was within 7.1% and the accuracy was within ± 8.0% of the nominal concentrations. In contrast to the center punch approach, the whole spot approach eliminated the effect of hematocrit and high lipids on the analysis of apixaban in human DBS when an accurate sample blood volume was collected on DBS cards. Copyright © 2015 Elsevier B.V. All rights reserved.

Targeted mutagenesis using zinc-finger nucleases in perennial fruit trees.

PubMed

Peer, Reut; Rivlin, Gil; Golobovitch, Sara; Lapidot, Moshe; Gal-On, Amit; Vainstein, Alexander; Tzfira, Tzvi; Flaishman, Moshe A

2015-04-01

Targeting a gene in apple or fig with ZFN, introduced by transient or stable transformation, should allow genome editing with high precision to advance basic science and breeding programs. Genome editing is a powerful tool for precise gene manipulation in any organism; it has recently been shown to be of great value for annual plants. Classical breeding strategies using conventional cross-breeding and induced mutations have played an important role in the development of new cultivars in fruit trees. However, fruit-tree breeding is a lengthy process with many limitations. Efficient and widely applied methods for targeted modification of fruit-tree genomes are not yet available. In this study, transgenic apple and fig lines carrying a zinc-finger nuclease (ZFNs) under the control of a heat-shock promoter were developed. Editing of a mutated uidA gene, following expression of the ZFN genes by heat shock, was confirmed by GUS staining and PCR product sequencing. Finally, whole plants with a repaired uidA gene due to deletion of a stop codon were regenerated. The ZFN-mediated gene modifications were stable and passed onto regenerants from ZFN-treated tissue cultures. This is the first demonstration of efficient and precise genome editing, using ZFN at a specific genomic locus, in two different perennial fruit trees-apple and fig. We conclude that targeting a gene in apple or fig with a ZFN introduced by transient or stable transformation should allow knockout of a gene of interest. Using this technology for genome editing allows for marker gene-independent and antibiotic selection-free genome engineering with high precision in fruit trees to advance basic science as well as nontransgenic breeding programs.

Dentate granule cell recruitment of feedforward inhibition governs engram maintenance and remote memory generalization.

PubMed

Guo, Nannan; Soden, Marta E; Herber, Charlotte; Kim, Michael TaeWoo; Besnard, Antoine; Lin, Paoyan; Ma, Xiang; Cepko, Constance L; Zweifel, Larry S; Sahay, Amar

2018-05-01

Memories become less precise and generalized over time as memory traces reorganize in hippocampal-cortical networks. Increased time-dependent loss of memory precision is characterized by an overgeneralization of fear in individuals with post-traumatic stress disorder (PTSD) or age-related cognitive impairments. In the hippocampal dentate gyrus (DG), memories are thought to be encoded by so-called 'engram-bearing' dentate granule cells (eDGCs). Here we show, using rodents, that contextual fear conditioning increases connectivity between eDGCs and inhibitory interneurons (INs) in the downstream hippocampal CA3 region. We identify actin-binding LIM protein 3 (ABLIM3) as a mossy-fiber-terminal-localized cytoskeletal factor whose levels decrease after learning. Downregulation of ABLIM3 expression in DGCs was sufficient to increase connectivity with CA3 stratum lucidum INs (SLINs), promote parvalbumin (PV)-expressing SLIN activation, enhance feedforward inhibition onto CA3 and maintain a fear memory engram in the DG over time. Furthermore, downregulation of ABLIM3 expression in DGCs conferred conditioned context-specific reactivation of memory traces in hippocampal-cortical and amygdalar networks and decreased fear memory generalization at remote (i.e., distal) time points. Consistent with the observation of age-related hyperactivity of CA3, learning failed to increase DGC-SLIN connectivity in 17-month-old mice, whereas downregulation of ABLIM3 expression was sufficient to restore DGC-SLIN connectivity, increase PV+ SLIN activation and improve the precision of remote memories. These studies exemplify a connectivity-based strategy that targets a molecular brake of feedforward inhibition in DG-CA3 and may be harnessed to decrease time-dependent memory generalization in individuals with PTSD and improve memory precision in aging individuals.

F-MAP: A Bayesian approach to infer the gene regulatory network using external hints

PubMed Central

Shahdoust, Maryam; Mahjub, Hossein; Sadeghi, Mehdi

2017-01-01

The Common topological features of related species gene regulatory networks suggest reconstruction of the network of one species by using the further information from gene expressions profile of related species. We present an algorithm to reconstruct the gene regulatory network named; F-MAP, which applies the knowledge about gene interactions from related species. Our algorithm sets a Bayesian framework to estimate the precision matrix of one species microarray gene expressions dataset to infer the Gaussian Graphical model of the network. The conjugate Wishart prior is used and the information from related species is applied to estimate the hyperparameters of the prior distribution by using the factor analysis. Applying the proposed algorithm on six related species of drosophila shows that the precision of reconstructed networks is improved considerably compared to the precision of networks constructed by other Bayesian approaches. PMID:28938012

Gradated assembly of multiple proteins into supramolecular nanomaterials

NASA Astrophysics Data System (ADS)

Hudalla, Gregory A.; Sun, Tao; Gasiorowski, Joshua Z.; Han, Huifang; Tian, Ye F.; Chong, Anita S.; Collier, Joel H.

2014-08-01

Biomaterials exhibiting precise ratios of different bioactive protein components are critical for applications ranging from vaccines to regenerative medicine, but their design is often hindered by limited choices and cross-reactivity of protein conjugation chemistries. Here, we describe a strategy for inducing multiple different expressed proteins of choice to assemble into nanofibres and gels with exceptional compositional control. The strategy employs ‘βTail’ tags, which allow for good protein expression in bacteriological cultures, yet can be induced to co-assemble into nanomaterials when mixed with additional β-sheet fibrillizing peptides. Multiple different βTail fusion proteins could be inserted into peptide nanofibres alone or in combination at predictable, smoothly gradated concentrations, providing a simple yet versatile route to install precise combinations of proteins into nanomaterials. The technology is illustrated by achieving precisely targeted hues using mixtures of fluorescent proteins, by creating nanofibres bearing enzymatic activity, and by adjusting antigenic dominance in vaccines.

Q Value of the Superallowed Decay of {sup 46}V and Its Influence on V{sub ud} and the Unitarity of the Cabibbo-Kobayashi-Maskawa Matrix

DOE Office of Scientific and Technical Information (OSTI.GOV)

Savard, G.; Department of Physics, University of Chicago, Chicago, Illinois 60637; Buchinger, F.

2005-09-02

The masses of the radioactive nuclei {sup 46}V and its decay daughter {sup 46}Ti have been measured with the Canadian Penning Trap on-line Penning trap mass spectrometer to a precision of 1x10{sup -8}. A Q{sub EC} value of 7052.90(40) keV for the superallowed beta decay of {sup 46}V is obtained from the difference of these two masses. With this precise Q value, the Ft value for this decay is determined with improved precision. An investigation of an earlier Q-value measurement for {sup 46}V uncovers a set of 7 measurements that cannot be reconciled with modern data and affects previous evaluationsmore » of V{sub ud} from superallowed Fermi decays. A new evaluation, adding our new data and removing the discredited subset, yields new values for G{sub V} and V{sub ud}. When combined with recent results for V{sub us}, this yields modified constraints for the unitarity of the Cabibbo-Kobayashi-Maskawa matrix and other extensions of the standard model.« less

Generalized Squashing Factors for Covariant Description of Magnetic Connectivity in the Solar Corona

NASA Technical Reports Server (NTRS)

Titov, V. S.

2007-01-01

The study of magnetic connectivity in the solar corona reveals a need to generalize the field line mapping technique to arbitrary geometry of the boundaries and systems of coordinates. Indeed, the global description of the connectivity in the corona requires the use of the photospheric and solar wind boundaries. Both are closed surfaces and therefore do not admit a global regular system of coordinates. At least two overlapping regular systems of coordinates for each of the boundaries are necessary in this case to avoid spherical-pole-like singularities in the coordinates of the footpoints. This implies that the basic characteristic of magnetic connectivity-the squashing degree or factor Q of elemental flux tubes, according to Titov and coworkers-must be rewritten in covariant form. Such a covariant expression of Q is derived in this work. The derived expression is very flexible and highly efficient for describing the global magnetic connectivity in the solar corona. In addition, a general expression for a new characteristic Q1, which defines a squashing of the flux tubes in the directions perpendicular to the field lines, is determined. This new quantity makes it possible to filter out the quasi-separatrix layers whose large values of Q are caused by a projection effect at the field lines nearly touching the photosphere. Thus, the value Q1 provides a much more precise description of the volumetric properties of the magnetic field structure. The difference between Q and Q1 is illustrated by comparing their distributions for two configurations, one of which is the Titov-Demoulin model of a twisted magnetic field.

Measurements of experimental precision for trials with cowpea (Vigna unguiculata L. Walp.) genotypes.

PubMed

Teodoro, P E; Torres, F E; Santos, A D; Corrêa, A M; Nascimento, M; Barroso, L M A; Ceccon, G

2016-05-09

The aim of this study was to evaluate the suitability of statistics as experimental precision degree measures for trials with cowpea (Vigna unguiculata L. Walp.) genotypes. Cowpea genotype yields were evaluated in 29 trials conducted in Brazil between 2005 and 2012. The genotypes were evaluated with a randomized block design with four replications. Ten statistics that were estimated for each trial were compared using descriptive statistics, Pearson correlations, and path analysis. According to the class limits established, selective accuracy and F-test values for genotype, heritability, and the coefficient of determination adequately estimated the degree of experimental precision. Using these statistics, 86.21% of the trials had adequate experimental precision. Selective accuracy and the F-test values for genotype, heritability, and the coefficient of determination were directly related to each other, and were more suitable than the coefficient of variation and the least significant difference (by the Tukey test) to evaluate experimental precision in trials with cowpea genotypes.

Precision experiments on mirror transitions at Notre Dame

NASA Astrophysics Data System (ADS)

Brodeur, Maxime; TwinSol Collaboration

2016-09-01

Thanks to extensive experimental efforts that led to a precise determination of important experimental quantities of superallowed pure Fermi transitions, we now have a very precise value for Vud that leads to a stringent test of the CKM matrix unitarity. Despite this achievement, measurements in other systems remain relevant as conflicting results could uncover unknown systematic effects or even new physics. One such system is the superallowed mixed transition, which can help refine theoretical corrections used for pure Fermi transitions and improve the accuracy of Vud. However, as a corrected Ft-value determination from these systems requires the more challenging determination of the Fermi Gamow-Teller mixing ratio, only five transitions, spreading from 19Ne to 37Ar, are currently fully characterized. To rectify the situation, an experimental program on precision experiment of mirror transitions that includes precision half-life measurements, and in the future, the determination of the Fermi Gamow-Teller mixing ratio, has started at the University of Notre Dame. This work is supported in part by the National Science Foundation.

Precision Half-life Measurement of 25Al

NASA Astrophysics Data System (ADS)

Long, Jacob; Ahn, Tan; Allen, Jacob; Bardayan, Daniel; Becchetti, Fredrich; Blankstein, Drew; Brodeur, Maxime; Burdette, Daniel; Frentz, Bryce; Hall, Matthew; Kelly, James; Kolata, James; O'Malley, Patrick; Schultz, Bradley; Strauss, Sabrina; Valverde, Adrian; TwinSol Collaboration

2017-09-01

In recent years, precision measurements have led to considerable advances in several areas of physics, including fundamental symmetry. Precise determination of ft values for superallowed mixed transitions between mirror nuclides could provide an avenue to test the theoretical corrections used to extract the Vud matrix element from superallowed pure Fermi transitions. Calculation of the ft value requires the half-life, branching ratio, and Q value. 25Al decay is of particular interest as its half-life is derived from a series of conflicting measurements, and the largest uncertainty on the ft value stems from the half-life uncertainty. The life-time was determined by the β counting of implanted 25Al on a Ta foil that was removed from the beam for counting. The 25Al beam was produced by a transfer reaction and separated by the TwinSol facility of the Nuclear Science Laboratory of the University of Notre Dame. The 25Al results will be presented with preliminary results of more recent half-life measurements. The National Science Foundation.

The theory precision analyse of RFM localization of satellite remote sensing imagery

NASA Astrophysics Data System (ADS)

Zhang, Jianqing; Xv, Biao

2009-11-01

The tradition method of detecting precision of Rational Function Model(RFM) is to make use of a great deal check points, and it calculates mean square error through comparing calculational coordinate with known coordinate. This method is from theory of probability, through a large number of samples to statistic estimate value of mean square error, we can think its estimate value approaches in its true when samples are well enough. This paper is from angle of survey adjustment, take law of propagation of error as the theory basis, and it calculates theory precision of RFM localization. Then take the SPOT5 three array imagery as experiment data, and the result of traditional method and narrated method in the paper are compared, while has confirmed tradition method feasible, and answered its theory precision question from the angle of survey adjustment.

O-Acetyl Side-Chains in Monosaccharides: Redundant NMR Spin-Couplings and Statistical Models for Acetate Ester Conformational Analysis.

PubMed

Turney, Toby; Pan, Qingfeng; Sernau, Luke; Carmichael, Ian; Zhang, Wenhui; Wang, Xiaocong; Woods, Robert J; Serianni, Anthony S

2017-01-12

α- and β-d-glucopyranose monoacetates 1-3 were prepared with selective 13 C enrichment in the O-acetyl side-chain, and ensembles of 13 C- 1 H and 13 C- 13 C NMR spin-couplings (J-couplings) were measured involving the labeled carbons. Density functional theory (DFT) was applied to a set of model structures to determine which J-couplings are sensitive to rotation of the ester bond θ. Eight J-couplings ( 1 J CC , 2 J CH , 2 J CC , 3 J CH , and 3 J CC ) were found to be sensitive to θ, and four equations were parametrized to allow quantitative interpretations of experimental J-values. Inspection of J-coupling ensembles in 1-3 showed that O-acetyl side-chain conformation depends on molecular context, with flanking groups playing a dominant role in determining the properties of θ in solution. To quantify these effects, ensembles of J-couplings containing four values were used to determine the precision and accuracy of several 2-parameter statistical models of rotamer distributions across θ in 1-3. The statistical method used to generate these models has been encoded in a newly developed program, MA'AT, which is available for public use. These models were compared to O-acetyl side-chain behavior observed in a representative sample of crystal structures, and in molecular dynamics (MD) simulations of O-acetylated model structures. While the functional form of the model had little effect on the precision of the calculated mean of θ in 1-3, platykurtic models were found to give more precise estimates of the width of the distribution about the mean (expressed as circular standard deviations). Validation of these 2-parameter models to interpret ensembles of redundant J-couplings using the O-acetyl system as a test case enables future extension of the approach to other flexible elements in saccharides, such as glycosidic linkage conformation.

Math expression retrieval using an inverted index over symbol pairs

NASA Astrophysics Data System (ADS)

Stalnaker, David; Zanibbi, Richard

2015-01-01

We introduce a new method for indexing and retrieving mathematical expressions, and a new protocol for evaluating math formula retrieval systems. The Tangent search engine uses an inverted index over pairs of symbols in math expressions. Each key in the index is a pair of symbols along with their relative distance and vertical displacement within an expression. Matched expressions are ranked by the harmonic mean of the percentage of symbol pairs matched in the query, and the percentage of symbol pairs matched in the candidate expression. We have found that our method is fast enough for use in real time and finds partial matches well, such as when subexpressions are re-arranged (e.g. expressions moved from the left to the right of an equals sign) or when individual symbols (e.g. variables) differ from a query expression. In an experiment using expressions from English Wikipedia, student and faculty participants (N=20) found expressions returned by Tangent significantly more similar than those from a text-based retrieval system (Lucene) adapted for mathematical expressions. Participants provided similarity ratings using a 5-point Likert scale, evaluating expressions from both algorithms one-at-a-time in a randomized order to avoid bias from the position of hits in search result lists. For the Lucene-based system, precision for the top 1 and 10 hits averaged 60% and 39% across queries respectively, while for Tangent mean precision at 1 and 10 were 99% and 60%. A demonstration and source code are publicly available.

[Evaluation of preexposed step wedges in acceptance tests of film processing in mammography].

PubMed

Blendl, C

2003-03-01

It was tested with 5 different types of mammography films in which manner the values of "Lightspeed" (LS) and "Lightcontrast" (LC), according DIN V 6868-55 will be changed, when preexposed film strips are used, stored at different climates and spaces of time in comparison to strips, which are exposed immediately before processing. It was proved, that the value LS of preexposed film strips in general will be lowered with increasing storage time compared to freshly exposed film strips, when both strips are processed simultaneously. This drift will be enhanced with increasing rel.humidity levels during storage. The value of LC increases in general with longer storage time and higher rel.humidity levels. The tested film types have all individual drifts in LS and LC. The precision of a single measurement using preexposed film strips was established over all different types of films at in about: Delta LS=0.06 and Delta LC (%)=16% [in the borders of 2 sigma (sigma)]. This uncertainty includes solely the precision of sensitometer, densitometer, the method to establish sensitometric values and unavoidable statistical fluctuations. Even when the systematic drift of the used film type is well established, the required precision, restricted to the listed items and prescribed in DIN V 6868-55, table D.1 to determine the values of LS with Delta LS=0.039 and the values of LC with Delta LC=7.2% is overstepped in so far, that it is impossible to draw a precise conclusion from the measured values to the performance of the subsystem film and processing. If any exceeding of the dose in image receptor plane is monitored, there is no tracking possible to a misadjustment of the subsystem film and processing.

Significance of structural changes in proteins: expected errors in refined protein structures.

PubMed Central

Stroud, R. M.; Fauman, E. B.

1995-01-01

A quantitative expression key to evaluating significant structural differences or induced shifts between any two protein structures is derived. Because crystallography leads to reports of a single (or sometimes dual) position for each atom, the significance of any structural change based on comparison of two structures depends critically on knowing the expected precision of each median atomic position reported, and on extracting it for each atom, from the information provided in the Protein Data Bank and in the publication. The differences between structures of protein molecules that should be identical, and that are normally distributed, indicating that they are not affected by crystal contacts, were analyzed with respect to many potential indicators of structure precision, so as to extract, essentially by "machine learning" principles, a generally applicable expression involving the highest correlates. Eighteen refined crystal structures from the Protein Data Bank, in which there are multiple molecules in the crystallographic asymmetric unit, were selected and compared. The thermal B factor, the connectivity of the atom, and the ratio of the number of reflections to the number of atoms used in refinement correlate best with the magnitude of the positional differences between regions of the structures that otherwise would be expected to be the same. These results are embodied in a six-parameter equation that can be applied to any crystallographically refined structure to estimate the expected uncertainty in position of each atom. Structure change in a macromolecule can thus be referenced to the expected uncertainty in atomic position as reflected in the variance between otherwise identical structures with the observed values of correlated parameters. PMID:8563637

Suspension-thermal noise in spring–antispring systems for future gravitational-wave detectors

NASA Astrophysics Data System (ADS)

Harms, Jan; Mow-Lowry, Conor M.

2018-01-01

Spring–antispring systems have been investigated in the context of low-frequency seismic isolation in high-precision optical experiments. These systems provide the possibility to tune the fundamental resonance frequency to, in principle, arbitrarily low values, and at the same time maintain a compact design. It was argued though that thermal noise in spring–antispring systems would not be as small as one may naively expect from lowering the fundamental resonance frequency. In this paper, we present calculations of suspension-thermal noise for spring–antispring systems potentially relevant in future gravitational-wave detectors, i.e. the beam-balance tiltmeter, and the Roberts linkage. We find a concise expression of the suspension-thermal noise spectrum, which assumes a form very similar to the well-known expression for a simple pendulum. For systems such as the Roberts linkage foreseen as passive seismic isolation, we find that while they can provide strong seismic isolation due to a very low fundamental resonance frequency, their thermal noise is determined by the dimension of the system and is insensitive to fine-tunings of the geometry that can strongly influence the resonance frequency. By analogy, i.e. formal similarity of the equations of motion, this is true for all horizontal mechanical isolation systems with spring–antispring dynamics. This imposes strict requirements on mechanical spring–antispring systems for seismic isolation in potential future low-frequency gravitational-wave detectors as we discuss for the four main concepts, atom-interferometric, superconducting, torsion-bars, and conventional laser interferometer, and generally suggests that thermal noise needs to be evaluated carefully for high-precision experiments implementing spring–antispring dynamics.

Computer processing of Mars Odyssey THEMIS IR imaging, MGS MOLA altimetry and Mars Express stereo imaging to locate Airy-0, the Mars prime meridian reference

NASA Astrophysics Data System (ADS)

Duxbury, Thomas; Neukum, Gerhard; Smith, David E.; Christensen, Philip; Neumann, Gregory; Albee, Arden; Caplinger, Michael; Seregina, N. V.; Kirk, Randolph L.

The small crater Airy-0 was selected from Mariner 9 images to be the reference for the Mars prime meridian. Initial analyses were made in year 2000 to tie Viking Orbiter and Mars Orbiter Camera images of Airy-0 to the evolving Mars Orbiter Laser Altimeter global digital terrain model to improve the location accuracy of Airy-0. Based upon this tie and radiometric tracking of landers / rovers from earth, new expressions for the Mars spin axis direction, spin rate and prime meridian epoch value were produced to define the orientation of the Martian surface in inertial space over time. Now that the Mars Global Surveyor mission and the Mars Orbiter Laser Altimeter global digital terrain model are complete, a more exhaustive study has been performed to determine the location of Airy-0 relative to the global terrain grid. THEMIS IR image cubes of the Airy and Gale crater regions were tied to the global terrain grid using precision stereo photogrammetric image processing techniques. The Airy-0 location was determined to be within 50 meters of the currently defined IAU prime meridian, with this offset at the limiting absolute accuracy of the global terrain grid. Additional outputs of this study were a controlled multi-band photomosaic of Airy, precision alignment and geometric models of the ten THEMIS IR bands and a controlled multi-band photomosaic of Gale crater used to validate the Mars Surface Laboratory operational map products supporting their successful landing on Mars.

Precise discussion of time-reversal asymmetries in B-meson decays

DOE PAGES

Morozumi, Takuya; Okane, Hideaki; Umeeda, Hiroyuki

2015-02-26

BaBar collaboration announced that they observed time reversal (T) asymmetry through B meson system. In the experiment, time dependencies of two distinctive processes, B_ →B¯ 0 and B¯ 0 → B_ (– expresses CP value) are compared with each other. In our study, we examine event number difference of these two processes. In contrast to the BaBar asymmetry, the asymmetry of events number includes the overall normalization difference for rates. Time dependence of the asymmetry is more general and it includes terms absent in one used by BaBar collaboration. Both of the BaBar asymmetry and ours are naively thought tomore » be T-odd since two processes compared are related with flipping time direction. We investigate the time reversal transformation property of our asymmetry. Using our notation, one can see that the asymmetry is not precisely a T-odd quantity, taking into account indirect CP and CPT violation of K meson systems. The effect of ϵK is extracted and gives rise to O(10 –3) contribution. The introduced parameters are invariant under rephasing of quarks so that the coefficients of our asymmetry are expressed as phase convention independent quantities. Some combinations of the asymmetry enable us to extract parameters for wrong sign decays of B d meson, CPT violation, etc. As a result, we also study the reason why the T-even terms are allowed to contribute to the asymmetry, and find that several conditions are needed for the asymmetry to be a T-odd quantity.« less

Dynamic Blue Light-Inducible T7 RNA Polymerases (Opto-T7RNAPs) for Precise Spatiotemporal Gene Expression Control.

PubMed

Baumschlager, Armin; Aoki, Stephanie K; Khammash, Mustafa

2017-11-17

Light has emerged as a control input for biological systems due to its precise spatiotemporal resolution. The limited toolset for light control in bacteria motivated us to develop a light-inducible transcription system that is independent from cellular regulation through the use of an orthogonal RNA polymerase. Here, we present our engineered blue light-responsive T7 RNA polymerases (Opto-T7RNAPs) that show properties such as low leakiness of gene expression in the dark state, high expression strength when induced with blue light, and an inducible range of more than 300-fold. Following optimization of the system to reduce expression variability, we created a variant that returns to the inactive dark state within minutes once the blue light is turned off. This allows for precise dynamic control of gene expression, which is a key aspect for most applications using optogenetic regulation. The regulators, which only require blue light from ordinary light-emitting diodes for induction, were developed and tested in the bacterium Escherichia coli, which is a crucial cell factory for biotechnology due to its fast and inexpensive cultivation and well understood physiology and genetics. Opto-T7RNAP, with minor alterations, should be extendable to other bacterial species as well as eukaryotes such as mammalian cells and yeast in which the T7 RNA polymerase and the light-inducible Vivid regulator have been shown to be functional. We anticipate that our approach will expand the applicability of using light as an inducer for gene expression independent from cellular regulation and allow for a more reliable dynamic control of synthetic and natural gene networks.

Asymptotic solutions for the case of nearly symmetric gravitational lens systems

NASA Astrophysics Data System (ADS)

Wertz, O.; Pelgrims, V.; Surdej, J.

2012-08-01

Gravitational lensing provides a powerful tool to determine the Hubble parameter H0 from the measurement of the time delay Δt between two lensed images of a background variable source. Nevertheless, knowledge of the deflector mass distribution constitutes a hurdle. We propose in the present work interesting solutions for the case of nearly symmetric gravitational lens systems. For the case of a small misalignment between the source, the deflector and the observer, we first consider power-law (ɛ) axially symmetric models for which we derive an analytical relation between the amplification ratio and source position which is independent of the power-law slope ɛ. According to this relation, we deduce an expression for H0 also irrespective of the value ɛ. Secondly, we consider the power-law axially symmetric lens models with an external large-scale gravitational field, the shear γ, resulting in the so-called ɛ-γ models, for which we deduce simple first-order equations linking the model parameters and the lensed image positions, the latter being observable quantities. We also deduce simple relations between H0 and observables quantities only. From these equations, we may estimate the value of the Hubble parameter in a robust way. Nevertheless, comparison between the ɛ-γ and singular isothermal ellipsoid (SIE) models leads to the conclusion that these models remain most often distinct. Therefore, even for the case of a small misalignment, use of the first-order equations and precise astrometric measurements of the positions of the lensed images with respect to the centre of the deflector enables one to discriminate between these two families of models. Finally, we confront the models with numerical simulations to evaluate the intrinsic error of the first-order expressions used when deriving the model parameters under the assumption of a quasi-alignment between the source, the deflector and the observer. From these same simulations, we estimate for the case of the ɛ-γ family of models that the standard deviation affecting H0 is ? which merely reflects the adopted astrometric uncertainties on the relative image positions, typically ? arcsec. In conclusions, we stress the importance of getting very accurate measurements of the relative positions of the multiple lensed images and of the time delays for the case of nearly symmetric gravitational lens systems, in order to derive robust and precise values of the Hubble parameter.

Integrative comparison of mRNA expression patterns in breast cancers from Caucasian and Asian Americans with implications for precision medicine

PubMed Central

Wang, Jianan; He, Max M; Li, Liren; Zhang, Jinfeng

2016-01-01

Asian Americans (AS) have significantly lower incidence and mortality rates of breast cancer (BRCA) than Caucasian Americans (CA). While this racial disparity has been documented the underlying pathogenetic factors explaining it are obscure. We addressed this issue by an integrative genomics approach to compare mRNA expression between AS and CA cases of BRCA. RNA-seq data from the Cancer Genome Atlas showed that mRNA expression revealed significant differences at gene and pathway levels. Increased susceptibility and severity in CA patients were likely the result of synergistic environmental and genetic risk factors, with arachidonic acid metabolism and PPAR signaling pathways implicated in linking environmental and genetic factors. An analysis that also added eQTL data from the Genotype-Tissue Expression Project and single nucleotide polymorphism (SNP) data from the 1000 Genomes Project identified several SNPs associated with differentially expressed genes. Overall, the associations we identified may enable a more focused study of genotypic differences that may help explain the disparity in BRCA incidence and mortality rates in CA and AS populations and inform precision medicine. PMID:28069798

Predicting biomedical metadata in CEDAR: A study of Gene Expression Omnibus (GEO).

PubMed

Panahiazar, Maryam; Dumontier, Michel; Gevaert, Olivier

2017-08-01

A crucial and limiting factor in data reuse is the lack of accurate, structured, and complete descriptions of data, known as metadata. Towards improving the quantity and quality of metadata, we propose a novel metadata prediction framework to learn associations from existing metadata that can be used to predict metadata values. We evaluate our framework in the context of experimental metadata from the Gene Expression Omnibus (GEO). We applied four rule mining algorithms to the most common structured metadata elements (sample type, molecular type, platform, label type and organism) from over 1.3million GEO records. We examined the quality of well supported rules from each algorithm and visualized the dependencies among metadata elements. Finally, we evaluated the performance of the algorithms in terms of accuracy, precision, recall, and F-measure. We found that PART is the best algorithm outperforming Apriori, Predictive Apriori, and Decision Table. All algorithms perform significantly better in predicting class values than the majority vote classifier. We found that the performance of the algorithms is related to the dimensionality of the GEO elements. The average performance of all algorithm increases due of the decreasing of dimensionality of the unique values of these elements (2697 platforms, 537 organisms, 454 labels, 9 molecules, and 5 types). Our work suggests that experimental metadata such as present in GEO can be accurately predicted using rule mining algorithms. Our work has implications for both prospective and retrospective augmentation of metadata quality, which are geared towards making data easier to find and reuse. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Automated extraction of ejection fraction for quality measurement using regular expressions in Unstructured Information Management Architecture (UIMA) for heart failure.

PubMed

Garvin, Jennifer H; DuVall, Scott L; South, Brett R; Bray, Bruce E; Bolton, Daniel; Heavirland, Julia; Pickard, Steve; Heidenreich, Paul; Shen, Shuying; Weir, Charlene; Samore, Matthew; Goldstein, Mary K

2012-01-01

Left ventricular ejection fraction (EF) is a key component of heart failure quality measures used within the Department of Veteran Affairs (VA). Our goals were to build a natural language processing system to extract the EF from free-text echocardiogram reports to automate measurement reporting and to validate the accuracy of the system using a comparison reference standard developed through human review. This project was a Translational Use Case Project within the VA Consortium for Healthcare Informatics. We created a set of regular expressions and rules to capture the EF using a random sample of 765 echocardiograms from seven VA medical centers. The documents were randomly assigned to two sets: a set of 275 used for training and a second set of 490 used for testing and validation. To establish the reference standard, two independent reviewers annotated all documents in both sets; a third reviewer adjudicated disagreements. System test results for document-level classification of EF of <40% had a sensitivity (recall) of 98.41%, a specificity of 100%, a positive predictive value (precision) of 100%, and an F measure of 99.2%. System test results at the concept level had a sensitivity of 88.9% (95% CI 87.7% to 90.0%), a positive predictive value of 95% (95% CI 94.2% to 95.9%), and an F measure of 91.9% (95% CI 91.2% to 92.7%). An EF value of <40% can be accurately identified in VA echocardiogram reports. An automated information extraction system can be used to accurately extract EF for quality measurement.

Validating internal controls for quantitative plant gene expression studies.

PubMed

Brunner, Amy M; Yakovlev, Igor A; Strauss, Steven H

2004-08-18

Real-time reverse transcription PCR (RT-PCR) has greatly improved the ease and sensitivity of quantitative gene expression studies. However, accurate measurement of gene expression with this method relies on the choice of a valid reference for data normalization. Studies rarely verify that gene expression levels for reference genes are adequately consistent among the samples used, nor compare alternative genes to assess which are most reliable for the experimental conditions analyzed. Using real-time RT-PCR to study the expression of 10 poplar (genus Populus) housekeeping genes, we demonstrate a simple method for determining the degree of stability of gene expression over a set of experimental conditions. Based on a traditional method for analyzing the stability of varieties in plant breeding, it defines measures of gene expression stability from analysis of variance (ANOVA) and linear regression. We found that the potential internal control genes differed widely in their expression stability over the different tissues, developmental stages and environmental conditions studied. Our results support that quantitative comparisons of candidate reference genes are an important part of real-time RT-PCR studies that seek to precisely evaluate variation in gene expression. The method we demonstrated facilitates statistical and graphical evaluation of gene expression stability. Selection of the best reference gene for a given set of experimental conditions should enable detection of biologically significant changes in gene expression that are too small to be revealed by less precise methods, or when highly variable reference genes are unknowingly used in real-time RT-PCR experiments.

Fluctuation localization imaging-based fluorescence in situ hybridization (fliFISH) for accurate detection and counting of RNA copies in single cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cui, Yi; Hu, Dehong; Markillie, Lye Meng

Quantitative gene expression analysis in intact single cells can be achieved using single molecule- based fluorescence in situ hybridization (smFISH). This approach relies on fluorescence intensity to distinguish between true signals, emitted from an RNA copy hybridized with multiple FISH sub-probes, and background noise. Thus, the precision in smFISH is often compromised by partial or nonspecific binding of sub-probes and tissue autofluorescence, limiting its accuracy. Here we provide an accurate approach for setting quantitative thresholds between true and false signals, which relies on blinking frequencies of photoswitchable dyes. This fluctuation localization imaging-based FISH (fliFISH) uses blinking frequency patterns, emitted frommore » a transcript bound to multiple sub-probes, which are distinct from blinking patterns emitted from partial or nonspecifically bound sub-probes and autofluorescence. Using multicolor fliFISH, we identified radial gene expression patterns in mouse pancreatic islets for insulin, the transcription factor, NKX2-2, and their ratio (Nkx2-2/Ins2). These radial patterns, showing higher values in β cells at the islet core and lower values in peripheral cells, were lost in diabetic mouse islets. In summary, fliFISH provides an accurate, quantitative approach for detecting and counting true RNA copies and rejecting false signals by their distinct blinking frequency patterns, laying the foundation for reliable single-cell transcriptomics.« less

NOMINAL VALUES FOR SELECTED SOLAR AND PLANETARY QUANTITIES: IAU 2015 RESOLUTION B3

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prša, Andrej; Harmanec, Petr; Torres, Guillermo

In this brief communication we provide the rationale for and the outcome of the International Astronomical Union (IAU) resolution vote at the XXIXth General Assembly in Honolulu, Hawaii, in 2015, on recommended nominal conversion constants for selected solar and planetary properties. The problem addressed by the resolution is a lack of established conversion constants between solar and planetary values and SI units: a missing standard has caused a proliferation of solar values (e.g., solar radius, solar irradiance, solar luminosity, solar effective temperature, and solar mass parameter) in the literature, with cited solar values typically based on best estimates at the timemore » of paper writing. As precision of observations increases, a set of consistent values becomes increasingly important. To address this, an IAU Working Group on Nominal Units for Stellar and Planetary Astronomy formed in 2011, uniting experts from the solar, stellar, planetary, exoplanetary, and fundamental astronomy, as well as from general standards fields to converge on optimal values for nominal conversion constants. The effort resulted in the IAU 2015 Resolution B3, passed at the IAU General Assembly by a large majority. The resolution recommends the use of nominal solar and planetary values, which are by definition exact and are expressed in SI units. These nominal values should be understood as conversion factors only, not as the true solar/planetary properties or current best estimates. Authors and journal editors are urged to join in using the standard values set forth by this resolution in future work and publications to help minimize further confusion.« less

Nominal Values for Selected Solar and Planetary Quantities: IAU 2015 Resolution B3

NASA Astrophysics Data System (ADS)

Prša, Andrej; Harmanec, Petr; Torres, Guillermo; Mamajek, Eric; Asplund, Martin; Capitaine, Nicole; Christensen-Dalsgaard, Jørgen; Depagne, Éric; Haberreiter, Margit; Hekker, Saskia; Hilton, James; Kopp, Greg; Kostov, Veselin; Kurtz, Donald W.; Laskar, Jacques; Mason, Brian D.; Milone, Eugene F.; Montgomery, Michele; Richards, Mercedes; Schmutz, Werner; Schou, Jesper; Stewart, Susan G.

2016-08-01

In this brief communication we provide the rationale for and the outcome of the International Astronomical Union (IAU) resolution vote at the XXIXth General Assembly in Honolulu, Hawaii, in 2015, on recommended nominal conversion constants for selected solar and planetary properties. The problem addressed by the resolution is a lack of established conversion constants between solar and planetary values and SI units: a missing standard has caused a proliferation of solar values (e.g., solar radius, solar irradiance, solar luminosity, solar effective temperature, and solar mass parameter) in the literature, with cited solar values typically based on best estimates at the time of paper writing. As precision of observations increases, a set of consistent values becomes increasingly important. To address this, an IAU Working Group on Nominal Units for Stellar and Planetary Astronomy formed in 2011, uniting experts from the solar, stellar, planetary, exoplanetary, and fundamental astronomy, as well as from general standards fields to converge on optimal values for nominal conversion constants. The effort resulted in the IAU 2015 Resolution B3, passed at the IAU General Assembly by a large majority. The resolution recommends the use of nominal solar and planetary values, which are by definition exact and are expressed in SI units. These nominal values should be understood as conversion factors only, not as the true solar/planetary properties or current best estimates. Authors and journal editors are urged to join in using the standard values set forth by this resolution in future work and publications to help minimize further confusion.

Infrared and Raman studies of hydrogen bonded complexes involving acetone, acetophenone and benzophenone—I. Thermodynamic constants and frequency shifts of the ν OH and ν CO stretching vibrations

NASA Astrophysics Data System (ADS)

Thijs, R.; Zeegers-Huyskens, Th.

The hydrogen bonded complexes between phenol derivatives and acetone ( I), acetophenone ( II) and benzophenone ( III) have been studied in carbon tetrachloride solution by i.r. spectroscopy. The formation constants, the enthalpies of complex formation, the Δν OH and Δν CO values have been determined. For a given phenol derivative, the thermodynamic constants and Δν OH are ordered according to I > II > III and the influence of a substituent implanted on the phenolic ring can be expressed by the Hammett relationship. The ϱ coefficients of the Hammett equation are related to the complexation enthalpies. The Badger—Bauer relation is valid for the three bases. The comparison with complexes involving other carbonyl bases allows to precise the influence of the substituent implanted on the carbonyl group. The Δν OH values obey the dual substituent parameter equation using σ I and σ +R; the ϱ I/ϱ R ratio is higher than one. The Δν CO values are shown to depend on the complexation enthalpy and on the delocalization effect of the substituents.

Determination of Vitamin E in Cereal Products and Biscuits by GC-FID.

PubMed

Pasias, Ioannis N; Kiriakou, Ioannis K; Papakonstantinou, Lila; Proestos, Charalampos

2018-01-01

A rapid, precise and accurate method for the determination of vitamin E (α-tocopherol) in cereal products and biscuits has been developed. The uncertainty was calculated for the first time, and the methods were performed for different cereal products and biscuits, characterized as "superfoods". The limits of detection and quantification were calculated. The accuracy and precision were estimated using the certified reference material FAPAS T10112QC, and the determined values were in good accordance with the certified values. The health claims according to the daily reference values for vitamin E were calculated, and the results proved that the majority of the samples examined showed a percentage daily value higher than 15%.

Determination of Vitamin E in Cereal Products and Biscuits by GC-FID

PubMed Central

Kiriakou, Ioannis K.; Papakonstantinou, Lila

2018-01-01

A rapid, precise and accurate method for the determination of vitamin E (α-tocopherol) in cereal products and biscuits has been developed. The uncertainty was calculated for the first time, and the methods were performed for different cereal products and biscuits, characterized as “superfoods”. The limits of detection and quantification were calculated. The accuracy and precision were estimated using the certified reference material FAPAS T10112QC, and the determined values were in good accordance with the certified values. The health claims according to the daily reference values for vitamin E were calculated, and the results proved that the majority of the samples examined showed a percentage daily value higher than 15%. PMID:29301245

In vivo precision of conventional and digital methods for obtaining quadrant dental impressions.

PubMed

Ender, Andreas; Zimmermann, Moritz; Attin, Thomas; Mehl, Albert

2016-09-01

Quadrant impressions are commonly used as alternative to full-arch impressions. Digital impression systems provide the ability to take these impressions very quickly; however, few studies have investigated the accuracy of the technique in vivo. The aim of this study is to assess the precision of digital quadrant impressions in vivo in comparison to conventional impression techniques. Impressions were obtained via two conventional (metal full-arch tray, CI, and triple tray, T-Tray) and seven digital impression systems (Lava True Definition Scanner, T-Def; Lava Chairside Oral Scanner, COS; Cadent iTero, ITE; 3Shape Trios, TRI; 3Shape Trios Color, TRC; CEREC Bluecam, Software 4.0, BC4.0; CEREC Bluecam, Software 4.2, BC4.2; and CEREC Omnicam, OC). Impressions were taken three times for each of five subjects (n = 15). The impressions were then superimposed within the test groups. Differences from model surfaces were measured using a normal surface distance method. Precision was calculated using the Perc90_10 value. The values for all test groups were statistically compared. The precision ranged from 18.8 (CI) to 58.5 μm (T-Tray), with the highest precision in the CI, T-Def, BC4.0, TRC, and TRI groups. The deviation pattern varied distinctly depending on the impression method. Impression systems with single-shot capture exhibited greater deviations at the tooth surface whereas high-frame rate impression systems differed more in gingival areas. Triple tray impressions displayed higher local deviation at the occlusal contact areas of upper and lower jaw. Digital quadrant impression methods achieve a level of precision, comparable to conventional impression techniques. However, there are significant differences in terms of absolute values and deviation pattern. With all tested digital impression systems, time efficient capturing of quadrant impressions is possible. The clinical precision of digital quadrant impression models is sufficient to cover a broad variety of restorative indications. Yet the precision differs significantly between the digital impression systems.

Superallowed Fermi β-Decay Studies with SCEPTAR and the 8π Gamma-Ray Spectrometer

NASA Astrophysics Data System (ADS)

Koopmans, K. A.

2005-04-01

The 8π Gamma-Ray Spectrometer, operating at TRIUMF in Vancouver Canada, is a high-precision instrument for detecting the decay radiations from exotic nuclei. In 2003, a new beta-scintillating array called SCEPTAR was installed within the 8π Spectrometer. With these two systems, precise measurements of half-lives and branching ratios can be made, specifically on certain nuclei which exhibit Superallowed Fermi 0+ → 0+ β-decay. These data can be used to determine the value of δC, an isospin symmetry-breaking (Coulomb) correction factor to good precision. As this correction factor is currently one of the leading sources of error in the unitarity test of the CKM matrix, a precise determination of its value could help to eliminate any possible "trivial" explanation of the seeming departure of current experimental data from Standard Model predictions.

Design of precise assembly equipment of large aperture optics

NASA Astrophysics Data System (ADS)

Pei, Guoqing; Xu, Xu; Xiong, Zhao; Yan, Han; Qin, Tinghai; Zhou, Hai; Yuan, Xiaodong

2017-05-01

High-energy solid-state laser is an important way to achieve laser fusion research. Laser fusion facility includes thousands of various types of large aperture optics. These large aperture optics should be assembled with high precision and high efficiency. Currently, however, the assembly of large aperture optics is by man's hand which is in low level of efficiency and labor-intensive. Here, according to the characteristics of the assembly of large aperture optics, we designed three kinds of grasping devices. Using Finite Element Method, we simulated the impact of the grasping device on the PV value and the RMS value of the large aperture optics. The structural strength of the grasping device's key part was analyzed. An experiment was performed to illustrate the reliability and precision of the grasping device. We anticipate that the grasping device would complete the assembly of large aperture optics precisely and efficiently.

Report of the IAU/IAG Working Group on cartographic coordinates and rotational elements: 2006

USGS Publications Warehouse

Seidelmann, P.K.; Archinal, B.A.; A'Hearn, M.F.; Conrad, A.; Consolmagno, G.J.; Hestroffer, D.; Hilton, J.L.; Krasinsky, G.A.; Neumann, G.; Oberst, J.; Stooke, P.; Tedesco, E.F.; Tholen, D.J.; Thomas, P.C.; Williams, I.P.

2007-01-01

Every three years the IAU/IAG Working Group on Cartographic Coordinates and Rotational Elements revises tables giving the directions of the poles of rotation and the prime meridians of the planets, satellites, minor planets, and comets. This report introduces improved values for the pole and rotation rate of Pluto, Charon, and Phoebe, the pole of Jupiter, the sizes and shapes of Saturn satellites and Charon, and the poles, rotation rates, and sizes of some minor planets and comets. A high precision realization for the pole and rotation rate of the Moon is provided. The expression for the Sun's rotation has been changed to be consistent with the planets and to account for light travel time ?? 2007 Springer Science+Business Media B.V.

Development of a Japanese version of the emotional skills and competence questionnaire.

PubMed

Toyota, Hiroshi; Morita, Taisuke; Taksic, Vladimir

2007-10-01

The present study described development of a Japanese version of the Emotional Skills and Competence Questionnaire and examined the relations of scores with those on Big Five scales of personality and self-esteem scales. The participants were 615 undergraduates. Factor analysis led to the shortened version of 24 items in three subscales. Although Cronbach alphas were low for the subscale, Manage and Regulate Emotion, values were satisfactory for the other two subscales, Express and Label Emotion and Perceive and Understand Emotion. Total scores of this version were positively correlated with score for self-esteem, Extraversion, and Openness but negatively correlated with scores on Neuroticism. This shorter Japanese versions shows suitable internal consistency and content validity, but other reliabilities and validities must be examined precisely.

QuantFusion: Novel Unified Methodology for Enhanced Coverage and Precision in Quantifying Global Proteomic Changes in Whole Tissues.

PubMed

Gunawardena, Harsha P; O'Brien, Jonathon; Wrobel, John A; Xie, Ling; Davies, Sherri R; Li, Shunqiang; Ellis, Matthew J; Qaqish, Bahjat F; Chen, Xian

2016-02-01

Single quantitative platforms such as label-based or label-free quantitation (LFQ) present compromises in accuracy, precision, protein sequence coverage, and speed of quantifiable proteomic measurements. To maximize the quantitative precision and the number of quantifiable proteins or the quantifiable coverage of tissue proteomes, we have developed a unified approach, termed QuantFusion, that combines the quantitative ratios of all peptides measured by both LFQ and label-based methodologies. Here, we demonstrate the use of QuantFusion in determining the proteins differentially expressed in a pair of patient-derived tumor xenografts (PDXs) representing two major breast cancer (BC) subtypes, basal and luminal. Label-based in-spectra quantitative peptides derived from amino acid-coded tagging (AACT, also known as SILAC) of a non-malignant mammary cell line were uniformly added to each xenograft with a constant predefined ratio, from which Ratio-of-Ratio estimates were obtained for the label-free peptides paired with AACT peptides in each PDX tumor. A mixed model statistical analysis was used to determine global differential protein expression by combining complementary quantifiable peptide ratios measured by LFQ and Ratio-of-Ratios, respectively. With minimum number of replicates required for obtaining the statistically significant ratios, QuantFusion uses the distinct mechanisms to "rescue" the missing data inherent to both LFQ and label-based quantitation. Combined quantifiable peptide data from both quantitative schemes increased the overall number of peptide level measurements and protein level estimates. In our analysis of the PDX tumor proteomes, QuantFusion increased the number of distinct peptide ratios by 65%, representing differentially expressed proteins between the BC subtypes. This quantifiable coverage improvement, in turn, not only increased the number of measurable protein fold-changes by 8% but also increased the average precision of quantitative estimates by 181% so that some BC subtypically expressed proteins were rescued by QuantFusion. Thus, incorporating data from multiple quantitative approaches while accounting for measurement variability at both the peptide and global protein levels make QuantFusion unique for obtaining increased coverage and quantitative precision for tissue proteomes. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

New target genes of MITF-induced microRNA-211 contribute to melanoma cell invasion.

PubMed

Margue, Christiane; Philippidou, Demetra; Reinsbach, Susanne E; Schmitt, Martina; Behrmann, Iris; Kreis, Stephanie

2013-01-01

The non-coding microRNAs (miRNA) have tissue- and disease-specific expression patterns. They down-regulate target mRNAs, which likely impacts on most fundamental cellular processes. Differential expression patterns of miRNAs are currently being exploited for identification of biomarkers for early disease diagnosis, prediction of progression for melanoma and other cancers and as promising drug targets, since they can easily be inhibited or replaced in a given cellular context. Before successfully manipulating miRNAs in clinical settings, their precise expression levels, endogenous functions and thus their target genes have to be determined. MiR-211, a melanocyte lineage-specific small non-coding miRNA, is located in an intron of TRPM1, a target gene of the microphtalmia-associated transcription factor (MITF). By transcriptionally up-regulating TRPM1, MITF, which is critical for both melanocyte differentiation and survival and for melanoma progression, indirectly drives the expression of miR-211. Expression of this miRNA is often reduced in melanoma samples. Here, we investigated functional roles of miR-211 by identifying and studying new target genes. We show that MITF-correlated miR-211 expression levels are mostly but not always reduced in a panel of 11 melanoma cell lines and in primary and metastatic melanoma compared to normal melanocytes and nevi, respectively. MiR-211 itself only marginally impacted on cell invasion and migration, while perturbation of some new miR-211 target genes, such as AP1S2, SOX11, IGFBP5, and SERINC3 significantly increased invasion. These results and the variable expression levels of miR-211 raise serious doubts on the value of miR-211 as a melanoma tumor-suppressing miRNA and/or as a biomarker for melanoma.

Smad, PI3K/Akt, and Wnt-dependent signaling pathways are involved in BMP-4-induced ESC self-renewal.

PubMed

Lee, Min Young; Lim, Hyun Woo; Lee, Sang Hun; Han, Ho Jae

2009-08-01

It is known that bone morphogenetic protein 4 (BMP-4) has a diverse effect on ESCs. However, its precise mechanism in mouse ESCs is not fully understood. We evaluated the effect of BMP-4 on ESC proliferation and its related signal cascades in this study. BMP-4 significantly increased the level of [(3)H]-thymidine incorporation in time- (> or =8 hours) and dose- (> or =10 ng/ml) dependent manners. Additionally, BMP-4 increased cyclin D1 and decreased p27(kip1) expression values in a time-dependent manner. The increases in BMP-4-induced [(3)H]-thymidine incorporation and cyclin D1 expression were inhibited by the BMP-4 receptor antagonist noggin. BMP-4 increased Wnt1 expression. Wnt1 expression was attenuated by Smad4 small interfering RNA (siRNA), and BMP-4-induced cyclin D1 expression was inhibited by Smad4 and Wnt1 siRNAs. BMP-4 also activated beta-catenin, which was blocked by Smad4 and Wnt1 siRNAs. In addition, BMP-4 induced Akt phosphorylation. BMP-4-induced beta-catenin activation and cyclin D1 expression were attenuated by phosphatidyl inositol 3-kinase (PI3K) siRNA and Akt inhibitor. Additionally, downregulation of Smad4, Wnt1, and PI3K expression by siRNA decreased the levels of pluripotency marker mRNAs of ESCs, including Oct4, Sox2, and FoxD3. Our results suggested that BMP-4-induced [(3)H]-thymidine incorporation was significantly attenuated by Smad4, Wnt1, and PI3K knockdown. In conclusion, BMP-4 contributed to the maintenance of cell proliferation and the pluripotent state by Smad, PI3K/Akt, and Wnt1/beta-catenin in mouse ESCs.

High Precision Determination of the β Decay QEC Value of 11C and Implications on the Tests of the Standard Model

NASA Astrophysics Data System (ADS)

Gulyuz, K.; Bollen, G.; Brodeur, M.; Bryce, R. A.; Cooper, K.; Eibach, M.; Izzo, C.; Kwan, E.; Manukyan, K.; Morrissey, D. J.; Naviliat-Cuncic, O.; Redshaw, M.; Ringle, R.; Sandler, R.; Schwarz, S.; Sumithrarachchi, C. S.; Valverde, A. A.; Villari, A. C. C.

2016-01-01

We report the determination of the QEC value of the mirror transition of 11C by measuring the atomic masses of 11C and 11B using Penning trap mass spectrometry. More than an order of magnitude improvement in precision is achieved as compared to the 2012 Atomic Mass Evaluation (Ame2012) [Chin. Phys. C 36, 1603 (2012)]. This leads to a factor of 3 improvement in the calculated F t value. Using the new value, QEC=1981.690 (61 ) keV , the uncertainty on F t is no longer dominated by the uncertainty on the QEC value. Based on this measurement, we provide an updated estimate of the Gamow-Teller to Fermi mixing ratio and standard model values of the correlation coefficients.

High Precision Determination of the β Decay Q(EC) Value of (11)C and Implications on the Tests of the Standard Model.

PubMed

Gulyuz, K; Bollen, G; Brodeur, M; Bryce, R A; Cooper, K; Eibach, M; Izzo, C; Kwan, E; Manukyan, K; Morrissey, D J; Naviliat-Cuncic, O; Redshaw, M; Ringle, R; Sandler, R; Schwarz, S; Sumithrarachchi, C S; Valverde, A A; Villari, A C C

2016-01-08

We report the determination of the Q(EC) value of the mirror transition of (11)C by measuring the atomic masses of (11)C and (11)B using Penning trap mass spectrometry. More than an order of magnitude improvement in precision is achieved as compared to the 2012 Atomic Mass Evaluation (Ame2012) [Chin. Phys. C 36, 1603 (2012)]. This leads to a factor of 3 improvement in the calculated Ft value. Using the new value, Q(EC)=1981.690(61)  keV, the uncertainty on Ft is no longer dominated by the uncertainty on the Q(EC) value. Based on this measurement, we provide an updated estimate of the Gamow-Teller to Fermi mixing ratio and standard model values of the correlation coefficients.

Range Precision of LADAR Systems

DTIC Science & Technology

2008-09-01

photodetector, which is small compared to the receiver aperture. The photodetector converts the focused optical field into an electrical signal...Range Precision of LADAR Systems DISSERTATION Steven Johnson, AFIT/DEE/ENG/08-15 DEPARTMENT OF THE AIR FORCE AIR UNIVERSITY AIR FORCE INSTITUTE OF...TECHNOLOGY Wright-Patterson Air Force Base, Ohio APPROVED FOR PUBLIC RELEASE; DISTRIBUTION UNLIMITED. The views expressed in this dissertation are those

Precision gravity studies at Cerro Prieto: a progress report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grannell, R.B.; Kroll, R.C.; Wyman, R.M.

A third and fourth year of precision gravity data collection and reduction have now been completed at the Cerro Prieto geothermal field. In summary, 66 permanently monumented stations were occupied between December and April of 1979 to 1980 and 1980 to 1981 by a LaCoste and Romberg gravity meter (G300) at least twice, with a minimum of four replicate values obtained each time. Station 20 alternate, a stable base located on Cerro Prieto volcano, was used as the reference base for the third year and all the stations were tied to this base, using four to five hour loops. Themore » field data were reduced to observed gravity values by (1) multiplication with the appropriate calibration factor; (2) removal of calculated tidal effects; (3) calculation of average values at each station, and (4) linear removal of accumulated instrumental drift which remained after carrying out the first three reductions. Following the reduction of values and calculation of gravity differences between individual stations and the base stations, standard deviations were calculated for the averaged occupation values (two to three per station). In addition, pooled variance calculations were carried out to estimate precision for the surveys as a whole.« less

Understanding disease mechanisms with models of signaling pathway activities.

PubMed

Sebastian-Leon, Patricia; Vidal, Enrique; Minguez, Pablo; Conesa, Ana; Tarazona, Sonia; Amadoz, Alicia; Armero, Carmen; Salavert, Francisco; Vidal-Puig, Antonio; Montaner, David; Dopazo, Joaquín

2014-10-25

Understanding the aspects of the cell functionality that account for disease or drug action mechanisms is one of the main challenges in the analysis of genomic data and is on the basis of the future implementation of precision medicine. Here we propose a simple probabilistic model in which signaling pathways are separated into elementary sub-pathways or signal transmission circuits (which ultimately trigger cell functions) and then transforms gene expression measurements into probabilities of activation of such signal transmission circuits. Using this model, differential activation of such circuits between biological conditions can be estimated. Thus, circuit activation statuses can be interpreted as biomarkers that discriminate among the compared conditions. This type of mechanism-based biomarkers accounts for cell functional activities and can easily be associated to disease or drug action mechanisms. The accuracy of the proposed model is demonstrated with simulations and real datasets. The proposed model provides detailed information that enables the interpretation disease mechanisms as a consequence of the complex combinations of altered gene expression values. Moreover, it offers a framework for suggesting possible ways of therapeutic intervention in a pathologically perturbed system.

Accuracy, precision, and economic efficiency for three methods of thrips (Thysanoptera: Thripidae) population density assessment.

PubMed

Sutherland, Andrew M; Parrella, Michael P

2011-08-01

Western flower thrips, Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae), is a major horticultural pest and an important vector of plant viruses in many parts of the world. Methods for assessing thrips population density for pest management decision support are often inaccurate or imprecise due to thrips' positive thigmotaxis, small size, and naturally aggregated populations. Two established methods, flower tapping and an alcohol wash, were compared with a novel method, plant desiccation coupled with passive trapping, using accuracy, precision and economic efficiency as comparative variables. Observed accuracy was statistically similar and low (37.8-53.6%) for all three methods. Flower tapping was the least expensive method, in terms of person-hours, whereas the alcohol wash method was the most expensive. Precision, expressed by relative variation, depended on location within the greenhouse, location on greenhouse benches, and the sampling week, but it was generally highest for the flower tapping and desiccation methods. Economic efficiency, expressed by relative net precision, was highest for the flower tapping method and lowest for the alcohol wash method. Advantages and disadvantages are discussed for all three methods used. If relative density assessment methods such as these can all be assumed to accurately estimate a constant proportion of absolute density, then high precision becomes the methodological goal in terms of measuring insect population density, decision making for pest management, and pesticide efficacy assessments.

Precision Modeling Of Targets Using The VALUE Computer Program

NASA Astrophysics Data System (ADS)

Hoffman, George A.; Patton, Ronald; Akerman, Alexander

1989-08-01

The 1976-vintage LASERX computer code has been augmented to produce realistic electro-optical images of targets. Capabilities lacking in LASERX but recently incorporated into its VALUE successor include: •Shadows cast onto the ground •Shadows cast onto parts of the target •See-through transparencies (e.g.,canopies) •Apparent images due both to atmospheric scattering and turbulence •Surfaces characterized by multiple bi-directional reflectance functions VALUE provides not only realistic target modeling by its precise and comprehensive representation of all target attributes, but additionally VALUE is very user friendly. Specifically, setup of runs is accomplished by screen prompting menus in a sequence of queries that is logical to the user. VALUE also incorporates the Optical Encounter (OPEC) software developed by Tricor Systems,Inc., Elgin, IL.

Accuracy and precision of occlusal contacts of stereolithographic casts mounted by digital interocclusal registrations.

PubMed

Krahenbuhl, Jason T; Cho, Seok-Hwan; Irelan, Jon; Bansal, Naveen K

2016-08-01

Little peer-reviewed information is available regarding the accuracy and precision of the occlusal contact reproduction of digitally mounted stereolithographic casts. The purpose of this in vitro study was to evaluate the accuracy and precision of occlusal contacts among stereolithographic casts mounted by digital occlusal registrations. Four complete anatomic dentoforms were arbitrarily mounted on a semi-adjustable articulator in maximal intercuspal position and served as the 4 different simulated patients (SP). A total of 60 digital impressions and digital interocclusal registrations were made with a digital intraoral scanner to fabricate 15 sets of mounted stereolithographic (SLA) definitive casts for each dentoform. After receiving a total of 60 SLA casts, polyvinyl siloxane (PVS) interocclusal records were made for each set. The occlusal contacts for each set of SLA casts were measured by recording the amount of light transmitted through the interocclusal records. To evaluate the accuracy between the SP and their respective SLA casts, the areas of actual contact (AC) and near contact (NC) were calculated. For precision analysis, the coefficient of variation (CoV) was used. The data was analyzed with t tests for accuracy and the McKay and Vangel test for precision (α=.05). The accuracy analysis showed a statistically significant difference between the SP and the SLA cast of each dentoform (P<.05). For the AC in all dentoforms, a significant increase was found in the areas of actual contact of SLA casts compared with the contacts present in the SP (P<.05). Conversely, for the NC in all dentoforms, a significant decrease was found in the occlusal contact areas of the SLA casts compared with the contacts in the SP (P<.05). The precision analysis demonstrated the different CoV values between AC (5.8 to 8.8%) and NC (21.4 to 44.6%) of digitally mounted SLA casts, indicating that the overall precision of the SLA cast was low. For the accuracy evaluation, statistically significant differences were found between the occlusal contacts of all digitally mounted SLA casts groups, with an increase in AC values and a decrease in NC values. For the precision assessment, the CoV values of the AC and NC showed the digitally articulated cast's inability to reproduce the uniform occlusal contacts. Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Precision-cut liver slices as a model for the early onset of liver fibrosis to test antifibrotic drugs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Westra, Inge M.; Oosterhuis, Dorenda; Groothuis, Geny M.M.

Induction of fibrosis during prolonged culture of precision-cut liver slices (PCLS) was reported. In this study, the use of rat PCLS was investigated to further characterize the mechanism of early onset of fibrosis in this model and the effects of antifibrotic compounds. Rat PCLS were incubated for 48 h, viability was assessed by ATP and gene expression of PDGF-B and TGF-β1 and the fibrosis markers Hsp47, αSma and Pcol1A1 and collagen1 protein expressions were determined. The effects of the antifibrotic drugs imatinib, sorafenib and sunitinib, PDGF-pathway inhibitors, and perindopril, valproic acid, rosmarinic acid, tetrandrine and pirfenidone, TGFβ-pathway inhibitors, were determined.more » After 48 h of incubation, viability of the PCLS was maintained and gene expression of PDGF-B was increased while TGF-β1 was not changed. Hsp47, αSma and Pcol1A1 gene expressions were significantly elevated in PCLS after 48 h, which was further increased by PDGF-BB and TGF-β1. The increased gene expression of fibrosis markers was inhibited by all three PDGF-inhibitors, while TGFβ-inhibitors showed marginal effects. The protein expression of collagen 1 was inhibited by imatinib, perindopril, tetrandrine and pirfenidone. In conclusion, the increased gene expression of PDGF-B and the down-regulation of fibrosis markers by PDGF-pathway inhibitors, together with the absence of elevated TGF-β1 gene expression and the limited effect of the TGFβ-pathway inhibitors, indicated the predominance of the PDGF pathway in the early onset of fibrosis in PCLS. PCLS appear a useful model for research of the early onset of fibrosis and for testing of antifibrotic drugs acting on the PDGF pathway. - Highlights: • During culture, fibrosis markers increased in precision-cut liver slices (PCLS). • Gene expression of PDGF-β was increased, while TGFβ was not changed in rat PCLS. • PDGF-pathway inhibitors down-regulated this increase of fibrosis markers. • TGFβ-pathway inhibitors had only minor effects on fibrosis markers. • Rat PCLS can be used to study the early onset of fibrosis.« less

The Development of Emotional Face Processing during Childhood

ERIC Educational Resources Information Center

Batty, Magali; Taylor, Margot J.

2006-01-01

Our facial expressions give others the opportunity to access our feelings, and constitute an important nonverbal tool for communication. Many recent studies have investigated emotional perception in adults, and our knowledge of neural processes involved in emotions is increasingly precise. Young children also use faces to express their internal…

Six Functions of Conducting: A New Foundation for Music Educators

ERIC Educational Resources Information Center

Gumm, Alan J.

2012-01-01

This article poses six functions of conducting as a new foundation for music educators. Two traditional functions focus on music: the mechanical precision function indicates beat, tempo, meter, rhythm, cues, entrances and cutoff releases, and the expressive function indicates dynamics and other expressive characteristics interpreted in a score.…

Developing Critical Thinking Skills and Improving Expressive Language through Creative Writing.

ERIC Educational Resources Information Center

Goodman, Harriet E.

A practicum was conducted to develop critical thinking and improve expression through creative written language utilizing precision teaching as an evaluation of student performance. Six students (grades second through sixth) with low idea generation and few organization skills were trained by three teachers and a teacher advisor using…

Terminology of Sexuality Expressions that Exclude Penetration: A Literature Review

ERIC Educational Resources Information Center

Menn, Mindy; Goodson, Patricia; Pruitt, Buzz; Peck-Parrott, Kelli

2011-01-01

Precise terminology is paramount in sexuality education. Most sexuality research focuses on the dichotomous concepts of sexual intercourse and virginity, yet there are many expressions of sexuality classified as neither. The purpose of this literature review is to identify and examine the various terms and definitions describing sexuality…

Validation of PCR methods for quantitation of genetically modified plants in food.

PubMed

Hübner, P; Waiblinger, H U; Pietsch, K; Brodmann, P

2001-01-01

For enforcement of the recently introduced labeling threshold for genetically modified organisms (GMOs) in food ingredients, quantitative detection methods such as quantitative competitive (QC-PCR) and real-time PCR are applied by official food control laboratories. The experiences of 3 European food control laboratories in validating such methods were compared to describe realistic performance characteristics of quantitative PCR detection methods. The limit of quantitation (LOQ) of GMO-specific, real-time PCR was experimentally determined to reach 30-50 target molecules, which is close to theoretical prediction. Starting PCR with 200 ng genomic plant DNA, the LOQ depends primarily on the genome size of the target plant and ranges from 0.02% for rice to 0.7% for wheat. The precision of quantitative PCR detection methods, expressed as relative standard deviation (RSD), varied from 10 to 30%. Using Bt176 corn containing test samples and applying Bt176 specific QC-PCR, mean values deviated from true values by -7to 18%, with an average of 2+/-10%. Ruggedness of real-time PCR detection methods was assessed in an interlaboratory study analyzing commercial, homogeneous food samples. Roundup Ready soybean DNA contents were determined in the range of 0.3 to 36%, relative to soybean DNA, with RSDs of about 25%. Taking the precision of quantitative PCR detection methods into account, suitable sample plans and sample sizes for GMO analysis are suggested. Because quantitative GMO detection methods measure GMO contents of samples in relation to reference material (calibrants), high priority must be given to international agreements and standardization on certified reference materials.

Estimation of the uncertainty of analyte concentration from the measurement uncertainty.

PubMed

Brown, Simon; Cooke, Delwyn G; Blackwell, Leonard F

2015-09-01

Ligand-binding assays, such as immunoassays, are usually analysed using standard curves based on the four-parameter and five-parameter logistic models. An estimate of the uncertainty of an analyte concentration obtained from such curves is needed for confidence intervals or precision profiles. Using a numerical simulation approach, it is shown that the uncertainty of the analyte concentration estimate becomes significant at the extremes of the concentration range and that this is affected significantly by the steepness of the standard curve. We also provide expressions for the coefficient of variation of the analyte concentration estimate from which confidence intervals and the precision profile can be obtained. Using three examples, we show that the expressions perform well.

Clinical Utility of a Precision Medicine Test Evaluating Outpatients with Suspected Obstructive Coronary Artery Disease.

PubMed

Ladapo, Joseph A; Budoff, Matt; Sharp, David; Zapien, Michael; Huang, Lin; Maniet, Bruce; Herman, Lee; Monane, Mark

2017-04-01

Identifying patients with obstructive coronary artery disease can be challenging for primary care physicians. Advances in precision medicine may help augment clinical tools and redefine the paradigm for evaluating coronary artery disease in the outpatient setting. A blood-based age/sex/gene expression score (ASGES) incorporating key features of precision medicine has shown clinical validity with a 96% negative predictive value and 89% sensitivity in estimating a symptomatic patient's current likelihood of obstructive coronary artery disease. To better characterize the clinical utility of the ASGES and measure its impact on clinician decision-making, a community-based registry was established. The prospective PRESET Registry (NCT01677156) enrolled stable, nonacute adult patients presenting with typical or atypical symptoms suggestive of obstructive coronary artery disease from 21 US primary care practices from August 2012 to August 2014. Demographics, clinical characteristics, and ASGES results (predefined as low [ASGES ≤15] or elevated [ASGES >15]) were collected, as were referrals to Cardiology or further functional/anatomic cardiac testing after ASGES testing. Patients were followed for 1 year post ASGES testing. Among the 566-patient cohort (median age 56 years), clinicians referred 26/252 (10%) of patients with low scores vs 137/314 (44%) of patients with elevated scores to Cardiology or advanced cardiac testing for further evaluation (unadjusted odds ratio 0.15, P <.0001; adjusted odds ratio after accounting for clinical covariates = 0.18, P <.0001). Data on 84 patients referred for advanced cardiac testing showed abnormal findings in 0 of 13 (0%) low ASGES and 10 of 71 (14%) elevated ASGES patients. Major adverse cardiovascular events and revascularization were noted in 3/252 (1.2%) patients with low ASGES and 14/314 (4.5%) patients with elevated ASGES score (P <.03). In this community-based cardiovascular registry, the ASGES demonstrated clinical utility in the evaluation of patients with suspected obstructive coronary artery disease. Low-score patients were less likely to undergo cardiac referral, were unlikely to have positive findings on further cardiac work-up, and had a low rate of adverse cardiovascular events in 1-year follow-up. Our work provides evidence supporting the value of using precision medicine in the delivery of cardiovascular care. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Principles of precision medicine in stroke.

PubMed

Hinman, Jason D; Rost, Natalia S; Leung, Thomas W; Montaner, Joan; Muir, Keith W; Brown, Scott; Arenillas, Juan F; Feldmann, Edward; Liebeskind, David S

2017-01-01

The era of precision medicine has arrived and conveys tremendous potential, particularly for stroke neurology. The diagnosis of stroke, its underlying aetiology, theranostic strategies, recurrence risk and path to recovery are populated by a series of highly individualised questions. Moreover, the phenotypic complexity of a clinical diagnosis of stroke makes a simple genetic risk assessment only partially informative on an individual basis. The guiding principles of precision medicine in stroke underscore the need to identify, value, organise and analyse the multitude of variables obtained from each individual to generate a precise approach to optimise cerebrovascular health. Existing data may be leveraged with novel technologies, informatics and practical clinical paradigms to apply these principles in stroke and realise the promise of precision medicine. Importantly, precision medicine in stroke will only be realised once efforts to collect, value and synthesise the wealth of data collected in clinical trials and routine care starts. Stroke theranostics, the ultimate vision of synchronising tailored therapeutic strategies based on specific diagnostic data, demand cerebrovascular expertise on big data approaches to clinically relevant paradigms. This review considers such challenges and delineates the principles on a roadmap for rational application of precision medicine to stroke and cerebrovascular health. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

METHODS OF DEALING WITH VALUES BELOW THE LIMIT OF DETECTION USING SAS

EPA Science Inventory

Due to limitations of chemical analysis procedures, small values cannot be precisely measured. These values are said to be below the limit of detection (LOD). In statistical analyses, these values are often censored and substituted with a constant value, such as half the LOD,...

HALO--a Java framework for precise transcript half-life determination.

PubMed

Friedel, Caroline C; Kaufmann, Stefanie; Dölken, Lars; Zimmer, Ralf

2010-05-01

Recent improvements in experimental technologies now allow measurements of de novo transcription and/or RNA decay at whole transcriptome level and determination of precise transcript half-lives. Such transcript half-lives provide important insights into the regulation of biological processes and the relative contributions of RNA decay and de novo transcription to differential gene expression. In this article, we present HALO (Half-life Organizer), the first software for the precise determination of transcript half-lives from measurements of RNA de novo transcription or decay determined with microarrays or RNA-seq. In addition, methods for quality control, filtering and normalization are supplied. HALO provides a graphical user interface, command-line tools and a well-documented Java application programming interface (API). Thus, it can be used both by biologists to determine transcript half-lives fast and reliably with the provided user interfaces as well as software developers integrating transcript half-life analysis into other gene expression profiling pipelines. Source code, executables and documentation are available at http://www.bio.ifi.lmu.de/software/halo.

Regulation of alternative splicing at the single-cell level.

PubMed

Faigenbloom, Lior; Rubinstein, Nimrod D; Kloog, Yoel; Mayrose, Itay; Pupko, Tal; Stein, Reuven

2015-12-28

Alternative splicing is a key cellular mechanism for generating distinct isoforms, whose relative abundances regulate critical cellular processes. It is therefore essential that inclusion levels of alternative exons be tightly regulated. However, how the precision of inclusion levels among individual cells is governed is poorly understood. Using single-cell gene expression, we show that the precision of inclusion levels of alternative exons is determined by the degree of evolutionary conservation at their flanking intronic regions. Moreover, the inclusion levels of alternative exons, as well as the expression levels of the transcripts harboring them, also contribute to this precision. We further show that alternative exons whose inclusion levels are considerably changed during stem cell differentiation are also subject to this regulation. Our results imply that alternative splicing is coordinately regulated to achieve accuracy in relative isoform abundances and that such accuracy may be important in determining cell fate. © 2015 The Authors. Published under the terms of the CC BY 4.0 license.

Repression by PRDM13 is critical for generating precision in neuronal identity

PubMed Central

Kollipara, Rahul K; Ma, Zhenzhong; Borromeo, Mark D; Chang, Joshua C

2017-01-01

The mechanisms that activate some genes while silencing others are critical to ensure precision in lineage specification as multipotent progenitors become restricted in cell fate. During neurodevelopment, these mechanisms are required to generate the diversity of neuronal subtypes found in the nervous system. Here we report interactions between basic helix-loop-helix (bHLH) transcriptional activators and the transcriptional repressor PRDM13 that are critical for specifying dorsal spinal cord neurons. PRDM13 inhibits gene expression programs for excitatory neuronal lineages in the dorsal neural tube. Strikingly, PRDM13 also ensures a battery of ventral neural tube specification genes such as Olig1, Olig2 and Prdm12 are excluded dorsally. PRDM13 does this via recruitment to chromatin by multiple neural bHLH factors to restrict gene expression in specific neuronal lineages. Together these findings highlight the function of PRDM13 in repressing the activity of bHLH transcriptional activators that together are required to achieve precise neuronal specification during mouse development. PMID:28850031

Myocardial blood flow quantification by Rb-82 cardiac PET/CT: A detailed reproducibility study between two semi-automatic analysis programs.

PubMed

Dunet, Vincent; Klein, Ran; Allenbach, Gilles; Renaud, Jennifer; deKemp, Robert A; Prior, John O

2016-06-01

Several analysis software packages for myocardial blood flow (MBF) quantification from cardiac PET studies exist, but they have not been compared using concordance analysis, which can characterize precision and bias separately. Reproducible measurements are needed for quantification to fully develop its clinical potential. Fifty-one patients underwent dynamic Rb-82 PET at rest and during adenosine stress. Data were processed with PMOD and FlowQuant (Lortie model). MBF and myocardial flow reserve (MFR) polar maps were quantified and analyzed using a 17-segment model. Comparisons used Pearson's correlation ρ (measuring precision), Bland and Altman limit-of-agreement and Lin's concordance correlation ρc = ρ·C b (C b measuring systematic bias). Lin's concordance and Pearson's correlation values were very similar, suggesting no systematic bias between software packages with an excellent precision ρ for MBF (ρ = 0.97, ρc = 0.96, C b = 0.99) and good precision for MFR (ρ = 0.83, ρc = 0.76, C b = 0.92). On a per-segment basis, no mean bias was observed on Bland-Altman plots, although PMOD provided slightly higher values than FlowQuant at higher MBF and MFR values (P < .0001). Concordance between software packages was excellent for MBF and MFR, despite higher values by PMOD at higher MBF values. Both software packages can be used interchangeably for quantification in daily practice of Rb-82 cardiac PET.

Value-Expressive Volunteer Motivation and Volunteering by Older Adults: Relationships With Religiosity and Spirituality.

PubMed

Okun, Morris A; O'Rourke, Holly P; Keller, Brian; Johnson, Kathryn A; Enders, Craig

2015-11-01

This study investigates the interplay among religiosity, spirituality, value-expressive volunteer motivation, and volunteering. We examined religiosity and spirituality as predictors of value-expressive volunteer motivation and volunteering and whether religiosity moderated the relations between (a) spirituality and value-expressive volunteer motivation and (b) value-expressive volunteer motivation and volunteering. After applying multiple imputation procedures to data from the Wisconsin Longitudinal Study among participants 64-67 years old who survived beyond 2004 (N = 8,148), we carried out regression analyses to predict value-expressive volunteer motivation and volunteering from religiosity and spirituality controlling for demographic variables, physical, emotional, and cognitive health, health risk behaviors, and personality traits. Both religiosity and spirituality were significant (p < .001) positive predictors of value-expressive volunteer motivation. Value-expressive volunteer motivation and religiosity were significant (p < .001) positive predictors, whereas spirituality was a significant (p < .001) negative predictor, of volunteering. Religiosity amplified the relation between value-expressive volunteer motivation and volunteering (p < .05) but did not moderate the relation between spirituality and value-expressive volunteer motivation (p > .45). Religiosity may provide the way, and value-expressive volunteer motivation the will, to volunteer. The implications of our findings for the forecasted shortage of older volunteers are discussed. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Precision Branching Ratio Measurement for the Superallowed β+ Emitter Ga62 and Isospin-Symmetry-Breaking Corrections in A≥62 Nuclei

NASA Astrophysics Data System (ADS)

Hyland, B.; Svensson, C. E.; Ball, G. C.; Leslie, J. R.; Achtzehn, T.; Albers, D.; Andreoiu, C.; Bricault, P.; Churchman, R.; Cross, D.; Dombsky, M.; Finlay, P.; Garrett, P. E.; Geppert, C.; Grinyer, G. F.; Hackman, G.; Hanemaayer, V.; Lassen, J.; Lavoie, J. P.; Melconian, D.; Morton, A. C.; Pearson, C. J.; Pearson, M. R.; Phillips, A. A.; Schumaker, M. A.; Smith, M. B.; Towner, I. S.; Valiente-Dobón, J. J.; Wendt, K.; Zganjar, E. F.

2006-09-01

A high-precision branching ratio measurement for the superallowed β+ decay of Ga62 was performed at the Isotope Separator and Accelerator radioactive ion beam facility. Nineteen γ rays emitted following β+ decay of Ga62 were identified, establishing the dominant superallowed branching ratio to be (99.861±0.011)%. Combined with recent half-life and Q-value measurements, this branching ratio yields a superallowed ft value of 3075.6±1.4s for Ga62 decay. These results demonstrate the feasibility of high-precision superallowed branching ratio measurements in the A≥62 mass region and provide the first stringent tests of the large isospin-symmetry-breaking effects predicted for these decays.

Hardware accuracy counters for application precision and quality feedback

DOE Office of Scientific and Technical Information (OSTI.GOV)

de Paula Rosa Piga, Leonardo; Majumdar, Abhinandan; Paul, Indrani

Methods, devices, and systems for capturing an accuracy of an instruction executing on a processor. An instruction may be executed on the processor, and the accuracy of the instruction may be captured using a hardware counter circuit. The accuracy of the instruction may be captured by analyzing bits of at least one value of the instruction to determine a minimum or maximum precision datatype for representing the field, and determining whether to adjust a value of the hardware counter circuit accordingly. The representation may be output to a debugger or logfile for use by a developer, or may be outputmore » to a runtime or virtual machine to automatically adjust instruction precision or gating of portions of the processor datapath.« less

Validating internal controls for quantitative plant gene expression studies

PubMed Central

Brunner, Amy M; Yakovlev, Igor A; Strauss, Steven H

2004-01-01

Background Real-time reverse transcription PCR (RT-PCR) has greatly improved the ease and sensitivity of quantitative gene expression studies. However, accurate measurement of gene expression with this method relies on the choice of a valid reference for data normalization. Studies rarely verify that gene expression levels for reference genes are adequately consistent among the samples used, nor compare alternative genes to assess which are most reliable for the experimental conditions analyzed. Results Using real-time RT-PCR to study the expression of 10 poplar (genus Populus) housekeeping genes, we demonstrate a simple method for determining the degree of stability of gene expression over a set of experimental conditions. Based on a traditional method for analyzing the stability of varieties in plant breeding, it defines measures of gene expression stability from analysis of variance (ANOVA) and linear regression. We found that the potential internal control genes differed widely in their expression stability over the different tissues, developmental stages and environmental conditions studied. Conclusion Our results support that quantitative comparisons of candidate reference genes are an important part of real-time RT-PCR studies that seek to precisely evaluate variation in gene expression. The method we demonstrated facilitates statistical and graphical evaluation of gene expression stability. Selection of the best reference gene for a given set of experimental conditions should enable detection of biologically significant changes in gene expression that are too small to be revealed by less precise methods, or when highly variable reference genes are unknowingly used in real-time RT-PCR experiments. PMID:15317655

Toward precise QEC values for the superallowed 0+→0+ β decays of T=2 nuclides: The masses of Na20, Al24, P28, and Cl32

NASA Astrophysics Data System (ADS)

Wrede, C.; Clark, J. A.; Deibel, C. M.; Faestermann, T.; Hertenberger, R.; Parikh, A.; Wirth, H.-F.; Bishop, S.; Chen, A. A.; Eppinger, K.; García, A.; Krücken, R.; Lepyoshkina, O.; Rugel, G.; Setoodehnia, K.

2010-05-01

High-precision measurements of superallowed 0+→0+ β decays of T=2 nuclides such as Mg20, Si24, S28, and Ar32 can contribute to searches for physics beyond the standard model of particle physics if the QEC values are accurate to a few keV or better. As a step toward providing precise QEC values for these decays, the ground-state masses of the respective daughter nuclei Na20, Al24, P28, and Cl32 have been determined by measuring the (He3,t) reactions leading to them with the Ar36(He3,t)K36 reaction as a calibration. A quadrupole-dipole-dipole-dipole (Q3D) magnetic spectrograph was used together with thin ion-implanted carbon-foil targets of Ne20, Mg24, Si28, S32, and Ar36. The masses of Na20 and Cl32 are found to be in good agreement with the values from the 2003 Atomic Mass Evaluation (AME03) [G. Audi, A. H. Wapstra, and C. Thibault, Nucl. Phys. ANUPABL0375-947410.1016/j.nuclphysa.2003.11.003 729, 337 (2003)], and the precision has been improved by a factor of 6 in both cases. The masses of Al24 and P28 are found to be higher than the values from AME03 by 9.5 keV (3.2σ) and 11.5 keV (3.6σ), respectively, and the precision has been improved by a factor of 2.5 in both cases. The new Cl32 mass is used together with the excitation energy of its lowest T=2 level and the mass of Ar32 to derive an improved superallowed QEC value of 6087.3(22) keV for this case. The effects on quantities related to standard-model tests including the β-ν correlation coefficient a and the isospin-symmetry-breaking correction δC are examined for the A=32 case.

How precise can atoms of a nanocluster be located in 3D using a tilt series of scanning transmission electron microscopy images?

PubMed

Alania, M; De Backer, A; Lobato, I; Krause, F F; Van Dyck, D; Rosenauer, A; Van Aert, S

2017-10-01

In this paper, we investigate how precise atoms of a small nanocluster can ultimately be located in three dimensions (3D) from a tilt series of images acquired using annular dark field (ADF) scanning transmission electron microscopy (STEM). Therefore, we derive an expression for the statistical precision with which the 3D atomic position coordinates can be estimated in a quantitative analysis. Evaluating this statistical precision as a function of the microscope settings also allows us to derive the optimal experimental design. In this manner, the optimal angular tilt range, required electron dose, optimal detector angles, and number of projection images can be determined. Copyright © 2016 Elsevier B.V. All rights reserved.

Omics Profiling in Precision Oncology*

PubMed Central

Yu, Kun-Hsing; Snyder, Michael

2016-01-01

Cancer causes significant morbidity and mortality worldwide, and is the area most targeted in precision medicine. Recent development of high-throughput methods enables detailed omics analysis of the molecular mechanisms underpinning tumor biology. These studies have identified clinically actionable mutations, gene and protein expression patterns associated with prognosis, and provided further insights into the molecular mechanisms indicative of cancer biology and new therapeutics strategies such as immunotherapy. In this review, we summarize the techniques used for tumor omics analysis, recapitulate the key findings in cancer omics studies, and point to areas requiring further research on precision oncology. PMID:27099341

Precise Penning trap measurements of double β-decay Q-values

NASA Astrophysics Data System (ADS)

Redshaw, M.; Brodeur, M.; Bollen, G.; Bustabad, S.; Eibach, M.; Gulyuz, K.; Izzo, C.; Lincoln, D. L.; Novario, S. J.; Ringle, R.; Sandler, R.; Schwarz, S.; Valverde, A. A.

2015-10-01

The double β-decay (ββ -decay) Q-value, defined as the mass difference between parent and daughter atoms, is an important parameter for both two-neutrino ββ -decay (2 νββ) and neutrinoless ββ -decay (0 νββ) experiments. The Q-value enters into the calculation of the phase space factors, which relate the measured ββ -decay half-life to the nuclear matrix element and, in the case of 0 νββ , the effective Majorana mass of the neutrino. In addition, the Q-value defines the total kinetic energy of the two electrons emitted in 0 νββ , corresponding to the location of the single peak that is the sought after signature of 0 νββ . Hence, it is essential to have a precise and accurate Q-value determination. Over the last decade, the Penning trap mass spectrometry community has made a significant effort to provide precise ββ -decay Q-value determinations. Here we report on recent measurements with the Low Energy Beam and Ion Trap (LEBIT) facility at the National Superconducting Cyclotron Laboratory (NSCL) of the 48Ca, 82Se, and 96Zr Q-values. These measurements complete the determination of ββ -decay Q-values for the 11 ``best'' candidates (those with Q >2 MeV). We also report on a measurement of the 78Kr double electron capture (2EC) Q-value and discuss ongoing Penning trap measurements relating to ββ -decay and 2EC. Support from NSF Contract No. PHY-1102511, and DOE Grant No. 03ER-41268.

Robotic-Arm Assisted Total Knee Arthroplasty Demonstrated Greater Accuracy and Precision to Plan Compared with Manual Techniques.

PubMed

Hampp, Emily L; Chughtai, Morad; Scholl, Laura Y; Sodhi, Nipun; Bhowmik-Stoker, Manoshi; Jacofsky, David J; Mont, Michael A

2018-05-01

This study determined if robotic-arm assisted total knee arthroplasty (RATKA) allows for more accurate and precise bone cuts and component position to plan compared with manual total knee arthroplasty (MTKA). Specifically, we assessed the following: (1) final bone cuts, (2) final component position, and (3) a potential learning curve for RATKA. On six cadaver specimens (12 knees), a MTKA and RATKA were performed on the left and right knees, respectively. Bone-cut and final-component positioning errors relative to preoperative plans were compared. Median errors and standard deviations (SDs) in the sagittal, coronal, and axial planes were compared. Median values of the absolute deviation from plan defined the accuracy to plan. SDs described the precision to plan. RATKA bone cuts were as or more accurate to plan based on nominal median values in 11 out of 12 measurements. RATKA bone cuts were more precise to plan in 8 out of 12 measurements ( p  ≤ 0.05). RATKA final component positions were as or more accurate to plan based on median values in five out of five measurements. RATKA final component positions were more precise to plan in four out of five measurements ( p  ≤ 0.05). Stacked error results from all cuts and implant positions for each specimen in procedural order showed that RATKA error was less than MTKA error. Although this study analyzed a small number of cadaver specimens, there were clear differences that separated these two groups. When compared with MTKA, RATKA demonstrated more accurate and precise bone cuts and implant positioning to plan. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Characteristic expression of fukutin in gastric cancer among atomic bomb survivors.

PubMed

Pham, Trang T B; Oue, Naohide; Yamamoto, Manabu; Fujihara, Megumu; Ishida, Teruyoshi; Mukai, Shoichiro; Sakamoto, Naoya; Sentani, Kazuhiro; Yasui, Wataru

2017-02-01

Approximately 70 years have passed since the atomic bombs were dropped on Nagasaki and Hiroshima. To elucidate potential biomarkers and possible mechanisms of radiation-induced cancer, the expression of FKTN , which encodes fukutin protein and causes Fukuyama-type congenital muscular dystrophy, was analyzed in gastric cancer (GC) tissue samples from atomic bomb survivors. Expression of cluster of differentiation (CD) 10 was also evaluated, as it has previously been observed that positive fukutin expression was frequently noted in CD10-positive GC cases. In the first cohort from Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital (Hiroshima, Japan; n=92), 102 (53%) of the GC cases were positive for fukutin. Expression of fukutin was not associated with exposure status, but was associated with CD10 expression (P=0.0001). The second cohort was from Hiroshima University Hospital (Hiroshima, Japan; n=86), and these patients were also in the Life Span Study cohort, in which atomic bomb radiation doses were precisely estimated using the DS02 system. Expression of fukutin was detected in 58 (67%) of GC cases. GC cases positive for fukutin were observed more frequently in the low dose-exposed group than in the high dose-exposed group (P=0.0001). Further studies with a larger cohort, including precise radiation dose estimation, may aid in clarifying whether fukutin could serve as a potential biomarker to define radiation-induced GC in atomic-bomb survivors.

Characteristic expression of fukutin in gastric cancer among atomic bomb survivors

PubMed Central

Pham, Trang T.B.; Oue, Naohide; Yamamoto, Manabu; Fujihara, Megumu; Ishida, Teruyoshi; Mukai, Shoichiro; Sakamoto, Naoya; Sentani, Kazuhiro; Yasui, Wataru

2017-01-01

Approximately 70 years have passed since the atomic bombs were dropped on Nagasaki and Hiroshima. To elucidate potential biomarkers and possible mechanisms of radiation-induced cancer, the expression of FKTN, which encodes fukutin protein and causes Fukuyama-type congenital muscular dystrophy, was analyzed in gastric cancer (GC) tissue samples from atomic bomb survivors. Expression of cluster of differentiation (CD) 10 was also evaluated, as it has previously been observed that positive fukutin expression was frequently noted in CD10-positive GC cases. In the first cohort from Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital (Hiroshima, Japan; n=92), 102 (53%) of the GC cases were positive for fukutin. Expression of fukutin was not associated with exposure status, but was associated with CD10 expression (P=0.0001). The second cohort was from Hiroshima University Hospital (Hiroshima, Japan; n=86), and these patients were also in the Life Span Study cohort, in which atomic bomb radiation doses were precisely estimated using the DS02 system. Expression of fukutin was detected in 58 (67%) of GC cases. GC cases positive for fukutin were observed more frequently in the low dose-exposed group than in the high dose-exposed group (P=0.0001). Further studies with a larger cohort, including precise radiation dose estimation, may aid in clarifying whether fukutin could serve as a potential biomarker to define radiation-induced GC in atomic-bomb survivors. PMID:28356981

Development of a stability-indicating UPLC method for determining olanzapine and its associated degradation products present in active pharmaceutical ingredients and pharmaceutical dosage forms.

PubMed

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.

Precision breeding for RNAi suppression of a major 4-coumarate:coenzyme A ligase gene improves cell wall saccharification from field grown sugarcane.

PubMed

Jung, Je Hyeong; Kannan, Baskaran; Dermawan, Hugo; Moxley, Geoffrey W; Altpeter, Fredy

2016-11-01

Sugarcane (Saccharum spp. hybrids) is a major feedstock for commercial bioethanol production. The recent integration of conversion technologies that utilize lignocellulosic sugarcane residues as well as sucrose from stem internodes has elevated bioethanol yields. RNAi suppression of lignin biosynthetic enzymes is a successful strategy to improve the saccharification of lignocellulosic biomass. 4-coumarate:coenzyme A ligase (4CL) is a key enzyme in the biosynthesis of phenylpropanoid metabolites, such as lignin and flavonoids. Identifying a major 4CL involved in lignin biosynthesis among multiple isoforms with functional divergence is key to manipulate lignin biosynthesis. In this study, two full length 4CL genes (Sh4CL1 and Sh4CL2) were isolated and characterized in sugarcane. Phylogenetic, expression and RNA interference (RNAi) analysis confirmed that Sh4CL1 is a major lignin biosynthetic gene. An intragenic precision breeding strategy may facilitate the regulatory approval of the genetically improved events and was used for RNAi suppression of Sh4CL1. Both, the RNAi inducing cassette and the expression cassette for the mutated ALS selection marker consisted entirely of DNA sequences from sugarcane or the sexually compatible species Sorghum bicolor. Field grown sugarcane with intragenic RNAi suppression of Sh4CL1 resulted in reduction of the total lignin content by up to 16.5 % along with altered monolignol ratios without reduction in biomass yield. Mature, field grown, intragenic sugarcane events displayed 52-76 % improved saccharification efficiency of lignocellulosic biomass compared to wild type (WT) controls. This demonstrates for the first time that an intragenic approach can add significant value to lignocellulosic feedstocks for biofuel and biochemical production.

First Results of Field Absolute Calibration of the GPS Receiver Antenna at Wuhan University.

PubMed

Hu, Zhigang; Zhao, Qile; Chen, Guo; Wang, Guangxing; Dai, Zhiqiang; Li, Tao

2015-11-13

GNSS receiver antenna phase center variations (PCVs), which arise from the non-spherical phase response of GNSS signals have to be well corrected for high-precision GNSS applications. Without using a precise antenna phase center correction (PCC) model, the estimated position of a station monument will lead to a bias of up to several centimeters. The Chinese large-scale research project "Crustal Movement Observation Network of China" (CMONOC), which requires high-precision positions in a comprehensive GPS observational network motived establishment of a set of absolute field calibrations of the GPS receiver antenna located at Wuhan University. In this paper the calibration facilities are firstly introduced and then the multipath elimination and PCV estimation strategies currently used are elaborated. The validation of estimated PCV values of test antenna are finally conducted, compared with the International GNSS Service (IGS) type values. Examples of TRM57971.00 NONE antenna calibrations from our calibration facility demonstrate that the derived PCVs and IGS type mean values agree at the 1 mm level.

Ideology and wildlands management: The case of Rondeau Provincial Park, Ontario

NASA Astrophysics Data System (ADS)

Mann, D. L.; Nelson, J. G.

1980-03-01

This is a critical examination of some of the basic concepts that have guided management of parks and related reserves, often termed wildlands. Study is focussed on Rondeau Provincial Park, Ontario, and on concepts such as wilderness, primeval forest, and the Carolinian forest. Deer culling and other management policies and practices have been based upon the idea that the highly valued sassafras, tulip, and other species of the Carolinian forest are decreasing due to browsing. Field mapping and analysis of historic vegetation records indicate that this trend is not in fact occurring. Historic research also reveals difficulties in defining the Carolinian or other perceived types of forest for management purposes. A major reassessment of ideology and management policy and practice seem to be required in Rondeau and other wildlands. Vague or general concepts such as wilderness or preservation should be strongly complemented and supported by more precise statements of objectives, a learning attitude, and experimentation and research. As a result of the technical uncertainties and value judgments frequently involved, management should also be based upon the expressed preferences and continuing involvement of citizens.

The Impact of Different Sources of Fluctuations on Mutual Information in Biochemical Networks

PubMed Central

Chevalier, Michael; Venturelli, Ophelia; El-Samad, Hana

2015-01-01

Stochastic fluctuations in signaling and gene expression limit the ability of cells to sense the state of their environment, transfer this information along cellular pathways, and respond to it with high precision. Mutual information is now often used to quantify the fidelity with which information is transmitted along a cellular pathway. Mutual information calculations from experimental data have mostly generated low values, suggesting that cells might have relatively low signal transmission fidelity. In this work, we demonstrate that mutual information calculations might be artificially lowered by cell-to-cell variability in both initial conditions and slowly fluctuating global factors across the population. We carry out our analysis computationally using a simple signaling pathway and demonstrate that in the presence of slow global fluctuations, every cell might have its own high information transmission capacity but that population averaging underestimates this value. We also construct a simple synthetic transcriptional network and demonstrate using experimental measurements coupled to computational modeling that its operation is dominated by slow global variability, and hence that its mutual information is underestimated by a population averaged calculation. PMID:26484538

Dollar$ & $en$e. Part VI: Knowledge management: the state of the art.

PubMed

Wilkinson, I

2001-01-01

In Part I of this series, I introduced the concept of memes (1). Memes are ideas or concepts--the information world equivalent of genes. The goal of this series of articles is to infect you with memes so you will assimilate, translate, and express them. No matter what our area of expertise or "-ology," we all are in the information business. Our goal is to be in the wisdom business. In the previous articles in this series, I showed that when we convert raw data into wisdom, we are moving along a value chain. Each step in the chain adds a different amount of value to the final product: timely, relevant, accurate, and precise knowledge that then can be applied to create the ultimate product in the value chain--wisdom. In part II of this series, I introduced a set of memes for measuring the cost of adding value (2). In part III of this series, I presented a new set of memes for measuring the added value of knowledge, i.e., intellectual capital (3). In part IV of this series, I discussed practical knowledge management tools for measuring the value of people, structural, and customer capital (4). In part V of this series, I applied intellectual capital and knowledge management concepts at the individual level, to help answer a fundamental question: what is my added value (5)? In the final part of this series, I will review the state of intellectual capital and knowledge management development to date and outline the direction of current knowledge management initiatives and research projects.

Precise integration of inducible transcriptional elements (PrIITE) enables absolute control of gene expression.

PubMed

Pinto, Rita; Hansen, Lars; Hintze, John; Almeida, Raquel; Larsen, Sylvester; Coskun, Mehmet; Davidsen, Johanne; Mitchelmore, Cathy; David, Leonor; Troelsen, Jesper Thorvald; Bennett, Eric Paul

2017-07-27

Tetracycline-based inducible systems provide powerful methods for functional studies where gene expression can be controlled. However, the lack of tight control of the inducible system, leading to leakiness and adverse effects caused by undesirable tetracycline dosage requirements, has proven to be a limitation. Here, we report that the combined use of genome editing tools and last generation Tet-On systems can resolve these issues. Our principle is based on precise integration of inducible transcriptional elements (coined PrIITE) targeted to: (i) exons of an endogenous gene of interest (GOI) and (ii) a safe harbor locus. Using PrIITE cells harboring a GFP reporter or CDX2 transcription factor, we demonstrate discrete inducibility of gene expression with complete abrogation of leakiness. CDX2 PrIITE cells generated by this approach uncovered novel CDX2 downstream effector genes. Our results provide a strategy for characterization of dose-dependent effector functions of essential genes that require absence of endogenous gene expression. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

The Influence of Normalization Weight in Population Pharmacokinetic Covariate Models.

PubMed

Goulooze, Sebastiaan C; Völler, Swantje; Välitalo, Pyry A J; Calvier, Elisa A M; Aarons, Leon; Krekels, Elke H J; Knibbe, Catherijne A J

2018-03-23

In covariate (sub)models of population pharmacokinetic models, most covariates are normalized to the median value; however, for body weight, normalization to 70 kg or 1 kg is often applied. In this article, we illustrate the impact of normalization weight on the precision of population clearance (CL pop ) parameter estimates. The influence of normalization weight (70, 1 kg or median weight) on the precision of the CL pop estimate, expressed as relative standard error (RSE), was illustrated using data from a pharmacokinetic study in neonates with a median weight of 2.7 kg. In addition, a simulation study was performed to show the impact of normalization to 70 kg in pharmacokinetic studies with paediatric or obese patients. The RSE of the CL pop parameter estimate in the neonatal dataset was lowest with normalization to median weight (8.1%), compared with normalization to 1 kg (10.5%) or 70 kg (48.8%). Typical clearance (CL) predictions were independent of the normalization weight used. Simulations showed that the increase in RSE of the CL pop estimate with 70 kg normalization was highest in studies with a narrow weight range and a geometric mean weight away from 70 kg. When, instead of normalizing with median weight, a weight outside the observed range is used, the RSE of the CL pop estimate will be inflated, and should therefore not be used for model selection. Instead, established mathematical principles can be used to calculate the RSE of the typical CL (CL TV ) at a relevant weight to evaluate the precision of CL predictions.

Steroid-Induced Ocular Hypertension/Glaucoma: Focus on Pharmacogenomics and Implications for Precision Medicine

PubMed Central

Fini, M. Elizabeth; Schwartz, Stephen G.; Gao, Xiaoyi; Jeong, Shinwu; Patel, Nitin; Itakura, Tatsuo; Price, Marianne O.; Price, Francis W.; Varma, Rohit; Stamer, W. Daniel

2016-01-01

Elevation of intraocular pressure (IOP) due to therapeutic use of glucocorticoids is called steroid-induced ocular hypertension (SIOH); this can lead to steroid-induced glaucoma (SIG). Glucocorticoids initiate signaling cascades ultimately affecting expression of hundreds of genes; this provides the potential for a highly personalized pharmacological response. Studies attempting to define genetic risk factors were undertaken early in the history of glucocorticoid use, however scientific tools available at that time were limited and progress stalled. In contrast, significant advances were made over the ensuing years in defining disease pathophysiology. As the genomics age emerged, it appeared the time was right to renew investigation into genetics. Pharmacogenomics is an unbiased discovery approach, not requiring an underlying hypothesis, and provides a way to pinpoint clinically significant genes and pathways that could not have been discovered any other way. Results of the first genome-wide association study to identify polymorphisms associated with SIOH, and follow-up on two novel genes linked to the disorder, GPR158 and HCG22, is discussed in the second half of the article. However, knowledge of genetic variants determining response to steroids in the eye also has value in its own right as a predictive and diagnostic tool. This article concludes with a discussion of how the Precision Medicine Initiative®, announced by U.S. President Obama in his 2015 State of the Union address, is beginning to touch the practice of ophthalmology. It is argued that SIOH/SIG may provide one of the next opportunities for effective application of precision medicine. PMID:27666015

The impact of composite AUC estimates on the prediction of systemic exposure in toxicology experiments.

PubMed

Sahota, Tarjinder; Danhof, Meindert; Della Pasqua, Oscar

2015-06-01

Current toxicity protocols relate measures of systemic exposure (i.e. AUC, Cmax) as obtained by non-compartmental analysis to observed toxicity. A complicating factor in this practice is the potential bias in the estimates defining safe drug exposure. Moreover, it prevents the assessment of variability. The objective of the current investigation was therefore (a) to demonstrate the feasibility of applying nonlinear mixed effects modelling for the evaluation of toxicokinetics and (b) to assess the bias and accuracy in summary measures of systemic exposure for each method. Here, simulation scenarios were evaluated, which mimic toxicology protocols in rodents. To ensure differences in pharmacokinetic properties are accounted for, hypothetical drugs with varying disposition properties were considered. Data analysis was performed using non-compartmental methods and nonlinear mixed effects modelling. Exposure levels were expressed as area under the concentration versus time curve (AUC), peak concentrations (Cmax) and time above a predefined threshold (TAT). Results were then compared with the reference values to assess the bias and precision of parameter estimates. Higher accuracy and precision were observed for model-based estimates (i.e. AUC, Cmax and TAT), irrespective of group or treatment duration, as compared with non-compartmental analysis. Despite the focus of guidelines on establishing safety thresholds for the evaluation of new molecules in humans, current methods neglect uncertainty, lack of precision and bias in parameter estimates. The use of nonlinear mixed effects modelling for the analysis of toxicokinetics provides insight into variability and should be considered for predicting safe exposure in humans.

ANALYTICAL METHOD COMPARISONS BY ESTIMATES OF PRECISION AND LOWER DETECTION LIMIT

EPA Science Inventory

The paper describes the use of principal component analysis to estimate the operating precision of several different analytical instruments or methods simultaneously measuring a common sample of a material whose actual value is unknown. This approach is advantageous when none of ...

Automated extraction of ejection fraction for quality measurement using regular expressions in Unstructured Information Management Architecture (UIMA) for heart failure

PubMed Central

DuVall, Scott L; South, Brett R; Bray, Bruce E; Bolton, Daniel; Heavirland, Julia; Pickard, Steve; Heidenreich, Paul; Shen, Shuying; Weir, Charlene; Samore, Matthew; Goldstein, Mary K

2012-01-01

Objectives Left ventricular ejection fraction (EF) is a key component of heart failure quality measures used within the Department of Veteran Affairs (VA). Our goals were to build a natural language processing system to extract the EF from free-text echocardiogram reports to automate measurement reporting and to validate the accuracy of the system using a comparison reference standard developed through human review. This project was a Translational Use Case Project within the VA Consortium for Healthcare Informatics. Materials and methods We created a set of regular expressions and rules to capture the EF using a random sample of 765 echocardiograms from seven VA medical centers. The documents were randomly assigned to two sets: a set of 275 used for training and a second set of 490 used for testing and validation. To establish the reference standard, two independent reviewers annotated all documents in both sets; a third reviewer adjudicated disagreements. Results System test results for document-level classification of EF of <40% had a sensitivity (recall) of 98.41%, a specificity of 100%, a positive predictive value (precision) of 100%, and an F measure of 99.2%. System test results at the concept level had a sensitivity of 88.9% (95% CI 87.7% to 90.0%), a positive predictive value of 95% (95% CI 94.2% to 95.9%), and an F measure of 91.9% (95% CI 91.2% to 92.7%). Discussion An EF value of <40% can be accurately identified in VA echocardiogram reports. Conclusions An automated information extraction system can be used to accurately extract EF for quality measurement. PMID:22437073

Temporally precise single-cell resolution optogenetics

PubMed Central

Shemesh, Or A.; Tanese, Dimitrii; Zampini, Valeria; Linghu, Changyang; Piatkevich, Kiryl; Ronzitti, Emiliano; Papagiakoumou, Eirini; Boyden, Edward S.; Emiliani, Valentina

2017-01-01

Optogenetic control of individual neurons with high temporal precision, within intact mammalian brain circuitry, would enable powerful explorations of how neural circuits operate. Two-photon computer generated holography enables precise sculpting of light, and could in principle enable simultaneous illumination of many neurons in a network, with the requisite temporal precision to simulate accurate neural codes. We designed a high efficacy soma-targeted opsin, finding that fusing the N-terminal 150 residues of kainate receptor subunit 2 (KA2) to the recently discovered high-photocurrent channelrhodopsin CoChR restricted expression of this opsin primarily to the cell body of mammalian cortical neurons. In combination with two-photon holographic stimulation, we found that this somatic CoChR (soCoChR) enabled photostimulation of individual cells in intact cortical circuits with single cell resolution and <1 millisecond temporal precision, and use soCoChR to perform connectivity mapping on intact cortical circuits. PMID:29184208

Simultaneous ATM/BRCA1/RAD51 expression variations associated with prognostic factors in Iranian sporadic breast cancer patients.

PubMed

Hallajian, Zeinab; Mahjoubi, Frouzandeh; Nafissi, Nahid

2017-07-01

DNA double-strand breaks (DSBs) as a serious lesion are repaired by non-homologous end-joining and homologous recombination pathways. ATM, BRCA1, RAD51 genes are involved in HR pathways. While some studies have revealed individual expression changes of these genes in different types of cancer, there are limited studies attempting to evaluate correlation of expression variations of these genes in breast cancer pathogenesis. This study aimed to determine RAD51, ATM and BRCA1 gene expression level and its association with clinicopathological factors in fresh breast cancer tissues. Moreover, this study evaluates potential correlations among expression levels of these genes. 50 breast cancer tissues were collected and examined for BRCA1, RAD51 and ATM gene expression by Real Time PCR. Expression changes were analyzed with REST software version 2009. mRNA expression was reduced in all these three genes when compared with β-Actin as a control gene (P value  < 0.001). Spearman's test demonstrated a significant positive correlation among ATM, BRCA1 and RAD51 gene down expression (P value  < 0.0001). There was a significant association between down expression of ATM with stage (P value  < 0.05), necrosis (P value  < 0.05), perineural invasion (P value  < 0.05), vascular invasion (P value  < 0.01), malignancy (P value  ≤ 0.001), PR (P value  < 0.05) and ER status (P value  < 0.01). In addition, there was a significant association between down expression of BRCA1 with Ki67 (P value  ≤ 0.001). Moreover, there was a significant association between down expression of RAD51 with lymph node involvement (P value  < 0.01), auxiliary lymph node metastasis (P value  = 0.01), age (P = 0.001), grade (P value  < 0.05) and PR status (P value  < 0.05). This study suggests association between expression changes in several DSB repair genes in a common functional pathway in breast cancer and the significant association between abnormal expression of these genes and important clinical prognostic factors.

Precision Measurement of Distribution of Film Thickness on Pendulum for Experiment of G

NASA Astrophysics Data System (ADS)

Liu, Lin-Xia; Guan, Sheng-Guo; Liu, Qi; Zhang, Ya-Ting; Shao, Cheng-Gang; Luo, Jun

2009-09-01

Distribution of film thickness coated on the pendulum of measuring the Newton gravitational constant G is determined with a weighing method by means of a precision mass comparator. The experimental result shows that the gold film on the pendulum will contribute a correction of -24.3 ppm to our G measurement with an uncertainty of 4.3 ppm, which is significant for improving the G value with high precision.

Precision of Readout at the hunchback Gene: Analyzing Short Transcription Time Traces in Living Fly Embryos

PubMed Central

Tran, Huy; Ferraro, Teresa; Lucas, Tanguy; Guillou, Aurelien; Coppey, Mathieu; Dostatni, Nathalie

2016-01-01

The simultaneous expression of the hunchback gene in the numerous nuclei of the developing fly embryo gives us a unique opportunity to study how transcription is regulated in living organisms. A recently developed MS2-MCP technique for imaging nascent messenger RNA in living Drosophila embryos allows us to quantify the dynamics of the developmental transcription process. The initial measurement of the morphogens by the hunchback promoter takes place during very short cell cycles, not only giving each nucleus little time for a precise readout, but also resulting in short time traces of transcription. Additionally, the relationship between the measured signal and the promoter state depends on the molecular design of the reporting probe. We develop an analysis approach based on tailor made autocorrelation functions that overcomes the short trace problems and quantifies the dynamics of transcription initiation. Based on live imaging data, we identify signatures of bursty transcription initiation from the hunchback promoter. We show that the precision of the expression of the hunchback gene to measure its position along the anterior-posterior axis is low both at the boundary and in the anterior even at cycle 13, suggesting additional post-transcriptional averaging mechanisms to provide the precision observed in fixed embryos. PMID:27942043

Role of spatial averaging in multicellular gradient sensing.

PubMed

Smith, Tyler; Fancher, Sean; Levchenko, Andre; Nemenman, Ilya; Mugler, Andrew

2016-05-20

Gradient sensing underlies important biological processes including morphogenesis, polarization, and cell migration. The precision of gradient sensing increases with the length of a detector (a cell or group of cells) in the gradient direction, since a longer detector spans a larger range of concentration values. Intuition from studies of concentration sensing suggests that precision should also increase with detector length in the direction transverse to the gradient, since then spatial averaging should reduce the noise. However, here we show that, unlike for concentration sensing, the precision of gradient sensing decreases with transverse length for the simplest gradient sensing model, local excitation-global inhibition. The reason is that gradient sensing ultimately relies on a subtraction of measured concentration values. While spatial averaging indeed reduces the noise in these measurements, which increases precision, it also reduces the covariance between the measurements, which results in the net decrease in precision. We demonstrate how a recently introduced gradient sensing mechanism, regional excitation-global inhibition (REGI), overcomes this effect and recovers the benefit of transverse averaging. Using a REGI-based model, we compute the optimal two- and three-dimensional detector shapes, and argue that they are consistent with the shapes of naturally occurring gradient-sensing cell populations.

Big Data’s Role in Precision Public Health

PubMed Central

Dolley, Shawn

2018-01-01

Precision public health is an emerging practice to more granularly predict and understand public health risks and customize treatments for more specific and homogeneous subpopulations, often using new data, technologies, and methods. Big data is one element that has consistently helped to achieve these goals, through its ability to deliver to practitioners a volume and variety of structured or unstructured data not previously possible. Big data has enabled more widespread and specific research and trials of stratifying and segmenting populations at risk for a variety of health problems. Examples of success using big data are surveyed in surveillance and signal detection, predicting future risk, targeted interventions, and understanding disease. Using novel big data or big data approaches has risks that remain to be resolved. The continued growth in volume and variety of available data, decreased costs of data capture, and emerging computational methods mean big data success will likely be a required pillar of precision public health into the future. This review article aims to identify the precision public health use cases where big data has added value, identify classes of value that big data may bring, and outline the risks inherent in using big data in precision public health efforts. PMID:29594091

Big Data's Role in Precision Public Health.

PubMed

Dolley, Shawn

2018-01-01

Precision public health is an emerging practice to more granularly predict and understand public health risks and customize treatments for more specific and homogeneous subpopulations, often using new data, technologies, and methods. Big data is one element that has consistently helped to achieve these goals, through its ability to deliver to practitioners a volume and variety of structured or unstructured data not previously possible. Big data has enabled more widespread and specific research and trials of stratifying and segmenting populations at risk for a variety of health problems. Examples of success using big data are surveyed in surveillance and signal detection, predicting future risk, targeted interventions, and understanding disease. Using novel big data or big data approaches has risks that remain to be resolved. The continued growth in volume and variety of available data, decreased costs of data capture, and emerging computational methods mean big data success will likely be a required pillar of precision public health into the future. This review article aims to identify the precision public health use cases where big data has added value, identify classes of value that big data may bring, and outline the risks inherent in using big data in precision public health efforts.

Role of spatial averaging in multicellular gradient sensing

NASA Astrophysics Data System (ADS)

Smith, Tyler; Fancher, Sean; Levchenko, Andre; Nemenman, Ilya; Mugler, Andrew

2016-06-01

Gradient sensing underlies important biological processes including morphogenesis, polarization, and cell migration. The precision of gradient sensing increases with the length of a detector (a cell or group of cells) in the gradient direction, since a longer detector spans a larger range of concentration values. Intuition from studies of concentration sensing suggests that precision should also increase with detector length in the direction transverse to the gradient, since then spatial averaging should reduce the noise. However, here we show that, unlike for concentration sensing, the precision of gradient sensing decreases with transverse length for the simplest gradient sensing model, local excitation-global inhibition. The reason is that gradient sensing ultimately relies on a subtraction of measured concentration values. While spatial averaging indeed reduces the noise in these measurements, which increases precision, it also reduces the covariance between the measurements, which results in the net decrease in precision. We demonstrate how a recently introduced gradient sensing mechanism, regional excitation-global inhibition (REGI), overcomes this effect and recovers the benefit of transverse averaging. Using a REGI-based model, we compute the optimal two- and three-dimensional detector shapes, and argue that they are consistent with the shapes of naturally occurring gradient-sensing cell populations.

Seasonal changes in gastric mucosal factors associated with peptic ulcer bleeding.

PubMed

Yuan, Xiao-Gang; Xie, Chuan; Chen, Jiang; Xie, Yong; Zhang, Kun-He; Lu, Nong-Hua

2015-01-01

A close association has been established between climate and peptic ulcer bleeding (PUB). The incidence of PUB in cold climates is significantly higher than that in hot climates. In this study, gastric mucosal damage and its barrier function (through associated barrier factors) in extreme climate conditions were examined to investigate the pathogenesis of PUB in extreme cold climates. Gastric juice and biopsy specimens were collected from 176 patients with peptic ulcer. Conventional hematoxylin and eosin staining was used to exclude malignant ulcers. Helicobacter pylori infections were detected by modified Giemsa staining. pH values of the gastric juice samples were obtained on-site by precise pH dipstick readings. The protein expression levels of heat shock protein (HSP) 70, occludin, nitric oxide synthase (NOS), epidermal growth factor (EGF) and EGF receptor (EGFR) in the gastric mucosa were detected by immunohistochemistry. No significant differences were identified between the high and low bleeding risk groups in the rates of H. pylori infection and the pH values of the gastric juices in the extreme hot or cold climates. Furthermore, no statistically significant differences were identified in the protein expression levels of occludin, NOS, EGF and EGFR between the high and low bleeding risk groups. In the extreme cold climate, the expression of HSP70 and the mucus thickness of the gastric antrum in the high bleeding risk group were significantly lower than those in the low bleeding risk group. The protein expression levels of occludin, HSP70, NOS and EGFR in the extreme cold climate were significantly lower than those in the extreme hot climate, whereas the gastric acid secretion was significantly higher in the extreme cold climate than that in the extreme hot climate. In conclusion, low expression of HSP70 in the gastric mucosa and reduced gastric mucus thickness may play key roles in the mechanism of PUB in extreme cold climates. The significant decrease in barrier factors and increase in damage in extreme cold climates may be associated with the seasonal pattern of peptic ulcers.

Seasonal changes in gastric mucosal factors associated with peptic ulcer bleeding

PubMed Central

YUAN, XIAO-GANG; XIE, CHUAN; CHEN, JIANG; XIE, YONG; ZHANG, KUN-HE; LU, NONG-HUA

2015-01-01

A close association has been established between climate and peptic ulcer bleeding (PUB). The incidence of PUB in cold climates is significantly higher than that in hot climates. In this study, gastric mucosal damage and its barrier function (through associated barrier factors) in extreme climate conditions were examined to investigate the pathogenesis of PUB in extreme cold climates. Gastric juice and biopsy specimens were collected from 176 patients with peptic ulcer. Conventional hematoxylin and eosin staining was used to exclude malignant ulcers. Helicobacter pylori infections were detected by modified Giemsa staining. pH values of the gastric juice samples were obtained on-site by precise pH dipstick readings. The protein expression levels of heat shock protein (HSP) 70, occludin, nitric oxide synthase (NOS), epidermal growth factor (EGF) and EGF receptor (EGFR) in the gastric mucosa were detected by immunohistochemistry. No significant differences were identified between the high and low bleeding risk groups in the rates of H. pylori infection and the pH values of the gastric juices in the extreme hot or cold climates. Furthermore, no statistically significant differences were identified in the protein expression levels of occludin, NOS, EGF and EGFR between the high and low bleeding risk groups. In the extreme cold climate, the expression of HSP70 and the mucus thickness of the gastric antrum in the high bleeding risk group were significantly lower than those in the low bleeding risk group. The protein expression levels of occludin, HSP70, NOS and EGFR in the extreme cold climate were significantly lower than those in the extreme hot climate, whereas the gastric acid secretion was significantly higher in the extreme cold climate than that in the extreme hot climate. In conclusion, low expression of HSP70 in the gastric mucosa and reduced gastric mucus thickness may play key roles in the mechanism of PUB in extreme cold climates. The significant decrease in barrier factors and increase in damage in extreme cold climates may be associated with the seasonal pattern of peptic ulcers. PMID:25452787

Identifiability of PBPK Models with Applications to ...

EPA Pesticide Factsheets

Any statistical model should be identifiable in order for estimates and tests using it to be meaningful. We consider statistical analysis of physiologically-based pharmacokinetic (PBPK) models in which parameters cannot be estimated precisely from available data, and discuss different types of identifiability that occur in PBPK models and give reasons why they occur. We particularly focus on how the mathematical structure of a PBPK model and lack of appropriate data can lead to statistical models in which it is impossible to estimate at least some parameters precisely. Methods are reviewed which can determine whether a purely linear PBPK model is globally identifiable. We propose a theorem which determines when identifiability at a set of finite and specific values of the mathematical PBPK model (global discrete identifiability) implies identifiability of the statistical model. However, we are unable to establish conditions that imply global discrete identifiability, and conclude that the only safe approach to analysis of PBPK models involves Bayesian analysis with truncated priors. Finally, computational issues regarding posterior simulations of PBPK models are discussed. The methodology is very general and can be applied to numerous PBPK models which can be expressed as linear time-invariant systems. A real data set of a PBPK model for exposure to dimethyl arsinic acid (DMA(V)) is presented to illustrate the proposed methodology. We consider statistical analy

Fluctuation localization imaging-based fluorescence in situ hybridization (fliFISH) for accurate detection and counting of RNA copies in single cells

DOE PAGES

Cui, Yi; Hu, Dehong; Markillie, Lye Meng; ...

2017-10-04

Here, quantitative gene expression analysis in intact single cells can be achieved using single molecule-based fluorescence in situ hybridization (smFISH). This approach relies on fluorescence intensity to distinguish between true signals, emitted from an RNA copy hybridized with multiple oligonucleotide probes, and background noise. Thus, the precision in smFISH is often compromised by partial or nonspecific probe binding and tissue autofluorescence, especially when only a small number of probes can be fitted to the target transcript. Here we provide an accurate approach for setting quantitative thresholds between true and false signals, which relies on on-off duty cycles of photoswitchable dyes.more » This fluctuation localization imaging-based FISH (fliFISH) uses on-time fractions (measured over a series of exposures) collected from transcripts bound to as low as 8 probes, which are distinct from on-time fractions collected from nonspecifically bound probes or autofluorescence. Using multicolor fliFISH, we identified radial gene expression patterns in mouse pancreatic islets for insulin, the transcription factor, NKX2-2 and their ratio ( Nkx2- 2/Ins2). These radial patterns, showing higher values in β cells at the islet core and lower values in peripheral cells, were lost in diabetic mouse islets. In summary, fliFISH provides an accurate, quantitative approach for detecting and counting true RNA copies and rejecting false signals by their distinct on-time fractions, laying the foundation for reliable single-cell transcriptomics.« less

Measuring the expressed abundance of the three phases of water with an imaging spectrometer over melting snow

NASA Astrophysics Data System (ADS)

Green, Robert O.; Painter, Thomas H.; Roberts, Dar A.; Dozier, Jeff

2006-10-01

From imaging spectrometer data, we simultaneously estimate the abundance of the three phases of water in an environment that includes melting snow, basing the analysis on the spectral shift in the absorption coefficient between water vapor, liquid water, and ice at 940, 980, and 1030 nm respectively. We apply a spectral fitting algorithm that measures the expressed abundance of the three phases of water to a data set acquired by the Airborne Visible/Infrared Imaging Spectrometer (AVIRIS) over Mount Rainier, Washington, on 14 June 1996. Precipitable water vapor varies from 1 mm over the summit of Mount Rainier to 10 mm over the lower valleys to the northwest. Equivalent path absorption of liquid water varies from 0 to 13 mm, with the zero values over rocky areas and high-elevation snow and the high values associated with liquid water held in vegetation canopies and in melting snow. Ice abundance varies from 0 to 30 mm equivalent path absorption in the snow- and glacier-covered portions of Mount Rainier. The water and ice abundances are related to the amount of liquid water and the sizes of the ice grains in the near-surface layer. Precision of the estimates, calculated over locally homogeneous areas, indicates an uncertainty of better than 1.5% for all three phases, except for liquid water in vegetation, where an optimally homogeneous site was not found. The analysis supports new strategies for hydrological research and applications as imaging spectrometers become more available.

Fluctuation localization imaging-based fluorescence in situ hybridization (fliFISH) for accurate detection and counting of RNA copies in single cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cui, Yi; Hu, Dehong; Markillie, Lye Meng

Here, quantitative gene expression analysis in intact single cells can be achieved using single molecule-based fluorescence in situ hybridization (smFISH). This approach relies on fluorescence intensity to distinguish between true signals, emitted from an RNA copy hybridized with multiple oligonucleotide probes, and background noise. Thus, the precision in smFISH is often compromised by partial or nonspecific probe binding and tissue autofluorescence, especially when only a small number of probes can be fitted to the target transcript. Here we provide an accurate approach for setting quantitative thresholds between true and false signals, which relies on on-off duty cycles of photoswitchable dyes.more » This fluctuation localization imaging-based FISH (fliFISH) uses on-time fractions (measured over a series of exposures) collected from transcripts bound to as low as 8 probes, which are distinct from on-time fractions collected from nonspecifically bound probes or autofluorescence. Using multicolor fliFISH, we identified radial gene expression patterns in mouse pancreatic islets for insulin, the transcription factor, NKX2-2 and their ratio ( Nkx2- 2/Ins2). These radial patterns, showing higher values in β cells at the islet core and lower values in peripheral cells, were lost in diabetic mouse islets. In summary, fliFISH provides an accurate, quantitative approach for detecting and counting true RNA copies and rejecting false signals by their distinct on-time fractions, laying the foundation for reliable single-cell transcriptomics.« less

Penning trap mass spectrometry Q-value determinations for highly forbidden β-decays

NASA Astrophysics Data System (ADS)

Sandler, Rachel; Bollen, Georg; Eibach, Martin; Gamage, Nadeesha; Gulyuz, Kerim; Hamaker, Alec; Izzo, Chris; Kandegedara, Rathnayake; Redshaw, Matt; Ringle, Ryan; Valverde, Adrian; Yandow, Isaac; Low Energy Beam Ion Trap Team

2017-09-01

Over the last several decades, extremely sensitive, ultra-low background beta and gamma detection techniques have been developed. These techniques have enabled the observation of very rare processes, such as highly forbidden beta decays e.g. of 113Cd, 50V and 138La. Half-life measurements of highly forbidden beta decays provide a testing ground for theoretical nuclear models, and the comparison of calculated and measured energy spectra could enable a determination of the values of the weak coupling constants. Precision Q-value measurements also allow for systematic tests of the beta-particle detection techniques. We will present the results and current status of Q value determinations for highly forbidden beta decays. The Q values, the mass difference between parent and daughter nuclides, are measured using the high precision Penning trap mass spectrometer LEBIT at the National Superconducting Cyclotron Laboratory.

Accuracy evaluation of intraoral optical impressions: A clinical study using a reference appliance.

PubMed

Atieh, Mohammad A; Ritter, André V; Ko, Ching-Chang; Duqum, Ibrahim

2017-09-01

Trueness and precision are used to evaluate the accuracy of intraoral optical impressions. Although the in vivo precision of intraoral optical impressions has been reported, in vivo trueness has not been evaluated because of limitations in the available protocols. The purpose of this clinical study was to compare the accuracy (trueness and precision) of optical and conventional impressions by using a novel study design. Five study participants consented and were enrolled. For each participant, optical and conventional (vinylsiloxanether) impressions of a custom-made intraoral Co-Cr alloy reference appliance fitted to the mandibular arch were obtained by 1 operator. Three-dimensional (3D) digital models were created for stone casts obtained from the conventional impression group and for the reference appliances by using a validated high-accuracy reference scanner. For the optical impression group, 3D digital models were obtained directly from the intraoral scans. The total mean trueness of each impression system was calculated by averaging the mean absolute deviations of the impression replicates from their 3D reference model for each participant, followed by averaging the obtained values across all participants. The total mean precision for each impression system was calculated by averaging the mean absolute deviations between all the impression replicas for each participant (10 pairs), followed by averaging the obtained values across all participants. Data were analyzed using repeated measures ANOVA (α=.05), first to assess whether a systematic difference in trueness or precision of replicate impressions could be found among participants and second to assess whether the mean trueness and precision values differed between the 2 impression systems. Statistically significant differences were found between the 2 impression systems for both mean trueness (P=.010) and mean precision (P=.007). Conventional impressions had higher accuracy with a mean trueness of 17.0 ±6.6 μm and mean precision of 16.9 ±5.8 μm than optical impressions with a mean trueness of 46.2 ±11.4 μm and mean precision of 61.1 ±4.9 μm. Complete arch (first molar-to-first molar) optical impressions were less accurate than conventional impressions but may be adequate for quadrant impressions. Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Clinical evaluation of the FreeStyle Precision Pro system.

PubMed

Brazg, Ronald; Hughes, Kristen; Martin, Pamela; Coard, Julie; Toffaletti, John; McDonnell, Elizabeth; Taylor, Elizabeth; Farrell, Lausanne; Patel, Mona; Ward, Jeanne; Chen, Ting; Alva, Shridhara; Ng, Ronald

2013-06-05

A new version of international standard (ISO 15197) and CLSI Guideline (POCT12) with more stringent accuracy criteria are near publication. We evaluated the glucose test performance of the FreeStyle Precision Pro system, a new blood glucose monitoring system (BGMS) designed to enhance accuracy for point-of-care testing (POCT). Precision, interference and system accuracy with 503 blood samples from capillary, venous and arterial sources were evaluated in a multicenter study. Study results were analyzed and presented in accordance with the specifications and recommendations of the final draft ISO 15197 and the new POCT12. The FreeStyle Precision Pro system demonstrated acceptable precision (CV <5%), no interference across a hematocrit range of 15-65%, and, except for xylose, no interference from 24 of 25 potentially interfering substances. It also met all accuracy criteria specified in the final draft ISO 15197 and POCT12, with 97.3-98.9% of the individual results of various blood sample types agreeing within ±12 mg/dl of the laboratory analyzer values at glucose concentrations <100mg/dl and within ±12.5% of the laboratory analyzer values at glucose concentrations ≥100 mg/dl. The FreeStyle Precision Pro system met the tighter accuracy requirements, providing a means for enhancing accuracy for point-of-care blood glucose monitoring. Copyright © 2013 Elsevier B.V. All rights reserved.

Thermodynamic properties by Equation of state of liquid sodium under pressure

NASA Astrophysics Data System (ADS)

Li, Huaming; Sun, Yongli; Zhang, Xiaoxiao; Li, Mo

Isothermal bulk modulus, molar volume and speed of sound of molten sodium are calculated through an equation of state of a power law form within good precision as compared with the experimental data. The calculated internal energy data show the minimum along the isothermal lines as the previous result but with slightly larger values. The calculated values of isobaric heat capacity show the unexpected minimum in the isothermal compression. The temperature and pressure derivative of various thermodynamic quantities in liquid Sodium are derived. It is discussed about the contribution from entropy to the temperature and pressure derivative of isothermal bulk modulus. The expressions for acoustical parameter and nonlinearity parameter are obtained based on thermodynamic relations from the equation of state. Both parameters for liquid Sodium are calculated under high pressure along the isothermal lines by using the available thermodynamic data and numeric derivations. By comparison with the results from experimental measurements and quasi-thermodynamic theory, the calculated values are found to be very close at melting point at ambient condition. Furthermore, several other thermodynamic quantities are also presented. Scientific Research Starting Foundation from Taiyuan university of Technology, Shanxi Provincial government (``100-talents program''), China Scholarship Council and National Natural Science Foundation of China (NSFC) under Grant No. 11204200.

E2F3a gene expression has prognostic significance in childhood acute lymphoblastic leukemia.

PubMed

Wang, Kai-Ling; Mei, Yan-Yan; Cui, Lei; Zhao, Xiao-Xi; Li, Wei-Jing; Gao, Chao; Liu, Shu-Guang; Jiao, Ying; Liu, Fei-Fei; Wu, Min-Yuan; Ding, Wei; Li, Zhi-Gang

2014-10-01

To study E2F3a expression and its clinical significance in children with acute lymphoblastic leukemia (ALL). We quantified E2F3a expression at diagnosis in 148 children with ALL by real-time PCR. In the test cohort (n = 48), receiver operating characteristic (ROC) curve was used to find the best cut-off point to divide the patients into E2F3a low- and high-expression groups. The prognostic significance of E2F3a expression was investigated in the test cohort and confirmed in the validation cohort (n = 100). The correlations of E2F3a expression with the clinical features and treatment outcome of these patients were analyzed. ROC curve analysis indicated that the best cut-off point of E2F3a expression was 0.3780. In the test cohort, leukemia-free survival (LFS) and event-free survival (EFS) of the low-expression group were lower than those of the high-expression group (log rank: P = 0.026 for both). This finding was verified in the validation cohort. LFS, EFS, and overall survival were also lower in the low-expression group than in the high-expression group (log rank, P = 0.015, 0.008, and 0.002 respectively). E2F3a low expression was correlated with the existence of BCR-ABL fusion. An algorithm composed of E2F3a expression and minimal residual disease (MRD) could predict relapse or induction failure more precisely than current risk stratification. These results were still significant in the ALL patients without BCR-ABL fusion. Low expression of E2F3a was associated with inferior prognosis in childhood ALL. An algorithm composed of E2F3a expression and MRD could predict relapse or induction failure more precisely than that of the current risk stratification. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Diurnal and circadian oscillations in expression of kisspeptin, kisspeptin receptor and gonadotrophin-releasing hormone 2 genes in the grass puffer, a semilunar-synchronised spawner.

PubMed

Ando, H; Ogawa, S; Shahjahan, Md; Ikegami, T; Doi, H; Hattori, A; Parhar, I

2014-07-01

In seasonally breeding animals, the circadian and photoperiodic regulation of neuroendocrine system is important for precisely-timed reproduction. Kisspeptin, encoded by the Kiss1 gene, acts as a principal positive regulator of the reproductive axis by stimulating gonadotrophin-releasing hormone (GnRH) neurone activity in vertebrates. However, the precise mechanisms underlying the cyclic regulation of the kisspeptin neuroendocrine system remain largely unknown. The grass puffer, Takifugu niphobles, exhibits a unique spawning rhythm: spawning occurs 1.5-2 h before high tide on the day of spring tide every 2 weeks, and the spawning rhythm is connected to circadian and lunar-/tide-related clock mechanisms. The grass puffer has only one kisspeptin gene (kiss2), which is expressed in a single neural population in the preoptic area (POA), and has one kisspeptin receptor gene (kiss2r), which is expressed in the POA and the nucleus dorsomedialis thalami. Both kiss2 and kiss2r show diurnal variations in expression levels, with a peak at Zeitgeber time (ZT) 6 (middle of day time) under the light/dark conditions. They also show circadian expression with a peak at circadian time 15 (beginning of subjective night-time) under constant darkness. The synchronous and diurnal oscillations of kiss2 and kiss2r expression suggest that the action of Kiss2 in the diencephalon is highly dependent on time. Moreover, midbrain GnRH2 gene (gnrh2) but not GnRH1 or GnRH3 genes show a unique semidiurnal oscillation with two peaks at ZT6 and ZT18 within a day. The cyclic expression of kiss2, kiss2r and gnrh2 may be important in the control of the precisely-timed diurnal and semilunar spawning rhythm of the grass puffer, possibly through the circadian clock and melatonin, which may transmit the photoperiodic information of daylight and moonlight to the reproductive neuroendocrine centre in the hypothalamus. © 2014 British Society for Neuroendocrinology.

Forecasting Nonlinear Chaotic Time Series with Function Expression Method Based on an Improved Genetic-Simulated Annealing Algorithm

PubMed Central

Wang, Jun; Zhou, Bi-hua; Zhou, Shu-dao; Sheng, Zheng

2015-01-01

The paper proposes a novel function expression method to forecast chaotic time series, using an improved genetic-simulated annealing (IGSA) algorithm to establish the optimum function expression that describes the behavior of time series. In order to deal with the weakness associated with the genetic algorithm, the proposed algorithm incorporates the simulated annealing operation which has the strong local search ability into the genetic algorithm to enhance the performance of optimization; besides, the fitness function and genetic operators are also improved. Finally, the method is applied to the chaotic time series of Quadratic and Rossler maps for validation. The effect of noise in the chaotic time series is also studied numerically. The numerical results verify that the method can forecast chaotic time series with high precision and effectiveness, and the forecasting precision with certain noise is also satisfactory. It can be concluded that the IGSA algorithm is energy-efficient and superior. PMID:26000011

The Glide/Gcm fate determinant controls initiation of collective cell migration by regulating Frazzled

PubMed Central

Gupta, Tripti; Kumar, Arun; Cattenoz, Pierre B.; VijayRaghavan, K; Giangrande, Angela

2016-01-01

Collective migration is a complex process that contributes to build precise tissue and organ architecture. Several molecules implicated in cell interactions also control collective migration, but their precise role and the finely tuned expression that orchestrates this complex developmental process are poorly understood. Here, we show that the timely and threshold expression of the Netrin receptor Frazzled triggers the initiation of glia migration in the developing Drosophila wing. Frazzled expression is induced by the transcription factor Glide/Gcm in a dose-dependent manner. Thus, the glial determinant also regulates the efficiency of collective migration. NetrinB but not NetrinA serves as a chemoattractant and Unc5 contributes as a repellant Netrin receptor for glia migration. Our model includes strict spatial localization of a ligand, a cell autonomously acting receptor and a fate determinant that act coordinately to direct glia toward their final destination. DOI: http://dx.doi.org/10.7554/eLife.15983.001 PMID:27740455

Expression patterns of genes encoding plasma membrane aquaporins during fruit development in cucumber (Cucumis sativus L.).

PubMed

Shi, Jin; Wang, Jinfang; Li, Ren; Li, Dianbo; Xu, Fengfeng; Sun, Qianqian; Zhao, Bin; Mao, Ai-Jun; Guo, Yang-Dong

2015-11-01

Aquaporins are membrane channels precisely regulating water movement through cell membranes in most living organisms. Despite the advances in the physiology of fruit development, their participation during fruit development in cucumber still barely understood. In this paper, the expressions of 12 genes encoding plasma membrane intrinsic proteins (PIPs) were analyzed during cucumber fruit development in our work. Based on the homology search with known PIPs from rice, Arabidopsis and strawberry, 12 cucumber PIP genes subfamily members were identified. Cellular localization assays indicated that CsPIPs were localized in the plasma membrane. The qRT-PCR analysis of CsPIPs showed that 12 CsPIPs were differentially expressed during fruit development. These results suggest that 12 genes encoding plasma membrane intrinsic proteins (CsPIPs) play very important roles in cucumber life cycle and the data generated will be helpful in understanding their precise roles during fruit development in cucumber. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Forecasting nonlinear chaotic time series with function expression method based on an improved genetic-simulated annealing algorithm.

PubMed

Wang, Jun; Zhou, Bi-hua; Zhou, Shu-dao; Sheng, Zheng

2015-01-01

The paper proposes a novel function expression method to forecast chaotic time series, using an improved genetic-simulated annealing (IGSA) algorithm to establish the optimum function expression that describes the behavior of time series. In order to deal with the weakness associated with the genetic algorithm, the proposed algorithm incorporates the simulated annealing operation which has the strong local search ability into the genetic algorithm to enhance the performance of optimization; besides, the fitness function and genetic operators are also improved. Finally, the method is applied to the chaotic time series of Quadratic and Rossler maps for validation. The effect of noise in the chaotic time series is also studied numerically. The numerical results verify that the method can forecast chaotic time series with high precision and effectiveness, and the forecasting precision with certain noise is also satisfactory. It can be concluded that the IGSA algorithm is energy-efficient and superior.

dREL: a relational expression language for dictionary methods.

PubMed

Spadaccini, Nick; Castleden, Ian R; du Boulay, Doug; Hall, Sydney R

2012-08-27

The provision of precise metadata is an important but a largely underrated challenge for modern science [Nature 2009, 461, 145]. We describe here a dictionary methods language dREL that has been designed to enable complex data relationships to be expressed as formulaic scripts in data dictionaries written in DDLm [Spadaccini and Hall J. Chem. Inf. Model.2012 doi:10.1021/ci300075z]. dREL describes data relationships in a simple but powerful canonical form that is easy to read and understand and can be executed computationally to evaluate or validate data. The execution of dREL expressions is not a substitute for traditional scientific computation; it is to provide precise data dependency information to domain-specific definitions and a means for cross-validating data. Some scientific fields apply conventional programming languages to methods scripts but these tend to inhibit both dictionary development and accessibility. dREL removes the programming barrier and encourages the production of the metadata needed for seamless data archiving and exchange in science.

METHODS OF DEALING WITH VALUES BELOW THE LIMIT OF DETECTION USING SAS

EPA Science Inventory

Due to limitations of chemical analysis procedures, small concentrations cannot be precisely measured. These concentrations are said to be below the limit of detection (LOD). In statistical analyses, these values are often censored and substituted with a constant value, such ...

Development of principles of two-cascaded laser speckle-microscopy with implication to high-precision express diagnostics of chlamydial infection

NASA Astrophysics Data System (ADS)

Ulianova, Onega; Moiseeva, Yulia; Filonova, Nadezhda; Subbotina, Irina; Zaitsev, Sergey; Saltykov, Yury; Polyanina, Tatiana; Lyapina, Anna; Ulyanov, Sergey; Larionova, Olga; Utz, Sergey; Feodorova, Valentina

2018-04-01

Principles of two-cascaded laser speckle-microscopy prospect for application to express diagnostics of chlamydial infection are developed. Prototype of two-cascaded speckle-microscope is designed and tested. Specific case of illumination of bacterial cells by dynamic speckles is considered. Express method of detection of epithelial cells, containing defects, which are caused by Chlamydia trachomatis bacteria, is suggested. Results of improved recognition of C. trachomatis bacteria are discussed.

Efficient and precise calculation of the b-matrix elements in diffusion-weighted imaging pulse sequences.

PubMed

Zubkov, Mikhail; Stait-Gardner, Timothy; Price, William S

2014-06-01

Precise NMR diffusion measurements require detailed knowledge of the cumulative dephasing effect caused by the numerous gradient pulses present in most NMR pulse sequences. This effect, which ultimately manifests itself as the diffusion-related NMR signal attenuation, is usually described by the b-value or the b-matrix in the case of multidirectional diffusion weighting, the latter being common in diffusion-weighted NMR imaging. Neglecting some of the gradient pulses introduces an error in the calculated diffusion coefficient reaching in some cases 100% of the expected value. Therefore, ensuring the b-matrix calculation includes all the known gradient pulses leads to significant error reduction. Calculation of the b-matrix for simple gradient waveforms is rather straightforward, yet it grows cumbersome when complexly shaped and/or numerous gradient pulses are introduced. Making three broad assumptions about the gradient pulse arrangement in a sequence results in an efficient framework for calculation of b-matrices as well providing some insight into optimal gradient pulse placement. The framework allows accounting for the diffusion-sensitising effect of complexly shaped gradient waveforms with modest computational time and power. This is achieved by using the b-matrix elements of the simple unmodified pulse sequence and minimising the integration of the complexly shaped gradient waveform in the modified sequence. Such re-evaluation of the b-matrix elements retains all the analytical relevance of the straightforward approach, yet at least halves the amount of symbolic integration required. The application of the framework is demonstrated with the evaluation of the expression describing the diffusion-sensitizing effect, caused by different bipolar gradient pulse modules. Copyright © 2014 Elsevier Inc. All rights reserved.

Real topological entropy versus metric entropy for birational measure-preserving transformations

NASA Astrophysics Data System (ADS)

Abarenkova, N.; Anglès d'Auriac, J.-Ch.; Boukraa, S.; Maillard, J.-M.

2000-10-01

We consider a family of birational measure-preserving transformations of two complex variables, depending on one parameter for which simple rational expressions for the dynamical zeta function have been conjectured, together with an equality between the topological entropy and the logarithm of the Arnold complexity (divided by the number of iterations). Similar results have been obtained for the adaptation of these two concepts to dynamical systems of real variables, yielding to introduce a “real topological entropy” and a “real Arnold complexity”. We try to compare, here, the Kolmogorov-Sinai metric entropy and this real Arnold complexity, or real topological entropy, on this particular example of a one-parameter dependent birational transformation of two variables. More precisely, we analyze, using an infinite precision calculation, the Lyapunov characteristic exponents for various values of the parameter of the birational transformation, in order to compare these results with the ones for the real Arnold complexity. We find a quite surprising result: for this very birational example, and, in fact, for a large set of birational measure-preserving mappings generated by involutions, the Lyapunov characteristic exponents seem to be equal to zero or, at least, extremely small, for all the orbits we have considered, and for all values of the parameter. Birational measure-preserving transformations, generated by involutions, could thus allow to better understand the difference between the topological description and the probabilistic description of discrete dynamical systems. Many birational measure-preserving transformations, generated by involutions, seem to provide examples of discrete dynamical systems which can be topologically chaotic while they are metrically almost quasi-periodic. Heuristically, this can be understood as a consequence of the fact that their orbits seem to form some kind of “transcendental foliation” of the two-dimensional space of variables.

Harnessing Solute Carrier Transporters for Precision Oncology.

PubMed

Nyquist, Michael D; Prasad, Bhagwat; Mostaghel, Elahe A

2017-03-28

Solute Carrier (SLC) transporters are a large superfamily of transmembrane carriers involved in the regulated transport of metabolites, nutrients, ions and drugs across cellular membranes. A subset of these solute carriers play a significant role in the cellular uptake of many cancer therapeutics, ranging from chemotherapeutics such as antimetabolites, topoisomerase inhibitors, platinum-based drugs and taxanes to targeted therapies such as tyrosine kinase inhibitors. SLC transporters are co-expressed in groups and patterns across normal tissues, suggesting they may comprise a coordinated regulatory circuit serving to mediate normal tissue functions. In cancer however, there are dramatic changes in expression patterns of SLC transporters. This frequently serves to feed the increased metabolic demands of the tumor cell for amino acids, nucleotides and other metabolites, but also presents a therapeutic opportunity, as increased transporter expression may serve to increase intracellular concentrations of substrate drugs. In this review, we examine the regulation of drug transporters in cancer and how this impacts therapy response, and discuss novel approaches to targeting therapies to specific cancers via tumor-specific aberrations in transporter expression. We propose that among the oncogenic changes in SLC transporter expression there exist emergent vulnerabilities that can be exploited therapeutically, extending the application of precision medicine from tumor-specific drug targets to tumor-specific determinants of drug uptake.

Production of 3-hydroxypropionic acid by balancing the pathway enzymes using synthetic cassette architecture.

PubMed

Sankaranarayanan, Mugesh; Somasundar, Ashok; Seol, Eunhee; Chauhan, Ashish Singh; Kwon, Seongjin; Jung, Gyoo Yeol; Park, Sunghoon

2017-10-10

Biological 3-hydroxypropionic acid (3-HP) production from glycerol is a two-step reaction catalyzed by glycerol dehydratase (GDHt) and aldehyde dehydrogenase (ALDH). Recombinant strains developed for 3-HP production often suffer from the accumulation of a toxic intermediate, 3-hydroxypropionaldehyde (3-HPA). In order to avoid 3-HPA accumulation, balancing of the two enzymatic activities, in the present study, was attempted by employment of synthetic-regulatory cassettes comprising varying-strength promoters and bicistronic ribosome-binding sites (RBSs). When tested in recombinant Escherichia coli, the cassettes could precisely and differentially control the gene expression in transcription, protein expression and enzymatic activity. Five recombinant strains showing different expressions for GDHt were developed and studied for 3-HPA accumulation and 3-HP production. It was found that 3-HPA accumulation could be completely abolished when expressing ALDH at a level approximately 8-fold higher than that of GDHt. One of the strains, SP4, produced 625mM (56.4g/L) of 3-HP in a fed-batch bioreactor, though late-period production was limited by acetate accumulation. Overall, this study demonstrated the importance of pathway balancing in 3-HP production as well as the utility of the synthetic cassette architecture for precise control of bacterial gene expression. Copyright © 2017 Elsevier B.V. All rights reserved.

Visualized and precise design of artificial small RNAs for regulating T7 RNA polymerase and enhancing recombinant protein folding in Escherichia coli.

PubMed

Zhao, Yujia; Fan, Jingjing; Li, Jinlin; Li, Jun; Zhou, Xiaohong; Li, Chun

2016-12-01

Small non-coding RNAs (sRNAs) have received much attention in recent years due to their unique biological properties, which can efficiently and specifically tune target gene expressions in bacteria. Inspired by natural sRNAs, recent works have proposed the use of artificial sRNAs (asRNAs) as genetic tools to regulate desired gene that has been applied in several fields, such as metabolic engineering and bacterial physiology studies. However, the rational design of asRNAs is still a challenge. In this study, we proposed structure and length as two criteria to implement rational visualized and precise design of asRNAs. T7 expression system was one of the most useful recombinant protein expression systems. However, it was deeply limited by the formation of inclusion body. To settle this problem, we designed a series of asRNAs to inhibit the T7 RNA polymerase (Gene1) expression to balance the rate between transcription and folding of recombinant protein. Based on the heterologous expression of Aspergillus oryzae Li-3 glucuronidase in E. coli , the asRNA-antigene1-17bp can effectively decrease the inclusion body and increase the enzyme activity by 169.9%.

The perceptual saliency of fearful eyes and smiles: A signal detection study

PubMed Central

Saban, Muhammet Ikbal; Rotshtein, Pia

2017-01-01

Facial features differ in the amount of expressive information they convey. Specifically, eyes are argued to be essential for fear recognition, while smiles are crucial for recognising happy expressions. In three experiments, we tested whether expression modulates the perceptual saliency of diagnostic facial features and whether the feature’s saliency depends on the face configuration. Participants were presented with masked facial features or noise at perceptual conscious threshold. The task was to indicate whether eyes (experiments 1-3A) or a mouth (experiment 3B) was present. The expression of the face and its configuration (i.e. spatial arrangement of the features) were manipulated. Experiment 1 compared fearful with neutral expressions, experiments 2 and 3 compared fearful versus happy expressions. The detection accuracy data was analysed using Signal Detection Theory (SDT), to examine the effects of expression and configuration on perceptual precision (d’) and response bias (c), separately. Across all three experiments, fearful eyes were detected better (higher d’) than neutral and happy eyes. Eyes were more precisely detected than mouths, whereas smiles were detected better than fearful mouths. The configuration of the features had no consistent effects across the experiments on the ability to detect expressive features. But facial configuration affected consistently the response bias. Participants used a more liberal criterion for detecting the eyes in canonical configuration and fearful expression. Finally, the power in low spatial frequency of a feature predicted its discriminability index. The results suggest that expressive features are perceptually more salient with a higher d’ due to changes at the low-level visual properties, with emotions and configuration affecting perception through top-down processes, as reflected by the response bias. PMID:28267761

Alterations in Hippocampal Oxidative Stress, Expression of AMPA Receptor GluR2 Subunit and Associated Spatial Memory Loss by Bacopa monnieri Extract (CDRI-08) in Streptozotocin-Induced Diabetes Mellitus Type 2 Mice.

PubMed

Pandey, Surya P; Singh, Hemant K; Prasad, S

2015-01-01

Bacopa monnieri extract has been implicated in the recovery of memory impairments due to various neurological disorders in animal models and humans. However, the precise molecular mechanism of the role of CDRI-08, a well characterized fraction of Bacopa monnieri extract, in recovery of the diabetes mellitus-induced memory impairments is not known. Here, we demonstrate that DM2 mice treated orally with lower dose of CDRI-08 (50- or 100 mg/kg BW) is able to significantly enhance spatial memory in STZ-DM2 mice and this is correlated with a significant decline in oxidative stress and up regulation of the AMPA receptor GluR2 subunit gene expression in the hippocampus. Treatment of DM2 mice with its higher dose (150 mg/kg BW or above) shows anti-diabetic effect in addition to its ability to recover the spatial memory impairment by reversing the DM2-induced elevated oxidative stress and decreased GluR2 subunit expression near to their values in normal and CDRI-08 treated control mice. Our results provide evidences towards molecular basis of the memory enhancing and anti diabetic role of the Bacopa monnieri extract in STZ-induced DM2 mice, which may have therapeutic implications.

Alterations in Hippocampal Oxidative Stress, Expression of AMPA Receptor GluR2 Subunit and Associated Spatial Memory Loss by Bacopa monnieri Extract (CDRI-08) in Streptozotocin-Induced Diabetes Mellitus Type 2 Mice

PubMed Central

Pandey, Surya P.; Singh, Hemant K.; Prasad, S.

2015-01-01

Bacopa monnieri extract has been implicated in the recovery of memory impairments due to various neurological disorders in animal models and humans. However, the precise molecular mechanism of the role of CDRI-08, a well characterized fraction of Bacopa monnieri extract, in recovery of the diabetes mellitus-induced memory impairments is not known. Here, we demonstrate that DM2 mice treated orally with lower dose of CDRI-08 (50- or 100 mg/kg BW) is able to significantly enhance spatial memory in STZ-DM2 mice and this is correlated with a significant decline in oxidative stress and up regulation of the AMPA receptor GluR2 subunit gene expression in the hippocampus. Treatment of DM2 mice with its higher dose (150 mg/kg BW or above) shows anti-diabetic effect in addition to its ability to recover the spatial memory impairment by reversing the DM2-induced elevated oxidative stress and decreased GluR2 subunit expression near to their values in normal and CDRI-08 treated control mice. Our results provide evidences towards molecular basis of the memory enhancing and anti diabetic role of the Bacopa monnieri extract in STZ-induced DM2 mice, which may have therapeutic implications. PMID:26161865

[Conversion methods of freshwater snail tissue dry mass and ash free dry mass].

PubMed

Zhao, Wei-Hua; Wang, Hai-Jun; Wang, Hong-Zhu; Liu, Xue-Qin

2009-06-01

Mollusk biomass is usually expressed as wet mass with shell, but this expression fails to represent real biomass due to the high calcium carbonate content in shells. Tissue dry mass and ash free dry mass are relatively close to real biomass. However, the determination process of these two parameters is very complicated, and thus, it is necessary to establish simple and practical conversion methods for these two parameters. A total of six taxa of freshwater snails (Bellamya sp., Alocinma longicornis, Parafossarulus striatulus, Parafossarulus eximius, Semisulcospira cancellata, and Radix sp.) common in the Yangtze Basin were selected to explore the relations of their five shell dimension parameters, dry and wet mass with shells with their tissue dry mass and ash free dry mass. The regressions of the tissue dry mass and ash free dry mass with the five shell dimension parameters were all exponential (y = ax(b)). Among them, shell width and shell length were more precise (the average percentage error between observed and predicted value being 22.0% and 22.5%, respectively) than the other three parameters in the conversion of dry mass. Wet mass with shell could be directly converted to tissue dry mass and ash free dry mass, with an average percentage error of 21.7%. According to the essence of definition and the errors of conversion, ash free dry mass would be the optimum parameter to express snail biomass.

Development of a direct competitive enzyme-linked immunosorbent assay for parathion residue in food samples.

PubMed

Gui, Wen-Jun; Liu, Yi-Hua; Wang, Chun-Mei; Liang, Xiao; Zhu, Guo-Nian

2009-10-01

A heterologous direct competitive enzyme-linked immunosorbent assay (ELISA) for parathion residue determination is described based on a monoclonal antibody and a new competitor. The effects of several physicochemical factors, such as methanol concentration, ionic strength, pH value, and sample matrix, on the performance of the ELISA were optimized for the sake of obtaining a satisfactory assay sensitivity. Results showed that when the assay medium was in the optimized condition (phosphate buffer solution [PBS] containing 10% [v/v] methanol and 0.2 mol/L NaCl at a pH value of 5.0), the sensitivity (estimated as the IC(50) value) and the limit of detection (LOD, estimated as the IC(10) value) were 1.19 and 0.08 ng/ml, respectively. The precision investigation indicated that the intraassay precision values all were below 10% and that the interassay precision values ranged from 4.89 to 19.12%. In addition, the developed ELISA showed a good linear correlation (r(2)=0.9962) to gas chromatography within the analyte's concentration range of 0.1 to 16 ng/ml. When applied to the fortified samples (parathion adding level: 5-15 microg/kg), the developed ELISA presented mean recoveries of 127.46, 122.52, 91.92, 124.01, 129.72, 99.37, and 87.17% for tomato, cucumber, banana, apple, orange, pear, and sugarcane, respectively. Results indicated that the established ELISA is a potential tool for parathion residue determination.

Automated method for determining Instron Residual Seal Force of glass vial/rubber closure systems.

PubMed

Ludwig, J D; Nolan, P D; Davis, C W

1993-01-01

Instron Residual Seal Force (IRSF) of glass vial/rubber closure systems was determined using an Instron 4501 Materials Testing System. Computer programs were written to process raw data and calculate IRSF values. Preliminary experiments indicated both the appearance of the stress-deformation curves and precision of the derived IRSF values were dependent on the internal dimensions and top surface geometry of the cap anvil. Therefore, a series of five cap anvils varying in shape and dimensions were machined to optimize performance and precision. Vials capped with West 4416/50 PURCOAT button closures or Helvoet compound 6207 lyophilization closures were tested with each cap anvil. Cap anvils with spherical top surfaces and narrow internal dimensions produced more precise results and more uniform stress-deformation curves than cap anvils with flat top surfaces and wider internal dimensions.

CT image reconstruction with half precision floating-point values.

PubMed

Maaß, Clemens; Baer, Matthias; Kachelrieß, Marc

2011-07-01

Analytic CT image reconstruction is a computationally demanding task. Currently, the even more demanding iterative reconstruction algorithms find their way into clinical routine because their image quality is superior to analytic image reconstruction. The authors thoroughly analyze a so far unconsidered but valuable tool of tomorrow's reconstruction hardware (CPU and GPU) that allows implementing the forward projection and backprojection steps, which are the computationally most demanding parts of any reconstruction algorithm, much more efficiently. Instead of the standard 32 bit floating-point values (float), a recently standardized floating-point value with 16 bit (half) is adopted for data representation in image domain and in rawdata domain. The reduction in the total data amount reduces the traffic on the memory bus, which is the bottleneck of today's high-performance algorithms, by 50%. In CT simulations and CT measurements, float reconstructions (gold standard) and half reconstructions are visually compared via difference images and by quantitative image quality evaluation. This is done for analytical reconstruction (filtered backprojection) and iterative reconstruction (ordered subset SART). The magnitude of quantization noise, which is caused by a reduction in the data precision of both rawdata and image data during image reconstruction, is negligible. This is clearly shown for filtered backprojection and iterative ordered subset SART reconstruction. In filtered backprojection, the implementation of the backprojection should be optimized for low data precision if the image data are represented in half format. In ordered subset SART image reconstruction, no adaptations are necessary and the convergence speed remains unchanged. Half precision floating-point values allow to speed up CT image reconstruction without compromising image quality.

Autonomous system for Web-based microarray image analysis.

PubMed

Bozinov, Daniel

2003-12-01

Software-based feature extraction from DNA microarray images still requires human intervention on various levels. Manual adjustment of grid and metagrid parameters, precise alignment of superimposed grid templates and gene spots, or simply identification of large-scale artifacts have to be performed beforehand to reliably analyze DNA signals and correctly quantify their expression values. Ideally, a Web-based system with input solely confined to a single microarray image and a data table as output containing measurements for all gene spots would directly transform raw image data into abstracted gene expression tables. Sophisticated algorithms with advanced procedures for iterative correction function can overcome imminent challenges in image processing. Herein is introduced an integrated software system with a Java-based interface on the client side that allows for decentralized access and furthermore enables the scientist to instantly employ the most updated software version at any given time. This software tool is extended from PixClust as used in Extractiff incorporated with Java Web Start deployment technology. Ultimately, this setup is destined for high-throughput pipelines in genome-wide medical diagnostics labs or microarray core facilities aimed at providing fully automated service to its users.

The Evolutionary History and Diverse Physiological Roles of the Grapevine Calcium-Dependent Protein Kinase Gene Family

PubMed Central

Chen, Fei; Fasoli, Marianna; Tornielli, Giovanni Battista; Dal Santo, Silvia; Pezzotti, Mario; Zhang, Liangsheng; Cai, Bin; Cheng, Zong-Ming

2013-01-01

Calcium-dependent protein kinases (CDPKs) are molecular switches that bind Ca2+, ATP, and protein substrates, acting as sensor relays and responders that convert Ca2+ signals, created by developmental processes and environmental stresses, into phosphorylation events. The precise functions of the CDPKs in grapevine (Vitis vinifera) are largely unknown. We therefore investigated the phylogenetic relationships and expression profiles of the 17 CDPK genes identified in the 12x grapevine genome sequence, resolving them into four subfamilies based on phylogenetic tree topology and gene structures. The origins of the CDPKs during grapevine evolution were characterized, involving 13 expansion events. Transcriptomic analysis using 54 tissues and developmental stages revealed three types of CDPK gene expression profiles: constitutive (housekeeping CDPKs), partitioned functions, and prevalent in pollen/stamen. We identified two duplicated CDPK genes that had evolved from housekeeping to pollen-prevalent functions and whose origin correlated with that of seed plants, suggesting neofunctionalization with an important role in pollen development and also potential value in the breeding of seedless varieties. We also found that CDPKs were involved in three abiotic stress signaling pathways and could therefore be used to investigate the crosstalk between stress responses. PMID:24324631

Compact perturbative expressions for neutrino oscillations in matter

DOE PAGES

Denton, Peter B.; Minakata, Hisakazu; Parke, Stephen J.

2016-06-08

We further develop and extend a recent perturbative framework for neutrino oscillations in uniform matter density so that the resulting oscillation probabilities are accurate for the complete matter potential versus baseline divided by neutrino energy plane. This extension also gives the exact oscillation probabilities in vacuum for all values of baseline divided by neutrino energy. The expansion parameter used is related to the ratio of the solar to the atmosphericmore » $$\\Delta m^2$$ scales but with a unique choice of the atmospheric $$\\Delta m^2$$ such that certain first-order effects are taken into account in the zeroth-order Hamiltonian. Using a mixing matrix formulation, this framework has the exceptional feature that the neutrino oscillation probability in matter has the same structure as in vacuum, to all orders in the expansion parameter. It also contains all orders in the matter potential and $$\\sin\\theta_{13}$$. It facilitates immediate physical interpretation of the analytic results, and makes the expressions for the neutrino oscillation probabilities extremely compact and very accurate even at zeroth order in our perturbative expansion. Furthermore, the first and second order results are also given which improve the precision by approximately two or more orders of magnitude per perturbative order.« less

Accurate quantitation for in vitro refolding of single domain antibody fragments expressed as inclusion bodies by referring the concomitant expression of a soluble form in the periplasms of Escherichia coli.

PubMed

Noguchi, Tomoaki; Nishida, Yuichi; Takizawa, Keiji; Cui, Yue; Tsutsumi, Koki; Hamada, Takashi; Nishi, Yoshisuke

2017-03-01

Single domain antibody fragments from two species, a camel V H H (PM1) and a shark V NAR (A6), were derived from inclusion bodies of E. coli and refolded in vitro following three refolding recipes for comparing refolding efficiencies: three-step cold dialysis refolding (TCDR), one-step hot dialysis refolding (OHDR), and one-step cold dialysis refolding (OCDR), as these fragments were expressed as 'a soluble form' either in cytoplasm or periplasm, but the amount were much less than those expressed as 'an insoluble form (inclusion body)' in cytoplasm and periplasm. In order to verify the refolding efficiencies from inclusion bodies correctly, proteins purified from periplasmic soluble fractions were used as reference samples. These samples showed far-UV spectra of a typical β-sheet-dominant structure in circular dichroism (CD) spectroscopy and so did the refolded samples as well. As the maximal magnitude of ellipticity in millidegrees (θ max ) observed at a given wave length was proportional to the concentrations of the respective reference samples, we could draw linear regression lines for the magnitudes vs. sample concentrations. By using these lines, we measured the concentrations for the refolded PM1 and A6 samples purified from solubilized cytoplasmic insoluble fractions. The refolding efficiency of PM1 was almost 50% following TCDR and 40% and 30% following OHDR and OCDR, respectively, whereas the value of A6 was around 30% following TCDR, and out of bound for quantitation following the other two recipes. The ELISA curves, which were derived from the refolded samples, coincided better with those obtained from the reference samples after converting the values from the protein-concentrations at recovery to the ones of refolded proteins using recovery ratios, indicating that such a correction gives better results for the accurate measure of the ELISA curves than those without correction. Our method require constructing a dual expression system, expressed both in periplasm as a soluble form and cytoplasm as an insoluble form; application of the different refolding recipes due to sequence-by-sequence-difference could be precisely monitored using CD spectra with the concomitant soluble samples as a reference. Copyright © 2016. Published by Elsevier B.V.

Superallowed Beta Decay Studies at TRIUMF --- Nuclear Structure and Fundamental Symmetries

NASA Astrophysics Data System (ADS)

Zganjar, E. F.; Achtzehn, T.; Albers, D.; Andreoiu, C.; Andreyev, A. N.; Austin, R. A. E.; Ball, G. C.; Behr, J. A.; Biosvert, G. C.; Bricault, P.; Bishop, S.; Chakrawarthy, R. S.; Churchman, R.; Cross, D.; Cunningham, E.; D'Auria, J. M.; Dombsky, M.; Finlay, P.; Garrett, P. E.; Grinyer, G. F.; Hackman, G.; Hanemaayer, V.; Hardy, J. C.; Hodgson, D. F.; Hyland, B.; Iacob, V.; Klages, P.; Koopmans, K. A.; Kulp, W. D.; Lassen, J.; Lavoie, J. P.; Leslie, J. R.; Linder, T.; MacDonald, J. A.; Mak, H.-B.; Melconian, D.; Morton, A. C.; Ormand, W. E.; Osborne, C. J.; Pearson, C. J.; Pearson, M. R.; Phillips, A. A.; Piechaczek, A.; Ressler, J.; Sarazin, F.; Savard, G.; Schumaker, M. A.; Scraggs, H. C.; Svensson, C. E.; Valiente-Dobon, J. J.; Towner, I. S.; Waddington, J. C.; Walker, P. M.; Wendt, K.; Wood, J. L.

2007-04-01

Precision measurement of the beta -decay half-life, Q-value, and branching ratio between nuclear analog states of Jpi = 0+ and T=1 can provide critical and fundamental tests of the Standard Model's description of electroweak interactions. A program has been initiated at TRIUMF-ISAC to measure the ft values of these superallowed beta transitions. Two Tz = 0, A > 60 cases, 74Rb and 62Ga, are presented. These are particularly relevant because they can provide critical tests of the calculated nuclear structure and isospin-symmetry breaking corrections that are predicted to be larger for heavier nuclei, and because they demonstrate the advance in the experimental precision on ft at TRIUMF-ISAC from 0.26% for 74Rb in 2002 to 0.05% for 62Ga in 2006. The high precision world data on experimental ft and corrected Ft values are discussed and shown to be consistent with CVC at the 10-4 level, yielding an average Ft = 3073.70(74) s. This Ft leads to Vud = 0.9737(4) for the up-down element of the Standard Model's CKM matrix. With this value and the Particle Data Group's 2006 values for Vus and Vub, the unitarity condition for the CKM matrix is met. Additional measurements and calculations are needed, however, to reduce the uncertainties in that evaluation. That objective is the focus of the continuing program on superallowed-beta decay at TRIUMF-ISAC.

β -decay Q values among the A = 50 Ti-V-Cr isobaric triplet and atomic masses of Ti 46 , 47 , 49 , 50 , V 50 , 51 , and Cr 50 , 52 – 54

DOE PAGES

Kandegedara, R. M. E. B.; Bollen, G.; Eibach, M.; ...

2017-10-20

This manuscript describes a measurement of the Q value for the highly forbidden beta-decays of 50V and the double electron capture decay of 50Cr. The Q value corresponds to the total energy released during the decay and is equivalent to the mass difference between parent and daughter atoms. This mass difference was measured using high precision Penning trap mass spectrometry with the Low Energy Beam and Ion Trap facility at the National Superconducting Cyclotron Laboratory. The Q value enters into theoretical calculations of the half-life and beta-decay spectrum for the decay, so improves these calculations. In addition the Q valuemore » corresponds to the end point energy of the beta-decay spectrum, which has been precisely measured for several highly-forbidden decays using modern low background detector techniques. Hence, our Q value measurements provide a test of systematics for these detectors. In addition, we have measured the absolute atomic masses of 46,47,49,50Ti, 50,51V, and 50,52-52Cr, providing improvements in precision by factors of up to 3. These atomic masses help to strengthen global evaluations of all atomic mass data, such as the Atomic Mass Evaluation.« less

β -decay Q values among the A = 50 Ti-V-Cr isobaric triplet and atomic masses of Ti 46 , 47 , 49 , 50 , V 50 , 51 , and Cr 50 , 52 – 54

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kandegedara, R. M. E. B.; Bollen, G.; Eibach, M.

This manuscript describes a measurement of the Q value for the highly forbidden beta-decays of 50V and the double electron capture decay of 50Cr. The Q value corresponds to the total energy released during the decay and is equivalent to the mass difference between parent and daughter atoms. This mass difference was measured using high precision Penning trap mass spectrometry with the Low Energy Beam and Ion Trap facility at the National Superconducting Cyclotron Laboratory. The Q value enters into theoretical calculations of the half-life and beta-decay spectrum for the decay, so improves these calculations. In addition the Q valuemore » corresponds to the end point energy of the beta-decay spectrum, which has been precisely measured for several highly-forbidden decays using modern low background detector techniques. Hence, our Q value measurements provide a test of systematics for these detectors. In addition, we have measured the absolute atomic masses of 46,47,49,50Ti, 50,51V, and 50,52-52Cr, providing improvements in precision by factors of up to 3. These atomic masses help to strengthen global evaluations of all atomic mass data, such as the Atomic Mass Evaluation.« less

Toward precise Q{sub EC} values for the superallowed 0{sup +}->0{sup +} beta decays of T=2 nuclides: The masses of {sup 20}Na, {sup 24}Al, {sup 28}P, and {sup 32}Cl

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wrede, C.; Wright Nuclear Structure Laboratory, Yale University, New Haven, Connecticut 06520; Clark, J. A.

High-precision measurements of superallowed 0{sup +}->0{sup +} beta decays of T=2 nuclides such as {sup 20}Mg, {sup 24}Si, {sup 28}S, and {sup 32}Ar can contribute to searches for physics beyond the standard model of particle physics if the Q{sub EC} values are accurate to a few keV or better. As a step toward providing precise Q{sub EC} values for these decays, the ground-state masses of the respective daughter nuclei {sup 20}Na, {sup 24}Al, {sup 28}P, and {sup 32}Cl have been determined by measuring the ({sup 3}He,t) reactions leading to them with the {sup 36}Ar({sup 3}He,t){sup 36}K reaction as a calibration.more » A quadrupole-dipole-dipole-dipole (Q3D) magnetic spectrograph was used together with thin ion-implanted carbon-foil targets of {sup 20}Ne, {sup 24}Mg, {sup 28}Si, {sup 32}S, and {sup 36}Ar. The masses of {sup 20}Na and {sup 32}Cl are found to be in good agreement with the values from the 2003 Atomic Mass Evaluation (AME03) [G. Audi, A. H. Wapstra, and C. Thibault, Nucl. Phys. A 729, 337 (2003)], and the precision has been improved by a factor of 6 in both cases. The masses of {sup 24}Al and {sup 28}P are found to be higher than the values from AME03 by 9.5 keV (3.2sigma) and 11.5 keV (3.6sigma), respectively, and the precision has been improved by a factor of 2.5 in both cases. The new {sup 32}Cl mass is used together with the excitation energy of its lowest T=2 level and the mass of {sup 32}Ar to derive an improved superallowed Q{sub EC} value of 6087.3(22) keV for this case. The effects on quantities related to standard-model tests including the beta-nu correlation coefficient a and the isospin-symmetry-breaking correction delta{sub C} are examined for the A=32 case.« less

Accuracy and precision of four value-added blood glucose meters: the Abbott Optium, the DDI Prodigy, the HDI True Track, and the HypoGuard Assure Pro.

PubMed

Sheffield, Catherine A; Kane, Michael P; Bakst, Gary; Busch, Robert S; Abelseth, Jill M; Hamilton, Robert A

2009-09-01

This study compared the accuracy and precision of four value-added glucose meters. Finger stick glucose measurements in diabetes patients were performed using the Abbott Diabetes Care (Alameda, CA) Optium, Diagnostic Devices, Inc. (Miami, FL) DDI Prodigy, Home Diagnostics, Inc. (Fort Lauderdale, FL) HDI True Track Smart System, and Arkray, USA (Minneapolis, MN) HypoGuard Assure Pro. Finger glucose measurements were compared with laboratory reference results. Accuracy was assessed by a Clarke error grid analysis (EGA), a Parkes EGA, and within 5%, 10%, 15%, and 20% of the laboratory value criteria (chi2 analysis). Meter precision was determined by calculating absolute mean differences in glucose values between duplicate samples (Kruskal-Wallis test). Finger sticks were obtained from 125 diabetes patients, of which 90.4% were Caucasian, 51.2% were female, 83.2% had type 2 diabetes, and average age of 59 years (SD 14 years). Mean venipuncture blood glucose was 151 mg/dL (SD +/-65 mg/dL; range, 58-474 mg/dL). Clinical accuracy by Clarke EGA was demonstrated in 94% of Optium, 82% of Prodigy, 61% of True Track, and 77% of the Assure Pro samples (P < 0.05 for Optium and True Track compared to all others). By Parkes EGA, the True Track was significantly less accurate than the other meters. Within 5% accuracy was achieved in 34%, 24%, 29%, and 13%, respectively (P < 0.05 for Optium, Prodigy, and Assure Pro compared to True Track). Within 10% accuracy was significantly greater for the Optium, Prodigy, and Assure Pro compared to True Track. Significantly more Optium results demonstrated within 15% and 20% accuracy compared to the other meter systems. The HDI True Track was significantly less precise than the other meter systems. The Abbott Optium was significantly more accurate than the other meter systems, whereas the HDI True Track was significantly less accurate and less precise compared to the other meter systems.

The economic case for precision medicine.

PubMed

Gavan, Sean P; Thompson, Alexander J; Payne, Katherine

2018-01-01

Introduction : The advancement of precision medicine into routine clinical practice has been highlighted as an agenda for national and international health care policy. A principle barrier to this advancement is in meeting requirements of the payer or reimbursement agency for health care. This special report aims to explain the economic case for precision medicine, by accounting for the explicit objectives defined by decision-makers responsible for the allocation of limited health care resources. Areas covered : The framework of cost-effectiveness analysis, a method of economic evaluation, is used to describe how precision medicine can, in theory, exploit identifiable patient-level heterogeneity to improve population health outcomes and the relative cost-effectiveness of health care. Four case studies are used to illustrate potential challenges when demonstrating the economic case for a precision medicine in practice. Expert commentary : The economic case for a precision medicine should be considered at an early stage during its research and development phase. Clinical and economic evidence can be generated iteratively and should be in alignment with the objectives and requirements of decision-makers. Programmes of further research, to demonstrate the economic case of a precision medicine, can be prioritized by the extent that they reduce the uncertainty expressed by decision-makers.

The economic case for precision medicine

PubMed Central

Gavan, Sean P.; Thompson, Alexander J.; Payne, Katherine

2018-01-01

ABSTRACT Introduction: The advancement of precision medicine into routine clinical practice has been highlighted as an agenda for national and international health care policy. A principle barrier to this advancement is in meeting requirements of the payer or reimbursement agency for health care. This special report aims to explain the economic case for precision medicine, by accounting for the explicit objectives defined by decision-makers responsible for the allocation of limited health care resources. Areas covered: The framework of cost-effectiveness analysis, a method of economic evaluation, is used to describe how precision medicine can, in theory, exploit identifiable patient-level heterogeneity to improve population health outcomes and the relative cost-effectiveness of health care. Four case studies are used to illustrate potential challenges when demonstrating the economic case for a precision medicine in practice. Expert commentary: The economic case for a precision medicine should be considered at an early stage during its research and development phase. Clinical and economic evidence can be generated iteratively and should be in alignment with the objectives and requirements of decision-makers. Programmes of further research, to demonstrate the economic case of a precision medicine, can be prioritized by the extent that they reduce the uncertainty expressed by decision-makers. PMID:29682615

Influence of non-ideal performance of lasers on displacement precision in single-grating heterodyne interferometry

NASA Astrophysics Data System (ADS)

Wang, Guochao; Xie, Xuedong; Yan, Shuhua

2010-10-01

Principle of the dual-wavelength single grating nanometer displacement measuring system, with a long range, high precision, and good stability, is presented. As a result of the nano-level high-precision displacement measurement, the error caused by a variety of adverse factors must be taken into account. In this paper, errors, due to the non-ideal performance of the dual-frequency laser, including linear error caused by wavelength instability and non-linear error caused by elliptic polarization of the laser, are mainly discussed and analyzed. On the basis of theoretical modeling, the corresponding error formulas are derived as well. Through simulation, the limit value of linear error caused by wavelength instability is 2nm, and on the assumption that 0.85 x T = , 1 Ty = of the polarizing beam splitter(PBS), the limit values of nonlinear-error caused by elliptic polarization are 1.49nm, 2.99nm, 4.49nm while the non-orthogonal angle is selected correspondingly at 1°, 2°, 3° respectively. The law of the error change is analyzed based on different values of Tx and Ty .

First Results of Field Absolute Calibration of the GPS Receiver Antenna at Wuhan University

PubMed Central

Hu, Zhigang; Zhao, Qile; Chen, Guo; Wang, Guangxing; Dai, Zhiqiang; Li, Tao

2015-01-01

GNSS receiver antenna phase center variations (PCVs), which arise from the non-spherical phase response of GNSS signals have to be well corrected for high-precision GNSS applications. Without using a precise antenna phase center correction (PCC) model, the estimated position of a station monument will lead to a bias of up to several centimeters. The Chinese large-scale research project “Crustal Movement Observation Network of China” (CMONOC), which requires high-precision positions in a comprehensive GPS observational network motived establishment of a set of absolute field calibrations of the GPS receiver antenna located at Wuhan University. In this paper the calibration facilities are firstly introduced and then the multipath elimination and PCV estimation strategies currently used are elaborated. The validation of estimated PCV values of test antenna are finally conducted, compared with the International GNSS Service (IGS) type values. Examples of TRM57971.00 NONE antenna calibrations from our calibration facility demonstrate that the derived PCVs and IGS type mean values agree at the 1 mm level. PMID:26580616

Precision Farming and Precision Pest Management: The Power of New Crop Production Technologies

PubMed Central

Strickland, R. Mack; Ess, Daniel R.; Parsons, Samuel D.

1998-01-01

The use of new technologies including Geographic Information Systems (GIS), the Global Positioning System (GPS), Variable Rate Technology (VRT), and Remote Sensing (RS) is gaining acceptance in the present high-technology, precision agricultural industry. GIS provides the ability to link multiple data values for the same geo-referenced location, and provides the user with a graphical visualization of such data. When GIS is coupled with GPS and RS, management decisions can be applied in a more precise "micro-managed" manner by using VRT techniques. Such technology holds the potential to reduce agricultural crop production costs as well as crop and environmental damage. PMID:19274236

Measurement of whole tire profile

NASA Astrophysics Data System (ADS)

Yang, Yongyue; Jiao, Wenguang

2010-08-01

In this paper, a precision measuring device is developed for obtaining characteristic curve of tire profile and its geometric parameters. It consists of a laser displacement measurement unit, a closed-loop precision two-dimensional coordinate table, a step motor control system and a fast data acquisition and analysis system. Based on the laser trigonometry, a data map of tire profile and coordinate values of all points can be obtained through corresponding data transformation. This device has a compact structure, a convenient control, a simple hardware circuit design and a high measurement precision. Experimental results indicate that measurement precision can meet the customer accuracy requirement of +/-0.02 mm.

Precision diamond grinding of ceramics and glass

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, S.; Paul, H.; Scattergood, R.O.

A new research initiative will be undertaken to investigate the effect of machine parameters and material properties on precision diamond grinding of ceramics and glass. The critical grinding depth to initiate the plastic flow-to-brittle fracture regime will be directly measured using plunge-grind tests. This information will be correlated with machine parameters such as wheel bonding and diamond grain size. Multiaxis grinding tests will then be made to provide data more closely coupled with production technology. One important aspect of the material property studies involves measuring fracture toughness at the very short crack sizes commensurate with grinding damage. Short crack toughnessmore » value`s can be much less than the long-crack toughness values measured in conventional fracture tests.« less

Precision spectroscopy of the 2S-4P transition in atomic hydrogen

NASA Astrophysics Data System (ADS)

Maisenbacher, Lothar; Beyer, Axel; Matveev, Arthur; Grinin, Alexey; Pohl, Randolf; Khabarova, Ksenia; Kolachevsky, Nikolai; Hänsch, Theodor W.; Udem, Thomas

2017-04-01

Precision measurements of atomic hydrogen have long been successfully used to extract fundamental constants and to test bound-state QED. However, both these applications are limited by measurements of hydrogen lines other than the very precisely known 1S-2S transition. Moreover, the proton r.m.s.charge radius rp extracted from electronic hydrogen measurements currently disagrees by 4 σ with the much more precise value extracted from muonic hydrogen spectroscopy. We have measured the 2S-4P transition in atomic hydrogen using a cryogenic beam of hydrogen atoms optically excited to the initial 2S state. The first order Doppler shift of the one-photon 2S-4P transition is suppressed by actively stabilized counter-propagating laser beams and time-of-flight resolved detection. Quantum interference between excitation paths can lead to significant line distortions in our system. We use an experimentally verified, simple line shape model to take these distortions into account. With this, we can extract a new value for rp and the Rydberg constant R∞ with comparable accuracy as the combined previous H world data.

Fat fraction bias correction using T1 estimates and flip angle mapping.

PubMed

Yang, Issac Y; Cui, Yifan; Wiens, Curtis N; Wade, Trevor P; Friesen-Waldner, Lanette J; McKenzie, Charles A

2014-01-01

To develop a new method of reducing T1 bias in proton density fat fraction (PDFF) measured with iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL). PDFF maps reconstructed from high flip angle IDEAL measurements were simulated and acquired from phantoms and volunteer L4 vertebrae. T1 bias was corrected using a priori T1 values for water and fat, both with and without flip angle correction. Signal-to-noise ratio (SNR) maps were used to measure precision of the reconstructed PDFF maps. PDFF measurements acquired using small flip angles were then compared to both sets of corrected large flip angle measurements for accuracy and precision. Simulations show similar results in PDFF error between small flip angle measurements and corrected large flip angle measurements as long as T1 estimates were within one standard deviation from the true value. Compared to low flip angle measurements, phantom and in vivo measurements demonstrate better precision and accuracy in PDFF measurements if images were acquired at a high flip angle, with T1 bias corrected using T1 estimates and flip angle mapping. T1 bias correction of large flip angle acquisitions using estimated T1 values with flip angle mapping yields fat fraction measurements of similar accuracy and superior precision compared to low flip angle acquisitions. Copyright © 2013 Wiley Periodicals, Inc.

Evaluation of MMP-9 and MMP-2 and their suppressor TIMP-1 and TIMP-2 in adenocarcinoma of esophagogastric junction.

PubMed

Lu, Xiaofei; Duan, Lingling; Xie, Hongqin; Lu, Xiaoxia; Lu, Daolin; Lu, Daopeng; Jiang, Nan; Chen, Yuxin

2016-01-01

Adenocarcinoma of esophagogastric junction (AEG) is a lethal malignancy featured with early metastasis, poor prognosis, and few treatment options. Matrix metalloproteinase (MMP) and metalloproteinase suppressor (TIMP) have been considered to be associated with cancer invasion and metastasis. In our study, we evaluated expressions of MMP-9, MMP-2, TIMP-1, and TIMP-2 in AEG and their correlation with clinicopathological parameters and the overall survival rate. Expressions of MMP-9, MMP-2, TIMP-1, and TIMP-2 in specimens from 120 AEGs were detected by immunohistochemistry. The correlations between expressions of these four proteins and clinicopathological characters were analyzed by chi-square test. Moreover, the prognostic value of these four biomarkers was evaluated by univariate analysis with Kaplan-Meier method and multivariate analysis with Cox regression model. The positive expression rate of MMP-9, MMP-2, TIMP-1, and TIMP-2 was 65%, 53%, 70%, and 49%, respectively, in the detected 120 AEG samples. MMP-9 was significantly associated with poorly histological differentiation (P=0.001), lymph node metastasis (P=0.007), and UICC stage (P=0.008). TIMP-1 showed significantly reversed correlations with histological differentiation (P=0.001), lymph node metastasis (P=0.007), and Union for International Cancer Control stage (P=0.008). Univariate analysis revealed that lymph node metastasis (P=0.002), depth of invasion (P=0.050), and MMP-9+/TIMP-1 phonotype (P<0.001) were significantly associated with the overall survival rate. Multivariate analyses demonstrated that MMP-9+/TIMP-1-phenotype was an independent prognostic factor in AEGs. Detection of MMP-9 and TIMP-1 expression allows stratification of AEG patients into different survival categories and can be useful for precise individual evaluation and survival prediction.

Automated simultaneous measurement of the δ(13) C and δ(2) H values of methane and the δ(13) C and δ(18) O values of carbon dioxide in flask air samples using a new multi cryo-trap/gas chromatography/isotope ratio mass spectrometry system.

PubMed

Brand, Willi A; Rothe, Michael; Sperlich, Peter; Strube, Martin; Wendeberg, Magnus

2016-07-15

The isotopic composition of greenhouse gases helps to constrain global budgets and to study sink and source processes. We present a new system for high-precision stable isotope measurements of carbon, hydrogen and oxygen in atmospheric methane and carbon dioxide. The design is intended for analyzing flask air samples from existing sampling programs without the need for extra sample air for methane analysis. CO2 and CH4 isotopes are measured simultaneously using two isotope ratio mass spectrometers, one for the analysis of δ(13) C and δ(18) O values and the second one for δ(2) H values. The inlet carousel delivers air from 16 sample positions (glass flasks 1-5 L and high-pressure cylinders). Three 10-port valves take aliquots from the sample stream. CH4 from 100-mL air aliquots is preconcentrated in 0.8-mL sample loops using a new cryo-trap system. A precisely calibrated working reference air is used in parallel with the sample according to the Principle of Identical Treatment. It takes about 36 hours for a fully calibrated analysis of a complete carousel including extractions of four working reference and one quality control reference air. Long-term precision values, as obtained from the quality control reference gas since 2012, account for 0.04 ‰ (δ(13) C values of CO2 ), 0.07 ‰ (δ(18) O values of CO2 ), 0.11 ‰ (δ(13) C values of CH4 ) and 1.0 ‰ (δ(2) H values of CH4 ). Within a single day, the system exhibits a typical methane δ(13) C standard deviation (1σ) of 0.06 ‰ for 10 repeated measurements. The system has been in routine operation at the MPI-BGC since 2012. Consistency of the data and compatibility with results from other laboratories at a high precision level are of utmost importance. A high sample throughput and reliability of operation are important achievements of the presented system to cope with the large number of air samples to be analyzed. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Direct Comparison of the Precision of the New Hologic Horizon Model With the Old Discovery Model.

PubMed

Whittaker, LaTarsha G; McNamara, Elizabeth A; Vath, Savoun; Shaw, Emily; Malabanan, Alan O; Parker, Robert A; Rosen, Harold N

2017-11-22

Previous publications suggested that the precision of the new Hologic Horizon densitometer might be better than that of the previous Discovery model, but these observations were confounded by not using the same participants and technologists on both densitometers. We sought to study this issue methodically by measuring in vivo precision in both densitometers using the same patients and technologists. Precision studies for the Horizon and Discovery models were done by acquiring spine, hip, and forearm bone mineral density twice on 30 participants. The set of 4 scans on each participant (2 on the Discovery, 2 on the Horizon) was acquired by the same technologist using the same scanning mode. The pairs of data were used to calculate the least significant change according to the International Society for Clinical Densitometry guidelines. The significance of the difference between least significant changes was assessed using a Wilcoxon signed-rank test of the difference between the mean square error of the absolute value of the differences between paired measurements on the Discovery (Δ-Discovery) and the mean square error of the absolute value of the differences between paired measurements on the Horizon (Δ-Horizon). At virtually all anatomic sites, there was a nonsignificant trend for the precision to be better for the Horizon than for the Discovery. As more vertebrae were excluded from analysis, the precision deteriorated on both densitometers. The precision between densitometers was almost identical when reporting only 1 vertebral body. (1) There was a nonsignificant trend for greater precision on the new Hologic Horizon compared with the older Discovery model. (2) The difference in precision of the spine bone mineral density between the Horizon and the Discovery models decreases as fewer vertebrae are included. (3) These findings are substantially similar to previously published results which had not controlled as well for confounding from using different subjects and technologists. Copyright © 2017 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

Identifying QT prolongation from ECG impressions using a general-purpose Natural Language Processor

PubMed Central

Denny, Joshua C.; Miller, Randolph A.; Waitman, Lemuel Russell; Arrieta, Mark; Peterson, Joshua F.

2009-01-01

Objective Typically detected via electrocardiograms (ECGs), QT interval prolongation is a known risk factor for sudden cardiac death. Since medications can promote or exacerbate the condition, detection of QT interval prolongation is important for clinical decision support. We investigated the accuracy of natural language processing (NLP) for identifying QT prolongation from cardiologist-generated, free-text ECG impressions compared to corrected QT (QTc) thresholds reported by ECG machines. Methods After integrating negation detection to a locally-developed natural language processor, the KnowledgeMap concept identifier, we evaluated NLP-based detection of QT prolongation compared to the calculated QTc on a set of 44,318 ECGs obtained from hospitalized patients. We also created a string query using regular expressions to identify QT prolongation. We calculated sensitivity and specificity of the methods using manual physician review of the cardiologist-generated reports as the gold standard. To investigate causes of “false positive” calculated QTc, we manually reviewed randomly selected ECGs with a long calculated QTc but no mention of QT prolongation. Separately, we validated the performance of the negation detection algorithm on 5,000 manually-categorized ECG phrases for any medical concept (not limited to QT prolongation) prior to developing the NLP query for QT prolongation. Results The NLP query for QT prolongation correctly identified 2,364 of 2,373 ECGs with QT prolongation with a sensitivity of 0.996 and a positive predictive value of 1.000. There were no false positives. The regular expression query had a sensitivity of 0.999 and positive predictive value of 0.982. In contrast, the positive predictive value of common QTc thresholds derived from ECG machines was 0.07–0.25 with corresponding sensitivities of 0.994–0.046. The negation detection algorithm had a recall of 0.973 and precision of 0.982 for 10,490 concepts found within ECG impressions. Conclusions NLP and regular expression queries of cardiologists’ ECG interpretations can more effectively identify QT prolongation than the automated QTc intervals reported by ECG machines. Future clinical decision support could employ NLP queries to detect QTc prolongation and other reported ECG abnormalities. PMID:18938105

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meeks, Kelsey; Pantoya, Michelle L.; Green, Micah

For dispersions containing a single type of particle, it has been observed that the onset of percolation coincides with a critical value of volume fraction. When the volume fraction is calculated based on excluded volume, this critical percolation threshold is nearly invariant to particle shape. The critical threshold has been calculated to high precision for simple geometries using Monte Carlo simulations, but this method is slow at best, and infeasible for complex geometries. This article explores an analytical approach to the prediction of percolation threshold in polydisperse mixtures. Specifically, this paper suggests an extension of the concept of excluded volume,more » and applies that extension to the 2D binary disk system. The simple analytical expression obtained is compared to Monte Carlo results from the literature. In conclusion, the result may be computed extremely rapidly and matches key parameters closely enough to be useful for composite material design.« less

A Small and Slim Coaxial Probe for Single Rice Grain Moisture Sensing

PubMed Central

You, Kok Yeow; Mun, Hou Kit; You, Li Ling; Salleh, Jamaliah; Abbas, Zulkifly

2013-01-01

A moisture detection of single rice grains using a slim and small open-ended coaxial probe is presented. The coaxial probe is suitable for the nondestructive measurement of moisture values in the rice grains ranging from from 9.5% to 26%. Empirical polynomial models are developed to predict the gravimetric moisture content of rice based on measured reflection coefficients using a vector network analyzer. The relationship between the reflection coefficient and relative permittivity were also created using a regression method and expressed in a polynomial model, whose model coefficients were obtained by fitting the data from Finite Element-based simulation. Besides, the designed single rice grain sample holder and experimental set-up were shown. The measurement of single rice grains in this study is more precise compared to the measurement in conventional bulk rice grains, as the random air gap present in the bulk rice grains is excluded. PMID:23493127

Finding and Exploring Health Information with a Slider-Based User Interface.

PubMed

Pang, Patrick Cheong-Iao; Verspoor, Karin; Pearce, Jon; Chang, Shanton

2016-01-01

Despite the fact that search engines are the primary channel to access online health information, there are better ways to find and explore health information on the web. Search engines are prone to problems when they are used to find health information. For instance, users have difficulties in expressing health scenarios with appropriate search keywords, search results are not optimised for medical queries, and the search process does not account for users' literacy levels and reading preferences. In this paper, we describe our approach to addressing these problems by introducing a novel design using a slider-based user interface for discovering health information without the need for precise search keywords. The user evaluation suggests that the interface is easy to use and able to assist users in the process of discovering new information. This study demonstrates the potential value of adopting slider controls in the user interface of health websites for navigation and information discovery.

MicroRNA function in Drosophila melanogaster.

PubMed

Carthew, Richard W; Agbu, Pamela; Giri, Ritika

2017-05-01

Over the last decade, microRNAs have emerged as critical regulators in the expression and function of animal genomes. This review article discusses the relationship between microRNA-mediated regulation and the biology of the fruit fly Drosophila melanogaster. We focus on the roles that microRNAs play in tissue growth, germ cell development, hormone action, and the development and activity of the central nervous system. We also discuss the ways in which microRNAs affect robustness. Many gene regulatory networks are robust; they are relatively insensitive to the precise values of reaction constants and concentrations of molecules acting within the networks. MicroRNAs involved in robustness appear to be nonessential under uniform conditions used in conventional laboratory experiments. However, the robust functions of microRNAs can be revealed when environmental or genetic variation otherwise has an impact on developmental outcomes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dissecting the indirect effects caused by vaccines into the basic elements.

PubMed

Scarbrough Lefebvre, Carla D; Terlinden, Augustin; Standaert, Baudouin

2015-01-01

Vaccination directly protects vaccinated individuals, but it also has the potential for indirectly protecting the unvaccinated in a population (herd protection). Unintended negative consequences such as the re-manifestation of infection, mainly expressed as age shifts, result from vaccination programs as well. We discuss the necessary conditions for achieving optimal herd protection (i.e., high quality vaccine-induced immunity, substantial effect on the force of infection, and appropriate vaccine coverage and distribution), as well as the conditions under which age shifts are likely to occur. We show examples to illustrate these effects. Substantial ambiguity in observing and quantifying these indirect vaccine effects makes accurate evaluation troublesome even though the nature of these outcomes may be critical for accurate assessment of the economic value when decision makers are evaluating a novel vaccine for introduction into a particular region or population group. More investigation is needed to identify and develop successful assessment methodologies for precisely analyzing these outcomes.

Generalized Arcsine Laws for Fractional Brownian Motion

NASA Astrophysics Data System (ADS)

Sadhu, Tridib; Delorme, Mathieu; Wiese, Kay Jörg

2018-01-01

The three arcsine laws for Brownian motion are a cornerstone of extreme-value statistics. For a Brownian Bt starting from the origin, and evolving during time T , one considers the following three observables: (i) the duration t+ the process is positive, (ii) the time tlast the process last visits the origin, and (iii) the time tmax when it achieves its maximum (or minimum). All three observables have the same cumulative probability distribution expressed as an arcsine function, thus the name arcsine laws. We show how these laws change for fractional Brownian motion Xt, a non-Markovian Gaussian process indexed by the Hurst exponent H . It generalizes standard Brownian motion (i.e., H =1/2 ). We obtain the three probabilities using a perturbative expansion in ɛ =H -1/2 . While all three probabilities are different, this distinction can only be made at second order in ɛ . Our results are confirmed to high precision by extensive numerical simulations.

Application of a microplate-based ORAC-pyrogallol red assay for the estimation ofantioxidant capacity: First Action 2012.03.

PubMed

Ortiz, Rocío; Antilén, Mónica; Speisky, Hernán; Aliaga, Margarita E; López-Alarcón, Camilo; Baugh, Steve

2012-01-01

A method was developed for microplate-based oxygen radicals absorbance capacity (ORAC) using pyrogallol red (PGR) as probe (ORAC-PGR). The method was evaluated for linearity, precision, and accuracy. In addition, the antioxidant capacity of commercial beverages, such as wines, fruit juices, and iced teas, was measured. Linearity of the area under the curve (AUC) versus Trolox concentration plots was [AUC = (845 +/- 110) + (23 +/- 2) [Trolox, microM]; R = 0.9961, n = 19]. Analyses showed better precision and accuracy at the highest Trolox concentration (40 microM) with RSD and recovery (REC) values of 1.7 and 101.0%, respectively. The method also showed good linearity for red wine [AUC = (787 +/- 77) + (690 +/- 60) [red wine, microL/mL]; R = 0.9926, n = 17], precision and accuracy with RSD values from 1.4 to 8.3%, and REC values that ranged from 89.7 to 103.8%. Red wines showed higher ORAC-PGR values than white wines, while the ORAC-PGR index of fruit juices and iced teas presented a wide range of results, from 0.6 to 21.6 mM of Trolox equivalents. Product-to-product variability was also observed for juices of the same fruit, showing the differences between brands on the ORAC-PGR index.

Accuracy and reliability of multi-GNSS real-time precise positioning: GPS, GLONASS, BeiDou, and Galileo

NASA Astrophysics Data System (ADS)

Li, Xingxing; Ge, Maorong; Dai, Xiaolei; Ren, Xiaodong; Fritsche, Mathias; Wickert, Jens; Schuh, Harald

2015-06-01

In this contribution, we present a GPS+GLONASS+BeiDou+Galileo four-system model to fully exploit the observations of all these four navigation satellite systems for real-time precise orbit determination, clock estimation and positioning. A rigorous multi-GNSS analysis is performed to achieve the best possible consistency by processing the observations from different GNSS together in one common parameter estimation procedure. Meanwhile, an efficient multi-GNSS real-time precise positioning service system is designed and demonstrated by using the multi-GNSS Experiment, BeiDou Experimental Tracking Network, and International GNSS Service networks including stations all over the world. The statistical analysis of the 6-h predicted orbits show that the radial and cross root mean square (RMS) values are smaller than 10 cm for BeiDou and Galileo, and smaller than 5 cm for both GLONASS and GPS satellites, respectively. The RMS values of the clock differences between real-time and batch-processed solutions for GPS satellites are about 0.10 ns, while the RMS values for BeiDou, Galileo and GLONASS are 0.13, 0.13 and 0.14 ns, respectively. The addition of the BeiDou, Galileo and GLONASS systems to the standard GPS-only processing, reduces the convergence time almost by 70 %, while the positioning accuracy is improved by about 25 %. Some outliers in the GPS-only solutions vanish when multi-GNSS observations are processed simultaneous. The availability and reliability of GPS precise positioning decrease dramatically as the elevation cutoff increases. However, the accuracy of multi-GNSS precise point positioning (PPP) is hardly decreased and few centimeter are still achievable in the horizontal components even with 40 elevation cutoff. At 30 and 40 elevation cutoffs, the availability rates of GPS-only solution drop significantly to only around 70 and 40 %, respectively. However, multi-GNSS PPP can provide precise position estimates continuously (availability rate is more than 99.5 %) even up to 40 elevation cutoff (e.g., in urban canyons).

Precision and accuracy of manual water-level measurements taken in the Yucca Mountain area, Nye County, Nevada, 1988-90

USGS Publications Warehouse

Boucher, M.S.

1994-01-01

Water-level measurements have been made in deep boreholes in the Yucca Mountain area, Nye County, Nevada, since 1983 in support of the U.S. Department of Energy's Yucca Mountain Project, which is an evaluation of the area to determine its suitability as a potential storage area for high-level nuclear waste. Water-level measurements were taken either manually, using various water-level measuring equipment such as steel tapes, or they were taken continuously, using automated data recorders and pressure transducers. This report presents precision range and accuracy data established for manual water-level measurements taken in the Yucca Mountain area, 1988-90. Precision and accuracy ranges were determined for all phases of the water-level measuring process, and overall accuracy ranges are presented. Precision ranges were determined for three steel tapes using a total of 462 data points. Mean precision ranges of these three tapes ranged from 0.014 foot to 0.026 foot. A mean precision range of 0.093 foot was calculated for the multiconductor cable, using 72 data points. Mean accuracy values were calculated on the basis of calibrations of the steel tapes and the multiconductor cable against a reference steel tape. The mean accuracy values of the steel tapes ranged from 0.053 foot, based on three data points to 0.078, foot based on six data points. The mean accuracy of the multiconductor cable was O. 15 foot, based on six data points. Overall accuracy of the water-level measurements was calculated by taking the square root of the sum of the squares of the individual accuracy values. Overall accuracy was calculated to be 0.36 foot for water-level measurements taken with steel tapes, without accounting for the inaccuracy of borehole deviations from vertical. An overall accuracy of 0.36 foot for measurements made with steel tapes is considered satisfactory for this project.

Statistics Refresher for Molecular Imaging Technologists, Part 2: Accuracy of Interpretation, Significance, and Variance.

PubMed

Farrell, Mary Beth

2018-06-01

This article is the second part of a continuing education series reviewing basic statistics that nuclear medicine and molecular imaging technologists should understand. In this article, the statistics for evaluating interpretation accuracy, significance, and variance are discussed. Throughout the article, actual statistics are pulled from the published literature. We begin by explaining 2 methods for quantifying interpretive accuracy: interreader and intrareader reliability. Agreement among readers can be expressed simply as a percentage. However, the Cohen κ-statistic is a more robust measure of agreement that accounts for chance. The higher the κ-statistic is, the higher is the agreement between readers. When 3 or more readers are being compared, the Fleiss κ-statistic is used. Significance testing determines whether the difference between 2 conditions or interventions is meaningful. Statistical significance is usually expressed using a number called a probability ( P ) value. Calculation of P value is beyond the scope of this review. However, knowing how to interpret P values is important for understanding the scientific literature. Generally, a P value of less than 0.05 is considered significant and indicates that the results of the experiment are due to more than just chance. Variance, standard deviation (SD), confidence interval, and standard error (SE) explain the dispersion of data around a mean of a sample drawn from a population. SD is commonly reported in the literature. A small SD indicates that there is not much variation in the sample data. Many biologic measurements fall into what is referred to as a normal distribution taking the shape of a bell curve. In a normal distribution, 68% of the data will fall within 1 SD, 95% will fall within 2 SDs, and 99.7% will fall within 3 SDs. Confidence interval defines the range of possible values within which the population parameter is likely to lie and gives an idea of the precision of the statistic being measured. A wide confidence interval indicates that if the experiment were repeated multiple times on other samples, the measured statistic would lie within a wide range of possibilities. The confidence interval relies on the SE. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

Half-life of {sup 221}Fr in Si and Au at 4 K and at millikelvin temperatures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wauters, F.; Breitenfeldt, M.; De Leebeeck, V.

2010-12-15

The half-life of the {alpha}-decaying nucleus {sup 221}Fr was determined in different environments, that is, embedded in Si at 4 K, and embedded in Au at 4 K and about 20 mK. No differences in half-life for these different conditions were observed within 0.1%. Furthermore, we quote a value for the absolute half-life of {sup 221}Fr of t{sub 1/2}=286.1(10) s that is of comparable precision to the most precise value available in the literature.

Frequencies and expression levels of programmed death ligand 1 (PD-L1) in circulating tumor RNA (ctRNA) in various cancer types.

PubMed

Ishiba, Toshiyuki; Hoffmann, Andreas-Claudius; Usher, Joshua; Elshimali, Yahya; Sturdevant, Todd; Dang, Mai; Jaimes, Yolanda; Tyagi, Rama; Gonzales, Ronald; Grino, Mary; Pinski, Jacek K; Barzi, Afsaneh; Raez, Luis E; Eberhardt, Wilfried E; Theegarten, Dirk; Lenz, Heinz-Josef; Uetake, Hiroyuki; Danenberg, Peter V; Danenberg, Kathleen

2018-06-07

Precision medicine and prediction of therapeutic response requires monitoring potential biomarkers before and after treatment. Liquid biopsies provide noninvasive prognostic markers such as circulating tumor DNA and RNA. Circulating tumor RNA (ctRNA) in blood is also used to identify mutations in genes of interest, but additionally, provides information about relative expression levels of important genes. In this study, we analyzed PD-L1 expression in ctRNA isolated from various cancer types. Tumors inhibit antitumor response by modulating the immune checkpoint proteins programmed death ligand 1 (PD-L1) and its cognate receptor PD1. The expression of these genes has been implicated in evasion of immune response and resistance to targeted therapies. Blood samples were collected from gastric (GC), colorectal (CRC), lung (NSCLC), breast (BC), prostate cancer (PC) patients, and a healthy control group. ctRNA was purified from fractionated plasma, and following reverse transcription, levels of PD-L1 expression were analyzed using qPCR. PD-L1 expression was detected in the plasma ctRNA of all cancer types at varying frequencies but no PD-L1 mRNA was detected in cancer-free individuals. The frequencies of PD-L1 expression were significantly different among the various cancer types but the median relative PD-L1 expression values were not significantly different. In 12 cases where plasma and tumor tissue were available from the same patients, there was a high degree of concordance between expression of PD-L1 protein in tumor tissues and PD-L1 gene expression in plasma, and both methods were equally predictive of response to nivolumab. PD-L1 mRNA can be detected and quantitated in ctRNA of cancer patients. These results pave the way for further studies aimed at determining whether monitoring the levels of PD-L1 mRNA in blood can identify patients who are most likely to benefit from the conventional treatment. Copyright © 2018 Elsevier Inc. All rights reserved.

Value of Sample Return and High Precision Analyses: Need for A Resource of Compelling Stories, Metaphors and Examples for Public Speakers

NASA Technical Reports Server (NTRS)

Allton, J. H.

2017-01-01

There is widespread agreement among planetary scientists that much of what we know about the workings of the solar system comes from accurate, high precision measurements on returned samples. Precision is a function of the number of atoms the instrumentation is able to count. Accuracy depends on the calibration or standardization technique. For Genesis, the solar wind sample return mission, acquiring enough atoms to ensure precise SW measurements and then accurately quantifying those measurements were steps known to be non-trivial pre-flight. The difficulty of precise and accurate measurements on returned samples, and why they cannot be made remotely, is not communicated well to the public. In part, this is be-cause "high precision" is abstract and error bars are not very exciting topics. This paper explores ideas for collecting and compiling compelling metaphors and colorful examples as a resource for planetary science public speakers.

Development of a PD-L1 Complementary Diagnostic Immunohistochemistry Assay (SP142) for Atezolizumab.

PubMed

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/.

Precision-cut rat, mouse, and human intestinal slices as novel models for the early-onset of intestinal fibrosis.

PubMed

Pham, Bao Tung; van Haaften, Wouter Tobias; Oosterhuis, Dorenda; Nieken, Judith; de Graaf, Inge Anne Maria; Olinga, Peter

2015-04-01

Intestinal fibrosis (IF) is a major complication of inflammatory bowel disease. IF research is limited by the lack of relevant in vitro and in vivo models. We evaluated precision-cut intestinal slices (PCIS) prepared from human, rat, and mouse intestine as ex vivo models mimicking the early-onset of (human) IF. Precision-cut intestinal slices prepared from human (h), rat (r), and mouse (m) jejunum, were incubated up to 72 h, the viability of PCIS was assessed by ATP content and morphology, and the gene expression of several fibrosis markers was determined. The viability of rPCIS decreased after 24 h of incubation, whereas mPCIS and hPCIS were viable up to 72 h of culturing. Furthermore, during this period, gene expression of heat shock protein 47 and plasminogen activator inhibitor 1 increased in all PCIS in addition to augmented expression of synaptophysin in hPCIS, fibronectin (Fn2) and TGF-β1 in rPCIS, and Fn2 and connective tissue growth factor (Ctgf) in mPCIS. Addition of TGF-β1 to rPCIS or mPCIS induced the gene expression of the fibrosis markers Pro-collagen1a1, Fn2, and Ctgf in both species. However, none of the fibrosis markers was further elevated in hPCIS. We successfully developed a novel ex vivo model that can mimic the early-onset of fibrosis in the intestine using human, rat, and mouse PCIS. Furthermore, in rat and mouse PCIS, TGF-β1 was able to even further increase the gene expression of fibrosis markers. This indicates that PCIS can be used as a model for the early-onset of IF. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Optimal weighted combinatorial forecasting model of QT dispersion of ECGs in Chinese adults.

PubMed

Wen, Zhang; Miao, Ge; Xinlei, Liu; Minyi, Cen

2016-07-01

This study aims to provide a scientific basis for unifying the reference value standard of QT dispersion of ECGs in Chinese adults. Three predictive models including regression model, principal component model, and artificial neural network model are combined to establish the optimal weighted combination model. The optimal weighted combination model and single model are verified and compared. Optimal weighted combinatorial model can reduce predicting risk of single model and improve the predicting precision. The reference value of geographical distribution of Chinese adults' QT dispersion was precisely made by using kriging methods. When geographical factors of a particular area are obtained, the reference value of QT dispersion of Chinese adults in this area can be estimated by using optimal weighted combinatorial model and reference value of the QT dispersion of Chinese adults anywhere in China can be obtained by using geographical distribution figure as well.

Precision Health Economics and Outcomes Research to Support Precision Medicine: Big Data Meets Patient Heterogeneity on the Road to Value.

PubMed

Chen, Yixi; Guzauskas, Gregory F; Gu, Chengming; Wang, Bruce C M; Furnback, Wesley E; Xie, Guotong; Dong, Peng; Garrison, Louis P

2016-11-02

The "big data" era represents an exciting opportunity to utilize powerful new sources of information to reduce clinical and health economic uncertainty on an individual patient level. In turn, health economic outcomes research (HEOR) practices will need to evolve to accommodate individual patient-level HEOR analyses. We propose the concept of "precision HEOR", which utilizes a combination of costs and outcomes derived from big data to inform healthcare decision-making that is tailored to highly specific patient clusters or individuals. To explore this concept, we discuss the current and future roles of HEOR in health sector decision-making, big data and predictive analytics, and several key HEOR contexts in which big data and predictive analytics might transform traditional HEOR into precision HEOR. The guidance document addresses issues related to the transition from traditional to precision HEOR practices, the evaluation of patient similarity analysis and its appropriateness for precision HEOR analysis, and future challenges to precision HEOR adoption. Precision HEOR should make precision medicine more realizable by aiding and adapting healthcare resource allocation. The combined hopes for precision medicine and precision HEOR are that individual patients receive the best possible medical care while overall healthcare costs remain manageable or become more cost-efficient.

Precision Health Economics and Outcomes Research to Support Precision Medicine: Big Data Meets Patient Heterogeneity on the Road to Value

PubMed Central

Chen, Yixi; Guzauskas, Gregory F.; Gu, Chengming; Wang, Bruce C. M.; Furnback, Wesley E.; Xie, Guotong; Dong, Peng; Garrison, Louis P.

2016-01-01

The “big data” era represents an exciting opportunity to utilize powerful new sources of information to reduce clinical and health economic uncertainty on an individual patient level. In turn, health economic outcomes research (HEOR) practices will need to evolve to accommodate individual patient–level HEOR analyses. We propose the concept of “precision HEOR”, which utilizes a combination of costs and outcomes derived from big data to inform healthcare decision-making that is tailored to highly specific patient clusters or individuals. To explore this concept, we discuss the current and future roles of HEOR in health sector decision-making, big data and predictive analytics, and several key HEOR contexts in which big data and predictive analytics might transform traditional HEOR into precision HEOR. The guidance document addresses issues related to the transition from traditional to precision HEOR practices, the evaluation of patient similarity analysis and its appropriateness for precision HEOR analysis, and future challenges to precision HEOR adoption. Precision HEOR should make precision medicine more realizable by aiding and adapting healthcare resource allocation. The combined hopes for precision medicine and precision HEOR are that individual patients receive the best possible medical care while overall healthcare costs remain manageable or become more cost-efficient. PMID:27827859

Lineal energy calibration of mini tissue-equivalent gas-proportional counters (TEPC)

NASA Astrophysics Data System (ADS)

Conte, V.; Moro, D.; Grosswendt, B.; Colautti, P.

2013-07-01

Mini TEPCs are cylindrical gas proportional counters of 1 mm or less of sensitive volume diameter. The lineal energy calibration of these tiny counters can be performed with an external gamma-ray source. However, to do that, first a method to get a simple and precise spectral mark has to be found and then the keV/μm value of this mark. A precise method (less than 1% of uncertainty) to identify this markis described here, and the lineal energy value of this mark has been measured for different simulated site sizes by using a 137Cs gamma source and a cylindrical TEPC equipped with a precision internal 244Cm alpha-particle source, and filled with propane-based tissue-equivalent gas mixture. Mini TEPCs can be calibrated in terms of lineal energy, by exposing them to 137Cesium sources, with an overall uncertainty of about 5%.

Precision half-life measurement of 17F

NASA Astrophysics Data System (ADS)

Brodeur, M.; Nicoloff, C.; Ahn, T.; Allen, J.; Bardayan, D. W.; Becchetti, F. D.; Gupta, Y. K.; Hall, M. R.; Hall, O.; Hu, J.; Kelly, J. M.; Kolata, J. J.; Long, J.; O'Malley, P.; Schultz, B. E.

2016-02-01

Background: The precise determination of f t values for superallowed mixed transitions between mirror nuclide are gaining attention as they could provide an avenue to test the theoretical corrections used to extract the Vu d matrix element from superallowed pure Fermi transitions. The 17F decay is particularly interesting as it proceeds completely to the ground state of 17O, removing the need for branching ratio measurements. The dominant uncertainty on the f t value of the 17F mirror transition stems from a number of conflicting half-life measurements. Purpose: A precision half-life measurement of 17F was performed and compared to previous results. Methods: The life-time was determined from the β counting of implanted 17F on a Ta foil that was removed from the beam for counting. The 17F beam was produced by transfers reaction and separated by the TwinSol facility of the Nuclear Science Laboratory of the University of Notre Dame. Results: The measured value of t1/2 new=64.402 (42) s is in agreement with several past measurements and represents one of the most precise measurements to date. In anticipation of future measurements of the correlation parameters for the decay and using the new world average t1/2 world=64.398 (61) s, we present a new estimate of the mixing ratio ρ for the mixed transition as well as the correlation parameters based on assuming Standard Model validity. Conclusions: The relative uncertainty on the new world average for the half-life is dominated by the large χ2=31 of the existing measurements. More precision measurements with different systematics are needed to remedy to the situation.

A 74 or 75 ka Age for the Toba Super-eruption? Resolving the Debate.

NASA Astrophysics Data System (ADS)

Storey, M.; Roberts, R. G.; Haslam, M.

2015-12-01

The Toba super-eruption in Sumatra, ~74,000 years ago, was the largest terrestrial volcanic event of the Quaternary. Some have proposed that the eruption produced widespread perturbations of climate and ecosystems. Evaluation of the environmental impact of the eruption and linkage to rapid climate oscillations recorded in ice core, sediment and speleothem records requires an accurate and precise age for the event, with uncertainties at the centurial level. Two recent studies, however, have proposed quite different 40Ar/39Ar ages for this volcanic event of 73.88 ± 0.32 ka (Storey et al., 2012) and 75.0 ± 0.9 ka (Mark et al, 2014), with both uncertainties expressed at 1σ, leading to radically different interpretations of its global impact. 40Ar/39Ar is a relative dating method, in which the unknown is run against a mineral standard of known age. Storey et al (2012) obtained their age estimate using a new-generation, multi-collector noble gas mass spectrometer (NU Instruments Noblesse) equipped with ion-counters, while Mark et al. (2014) used an earlier generation of lower resolution, single-collector mass spectrometer (MAP 215-50). Both studies used the same mineral standard (Alder Creek sanidine, ACs), except that Mark et al. (2014) used an older value, which accounts for the discrepancy in ages between the two studies. The value used by Mark et al. for ACs is geologically implausible, because it results in older 40Ar/39Ar dates than the youngest co-existing zircon U/Pb CATIMS ages (e.g., Rivera et al., 2013, 2014). Use of the same value for ACs as used by Storey et al. (2012) results in an identical, but less precise, astronomically calibrated age of 73.9 ± 0.9 ka for the Mark et al. data. Here, we review combined U/Pb and 40Ar/39Ar age data (both published and unpublished) for a number of Quaternary and older volcanic ash deposits, and U/Th ages for late Quaternary speleothems. These data strongly support the age assigned to ACs by Storey et al. (2012) and Rivera et al. (2013) and, hence, an astronomically calibrated age of 73.9 ka age for the Toba super-eruption. This confirms the original high-precision 40Ar/39Ar age determination of Storey et al. (2012) Storey et al., 2012, PNAS, 109, 18684-18688; Rivera et al., 2013, Chem. Geol., 345, 87-98; Rivera et al., 2014, Geol. 42 643-646; Mark et al, 2014, Quat. Geochron. 21, 90-103

AMCP Partnership Forum: Managing Care in the Wave of Precision Medicine.

PubMed

2018-05-23

Precision medicine, the customization of health care to an individual's genetic profile while accounting for biomarkers and lifestyle, has increasingly been adopted by health care stakeholders to guide the development of treatment options, improve treatment decision making, provide more patient-centered care, and better inform coverage and reimbursement decisions. Despite these benefits, key challenges prevent its broader use and adoption. On December 7-8, 2017, the Academy of Managed Care Pharmacy convened a group of stakeholders to discuss these challenges and provide recommendations to facilitate broader adoption and use of precision medicine across health care settings. These stakeholders represented the pharmaceutical industry, clinicians, patient advocacy, private payers, device manufacturers, health analytics, information technology, academia, and government agencies. Throughout the 2-day forum, participants discussed evidence requirements for precision medicine, including consistent ways to measure the utility and validity of precision medicine tests and therapies, limitations of traditional clinical trial designs, and limitations of value assessment framework methods. They also highlighted the challenges with evidence collection and data silos in precision medicine. Interoperability within and across health systems is hindering clinical advancements. Current medical coding systems also cannot account for the heterogeneity of many diseases, preventing health systems from having a complete understanding of their patient population to inform resource allocation. Challenges faced by payers, such as evidence limitations, to inform coverage and reimbursement decisions in precision medicine, as well as legal and regulatory barriers that inhibit more widespread data sharing, were also identified. While a broad range of perspectives was shared throughout the forum, participants reached consensus across 2 overarching areas. First, there is a greater need for common definitions, thresholds, and standards to guide evidence generation in precision medicine. Second, current information silos are preventing the sharing of valuable data. Collaboration among stakeholders is needed to support better information sharing, awareness, and education of precision medicine for patients. The recommendations brought forward by this diverse group of experts provide a set of solutions to spur widespread use and application of precision medicine. Taken together, successful adoption and use of precision medicine will require input and collaboration from all sectors of health care, especially patients. DISCLOSURES This AMCP Partnership Forum and the development of the proceedings document were supported by Amgen, Foundation Medicine, Genentech, Gilead, MedImpact, National Pharmaceutical Council, Precision for Value, Sanofi, Takeda, and Xcenda.

A numerical method of detecting singularity

NASA Technical Reports Server (NTRS)

Laporte, M.; Vignes, J.

1978-01-01

A numerical method is reported which determines a value C for the degree of conditioning of a matrix. This value is C = 0 for a singular matrix and has progressively larger values for matrices which are increasingly well-conditioned. This value is C sub = C max sub max (C defined by the precision of the computer) when the matrix is perfectly well conditioned.

Spectrophotometer-Based Color Measurements

DTIC Science & Technology

2017-10-24

public release; distribution is unlimited. AD U.S. ARMY ARMAMENT RESEARCH , DEVELOPMENT AND ENGINEERING CENTER Weapons and Software Engineering Center...for public release; distribution is unlimited. UNCLASSIFIED i CONTENTS Page Summary 1 Introduction 1 Methods , Assumptions, and Procedures 1...Values for Federal Color Standards 15 Distribution List 25 TABLES 1 Instrument precision 3 2 Method precision and operator variability 4 3

Sample Size and Item Parameter Estimation Precision When Utilizing the One-Parameter "Rasch" Model

ERIC Educational Resources Information Center

Custer, Michael

2015-01-01

This study examines the relationship between sample size and item parameter estimation precision when utilizing the one-parameter model. Item parameter estimates are examined relative to "true" values by evaluating the decline in root mean squared deviation (RMSD) and the number of outliers as sample size increases. This occurs across…

The heterogeneity of human mesenchymal stem cell preparations--evidence from simultaneous analysis of proteomes and transcriptomes.

PubMed

Wagner, Wolfgang; Feldmann, Robert E; Seckinger, Anja; Maurer, Martin H; Wein, Frederik; Blake, Jonathon; Krause, Ulf; Kalenka, Armin; Bürgers, Heinrich F; Saffrich, Rainer; Wuchter, Patrick; Kuschinsky, Wolfgang; Ho, Anthony D

2006-04-01

Mesenchymal stem cells (MSC) raise high hopes in clinical applications. However, the lack of common standards and a precise definition of MSC preparations remains a major obstacle in research and application of MSC. Whereas surface antigen markers have failed to precisely define this population, a combination of proteomic data and microarray data provides a new dimension for the definition of MSC preparations. In our continuing effort to characterize MSC, we have analyzed the differential transcriptome and proteome expression profiles of MSC preparations isolated from human bone marrow under two different expansion media (BM-MSC-M1 and BM-MSC-M2). In proteomics, 136 protein spots were unambiguously identified by MALDI-TOF-MS and corresponding cDNA spots were selected on our "Human Transcriptome cDNA Microarray." Combination of datasets revealed a correlation in differential gene expression and protein expression of BM-MSC-M1 vs BM-MSC-M2. Genes involved in metabolism were more highly expressed in BM-MSC-M1, whereas genes involved in development, morphogenesis, extracellular matrix, and differentiation were more highly expressed in BM-MSC-M2. Interchanging culture conditions for 8 days revealed that differential expression was retained in several genes whereas it was altered in others. Our results have provided evidence that homogeneous BM-MSC preparations can reproducibly be isolated under standardized conditions, whereas culture conditions exert a prominent impact on transcriptome, proteome, and cellular organization of BM-MSC.

Systematic comparison of co-expression of multiple recombinant thermophilic enzymes in Escherichia coli BL21(DE3).

PubMed

Chen, Hui; Huang, Rui; Zhang, Y-H Percival

2017-06-01

The precise control of multiple heterologous enzyme expression levels in one Escherichia coli strain is important for cascade biocatalysis, metabolic engineering, synthetic biology, natural product synthesis, and studies of complexed proteins. We systematically investigated the co-expression of up to four thermophilic enzymes (i.e., α-glucan phosphorylase (αGP), phosphoglucomutase (PGM), glucose 6-phosphate dehydrogenase (G6PDH), and 6-phosphogluconate dehydrogenase (6PGDH)) in E. coli BL21(DE3) by adding T7 promoter or T7 terminator of each gene for multiple genes in tandem, changing gene alignment, and comparing one or two plasmid systems. It was found that the addition of T7 terminator after each gene was useful to decrease the influence of the upstream gene. The co-expression of the four enzymes in E. coli BL21(DE3) was demonstrated to generate two NADPH molecules from one glucose unit of maltodextrin, where NADPH was oxidized to convert xylose to xylitol. The best four-gene co-expression system was based on two plasmids (pET and pACYC) which harbored two genes. As a result, apparent enzymatic activities of the four enzymes were regulated to be at similar levels and the overall four-enzyme activity was the highest based on the formation of xylitol. This study provides useful information for the precise control of multi-enzyme-coordinated expression in E. coli BL21(DE3).

Ventilatory parameters and maximal respiratory pressure changes with age in Duchenne muscular dystrophy patients.

PubMed

Gayraud, Jerome; Ramonatxo, Michele; Rivier, François; Humberclaude, Véronique; Petrof, Basil; Matecki, Stefan

2010-06-01

The aim of this longitudinal study was to precise, in children with Duchenne muscular dystrophy, the respective functional interest of ventilatory parameters (Vital capacity, total lung capacity and forced expiratory volume in one second [FEV(1)]) in comparison to maximal inspiratory pressure (Pimax) during growth. In ten boys the mean age of 9.1 +/- 1 years) to mean age of 16 +/- 1.4 years followed over a period of 7 years, we found that: (1) ventilatory parameters expressed in percentage of predicted value, after a normal ascending phase, start to decrease between 11 and 12 years, (2) Pimax presented only a decreasing phase since the beginning of the study and thus was already at 67% of predicted value at 12 years while ventilatory parameters was still normal, (3) after 12 years the mean slopes of decrease per year of vital capacity and FEV1 were higher (10.7 and 10.4%) than that of Pimax (6.9%), (4) at 15 years mean values of vital capacity and FEV1 (53.3 and 49.5% of predicted values) was simlar to that of Pimax (48.3%). In conclusion, if at early stages of the disease, Pimax is a more reliable index of respiratory impaiment than ventilatory parameters, the follow-up of ventilatory parameters, when they start to decrease, is a better indicator of disease progression and, at advanced stages they provided same information about the functional impact of disease.

Analysis of the Precision of Variable Flip Angle T1 Mapping with Emphasis on the Noise Propagated from RF Transmit Field Maps.

PubMed

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.

Genomically Encoded Analog Memory with Precise In vivo DNA Writing in Living Cell Populations

PubMed Central

Farzadfard, Fahim; Lu, Timothy K.

2014-01-01

Cellular memory is crucial to many natural biological processes and for sophisticated synthetic-biology applications. Existing cellular memories rely on epigenetic switches or recombinases, which are limited in scalability and recording capacity. Here, we use the DNA of living cell populations as genomic ‘tape recorders’ for the analog and distributed recording of long-term event histories. We describe a platform for generating single-stranded DNA (ssDNA) in vivo in response to arbitrary transcriptional signals. When co-expressed with a recombinase, these intracellularly expressed ssDNAs target specific genomic DNA addresses, resulting in precise mutations that accumulate in cell populations as a function of the magnitude and duration of the inputs. This platform could enable long-term cellular recorders for environmental and biomedical applications, biological state machines, and enhanced genome engineering strategies. PMID:25395541

Reproducibility of Fluorescent Expression from Engineered Biological Constructs in E. coli

PubMed Central

Beal, Jacob; Haddock-Angelli, Traci; Gershater, Markus; de Mora, Kim; Lizarazo, Meagan; Hollenhorst, Jim; Rettberg, Randy

2016-01-01

We present results of the first large-scale interlaboratory study carried out in synthetic biology, as part of the 2014 and 2015 International Genetically Engineered Machine (iGEM) competitions. Participants at 88 institutions around the world measured fluorescence from three engineered constitutive constructs in E. coli. Few participants were able to measure absolute fluorescence, so data was analyzed in terms of ratios. Precision was strongly related to fluorescent strength, ranging from 1.54-fold standard deviation for the ratio between strong promoters to 5.75-fold for the ratio between the strongest and weakest promoter, and while host strain did not affect expression ratios, choice of instrument did. This result shows that high quantitative precision and reproducibility of results is possible, while at the same time indicating areas needing improved laboratory practices. PMID:26937966

Diffractometric measurement of the temperature dependence of piezoelectric tensor in GMO monocrystal

NASA Astrophysics Data System (ADS)

Breczko, Teodor; Lempaszek, Andrzej

2007-04-01

Functional materials, of which an example is ferroelectric, ferroelastic monocrystal of molybdate (III) gadolinium (VI), are often used in the micro-motor operators (micro-servo motors) working in changeable environment conditions. Most frequently this change refers to temperature. That is why the important practical problem is the precise measurement of the value of piezoelectric tensor elements in dependence on the temperature of a particular monocrystal. In the presented article for this kind of measurements, the use of X-ray diffractometer has been shown. The advantage of the method presented is that, apart from precise dependence measurement between the temperature of a monocrystal and the value of piezoelectric tensor elements, it enables synchronous measurement of the value of thermal expansion tensor elements for a monocrystal.

New validated high-performance liquid chromatographic method for simultaneous analysis of ten flavonoid aglycones in plant extracts using a C18 fused-core column and acetonitrile-tetrahydrofuran gradient.

PubMed

Olszewska, Monika A

2012-09-01

An HPLC method of high resolution has been developed and validated for the simultaneous determination of ten prominent flavonoid aglycones in plant materials using a fused-core C18-silica column (Ascentis® Express, 4.6 mm × 150 mm, 2.7 μm). The separation was accomplished with an acetonitrile-tetrahydrofuran gradient elution at a flow rate of 1 mL/min and temperature of 30°C. UV spectrophotometric detection was employed at 370 nm for flavonols (quercetin [QU], myricetin [MY], isorhamnetin [IS], kaempferol [KA], sexangularetin [SX], and limocitrin [LM]) and 340 nm for flavones (apigenin [AP], acacetin [AC], chrysoeriol [CH], and luteolin [LU]). The high resolution of critical pairs QU/LU (10.50), QU/CH (3.40), AP/CH (2.51), SX/LM (2.30), and IS/KA (2.70) was achieved within 30.3 min. The observed column back pressure was less than 4300 psi, thus acceptable for conventional HPLC equipment. The method was sensitive enough having LODs of 0.115-0.525 ng and good linearity (r > 0.9999) over the test range. The precision values, expressed as RSD values, were <7.5%, and the accuracy was in the range of 95.3-100.2% for all analytes except MY (73.8%). The method was successfully employed for the determination of flavonoids in several medicinal plants, such as Ginkgo biloba, Betula pendula, and a variety of Sorbus species. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

How precise are reported protein coordinate data?

PubMed

Konagurthu, Arun S; Allison, Lloyd; Abramson, David; Stuckey, Peter J; Lesk, Arthur M

2014-03-01

Atomic coordinates in the Worldwide Protein Data Bank (wwPDB) are generally reported to greater precision than the experimental structure determinations have actually achieved. By using information theory and data compression to study the compressibility of protein atomic coordinates, it is possible to quantify the amount of randomness in the coordinate data and thereby to determine the realistic precision of the reported coordinates. On average, the value of each C(α) coordinate in a set of selected protein structures solved at a variety of resolutions is good to about 0.1 Å.

Quantum Metrology Assisted by Abstention

NASA Astrophysics Data System (ADS)

Gendra, B.; Ronco-Bonvehi, E.; Calsamiglia, J.; Muñoz-Tapia, R.; Bagan, E.

2013-03-01

The main goal of quantum metrology is to obtain accurate values of physical parameters using quantum probes. In this context, we show that abstention, i.e., the possibility of getting an inconclusive answer at readout, can drastically improve the measurement precision and even lead to a change in its asymptotic behavior, from the shot-noise to the Heisenberg scaling. We focus on phase estimation and quantify the required amount of abstention for a given precision. We also develop analytical tools to obtain the asymptotic behavior of the precision and required rate of abstention for arbitrary pure states.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grout, Ray W. S.

Convergence of spectral deferred correction (SDC), where low-order time integration methods are used to construct higher-order methods through iterative refinement, can be accelerated in terms of computational effort by using mixed-precision methods. Using ideas from multi-level SDC (in turn based on FAS multigrid ideas), some of the SDC correction sweeps can use function values computed in reduced precision without adversely impacting the accuracy of the final solution. This is particularly beneficial for the performance of combustion solvers such as S3D [6] which require double precision accuracy but are performance limited by the cost of data motion.

Agreement of NP and VP Coordination in English and Korean

ERIC Educational Resources Information Center

Hong, Sung-Ryong; Na, Won-Shik

2011-01-01

There have been long argumentations about this topic and people are still having difficulty in explaining precisely what the agreement values the mother NP phrase should have from two conjunct daughters which have different AGR (Agreement) values. Especially, this could be more complicated when the values of gender, number, and person of each…

Delay Discounting: I'm a "K", You're a "K"

ERIC Educational Resources Information Center

Odum, Amy L.

2011-01-01

Delay discounting is the decline in the present value of a reward with delay to its receipt. Across a variety of species, populations, and reward types, value declines hyperbolically with delay. Value declines steeply with shorter delays, but more shallowly with longer delays. Quantitative modeling provides precise measures to characterize the…

Efficacy of passive sampler collection for atmospheric NO2 isotopes under simulated environmental conditions.

PubMed

Coughlin, Justin G; Yu, Zhongjie; Elliott, Emily M

2017-07-30

Nitrogen oxides or NO x (NO x = NO + NO 2 ) play an important role in air quality, atmospheric chemistry, and climate. The isotopic compositions of anthropogenic and natural NO 2 sources are wide-ranging, and they can be used to constrain sources of ambient NO 2 and associated atmospheric deposition of nitrogen compounds. While passive sample collection of NO 2 isotopes has been used in field studies to determine NO x source influences on atmospheric deposition, this approach has not been evaluated for accuracy or precision under different environmental conditions. The efficacy of NO 2 passive sampler collection for NO 2 isotopes was evaluated under varied temperature and relative humidity (RH) conditions in a dynamic flux chamber. The precision and accuracy of the filter NO 2 collection as nitrite (NO 2 - ) for isotopic analysis were determined using a reference NO 2 gas tank and through inter-calibration with a modified EPA Method 7. The bacterial denitrifer method was used to convert 20 μM of collected NO 2 - or nitrate (NO 3 - ) into N 2 O and was carried out on an Isoprime continuous flow isotope ratio mass spectrometer. δ 15 N-NO 2 values determined from passive NO 2 collection, in conditions of 11-34 °C, 1-78% RH, have an overall accuracy and precision of ±2.1 ‰, and individual run precision of ±0.6 ‰. δ 18 O-NO 2 values obtained from passive NO 2 sampler collection, under the same conditions, have an overall precision of ± 1.3 ‰. Suitable conditions for passive sampler collection of NO 2 isotopes are in environments ranging from 11 to 34 °C and 1 to 78% RH. The passive NO 2 isotope measurement technique provides an accurate method to determine variations in atmospheric δ 15 N-NO 2 values and a precise method for determining atmospheric δ 18 O-NO 2 values. The ability to measure NO 2 isotopes over spatial gradients at the same temporal resolution provides a unique perspective on the extent and seasonality of fluctuations in atmospheric NO 2 isotopic compositions. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Analysis of acrylamide in coffee and cocoa by isotope dilution liquid chromatography-tandem mass spectrometry.

PubMed

Aguas, Patricia C; Fitzhenry, Matthew J; Giannikopoulos, Georgina; Varelis, Peter

2006-08-01

An accurate and precise method for the quantification of acrylamide using stable isotope dilution liquid chromatography-tandem mass spectrometry was developed and used to measure acrylamide in coffee and cocoa samples. The sample preparation involved extraction of the analyte and its internal standard, 13C3-acrylamide, into water and subsequent defatting of the aqueous extract with dichloromethane. An aliquot of the resulting aqueous extract was then azeotropically dried under reduced pressure and subsequently purified using an aminopropyl-bonded silica cartridge. The purified extracts were then chromatographed on a 5-microm 2.1 x 150 mm Hypercarb column, the effluent of which was monitored for the analyte and its internal standard using positive-ion APCI-selected reaction monitoring. The intra-laboratory reproducibility of the method, expressed as a relative coefficient of variation (%, n=5), was determined at four levels of concentration (12.3, 42.3, 139.3 and 464.8 microg kg(-1)) and was found to vary between 0.6-2.5%. The accuracy of the method was assessed using a reference sample of coffee. The average result obtained using our method differed from the assigned value of the reference material by less than 1%. An analysis of a cocoa sample revealed that the method is capable of precisely estimating acrylamide in challenging matrices down to a level of at least 12.3 microg kg(-1).

Dock and Pak regulate olfactory axon pathfinding in Drosophila.

PubMed

Ang, Lay-Hong; Kim, Jenny; Stepensky, Vitaly; Hing, Huey

2003-04-01

The convergence of olfactory axons expressing particular odorant receptor (Or) genes on spatially invariant glomeruli in the brain is one of the most dramatic examples of precise axon targeting in developmental neurobiology. The cellular and molecular mechanisms by which olfactory axons pathfind to their targets are poorly understood. We report here that the SH2/SH3 adapter Dock and the serine/threonine kinase Pak are necessary for the precise guidance of olfactory axons. Using antibody localization, mosaic analyses and cell-type specific rescue, we observed that Dock and Pak are expressed in olfactory axons and function autonomously in olfactory neurons to regulate the precise wiring of the olfactory map. Detailed analyses of the mutant phenotypes in whole mutants and in small multicellular clones indicate that Dock and Pak do not control olfactory neuron (ON) differentiation, but specifically regulate multiple aspects of axon trajectories to guide them to their cognate glomeruli. Structure/function studies show that Dock and Pak form a signaling pathway that mediates the response of olfactory axons to guidance cues in the developing antennal lobe (AL). Our findings therefore identify a central signaling module that is used by ONs to project to their cognate glomeruli.

Gene mutation-based and specific therapies in precision medicine.

PubMed

Wang, Xiangdong

2016-04-01

Precision medicine has been initiated and gains more and more attention from preclinical and clinical scientists. A number of key elements or critical parts in precision medicine have been described and emphasized to establish a systems understanding of precision medicine. The principle of precision medicine is to treat patients on the basis of genetic alterations after gene mutations are identified, although questions and challenges still remain before clinical application. Therapeutic strategies of precision medicine should be considered according to gene mutation, after biological and functional mechanisms of mutated gene expression or epigenetics, or the correspondent protein, are clearly validated. It is time to explore and develop a strategy to target and correct mutated genes by direct elimination, restoration, correction or repair of mutated sequences/genes. Nevertheless, there are still numerous challenges to integrating widespread genomic testing into individual cancer therapies and into decision making for one or another treatment. There are wide-ranging and complex issues to be solved before precision medicine becomes clinical reality. Thus, the precision medicine can be considered as an extension and part of clinical and translational medicine, a new alternative of clinical therapies and strategies, and have an important impact on disease cures and patient prognoses. © 2015 The Author. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Advances in genetic circuit design: novel biochemistries, deep part mining, and precision gene expression.

PubMed

Nielsen, Alec A K; Segall-Shapiro, Thomas H; Voigt, Christopher A

2013-12-01

Cells use regulatory networks to perform computational operations to respond to their environment. Reliably manipulating such networks would be valuable for many applications in biotechnology; for example, in having genes turn on only under a defined set of conditions or implementing dynamic or temporal control of expression. Still, building such synthetic regulatory circuits remains one of the most difficult challenges in genetic engineering and as a result they have not found widespread application. Here, we review recent advances that address the key challenges in the forward design of genetic circuits. First, we look at new design concepts, including the construction of layered digital and analog circuits, and new approaches to control circuit response functions. Second, we review recent work to apply part mining and computational design to expand the number of regulators that can be used together within one cell. Finally, we describe new approaches to obtain precise gene expression and to reduce context dependence that will accelerate circuit design by more reliably balancing regulators while reducing toxicity. Copyright © 2013. Published by Elsevier Ltd.

High precision isotope ratio measurements of mercury isotopes in cinnabar ores using multi-collector inductively coupled plasma mass spectrometry.

PubMed

Hintelmann, Holger; Lu, ShengYong

2003-06-01

Variations in Hg isotope ratios in cinnabar ores obtained from different countries were detected by high precision isotope ratio measurements using multi-collector inductively coupled mass spectrometry (MC-ICP-MS). Values of delta198/202Hg varied from 0.0-1.3 percent per thousand relative to a NIST SRM 1641d Hg solution. The typical external uncertainty of the delta values was 0.06 to 0.26 percent per thousand. Hg was introduced into the plasma as elemental Hg after reduction by sodium borohydride. A significant fractionation of lead isotopes was observed during the simultaneous generation of lead hydride, preventing normalization of the Hg isotope ratios using the measured 208/206Pb ratio. Hg ratios were instead corrected employing the simultaneously measured 205/203T1 ratio. Using a 10 ng ml(-1) Hg solution and 10 min of sampling, introducing 60 ng of Hg, the internal precision of the isotope ratio measurements was as low as 14 ppm. Absolute Hg ratios deviated from the representative IUPAC values by approximately 0.2% per u. This observation is explained by the inadequacy of the exponential law to correct for mass bias in MC-ICP-MS measurements. In the absence of a precisely characterized Hg isotope ratio standard, we were not able to determine unambiguously the absolute Hg ratios of the ore samples, highlighting the urgent need for certified standard materials.

Layered compression for high-precision depth data.

PubMed

Miao, Dan; Fu, Jingjing; Lu, Yan; Li, Shipeng; Chen, Chang Wen

2015-12-01

With the development of depth data acquisition technologies, access to high-precision depth with more than 8-b depths has become much easier and determining how to efficiently represent and compress high-precision depth is essential for practical depth storage and transmission systems. In this paper, we propose a layered high-precision depth compression framework based on an 8-b image/video encoder to achieve efficient compression with low complexity. Within this framework, considering the characteristics of the high-precision depth, a depth map is partitioned into two layers: 1) the most significant bits (MSBs) layer and 2) the least significant bits (LSBs) layer. The MSBs layer provides rough depth value distribution, while the LSBs layer records the details of the depth value variation. For the MSBs layer, an error-controllable pixel domain encoding scheme is proposed to exploit the data correlation of the general depth information with sharp edges and to guarantee the data format of LSBs layer is 8 b after taking the quantization error from MSBs layer. For the LSBs layer, standard 8-b image/video codec is leveraged to perform the compression. The experimental results demonstrate that the proposed coding scheme can achieve real-time depth compression with satisfactory reconstruction quality. Moreover, the compressed depth data generated from this scheme can achieve better performance in view synthesis and gesture recognition applications compared with the conventional coding schemes because of the error control algorithm.

Stabilometer "S" value study on asphalt concrete samples.

DOT National Transportation Integrated Search

1985-07-01

During the late fall of 1969 a study was made to determine the precision when testing asphalt concrete specimens for the Hveem stabilometer ("S") value (AASHTO T 246). Fifty samples, using Chevron 85-100 asphalt cement and aggregate from Walling Sand...

Tables for determining lead, uranium, and thorium isotope ages

NASA Technical Reports Server (NTRS)

Schonfeld, E.

1974-01-01

Tables for determining lead, uranium, and thorium isotope ages are presented in the form of computer printouts. Decay constants, analytical expressions for the functions evaluated, and the precision of the calculations are briefly discussed.

Effect of Transcutaneous Electrode Temperature on Accuracy and Precision of Carbon Dioxide and Oxygen Measurements in the Preterm Infants.

PubMed

Jakubowicz, Jessica F; Bai, Shasha; Matlock, David N; Jones, Michelle L; Hu, Zhuopei; Proffitt, Betty; Courtney, Sherry E

2018-05-01

High electrode temperature during transcutaneous monitoring is associated with skin burns in extremely premature infants. We evaluated the accuracy and precision of CO 2 and O 2 measurements using lower transcutaneous electrode temperatures below 42°C. We enrolled 20 neonates. Two transcutaneous monitors were placed simultaneously on each neonate, with one electrode maintained at 42°C and the other randomized to temperatures of 38, 39, 40, 41, and 42°C. Arterial blood was collected twice at each temperature. At the time of arterial blood sampling, values for transcutaneously measured partial pressure of CO 2 (P tcCO 2 ) were not significantly different among test temperatures. There was no evidence of skin burning at any temperature. For P tcCO 2 , Bland-Altman analyses of all test temperatures versus 42°C showed good precision and low bias. Transcutaneously measured partial pressure of O 2 (P tcO 2 ) values trended arterial values but had large negative bias. Transcutaneous electrode temperatures as low as 38°C allow an assessment of P tcCO 2 as accurate as that with electrodes at 42°C. Copyright © 2018 by Daedalus Enterprises.

High-precision Q EC -value measurement of the superallowed β + emitter Mg 22 and an ab initio evaluation of the A = 22 isobaric triplet

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reiter, M. P.; Leach, K. G.; Drozdowski, O. M.

The direct atomic mass difference between 22Mg and 22Na was measured using TRIUMF's Ion Trap for Atomic and Nuclear Science (TITAN) and was determined to be Q=4781.40(22) keV. This measurement represents the most precise single measurement of this quantity to date.

Measuring "g" Using a Magnetic Pendulum and Telephone Pickup

ERIC Educational Resources Information Center

Sinacore, J.; Takai, H.

2010-01-01

The simple pendulum has long been used to measure "g", the acceleration due to gravity, with a precision of a few percent. Achieving agreement with the accepted value of less than 1% is feasible in the high school laboratory, though it requires some care. The precision of the measurement is bound by how accurately the period and the pendulum…

High-precision Q EC -value measurement of the superallowed β + emitter Mg 22 and an ab initio evaluation of the A = 22 isobaric triplet

DOE PAGES

Reiter, M. P.; Leach, K. G.; Drozdowski, O. M.; ...

2017-11-06

The direct atomic mass difference between 22Mg and 22Na was measured using TRIUMF's Ion Trap for Atomic and Nuclear Science (TITAN) and was determined to be Q=4781.40(22) keV. This measurement represents the most precise single measurement of this quantity to date.

Precise Correction of Disease Mutations in Induced Pluripotent Stem Cells Derived From Patients With Limb Girdle Muscular Dystrophy.

PubMed

Turan, Soeren; Farruggio, Alfonso P; Srifa, Waracharee; Day, John W; Calos, Michele P

2016-04-01

Limb girdle muscular dystrophies types 2B (LGMD2B) and 2D (LGMD2D) are degenerative muscle diseases caused by mutations in the dysferlin and alpha-sarcoglycan genes, respectively. Using patient-derived induced pluripotent stem cells (iPSC), we corrected the dysferlin nonsense mutation c.5713C>T; p.R1905X and the most common alpha-sarcoglycan mutation, missense c.229C>T; p.R77C, by single-stranded oligonucleotide-mediated gene editing, using the CRISPR/Cas9 gene-editing system to enhance the frequency of homology-directed repair. We demonstrated seamless, allele-specific correction at efficiencies of 0.7-1.5%. As an alternative, we also carried out precise gene addition strategies for correction of the LGMD2B iPSC by integration of wild-type dysferlin cDNA into the H11 safe harbor locus on chromosome 22, using dual integrase cassette exchange (DICE) or TALEN-assisted homologous recombination for insertion precise (THRIP). These methods employed TALENs and homologous recombination, and DICE also utilized site-specific recombinases. With DICE and THRIP, we obtained targeting efficiencies after selection of ~20%. We purified iPSC corrected by all methods and verified rescue of appropriate levels of dysferlin and alpha-sarcoglycan protein expression and correct localization, as shown by immunoblot and immunocytochemistry. In summary, we demonstrate for the first time precise correction of LGMD iPSC and validation of expression, opening the possibility of cell therapy utilizing these corrected iPSC.

Phosphorus Concentrations in Stream-Water and Reference Samples - An Assessment of Laboratory Comparability

USGS Publications Warehouse

McHale, Michael R.; McChesney, Dennis

2007-01-01

In 2003, a study was conducted to evaluate the accuracy and precision of 10 laboratories that analyze water-quality samples for phosphorus concentrations in the Catskill Mountain region of New York State. Many environmental studies in this region rely on data from these different laboratories for water-quality analyses, and the data may be used in watershed modeling and management decisions. Therefore, it is important to determine whether the data reported by these laboratories are of comparable accuracy and precision. Each laboratory was sent 12 samples for triplicate analysis for total phosphorus, total dissolved phosphorus, and soluble reactive phosphorus. Eight of these laboratories reported results that met comparability criteria for all samples; the remaining two laboratories met comparability criteria for only about half of the analyses. Neither the analytical method used nor the sample concentration ranges appeared to affect the comparability of results. The laboratories whose results were comparable gave consistently comparable results throughout the concentration range analyzed, and the differences among methods did not diminish comparability. All laboratories had high data precision as indicated by sample triplicate results. In addition, the laboratories consistently reported total phosphorus values greater than total dissolved phosphorus values, and total dissolved phosphorus values greater than soluble reactive phosphorus values, as would be expected. The results of this study emphasize the importance of regular laboratory participation in sample-exchange programs.

A new world survey expression for cosmic ray vertical intensity vs. depth in standard rock

NASA Technical Reports Server (NTRS)

Crouch, M.

1985-01-01

The cosmic ray data on vertical intensity versus depth below 10 to the 5th power g sq cm is fitted to a 5 parameter empirical formula to give an analytical expression for interpretation of muon fluxes in underground measurements. This expression updates earlier published results and complements the more precise curves obtained by numerical integration or Monte Carlo techniques in which the fit is made to an energy spectrum at the top of the atmosphere. The expression is valid in the transitional region where neutrino induced muons begin to be important, as well as at great depths where this component becomes dominant.

ICan: an integrated co-alteration network to identify ovarian cancer-related genes.

PubMed

Zhou, Yuanshuai; Liu, Yongjing; Li, Kening; Zhang, Rui; Qiu, Fujun; Zhao, Ning; Xu, Yan

2015-01-01

Over the last decade, an increasing number of integrative studies on cancer-related genes have been published. Integrative analyses aim to overcome the limitation of a single data type, and provide a more complete view of carcinogenesis. The vast majority of these studies used sample-matched data of gene expression and copy number to investigate the impact of copy number alteration on gene expression, and to predict and prioritize candidate oncogenes and tumor suppressor genes. However, correlations between genes were neglected in these studies. Our work aimed to evaluate the co-alteration of copy number, methylation and expression, allowing us to identify cancer-related genes and essential functional modules in cancer. We built the Integrated Co-alteration network (ICan) based on multi-omics data, and analyzed the network to uncover cancer-related genes. After comparison with random networks, we identified 155 ovarian cancer-related genes, including well-known (TP53, BRCA1, RB1 and PTEN) and also novel cancer-related genes, such as PDPN and EphA2. We compared the results with a conventional method: CNAmet, and obtained a significantly better area under the curve value (ICan: 0.8179, CNAmet: 0.5183). In this paper, we describe a framework to find cancer-related genes based on an Integrated Co-alteration network. Our results proved that ICan could precisely identify candidate cancer genes and provide increased mechanistic understanding of carcinogenesis. This work suggested a new research direction for biological network analyses involving multi-omics data.

ICan: An Integrated Co-Alteration Network to Identify Ovarian Cancer-Related Genes

PubMed Central

Zhou, Yuanshuai; Liu, Yongjing; Li, Kening; Zhang, Rui; Qiu, Fujun; Zhao, Ning; Xu, Yan

2015-01-01

Background Over the last decade, an increasing number of integrative studies on cancer-related genes have been published. Integrative analyses aim to overcome the limitation of a single data type, and provide a more complete view of carcinogenesis. The vast majority of these studies used sample-matched data of gene expression and copy number to investigate the impact of copy number alteration on gene expression, and to predict and prioritize candidate oncogenes and tumor suppressor genes. However, correlations between genes were neglected in these studies. Our work aimed to evaluate the co-alteration of copy number, methylation and expression, allowing us to identify cancer-related genes and essential functional modules in cancer. Results We built the Integrated Co-alteration network (ICan) based on multi-omics data, and analyzed the network to uncover cancer-related genes. After comparison with random networks, we identified 155 ovarian cancer-related genes, including well-known (TP53, BRCA1, RB1 and PTEN) and also novel cancer-related genes, such as PDPN and EphA2. We compared the results with a conventional method: CNAmet, and obtained a significantly better area under the curve value (ICan: 0.8179, CNAmet: 0.5183). Conclusion In this paper, we describe a framework to find cancer-related genes based on an Integrated Co-alteration network. Our results proved that ICan could precisely identify candidate cancer genes and provide increased mechanistic understanding of carcinogenesis. This work suggested a new research direction for biological network analyses involving multi-omics data. PMID:25803614

High-precision half-life determination for 21Na using a 4 π gas-proportional counter

NASA Astrophysics Data System (ADS)

Finlay, P.; Laffoley, A. T.; Ball, G. C.; Bender, P. C.; Dunlop, M. R.; Dunlop, R.; Hackman, G.; Leslie, J. R.; MacLean, A. D.; Miller, D.; Moukaddam, M.; Olaizola, B.; Severijns, N.; Smith, J. K.; Southall, D.; Svensson, C. E.

2017-08-01

A high-precision half-life measurement for the superallowed β+ transition between the isospin T =1 /2 mirror nuclei 21Na and 21Ne has been performed at the TRIUMF-ISAC radioactive ion beam facility yielding T1 /2=22.4506 (33 ) s, a result that is a factor of 4 more precise than the previous world-average half-life for 21Na and represents the single most precisely determined half-life for a transition between mirror nuclei to date. The contribution to the uncertainty in the 21Na F tmirror value due to the half-life is now reduced to the level of the nuclear-structure-dependent theoretical corrections, leaving the branching ratio as the dominant experimental uncertainty.

External quality-assurance results for the National Atmospheric Deposition Program and the National Trends Network during 1986

USGS Publications Warehouse

See, Randolph B.; Schroder, LeRoy J.; Willoughby, Timothy C.

1988-01-01

During 1986, the U.S. Geological Survey operated three programs to provide external quality-assurance monitoring of the National Atmospheric Deposition Program and National Trends Network. An intersite-comparison program was used to assess the accuracy of onsite pH and specific-conductance determinations at quarterly intervals. The blind-audit program was used to assess the effect of routine sample handling on the precision and bias of program and network wet-deposition data. Analytical results from four laboratories, which routinely analyze wet-deposition samples, were examined to determine if differences existed between laboratory analytical results and to provide estimates of the analytical precision of each laboratory. An average of 78 and 89 percent of the site operators participating in the intersite-comparison met the network goals for pH and specific conductance. A comparison of analytical values versus actual values for samples submitted as part of the blind-audit program indicated that analytical values were slightly but significantly (a = 0.01) larger than actual values for pH, magnesium, sodium, and sulfate; analytical values for specific conductance were slightly less than actual values. The decreased precision in the analyses of blind-audit samples when compared to interlaboratory studies indicates that a large amount of uncertainty in network deposition data may be a result of routine field operations. The results of the interlaboratory comparison study indicated that the magnitude of the difference between laboratory analyses was small for all analytes. Analyses of deionized, distilled water blanks by participating laboratories indicated that the laboratories had difficulty measuring analyte concentrations near their reported detection limits. (USGS)

High-Precision Mass Measurement of Cu 56 and the Redirection of the r p -Process Flow

NASA Astrophysics Data System (ADS)

Valverde, A. A.; Brodeur, M.; Bollen, G.; Eibach, M.; Gulyuz, K.; Hamaker, A.; Izzo, C.; Ong, W.-J.; Puentes, D.; Redshaw, M.; Ringle, R.; Sandler, R.; Schwarz, S.; Sumithrarachchi, C. S.; Surbrook, J.; Villari, A. C. C.; Yandow, I. T.

2018-01-01

We report the mass measurement of Cu 56 , using the LEBIT 9.4 T Penning trap mass spectrometer at the National Superconducting Cyclotron Laboratory at Michigan State University. The mass of Cu 56 is critical for constraining the reaction rates of the Ni 55 (p ,γ ) Cu 56 (p ,γ ) Zn 57 (β+) Cu 57 bypass around the Ni 56 waiting point. Previous recommended mass excess values have disagreed by several hundred keV. Our new value, ME =-38 626.7 (7.1 ) keV , is a factor of 30 more precise than the extrapolated value suggested in the 2012 atomic mass evaluation [Chin. Phys. C 36, 1603 (2012), 10.1088/1674-1137/36/12/003], and more than a factor of 12 more precise than values calculated using local mass extrapolations, while agreeing with the newest 2016 atomic mass evaluation value [Chin. Phys. C 41, 030003 (2017), 10.1088/1674-1137/41/3/030003]. The new experimental average, using our new mass and the value from AME2016, is used to calculate the astrophysical Ni 55 (p ,γ ) and Cu 56 (p ,γ ) forward and reverse rates and perform reaction network calculations of the r p process. These show that the r p -process flow redirects around the Ni 56 waiting point through the Ni 55 (p ,γ ) route, allowing it to proceed to higher masses more quickly and resulting in a reduction in ashes around this waiting point and an enhancement to higher-mass ashes.

Brief communication: the relation between standard error of the estimate and sample size of histomorphometric aging methods.

PubMed

Hennig, Cheryl; Cooper, David

2011-08-01

Histomorphometric aging methods report varying degrees of precision, measured through Standard Error of the Estimate (SEE). These techniques have been developed from variable samples sizes (n) and the impact of n on reported aging precision has not been rigorously examined in the anthropological literature. This brief communication explores the relation between n and SEE through a review of the literature (abstracts, articles, book chapters, theses, and dissertations), predictions based upon sampling theory and a simulation. Published SEE values for age prediction, derived from 40 studies, range from 1.51 to 16.48 years (mean 8.63; sd: 3.81 years). In general, these values are widely distributed for smaller samples and the distribution narrows as n increases--a pattern expected from sampling theory. For the two studies that have samples in excess of 200 individuals, the SEE values are very similar (10.08 and 11.10 years) with a mean of 10.59 years. Assuming this mean value is a 'true' characterization of the error at the population level, the 95% confidence intervals for SEE values from samples of 10, 50, and 150 individuals are on the order of ± 4.2, 1.7, and 1.0 years, respectively. While numerous sources of variation potentially affect the precision of different methods, the impact of sample size cannot be overlooked. The uncertainty associated with SEE values derived from smaller samples complicates the comparison of approaches based upon different methodology and/or skeletal elements. Meaningful comparisons require larger samples than have frequently been used and should ideally be based upon standardized samples. Copyright © 2011 Wiley-Liss, Inc.

[Evaluation of the quality of three-dimensional data acquired by using two kinds of structure light intra-oral scanner to scan the crown preparation model].

PubMed

Zhang, X Y; Li, H; Zhao, Y J; Wang, Y; Sun, Y C

2016-07-01

To quantitatively evaluate the quality and accuracy of three-dimensional (3D) data acquired by using two kinds of structure intra-oral scanner to scan the typical teeth crown preparations. Eight typical teeth crown preparations model were scanned 3 times with two kinds of structured light intra-oral scanner(A, B), as test group. A high precision model scanner were used to scan the model as true value group. The data above the cervical margin was extracted. The indexes of quality including non-manifold edges, the self-intersections, highly-creased edges, spikes, small components, small tunnels, small holes and the anount of triangles were measured with the tool of mesh doctor in Geomagic studio 2012. The scanned data of test group were aligned to the data of true value group. 3D deviations of the test group compared with true value group were measured for each scanned point, each preparation and each group. Independent-samples Mann-Whitney U test was applied to analyze 3D deviations for each scanned point of A and B group. Correlation analysis was applied to index values and 3D deviation values. The total number of spikes in A group was 96, and that in B group and true value group were 5 and 0 respectively. Trueness: A group 8.0 (8.3) μm, B group 9.5 (11.5) μm(P>0.05). Correlation analysis of the number of spikes with data precision of A group was r=0.46. In the study, the qulity of the scanner B is better than scanner A, the difference of accuracy is not statistically significant. There is correlation between quality and data precision of the data scanned with scanner A.

Spatiotemporal genomic architecture informs precision oncology in glioblastoma

PubMed Central

Lee, Jin-Ku; Wang, Jiguang; Sa, Jason K.; Ladewig, Erik; Lee, Hae-Ock; Lee, In-Hee; Kang, Hyun Ju; Rosenbloom, Daniel S.; Camara, Pablo G.; Liu, Zhaoqi; van Nieuwenhuizen, Patrick; Jung, Sang Won; Choi, Seung Won; Kim, Junhyung; Chen, Andrew; Kim, Kyu-Tae; Shin, Sang; Seo, Yun Jee; Oh, Jin-Mi; Shin, Yong Jae; Park, Chul-Kee; Kong, Doo-Sik; Seol, Ho Jun; Blumberg, Andrew; Lee, Jung-Il; Iavarone, Antonio; Park, Woong-Yang; Rabadan, Raul; Nam, Do-Hyun

2017-01-01

Precision medicine in cancer proposes that genomic characterization of tumors can inform personalized targeted therapies1–5. This proposition, however, is complicated by spatial and temporal heterogeneity6–14. Here we study genomic and expression profiles across 127 multi-sector or longitudinal specimens from 52 glioblastoma (GBM) patients. Using bulk and single-cell data, we find that samples from the same tumor mass share genomic and expression signatures, while geographically separated multifocal tumors and/or long-term recurrent tumors are seeded from different clones. Chemical screening of patient-derived glioma cells (PDCs) shows that therapeutic response is associated to genetic similarity, and multifocal tumors enriched with PIK3CA mutations have a heterogeneous drug response pattern. Importantly, we show that targeting truncal events is more efficacious in reducing tumor burden. In summary, this work demonstrates that evolutionary inference from integrated genomic analysis in multi-sector biopsies can inform targeted therapeutic interventions for GBM patients. PMID:28263318

TREATING HEMOGLOBINOPATHIES USING GENE CORRECTION APPROACHES: PROMISES AND CHALLENGES

PubMed Central

Cottle, Renee N.; Lee, Ciaran M.; Bao, Gang

2016-01-01

Hemoglobinopathies are genetic disorders caused by aberrant hemoglobin expression or structure changes, resulting in severe mortality and health disparities worldwide. Sickle cell disease (SCD) and β-thalassemia, the most common forms of hemoglobinopathies, are typically treated using transfusions and pharmacological agents. Allogeneic hematopoietic stem cell transplantation is the only curative therapy, but has limited clinical applicability. Although gene therapy approaches have been proposed based on the insertion and forced expression of wild-type or anti-sickling β-globin variants, safety concerns may impede their clinical application. A novel curative approach is nuclease-based gene correction, which involves the application of precision genome editing tools to correct the disease-causing mutation. This review describes the development and potential application of gene therapy and precision genome editing approaches for treating SCD and β-thalassemia. The opportunities and challenges in advancing a curative therapy for hemoglobinopathies are also discussed. PMID:27314256

Accuracy and precision of protein-ligand interaction kinetics determined from chemical shift titrations.

PubMed

Markin, Craig J; Spyracopoulos, Leo

2012-12-01

NMR-monitored chemical shift titrations for the study of weak protein-ligand interactions represent a rich source of information regarding thermodynamic parameters such as dissociation constants (K ( D )) in the micro- to millimolar range, populations for the free and ligand-bound states, and the kinetics of interconversion between states, which are typically within the fast exchange regime on the NMR timescale. We recently developed two chemical shift titration methods wherein co-variation of the total protein and ligand concentrations gives increased precision for the K ( D ) value of a 1:1 protein-ligand interaction (Markin and Spyracopoulos in J Biomol NMR 53: 125-138, 2012). In this study, we demonstrate that classical line shape analysis applied to a single set of (1)H-(15)N 2D HSQC NMR spectra acquired using precise protein-ligand chemical shift titration methods we developed, produces accurate and precise kinetic parameters such as the off-rate (k ( off )). For experimentally determined kinetics in the fast exchange regime on the NMR timescale, k ( off ) ~ 3,000 s(-1) in this work, the accuracy of classical line shape analysis was determined to be better than 5 % by conducting quantum mechanical NMR simulations of the chemical shift titration methods with the magnetic resonance toolkit GAMMA. Using Monte Carlo simulations, the experimental precision for k ( off ) from line shape analysis of NMR spectra was determined to be 13 %, in agreement with the theoretical precision of 12 % from line shape analysis of the GAMMA simulations in the presence of noise and protein concentration errors. In addition, GAMMA simulations were employed to demonstrate that line shape analysis has the potential to provide reasonably accurate and precise k ( off ) values over a wide range, from 100 to 15,000 s(-1). The validity of line shape analysis for k ( off ) values approaching intermediate exchange (~100 s(-1)), may be facilitated by more accurate K ( D ) measurements from NMR-monitored chemical shift titrations, for which the dependence of K ( D ) on the chemical shift difference (Δω) between free and bound states is extrapolated to Δω = 0. The demonstrated accuracy and precision for k ( off ) will be valuable for the interpretation of biological kinetics in weakly interacting protein-protein networks, where a small change in the magnitude of the underlying kinetics of a given pathway may lead to large changes in the associated downstream signaling cascade.

Kinetics of the Reactions of Cl((sup 2)P(sub J)) and Br((sup 2)P(sub 3/2)) with O3

NASA Technical Reports Server (NTRS)

Nicovich, J. M.; Kreutter, K. D.; Wine, P. H.

1997-01-01

A laser flash photolysis-resonance fluorescence technique has been employed to study the kinetics of the important stratospheric reactions Cl((sup 2)P(sub J)) + O3 yields ClO + O2 and Br((sup 2)P(sub 3/2)) + O3 yields BrO + O2 as a function of temperature. The temperature dependence observed for the Cl((sup 2)P(sub J)) + O3 reaction is nonArrhenius, but can be adequately described by the following two Arrhenius expressions (units are cu cm/(molecule.s), errors are 2 sigma and represent precision only): k(sub 1)(T) = (1.19 +/- 0.21) x 10(exp -11) exp[(-33 +/- 37)/T] for T = 189-269 K and k(sub 1)(T) = (2.49 +/- 0.38) x 10(exp -11) exp[(-233 +/- 46)/T] for 269-385 K. At temperatures below 230 K, the rate coefficients determined in this study are faster than any reported previously. Incorporation of our values for k(sub 1)(T) into stratospheric models would increase calculated ClO levels and decrease calculated HCI levels; hence the calculated efficiency of ClO catalyzed ozone destruction would increase. The temperature dependence observed for the Br((sup 2)P(sub 3/2)) + O3 reaction is adequately described by the following Arrhenius expression (units are cu cm/(molecule.s), errors are 2 sigma and represent precision only): k(sub 2)(T) = (1.50 +/- 0.16) x 10(exp -11)exp[(-775 +/- 30)/T for 195-392 K. While not in quantitative agreement with Arrhenius parameters reported in most previous studies, our results almost exactly reproduce the average of all earlier studies and therefore will not affect the choice of k(sub 2)(T) for use in modeling stratospheric BrO2 chemistry.

New Spectrophotometric Assay of Pyrantel Pamoate in Pharmaceuticals and Spiked Human Urine Using Three Complexing Agents

NASA Astrophysics Data System (ADS)

Swamy, N.; Prashanth, K. N.; Basavaiah, K.

2015-07-01

Three simple, rapid, inexpensive, and highly sensitive spectrophotometric methods are described for the quantifi cation of pyrantel pamoate (PYP) in pure drug and formulations. The methods are based on the molecular charge-transfer (CT) complexation reaction involving pyrantel base (PYL) as n-donor and iodine as σ-acceptor (I 2 , method A), and 2,4-dinitrophenol (DNP, method B) or picric acid (PA, method C) as π-acceptors. Spectrophotometrically, the CT complexes showed absorption maxima at 380, 420, and 430 nm, for methods A, B, and C, respectively. Under optimum conditions, Beer's law was obeyed over the concentration ranges 0.12-2.9, 0.12-3.75, and 0.12-2.9 μg/ml for methods A, B, and C, respectively. The apparent molar absorptivity of the CT complexes at the respective λmax are calculated to be 2.63 × 10 5 , 6.91 × 10 4 , and 1.73 × 10 5 l/mol· cm respectively and the corresponding Sandell sensitivity values are 0.0009, 0.003, and 0.0012. The limits of detection (LOD) and quantification (LOQ) are calculated to be (0.02 and 0.07), (0.05 and 0.15), and (0.02 and 0.07) μg/ml with methods A, B, and C, respectively. The intra-day and inter-day accuracy expressed as %RE and precision expressed as %RSD are less than 3%. The methods have been applied to the determination of PYP in tablets, suspensions, and spiked human urine. Parallel assay by a reference method and statistical analysis of the results obtained show no significant difference between the proposed methods and the reference method with respect to accuracy and precision, as evident from the Student's t and variation ratio tests. The accuracy of the methods has been further ascertained by recovery tests via the standard addition technique.

Optogenetic conditioning of paradigm and pattern discrimination in the rat somatosensory system

PubMed Central

Abe, Kenta

2017-01-01

The rodent whisker-barrel cortical system is a model for studying somatosensory discrimination at high spatiotemporal precision. Here, we applied optogenetics to produce somatosensory inputs in the whisker area using one of transgenic rat lines, W-TChR2V4, which expresses channelrhodopsin-2 (ChR2) in the mechanoreceptive nerve endings around whisker follicles. An awake W-TChR2V4 rat was head-fixed and irradiated by blue LED light on the whisker area with a paradigm conditioned with a reward. The Go task was designed so the rat is allowed to receive a reward, when it licked the nozzle within 5 s after photostimulation. The No-go task was designed so as the rat has to withhold licking for at least 5 s to obtain a reward after photostimulation. The Go-task conditioning was established within 1 hr of training with a reduction in the reaction time and increase of the success rate. To investigate the relationship between the spatiotemporal pattern of sensory inputs and the behavioral output, we designed a multi-optical fiber system that irradiates the whisker area at 9 spots in a 3×3 matrix. Although the Go-task conditioning was established using synchronous irradiation of 9 spots, the success rate was decreased with an increase of the reaction time for the asynchronous irradiation. After conditioning to the Go task, the rat responded to the blue LED flash irradiated on the barrel cortex, where many neurons also express ChR2, or photostimulation of the contralateral whisker area with a similar reaction time and success rate. Synchronous activation of the peripheral mechanoreceptive nerves is suggested to drive a neural circuit in the somatosensory cortex that efficiently couples with the decision. Our optogenetic system would enable the precise evaluation of the psychophysical values, such as the reaction time and success rate, to gain some insight into the brain mechanisms underlying conditioned behaviors. PMID:29267341

Double-trap measurement of the proton magnetic moment at 0.3 parts per billion precision.

PubMed

Schneider, Georg; Mooser, Andreas; Bohman, Matthew; Schön, Natalie; Harrington, James; Higuchi, Takashi; Nagahama, Hiroki; Sellner, Stefan; Smorra, Christian; Blaum, Klaus; Matsuda, Yasuyuki; Quint, Wolfgang; Walz, Jochen; Ulmer, Stefan

2017-11-24

Precise knowledge of the fundamental properties of the proton is essential for our understanding of atomic structure as well as for precise tests of fundamental symmetries. We report on a direct high-precision measurement of the magnetic moment μ p of the proton in units of the nuclear magneton μ N The result, μ p = 2.79284734462 (±0.00000000082) μ N , has a fractional precision of 0.3 parts per billion, improves the previous best measurement by a factor of 11, and is consistent with the currently accepted value. This was achieved with the use of an optimized double-Penning trap technique. Provided a similar measurement of the antiproton magnetic moment can be performed, this result will enable a test of the fundamental symmetry between matter and antimatter in the baryonic sector at the 10 -10 level. Copyright © 2017, American Association for the Advancement of Science.

Fixed precision sampling plans for white apple leafhopper (Homoptera: Cicadellidae) on apple.

PubMed

Beers, Elizabeth H; Jones, Vincent P

2004-10-01

Constant precision sampling plans for the white apple leafhopper, Typhlocyba pomaria McAtee, were developed so that it could be used as an indicator species for system stability as new integrated pest management programs without broad-spectrum pesticides are developed. Taylor's power law was used to model the relationship between the mean and the variance, and Green's constant precision sequential sample equation was used to develop sampling plans. Bootstrap simulations of the sampling plans showed greater precision (D = 0.25) than the desired precision (Do = 0.3), particularly at low mean population densities. We found that by adjusting the Do value in Green's equation to 0.4, we were able to reduce the average sample number by 25% and provided an average D = 0.31. The sampling plan described allows T. pomaria to be used as reasonable indicator species of agroecosystem stability in Washington apple orchards.

Robust multiscale field-only formulation of electromagnetic scattering

NASA Astrophysics Data System (ADS)

Sun, Qiang; Klaseboer, Evert; Chan, Derek Y. C.

2017-01-01

We present a boundary integral formulation of electromagnetic scattering by homogeneous bodies that are characterized by linear constitutive equations in the frequency domain. By working with the Cartesian components of the electric E and magnetic H fields and with the scalar functions (r .E ) and (r .H ) where r is a position vector, the problem can be cast as having to solve a set of scalar Helmholtz equations for the field components that are coupled by the usual electromagnetic boundary conditions at material boundaries. This facilitates a direct solution for the surface values of E and H rather than having to work with surface currents or surface charge densities as intermediate quantities in existing methods. Consequently, our formulation is free of the well-known numerical instability that occurs in the zero-frequency or long-wavelength limit in traditional surface integral solutions of Maxwell's equations and our numerical results converge uniformly to the static results in the long-wavelength limit. Furthermore, we use a formulation of the scalar Helmholtz equation that is expressed as classically convergent integrals and does not require the evaluation of principal value integrals or any knowledge of the solid angle. Therefore, standard quadrature and higher order surface elements can readily be used to improve numerical precision for the same number of degrees of freedom. In addition, near and far field values can be calculated with equal precision, and multiscale problems in which the scatterers possess characteristic length scales that are both large and small relative to the wavelength can be easily accommodated. From this we obtain results for the scattering and transmission of electromagnetic waves at dielectric boundaries that are valid for any ratio of the local surface curvature to the wave number. This is a generalization of the familiar Fresnel formula and Snell's law, valid at planar dielectric boundaries, for the scattering and transmission of electromagnetic waves at surfaces of arbitrary curvature. Implementation details are illustrated with scattering by multiple perfect electric conductors as well as dielectric bodies with complex geometries and composition.

Precision Penning Trap Mass Spectrometry of S, Kr and Xe

NASA Astrophysics Data System (ADS)

Redshaw, Matthew

2005-04-01

Using a phase coherent technique to measure the cyclotron frequency of single ions in a Penning trap [1], we have performed mass measurements on ^32S and the two most abundant krypton and xenon isotopes ^84Kr, ^86Kr, ^ 129Xe and ^132Xe, to relative precisions of 0.1 ppb. This is a factor of ˜10-100 improvement in precision over current values [2]. [1] M.P. Bradley, J.V. Porto, S. Rainville, J.K. Thompson, and D.E. Pritchard, PRL 83, 4510 (1999). [2] G. Audi, A.H. Wapstra, and C. Thibault, Nucl Phys A729, 337 (2003).

Novel 384-well population patch clamp electrophysiology assays for Ca2+-activated K+ channels.

PubMed

John, Victoria H; Dale, Tim J; Hollands, Emma C; Chen, Mao Xiang; Partington, Leanne; Downie, David L; Meadows, Helen J; Trezise, Derek J

2007-02-01

Planar array electrophysiology techniques were applied to assays for modulators of recombinant hIK and hSK3 Ca2+-activated K+ channels. In CHO-hIK-expressing cells, under asymmetric K+ gradients, small-molecule channel activators evoked time- and voltage-independent currents characteristic of those previously described by classical patch clamp electrophysiology methods. In single-hole (cell) experiments, the large cell-to-cell heterogeneity in channel expression rendered it difficult to generate activator concentration-response curves. However, in population patch clamp mode, in which signals are averaged from up to 64 cells, well-to-well variation was substantially reduced such that concentration-response curves could be easily constructed. The absolute EC50 values and rank order of potency for a range of activators, including 1-EBIO and DC-EBIO, corresponded well with conventional patch clamp data. Activator responses of hIK and hSK3 channels could be fully and specifically blocked by the selective inhibitors TRAM-34 and apamin, with IC50 values of 0.31 microM and 3 nM, respectively. To demonstrate assay precision and robustness, a test set of 704 compounds was screened in a 384-well format of the hIK assay. All plates had Z' values greater than 0.6, and the statistical cutoff for activity was 8%. Eleven hits (1.6%) were identified from this set, in addition to the randomly spiked wells with known activators. Overall, our findings demonstrate that population patch clamp is a powerful and enabling method for screening Ca2+-activated K+ channels and provides significant advantages over single-cell electrophysiology (IonWorks(HT)) and other previously published approaches. Moreover, this work demonstrates for the 1st time the utility of population patch clamp for ion channel activator assays and for non-voltage-gated ion channels.

Solving Ordinary Differential Equations

NASA Technical Reports Server (NTRS)

Krogh, F. T.

1987-01-01

Initial-value ordinary differential equation solution via variable order Adams method (SIVA/DIVA) package is collection of subroutines for solution of nonstiff ordinary differential equations. There are versions for single-precision and double-precision arithmetic. Requires fewer evaluations of derivatives than other variable-order Adams predictor/ corrector methods. Option for direct integration of second-order equations makes integration of trajectory problems significantly more efficient. Written in FORTRAN 77.

Accurate Measurements of Refractive Indices for Dielectrics in an Undergraduate Optics Laboratory for Science and Engineering Students

ERIC Educational Resources Information Center

Hsu, Wei-Tai; Bahrim, Cristian

2009-01-01

Based on our novel method recently published in the "Am. J. Phys." 77 337-43 (2009) for finding precise values of the indices of refraction for dielectrics from measurements of the polarized light reflected by the surface, in this paper we propose an improved technique for finding Brewster angles with a better precision, of 0.001 degrees, using…

Numerically stable formulas for a particle-based explicit exponential integrator

NASA Astrophysics Data System (ADS)

Nadukandi, Prashanth

2015-05-01

Numerically stable formulas are presented for the closed-form analytical solution of the X-IVAS scheme in 3D. This scheme is a state-of-the-art particle-based explicit exponential integrator developed for the particle finite element method. Algebraically, this scheme involves two steps: (1) the solution of tangent curves for piecewise linear vector fields defined on simplicial meshes and (2) the solution of line integrals of piecewise linear vector-valued functions along these tangent curves. Hence, the stable formulas presented here have general applicability, e.g. exact integration of trajectories in particle-based (Lagrangian-type) methods, flow visualization and computer graphics. The Newton form of the polynomial interpolation definition is used to express exponential functions of matrices which appear in the analytical solution of the X-IVAS scheme. The divided difference coefficients in these expressions are defined in a piecewise manner, i.e. in a prescribed neighbourhood of removable singularities their series approximations are computed. An optimal series approximation of divided differences is presented which plays a critical role in this methodology. At least ten significant decimal digits in the formula computations are guaranteed to be exact using double-precision floating-point arithmetic. The worst case scenarios occur in the neighbourhood of removable singularities found in fourth-order divided differences of the exponential function.

The nucleolar protein NIFK promotes cancer progression via CK1α/β-catenin in metastasis and Ki-67-dependent cell proliferation

PubMed Central

Lin, Tsung-Chieh; Su, Chia-Yi; Wu, Pei-Yu; Lai, Tsung-Ching; Pan, Wen-An; Jan, Yi-Hua; Chang, Yu-Chang; Yeh, Chi-Tai; Chen, Chi-Long; Ger, Luo-Ping; Chang, Hong-Tai; Yang, Chih-Jen; Huang, Ming-Shyan; Liu, Yu-Peng; Lin, Yuan-Feng; Shyy, John Y-J; Tsai, Ming-Daw; Hsiao, Michael

2016-01-01

Nucleolar protein interacting with the FHA domain of pKi-67 (NIFK) is a Ki-67-interacting protein. However, its precise function in cancer remains largely uninvestigated. Here we show the clinical significance and metastatic mechanism of NIFK in lung cancer. NIFK expression is clinically associated with poor prognosis and metastasis. Furthermore, NIFK enhances Ki-67-dependent proliferation, and promotes migration, invasion in vitro and metastasis in vivo via downregulation of casein kinase 1α (CK1α), a suppressor of pro-metastatic TCF4/β-catenin signaling. Inversely, CK1α is upregulated upon NIFK knockdown. The silencing of CK1α expression in NIFK-silenced cells restores TCF4/β-catenin transcriptional activity, cell migration, and metastasis. Furthermore, RUNX1 is identified as a transcription factor of CSNK1A1 (CK1α) that is negatively regulated by NIFK. Our results demonstrate the prognostic value of NIFK, and suggest that NIFK is required for lung cancer progression via the RUNX1-dependent CK1α repression, which activates TCF4/β-catenin signaling in metastasis and the Ki-67-dependent regulation in cell proliferation. DOI: http://dx.doi.org/10.7554/eLife.11288.001 PMID:26984280

Solid-phase extraction assisted dispersive liquid-liquid microextraction based on solidification of floating organic droplet to determine sildenafil and its analogues in dietary supplements.

PubMed

Li, Jing; Roh, Si Hun; Shaodong, Jia; Hong, Ji Yeon; Lee, Dong-Kyu; Shin, Byong-Kyu; Park, Jeong Hill; Lee, Jeongmi; Kwon, Sung Won

2017-08-01

A novel analytical method for the simultaneous determination of the concentration of sildenafil and its five analogues in dietary supplements using solid-phase extraction assisted reversed-phase dispersive liquid-liquid microextraction based on solidification of floating organic droplet combined with ion-pairing liquid chromatography with an ultraviolet detector was developed. Parameters that affect extraction efficiency were systematically investigated, including the type of solid-phase extraction cartridge, pH of the extraction environment, and the type and volume of extraction and dispersive solvent. The method linearity was in the range of 5.0-100 ng/mL for sildenafil, homosildenafil, udenafil, benzylsildenafil, and thiosildenafil and 10-100 ng/mL for acetildenafil. The coefficients of determination were ≥0.996 for all regression curves. The sensitivity values expressed as limit of detection were between 2.5 and 7.5 ng/mL. Furthermore, intraday and interday precisions expressed as relative standard deviations were less than 5.7 and 9.9%, respectively. The proposed method was successfully applied to the analysis of sildenafil and its five analogues in complex dietary supplements. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Extending applicability of the oxygen radical absorbance capacity (ORAC-fluorescein) assay.

PubMed

Dávalos, Alberto; Gómez-Cordovés, Carmen; Bartolomé, Begoña

2004-01-14

The ORAC-fluorescein (ORAC-FL) method recently validated using automatic liquid handling systems has now been adapted to manual handling and using a conventional fluorescence microplate reader. As calculated for Trolox, the precision of the method was <3.0, expressed as percent coefficient of variation. The accuracy of the method was <2.3, expressed as percent variation of the mean. The detection and quantification limits were those corresponding to 0.5- and 1-microM Trolox standard solutions, respectively. The method has been applied to 10 pure compounds (benzoic and cinnamic acids and aldehydes, flavonoids, and butylated hydroxyanisole), to 30 white, rose, and bottled- and oak-aged red wines, and to 7 commercial dietary antioxidant supplements. All samples exhibited a good linear response with concentration. As seen by other methodologies, the chemical structure of a compound determines its antioxidant activity (ORAC-FL value). Of particular interest were the results with oak-aged red wines from different vintages (1989-2002) that confirm influence of vintage, but not origin of the oak, in the antioxidant activity of wines from the same variety. Dietary antioxidant supplements presented a great variability (170-fold difference) in their antioxidant potency. This work proves applicability of the ORAC-FL assay in evaluating the antioxidant activity of diverse food samples.

Proceedings of the Thirteenth Annual Precise Time and Time Interval (PTTI) Applications and Planning Meeting

NASA Technical Reports Server (NTRS)

Wardrip, S. C.

1982-01-01

Proceedings of an annual Precise Time and Time Interval (PTTI) Applications and Planning Meeting are summarized. A transparent view of the state-of-the-art, an opportunity to express needs, a view of important future trends, and a review of relevant past accomplishments were considered for PTTI managers, systems engineers, and program planner. Specific aims were: to provide PTTI users with new and useful applications, procedures, and techniques; to allow the PTTI researcher to better assess fruitful directions for research efforts.

Posttranscriptional control of neuronal development by microRNA networks.

PubMed

Gao, Fen-Biao

2008-01-01

The proper development of the nervous system requires precise spatial and temporal control of gene expression at both the transcriptional and translational levels. In different experimental model systems, microRNAs (miRNAs) - a class of small, endogenous, noncoding RNAs that control the translation and stability of many mRNAs - are emerging as important regulators of various aspects of neuronal development. Further dissection of the in vivo physiological functions of individual miRNAs promises to offer novel mechanistic insights into the gene regulatory networks that ensure the precise assembly of a functional nervous system.

Spatially constrained incoherent motion method improves diffusion-weighted MRI signal decay analysis in the liver and spleen

PubMed Central

Taimouri, Vahid; Afacan, Onur; Perez-Rossello, Jeannette M.; Callahan, Michael J.; Mulkern, Robert V.; Warfield, Simon K.; Freiman, Moti

2015-01-01

Purpose: To evaluate the effect of the spatially constrained incoherent motion (SCIM) method on improving the precision and robustness of fast and slow diffusion parameter estimates from diffusion-weighted MRI in liver and spleen in comparison to the independent voxel-wise intravoxel incoherent motion (IVIM) model. Methods: We collected diffusion-weighted MRI (DW-MRI) data of 29 subjects (5 healthy subjects and 24 patients with Crohn’s disease in the ileum). We evaluated parameters estimates’ robustness against different combinations of b-values (i.e., 4 b-values and 7 b-values) by comparing the variance of the estimates obtained with the SCIM and the independent voxel-wise IVIM model. We also evaluated the improvement in the precision of parameter estimates by comparing the coefficient of variation (CV) of the SCIM parameter estimates to that of the IVIM. Results: The SCIM method was more robust compared to IVIM (up to 70% in liver and spleen) for different combinations of b-values. Also, the CV values of the parameter estimations using the SCIM method were significantly lower compared to repeated acquisition and signal averaging estimated using IVIM, especially for the fast diffusion parameter in liver (CVIV IM = 46.61 ± 11.22, CVSCIM = 16.85 ± 2.160, p < 0.001) and spleen (CVIV IM = 95.15 ± 19.82, CVSCIM = 52.55 ± 1.91, p < 0.001). Conclusions: The SCIM method characterizes fast and slow diffusion more precisely compared to the independent voxel-wise IVIM model fitting in the liver and spleen. PMID:25832079

Northern Hemisphere moisture variability during the Last Glacial period

NASA Astrophysics Data System (ADS)

Asmerom, Y.; Polyak, V. J.; Lachniet, M. S.

2013-12-01

It was previously shown that large oxygen isotope variability related to changing moisture sources in the southwestern United States (SW) match the Greenland ice core temperature record. The variations were attributed to changes in the ratio of winter to summer precipitation delivered to the SW, with lighter winter δ18O values compared to summer monsoon rainfall, due to meridonial shifts in the position of the polar jet stream, which directs winter storm tracks. Cold stadial δ18O excursions are associated with strongly negative values, while interstadials have higher than average δ18O values. Although these data documented moisture source variability to the SW, the question of effective moisture variability remains unanswered. Here we present new high-resolution δ18O and δ13C isotopic data from a precisely dated speleothem, FS-AH1, from Fort Stanton Cave, New Mexico USA. The sample grew continuously between 47.6 and 11.1 kyr. The new chronology is more precise than previous work due to high sample growth rate, new gains in efficiency provided by our upgraded Neptune MC-ICPMS and new more precise determinations of the half-lives of 230Th and 234U. The FS-AH1 δ18O and the Greenland δ18O data (on the GICC05 time scale) show a remarkable match, both with respect to stadials/interstadial amplitudes and variability, and in the overall long-term trend. Our interpretation of the δ18O data remains the same, an indicator of moisture source variability. The δ18O and δ13C isotopic data show no correlation (R2 <0.0001) because the δ18O primarily reflects differences in moisture sources and temperature (at least during large-scale excursions), while δ13C variability reflects the amount of effective moisture in the soil zone overlying the cave, with low δ13C attributed to high soil productivity, high effective moisture, and wet conditions. The stadial and interstadial events are expressed mutely, if at all, in the δ13C data, while the secular variation follows the change in Northern Hemisphere summer insolation (insolation), similar to other Northern Hemisphere data, such as the strength of the East Asian summer monsoon as recorded in the Hulu speleothem, although the match to the East Asian monsoon is inverse. The much diminished expression of stadials and interstadials and secular variations in the effective moisture proxy data that match insolation seem to be hemispherical in scale. In humid settings, such as east Asia monsoon regions, warm temperatures lead to northward shift of the ITCZ and increase in the strength of the Asian monsoon, while in the desert SW any increase in the strength in the North American monsoon is counterbalanced by decrease in winter moisture due to the northward shift of the polar jet stream and more importantly, the onset of more evaporative conditions. In contrast to the large and rapid shifts seen in the Greenland ice core data and the apparent shift in position in air masses, as indicated by our δ18O data, large-scale changes in moisture regimes in the Northern Hemisphere seem to be driven by changes in insolation. Locations that are sensitive to small changes in atmospheric pressure and/or sea surface temperature gradients may be the exception.

WP1: transgenic opto-animals

NASA Astrophysics Data System (ADS)

UŻarowska, E.; Czajkowski, Rafał; Konopka, W.

2014-11-01

We aim to create a set of genetic tools where permanent opsin expression (ChR or NpHR) is precisely limited to the population of neurons that express immediate early gene c-fos during a specific temporal window of behavioral training. Since the c-fos gene is only expressed in neurons that form experience-dependent ensemble, this approach will result in specific labeling of a small subset of cells that create memory trace for the learned behavior. To this end we employ two alternative inducible gene expression systems: Tet Expression System and Cre/lox System. In both cases, the temporal window for opsin induction is controlled pharmacologically, by doxycycline or tamoxifen, respectively. Both systems will be used for creating lines of transgenic animals.

Precision measurements of the top quark mass from the Tevatron in the pre-LHC era.

PubMed

Galtieri, Angela Barbaro; Margaroli, Fabrizio; Volobouev, Igor

2012-05-01

The top quark is the heaviest of the six quarks of the standard model (SM). Precise knowledge of its mass is important for imposing constraints on a number of physics processes, including interactions of the as yet unobserved Higgs boson. The Higgs boson is the only missing particle of the SM, central to the electroweak symmetry breaking mechanism and generation of particle masses. In this review, experimental measurements of the top quark mass accomplished at the Tevatron, a proton-antiproton collider located at the Fermi National Accelerator Laboratory, are described. Topologies of top quark events and the methods used to separate signal events from background sources are discussed. Data analysis techniques used to extract information about the top mass value are reviewed. The combination of several of the most precise measurements performed with the two Tevatron particle detectors, CDF and DØ, yields a value of M(t) = 173.2 ± 0.9 GeV/c(2).

Julius Edgar Lilienfeld Prize Talk: Measuring the Electron Magnetic Moment and the Fine Structure Constant

NASA Astrophysics Data System (ADS)

Gabrielse, Gerald

2011-05-01

The electron magnetic moment in Bohr magnetons has been measured to a precision of 3 parts in 1013. This measurement, with quantum electrodynamics (AED) theory, provides the most precise value of the fine structure constant. This measurement, with a value of the fine structure from other measurements, also tests QED and sets a limit on the internal structure of the electron. A one-electron quantum cyclotron is at the heart of the measurement -- an electron suspended in a magnetic field and cooled enough that its lowest cyclotron and spin quantum states can be deduced with quantum nondemolition (QND) measurements. A cylindrical Penning trap cavity inhibits spontaneous emission and feedback methods make the electron excite and sustain its own motion for detection. A new apparatus is being commissioned in pursuit of more precise measurements. Adapted methods are promising for observing a proton spin flip, which should make it possible to compare the antiproton and proton magnetic moments a million times more accurately than is currently possible.

Feeding-Related Traits Are Affected by Dosage of the foraging Gene in Drosophila melanogaster

PubMed Central

Allen, Aaron M.; Anreiter, Ina; Neville, Megan C.; Sokolowski, Marla B.

2017-01-01

Nutrient acquisition and energy storage are critical parts of achieving metabolic homeostasis. The foraging gene in Drosophila melanogaster has previously been implicated in multiple feeding-related and metabolic traits. Before foraging’s functions can be further dissected, we need a precise genetic null mutant to definitively map its amorphic phenotypes. We used homologous recombination to precisely delete foraging, generating the for0 null allele, and used recombineering to reintegrate a full copy of the gene, generating the {forBAC} rescue allele. We show that a total loss of foraging expression in larvae results in reduced larval path length and food intake behavior, while conversely showing an increase in triglyceride levels. Furthermore, varying foraging gene dosage demonstrates a linear dose-response on these phenotypes in relation to foraging gene expression levels. These experiments have unequivocally proven a causal, dose-dependent relationship between the foraging gene and its pleiotropic influence on these feeding-related traits. Our analysis of foraging’s transcription start sites, termination sites, and splicing patterns using rapid amplification of cDNA ends (RACE) and full-length cDNA sequencing, revealed four independent promoters, pr1–4, that produce 21 transcripts with nine distinct open reading frames (ORFs). The use of alternative promoters and alternative splicing at the foraging locus creates diversity and flexibility in the regulation of gene expression, and ultimately function. Future studies will exploit these genetic tools to precisely dissect the isoform- and tissue-specific requirements of foraging’s functions and shed light on the genetic control of feeding-related traits involved in energy homeostasis. PMID:28007892

Identification of micro-RNA expression profile related to recurrence in women with ESMO low-risk endometrial cancer.

PubMed

de Foucher, Tiphaine; Sbeih, Maria; Uzan, Jenifer; Bendifallah, Sofiane; Lefevre, Marine; Chabbert-Buffet, Nathalie; Aractingi, Selim; Uzan, Catherine; Abd Alsalam, Issam; Mitri, Rana; Fontaine, Romain H; Daraï, Emile; Haddad, Bassam; Méhats, Céline; Ballester, Marcos; Canlorbe, Geoffroy; Touboul, Cyril

2018-05-21

Actual European pathological classification of early-stage endometrial cancer (EC) may show insufficient accuracy to precisely stratify recurrence risk, leading to potential over or under treatment. Micro-RNAs are post-transcriptional regulators involved in carcinogenic mechanisms, with some micro-RNA patterns of expression associated with EC characteristics and prognosis. We previously demonstrated that downregulation of micro-RNA-184 was associated with lymph node involvement in low-risk EC (LREC). The aim of this study was to evaluate whether micro-RNA signature in tumor tissues from LREC women can be correlated with the occurrence of recurrences. MicroRNA expression was assessed by chip analysis and qRT-PCR in 7 formalin-fixed paraffin-embedded (FFPE) LREC primary tumors from women whose follow up showed recurrences (R+) and in 14 FFPE LREC primary tumors from women whose follow up did not show any recurrence (R-), matched for grade and age. Various statistical analyses, including enrichment analysis and a minimum p-value approach, were performed. The expression levels of micro-RNAs-184, -497-5p, and -196b-3p were significantly lower in R+ compared to R- women. Women with a micro-RNA-184 fold change < 0.083 were more likely to show recurrence (n = 6; 66%) compared to those with a micro-RNA-184 fold change > 0.083 (n = 1; 8%), p = 0.016. Women with a micro-RNA-196 fold change < 0.56 were more likely to show recurrence (n = 5; 100%) compared to those with a micro-RNA-196 fold change > 0.56 (n = 2; 13%), p = 0.001. These findings confirm the great interest of micro-RNA-184 as a prognostic tool to improve the management of LREC women.

SigEMD: A powerful method for differential gene expression analysis in single-cell RNA sequencing data.

PubMed

Wang, Tianyu; Nabavi, Sheida

2018-04-24

Differential gene expression analysis is one of the significant efforts in single cell RNA sequencing (scRNAseq) analysis to discover the specific changes in expression levels of individual cell types. Since scRNAseq exhibits multimodality, large amounts of zero counts, and sparsity, it is different from the traditional bulk RNA sequencing (RNAseq) data. The new challenges of scRNAseq data promote the development of new methods for identifying differentially expressed (DE) genes. In this study, we proposed a new method, SigEMD, that combines a data imputation approach, a logistic regression model and a nonparametric method based on the Earth Mover's Distance, to precisely and efficiently identify DE genes in scRNAseq data. The regression model and data imputation are used to reduce the impact of large amounts of zero counts, and the nonparametric method is used to improve the sensitivity of detecting DE genes from multimodal scRNAseq data. By additionally employing gene interaction network information to adjust the final states of DE genes, we further reduce the false positives of calling DE genes. We used simulated datasets and real datasets to evaluate the detection accuracy of the proposed method and to compare its performance with those of other differential expression analysis methods. Results indicate that the proposed method has an overall powerful performance in terms of precision in detection, sensitivity, and specificity. Copyright © 2018 Elsevier Inc. All rights reserved.

An RGS4-mediated phenotypic switch of bronchial smooth muscle cells promotes fixed airway obstruction in asthma.

PubMed

Damera, Gautam; Druey, Kirk M; Cooper, Philip R; Krymskaya, Vera P; Soberman, Roy J; Amrani, Yassine; Hoshi, Toshinori; Brightling, Christopher E; Panettieri, Reynold A

2012-01-01

In severe asthma, bronchodilator- and steroid-insensitive airflow obstruction develops through unknown mechanisms characterized by increased lung airway smooth muscle (ASM) mass and stiffness. We explored the role of a Regulator of G-protein Signaling protein (RGS4) in the ASM hyperplasia and reduced contractile capacity characteristic of advanced asthma. Using immunocytochemical staining, ASM expression of RGS4 was determined in endobronchial biopsies from healthy subjects and those from subjects with mild, moderate and severe asthma. Cell proliferation assays, agonist-induced calcium mobilization and bronchoconstriction were determined in cultured human ASM cells and in human precision cut lung slices. Using gain- and loss-of-function approaches, the precise role of RGS proteins was determined in stimulating human ASM proliferation and inhibiting bronchoconstriction. RGS4 expression was restricted to a subpopulation of ASM and was specifically upregulated by mitogens, which induced a hyperproliferative and hypocontractile ASM phenotype similar to that observed in recalcitrant asthma. RGS4 expression was markedly increased in bronchial smooth muscle of patients with severe asthma, and expression correlated significantly with reduced pulmonary function. Whereas RGS4 inhibited G protein-coupled receptor (GPCR)-mediated bronchoconstriction, unexpectedly RGS4 was required for PDGF-induced proliferation and sustained activation of PI3K, a mitogenic signaling molecule that regulates ASM proliferation. These studies indicate that increased RGS4 expression promotes a phenotypic switch of ASM, evoking irreversible airway obstruction in subjects with severe asthma.

A Transient Expression of Prospero Promotes Cell Cycle Exit of Drosophila Postembryonic Neurons through the Regulation of Dacapo

PubMed Central

Colonques, Jordi; Ceron, Julian; Reichert, Heinrich; Tejedor, Francisco J.

2011-01-01

Cell proliferation, specification and terminal differentiation must be precisely coordinated during brain development to ensure the correct production of different neuronal populations. Most Drosophila neuroblasts (NBs) divide asymmetrically to generate a new NB and an intermediate progenitor called ganglion mother cell (GMC) which divides only once to generate two postmitotic cells called ganglion cells (GCs) that subsequently differentiate into neurons. During the asymmetric division of NBs, the homeodomain transcription factor PROSPERO is segregated into the GMC where it plays a key role as cell fate determinant. Previous work on embryonic neurogenesis has shown that PROSPERO is not expressed in postmitotic neuronal progeny. Thus, PROSPERO is thought to function in the GMC by repressing genes required for cell-cycle progression and activating genes involved in terminal differentiation. Here we focus on postembryonic neurogenesis and show that the expression of PROSPERO is transiently upregulated in the newly born neuronal progeny generated by most of the larval NBs of the OL and CB. Moreover, we provide evidence that this expression of PROSPERO in GCs inhibits their cell cycle progression by activating the expression of the cyclin-dependent kinase inhibitor (CKI) DACAPO. These findings imply that PROSPERO, in addition to its known role as cell fate determinant in GMCs, provides a transient signal to ensure a precise timing for cell cycle exit of prospective neurons, and hence may link the mechanisms that regulate neurogenesis and those that control cell cycle progression in postembryonic brain development. PMID:21552484

Genetics Home Reference: Birt-Hogg-Dubé syndrome

MedlinePlus

... B, Schmidt LS. Expression of Birt-Hogg-Dubé gene mRNA in normal and neoplastic human tissues. Mod Pathol. 2004 Aug;17(8):998-1011. ... are genome editing and CRISPR-Cas9? What is precision medicine? What ...

Active inference and epistemic value.

PubMed

Friston, Karl; Rigoli, Francesco; Ognibene, Dimitri; Mathys, Christoph; Fitzgerald, Thomas; Pezzulo, Giovanni

2015-01-01

We offer a formal treatment of choice behavior based on the premise that agents minimize the expected free energy of future outcomes. Crucially, the negative free energy or quality of a policy can be decomposed into extrinsic and epistemic (or intrinsic) value. Minimizing expected free energy is therefore equivalent to maximizing extrinsic value or expected utility (defined in terms of prior preferences or goals), while maximizing information gain or intrinsic value (or reducing uncertainty about the causes of valuable outcomes). The resulting scheme resolves the exploration-exploitation dilemma: Epistemic value is maximized until there is no further information gain, after which exploitation is assured through maximization of extrinsic value. This is formally consistent with the Infomax principle, generalizing formulations of active vision based upon salience (Bayesian surprise) and optimal decisions based on expected utility and risk-sensitive (Kullback-Leibler) control. Furthermore, as with previous active inference formulations of discrete (Markovian) problems, ad hoc softmax parameters become the expected (Bayes-optimal) precision of beliefs about, or confidence in, policies. This article focuses on the basic theory, illustrating the ideas with simulations. A key aspect of these simulations is the similarity between precision updates and dopaminergic discharges observed in conditioning paradigms.

Study of Electron G-2 From 1947 To Present

NASA Astrophysics Data System (ADS)

Kinoshita, Toichiro

2014-03-01

In 1947 Kusch and Foley discovered in the study of Zeeman splitting of Ga atom that the electron g-factor was about 0.2% larger than the value 2 predicted by the Dirac equation. Soon afterwards Schwinger showed that it can be explained as the effect of radiative correction. His calculation, in the second order perturbation theory of the Lorentz invariant formulation of renormalized quantum electrodynamics, showed that the electron has an excess magnetic moment ae ≡ (g - 2) / 2 = α / (2 π) , where α is the fine structure constant, in agreement with the measurement within 3%. Thus began a long series of friendly competition between experimentalists and theorists to improve the precision of ae. Over the period of more than 60 years measurement precision of ae was improved by more than 104 by the spin precession technique, and further 103 by the Penning trap experiments. In step with the progress of measurement, the theory of ae, expressed as a power series in α, has been pushed to the fifth power of α. Including small contributions from hadronic effects and weak interaction effect and using the best non-QED value of α: α-1 = 137 . 035999049 (90) , one finds ae (theory) = 1159652181 . 72 (77) ×10-12 . The uncertainty is about 0 . 66 ppb , where 1 ppb =10-9 . The intrinsic uncertainty of theory itself is less than 0 . 1 ppb . The over all uncertainty comes mostly from the uncertainty of non-QED α mentioned above, which is about 0 . 66 ppb . This is in good agreement with the latest measurement: ae (experiment) = 1159652180 . 73 (28) ×10-12 . The uncertainty of measurement is 0 . 24 ppb . An alternate approach to test QED is to assume the validity of QED (and the Standard Model of particle physics) and obtain α by solving the equation ae (experiment) =ae (theory) . This yields α-1 (ae) = 137 . 0359991727 (342) , whose uncertainty is 0 . 25 ppb , better than α obtained by any other means. Although comparison of theory and experiment of ae began historically as a test of the validity of QED, it has now evolved into a precision test of fine structure constant at the level exceeding 1 ppb , which may be regarded as a test of internal consistency of quantum mechanics as a whole. Supported in part by the U. S. National Science Foundation under Grant No. NSF-PHY-0757868.

Crossed-Beam Spectroscopy of Hydrogen: A New Value for the Rydberg Constant

NASA Astrophysics Data System (ADS)

Amin, S. R.; Caldwell, C. D.; Lichten, W.

1981-11-01

In a crossed laser-atomic beam experiment the wavelengths of the 2s-3p transitions are measured in H and D to a precision of one part in 109. Our value for the Rydberg constant is R∞=109 737.315 21(11) cm-1. The fine-structure splittings of the 3p states in H and D are 3249.8(8) and 3251.7(7) MHz, respectively; the isotope shifts for the 2s-3p12 and 2s-3p32 transitions are 124 260.7(7) and 124 262.6(7) MHz, respectively. Our results largely agree with previous, less precise experiments and with theory.

High-precision optical measurement of the 2S hyperfine interval in atomic hydrogen.

PubMed

Kolachevsky, N; Fischer, M; Karshenboim, S G; Hänsch, T W

2004-01-23

We have applied an optical method to the measurement of the 2S hyperfine interval in atomic hydrogen. The interval has been measured by means of two-photon spectroscopy of the 1S-2S transition on a hydrogen atomic beam shielded from external magnetic fields. The measured value of the 2S hyperfine interval is equal to 177 556 860(16) Hz and represents the most precise measurement of this interval to date. The theoretical evaluation of the specific combination of 1S and 2S hyperfine intervals D21 is in fair agreement (within 1.4 sigma) with the value for D21 deduced from our measurement.

Half-lives of 132La and 135La

NASA Astrophysics Data System (ADS)

Abel, E. P.; Clause, H. K.; Fonslet, J.; Nickles, R. J.; Severin, G. W.

2018-03-01

The half-lives of 135La and 132La were determined via serial gamma spectroscopy, and the half-life of 135La was further determined by a high-precision ionization-chamber measurement. The results are 18.91(2) hr for 135La and 4.59(4) hr for 132La compared with the previously compiled values of 19.5(2) hr and 4.8(2) hr, respectively. These lanthanum isotopes comprise a medically interesting system with positron emitter 132La and Auger-electron emitter 135La forming a theranostic pair for internal diagnostics and therapeutics. The precise half-lives are necessary for proper evaluation of their value in medicine and for a more representative tabulation of nuclear data.

Computational Calorimetry: High-Precision Calculation of Host–Guest Binding Thermodynamics

PubMed Central

2015-01-01

We present a strategy for carrying out high-precision calculations of binding free energy and binding enthalpy values from molecular dynamics simulations with explicit solvent. The approach is used to calculate the thermodynamic profiles for binding of nine small molecule guests to either the cucurbit[7]uril (CB7) or β-cyclodextrin (βCD) host. For these systems, calculations using commodity hardware can yield binding free energy and binding enthalpy values with a precision of ∼0.5 kcal/mol (95% CI) in a matter of days. Crucially, the self-consistency of the approach is established by calculating the binding enthalpy directly, via end point potential energy calculations, and indirectly, via the temperature dependence of the binding free energy, i.e., by the van’t Hoff equation. Excellent agreement between the direct and van’t Hoff methods is demonstrated for both host–guest systems and an ion-pair model system for which particularly well-converged results are attainable. Additionally, we find that hydrogen mass repartitioning allows marked acceleration of the calculations with no discernible cost in precision or accuracy. Finally, we provide guidance for accurately assessing numerical uncertainty of the results in settings where complex correlations in the time series can pose challenges to statistical analysis. The routine nature and high precision of these binding calculations opens the possibility of including measured binding thermodynamics as target data in force field optimization so that simulations may be used to reliably interpret experimental data and guide molecular design. PMID:26523125

Optimization and validation of liquid chromatography and headspace-gas chromatography based methods for the quantitative determination of capsaicinoids, salicylic acid, glycol monosalicylate, methyl salicylate, ethyl salicylate, camphor and l-menthol in a topical formulation.

PubMed

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.

Charging-choke circuit with a crowbar for precision control of voltage

DOEpatents

Praeg, W.F.

1975-11-25

The operation of a circuit using a charging choke to obtain dc voltages is improved by constructing the circuit to be capable of producing a higher voltage than the desired value and crowbarring the charging choke when the load voltage reaches the desired value.

Benchmark dose and the three Rs. Part I. Getting more information from the same number of animals.

PubMed

Slob, Wout

2014-08-01

Evaluating dose-response data using the Benchmark dose (BMD) approach rather than by the no observed adverse effect (NOAEL) approach implies a considerable step forward from the perspective of the Reduction, Replacement, and Refinement, three Rs, in particular the R of reduction: more information is obtained from the same number of animals, or, vice versa, similar information may be obtained from fewer animals. The first part of this twin paper focusses on the former, the second on the latter aspect. Regarding the former, the BMD approach provides more information from any given dose-response dataset in various ways. First, the BMDL (= BMD lower confidence bound) provides more information by its more explicit definition. Further, as compared to the NOAEL approach the BMD approach results in more statistical precision in the value of the point of departure (PoD), for deriving exposure limits. While part of the animals in the study do not directly contribute to the numerical value of a NOAEL, all animals are effectively used and do contribute to a BMDL. In addition, the BMD approach allows for combining similar datasets for the same chemical (e.g., both sexes) in a single analysis, which further increases precision. By combining a dose-response dataset with similar historical data for other chemicals, the precision can even be substantially increased. Further, the BMD approach results in more precise estimates for relative potency factors (RPFs, or TEFs). And finally, the BMD approach is not only more precise, it also allows for quantification of the precision in the BMD estimate, which is not possible in the NOAEL approach.

Research on the improvement of traditional dial instrument precision based on C8051F020.

NASA Astrophysics Data System (ADS)

Sun, Guiling; Liu, Yi; Lu, Li

2006-11-01

Two essential parameters to weigh the quality of a reinforcing steel bar are the value of its bending force and the maximum pull it can withstand, in order to measure them with higher precision, it is significant to describe the changing tendency of force with time and displacement by drawing a real-time curve directly during the process examining the quality of a bar when the pull exerted is variable continuously. Using C8051F020 as the core component, this paper improves traditional dial instruments whose precision can only reach the second level. Adopting a high precision pulling/pressing force sensor, an amplifier, a two-order Butterworth low-pass filter and a 12-bit AD converter which is in the C8051F020, the first level of precision can be obtained. A rotary encoder is used to measure the length increment of the bar during the pulling process, based on an algorithm, a force-displacement (or time) curve which is quite important for operators to control the course of experiment can be displayed on the LCD. Meanwhile, real-time experimental data can be stored in local flash, or uploaded to PC by RS-485 and stored in the center database. A real-time clock is also adopted to mark the time of each experiment that is useful to index the data. The measure system we describe here is characterized by simple structure, high precision and stabilization, and convenience operation, can be used in other actual measure systems by only changing the front sensor, so it is of great value of application and popularization.

"Express yourself": culture and the effect of self-expression on choice.

PubMed

Kim, Heejung S; Sherman, David K

2007-01-01

Whereas self-expression is valued in the United States, it is not privileged with such a cultural emphasis in East Asia. Four studies demonstrate the psychological implications of this cultural difference. Studies 1 and 2 found that European Americans value self-expression more than East Asians/East Asian Americans. Studies 3 and 4 examined the roles of expression in preference judgments. In Study 3, the expression of choice led European Americans but not East Asian Americans to be more invested in what they chose. Study 4 examined the connection between the value of expression and the effect of choice expression and showed that European Americans place greater emphasis on self-expression than East Asian Americans, and this difference explained the cultural difference in Study 3. This research highlights the importance of the cultural meanings of self-expression and the moderating role of cultural beliefs on the psychological effect of self-expression. 2007 APA, all rights reserved

Amplion, Inc.

PubMed

Taylor, Seth; Carroll, Adam; Lord, Jessi

2016-07-01

Amplion, Inc. (OR, USA) is focused on progressing the primary drivers of precision medicine. Focused on enabling the front end of the healthcare value chain, pharmaceutical developers and diagnostic test developers, Amplion zeros in on the research and market components that will make precision medicine a reality. With BiomarkerBase™, Amplion's flagship product, Amplion provides evidence-based biomarker information that support the key strategic decisions pharmaceutical and diagnostic developers need to make to be successful in the emerging world of precision medicine. A passion for saving lives and improving patient outcomes using precision medicine inspires Amplion's product BiomarkerBase™. A unique combination of hard science and data science positions Amplion to surface the relationships of biomarkers and clinical evidence that gives pharmaceutical and diagnostic companies unique insight into the technical realities and market opportunities provided by biomarkers.

Automatic small target detection in synthetic infrared images

NASA Astrophysics Data System (ADS)

Yardımcı, Ozan; Ulusoy, Ä.°lkay

2017-05-01

Automatic detection of targets from far distances is a very challenging problem. Background clutter and small target size are the main difficulties which should be solved while reaching a high detection performance as well as a low computational load. The pre-processing, detection and post-processing approaches are very effective on the final results. In this study, first of all, various methods in the literature were evaluated separately for each of these stages using the simulated test scenarios. Then, a full system of detection was constructed among available solutions which resulted in the best performance in terms of detection. However, although a precision rate as 100% was reached, the recall values stayed low around 25-45%. Finally, a post-processing method was proposed which increased the recall value while keeping the precision at 100%. The proposed post-processing method, which is based on local operations, increased the recall value to 65-95% in all test scenarios.

Extraction of the neutron magnetic form factor from quasielastic 3He→(e→,e') at Q2=0.1-0.6(GeV/c)2

NASA Astrophysics Data System (ADS)

Anderson, B.; Auberbach, L.; Averett, T.; Bertozzi, W.; Black, T.; Calarco, J.; Cardman, L.; Cates, G. D.; Chai, Z. W.; Chen, J. P.; Choi, Seonho; Chudakov, E.; Churchwell, S.; Corrado, G. S.; Crawford, C.; Dale, D.; Deur, A.; Djawotho, P.; Dutta, D.; Finn, J. M.; Gao, H.; Gilman, R.; Glamazdin, A. V.; Glashausser, C.; Glöckle, W.; Golak, J.; Gomez, J.; Gorbenko, V. G.; Hansen, J.-O.; Hersman, F. W.; Higinbotham, D. W.; Holmes, R.; Howell, C. R.; Hughes, E.; Humensky, B.; Incerti, S.; Jager, C. W. De; Jensen, J. S.; Jiang, X.; Jones, C. E.; Jones, M.; Kahl, R.; Kamada, H.; Kievsky, A.; Kominis, I.; Korsch, W.; Kramer, K.; Kumbartzki, G.; Kuss, M.; Lakuriqi, E.; Liang, M.; Liyanage, N.; Lerose, J.; Malov, S.; Margaziotis, D. J.; Martin, J. W.; McCormick, K.; McKeown, R. D.; McIlhany, K.; Meziani, Z.-E.; Michaels, R.; Miller, G. W.; Mitchell, J.; Nanda, S.; Pace, E.; Pavlin, T.; Petratos, G. G.; Pomatsalyuk, R. I.; Pripstein, D.; Prout, D.; Ransome, R. D.; Roblin, Y.; Rvachev, M.; Saha, A.; Salmè, G.; Schnee, M.; Seely, J.; Shin, T.; Slifer, K.; Souder, P. A.; Strauch, S.; Suleiman, R.; Sutter, M.; Tipton, B.; Todor, L.; Viviani, M.; Vlahovic, B.; Watson, J.; Williamson, C. F.; Witała, H.; Wojtsekhowski, B.; Xiong, F.; Xu, W.; Yeh, J.; Żołnierczuk, P.

2007-03-01

We have measured the transverse asymmetry AT' in the quasielastic 3He→(e→,e') process with high precision at Q2 values from 0.1 to 0.6(GeV/c)2. The neutron magnetic form factor GMn was extracted at Q2 values of 0.1 and 0.2(GeV/c)2 using a nonrelativistic Faddeev calculation which includes both final-state interactions (FSI) and meson-exchange currents (MEC). Theoretical uncertainties due to the FSI and MEC effects were constrained with a precision measurement of the spin-dependent asymmetry in the threshold region of 3He→(e→,e'). We also extracted the neutron magnetic form factor GMn at Q2 values of 0.3 to 0.6(GeV/c)2 based on plane wave impulse approximation calculations.

Bedside ketone determination in diabetic children with hyperglycemia and ketosis in the acute care setting.

PubMed

Ham, Melissa R; Okada, Pamela; White, Perrin C

2004-03-01

Diabetic ketoacidosis (DKA) is a serious complication of diabetes mellitus marked by characteristic biochemical derangements. Diagnosis and management involve frequent evaluation of these biochemical parameters. Reliable bedside equivalents for these laboratory studies may help reduce the time to treatment and reduce costs. We evaluated the precision and bias of a bedside serum ketone meter in the acute care setting. Serum ketone results using the Precision Xtra glucometer/ketone meter (Abbott Laboratories, MediSense Products Inc., Bedford, MA, USA) correlated strongly with the Children's Medical Center of Dallas' laboratory values within the meter's value range. Meter ketone values steadily decreased during the treatment of DKA as pH and CO(2) levels increased and acidosis resolved. Therefore, the meter may be useful in monitoring therapy for DKA. This meter may also prove useful in identifying patients at risk for DKA in physicians' offices or at home.

High-precision gravimetric survey in support of lunar laser ranging at Haleakala, Maui, 1976 - 1978

NASA Technical Reports Server (NTRS)

Schenck, B. E.; Laurila, S. H.

1978-01-01

The planning, observations and adjustment of high-precision gravity survey networks established on the islands of Maui and Oahu as part of the geodetic-geophysical program in support of lunar laser ranging at Haleakala, Maui, Hawaii are described. The gravity survey networks include 43 independently measured gravity differences along the gravity calibration line from Kahului Airport to the summit of Mt. Haleakala, together with some key points close to tidal gauges on Maui, and 40 gravity differences within metropolitan Honolulu. The results of the 1976-1978 survey are compared with surveys made in 1961 and in 1964-1965. All final gravity values are given in the system of the international gravity standardization net 1971 (IGSN 71); values are obtained by subtracting 14.57 mgal from the Potsdam value at the gravity base station at the Hickam Air Force Base, Honolulu.

Longitudinal double-spin asymmetry A1p and spin-dependent structure function g1p of the proton at small values of x and Q2

NASA Astrophysics Data System (ADS)

Aghasyan, M.; Alexeev, M. G.; Alexeev, G. D.; Amoroso, A.; Andrieux, V.; Anfimov, N. V.; Anosov, V.; Antoshkin, A.; Augsten, K.; Augustyniak, W.; Austregesilo, A.; Azevedo, C. D. R.; Badełek, B.; Balestra, F.; Ball, M.; Barth, J.; Beck, R.; Bedfer, Y.; Bernhard, J.; Bicker, K.; Bielert, E. R.; Birsa, R.; Bodlak, M.; Bordalo, P.; Bradamante, F.; Bressan, A.; Büchele, M.; Burtsev, V. E.; Capozza, L.; Chang, W.-C.; Chatterjee, C.; Chiosso, M.; Choi, I.; Chumakov, A. G.; Chung, S.-U.; Cicuttin, A.; Crespo, M. L.; Dalla Torre, S.; Dasgupta, S. S.; Dasgupta, S.; Denisov, O. Yu.; Dhara, L.; Donskov, S. V.; Doshita, N.; Dreisbach, Ch.; Dünnweber, W.; Dusaev, R. R.; Dziewiecki, M.; Efremov, A.; Eversheim, P. D.; Faessler, M.; Ferrero, A.; Finger, M.; Finger, M.; Fischer, H.; Franco, C.; Du Fresne von Hohenesche, N.; Friedrich, J. M.; Frolov, V.; Fuchey, E.; Gautheron, F.; Gavrichtchouk, O. P.; Gerassimov, S.; Giarra, J.; Giordano, F.; Gnesi, I.; Gorzellik, M.; Grasso, A.; Gridin, A.; Grosse Perdekamp, M.; Grube, B.; Grussenmeyer, T.; Guskov, A.; Hahne, D.; Hamar, G.; von Harrach, D.; Heinsius, F. H.; Heitz, R.; Herrmann, F.; Horikawa, N.; D'Hose, N.; Hsieh, C.-Y.; Huber, S.; Ishimoto, S.; Ivanov, A.; Iwata, T.; Jary, V.; Joosten, R.; Jörg, P.; Kabuß, E.; Kerbizi, A.; Ketzer, B.; Khaustov, G. V.; Khokhlov, Yu. A.; Kisselev, Yu.; Klein, F.; Koivuniemi, J. H.; Kolosov, V. N.; Kondo, K.; Königsmann, K.; Konorov, I.; Konstantinov, V. F.; Kotzinian, A. M.; Kouznetsov, O. M.; Kral, Z.; Krämer, M.; Kremser, P.; Krinner, F.; Kroumchtein, Z. V.; Kulinich, Y.; Kunne, F.; Kurek, K.; Kurjata, R. P.; Kuznetsov, I. I.; Kveton, A.; Lednev, A. A.; Levchenko, E. A.; Levillain, M.; Levorato, S.; Lian, Y.-S.; Lichtenstadt, J.; Longo, R.; Lyubovitskij, V. E.; Maggiora, A.; Magnon, A.; Makins, N.; Makke, N.; Mallot, G. K.; Mamon, S. A.; Marianski, B.; Martin, A.; Marzec, J.; Matoušek, J.; Matsuda, H.; Matsuda, T.; Meshcheryakov, G. V.; Meyer, M.; Meyer, W.; Mikhailov, Yu. V.; Mikhasenko, M.; Mitrofanov, E.; Mitrofanov, N.; Miyachi, Y.; Moretti, A.; Nagaytsev, A.; Nerling, F.; Neyret, D.; Nový, J.; Nowak, W.-D.; Nukazuka, G.; Nunes, A. S.; Olshevsky, A. G.; Orlov, I.; Ostrick, M.; Panzieri, D.; Parsamyan, B.; Paul, S.; Peng, J.-C.; Pereira, F.; Pešek, M.; Pešková, M.; Peshekhonov, D. V.; Pierre, N.; Platchkov, S.; Pochodzalla, J.; Polyakov, V. A.; Pretz, J.; Quaresma, M.; Quintans, C.; Ramos, S.; Regali, C.; Reicherz, G.; Riedl, C.; Rogacheva, N. S.; Ryabchikov, D. I.; Rybnikov, A.; Rychter, A.; Salac, R.; Samoylenko, V. D.; Sandacz, A.; Santos, C.; Sarkar, S.; Savin, I. A.; Sawada, T.; Sbrizzai, G.; Schiavon, P.; Schmidt, K.; Schmieden, H.; Schönning, K.; Seder, E.; Selyunin, A.; Silva, L.; Sinha, L.; Sirtl, S.; Slunecka, M.; Smolik, J.; Srnka, A.; Steffen, D.; Stolarski, M.; Subrt, O.; Sulc, M.; Suzuki, H.; Szabelski, A.; Szameitat, T.; Sznajder, P.; Tasevsky, M.; Tessaro, S.; Tessarotto, F.; Thiel, A.; Tomsa, J.; Tosello, F.; Tskhay, V.; Uhl, S.; Vasilishin, B. I.; Vauth, A.; Veloso, J.; Vidon, A.; Virius, M.; Wallner, S.; Weisrock, T.; Wilfert, M.; Windmolders, R.; Ter Wolbeek, J.; Zaremba, K.; Zavada, P.; Zavertyaev, M.; Zemlyanichkina, E.; Ziembicki, M.; Compass Collaboration

2018-06-01

We present a precise measurement of the proton longitudinal double-spin asymmetry A1p and the proton spin-dependent structure function g1p at photon virtualities 0.006(GeV / c) 2

Negligible senescence: how will we know it when we see it?

PubMed

Heward, Christopher B

2006-01-01

The recent public claim that "SENS is a practical, foreseeable approach to curing aging" has stirred considerable controversy among bio-gerontologists. Testing this hypothesis will not only require precise definitions for the somewhat subjective terms "practical," "foreseeable," and "curing," it will require a precise definition of the term "aging." To facilitate proper experimental design, this definition must focus on the nature of aging itself, not its causes or consequences. Aging in mammals is a process that begins early in adult life and continues steadily thereafter until death. It is manifested by a decline in the functional capacity (or, more precisely, reserve capacity) of a variety of vital physiologic systems leading to increasing risk of morbidity and mortality over time. Aging, however, cannot be measured by simply monitoring morbidity and/or mortality. Aging can only be measured by monitoring the decline of global functional capacity itself. This, in turn, will require an operational definition of aging expressed as a rate function (i.e., it will have units expressing aging as an overall rate of functional change per unit time). Widespread acceptance of such global indexes of aging rate in animal models and humans will greatly facilitate research activity specifically designed to increase the understanding of aging mechanisms and antiaging interventions.

Comparison of Total Evaporation (TE) and Direct Total Evaporation (DTE) methods in TIMS by using NBL CRMs

NASA Astrophysics Data System (ADS)

Hasözbek, Altug; Mathew, Kattathu; Wegener, Michael

2013-04-01

The total evaporation (TE) is a well-established analytical method for safeguards measurement of uranium and plutonium isotope-amount ratios using the thermal ionization mass spectrometry (TIMS). High accuracy and precision isotopic measurements find many applications in nuclear safeguards, for e.g. assay measurements using isotope dilution mass spectrometry. To achieve high accuracy and precision in TIMS measurements, mass dependent fractionation effects are minimized by either the measurement technique or changes in the hardware components that are used to control sample heating and evaporation process. At NBL, direct total evaporation (DTE) method on the modified MAT261 instrument, uses the data system to read the ion signal intensity and its difference from a pre-determined target intensity, is used to control the incremental step at which the evaporation filament is heated. The feedback and control is achieved by proprietary hardware from SPECTROMAT that uses an analog regulator in the filament power supply with direct feedback of the detector intensity. Compared to traditional TE method on this instrument, DTE provides better precision (relative standard deviation, expressed as a percent) and accuracy (relative difference, expressed as a percent) of 0.05 to 0.08 % for low enriched and high enriched NBL uranium certified reference materials.

Test-particle dynamics in general spherically symmetric black hole spacetimes

NASA Astrophysics Data System (ADS)

De Laurentis, Mariafelicia; Younsi, Ziri; Porth, Oliver; Mizuno, Yosuke; Rezzolla, Luciano

2018-05-01

To date, the most precise tests of general relativity have been achieved through pulsar timing, albeit in the weak-field regime. Since pulsars are some of the most precise and stable "clocks" in the Universe, present observational efforts are focused on detecting pulsars in the vicinity of supermassive black holes (most notably in the Galactic Centre), enabling pulsar timing to be used as an extremely precise probe of strong-field gravity. In this paper, a mathematical framework to describe test-particle dynamics in general black-hole spacetimes is presented and subsequently used to study a binary system comprising a pulsar orbiting a black hole. In particular, taking into account the parameterization of a general spherically symmetric black-hole metric, general analytic expressions for both the advance of the periastron and for the orbital period of a massive test particle are derived. Furthermore, these expressions are applied to four representative cases of solutions arising in both general relativity and in alternative theories of gravity. Finally, this framework is applied to the Galactic center S -stars and four distinct pulsar toy models. It is shown that by adopting a fully general-relativistic description of test-particle motion which is independent of any particular theory of gravity, observations of pulsars can help impose better constraints on alternative theories of gravity than is presently possible.

3D-printed gelatin scaffolds of differing pore geometry modulate hepatocyte function and gene expression.

PubMed

Lewis, Phillip L; Green, Richard M; Shah, Ramille N

2018-03-15

Three dimensional (3D) printing is highly amenable to the fabrication of tissue-engineered organs of a repetitive microstructure such as the liver. The creation of uniform and geometrically repetitive tissue scaffolds can also allow for the control over cellular aggregation and nutrient diffusion. However, the effect of differing geometries, while controlling for pore size, has yet to be investigated in the context of hepatocyte function. In this study, we show the ability to precisely control pore geometry of 3D-printed gelatin scaffolds. An undifferentiated hepatocyte cell line (HUH7) demonstrated high viability and proliferation when seeded on 3D-printed scaffolds of two different geometries. However, hepatocyte specific functions (albumin secretion, CYP activity, and bile transport) increases in more interconnected 3D-printed gelatin cultures compared to a less interconnected geometry and to 2D controls. Additionally, we also illustrate the disparity between gene expression and protein function in simple 2D culture modes, and that recreation of a physiologically mimetic 3D environment is necessary to induce both expression and function of cultured hepatocytes. Three dimensional (3D) printing provides tissue engineers the ability spatially pattern cells and materials in precise geometries, however the biological effects of scaffold geometry on soft tissues such as the liver have not been rigorously investigated. In this manuscript, we describe a method to 3D print gelatin into well-defined repetitive geometries that show clear differences in biological effects on seeded hepatocytes. We show that a relatively simple and widely used biomaterial, such as gelatin, can significantly modulate biological processes when fabricated into specific 3D geometries. Furthermore, this study expands upon past research into hepatocyte aggregation by demonstrating how it can be manipulated to enhance protein function, and how function and expression may not precisely correlate in 2D models. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

SCF-KIT signaling induces endothelin-3 synthesis and secretion: Thereby activates and regulates endothelin-B-receptor for generating temporally- and spatially-precise nitric oxide to modulate SCF- and or KIT-expressing cell functions.

PubMed

Chen, Lei L; Zhu, Jing; Schumacher, Jonathan; Wei, Chongjuan; Ramdas, Latha; Prieto, Victor G; Jimenez, Arnie; Velasco, Marco A; Tripp, Sheryl R; Andtbacka, Robert H I; Gouw, Launce; Rodgers, George M; Zhang, Liansheng; Chan, Benjamin K; Cassidy, Pamela B; Benjamin, Robert S; Leachman, Sancy A; Frazier, Marsha L

2017-01-01

We demonstrate that SCF-KIT signaling induces synthesis and secretion of endothelin-3 (ET3) in human umbilical vein endothelial cells and melanoma cells in vitro, gastrointestinal stromal tumors, human sun-exposed skin, and myenteric plexus of human colon post-fasting in vivo. This is the first report of a physiological mechanism of ET3 induction. Integrating our finding with supporting data from literature leads us to discover a previously unreported pathway of nitric oxide (NO) generation derived from physiological endothelial NO synthase (eNOS) or neuronal NOS (nNOS) activation (referred to as the KIT-ET3-NO pathway). It involves: (1) SCF-expressing cells communicate with neighboring KIT-expressing cells directly or indirectly (cleaved soluble SCF). (2) SCF-KIT signaling induces timely local ET3 synthesis and secretion. (3) ET3 binds to ETBR on both sides of intercellular space. (4) ET3-binding-initiated-ETBR activation increases cytosolic Ca2+, activates cell-specific eNOS or nNOS. (5) Temporally- and spatially-precise NO generation. NO diffuses into neighboring cells, thus acts in both SCF- and KIT-expressing cells. (6) NO modulates diverse cell-specific functions by NO/cGMP pathway, controlling transcriptional factors, or other mechanisms. We demonstrate the critical physiological role of the KIT-ET3-NO pathway in fulfilling high demand (exceeding basal level) of endothelium-dependent NO generation for coping with atherosclerosis, pregnancy, and aging. The KIT-ET3-NO pathway most likely also play critical roles in other cell functions that involve dual requirement of SCF-KIT signaling and NO. New strategies (e.g. enhancing the KIT-ET3-NO pathway) to harness the benefit of endogenous eNOS and nNOS activation and precise NO generation for correcting pathophysiology and restoring functions warrant investigation.

SCF-KIT signaling induces endothelin-3 synthesis and secretion: Thereby activates and regulates endothelin-B-receptor for generating temporally- and spatially-precise nitric oxide to modulate SCF- and or KIT-expressing cell functions

PubMed Central

Zhu, Jing; Schumacher, Jonathan; Wei, Chongjuan; Ramdas, Latha; Prieto, Victor G.; Jimenez, Arnie; Velasco, Marco A.; Tripp, Sheryl R.; Andtbacka, Robert H. I.; Gouw, Launce; Rodgers, George M.; Zhang, Liansheng; Chan, Benjamin K.; Cassidy, Pamela B.; Benjamin, Robert S.; Leachman, Sancy A.; Frazier, Marsha L.

2017-01-01

We demonstrate that SCF-KIT signaling induces synthesis and secretion of endothelin-3 (ET3) in human umbilical vein endothelial cells and melanoma cells in vitro, gastrointestinal stromal tumors, human sun-exposed skin, and myenteric plexus of human colon post-fasting in vivo. This is the first report of a physiological mechanism of ET3 induction. Integrating our finding with supporting data from literature leads us to discover a previously unreported pathway of nitric oxide (NO) generation derived from physiological endothelial NO synthase (eNOS) or neuronal NOS (nNOS) activation (referred to as the KIT-ET3-NO pathway). It involves: (1) SCF-expressing cells communicate with neighboring KIT-expressing cells directly or indirectly (cleaved soluble SCF). (2) SCF-KIT signaling induces timely local ET3 synthesis and secretion. (3) ET3 binds to ETBR on both sides of intercellular space. (4) ET3-binding-initiated-ETBR activation increases cytosolic Ca2+, activates cell-specific eNOS or nNOS. (5) Temporally- and spatially-precise NO generation. NO diffuses into neighboring cells, thus acts in both SCF- and KIT-expressing cells. (6) NO modulates diverse cell-specific functions by NO/cGMP pathway, controlling transcriptional factors, or other mechanisms. We demonstrate the critical physiological role of the KIT-ET3-NO pathway in fulfilling high demand (exceeding basal level) of endothelium-dependent NO generation for coping with atherosclerosis, pregnancy, and aging. The KIT-ET3-NO pathway most likely also play critical roles in other cell functions that involve dual requirement of SCF-KIT signaling and NO. New strategies (e.g. enhancing the KIT-ET3-NO pathway) to harness the benefit of endogenous eNOS and nNOS activation and precise NO generation for correcting pathophysiology and restoring functions warrant investigation. PMID:28880927

Quantitative imaging biomarkers: Effect of sample size and bias on confidence interval coverage.

PubMed

Obuchowski, Nancy A; Bullen, Jennifer

2017-01-01

Introduction Quantitative imaging biomarkers (QIBs) are being increasingly used in medical practice and clinical trials. An essential first step in the adoption of a quantitative imaging biomarker is the characterization of its technical performance, i.e. precision and bias, through one or more performance studies. Then, given the technical performance, a confidence interval for a new patient's true biomarker value can be constructed. Estimating bias and precision can be problematic because rarely are both estimated in the same study, precision studies are usually quite small, and bias cannot be measured when there is no reference standard. Methods A Monte Carlo simulation study was conducted to assess factors affecting nominal coverage of confidence intervals for a new patient's quantitative imaging biomarker measurement and for change in the quantitative imaging biomarker over time. Factors considered include sample size for estimating bias and precision, effect of fixed and non-proportional bias, clustered data, and absence of a reference standard. Results Technical performance studies of a quantitative imaging biomarker should include at least 35 test-retest subjects to estimate precision and 65 cases to estimate bias. Confidence intervals for a new patient's quantitative imaging biomarker measurement constructed under the no-bias assumption provide nominal coverage as long as the fixed bias is <12%. For confidence intervals of the true change over time, linearity must hold and the slope of the regression of the measurements vs. true values should be between 0.95 and 1.05. The regression slope can be assessed adequately as long as fixed multiples of the measurand can be generated. Even small non-proportional bias greatly reduces confidence interval coverage. Multiple lesions in the same subject can be treated as independent when estimating precision. Conclusion Technical performance studies of quantitative imaging biomarkers require moderate sample sizes in order to provide robust estimates of bias and precision for constructing confidence intervals for new patients. Assumptions of linearity and non-proportional bias should be assessed thoroughly.

Water vapor δ17O measurements using an off-axis integrated cavity output spectrometer and seasonal variation in 17O-excess of precipitation in the east-central United States

NASA Astrophysics Data System (ADS)

Tian, C.; Wang, L.; Novick, K. A.

2016-12-01

High-precision triple oxygen isotope analysis can be used to improve our understanding of multiple hydrological and meteorological processes. Recent studies focus on understanding 17O-excess variation of tropical storms, high-latitude snow and ice-core as well as spatial distribution of meteoric water (tap water). The temporal scale of 17O-excess variation in middle-latitude precipitation is needed to better understand which processes control on the 17O-excess variations. This study focused on assessing how the accuracy and precision of vapor δ17O laser spectroscopy measurements depend on vapor concentration, delta range, and averaging-time. Meanwhile, we presented 17O-excess data from two-year, event based precipitation sampling in the east-central United States. A Triple Water Vapor Isotope Analyzer (T-WVIA) was used to evaluate the accuracy and precision of δ2H, δ18O and δ17O measurements. GISP and SLAP2 from IAEA and four working standards were used to evaluate the sensitivity in the three factors. Overall, the accuracy and precision of all isotope measurements were sensitive to concentration, with higher accuracy and precision generally observed under moderate vapor concentrations (i.e., 10000-15000 ppm) for all isotopes. Precision was also sensitive to the range of delta values, though the effect was not as large when compared to the sensitivity to concentration. The precision was much less sensitive to averaging time when compared with concentration and delta range effects. The preliminary results showed that 17O-excess variation was lower in summer (23±17 per meg) than in winter (34±16 per meg), whereas spring values (30±21 per meg) was similar to fall (29±13 per meg). That means kinetic fractionation influences the isotopic composition and 17O-excess in different seasons.

A three dimensional scaffold with precise micro-architecture and surface micro-textures

PubMed Central

Mata, Alvaro; Kim, Eun Jung; Boehm, Cynthia A.; Fleischman, Aaron J.; Muschler, George F.; Roy, Shuvo

2013-01-01

A three-dimensional (3D) structure comprising precisely defined microarchitecture and surface micro-textures, designed to present specific physical cues to cells and tissues, may provide an efficient scaffold in a variety of tissue engineering and regenerative medicine applications. We report a fabrication technique based on microfabrication and soft lithography that permits for the development of 3D scaffolds with both precisely engineered architecture and tailored surface topography. The scaffold fabrication technique consists of three key steps starting with microfabrication of a mold using an epoxy-based photoresist (SU-8), followed by dual-sided molding of a single layer of polydimethylsiloxane (PDMS) using a mechanical jig for precise motion control; and finally, alignment, stacking, and adhesion of multiple PDMS layers to achieve a 3D structure. This technique was used to produce 3D Texture and 3D Smooth PDMS scaffolds, where the surface topography comprised 10 μm-diameter/height posts and smooth surfaces, respectively. The potential utility of the 3D microfabricated scaffolds, and the role of surface topography, were subsequently investigated in vitro with a combined heterogeneous population of adult human stem cells and their resultant progenitor cells, collectively termed connective tissue progenitors (CTPs), under conditions promoting the osteoblastic phenotype. Examination of bone-marrow derived CTPs cultured on the 3D Texture scaffold for 9 days revealed cell growth in three dimensions and increased cell numbers compared to those on the 3D Smooth scaffold. Furthermore, expression of alkaline phosphatase mRNA was higher on the 3D Texture scaffold, while osteocalcin mRNA expression was comparable for both types of scaffolds. PMID:19524292

Analytical parameters of the microplate-based ORAC-pyrogallol red assay.

PubMed

Ortiz, Rocío; Antilén, Mónica; Speisky, Hernán; Aliaga, Margarita E; López-Alarcón, Camilo

2011-01-01

The analytical parameters of the microplate-based oxygen radicals absorbance capacity (ORAC) method using pyrogallol red (PGR) as probe (ORAC-PGR) are presented. In addition, the antioxidant capacity of commercial beverages, such as wines, fruit juices, and iced teas, is estimated. A good linearity of the area under the curve (AUC) versus Trolox concentration plots was obtained [AUC = (845 +/- 110) + (23 +/- 2) [Trolox, microM], R = 0.9961, n = 19]. QC experiments showed better precision and accuracy at the highest Trolox concentration (40 microM) with RSD and REC (recuperation) values of 1.7 and 101.0%, respectively. When red wine was used as sample, the method also showed good linearity [AUC = (787 +/- 77) + (690 +/- 60) [red wine, microL/mL]; R = 0.9926, n = 17], precision and accuracy with RSD values from 1.4 to 8.3%, and REC values that ranged from 89.7 to 103.8%. Additivity assays using solutions containing gallic acid and Trolox (or red wine) showed an additive protection of PGR given by the samples. Red wines showed higher ORAC-PGR values than white wines, while the ORAC-PGR index of fruit juices and iced teas presented a great variability, ranging from 0.6 to 21.6 mM of Trolox equivalents. This variability was also observed for juices of the same fruit, showing the influence of the brand on the ORAC-PGR index. The ORAC-PGR methodology can be applied in a microplate reader with good linearity, precision, and accuracy.

Precise determination of anthropometric dimensions by means of image processing methods for estimating human body segment parameter values.

PubMed

Baca, A

1996-04-01

A method has been developed for the precise determination of anthropometric dimensions from the video images of four different body configurations. High precision is achieved by incorporating techniques for finding the location of object boundaries with sub-pixel accuracy, the implementation of calibration algorithms, and by taking into account the varying distances of the body segments from the recording camera. The system allows automatic segment boundary identification from the video image, if the boundaries are marked on the subject by black ribbons. In connection with the mathematical finite-mass-element segment model of Hatze, body segment parameters (volumes, masses, the three principal moments of inertia, the three local coordinates of the segmental mass centers etc.) can be computed by using the anthropometric data determined videometrically as input data. Compared to other, recently published video-based systems for the estimation of the inertial properties of body segments, the present algorithms reduce errors originating from optical distortions, inaccurate edge-detection procedures, and user-specified upper and lower segment boundaries or threshold levels for the edge-detection. The video-based estimation of human body segment parameters is especially useful in situations where ease of application and rapid availability of comparatively precise parameter values are of importance.

Shooting for the Moon or Flying Too Near the Sun? Crossing the Value Rubicon in Precision Cancer Care.

PubMed

Lawler, Mark; French, Declan; Henderson, Raymond; Aggarwal, Ajay; Sullivan, Richard

In his last two State of the Union addresses, President Barack Obama has focused on the need to deliver innovative solutions to improve human health, through the Precision Medicine Initiative in 2015 and the recently announced Cancer Moonshot in 2016. Precision cancer care has delivered clear patient benefit, but even for high-impact medicines such as imatinib mesylate (Glivec) in chronic myeloid leukaemia, the excitement at the success of this practice-changing clinical intervention has been somewhat tempered by the escalating price of this 'poster child' for precision cancer medicine (PCM). Recent studies on the costs of cancer drugs have revealed significant price differentials, which are a major causative factor behind disparities in the access to new generations of immunological and molecularly targeted agents. In this perspective, we will discuss the benefits of PCM to modern cancer control, but also emphasise how increasing costs are rendering the current approaches to integrating the paradigm of PCM unsustainable. Despite the ever increasing pressure on cancer and health care budgets, innovation will and must continue. Value-based frameworks offer one of the most rational approaches for policymakers committed to improving cancer outcomes through a public health approach. © 2016 S. Karger AG, Basel.

Thermal motion in proteins: Large effects on the time-averaged interaction energies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goethe, Martin, E-mail: martingoethe@ub.edu; Rubi, J. Miguel; Fita, Ignacio

As a consequence of thermal motion, inter-atomic distances in proteins fluctuate strongly around their average values, and hence, also interaction energies (i.e. the pair-potentials evaluated at the fluctuating distances) are not constant in time but exhibit pronounced fluctuations. These fluctuations cause that time-averaged interaction energies do generally not coincide with the energy values obtained by evaluating the pair-potentials at the average distances. More precisely, time-averaged interaction energies behave typically smoother in terms of the average distance than the corresponding pair-potentials. This averaging effect is referred to as the thermal smoothing effect. Here, we estimate the strength of the thermal smoothingmore » effect on the Lennard-Jones pair-potential for globular proteins at ambient conditions using x-ray diffraction and simulation data of a representative set of proteins. For specific atom species, we find a significant smoothing effect where the time-averaged interaction energy of a single atom pair can differ by various tens of cal/mol from the Lennard-Jones potential at the average distance. Importantly, we observe a dependency of the effect on the local environment of the involved atoms. The effect is typically weaker for bulky backbone atoms in beta sheets than for side-chain atoms belonging to other secondary structure on the surface of the protein. The results of this work have important practical implications for protein software relying on free energy expressions. We show that the accuracy of free energy expressions can largely be increased by introducing environment specific Lennard-Jones parameters accounting for the fact that the typical thermal motion of protein atoms depends strongly on their local environment.« less

Thermal motion in proteins: Large effects on the time-averaged interaction energies

NASA Astrophysics Data System (ADS)

Goethe, Martin; Fita, Ignacio; Rubi, J. Miguel

2016-03-01

As a consequence of thermal motion, inter-atomic distances in proteins fluctuate strongly around their average values, and hence, also interaction energies (i.e. the pair-potentials evaluated at the fluctuating distances) are not constant in time but exhibit pronounced fluctuations. These fluctuations cause that time-averaged interaction energies do generally not coincide with the energy values obtained by evaluating the pair-potentials at the average distances. More precisely, time-averaged interaction energies behave typically smoother in terms of the average distance than the corresponding pair-potentials. This averaging effect is referred to as the thermal smoothing effect. Here, we estimate the strength of the thermal smoothing effect on the Lennard-Jones pair-potential for globular proteins at ambient conditions using x-ray diffraction and simulation data of a representative set of proteins. For specific atom species, we find a significant smoothing effect where the time-averaged interaction energy of a single atom pair can differ by various tens of cal/mol from the Lennard-Jones potential at the average distance. Importantly, we observe a dependency of the effect on the local environment of the involved atoms. The effect is typically weaker for bulky backbone atoms in beta sheets than for side-chain atoms belonging to other secondary structure on the surface of the protein. The results of this work have important practical implications for protein software relying on free energy expressions. We show that the accuracy of free energy expressions can largely be increased by introducing environment specific Lennard-Jones parameters accounting for the fact that the typical thermal motion of protein atoms depends strongly on their local environment.

Otolith oxygen isotopes measured by high-precision secondary ion mass spectrometry reflect life history of a yellowfin sole (Limanda aspera).

PubMed

Matta, Mary Elizabeth; Orland, Ian J; Ushikubo, Takayuki; Helser, Thomas E; Black, Bryan A; Valley, John W

2013-03-30

The oxygen isotope ratio (δ(18)O value) of aragonite fish otoliths is dependent on the temperature and the δ(18)O value of the ambient water and can thus reflect the environmental history of a fish. Secondary ion mass spectrometry (SIMS) offers a spatial-resolution advantage over conventional acid-digestion techniques for stable isotope analysis of otoliths, especially given their compact nature. High-precision otolith δ(18)O analysis was conducted with an IMS-1280 ion microprobe to investigate the life history of a yellowfin sole (Limanda aspera), a Bering Sea species known to migrate ontogenetically. The otolith was cut transversely through its core and one half was roasted to eliminate organic contaminants. Values of δ(18)O were measured in 10-µm spots along three transects (two in the roasted half, one in the unroasted half) from the core toward the edge. Otolith annual growth zones were dated using the dendrochronology technique of crossdating. Measured values of δ(18)O ranged from 29.0 to 34.1‰ (relative to Vienna Standard Mean Ocean Water). Ontogenetic migration from shallow to deeper waters was reflected in generally increasing δ(18)O values from age-0 to approximately age-7 and subsequent stabilization after the expected onset of maturity at age-7. Cyclical variations of δ(18)O values within juvenile otolith growth zones, up to 3.9‰ in magnitude, were caused by a combination of seasonal changes in the temperature and the δ(18)O value of the ambient water. The ion microprobe produced a high-precision and high-resolution record of the relative environmental conditions experienced by a yellowfin sole that was consistent with population-level studies of ontogeny. Furthermore, this study represents the first time that crossdating has been used to ensure the dating accuracy of δ(18)O measurements in otoliths. Copyright © 2013 John Wiley & Sons, Ltd.

Systems genetics: a paradigm to improve discovery of candidate genes and mechanisms underlying complex traits.

PubMed

Feltus, F Alex

2014-06-01

Understanding the control of any trait optimally requires the detection of causal genes, gene interaction, and mechanism of action to discover and model the biochemical pathways underlying the expressed phenotype. Functional genomics techniques, including RNA expression profiling via microarray and high-throughput DNA sequencing, allow for the precise genome localization of biological information. Powerful genetic approaches, including quantitative trait locus (QTL) and genome-wide association study mapping, link phenotype with genome positions, yet genetics is less precise in localizing the relevant mechanistic information encoded in DNA. The coupling of salient functional genomic signals with genetically mapped positions is an appealing approach to discover meaningful gene-phenotype relationships. Techniques used to define this genetic-genomic convergence comprise the field of systems genetics. This short review will address an application of systems genetics where RNA profiles are associated with genetically mapped genome positions of individual genes (eQTL mapping) or as gene sets (co-expression network modules). Both approaches can be applied for knowledge independent selection of candidate genes (and possible control mechanisms) underlying complex traits where multiple, likely unlinked, genomic regions might control specific complex traits. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

An anatomically comprehensive atlas of the adult human brain transcriptome

PubMed Central

Guillozet-Bongaarts, Angela L.; Shen, Elaine H.; Ng, Lydia; Miller, Jeremy A.; van de Lagemaat, Louie N.; Smith, Kimberly A.; Ebbert, Amanda; Riley, Zackery L.; Abajian, Chris; Beckmann, Christian F.; Bernard, Amy; Bertagnolli, Darren; Boe, Andrew F.; Cartagena, Preston M.; Chakravarty, M. Mallar; Chapin, Mike; Chong, Jimmy; Dalley, Rachel A.; David Daly, Barry; Dang, Chinh; Datta, Suvro; Dee, Nick; Dolbeare, Tim A.; Faber, Vance; Feng, David; Fowler, David R.; Goldy, Jeff; Gregor, Benjamin W.; Haradon, Zeb; Haynor, David R.; Hohmann, John G.; Horvath, Steve; Howard, Robert E.; Jeromin, Andreas; Jochim, Jayson M.; Kinnunen, Marty; Lau, Christopher; Lazarz, Evan T.; Lee, Changkyu; Lemon, Tracy A.; Li, Ling; Li, Yang; Morris, John A.; Overly, Caroline C.; Parker, Patrick D.; Parry, Sheana E.; Reding, Melissa; Royall, Joshua J.; Schulkin, Jay; Sequeira, Pedro Adolfo; Slaughterbeck, Clifford R.; Smith, Simon C.; Sodt, Andy J.; Sunkin, Susan M.; Swanson, Beryl E.; Vawter, Marquis P.; Williams, Derric; Wohnoutka, Paul; Zielke, H. Ronald; Geschwind, Daniel H.; Hof, Patrick R.; Smith, Stephen M.; Koch, Christof; Grant, Seth G. N.; Jones, Allan R.

2014-01-01

Neuroanatomically precise, genome-wide maps of transcript distributions are critical resources to complement genomic sequence data and to correlate functional and genetic brain architecture. Here we describe the generation and analysis of a transcriptional atlas of the adult human brain, comprising extensive histological analysis and comprehensive microarray profiling of ~900 neuroanatomically precise subdivisions in two individuals. Transcriptional regulation varies enormously by anatomical location, with different regions and their constituent cell types displaying robust molecular signatures that are highly conserved between individuals. Analysis of differential gene expression and gene co-expression relationships demonstrates that brain-wide variation strongly reflects the distributions of major cell classes such as neurons, oligodendrocytes, astrocytes and microglia. Local neighbourhood relationships between fine anatomical subdivisions are associated with discrete neuronal subtypes and genes involved with synaptic transmission. The neocortex displays a relatively homogeneous transcriptional pattern, but with distinct features associated selectively with primary sensorimotor cortices and with enriched frontal lobe expression. Notably, the spatial topography of the neocortex is strongly reflected in its molecular topography— the closer two cortical regions, the more similar their transcriptomes. This freely accessible online data resource forms a high-resolution transcriptional baseline for neurogenetic studies of normal and abnormal human brain function. PMID:22996553

Current knowledge of microRNA-mediated regulation of drug metabolism in humans.

PubMed

Nakano, Masataka; Nakajima, Miki

2018-05-01

Understanding the factors causing inter- and intra-individual differences in drug metabolism potencies is required for the practice of personalized or precision medicine, as well as for the promotion of efficient drug development. The expression of drug-metabolizing enzymes is controlled by transcriptional regulation by nuclear receptors and transcriptional factors, epigenetic regulation, such as DNA methylation and histone acetylation, and post-translational modification. In addition to such regulation mechanisms, recent studies revealed that microRNAs (miRNAs), endogenous ~22-nucleotide non-coding RNAs that regulate gene expression through the translational repression and degradation of mRNAs, significantly contribute to post-transcriptional regulation of drug-metabolizing enzymes. Areas covered: This review summarizes the current knowledge regarding miRNAs-dependent regulation of drug-metabolizing enzymes and transcriptional factors and its physiological and clinical significance. We also describe recent advances in miRNA-dependent regulation research, showing that the presence of pseudogenes, single-nucleotide polymorphisms, and RNA editing affects miRNA targeting. Expert opinion: It is unwavering fact that miRNAs are critical factors causing inter- and intra-individual differences in the expression of drug-metabolizing enzymes. Consideration of miRNA-dependent regulation would be a helpful tool for optimizing personalized and precision medicine.

[Precision and accuracy of a dental spectrophotometer in gingival color measurement of maxillary anterior gingival].

PubMed

Du, Yang; Tan, Jian-guo; Chen, Li; Wang, Fang-ping; Tan, Yao; Zhou, Jian-feng

2012-08-18

To explore a gingival shade matching method and to evaluate the precision and accuracy of a dental spectrophotometer modified to be used in gingival color measurement. Crystaleye, a dental spectrophotometer (Olympus, Tokyo, Japan) with a custom shading cover was tested. For precision assessment, two experienced experimenters measured anterior maxillary incisors five times for each tooth. A total of 20 healthy gingival sites (attached gingiva, free gingiva and medial gingival papilla in anterior maxillary region) were measured,the Commission Internationale de I' Eclairage (CIE) color parameters (CIE L*a*b*) of which were analyzed using the supporting software. For accuracy assessment, a rectangular area of approximately 3 mm×3 mm was chosen in the attached gingival portion for spectral analysis. PR715 (SpectraScan;Photo Research Inc.,California, USA), a spectroradiometer, was utilized as standard control. Average color differences (ΔE) between the values from PR715 and Crystaleye were calculated. In precision assessment,ΔL* between the values in all the test sites and average values were from(0.28±0.16)to(0.78±0.57), with Δa*and Δb* from(0.28±0.15)to (0.87±0.65),from(0.19±0.09)to( 0.58±0.78), respectively. Average ΔE between values in all test sites and average values were from (0.62 ± 0.17) to (1.25 ± 0.98) CIELAB units, with a total average ΔE(0.90 ± 0.18). In accuracy assessment, ΔL* with control device were from(0.58±0.50)to(2.22±1.89),with Δa*and Δb* from(1.03±0.67)to(2.99±1.32),from(0.68±0.78)to(1.26±0.83), respectively. Average ΔE with the control device were from (2.44±0.82) to (3.51±1.03) CIELAB units, with a total average ΔE (2.96 ± 1.08). With appropriate modification, Crystaleye, the spectrophotometer, has demonstrated relative minor color variations that can be useful in gingival color measurement.

A Dynamic Precision Evaluation Method for the Star Sensor in the Stellar-Inertial Navigation System.

PubMed

Lu, Jiazhen; Lei, Chaohua; Yang, Yanqiang

2017-06-28

Integrating the advantages of INS (inertial navigation system) and the star sensor, the stellar-inertial navigation system has been used for a wide variety of applications. The star sensor is a high-precision attitude measurement instrument; therefore, determining how to validate its accuracy is critical in guaranteeing its practical precision. The dynamic precision evaluation of the star sensor is more difficult than a static precision evaluation because of dynamic reference values and other impacts. This paper proposes a dynamic precision verification method of star sensor with the aid of inertial navigation device to realize real-time attitude accuracy measurement. Based on the gold-standard reference generated by the star simulator, the altitude and azimuth angle errors of the star sensor are calculated for evaluation criteria. With the goal of diminishing the impacts of factors such as the sensors' drift and devices, the innovative aspect of this method is to employ static accuracy for comparison. If the dynamic results are as good as the static results, which have accuracy comparable to the single star sensor's precision, the practical precision of the star sensor is sufficiently high to meet the requirements of the system specification. The experiments demonstrate the feasibility and effectiveness of the proposed method.

Multi-Attribute Sequential Search

ERIC Educational Resources Information Center

Bearden, J. Neil; Connolly, Terry

2007-01-01

This article describes empirical and theoretical results from two multi-attribute sequential search tasks. In both tasks, the DM sequentially encounters options described by two attributes and must pay to learn the values of the attributes. In the "continuous" version of the task the DM learns the precise numerical value of an attribute when she…

78 FR 6066 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-29

... to conduct a pilot study to test the Elwha River Dam Removal and Floodplain Restoration Ecosystem... and nonuse values provided by habitat restoration. A study of the value of ecological restoration is... reservoir. The ability to link results of the study to precise measures of ecosystem changes will be useful...

Improved accuracy and precision in δ15 NAIR measurements of explosives, urea, and inorganic nitrates by elemental analyzer/isotope ratio mass spectrometry using thermal decomposition.

PubMed

Lott, Michael J; Howa, John D; Chesson, Lesley A; Ehleringer, James R

2015-08-15

Elemental analyzer systems generate N(2) and CO(2) for elemental composition and isotope ratio measurements. As quantitative conversion of nitrogen in some materials (i.e., nitrate salts and nitro-organic compounds) is difficult, this study tests a recently published method - thermal decomposition without the addition of O(2) - for the analysis of these materials. Elemental analyzer/isotope ratio mass spectrometry (EA/IRMS) was used to compare the traditional combustion method (CM) and the thermal decomposition method (TDM), where additional O(2) is eliminated from the reaction. The comparisons used organic and inorganic materials with oxidized and/or reduced nitrogen and included ureas, nitrate salts, ammonium sulfate, nitro esters, and nitramines. Previous TDM applications were limited to nitrate salts and ammonium sulfate. The measurement precision and accuracy were compared to determine the effectiveness of converting materials containing different fractions of oxidized nitrogen into N(2). The δ(13) C(VPDB) values were not meaningfully different when measured via CM or TDM, allowing for the analysis of multiple elements in one sample. For materials containing oxidized nitrogen, (15) N measurements made using thermal decomposition were more precise than those made using combustion. The precision was similar between the methods for materials containing reduced nitrogen. The %N values were closer to theoretical when measured by TDM than by CM. The δ(15) N(AIR) values of purchased nitrate salts and ureas were nearer to the known values when analyzed using thermal decomposition than using combustion. The thermal decomposition method addresses insufficient recovery of nitrogen during elemental analysis in a variety of organic and inorganic materials. Its implementation requires relatively few changes to the elemental analyzer. Using TDM, it is possible to directly calibrate certain organic materials to international nitrate isotope reference materials without off-line preparation. Copyright © 2015 John Wiley & Sons, Ltd.

Weak value controversy

NASA Astrophysics Data System (ADS)

Vaidman, L.

2017-10-01

Recent controversy regarding the meaning and usefulness of weak values is reviewed. It is argued that in spite of recent statistical arguments by Ferrie and Combes, experiments with anomalous weak values provide useful amplification techniques for precision measurements of small effects in many realistic situations. The statistical nature of weak values is questioned. Although measuring weak values requires an ensemble, it is argued that the weak value, similarly to an eigenvalue, is a property of a single pre- and post-selected quantum system. This article is part of the themed issue `Second quantum revolution: foundational questions'.

Shaping skeletal growth by modular regulatory elements in the Bmp5 gene.

PubMed

Guenther, Catherine; Pantalena-Filho, Luiz; Kingsley, David M

2008-12-01

Cartilage and bone are formed into a remarkable range of shapes and sizes that underlie many anatomical adaptations to different lifestyles in vertebrates. Although the morphological blueprints for individual cartilage and bony structures must somehow be encoded in the genome, we currently know little about the detailed genomic mechanisms that direct precise growth patterns for particular bones. We have carried out large-scale enhancer surveys to identify the regulatory architecture controlling developmental expression of the mouse Bmp5 gene, which encodes a secreted signaling molecule required for normal morphology of specific skeletal features. Although Bmp5 is expressed in many skeletal precursors, different enhancers control expression in individual bones. Remarkably, we show here that different enhancers also exist for highly restricted spatial subdomains along the surface of individual skeletal structures, including ribs and nasal cartilages. Transgenic, null, and regulatory mutations confirm that these anatomy-specific sequences are sufficient to trigger local changes in skeletal morphology and are required for establishing normal growth rates on separate bone surfaces. Our findings suggest that individual bones are composite structures whose detailed growth patterns are built from many smaller lineage and gene expression domains. Individual enhancers in BMP genes provide a genomic mechanism for controlling precise growth domains in particular cartilages and bones, making it possible to separately regulate skeletal anatomy at highly specific locations in the body.

Structure-function relationships between aldolase C/zebrin II expression and complex spike synchrony in the cerebellum.

PubMed

Tsutsumi, Shinichiro; Yamazaki, Maya; Miyazaki, Taisuke; Watanabe, Masahiko; Sakimura, Kenji; Kano, Masanobu; Kitamura, Kazuo

2015-01-14

Simple and regular anatomical structure is a hallmark of the cerebellar cortex. Parasagittally arrayed alternate expression of aldolase C/zebrin II in Purkinje cells (PCs) has been extensively studied, but surprisingly little is known about its functional significance. Here we found a precise structure-function relationship between aldolase C expression and synchrony of PC complex spike activities that reflect climbing fiber inputs to PCs. We performed two-photon calcium imaging in transgenic mice in which aldolase C compartments can be visualized in vivo, and identified highly synchronous complex spike activities among aldolase C-positive or aldolase C-negative PCs, but not across these populations. The boundary of aldolase C compartments corresponded to that of complex spike synchrony at single-cell resolution. Sensory stimulation evoked aldolase C compartment-specific complex spike responses and synchrony. This result further revealed the structure-function segregation. In awake animals, complex spike synchrony both within and between PC populations across the aldolase C boundary were enhanced in response to sensory stimuli, in a way that two functionally distinct PC ensembles are coactivated. These results suggest that PC populations characterized by aldolase C expression precisely represent distinct functional units of the cerebellar cortex, and these functional units can cooperate to process sensory information in awake animals. Copyright © 2015 the authors 0270-6474/15/350843-10$15.00/0.

Precision Penning Trap Mass Spectrometry of ^32S, ^84,86Kr and ^129,132Xe

NASA Astrophysics Data System (ADS)

Redshaw, Matthew

2005-05-01

Using a phase coherent technique to measure the cyclotron frequency of single ions in a Penning trap [1], we have performed mass measurements on ^32S and the two most abundant krypton and xenon isotopes ^84Kr, ^86Kr, ^ 129Xe and ^132Xe, to relative precisions of 0.1 ppb. This is a factor of ˜10-100 improvement in precision over current values [2]. [1] M.P. Bradley, J.V. Porto, S. Rainville, J.K. Thompson, and D.E. Pritchard, PRL 83, 4510 (1999). [2] G. Audi, A.H. Wapstra, and C. Thibault, Nucl Phys A729, 337 (2003).

[Value of the space perception test for evaluation of the aptitude for precision work in geodesy].

PubMed

Remlein-Mozolewska, G

1982-01-01

The visual spatial localization ability of geodesy and cartography - employers and of the pupils trained for the mentioned profession has been examined. The examination has been based on work duration and the time of its performance. A correlation between the localization ability and the precision of the hand - movements required in everyday work has been proven. The better the movement precision, the more efficient the visual spatial localization. The length of work has not been significant. The test concerned appeared to be highly useful in geodesy for qualifying workers for the posts requiring good hands efficiency.

[Medical big data and precision medicine: prospects of epidemiology].

PubMed

Song, J; Hu, Y H

2016-08-10

Since the development of high-throughput technology, electronic medical record system and big data technology, the value of medical data has caused more attention. On the other hand, the proposal of Precision Medicine Initiative opens up the prospect for medical big data. As a Tool-related Discipline, Epidemiology is, focusing on exploitation the resources of existing big data and promoting the integration of translational research and knowledge to completely unlocking the "black box" of exposure-disease continuum. It also tries to accelerating the realization of the ultimate goal on precision medicine. The overall purpose, however is to translate the evidence from scientific research to improve the health of the people.

The effect of technical replicate (repeats) on Nix Pro Color Sensor™ measurement precision for meat: A case-study on aged beef colour stability.

PubMed

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.

High Precision Prediction of Functional Sites in Protein Structures

PubMed Central

Buturovic, Ljubomir; Wong, Mike; Tang, Grace W.; Altman, Russ B.; Petkovic, Dragutin

2014-01-01

We address the problem of assigning biological function to solved protein structures. Computational tools play a critical role in identifying potential active sites and informing screening decisions for further lab analysis. A critical parameter in the practical application of computational methods is the precision, or positive predictive value. Precision measures the level of confidence the user should have in a particular computed functional assignment. Low precision annotations lead to futile laboratory investigations and waste scarce research resources. In this paper we describe an advanced version of the protein function annotation system FEATURE, which achieved 99% precision and average recall of 95% across 20 representative functional sites. The system uses a Support Vector Machine classifier operating on the microenvironment of physicochemical features around an amino acid. We also compared performance of our method with state-of-the-art sequence-level annotator Pfam in terms of precision, recall and localization. To our knowledge, no other functional site annotator has been rigorously evaluated against these key criteria. The software and predictive models are incorporated into the WebFEATURE service at http://feature.stanford.edu/wf4.0-beta. PMID:24632601

Advances in the Metrology of Absolute Value Assignments to Isotopic Reference Materials: Consequences from the Avogadro Project

NASA Astrophysics Data System (ADS)

Vocke, Robert; Rabb, Savelas

2015-04-01

All isotope amount ratios (hereafter referred to as isotope ratios) produced and measured on any mass spectrometer are biased. This unfortunate situation results mainly from the physical processes in the source area where ions are produced. Because the ionized atoms in poly-isotopic elements have different masses, such processes are typically mass dependent and lead to what is commonly referred to as mass fractionation (for thermal ionization and electron impact sources) and mass bias (for inductively coupled plasma sources.) This biasing process produces a measured isotope ratio that is either larger or smaller than the "true" ratio in the sample. This has led to the development of numerous fractionation "laws" that seek to correct for these effects, many of which are not based on the physical processes giving rise to the biases. The search for tighter and reproducible precisions has led to two isotope ratio measurement systems that exist side-by-side. One still seeks to measure "absolute" isotope ratios while the other utilizes an artifact based measurement system called a delta-scale. The common element between these two measurement systems is the utilization of isotope reference materials (iRMs). These iRMs are used to validate a fractionation "law" in the former case and function as a scale anchor in the latter. Many value assignments of iRMs are based on "best measurements" by the original groups producing the reference material, a not entirely satisfactory approach. Other iRMs, with absolute isotope ratio values, have been produced by calibrated measurements following the Atomic Weight approach (AW) pioneered by NBS nearly 50 years ago. Unfortunately, the AW is not capable of calibrating the new generation of iRMs to sufficient precision. So how do we get iRMs with isotope ratios of sufficient precision and without bias? Such a focus is not to denigrate the extremely precise delta-scale measurements presently being made on non-traditional and tradition stable isotope systems. But even absolute isotope ratio measurements have an important role to play in delta-scale schemes. Highly precise and unbiased measurements of the artifact anchor for any scale facilitates the replacement of that scale's anchor once the initial supply of the iRM is exhausted. Absolute isotope ratio measurements of artifacts at the positive and negative extremes of a delta-scale will allow the appropriate assignment of delta-values to these normalizing iRMs, thereby minimizing any scale contractions or expansions to either side of the anchor artifact. And finally, absolute values for critical iRMs with also allow delta-scale results to be used in other scientific disciplines that employ other units of measure. Precise absolute isotope ratios of Si has been one of the consequences of the Avogadro Project (an international effort to replace the original kilogram artifact with a natural constant, the Planck constant.) We will present the results of applying such measurements to the principal iRMs for the Si isotope system (SRM 990, Big Batch and Diatomite) and its consequences for their delta-Si29 and delta-Si30 values.

Localization of nucleolar chromatin by immunocytochemistry and in situ hybridization at the electron microscopic level.

PubMed

Thiry, M; Scheer, U; Goessens, G

1991-01-01

Nucleoli are the morphological expression of the activity of a defined set of chromosomal segments bearing rRNA genes. The topological distribution and composition of the intranucleolar chromatin as well as the definition of nucleolar structures in which enzymes of the rDNA transcription machinery reside have been investigated in mammalian cells by various immunogold labelling approaches at the ultrastructural level. The precise intranucleolar location of rRNA genes has been further specified by electron microscopic in situ hybridization with a non-autoradiographic procedure. Our results indicate that the fibrillar centers are the sole nucleolar structures where rDNA, core histones, RNA polymerase I and DNA topoisomerase I are located together. Taking into account the potential value and limitations of immunoelectron microscopic techniques, we propose that transcription of the rRNA genes takes place within the confines of the fibrillar centers, probably close to the boundary regions to the surrounding dense fibrillar component.

[Diagnostic value of STAT6 immunohistochemistry in solitary fibrous tumor/meningeal hemangiopericytoma].

PubMed

Zhang, Xialing; Cheng, Haixia; Bao, Yun; Tang, Feng; Wang, Yin

2016-02-01

To investigate the diagnostic role of STAT6 immunohistochemistry in solitary fibrous tumors (SFT)/meningeal hemangiopericytomas (HPC). Evaluated the expression of STAT6, vimentin, CD34, EMA, PR, S-100, CD56, GFAP and Ki-67 in a cohort of 37 SFT/meningeal HPC, 30 meningiomas and 30 schwannomas by immunohistochemistry staining. All SFT/meningeal HPC demonstrated nuclear positivity for STAT6, and the proportion of positive tumor cells ranged from 60% to 95%, with no significant difference cases.Vimentin was strongly positive in all cases. CD34, EMA and PR positivity was found in 32 cases, 1 case and 4 cases, respectively.S-100 protein, CD56 and GFAP were negative; Ki-67 labeling index was 1%-8%. However, the meningiomas and schwannomas were negative for STAT6. STAT6 is a relatively specific biomarker for SFT/meningeal HPC, and may be used in the diagnosis and differential diagnosis of SFT/meningeal HPC, especially for the atypical cases, and allows the precise pathologic diagnosis of SFT/meningeal HPC.

Determination of alkenylbenzenes and related flavour compounds in food samples by on-column preconcentration-capillary liquid chromatography.

PubMed

Avila, Mónica; Zougagh, Mohammed; Escarpa, Alberto; Ríos, Angel

2009-10-23

A new, simple and versatile method is presented for the determination of different concentration levels of alkenylbenzenes (eugenol, isoeugenol, eugenol methyl ether, myristicin, anethole and estragole) and the related flavour compounds (coumarin and pulegone) in food samples. The method involves the use of a stationary phase (capillary column) for the enrichment with appropriate elution. After the sample had completely passed through the capillary column the eluent was changed and the separation/detection was achieved. Excellent linearity was obtained under the proposed conditions for a direct determination method and a method including on-line preconcentration. The limits of detection were in the ranges 97-148 and 9.5-14.2 ng/mL, respectively. Evidence for a matrix effect was not found and recoveries between 92 and 110% were obtained. The precision of the method, expressed as relative standard deviation values, was below 5% in all cases. The applicability of this methodology was tested by analyzing synthetic and real food samples.

High-precision simulation of the height distribution for the KPZ equation

NASA Astrophysics Data System (ADS)

Hartmann, Alexander K.; Le Doussal, Pierre; Majumdar, Satya N.; Rosso, Alberto; Schehr, Gregory

2018-03-01

The one-point distribution of the height for the continuum Kardar-Parisi-Zhang (KPZ) equation is determined numerically using the mapping to the directed polymer in a random potential at high temperature. Using an importance sampling approach, the distribution is obtained over a large range of values, down to a probability density as small as 10-1000 in the tails. Both short and long times are investigated and compared with recent analytical predictions for the large-deviation forms of the probability of rare fluctuations. At short times the agreement with the analytical expression is spectacular. We observe that the far left and right tails, with exponents 5/2 and 3/2, respectively, are preserved also in the region of long times. We present some evidence for the predicted non-trivial crossover in the left tail from the 5/2 tail exponent to the cubic tail of the Tracy-Widom distribution, although the details of the full scaling form remain beyond reach.

Anomalous magnetic moment of the muon: A hybrid approach

NASA Astrophysics Data System (ADS)

Dominguez, C. A.; Horch, H.; Jäger, B.; Nasrallah, N. F.; Schilcher, K.; Spiesberger, H.; Wittig, H.

2017-10-01

A new QCD sum rule determination of the leading order hadronic vacuum polarization contribution to the anomalous magnetic moment of the muon, aμhvp, is proposed. This approach combines data on e+e- annihilation into hadrons, perturbative QCD and lattice QCD results for the first derivative of the electromagnetic current correlator at zero momentum transfer, ΠEM'(0 ). The idea is based on the observation that, in the relevant kinematic domain, the integration kernel K (s ), entering the formula relating aμhvp to e+e- annihilation data, behaves like 1 /s times a very smooth function of s , the squared energy. We find an expression for aμ in terms of ΠEM'(0 ), which can be calculated in lattice QCD. Using recent lattice results we find a good approximation for aμhvp, but the precision is not yet sufficient to resolve the discrepancy between the R (s ) data-based results and the experimentally measured value.

Reconcile Planck-scale discreteness and the Lorentz-Fitzgerald contraction

NASA Astrophysics Data System (ADS)

Rovelli, Carlo; Speziale, Simone

2003-03-01

A Planck-scale minimal observable length appears in many approaches to quantum gravity. It is sometimes argued that this minimal length might conflict with Lorentz invariance, because a boosted observer can see the minimal length further Lorentz contracted. We show that this is not the case within loop quantum gravity. In loop quantum gravity the minimal length (more precisely, minimal area) does not appear as a fixed property of geometry, but rather as the minimal (nonzero) eigenvalue of a quantum observable. The boosted observer can see the same observable spectrum, with the same minimal area. What changes continuously in the boost transformation is not the value of the minimal length: it is the probability distribution of seeing one or the other of the discrete eigenvalues of the area. We discuss several difficulties associated with boosts and area measurement in quantum gravity. We compute the transformation of the area operator under a local boost, propose an explicit expression for the generator of local boosts, and give the conditions under which its action is unitary.

Generalized Arcsine Laws for Fractional Brownian Motion.

PubMed

Sadhu, Tridib; Delorme, Mathieu; Wiese, Kay Jörg

2018-01-26

The three arcsine laws for Brownian motion are a cornerstone of extreme-value statistics. For a Brownian B_{t} starting from the origin, and evolving during time T, one considers the following three observables: (i) the duration t_{+} the process is positive, (ii) the time t_{last} the process last visits the origin, and (iii) the time t_{max} when it achieves its maximum (or minimum). All three observables have the same cumulative probability distribution expressed as an arcsine function, thus the name arcsine laws. We show how these laws change for fractional Brownian motion X_{t}, a non-Markovian Gaussian process indexed by the Hurst exponent H. It generalizes standard Brownian motion (i.e., H=1/2). We obtain the three probabilities using a perturbative expansion in ϵ=H-1/2. While all three probabilities are different, this distinction can only be made at second order in ϵ. Our results are confirmed to high precision by extensive numerical simulations.

Genome-wide analytical approaches for reverse metabolic engineering of industrially relevant phenotypes in yeast

PubMed Central

Oud, Bart; Maris, Antonius J A; Daran, Jean-Marc; Pronk, Jack T

2012-01-01

Successful reverse engineering of mutants that have been obtained by nontargeted strain improvement has long presented a major challenge in yeast biotechnology. This paper reviews the use of genome-wide approaches for analysis of Saccharomyces cerevisiae strains originating from evolutionary engineering or random mutagenesis. On the basis of an evaluation of the strengths and weaknesses of different methods, we conclude that for the initial identification of relevant genetic changes, whole genome sequencing is superior to other analytical techniques, such as transcriptome, metabolome, proteome, or array-based genome analysis. Key advantages of this technique over gene expression analysis include the independency of genome sequences on experimental context and the possibility to directly and precisely reproduce the identified changes in naive strains. The predictive value of genome-wide analysis of strains with industrially relevant characteristics can be further improved by classical genetics or simultaneous analysis of strains derived from parallel, independent strain improvement lineages. PMID:22152095

Evaluating Symptom Expression as a Function of a Posttraumatic Stress Disorder Severity

PubMed Central

Palm, Kathleen M.; Strong, David R.; MacPherson, Laura

2009-01-01

Little is known about the relative severity or typical sequence of Diagnostic and Statistical Manual (DSM-IV) symptoms of posttraumatic stress disorder (PTSD). Using data from the National Comorbidity Study – Replication (Kessler et al., 2004), the current study used a logistic item response model to assess the degree to which DSM-IV symptoms combine to define a primary construct underlying PTSD, to identify which symptoms are associated with greater severity of PTSD, and to determine whether the symptoms and symptom patterns are influenced by gender. Results suggested that PTSD symptoms can be combined to assess a single dimension of PTSD severity, providing support for a continuum of symptom severity. However, several DSM-IV symptoms provided overlapping information, potentially reducing the effectiveness of these symptoms in describing a broad range of PTSD. More precise assessment of PTSD severity may help improve the descriptive value of PTSD measures relationship to continuous measures of treatment outcomes, and ultimately inform more effective treatments. PMID:18434083

Dissecting the indirect effects caused by vaccines into the basic elements

PubMed Central

Scarbrough Lefebvre, Carla D; Terlinden, Augustin; Standaert, Baudouin

2015-01-01

Vaccination directly protects vaccinated individuals, but it also has the potential for indirectly protecting the unvaccinated in a population (herd protection). Unintended negative consequences such as the re-manifestation of infection, mainly expressed as age shifts, result from vaccination programs as well. We discuss the necessary conditions for achieving optimal herd protection (i.e., high quality vaccine-induced immunity, substantial effect on the force of infection, and appropriate vaccine coverage and distribution), as well as the conditions under which age shifts are likely to occur. We show examples to illustrate these effects. Substantial ambiguity in observing and quantifying these indirect vaccine effects makes accurate evaluation troublesome even though the nature of these outcomes may be critical for accurate assessment of the economic value when decision makers are evaluating a novel vaccine for introduction into a particular region or population group. More investigation is needed to identify and develop successful assessment methodologies for precisely analyzing these outcomes. PMID:26186100

Genome-wide analytical approaches for reverse metabolic engineering of industrially relevant phenotypes in yeast.

PubMed

Oud, Bart; van Maris, Antonius J A; Daran, Jean-Marc; Pronk, Jack T

2012-03-01

Successful reverse engineering of mutants that have been obtained by nontargeted strain improvement has long presented a major challenge in yeast biotechnology. This paper reviews the use of genome-wide approaches for analysis of Saccharomyces cerevisiae strains originating from evolutionary engineering or random mutagenesis. On the basis of an evaluation of the strengths and weaknesses of different methods, we conclude that for the initial identification of relevant genetic changes, whole genome sequencing is superior to other analytical techniques, such as transcriptome, metabolome, proteome, or array-based genome analysis. Key advantages of this technique over gene expression analysis include the independency of genome sequences on experimental context and the possibility to directly and precisely reproduce the identified changes in naive strains. The predictive value of genome-wide analysis of strains with industrially relevant characteristics can be further improved by classical genetics or simultaneous analysis of strains derived from parallel, independent strain improvement lineages. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

Limits of detection and decision. Part 3

NASA Astrophysics Data System (ADS)

Voigtman, E.

2008-02-01

It has been shown that the MARLAP (Multi-Agency Radiological Laboratory Analytical Protocols) for estimating the Currie detection limit, which is based on 'critical values of the non-centrality parameter of the non-central t distribution', is intrinsically biased, even if no calibration curve or regression is used. This completed the refutation of the method, begun in Part 2. With the field cleared of obstructions, the true theory underlying Currie's limits of decision, detection and quantification, as they apply in a simple linear chemical measurement system (CMS) having heteroscedastic, Gaussian measurement noise and using weighted least squares (WLS) processing, was then derived. Extensive Monte Carlo simulations were performed, on 900 million independent calibration curves, for linear, "hockey stick" and quadratic noise precision models (NPMs). With errorless NPM parameters, all the simulation results were found to be in excellent agreement with the derived theoretical expressions. Even with as much as 30% noise on all of the relevant NPM parameters, the worst absolute errors in rates of false positives and false negatives, was only 0.3%.

Extending the excluded volume for percolation threshold estimates in polydisperse systems: The binary disk system

DOE PAGES

Meeks, Kelsey; Pantoya, Michelle L.; Green, Micah; ...

2017-06-01

For dispersions containing a single type of particle, it has been observed that the onset of percolation coincides with a critical value of volume fraction. When the volume fraction is calculated based on excluded volume, this critical percolation threshold is nearly invariant to particle shape. The critical threshold has been calculated to high precision for simple geometries using Monte Carlo simulations, but this method is slow at best, and infeasible for complex geometries. This article explores an analytical approach to the prediction of percolation threshold in polydisperse mixtures. Specifically, this paper suggests an extension of the concept of excluded volume,more » and applies that extension to the 2D binary disk system. The simple analytical expression obtained is compared to Monte Carlo results from the literature. In conclusion, the result may be computed extremely rapidly and matches key parameters closely enough to be useful for composite material design.« less

Two-pass imputation algorithm for missing value estimation in gene expression time series.

PubMed

Tsiporkova, Elena; Boeva, Veselka

2007-10-01

Gene expression microarray experiments frequently generate datasets with multiple values missing. However, most of the analysis, mining, and classification methods for gene expression data require a complete matrix of gene array values. Therefore, the accurate estimation of missing values in such datasets has been recognized as an important issue, and several imputation algorithms have already been proposed to the biological community. Most of these approaches, however, are not particularly suitable for time series expression profiles. In view of this, we propose a novel imputation algorithm, which is specially suited for the estimation of missing values in gene expression time series data. The algorithm utilizes Dynamic Time Warping (DTW) distance in order to measure the similarity between time expression profiles, and subsequently selects for each gene expression profile with missing values a dedicated set of candidate profiles for estimation. Three different DTW-based imputation (DTWimpute) algorithms have been considered: position-wise, neighborhood-wise, and two-pass imputation. These have initially been prototyped in Perl, and their accuracy has been evaluated on yeast expression time series data using several different parameter settings. The experiments have shown that the two-pass algorithm consistently outperforms, in particular for datasets with a higher level of missing entries, the neighborhood-wise and the position-wise algorithms. The performance of the two-pass DTWimpute algorithm has further been benchmarked against the weighted K-Nearest Neighbors algorithm, which is widely used in the biological community; the former algorithm has appeared superior to the latter one. Motivated by these findings, indicating clearly the added value of the DTW techniques for missing value estimation in time series data, we have built an optimized C++ implementation of the two-pass DTWimpute algorithm. The software also provides for a choice between three different initial rough imputation methods.

Elastase-Induced Parenchymal Disruption and Airway Hyper Responsiveness in Mouse Precision Cut Lung Slices: Toward an Ex vivo COPD Model.

PubMed

Van Dijk, Eline M; Culha, Sule; Menzen, Mark H; Bidan, Cécile M; Gosens, Reinoud

2016-01-01

Background: COPD is a progressive lung disease characterized by emphysema and enhanced bronchoconstriction. Current treatments focused on bronchodilation can delay disease progression to some extent, but recovery or normalization of loss of lung function is impossible. Therefore, novel therapeutic targets are needed. The importance of the parenchyma in airway narrowing is increasingly recognized. In COPD, the parenchyma and extracellular matrix are altered, possibly affecting airway mechanics and enhancing bronchoconstriction. Our aim was to set up a comprehensive ex vivo Precision Cut Lung Slice (PCLS) model with a pathophysiology resembling that of COPD and integrate multiple readouts in order to study the relationship between parenchyma, airway functionality, and lung repair processes. Methods: Lungs of C57Bl/6J mice were sliced and treated ex vivo with elastase (2.5 μg/ml) or H 2 O 2 (200 μM) for 16 h. Following treatment, parenchymal structure, airway narrowing, and gene expression levels of alveolar Type I and II cell repair were assessed. Results: Following elastase, but not H 2 O 2 treatment, slices showed a significant increase in mean linear intercept (Lmi), reflective of emphysema. Only elastase-treated slices showed disorganization of elastin and collagen fibers. In addition, elastase treatment lowered both alveolar Type I and II marker expression, whereas H 2 O 2 stimulation lowered alveolar Type I marker expression only. Furthermore, elastase-treated slices showed enhanced methacholine-induced airway narrowing as reflected by increased pEC50 (5.87 at basal vs. 6.50 after elastase treatment) and Emax values (47.96 vs. 67.30%), and impaired chloroquine-induced airway opening. The increase in pEC50 correlated with an increase in mean Lmi. Conclusion: Using this model, we show that structural disruption of elastin fibers leads to impaired alveolar repair, disruption of the parenchymal compartment, and altered airway biomechanics, enhancing airway contraction. This finding may have implications for COPD, as the amount of elastin fiber and parenchymal tissue disruption is associated with disease severity. Therefore, we suggest that PCLS can be used to model certain aspects of COPD pathophysiology and that the parenchymal tissue damage observed in COPD contributes to lung function decline by disrupting airway biomechanics. Targeting the parenchymal compartment may therefore be a promising therapeutic target in the treatment of COPD.

The Precise Measurement of Vapor-Liquid Equilibrium Properties of the CO2/Isopentane Binary Mixture, and Fitted Parameters for a Helmholtz Energy Mixture Model

NASA Astrophysics Data System (ADS)

Miyamoto, H.; Shoji, Y.; Akasaka, R.; Lemmon, E. W.

2017-10-01

Natural working fluid mixtures, including combinations of CO2, hydrocarbons, water, and ammonia, are expected to have applications in energy conversion processes such as heat pumps and organic Rankine cycles. However, the available literature data, much of which were published between 1975 and 1992, do not incorporate the recommendations of the Guide to the Expression of Uncertainty in Measurement. Therefore, new and more reliable thermodynamic property measurements obtained with state-of-the-art technology are required. The goal of the present study was to obtain accurate vapor-liquid equilibrium (VLE) properties for complex mixtures based on two different gases with significant variations in their boiling points. Precise VLE data were measured with a recirculation-type apparatus with a 380 cm3 equilibration cell and two windows allowing observation of the phase behavior. This cell was equipped with recirculating and expansion loops that were immersed in temperature-controlled liquid and air baths, respectively. Following equilibration, the composition of the sample in each loop was ascertained by gas chromatography. VLE data were acquired for CO2/ethanol and CO2/isopentane binary mixtures within the temperature range from 300 K to 330 K and at pressures up to 7 MPa. These data were used to fit interaction parameters in a Helmholtz energy mixture model. Comparisons were made with the available literature data and values calculated by thermodynamic property models.

Reliable and sensitive determination of dutasteride in human plasma by liquid chromatography-tandem mass spectrometry.

PubMed

Contractor, Pritesh; Kurani, Hemal; Guttikar, Swati; Shrivastav, Pranav S

2013-09-01

An accurate and precise method was developed and validated using LC-MS/MS to quantify dutasteride in human plasma. The analyte and dutasteride-13C6 as internal standard (IS) were extracted from 300 μL plasma volume using methyl tert-butyl ether-n-hexane (80:20, v/v). Chromatographic analysis was performed on a Gemini C18 (150 × 4.6 mm, 5 µm) column using acetonitrile-5 mm ammonium formate, pH adjusted to 4.0 with formic acid (85:15, v/v) as the mobile phase. Tandem mass spectrometry in positive ionization mode was used to quantify dutasteride by multiple reaction monitoring. The entire data processing was done using Watson LIMS(TM) software, which provided excellent data integrity and high throughput with improved operational efficiency. The calibration curve was linear in the range of 0.1-25 ng/mL, with intra-and inter-batch values for accuracy and precision (coefficient of variation) ranging from 95.8 to 104.0 and from 0.7 to 5.3%, respectively. The mean overall recovery across quality controls was ≥95% for the analyte and IS, while the interference of matrix expressed as IS-normalized matrix factors ranged from 1.01 to 1.02. The method was successfully applied to support a bioequivalence study of 0.5 mg dutasteride capsules in 24 healthy subjects. Assay reproducibility was demonstrated by reanalysis of 103 incurred samples. Copyright © 2013 John Wiley & Sons, Ltd.

Metrology for stable isotope reference materials: 13C/12C and 18O/16O isotope ratio value assignment of pure carbon dioxide gas samples on the Vienna PeeDee Belemnite-CO2 scale using dual-inlet mass spectrometry.

PubMed

Srivastava, Abneesh; Michael Verkouteren, R

2018-07-01

Isotope ratio measurements have been conducted on a series of isotopically distinct pure CO 2 gas samples using the technique of dual-inlet isotope ratio mass spectrometry (DI-IRMS). The influence of instrumental parameters, data normalization schemes on the metrological traceability and uncertainty of the sample isotope composition have been characterized. Traceability to the Vienna PeeDee Belemnite(VPDB)-CO 2 scale was realized using the pure CO 2 isotope reference materials(IRMs) 8562, 8563, and 8564. The uncertainty analyses include contributions associated with the values of iRMs and the repeatability and reproducibility of our measurements. Our DI-IRMS measurement system is demonstrated to have high long-term stability, approaching a precision of 0.001 parts-per-thousand for the 45/44 and 46/44 ion signal ratios. The single- and two-point normalization bias for the iRMs were found to be within their published standard uncertainty values. The values of 13 C/ 12 C and 18 O/ 16 O isotope ratios are expressed relative to VPDB-CO 2 using the [Formula: see text] and [Formula: see text] notation, respectively, in parts-per-thousand (‰ or per mil). For the samples, value assignments between (-25 to +2) ‰ and (-33 to -1) ‰ with nominal combined standard uncertainties of (0.05, 0.3) ‰ for [Formula: see text] and [Formula: see text], respectively were obtained. These samples are used as laboratory reference to provide anchor points for value assignment of isotope ratios (with VPDB traceability) to pure CO 2 samples. Additionally, they serve as potential parent isotopic source material required for the development of gravimetric based iRMs of CO 2 in CO 2 -free dry air in high pressure gas cylinder packages at desired abundance levels and isotopic composition values. Graphical abstract CO 2 gas isotope ratio metrology.

A Prospective Multicenter Evaluation of the Accuracy of a Novel Implanted Continuous Glucose Sensor: PRECISE II.

PubMed

Christiansen, Mark P; Klaff, Leslie J; Brazg, Ronald; Chang, Anna R; Levy, Carol J; Lam, David; Denham, Douglas S; Atiee, George; Bode, Bruce W; Walters, Steven J; Kelley, Lynne; Bailey, Timothy S

2018-03-01

Persistent use of real-time continuous glucose monitoring (CGM) improves diabetes control in individuals with type 1 diabetes (T1D) and type 2 diabetes (T2D). PRECISE II was a nonrandomized, blinded, prospective, single-arm, multicenter study that evaluated the accuracy and safety of the implantable Eversense CGM system among adult participants with T1D and T2D (NCT02647905). The primary endpoint was the mean absolute relative difference (MARD) between paired Eversense and Yellow Springs Instrument (YSI) reference measurements through 90 days postinsertion for reference glucose values from 40 to 400 mg/dL. Additional endpoints included Clarke Error Grid analysis and sensor longevity. The primary safety endpoint was the incidence of device-related or sensor insertion/removal procedure-related serious adverse events (SAEs) through 90 days postinsertion. Ninety participants received the CGM system. The overall MARD value against reference glucose values was 8.8% (95% confidence interval: 8.1%-9.3%), which was significantly lower than the prespecified 20% performance goal for accuracy (P < 0.0001). Ninety-three percent of CGM values were within 20/20% of reference values over the total glucose range of 40-400 mg/dL. Clarke Error Grid analysis showed 99.3% of samples in the clinically acceptable error zones A (92.8%) and B (6.5%). Ninety-one percent of sensors were functional through day 90. One related SAE (1.1%) occurred during the study for removal of a sensor. The PRECISE II trial demonstrated that the Eversense CGM system provided accurate glucose readings through the intended 90-day sensor life with a favorable safety profile.

An improved CeO2 method for high-precision measurements of 17O/16O ratios for atmospheric carbon dioxide.

PubMed

Mahata, Sasadhar; Bhattacharya, Sourandra K; Wang, Chung-Ho; Liang, Mao-Chang

2012-09-15

The oxygen isotopic composition of carbon dioxide originating at the Earth's surface is modified in the stratosphere by interaction with ozone which has anomalous oxygen isotope ratio (Δ(17)O = 1000 * ln(1 + δ(17)O/1000) - 0.522 * 1000 * ln (1 + δ(18)O/1000) >0). The inherited anomaly provides a powerful tracer for studying biogeochemical cycles involving CO(2). However, the existing methods are either too imprecise or have difficulty in determining the small Δ(17)O variations found in the tropospheric CO(2). In this study an earlier published CeO(2) and CO(2) exchange method has been modified and improved for measuring the Δ(17)O values of atmospheric carbon dioxide with high precision. The CO(2) fraction from air samples was separated by cryogenic means and purified using gas chromatography. This CO(2) was first analyzed in an isotope ratio mass spectrometer, then artificially equilibrated with hot CeO(2) to alter its oxygen isotopes mass-dependently and re-analyzed. From these data the (17)O/(16)O and (18)O/(16)O ratios were calculated and the Δ(17)O value was determined. The validity of the method was established in several tests by using artificially prepared CO(2) with zero and non-zero Δ(17)O values. The published value of the CO(2)-H(2) O equilibrium slope was also reproduced. The CO(2)-CeO(2) equilibration method has been improved to measure the oxygen isotope anomaly (Δ(17)O value) of atmospheric CO(2) with an analytical precision of ±0.12‰ (2σ). Copyright © 2012 John Wiley & Sons, Ltd.

Single-Step BLUP with Varying Genotyping Effort in Open-Pollinated Picea glauca.

PubMed

Ratcliffe, Blaise; El-Dien, Omnia Gamal; Cappa, Eduardo P; Porth, Ilga; Klápště, Jaroslav; Chen, Charles; El-Kassaby, Yousry A

2017-03-10

Maximization of genetic gain in forest tree breeding programs is contingent on the accuracy of the predicted breeding values and precision of the estimated genetic parameters. We investigated the effect of the combined use of contemporary pedigree information and genomic relatedness estimates on the accuracy of predicted breeding values and precision of estimated genetic parameters, as well as rankings of selection candidates, using single-step genomic evaluation (HBLUP). In this study, two traits with diverse heritabilities [tree height (HT) and wood density (WD)] were assessed at various levels of family genotyping efforts (0, 25, 50, 75, and 100%) from a population of white spruce ( Picea glauca ) consisting of 1694 trees from 214 open-pollinated families, representing 43 provenances in Québec, Canada. The results revealed that HBLUP bivariate analysis is effective in reducing the known bias in heritability estimates of open-pollinated populations, as it exposes hidden relatedness, potential pedigree errors, and inbreeding. The addition of genomic information in the analysis considerably improved the accuracy in breeding value estimates by accounting for both Mendelian sampling and historical coancestry that were not captured by the contemporary pedigree alone. Increasing family genotyping efforts were associated with continuous improvement in model fit, precision of genetic parameters, and breeding value accuracy. Yet, improvements were observed even at minimal genotyping effort, indicating that even modest genotyping effort is effective in improving genetic evaluation. The combined utilization of both pedigree and genomic information may be a cost-effective approach to increase the accuracy of breeding values in forest tree breeding programs where shallow pedigrees and large testing populations are the norm. Copyright © 2017 Ratcliffe et al.

Simultaneous spectrophotometric determination of glimepiride and pioglitazone in binary mixture and combined dosage form using chemometric-assisted techniques

NASA Astrophysics Data System (ADS)

El-Zaher, Asmaa A.; Elkady, Ehab F.; Elwy, Hanan M.; Saleh, Mahmoud Abo El Makarim

2017-07-01

In the present work, pioglitazone and glimepiride, 2 widely used antidiabetics, were simultaneously determined by a chemometric-assisted UV-spectrophotometric method which was applied to a binary synthetic mixture and a pharmaceutical preparation containing both drugs. Three chemometric techniques - Concentration residual augmented classical least-squares (CRACLS), principal component regression (PCR), and partial least-squares (PLS) were implemented by using the synthetic mixtures containing the two drugs in acetonitrile. The absorbance data matrix corresponding to the concentration data matrix was obtained by the measurements of absorbencies in the range between 215 and 235 nm in the intervals with Δλ = 0.4 nm in their zero-order spectra. Then, calibration or regression was obtained by using the absorbance data matrix and concentration data matrix for the prediction of the unknown concentrations of pioglitazone and glimepiride in their mixtures. The described techniques have been validated by analyzing synthetic mixtures containing the two drugs showing good mean recovery values lying between 98 and 100%. In addition, accuracy and precision of the three methods have been assured by recovery values lying between 98 and 102% and R.S.D. % ˂0.6 for intra-day precision and ˂1.2 for inter-day precision. The proposed chemometric techniques were successfully applied to a pharmaceutical preparation containing a combination of pioglitazone and glimepiride in the ratio of 30: 4, showing good recovery values. Finally, statistical analysis was carried out to add a value to the verification of the proposed methods. It was carried out by an intrinsic comparison between the 3 chemometric techniques and by comparing values of present methods with those obtained by implementing reference pharmacopeial methods for each of pioglitazone and glimepiride.

Interval-valued distributed preference relation and its application to group decision making

PubMed Central

Liu, Yin; Xue, Min; Chang, Wenjun; Yang, Shanlin

2018-01-01

As an important way to help express the preference relation between alternatives, distributed preference relation (DPR) can represent the preferred, non-preferred, indifferent, and uncertain degrees of one alternative over another simultaneously. DPR, however, is unavailable in some situations where a decision maker cannot provide the precise degrees of one alternative over another due to lack of knowledge, experience, and data. In this paper, to address this issue, we propose interval-valued DPR (IDPR) and present its properties of validity and normalization. Through constructing two optimization models, an IDPR matrix is transformed into a score matrix to facilitate the comparison between any two alternatives. The properties of the score matrix are analyzed. To guarantee the rationality of the comparisons between alternatives derived from the score matrix, the additive consistency of the score matrix is developed. In terms of these, IDPR is applied to model and solve multiple criteria group decision making (MCGDM) problem. Particularly, the relationship between the parameters for the consistency of the score matrix associated with each decision maker and those for the consistency of the score matrix associated with the group of decision makers is analyzed. A manager selection problem is investigated to demonstrate the application of IDPRs to MCGDM problems. PMID:29889871

Selection of effective cocrystals former for dissolution rate improvement of active pharmaceutical ingredients based on lipoaffinity index.

PubMed

Cysewski, Piotr; Przybyłek, Maciej

2017-09-30

New theoretical screening procedure was proposed for appropriate selection of potential cocrystal formers possessing the ability of enhancing dissolution rates of drugs. The procedure relies on the training set comprising 102 positive and 17 negative cases of cocrystals found in the literature. Despite the fact that the only available data were of qualitative character, performed statistical analysis using binary classification allowed to formulate quantitative criterions. Among considered 3679 molecular descriptors the relative value of lipoaffinity index, expressed as the difference between values calculated for active compound and excipient, has been found as the most appropriate measure suited for discrimination of positive and negative cases. Assuming 5% precision, the applied classification criterion led to inclusion of 70% positive cases in the final prediction. Since lipoaffinity index is a molecular descriptor computed using only 2D information about a chemical structure, its estimation is straightforward and computationally inexpensive. The inclusion of an additional criterion quantifying the cocrystallization probability leads to the following conjunction criterions H mix <-0.18 and ΔLA>3.61, allowing for identification of dissolution rate enhancers. The screening procedure was applied for finding the most promising coformers of such drugs as Iloperidone, Ritonavir, Carbamazepine and Enthenzamide. Copyright © 2017 Elsevier B.V. All rights reserved.

Non-rigid Earth rotation series

NASA Astrophysics Data System (ADS)

Pashkevich, V. V.

2008-04-01

The last years a lot of attempts to derive a high-precision theory of the non-rigid Earth rotation was carried out. For these purposes the different transfer functions are used. Usually these transfer func- tions are applied to the series representing the nutation in longitude and in obliquity of the rigid Earth rotation with respect to the ecliptic of date. The aim of this investigation is a construction of the new high- precision non-rigid Earth rotation series (SN9000), dynamically adequate to the DE404/LE404 ephemeris over 2000 years, which are expressed as a function of Euler angles ψ, θ and φ with respect to the fixed ecliptic plane and equinox J2000.0. The early stages of the previous investigation: 1. The high-precision numerical solution of the rigid Earth rotation have been constructed (V.V.Pashkevich, G.I.Eroshkin and A.Brzezinski, 2004), (V.V.Pashkevich and G.I.Eroshkin, Proceedings of Journees 2004). The initial con- ditions have been calculated from SMART97 (P.Bretagnon, G.Francou, P.Rocher, J.L.Simon,1998). The discrepancies between the numerical solution and the semi-analytical solution SMART97 were obtained in Euler angles over 2000 years with one-day spacing. 2. Investigation of the discrepancies is carried out by the least squares and by the spectral analysis algorithms (V.V.Pashkevich and G.I.Eroshkin, Proceedings of Journees 2005). The high-precision rigid Earth rotation series S9000 are determined (V.V.Pashkevich and G.I.Eroshkin, 2005 ). The next stage of this investigation: 3. The new high-precision non-rigid Earth rotation series (SN9000), which are expressed as a function of Euler angles, are constructed by using the method (P.Bretagnon, P.M.Mathews, J.-L.Simon: 1999) and the transfer function MHB2002 (Mathews, P. M., Herring, T. A., and Buffett B. A., 2002).

A high-quality annotated transcriptome of swine peripheral blood

USDA-ARS?s Scientific Manuscript database

Background: High throughput gene expression profiling assays of peripheral blood are widely used in biomedicine, as well as in animal genetics and physiology research. Accurate, comprehensive, and precise interpretation of such high throughput assays relies on well-characterized reference genomes an...

Gene Expression of Normal Human Epidermal Keratinocytes Modulated by Trivalent Arsenicals

EPA Science Inventory

Chronic exposure to inorganic arsenic (iAs) is associated with the development of benign and malignant human skin lesions including nonmelanoma skin cancers. The precise arsenical form(s) responsible for this carcinogenic effect are unknown, although trivalent inorganic arsenic (...

Expression map of a complete set of gustatory receptor genes in chemosensory organs of Bombyx mori.

PubMed

Guo, Huizhen; Cheng, Tingcai; Chen, Zhiwei; Jiang, Liang; Guo, Youbing; Liu, Jianqiu; Li, Shenglong; Taniai, Kiyoko; Asaoka, Kiyoshi; Kadono-Okuda, Keiko; Arunkumar, Kallare P; Wu, Jiaqi; Kishino, Hirohisa; Zhang, Huijie; Seth, Rakesh K; Gopinathan, Karumathil P; Montagné, Nicolas; Jacquin-Joly, Emmanuelle; Goldsmith, Marian R; Xia, Qingyou; Mita, Kazuei

2017-03-01

Most lepidopteran species are herbivores, and interaction with host plants affects their gene expression and behavior as well as their genome evolution. Gustatory receptors (Grs) are expected to mediate host plant selection, feeding, oviposition and courtship behavior. However, due to their high diversity, sequence divergence and extremely low level of expression it has been difficult to identify precisely a complete set of Grs in Lepidoptera. By manual annotation and BAC sequencing, we improved annotation of 43 gene sequences compared with previously reported Grs in the most studied lepidopteran model, the silkworm, Bombyx mori, and identified 7 new tandem copies of BmGr30 on chromosome 7, bringing the total number of BmGrs to 76. Among these, we mapped 68 genes to chromosomes in a newly constructed chromosome distribution map and 8 genes to scaffolds; we also found new evidence for large clusters of BmGrs, especially from the bitter receptor family. RNA-seq analysis of diverse BmGr expression patterns in chemosensory organs of larvae and adults enabled us to draw a precise organ specific map of BmGr expression. Interestingly, most of the clustered genes were expressed in the same tissues and more than half of the genes were expressed in larval maxillae, larval thoracic legs and adult legs. For example, BmGr63 showed high expression levels in all organs in both larval and adult stages. By contrast, some genes showed expression limited to specific developmental stages or organs and tissues. BmGr19 was highly expressed in larval chemosensory organs (especially antennae and thoracic legs), the single exon genes BmGr53 and BmGr67 were expressed exclusively in larval tissues, the BmGr27-BmGr31 gene cluster on chr7 displayed a high expression level limited to adult legs and the candidate CO 2 receptor BmGr2 was highly expressed in adult antennae, where few other Grs were expressed. Transcriptional analysis of the Grs in B. mori provides a valuable new reference for finding genes involved in plant-insect interactions in Lepidoptera and establishing correlations between these genes and vital insect behaviors like host plant selection and courtship for mating. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

pyGeno: A Python package for precision medicine and proteogenomics.

PubMed

Daouda, Tariq; Perreault, Claude; Lemieux, Sébastien

2016-01-01

pyGeno is a Python package mainly intended for precision medicine applications that revolve around genomics and proteomics. It integrates reference sequences and annotations from Ensembl, genomic polymorphisms from the dbSNP database and data from next-gen sequencing into an easy to use, memory-efficient and fast framework, therefore allowing the user to easily explore subject-specific genomes and proteomes. Compared to a standalone program, pyGeno gives the user access to the complete expressivity of Python, a general programming language. Its range of application therefore encompasses both short scripts and large scale genome-wide studies.

pyGeno: A Python package for precision medicine and proteogenomics

PubMed Central

Daouda, Tariq; Perreault, Claude; Lemieux, Sébastien

2016-01-01

pyGeno is a Python package mainly intended for precision medicine applications that revolve around genomics and proteomics. It integrates reference sequences and annotations from Ensembl, genomic polymorphisms from the dbSNP database and data from next-gen sequencing into an easy to use, memory-efficient and fast framework, therefore allowing the user to easily explore subject-specific genomes and proteomes. Compared to a standalone program, pyGeno gives the user access to the complete expressivity of Python, a general programming language. Its range of application therefore encompasses both short scripts and large scale genome-wide studies. PMID:27785359

The critical distance in laser-induced plasmas: an operative definition

NASA Astrophysics Data System (ADS)

Delle Side, D.; Giuffreda, E.; Nassisi, V.

2016-05-01

We propose a method to estimate a precise value for the critical distance Lcr after which three-body recombination stops to produce charge losses in an expanding laser-induced plasma. We show in particular that the total charge collected has a ``reversed sigmoid'' shape as a function of the target-to-detector distance. Fitting the total charge data with a logistic related function, we could consider as Lcr the intercept of the tangent to this curve in its inflection point. Furthermore, this value scales well with theoretical predictions. From the application point of view, this could be of great practical interest, since it provide a reliable way to precisely determine the geometry of the extraction system in Laser Ion Sources.

Pseudospectral calculation of helium wave functions, expectation values, and oscillator strength

NASA Astrophysics Data System (ADS)

Grabowski, Paul E.; Chernoff, David F.

2011-10-01

We show that the pseudospectral method is a powerful tool for finding precise solutions of Schrödinger’s equation for two-electron atoms with general angular momentum. Realizing the method’s full promise for atomic calculations requires special handling of singularities due to two-particle Coulomb interactions. We give a prescription for choosing coordinates and subdomains whose efficacy we illustrate by solving several challenging problems. One test centers on the determination of the nonrelativistic electric dipole oscillator strength for the helium 11S→21P transition. The result achieved, 0.27616499(27), is comparable to the best in the literature. The formally equivalent length, velocity, and acceleration expressions for the oscillator strength all yield roughly the same accuracy. We also calculate a diverse set of helium ground-state expectation values, reaching near state-of-the-art accuracy without the necessity of implementing any special-purpose numerics. These successes imply that general matrix elements are directly and reliably calculable with pseudospectral methods. A striking result is that all the relevant quantities tested in this paper—energy eigenvalues, S-state expectation values and a bound-bound dipole transition between the lowest energy S and P states—converge exponentially with increasing resolution and at roughly the same rate. Each individual calculation samples and weights the configuration space wave function uniquely but all behave in a qualitatively similar manner. These results suggest that the method has great promise for similarly accurate treatment of few-particle systems.

Ultra-High Precision Half-Life Measurement for the Superallowed &+circ; Emitter ^26Al^m

NASA Astrophysics Data System (ADS)

Finlay, P.; Demand, G.; Garrett, P. E.; Leach, K. G.; Phillips, A. A.; Sumithrarachchi, C. S.; Svensson, C. E.; Triambak, S.; Grinyer, G. F.; Leslie, J. R.; Andreoiu, C.; Cross, D.; Austin, R. A. E.; Ball, G. C.; Bandyopadhyay, D.; Djongolov, M.; Ettenauer, S.; Hackman, G.; Pearson, C. J.; Williams, S. J.

2009-10-01

The calculated nuclear structure dependent correction for ^26Al^m (δC-δNS= 0.305(27)% [1]) is smaller by nearly a factor of two than the other twelve precision superallowed cases, making it an ideal case to pursue a reduction in the experimental errors contributing to the Ft value. An ultra-high precision half-life measurement for the superallowed &+circ; emitter ^26Al^m has been made at the Isotope Separator and Accelerator (ISAC) facility at TRIUMF in Vancouver, Canada. A beam of ˜10^5 ^26Al^m/s was delivered in October 2007 and its decay was observed using a 4π continuous gas flow proportional counter as part of an ongoing experimental program in superallowed Fermi β decay studies. With a statistical precision of ˜0.008%, the present work represents the single most precise measurement of any superallowed half-life to date. [4pt] [1] I.S. Towner and J.C. Hardy, Phys. Rev. C 79, 055502 (2009).

Ultra-High Precision Half-Life Measurement for the Superallowed &+circ; Emitter ^26Al^m

NASA Astrophysics Data System (ADS)

Finlay, P.; Demand, G.; Garrett, P. E.; Leach, K. G.; Phillips, A. A.; Sumithrarachchi, C. S.; Svensson, C. E.; Triambak, S.; Ball, G. C.; Bandyopadhyay, D.; Djongolov, M.; Ettenauer, S.; Hackman, G.; Pearson, C. J.; Williams, S. J.; Andreoiu, C.; Cross, D.; Austin, R. A. E.; Grinyer, G. F.; Leslie, J. R.

2008-10-01

The calculated nuclear structure dependent correction for ^26Al^m (δC-δNS= 0.305(27)% [1]) is smaller by nearly a factor of two than the other twelve precision superallowed cases, making it an ideal case to pursue a reduction in the experimental errors contributing to the Ft value. An ultra-high precision half-life measurement for the superallowed &+circ; emitter ^26Al^m has been made using a 4π continuous gas flow proportional counter as part of an ongoing experimental program in superallowed Fermi β decay studies at the Isotope Separator and Accelerator (ISAC) facility at TRIUMF in Vancouver, Canada, which delivered a beam of ˜10^5 ^26Al^m/s in October 2007. With a statistical precision of ˜0.008%, the present work represents the single most precise measurement of any superallowed half-life to date. [1] I.S. Towner and J.C. Hardy, Phys. Rev. C 77, 025501 (2008).

Precision Medicine: From Science To Value.

PubMed

Ginsburg, Geoffrey S; Phillips, Kathryn A

2018-05-01

Precision medicine is making an impact on patients, health care delivery systems, and research participants in ways that were only imagined fifteen years ago when the human genome was first sequenced. Discovery of disease-causing and drug-response genetic variants has accelerated, while adoption into clinical medicine has lagged. We define precision medicine and the stakeholder community required to enable its integration into research and health care. We explore the intersection of data science, analytics, and precision medicine in the formation of health systems that carry out research in the context of clinical care and that optimize the tools and information used to deliver improved patient outcomes. We provide examples of real-world impact and conclude with a policy and economic agenda necessary for the adoption of this new paradigm of health care both in the United States and globally.

Target tracking system based on preliminary and precise two-stage compound cameras

NASA Astrophysics Data System (ADS)

Shen, Yiyan; Hu, Ruolan; She, Jun; Luo, Yiming; Zhou, Jie

2018-02-01

Early detection of goals and high-precision of target tracking is two important performance indicators which need to be balanced in actual target search tracking system. This paper proposed a target tracking system with preliminary and precise two - stage compound. This system using a large field of view to achieve the target search. After the target was searched and confirmed, switch into a small field of view for two field of view target tracking. In this system, an appropriate filed switching strategy is the key to achieve tracking. At the same time, two groups PID parameters are add into the system to reduce tracking error. This combination way with preliminary and precise two-stage compound can extend the scope of the target and improve the target tracking accuracy and this method has practical value.

Towards precision medicine; a new biomedical cosmology.

PubMed

Vegter, M W

2018-02-10

Precision Medicine has become a common label for data-intensive and patient-driven biomedical research. Its intended future is reflected in endeavours such as the Precision Medicine Initiative in the USA. This article addresses the question whether it is possible to discern a new 'medical cosmology' in Precision Medicine, a concept that was developed by Nicholas Jewson to describe comprehensive transformations involving various dimensions of biomedical knowledge and practice, such as vocabularies, the roles of patients and physicians and the conceptualisation of disease. Subsequently, I will elaborate my assessment of the features of Precision Medicine with the help of Michel Foucault, by exploring how precision medicine involves a transformation along three axes: the axis of biomedical knowledge, of biomedical power and of the patient as a self. Patients are encouraged to become the managers of their own health status, while the medical domain is reframed as a data-sharing community, characterised by changing power relationships between providers and patients, producers and consumers. While the emerging Precision Medicine cosmology may surpass existing knowledge frameworks; it obscures previous traditions and reduces research-subjects to mere data. This in turn, means that the individual is both subjected to the neoliberal demand to share personal information, and at the same time has acquired the positive 'right' to become a member of the data-sharing community. The subject has to constantly negotiate the meaning of his or her data, which can either enable self-expression, or function as a commanding Superego.

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.

Superallowed nuclear beta decay: Precision measurements for basic physics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hardy, J. C.

2012-11-20

For 60 years, superallowed 0{sup +}{yields}0{sup +} nuclear beta decay has been used to probe the weak interaction, currently verifying the conservation of the vector current (CVC) to high precision ({+-}0.01%) and anchoring the most demanding available test of the unitarity of the Cabibbo-Kobayashi-Maskawa (CKM) matrix ({+-}0.06%), a fundamental pillar of the electroweak standard model. Each superallowed transition is characterized by its ft-value, a result obtained from three measured quantities: the total decay energy of the transition, its branching ratio, and the half-life of the parent state. Today's data set is composed of some 150 independent measurements of 13 separatemore » superallowed transitions covering a wide range of parent nuclei from {sup 10}C to {sup 74}Rb. Excellent consistency among the average results for all 13 transitions - a prediction of CVC - also confirms the validity of the small transition-dependent theoretical corrections that have been applied to account for isospin symmetry breaking. With CVC consistency established, the value of the vector coupling constant, G{sub V}, has been extracted from the data and used to determine the top left element of the CKM matrix, V{sub ud}. With this result the top-row unitarity test of the CKM matrix yields the value 0.99995(61), a result that sets a tight limit on possible new physics beyond the standard model. To have any impact on these fundamental weak-interaction tests, any measurement must be made with a precision of 0.1% or better - a substantial experimental challenge well beyond the requirements of most nuclear physics measurements. I overview the current state of the field and outline some of the requirements that need to be met by experimentalists if they aim to make measurements with this high level of precision.« less

Impact of orbit modeling on DORIS station position and Earth rotation estimates

NASA Astrophysics Data System (ADS)

Štěpánek, Petr; Rodriguez-Solano, Carlos Javier; Hugentobler, Urs; Filler, Vratislav

2014-04-01

The high precision of estimated station coordinates and Earth rotation parameters (ERP) obtained from satellite geodetic techniques is based on the precise determination of the satellite orbit. This paper focuses on the analysis of the impact of different orbit parameterizations on the accuracy of station coordinates and the ERPs derived from DORIS observations. In a series of experiments the DORIS data from the complete year 2011 were processed with different orbit model settings. First, the impact of precise modeling of the non-conservative forces on geodetic parameters was compared with results obtained with an empirical-stochastic modeling approach. Second, the temporal spacing of drag scaling parameters was tested. Third, the impact of estimating once-per-revolution harmonic accelerations in cross-track direction was analyzed. And fourth, two different approaches for solar radiation pressure (SRP) handling were compared, namely adjusting SRP scaling parameter or fixing it on pre-defined values. Our analyses confirm that the empirical-stochastic orbit modeling approach, which does not require satellite attitude information and macro models, results for most of the monitored station parameters in comparable accuracy as the dynamical model that employs precise non-conservative force modeling. However, the dynamical orbit model leads to a reduction of the RMS values for the estimated rotation pole coordinates by 17% for x-pole and 12% for y-pole. The experiments show that adjusting atmospheric drag scaling parameters each 30 min is appropriate for DORIS solutions. Moreover, it was shown that the adjustment of cross-track once-per-revolution empirical parameter increases the RMS of the estimated Earth rotation pole coordinates. With recent data it was however not possible to confirm the previously known high annual variation in the estimated geocenter z-translation series as well as its mitigation by fixing the SRP parameters on pre-defined values.

Numerical and clinical precision of continuous glucose monitoring in Colombian patients treated with insulin infusion pump with automated suspension in hypoglycemia.

PubMed

Gómez, Ana M; Marín Sánchez, Alejandro; Muñoz, Oscar M; Colón Peña, Christian Alejandro

2015-12-01

Insulin pump therapy associated with continuous glucose monitoring has shown a positive clinical impact on diabetes control and reduction of hypoglycemia episodes. There are descriptions of the performance of this device in other populations, but its precision and accuracy in Colombia and Latin America are unknown, especially in the routine outpatient setting. Data from 33 type 1 and type 2 diabetes patients with sensor-augmented pump therapy with threshold suspend automation, MiniMed Paradigm® Veo™ (Medtronic, Northridge, California), managed at Hospital Universitario San Ignacio (Bogotá, Colombia) and receiving outpatient treatment, were analyzed. Simultaneous data from continuous glucose monitoring and capillary blood glucose were compared, and their precision and accuracy were calculating with different methods, including Clarke error grid. Analyses included 2,262 continuous glucose monitoring -reference paired glucose values. A mean absolute relative difference of 20.1% was found for all measurements, with a value higher than 23% for glucose levels ≤75mg/dL. Global compliance with the ISO criteria was 64.9%. It was higher for values >75mg/dl (68.3%, 1,308 of 1,916 readings), than for those ≤ 75mg/dl (49.4%, 171 of 346 readings). Clinical accuracy, as assessed by the Clarke error grid, showed that 91.77% of data were within the A and B zones (75.6% in hypoglycemia). A good numerical accuracy was found for continuous glucose monitoring in normo and hyperglycemia situations, with low precision in hypoglycemia. The clinical accuracy of the device was adequate, with no significant safety concerns for patients. Copyright © 2015 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

Evaluation of consumer monitors to measure particulate matter.

PubMed

Sousan, Sinan; Koehler, Kirsten; Hallett, Laura; Peters, Thomas M

2017-05-01

Recently, inexpensive (<$300) consumer aerosol monitors (CAMs) targeted for use in homes have become available. We evaluated the accuracy, bias, and precision of three CAMs (Foobot from Airoxlab, Speck from Carnegie Mellon University, and AirBeam from HabitatMap) for measuring mass concentrations in occupational settings. In a laboratory study, PM 2.5 measured with the CAMs and a medium-cost aerosol photometer (personal DataRAM 1500, Thermo Scientific) were compared to that from reference instruments for three aerosols (salt, welding fume, and Arizona road dust, ARD) at concentrations up to 8500 μg/m 3 . Three of each type of CAM were included to estimate precision. Compared to reference instruments, mass concentrations measured with the Foobot (r-value = 0.99) and medium-cost photometer (r-value = 0.99) show strong correlation, whereas those from the Speck (r-value range 0.88 - 0.99) and AirBeam (0.7 - 0.96) were less correlated. The Foobot bias was (-12%) for ARD and measurements were similar to the medium-cost instrument. Foobot bias was (< -46%) for salt and welding fume aerosols. Speck bias was at 18% salt for ARD and -86% for welding fume. AirBeam bias was (-36%) for salt and (-83%) for welding fume. All three photometers had a bias (< -82%) for welding fume. Precision was excellent for the Foobot (coefficient of variation range: 5% to 8%) and AirBeam (2% to 9%), but poorer for the Speck (8% to 25%). These findings suggest that the Foobot, with a linear response to different aerosol types and good precision, can provide reasonable estimates of PM 2.5 in the workplace after site-specific calibration to account for particle size and composition.

Mechanism of bisphenol AF-induced progesterone inhibition in human chorionic gonadotrophin-stimulated mouse Leydig tumor cell line (mLTC-1) cells.

PubMed

Feng, Yixing; Shi, Jiachen; Jiao, Zhihao; Duan, Hejun; Shao, Bing

2018-06-01

Bisphenol AF (BPAF) has been shown to inhibit testicular steroidogenesis in male rats. However, the precise mechanisms related to the toxic effects of BPAF on reproduction remain poorly understood. In the present study, a mouse Leydig tumor cell line (mLTC-1) was used as a model to investigate the mechanism of steroidogenic inhibition and to identify the molecular target of BPAF. Levels of progesterone and the concentration of cyclic adenosine monophosphate (cAMP) in cells exposed to BPAF were detected, and expression of key genes and proteins in steroid biosynthesis was assessed. The results showed that BPAF exposure decreased human chorionic gonadotrophin (hCG)-stimulated progesterone production in a dose-dependent manner. The 24-h IC 50 (half maximal inhibitory concentration) value for BPAF regarding progesterone production was 70.2 µM. A dramatic decrease in cellular cAMP concentration was also observed. Furthermore, BPAF exposure inhibited expression of genes and proteins involved in cholesterol transport and progesterone biosynthesis. Conversely, the protein levels of steroidogenic acute regulatory protein (StAR) were not altered, and those of progesterone were still decreased upon 22R-hydroxycholesterol treatment of cells exposed to higher doses of BPAF. Together, these data indicate that BPAF exposure inhibits progesterone secretion in hCG-stimulated mLTC-1 cells by reducing expression of scavenger receptor class B type I (SR-B1) and cytochrome P450 (P450scc) due to the adverse effects of cAMP. However, StAR might not be the molecular target in this process. © 2018 Wiley Periodicals, Inc.

The developmental transcriptome atlas of the spoon worm Urechis unicinctus (Echiurida: Annelida).

PubMed

Park, Chungoo; Han, Yong-Hee; Lee, Sung-Gwon; Ry, Kyoung-Bin; Oh, Jooseong; Kern, Elizabeth M A; Park, Joong-Ki; Cho, Sung-Jin

2018-03-01

Echiurida is one of the most intriguing major subgroups of annelida because, unlike most other annelids, echiurids lack metameric body segmentation as adults. For this reason, transcriptome analyses from various developmental stages of echiurid species can be of substantial value for understanding precise expression levels and the complex regulatory networks during early and larval development. A total of 914 million raw RNA-Seq reads were produced from 14 developmental stages of Urechis unicinctus and were de novo assembled into contigs spanning 63,928,225 bp with an N50 length of 2700 bp. The resulting comprehensive transcriptome database of the early developmental stages of U. unicinctus consists of 20,305 representative functional protein-coding transcripts. Approximately 66% of unigenes were assigned to superphylum-level taxa, including Lophotrochozoa (40%). The completeness of the transcriptome assembly was assessed using benchmarking universal single-copy orthologs; 75.7% of the single-copy orthologs were presented in our transcriptome database. We observed 3 distinct patterns of global transcriptome profiles from 14 developmental stages and identified 12,705 genes that showed dynamic regulation patterns during the differentiation and maturation of U. unicinctus cells. We present the first large-scale developmental transcriptome dataset of U. unicinctus and provide a general overview of the dynamics of global gene expression changes during its early developmental stages. The analysis of time-course gene expression data is a first step toward understanding the complex developmental gene regulatory networks in U. unicinctus and will furnish a valuable resource for analyzing the functions of gene repertoires in various developmental phases.

Gene expression in thiazide diuretic or statin users in relation to incident type 2 diabetes.

PubMed

Suchy-Dicey, Astrid; Heckbert, Susan R; Smith, Nicholas L; McKnight, Barbara; Rotter, Jerome I; Chen, Yd Ida; Psaty, Bruce M; Enquobahrie, Daniel A

2014-01-01

Thiazide diuretics and statins are used to improve cardiovascular outcomes, but may also cause type 2 diabetes (T2DM), although mechanisms are unknown. Gene expression studies may facilitate understanding of these associations. Participants from ongoing population-based studies were sampled for these longitudinal studies of peripheral blood microarray gene expression, and followed to incident diabetes. All sampled subjects were statin or thiazide users. Those who developed diabetes during follow-up comprised cases (44 thiazide users; 19 statin users), and were matched to drug-using controls who did not develop diabetes on several factors. Supervised normalization, surrogate variable analyses removed technical bias and confounding. Differentially-expressed genes were those with a false discovery rate Q-value<0.05. Among thiazide users, diabetes cases had significantly different expression of CCL14 (down-regulated 6%, Q-value=0.0257), compared with controls. Among statin users, diabetes cases had marginal but insignificantly different expression of ZNF532 (up-regulated 15%, Q-value=0.0584), CXORF21 (up-regulated 11%, Q-value=0.0584), and ZNHIT3 (up-regulated 19%, Q-value=0.0959), compared with controls. These genes comprise potential targets for future expression or mechanistic research on medication-related diabetes development.

Genome editing for crop improvement: Challenges and opportunities

PubMed Central

Abdallah, Naglaa A; Prakash, Channapatna S; McHughen, Alan G

2015-01-01

ABSTRACT Genome or gene editing includes several new techniques to help scientists precisely modify genome sequences. The techniques also enables us to alter the regulation of gene expression patterns in a pre-determined region and facilitates novel insights into the functional genomics of an organism. Emergence of genome editing has brought considerable excitement especially among agricultural scientists because of its simplicity, precision and power as it offers new opportunities to develop improved crop varieties with clear-cut addition of valuable traits or removal of undesirable traits. Research is underway to improve crop varieties with higher yields, strengthen stress tolerance, disease and pest resistance, decrease input costs, and increase nutritional value. Genome editing encompasses a wide variety of tools using either a site-specific recombinase (SSR) or a site-specific nuclease (SSN) system. Both systems require recognition of a known sequence. The SSN system generates single or double strand DNA breaks and activates endogenous DNA repair pathways. SSR technology, such as Cre/loxP and Flp/FRT mediated systems, are able to knockdown or knock-in genes in the genome of eukaryotes, depending on the orientation of the specific sites (loxP, FLP, etc.) flanking the target site. There are 4 main classes of SSN developed to cleave genomic sequences, mega-nucleases (homing endonuclease), zinc finger nucleases (ZFNs), transcriptional activator-like effector nucleases (TALENs), and the CRISPR/Cas nuclease system (clustered regularly interspaced short palindromic repeat/CRISPR-associated protein). The recombinase mediated genome engineering depends on recombinase (sub-) family and target-site and induces high frequencies of homologous recombination. Improving crops with gene editing provides a range of options: by altering only a few nucleotides from billions found in the genomes of living cells, altering the full allele or by inserting a new gene in a targeted region of the genome. Due to its precision, gene editing is more precise than either conventional crop breeding methods or standard genetic engineering methods. Thus this technology is a very powerful tool that can be used toward securing the world's food supply. In addition to improving the nutritional value of crops, it is the most effective way to produce crops that can resist pests and thrive in tough climates. There are 3 types of modifications produced by genome editing; Type I includes altering a few nucleotides, Type II involves replacing an allele with a pre-existing one and Type III allows for the insertion of new gene(s) in predetermined regions in the genome. Because most genome-editing techniques can leave behind traces of DNA alterations evident in a small number of nucleotides, crops created through gene editing could avoid the stringent regulation procedures commonly associated with GM crop development. For this reason many scientists believe plants improved with the more precise gene editing techniques will be more acceptable to the public than transgenic plants. With genome editing comes the promise of new crops being developed more rapidly with a very low risk of off-target effects. It can be performed in any laboratory with any crop, even those that have complex genomes and are not easily bred using conventional methods. PMID:26930114

Asian American Client Adherence to Asian Cultural Values, Counselor Expression of Cultural Values, Counselor Ethnicity, and Career Counseling Process

ERIC Educational Resources Information Center

Kim, Bryan S. K.; Atkinson, Donald R.

2002-01-01

This study investigated the relationships among client adherence to Asian cultural values, counselor expression of cultural values, counselor ethnicity, and career counseling process with Asian American college students. Clients who had high adherence to Asian cultural values evaluated Asian American counselors as more empathic and credible than…

Systematic analysis of transcription start sites in avian development.

PubMed

Lizio, Marina; Deviatiiarov, Ruslan; Nagai, Hiroki; Galan, Laura; Arner, Erik; Itoh, Masayoshi; Lassmann, Timo; Kasukawa, Takeya; Hasegawa, Akira; Ros, Marian A; Hayashizaki, Yoshihide; Carninci, Piero; Forrest, Alistair R R; Kawaji, Hideya; Gusev, Oleg; Sheng, Guojun

2017-09-01

Cap Analysis of Gene Expression (CAGE) in combination with single-molecule sequencing technology allows precision mapping of transcription start sites (TSSs) and genome-wide capture of promoter activities in differentiated and steady state cell populations. Much less is known about whether TSS profiling can characterize diverse and non-steady state cell populations, such as the approximately 400 transitory and heterogeneous cell types that arise during ontogeny of vertebrate animals. To gain such insight, we used the chick model and performed CAGE-based TSS analysis on embryonic samples covering the full 3-week developmental period. In total, 31,863 robust TSS peaks (>1 tag per million [TPM]) were mapped to the latest chicken genome assembly, of which 34% to 46% were active in any given developmental stage. ZENBU, a web-based, open-source platform, was used for interactive data exploration. TSSs of genes critical for lineage differentiation could be precisely mapped and their activities tracked throughout development, suggesting that non-steady state and heterogeneous cell populations are amenable to CAGE-based transcriptional analysis. Our study also uncovered a large set of extremely stable housekeeping TSSs and many novel stage-specific ones. We furthermore demonstrated that TSS mapping could expedite motif-based promoter analysis for regulatory modules associated with stage-specific and housekeeping genes. Finally, using Brachyury as an example, we provide evidence that precise TSS mapping in combination with Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-on technology enables us, for the first time, to efficiently target endogenous avian genes for transcriptional activation. Taken together, our results represent the first report of genome-wide TSS mapping in birds and the first systematic developmental TSS analysis in any amniote species (birds and mammals). By facilitating promoter-based molecular analysis and genetic manipulation, our work also underscores the value of avian models in unravelling the complex regulatory mechanism of cell lineage specification during amniote development.

One Percent Determination of the Primordial Deuterium Abundance

NASA Astrophysics Data System (ADS)

Cooke, Ryan J.; Pettini, Max; Steidel, Charles C.

2018-03-01

We report a reanalysis of a near-pristine absorption system, located at a redshift {z}abs}=2.52564 toward the quasar Q1243+307, based on the combination of archival and new data obtained with the HIRES echelle spectrograph on the Keck telescope. This absorption system, which has an oxygen abundance [O/H] = ‑2.769 ± 0.028 (≃1/600 of the solar abundance), is among the lowest metallicity systems currently known where a precise measurement of the deuterium abundance is afforded. Our detailed analysis of this system concludes, on the basis of eight D I absorption lines, that the deuterium abundance of this gas cloud is {log}}10({{D}}/{{H}})=-4.622+/- 0.015, which is in very good agreement with the results previously reported by Kirkman et al., but with an improvement on the precision of this single measurement by a factor of ∼3.5. Combining this new estimate with our previous sample of six high precision and homogeneously analyzed D/H measurements, we deduce that the primordial deuterium abundance is {log}}10{({{D}}/{{H}})}{{P}}=-4.5974+/- 0.0052 or, expressed as a linear quantity, {10}5{({{D}}/{{H}})}{{P}}=2.527+/- 0.030; this value corresponds to a one percent determination of the primordial deuterium abundance. Combining our result with a big bang nucleosynthesis (BBN) calculation that uses the latest nuclear physics input, we find that the baryon density derived from BBN agrees to within 2σ of the latest results from the Planck cosmic microwave background data. Based on observations collected at the W.M. Keck Observatory which is operated as a scientific partnership among the California Institute of Technology, the University of California, and the National Aeronautics and Space Administration. The Observatory was made possible by the generous financial support of the W.M. Keck Foundation.

Ionic liquids intercalated in montmorillonite as the sorptive phase for the extraction of low-polarity organic compounds from water by rotating-disk sorptive extraction.

PubMed

Fiscal-Ladino, Jhon A; Obando-Ceballos, Mónica; Rosero-Moreano, Milton; Montaño, Diego F; Cardona, Wilson; Giraldo, Luis F; Richter, Pablo

2017-02-08

Montmorillonite (MMT) clays were modified by the intercalation into their galleries of ionic liquids (IL) based on imidazolium quaternary ammonium salts. This new eco-materials exhibited good features for use as a sorptive phase in the extraction of low-polarity analytes from aqueous samples. Spectroscopic analyses of the modified clays were conducted and revealed an increase in the basal spacing and a shifting of the reflection plane towards lower values as a consequence of the effective intercalation of organic cations into the MMT structure. The novel sorbent developed herein was assayed as the sorptive phase in rotating-disk sorptive extraction (RDSE), using polychlorinated biphenyls (PCBs), representative of low-polarity pollutants, as model analytes. The final determination was made by gas chromatography with electron capture detection. Among the synthetized sorptive phases, the selected system for analytical purposes consisted of MMT modified with the 1-hexadecyl-3-methylimidazolium bromide (HDMIM-Br) IL. Satisfactory analytical features were achieved using a sample volume of 5 mL: the relative recoveries from a wastewater sample were higher than 80%, the detection limits were between 3 ng L -1 and 43 ng L -1 , the precision (within-run precision) expressed as the relative standard deviation ranged from 2% to 24%, and the enrichment factors ranged between 18 and 28. Using RDSE, the extraction efficiency achieved for the selected MMT-HDMIM-Br phase was compared with other commercial solid phases/supports, such as polypropylene, polypropylene with 1-octanol (as a supported liquid membrane), octadecyl (C18) and octyl (C8), and showed the highest response for all the studied analytes. Under the optimized extraction conditions, this new device was applied in the analysis of the influent of a wastewater treatment plant in Santiago (Chile), demonstrating its applicability through the good recoveries and precision achieved with real samples. Copyright © 2016 Elsevier B.V. All rights reserved.

CD4 Enumeration Technologies: A Systematic Review of Test Performance for Determining Eligibility for Antiretroviral Therapy

PubMed Central

Peeling, Rosanna W.; Sollis, Kimberly A.; Glover, Sarah; Crowe, Suzanne M.; Landay, Alan L.; Cheng, Ben; Barnett, David; Denny, Thomas N.; Spira, Thomas J.; Stevens, Wendy S.; Crowley, Siobhan; Essajee, Shaffiq; Vitoria, Marco; Ford, Nathan

2015-01-01

Background Measurement of CD4+ T-lymphocytes (CD4) is a crucial parameter in the management of HIV patients, particularly in determining eligibility to initiate antiretroviral treatment (ART). A number of technologies exist for CD4 enumeration, with considerable variation in cost, complexity, and operational requirements. We conducted a systematic review of the performance of technologies for CD4 enumeration. Methods and Findings Studies were identified by searching electronic databases MEDLINE and EMBASE using a pre-defined search strategy. Data on test accuracy and precision included bias and limits of agreement with a reference standard, and misclassification probabilities around CD4 thresholds of 200 and 350 cells/μl over a clinically relevant range. The secondary outcome measure was test imprecision, expressed as % coefficient of variation. Thirty-two studies evaluating 15 CD4 technologies were included, of which less than half presented data on bias and misclassification compared to the same reference technology. At CD4 counts <350 cells/μl, bias ranged from -35.2 to +13.1 cells/μl while at counts >350 cells/μl, bias ranged from -70.7 to +47 cells/μl, compared to the BD FACSCount as a reference technology. Misclassification around the threshold of 350 cells/μl ranged from 1-29% for upward classification, resulting in under-treatment, and 7-68% for downward classification resulting in overtreatment. Less than half of these studies reported within laboratory precision or reproducibility of the CD4 values obtained. Conclusions A wide range of bias and percent misclassification around treatment thresholds were reported on the CD4 enumeration technologies included in this review, with few studies reporting assay precision. The lack of standardised methodology on test evaluation, including the use of different reference standards, is a barrier to assessing relative assay performance and could hinder the introduction of new point-of-care assays in countries where they are most needed. PMID:25790185

The economic value of remote sensing of earth resources from space: An ERTS overview and the value of continuity of service. Volume 8: Atmosphere

NASA Technical Reports Server (NTRS)

Miles, R.; Fawkes, G.

1974-01-01

The economic value of an ERS system in the resource area of atmosphere is determined. Benefits which arise from air pollution and cloud observations correlated to ground stations are discussed along with cost savings associated with air pollution monitoring by satellite. Social benefits due to more precise knowledge of the effects of pollution are presented.

Accuracy and Precision of USNO GPS Carrier-Phase Time Transfer

DTIC Science & Technology

2010-01-01

values. Comparison measures used include estimates obtained from two-way satellite time/frequency transfer ( TWSTFT ), and GPS-based estimates obtained...the IGS are used as a benchmark in the computation. Frequency values have a few times 10 -15 fractional frequency uncertainty. TWSTFT values confirm...obtained from two-way satellite time/frequency transfer ( TWSTFT ), BIPM Circular T, and the International GNSS Service (IGS). At present, it is known that

The Intertemporal Stability of Teacher Effect Estimates. Working Paper 2008-22

ERIC Educational Resources Information Center

McCaffrey, Daniel F.; Sass, Tim R.; Lockwood, J.R.

2008-01-01

Recently, a number of school districts have begun using measures of teachers' contributions to student test scores or teacher "value added" to determine salaries and other monetary rewards. In this paper we investigate the precision of value-added measures by analyzing their inter-temporal stability. We find that these measures of…