Sample records for labelling improves reproducibility

  1. Label-free protein quantification using LC-coupled ion trap or FT mass spectrometry: Reproducibility, linearity, and application with complex proteomes.

    PubMed

    Wang, Guanghui; Wu, Wells W; Zeng, Weihua; Chou, Chung-Lin; Shen, Rong-Fong

    2006-05-01

    A critical step in protein biomarker discovery is the ability to contrast proteomes, a process referred generally as quantitative proteomics. While stable-isotope labeling (e.g., ICAT, 18O- or 15N-labeling, or AQUA) remains the core technology used in mass spectrometry-based proteomic quantification, increasing efforts have been directed to the label-free approach that relies on direct comparison of peptide peak areas between LC-MS runs. This latter approach is attractive to investigators for its simplicity as well as cost effectiveness. In the present study, the reproducibility and linearity of using a label-free approach to highly complex proteomes were evaluated. Various amounts of proteins from different proteomes were subjected to repeated LC-MS analyses using an ion trap or Fourier transform mass spectrometer. Highly reproducible data were obtained between replicated runs, as evidenced by nearly ideal Pearson's correlation coefficients (for ion's peak areas or retention time) and average peak area ratios. In general, more than 50% and nearly 90% of the peptide ion ratios deviated less than 10% and 20%, respectively, from the average in duplicate runs. In addition, the multiplicity ratios of the amounts of proteins used correlated nicely with the observed averaged ratios of peak areas calculated from detected peptides. Furthermore, the removal of abundant proteins from the samples led to an improvement in reproducibility and linearity. A computer program has been written to automate the processing of data sets from experiments with groups of multiple samples for statistical analysis. Algorithms for outlier-resistant mean estimation and for adjusting statistical significance threshold in multiplicity of testing were incorporated to minimize the rate of false positives. The program was applied to quantify changes in proteomes of parental and p53-deficient HCT-116 human cells and found to yield reproducible results. Overall, this study demonstrates an alternative

  2. Comparing the Ability of Enhanced Sampling Molecular Dynamics Methods To Reproduce the Behavior of Fluorescent Labels on Proteins.

    PubMed

    Walczewska-Szewc, Katarzyna; Deplazes, Evelyne; Corry, Ben

    2015-07-14

    Adequately sampling the large number of conformations accessible to proteins and other macromolecules is one of the central challenges in molecular dynamics (MD) simulations; this activity can be difficult, even for relatively simple systems. An example where this problem arises is in the simulation of dye-labeled proteins, which are now being widely used in the design and interpretation of Förster resonance energy transfer (FRET) experiments. In this study, MD simulations are used to characterize the motion of two commonly used FRET dyes attached to an immobilized chain of polyproline. Even in this simple system, the dyes exhibit complex behavior that is a mixture of fast and slow motions. Consequently, very long MD simulations are required to sufficiently sample the entire range of dye motion. Here, we compare the ability of enhanced sampling methods to reproduce the behavior of fluorescent labels on proteins. In particular, we compared Accelerated Molecular Dynamics (AMD), metadynamics, Replica Exchange Molecular Dynamics (REMD), and High Temperature Molecular Dynamics (HTMD) to equilibrium MD simulations. We find that, in our system, all of these methods improve the sampling of the dye motion, but the most significant improvement is achieved using REMD.

  3. Highly Reproducible Label Free Quantitative Proteomic Analysis of RNA Polymerase Complexes*

    PubMed Central

    Mosley, Amber L.; Sardiu, Mihaela E.; Pattenden, Samantha G.; Workman, Jerry L.; Florens, Laurence; Washburn, Michael P.

    2011-01-01

    The use of quantitative proteomics methods to study protein complexes has the potential to provide in-depth information on the abundance of different protein components as well as their modification state in various cellular conditions. To interrogate protein complex quantitation using shotgun proteomic methods, we have focused on the analysis of protein complexes using label-free multidimensional protein identification technology and studied the reproducibility of biological replicates. For these studies, we focused on three highly related and essential multi-protein enzymes, RNA polymerase I, II, and III from Saccharomyces cerevisiae. We found that label-free quantitation using spectral counting is highly reproducible at the protein and peptide level when analyzing RNA polymerase I, II, and III. In addition, we show that peptide sampling does not follow a random sampling model, and we show the need for advanced computational models to predict peptide detection probabilities. In order to address these issues, we used the APEX protocol to model the expected peptide detectability based on whole cell lysate acquired using the same multidimensional protein identification technology analysis used for the protein complexes. Neither method was able to predict the peptide sampling levels that we observed using replicate multidimensional protein identification technology analyses. In addition to the analysis of the RNA polymerase complexes, our analysis provides quantitative information about several RNAP associated proteins including the RNAPII elongation factor complexes DSIF and TFIIF. Our data shows that DSIF and TFIIF are the most highly enriched RNAP accessory factors in Rpb3-TAP purifications and demonstrate our ability to measure low level associated protein abundance across biological replicates. In addition, our quantitative data supports a model in which DSIF and TFIIF interact with RNAPII in a dynamic fashion in agreement with previously published reports. PMID

  4. Systematic Comparison of Label-Free, Metabolic Labeling, and Isobaric Chemical Labeling for Quantitative Proteomics on LTQ Orbitrap Velos

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

    Li, Zhou; Adams, Rachel M; Chourey, Karuna

    2012-01-01

    A variety of quantitative proteomics methods have been developed, including label-free, metabolic labeling, and isobaric chemical labeling using iTRAQ or TMT. Here, these methods were compared in terms of the depth of proteome coverage, quantification accuracy, precision, and reproducibility using a high-performance hybrid mass spectrometer, LTQ Orbitrap Velos. Our results show that (1) the spectral counting method provides the deepest proteome coverage for identification, but its quantification performance is worse than labeling-based approaches, especially the quantification reproducibility; (2) metabolic labeling and isobaric chemical labeling are capable of accurate, precise, and reproducible quantification and provide deep proteome coverage for quantification. Isobaricmore » chemical labeling surpasses metabolic labeling in terms of quantification precision and reproducibility; (3) iTRAQ and TMT perform similarly in all aspects compared in the current study using a CID-HCD dual scan configuration. Based on the unique advantages of each method, we provide guidance for selection of the appropriate method for a quantitative proteomics study.« less

  5. The quest for improved reproducibility in MALDI mass spectrometry.

    PubMed

    O'Rourke, Matthew B; Djordjevic, Steven P; Padula, Matthew P

    2018-03-01

    Reproducibility has been one of the biggest hurdles faced when attempting to develop quantitative protocols for MALDI mass spectrometry. The heterogeneous nature of sample recrystallization has made automated sample acquisition somewhat "hit and miss" with manual intervention needed to ensure that all sample spots have been analyzed. In this review, we explore the last 30 years of literature and anecdotal evidence that has attempted to address and improve reproducibility in MALDI MS. Though many methods have been attempted, we have discovered a significant publication history surrounding the use of nitrocellulose as a substrate to improve homogeneity of crystal formation and therefore reproducibility. We therefore propose that this is the most promising avenue of research for developing a comprehensive and universal preparation protocol for quantitative MALDI MS analysis. © 2016 Wiley Periodicals, Inc. Mass Spec Rev 37:217-228, 2018. © 2016 Wiley Periodicals, Inc.

  6. Inter-Vendor Reproducibility of Pseudo-Continuous Arterial Spin Labeling at 3 Tesla

    PubMed Central

    Mutsaerts, Henri J. M. M.; Steketee, Rebecca M. E.; Heijtel, Dennis F. R.; Kuijer, Joost P. A.; van Osch, Matthias J. P.; Majoie, Charles B. L. M.; Smits, Marion; Nederveen, Aart J.

    2014-01-01

    Purpose Prior to the implementation of arterial spin labeling (ASL) in clinical multi-center studies, it is important to establish its status quo inter-vendor reproducibility. This study evaluates and compares the intra- and inter-vendor reproducibility of pseudo-continuous ASL (pCASL) as clinically implemented by GE and Philips. Material and Methods 22 healthy volunteers were scanned twice on both a 3T GE and a 3T Philips scanner. The main difference in implementation between the vendors was the readout module: spiral 3D fast spin echo vs. 2D gradient-echo echo-planar imaging respectively. Mean and variation of cerebral blood flow (CBF) were compared for the total gray matter (GM) and white matter (WM), and on a voxel-level. Results Whereas the mean GM CBF of both vendors was almost equal (p = 1.0), the mean WM CBF was significantly different (p<0.01). The inter-vendor GM variation did not differ from the intra-vendor GM variation (p = 0.3 and p = 0.5 for GE and Philips respectively). Spatial inter-vendor CBF and variation differences were observed in several GM regions and in the WM. Conclusion These results show that total GM CBF-values can be exchanged between vendors. For the inter-vendor comparison of GM regions or WM, these results encourage further standardization of ASL implementation among vendors. PMID:25090654

  7. Inter-vendor reproducibility of pseudo-continuous arterial spin labeling at 3 Tesla.

    PubMed

    Mutsaerts, Henri J M M; Steketee, Rebecca M E; Heijtel, Dennis F R; Kuijer, Joost P A; van Osch, Matthias J P; Majoie, Charles B L M; Smits, Marion; Nederveen, Aart J

    2014-01-01

    Prior to the implementation of arterial spin labeling (ASL) in clinical multi-center studies, it is important to establish its status quo inter-vendor reproducibility. This study evaluates and compares the intra- and inter-vendor reproducibility of pseudo-continuous ASL (pCASL) as clinically implemented by GE and Philips. 22 healthy volunteers were scanned twice on both a 3T GE and a 3T Philips scanner. The main difference in implementation between the vendors was the readout module: spiral 3D fast spin echo vs. 2D gradient-echo echo-planar imaging respectively. Mean and variation of cerebral blood flow (CBF) were compared for the total gray matter (GM) and white matter (WM), and on a voxel-level. Whereas the mean GM CBF of both vendors was almost equal (p = 1.0), the mean WM CBF was significantly different (p<0.01). The inter-vendor GM variation did not differ from the intra-vendor GM variation (p = 0.3 and p = 0.5 for GE and Philips respectively). Spatial inter-vendor CBF and variation differences were observed in several GM regions and in the WM. These results show that total GM CBF-values can be exchanged between vendors. For the inter-vendor comparison of GM regions or WM, these results encourage further standardization of ASL implementation among vendors.

  8. Improved estimates of fixed reproducible tangible wealth, 1929-95

    DOT National Transportation Integrated Search

    1997-05-01

    This article presents revised estimates of the value of fixed reproducible tangible wealth in the United States for 192995; these estimates incorporate the definitional and statistical : improvements introduced in last years comprehensive revis...

  9. Improved specificity of hippocampal memory trace labeling.

    PubMed

    Cazzulino, Alejandro S; Martinez, Randy; Tomm, Nicole K; Denny, Christine A

    2016-06-01

    Recent studies have focused on the identification and manipulation of memory traces in rodent models. The two main mouse models utilized are either a CreER(T2) /loxP tamoxifen (TAM)- or a tetracycline transactivator/tetracycline-response element doxycycline-inducible system. These systems, however, could be improved to label a more specific population of activated neurons corresponding to behavior. Here, we sought to identify an improved selective estrogen receptor (ER) modulator (SERM) in which we could label an individual memory trace in ArcCreER(T2) mice. We found that 4-hydroxytamoxifen (4-OHT) is a selective SERM in the ArcCreER(T2) × Rosa26-CAG-stop(flox) -channelrhodospin (ChR2)-enhanced yellow fluorescent protein (eYFP) mice. The half-life of 4-OHT is shorter than TAM, allowing for more specificity of memory trace labeling. Furthermore, 4-OHT allowed for context-specific labeling in the dentate gyrus and CA3. In summary, we believe that 4-OHT improves the specificity of memory trace labeling and will allow for refined memory trace studies in the future. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  10. Bad Behavior: Improving Reproducibility in Behavior Testing.

    PubMed

    Andrews, Anne M; Cheng, Xinyi; Altieri, Stefanie C; Yang, Hongyan

    2018-01-24

    Systems neuroscience research is increasingly possible through the use of integrated molecular and circuit-level analyses. These studies depend on the use of animal models and, in many cases, molecular and circuit-level analyses. Associated with genetic, pharmacologic, epigenetic, and other types of environmental manipulations. We illustrate typical pitfalls resulting from poor validation of behavior tests. We describe experimental designs and enumerate controls needed to improve reproducibility in investigating and reporting of behavioral phenotypes.

  11. Respiratory effort correction strategies to improve the reproducibility of lung expansion measurements

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

    Du, Kaifang; Reinhardt, Joseph M.; Christensen, Gary E.

    2013-12-15

    Purpose: Four-dimensional computed tomography (4DCT) can be used to make measurements of pulmonary function longitudinally. The sensitivity of such measurements to identify change depends on measurement uncertainty. Previously, intrasubject reproducibility of Jacobian-based measures of lung tissue expansion was studied in two repeat prior-RT 4DCT human acquisitions. Difference in respiratory effort such as breathing amplitude and frequency may affect longitudinal function assessment. In this study, the authors present normalization schemes that correct ventilation images for variations in respiratory effort and assess the reproducibility improvement after effort correction.Methods: Repeat 4DCT image data acquired within a short time interval from 24 patients priormore » to radiation therapy (RT) were used for this analysis. Using a tissue volume preserving deformable image registration algorithm, Jacobian ventilation maps in two scanning sessions were computed and compared on the same coordinate for reproducibility analysis. In addition to computing the ventilation maps from end expiration to end inspiration, the authors investigated the effort normalization strategies using other intermediated inspiration phases upon the principles of equivalent tidal volume (ETV) and equivalent lung volume (ELV). Scatter plots and mean square error of the repeat ventilation maps and the Jacobian ratio map were generated for four conditions: no effort correction, global normalization, ETV, and ELV. In addition, gamma pass rate was calculated from a modified gamma index evaluation between two ventilation maps, using acceptance criterions of 2 mm distance-to-agreement and 5% ventilation difference.Results: The pattern of regional pulmonary ventilation changes as lung volume changes. All effort correction strategies improved reproducibility when changes in respiratory effort were greater than 150 cc (p < 0.005 with regard to the gamma pass rate). Improvement of reproducibility was

  12. A Practical Guide for Improving Transparency and Reproducibility in Neuroimaging Research

    PubMed Central

    Poldrack, Russell A.

    2016-01-01

    Recent years have seen an increase in alarming signals regarding the lack of replicability in neuroscience, psychology, and other related fields. To avoid a widespread crisis in neuroimaging research and consequent loss of credibility in the public eye, we need to improve how we do science. This article aims to be a practical guide for researchers at any stage of their careers that will help them make their research more reproducible and transparent while minimizing the additional effort that this might require. The guide covers three major topics in open science (data, code, and publications) and offers practical advice as well as highlighting advantages of adopting more open research practices that go beyond improved transparency and reproducibility. PMID:27389358

  13. Measurement of arterial transit time and renal blood flow using pseudocontinuous ASL MRI with multiple post-labeling delays: Feasibility, reproducibility, and variation.

    PubMed

    Kim, Dong Won; Shim, Woo Hyun; Yoon, Seong Kuk; Oh, Jong Yeong; Kim, Jeong Kon; Jung, Hoesu; Matsuda, Tsuyoshi; Kim, Dongeun

    2017-09-01

    To evaluate the feasibility, reproducibility, and variation of renal perfusion and arterial transit time (ATT) using pseudocontinuous arterial spin labeling magnetic resonance imaging (PCASL MRI) in healthy volunteers. PCASL MRI at 3T was performed in 25 healthy volunteers on two different occasions. The ATT and ATT-corrected renal blood flow (ATT-cRBF) were calculated at four different post-labeling delay points (0.5, 1.0, 1.5, and 2.0 s) and evaluated for each kidney and subject. The intraclass correlation (ICC) and Bland-Altman plot were used to assess the reproducibility of the PCASL MRI technique. The within-subject coefficient of variance was determined. Results were obtained for 46 kidneys of 23 subjects with a mean age of 38.6 ± 9.8 years and estimated glomerular filtration rate (eGFR) of 89.1 ± 21.2 ml/min/1.73 m 2 . Two subjects failed in the ASL MRI examination. The mean cortical and medullary ATT-cRBF for the subjects were 215 ± 65 and 81 ± 21 ml/min/100 g, respectively, and the mean cortical and medullary ATT were 1141 ± 262 and 1123 ± 245 msec, correspondingly. The ICC for the cortical ATT-cRBF was 0.927 and the within-subject coefficient of variance was 14.4%. The ICCs for the medullary ATT-cRBF and the cortical and medullary ATT were poor. The Bland-Altman plot for cortical RBF showed good agreement between the two measurements. PCASL MRI is a feasible and reproducible method for measuring renal cortical perfusion. In contrast, ATT for the renal cortex and medulla has poor reproducibility and high variation. 2 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:813-819. © 2017 International Society for Magnetic Resonance in Medicine.

  14. The QUASAR reproducibility study, Part II: Results from a multi center Arterial Spin Labeling test-retest Study

    PubMed Central

    Petersen, Esben Thade; Mouridsen, Kim; Golay, Xavier

    2009-01-01

    Arterial Spin Labeling (ASL) is a method to measure perfusion using magnetically labeled blood water as an endogenous tracer. Being fully non-invasive, this technique is attractive for longitudinal studies of cerebral blood flow in healthy and diseased individuals, or as a surrogate marker of metabolism. So far, ASL has been restricted mostly to specialist centers due to a generally low SNR of the method and potential issues with user-dependent analysis needed to obtain quantitative measurement of cerebral blood flow (CBF). Here, we evaluated a particular implementation of ASL (called Quantitative STAR labeling of Arterial Regions or QUASAR), a method providing user independent quantification of CBF in a large test-retest study across sites from around the world, dubbed “The QUASAR reproducibility study”. Altogether, 28 sites located in Asia, Europe and North America participated and a total of 284 healthy volunteers were scanned. Minimal operator dependence was assured by using an automatic planning tool and its accuracy and potential usefulness in multi-center trials was evaluated as well. Accurate repositioning between sessions was achieved with the automatic planning tool showing mean displacements of 1.87±0.95mm and rotations of 1.56±0.66°. Mean gray matter CBF was 47.4±7.5 [ml/100g/min] with a between subject standard variation SDb = 5.5 [ml/100g/min] and a within subject standard deviation SDw = 4.7 [ml/100g/min]. The corresponding repeatability was 13.0 [ml/100g/min] and was found to be within the range of previous studies. PMID:19660557

  15. The QUASAR reproducibility study, Part II: Results from a multi-center Arterial Spin Labeling test-retest study.

    PubMed

    Petersen, Esben Thade; Mouridsen, Kim; Golay, Xavier

    2010-01-01

    Arterial Spin Labeling (ASL) is a method to measure perfusion using magnetically labeled blood water as an endogenous tracer. Being fully non-invasive, this technique is attractive for longitudinal studies of cerebral blood flow in healthy and diseased individuals, or as a surrogate marker of metabolism. So far, ASL has been restricted mostly to specialist centers due to a generally low SNR of the method and potential issues with user-dependent analysis needed to obtain quantitative measurement of cerebral blood flow (CBF). Here, we evaluated a particular implementation of ASL (called Quantitative STAR labeling of Arterial Regions or QUASAR), a method providing user independent quantification of CBF in a large test-retest study across sites from around the world, dubbed "The QUASAR reproducibility study". Altogether, 28 sites located in Asia, Europe and North America participated and a total of 284 healthy volunteers were scanned. Minimal operator dependence was assured by using an automatic planning tool and its accuracy and potential usefulness in multi-center trials was evaluated as well. Accurate repositioning between sessions was achieved with the automatic planning tool showing mean displacements of 1.87+/-0.95 mm and rotations of 1.56+/-0.66 degrees . Mean gray matter CBF was 47.4+/-7.5 [ml/100 g/min] with a between-subject standard variation SD(b)=5.5 [ml/100 g/min] and a within-subject standard deviation SD(w)=4.7 [ml/100 g/min]. The corresponding repeatability was 13.0 [ml/100 g/min] and was found to be within the range of previous studies.

  16. Reproducibility in science: improving the standard for basic and preclinical research.

    PubMed

    Begley, C Glenn; Ioannidis, John P A

    2015-01-02

    Medical and scientific advances are predicated on new knowledge that is robust and reliable and that serves as a solid foundation on which further advances can be built. In biomedical research, we are in the midst of a revolution with the generation of new data and scientific publications at a previously unprecedented rate. However, unfortunately, there is compelling evidence that the majority of these discoveries will not stand the test of time. To a large extent, this reproducibility crisis in basic and preclinical research may be as a result of failure to adhere to good scientific practice and the desperation to publish or perish. This is a multifaceted, multistakeholder problem. No single party is solely responsible, and no single solution will suffice. Here we review the reproducibility problems in basic and preclinical biomedical research, highlight some of the complexities, and discuss potential solutions that may help improve research quality and reproducibility. © 2015 American Heart Association, Inc.

  17. Reproducibility of the vertical dimension of occlusion with an improved measuring gauge.

    PubMed

    Morikawa, M; Kozono, Y; Noguchi, B S; Toyoda, S

    1988-07-01

    An improved gauge using an eyeglass frame, the TOM gauge, was devised. The reproducibility of the record of vertical dimension with this gauge was evaluated through repeated measurements on subjects having a definite centric stop with the natural dentition. Because of the stabilization provided by the frame and the reference point on the apex nasi, the TOM gauge showed excellent reproducibility of the record compared with the conventional gauges. The TOM gauge can be expected to significantly reduce the risk of errors in measuring the vertical dimension of occlusion especially in complete denture fabrication.

  18. PSEA-Quant: a protein set enrichment analysis on label-free and label-based protein quantification data.

    PubMed

    Lavallée-Adam, Mathieu; Rauniyar, Navin; McClatchy, Daniel B; Yates, John R

    2014-12-05

    The majority of large-scale proteomics quantification methods yield long lists of quantified proteins that are often difficult to interpret and poorly reproduced. Computational approaches are required to analyze such intricate quantitative proteomics data sets. We propose a statistical approach to computationally identify protein sets (e.g., Gene Ontology (GO) terms) that are significantly enriched with abundant proteins with reproducible quantification measurements across a set of replicates. To this end, we developed PSEA-Quant, a protein set enrichment analysis algorithm for label-free and label-based protein quantification data sets. It offers an alternative approach to classic GO analyses, models protein annotation biases, and allows the analysis of samples originating from a single condition, unlike analogous approaches such as GSEA and PSEA. We demonstrate that PSEA-Quant produces results complementary to GO analyses. We also show that PSEA-Quant provides valuable information about the biological processes involved in cystic fibrosis using label-free protein quantification of a cell line expressing a CFTR mutant. Finally, PSEA-Quant highlights the differences in the mechanisms taking place in the human, rat, and mouse brain frontal cortices based on tandem mass tag quantification. Our approach, which is available online, will thus improve the analysis of proteomics quantification data sets by providing meaningful biological insights.

  19. PSEA-Quant: A Protein Set Enrichment Analysis on Label-Free and Label-Based Protein Quantification Data

    PubMed Central

    2015-01-01

    The majority of large-scale proteomics quantification methods yield long lists of quantified proteins that are often difficult to interpret and poorly reproduced. Computational approaches are required to analyze such intricate quantitative proteomics data sets. We propose a statistical approach to computationally identify protein sets (e.g., Gene Ontology (GO) terms) that are significantly enriched with abundant proteins with reproducible quantification measurements across a set of replicates. To this end, we developed PSEA-Quant, a protein set enrichment analysis algorithm for label-free and label-based protein quantification data sets. It offers an alternative approach to classic GO analyses, models protein annotation biases, and allows the analysis of samples originating from a single condition, unlike analogous approaches such as GSEA and PSEA. We demonstrate that PSEA-Quant produces results complementary to GO analyses. We also show that PSEA-Quant provides valuable information about the biological processes involved in cystic fibrosis using label-free protein quantification of a cell line expressing a CFTR mutant. Finally, PSEA-Quant highlights the differences in the mechanisms taking place in the human, rat, and mouse brain frontal cortices based on tandem mass tag quantification. Our approach, which is available online, will thus improve the analysis of proteomics quantification data sets by providing meaningful biological insights. PMID:25177766

  20. On the Reproducibility of Label-Free Quantitative Cross-Linking/Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Müller, Fränze; Fischer, Lutz; Chen, Zhuo Angel; Auchynnikava, Tania; Rappsilber, Juri

    2018-02-01

    Quantitative cross-linking/mass spectrometry (QCLMS) is an emerging approach to study conformational changes of proteins and multi-subunit complexes. Distinguishing protein conformations requires reproducibly identifying and quantifying cross-linked peptides. Here we analyzed the variation between multiple cross-linking reactions using bis[sulfosuccinimidyl] suberate (BS3)-cross-linked human serum albumin (HSA) and evaluated how reproducible cross-linked peptides can be identified and quantified by LC-MS analysis. To make QCLMS accessible to a broader research community, we developed a workflow that integrates the established software tools MaxQuant for spectra preprocessing, Xi for cross-linked peptide identification, and finally Skyline for quantification (MS1 filtering). Out of the 221 unique residue pairs identified in our sample, 124 were subsequently quantified across 10 analyses with coefficient of variation (CV) values of 14% (injection replica) and 32% (reaction replica). Thus our results demonstrate that the reproducibility of QCLMS is in line with the reproducibility of general quantitative proteomics and we establish a robust workflow for MS1-based quantitation of cross-linked peptides.

  1. The Need for Reproducibility

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

    Robey, Robert W.

    2016-06-27

    The purpose of this presentation is to consider issues of reproducibility, specifically it determines whether bitwise reproducible computation is possible, if computational research in DOE improves its publication process, and if reproducible results can be achieved apart from the peer review process?

  2. Assessing the reproducibility of discriminant function analyses

    PubMed Central

    Andrew, Rose L.; Albert, Arianne Y.K.; Renaut, Sebastien; Rennison, Diana J.; Bock, Dan G.

    2015-01-01

    Data are the foundation of empirical research, yet all too often the datasets underlying published papers are unavailable, incorrect, or poorly curated. This is a serious issue, because future researchers are then unable to validate published results or reuse data to explore new ideas and hypotheses. Even if data files are securely stored and accessible, they must also be accompanied by accurate labels and identifiers. To assess how often problems with metadata or data curation affect the reproducibility of published results, we attempted to reproduce Discriminant Function Analyses (DFAs) from the field of organismal biology. DFA is a commonly used statistical analysis that has changed little since its inception almost eight decades ago, and therefore provides an opportunity to test reproducibility among datasets of varying ages. Out of 100 papers we initially surveyed, fourteen were excluded because they did not present the common types of quantitative result from their DFA or gave insufficient details of their DFA. Of the remaining 86 datasets, there were 15 cases for which we were unable to confidently relate the dataset we received to the one used in the published analysis. The reasons ranged from incomprehensible or absent variable labels, the DFA being performed on an unspecified subset of the data, or the dataset we received being incomplete. We focused on reproducing three common summary statistics from DFAs: the percent variance explained, the percentage correctly assigned and the largest discriminant function coefficient. The reproducibility of the first two was fairly high (20 of 26, and 44 of 60 datasets, respectively), whereas our success rate with the discriminant function coefficients was lower (15 of 26 datasets). When considering all three summary statistics, we were able to completely reproduce 46 (65%) of 71 datasets. While our results show that a majority of studies are reproducible, they highlight the fact that many studies still are not the

  3. An Interactive User Interface for Drug Labeling to Improve Readability and Decision-Making.

    PubMed

    Abedtash, Hamed; Duke, Jon D

    FDA-approved prescribing information (also known as product labeling or labels) contain critical safety information for health care professionals. Drug labels have often been criticized, however, for being overly complex, difficult to read, and rife with overwarning, leading to high cognitive load. In this project, we aimed to improve the usability of drug labels by increasing the 'signal-to-noise ratio' and providing meaningful information to care providers based on patient-specific comorbidities and concomitant medications. In the current paper, we describe the design process and resulting web application, known as myDrugLabel. Using the Structured Product Label documents as a base, we describe the process of label personalization, readability improvements, and integration of diverse evidence sources, including the medical literature from PubMed, pharmacovigilance reports from FDA adverse event reporting system (FAERS), and social media signals directly into the label.

  4. The effect of column purification on cDNA indirect labelling for microarrays

    PubMed Central

    Molas, M Lia; Kiss, John Z

    2007-01-01

    Background The success of the microarray reproducibility is dependent upon the performance of standardized procedures. Since the introduction of microarray technology for the analysis of global gene expression, reproducibility of results among different laboratories has been a major problem. Two of the main contributors to this variability are the use of different microarray platforms and different laboratory practices. In this paper, we address the latter question in terms of how variation in one of the steps of a labelling procedure affects the cDNA product prior to microarray hybridization. Results We used a standard procedure to label cDNA for microarray hybridization and employed different types of column chromatography for cDNA purification. After purifying labelled cDNA, we used the Agilent 2100 Bioanalyzer and agarose gel electrophoresis to assess the quality of the labelled cDNA before its hybridization onto a microarray platform. There were major differences in the cDNA profile (i.e. cDNA fragment lengths and abundance) as a result of using four different columns for purification. In addition, different columns have different efficiencies to remove rRNA contamination. This study indicates that the appropriate column to use in this type of protocol has to be experimentally determined. Finally, we present new evidence establishing the importance of testing the method of purification used during an indirect labelling procedure. Our results confirm the importance of assessing the quality of the sample in the labelling procedure prior to hybridization onto a microarray platform. Conclusion Standardization of column purification systems to be used in labelling procedures will improve the reproducibility of microarray results among different laboratories. In addition, implementation of a quality control check point of the labelled samples prior to microarray hybridization will prevent hybridizing a poor quality sample to expensive micorarrays. PMID:17597522

  5. The effect of column purification on cDNA indirect labelling for microarrays.

    PubMed

    Molas, M Lia; Kiss, John Z

    2007-06-27

    The success of the microarray reproducibility is dependent upon the performance of standardized procedures. Since the introduction of microarray technology for the analysis of global gene expression, reproducibility of results among different laboratories has been a major problem. Two of the main contributors to this variability are the use of different microarray platforms and different laboratory practices. In this paper, we address the latter question in terms of how variation in one of the steps of a labelling procedure affects the cDNA product prior to microarray hybridization. We used a standard procedure to label cDNA for microarray hybridization and employed different types of column chromatography for cDNA purification. After purifying labelled cDNA, we used the Agilent 2100 Bioanalyzer and agarose gel electrophoresis to assess the quality of the labelled cDNA before its hybridization onto a microarray platform. There were major differences in the cDNA profile (i.e. cDNA fragment lengths and abundance) as a result of using four different columns for purification. In addition, different columns have different efficiencies to remove rRNA contamination. This study indicates that the appropriate column to use in this type of protocol has to be experimentally determined. Finally, we present new evidence establishing the importance of testing the method of purification used during an indirect labelling procedure. Our results confirm the importance of assessing the quality of the sample in the labelling procedure prior to hybridization onto a microarray platform. Standardization of column purification systems to be used in labelling procedures will improve the reproducibility of microarray results among different laboratories. In addition, implementation of a quality control check point of the labelled samples prior to microarray hybridization will prevent hybridizing a poor quality sample to expensive micorarrays.

  6. An effect size filter improves the reproducibility in spectral counting-based comparative proteomics.

    PubMed

    Gregori, Josep; Villarreal, Laura; Sánchez, Alex; Baselga, José; Villanueva, Josep

    2013-12-16

    The microarray community has shown that the low reproducibility observed in gene expression-based biomarker discovery studies is partially due to relying solely on p-values to get the lists of differentially expressed genes. Their conclusions recommended complementing the p-value cutoff with the use of effect-size criteria. The aim of this work was to evaluate the influence of such an effect-size filter on spectral counting-based comparative proteomic analysis. The results proved that the filter increased the number of true positives and decreased the number of false positives and the false discovery rate of the dataset. These results were confirmed by simulation experiments where the effect size filter was used to evaluate systematically variable fractions of differentially expressed proteins. Our results suggest that relaxing the p-value cut-off followed by a post-test filter based on effect size and signal level thresholds can increase the reproducibility of statistical results obtained in comparative proteomic analysis. Based on our work, we recommend using a filter consisting of a minimum absolute log2 fold change of 0.8 and a minimum signal of 2-4 SpC on the most abundant condition for the general practice of comparative proteomics. The implementation of feature filtering approaches could improve proteomic biomarker discovery initiatives by increasing the reproducibility of the results obtained among independent laboratories and MS platforms. Quality control analysis of microarray-based gene expression studies pointed out that the low reproducibility observed in the lists of differentially expressed genes could be partially attributed to the fact that these lists are generated relying solely on p-values. Our study has established that the implementation of an effect size post-test filter improves the statistical results of spectral count-based quantitative proteomics. The results proved that the filter increased the number of true positives whereas decreased

  7. A randomized trial of a brief multimedia intervention to improve comprehension of food labels.

    PubMed

    Jay, Melanie; Adams, Jennifer; Herring, Sharon J; Gillespie, Colleen; Ark, Tavinder; Feldman, Henry; Jones, Vicky; Zabar, Sondra; Stevens, David; Kalet, Adina

    2009-01-01

    Food label use is associated with better food choices, an essential part of the management of many chronic diseases. Previous studies suggest lack of comprehension of food labels. We studied a multimedia intervention to improve food label comprehension in a sample of low income patients in New York City. This randomized study took place at Gouverneur Healthcare Services from 2005 until 2007. The intervention group (n=29) received a Nutrition Facts Label pocket card and viewed a video explaining card use. The control group (n=27) received written materials. Participants completed a 12-item pre- and post-intervention nutrition food label quiz. Quiz scores were analyzed using repeated measures analysis of variance. The intervention group had greater improvement on the quiz than the control group (p<0.001). There was a three way interaction by time with health literacy and treatment group where the greatest improvement occurred in patients with adequate health literacy in the intervention group (p<0.05). There was no improvement in patients with limited health literacy. A multimedia intervention is an effective way to improve short-term food label comprehension in patients with adequate health literacy. Further research is necessary to improve understanding of food labels in patients with limited health literacy.

  8. Robust tissue classification for reproducible wound assessment in telemedicine environments

    NASA Astrophysics Data System (ADS)

    Wannous, Hazem; Treuillet, Sylvie; Lucas, Yves

    2010-04-01

    In telemedicine environments, a standardized and reproducible assessment of wounds, using a simple free-handled digital camera, is an essential requirement. However, to ensure robust tissue classification, particular attention must be paid to the complete design of the color processing chain. We introduce the key steps including color correction, merging of expert labeling, and segmentation-driven classification based on support vector machines. The tool thus developed ensures stability under lighting condition, viewpoint, and camera changes, to achieve accurate and robust classification of skin tissues. Clinical tests demonstrate that such an advanced tool, which forms part of a complete 3-D and color wound assessment system, significantly improves the monitoring of the healing process. It achieves an overlap score of 79.3 against 69.1% for a single expert, after mapping on the medical reference developed from the image labeling by a college of experts.

  9. An Interactive User Interface for Drug Labeling to Improve Readability and Decision-Making

    PubMed Central

    Abedtash, Hamed; Duke, Jon D.

    2015-01-01

    FDA-approved prescribing information (also known as product labeling or labels) contain critical safety information for health care professionals. Drug labels have often been criticized, however, for being overly complex, difficult to read, and rife with overwarning, leading to high cognitive load. In this project, we aimed to improve the usability of drug labels by increasing the ‘signal-to-noise ratio’ and providing meaningful information to care providers based on patient-specific comorbidities and concomitant medications. In the current paper, we describe the design process and resulting web application, known as myDrugLabel. Using the Structured Product Label documents as a base, we describe the process of label personalization, readability improvements, and integration of diverse evidence sources, including the medical literature from PubMed, pharmacovigilance reports from FDA adverse event reporting system (FAERS), and social media signals directly into the label. PMID:26958158

  10. Rapid in vitro labeling procedures for two-dimensional gel fingerprinting

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

    Lee, Y.F.; Fowlks, E.R.

    1982-01-15

    Improvements of existing in vitro procedures for labeling RNA radioactively, and modifications of the two-dimensional polyacrylamide gel electrophoresis system for making RNA fingerprints are described. These improvements are (a) inactivation of phosphatase with nitric acid at pH 2.0 eliminated the phenol-cholorform extraction step during 5'-end labeling with polynucleotide kinase and (..gamma..-/sup 32/P)ATP; (b) ZnSO/sub 4/ inactivation of R Nase T/sub 1/ results in a highly efficient procedure for 3'-end labeling with T4 ligase and (5'-/sup 32/P)pCp; and (c) a rapid 4-min procedure for variable quantity range of /sup 125/I and RNA results in a qualitative and quantitative sample for high-molecularmore » weight RNA fingerprinting. Thus, these in vitro procedures become rapid and reproducible when combined with two-dimensional gel electrophoresis which eliminates simultaneously labeled impurities. Each labeling procedure is compared, using tobacco mosaic virus, Brome mosaic virus, and polio RNA. A series of Ap-rich oligonucleotides was discovered in the inner genome of Brome mosaic Virus RNA-3.« less

  11. Enhancing reproducibility: Failures from Reproducibility Initiatives underline core challenges.

    PubMed

    Mullane, Kevin; Williams, Michael

    2017-08-15

    Efforts to address reproducibility concerns in biomedical research include: initiatives to improve journal publication standards and peer review; increased attention to publishing methodological details that enable experiments to be reconstructed; guidelines on standards for study design, implementation, analysis and execution; meta-analyses of multiple studies within a field to synthesize a common conclusion and; the formation of consortia to adopt uniform protocols and internally reproduce data. Another approach to addressing reproducibility are Reproducibility Initiatives (RIs), well-intended, high-profile, systematically peer-vetted initiatives that are intended to replace the traditional process of scientific self-correction. Outcomes from the RIs reported to date have questioned the usefulness of this approach, particularly when the RI outcome differs from other independent self-correction studies that have reproduced the original finding. As a failed RI attempt is a single outcome distinct from the original study, it cannot provide any definitive conclusions necessitating additional studies that the RI approach has neither the ability nor intent of conducting making it a questionable replacement for self-correction. A failed RI attempt also has the potential to damage the reputation of the author of the original finding. Reproduction is frequently confused with replication, an issue that is more than semantic with the former denoting "similarity" and the latter an "exact copy" - an impossible outcome in research because of known and unknown technical, environmental and motivational differences between the original and reproduction studies. To date, the RI framework has negatively impacted efforts to improve reproducibility, confounding attempts to determine whether a research finding is real. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Do nutrition labels improve dietary outcomes?

    PubMed

    Variyam, Jayachandran N

    2008-06-01

    The disclosure of nutritional characteristics of most packaged foods became mandatory in the United States with the implementation of the Nutrition Labeling and Education Act (NLEA) in 1994. Under the NLEA regulations, a 'Nutrition Facts' panel displays information on nutrients such as calories, total and saturated fats, cholesterol, and sodium in a standardized format. By providing nutrition information in a credible, distinctive, and easy-to-read format, the new label was expected to help consumers choose healthier, more nutritious diets. This paper examines whether the disclosure of nutrition information through the mandatory labels impacted consumer diets. Assessing the dietary effects of labeling is problematic due to the confounding of the label effect with unobserved label user characteristics. This self-selection problem is addressed by exploiting the fact that the NLEA exempts away-from-home foods from mandatory labeling. Difference-in-differences models that account for zero away-from-home intakes suggest that the labels increase fiber and iron intakes of label users compared with label nonusers. In comparison, a model that does not account for self-selection implies significant label effects for all but two of the 13 nutrients that are listed on the label.

  13. Reproducibility of preclinical animal research improves with heterogeneity of study samples

    PubMed Central

    Vogt, Lucile; Sena, Emily S.; Würbel, Hanno

    2018-01-01

    Single-laboratory studies conducted under highly standardized conditions are the gold standard in preclinical animal research. Using simulations based on 440 preclinical studies across 13 different interventions in animal models of stroke, myocardial infarction, and breast cancer, we compared the accuracy of effect size estimates between single-laboratory and multi-laboratory study designs. Single-laboratory studies generally failed to predict effect size accurately, and larger sample sizes rendered effect size estimates even less accurate. By contrast, multi-laboratory designs including as few as 2 to 4 laboratories increased coverage probability by up to 42 percentage points without a need for larger sample sizes. These findings demonstrate that within-study standardization is a major cause of poor reproducibility. More representative study samples are required to improve the external validity and reproducibility of preclinical animal research and to prevent wasting animals and resources for inconclusive research. PMID:29470495

  14. Estimation of contrast agent bolus arrival delays for improved reproducibility of liver DCE MRI

    NASA Astrophysics Data System (ADS)

    Chouhan, Manil D.; Bainbridge, Alan; Atkinson, David; Punwani, Shonit; Mookerjee, Rajeshwar P.; Lythgoe, Mark F.; Taylor, Stuart A.

    2016-10-01

    Delays between contrast agent (CA) arrival at the site of vascular input function (VIF) sampling and the tissue of interest affect dynamic contrast enhanced (DCE) MRI pharmacokinetic modelling. We investigate effects of altering VIF CA bolus arrival delays on liver DCE MRI perfusion parameters, propose an alternative approach to estimating delays and evaluate reproducibility. Thirteen healthy volunteers (28.7  ±  1.9 years, seven males) underwent liver DCE MRI using dual-input single compartment modelling, with reproducibility (n  =  9) measured at 7 days. Effects of VIF CA bolus arrival delays were assessed for arterial and portal venous input functions. Delays were pre-estimated using linear regression, with restricted free modelling around the pre-estimated delay. Perfusion parameters and 7 days reproducibility were compared using this method, freely modelled delays and no delays using one-way ANOVA. Reproducibility was assessed using Bland-Altman analysis of agreement. Maximum percent change relative to parameters obtained using zero delays, were  -31% for portal venous (PV) perfusion, +43% for total liver blood flow (TLBF), +3247% for hepatic arterial (HA) fraction, +150% for mean transit time and  -10% for distribution volume. Differences were demonstrated between the 3 methods for PV perfusion (p  =  0.0085) and HA fraction (p  <  0.0001), but not other parameters. Improved mean differences and Bland-Altman 95% Limits-of-Agreement for reproducibility of PV perfusion (9.3 ml/min/100 g, ±506.1 ml/min/100 g) and TLBF (43.8 ml/min/100 g, ±586.7 ml/min/100 g) were demonstrated using pre-estimated delays with constrained free modelling. CA bolus arrival delays cause profound differences in liver DCE MRI quantification. Pre-estimation of delays with constrained free modelling improved 7 days reproducibility of perfusion parameters in volunteers.

  15. Transparency, usability, and reproducibility: Guiding principles for improving comparative databases using primates as examples.

    PubMed

    Borries, Carola; Sandel, Aaron A; Koenig, Andreas; Fernandez-Duque, Eduardo; Kamilar, Jason M; Amoroso, Caroline R; Barton, Robert A; Bray, Joel; Di Fiore, Anthony; Gilby, Ian C; Gordon, Adam D; Mundry, Roger; Port, Markus; Powell, Lauren E; Pusey, Anne E; Spriggs, Amanda; Nunn, Charles L

    2016-09-01

    Recent decades have seen rapid development of new analytical methods to investigate patterns of interspecific variation. Yet these cutting-edge statistical analyses often rely on data of questionable origin, varying accuracy, and weak comparability, which seem to have reduced the reproducibility of studies. It is time to improve the transparency of comparative data while also making these improved data more widely available. We, the authors, met to discuss how transparency, usability, and reproducibility of comparative data can best be achieved. We propose four guiding principles: 1) data identification with explicit operational definitions and complete descriptions of methods; 2) inclusion of metadata that capture key characteristics of the data, such as sample size, geographic coordinates, and nutrient availability (for example, captive versus wild animals); 3) documentation of the original reference for each datum; and 4) facilitation of effective interactions with the data via user friendly and transparent interfaces. We urge reviewers, editors, publishers, database developers and users, funding agencies, researchers publishing their primary data, and those performing comparative analyses to embrace these standards to increase the transparency, usability, and reproducibility of comparative studies. © 2016 Wiley Periodicals, Inc.

  16. Experience with the use of the Codonics Safe Label System(™) to improve labelling compliance of anaesthesia drugs.

    PubMed

    Ang, S B L; Hing, W C; Tung, S Y; Park, T

    2014-07-01

    The Codonics Safe Labeling System(™) (http://www.codonics.com/Products/SLS/flash/) is a piece of equipment that is able to barcode scan medications, read aloud the medication and the concentration and print a label of the appropriate concentration in the appropriate colour code. We decided to test this system in our facility to identify risks, benefits and usability. Our project comprised a baseline survey (25 anaesthesia cases during which 212 syringes were prepared from 223 drugs), an observational study (47 cases with 330 syringes prepared) and a user acceptability survey. The baseline compliance with all labelling requirements was 58%. In the observational study the compliance using the Codonics system was 98.6% versus 63.8% with conventional labelling. In the user acceptability survey the majority agreed the Codonics machine was easy to use, more legible and adhered with better security than the conventional preprinted label. However, most were neutral when asked about the likelihood of flexibility and customisation and were dissatisfied with the increased workload. Our findings suggest that the Codonics labelling machine is user-friendly and it improved syringe labelling compliance in our study. However, staff need to be willing to follow proper labelling workflow rather than batch label during preparation. Future syringe labelling equipment developers need to concentrate on user interface issues to reduce human factor and workflow problems. Support logistics are also an important consideration prior to implementation of any new labelling system.

  17. Improving the design of nutrition labels to promote healthier food choices and reasonable portion sizes.

    PubMed

    Roberto, C A; Khandpur, N

    2014-07-01

    Accurate and easy-to-understand nutrition labeling is a worthy public health goal that should be considered an important strategy among many to address obesity and poor diet. Updating the Nutrition Facts Panel on packaged foods, developing a uniform front-of-package labeling system and providing consumers with nutrition information on restaurant menus offer important opportunities to educate people about food's nutritional content, increase awareness of reasonable portion sizes and motivate consumers to make healthier choices. The aims of this paper were to identify and discuss: (1) current concerns with nutrition label communication strategies; (2) opportunities to improve the communication of nutrition information via food labels, with a specific focus on serving size information; and (3) important future areas of research on nutrition labeling as a tool to improve diet. We suggest that research on nutrition labeling should focus on ways to improve food labels' ability to capture consumer attention, reduce label complexity and convey numeric nutrition information in simpler and more meaningful ways, such as through interpretive food labels, the addition of simple text, reduced use of percentages and easy-to-understand presentation of serving size information.

  18. Microwave-assisted deuterium exchange: the convenient preparation of isotopically labelled analogues for stable isotope dilution analysis of volatile wine phenols.

    PubMed

    Crump, Anna M; Sefton, Mark A; Wilkinson, Kerry L

    2014-11-01

    This study reports the convenient, low cost, one-step synthesis of labelled analogues of six volatile phenols, guaiacol, 4-methylguaiacol, 4-ethylguaiacol, 4-ethylphenol, eugenol and vanillin, using microwave-assisted deuterium exchange, for use as internal standards for stable isotope dilution analysis. The current method improves on previous strategies in that it enables incorporation of deuterium atoms on the aromatic ring, thereby ensuring retention of the isotope label during mass spectrometry fragmentation. When used as standards for SIDA, these labelled volatile phenols will improve the accuracy and reproducibility of quantitative food and beverage analysis. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Toward improved pregnancy labelling.

    PubMed

    Koren, Gideon; Sakaguchi, Sachi; Klieger, Chagit; Kazmin, Alex; Osadchy, Alla; Yazdani-Brojeni, Parvaneh; Matok, Ilan

    2010-01-01

    Information about the use of a medication in pregnancy is part of overall drug labelling as prepared by the pharmaceutical company and approved by the regulators. It is aimed at assisting clinicians in prescribing, however, very few drugs are labelled for specific indications in pregnancy, since there is rarely information about the use of a drug in this condition. Recently the FDA has drafted new guidelines for the labeling of drugs in pregnancy and breastfeeding, to replace the A,B,C,D,X system that was used for more than 30 years. Here we document the use of the new system through 3 different medications; each representing a different clinical situation in pregnancy--acute infection, chronic pain, and drug use during labor. Advantages and challenges in the new system are being highlighted.

  20. Hierarchical Nanogold Labels to Improve the Sensitivity of Lateral Flow Immunoassay

    NASA Astrophysics Data System (ADS)

    Serebrennikova, Kseniya; Samsonova, Jeanne; Osipov, Alexander

    2018-06-01

    Lateral flow immunoassay (LFIA) is a widely used express method and offers advantages such as a short analysis time, simplicity of testing and result evaluation. However, an LFIA based on gold nanospheres lacks the desired sensitivity, thereby limiting its wide applications. In this study, spherical nanogold labels along with new types of nanogold labels such as gold nanopopcorns and nanostars were prepared, characterized, and applied for LFIA of model protein antigen procalcitonin. It was found that the label with a structure close to spherical provided more uniform distribution of specific antibodies on its surface, indicative of its suitability for this type of analysis. LFIA using gold nanopopcorns as a label allowed procalcitonin detection over a linear range of 0.5-10 ng mL-1 with the limit of detection of 0.1 ng mL-1, which was fivefold higher than the sensitivity of the assay with gold nanospheres. Another approach to improve the sensitivity of the assay included the silver enhancement method, which was used to compare the amplification of LFIA for procalcitonin detection. The sensitivity of procalcitonin determination by this method was 10 times better the sensitivity of the conventional LFIA with gold nanosphere as a label. The proposed approach of LFIA based on gold nanopopcorns improved the detection sensitivity without additional steps and prevented the increased consumption of specific reagents (antibodies).

  1. New dye-labeled terminators for improved DNA sequencing patterns.

    PubMed Central

    Rosenblum, B B; Lee, L G; Spurgeon, S L; Khan, S H; Menchen, S M; Heiner, C R; Chen, S M

    1997-01-01

    We have used two new dye sets for automated dye-labeled terminator DNA sequencing. One set consists of four, 4,7-dichlororhodamine dyes (d-rhodamines). The second set consists of energy-transfer dyes that use the 5-carboxy-d-rhodamine dyes as acceptor dyes and the 5- or 6-carboxy isomers of 4'-aminomethylfluorescein as the donor dye. Both dye sets utilize a new linker between the dye and the nucleotide, and both provide more even peak heights in terminator sequencing than the dye-terminators consisting of unsubstituted rhodamine dyes. The unsubstituted rhodamine terminators produced electropherograms in which weak G peaks are observed after A peaks and occasionally C peaks. The number of weak G peaks has been reduced or eliminated with the new dye terminators. The general improvement in peak evenness improves accuracy for the automated base-calling software. The improved signal-to-noise ratio of the energy-transfer dye-labeled terminators combined with more even peak heights results in successful sequencing of high molecular weight DNA templates such as bacterial artificial chromosome DNA. PMID:9358158

  2. Using Ensemble Decisions and Active Selection to Improve Low-Cost Labeling for Multi-View Data

    NASA Technical Reports Server (NTRS)

    Rebbapragada, Umaa; Wagstaff, Kiri L.

    2011-01-01

    This paper seeks to improve low-cost labeling in terms of training set reliability (the fraction of correctly labeled training items) and test set performance for multi-view learning methods. Co-training is a popular multiview learning method that combines high-confidence example selection with low-cost (self) labeling. However, co-training with certain base learning algorithms significantly reduces training set reliability, causing an associated drop in prediction accuracy. We propose the use of ensemble labeling to improve reliability in such cases. We also discuss and show promising results on combining low-cost ensemble labeling with active (low-confidence) example selection. We unify these example selection and labeling strategies under collaborative learning, a family of techniques for multi-view learning that we are developing for distributed, sensor-network environments.

  3. Multispectral Image Compression for Improvement of Colorimetric and Spectral Reproducibility by Nonlinear Spectral Transform

    NASA Astrophysics Data System (ADS)

    Yu, Shanshan; Murakami, Yuri; Obi, Takashi; Yamaguchi, Masahiro; Ohyama, Nagaaki

    2006-09-01

    The article proposes a multispectral image compression scheme using nonlinear spectral transform for better colorimetric and spectral reproducibility. In the method, we show the reduction of colorimetric error under a defined viewing illuminant and also that spectral accuracy can be improved simultaneously using a nonlinear spectral transform called Labplus, which takes into account the nonlinearity of human color vision. Moreover, we show that the addition of diagonal matrices to Labplus can further preserve the spectral accuracy and has a generalized effect of improving the colorimetric accuracy under other viewing illuminants than the defined one. Finally, we discuss the usage of the first-order Markov model to form the analysis vectors for the higher order channels in Labplus to reduce the computational complexity. We implement a multispectral image compression system that integrates Labplus with JPEG2000 for high colorimetric and spectral reproducibility. Experimental results for a 16-band multispectral image show the effectiveness of the proposed scheme.

  4. Self-assessed performance improves statistical fusion of image labels

    PubMed Central

    Bryan, Frederick W.; Xu, Zhoubing; Asman, Andrew J.; Allen, Wade M.; Reich, Daniel S.; Landman, Bennett A.

    2014-01-01

    . Statistical fusion resulted in statistically indistinguishable performance from self-assessed weighted voting. The authors developed a new theoretical basis for using self-assessed performance in the framework of statistical fusion and demonstrated that the combined sources of information (both statistical assessment and self-assessment) yielded statistically significant improvement over the methods considered separately. Conclusions: The authors present the first systematic characterization of self-assessed performance in manual labeling. The authors demonstrate that self-assessment and statistical fusion yield similar, but complementary, benefits for label fusion. Finally, the authors present a new theoretical basis for combining self-assessments with statistical label fusion. PMID:24593721

  5. Improving the Effectiveness of Penicillin Allergy De-labeling.

    PubMed

    Bourke, Jack; Pavlos, Rebecca; James, Ian; Phillips, Elizabeth

    2015-01-01

    Approximately 10-20% of hospitalized patients are labeled as penicillin allergic, and this is associated with significant health and economic costs. We looked at the effectiveness of penicillin allergy de-labeling in clinical practice with the aim of deriving risk stratification models to guide testing strategies. Consecutive patients aged 15 years or more, referred to a Western Australian public hospital drug allergy service between 2008 and 2013 for beta-lactam allergy, were included. Follow-up surveys were conducted. Results of skin prick testing and intradermal testing (SPT/IDT) and oral challenge (OC), and follow-up of post testing antibiotic usage were the main outcomes. SPT/IDT was performed in 401 consecutive patients with immediate (IMM) (≤ 1 hour) (n = 151) and nonimmediate (NIM) (>1 hour) (n = 250) reactions. Of 341 patients, 42 (12.3%) were SPT/IDT+ to ≥ 1 penicillin reagents, including 35/114 (30.4%) in the IMM group and 7/227 (3.1%) in the NIM group (P < .0001). Of 355 SPT/IDT patients, 3 (0.8%), all in the IMM group, had nonserious positive OC reactions to single dose penicillin VK (SPT/IDT negative predictive value [NPV] 99.2%). Selective or unrestricted beta-lactam was recommended in almost 90% overall, including 238/250 (95.2%) in the NIM group and 126/151 (83.4%) in the IMM group (P = .0001). Of 182 patients, 137 (75.3%) were following the allergy label modifications (ALM) at the time of follow-up. Penicillin SPT/IDT/OC safely de-labels penicillin-allergic patients and identifies selective beta-lactam allergies; however, incomplete adherence to ALM recommendations impairs effectiveness. Infrequent SPT/IDT+ and absent OC reactions in patients with NIM reactions suggest OC alone to be a safe and cost-effective de-labeling strategy that could improve the coverage of penicillin allergy de-labeling in lower risk populations. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  6. Readability of product ingredient labels can be improved by simple means: an experimental study.

    PubMed

    Yazar, Kerem; Seimyr, Gustaf Ö; Novak, Jiri A; White, Ian R; Lidén, Carola

    2014-10-01

    Ingredient labels on products used by consumers and workers every day, such as food, cosmetics, and detergents, can be difficult to read and understand. To assess whether typographical design and ordering of ingredients can improve the readability of product ingredient labels. The study subjects (n = 16) had to search for two target ingredients in 30 cosmetic product labels and three alternative formats of each. Outcome measures were completion time (reading speed), recognition rate, eye movements, task load and subjective rating when the reading of ingredient labels was assessed by video recording, an eye tracking device, and questionnaires. The completion time was significantly lower (p < 0.001) when subjects were reading all alternative formats than when they were reading the original. The recognition rate was generally high, and improved slightly with the alternative formats. The eye movement measures confirmed that the alternative formats were easier to read than the original product labels. Mental and physical demand and effort were significantly lower (p < 0.036) and experience rating was higher (p < 0.042) for the alternative formats. There were also differences between the alternative formats. Simple adjustments in the design of product ingredient labels would significantly improve their readability, benefiting the many allergic individuals and others in their daily struggle to avoid harmful or unwanted exposure. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. LPA-CBD an improved label propagation algorithm based on community belonging degree for community detection

    NASA Astrophysics Data System (ADS)

    Gui, Chun; Zhang, Ruisheng; Zhao, Zhili; Wei, Jiaxuan; Hu, Rongjing

    In order to deal with stochasticity in center node selection and instability in community detection of label propagation algorithm, this paper proposes an improved label propagation algorithm named label propagation algorithm based on community belonging degree (LPA-CBD) that employs community belonging degree to determine the number and the center of community. The general process of LPA-CBD is that the initial community is identified by the nodes with the maximum degree, and then it is optimized or expanded by community belonging degree. After getting the rough structure of network community, the remaining nodes are labeled by using label propagation algorithm. The experimental results on 10 real-world networks and three synthetic networks show that LPA-CBD achieves reasonable community number, better algorithm accuracy and higher modularity compared with other four prominent algorithms. Moreover, the proposed algorithm not only has lower algorithm complexity and higher community detection quality, but also improves the stability of the original label propagation algorithm.

  8. Improving labeling efficiency in automatic quality control of MRSI data.

    PubMed

    Pedrosa de Barros, Nuno; McKinley, Richard; Wiest, Roland; Slotboom, Johannes

    2017-12-01

    To improve the efficiency of the labeling task in automatic quality control of MR spectroscopy imaging data. 28'432 short and long echo time (TE) spectra (1.5 tesla; point resolved spectroscopy (PRESS); repetition time (TR)= 1,500 ms) from 18 different brain tumor patients were labeled by two experts as either accept or reject, depending on their quality. For each spectrum, 47 signal features were extracted. The data was then used to run several simulations and test an active learning approach using uncertainty sampling. The performance of the classifiers was evaluated as a function of the number of patients in the training set, number of spectra in the training set, and a parameter α used to control the level of classification uncertainty required for a new spectrum to be selected for labeling. The results showed that the proposed strategy allows reductions of up to 72.97% for short TE and 62.09% for long TE in the amount of data that needs to be labeled, without significant impact in classification accuracy. Further reductions are possible with significant but minimal impact in performance. Active learning using uncertainty sampling is an effective way to increase the labeling efficiency for training automatic quality control classifiers. Magn Reson Med 78:2399-2405, 2017. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

  9. Device Engineering Towards Improved Tin Sulfide Solar Cell Performance and Performance Reproducibility

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

    Steinmann, Vera; Chakraborty, Rupak; Rekemeyer, Paul

    2016-11-21

    As novel absorber materials are developed and screened for their photovoltaic (PV) properties, the challenge remains to rapidly test promising candidates in high-performing PV devices. There is a need to engineer new compatible device architectures, including the development of novel transparent conductive oxides and buffer layers. Here, we consider the two approaches of a substrate-style and a superstrate-style device architecture for novel thin-film solar cells. We use tin sulfide as a test absorber material. Upon device engineering, we demonstrate new approaches to improve device performance and performance reproducibility.

  10. Quantitative colorectal cancer perfusion measurement by multidetector-row CT: does greater tumour coverage improve measurement reproducibility?

    PubMed

    Goh, V; Halligan, S; Gartner, L; Bassett, P; Bartram, C I

    2006-07-01

    The purpose of this study was to determine if greater z-axis tumour coverage improves the reproducibility of quantitative colorectal cancer perfusion measurements using CT. A 65 s perfusion study was acquired following intravenous contrast administration in 10 patients with proven colorectal cancer using a four-detector row scanner. This was repeated within 48 h using identical technical parameters to allow reproducibility assessment. Quantitative tumour blood volume, blood flow, mean transit time and permeability measurements were determined using commercially available software (Perfusion 3.0; GE Healthcare, Waukesha, WI) for data obtained from a 5 mm z-axis tumour coverage, and from a 20 mm z-axis tumour coverage. Measurement reproducibility was assessed using Bland-Altman statistics, for a 5 mm z-axis tumour coverage, and 20 mm z-axis tumour coverage, respectively. The mean difference (95% limits of agreement) for blood volume, blood flow, mean transit time and permeability were 0.04 (-2.50 to +2.43) ml/100 g tissue; +8.80 (-50.5 to +68.0) ml/100 g tissue/min; -0.99 (-8.19 to +6.20) seconds; and +1.20 (-5.42 to +7.83) ml/100 g tissue/min, respectively, for a 5 mm coverage, and -0.04 (-2.61 to +2.53) ml/100 g tissue; +7.40 (-50.3 to +65.0) ml/100 g tissue/min; -2.46 (-12.61 to +7.69) seconds; and -0.23 (-8.31 to +7.85) ml/100 g tissue/min, respectively, for a 20 mm coverage, indicating similar levels of agreement. In conclusion, increasing z-axis coverage does not improve reproducibility of quantitative colorectal cancer perfusion measurements.

  11. Digital image analysis: improving accuracy and reproducibility of radiographic measurement.

    PubMed

    Bould, M; Barnard, S; Learmonth, I D; Cunningham, J L; Hardy, J R

    1999-07-01

    To assess the accuracy and reproducibility of a digital image analyser and the human eye, in measuring radiographic dimensions. We experimentally compared radiographic measurement using either an image analyser system or the human eye with digital caliper. The assessment of total hip arthroplasty wear from radiographs relies on both the accuracy of radiographic images and the accuracy of radiographic measurement. Radiographs were taken of a slip gauge (30+/-0.00036 mm) and slip gauge with a femoral stem. The projected dimensions of the radiographic images were calculated by trigonometry. The radiographic dimensions were then measured by blinded observers using both techniques. For a single radiograph, the human eye was accurate to 0.26 mm and reproducible to +/-0.1 mm. In comparison the digital image analyser system was accurate to 0.01 mm with a reproducibility of +/-0.08 mm. In an arthroplasty model, where the dimensions of an object were corrected for magnification by the known dimensions of a femoral head, the human eye was accurate to 0.19 mm, whereas the image analyser system was accurate to 0.04 mm. The digital image analysis system is up to 20 times more accurate than the human eye, and in an arthroplasty model the accuracy of measurement increases four-fold. We believe such image analysis may allow more accurate and reproducible measurement of wear from standard follow-up radiographs.

  12. Measuring the labeling efficiency of pseudocontinuous arterial spin labeling.

    PubMed

    Chen, Zhensen; Zhang, Xingxing; Yuan, Chun; Zhao, Xihai; van Osch, Matthias J P

    2017-05-01

    Optimization and validation of a sequence for measuring the labeling efficiency of pseudocontinuous arterial spin labeling (pCASL) perfusion MRI. The proposed sequence consists of a labeling module and a single slice Look-Locker echo planar imaging readout. A model-based algorithm was used to calculate labeling efficiency from the signal acquired from the main brain-feeding arteries. Stability of the labeling efficiency measurement was evaluated with regard to the use of cardiac triggering, flow compensation and vein signal suppression. Accuracy of the measurement was assessed by comparing the measured labeling efficiency to mean brain pCASL signal intensity over a wide range of flip angles as applied in the pCASL labeling. Simulations show that the proposed algorithm can effectively calculate labeling efficiency when correcting for T1 relaxation of the blood spins. Use of cardiac triggering and vein signal suppression improved stability of the labeling efficiency measurement, while flow compensation resulted in little improvement. The measured labeling efficiency was found to be linearly (R = 0.973; P < 0.001) related to brain pCASL signal intensity over a wide range of pCASL flip angles. The optimized labeling efficiency sequence provides robust artery-specific labeling efficiency measurement within a short acquisition time (∼30 s), thereby enabling improved accuracy of pCASL CBF quantification. Magn Reson Med 77:1841-1852, 2017. © 2016 International Society for Magnetic Resonance in Medicine Magn Reson Med 77:1841-1852, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

  13. Improved 68 Ga-labeling method using ethanol addition: Application to the α-helical peptide DOTA-FAMP.

    PubMed

    Hasegawa, Koki; Kawachi, Emi; Uehara, Yoshinari; Yoshida, Tsuyoshi; Imaizumi, Satoshi; Ogawa, Masahiro; Miura, Shin-Ichiro; Saku, Keijiro

    2017-01-01

    We examined the 68 Ga labeling of the α-helical peptide, DOTA-FAMP, and evaluated conformational changes during radiolabeling. 68 Ga-DOTA-FAMP is a positron emission tomography probe candidate for atherosclerotic plaques. The labeling yield achieved by Zhernosekov's method (using acetone for 68 Ga purification) was compared with that achieved by the original and 2 modified Mueller's methods (using NaCl solution). Modified method I involves desalting the 68 Ga prior to labeling, and modified method II involves the inclusion of ethanol in the labeling solution. The labeling yield using Zhernosekov's method was 62% ± 5.4%. In comparison, Mueller's original method gave 8.9% ± 1.7%. Modified method I gave a slight improvement of 32% ± 2.1%. Modified method II further increased the yield to 66% ± 3.4%. Conformational changes were determined by circular dichroism spectroscopy, revealing that these differences could be attributed to conformational changes. Heat treatment affects peptide conformation, which leads to aggregation and decreases the labeling yield. Mueller's method is simpler, but harsh conditions preclude its application to biomolecules. To suppress aggregation, we included a desalting process and added ethanol in the labeling solution. These changes significantly improved the labeling yield. Before use for imaging, conformational changes of biomolecules during radiolabeling should be evaluated by circular dichroism spectroscopy to ensure the homogeneity of the labeled product. Copyright © 2016 John Wiley & Sons, Ltd.

  14. Reproducible surface-enhanced Raman quantification of biomarkers in multicomponent mixtures.

    PubMed

    De Luca, Anna Chiara; Reader-Harris, Peter; Mazilu, Michael; Mariggiò, Stefania; Corda, Daniela; Di Falco, Andrea

    2014-03-25

    Direct and quantitative detection of unlabeled glycerophosphoinositol (GroPIns), an abundant cytosolic phosphoinositide derivative, would allow rapid evaluation of several malignant cell transformations. Here we report label-free analysis of GroPIns via surface-enhanced Raman spectroscopy (SERS) with a sensitivity of 200 nM, well below its apparent concentration in cells. Crucially, our SERS substrates, based on lithographically defined gold nanofeatures, can be used to predict accurately the GroPIns concentration even in multicomponent mixtures, avoiding the preliminary separation of individual compounds. Our results represent a critical step toward the creation of SERS-based biosensor for rapid, label-free, and reproducible detection of specific molecules, overcoming limits of current experimental methods.

  15. Gold Nanoparticle Labels and Heterogeneous Immunoassays: The Case for the Inverted Substrate.

    PubMed

    Crawford, Alexis C; Young, Colin C; Porter, Marc D

    2018-06-15

    This paper examines how the difference in the spatial orientation of the capture substrate influences the analytical sensitivity and limits of detection for immunoassays that use gold nanoparticle labels (AuNPs) and rely on diffusion in quiet solution in the antigen capture and labeling steps. Ideally, the accumulation of both reactants should follow a dependence governed by the rate in which diffusion delivers reactants to the capture surface. In other words, the accumulation of reactants should increase with the square root of the incubation time, i.e., t1/2. The work herein shows, however, that this expectation is only obeyed when the capture substrate is oriented to direct the gravity-induced sedimentation of the AuNP labels away from the substrate. Using an assay for human IgG, the results show that circumventing the sedimentation of the gold nanoparticle labels by substrate inversion enables the dependence of the labeling step on diffusion, reduces nonspecific label adsorption, and improves the estimated detection limit by ~30×. High-density maps of the signal across the two types of substrates also demonstrate that inversion in the labeling step results in a more uniform distribution of AuNP labels across the surface, which translates to a greater measurement reproducibility. These results, which are supported by model simulations via the Mason-Weaver sedimentation-diffusion equation, and their potential implications when using other nanoparticle labels and related materials in diagnostic tests and other applications, are briefly discussed.

  16. Systematic heterogenization for better reproducibility in animal experimentation.

    PubMed

    Richter, S Helene

    2017-08-31

    The scientific literature is full of articles discussing poor reproducibility of findings from animal experiments as well as failures to translate results from preclinical animal studies to clinical trials in humans. Critics even go so far as to talk about a "reproducibility crisis" in the life sciences, a novel headword that increasingly finds its way into numerous high-impact journals. Viewed from a cynical perspective, Fett's law of the lab "Never replicate a successful experiment" has thus taken on a completely new meaning. So far, poor reproducibility and translational failures in animal experimentation have mostly been attributed to biased animal data, methodological pitfalls, current publication ethics and animal welfare constraints. More recently, the concept of standardization has also been identified as a potential source of these problems. By reducing within-experiment variation, rigorous standardization regimes limit the inference to the specific experimental conditions. In this way, however, individual phenotypic plasticity is largely neglected, resulting in statistically significant but possibly irrelevant findings that are not reproducible under slightly different conditions. By contrast, systematic heterogenization has been proposed as a concept to improve representativeness of study populations, contributing to improved external validity and hence improved reproducibility. While some first heterogenization studies are indeed very promising, it is still not clear how this approach can be transferred into practice in a logistically feasible and effective way. Thus, further research is needed to explore different heterogenization strategies as well as alternative routes toward better reproducibility in animal experimentation.

  17. An International Ki67 Reproducibility Study in Adrenal Cortical Carcinoma.

    PubMed

    Papathomas, Thomas G; Pucci, Eugenio; Giordano, Thomas J; Lu, Hao; Duregon, Eleonora; Volante, Marco; Papotti, Mauro; Lloyd, Ricardo V; Tischler, Arthur S; van Nederveen, Francien H; Nose, Vania; Erickson, Lori; Mete, Ozgur; Asa, Sylvia L; Turchini, John; Gill, Anthony J; Matias-Guiu, Xavier; Skordilis, Kassiani; Stephenson, Timothy J; Tissier, Frédérique; Feelders, Richard A; Smid, Marcel; Nigg, Alex; Korpershoek, Esther; van der Spek, Peter J; Dinjens, Winand N M; Stubbs, Andrew P; de Krijger, Ronald R

    2016-04-01

    Despite the established role of Ki67 labeling index in prognostic stratification of adrenocortical carcinomas and its recent integration into treatment flow charts, the reproducibility of the assessment method has not been determined. The aim of this study was to investigate interobserver variability among endocrine pathologists using a web-based virtual microscopy approach. Ki67-stained slides of 76 adrenocortical carcinomas were analyzed independently by 14 observers, each according to their method of preference including eyeballing, formal manual counting, and digital image analysis. The interobserver variation was statistically significant (P<0.001) in the absence of any correlation between the various methods. Subsequently, 61 static images were distributed among 15 observers who were instructed to follow a category-based scoring approach. Low levels of interobserver (F=6.99; Fcrit=1.70; P<0.001) as well as intraobserver concordance (n=11; Cohen κ ranging from -0.057 to 0.361) were detected. To improve harmonization of Ki67 analysis, we tested the utility of an open-source Galaxy virtual machine application, namely Automated Selection of Hotspots, in 61 virtual slides. The software-provided Ki67 values were validated by digital image analysis in identical images, displaying a strong correlation of 0.96 (P<0.0001) and dividing the cases into 3 classes (cutoffs of 0%-15%-30% and/or 0%-10%-20%) with significantly different overall survivals (P<0.05). We conclude that current practices in Ki67 scoring assessment vary greatly, and interobserver variation sets particular limitations to its clinical utility, especially around clinically relevant cutoff values. Novel digital microscopy-enabled methods could provide critical aid in reducing variation, increasing reproducibility, and improving reliability in the clinical setting.

  18. A Simple Picaxe Microcontroller Pulse Source for Juxtacellular Neuronal Labelling.

    PubMed

    Verberne, Anthony J M

    2016-10-19

    Juxtacellular neuronal labelling is a method which allows neurophysiologists to fill physiologically-identified neurons with small positively-charged marker molecules. Labelled neurons are identified by histochemical processing of brain sections along with immunohistochemical identification of neuropeptides, neurotransmitters, neurotransmitter transporters or biosynthetic enzymes. A microcontroller-based pulser circuit and associated BASIC software script is described for incorporation into the design of a commercially-available intracellular electrometer for use in juxtacellular neuronal labelling. Printed circuit board construction has been used for reliability and reproducibility. The current design obviates the need for a separate digital pulse source and simplifies the juxtacellular neuronal labelling procedure.

  19. Improving machine learning reproducibility in genetic association studies with proportional instance cross validation (PICV).

    PubMed

    Piette, Elizabeth R; Moore, Jason H

    2018-01-01

    Machine learning methods and conventions are increasingly employed for the analysis of large, complex biomedical data sets, including genome-wide association studies (GWAS). Reproducibility of machine learning analyses of GWAS can be hampered by biological and statistical factors, particularly so for the investigation of non-additive genetic interactions. Application of traditional cross validation to a GWAS data set may result in poor consistency between the training and testing data set splits due to an imbalance of the interaction genotypes relative to the data as a whole. We propose a new cross validation method, proportional instance cross validation (PICV), that preserves the original distribution of an independent variable when splitting the data set into training and testing partitions. We apply PICV to simulated GWAS data with epistatic interactions of varying minor allele frequencies and prevalences and compare performance to that of a traditional cross validation procedure in which individuals are randomly allocated to training and testing partitions. Sensitivity and positive predictive value are significantly improved across all tested scenarios for PICV compared to traditional cross validation. We also apply PICV to GWAS data from a study of primary open-angle glaucoma to investigate a previously-reported interaction, which fails to significantly replicate; PICV however improves the consistency of testing and training results. Application of traditional machine learning procedures to biomedical data may require modifications to better suit intrinsic characteristics of the data, such as the potential for highly imbalanced genotype distributions in the case of epistasis detection. The reproducibility of genetic interaction findings can be improved by considering this variable imbalance in cross validation implementation, such as with PICV. This approach may be extended to problems in other domains in which imbalanced variable distributions are a concern.

  20. Combinatorial Labeling Method for Improving Peptide Fragmentation in Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Kuchibhotla, Bhanuramanand; Kola, Sankara Rao; Medicherla, Jagannadham V.; Cherukuvada, Swamy V.; Dhople, Vishnu M.; Nalam, Madhusudhana Rao

    2017-06-01

    Annotation of peptide sequence from tandem mass spectra constitutes the central step of mass spectrometry-based proteomics. Peptide mass spectra are obtained upon gas-phase fragmentation. Identification of the protein from a set of experimental peptide spectral matches is usually referred as protein inference. Occurrence and intensity of these fragment ions in the MS/MS spectra are dependent on many factors such as amino acid composition, peptide basicity, activation mode, protease, etc. Particularly, chemical derivatizations of peptides were known to alter their fragmentation. In this study, the influence of acetylation, guanidinylation, and their combination on peptide fragmentation was assessed initially on a lipase (LipA) from Bacillus subtilis followed by a bovine six protein mix digest. The dual modification resulted in improved fragment ion occurrence and intensity changes, and this resulted in the equivalent representation of b- and y-type fragment ions in an ion trap MS/MS spectrum. The improved representation has allowed us to accurately annotate the peptide sequences de novo. Dual labeling has significantly reduced the false positive protein identifications in standard bovine six peptide digest. Our study suggests that the combinatorial labeling of peptides is a useful method to validate protein identifications for high confidence protein inference. [Figure not available: see fulltext.

  1. Where next for the reproducibility agenda in computational biology?

    PubMed

    Lewis, Joanna; Breeze, Charles E; Charlesworth, Jane; Maclaren, Oliver J; Cooper, Jonathan

    2016-07-15

    The concept of reproducibility is a foundation of the scientific method. With the arrival of fast and powerful computers over the last few decades, there has been an explosion of results based on complex computational analyses and simulations. The reproducibility of these results has been addressed mainly in terms of exact replicability or numerical equivalence, ignoring the wider issue of the reproducibility of conclusions through equivalent, extended or alternative methods. We use case studies from our own research experience to illustrate how concepts of reproducibility might be applied in computational biology. Several fields have developed 'minimum information' checklists to support the full reporting of computational simulations, analyses and results, and standardised data formats and model description languages can facilitate the use of multiple systems to address the same research question. We note the importance of defining the key features of a result to be reproduced, and the expected agreement between original and subsequent results. Dynamic, updatable tools for publishing methods and results are becoming increasingly common, but sometimes come at the cost of clear communication. In general, the reproducibility of computational research is improving but would benefit from additional resources and incentives. We conclude with a series of linked recommendations for improving reproducibility in computational biology through communication, policy, education and research practice. More reproducible research will lead to higher quality conclusions, deeper understanding and more valuable knowledge.

  2. Reproducible research in palaeomagnetism

    NASA Astrophysics Data System (ADS)

    Lurcock, Pontus; Florindo, Fabio

    2015-04-01

    The reproducibility of research findings is attracting increasing attention across all scientific disciplines. In palaeomagnetism as elsewhere, computer-based analysis techniques are becoming more commonplace, complex, and diverse. Analyses can often be difficult to reproduce from scratch, both for the original researchers and for others seeking to build on the work. We present a palaeomagnetic plotting and analysis program designed to make reproducibility easier. Part of the problem is the divide between interactive and scripted (batch) analysis programs. An interactive desktop program with a graphical interface is a powerful tool for exploring data and iteratively refining analyses, but usually cannot operate without human interaction. This makes it impossible to re-run an analysis automatically, or to integrate it into a larger automated scientific workflow - for example, a script to generate figures and tables for a paper. In some cases the parameters of the analysis process itself are not saved explicitly, making it hard to repeat or improve the analysis even with human interaction. Conversely, non-interactive batch tools can be controlled by pre-written scripts and configuration files, allowing an analysis to be 'replayed' automatically from the raw data. However, this advantage comes at the expense of exploratory capability: iteratively improving an analysis entails a time-consuming cycle of editing scripts, running them, and viewing the output. Batch tools also tend to require more computer expertise from their users. PuffinPlot is a palaeomagnetic plotting and analysis program which aims to bridge this gap. First released in 2012, it offers both an interactive, user-friendly desktop interface and a batch scripting interface, both making use of the same core library of palaeomagnetic functions. We present new improvements to the program that help to integrate the interactive and batch approaches, allowing an analysis to be interactively explored and refined

  3. 18O-labeled proteome reference as global internal standards for targeted quantification by selected reaction monitoring-mass spectrometry.

    PubMed

    Kim, Jong-Seo; Fillmore, Thomas L; Liu, Tao; Robinson, Errol; Hossain, Mahmud; Champion, Boyd L; Moore, Ronald J; Camp, David G; Smith, Richard D; Qian, Wei-Jun

    2011-12-01

    Selected reaction monitoring (SRM)-MS is an emerging technology for high throughput targeted protein quantification and verification in biomarker discovery studies; however, the cost associated with the application of stable isotope-labeled synthetic peptides as internal standards can be prohibitive for screening a large number of candidate proteins as often required in the preverification phase of discovery studies. Herein we present a proof of concept study using an (18)O-labeled proteome reference as global internal standards (GIS) for SRM-based relative quantification. The (18)O-labeled proteome reference (or GIS) can be readily prepared and contains a heavy isotope ((18)O)-labeled internal standard for every possible tryptic peptide. Our results showed that the percentage of heavy isotope ((18)O) incorporation applying an improved protocol was >99.5% for most peptides investigated. The accuracy, reproducibility, and linear dynamic range of quantification were further assessed based on known ratios of standard proteins spiked into the labeled mouse plasma reference. Reliable quantification was observed with high reproducibility (i.e. coefficient of variance <10%) for analyte concentrations that were set at 100-fold higher or lower than those of the GIS based on the light ((16)O)/heavy ((18)O) peak area ratios. The utility of (18)O-labeled GIS was further illustrated by accurate relative quantification of 45 major human plasma proteins. Moreover, quantification of the concentrations of C-reactive protein and prostate-specific antigen was illustrated by coupling the GIS with standard additions of purified protein standards. Collectively, our results demonstrated that the use of (18)O-labeled proteome reference as GIS provides a convenient, low cost, and effective strategy for relative quantification of a large number of candidate proteins in biological or clinical samples using SRM.

  4. Improved Facial Nerve Identification During Parotidectomy With Fluorescently Labeled Peptide

    PubMed Central

    Hussain, Timon; Nguyen, Linda T.; Whitney, Michael; Hasselmann, Jonathan; Nguyen, Quyen T.

    2016-01-01

    Objectives/Hypothesis Additional intraoperative guidance could reduce the risk of iatrogenic injury during parotid gland cancer surgery. We evaluated the intraoperative use of fluorescently labeled nerve binding peptide NP41 to aid facial nerve identification and preservation during parotidectomy in an orthotopic model of murine parotid gland cancer. We also quantified the accuracy of intraoperative nerve detection for surface and buried nerves in the head and neck with NP41 versus white light (WL) alone. Study Design Twenty-eight mice underwent parotid gland cancer surgeries with additional fluorescence (FL) guidance versus WL reflectance (WLR) alone. Eight mice were used for additional nerve-imaging experiments. Methods Twenty-eight parotid tumor-bearing mice underwent parotidectomy. Eight mice underwent imaging of both sides of the face after skin removal. Postoperative assessment of facial nerve function measured by automated whisker tracking were compared between FL guidance (n = 13) versus WL alone (n = 15). In eight mice, nerve to surrounding tissue contrast was measured under FL versus WLR for all nerve branches detectable in the field of view. Results Postoperative facial nerve function after parotid gland cancer surgery tended to be better with additional FL guidance. Fluorescent labeling significantly improved nerve to surrounding tissue contrast for both large and smaller buried nerve branches compared to WLR visualization and improved detection sensitivity and specificity. Conclusions NP41 FL imaging significantly aids the intraoperative identification of nerve braches otherwise nearly invisible to the naked eye. Its application in a murine model of parotid gland cancer surgery tended to improve functional preservation of the facial nerve. PMID:27171862

  5. Exploring the Role of Information Professionals in Improving Research Reproducibility:A Case Study in Geosciences

    NASA Astrophysics Data System (ADS)

    Yan, A.; West, J.

    2016-12-01

    The validity of Geosciences research is of great significance to general public and policy-makers. In an earlier study, we surveyed 136 faculty and graduate students in geosciences. The result indicated that nearly 80% of respondents who had ever reproduced a published study had failed at least one time in reproducing, suggesting a general lack of research reproducibility in geosciences. Although there is much enthusiasm for creation of technologies such as workflow system, literate programming, and cloud-based system to facilitate reproducibility, much less emphasis has been placed on the information services essential for meaningful use of these tools. Library and Information Science (LIS) has a rich tradition of providing customized service for research communities. LIS professionals such as academic librarians have made strong contribution to resources locating, software recommending, data curation, metadata guidance, project management, submission review and author training. In particular, university libraries have been actively developing tools and offering guidelines, consultations, and trainings on Data Management Plan (DMP) required by National Science Foundation (NSF). And effective data management is a significant first step towards reproducible research. Hereby we argue that LIS professionals may be well-positioned to assist researchers to make their research reproducible. In this study, we aim to answer the question: how can LIS professionals assist geoscience researchers in making their research capable of being reproduced? We first synthesize different definitions of "reproducibility" and provide a conceptual framework of "reproducibility" in geosciences to resolve some of the misunderstandings around related terminology. Using a case study approach, we then examine 1) university librarians' technical skills, domain knowledge, professional activities, together with their awareness of, readiness for, and attitudes towards research reproducibility and

  6. A Simple Picaxe Microcontroller Pulse Source for Juxtacellular Neuronal Labelling

    PubMed Central

    Verberne, Anthony J. M.

    2016-01-01

    Juxtacellular neuronal labelling is a method which allows neurophysiologists to fill physiologically-identified neurons with small positively-charged marker molecules. Labelled neurons are identified by histochemical processing of brain sections along with immunohistochemical identification of neuropeptides, neurotransmitters, neurotransmitter transporters or biosynthetic enzymes. A microcontroller-based pulser circuit and associated BASIC software script is described for incorporation into the design of a commercially-available intracellular electrometer for use in juxtacellular neuronal labelling. Printed circuit board construction has been used for reliability and reproducibility. The current design obviates the need for a separate digital pulse source and simplifies the juxtacellular neuronal labelling procedure. PMID:28952589

  7. Improving accuracy of medication identification in an older population using a medication bottle color symbol label system

    PubMed Central

    2011-01-01

    Background The purpose of this pilot study was to evaluate and refine an adjuvant system of color-specific symbols that are added to medication bottles and to assess whether this system would increase the ability of patients 65 years of age or older in matching their medication to the indication for which it was prescribed. Methods This study was conducted in two phases, consisting of three focus groups of patients from a family medicine clinic (n = 25) and a pre-post medication identification test in a second group of patient participants (n = 100). Results of focus group discussions were used to refine the medication label symbols according to themes and messages identified through qualitative triangulation mechanisms and data analysis techniques. A pre-post medication identification test was conducted in the second phase of the study to assess differences between standard labeling alone and the addition of the refined color-specific symbols. The pre-post test examined the impact of the added labels on participants' ability to accurately match their medication to the indication for which it was prescribed when placed in front of participants and then at a distance of two feet. Results Participants appreciated the addition of a visual aid on existing medication labels because it would not be necessary to learn a completely new system of labeling, and generally found the colors and symbols used in the proposed labeling system easy to understand and relevant. Concerns were raised about space constraints on medication bottles, having too much information on the bottle, and having to remember what the colors meant. Symbols and colors were modified if they were found unclear or inappropriate by focus group participants. Pre-post medication identification test results in a second set of participants demonstrated that the addition of the symbol label significantly improved the ability of participants to match their medication to the appropriate medical indication at a

  8. Improving accuracy of medication identification in an older population using a medication bottle color symbol label system.

    PubMed

    Cardarelli, Roberto; Mann, Christopher; Fulda, Kimberly G; Balyakina, Elizabeth; Espinoza, Anna; Lurie, Sue

    2011-12-29

    The purpose of this pilot study was to evaluate and refine an adjuvant system of color-specific symbols that are added to medication bottles and to assess whether this system would increase the ability of patients 65 years of age or older in matching their medication to the indication for which it was prescribed. This study was conducted in two phases, consisting of three focus groups of patients from a family medicine clinic (n = 25) and a pre-post medication identification test in a second group of patient participants (n = 100). Results of focus group discussions were used to refine the medication label symbols according to themes and messages identified through qualitative triangulation mechanisms and data analysis techniques. A pre-post medication identification test was conducted in the second phase of the study to assess differences between standard labeling alone and the addition of the refined color-specific symbols. The pre-post test examined the impact of the added labels on participants' ability to accurately match their medication to the indication for which it was prescribed when placed in front of participants and then at a distance of two feet. Participants appreciated the addition of a visual aid on existing medication labels because it would not be necessary to learn a completely new system of labeling, and generally found the colors and symbols used in the proposed labeling system easy to understand and relevant. Concerns were raised about space constraints on medication bottles, having too much information on the bottle, and having to remember what the colors meant. Symbols and colors were modified if they were found unclear or inappropriate by focus group participants. Pre-post medication identification test results in a second set of participants demonstrated that the addition of the symbol label significantly improved the ability of participants to match their medication to the appropriate medical indication at a distance of two feet (p < 0

  9. Reproducibility of Brain Morphometry from Short-Term Repeat Clinical MRI Examinations: A Retrospective Study

    PubMed Central

    Liu, Hon-Man; Chen, Shan-Kai; Chen, Ya-Fang; Lee, Chung-Wei; Yeh, Lee-Ren

    2016-01-01

    Purpose To assess the inter session reproducibility of automatic segmented MRI-derived measures by FreeSurfer in a group of subjects with normal-appearing MR images. Materials and Methods After retrospectively reviewing a brain MRI database from our institute consisting of 14,758 adults, those subjects who had repeat scans and had no history of neurodegenerative disorders were selected for morphometry analysis using FreeSurfer. A total of 34 subjects were grouped by MRI scanner model. After automatic segmentation using FreeSurfer, label-wise comparison (involving area, thickness, and volume) was performed on all segmented results. An intraclass correlation coefficient was used to estimate the agreement between sessions. Wilcoxon signed rank test was used to assess the population mean rank differences across sessions. Mean-difference analysis was used to evaluate the difference intervals across scanners. Absolute percent difference was used to estimate the reproducibility errors across the MRI models. Kruskal-Wallis test was used to determine the across-scanner effect. Results The agreement in segmentation results for area, volume, and thickness measurements of all segmented anatomical labels was generally higher in Signa Excite and Verio models when compared with Sonata and TrioTim models. There were significant rank differences found across sessions in some labels of different measures. Smaller difference intervals in global volume measurements were noted on images acquired by Signa Excite and Verio models. For some brain regions, significant MRI model effects were observed on certain segmentation results. Conclusions Short-term scan-rescan reliability of automatic brain MRI morphometry is feasible in the clinical setting. However, since repeatability of software performance is contingent on the reproducibility of the scanner performance, the scanner performance must be calibrated before conducting such studies or before using such software for retrospective

  10. A label distance maximum-based classifier for multi-label learning.

    PubMed

    Liu, Xiaoli; Bao, Hang; Zhao, Dazhe; Cao, Peng

    2015-01-01

    Multi-label classification is useful in many bioinformatics tasks such as gene function prediction and protein site localization. This paper presents an improved neural network algorithm, Max Label Distance Back Propagation Algorithm for Multi-Label Classification. The method was formulated by modifying the total error function of the standard BP by adding a penalty term, which was realized by maximizing the distance between the positive and negative labels. Extensive experiments were conducted to compare this method against state-of-the-art multi-label methods on three popular bioinformatic benchmark datasets. The results illustrated that this proposed method is more effective for bioinformatic multi-label classification compared to commonly used techniques.

  11. Improved facial nerve identification during parotidectomy with fluorescently labeled peptide.

    PubMed

    Hussain, Timon; Nguyen, Linda T; Whitney, Michael; Hasselmann, Jonathan; Nguyen, Quyen T

    2016-12-01

    Additional intraoperative guidance could reduce the risk of iatrogenic injury during parotid gland cancer surgery. We evaluated the intraoperative use of fluorescently labeled nerve binding peptide NP41 to aid facial nerve identification and preservation during parotidectomy in an orthotopic model of murine parotid gland cancer. We also quantified the accuracy of intraoperative nerve detection for surface and buried nerves in the head and neck with NP41 versus white light (WL) alone. Twenty-eight mice underwent parotid gland cancer surgeries with additional fluorescence (FL) guidance versus WL reflectance (WLR) alone. Eight mice were used for additional nerve-imaging experiments. Twenty-eight parotid tumor-bearing mice underwent parotidectomy. Eight mice underwent imaging of both sides of the face after skin removal. Postoperative assessment of facial nerve function measured by automated whisker tracking were compared between FL guidance (n = 13) versus WL alone (n=15). In eight mice, nerve to surrounding tissue contrast was measured under FL versus WLR for all nerve branches detectable in the field of view. Postoperative facial nerve function after parotid gland cancer surgery tended to be better with additional FL guidance. Fluorescent labeling significantly improved nerve to surrounding tissue contrast for both large and smaller buried nerve branches compared to WLR visualization and improved detection sensitivity and specificity. NP41 FL imaging significantly aids the intraoperative identification of nerve braches otherwise nearly invisible to the naked eye. Its application in a murine model of parotid gland cancer surgery tended to improve functional preservation of the facial nerve. NA Laryngoscope, 126:2711-2717, 2016. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  12. Quantifying reproducibility in computational biology: the case of the tuberculosis drugome.

    PubMed

    Garijo, Daniel; Kinnings, Sarah; Xie, Li; Xie, Lei; Zhang, Yinliang; Bourne, Philip E; Gil, Yolanda

    2013-01-01

    How easy is it to reproduce the results found in a typical computational biology paper? Either through experience or intuition the reader will already know that the answer is with difficulty or not at all. In this paper we attempt to quantify this difficulty by reproducing a previously published paper for different classes of users (ranging from users with little expertise to domain experts) and suggest ways in which the situation might be improved. Quantification is achieved by estimating the time required to reproduce each of the steps in the method described in the original paper and make them part of an explicit workflow that reproduces the original results. Reproducing the method took several months of effort, and required using new versions and new software that posed challenges to reconstructing and validating the results. The quantification leads to "reproducibility maps" that reveal that novice researchers would only be able to reproduce a few of the steps in the method, and that only expert researchers with advance knowledge of the domain would be able to reproduce the method in its entirety. The workflow itself is published as an online resource together with supporting software and data. The paper concludes with a brief discussion of the complexities of requiring reproducibility in terms of cost versus benefit, and a desiderata with our observations and guidelines for improving reproducibility. This has implications not only in reproducing the work of others from published papers, but reproducing work from one's own laboratory.

  13. Improved Photoinduced Fluorogenic Alkene-Tetrazole Reaction for Protein Labeling.

    PubMed

    Shang, Xin; Lai, Rui; Song, Xi; Li, Hui; Niu, Wei; Guo, Jiantao

    2017-11-15

    The 1,3-dipolar cycloaddition reaction between an alkene and a tetrazole represents one elegant and rare example of fluorophore-forming bioorthogonal chemistry. This is an attractive reaction for imaging applications in live cells that requires less intensive washing steps and/or needs spatiotemporal resolutions. In the present work, as an effort to improve the fluorogenic property of the alkene-tetrazole reaction, an aromatic alkene (styrene) was investigated as the dipolarophile. Over 30-fold improvement in quantum yield of the reaction product was achieved in aqueous solution. According to our mechanistic studies, the observed improvement is likely due to an insufficient protonation of the styrene-tetrazole reaction product. This finding provides useful guidance to the future design of alkene-tetrazole reactions for biological studies. Fluorogenic protein labeling using the styrene-tetrazole reaction was demonstrated both in vitro and in vivo. This was realized by the genetic incorporation of an unnatural amino acid containing the styrene moiety. It is anticipated that the combination of styrene with different tetrazole derivatives can generally improve and broaden the application of alkene-tetrazole chemistry in real-time imaging in live cells.

  14. Reproducibility of Differential Proteomic Technologies in CPTAC Fractionated Xenografts

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

    Tabb, David L.; Wang, Xia; Carr, Steven A.

    2016-03-04

    The NCI Clinical Proteomic Tumor Analysis Consortium (CPTAC) employed a pair of reference xenograft proteomes for initial platform validation and ongoing quality control of its data collection for The Cancer Genome Atlas (TCGA) tumors. These two xenografts, representing basal and luminal-B human breast cancer, were fractionated and analyzed on six mass spectrometers in a total of 46 replicates divided between iTRAQ and label-free technologies, spanning a total of 1095 LC-MS/MS experiments. These data represent a unique opportunity to evaluate the stability of proteomic differentiation by mass spectrometry over many months of time for individual instruments or across instruments running dissimilarmore » workflows. We evaluated iTRAQ reporter ions, label-free spectral counts, and label-free extracted ion chromatograms as strategies for data interpretation. From these assessments we found that differential genes from a single replicate were confirmed by other replicates on the same instrument from 61-93% of the time. When comparing across different instruments and quantitative technologies, differential genes were reproduced by other data sets from 67-99% of the time. Projecting gene differences to biological pathways and networks increased the similarities. These overlaps send an encouraging message about the maturity of technologies for proteomic differentiation.« less

  15. Improved reproducibility of unit-cell parameters in macromolecular cryocrystallography by limiting dehydration during crystal mounting.

    PubMed

    Farley, Christopher; Burks, Geoffry; Siegert, Thomas; Juers, Douglas H

    2014-08-01

    In macromolecular cryocrystallography unit-cell parameters can have low reproducibility, limiting the effectiveness of combining data sets from multiple crystals and inhibiting the development of defined repeatable cooling protocols. Here, potential sources of unit-cell variation are investigated and crystal dehydration during loop-mounting is found to be an important factor. The amount of water lost by the unit cell depends on the crystal size, the loop size, the ambient relative humidity and the transfer distance to the cooling medium. To limit water loss during crystal mounting, a threefold strategy has been implemented. Firstly, crystal manipulations are performed in a humid environment similar to the humidity of the crystal-growth or soaking solution. Secondly, the looped crystal is transferred to a vial containing a small amount of the crystal soaking solution. Upon loop transfer, the vial is sealed, which allows transport of the crystal at its equilibrated humidity. Thirdly, the crystal loop is directly mounted from the vial into the cold gas stream. This strategy minimizes the exposure of the crystal to relatively low humidity ambient air, improves the reproducibility of low-temperature unit-cell parameters and offers some new approaches to crystal handling and cryoprotection.

  16. Improved reproducibility of unit-cell parameters in macromolecular cryocrystallography by limiting dehydration during crystal mounting

    PubMed Central

    Farley, Christopher; Burks, Geoffry; Siegert, Thomas; Juers, Douglas H.

    2014-01-01

    In macromolecular cryocrystallography unit-cell parameters can have low reproducibility, limiting the effectiveness of combining data sets from multiple crystals and inhibiting the development of defined repeatable cooling protocols. Here, potential sources of unit-cell variation are investigated and crystal dehydration during loop-mounting is found to be an important factor. The amount of water lost by the unit cell depends on the crystal size, the loop size, the ambient relative humidity and the transfer distance to the cooling medium. To limit water loss during crystal mounting, a threefold strategy has been implemented. Firstly, crystal manipulations are performed in a humid environment similar to the humidity of the crystal-growth or soaking solution. Secondly, the looped crystal is transferred to a vial containing a small amount of the crystal soaking solution. Upon loop transfer, the vial is sealed, which allows transport of the crystal at its equilibrated humidity. Thirdly, the crystal loop is directly mounted from the vial into the cold gas stream. This strategy minimizes the exposure of the crystal to relatively low humidity ambient air, improves the reproducibility of low-temperature unit-cell parameters and offers some new approaches to crystal handling and cryoprotection. PMID:25084331

  17. Improving Labels to Reduce Pesticide Drift

    EPA Pesticide Factsheets

    We encourage pesticide manufacturers to state on their product labels that applicators should use DRT-rated technologies in applying pesticide products. The page includes information on how to obtain approval to add these instructions.

  18. PRN 83-3: Label Improvement Program - Storage and Disposal Label Statements

    EPA Pesticide Factsheets

    This Notice is to inform all registrants that the label of all pesticide products must include updated storage and disposal statements. No application for amended registration is required if you use the exact wording contained in this Notice.

  19. Label-Enhanced Surface Plasmon Resonance: A New Concept for Improved Performance in Optical Biosensor Analysis

    PubMed Central

    Granqvist, Niko; Hanning, Anders; Eng, Lars; Tuppurainen, Jussi; Viitala, Tapani

    2013-01-01

    Surface plasmon resonance (SPR) is a well-established optical biosensor technology with many proven applications in the study of molecular interactions as well as in surface and material science. SPR is usually applied in the label-free mode which may be advantageous in cases where the presence of a label may potentially interfere with the studied interactions per se. However, the fundamental challenges of label-free SPR in terms of limited sensitivity and specificity are well known. Here we present a new concept called label-enhanced SPR, which is based on utilizing strongly absorbing dye molecules in combination with the evaluation of the full shape of the SPR curve, whereby the sensitivity as well as the specificity of SPR is significantly improved. The performance of the new label-enhanced SPR method was demonstrated by two simple model assays: a small molecule assay and a DNA hybridization assay. The small molecule assay was used to demonstrate the sensitivity enhancement of the method, and how competitive assays can be used for relative affinity determination. The DNA assay was used to demonstrate the selectivity of the assay, and the capabilities in eliminating noise from bulk liquid composition variations. PMID:24217357

  20. Nutrient profiling for front of pack labelling: how to align logical consumer choice with improvement of products?

    PubMed

    Roodenburg, Annet J C

    2017-08-01

    The primary goal of front of pack (FOP) labelling is to help consumers make healthier choices through communication. A secondary goal is to encourage producers to improve the nutritional composition of their products. Evidence has shown that (FOP) labelling can help consumers to make healthier food choices and has been an incentive for producers to improve product composition. As FOP labelling is seen as an important tool to improve food environments for public health purposes, the WHO supports initiatives of governments to implement an FOP labelling system. Based on the experiences of a wide range of countries over many years, possible success factors for such an FOP system have been defined, six of which are discussed in the present paper and used to evaluate the Dutch Choices Programme that was started in 2006. In the course of time a large number of producers joined the programme and the logo was recognised by more than 90 % of the consumers, but by 2016 the Dutch consumer organisation argued on the basis of their own research that a quarter of the consumers did not understand the colour coding of the logo and as a result the Dutch government decided to no longer support this logo and to introduce a nutrition app. The challenge that remains is to find a system that consumers understand well and that still encourages manufacturers of food to improve product composition. New technology-based data collecting initiatives might provide the right tools to develop such a system.

  1. Evaluation of a novel educational strategy, including inhaler-based reminder labels, to improve asthma inhaler technique.

    PubMed

    Basheti, Iman A; Armour, Carol L; Bosnic-Anticevich, Sinthia Z; Reddel, Helen K

    2008-07-01

    To evaluate the feasibility, acceptability and effectiveness of a brief intervention about inhaler technique, delivered by community pharmacists to asthma patients. Thirty-one pharmacists received brief workshop education (Active: n=16, CONTROL: n=15). Active Group pharmacists were trained to assess and teach dry powder inhaler technique, using patient-centered educational tools including novel Inhaler Technique Labels. Interventions were delivered to patients at four visits over 6 months. At baseline, patients (Active: 53, CONTROL: 44) demonstrated poor inhaler technique (mean+/-S.D. score out of 9, 5.7+/-1.6). At 6 months, improvement in inhaler technique score was significantly greater in Active cf. CONTROL patients (2.8+/-1.6 cf. 0.9+/-1.4, p<0.001), and asthma severity was significantly improved (p=0.015). Qualitative responses from patients and pharmacists indicated a high level of satisfaction with the intervention and educational tools, both for their effectiveness and for their impact on the patient-pharmacist relationship. A simple feasible intervention in community pharmacies, incorporating daily reminders via Inhaler Technique Labels on inhalers, can lead to improvement in inhaler technique and asthma outcomes. Brief training modules and simple educational tools, such as Inhaler Technique Labels, can provide a low-cost and sustainable way of changing patient behavior in asthma, using community pharmacists as educators.

  2. Comparison of ASL and DCE MRI for the non-invasive measurement of renal blood flow: quantification and reproducibility.

    PubMed

    Cutajar, Marica; Thomas, David L; Hales, Patrick W; Banks, T; Clark, Christopher A; Gordon, Isky

    2014-06-01

    To investigate the reproducibility of arterial spin labelling (ASL) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) and quantitatively compare these techniques for the measurement of renal blood flow (RBF). Sixteen healthy volunteers were examined on two different occasions. ASL was performed using a multi-TI FAIR labelling scheme with a segmented 3D-GRASE imaging module. DCE MRI was performed using a 3D-FLASH pulse sequence. A Bland-Altman analysis was used to assess repeatability of each technique, and determine the degree of correspondence between the two methods. The overall mean cortical renal blood flow (RBF) of the ASL group was 263 ± 41 ml min(-1) [100 ml tissue](-1), and using DCE MRI was 287 ± 70 ml min(-1) [100 ml tissue](-1). The group coefficient of variation (CVg) was 18 % for ASL and 28 % for DCE-MRI. Repeatability studies showed that ASL was more reproducible than DCE with CVgs of 16 % and 25 % for ASL and DCE respectively. Bland-Altman analysis comparing the two techniques showed a good agreement. The repeated measures analysis shows that the ASL technique has better reproducibility than DCE-MRI. Difference analysis shows no significant difference between the RBF values of the two techniques. Reliable non-invasive monitoring of renal blood flow is currently clinically unavailable. Renal arterial spin labelling MRI is robust and repeatable. Renal dynamic contrast-enhanced MRI is robust and repeatable. ASL blood flow values are similar to those obtained using DCE-MRI.

  3. Characterization and relative quantification of phospholipids based on methylation and stable isotopic labeling[S

    PubMed Central

    Cai, Tanxi; Shu, Qingbo; Liu, Peibin; Niu, Lili; Guo, Xiaojing; Ding, Xiang; Xue, Peng; Xie, Zhensheng; Wang, Jifeng; Zhu, Nali; Wu, Peng; Niu, Lili; Yang, Fuquan

    2016-01-01

    Phospholipids (PLs), one of the lipid categories, are not only the primary building blocks of cellular membranes, but also can be split to produce products that function as second messengers in signal transduction and play a pivotal role in numerous cellular processes, including cell growth, survival, and motility. Here, we present an integrated novel method that combines a fast and robust TMS-diazomethane-based phosphate derivatization and isotopic labeling strategy, which enables simultaneous profiling and relative quantification of PLs from biological samples. Our results showed that phosphate methylation allows fast and sensitive identification of the six major PL classes, including their lysophospholipid counterparts, under positive ionization mode. The isotopic labeling of endogenous PLs was achieved by deuterated diazomethane, which was generated through acid-catalyzed hydrogen/deuterium (H/D) exchange and methanolysis of TMS-diazomethane during the process of phosphate derivatization. The measured H/D ratios of unlabeled and labeled PLs, which were mixed in known proportions, indicated that the isotopic labeling strategy is capable of providing relative quantitation with adequate accuracy, reproducibility, and a coefficient of variation of 9.1%, on average. This novel method offers unique advantages over existing approaches and presents a powerful tool for research of PL metabolism and signaling. PMID:26733148

  4. Combining Perfluorocarbon and Superparamagnetic Iron-oxide Cell Labeling for Improved and Expanded Applications of Cellular MRI

    PubMed Central

    Hitchens, T. Kevin; Liu, Li; Foley, Lesley M.; Simplaceanu, Virgil; Ahrens, Eric T.; Ho, Chien

    2014-01-01

    Purpose The ability to detect the migration of cells in living organisms is fundamental in understanding biological processes and important for the development of novel cell-based therapies to treat disease. MRI can be used to detect the migration of cells labeled with superparamagnetic iron-oxide (SPIO) or perfluorocarbon (PFC) agents. In this study, we explored combining these two cell-labeling approaches to overcome current limitations and enable new applications for cellular MRI. Methods We characterized 19F-NMR relaxation properties of PFC-labeled cells in the presence of SPIO and imaged cells both ex vivo and in vivo in a rodent inflammation model to demonstrate selective visualization of cell populations. Results We show that with UTE3D, RARE and FLASH 19F images one can uniquely identify PFC-labeled cells, co-localized PFC- and SPIO-labeled cells, and PFC/SPIO co-labeled cells. Conclusion This new methodology has the ability to improve and expand applications of MRI cell tracking. Combining PFC and SPIO strategies can potentially provide a method to quench PFC signal transferred from dead cells to macrophages, thereby eliminating false positives. In addition, combining these techniques could also be used to track two cell types simultaneously and probe cell-cell proximity in vivo with MRI. PMID:24478194

  5. Structured product labeling improves detection of drug-intolerance issues.

    PubMed

    Schadow, Gunther

    2009-01-01

    This study sought to assess the value of the Health Level 7/U.S. Food and Drug Administration Structured Product Labeling (SPL) drug knowledge representation standard and its associated terminology sources for drug-intolerance (allergy) decision support in computerized provider order entry (CPOE) systems. The Regenstrief Institute CPOE drug-intolerance issue detection system and its knowledge base was compared with a method based on existing SPL label content enriched with knowledge sources used with SPL (NDF-RT/MeSH). Both methods were applied to a large set of drug-intolerance (allergy) records, drug orders, and medication dispensing records covering >50,000 patients over 30 years. The number of drug-intolerance issues detected by both methods was counted, as well as the number of patients with issues, number of distinct drugs, and number of distinct intolerances. The difference between drug-intolerance issues detected or missed by either method was qualitatively analyzed. Although <70% of terms were mapped to SPL, the new approach detected four times as many drug-intolerance issues on twice as many patients. The SPL-based approach is more sensitive and suggests that mapping local dictionaries to SPL, and enhancing the depth and breadth of coverage of SPL content are worth accelerating. The study also highlights specificity problems known to trouble drug-intolerance decision support and suggests how terminology and methods of recording drug intolerances could be improved.

  6. Effectiveness of FDA's new over-the-counter acetaminophen warning label in improving consumer risk perception of liver damage.

    PubMed

    Goyal, R K; Rajan, S S; Essien, E J; Sansgiry, S S

    2012-12-01

    The Food and Drug Administration (FDA) issued new organ-specific warning label requirements for over-the-counter (OTC) analgesic products in order to make consumers aware of the risk of liver damage when using acetaminophen. However, awareness of a health risk alone cannot ensure consumers' engagement in safe and preventive behaviour. In this study, we attempted to: (i) measure consumer risk perception of liver damage due to the OTC acetaminophen products and (ii) analyse the effectiveness of the new organ-specific warning label in improving consumer risk perception of liver damage and intention to perform protective behaviours while using OTC acetaminophen products. This within-subject experimental study used a convenience sample of English-speaking adults visiting OTC segments of selected pharmacy stores in Houston. Participants were randomly exposed to the old and new warning labels and their respective risk perception (measured on a visual analogue scale, 0%, no risk, to 100%, extreme risk) and behavioural intention (measured on a 7-point Likert scale) were recorded using a validated, self-administered questionnaire. Descriptive statistics and non-parametric Wilcoxon signed-rank tests were performed using sas statistical software (v 9.2) at a priori significance level of 0.05. Majority of participants (74.4%) were not aware of the new warnings; however, majority (67.8%) had prior knowledge of the risk. The mean risk perception score for the new warning label was found to be significantly higher (72.2% vs. 65.9%, P < 0.0001) than the old warning label. Similarly, the average intention score for the new warning label was significantly higher (5.06 vs. 4.86, P < 0.0001) than the old warning label. The new warning label mandated by FDA is effective in improving consumer risk perception of potential liver damage and may encourage protective behaviour. However, future studies are essential to assess the impact of the new label on actual changes in consumer behaviour

  7. Saturation Fluorescence Labeling of Proteins for Proteomic Analyses

    PubMed Central

    Pretzer, Elizabeth; Wiktorowicz, John E.

    2008-01-01

    We present here an optimized and cost-effective approach to saturation fluorescence labeling of protein thiols for proteomic analysis. We investigated a number of conditions and reagent concentrations including a disulfide reducing agent (TCEP), pH, incubation time, linearity of labeling, and saturating dye: protein thiol ratio with protein standards to gauge specific and non-specific labeling. Efficacy of labeling under these conditions was quantified using specific fluorescence estimation, defined as the ratio of fluorescence pixel intensities and Coomassie-stained pixel intensities of bands after digital imaging. Factors leading to specific vs. non-specific labeling in the presence of thiourea are also discussed. We have found that reproducible saturation of available Cys residues of the proteins used as labeling standards (human carbonic anhydrase I, enolase, α-lactalbumin) is achieved at 50-100-fold excess of the uncharged maleimide-functionalized BODIPY™ dyes over Cys. We confirm our previous findings and those of others that the maleimide dyes are not impacted by the presence of 2M thiourea. Moreover, we establish that 2 mM TCEP used as reductant is optimal. We also establish further that labeling is optimal at pH 7.5 and complete after 30 min. Low non-specific labeling was gauged by the inclusion of non-Cys containing proteins (horse myoglobin, bovine carbonic anhydrase) to the labeling mixture. We also show that the dye exhibits little to no effect on the two dimensional mobilities of labeled proteins derived from cells. PMID:18191033

  8. Undefined cellulase formulations hinder scientific reproducibility

    DOE PAGES

    Himmel, Michael E.; Abbas, Charles A.; Baker, John O.; ...

    2017-11-28

    In the shadow of a burgeoning biomass-to-fuels industry, biological conversion of lignocellulose to fermentable sugars in a cost-effective manner is key to the success of second-generation and advanced biofuel production. For the effective comparison of one cellulase preparation to another, cellulase assays are typically carried out with one or more engineered cellulase formulations or natural exoproteomes of known performance serving as positive controls. When these formulations have unknown composition, as is the case with several widely used commercial products, it becomes impossible to compare or reproduce work done today to work done in the future, where, for example, such preparationsmore » may not be available. Therefore, being a critical tenet of science publishing, experimental reproducibility is endangered by the continued use of these undisclosed products. We propose the introduction of standard procedures and materials to produce specific and reproducible cellulase formulations. These formulations are to serve as yardsticks to measure improvements and performance of new cellulase formulations.« less

  9. Undefined cellulase formulations hinder scientific reproducibility

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

    Himmel, Michael E.; Abbas, Charles A.; Baker, John O.

    In the shadow of a burgeoning biomass-to-fuels industry, biological conversion of lignocellulose to fermentable sugars in a cost-effective manner is key to the success of second-generation and advanced biofuel production. For the effective comparison of one cellulase preparation to another, cellulase assays are typically carried out with one or more engineered cellulase formulations or natural exoproteomes of known performance serving as positive controls. When these formulations have unknown composition, as is the case with several widely used commercial products, it becomes impossible to compare or reproduce work done today to work done in the future, where, for example, such preparationsmore » may not be available. Therefore, being a critical tenet of science publishing, experimental reproducibility is endangered by the continued use of these undisclosed products. We propose the introduction of standard procedures and materials to produce specific and reproducible cellulase formulations. These formulations are to serve as yardsticks to measure improvements and performance of new cellulase formulations.« less

  10. 3D GRASE PROPELLER: improved image acquisition technique for arterial spin labeling perfusion imaging.

    PubMed

    Tan, Huan; Hoge, W Scott; Hamilton, Craig A; Günther, Matthias; Kraft, Robert A

    2011-07-01

    Arterial spin labeling is a noninvasive technique that can quantitatively measure cerebral blood flow. While traditionally arterial spin labeling employs 2D echo planar imaging or spiral acquisition trajectories, single-shot 3D gradient echo and spin echo (GRASE) is gaining popularity in arterial spin labeling due to inherent signal-to-noise ratio advantage and spatial coverage. However, a major limitation of 3D GRASE is through-plane blurring caused by T(2) decay. A novel technique combining 3D GRASE and a periodically rotated overlapping parallel lines with enhanced reconstruction trajectory (PROPELLER) is presented to minimize through-plane blurring without sacrificing perfusion sensitivity or increasing total scan time. Full brain perfusion images were acquired at a 3 × 3 × 5 mm(3) nominal voxel size with pulsed arterial spin labeling preparation sequence. Data from five healthy subjects was acquired on a GE 1.5T scanner in less than 4 minutes per subject. While showing good agreement in cerebral blood flow quantification with 3D gradient echo and spin echo, 3D GRASE PROPELLER demonstrated reduced through-plane blurring, improved anatomical details, high repeatability and robustness against motion, making it suitable for routine clinical use. Copyright © 2011 Wiley-Liss, Inc.

  11. Application of Cardiac Gating to Improve the Reproducibility of Intravoxel Incoherent Motion Measurements in the Head and Neck.

    PubMed

    Kang, Koung Mi; Choi, Seung Hong; Kim, Dong Eun; Yun, Tae Jin; Kim, Ji-Hoon; Sohn, Chul-Ho; Park, Sun-Won

    2017-07-10

    To prospectively evaluate whether cardiac gating can improve the reproducibility of intravoxel incoherent motion (IVIM) parameters in the head and neck, we performed IVIM diffusion-weighted imaging (DWI) using 4 b values (4b), 4 b values with cardiac gating (4b gating) and 17 b values (17b). We performed IVIM DWI twice per person on nine healthy volunteers using 4b, 4b gating and 17b and five patients with head and neck masses using 4b gating and 17b. The ADC, perfusion fraction (f), diffusion coefficient (D) and perfusion-related diffusion coefficient (D*) were calculated in the brain, masticator muscle, parotid gland, submandibular gland, tonsil and masses. Intraclass coefficient (ICC), Bland-Altman analysis (BAA) and coefficient of variation (CV) were used to assess short-term test-retest reproducibility. Kruskal-Wallis test and Mann-Whitney test were used to investigate whether 4b, 4b gating or 17b had significant influences on the parameters. For normal tissues and masses, ICC was excellent for all maps except the D* map. All parameters showed the lowest CV in the 4b gating. BAA also revealed the narrowest 95% limits of agreement using 4b gating for all parameters. In the subgroup analysis, almost all parameters in brain, muscle, parotid gland and submandibular gland showed the best reproducibility using 4b gating. In the muscle, parotid gland and submandibular gland, the values of ADC, f and D were not significantly different between among the three methods. 4b gating was more reproducible with respect to measurements of IVIM parameters in comparison with 4b or 17b.

  12. Co-Labeling for Multi-View Weakly Labeled Learning.

    PubMed

    Xu, Xinxing; Li, Wen; Xu, Dong; Tsang, Ivor W

    2016-06-01

    It is often expensive and time consuming to collect labeled training samples in many real-world applications. To reduce human effort on annotating training samples, many machine learning techniques (e.g., semi-supervised learning (SSL), multi-instance learning (MIL), etc.) have been studied to exploit weakly labeled training samples. Meanwhile, when the training data is represented with multiple types of features, many multi-view learning methods have shown that classifiers trained on different views can help each other to better utilize the unlabeled training samples for the SSL task. In this paper, we study a new learning problem called multi-view weakly labeled learning, in which we aim to develop a unified approach to learn robust classifiers by effectively utilizing different types of weakly labeled multi-view data from a broad range of tasks including SSL, MIL and relative outlier detection (ROD). We propose an effective approach called co-labeling to solve the multi-view weakly labeled learning problem. Specifically, we model the learning problem on each view as a weakly labeled learning problem, which aims to learn an optimal classifier from a set of pseudo-label vectors generated by using the classifiers trained from other views. Unlike traditional co-training approaches using a single pseudo-label vector for training each classifier, our co-labeling approach explores different strategies to utilize the predictions from different views, biases and iterations for generating the pseudo-label vectors, making our approach more robust for real-world applications. Moreover, to further improve the weakly labeled learning on each view, we also exploit the inherent group structure in the pseudo-label vectors generated from different strategies, which leads to a new multi-layer multiple kernel learning problem. Promising results for text-based image retrieval on the NUS-WIDE dataset as well as news classification and text categorization on several real-world multi

  13. Progress toward openness, transparency, and reproducibility in cognitive neuroscience.

    PubMed

    Gilmore, Rick O; Diaz, Michele T; Wyble, Brad A; Yarkoni, Tal

    2017-05-01

    Accumulating evidence suggests that many findings in psychological science and cognitive neuroscience may prove difficult to reproduce; statistical power in brain imaging studies is low and has not improved recently; software errors in analysis tools are common and can go undetected for many years; and, a few large-scale studies notwithstanding, open sharing of data, code, and materials remain the rare exception. At the same time, there is a renewed focus on reproducibility, transparency, and openness as essential core values in cognitive neuroscience. The emergence and rapid growth of data archives, meta-analytic tools, software pipelines, and research groups devoted to improved methodology reflect this new sensibility. We review evidence that the field has begun to embrace new open research practices and illustrate how these can begin to address problems of reproducibility, statistical power, and transparency in ways that will ultimately accelerate discovery. © 2017 New York Academy of Sciences.

  14. Skin protection by sunscreens is improved by explicit labeling and providing free sunscreen.

    PubMed

    Nicol, Isabelle; Gaudy, Caroline; Gouvernet, Joanny; Richard, Marie A; Grob, Jean J

    2007-01-01

    Whatever the improvement in the protection spectrum of sunscreens (SCs), actual skin protection mainly depends on the way they are used, especially on the quantity applied. This prospective randomized study assessed how much sun protection factor (SPF) labeling, which is hardly understandable by a layman, and high cost account for misuse of SCs. In three beach resorts in France, 364 individuals were blindly randomized during their holidays to three arms (1) free SCs intervention (FS) = four types of SCs with their usual SPF label (60B-A, 20B-A, 12B-A, 6B-3A) at free disposal; (2) same free SCs with an explicit labeling (FNL), including sunburn protection, likely protection against long-term effects of UV, and possibility to get a tan; and (3) no intervention (NI). As compared to FS, FNL increased the quantity of SCs applied, mainly in the minority of people who were not "tan-seekers", reduced sunburns particularly in sun-sensitive individuals (25.6 vs 58.3%, P=0.005), and induced a shift in the level of SCs chosen. Free delivery SCs were associated with a more systematic application of SCs in case of exposure, and a decreased sunburn occurrence, without increase of exposure. These results suggest that a labeling more explicit for the public would result in a better protection in SC users and that cost could be a limiting factor to use SC as often as necessary.

  15. Mass Defect Labeling of Cysteine for Improving Peptide Assignment in Shotgun Proteomic Analyses

    PubMed Central

    Hernandez, Hilda; Niehauser, Sarah; Boltz, Stacey A.; Gawandi, Vijay; Phillips, Robert S.; Amster, I. Jonathan

    2006-01-01

    A method for improving the identification of peptides in a shotgun proteome analysis using accurate mass measurement has been developed. The improvement is based upon the derivatization of cysteine residues with a novel reagent, 2,4-dibromo-(2′-iodo)acetanilide. The derivitization changes the mass defect of cysteine-containing proteolytic peptides in a manner that increases their identification specificity. Peptide masses were measured using matrix-assisted laser desorption/ionization Fourier transform ion cyclotron mass spectrometry. Reactions with protein standards show that the derivatization of cysteine is rapid and quantitative, and the data suggest that the derivatized peptides are more easily ionized or detected than unlabeled cysteine-containing peptides. The reagent was tested on a 15N-metabolically labeled proteome from M. maripaludis. Proteins were identified by their accurate mass values and from their nitrogen stoichiometry. A total of 47% of the labeled peptides are identified versus 27% for the unlabeled peptides. This procedure permits the identification of proteins from the M. maripaludis proteome that are not usually observed by the standard protocol and shows that better protein coverage is obtained with this methodology. PMID:16689545

  16. Using label-free screening technology to improve efficiency in drug discovery.

    PubMed

    Halai, Reena; Cooper, Matthew A

    2012-02-01

    Screening assays have traditionally utilized reporter labels to quantify biological responses relevant to the disease state of interest. However, there are limitations associated with the use of labels that may be overcome with temporal measurements possible with label-free. This review comprises general and system-specific information from literature searches using PubMed, published books and the authors' personal experience. This review highlights the label-free approaches in the context of various applications. The authors also note technical issues relevant to the development of label-free assays and their application to HTS. The limitations associated with the use of transfected cell lines and the use of label-based assays are gradually being realized. As such, greater emphasis is being placed on label-free biophysical techniques using native cell lines. The introduction of 96- and 384-well plate label-free systems is helping to broker a wider acceptance of these approaches in high-throughput screening. However, potential users of the technologies remain skeptical, primarily because the physical basis of the signals generated, and their contextual relevance to cell biology and signal transduction, has not been fully elucidated. Until this is done, these new technology platforms are more likely to complement, rather than replace, traditional screening platforms.

  17. High-throughput profiling of nanoparticle-protein interactions by fluorescamine labeling.

    PubMed

    Ashby, Jonathan; Duan, Yaokai; Ligans, Erik; Tamsi, Michael; Zhong, Wenwan

    2015-02-17

    A rapid, high throughput fluorescence assay was designed to screen interactions between proteins and nanoparticles. The assay employs fluorescamine, a primary-amine specific fluorogenic dye, to label proteins. Because fluorescamine could specifically target the surface amines on proteins, a conformational change of the protein upon interaction with nanoparticles will result in a change in fluorescence. In the present study, the assay was applied to test the interactions between a selection of proteins and nanoparticles made of polystyrene, silica, or iron oxide. The particles were also different in their hydrodynamic diameter, synthesis procedure, or surface modification. Significant labeling differences were detected when the same protein incubated with different particles. Principal component analysis (PCA) on the collected fluorescence profiles revealed clear grouping effects of the particles based on their properties. The results prove that fluorescamine labeling is capable of detecting protein-nanoparticle interactions, and the resulting fluorescence profile is sensitive to differences in nanoparticle's physical properties. The assay can be carried out in a high-throughput manner, and is rapid with low operation cost. Thus, it is well suited for evaluating interactions between a larger number of proteins and nanoparticles. Such assessment can help to improve our understanding on the molecular basis that governs the biological behaviors of nanomaterials. It will also be useful for initial examination of the bioactivity and reproducibility of nanomaterials employed in biomedical fields.

  18. Personalized, Shareable Geoscience Dataspaces For Simplifying Data Management and Improving Reproducibility

    NASA Astrophysics Data System (ADS)

    Malik, T.; Foster, I.; Goodall, J. L.; Peckham, S. D.; Baker, J. B. H.; Gurnis, M.

    2015-12-01

    Research activities are iterative, collaborative, and now data- and compute-intensive. Such research activities mean that even the many researchers who work in small laboratories must often create, acquire, manage, and manipulate much diverse data and keep track of complex software. They face difficult data and software management challenges, and data sharing and reproducibility are neglected. There is signficant federal investment in powerful cyberinfrastructure, in part to lesson the burden associated with modern data- and compute-intensive research. Similarly, geoscience communities are establishing research repositories to facilitate data preservation. Yet we observe a large fraction of the geoscience community continues to struggle with data and software management. The reason, studies suggest, is not lack of awareness but rather that tools do not adequately support time-consuming data life cycle activities. Through NSF/EarthCube-funded GeoDataspace project, we are building personalized, shareable dataspaces that help scientists connect their individual or research group efforts with the community at large. The dataspaces provide a light-weight multiplatform research data management system with tools for recording research activities in what we call geounits, so that a geoscientist can at any time snapshot and preserve, both for their own use and to share with the community, all data and code required to understand and reproduce a study. A software-as-a-service (SaaS) deployment model enhances usability of core components, and integration with widely used software systems. In this talk we will present the open-source GeoDataspace project and demonstrate how it is enabling reproducibility across geoscience domains of hydrology, space science, and modeling toolkits.

  19. Structured Product Labeling Improves Detection of Drug-intolerance Issues

    PubMed Central

    Schadow, Gunther

    2009-01-01

    Objectives This study sought to assess the value of the Health Level 7/U.S. Food and Drug Administration Structured Product Labeling (SPL) drug knowledge representation standard and its associated terminology sources for drug-intolerance (allergy) decision support in computerized provider order entry (CPOE) systems. Design The Regenstrief Institute CPOE drug-intolerance issue detection system and its knowledge base was compared with a method based on existing SPL label content enriched with knowledge sources used with SPL (NDF-RT/MeSH). Both methods were applied to a large set of drug-intolerance (allergy) records, drug orders, and medication dispensing records covering >50,000 patients over 30 years. Measurements The number of drug-intolerance issues detected by both methods was counted, as well as the number of patients with issues, number of distinct drugs, and number of distinct intolerances. The difference between drug-intolerance issues detected or missed by either method was qualitatively analyzed. Results Although <70% of terms were mapped to SPL, the new approach detected four times as many drug-intolerance issues on twice as many patients. Conclusion The SPL-based approach is more sensitive and suggests that mapping local dictionaries to SPL, and enhancing the depth and breadth of coverage of SPL content are worth accelerating. The study also highlights specificity problems known to trouble drug-intolerance decision support and suggests how terminology and methods of recording drug intolerances could be improved. PMID:18952933

  20. 101 Labeled Brain Images and a Consistent Human Cortical Labeling Protocol

    PubMed Central

    Klein, Arno; Tourville, Jason

    2012-01-01

    We introduce the Mindboggle-101 dataset, the largest and most complete set of free, publicly accessible, manually labeled human brain images. To manually label the macroscopic anatomy in magnetic resonance images of 101 healthy participants, we created a new cortical labeling protocol that relies on robust anatomical landmarks and minimal manual edits after initialization with automated labels. The “Desikan–Killiany–Tourville” (DKT) protocol is intended to improve the ease, consistency, and accuracy of labeling human cortical areas. Given how difficult it is to label brains, the Mindboggle-101 dataset is intended to serve as brain atlases for use in labeling other brains, as a normative dataset to establish morphometric variation in a healthy population for comparison against clinical populations, and contribute to the development, training, testing, and evaluation of automated registration and labeling algorithms. To this end, we also introduce benchmarks for the evaluation of such algorithms by comparing our manual labels with labels automatically generated by probabilistic and multi-atlas registration-based approaches. All data and related software and updated information are available on the http://mindboggle.info/data website. PMID:23227001

  1. Reproducible research: a minority opinion

    NASA Astrophysics Data System (ADS)

    Drummond, Chris

    2018-01-01

    Reproducible research, a growing movement within many scientific fields, including machine learning, would require the code, used to generate the experimental results, be published along with any paper. Probably the most compelling argument for this is that it is simply following good scientific practice, established over the years by the greats of science. The implication is that failure to follow such a practice is unscientific, not a label any machine learning researchers would like to carry. It is further claimed that misconduct is causing a growing crisis of confidence in science. That, without this practice being enforced, science would inevitably fall into disrepute. This viewpoint is becoming ubiquitous but here I offer a differing opinion. I argue that far from being central to science, what is being promulgated is a narrow interpretation of how science works. I contend that the consequences are somewhat overstated. I would also contend that the effort necessary to meet the movement's aims, and the general attitude it engenders would not serve well any of the research disciplines, including our own.

  2. Reproducible and controllable induction voltage adder for scaled beam experiments

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

    Sakai, Yasuo; Nakajima, Mitsuo; Horioka, Kazuhiko

    2016-08-15

    A reproducible and controllable induction adder was developed using solid-state switching devices and Finemet cores for scaled beam compression experiments. A gate controlled MOSFET circuit was developed for the controllable voltage driver. The MOSFET circuit drove the induction adder at low magnetization levels of the cores which enabled us to form reproducible modulation voltages with jitter less than 0.3 ns. Preliminary beam compression experiments indicated that the induction adder can improve the reproducibility of modulation voltages and advance the beam physics experiments.

  3. Improvements in low-cost label-free QPI microscope for live cell imaging

    NASA Astrophysics Data System (ADS)

    Seniya, C.; Towers, C. E.; Towers, D. P.

    2017-07-01

    This paper reports an improvement in the development of a low-cost QPI microscope offering new capabilities in term of phase measurement accuracy for label-free live samples in the longer term (i.e., hours to days). The spatially separated scattered and non-scattered image light fields are reshaped in the Fourier plane and modulated to form an interference image at a CCD camera. The apertures that enable these two beams to be generated have been optimised by means of laser-cut apertures placed on the mirrors of a Michelson interferometer and has improved the phase measuring and reconstruction capability of the QPI microscope. The microscope was tested with transparent onion cells as an object of interest.

  4. Cell-free measurements of brightness of fluorescently labeled antibodies

    PubMed Central

    Zhou, Haiying; Tourkakis, George; Shi, Dennis; Kim, David M.; Zhang, Hairong; Du, Tommy; Eades, William C.; Berezin, Mikhail Y.

    2017-01-01

    Validation of imaging contrast agents, such as fluorescently labeled imaging antibodies, has been recognized as a critical challenge in clinical and preclinical studies. As the number of applications for imaging antibodies grows, these materials are increasingly being subjected to careful scrutiny. Antibody fluorescent brightness is one of the key parameters that is of critical importance. Direct measurements of the brightness with common spectroscopy methods are challenging, because the fluorescent properties of the imaging antibodies are highly sensitive to the methods of conjugation, degree of labeling, and contamination with free dyes. Traditional methods rely on cell-based assays that lack reproducibility and accuracy. In this manuscript, we present a novel and general approach for measuring the brightness using antibody-avid polystyrene beads and flow cytometry. As compared to a cell-based method, the described technique is rapid, quantitative, and highly reproducible. The proposed method requires less than ten microgram of sample and is applicable for optimizing synthetic conjugation procedures, testing commercial imaging antibodies, and performing high-throughput validation of conjugation procedures. PMID:28150730

  5. Reproducibility in science.

    PubMed

    Yaffe, Michael B

    2015-04-07

    The issue of reproducibility and reliability in science has come to the forefront in light of several high-profile studies that could not be reproduced. Whereas some errors in reliability can be attributed to the application of new techniques that have unappreciated caveats, some problems with reproducibility lie in the climate of intense pressure for funding and to publish faced by many researchers. Copyright © 2015, American Association for the Advancement of Science.

  6. A prescan method improving the reproducibility of force-distance curves obtained with a piezoelectric tube scanner

    NASA Astrophysics Data System (ADS)

    Wigren, Roger; Erlandsson, Ragnar

    1996-01-01

    We present a method based on pre- and postscanning a piezoelectric tube scanner used in a force probe that improves the reproducibility of the scan lengths. Instead of prescanning in the same direction as when acquiring data (the z direction), which could destroy a sensitive surface, we perform lateral (x/y direction) prescans. As lateral motions of the tube scanner involve out of phase elongations and compressions of the tube in the z direction, these kinds of prescans will have a stabilizing effect on the z motion as well. By adding an additional postscan in the ±z directions, we reduce the piezoelectric creep following the data acquisition scan. When comparing the lengths of z scans with and without the pre/postscan procedure, preceded by a z voltage step 60 s before data acquisition, the deviation between four consecutive scans improved from 12% to 1.4%.

  7. The use of radiocobalt as a label improves imaging of EGFR using DOTA-conjugated Affibody molecule.

    PubMed

    Garousi, Javad; Andersson, Ken G; Dam, Johan H; Olsen, Birgitte B; Mitran, Bogdan; Orlova, Anna; Buijs, Jos; Ståhl, Stefan; Löfblom, John; Thisgaard, Helge; Tolmachev, Vladimir

    2017-07-20

    Several anti-cancer therapies target the epidermal growth factor receptor (EGFR). Radionuclide imaging of EGFR expression in tumours may aid in selection of optimal cancer therapy. The 111 In-labelled DOTA-conjugated Z EGFR:2377 Affibody molecule was successfully used for imaging of EGFR-expressing xenografts in mice. An optimal combination of radionuclide, chelator and targeting protein may further improve the contrast of radionuclide imaging. The aim of this study was to evaluate the targeting properties of radiocobalt-labelled DOTA-Z EGFR:2377 . DOTA-Z EGFR:2377 was labelled with 57 Co (T 1/2  = 271.8 d), 55 Co (T 1/2  = 17.5 h), and, for comparison, with the positron-emitting radionuclide 68 Ga (T 1/2  = 67.6 min) with preserved specificity of binding to EGFR-expressing A431 cells. The long-lived cobalt radioisotope 57 Co was used in animal studies. Both 57 Co-DOTA-Z EGFR:2377 and 68 Ga-DOTA-Z EGFR:2377 demonstrated EGFR-specific accumulation in A431 xenografts and EGFR-expressing tissues in mice. Tumour-to-organ ratios for the radiocobalt-labelled DOTA-Z EGFR:2377 were significantly higher than for the gallium-labelled counterpart already at 3 h after injection. Importantly, 57 Co-DOTA-Z EGFR:2377 demonstrated a tumour-to-liver ratio of 3, which is 7-fold higher than the tumour-to-liver ratio for 68 Ga-DOTA-Z EGFR:2377 . The results of this study suggest that the positron-emitting cobalt isotope 55 Co would be an optimal label for DOTA-Z EGFR:2377 and further development should concentrate on this radionuclide as a label.

  8. Learning classification models with soft-label information.

    PubMed

    Nguyen, Quang; Valizadegan, Hamed; Hauskrecht, Milos

    2014-01-01

    Learning of classification models in medicine often relies on data labeled by a human expert. Since labeling of clinical data may be time-consuming, finding ways of alleviating the labeling costs is critical for our ability to automatically learn such models. In this paper we propose a new machine learning approach that is able to learn improved binary classification models more efficiently by refining the binary class information in the training phase with soft labels that reflect how strongly the human expert feels about the original class labels. Two types of methods that can learn improved binary classification models from soft labels are proposed. The first relies on probabilistic/numeric labels, the other on ordinal categorical labels. We study and demonstrate the benefits of these methods for learning an alerting model for heparin induced thrombocytopenia. The experiments are conducted on the data of 377 patient instances labeled by three different human experts. The methods are compared using the area under the receiver operating characteristic curve (AUC) score. Our AUC results show that the new approach is capable of learning classification models more efficiently compared to traditional learning methods. The improvement in AUC is most remarkable when the number of examples we learn from is small. A new classification learning framework that lets us learn from auxiliary soft-label information provided by a human expert is a promising new direction for learning classification models from expert labels, reducing the time and cost needed to label data.

  9. Methods to increase reproducibility in differential gene expression via meta-analysis

    PubMed Central

    Sweeney, Timothy E.; Haynes, Winston A.; Vallania, Francesco; Ioannidis, John P.; Khatri, Purvesh

    2017-01-01

    Findings from clinical and biological studies are often not reproducible when tested in independent cohorts. Due to the testing of a large number of hypotheses and relatively small sample sizes, results from whole-genome expression studies in particular are often not reproducible. Compared to single-study analysis, gene expression meta-analysis can improve reproducibility by integrating data from multiple studies. However, there are multiple choices in designing and carrying out a meta-analysis. Yet, clear guidelines on best practices are scarce. Here, we hypothesized that studying subsets of very large meta-analyses would allow for systematic identification of best practices to improve reproducibility. We therefore constructed three very large gene expression meta-analyses from clinical samples, and then examined meta-analyses of subsets of the datasets (all combinations of datasets with up to N/2 samples and K/2 datasets) compared to a ‘silver standard’ of differentially expressed genes found in the entire cohort. We tested three random-effects meta-analysis models using this procedure. We showed relatively greater reproducibility with more-stringent effect size thresholds with relaxed significance thresholds; relatively lower reproducibility when imposing extraneous constraints on residual heterogeneity; and an underestimation of actual false positive rate by Benjamini–Hochberg correction. In addition, multivariate regression showed that the accuracy of a meta-analysis increased significantly with more included datasets even when controlling for sample size. PMID:27634930

  10. PRN 84-1: Clarification of Label Improvement Program for Farmworker Safety and Pesticide Storage and Disposal Instructions

    EPA Pesticide Factsheets

    This PR notice clarifies EPA's intentions regarding the Pesticide Label Improvement Program for Farmworker Safety (PR Notice 83-2) and Pesticide Storage and Disposal Instructions (PR Notice 83-3) issued on March 26, 1983.

  11. Dysplastic naevus: histological criteria and their inter-observer reproducibility.

    PubMed

    Hastrup, N; Clemmensen, O J; Spaun, E; Søndergaard, K

    1994-06-01

    Forty melanocytic lesions were examined in a pilot study, which was followed by a final series of 100 consecutive melanocytic lesions, in order to evaluate the inter-observer reproducibility of the histological criteria proposed for the dysplastic naevus. The specimens were examined in a blind fashion by four observers. Analysis by kappa statistics showed poor reproducibility of nuclear features, while reproducibility of architectural features was acceptable, improving in the final series. Consequently, we cannot apply the combined criteria of cytological and architectural features with any confidence in the diagnosis of dysplastic naevus, and, until further studies have documented that architectural criteria alone will suffice in the diagnosis of dysplastic naevus, we, as pathologists, shall avoid this term.

  12. Simple and Robust N-Glycan Analysis Based on Improved 2-Aminobenzoic Acid Labeling for Recombinant Therapeutic Glycoproteins.

    PubMed

    Jeong, Yeong Ran; Kim, Sun Young; Park, Young Sam; Lee, Gyun Min

    2018-03-21

    N-glycans of therapeutic glycoproteins are critical quality attributes that should be monitored throughout all stages of biopharmaceutical development. To reduce both the time for sample preparation and the variations in analytical results, we have developed an N-glycan analysis method that includes improved 2-aminobenzoic acid (2-AA) labeling to easily remove deglycosylated proteins. Using this analytical method, 15 major 2-AA-labeled N-glycans of Enbrel ® were separated into single peaks in hydrophilic interaction chromatography mode and therefore could be quantitated. 2-AA-labeled N-glycans were also highly compatible with in-line quadrupole time-of-flight mass spectrometry (MS) for structural identification. The structures of 15 major and 18 minor N-glycans were identified from their mass values determined by quadrupole time-of-flight MS. Furthermore, the structures of 14 major N-glycans were confirmed by interpreting the MS/MS data of each N-glycan. This analytical method was also successfully applied to neutral N-glycans of Humira ® and highly sialylated N-glycans of NESP ® . Furthermore, the analysis data of Enbrel ® that were accumulated for 2.5 years demonstrated the high-level consistency of this analytical method. Taken together, the results show that a wide repertoire of N-glycans of therapeutic glycoproteins can be analyzed with high efficiency and consistency using the improved 2-AA labeling-based N-glycan analysis method. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  13. Multiplexed MRM-Based Protein Quantitation Using Two Different Stable Isotope-Labeled Peptide Isotopologues for Calibration.

    PubMed

    LeBlanc, André; Michaud, Sarah A; Percy, Andrew J; Hardie, Darryl B; Yang, Juncong; Sinclair, Nicholas J; Proudfoot, Jillaine I; Pistawka, Adam; Smith, Derek S; Borchers, Christoph H

    2017-07-07

    When quantifying endogenous plasma proteins for fundamental and biomedical research - as well as for clinical applications - precise, reproducible, and robust assays are required. Targeted detection of peptides in a bottom-up strategy is the most common and precise mass spectrometry-based quantitation approach when combined with the use of stable isotope-labeled peptides. However, when measuring protein in plasma, the unknown endogenous levels prevent the implementation of the best calibration strategies, since no blank matrix is available. Consequently, several alternative calibration strategies are employed by different laboratories. In this study, these methods were compared to a new approach using two different stable isotope-labeled standard (SIS) peptide isotopologues for each endogenous peptide to be quantified, enabling an external calibration curve as well as the quality control samples to be prepared in pooled human plasma without interference from endogenous peptides. This strategy improves the analytical performance of the assay and enables the accuracy of the assay to be monitored, which can also facilitate method development and validation.

  14. An optimized velocity selective arterial spin labeling module with reduced eddy current sensitivity for improved perfusion quantification.

    PubMed

    Meakin, James A; Jezzard, Peter

    2013-03-01

    Velocity-selective (VS) arterial spin labeling is a promising method for measuring perfusion in areas of slow or collateral flow by eliminating the bolus arrival delay associated with other spin labeling techniques. However, B(0) and B(1) inhomogeneities and eddy currents during the VS preparation hinder accurate quantification of perfusion with VS arterial spin labeling. In this study, it is demonstrated through simulations and experiments in healthy volunteers that eddy currents cause erroneous tagging of static tissue. Consequently, mean gray matter perfusion is overestimated by up to a factor of 2, depending on the VS preparation used. A novel eight-segment B(1) insensitive rotation VS preparation is proposed to reduce eddy current effects while maintaining the B(0) and B(1) insensitivity of previous preparations. Compared to two previous VS preparations, the eight-segment B(1) insensitive rotation is the most robust to eddy currents and should improve the quality and reliability of VS arterial spin labeling measurements in future studies. Copyright © 2012 Wiley Periodicals, Inc.

  15. Effect of Initial Conditions on Reproducibility of Scientific Research

    PubMed Central

    Djulbegovic, Benjamin; Hozo, Iztok

    2014-01-01

    Background: It is estimated that about half of currently published research cannot be reproduced. Many reasons have been offered as explanations for failure to reproduce scientific research findings- from fraud to the issues related to design, conduct, analysis, or publishing scientific research. We also postulate a sensitive dependency on initial conditions by which small changes can result in the large differences in the research findings when attempted to be reproduced at later times. Methods: We employed a simple logistic regression equation to model the effect of covariates on the initial study findings. We then fed the input from the logistic equation into a logistic map function to model stability of the results in repeated experiments over time. We illustrate the approach by modeling effects of different factors on the choice of correct treatment. Results: We found that reproducibility of the study findings depended both on the initial values of all independent variables and the rate of change in the baseline conditions, the latter being more important. When the changes in the baseline conditions vary by about 3.5 to about 4 in between experiments, no research findings could be reproduced. However, when the rate of change between the experiments is ≤2.5 the results become highly predictable between the experiments. Conclusions: Many results cannot be reproduced because of the changes in the initial conditions between the experiments. Better control of the baseline conditions in-between the experiments may help improve reproducibility of scientific findings. PMID:25132705

  16. Effect of initial conditions on reproducibility of scientific research.

    PubMed

    Djulbegovic, Benjamin; Hozo, Iztok

    2014-06-01

    It is estimated that about half of currently published research cannot be reproduced. Many reasons have been offered as explanations for failure to reproduce scientific research findings- from fraud to the issues related to design, conduct, analysis, or publishing scientific research. We also postulate a sensitive dependency on initial conditions by which small changes can result in the large differences in the research findings when attempted to be reproduced at later times. We employed a simple logistic regression equation to model the effect of covariates on the initial study findings. We then fed the input from the logistic equation into a logistic map function to model stability of the results in repeated experiments over time. We illustrate the approach by modeling effects of different factors on the choice of correct treatment. We found that reproducibility of the study findings depended both on the initial values of all independent variables and the rate of change in the baseline conditions, the latter being more important. When the changes in the baseline conditions vary by about 3.5 to about 4 in between experiments, no research findings could be reproduced. However, when the rate of change between the experiments is ≤2.5 the results become highly predictable between the experiments. Many results cannot be reproduced because of the changes in the initial conditions between the experiments. Better control of the baseline conditions in-between the experiments may help improve reproducibility of scientific findings.

  17. The efficacy of sugar labeling formats: Implications for labeling policy.

    PubMed

    Vanderlee, Lana; White, Christine M; Bordes, Isabelle; Hobin, Erin P; Hammond, David

    2015-12-01

    To examine knowledge of sugar recommendations and test the efficacy of formats for labeling total and added sugar on pre-packaged foods. Online surveys were conducted among 2008 Canadians aged 16-24. Participants were asked to identify recommended limits for total and added sugar consumption. In Experiment 1, participants were randomized to one of six labeling conditions with varying information for total sugar for a high- or low-sugar product and were asked to identify the relative amount of total sugar in the product. In Experiment 2, participants were randomized to one of three labels with different added sugar formats and were asked if the product contained added sugar and the relative amount of added sugar. Few young people correctly identified recommendations for total sugar (5%) or added sugar (7%). In Experiment 1, those who were shown percent daily value information were more likely to correctly identify the relative amount of total sugar (P < 0.05). In Experiment 2, those shown added sugar information were more likely to correctly identify that the product contained added sugar and the relative amount of added sugar in the product (P < 0.05). Improved labeling may improve consumer understanding of the amount of sugars in food products. © 2015 The Obesity Society.

  18. Guidelines for improving the reproducibility of quantitative multiparameter immunofluorescence measurements by laser scanning cytometry on fixed cell suspensions from human solid tumors.

    PubMed

    Shackney, Stanley; Emlet, David R; Pollice, Agnese; Smith, Charles; Brown, Kathryn; Kociban, Deborah

    2006-01-01

    Laser scanning Cytometry (LSC) is a versatile technology that makes it possible to perform multiple measurements on individual cells and correlate them cell by cell with other cellular features. It would be highly desirable to be able to perform reproducible, quantitative, correlated cell-based immunofluorescence studies on individual cells from human solid tumors. However, such studies can be challenging because of the presence of large numbers of cell aggregates and other confounding factors. Techniques have been developed to deal with cell aggregates in data sets collected by LSC. Experience has also been gained in addressing other key technical and methodological issues that can affect the reproducibility of such cell-based immunofluorescence measurements. We describe practical aspects of cell sample collection, cell fixation and staining, protocols for performing multiparameter immunofluorescence measurements by LSC, use of controls and reference samples, and approaches to data analysis that we have found useful in improving the accuracy and reproducibility of LSC data obtained in human tumor samples. We provide examples of the potential advantages of LSC in examining quantitative aspects of cell-based analysis. Improvements in the quality of cell-based multiparameter immunofluorescence measurements make it possible to extract useful information from relatively small numbers of cells. This, in turn, permits the performance of multiple multicolor panels on each tumor sample. With links among the different panels that are provided by overlapping measurements, it is possible to develop increasingly more extensive profiles of intracellular expression of multiple proteins in clinical samples of human solid tumors. Examples of such linked panels of measurements are provided. Advances in methodology can improve cell-based multiparameter immunofluorescence measurements on cell suspensions from human solid tumors by LSC for use in prognostic and predictive clinical

  19. Production of stable isotope-labeled acyl-coenzyme A thioesters by yeast stable isotope labeling by essential nutrients in cell culture

    PubMed Central

    Snyder, Nathaniel W.; Tombline, Gregory; Worth, Andrew J.; Parry, Robert C.; Silvers, Jacob A.; Gillespie, Kevin P.; Basu, Sankha S.; Millen, Jonathan; Goldfarb, David S.; Blair, Ian A.

    2015-01-01

    Acyl-coenzyme A (CoA) thioesters are key metabolites in numerous anabolic and catabolic pathways, including fatty acid biosynthesis and β-oxidation, the Krebs cycle, and cholesterol and isoprenoid biosynthesis. Stable isotope dilution-based methodology is the gold standard for quantitative analyses by mass spectrometry. However, chemical synthesis of families of stable isotope labeled metabolites such as acyl-coenzyme A thioesters is impractical. Previously, we biosynthetically generated a library of stable isotope internal standard analogs of acyl-CoA thioesters by exploiting the essential requirement in mammals and insects for pantothenic acid (vitamin B5) as a metabolic precursor for the CoA backbone. By replacing pantothenic acid in the cell media with commercially available [13C3 15N1]-pantothenic acid, mammalian cells exclusively incorporated [13C3 15N1]-pantothenate into the biosynthesis of acyl-CoA and acyl-CoA thioesters. We have now developed a much more efficient method for generating stable isotope labeled CoA and acyl-CoAs from [13C3 15N1]-pantothenate using Stable Isotope Labeling by Essential nutrients in Cell culture (SILEC) in Pan6 deficient yeast cells. Efficiency and consistency of labeling were also increased, likely due to the stringently defined and reproducible conditions used for yeast culture. The yeast SILEC method greatly enhances the ease of use and accessibility of labeled CoA thioesters and also provides proof-of-concept for generating other labeled metabolites in yeast mutants. PMID:25572876

  20. Community-based Approaches to Improving Accuracy, Precision, and Reproducibility in U-Pb and U-Th Geochronology

    NASA Astrophysics Data System (ADS)

    McLean, N. M.; Condon, D. J.; Bowring, S. A.; Schoene, B.; Dutton, A.; Rubin, K. H.

    2015-12-01

    The last two decades have seen a grassroots effort by the international geochronology community to "calibrate Earth history through teamwork and cooperation," both as part of the EARTHTIME initiative and though several daughter projects with similar goals. Its mission originally challenged laboratories "to produce temporal constraints with uncertainties approaching 0.1% of the radioisotopic ages," but EARTHTIME has since exceeded its charge in many ways. Both the U-Pb and Ar-Ar chronometers first considered for high-precision timescale calibration now regularly produce dates at the sub-per mil level thanks to instrumentation, laboratory, and software advances. At the same time new isotope systems, including U-Th dating of carbonates, have developed comparable precision. But the larger, inter-related scientific challenges envisioned at EARTHTIME's inception remain - for instance, precisely calibrating the global geologic timescale, estimating rates of change around major climatic perturbations, and understanding evolutionary rates through time - and increasingly require that data from multiple geochronometers be combined. To solve these problems, the next two decades of uranium-daughter geochronology will require further advances in accuracy, precision, and reproducibility. The U-Th system has much in common with U-Pb, in that both parent and daughter isotopes are solids that can easily be weighed and dissolved in acid, and have well-characterized reference materials certified for isotopic composition and/or purity. For U-Pb, improving lab-to-lab reproducibility has entailed dissolving precisely weighed U and Pb metals of known purity and isotopic composition together to make gravimetric solutions, then using these to calibrate widely distributed tracers composed of artificial U and Pb isotopes. To mimic laboratory measurements, naturally occurring U and Pb isotopes were also mixed in proportions to mimic samples of three different ages, to be run as internal

  1. Language-Agnostic Reproducible Data Analysis Using Literate Programming.

    PubMed

    Vassilev, Boris; Louhimo, Riku; Ikonen, Elina; Hautaniemi, Sampsa

    2016-01-01

    A modern biomedical research project can easily contain hundreds of analysis steps and lack of reproducibility of the analyses has been recognized as a severe issue. While thorough documentation enables reproducibility, the number of analysis programs used can be so large that in reality reproducibility cannot be easily achieved. Literate programming is an approach to present computer programs to human readers. The code is rearranged to follow the logic of the program, and to explain that logic in a natural language. The code executed by the computer is extracted from the literate source code. As such, literate programming is an ideal formalism for systematizing analysis steps in biomedical research. We have developed the reproducible computing tool Lir (literate, reproducible computing) that allows a tool-agnostic approach to biomedical data analysis. We demonstrate the utility of Lir by applying it to a case study. Our aim was to investigate the role of endosomal trafficking regulators to the progression of breast cancer. In this analysis, a variety of tools were combined to interpret the available data: a relational database, standard command-line tools, and a statistical computing environment. The analysis revealed that the lipid transport related genes LAPTM4B and NDRG1 are coamplified in breast cancer patients, and identified genes potentially cooperating with LAPTM4B in breast cancer progression. Our case study demonstrates that with Lir, an array of tools can be combined in the same data analysis to improve efficiency, reproducibility, and ease of understanding. Lir is an open-source software available at github.com/borisvassilev/lir.

  2. Language-Agnostic Reproducible Data Analysis Using Literate Programming

    PubMed Central

    Vassilev, Boris; Louhimo, Riku; Ikonen, Elina; Hautaniemi, Sampsa

    2016-01-01

    A modern biomedical research project can easily contain hundreds of analysis steps and lack of reproducibility of the analyses has been recognized as a severe issue. While thorough documentation enables reproducibility, the number of analysis programs used can be so large that in reality reproducibility cannot be easily achieved. Literate programming is an approach to present computer programs to human readers. The code is rearranged to follow the logic of the program, and to explain that logic in a natural language. The code executed by the computer is extracted from the literate source code. As such, literate programming is an ideal formalism for systematizing analysis steps in biomedical research. We have developed the reproducible computing tool Lir (literate, reproducible computing) that allows a tool-agnostic approach to biomedical data analysis. We demonstrate the utility of Lir by applying it to a case study. Our aim was to investigate the role of endosomal trafficking regulators to the progression of breast cancer. In this analysis, a variety of tools were combined to interpret the available data: a relational database, standard command-line tools, and a statistical computing environment. The analysis revealed that the lipid transport related genes LAPTM4B and NDRG1 are coamplified in breast cancer patients, and identified genes potentially cooperating with LAPTM4B in breast cancer progression. Our case study demonstrates that with Lir, an array of tools can be combined in the same data analysis to improve efficiency, reproducibility, and ease of understanding. Lir is an open-source software available at github.com/borisvassilev/lir. PMID:27711123

  3. Molecular Interactions of the Min Protein System Reproduce Spatiotemporal Patterning in Growing and Dividing Escherichia coli Cells.

    PubMed

    Walsh, James C; Angstmann, Christopher N; Duggin, Iain G; Curmi, Paul M G

    2015-01-01

    Oscillations of the Min protein system are involved in the correct midcell placement of the divisome during Escherichia coli cell division. Based on molecular interactions of the Min system, we formulated a mathematical model that reproduces Min patterning during cell growth and division. Specifically, the increase in the residence time of MinD attached to the membrane as its own concentration increases, is accounted for by dimerisation of membrane-bound MinD and its interaction with MinE. Simulation of this system generates unparalleled correlation between the waveshape of experimental and theoretical MinD distributions, suggesting that the dominant interactions of the physical system have been successfully incorporated into the model. For cells where MinD is fully-labelled with GFP, the model reproduces the stationary localization of MinD-GFP for short cells, followed by oscillations from pole to pole in larger cells, and the transition to the symmetric distribution during cell filamentation. Cells containing a secondary, GFP-labelled MinD display a contrasting pattern. The model is able to account for these differences, including temporary midcell localization just prior to division, by increasing the rate constant controlling MinD ATPase and heterotetramer dissociation. For both experimental conditions, the model can explain how cell division results in an equal distribution of MinD and MinE in the two daughter cells, and accounts for the temperature dependence of the period of Min oscillations. Thus, we show that while other interactions may be present, they are not needed to reproduce the main characteristics of the Min system in vivo.

  4. Evaluation of a High Intensity Focused Ultrasound-Immobilized Trypsin Digestion and 18O-Labeling Method for Quantitative Proteomics

    PubMed Central

    López-Ferrer, Daniel; Hixson, Kim K.; Smallwood, Heather; Squier, Thomas C.; Petritis, Konstantinos; Smith, Richard D.

    2009-01-01

    A new method that uses immobilized trypsin concomitant with ultrasonic irradiation results in ultra-rapid digestion and thorough 18O labeling for quantitative protein comparisons. The reproducible and highly efficient method provided effective digestions in <1 min with a minimized amount of enzyme required compared to traditional methods. This method was demonstrated for digestion of both simple and complex protein mixtures, including bovine serum albumin, a global proteome extract from the bacteria Shewanella oneidensis, and mouse plasma, as well as 18O labeling of such complex protein mixtures, which validated the application of this method for differential proteomic measurements. This approach is simple, reproducible, cost effective, rapid, and thus well-suited for automation. PMID:19555078

  5. PRN 84-5: Label Improvement Program for Fumigants

    EPA Pesticide Factsheets

    This notice required registrants of fumigant products to revise the labeling of products registered under FIFRA section 3 or 24(c) to include additional precautionary statements and other statements described in the notice.

  6. Consumer preferences for food allergen labeling.

    PubMed

    Marra, Carlo A; Harvard, Stephanie; Grubisic, Maja; Galo, Jessica; Clarke, Ann; Elliott, Susan; Lynd, Larry D

    2017-01-01

    Food allergen labeling is an important tool to reduce risk of exposure and prevent anaphylaxis for individuals with food allergies. Health Canada released a Canadian food allergen labeling regulation (2008) and subsequent update (2012) suggesting that research is needed to guide further iterations of the regulation to improve food allergen labeling and reduce risk of exposure. The primary objective of this study was to examine consumer preferences in food labeling for allergy avoidance and anaphylaxis prevention. A secondary objective was to identify whether different subgroups within the consumer population emerged. A discrete choice experiment using a fractional factorial design divided into ten different versions with 18 choice-sets per version was developed to examine consumer preferences for different attributes of food labeling. Three distinct subgroups of Canadian consumers with different allergen considerations and food allergen labeling needs were identified. Overall, preferences for standardized precautionary and safety symbols at little or no increased cost emerged. While three distinct groups with different preferences were identified, in general the results revealed that the current Canadian food allergen labeling regulation can be improved by enforcing the use of standardized precautionary and safety symbols and educating the public on the use of these symbols.

  7. Simplifying mental math: Changing how added sugars are displayed on the nutrition facts label can improve consumer understanding.

    PubMed

    Khandpur, Neha; Graham, Dan J; Roberto, Christina A

    2017-07-01

    Proposed variations to Nutrition Facts Labels (NFL) have included the display of added sugars (AS) content, but its impact on consumer understanding is poorly understood. To examine the degree to which different formats for displaying AS influence consumer understanding, perceptions, and purchase intentions. Randomized-controlled online experiment. A sample of 2509 U.S adults. Participants were randomized to 1 of 8 conditions and viewed 10 food or beverage images with either: (1) no label (control); (2) the current NFL (without AS); (3) the proposed NFL without AS; or the proposed NFL with AS in (4) grams, (5) grams and teaspoons, (6) grams and percent Daily Value (%DV), (7) grams with high/medium/low text, or (8) grams with high/medium/low text and %DV. ANCOVAs compared scores on quizzes that assessed the accuracy of judgments about AS, overall nutrition understanding and purchase intentions. Presenting AS in grams plus high/medium/low text with and without %DV led to the highest AS understanding scores (85% and 83% correct, respectively) compared to 70% correct when AS was not on the label or was displayed in grams only (74% correct). Displaying AS in teaspoons did not significantly improve understanding beyond grams alone. Consumers were best able to determine which of two products was healthier when AS was presented as %DV (68% correct) versus displayed in grams alone (60% correct), but %DV did not differ from high/medium/low text or teaspoons. None of the labels influenced purchase intentions relative to no label. Displaying AS on the NFL in grams with high/medium/low text, %DV, or the combination of the two, improved consumer understanding more than presenting it in grams or teaspoons. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. An Open, Large-Scale, Collaborative Effort to Estimate the Reproducibility of Psychological Science.

    PubMed

    2012-11-01

    Reproducibility is a defining feature of science. However, because of strong incentives for innovation and weak incentives for confirmation, direct replication is rarely practiced or published. The Reproducibility Project is an open, large-scale, collaborative effort to systematically examine the rate and predictors of reproducibility in psychological science. So far, 72 volunteer researchers from 41 institutions have organized to openly and transparently replicate studies published in three prominent psychological journals in 2008. Multiple methods will be used to evaluate the findings, calculate an empirical rate of replication, and investigate factors that predict reproducibility. Whatever the result, a better understanding of reproducibility will ultimately improve confidence in scientific methodology and findings. © The Author(s) 2012.

  9. Reproducibility of radiomics for deciphering tumor phenotype with imaging

    NASA Astrophysics Data System (ADS)

    Zhao, Binsheng; Tan, Yongqiang; Tsai, Wei-Yann; Qi, Jing; Xie, Chuanmiao; Lu, Lin; Schwartz, Lawrence H.

    2016-03-01

    Radiomics (radiogenomics) characterizes tumor phenotypes based on quantitative image features derived from routine radiologic imaging to improve cancer diagnosis, prognosis, prediction and response to therapy. Although radiomic features must be reproducible to qualify as biomarkers for clinical care, little is known about how routine imaging acquisition techniques/parameters affect reproducibility. To begin to fill this knowledge gap, we assessed the reproducibility of a comprehensive, commonly-used set of radiomic features using a unique, same-day repeat computed tomography data set from lung cancer patients. Each scan was reconstructed at 6 imaging settings, varying slice thicknesses (1.25 mm, 2.5 mm and 5 mm) and reconstruction algorithms (sharp, smooth). Reproducibility was assessed using the repeat scans reconstructed at identical imaging setting (6 settings in total). In separate analyses, we explored differences in radiomic features due to different imaging parameters by assessing the agreement of these radiomic features extracted from the repeat scans reconstructed at the same slice thickness but different algorithms (3 settings in total). Our data suggest that radiomic features are reproducible over a wide range of imaging settings. However, smooth and sharp reconstruction algorithms should not be used interchangeably. These findings will raise awareness of the importance of properly setting imaging acquisition parameters in radiomics/radiogenomics research.

  10. Hip Hop HEALS: Pilot Study of a Culturally Targeted Calorie Label Intervention to Improve Food Purchases of Children.

    PubMed

    Williams, Olajide; DeSorbo, Alexandra; Sawyer, Vanessa; Apakama, Donald; Shaffer, Michele; Gerin, William; Noble, James

    2016-02-01

    We explored the effect of a culturally targeted calorie label intervention on food purchasing behavior of elementary school students. We used a quasi-experimental design with two intervention schools and one control school to assess food purchases of third through fifth graders at standardized school food sales before and after the intervention (immediate and delayed) in schools. The intervention comprised three 1-hour assembly-style hip-hop-themed multimedia classes. A mean total of 225 children participated in two baseline preintervention sales with and without calorie labels; 149 children participated in immediate postintervention food sales, while 133 children participated in the delayed sales. No significant change in purchased calories was observed in response to labels alone before the intervention. However, a mean decline in purchased calories of 20% (p < .01) and unhealthy foods (p < .01) was seen in immediately following the intervention compared to baseline purchases, and this persisted without significant decay after 7 days and 12 days. A 3-hour culturally targeted calorie label intervention may improve food-purchasing behavior of children. © 2015 Society for Public Health Education.

  11. Track-before-detect labeled multi-bernoulli particle filter with label switching

    NASA Astrophysics Data System (ADS)

    Garcia-Fernandez, Angel F.

    2016-10-01

    This paper presents a multitarget tracking particle filter (PF) for general track-before-detect measurement models. The PF is presented in the random finite set framework and uses a labelled multi-Bernoulli approximation. We also present a label switching improvement algorithm based on Markov chain Monte Carlo that is expected to increase filter performance if targets get in close proximity for a sufficiently long time. The PF is tested in two challenging numerical examples.

  12. Examining the Reproducibility of 6 Published Studies in Public Health Services and Systems Research.

    PubMed

    Harris, Jenine K; B Wondmeneh, Sarah; Zhao, Yiqiang; Leider, Jonathon P

    2018-02-23

    Research replication, or repeating a study de novo, is the scientific standard for building evidence and identifying spurious results. While replication is ideal, it is often expensive and time consuming. Reproducibility, or reanalysis of data to verify published findings, is one proposed minimum alternative standard. While a lack of research reproducibility has been identified as a serious and prevalent problem in biomedical research and a few other fields, little work has been done to examine the reproducibility of public health research. We examined reproducibility in 6 studies from the public health services and systems research subfield of public health research. Following the methods described in each of the 6 papers, we computed the descriptive and inferential statistics for each study. We compared our results with the original study results and examined the percentage differences in descriptive statistics and differences in effect size, significance, and precision of inferential statistics. All project work was completed in 2017. We found consistency between original and reproduced results for each paper in at least 1 of the 4 areas examined. However, we also found some inconsistency. We identified incorrect transcription of results and omitting detail about data management and analyses as the primary contributors to the inconsistencies. Increasing reproducibility, or reanalysis of data to verify published results, can improve the quality of science. Researchers, journals, employers, and funders can all play a role in improving the reproducibility of science through several strategies including publishing data and statistical code, using guidelines to write clear and complete methods sections, conducting reproducibility reviews, and incentivizing reproducible science.

  13. The Road to Reproducibility in Animal Research.

    PubMed

    Jilka, Robert L

    2016-07-01

    Reproducibility of research findings is the hallmark of scientific advance. However, the recently noted lack of reproducibility and transparency of published research using animal models of human biology and disease has alarmed funders, scientists, and the public. Improved reporting of methodology and better use of statistical tools are needed to enhance the quality and utility of published research. Reporting guidelines like Animal Research: Reporting In Vivo Experiments (ARRIVE) have been devised to achieve these goals, but most biomedical research journals, including the JBMR, have not been able to obtain high compliance. Cooperative efforts among authors, reviewers and editors-empowered by increased awareness of their responsibilities, and enabled by user-friendly guidelines-are needed to solve this problem. © 2016 American Society for Bone and Mineral Research. © 2016 American Society for Bone and Mineral Research.

  14. Running an open experiment: transparency and reproducibility in soil and ecosystem science

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

    Bond-Lamberty, Benjamin; Smith, Ashly P.; Bailey, Vanessa L.

    Researchers in soil and ecosystem science, and almost every other field, are being pushed--by funders, journals, governments, and their peers--to increase transparency and reproducibility of their work. A key part of this effort is a move towards open data as a way to fight post-publication data loss, improve data and code quality, enable powerful meta- and cross-disciplinary analyses, and increase trust in, and the efficiency of, publicly-funded research. Many scientists however lack experience in, and may be unsure of the benefits of, making their data and fully-reproducible analyses publicly available. Here we describe a recent "open experiment", in which wemore » documented every aspect of a soil incubation online, making all raw data, scripts, diagnostics, final analyses, and manuscripts available in real time. We found that using tools such as version control, issue tracking, and open-source statistical software improved data integrity, accelerated our team's communication and productivity, and ensured transparency. There are many avenues to improve scientific reproducibility and data availability, of which is this only one example, and it is not an approach suited for every experiment or situation. Nonetheless, we encourage the communities in our respective fields to consider its advantages, and to lead rather than follow with respect to scientific reproducibility, transparency, and data availability.« less

  15. Running an open experiment: transparency and reproducibility in soil and ecosystem science

    NASA Astrophysics Data System (ADS)

    Bond-Lamberty, Ben; Peyton Smith, A.; Bailey, Vanessa

    2016-08-01

    Researchers in soil and ecosystem science, and almost every other field, are being pushed—by funders, journals, governments, and their peers—to increase transparency and reproducibility of their work. A key part of this effort is a move towards open data as a way to fight post-publication data loss, improve data and code quality, enable powerful meta- and cross-disciplinary analyses, and increase trust in, and the efficiency of, publicly-funded research. Many scientists however lack experience in, and may be unsure of the benefits of, making their data and fully-reproducible analyses publicly available. Here we describe a recent ‘open experiment’, in which we documented every aspect of a soil incubation online, making all raw data, scripts, diagnostics, final analyses, and manuscripts available in real time. We found that using tools such as version control, issue tracking, and open-source statistical software improved data integrity, accelerated our team’s communication and productivity, and ensured transparency. There are many avenues to improve scientific reproducibility and data availability, of which is this only one example, and it is not an approach suited for every experiment or situation. Nonetheless, we encourage the communities in our respective fields to consider its advantages, and to lead rather than follow with respect to scientific reproducibility, transparency, and data availability.

  16. Using induced electroosmotic micromixer to enhance the reproducibility of chemiluminescence intensity.

    PubMed

    Chen, Hsiao-Ping; Yeh, Chun-Yi; Hung, Pei-Chin; Wang, Shau-Chun

    2014-02-01

    In this study, induced electroosmotic vortex flows were generated using an AC electric field by one pair of external electrodes to rapidly mix luminescence reagents in a 30 μL micromixer and enhance the reproducibility of chemiluminescence (CL) assays. A solution containing the catalyst reagent ferricyanide ions (4 μL) was pipetted into a reservoir containing luminol to produce CL in the presence of hydrogen peroxide. When the added ferricyanide aliquot contacted the reservoir solution, the CL began flashing, but rapidly diminished as the ferricyanide was consumed. In such a short illumination period, the solutes could not mix homogeneously. Therefore, the reproducibility of CL intensities collected using a CCD and multiple aliquot additions was determined to be inadequate. By contrast, when the solutes were efficiently mixed after adding a ferricyanide aliquot to a micromixer, the intensity reproducibility was significantly improved. When the CL temporal profile was analyzed using a PMT, a consistent improvement in reproducibility was observed between the CL intensity and estimated CL reaction rate. Replicating the proposed device would create a multiple well plate that contains a micromixer in each reservoir; this system is compatible with conventional CL instrumentation and requires no CL enhancer to slow a reaction. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Reproducibility of serum IgE, Ara h2 skin prick testing and fraction of exhaled nitric oxide for predicting clinical peanut allergy in children.

    PubMed

    Percival, Elizabeth; Bhatia, Rani; Preece, Kahn; McElduff, Patrick; McEvoy, Mark; Collison, Adam; Mattes, Joerg

    2016-01-01

    Ara h2 sIgE serum levels improve the diagnostic accuracy for predicting peanut allergy, but the use of Ara h2 purified protein as a skin prick test (SPT), has not been substantially evaluated. The fraction of exhaled nitric oxide (FeNO) shows promise as a novel biomarker of peanut allergy. Reproducibility of these measures has not been determined. The aim was to assess the accuracy and reproducibility (over a time-period of at least 12 months) of SPT to Ara h2 in comparison with four predictors of clinical peanut allergy (Peanut SPT, Ara h2 specific Immunoglobulin E (sIgE), Peanut sIgE and FeNO). Twenty-seven children were recruited in a follow-up of a prospective cohort of fifty-six children at least 12 months after an open-labelled peanut food challenge. Their repeat assessment involved a questionnaire, SPT to peanut and Ara h2 purified protein, FeNO and sIgE to peanut and Ara h2 measurements. Ara h2 SPT was no worse in accuracy when compared with peanut SPT, FeNO, Ara h2 sIgE and peanut sIgE (AUC 0.908 compared with 0.887, 0.889, 0.935 and 0.804 respectively) for predicting allergic reaction at previous food challenge. SPT for peanut and Ara h2 demonstrated limited reproducibility (ICC = 0.51 and 0.44); while FeNO demonstrated good reproducibility (ICC = 0.73) and sIgE for peanut and Ara h2 were highly reproducible (ICC = 0.81 and 0.85). In this population, Ara h2 SPT was no worse in accuracy when compared with current testing for the evaluation of clinical peanut allergy, but had-like peanut SPT-poor reproducibility. FeNO, peanut sIgE and Ara h2 sIgE were consistently reproducible despite an interval of at least 12 months between the repeated measurements.

  18. A catalyzing phantom for reproducible dynamic conversion of hyperpolarized [1-¹³C]-pyruvate.

    PubMed

    Walker, Christopher M; Lee, Jaehyuk; Ramirez, Marc S; Schellingerhout, Dawid; Millward, Steven; Bankson, James A

    2013-01-01

    In vivo real time spectroscopic imaging of hyperpolarized ¹³C labeled metabolites shows substantial promise for the assessment of physiological processes that were previously inaccessible. However, reliable and reproducible methods of measurement are necessary to maximize the effectiveness of imaging biomarkers that may one day guide personalized care for diseases such as cancer. Animal models of human disease serve as poor reference standards due to the complexity, heterogeneity, and transient nature of advancing disease. In this study, we describe the reproducible conversion of hyperpolarized [1-¹³C]-pyruvate to [1-¹³C]-lactate using a novel synthetic enzyme phantom system. The rate of reaction can be controlled and tuned to mimic normal or pathologic conditions of varying degree. Variations observed in the use of this phantom compare favorably against within-group variations observed in recent animal studies. This novel phantom system provides crucial capabilities as a reference standard for the optimization, comparison, and certification of quantitative imaging strategies for hyperpolarized tracers.

  19. ITK: enabling reproducible research and open science

    PubMed Central

    McCormick, Matthew; Liu, Xiaoxiao; Jomier, Julien; Marion, Charles; Ibanez, Luis

    2014-01-01

    Reproducibility verification is essential to the practice of the scientific method. Researchers report their findings, which are strengthened as other independent groups in the scientific community share similar outcomes. In the many scientific fields where software has become a fundamental tool for capturing and analyzing data, this requirement of reproducibility implies that reliable and comprehensive software platforms and tools should be made available to the scientific community. The tools will empower them and the public to verify, through practice, the reproducibility of observations that are reported in the scientific literature. Medical image analysis is one of the fields in which the use of computational resources, both software and hardware, are an essential platform for performing experimental work. In this arena, the introduction of the Insight Toolkit (ITK) in 1999 has transformed the field and facilitates its progress by accelerating the rate at which algorithmic implementations are developed, tested, disseminated and improved. By building on the efficiency and quality of open source methodologies, ITK has provided the medical image community with an effective platform on which to build a daily workflow that incorporates the true scientific practices of reproducibility verification. This article describes the multiple tools, methodologies, and practices that the ITK community has adopted, refined, and followed during the past decade, in order to become one of the research communities with the most modern reproducibility verification infrastructure. For example, 207 contributors have created over 2400 unit tests that provide over 84% code line test coverage. The Insight Journal, an open publication journal associated with the toolkit, has seen over 360,000 publication downloads. The median normalized closeness centrality, a measure of knowledge flow, resulting from the distributed peer code review system was high, 0.46. PMID:24600387

  20. ITK: enabling reproducible research and open science.

    PubMed

    McCormick, Matthew; Liu, Xiaoxiao; Jomier, Julien; Marion, Charles; Ibanez, Luis

    2014-01-01

    Reproducibility verification is essential to the practice of the scientific method. Researchers report their findings, which are strengthened as other independent groups in the scientific community share similar outcomes. In the many scientific fields where software has become a fundamental tool for capturing and analyzing data, this requirement of reproducibility implies that reliable and comprehensive software platforms and tools should be made available to the scientific community. The tools will empower them and the public to verify, through practice, the reproducibility of observations that are reported in the scientific literature. Medical image analysis is one of the fields in which the use of computational resources, both software and hardware, are an essential platform for performing experimental work. In this arena, the introduction of the Insight Toolkit (ITK) in 1999 has transformed the field and facilitates its progress by accelerating the rate at which algorithmic implementations are developed, tested, disseminated and improved. By building on the efficiency and quality of open source methodologies, ITK has provided the medical image community with an effective platform on which to build a daily workflow that incorporates the true scientific practices of reproducibility verification. This article describes the multiple tools, methodologies, and practices that the ITK community has adopted, refined, and followed during the past decade, in order to become one of the research communities with the most modern reproducibility verification infrastructure. For example, 207 contributors have created over 2400 unit tests that provide over 84% code line test coverage. The Insight Journal, an open publication journal associated with the toolkit, has seen over 360,000 publication downloads. The median normalized closeness centrality, a measure of knowledge flow, resulting from the distributed peer code review system was high, 0.46.

  1. Hierarchical Multi-atlas Label Fusion with Multi-scale Feature Representation and Label-specific Patch Partition

    PubMed Central

    Wu, Guorong; Kim, Minjeong; Sanroma, Gerard; Wang, Qian; Munsell, Brent C.; Shen, Dinggang

    2014-01-01

    Multi-atlas patch-based label fusion methods have been successfully used to improve segmentation accuracy in many important medical image analysis applications. In general, to achieve label fusion a single target image is first registered to several atlas images, after registration a label is assigned to each target point in the target image by determining the similarity between the underlying target image patch (centered at the target point) and the aligned image patch in each atlas image. To achieve the highest level of accuracy during the label fusion process it’s critical the chosen patch similarity measurement accurately captures the tissue/shape appearance of the anatomical structure. One major limitation of existing state-of-the-art label fusion methods is that they often apply a fixed size image patch throughout the entire label fusion procedure. Doing so may severely affect the fidelity of the patch similarity measurement, which in turn may not adequately capture complex tissue appearance patterns expressed by the anatomical structure. To address this limitation, we advance state-of-the-art by adding three new label fusion contributions: First, each image patch now characterized by a multi-scale feature representation that encodes both local and semi-local image information. Doing so will increase the accuracy of the patch-based similarity measurement. Second, to limit the possibility of the patch-based similarity measurement being wrongly guided by the presence of multiple anatomical structures in the same image patch, each atlas image patch is further partitioned into a set of label-specific partial image patches according to the existing labels. Since image information has now been semantically divided into different patterns, these new label-specific atlas patches make the label fusion process more specific and flexible. Lastly, in order to correct target points that are mislabeled during label fusion, a hierarchically approach is used to improve the

  2. Combining Metabolic ¹⁵N Labeling with Improved Tandem MOAC for Enhanced Probing of the Phosphoproteome.

    PubMed

    Thomas, Martin; Huck, Nicola; Hoehenwarter, Wolfgang; Conrath, Uwe; Beckers, Gerold J M

    2015-01-01

    In eukaryotic cells many diverse cellular functions are regulated by reversible protein phosphorylation. In recent years, phosphoproteomics has become a powerful tool for studying protein phosphorylation because it enables unbiased localization, and site-specific quantification of in vivo phosphorylation of hundreds of proteins in a single experiment. A common strategy for identifying phosphoproteins and their phosphorylation sites from complex biological samples is the enrichment of phosphopeptides from digested cellular lysates followed by mass spectrometry. However, despite high sensitivity of modern mass spectrometers the large dynamic range of protein abundance and the transient nature of protein phosphorylation remained major pitfalls in MS-based phosphoproteomics. This is particularly true for plants in which the presence of secondary metabolites and endogenous compounds, the overabundance of ribulose-1,5-bisphosphate carboxylase and other components of the photosynthetic apparatus, and the concurrent difficulties in protein extraction necessitate two-step phosphoprotein/phosphopeptide enrichment strategies (Nakagami et al., Plant Cell Physiol 53:118-124, 2012).Approaches for label-free peptide quantification are advantageous due to their low cost and experimental simplicity, but they lack precision. These drawbacks can be overcome by metabolic labeling of whole plants with heavy nitrogen ((15)N) which allows combining two samples very early in the phosphoprotein enrichment workflow. This avoids sample-to-sample variation introduced by the analytical procedures and it results in robust relative quantification values that need no further standardization. The integration of (15)N metabolic labeling into tandem metal-oxide affinity chromatography (MOAC) (Hoehenwarter et al., Mol Cell Proteomics 12:369-380, 2013) presents an improved and highly selective approach for the identification and accurate site-specific quantification of low-abundance phosphoproteins

  3. Towards Reproducibility in Computational Hydrology

    NASA Astrophysics Data System (ADS)

    Hutton, Christopher; Wagener, Thorsten; Freer, Jim; Han, Dawei; Duffy, Chris; Arheimer, Berit

    2017-04-01

    Reproducibility is a foundational principle in scientific research. The ability to independently re-run an experiment helps to verify the legitimacy of individual findings, and evolve (or reject) hypotheses and models of how environmental systems function, and move them from specific circumstances to more general theory. Yet in computational hydrology (and in environmental science more widely) the code and data that produces published results are not regularly made available, and even if they are made available, there remains a multitude of generally unreported choices that an individual scientist may have made that impact the study result. This situation strongly inhibits the ability of our community to reproduce and verify previous findings, as all the information and boundary conditions required to set up a computational experiment simply cannot be reported in an article's text alone. In Hutton et al 2016 [1], we argue that a cultural change is required in the computational hydrological community, in order to advance and make more robust the process of knowledge creation and hypothesis testing. We need to adopt common standards and infrastructures to: (1) make code readable and re-useable; (2) create well-documented workflows that combine re-useable code together with data to enable published scientific findings to be reproduced; (3) make code and workflows available, easy to find, and easy to interpret, using code and code metadata repositories. To create change we argue for improved graduate training in these areas. In this talk we reflect on our progress in achieving reproducible, open science in computational hydrology, which are relevant to the broader computational geoscience community. In particular, we draw on our experience in the Switch-On (EU funded) virtual water science laboratory (http://www.switch-on-vwsl.eu/participate/), which is an open platform for collaboration in hydrological experiments (e.g. [2]). While we use computational hydrology as

  4. Determination of phagocytosis of /sup 32/P-labeled Staphylococcus aureus by bovine polymorphonuclear leukocytes

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

    Dulin, A.M.; Paape, M.J.; Weinland, B.T.

    1984-04-01

    A procedure for the measurement of phagocytosis by bovine polymorphonuclear leukocytes (PMN) of /sup 32/P-labeled Staphylococcus aureus was modified so that a larger number of samples could be compared in a single run, and smaller volumes of sample, PMN, and /sup 32/P-labeled S aureus could be used. Results were highly reproducible, with a coefficient of variation between duplicate determinations of less than or equal to 2%. Lysostaphin was prepared from the supernatant of S staphylolyticus and was compared with a commercially available preparation. Effects of lysostaphin on PMN and influence of incubation media on release of /sup 32/P from /supmore » 32/P-labeled S aureus by lysostaphin were examined.« less

  5. A 2-phase labeling and choice architecture intervention to improve healthy food and beverage choices.

    PubMed

    Thorndike, Anne N; Sonnenberg, Lillian; Riis, Jason; Barraclough, Susan; Levy, Douglas E

    2012-03-01

    We assessed whether a 2-phase labeling and choice architecture intervention would increase sales of healthy food and beverages in a large hospital cafeteria. Phase 1 was a 3-month color-coded labeling intervention (red = unhealthy, yellow = less healthy, green = healthy). Phase 2 added a 3-month choice architecture intervention that increased the visibility and convenience of some green items. We compared relative changes in 3-month sales from baseline to phase 1 and from phase 1 to phase 2. At baseline (977,793 items, including 199,513 beverages), 24.9% of sales were red and 42.2% were green. Sales of red items decreased in both phases (P < .001), and green items increased in phase 1 (P < .001). The largest changes occurred among beverages. Red beverages decreased 16.5% during phase 1 (P < .001) and further decreased 11.4% in phase 2 (P < .001). Green beverages increased 9.6% in phase 1 (P < .001) and further increased 4.0% in phase 2 (P < .001). Bottled water increased 25.8% during phase 2 (P < .001) but did not increase at 2 on-site comparison cafeterias (P < .001). A color-coded labeling intervention improved sales of healthy items and was enhanced by a choice architecture intervention.

  6. Effect of Population Heterogenization on the Reproducibility of Mouse Behavior: A Multi-Laboratory Study

    PubMed Central

    Richter, S. Helene; Garner, Joseph P.; Zipser, Benjamin; Lewejohann, Lars; Sachser, Norbert; Touma, Chadi; Schindler, Britta; Chourbaji, Sabine; Brandwein, Christiane; Gass, Peter; van Stipdonk, Niek; van der Harst, Johanneke; Spruijt, Berry; Võikar, Vootele; Wolfer, David P.; Würbel, Hanno

    2011-01-01

    In animal experiments, animals, husbandry and test procedures are traditionally standardized to maximize test sensitivity and minimize animal use, assuming that this will also guarantee reproducibility. However, by reducing within-experiment variation, standardization may limit inference to the specific experimental conditions. Indeed, we have recently shown in mice that standardization may generate spurious results in behavioral tests, accounting for poor reproducibility, and that this can be avoided by population heterogenization through systematic variation of experimental conditions. Here, we examined whether a simple form of heterogenization effectively improves reproducibility of test results in a multi-laboratory situation. Each of six laboratories independently ordered 64 female mice of two inbred strains (C57BL/6NCrl, DBA/2NCrl) and examined them for strain differences in five commonly used behavioral tests under two different experimental designs. In the standardized design, experimental conditions were standardized as much as possible in each laboratory, while they were systematically varied with respect to the animals' test age and cage enrichment in the heterogenized design. Although heterogenization tended to improve reproducibility by increasing within-experiment variation relative to between-experiment variation, the effect was too weak to account for the large variation between laboratories. However, our findings confirm the potential of systematic heterogenization for improving reproducibility of animal experiments and highlight the need for effective and practicable heterogenization strategies. PMID:21305027

  7. Planar heterojunction perovskite solar cells with superior reproducibility

    PubMed Central

    Jeon, Ye-Jin; Lee, Sehyun; Kang, Rira; Kim, Jueng-Eun; Yeo, Jun-Seok; Lee, Seung-Hoon; Kim, Seok-Soon; Yun, Jin-Mun; Kim, Dong-Yu

    2014-01-01

    Perovskite solar cells (PeSCs) have been considered one of the competitive next generation power sources. To date, light-to-electric conversion efficiencies have rapidly increased to over 10%, and further improvements are expected. However, the poor device reproducibility of PeSCs ascribed to their inhomogeneously covered film morphology has hindered their practical application. Here, we demonstrate high-performance PeSCs with superior reproducibility by introducing small amounts of N-cyclohexyl-2-pyrrolidone (CHP) as a morphology controller into N,N-dimethylformamide (DMF). As a result, highly homogeneous film morphology, similar to that achieved by vacuum-deposition methods, as well as a high PCE of 10% and an extremely small performance deviation within 0.14% were achieved. This study represents a method for realizing efficient and reproducible planar heterojunction (PHJ) PeSCs through morphology control, taking a major step forward in the low-cost and rapid production of PeSCs by solving one of the biggest problems of PHJ perovskite photovoltaic technology through a facile method. PMID:25377945

  8. An algorithm for optimal fusion of atlases with different labeling protocols

    PubMed Central

    Iglesias, Juan Eugenio; Sabuncu, Mert Rory; Aganj, Iman; Bhatt, Priyanka; Casillas, Christen; Salat, David; Boxer, Adam; Fischl, Bruce; Van Leemput, Koen

    2014-01-01

    In this paper we present a novel label fusion algorithm suited for scenarios in which different manual delineation protocols with potentially disparate structures have been used to annotate the training scans (hereafter referred to as “atlases”). Such scenarios arise when atlases have missing structures, when they have been labeled with different levels of detail, or when they have been taken from different heterogeneous databases. The proposed algorithm can be used to automatically label a novel scan with any of the protocols from the training data. Further, it enables us to generate new labels that are not present in any delineation protocol by defining intersections on the underling labels. We first use probabilistic models of label fusion to generalize three popular label fusion techniques to the multi-protocol setting: majority voting, semi-locally weighted voting and STAPLE. Then, we identify some shortcomings of the generalized methods, namely the inability to produce meaningful posterior probabilities for the different labels (majority voting, semi-locally weighted voting) and to exploit the similarities between the atlases (all three methods). Finally, we propose a novel generative label fusion model that can overcome these drawbacks. We use the proposed method to combine four brain MRI datasets labeled with different protocols (with a total of 102 unique labeled structures) to produce segmentations of 148 brain regions. Using cross-validation, we show that the proposed algorithm outperforms the generalizations of majority voting, semi-locally weighted voting and STAPLE (mean Dice score 83%, vs. 77%, 80% and 79%, respectively). We also evaluated the proposed algorithm in an aging study, successfully reproducing some well-known results in cortical and subcortical structures. PMID:25463466

  9. Fluorescently labeled chimeric anti-CEA antibody improves detection and resection of human colon cancer in a patient-derived orthotopic xenograft (PDOX) nude mouse model.

    PubMed

    Metildi, Cristina A; Kaushal, Sharmeela; Luiken, George A; Talamini, Mark A; Hoffman, Robert M; Bouvet, Michael

    2014-04-01

    The aim of this study was to evaluate a new fluorescently labeled chimeric anti-CEA antibody for improved detection and resection of colon cancer. Frozen tumor and normal human tissue samples were stained with chimeric and mouse antibody-fluorophore conjugates for comparison. Mice with patient-derived orthotopic xenografts (PDOX) of colon cancer underwent fluorescence-guided surgery (FGS) or bright-light surgery (BLS) 24 hr after tail vein injection of fluorophore-conjugated chimeric anti-CEA antibody. Resection completeness was assessed using postoperative images. Mice were followed for 6 months for recurrence. The fluorophore conjugation efficiency (dye/mole ratio) improved from 3-4 to >5.5 with the chimeric CEA antibody compared to mouse anti-CEA antibody. CEA-expressing tumors labeled with chimeric CEA antibody provided a brighter fluorescence signal on frozen human tumor tissues (P = 0.046) and demonstrated consistently lower fluorescence signals in normal human tissues compared to mouse antibody. Chimeric CEA antibody accurately labeled PDOX colon cancer in nude mice, enabling improved detection of tumor margins for more effective FGS. The R0 resection rate increased from 86% to 96% with FGS compared to BLS. Improved conjugating efficiency and labeling with chimeric fluorophore-conjugated antibody resulted in better detection and resection of human colon cancer in an orthotopic mouse model. © 2013 Wiley Periodicals, Inc.

  10. The Harm Done to Reproducibility by the Culture of Null Hypothesis Significance Testing.

    PubMed

    Lash, Timothy L

    2017-09-15

    In the last few years, stakeholders in the scientific community have raised alarms about a perceived lack of reproducibility of scientific results. In reaction, guidelines for journals have been promulgated and grant applicants have been asked to address the rigor and reproducibility of their proposed projects. Neither solution addresses a primary culprit, which is the culture of null hypothesis significance testing that dominates statistical analysis and inference. In an innovative research enterprise, selection of results for further evaluation based on null hypothesis significance testing is doomed to yield a low proportion of reproducible results and a high proportion of effects that are initially overestimated. In addition, the culture of null hypothesis significance testing discourages quantitative adjustments to account for systematic errors and quantitative incorporation of prior information. These strategies would otherwise improve reproducibility and have not been previously proposed in the widely cited literature on this topic. Without discarding the culture of null hypothesis significance testing and implementing these alternative methods for statistical analysis and inference, all other strategies for improving reproducibility will yield marginal gains at best. © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  11. EBprot: Statistical analysis of labeling-based quantitative proteomics data.

    PubMed

    Koh, Hiromi W L; Swa, Hannah L F; Fermin, Damian; Ler, Siok Ghee; Gunaratne, Jayantha; Choi, Hyungwon

    2015-08-01

    Labeling-based proteomics is a powerful method for detection of differentially expressed proteins (DEPs). The current data analysis platform typically relies on protein-level ratios, which is obtained by summarizing peptide-level ratios for each protein. In shotgun proteomics, however, some proteins are quantified with more peptides than others, and this reproducibility information is not incorporated into the differential expression (DE) analysis. Here, we propose a novel probabilistic framework EBprot that directly models the peptide-protein hierarchy and rewards the proteins with reproducible evidence of DE over multiple peptides. To evaluate its performance with known DE states, we conducted a simulation study to show that the peptide-level analysis of EBprot provides better receiver-operating characteristic and more accurate estimation of the false discovery rates than the methods based on protein-level ratios. We also demonstrate superior classification performance of peptide-level EBprot analysis in a spike-in dataset. To illustrate the wide applicability of EBprot in different experimental designs, we applied EBprot to a dataset for lung cancer subtype analysis with biological replicates and another dataset for time course phosphoproteome analysis of EGF-stimulated HeLa cells with multiplexed labeling. Through these examples, we show that the peptide-level analysis of EBprot is a robust alternative to the existing statistical methods for the DE analysis of labeling-based quantitative datasets. The software suite is freely available on the Sourceforge website http://ebprot.sourceforge.net/. All MS data have been deposited in the ProteomeXchange with identifier PXD001426 (http://proteomecentral.proteomexchange.org/dataset/PXD001426/). © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Automated selected reaction monitoring software for accurate label-free protein quantification.

    PubMed

    Teleman, Johan; Karlsson, Christofer; Waldemarson, Sofia; Hansson, Karin; James, Peter; Malmström, Johan; Levander, Fredrik

    2012-07-06

    Selected reaction monitoring (SRM) is a mass spectrometry method with documented ability to quantify proteins accurately and reproducibly using labeled reference peptides. However, the use of labeled reference peptides becomes impractical if large numbers of peptides are targeted and when high flexibility is desired when selecting peptides. We have developed a label-free quantitative SRM workflow that relies on a new automated algorithm, Anubis, for accurate peak detection. Anubis efficiently removes interfering signals from contaminating peptides to estimate the true signal of the targeted peptides. We evaluated the algorithm on a published multisite data set and achieved results in line with manual data analysis. In complex peptide mixtures from whole proteome digests of Streptococcus pyogenes we achieved a technical variability across the entire proteome abundance range of 6.5-19.2%, which was considerably below the total variation across biological samples. Our results show that the label-free SRM workflow with automated data analysis is feasible for large-scale biological studies, opening up new possibilities for quantitative proteomics and systems biology.

  13. Category labels versus feature labels: category labels polarize inferential predictions.

    PubMed

    Yamauchi, Takashi; Yu, Na-Yung

    2008-04-01

    What makes category labels different from feature labels in predictive inference? This study suggests that category labels tend to make inductive reasoning polarized and homogeneous. In two experiments, participants were shown two schematic pictures of insects side by side and predicted the value of a hidden feature of one insect on the basis of the other insect. Arbitrary verbal labels were shown above the two pictures, and the meanings of the labels were manipulated in the instructions. In one condition, the labels represented the category membership of the insects, and in the other conditions, the same labels represented attributes of the insects. When the labels represented category membership, participants' responses became substantially polarized and homogeneous, indicating that the mere reference to category membership can modify reasoning processes.

  14. Reporting to Improve Reproducibility and Facilitate Validity Assessment for Healthcare Database Studies V1.0.

    PubMed

    Wang, Shirley V; Schneeweiss, Sebastian; Berger, Marc L; Brown, Jeffrey; de Vries, Frank; Douglas, Ian; Gagne, Joshua J; Gini, Rosa; Klungel, Olaf; Mullins, C Daniel; Nguyen, Michael D; Rassen, Jeremy A; Smeeth, Liam; Sturkenboom, Miriam

    2017-09-01

    Defining a study population and creating an analytic dataset from longitudinal healthcare databases involves many decisions. Our objective was to catalogue scientific decisions underpinning study execution that should be reported to facilitate replication and enable assessment of validity of studies conducted in large healthcare databases. We reviewed key investigator decisions required to operate a sample of macros and software tools designed to create and analyze analytic cohorts from longitudinal streams of healthcare data. A panel of academic, regulatory, and industry experts in healthcare database analytics discussed and added to this list. Evidence generated from large healthcare encounter and reimbursement databases is increasingly being sought by decision-makers. Varied terminology is used around the world for the same concepts. Agreeing on terminology and which parameters from a large catalogue are the most essential to report for replicable research would improve transparency and facilitate assessment of validity. At a minimum, reporting for a database study should provide clarity regarding operational definitions for key temporal anchors and their relation to each other when creating the analytic dataset, accompanied by an attrition table and a design diagram. A substantial improvement in reproducibility, rigor and confidence in real world evidence generated from healthcare databases could be achieved with greater transparency about operational study parameters used to create analytic datasets from longitudinal healthcare databases. © 2017 The Authors. Pharmacoepidemiology & Drug Safety Published by John Wiley & Sons Ltd.

  15. Toddlers benefit from labeling on an executive function search task.

    PubMed

    Miller, Stephanie E; Marcovitch, Stuart

    2011-03-01

    Although labeling improves executive function (EF) performance in children older than 3years, the results from studies with younger children have been equivocal. In the current study, we assessed performance in a computerized multistep multilocation search task with older 2-year-olds. The correct search location was either (a) not marked by a familiar picture or given a distinct label, (b) marked by a familiar picture but not given a distinct label, (c) marked by a familiar picture and labeled by the experimenter, or (d) marked by a familiar picture and labeled by the participant. The results revealed that accuracy improved across conditions such that children made the fewest errors when they generated the label for the hiding location. These findings support the hierarchical competing systems model, which postulates that improved performance can be explained by more powerful representations that guide search behavior. Copyright © 2010 Elsevier Inc. All rights reserved.

  16. Bioorthogonal Metabolic Labeling of Nascent RNA in Neurons Improves the Sensitivity of Transcriptome-Wide Profiling.

    PubMed

    Zajaczkowski, Esmi L; Zhao, Qiong-Yi; Zhang, Zong Hong; Li, Xiang; Wei, Wei; Marshall, Paul R; Leighton, Laura J; Nainar, Sarah; Feng, Chao; Spitale, Robert C; Bredy, Timothy W

    2018-06-15

    Transcriptome-wide expression profiling of neurons has provided important insights into the underlying molecular mechanisms and gene expression patterns that transpire during learning and memory formation. However, there is a paucity of tools for profiling stimulus-induced RNA within specific neuronal cell populations. A bioorthogonal method to chemically label nascent (i.e., newly transcribed) RNA in a cell-type-specific and temporally controlled manner, which is also amenable to bioconjugation via click chemistry, was recently developed and optimized within conventional immortalized cell lines. However, its value within a more fragile and complicated cellular system such as neurons, as well as for transcriptome-wide expression profiling, has yet to be demonstrated. Here, we report the visualization and sequencing of activity-dependent nascent RNA derived from neurons using this labeling method. This work has important implications for improving transcriptome-wide expression profiling and visualization of nascent RNA in neurons, which has the potential to provide valuable insights into the mechanisms underlying neural plasticity, learning, and memory.

  17. Film labels: a new look.

    PubMed

    Hunter, T B

    1994-02-01

    Every diagnostic image should be properly labeled. To improve the labeling of radiographs in the Department of Radiology at the University Medical Center, Tucson, Arizona, a special computer program was written to control the printing of the department's film flashcards. This program captures patient data from the hospital's radiology information system and uses it to create a film flashcard that contains the patient's name, hospital number, date of birth, age, the time the patient checked into the radiology department, and the date of the examination. The resulting film labels are legible and aesthetically pleasing. Having the patient's age and date of birth on the labels is a useful quality assurance measure to make certain the proper study has been performed on the correct patient. All diagnostic imaging departments should institute measures to assure their film labeling is as legible and informative as possible.

  18. A 2-Phase Labeling and Choice Architecture Intervention to Improve Healthy Food and Beverage Choices

    PubMed Central

    Sonnenberg, Lillian; Riis, Jason; Barraclough, Susan; Levy, Douglas E.

    2012-01-01

    Objectives. We assessed whether a 2-phase labeling and choice architecture intervention would increase sales of healthy food and beverages in a large hospital cafeteria. Methods. Phase 1 was a 3-month color-coded labeling intervention (red = unhealthy, yellow = less healthy, green = healthy). Phase 2 added a 3-month choice architecture intervention that increased the visibility and convenience of some green items. We compared relative changes in 3-month sales from baseline to phase 1 and from phase 1 to phase 2. Results. At baseline (977 793 items, including 199 513 beverages), 24.9% of sales were red and 42.2% were green. Sales of red items decreased in both phases (P < .001), and green items increased in phase 1 (P < .001). The largest changes occurred among beverages. Red beverages decreased 16.5% during phase 1 (P < .001) and further decreased 11.4% in phase 2 (P < .001). Green beverages increased 9.6% in phase 1 (P < .001) and further increased 4.0% in phase 2 (P < .001). Bottled water increased 25.8% during phase 2 (P < .001) but did not increase at 2 on-site comparison cafeterias (P < .001). Conclusions. A color-coded labeling intervention improved sales of healthy items and was enhanced by a choice architecture intervention. PMID:22390518

  19. Triple-Label β Liquid Scintillation Counting

    PubMed Central

    Bukowski, Thomas R.; Moffett, Tyler C.; Revkin, James H.; Ploger, James D.; Bassingthwaighte, James B.

    2010-01-01

    The detection of radioactive compounds by liquid scintillation has revolutionized modern biology, yet few investigators make full use of the power of this technique. Even though multiple isotope counting is considerably more difficult than single isotope counting, many experimental designs would benefit from using more than one isotope. The development of accurate isotope counting techniques enabling the simultaneous use of three β-emitting tracers has facilitated studies in our laboratory using the multiple tracer indicator dilution technique for assessing rates of transmembrane transport and cellular metabolism. The details of sample preparation, and of stabilizing the liquid scintillation spectra of the tracers, are critical to obtaining good accuracy. Reproducibility is enhanced by obtaining detailed efficiency/quench curves for each particular set of tracers and solvent media. The numerical methods for multiple-isotope quantitation depend on avoiding error propagation (inherent to successive subtraction techniques) by using matrix inversion. Experimental data obtained from triple-label β counting illustrate reproducibility and good accuracy even when the relative amounts of different tracers in samples of protein/electrolyte solutions, plasma, and blood are changed. PMID:1514684

  20. Improved labelling of DTPA- and DOTA-conjugated peptides and antibodies with 111In in HEPES and MES buffer.

    PubMed

    Brom, Maarten; Joosten, Lieke; Oyen, Wim Jg; Gotthardt, Martin; Boerman, Otto C

    2012-01-27

    efficiency, whereas Cd2+ concentrations up to 0.1 nM did not affect the labelling efficiency in MES and HEPES buffer. We showed improved labelling of DTPA- and DOTA-conjugated compounds with 111In in HEPES and MES buffer. The enhanced labelling efficiency appears to be due to the reduced competitive chelation of cadmium. The enhanced labelling efficiency will allow more sensitive imaging of the biomarkers with SPECT.

  1. Far-Red Fluorescent Lipid-Polymer Probes for an Efficient Labeling of Enveloped Viruses.

    PubMed

    Lacour, William; Adjili, Salim; Blaising, Julie; Favier, Arnaud; Monier, Karine; Mezhoud, Sarra; Ladavière, Catherine; Place, Christophe; Pécheur, Eve-Isabelle; Charreyre, Marie-Thérèse

    2016-08-01

    Far-red emitting fluorescent lipid probes are desirable to label enveloped viruses, for their efficient tracking by optical microscopy inside autofluorescent cells. Most used probes are rapidly released from membranes, leading to fluorescence signal decay and loss of contrast. Here, water-soluble lipid-polymer probes are synthesized harboring hydrophilic or hydrophobic far-red emitting dyes, and exhibiting enhanced brightness. They efficiently label Hepatitis C Virus pseudotyped particles (HCVpp), more stably and reproducibly than commercial probes, and a strong fluorescence signal is observed with a high contrast. Labeling with such probes do not alter virion morphology, integrity, nor infectivity. Finally, it is shown by fluorescence microscopy that these probes enable efficient tracking of labeled HCVpp inside hepatocarcinoma cells used as model hepatocytes, in spite of their autofluorescence up to 700 nm. These novel fluorescent lipid-polymer probes should therefore enable a better characterization of early stages of infection of autofluorescent cells by enveloped viruses. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Reproducibility in a multiprocessor system

    DOEpatents

    Bellofatto, Ralph A; Chen, Dong; Coteus, Paul W; Eisley, Noel A; Gara, Alan; Gooding, Thomas M; Haring, Rudolf A; Heidelberger, Philip; Kopcsay, Gerard V; Liebsch, Thomas A; Ohmacht, Martin; Reed, Don D; Senger, Robert M; Steinmacher-Burow, Burkhard; Sugawara, Yutaka

    2013-11-26

    Fixing a problem is usually greatly aided if the problem is reproducible. To ensure reproducibility of a multiprocessor system, the following aspects are proposed; a deterministic system start state, a single system clock, phase alignment of clocks in the system, system-wide synchronization events, reproducible execution of system components, deterministic chip interfaces, zero-impact communication with the system, precise stop of the system and a scan of the system state.

  3. Comparison of /sup 125/I-labeled and /sup 14/C-Labeled peptides of the major outer membrane protein of Chlamydia Trachomatis Strain L2/434 separated by high-performance liquid chromatography

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

    Judd, R.C.; Caldwell, H.D.

    1985-01-01

    The objective of this study was to determine if in-gel chloramine-T radioiodination adequately labels OM proteins to allow for accurate and precise structural comparison of these molecules. Therefore, intrinsically /sup 14/C-amino acid labeled proteins and /sup 125/I-labeled proteins were cleaved with two endopeptidic reagents and the peptide fragments separated by HPLC. A comparison of retention times of the fragments, as determined by differential radiation counting, thus indicated whether /sup 125/Ilabeling identified of all the peptide peaks seen in the /sup 14/Clabeled proteins. Results demonstrated that radioiodination yields complete and accurate information about the primary structure of outer membrane proteins. Inmore » addition, it permits the use of extremely small amounts of protein allowing for method optimization and multiple separations to insure reproducibility.« less

  4. Label propagation algorithm for community detection based on node importance and label influence

    NASA Astrophysics Data System (ADS)

    Zhang, Xian-Kun; Ren, Jing; Song, Chen; Jia, Jia; Zhang, Qian

    2017-09-01

    Recently, the detection of high-quality community has become a hot spot in the research of social network. Label propagation algorithm (LPA) has been widely concerned since it has the advantages of linear time complexity and is unnecessary to define objective function and the number of community in advance. However, LPA has the shortcomings of uncertainty and randomness in the label propagation process, which affects the accuracy and stability of the community. For large-scale social network, this paper proposes a novel label propagation algorithm for community detection based on node importance and label influence (LPA_NI). The experiments with comparative algorithms on real-world networks and synthetic networks have shown that LPA_NI can significantly improve the quality of community detection and shorten the iteration period. Also, it has better accuracy and stability in the case of similar complexity.

  5. Transformation of cell-derived microparticles into quantum-dot-labeled nanovectors for antitumor siRNA delivery.

    PubMed

    Chen, Gang; Zhu, Jun-Yi; Zhang, Zhi-Ling; Zhang, Wei; Ren, Jian-Gang; Wu, Min; Hong, Zheng-Yuan; Lv, Cheng; Pang, Dai-Wen; Zhao, Yi-Fang

    2015-01-12

    Cell-derived microparticles (MPs) have been recently recognized as critical intercellular information conveyors. However, further understanding of their biological behavior and potential application has been hampered by the limitations of current labeling techniques. Herein, a universal donor-cell-assisted membrane biotinylation strategy was proposed for labeling MPs by skillfully utilizing the natural membrane phospholipid exchange of their donor cells. This innovative strategy conveniently led to specific, efficient, reproducible, and biocompatible quantum dot (QD) labeling of MPs, thereby reliably conferring valuable traceability on MPs. By further loading with small interference RNA, QD-labeled MPs that had inherent cell-targeting and biomolecule-conveying ability were successfully employed for combined bioimaging and tumor-targeted therapy. This study provides the first reliable and biofriendly strategy for transforming biogenic MPs into functionalized nanovectors. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Toddlers Benefit from Labeling on an Executive Function Search Task

    PubMed Central

    Miller, Stephanie E.; Marcovitch, Stuart

    2010-01-01

    Although labeling improves executive function (EF) performance in children older than 3 (e.g., Kirkham, Cruess, & Diamond, 2003), the results from studies with younger children have been equivocal (e.g., Sophian & Wellman, 1983). In the present study, we assessed performance in a computerized multistep multilocation search task with older 2-year-old children. The correct search location was either: (a) not marked by a familiar picture nor given a distinct label, (b) marked by a familiar picture but not given a distinct label (c) marked by a familiar picture and labeled by the experimenter, or (d) marked by a familiar picture and labeled by the participant. The results revealed that accuracy improved across conditions such that children made fewest errors when they generated the label for the hiding location. These findings support the hierarchical competing systems model (Marcovitch & Zelazo, 2006, 2009) that postulates that improved performance can be explained by more powerful representations that guide search behavior. PMID:21112597

  7. Contextual sensitivity in scientific reproducibility

    PubMed Central

    Van Bavel, Jay J.; Mende-Siedlecki, Peter; Brady, William J.; Reinero, Diego A.

    2016-01-01

    In recent years, scientists have paid increasing attention to reproducibility. For example, the Reproducibility Project, a large-scale replication attempt of 100 studies published in top psychology journals found that only 39% could be unambiguously reproduced. There is a growing consensus among scientists that the lack of reproducibility in psychology and other fields stems from various methodological factors, including low statistical power, researcher’s degrees of freedom, and an emphasis on publishing surprising positive results. However, there is a contentious debate about the extent to which failures to reproduce certain results might also reflect contextual differences (often termed “hidden moderators”) between the original research and the replication attempt. Although psychologists have found extensive evidence that contextual factors alter behavior, some have argued that context is unlikely to influence the results of direct replications precisely because these studies use the same methods as those used in the original research. To help resolve this debate, we recoded the 100 original studies from the Reproducibility Project on the extent to which the research topic of each study was contextually sensitive. Results suggested that the contextual sensitivity of the research topic was associated with replication success, even after statistically adjusting for several methodological characteristics (e.g., statistical power, effect size). The association between contextual sensitivity and replication success did not differ across psychological subdisciplines. These results suggest that researchers, replicators, and consumers should be mindful of contextual factors that might influence a psychological process. We offer several guidelines for dealing with contextual sensitivity in reproducibility. PMID:27217556

  8. Contextual sensitivity in scientific reproducibility.

    PubMed

    Van Bavel, Jay J; Mende-Siedlecki, Peter; Brady, William J; Reinero, Diego A

    2016-06-07

    In recent years, scientists have paid increasing attention to reproducibility. For example, the Reproducibility Project, a large-scale replication attempt of 100 studies published in top psychology journals found that only 39% could be unambiguously reproduced. There is a growing consensus among scientists that the lack of reproducibility in psychology and other fields stems from various methodological factors, including low statistical power, researcher's degrees of freedom, and an emphasis on publishing surprising positive results. However, there is a contentious debate about the extent to which failures to reproduce certain results might also reflect contextual differences (often termed "hidden moderators") between the original research and the replication attempt. Although psychologists have found extensive evidence that contextual factors alter behavior, some have argued that context is unlikely to influence the results of direct replications precisely because these studies use the same methods as those used in the original research. To help resolve this debate, we recoded the 100 original studies from the Reproducibility Project on the extent to which the research topic of each study was contextually sensitive. Results suggested that the contextual sensitivity of the research topic was associated with replication success, even after statistically adjusting for several methodological characteristics (e.g., statistical power, effect size). The association between contextual sensitivity and replication success did not differ across psychological subdisciplines. These results suggest that researchers, replicators, and consumers should be mindful of contextual factors that might influence a psychological process. We offer several guidelines for dealing with contextual sensitivity in reproducibility.

  9. Chemiluminescent labels released from long spacer arm-functionalized magnetic particles: a novel strategy for ultrasensitive and highly selective detection of pathogen infections.

    PubMed

    Yang, Haowen; Liang, Wenbiao; He, Nongyue; Deng, Yan; Li, Zhiyang

    2015-01-14

    Previously, the unique advantages provided by chemiluminescence (CL) and magnetic particles (MPs) have resulted in the development of many useful nucleic acid detection methods. CL is highly sensitive, but when applied to MPs, its intensity is limited by the inner filter-like effect arising from excess dark MPs. Herein, we describe a modified strategy whereby CL labels are released from MPs to eliminate this negative effect. This approach relies on (1) the magnetic capture of target molecules on long spacer arm-functionalized magnetic particles (LSA-MPs), (2) the conjugation of streptavidin-alkaline phosphatase (SA-AP) to biotinylated amplicons of target pathogens, (3) the release of CL labels (specifically, AP tags), and (4) the detection of the released labels. CL labels were released from LSA-MPs through LSA ultrasonication or DNA enzymolysis, which proved to be the superior method. In contrast to conventional MPs, LSA-MPs exhibited significantly improved CL detection, because of the introduction of LSA, which was made of water-soluble carboxymethylated β-1,3-glucan. Detection of hepatitis B virus with this technique revealed a low detection limit of 50 fM, high selectivity, and excellent reproducibility. Thus, this approach may hold great potential for early stage clinical diagnosis of infectious diseases.

  10. GEO Label: User and Producer Perspectives on a Label for Geospatial Data

    NASA Astrophysics Data System (ADS)

    Lush, V.; Lumsden, J.; Masó, J.; Díaz, P.; McCallum, I.

    2012-04-01

    One of the aims of the Science and Technology Committee (STC) of the Group on Earth Observations (GEO) was to establish a GEO Label- a label to certify geospatial datasets and their quality. As proposed, the GEO Label will be used as a value indicator for geospatial data and datasets accessible through the Global Earth Observation System of Systems (GEOSS). It is suggested that the development of such a label will significantly improve user recognition of the quality of geospatial datasets and that its use will help promote trust in datasets that carry the established GEO Label. Furthermore, the GEO Label is seen as an incentive to data providers. At the moment GEOSS contains a large amount of data and is constantly growing. Taking this into account, a GEO Label could assist in searching by providing users with visual cues of dataset quality and possibly relevance; a GEO Label could effectively stand as a decision support mechanism for dataset selection. Currently our project - GeoViQua, - together with EGIDA and ID-03 is undertaking research to define and evaluate the concept of a GEO Label. The development and evaluation process will be carried out in three phases. In phase I we have conducted an online survey (GEO Label Questionnaire) to identify the initial user and producer views on a GEO Label or its potential role. In phase II we will conduct a further study presenting some GEO Label examples that will be based on Phase I. We will elicit feedback on these examples under controlled conditions. In phase III we will create physical prototypes which will be used in a human subject study. The most successful prototypes will then be put forward as potential GEO Label options. At the moment we are in phase I, where we developed an online questionnaire to collect the initial GEO Label requirements and to identify the role that a GEO Label should serve from the user and producer standpoint. The GEO Label Questionnaire consists of generic questions to identify whether

  11. Experimental and Numerical Models of Complex Clinical Scenarios; Strategies to Improve Relevance and Reproducibility of Joint Replacement Research

    PubMed Central

    Bechtold, Joan E.; Swider, Pascal; Goreham-Voss, Curtis; Soballe, Kjeld

    2016-01-01

    This research review aims to focus attention on the effect of specific surgical and host factors on implant fixation, and the importance of accounting for them in experimental and numerical models. These factors affect (a) eventual clinical applicability and (b) reproducibility of findings across research groups. Proper function and longevity for orthopedic joint replacement implants relies on secure fixation to the surrounding bone. Technology and surgical technique has improved over the last 50 years, and robust ingrowth and decades of implant survival is now routinely achieved for healthy patients and first-time (primary) implantation. Second-time (revision) implantation presents with bone loss with interfacial bone gaps in areas vital for secure mechanical fixation. Patients with medical comorbidities such as infection, smoking, congestive heart failure, kidney disease, and diabetes have a diminished healing response, poorer implant fixation, and greater revision risk. It is these more difficult clinical scenarios that require research to evaluate more advanced treatment approaches. Such treatments can include osteogenic or antimicrobial implant coatings, allo- or autogenous cellular or tissue-based approaches, local and systemic drug delivery, surgical approaches. Regarding implant-related approaches, most experimental and numerical models do not generally impose conditions that represent mechanical instability at the implant interface, or recalcitrant healing. Many treatments will work well in forgiving settings, but fail in complex human settings with disease, bone loss, or previous surgery. Ethical considerations mandate that we justify and limit the number of animals tested, which restricts experimental permutations of treatments. Numerical models provide flexibility to evaluate multiple parameters and combinations, but generally need to employ simplifying assumptions. The objectives of this paper are to (a) to highlight the importance of mechanical

  12. Reproducibility of techniques using Archimedes' principle in measuring cancellous bone volume.

    PubMed

    Zou, L; Bloebaum, R D; Bachus, K N

    1997-01-01

    Researchers have been interested in developing techniques to accurately and reproducibly measure the volume fraction of cancellous bone. Historically bone researchers have used Archimedes' principle with water to measure the volume fraction of cancellous bone. Preliminary results in our lab suggested that the calibrated water technique did not provide reproducible results. Because of this difficulty, it was decided to compare the conventional water method to a water with surfactant and a helium method using a micropycnometer. The water/surfactant and the helium methods were attempts to improve the fluid penetration into the small voids present in the cancellous bone structure. In order to compare the reproducibility of the new methods with the conventional water method, 16 cancellous bone specimens were obtained from femoral condyles of human and greyhound dog femora. The volume fraction measurements on each specimen were repeated three times with all three techniques. The results showed that the helium displacement method was more than an order of magnitudes more reproducible than the two other water methods (p < 0.05). Statistical analysis also showed that the conventional water method produced the lowest reproducibility (p < 0.05). The data from this study indicate that the helium displacement technique is a very useful, rapid and reproducible tool for quantitatively characterizing anisotropic porous tissue structures such as cancellous bone.

  13. The MIMIC Code Repository: enabling reproducibility in critical care research.

    PubMed

    Johnson, Alistair Ew; Stone, David J; Celi, Leo A; Pollard, Tom J

    2018-01-01

    Lack of reproducibility in medical studies is a barrier to the generation of a robust knowledge base to support clinical decision-making. In this paper we outline the Medical Information Mart for Intensive Care (MIMIC) Code Repository, a centralized code base for generating reproducible studies on an openly available critical care dataset. Code is provided to load the data into a relational structure, create extractions of the data, and reproduce entire analysis plans including research studies. Concepts extracted include severity of illness scores, comorbid status, administrative definitions of sepsis, physiologic criteria for sepsis, organ failure scores, treatment administration, and more. Executable documents are used for tutorials and reproduce published studies end-to-end, providing a template for future researchers to replicate. The repository's issue tracker enables community discussion about the data and concepts, allowing users to collaboratively improve the resource. The centralized repository provides a platform for users of the data to interact directly with the data generators, facilitating greater understanding of the data. It also provides a location for the community to collaborate on necessary concepts for research progress and share them with a larger audience. Consistent application of the same code for underlying concepts is a key step in ensuring that research studies on the MIMIC database are comparable and reproducible. By providing open source code alongside the freely accessible MIMIC-III database, we enable end-to-end reproducible analysis of electronic health records. © The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association.

  14. What is prescription labeling communicating to doctors about hepatotoxic drugs? A study of FDA approved product labeling.

    PubMed

    Willy, Mary E; Li, Zili

    2004-04-01

    The objective of this study was to evaluate the informativeness and consistency of product labeling of hepatotoxic drugs marketed in the United States. We searched the Physicians' Desk Reference-2000 for prescription drugs with hepatic failure and/or hepatic necrosis listed in the labeling. We used a six-item checklist to evaluate the 'informativeness' and consistency of the labeling content. An informativeness score equaled the proportion of checklist items present in each drug's labeling. Ninety-five prescription drugs were included in the study. Eleven (12%) of the drugs had information related to hepatic failure in a Black Boxed Warning, 52 (54%) in the Warnings section and 32 (34%) in the Adverse Reactions section of the label. The mean informativeness score was 35%; the score was significantly higher, 61%, when the risk was perceived to be high. The informativeness of labeling was not affected by the time of the labeling, but differed across the Center for Drug Evaluation and Research (CDER) Review Division responsible for the labeling. The information provided in labeling is variable and affected by many factors, including the perceived level of risk and review division strategy. Product labeling may benefit from current FDA initiatives to improve the consistency of risk-related labeling.

  15. Audit of manufactured products: use of allergen advisory labels and identification of labeling ambiguities.

    PubMed

    Pieretti, Mariah M; Chung, Danna; Pacenza, Robert; Slotkin, Todd; Sicherer, Scott H

    2009-08-01

    The Food Allergy Labeling and Consumer Protection Act became effective January 1, 2006, and mandates disclosure of the 8 major allergens in plain English and as a source of ingredients in the ingredient statement. It does not regulate advisory labels. We sought to determine the frequency and language used in voluntary advisory labels among commercially available products and to identify labeling ambiguities affecting consumers with allergy. Trained surveyors performed a supermarket survey of 20,241 unique manufactured food products (from an original assessment of 49,604 products) for use of advisory labels. A second detailed survey of 744 unique products evaluated additional labeling practices. Overall, 17% of 20,241 products surveyed contain advisory labels. Chocolate candy, cookies, and baking mixes were the 3 categories of 24 with the greatest frequency (> or = 40%). Categorically, advisory warnings included "may contain" (38%), "shared equipment" (33%), and "within plant" (29%). The subsurvey disclosed 25 different types of advisory terminology. Nonspecific terms, such as "natural flavors" and "spices," were found on 65% of products and were not linked to a specific ingredient for 83% of them. Additional ambiguities included unclear sources of soy (lecithin vs protein), nondisclosure of sources of gelatin and lecithin, and simultaneous disclosure of "contains" and "may contain" for the same allergen, among others. Numerous products have advisory labeling and ambiguities that present challenges to consumers with food allergy. Additional allergen labeling regulation could improve safety and quality of life for individuals with food allergy.

  16. An empirical analysis of journal policy effectiveness for computational reproducibility.

    PubMed

    Stodden, Victoria; Seiler, Jennifer; Ma, Zhaokun

    2018-03-13

    A key component of scientific communication is sufficient information for other researchers in the field to reproduce published findings. For computational and data-enabled research, this has often been interpreted to mean making available the raw data from which results were generated, the computer code that generated the findings, and any additional information needed such as workflows and input parameters. Many journals are revising author guidelines to include data and code availability. This work evaluates the effectiveness of journal policy that requires the data and code necessary for reproducibility be made available postpublication by the authors upon request. We assess the effectiveness of such a policy by ( i ) requesting data and code from authors and ( ii ) attempting replication of the published findings. We chose a random sample of 204 scientific papers published in the journal Science after the implementation of their policy in February 2011. We found that we were able to obtain artifacts from 44% of our sample and were able to reproduce the findings for 26%. We find this policy-author remission of data and code postpublication upon request-an improvement over no policy, but currently insufficient for reproducibility.

  17. An empirical analysis of journal policy effectiveness for computational reproducibility

    PubMed Central

    Seiler, Jennifer; Ma, Zhaokun

    2018-01-01

    A key component of scientific communication is sufficient information for other researchers in the field to reproduce published findings. For computational and data-enabled research, this has often been interpreted to mean making available the raw data from which results were generated, the computer code that generated the findings, and any additional information needed such as workflows and input parameters. Many journals are revising author guidelines to include data and code availability. This work evaluates the effectiveness of journal policy that requires the data and code necessary for reproducibility be made available postpublication by the authors upon request. We assess the effectiveness of such a policy by (i) requesting data and code from authors and (ii) attempting replication of the published findings. We chose a random sample of 204 scientific papers published in the journal Science after the implementation of their policy in February 2011. We found that we were able to obtain artifacts from 44% of our sample and were able to reproduce the findings for 26%. We find this policy—author remission of data and code postpublication upon request—an improvement over no policy, but currently insufficient for reproducibility. PMID:29531050

  18. Autonomous magnetic labelling of functional mesenchymal stem cells for improved traceability and spatial control in cell therapy applications.

    PubMed

    Harrison, Richard; Markides, Hareklea; Morris, Robert H; Richards, Paula; El Haj, Alicia J; Sottile, Virginie

    2017-08-01

    Mesenchymal stem cells (MSCs) represent a valuable resource for regenerative medicine treatments for orthopaedic repair and beyond. Following developments in isolation, expansion and differentiation protocols, efforts to promote clinical translation of emerging cellular strategies now seek to improve cell delivery and targeting. This study shows efficient live MSC labelling using silica-coated magnetic particles (MPs), which enables 3D tracking and guidance of stem cells. A procedure developed for the efficient and unassisted particle uptake was shown to support MSC viability and integrity, while surface marker expression and MSC differentiation capability were also maintained. In vitro, MSCs showed a progressive decrease in labelling over increasing culture time, which appeared to be linked to the dilution effect of cell division, rather than to particle release, and did not lead to detectable secondary particle uptake. Labelled MSC populations demonstrated magnetic responsiveness in vitro through directed migration in culture and, when seeded onto a scaffold, supporting MP-based approaches to cell targeting. The potential of these silica-coated MPs for MRI cell tracking of MSC populations was validated in 2D and in a cartilage repair model following cell delivery. These results highlight silica-coated magnetic particles as a simple, safe and effective resource to enhance MSC targeting for therapeutic applications and improve patient outcomes. © 2016 The Authors Journal of Tissue Engineering and Regenerative Medicine Published by John Wiley & Sons Ltd. © 2016 The Authors Journal of Tissue Engineering and Regenerative Medicine Published by John Wiley & Sons Ltd.

  19. Preprocessing Significantly Improves the Peptide/Protein Identification Sensitivity of High-resolution Isobarically Labeled Tandem Mass Spectrometry Data*

    PubMed Central

    Sheng, Quanhu; Li, Rongxia; Dai, Jie; Li, Qingrun; Su, Zhiduan; Guo, Yan; Li, Chen; Shyr, Yu; Zeng, Rong

    2015-01-01

    Isobaric labeling techniques coupled with high-resolution mass spectrometry have been widely employed in proteomic workflows requiring relative quantification. For each high-resolution tandem mass spectrum (MS/MS), isobaric labeling techniques can be used not only to quantify the peptide from different samples by reporter ions, but also to identify the peptide it is derived from. Because the ions related to isobaric labeling may act as noise in database searching, the MS/MS spectrum should be preprocessed before peptide or protein identification. In this article, we demonstrate that there are a lot of high-frequency, high-abundance isobaric related ions in the MS/MS spectrum, and removing isobaric related ions combined with deisotoping and deconvolution in MS/MS preprocessing procedures significantly improves the peptide/protein identification sensitivity. The user-friendly software package TurboRaw2MGF (v2.0) has been implemented for converting raw TIC data files to mascot generic format files and can be downloaded for free from https://github.com/shengqh/RCPA.Tools/releases as part of the software suite ProteomicsTools. The data have been deposited to the ProteomeXchange with identifier PXD000994. PMID:25435543

  20. Review of nutrition labeling formats.

    PubMed

    Geiger, C J; Wyse, B W; Parent, C R; Hansen, R G

    1991-07-01

    This article examines nutrition labeling history as well as the findings of nine research studies of nutrition labeling formats. Nutrition labeling regulations were announced in 1973 and have been periodically amended since then. In response to requests from consumers and health care professionals for revision of the labeling system, the Food and Drug Administration initiated a three-phase plan for reform of nutrition labeling in 1990. President Bush signed the Nutrition Labeling and Education Act in November 1990. Literature analysis revealed that only nine studies with an experimental design have focused on nutrition labeling since 1971. Four were conducted before 1975, which was the year that nutrition labeling was officially implemented, two were conducted in 1980, and three were conducted after 1986. Only two of the nine studies supported the traditional label format mandated by the Code of Federal Regulations, and one study partially supported it. Four of the nine studies that evaluated graphic presentations of nutrition information found that consumer comprehension of nutrition information was improved with a graphic format for nutrition labeling: three studies supported the use of bar graphs and one study supported the use of a pie chart. Full disclosure (ie, complete nutrient and ingredient labeling) was preferred by consumers in two of the three studies that examined this variable. The third study supported three types of information disclosure dependent upon socioeconomic class. In those studies that tested graphics, a bar graph format was significantly preferred and showed better consumer comprehension than the traditional format.

  1. A regenerated electrochemical biosensor for label-free detection of glucose and urea based on conformational switch of i-motif oligonucleotide probe.

    PubMed

    Gao, Zhong Feng; Chen, Dong Mei; Lei, Jing Lei; Luo, Hong Qun; Li, Nian Bing

    2015-10-15

    Improving the reproducibility of electrochemical signal remains a great challenge over the past decades. In this work, i-motif oligonucleotide probe-based electrochemical DNA (E-DNA) sensor is introduced for the first time as a regenerated sensing platform, which enhances the reproducibility of electrochemical signal, for label-free detection of glucose and urea. The addition of glucose or urea is able to activate glucose oxidase-catalyzed or urease-catalyzed reaction, inducing or destroying the formation of i-motif oligonucleotide probe. The conformational switch of oligonucleotide probe can be recorded by electrochemical impedance spectroscopy. Thus, the difference of electron transfer resistance is utilized for the quantitative determination of glucose and urea. We further demonstrate that the E-DNA sensor exhibits high selectivity, excellent stability, and remarkable regenerated ability. The human serum analysis indicates that this simple and regenerated strategy holds promising potential in future biosensing applications. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Relationships among grocery nutrition label users and consumers' attitudes and behavior toward restaurant menu labeling.

    PubMed

    Roseman, Mary G; Mathe-Soulek, Kimberly; Higgins, Joseph A

    2013-12-01

    In the United States (US), based on the 2010 Affordable Care Act, restaurant chains and similar retail food establishments with 20 or more locations are required to begin implementing calorie information on their menus. As enacting of the law begins, it is important to understand its potential for improving consumers' healthful behaviors. Therefore, the objective of this study was to explore relationships among users of grocery nutrition labels and attitudes toward restaurant menu labeling, along with the caloric content of their restaurant menu selection. Study participants were surveyed and then provided identical mock restaurant menus with or without calories. Results found that participants who used grocery nutrition labels and believed they would make healthy menu selections with nutrition labels on restaurant menus made healthier menu selections, regardless of whether the menu displayed calories or not. Consumers' nutrition knowledge and behaviors gained from using grocery nutrition labels and consumers' desire for restaurants to provide nutrition menu labels have a positive effect on their choosing healthful restaurant menu items. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Novel image processing method study for a label-free optical biosensor

    NASA Astrophysics Data System (ADS)

    Yang, Chenhao; Wei, Li'an; Yang, Rusong; Feng, Ying

    2015-10-01

    Optical biosensor is generally divided into labeled type and label-free type, the former mainly contains fluorescence labeled method and radioactive-labeled method, while fluorescence-labeled method is more mature in the application. The mainly image processing methods of fluorescent-labeled biosensor includes smooth filtering, artificial gridding and constant thresholding. Since some fluorescent molecules may influence the biological reaction, label-free methods have been the main developing direction of optical biosensors nowadays. The using of wider field of view and larger angle of incidence light path which could effectively improve the sensitivity of the label-free biosensor also brought more difficulties in image processing, comparing with the fluorescent-labeled biosensor. Otsu's method is widely applied in machine vision, etc, which choose the threshold to minimize the intraclass variance of the thresholded black and white pixels. It's capacity-constrained with the asymmetrical distribution of images as a global threshold segmentation. In order to solve the irregularity of light intensity on the transducer, we improved the algorithm. In this paper, we present a new image processing algorithm based on a reflectance modulation biosensor platform, which mainly comprises the design of sliding normalization algorithm for image rectification and utilizing the improved otsu's method for image segmentation, in order to implement automatic recognition of target areas. Finally we used adaptive gridding method extracting the target parameters for analysis. Those methods could improve the efficiency of image processing, reduce human intervention, enhance the reliability of experiments and laid the foundation for the realization of high throughput of label-free optical biosensors.

  4. Quenched substrates for live-cell labeling of SNAP-tagged fusion proteins with improved fluorescent background.

    PubMed

    Stöhr, Katharina; Siegberg, Daniel; Ehrhard, Tanja; Lymperopoulos, Konstantinos; Öz, Simin; Schulmeister, Sonja; Pfeifer, Andrea C; Bachmann, Julie; Klingmüller, Ursula; Sourjik, Victor; Herten, Dirk-Peter

    2010-10-01

    Recent developments in fluorescence microscopy raise the demands for bright and photostable fluorescent tags for specific and background free labeling in living cells. Aside from fluorescent proteins and other tagging methods, labeling of SNAP-tagged proteins has become available thereby increasing the pool of potentially applicable fluorescent dyes for specific labeling of proteins. Here, we report on novel conjugates of benzylguanine (BG) which are quenched in their fluorescence and become highly fluorescent upon labeling of the SNAP-tag, the commercial variant of the human O(6)-alkylguanosyltransferase (hAGT). We identified four conjugates showing a strong increase, i.e., >10-fold, in fluorescence intensity upon labeling of SNAP-tag in vitro. Moreover, we screened a subset of nine BG-dye conjugates in living Escherichia coli and found them all suited for labeling of the SNAP-tag. Here, quenched BG-dye conjugates yield a higher specificity due to reduced contribution from excess conjugate to the fluorescence signal. We further extended the application of these conjugates by labeling a SNAP-tag fusion of the Tar chemoreceptor in live E. coli cells and the eukaryotic transcription factor STAT5b in NIH 3T3 mouse fibroblast cells. Aside from the labeling efficiency and specificity in living cells, we discuss possible mechanisms that might be responsible for the changes in fluorescence emission upon labeling of the SNAP-tag, as well as problems we encountered with nonspecific labeling with certain conjugates in eukaryotic cells.

  5. Reproducibility Issues: Avoiding Pitfalls in Animal Inflammation Models.

    PubMed

    Laman, Jon D; Kooistra, Susanne M; Clausen, Björn E

    2017-01-01

    In light of an enhanced awareness of ethical questions and ever increasing costs when working with animals in biomedical research, there is a dedicated and sometimes fierce debate concerning the (lack of) reproducibility of animal models and their relevance for human inflammatory diseases. Despite evident advancements in searching for alternatives, that is, replacing, reducing, and refining animal experiments-the three R's of Russel and Burch (1959)-understanding the complex interactions of the cells of the immune system, the nervous system and the affected tissue/organ during inflammation critically relies on in vivo models. Consequently, scientific advancement and ultimately novel therapeutic interventions depend on improving the reproducibility of animal inflammation models. As a prelude to the remaining hands-on protocols described in this volume, here, we summarize potential pitfalls of preclinical animal research and provide resources and background reading on how to avoid them.

  6. In vivo biotinylation and incorporation of a photo-inducible unnatural amino acid to an antibody-binding domain improve site-specific labeling of antibodies.

    PubMed

    Kanje, Sara; Hober, Sophia

    2015-04-01

    Antibodies are important molecules in many research fields, where they play a key role in various assays. Antibody labeling is therefore of great importance. Currently, most labeling techniques take advantage of certain amino acid side chains that commonly appear throughout proteins. This makes it hard to control the position and exact degree of labeling of each antibody. Hence, labeling of the antibody may affect the antibody-binding site. This paper presents a novel protein domain based on the IgG-binding domain C2 of streptococcal protein G, containing the unnatural amino acid BPA, that can cross-link other molecules. This novel domain can, with improved efficiency compared to previously reported similar domains, site-specifically cross-link to IgG at the Fc region. An efficient method for simultaneous in vivo incorporation of BPA and specific biotinylation in a flask cultivation of Escherichia coli is described. In comparison to a traditionally labeled antibody sample, the C2-labeled counterpart proved to have a higher proportion of functional antibodies when immobilized on a solid surface and the same limit of detection in an ELISA. This method of labeling is, due to its efficiency and simplicity, of high interest for all antibody-based assays where it is important that labeling does not interfere with the antibody-binding site. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Reproducibility2020: Progress and priorities

    PubMed Central

    Freedman, Leonard P.; Venugopalan, Gautham; Wisman, Rosann

    2017-01-01

    The preclinical research process is a cycle of idea generation, experimentation, and reporting of results. The biomedical research community relies on the reproducibility of published discoveries to create new lines of research and to translate research findings into therapeutic applications. Since 2012, when scientists from Amgen reported that they were able to reproduce only 6 of 53 “landmark” preclinical studies, the biomedical research community began discussing the scale of the reproducibility problem and developing initiatives to address critical challenges. Global Biological Standards Institute (GBSI) released the “Case for Standards” in 2013, one of the first comprehensive reports to address the rising concern of irreproducible biomedical research. Further attention was drawn to issues that limit scientific self-correction, including reporting and publication bias, underpowered studies, lack of open access to methods and data, and lack of clearly defined standards and guidelines in areas such as reagent validation. To evaluate the progress made towards reproducibility since 2013, GBSI identified and examined initiatives designed to advance quality and reproducibility. Through this process, we identified key roles for funders, journals, researchers and other stakeholders and recommended actions for future progress. This paper describes our findings and conclusions. PMID:28620458

  8. Opening Reproducible Research

    NASA Astrophysics Data System (ADS)

    Nüst, Daniel; Konkol, Markus; Pebesma, Edzer; Kray, Christian; Klötgen, Stephanie; Schutzeichel, Marc; Lorenz, Jörg; Przibytzin, Holger; Kussmann, Dirk

    2016-04-01

    Open access is not only a form of publishing such that research papers become available to the large public free of charge, it also refers to a trend in science that the act of doing research becomes more open and transparent. When science transforms to open access we not only mean access to papers, research data being collected, or data being generated, but also access to the data used and the procedures carried out in the research paper. Increasingly, scientific results are generated by numerical manipulation of data that were already collected, and may involve simulation experiments that are completely carried out computationally. Reproducibility of research findings, the ability to repeat experimental procedures and confirm previously found results, is at the heart of the scientific method (Pebesma, Nüst and Bivand, 2012). As opposed to the collection of experimental data in labs or nature, computational experiments lend themselves very well for reproduction. Some of the reasons why scientists do not publish data and computational procedures that allow reproduction will be hard to change, e.g. privacy concerns in the data, fear for embarrassment or of losing a competitive advantage. Others reasons however involve technical aspects, and include the lack of standard procedures to publish such information and the lack of benefits after publishing them. We aim to resolve these two technical aspects. We propose a system that supports the evolution of scientific publications from static papers into dynamic, executable research documents. The DFG-funded experimental project Opening Reproducible Research (ORR) aims for the main aspects of open access, by improving the exchange of, by facilitating productive access to, and by simplifying reuse of research results that are published over the Internet. Central to the project is a new form for creating and providing research results, the executable research compendium (ERC), which not only enables third parties to

  9. Microbiologic tests in epidemiologic studies: are they reproducible?

    PubMed

    Aass, A M; Preus, H R; Zambon, J J; Gjermo, P

    1994-12-01

    Microbiologic assessments are often included in longitudinal studies to elucidate the significance of the association of certain Gram-negative bacteria and the development of periodontal diseases. In such studies, the reliability of methods is crucial. There are several methods to identify putative pathogens, and some of them are commercially available. The purpose of the present study was to compare the reproducibility of four different methods for detecting Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and Prevotella intermedia in order to evaluate their usefulness in epidemiologic studies. The test panel consisted of 10 young subjects and 10 adult periodontitis patients. Subgingival plaque was sampled from sites showing bone loss and "healthy" control sites. The four different methods for detecting the target bacteria were 1) cultivation, 2) Evalusite (a chair-side kit based on ELISA), 3) OmniGene, Inc, based on DNA probes, and 4) indirect immunofluorescence (IIF). The test procedure was repeated after a 1-wk interval and was performed by one examiner. Sites reported to be positive for a microorganism by any of the four methods at one or both examinations were considered to be positive for that organism and included in the analysis. The reproducibility of the four methods was low. The IIF and the cultivation methods showed somewhat higher reproducibility than did the commercial systems. A second test was done for Evalusite, three paper points for sampling being used instead of one as described in the manual. The reproducibility of the second test was improved, indicating that the detection level of the system may influence the reliability.

  10. [Application of rational ant colony optimization to improve the reproducibility degree of laser three-dimensional copy].

    PubMed

    Cui, Xiao-Yan; Huo, Zhong-Gang; Xin, Zhong-Hua; Tian, Xiao; Zhang, Xiao-Dong

    2013-07-01

    Three-dimensional (3D) copying of artificial ears and pistol printing are pushing laser three-dimensional copying technique to a new page. Laser three-dimensional scanning is a fresh field in laser application, and plays an irreplaceable part in three-dimensional copying. Its accuracy is the highest among all present copying techniques. Reproducibility degree marks the agreement of copied object with the original object on geometry, being the most important index property in laser three-dimensional copying technique. In the present paper, the error of laser three-dimensional copying was analyzed. The conclusion is that the data processing to the point cloud of laser scanning is the key technique to reduce the error and increase the reproducibility degree. The main innovation of this paper is as follows. On the basis of traditional ant colony optimization, rational ant colony optimization algorithm proposed by the author was applied to the laser three-dimensional copying as a new algorithm, and was put into practice. Compared with customary algorithm, rational ant colony optimization algorithm shows distinct advantages in data processing of laser three-dimensional copying, reducing the error and increasing the reproducibility degree of the copy.

  11. Reproducibility Between Brain Uptake Ratio Using Anatomic Standardization and Patlak-Plot Methods.

    PubMed

    Shibutani, Takayuki; Onoguchi, Masahisa; Noguchi, Atsushi; Yamada, Tomoki; Tsuchihashi, Hiroko; Nakajima, Tadashi; Kinuya, Seigo

    2015-12-01

    The Patlak-plot and conventional methods of determining brain uptake ratio (BUR) have some problems with reproducibility. We formulated a method of determining BUR using anatomic standardization (BUR-AS) in a statistical parametric mapping algorithm to improve reproducibility. The objective of this study was to demonstrate the inter- and intraoperator reproducibility of mean cerebral blood flow as determined using BUR-AS in comparison to the conventional-BUR (BUR-C) and Patlak-plot methods. The images of 30 patients who underwent brain perfusion SPECT were retrospectively used in this study. The images were reconstructed using ordered-subset expectation maximization and processed using an automatic quantitative analysis for cerebral blood flow of ECD tool. The mean SPECT count was calculated from axial basal ganglia slices of the normal side (slices 31-40) drawn using a 3-dimensional stereotactic region-of-interest template after anatomic standardization. The mean cerebral blood flow was calculated from the mean SPECT count. Reproducibility was evaluated using coefficient of variation and Bland-Altman plotting. For both inter- and intraoperator reproducibility, the BUR-AS method had the lowest coefficient of variation and smallest error range about the Bland-Altman plot. Mean CBF obtained using the BUR-AS method had the highest reproducibility. Compared with the Patlak-plot and BUR-C methods, the BUR-AS method provides greater inter- and intraoperator reproducibility of cerebral blood flow measurement. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  12. Using 2H labelling to improve the NMR detectability of pyridine and its derivatives by SABRE

    PubMed Central

    Norcott, Philip; Burns, Michael J.; Rayner, Peter J.; Mewis, Ryan E.

    2018-01-01

    By introducing a range of 2H labels into pyridine and the para‐substituted agents, methyl isonicotinate and isonicotinamide, we significantly improve their NMR detectability in conjunction with the signal amplification by reversible exchange process. We describe how the rates of T 1 relaxation for the remaining 1H nuclei are increased and show how this leads to a concomitant increase in the level of 1H and 13C hyperpolarization that can ultimately be detected. PMID:29274294

  13. Quantitative detection of codeine in human plasma using surface-enhanced Raman scattering via adaptation of the isotopic labelling principle.

    PubMed

    Subaihi, Abdu; Muhamadali, Howbeer; Mutter, Shaun T; Blanch, Ewan; Ellis, David I; Goodacre, Royston

    2017-03-27

    In this study surface enhanced Raman scattering (SERS) combined with the isotopic labelling (IL) principle has been used for the quantification of codeine spiked into both water and human plasma. Multivariate statistical approaches were employed for the analysis of these SERS spectral data, particularly partial least squares regression (PLSR) which was used to generate models using the full SERS spectral data for quantification of codeine with, and without, an internal isotopic labelled standard. The PLSR models provided accurate codeine quantification in water and human plasma with high prediction accuracy (Q 2 ). In addition, the employment of codeine-d 6 as the internal standard further improved the accuracy of the model, by increasing the Q 2 from 0.89 to 0.94 and decreasing the low root-mean-square error of predictions (RMSEP) from 11.36 to 8.44. Using the peak area at 1281 cm -1 assigned to C-N stretching, C-H wagging and ring breathing, the limit of detection was calculated in both water and human plasma to be 0.7 μM (209.55 ng mL -1 ) and 1.39 μM (416.12 ng mL -1 ), respectively. Due to a lack of definitive codeine vibrational assignments, density functional theory (DFT) calculations have also been used to assign the spectral bands with their corresponding vibrational modes, which were in excellent agreement with our experimental Raman and SERS findings. Thus, we have successfully demonstrated the application of SERS with isotope labelling for the absolute quantification of codeine in human plasma for the first time with a high degree of accuracy and reproducibility. The use of the IL principle which employs an isotopolog (that is to say, a molecule which is only different by the substitution of atoms by isotopes) improves quantification and reproducibility because the competition of the codeine and codeine-d 6 for the metal surface used for SERS is equal and this will offset any difference in the number of particles under analysis or any fluctuations in

  14. Facile purification and click labeling with 2-[ 18F]fluoroethyl azide using solid phase extraction cartridges

    DOE PAGES

    Zhou, Dong; Chu, Wenhua; Peng, Xin; ...

    2014-11-04

    In this paper, a facile method was developed to purify 2-[ 18F]fluoroethyl azide ([ 18F]FEA) using a C18 cartridge and an Oasis® HLB cartridge in series, in which [18F]FEA was exclusively trapped on the HLB cartridge. [ 18F]FEA can be eluted for reactions in solution; alternatively click labeling can be carried out on the HLB cartridge itself by loading an alkyne substrate and copper (I) catalyst dissolved in DMF onto the cartridge. Finally, this solid phase extraction methodology for purification and click labeling with [ 18F]FEA, either in solution or on the cartridge, is safe, simple, reproducible in high yield,more » and compatible with automated synthesis of 18F-labeled PET tracers.« less

  15. Reproducible detection of disease-associated markers from gene expression data.

    PubMed

    Omae, Katsuhiro; Komori, Osamu; Eguchi, Shinto

    2016-08-18

    Detection of disease-associated markers plays a crucial role in gene screening for biological studies. Two-sample test statistics, such as the t-statistic, are widely used to rank genes based on gene expression data. However, the resultant gene ranking is often not reproducible among different data sets. Such irreproducibility may be caused by disease heterogeneity. When we divided data into two subsets, we found that the signs of the two t-statistics were often reversed. Focusing on such instability, we proposed a sign-sum statistic that counts the signs of the t-statistics for all possible subsets. The proposed method excludes genes affected by heterogeneity, thereby improving the reproducibility of gene ranking. We compared the sign-sum statistic with the t-statistic by a theoretical evaluation of the upper confidence limit. Through simulations and applications to real data sets, we show that the sign-sum statistic exhibits superior performance. We derive the sign-sum statistic for getting a robust gene ranking. The sign-sum statistic gives more reproducible ranking than the t-statistic. Using simulated data sets we show that the sign-sum statistic excludes hetero-type genes well. Also for the real data sets, the sign-sum statistic performs well in a viewpoint of ranking reproducibility.

  16. Reproducibility in Data-Scarce Environments

    NASA Astrophysics Data System (ADS)

    Darch, P. T.

    2016-12-01

    Among the usual requirements for reproducibility are large volumes of data and computationally intensive methods. Many fields within earth sciences, however, do not meet these requirements. Data are scarce and data-intensive methods are not well established. How can science be reproducible under these conditions? What changes, both infrastructural and cultural, are needed to advance reproducibility? This paper presents findings from a long-term social scientific case study of an emergent and data scarce field, the deep subseafloor biosphere. This field studies interactions between microbial communities living in the seafloor and the physical environments they inhabit. Factors such as these make reproducibility seem a distant goal for this community: - The relative newness of the field. Serious study began in the late 1990s; - The highly multidisciplinary nature of the field. Researchers come from a range of physical and life science backgrounds; - Data scarcity. Domain researchers produce much of these data in their own onshore laboratories by analyzing cores from international ocean drilling expeditions. Allocation of cores is negotiated between researchers from many fields. These factors interact in multiple ways to inhibit reproducibility: - Incentive structures emphasize producing new data and new knowledge rather than reanalysing extant data; - Only a few steps of laboratory analyses can be reproduced - such as analysis of DNA sequences, but not extraction of DNA from cores -, due to scarcity of cores; - Methodological heterogeneity is a consequence of multidisciplinarity, as researchers bring different techniques from diverse fields. - Few standards for data collection or analysis are available at this early stage of the field; - While datasets from multiple biological and physical phenomena can be integrated into a single workflow, curation tends to be divergent. Each type of dataset may be subject to different disparate policies and contributed to different

  17. Improved quantitation and reproducibility in multi-PET/CT lung studies by combining CT information.

    PubMed

    Holman, Beverley F; Cuplov, Vesna; Millner, Lynn; Endozo, Raymond; Maher, Toby M; Groves, Ashley M; Hutton, Brian F; Thielemans, Kris

    2018-06-05

    Matched attenuation maps are vital for obtaining accurate and reproducible kinetic and static parameter estimates from PET data. With increased interest in PET/CT imaging of diffuse lung diseases for assessing disease progression and treatment effectiveness, understanding the extent of the effect of respiratory motion and establishing methods for correction are becoming more important. In a previous study, we have shown that using the wrong attenuation map leads to large errors due to density mismatches in the lung, especially in dynamic PET scans. Here, we extend this work to the case where the study is sub-divided into several scans, e.g. for patient comfort, each with its own CT (cine-CT and 'snap shot' CT). A method to combine multi-CT information into a combined-CT has then been developed, which averages the CT information from each study section to produce composite CT images with the lung density more representative of that in the PET data. This combined-CT was applied to nine patients with idiopathic pulmonary fibrosis, imaged with dynamic 18 F-FDG PET/CT to determine the improvement in the precision of the parameter estimates. Using XCAT simulations, errors in the influx rate constant were found to be as high as 60% in multi-PET/CT studies. Analysis of patient data identified displacements between study sections in the time activity curves, which led to an average standard error in the estimates of the influx rate constant of 53% with conventional methods. This reduced to within 5% after use of combined-CTs for attenuation correction of the study sections. Use of combined-CTs to reconstruct the sections of a multi-PET/CT study, as opposed to using the individually acquired CTs at each study stage, produces more precise parameter estimates and may improve discrimination between diseased and normal lung.

  18. In vitro labelling and detection of mesenchymal stromal cells: a comparison between magnetic resonance imaging of iron-labelled cells and magnetic resonance spectroscopy of fluorine-labelled cells.

    PubMed

    Rizzo, Stefania; Petrella, Francesco; Zucca, Ileana; Rinaldi, Elena; Barbaglia, Andrea; Padelli, Francesco; Baggi, Fulvio; Spaggiari, Lorenzo; Bellomi, Massimo; Bruzzone, Maria Grazia

    2017-01-01

    Among the various stem cell populations used for cell therapy, adult mesenchymal stromal cells (MSCs) have emerged as a major new cell technology. These cells must be tracked after transplantation to monitor their migration within the body and quantify their accumulation at the target site. This study assessed whether rat bone marrow MSCs can be labelled with superparamagnetic iron oxide (SPIO) nanoparticles and perfluorocarbon (PFC) nanoemulsion formulations without altering cell viability and compared magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) results from iron-labelled and fluorine-labelled MSCs, respectively. Of MSCs, 2 × 10 6 were labelled with Molday ION Rhodamine-B (MIRB) and 2 × 10 6 were labelled with Cell Sense. Cell viability was evaluated by trypan blue exclusion method. Labelled MSCs were divided into four samples containing increasing cell numbers (0.125 × 10 6 , 0.25 × 10 6 , 0.5 × 10 6 , 1 × 10 6 ) and scanned on a 7T MRI: for MIRB-labelled cells, phantoms and cells negative control, T1, T2 and T2* maps were acquired; for Cell Sense labelled cells, phantoms and unlabelled cells, a 19 F non-localised single-pulse MRS sequence was acquired. In total, 86.8% and 83.6% of MIRB-labelled cells and Cell Sense-labelled cells were viable, respectively. MIRB-labelled cells were visible in all samples with different cell numbers; pellets containing 0.5 × 10 6 and 1 × 10 6 of Cell Sense-labelled cells showed a detectable 19 F signal. Our data support the use of both types of contrast material (SPIO and PFC) for MSCs labelling, although further efforts should be dedicated to improve the efficiency of PFC labelling.

  19. The association between flavor labeling and flavor recall ability in children.

    PubMed

    Lumeng, Julie C; Zuckerman, Matthew D; Cardinal, Tiffany; Kaciroti, Niko

    2005-09-01

    This study sought to determine if the ability to label a flavor is associated with an improved ability to recall having tasted the flavor in preschool-aged children. A total of 120 3- to 6-year-old English-speaking children tasted and labeled 20 different flavors, blinded to color. Children's labels for the flavors were scored for consistency and accuracy. Recall for having tasted the flavor was tested. Both labeling ability and recall ability improved rapidly between the ages of 3 and 6 years in this cohort. Regression analysis indicated that independent of the child's age, consistent accurate labeling was positively associated with recall ability. Higher maternal education was an independent and marginal contributor to greater recall ability. The combination of consistent and accurate labeling, age, and maternal education accounted for 28% of the variance in flavor recall ability. Consistent but inaccurate labeling alone contributed little to the variance in flavor recall ability. We conclude from these findings that children's ability to recall having tasted a flavor develops rapidly during the preschool age range and that improved recall ability is associated with the ability to consistently and accurately label the flavor. We conclude that language mediates memory for flavors in young children.

  20. Extracorporeal adsorption therapy: A Method to improve targeted radiation delivered by radiometal-labeled monoclonal antibodies.

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

    Nemecek, Eneida R.; Green, Damian J.; Fisher, Darrell R.

    2008-04-01

    anti-CD20 antibody labeled with indium-111 (111In), seven patients received RIT with anti-CD20 antibody labeled with indium-111 for biokinetics and dosimetry, and therapeutic doses of antibody labeled with yttrium-90 (90Y). Performing the ECAT procedure at a rate that such that one blood volume per hour were circulated for 3 hours, resulted in mean radioactivity depletion of 96% in whole blood, 49% in whole body 49%, 62% in the lungs and 40% in liver and kidneys. There was no sufficient data to determine whether there was an improvement in the relative delivery of radiation to the tumor compared to normal organs by performing ECAT, but pharmacokinetic modeling studies suggested a potential therapeutic advantage using this approach. [refs] To evaluate the potential therapeutic advantages of ECAT, we performed biodistribution studies in nonhuman primates comparing the therapeutic ratios of radiation delivered using this approach to those delivered by conventional RIT alone. In addition, we evaluated lutetium-177 (177Lu) as an alternative isotope to optimize the delivery of RIT by improving the therapeutic index (target to non-target ratio)« less

  1. Reproducibility of studies on text mining for citation screening in systematic reviews: Evaluation and checklist.

    PubMed

    Olorisade, Babatunde Kazeem; Brereton, Pearl; Andras, Peter

    2017-09-01

    Independent validation of published scientific results through study replication is a pre-condition for accepting the validity of such results. In computation research, full replication is often unrealistic for independent results validation, therefore, study reproduction has been justified as the minimum acceptable standard to evaluate the validity of scientific claims. The application of text mining techniques to citation screening in the context of systematic literature reviews is a relatively young and growing computational field with high relevance for software engineering, medical research and other fields. However, there is little work so far on reproduction studies in the field. In this paper, we investigate the reproducibility of studies in this area based on information contained in published articles and we propose reporting guidelines that could improve reproducibility. The study was approached in two ways. Initially we attempted to reproduce results from six studies, which were based on the same raw dataset. Then, based on this experience, we identified steps considered essential to successful reproduction of text mining experiments and characterized them to measure how reproducible is a study given the information provided on these steps. 33 articles were systematically assessed for reproducibility using this approach. Our work revealed that it is currently difficult if not impossible to independently reproduce the results published in any of the studies investigated. The lack of information about the datasets used limits reproducibility of about 80% of the studies assessed. Also, information about the machine learning algorithms is inadequate in about 27% of the papers. On the plus side, the third party software tools used are mostly free and available. The reproducibility potential of most of the studies can be significantly improved if more attention is paid to information provided on the datasets used, how they were partitioned and utilized, and

  2. Long-term reproducibility of relative sensitivity factors obtained with CAMECA Wf

    NASA Astrophysics Data System (ADS)

    Gui, D.; Xing, Z. X.; Huang, Y. H.; Mo, Z. Q.; Hua, Y. N.; Zhao, S. P.; Cha, L. Z.

    2008-12-01

    As the wafer size continues to increase and the feature size of the integrated circuits (IC) continues to shrink, process control of IC manufacturing becomes ever more important to reduce the cost of failures caused by the drift of processes or equipments. Characterization tools with high precision and reproducibility are required to capture any abnormality of the process. Although Secondary ion mass spectrometry (SIMS) has been widely used in dopant profile control, it was reported that magnetic sector SIMS, compared to quadrupole SIMS, has lower short-term repeatability and long-term reproducibility due to the high extraction field applied between sample and extraction lens. In this paper, we demonstrate that CAMECA Wf can deliver high long-term reproducibility because of its high-level automation and improved design of immersion lens. The relative standard deviation (R.S.D.) of the relative sensitivity factors (RSF) of three typical elements, i.e., boron (B), phosphorous (P) and nitrogen (N), over 3 years are 3.7%, 5.5% and 4.1%, respectively. The high reproducibility results have a practical implication that deviation can be estimated without testing the standards.

  3. Accessing the reproducibility and specificity of pepsin and other aspartic proteases.

    PubMed

    Ahn, Joomi; Cao, Min-Jie; Yu, Ying Qing; Engen, John R

    2013-06-01

    The aspartic protease pepsin is less specific than other endoproteinases. Because aspartic proteases like pepsin are active at low pH, they are utilized in hydrogen deuterium exchange mass spectrometry (HDX MS) experiments for digestion under hydrogen exchange quench conditions. We investigated the reproducibility, both qualitatively and quantitatively, of online and offline pepsin digestion to understand the compliment of reproducible pepsin fragments that can be expected during a typical pepsin digestion. The collection of reproducible peptides was identified from >30 replicate digestions of the same protein and it was found that the number of reproducible peptides produced during pepsin digestion becomes constant above 5-6 replicate digestions. We also investigated a new aspartic protease from the stomach of the rice field eel (Monopterus albus Zuiew) and compared digestion efficiency and specificity to porcine pepsin and aspergillopepsin. Unique cleavage specificity was found for rice field eel pepsin at arginine, asparagine, and glycine. Different peptides produced by the various proteases can enhance protein sequence coverage and improve the spatial resolution of HDX MS data. This article is part of a Special Issue entitled: Mass spectrometry in structural biology. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. Analytical performance of reciprocal isotope labeling of proteome digests for quantitative proteomics and its application for comparative studies of aerobic and anaerobic Escherichia coli proteomes.

    PubMed

    Lo, Andy; Weiner, Joel H; Li, Liang

    2013-09-17

    Due to limited sample amounts, instrument time considerations, and reagent costs, only a small number of replicate experiments are typically performed for quantitative proteome analyses. Generation of reproducible data that can be readily assessed for consistency within a small number of datasets is critical for accurate quantification. We report our investigation of a strategy using reciprocal isotope labeling of two comparative samples as a tool for determining proteome changes. Reciprocal labeling was evaluated to determine the internal consistency of quantified proteome changes from Escherichia coli grown under aerobic and anaerobic conditions. Qualitatively, the peptide overlap between replicate analyses of the same sample and reverse labeled samples were found to be within 8%. Quantitatively, reciprocal analyses showed only a slight increase in average overall inconsistency when compared with replicate analyses (1.29 vs. 1.24-fold difference). Most importantly, reverse labeling was successfully used to identify spurious values resulting from incorrect peptide identifications and poor peak fitting. After removal of 5% of the peptide data with low reproducibility, a total of 275 differentially expressed proteins (>1.50-fold difference) were consistently identified and were then subjected to bioinformatics analysis. General considerations and guidelines for reciprocal labeling experimental design and biological significance of obtained results are discussed. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Production of isotopically labeled standards from a uniformly labeled precursor for quantitative volatile metabolomic studies.

    PubMed

    Gómez-Cortés, Pilar; Brenna, J Thomas; Sacks, Gavin L

    2012-06-19

    Optimal accuracy and precision in small-molecule profiling by mass spectrometry generally requires isotopically labeled standards chemically representative of all compounds of interest. However, preparation of mixed standards from commercially available pure compounds is often prohibitively expensive and time-consuming, and many labeled compounds are not available in pure form. We used a single-prototype uniformly labeled [U-(13)C]compound to generate [U-(13)C]-labeled volatile standards for use in subsequent experimental profiling studies. [U-(13)C]-α-Linolenic acid (18:3n-3, ALA) was thermally oxidized to produce labeled lipid degradation volatiles which were subsequently characterized qualitatively and quantitatively. Twenty-five [U-(13)C]-labeled volatiles were identified by headspace solid-phase microextraction-gas chromatography/time-of-flight mass spectrometry (HS-SPME-GC/TOF-MS) by comparison of spectra with unlabeled volatiles. Labeled volatiles were quantified by a reverse isotope dilution procedure. Using the [U-(13)C]-labeled standards, limits of detection comparable to or better than those of previous HS-SPME reports were achieved, 0.010-1.04 ng/g. The performance of the [U-(13)C]-labeled volatile standards was evaluated using a commodity soybean oil (CSO) oxidized at 60 °C from 0 to 15 d. Relative responses of n-decane, an unlabeled internal standard otherwise absent from the mixture, and [U-(13)C]-labeled oxidation products changed by up to 8-fold as the CSO matrix was oxidized, demonstrating that reliance on a single standard in volatile profiling studies yields inaccurate results due to changing matrix effects. The [U-(13)C]-labeled standard mixture was used to quantify 25 volatiles in oxidized CSO and low-ALA soybean oil with an average relative standard deviation of 8.5%. Extension of this approach to other labeled substrates, e.g., [U-(13)C]-labeled sugars and amino acids, for profiling studies should be feasible and can dramatically improve

  6. Discriminative confidence estimation for probabilistic multi-atlas label fusion.

    PubMed

    Benkarim, Oualid M; Piella, Gemma; González Ballester, Miguel Angel; Sanroma, Gerard

    2017-12-01

    Quantitative neuroimaging analyses often rely on the accurate segmentation of anatomical brain structures. In contrast to manual segmentation, automatic methods offer reproducible outputs and provide scalability to study large databases. Among existing approaches, multi-atlas segmentation has recently shown to yield state-of-the-art performance in automatic segmentation of brain images. It consists in propagating the labelmaps from a set of atlases to the anatomy of a target image using image registration, and then fusing these multiple warped labelmaps into a consensus segmentation on the target image. Accurately estimating the contribution of each atlas labelmap to the final segmentation is a critical step for the success of multi-atlas segmentation. Common approaches to label fusion either rely on local patch similarity, probabilistic statistical frameworks or a combination of both. In this work, we propose a probabilistic label fusion framework based on atlas label confidences computed at each voxel of the structure of interest. Maximum likelihood atlas confidences are estimated using a supervised approach, explicitly modeling the relationship between local image appearances and segmentation errors produced by each of the atlases. We evaluate different spatial pooling strategies for modeling local segmentation errors. We also present a novel type of label-dependent appearance features based on atlas labelmaps that are used during confidence estimation to increase the accuracy of our label fusion. Our approach is evaluated on the segmentation of seven subcortical brain structures from the MICCAI 2013 SATA Challenge dataset and the hippocampi from the ADNI dataset. Overall, our results indicate that the proposed label fusion framework achieves superior performance to state-of-the-art approaches in the majority of the evaluated brain structures and shows more robustness to registration errors. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Label Distribution in Tissues of Wheat Seedlings Cultivated with Tritium-Labeled Leonardite Humic Acid

    PubMed Central

    Kulikova, Natalia A.; Abroskin, Dmitry P.; Badun, Gennady A.; Chernysheva, Maria G.; Korobkov, Viktor I.; Beer, Anton S.; Tsvetkova, Eugenia A.; Senik, Svetlana V.; Klein, Olga I.; Perminova, Irina V.

    2016-01-01

    Humic substances (HS) play important roles in the biotic-abiotic interactions of the root plant and soil contributing to plant adaptation to external environments. However, their mode of action on plants remains largely unknown. In this study the HS distribution in tissues of wheat seedlings was examined using tritium-labeled humic acid (HA) derived from leonardite (a variety of lignites) and microautoradiography (MAR). Preferential accumulation of labeled products from tritiated HA was found in the roots as compared to the shoots, and endodermis was shown to be the major control point for radial transport of label into vascular system of plant. Tritium was also found in the stele and xylem tissues indicating that labeled products from tritiated HA could be transported to shoot tissues via the transpiration stream. Treatment with HA lead to an increase in the content of polar lipids of photosynthetic membranes. The observed accumulation of labeled HA products in root endodermis and positive impact on lipid synthesis are consistent with prior reported observations on physiological effects of HS on plants such as enhanced growth and development of lateral roots and improvement/repairs of the photosynthetic status of plants under stress conditions. PMID:27350412

  8. Label Distribution in Tissues of Wheat Seedlings Cultivated with Tritium-Labeled Leonardite Humic Acid

    NASA Astrophysics Data System (ADS)

    Kulikova, Natalia A.; Abroskin, Dmitry P.; Badun, Gennady A.; Chernysheva, Maria G.; Korobkov, Viktor I.; Beer, Anton S.; Tsvetkova, Eugenia A.; Senik, Svetlana V.; Klein, Olga I.; Perminova, Irina V.

    2016-06-01

    Humic substances (HS) play important roles in the biotic-abiotic interactions of the root plant and soil contributing to plant adaptation to external environments. However, their mode of action on plants remains largely unknown. In this study the HS distribution in tissues of wheat seedlings was examined using tritium-labeled humic acid (HA) derived from leonardite (a variety of lignites) and microautoradiography (MAR). Preferential accumulation of labeled products from tritiated HA was found in the roots as compared to the shoots, and endodermis was shown to be the major control point for radial transport of label into vascular system of plant. Tritium was also found in the stele and xylem tissues indicating that labeled products from tritiated HA could be transported to shoot tissues via the transpiration stream. Treatment with HA lead to an increase in the content of polar lipids of photosynthetic membranes. The observed accumulation of labeled HA products in root endodermis and positive impact on lipid synthesis are consistent with prior reported observations on physiological effects of HS on plants such as enhanced growth and development of lateral roots and improvement/repairs of the photosynthetic status of plants under stress conditions.

  9. Testing Reproducibility in Earth Sciences

    NASA Astrophysics Data System (ADS)

    Church, M. A.; Dudill, A. R.; Frey, P.; Venditti, J. G.

    2017-12-01

    Reproducibility represents how closely the results of independent tests agree when undertaken using the same materials but different conditions of measurement, such as operator, equipment or laboratory. The concept of reproducibility is fundamental to the scientific method as it prevents the persistence of incorrect or biased results. Yet currently the production of scientific knowledge emphasizes rapid publication of previously unreported findings, a culture that has emerged from pressures related to hiring, publication criteria and funding requirements. Awareness and critique of the disconnect between how scientific research should be undertaken, and how it actually is conducted, has been prominent in biomedicine for over a decade, with the fields of economics and psychology more recently joining the conversation. The purpose of this presentation is to stimulate the conversation in earth sciences where, despite implicit evidence in widely accepted classifications, formal testing of reproducibility is rare.As a formal test of reproducibility, two sets of experiments were undertaken with the same experimental procedure, at the same scale, but in different laboratories. Using narrow, steep flumes and spherical glass beads, grain size sorting was examined by introducing fine sediment of varying size and quantity into a mobile coarse bed. The general setup was identical, including flume width and slope; however, there were some variations in the materials, construction and lab environment. Comparison of the results includes examination of the infiltration profiles, sediment mobility and transport characteristics. The physical phenomena were qualitatively reproduced but not quantitatively replicated. Reproduction of results encourages more robust research and reporting, and facilitates exploration of possible variations in data in various specific contexts. Following the lead of other fields, testing of reproducibility can be incentivized through changes to journal

  10. An improved stable isotope N-terminal labeling approach with light/heavy TMPP to automate proteogenomics data validation: dN-TOP.

    PubMed

    Bertaccini, Diego; Vaca, Sebastian; Carapito, Christine; Arsène-Ploetze, Florence; Van Dorsselaer, Alain; Schaeffer-Reiss, Christine

    2013-06-07

    In silico gene prediction has proven to be prone to errors, especially regarding precise localization of start codons that spread in subsequent biological studies. Therefore, the high throughput characterization of protein N-termini is becoming an emerging challenge in the proteomics and especially proteogenomics fields. The trimethoxyphenyl phosphonium (TMPP) labeling approach (N-TOP) is an efficient N-terminomic approach that allows the characterization of both N-terminal and internal peptides in a single experiment. Due to its permanent positive charge, TMPP labeling strongly affects MS/MS fragmentation resulting in unadapted scoring of TMPP-derivatized peptide spectra by classical search engines. This behavior has led to difficulties in validating TMPP-derivatized peptide identifications with usual score filtering and thus to low/underestimated numbers of identified N-termini. We present herein a new strategy (dN-TOP) that overwhelmed the previous limitation allowing a confident and automated N-terminal peptide validation thanks to a combined labeling with light and heavy TMPP reagents. We show how this double labeling allows increasing the number of validated N-terminal peptides. This strategy represents a considerable improvement to the well-established N-TOP method with an enhanced and accelerated data processing making it now fully compatible with high-throughput proteogenomics studies.

  11. Quantitative isomer-specific N-glycan fingerprinting using isotope coded labeling and high performance liquid chromatography-electrospray ionization-mass spectrometry with graphitic carbon stationary phase.

    PubMed

    Michael, Claudia; Rizzi, Andreas M

    2015-02-27

    Glycan reductive isotope labeling (GRIL) using (12)C6-/(13)C6-aniline as labeling reagent is reported with the aim of quantitative N-glycan fingerprinting. Porous graphitized carbon (PGC) as stationary phase in capillary scale HPLC coupled to electrospray mass spectrometry with time of flight analyzer was applied for the determination of labeled N-glycans released from glycoproteins. The main benefit of using stable isotope-coding in the context of comparative glycomics lies in the improved accuracy and precision of the quantitative analysis in combined samples and in the potential of correcting for structure-dependent incomplete enzymatic release of oligosaccharides when comparing identical target proteins. The method was validated with respect to mobile phase parameters, reproducibility, accuracy, linearity and limit of detection/quantification (LOD/LOQ) using test glycoproteins. It is shown that the developed method is capable of determining relative amounts of N-glycans (including isomers) comparing two samples in one single HPLC-MS run. The analytical potential and usefulness of GRIL in combination with PGC-ESI-TOF-MS is demonstrated comparing glycosylation in human monoclonal antibodies produced in Chinese hamster ovary cells (CHO) and hybridoma cell lines. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Food labelling: Regulations and Public Health implications.

    PubMed

    Marcotrigiano, V; Lanzilotti, C; Rondinone, D; De Giglio, O; Caggiano, G; Diella, G; Orsi, G B; Montagna, M T; Napoli, C

    2018-01-01

    Legislators have implemented policies to improve food labelling to protect consumers and to make the presentation of ingredients and nutritional information more transparent. Proper food labelling allows consumers who may suffer from food allergies or intolerances to know exactly what ingredients a product contains, and it also helps them make more informed health and nutrition choices. This paper deals with the most current European and Italian legislation on food labelling, actions taken in non-EU countries to increase health choices, and the expected impact on Public Health.

  13. Reproducibility in cyclostratigraphy: initiating an intercomparison project

    NASA Astrophysics Data System (ADS)

    Sinnesael, Matthias; De Vleeschouwer, David; Zeeden, Christian; Claeys, Philippe

    2017-04-01

    The study of astronomical climate forcing and the application of cyclostratigraphy have experienced a spectacular growth over the last decades. In the field of cyclostratigraphy a broad range in methodological approaches exist. However, comparative study between the different approaches is lacking. Different cases demand different approaches, but with the growing importance of the field, questions arise about reproducibility, uncertainties and standardization of results. The radioisotopic dating community, in particular, has done far-reaching efforts to improve reproducibility and intercomparison of radioisotopic dates and their errors. To satisfy this need in cyclostratigraphy, we initiate a comparable framework for the community. The aims are to investigate and quantify reproducibility of, and uncertainties related to cyclostratigraphic studies and to provide a platform to discuss the merits and pitfalls of different methodologies, and their applicabilities. With this poster, we ask the feedback from the community on how to design this comparative framework in a useful, meaningful and productive manner. In parallel, we would like to discuss how reproducibility should be tested and what uncertainties should stand for in cyclostratigraphy. On the other hand, we intend to trigger interest for a cyclostratigraphic intercomparison project. This intercomparison project would imply the analysis of artificial and genuine geological records by individual researchers. All participants would be free to determine their method of choice. However, a handful of criterions will be required for an outcome to be comparable. The different results would be compared (e.g. during a workshop or a special session), and the lessons learned from the comparison could potentially be reported in a review paper. The aim of an intercomparison project is not to rank the different methods according to their merits, but to get insight into which specific methods are most suitable for which

  14. Influence of parameter settings in voxel-based morphometry 8. Using DARTEL and region-of-interest on reproducibility in gray matter volumetry.

    PubMed

    Goto, M; Abe, O; Aoki, S; Hayashi, N; Miyati, T; Takao, H; Matsuda, H; Yamashita, F; Iwatsubo, T; Mori, H; Kunimatsu, A; Ino, K; Yano, K; Ohtomo, K

    2015-01-01

    To investigate whether reproducibility of gray matter volumetry is influenced by parameter settings for VBM 8 using Diffeomorphic Anatomical Registration Through Exponentiated Lie Algebra (DARTEL) with region-of-interest (ROI) analyses. We prepared three-dimensional T1-weighted magnetic resonance images (3D-T1WIs) of 21 healthy subjects. All subjects were imaged with each of five MRI systems. Voxel-based morphometry 8 (VBM 8) and WFU PickAtlas software were used for gray matter volumetry. The bilateral ROI labels used were those provided as default settings with the software: Frontal Lobe, Hippocampus, Occipital Lobe, Orbital Gyrus, Parietal Lobe, Putamen, and Temporal Lobe. All 3D-T1WIs were segmented to gray matter with six parameters of VBM 8, with each parameter having between three and eight selectable levels. Reproducibility was evaluated as the standard deviation (mm³) of measured values for the five MRI systems. Reproducibility was influenced by 'Bias regularization (BiasR)', 'Bias FWHM', and 'De-noising filter' settings, but not by 'MRF weighting', 'Sampling distance', or 'Warping regularization' settings. Reproducibility in BiasR was influenced by ROI. Superior reproducibility was observed in Frontal Lobe with the BiasR1 setting, and in Hippocampus, Parietal Lobe, and Putamen with the BiasR3*, BiasR1, and BiasR5 settings, respectively. Reproducibility of gray matter volumetry was influenced by parameter settings in VBM 8 using DARTEL and ROI. In multi-center studies, the use of appropriate settings in VBM 8 with DARTEL results in reduced scanner effect.

  15. Evaluating Varied Label Designs for Use with Medical Devices: Optimized Labels Outperform Existing Labels in the Correct Selection of Devices and Time to Select.

    PubMed

    Bix, Laura; Seo, Do Chan; Ladoni, Moslem; Brunk, Eric; Becker, Mark W

    2016-01-01

    Effective standardization of medical device labels requires objective study of varied designs. Insufficient empirical evidence exists regarding how practitioners utilize and view labeling. Measure the effect of graphic elements (boxing information, grouping information, symbol use and color-coding) to optimize a label for comparison with those typical of commercial medical devices. Participants viewed 54 trials on a computer screen. Trials were comprised of two labels that were identical with regard to graphics, but differed in one aspect of information (e.g., one had latex, the other did not). Participants were instructed to select the label along a given criteria (e.g., latex containing) as quickly as possible. Dependent variables were binary (correct selection) and continuous (time to correct selection). Eighty-nine healthcare professionals were recruited at Association of Surgical Technologists (AST) conferences, and using a targeted e-mail of AST members. Symbol presence, color coding and grouping critical pieces of information all significantly improved selection rates and sped time to correct selection (α = 0.05). Conversely, when critical information was graphically boxed, probability of correct selection and time to selection were impaired (α = 0.05). Subsequently, responses from trials containing optimal treatments (color coded, critical information grouped with symbols) were compared to two labels created based on a review of those commercially available. Optimal labels yielded a significant positive benefit regarding the probability of correct choice ((P<0.0001) LSM; UCL, LCL: 97.3%; 98.4%, 95.5%)), as compared to the two labels we created based on commercial designs (92.0%; 94.7%, 87.9% and 89.8%; 93.0%, 85.3%) and time to selection. Our study provides data regarding design factors, namely: color coding, symbol use and grouping of critical information that can be used to significantly enhance the performance of medical device labels.

  16. Quantitative blood flow measurements in gliomas using arterial spin-labeling at 3T: intermodality agreement and inter- and intraobserver reproducibility study.

    PubMed

    Hirai, T; Kitajima, M; Nakamura, H; Okuda, T; Sasao, A; Shigematsu, Y; Utsunomiya, D; Oda, S; Uetani, H; Morioka, M; Yamashita, Y

    2011-12-01

    QUASAR is a particular application of the ASL method and facilitates the user-independent quantification of brain perfusion. The purpose of this study was to assess the intermodality agreement of TBF measurements obtained with ASL and DSC MR imaging and the inter- and intraobserver reproducibility of glioma TBF measurements acquired by ASL at 3T. Two observers independently measured TBF in 24 patients with histologically proved glioma. ASL MR imaging with QUASAR and DSC MR imaging were performed on 3T scanners. The observers placed 5 regions of interest in the solid tumor on rCBF maps derived from ASL and DSC MR images and 1 region of interest in the contralateral brain and recorded the measured values. Maximum and average sTBF values were calculated. Intermodality and intra- and interobsever agreement were determined by using 95% Bland-Altman limits of agreement and ICCs. The intermodality agreement for maximum sTBF was good to excellent on DSC and ASL images; ICCs ranged from 0.718 to 0.884. The 95% limits of agreement ranged from 59.2% to 65.4% of the mean. ICCs for intra- and interobserver agreement for maximum sTBF ranged from 0.843 to 0.850 and from 0.626 to 0.665, respectively. The reproducibility of maximum sTBF measurements obtained by methods was similar. In the evaluation of sTBF in gliomas, ASL with QUASAR at 3T yielded measurements and reproducibility similar to those of DSC perfusion MR imaging.

  17. 75 FR 82011 - Web-Distributed Labeling of Pesticides

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-29

    ... with pesticide labeling, thereby improving protection of human health and the environment from risks... pesticide products will not pose unreasonable adverse effects to human health or the environment. EPA..., when EPA amends the labeling of a pesticide product to incorporate new protections for human health or...

  18. Pre-labeling of diverse protein samples with a fixed amount of Cy5 for sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis.

    PubMed

    Bjerneld, Erik J; Johansson, Johan D; Laurin, Ylva; Hagner-McWhirter, Åsa; Rönn, Ola; Karlsson, Robert

    2015-09-01

    A pre-labeling protocol based on Cy5 N-hydroxysuccinimide (NHS) ester labeling of proteins has been developed for one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis. We show that a fixed amount of sulfonated Cy5 can be used in the labeling reaction to label proteins over a broad concentration range-more than three orders of magnitude. The optimal amount of Cy5 was found to be 50 to 250pmol in 20μl using a Tris-HCl labeling buffer at pH 8.7. Labeling protein samples with a fixed amount of dye in this range balances the requirements of sub-nanogram detection sensitivity and low dye-to-protein (D/P) ratios for SDS-PAGE. Simulations of the labeling reaction reproduced experimental observations of both labeling kinetics and D/P ratios. Two-dimensional electrophoresis was used to examine the labeling of proteins in a cell lysate using both sulfonated and non-sulfonated Cy5. For both types of Cy5, we observed efficient labeling across a broad range of molecular weights and isoelectric points. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Advancing The Cancer Genome Atlas glioma MRI collections with expert segmentation labels and radiomic features

    PubMed Central

    Bakas, Spyridon; Akbari, Hamed; Sotiras, Aristeidis; Bilello, Michel; Rozycki, Martin; Kirby, Justin S.; Freymann, John B.; Farahani, Keyvan; Davatzikos, Christos

    2017-01-01

    Gliomas belong to a group of central nervous system tumors, and consist of various sub-regions. Gold standard labeling of these sub-regions in radiographic imaging is essential for both clinical and computational studies, including radiomic and radiogenomic analyses. Towards this end, we release segmentation labels and radiomic features for all pre-operative multimodal magnetic resonance imaging (MRI) (n=243) of the multi-institutional glioma collections of The Cancer Genome Atlas (TCGA), publicly available in The Cancer Imaging Archive (TCIA). Pre-operative scans were identified in both glioblastoma (TCGA-GBM, n=135) and low-grade-glioma (TCGA-LGG, n=108) collections via radiological assessment. The glioma sub-region labels were produced by an automated state-of-the-art method and manually revised by an expert board-certified neuroradiologist. An extensive panel of radiomic features was extracted based on the manually-revised labels. This set of labels and features should enable i) direct utilization of the TCGA/TCIA glioma collections towards repeatable, reproducible and comparative quantitative studies leading to new predictive, prognostic, and diagnostic assessments, as well as ii) performance evaluation of computer-aided segmentation methods, and comparison to our state-of-the-art method. PMID:28872634

  20. Using 2 H labelling to improve the NMR detectability of pyridine and its derivatives by SABRE.

    PubMed

    Norcott, Philip; Burns, Michael J; Rayner, Peter J; Mewis, Ryan E; Duckett, Simon B

    2018-07-01

    By introducing a range of 2 H labels into pyridine and the para-substituted agents, methyl isonicotinate and isonicotinamide, we significantly improve their NMR detectability in conjunction with the signal amplification by reversible exchange process. We describe how the rates of T 1 relaxation for the remaining 1 H nuclei are increased and show how this leads to a concomitant increase in the level of 1 H and 13 C hyperpolarization that can ultimately be detected. © 2017 The Authors. Magnetic Resonance in Chemistry published by John Wiley & Sons Ltd.

  1. Potential utility of three-dimensional temperature and salinity fields estimated from satellite altimetry and Argo data for improving mesoscale reproducibility in regional ocean modeling

    NASA Astrophysics Data System (ADS)

    Kanki, R.; Uchiyama, Y.; Miyazaki, D.; Takano, A.; Miyazawa, Y.; Yamazaki, H.

    2014-12-01

    Mesoscale oceanic structure and variability are required to be reproduced as accurately as possible in realistic regional ocean modeling. Uchiyama et al. (2012) demonstrated with a submesoscale eddy-resolving JCOPE2-ROMS downscaling oceanic modeling system that the mesoscale reproducibility of the Kuroshio meandering along Japan is significantly improved by introducing a simple restoration to data which we call "TS nudging" (a.k.a. robust diagnosis) where the prognostic temperature and salinity fields are weakly nudged four-dimensionally towards the assimilative JCOPE2 reanalysis (Miyazawa et al., 2009). However, there is not always a reliable reanalysis for oceanic downscaling in an arbitrary region and at an arbitrary time, and therefore alternative dataset should be prepared. Takano et al. (2009) proposed an empirical method to estimate mesoscale 3-D thermal structure from the near real-time AVISO altimetry data along with the ARGO float data based on the two-layer model of Goni et al. (1996). In the present study, we consider the TS data derived from this method as a candidate. We thus conduct a synoptic forward modeling of the Kuroshio using the JCOPE2-ROMS downscaling system to explore potential utility of this empirical TS dataset (hereinafter TUM-TS) by carrying out two runs with the T-S nudging towards 1) the JCOPE2-TS and 2) TUM-TS fields. An example of the comparison between the two ROMS test runs is shown in the attached figure showing the annually averaged surface EKE. Both of TUM-TS and JCOPE2-TS are found to help reproducing the mesoscale variance of the Koroshio and its extension as well as its mean paths, surface KE and EKE reasonably well. Therefore, the AVISO-ARGO derived empirical 3-D TS estimation is potentially exploitable for the dataset to conduct the T-S nudging to reproduce mesoscale oceanic structure.

  2. [Reproducibility of subjective refraction measurement].

    PubMed

    Grein, H-J; Schmidt, O; Ritsche, A

    2014-11-01

    Reproducibility of subjective refraction measurement is limited by various factors. The main factors affecting reproducibility include the characteristics of the measurement method and of the subject and the examiner. This article presents the results of a study on this topic, focusing on the reproducibility of subjective refraction measurement in healthy eyes. The results of previous studies are not all presented in the same way by the respective authors and cannot be fully standardized without consulting the original scientific data. To the extent that they are comparable, the results of our study largely correspond largely with those of previous investigations: During repeated subjective refraction measurement, 95% of the deviation from the mean value was approximately ±0.2 D to ±0.65 D for the spherical equivalent and cylindrical power. The reproducibility of subjective refraction measurement in healthy eyes is limited, even under ideal conditions. Correct assessment of refraction results is only feasible after identifying individual variability. Several measurements are required. Refraction cannot be measured without a tolerance range. The English full-text version of this article is available at SpringerLink (under supplemental).

  3. Reproducing Epidemiologic Research and Ensuring Transparency.

    PubMed

    Coughlin, Steven S

    2017-08-15

    Measures for ensuring that epidemiologic studies are reproducible include making data sets and software available to other researchers so they can verify published findings, conduct alternative analyses of the data, and check for statistical errors or programming errors. Recent developments related to the reproducibility and transparency of epidemiologic studies include the creation of a global platform for sharing data from clinical trials and the anticipated future extension of the global platform to non-clinical trial data. Government agencies and departments such as the US Department of Veterans Affairs Cooperative Studies Program have also enhanced their data repositories and data sharing resources. The Institute of Medicine and the International Committee of Medical Journal Editors released guidance on sharing clinical trial data. The US National Institutes of Health has updated their data-sharing policies. In this issue of the Journal, Shepherd et al. (Am J Epidemiol. 2017;186:387-392) outline a pragmatic approach for reproducible research with sensitive data for studies for which data cannot be shared because of legal or ethical restrictions. Their proposed quasi-reproducible approach facilitates the dissemination of statistical methods and codes to independent researchers. Both reproducibility and quasi-reproducibility can increase transparency for critical evaluation, further dissemination of study methods, and expedite the exchange of ideas among researchers. © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. Analysis of fluorescently labeled glycosphingolipid-derived oligosaccharides following ceramide glycanase digestion and anthranilic acid labeling.

    PubMed

    Neville, David C A; Coquard, Virginie; Priestman, David A; te Vruchte, Danielle J M; Sillence, Daniel J; Dwek, Raymond A; Platt, Frances M; Butters, Terry D

    2004-08-15

    Interest in cellular glycosphingolipid (GSL) function has necessitated the development of a rapid and sensitive method to both analyze and characterize the full complement of structures present in various cells and tissues. An optimized method to characterize oligosaccharides released from glycosphingolipids following ceramide glycanase digestion has been developed. The procedure uses the fluorescent compound anthranilic acid (2-aminobenzoic acid; 2-AA) to label oligosaccharides prior to analysis using normal-phase high-performance liquid chromatography. The labeling procedure is rapid, selective, and easy to perform and is based on the published method of Anumula and Dhume [Glycobiology 8 (1998) 685], originally used to analyze N-linked oligosaccharides. It is less time consuming than a previously published 2-aminobenzamide labeling method [Anal. Biochem. 298 (2001) 207] for analyzing GSL-derived oligosaccharides, as the fluorescent labeling is performed on the enzyme reaction mixture. The purification of 2-AA-labeled products has been improved to ensure recovery of oligosaccharides containing one to four monosaccharide units, which was not previously possible using the Anumula and Dhume post-derivatization purification procedure. This new approach may also be used to analyze both N- and O-linked oligosaccharides.

  5. Faster, More Reproducible DESI-MS for Biological Tissue Imaging

    NASA Astrophysics Data System (ADS)

    Tillner, Jocelyn; Wu, Vincen; Jones, Emrys A.; Pringle, Steven D.; Karancsi, Tamas; Dannhorn, Andreas; Veselkov, Kirill; McKenzie, James S.; Takats, Zoltan

    2017-10-01

    A new, more robust sprayer for desorption electrospray ionization (DESI) mass spectrometry imaging is presented. The main source of variability in DESI is thought to be the uncontrolled variability of various geometric parameters of the sprayer, primarily the position of the solvent capillary, or more specifically, its positioning within the gas capillary or nozzle. If the solvent capillary is off-center, the sprayer becomes asymmetrical, making the geometry difficult to control and compromising reproducibility. If the stiffness, tip quality, and positioning of the capillary are improved, sprayer reproducibility can be improved by an order of magnitude. The quality of the improved sprayer and its potential for high spatial resolution imaging are demonstrated on human colorectal tissue samples by acquisition of images at pixel sizes of 100, 50, and 20 μm, which corresponds to a lateral resolution of 40-60 μm, similar to the best values published in the literature. The high sensitivity of the sprayer also allows combination with a fast scanning quadrupole time-of-flight mass spectrometer. This provides up to 30 times faster DESI acquisition, reducing the overall acquisition time for a 10 mm × 10 mm rat brain sample to approximately 1 h. Although some spectral information is lost with increasing analysis speed, the resulting data can still be used to classify tissue types on the basis of a previously constructed model. This is particularly interesting for clinical applications, where fast, reliable diagnosis is required. [Figure not available: see fulltext.

  6. Improved compliance with the World Health Organization Surgical Safety Checklist is associated with reduced surgical specimen labelling errors.

    PubMed

    Martis, Walston R; Hannam, Jacqueline A; Lee, Tracey; Merry, Alan F; Mitchell, Simon J

    2016-09-09

    A new approach to administering the surgical safety checklist (SSC) at our institution using wall-mounted charts for each SSC domain coupled with migrated leadership among operating room (OR) sub-teams, led to improved compliance with the Sign Out domain. Since surgical specimens are reviewed at Sign Out, we aimed to quantify any related change in surgical specimen labelling errors. Prospectively maintained error logs for surgical specimens sent to pathology were examined for the six months before and after introduction of the new SSC administration paradigm. We recorded errors made in the labelling or completion of the specimen pot and on the specimen laboratory request form. Total error rates were calculated from the number of errors divided by total number of specimens. Rates from the two periods were compared using a chi square test. There were 19 errors in 4,760 specimens (rate 3.99/1,000) and eight errors in 5,065 specimens (rate 1.58/1,000) before and after the change in SSC administration paradigm (P=0.0225). Improved compliance with administering the Sign Out domain of the SSC can reduce surgical specimen errors. This finding provides further evidence that OR teams should optimise compliance with the SSC.

  7. Submissions to the Australian and New Zealand Review of Food Labelling Law and Policy support traffic light nutrition labelling.

    PubMed

    White, John; Signal, Louise

    2012-10-01

    Food labels to support healthier choices are an important potential intervention for improving population health by reducing obesity and diet-related disease. This study examines the use of research evidence about traffic light nutrition labelling in submissions to the Review of Food Labelling Law and Policy conducted in Australia and New Zealand. Content analysis of final submissions to the Review and a literature review of documents reporting research evidence about traffic light labelling. Sixty-two submitters to the Review were categorised as 'supporters' of traffic light labelling and 29 as 'opponents'. Supporters focused on studies showing traffic light labels were better than other systems at helping consumers identify healthier food options. Opponents cited evidence that traffic light labels were no better than other systems in this respect and noted a lack of evidence that they led to changes in food consumption. A literature review demonstrated that, as a group, submitters had drawn attention to most of the relevant research evidence on traffic light labelling. Both supporters and opponents were, however, selective in their use of evidence. The weight of evidence suggested that traffic light labelling has strengths in helping consumers to identify healthier food options. Further research would be valuable in informing the development of an interpretive front-of-pack labelling system. The findings have significant implications for the development of front-of-pack nutrition labelling currently being considered in Australia and New Zealand. © 2012 The Authors. ANZJPH © 2012 Public Health Association of Australia.

  8. Flow-aggregated traffic-driven label mapping in label-switching networks

    NASA Astrophysics Data System (ADS)

    Nagami, Kenichi; Katsube, Yasuhiro; Esaki, Hiroshi; Nakamura, Osamu

    1998-12-01

    Label switching technology enables high performance, flexible, layer-3 packet forwarding based on the fixed length label information mapped to the layer-3 packet stream. A Label Switching Router (LSR) forwards layer-3 packets based on their label information mapped to the layer-3 address information as well as their layer-3 address information. This paper evaluates the required number of labels under traffic-driven label mapping policy using the real backbone traffic traces. The evaluation shows that the label mapping policy requires a large number of labels. In order to reduce the required number of labels, we propose a label mapping policy which is a traffic-driven label mapping for the traffic toward the same destination network. The evaluation shows that the proposed label mapping policy requires only about one tenth as many labels compared with the traffic-driven label mapping for the host-pair packet stream,and the topology-driven label mapping for the destination network packet stream.

  9. Nutrition Label Viewing during a Food-Selection Task: Front-of-Package Labels vs Nutrition Facts Labels.

    PubMed

    Graham, Dan J; Heidrick, Charles; Hodgin, Katie

    2015-10-01

    Earlier research has identified consumer characteristics associated with viewing Nutrition Facts labels; however, little is known about those who view front-of-package nutrition labels. Front-of-package nutrition labels might appeal to more consumers than do Nutrition Facts labels, but it might be necessary to provide consumers with information about how to locate and use these labels. This study quantifies Nutrition Facts and front-of-package nutrition label viewing among American adult consumers. Attention to nutrition information was measured during a food-selection task. One hundred and twenty-three parents (mean age=38 years, mean body mass index [calculated as kg/m(2)]=28) and one of their children (aged 6 to 9 years) selected six foods from a university laboratory-turned-grocery aisle. Participants were randomized to conditions in which front-of-package nutrition labels were present or absent, and signage explaining front-of-package nutrition labels was present or absent. Adults' visual attention to Nutrition Facts labels and front-of-package nutrition labels was objectively measured via eye-tracking glasses. To examine whether there were significant differences in the percentages of participants who viewed Nutrition Facts labels vs front-of-package nutrition labels, McNemar's tests were conducted across all participants, as well as within various sociodemographic categories. To determine whether hypothesized factors, such as health literacy and education, had stronger relationships with front-of-package nutrition label vs Nutrition Facts label viewing, linear regression assessed the magnitude of relationships between theoretically and empirically derived factors and each type of label viewing. Overall, front-of-package nutrition labels were more likely to be viewed than Nutrition Facts labels; however, for all subgroups, higher rates of front-of-package nutrition label viewership occurred only when signage was present drawing attention to the presence and

  10. 99M-Technetium labeled tin colloid radiopharmaceuticals

    DOEpatents

    Winchell, Harry S.; Barak, Morton; Van Fleet, III, Parmer

    1976-07-06

    An improved 99m-technetium labeled tin(II) colloid, size-stabilized for reticuloendothelial organ imaging without the use of macromolecular stabilizers and a packaged tin base reagent and an improved method for making it are disclosed.

  11. International Implications of Labeling Foods Containing Engineered Nanomaterials.

    PubMed

    Grieger, Khara D; Hansen, Steffen Foss; Mortensen, Ninell P; Cates, Sheryl; Kowalcyk, Barbara

    2016-05-01

    To provide greater transparency and comprehensive information to consumers regarding their purchase choices, the European Parliament and the Council have mandated via Regulation 1169/2011 that foods containing engineered nanomaterials (ENMs) be labeled. This review covers the main concerns related to the use of ENMs in foods and the potential impacts that this type of food labeling might have on diverse stakeholder groups, including those outside the European Union (EU), e.g., in the United States. We also provide recommendations to stakeholders for overcoming existing challenges related to labeling foods containing ENMs. The revised EU food labeling requirements will likely result in a number of positive developments and a number of challenges for stakeholders in both EU and non-EU countries. Although labeling of foods containing ENMs will likely improve transparency, provide more information to facilitate consumer decisions, and build trust among food safety authorities and consumers, critical obstacles to the successful implementation of these labeling requirements remain, including the need for (i) harmonized information requirements or regulations between countries in different regions of the world, (ii) clarification of the regulatory definitions of the ENMs to be used for food labeling, (iii) robust techniques to detect, measure, and characterize diverse ENMs in food matrices, and (iv) clarification of the list of ENMs that may be exempt from labeling requirements, such as several food additives used for decades. We recommend that food industries and food safety authorities be more proactive in communicating with the public and consumer groups regarding the potential benefits and risks of using ENMs in foods. Efforts should be made to improve harmonization of information requirements between countries to avoid potential international trade barriers.

  12. Understanding reproducibility of human IVF traits to predict next IVF cycle outcome.

    PubMed

    Wu, Bin; Shi, Juanzi; Zhao, Wanqiu; Lu, Suzhen; Silva, Marta; Gelety, Timothy J

    2014-10-01

    Evaluating the failed IVF cycle often provides useful prognostic information. Before undergoing another attempt, patients experiencing an unsuccessful IVF cycle frequently request information about the probability of future success. Here, we introduced the concept of reproducibility and formulae to predict the next IVF cycle outcome. The experimental design was based on the retrospective review of IVF cycle data from 2006 to 2013 in two different IVF centers and statistical analysis. The reproducibility coefficients (r) of IVF traits including number of oocytes retrieved, oocyte maturity, fertilization, embryo quality and pregnancy were estimated using the interclass correlation coefficient between the repeated IVF cycle measurements for the same patient by variance component analysis. The formulae were designed to predict next IVF cycle outcome. The number of oocytes retrieved from patients and their fertilization rate had the highest reproducibility coefficients (r = 0.81 ~ 0.84), which indicated a very close correlation between the first retrieval cycle and subsequent IVF cycles. Oocyte maturity and number of top quality embryos had middle level reproducibility (r = 0.38 ~ 0.76) and pregnancy rate had a relative lower reproducibility (r = 0.23 ~ 0.27). Based on these parameters, the next outcome for these IVF traits might be accurately predicted by the designed formulae. The introduction of the concept of reproducibility to our human IVF program allows us to predict future IVF cycle outcomes. The traits of oocyte numbers retrieved, oocyte maturity, fertilization, and top quality embryos had higher or middle reproducibility, which provides a basis for accurate prediction of future IVF outcomes. Based on this prediction, physicians may counsel their patients or change patient's stimulation plans, and laboratory embryologists may improve their IVF techniques accordingly.

  13. Gene expression profiling of whole blood: Comparison of target preparation methods for accurate and reproducible microarray analysis

    PubMed Central

    Vartanian, Kristina; Slottke, Rachel; Johnstone, Timothy; Casale, Amanda; Planck, Stephen R; Choi, Dongseok; Smith, Justine R; Rosenbaum, James T; Harrington, Christina A

    2009-01-01

    Background Peripheral blood is an accessible and informative source of transcriptomal information for many human disease and pharmacogenomic studies. While there can be significant advantages to analyzing RNA isolated from whole blood, particularly in clinical studies, the preparation of samples for microarray analysis is complicated by the need to minimize artifacts associated with highly abundant globin RNA transcripts. The impact of globin RNA transcripts on expression profiling data can potentially be reduced by using RNA preparation and labeling methods that remove or block globin RNA during the microarray assay. We compared four different methods for preparing microarray hybridization targets from human whole blood collected in PAXGene tubes. Three of the methods utilized the Affymetrix one-cycle cDNA synthesis/in vitro transcription protocol but varied treatment of input RNA as follows: i. no treatment; ii. treatment with GLOBINclear; or iii. treatment with globin PNA oligos. In the fourth method cDNA targets were prepared with the Ovation amplification and labeling system. Results We find that microarray targets generated with labeling methods that reduce globin mRNA levels or minimize the impact of globin transcripts during hybridization detect more transcripts in the microarray assay compared with the standard Affymetrix method. Comparison of microarray results with quantitative PCR analysis of a panel of genes from the NF-kappa B pathway shows good correlation of transcript measurements produced with all four target preparation methods, although method-specific differences in overall correlation were observed. The impact of freezing blood collected in PAXGene tubes on data reproducibility was also examined. Expression profiles show little or no difference when RNA is extracted from either fresh or frozen blood samples. Conclusion RNA preparation and labeling methods designed to reduce the impact of globin mRNA transcripts can significantly improve the

  14. Exhaled breath temperature in children: reproducibility and influencing factors.

    PubMed

    Vermeulen, S; Barreto, M; La Penna, F; Prete, A; Martella, S; Biagiarelli, F; Villa, M P

    2014-09-01

    This study will investigate the reproducibility and influencing factors of exhaled breath temperature measured with the tidal breathing technique in asthmatic patients and healthy children. Exhaled breath temperature, fractional exhaled nitric oxide, and spirometry were assessed in 124 children (63 healthy and 61 asthmatic), aged 11.2 ± 2.5 year, M/F 73/51. A modified version of the American Thoracic Society questionnaire on the child's present and past respiratory history was obtained from parents. Parents were also asked to provide detailed information on their child's medication use during the previous 4 weeks. Ear temperature, ambient temperature, and relative-ambient humidity were also recorded. Exhaled breath temperature measurements were highly reproducible; the second measurement was higher than the first measurement, consistent with a test-retest situation. In 13 subjects, between-session within-day reproducibility of exhaled breath temperature was still high. Exhaled breath temperature increased with age and relative-ambient humidity. Exhaled breath temperature was comparable in healthy and asthmatic children; when adjusted for potential confounders (i.e. ambient conditions and subject characteristics), thermal values of asthmatic patients exceeded those of the healthy children by 1.1 °C. Normalized exhaled breath temperature, by subtracting ambient temperature, was lower in asthmatic patients treated with inhaled corticosteroids than in those who were corticosteroid-naive. Measurements of exhaled breath temperature are highly reproducible, yet influenced by several factors. Corrected values, i.e. normalized exhaled breath temperature, could help us to assess the effect of therapy with inhaled corticosteroids. More studies are needed to improve the usefulness of the exhaled breath temperature measured with the tidal breathing technique in children.

  15. [Influence of the duration of recording in the reproducibility of the signal averaged electrocardiogram].

    PubMed

    Copie, X; Blankoff, I; Hnatkova, K; Fei, L; Camm, A J; Malik, M

    1996-06-01

    The authors studied the possibility of improving the reproducibility of the signal averaged ECG by increasing the number of averaged QRS complexes. One hundred patients were included in the study. In each cases, 400 QRS complexes were recorded on twice, consecutively, in strictly identical conditions. During each recording, the total duration of the amplified and averaged QRS complex (tQRS), the duration of the terminal signal below 40 microV (LAS) and the root mean square of the amplitude of the last 40 ms (RMS) were determined for 100, 200, 300 and 400 recorded QRS complexes. The presence of late potentials was defined as the positivity of two of the following criteria: tQRS > 114 ms, LAS > 38 ms, RMS < 20 microV. The number of contradictory diagnostic conclusions between two successive recordings of the same duration decreased progressively with the number of averaged QRS complexes: 10 for 100 QRS, 10 for 200 QRS, 9 for 300 QRS and 6 for 400 QRS complexes, but this improvement was not statistically significant. The absolute differences of tQRS and RMS between two successive recordings of the same duration were statistically different for the four durations of recording (p = 0.05) and there was a tendency towards statistical significance for LAS (p = 0.09). The best quantitative reproducibility of the 3 parameters was obtained with the recording of 300 QRS complexes. In conclusion, the reproducibility of the signal averaged ECG is improved when the number of average QRS complexes is increased. The authors' results suggests that reproducibility this is optimal with the amplification and averaging of 300 QRS complexes.

  16. Symbol labelling improves advantageous decision-making on the Iowa Gambling Task in people with intellectual disabilities.

    PubMed

    Dymond, Simon; Bailey, Rebecca; Willner, Paul; Parry, Rhonwen

    2010-01-01

    Individuals with intellectual and developmental disabilities often have difficulties foregoing short-term loss for long-term gain. The Iowa Gambling Task (IGT) has been extensively adopted as a laboratory measure of this ability. In the present study, we undertook the first investigation with people with intellectual disabilities using a two-choice child version of the IGT, with measures of intellectual and executive functioning. Compared to a group of matched controls, people with intellectual disabilities performed advantageously and showed high levels of subjective awareness about the relative goodness and badness of the decks. A symbol labelling intervention, in which participants were taught to label the good and bad decks at regular intervals significantly improved advantageous decision-making to levels approximating that of controls. Factor analysis of executive functioning scores identified working memory and mental flexibility (response initiation and set shifting), with a near-significant inverse correlation between the extent to which the intervention was required and mental flexibility. These findings show, for the first time, that people with intellectual disabilities are capable of performing advantageously on the IGT and add to the growing clinical literature on decision-making. Copyright 2009 Elsevier Ltd. All rights reserved.

  17. Increased liver uptake of liposomes and improved targeting efficacy by labeling with asialofetuin in rodents.

    PubMed

    Wu, J; Liu, P; Zhu, J L; Maddukuri, S; Zern, M A

    1998-03-01

    To improve liposome-directed therapy of liver disease and gene delivery, it would be beneficial to selectively target hepatocytes. For this purpose, conventional liposomes (CL) were labeled with asialofetuin (AF), an asialoglycoprotein. The biodistribution of AF-labeled liposomes (AF-L) in mice and their incorporation into rat hepatocytes, and their potential use in acute liver injury, were investigated. AF-L displayed a quicker plasma clearance than CL, and 25.4%, 2.7%, and 1.2% of the injected dose remained in the plasma versus 47.0%, 26.1%, and 9.5% of CL, respectively at 2, 4, and 20 hours after the injection. Total liver uptake of AF-L (73%+/-3.9%) was markedly higher (P < .005) than CL (16.5%+/-1.8%) 4 hours after the injection. Liposomal radioactivity (cpm/mg) was greatly enhanced in the liver (11-fold) during the first 4 hours after the administration of 14C-AF-L, and was much higher than in 14C-CL-injected mice (1.5-fold). In vitro incubation of isolated rat hepatocytes with 14C-AF-L or intravenous injection of 14C-AF-L in rats resulted in higher hepatocyte-bound radioactivity compared with 14C-CL (P < .01-.005). AF-L-associated 1,1'-dilinoleyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) fluorescent signals were not only located in Kupffer cells, but also in hepatocytes, in which bile canaliculus networks were imaged. Intravenous administration of vitamin E (VE)-associated CL (VE-CL, 1 mg/mouse) significantly lowered alanine transaminase (ALT) levels in CCl4-treated mice (196+/-79 vs. 2,107+/-235 U/mL; P < .01). The ALT level in CCl4 + VE-AF-L group was decreased to 38+/-16 units/mL, which was significantly lower than the CC14 + VE-CL group (P < .05). In conclusion, labeling liposomes with AF led to a shortened liposome plasma half-life and greatly enhanced uptake of AF-L liposome by the liver. The enhanced uptake resulted from an increased incorporation of hepatocytes with AF-L liposomes. VE-associated AF liposomes further improved the

  18. Textural-Contextual Labeling and Metadata Generation for Remote Sensing Applications

    NASA Technical Reports Server (NTRS)

    Kiang, Richard K.

    1999-01-01

    Despite the extensive research and the advent of several new information technologies in the last three decades, machine labeling of ground categories using remotely sensed data has not become a routine process. Considerable amount of human intervention is needed to achieve a level of acceptable labeling accuracy. A number of fundamental reasons may explain why machine labeling has not become automatic. In addition, there may be shortcomings in the methodology for labeling ground categories. The spatial information of a pixel, whether textural or contextual, relates a pixel to its surroundings. This information should be utilized to improve the performance of machine labeling of ground categories. Landsat-4 Thematic Mapper (TM) data taken in July 1982 over an area in the vicinity of Washington, D.C. are used in this study. On-line texture extraction by neural networks may not be the most efficient way to incorporate textural information into the labeling process. Texture features are pre-computed from cooccurrence matrices and then combined with a pixel's spectral and contextual information as the input to a neural network. The improvement in labeling accuracy with spatial information included is significant. The prospect of automatic generation of metadata consisting of ground categories, textural and contextual information is discussed.

  19. Parametric studies on droplet generation reproducibility for applications with biological relevant fluids

    PubMed Central

    Eichler, Marko; Römer, Robert; Grodrian, Andreas; Lemke, Karen; Nagel, Krees; Klages, Claus‐Peter; Gastrock, Gunter

    2017-01-01

    Abstract Although the great potential of droplet based microfluidic technologies for routine applications in industry and academia has been successfully demonstrated over the past years, its inherent potential is not fully exploited till now. Especially regarding to the droplet generation reproducibility and stability, two pivotally important parameters for successful applications, there is still a need for improvement. This is even more considerable when droplets are created to investigate tissue fragments or cell cultures (e.g. suspended cells or 3D cell cultures) over days or even weeks. In this study we present microfluidic chips composed of a plasma coated polymer, which allow surfactants‐free, highly reproducible and stable droplet generation from fluids like cell culture media. We demonstrate how different microfluidic designs and different flow rates (and flow rate ratios) affect the reproducibility of the droplet generation process and display the applicability for a wide variety of bio(techno)logically relevant media. PMID:29399017

  20. Thou Shalt Be Reproducible! A Technology Perspective

    PubMed Central

    Mair, Patrick

    2016-01-01

    This article elaborates on reproducibility in psychology from a technological viewpoint. Modern open source computational environments are shown and explained that foster reproducibility throughout the whole research life cycle, and to which emerging psychology researchers should be sensitized, are shown and explained. First, data archiving platforms that make datasets publicly available are presented. Second, R is advocated as the data-analytic lingua franca in psychology for achieving reproducible statistical analysis. Third, dynamic report generation environments for writing reproducible manuscripts that integrate text, data analysis, and statistical outputs such as figures and tables in a single document are described. Supplementary materials are provided in order to get the reader started with these technologies. PMID:27471486

  1. Efficient Thread Labeling for Monitoring Programs with Nested Parallelism

    NASA Astrophysics Data System (ADS)

    Ha, Ok-Kyoon; Kim, Sun-Sook; Jun, Yong-Kee

    It is difficult and cumbersome to detect data races occurred in an execution of parallel programs. Any on-the-fly race detection techniques using Lamport's happened-before relation needs a thread labeling scheme for generating unique identifiers which maintain logical concurrency information for the parallel threads. NR labeling is an efficient thread labeling scheme for the fork-join program model with nested parallelism, because its efficiency depends only on the nesting depth for every fork and join operation. This paper presents an improved NR labeling, called e-NR labeling, in which every thread generates its label by inheriting the pointer to its ancestor list from the parent threads or by updating the pointer in a constant amount of time and space. This labeling is more efficient than the NR labeling, because its efficiency does not depend on the nesting depth for every fork and join operation. Some experiments were performed with OpenMP programs having nesting depths of three or four and maximum parallelisms varying from 10,000 to 1,000,000. The results show that e-NR is 5 times faster than NR labeling and 4.3 times faster than OS labeling in the average time for creating and maintaining the thread labels. In average space required for labeling, it is 3.5 times smaller than NR labeling and 3 times smaller than OS labeling.

  2. The legibility of prescription medication labelling in Canada

    PubMed Central

    Ahrens, Kristina; Krishnamoorthy, Abinaya; Gold, Deborah; Rojas-Fernandez, Carlos H.

    2014-01-01

    Introduction: The legibility of medication labelling is a concern for all Canadians, because poor or illegible labelling may lead to miscommunication of medication information and poor patient outcomes. There are currently few guidelines and no regulations regarding print standards on medication labels. This study analyzed sample prescription labels from Ontario, Canada, and compared them with print legibility guidelines (both generic and specific to medication labels). Methods: Cluster sampling was used to randomly select a total of 45 pharmacies in the tri-cities of Kitchener, Waterloo and Cambridge. Pharmacies were asked to supply a regular label with a hypothetical prescription. The print characteristics of patient-critical information were compared against the recommendations for prescription labels by pharmaceutical and health organizations and for print accessibility by nongovernmental organizations. Results: More than 90% of labels followed the guidelines for font style, contrast, print colour and nonglossy paper. However, only 44% of the medication instructions met the minimum guideline of 12-point print size, and none of the drug or patient names met this standard. Only 5% of the labels were judged to make the best use of space, and 51% used left alignment. None of the instructions were in sentence case, as is recommended. Discussion: We found discrepancies between guidelines and current labels in print size, justification, spacing and methods of emphasis. Conclusion: Improvements in pharmacy labelling are possible without moving to new technologies or changing the size of labels and would be expected to enhance patient outcomes. PMID:24847371

  3. Calorie labeling and consumer estimation of calories purchased.

    PubMed

    Taksler, Glen B; Elbel, Brian

    2014-07-12

    Studies rarely find fewer calories purchased following calorie labeling implementation. However, few studies consider whether estimates of the number of calories purchased improved following calorie labeling legislation. Researchers surveyed customers and collected purchase receipts at fast food restaurants in the United States cities of Philadelphia (which implemented calorie labeling policies) and Baltimore (a matched comparison city) in December 2009 (pre-implementation) and June 2010 (post-implementation). A difference-in-difference design was used to examine the difference between estimated and actual calories purchased, and the odds of underestimating calories.Participants in both cities, both pre- and post-calorie labeling, tended to underestimate calories purchased, by an average 216-409 calories. Adjusted difference-in-differences in estimated-actual calories were significant for individuals who ordered small meals and those with some college education (accuracy in Philadelphia improved by 78 and 231 calories, respectively, relative to Baltimore, p = 0.03-0.04). However, categorical accuracy was similar; the adjusted odds ratio [AOR] for underestimation by >100 calories was 0.90 (p = 0.48) in difference-in-difference models. Accuracy was most improved for subjects with a BA or higher education (AOR = 0.25, p < 0.001) and for individuals ordering small meals (AOR = 0.54, p = 0.001). Accuracy worsened for females (AOR = 1.38, p < 0.001) and for individuals ordering large meals (AOR = 1.27, p = 0.028). We concluded that the odds of underestimating calories varied by subgroup, suggesting that at some level, consumers may incorporate labeling information.

  4. Reproducible, high-throughput synthesis of colloidal nanocrystals for optimization in multidimensional parameter space.

    PubMed

    Chan, Emory M; Xu, Chenxu; Mao, Alvin W; Han, Gang; Owen, Jonathan S; Cohen, Bruce E; Milliron, Delia J

    2010-05-12

    While colloidal nanocrystals hold tremendous potential for both enhancing fundamental understanding of materials scaling and enabling advanced technologies, progress in both realms can be inhibited by the limited reproducibility of traditional synthetic methods and by the difficulty of optimizing syntheses over a large number of synthetic parameters. Here, we describe an automated platform for the reproducible synthesis of colloidal nanocrystals and for the high-throughput optimization of physical properties relevant to emerging applications of nanomaterials. This robotic platform enables precise control over reaction conditions while performing workflows analogous to those of traditional flask syntheses. We demonstrate control over the size, size distribution, kinetics, and concentration of reactions by synthesizing CdSe nanocrystals with 0.2% coefficient of variation in the mean diameters across an array of batch reactors and over multiple runs. Leveraging this precise control along with high-throughput optical and diffraction characterization, we effectively map multidimensional parameter space to tune the size and polydispersity of CdSe nanocrystals, to maximize the photoluminescence efficiency of CdTe nanocrystals, and to control the crystal phase and maximize the upconverted luminescence of lanthanide-doped NaYF(4) nanocrystals. On the basis of these demonstrative examples, we conclude that this automated synthesis approach will be of great utility for the development of diverse colloidal nanomaterials for electronic assemblies, luminescent biological labels, electroluminescent devices, and other emerging applications.

  5. Label Review Training: Module 1: Label Basics, Page 21

    EPA Pesticide Factsheets

    This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. Learn about types of labels.

  6. Robust Statistical Fusion of Image Labels

    PubMed Central

    Landman, Bennett A.; Asman, Andrew J.; Scoggins, Andrew G.; Bogovic, John A.; Xing, Fangxu; Prince, Jerry L.

    2011-01-01

    Image labeling and parcellation (i.e. assigning structure to a collection of voxels) are critical tasks for the assessment of volumetric and morphometric features in medical imaging data. The process of image labeling is inherently error prone as images are corrupted by noise and artifacts. Even expert interpretations are subject to subjectivity and the precision of the individual raters. Hence, all labels must be considered imperfect with some degree of inherent variability. One may seek multiple independent assessments to both reduce this variability and quantify the degree of uncertainty. Existing techniques have exploited maximum a posteriori statistics to combine data from multiple raters and simultaneously estimate rater reliabilities. Although quite successful, wide-scale application has been hampered by unstable estimation with practical datasets, for example, with label sets with small or thin objects to be labeled or with partial or limited datasets. As well, these approaches have required each rater to generate a complete dataset, which is often impossible given both human foibles and the typical turnover rate of raters in a research or clinical environment. Herein, we propose a robust approach to improve estimation performance with small anatomical structures, allow for missing data, account for repeated label sets, and utilize training/catch trial data. With this approach, numerous raters can label small, overlapping portions of a large dataset, and rater heterogeneity can be robustly controlled while simultaneously estimating a single, reliable label set and characterizing uncertainty. The proposed approach enables many individuals to collaborate in the construction of large datasets for labeling tasks (e.g., human parallel processing) and reduces the otherwise detrimental impact of rater unavailability. PMID:22010145

  7. 10 CFR 95.43 - Authority to reproduce.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... CSA, Secret and Confidential documents may be reproduced. Reproduced copies of classified documents... material must be conspicuously marked with the same classification markings as the material being...

  8. 10 CFR 95.43 - Authority to reproduce.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... CSA, Secret and Confidential documents may be reproduced. Reproduced copies of classified documents... material must be conspicuously marked with the same classification markings as the material being...

  9. 10 CFR 95.43 - Authority to reproduce.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... CSA, Secret and Confidential documents may be reproduced. Reproduced copies of classified documents... material must be conspicuously marked with the same classification markings as the material being...

  10. 10 CFR 95.43 - Authority to reproduce.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... CSA, Secret and Confidential documents may be reproduced. Reproduced copies of classified documents... material must be conspicuously marked with the same classification markings as the material being...

  11. 10 CFR 95.43 - Authority to reproduce.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... CSA, Secret and Confidential documents may be reproduced. Reproduced copies of classified documents... material must be conspicuously marked with the same classification markings as the material being...

  12. PRN 2000-5: Guidance for Mandatory and Advisory Labeling Statements

    EPA Pesticide Factsheets

    This notice provides guidance for improving the clarity of labeling statements in order to avoid confusing directions and precautions and to prevent the misuse of pesticides. It includes definitions and examples for mandatory and advisory label statements.

  13. Label Review Training: Module 1: Label Basics, Page 20

    EPA Pesticide Factsheets

    This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. This section focuses on supplemental labeling.

  14. Label Review Training: Module 1: Label Basics, Page 22

    EPA Pesticide Factsheets

    This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. Learn about what labels require review.

  15. Label Review Training: Module 1: Label Basics, Page 19

    EPA Pesticide Factsheets

    This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. This section covers supplemental distributor labeling.

  16. Progressive multi-atlas label fusion by dictionary evolution.

    PubMed

    Song, Yantao; Wu, Guorong; Bahrami, Khosro; Sun, Quansen; Shen, Dinggang

    2017-02-01

    Accurate segmentation of anatomical structures in medical images is important in recent imaging based studies. In the past years, multi-atlas patch-based label fusion methods have achieved a great success in medical image segmentation. In these methods, the appearance of each input image patch is first represented by an atlas patch dictionary (in the image domain), and then the latent label of the input image patch is predicted by applying the estimated representation coefficients to the corresponding anatomical labels of the atlas patches in the atlas label dictionary (in the label domain). However, due to the generally large gap between the patch appearance in the image domain and the patch structure in the label domain, the estimated (patch) representation coefficients from the image domain may not be optimal for the final label fusion, thus reducing the labeling accuracy. To address this issue, we propose a novel label fusion framework to seek for the suitable label fusion weights by progressively constructing a dynamic dictionary in a layer-by-layer manner, where the intermediate dictionaries act as a sequence of guidance to steer the transition of (patch) representation coefficients from the image domain to the label domain. Our proposed multi-layer label fusion framework is flexible enough to be applied to the existing labeling methods for improving their label fusion performance, i.e., by extending their single-layer static dictionary to the multi-layer dynamic dictionary. The experimental results show that our proposed progressive label fusion method achieves more accurate hippocampal segmentation results for the ADNI dataset, compared to the counterpart methods using only the single-layer static dictionary. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. SCF increases in utero-labeled stem cells migration and improves wound healing.

    PubMed

    Zgheib, Carlos; Xu, Junwang; Mallette, Andrew C; Caskey, Robert C; Zhang, Liping; Hu, Junyi; Liechty, Kenneth W

    2015-01-01

    Diabetic skin wounds lack the ability to heal properly and constitute a major and significant complication of diabetes. Nontraumatic lower extremity amputations are the number one complication of diabetic skin wounds. The complexity of their pathophysiology requires an intervention at many levels to enhance healing and wound closure. Stem cells are a promising treatment for diabetic skin wounds as they have the ability to correct abnormal healing. Stem cell factor (SCF), a chemokine expressed in the skin, can induce stem cells migration, however the role of SCF in diabetic skin wound healing is still unknown. We hypothesize that SCF would correct the impairment and promote the healing of diabetic skin wounds. Our results show that SCF improved wound closure in diabetic mice and increased HIF-1α and vascular endothelial growth factor (VEGF) expression levels in these wounds. SCF treatment also enhanced the migration of red fluorescent protein (RFP)-labeled skin stem cells via in utero intra-amniotic injection of lenti-RFP at E8. Interestingly these RFP+ cells are present in the epidermis, stain negative for K15, and appear to be distinct from the already known hair follicle stem cells. These results demonstrate that SCF improves diabetic wound healing in part by increasing the recruitment of a unique stem cell population present in the skin. © 2015 by the Wound Healing Society.

  18. Label Review Training: Module 1: Label Basics, Page 18

    EPA Pesticide Factsheets

    This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. This section discusses the types of labels.

  19. Label Review Training: Module 1: Label Basics, Page 26

    EPA Pesticide Factsheets

    This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. Learn about mandatory and advisory label statements.

  20. Label Review Training: Module 1: Label Basics, Page 15

    EPA Pesticide Factsheets

    This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. Learn about the consequences of improper labeling.

  1. Label Review Training: Module 1: Label Basics, Page 14

    EPA Pesticide Factsheets

    This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. Learn about positive effects from proper labeling.

  2. Label Review Training: Module 1: Label Basics, Page 24

    EPA Pesticide Factsheets

    This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. This page is about which labels require review.

  3. Label Review Training: Module 1: Label Basics, Page 17

    EPA Pesticide Factsheets

    This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. See an overview of the importance of labels.

  4. Label Review Training: Module 1: Label Basics, Page 27

    EPA Pesticide Factsheets

    This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. See examples of mandatory and advisory label statements.

  5. IMPY: an improved thioflavin-T derivative for in vivo labeling of beta-amyloid plaques.

    PubMed

    Kung, Mei-Ping; Hou, Catherine; Zhuang, Zhi-Ping; Zhang, Bin; Skovronsky, Daniel; Trojanowski, John Q; Lee, Virginia M-Y; Kung, Hank F

    2002-11-29

    Development of small molecular probes for in vivo labeling and detection of beta-amyloid (Abeta) plaques in patients of Alzheimer's disease (AD) is of significant scientific interest, and it may also assist the development of drugs targeting Abeta plaques for treatment of AD. A novel probe, [123I/(125)I]IMPY, 6-iodo-2-(4'-dimethylamino-)phenyl-imidazo[1,2-a]pyridine, was successfully prepared with an iododestannylation reaction catalyzed by hydrogen peroxide. The modified thioflavin-T derivative displayed a good binding affinity for preformed synthetic Abeta40 aggregates in solution (K(i)=15+/-5 nM) and showed selective plaque labeling on postmortem AD brain sections. Biodistribution study in normal mice after an iv injection of [125I]IMPY exhibited excellent brain uptake (2.9% initial dose/brain at 2 min) and fast washout (0.2% initial dose/brain at 60 min). These properties are highly desirable for amyloid plaque imaging agents. In vivo plaque labeling was evaluated in a transgenic mouse model (Tg2576) engineered to produce excess amyloid plaques in the brain. Ex vivo autoradiograms of brain sections of the Tg 2576 mouse obtained at 4 h after an i.v. injection of [125I]IMPY clearly displayed a distinct plaque labeling with a low background activity. When the same brain section was stained with a fluorescent dye, thioflavin-S, the same Abeta plaques showed prominent fluorescent labeling consistent with the results of the autoradiogram. In conclusion, these findings clearly suggest that radioiodinated IMPY demonstrates desirable characteristics for in vivo labeling of Abeta plaques and it may be useful as a molecular imaging agent to study amyloidogenesis in the brain of living AD patients. Copyright 2002 Elsevier Science B.V.

  6. Soft and hard classification by reproducing kernel Hilbert space methods.

    PubMed

    Wahba, Grace

    2002-12-24

    Reproducing kernel Hilbert space (RKHS) methods provide a unified context for solving a wide variety of statistical modelling and function estimation problems. We consider two such problems: We are given a training set [yi, ti, i = 1, em leader, n], where yi is the response for the ith subject, and ti is a vector of attributes for this subject. The value of y(i) is a label that indicates which category it came from. For the first problem, we wish to build a model from the training set that assigns to each t in an attribute domain of interest an estimate of the probability pj(t) that a (future) subject with attribute vector t is in category j. The second problem is in some sense less ambitious; it is to build a model that assigns to each t a label, which classifies a future subject with that t into one of the categories or possibly "none of the above." The approach to the first of these two problems discussed here is a special case of what is known as penalized likelihood estimation. The approach to the second problem is known as the support vector machine. We also note some alternate but closely related approaches to the second problem. These approaches are all obtained as solutions to optimization problems in RKHS. Many other problems, in particular the solution of ill-posed inverse problems, can be obtained as solutions to optimization problems in RKHS and are mentioned in passing. We caution the reader that although a large literature exists in all of these topics, in this inaugural article we are selectively highlighting work of the author, former students, and other collaborators.

  7. Optimization of immunolabeling and clearing techniques for indelibly-labeled memory traces.

    PubMed

    Pavlova, Ina P; Shipley, Shannon C; Lanio, Marcos; Hen, René; Denny, Christine A

    2018-04-16

    Recent genetic tools have allowed researchers to visualize and manipulate memory traces (i.e. engrams) in small brain regions. However, the ultimate goal is to visualize memory traces across the entire brain in order to better understand how memories are stored in neural networks and how multiple memories may coexist. Intact tissue clearing and imaging is a new and rapidly growing area of focus that could accomplish this task. Here, we utilized the leading protocols for whole-brain clearing and applied them to the ArcCreER T2 mice, a murine line that allows for the indelible labeling of memory traces. We found that CLARITY and PACT greatly distorted the tissue, and iDISCO quenched enhanced yellow fluorescent protein (EYFP) fluorescence and hindered immunolabeling. Alternative clearing solutions, such as tert-Butanol, circumvented these harmful effects, but still did not permit whole-brain immunolabeling. CUBIC and CUBIC with Reagent 1A produced improved antibody penetration and preserved EYFP fluorescence, but also did not allow for whole-brain memory trace visualization. Modification of CUBIC with Reagent-1A resulted in EYFP fluorescence preservation and immunolabeling of the immediate early gene (IEG) Arc in deep brain areas; however, optimized memory trace labeling still required tissue slicing into mm-thick tissue sections. In summary, our data show that CUBIC with Reagent-1A* is the ideal method for reproducible clearing and immunolabeling for the visualization of memory traces in mm-thick tissue sections from ArcCreER T2 mice. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

  8. Label Review Training: Module 1: Label Basics, Page 23

    EPA Pesticide Factsheets

    This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. Lists types of labels that do not require review.

  9. Label Review Training: Module 1: Label Basics, Page 16

    EPA Pesticide Factsheets

    This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. Learn about the importance of labels and the role in enforcement.

  10. Relative quantitation of glycosylation variants by stable isotope labeling of enzymatically released N-glycans using [12C]/[13C] aniline and ZIC-HILIC-ESI-TOF-MS.

    PubMed

    Giménez, Estela; Sanz-Nebot, Victòria; Rizzi, Andreas

    2013-09-01

    Glycan reductive isotope labeling (GRIL) using [(12)C]- and [(13)C]-coded aniline was used for relative quantitation of N-glycans. In a first step, the labeling method by reductive amination was optimized for this reagent. It could be demonstrated that selecting aniline as limiting reactant and using the reductant in excess is critical for achieving high derivatization yields (over 95 %) and good reproducibility (relative standard deviations ∼1-5 % for major and ∼5-10 % for minor N-glycans). In a second step, zwitterionic-hydrophilic interaction liquid chromatography in capillary columns coupled to electrospray mass spectrometry with time-of-flight analyzer (μZIC-HILIC-ESI-TOF-MS) was applied for the analysis of labeled N-glycans released from intact glycoproteins. Ovalbumin, bovine α1-acid-glycoprotein and bovine fetuin were used as test glycoproteins to establish and evaluate the methodology. Excellent separation of isomeric N-glycans and reproducible quantitation via the extracted ion chromatograms indicate a great potential of the proposed methodology for glycoproteomic analysis and for reliable relative quantitation of glycosylation variants in biological samples.

  11. Affect labeling enhances exposure effectiveness for public speaking anxiety.

    PubMed

    Niles, Andrea N; Craske, Michelle G; Lieberman, Matthew D; Hur, Christopher

    2015-05-01

    Exposure is an effective treatment for anxiety but many patients do not respond fully. Affect labeling (labeling emotional experience) attenuates emotional responding. The current project examined whether affect labeling enhances exposure effectiveness in participants with public speaking anxiety. Participants were randomized to exposure with or without affect labeling. Physiological arousal and self-reported fear were assessed before and after exposure and compared between groups. Consistent with hypotheses, participants assigned to Affect Labeling, especially those who used more labels during exposure, showed greater reduction in physiological activation than Control participants. No effect was found for self-report measures. Also, greater emotion regulation deficits at baseline predicted more benefit in physiological arousal from exposure combined with affect labeling than exposure alone. The current research provides evidence that behavioral strategies that target prefrontal-amygdala circuitry can improve treatment effectiveness for anxiety and these effects are particularly pronounced for patients with the greatest deficits in emotion regulation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Menu labels, for better, and worse? Exploring socio-economic and race-ethnic differences in menu label use in a national sample.

    PubMed

    Feng, Wenhui; Fox, Ashley

    2018-06-09

    Menu calorie labeling aims to empower customers to make healthier food choices, but researchers have questioned whether labels will empower those with greater health literacy, literacy or numeracy more, possibly reinforcing race-ethnic or socioeconomic inequalities in obesity. The goal of this study was to investigate differences in seeing and using restaurant menu calorie labels and whether differences have compounded over time. Using data from three rounds of the National Health and Nutrition Examination Survey covering the period 2007-2014, we investigate race-ethnic and socio-economic differences in menu label usage over time adjusting for sex, age and body weight. While menu label usage increased over time, not all groups increased their use equally. While we find that Blacks and Hispanics use labels more than Whites in sit-down restaurants, more educated individuals, higher income groups and Whites each increased the degree to which they saw and/or used labels in certain settings compared with other groups. This study reinforces concerns that menu-calorie labeling may exacerbate socio-economic and certain race-ethnic obesity differences. As menu labeling policy moves forward to be implemented federally, more attention may need to be diverted to educational campaigns accompanying the implementation and improving the labels so the information is easier to use. Copyright © 2018 Elsevier Ltd. All rights reserved.

  13. Comprehension of hazard communication: effects of pictograms on safety data sheets and labels.

    PubMed

    Boelhouwer, Eric; Davis, Jerry; Franco-Watkins, Ana; Dorris, Nathan; Lungu, Claudiu

    2013-09-01

    The United Nations has proposed the Globally Harmonized System (GHS) of Classification and Labelling of Chemicals to make hazard communication more uniform and to improve comprehension. Two experiments were conducted to test whether the addition of hazard and precautionary pictograms to safety data sheets and product labels would improve the transfer of information to users compared to safety data sheets and product labels containing text only. Additionally, naïve users, workers, and experts were tested to determine any potential differences among users. The effect of adding pictograms to safety data sheets and labels was statistically significant for some conditions, but was not significant across all conditions. One benefit of the addition of pictograms was that the time to respond to the survey questions decreased when the pictograms were present for both the SDS and the labels. GHS format SDS and labels do provide benefits to users, but the system will need further enhancements and modifications to continue to improve the effectiveness of hazard communication. The final rule to modify the HCS to include the Globally Harmonized System (GHS) for the Classification and Labelling of Chemicals announced by OSHA (2012b) will change the information content of every chemical SDS and label used in commerce. This study suggests that the inclusion of GHS hazard pictograms and precautionary pictograms to SDS and labels may benefit the user. Copyright © 2013 National Safety Council and Elsevier Ltd. All rights reserved.

  14. Reproducibility measurements of three methods for calculating in vivo MR-based knee kinematics.

    PubMed

    Lansdown, Drew A; Zaid, Musa; Pedoia, Valentina; Subburaj, Karupppasamy; Souza, Richard; Benjamin, C; Li, Xiaojuan

    2015-08-01

    To describe three quantification methods for magnetic resonance imaging (MRI)-based knee kinematic evaluation and to report on the reproducibility of these algorithms. T2 -weighted, fast-spin echo images were obtained of the bilateral knees in six healthy volunteers. Scans were repeated for each knee after repositioning to evaluate protocol reproducibility. Semiautomatic segmentation defined regions of interest for the tibia and femur. The posterior femoral condyles and diaphyseal axes were defined using the previously defined tibia and femur. All segmentation was performed twice to evaluate segmentation reliability. Anterior tibial translation (ATT) and internal tibial rotation (ITR) were calculated using three methods: a tibial-based registration system, a combined tibiofemoral-based registration method with all manual segmentation, and a combined tibiofemoral-based registration method with automatic definition of condyles and axes. Intraclass correlation coefficients and standard deviations across multiple measures were determined. Reproducibility of segmentation was excellent (ATT = 0.98; ITR = 0.99) for both combined methods. ATT and ITR measurements were also reproducible across multiple scans in the combined registration measurements with manual (ATT = 0.94; ITR = 0.94) or automatic (ATT = 0.95; ITR = 0.94) condyles and axes. The combined tibiofemoral registration with automatic definition of the posterior femoral condyle and diaphyseal axes allows for improved knee kinematics quantification with excellent in vivo reproducibility. © 2014 Wiley Periodicals, Inc.

  15. Research Reproducibility in Geosciences: Current Landscape, Practices and Perspectives

    NASA Astrophysics Data System (ADS)

    Yan, An

    2016-04-01

    Reproducibility of research can gauge the validity of its findings. Yet currently we lack understanding of how much of a problem research reproducibility is in geosciences. We developed an online survey on faculty and graduate students in geosciences, and received 136 responses from research institutions and universities in Americas, Asia, Europe and other parts of the world. This survey examined (1) the current state of research reproducibility in geosciences by asking researchers' experiences with unsuccessful replication work, and what obstacles that lead to their replication failures; (2) the current reproducibility practices in community by asking what efforts researchers made to try to reproduce other's work and make their own work reproducible, and what the underlying factors that contribute to irreproducibility are; (3) the perspectives on reproducibility by collecting researcher's thoughts and opinions on this issue. The survey result indicated that nearly 80% of respondents who had ever reproduced a published study had failed at least one time in reproducing. Only one third of the respondents received helpful feedbacks when they contacted the authors of a published study for data, code, or other information. The primary factors that lead to unsuccessful replication attempts are insufficient details of instructions in published literature, and inaccessibility of data, code and tools needed in the study. Our findings suggest a remarkable lack of research reproducibility in geoscience. Changing the incentive mechanism in academia, as well as developing policies and tools that facilitate open data and code sharing are the promising ways for geosciences community to alleviate this reproducibility problem.

  16. Expanding probe repertoire and improving reproducibility in human genomic hybridization

    PubMed Central

    Dorman, Stephanie N.; Shirley, Ben C.; Knoll, Joan H. M.; Rogan, Peter K.

    2013-01-01

    Diagnostic DNA hybridization relies on probes composed of single copy (sc) genomic sequences. Sc sequences in probe design ensure high specificity and avoid cross-hybridization to other regions of the genome, which could lead to ambiguous results that are difficult to interpret. We examine how the distribution and composition of repetitive sequences in the genome affects sc probe performance. A divide and conquer algorithm was implemented to design sc probes. With this approach, sc probes can include divergent repetitive elements, which hybridize to unique genomic targets under higher stringency experimental conditions. Genome-wide custom probe sets were created for fluorescent in situ hybridization (FISH) and microarray genomic hybridization. The scFISH probes were developed for detection of copy number changes within small tumour suppressor genes and oncogenes. The microarrays demonstrated increased reproducibility by eliminating cross-hybridization to repetitive sequences adjacent to probe targets. The genome-wide microarrays exhibited lower median coefficients of variation (17.8%) for two HapMap family trios. The coefficients of variations of commercial probes within 300 nt of a repetitive element were 48.3% higher than the nearest custom probe. Furthermore, the custom microarray called a chromosome 15q11.2q13 deletion more consistently. This method for sc probe design increases probe coverage for FISH and lowers variability in genomic microarrays. PMID:23376933

  17. Calorie labeling and consumer estimation of calories purchased

    PubMed Central

    2014-01-01

    Background Studies rarely find fewer calories purchased following calorie labeling implementation. However, few studies consider whether estimates of the number of calories purchased improved following calorie labeling legislation. Findings Researchers surveyed customers and collected purchase receipts at fast food restaurants in the United States cities of Philadelphia (which implemented calorie labeling policies) and Baltimore (a matched comparison city) in December 2009 (pre-implementation) and June 2010 (post-implementation). A difference-in-difference design was used to examine the difference between estimated and actual calories purchased, and the odds of underestimating calories. Participants in both cities, both pre- and post-calorie labeling, tended to underestimate calories purchased, by an average 216–409 calories. Adjusted difference-in-differences in estimated-actual calories were significant for individuals who ordered small meals and those with some college education (accuracy in Philadelphia improved by 78 and 231 calories, respectively, relative to Baltimore, p = 0.03-0.04). However, categorical accuracy was similar; the adjusted odds ratio [AOR] for underestimation by >100 calories was 0.90 (p = 0.48) in difference-in-difference models. Accuracy was most improved for subjects with a BA or higher education (AOR = 0.25, p < 0.001) and for individuals ordering small meals (AOR = 0.54, p = 0.001). Accuracy worsened for females (AOR = 1.38, p < 0.001) and for individuals ordering large meals (AOR = 1.27, p = 0.028). Conclusions We concluded that the odds of underestimating calories varied by subgroup, suggesting that at some level, consumers may incorporate labeling information. PMID:25015547

  18. Precautionary labelling of foods for allergen content: are we ready for a global framework?

    PubMed

    Allen, Katrina J; Turner, Paul J; Pawankar, Ruby; Taylor, Stephen; Sicherer, Scott; Lack, Gideon; Rosario, Nelson; Ebisawa, Motohiro; Wong, Gary; Mills, E N Clare; Beyer, Kirsten; Fiocchi, Alessandro; Sampson, Hugh A

    2014-01-01

    Food allergy appears to be on the rise with the current mainstay of treatment centred on allergen avoidance. Mandatory allergen labelling has improved the safety of food for allergic consumers. However an additional form of voluntary labelling (termed precautionary allergen labelling) has evolved on a wide range of packaged goods, in a bid by manufacturers to minimise risk to customers, and the negative impact on business that might result from exposure to trace amounts of food allergen present during cross-contamination during production. This has resulted in near ubiquitous utilisation of a multitude of different precautionary allergen labels with subsequent confusion amongst many consumers as to their significance. The global nature of food production and manufacturing makes harmonisation of allergen labelling regulations across the world a matter of increasing importance. Addressing inconsistencies across countries with regards to labelling legislation, as well as improvement or even banning of precautionary allergy labelling are both likely to be significant steps forward in improved food safety for allergic families. This article outlines the current status of allergen labelling legislation around the world and reviews the value of current existing precautionary allergen labelling for the allergic consumer. We strongly urge for an international framework to be considered to help roadmap a solution to the weaknesses of the current systems, and discuss the role of legislation in facilitating this.

  19. Precautionary labelling of foods for allergen content: are we ready for a global framework?

    PubMed Central

    2014-01-01

    Food allergy appears to be on the rise with the current mainstay of treatment centred on allergen avoidance. Mandatory allergen labelling has improved the safety of food for allergic consumers. However an additional form of voluntary labelling (termed precautionary allergen labelling) has evolved on a wide range of packaged goods, in a bid by manufacturers to minimise risk to customers, and the negative impact on business that might result from exposure to trace amounts of food allergen present during cross-contamination during production. This has resulted in near ubiquitous utilisation of a multitude of different precautionary allergen labels with subsequent confusion amongst many consumers as to their significance. The global nature of food production and manufacturing makes harmonisation of allergen labelling regulations across the world a matter of increasing importance. Addressing inconsistencies across countries with regards to labelling legislation, as well as improvement or even banning of precautionary allergy labelling are both likely to be significant steps forward in improved food safety for allergic families. This article outlines the current status of allergen labelling legislation around the world and reviews the value of current existing precautionary allergen labelling for the allergic consumer. We strongly urge for an international framework to be considered to help roadmap a solution to the weaknesses of the current systems, and discuss the role of legislation in facilitating this. PMID:24791183

  20. Increasing magnetite contents of polymeric magnetic particles dramatically improves labeling of neural stem cell transplant populations.

    PubMed

    Adams, Christopher F; Rai, Ahmad; Sneddon, Gregor; Yiu, Humphrey H P; Polyak, Boris; Chari, Divya M

    2015-01-01

    Safe and efficient delivery of therapeutic cells to sites of injury/disease in the central nervous system is a key goal for the translation of clinical cell transplantation therapies. Recently, 'magnetic cell localization strategies' have emerged as a promising and safe approach for targeted delivery of magnetic particle (MP) labeled stem cells to pathology sites. For neuroregenerative applications, this approach is limited by the lack of available neurocompatible MPs, and low cell labeling achieved in neural stem/precursor populations. We demonstrate that high magnetite content, self-sedimenting polymeric MPs [unfunctionalized poly(lactic acid) coated, without a transfecting component] achieve efficient labeling (≥90%) of primary neural stem cells (NSCs)-a 'hard-to-label' transplant population of major clinical relevance. Our protocols showed high safety with respect to key stem cell regenerative parameters. Critically, labeled cells were effectively localized in an in vitro flow system by magnetic force highlighting the translational potential of the methods used. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Improving Arterial Spin Labeling by Using Deep Learning.

    PubMed

    Kim, Ki Hwan; Choi, Seung Hong; Park, Sung-Hong

    2018-05-01

    Purpose To develop a deep learning algorithm that generates arterial spin labeling (ASL) perfusion images with higher accuracy and robustness by using a smaller number of subtraction images. Materials and Methods For ASL image generation from pair-wise subtraction, we used a convolutional neural network (CNN) as a deep learning algorithm. The ground truth perfusion images were generated by averaging six or seven pairwise subtraction images acquired with (a) conventional pseudocontinuous arterial spin labeling from seven healthy subjects or (b) Hadamard-encoded pseudocontinuous ASL from 114 patients with various diseases. CNNs were trained to generate perfusion images from a smaller number (two or three) of subtraction images and evaluated by means of cross-validation. CNNs from the patient data sets were also tested on 26 separate stroke data sets. CNNs were compared with the conventional averaging method in terms of mean square error and radiologic score by using a paired t test and/or Wilcoxon signed-rank test. Results Mean square errors were approximately 40% lower than those of the conventional averaging method for the cross-validation with the healthy subjects and patients and the separate test with the patients who had experienced a stroke (P < .001). Region-of-interest analysis in stroke regions showed that cerebral blood flow maps from CNN (mean ± standard deviation, 19.7 mL per 100 g/min ± 9.7) had smaller mean square errors than those determined with the conventional averaging method (43.2 ± 29.8) (P < .001). Radiologic scoring demonstrated that CNNs suppressed noise and motion and/or segmentation artifacts better than the conventional averaging method did (P < .001). Conclusion CNNs provided superior perfusion image quality and more accurate perfusion measurement compared with those of the conventional averaging method for generation of ASL images from pair-wise subtraction images. © RSNA, 2017.

  2. The reproducibility issue and preclinical academic drug discovery: educational and institutional initiatives fostering translation success.

    PubMed

    Janero, David R

    2016-09-01

    Drug discovery depends critically upon published results from the academy. The reproducibility of preclinical research findings reported by academia in the peer-reviewed literature has been called into question, seriously jeopardizing the value of academic science for inventing therapeutics. The corrosive effects of the reproducibility issue on drug discovery are considered. Purported correctives imposed upon academia from the outside deal mainly with expunging fraudulent literature and imposing punitive sanctions on the responsible authors. The salutary influence of such post facto actions on the reproducibility of discovery-relevant preclinical research data from academia appears limited. Rather, intentional doctoral-scientist education focused on data replicability and translationally-meaningful science and active participation of university entities charged with research innovation and asset commercialization toward ensuring data quality are advocated as key academic initiatives for addressing the reproducibility issue. A mindset shift on the part of both senior university faculty and the academy to take responsibility for the data reproducibility crisis and commit proactively to positive educational, incentivization, and risk- and reward-sharing practices will be fundamental for improving the value of published preclinical academic research to drug discovery.

  3. Rotigotine Objectively Improves Sleep in Parkinson's Disease: An Open-Label Pilot Study with Actigraphic Recording.

    PubMed

    Calandra-Buonaura, Giovanna; Guaraldi, Pietro; Doria, Andrea; Zanigni, Stefano; Nassetti, Stefania; Favoni, Valentina; Cevoli, Sabina; Provini, Federica; Cortelli, Pietro

    2016-01-01

    Sleep disturbances represent important predictors of poor quality of life (QoL) in Parkinson's disease (PD). This open-label pilot study aimed to objectively assess, by means of actigraphic recording, effect of rotigotine on sleep in PD patients with self-reported sleep complaints. 15 PD patients underwent one-week actigraphic recording before (T0) and during (T1) rotigotine treatment, which was titrated to the dose subjectively improving motor symptoms (4-8 mg/24 h). Sleep disturbances, daytime sleepiness, cognitive performance, QoL, and depression were also evaluated with questionnaires. Actigraphic recordings showed a significant reduction in nocturnal motor activity and mean duration of wake episodes after sleep onset during rotigotine treatment compared to baseline. In 10 patients presenting objective evidence of poor sleep quality at T0 (sleep efficiency ≤ 85%), rotigotine also significantly improved other sleep parameters and further reduced nocturnal motor activity and mean duration of wake episodes. A significant decrease in number and duration of daytime sleep episodes was also observed at T1. Finally we confirmed that rotigotine significantly improves perceived sleep quality and QoL. Our study showed for the first time that rotigotine is associated with an objective improvement of nocturnal and diurnal sleep disturbances in PD patients with self-reported sleep complaints. This study is registered with AIFA-observational study registry number 12021.

  4. Improved tracking and resolution of bacteria in holographic microscopy using dye and fluorescent protein labeling

    NASA Astrophysics Data System (ADS)

    Nadeau, Jay; Cho, YongBin; Kühn, Jonas; Liewer, Kurt

    2016-04-01

    Digital holographic microscopy (DHM) is an emerging imaging technique that permits instantaneous capture of a relatively large sample volume. However, large volumes usually come at the expense of lower spatial resolution, and the technique has rarely been used with prokaryotic cells due to their small size and low contrast. In this paper we demonstrate the use of a Mach-Zehnder dual-beam instrument for imaging of labeled and unlabeled bacteria and microalgae. Spatial resolution of 0.3 micrometers is achieved, providing a sampling of several pixels across a typical prokaryotic cell. Both cellular motility and morphology are readily recorded. The use of dyes provides both amplitude and phase contrast improvement and is of use to identify cells in dense samples.

  5. Standard terminology and labeling of ocular tissue for transplantation.

    PubMed

    Armitage, W John; Ashford, Paul; Crow, Barbara; Dahl, Patricia; DeMatteo, Jennifer; Distler, Pat; Gopinathan, Usha; Madden, Peter W; Mannis, Mark J; Moffatt, S Louise; Ponzin, Diego; Tan, Donald

    2013-06-01

    To develop an internationally agreed terminology for describing ocular tissue grafts to improve the accuracy and reliability of information transfer, to enhance tissue traceability, and to facilitate the gathering of comparative global activity data, including denominator data for use in biovigilance analyses. ICCBBA, the international standards organization for terminology, coding, and labeling of blood, cells, and tissues, approached the major Eye Bank Associations to form an expert advisory group. The group met by regular conference calls to develop a standard terminology, which was released for public consultation and amended accordingly. The terminology uses broad definitions (Classes) with modifying characteristics (Attributes) to define each ocular tissue product. The terminology may be used within the ISBT 128 system to label tissue products with standardized bar codes enabling the electronic capture of critical data in the collection, processing, and distribution of tissues. Guidance on coding and labeling has also been developed. The development of a standard terminology for ocular tissue marks an important step for improving traceability and reducing the risk of mistakes due to transcription errors. ISBT 128 computer codes have been assigned and may now be used to label ocular tissues. Eye banks are encouraged to adopt this standard terminology and move toward full implementation of ISBT 128 nomenclature, coding, and labeling.

  6. Multi-Label Learning via Random Label Selection for Protein Subcellular Multi-Locations Prediction.

    PubMed

    Wang, Xiao; Li, Guo-Zheng

    2013-03-12

    Prediction of protein subcellular localization is an important but challenging problem, particularly when proteins may simultaneously exist at, or move between, two or more different subcellular location sites. Most of the existing protein subcellular localization methods are only used to deal with the single-location proteins. In the past few years, only a few methods have been proposed to tackle proteins with multiple locations. However, they only adopt a simple strategy, that is, transforming the multi-location proteins to multiple proteins with single location, which doesn't take correlations among different subcellular locations into account. In this paper, a novel method named RALS (multi-label learning via RAndom Label Selection), is proposed to learn from multi-location proteins in an effective and efficient way. Through five-fold cross validation test on a benchmark dataset, we demonstrate our proposed method with consideration of label correlations obviously outperforms the baseline BR method without consideration of label correlations, indicating correlations among different subcellular locations really exist and contribute to improvement of prediction performance. Experimental results on two benchmark datasets also show that our proposed methods achieve significantly higher performance than some other state-of-the-art methods in predicting subcellular multi-locations of proteins. The prediction web server is available at http://levis.tongji.edu.cn:8080/bioinfo/MLPred-Euk/ for the public usage.

  7. The flux qubit revisited to enhance coherence and reproducibility

    PubMed Central

    Yan, Fei; Gustavsson, Simon; Kamal, Archana; Birenbaum, Jeffrey; Sears, Adam P; Hover, David; Gudmundsen, Ted J.; Rosenberg, Danna; Samach, Gabriel; Weber, S; Yoder, Jonilyn L.; Orlando, Terry P.; Clarke, John; Kerman, Andrew J.; Oliver, William D.

    2016-01-01

    The scalable application of quantum information science will stand on reproducible and controllable high-coherence quantum bits (qubits). Here, we revisit the design and fabrication of the superconducting flux qubit, achieving a planar device with broad-frequency tunability, strong anharmonicity, high reproducibility and relaxation times in excess of 40 μs at its flux-insensitive point. Qubit relaxation times T1 across 22 qubits are consistently matched with a single model involving resonator loss, ohmic charge noise and 1/f-flux noise, a noise source previously considered primarily in the context of dephasing. We furthermore demonstrate that qubit dephasing at the flux-insensitive point is dominated by residual thermal-photons in the readout resonator. The resulting photon shot noise is mitigated using a dynamical decoupling protocol, resulting in T2≈85 μs, approximately the 2T1 limit. In addition to realizing an improved flux qubit, our results uniquely identify photon shot noise as limiting T2 in contemporary qubits based on transverse qubit–resonator interaction. PMID:27808092

  8. Three Dimensions of Reproducibility in Natural Language Processing.

    PubMed

    Cohen, K Bretonnel; Xia, Jingbo; Zweigenbaum, Pierre; Callahan, Tiffany J; Hargraves, Orin; Goss, Foster; Ide, Nancy; Névéol, Aurélie; Grouin, Cyril; Hunter, Lawrence E

    2018-05-01

    Despite considerable recent attention to problems with reproducibility of scientific research, there is a striking lack of agreement about the definition of the term. That is a problem, because the lack of a consensus definition makes it difficult to compare studies of reproducibility, and thus to have even a broad overview of the state of the issue in natural language processing. This paper proposes an ontology of reproducibility in that field. Its goal is to enhance both future research and communication about the topic, and retrospective meta-analyses. We show that three dimensions of reproducibility, corresponding to three kinds of claims in natural language processing papers, can account for a variety of types of research reports. These dimensions are reproducibility of a conclusion , of a finding , and of a value. Three biomedical natural language processing papers by the authors of this paper are analyzed with respect to these dimensions.

  9. A diagram retrieval method with multi-label learning

    NASA Astrophysics Data System (ADS)

    Fu, Songping; Lu, Xiaoqing; Liu, Lu; Qu, Jingwei; Tang, Zhi

    2015-01-01

    In recent years, the retrieval of plane geometry figures (PGFs) has attracted increasing attention in the fields of mathematics education and computer science. However, the high cost of matching complex PGF features leads to the low efficiency of most retrieval systems. This paper proposes an indirect classification method based on multi-label learning, which improves retrieval efficiency by reducing the scope of compare operation from the whole database to small candidate groups. Label correlations among PGFs are taken into account for the multi-label classification task. The primitive feature selection for multi-label learning and the feature description of visual geometric elements are conducted individually to match similar PGFs. The experiment results show the competitive performance of the proposed method compared with existing PGF retrieval methods in terms of both time consumption and retrieval quality.

  10. Tritium labeling of organic compounds deposited on porous structures

    DOEpatents

    Ehrenkaufer, Richard L. E.; Wolf, Alfred P.; Hembree, Wylie C.

    1979-01-01

    An improved process for labeling organic compounds with tritium is carried out by depositing the selected compound on the extensive surface of a porous structure such as a membrane filter and exposing the membrane containing the compound to tritium gas activated by the microwave discharge technique. The labeled compound is then recovered from the porous structure.

  11. ALE: automated label extraction from GEO metadata.

    PubMed

    Giles, Cory B; Brown, Chase A; Ripperger, Michael; Dennis, Zane; Roopnarinesingh, Xiavan; Porter, Hunter; Perz, Aleksandra; Wren, Jonathan D

    2017-12-28

    NCBI's Gene Expression Omnibus (GEO) is a rich community resource containing millions of gene expression experiments from human, mouse, rat, and other model organisms. However, information about each experiment (metadata) is in the format of an open-ended, non-standardized textual description provided by the depositor. Thus, classification of experiments for meta-analysis by factors such as gender, age of the sample donor, and tissue of origin is not feasible without assigning labels to the experiments. Automated approaches are preferable for this, primarily because of the size and volume of the data to be processed, but also because it ensures standardization and consistency. While some of these labels can be extracted directly from the textual metadata, many of the data available do not contain explicit text informing the researcher about the age and gender of the subjects with the study. To bridge this gap, machine-learning methods can be trained to use the gene expression patterns associated with the text-derived labels to refine label-prediction confidence. Our analysis shows only 26% of metadata text contains information about gender and 21% about age. In order to ameliorate the lack of available labels for these data sets, we first extract labels from the textual metadata for each GEO RNA dataset and evaluate the performance against a gold standard of manually curated labels. We then use machine-learning methods to predict labels, based upon gene expression of the samples and compare this to the text-based method. Here we present an automated method to extract labels for age, gender, and tissue from textual metadata and GEO data using both a heuristic approach as well as machine learning. We show the two methods together improve accuracy of label assignment to GEO samples.

  12. Rotary head type reproducing apparatus

    DOEpatents

    Takayama, Nobutoshi; Edakubo, Hiroo; Kozuki, Susumu; Takei, Masahiro; Nagasawa, Kenichi

    1986-01-01

    In an apparatus of the kind arranged to reproduce, with a plurality of rotary heads, an information signal from a record bearing medium having many recording tracks which are parallel to each other with the information signal recorded therein and with a plurality of different pilot signals of different frequencies also recorded one by one, one in each of the recording tracks, a plurality of different reference signals of different frequencies are simultaneously generated. A tracking error is detected by using the different reference signals together with the pilot signals which are included in signals reproduced from the plurality of rotary heads.

  13. Rapid Verification of Candidate Serological Biomarkers Using Gel-based, Label-free Multiple Reaction Monitoring

    PubMed Central

    Tang, Hsin-Yao; Beer, Lynn A.; Barnhart, Kurt T.; Speicher, David W.

    2011-01-01

    Stable isotope dilution-multiple reaction monitoring-mass spectrometry (SID-MRM-MS) has emerged as a promising platform for verification of serological candidate biomarkers. However, cost and time needed to synthesize and evaluate stable isotope peptides, optimize spike-in assays, and generate standard curves, quickly becomes unattractive when testing many candidate biomarkers. In this study, we demonstrate that label-free multiplexed MRM-MS coupled with major protein depletion and 1-D gel separation is a time-efficient, cost-effective initial biomarker verification strategy requiring less than 100 μl serum. Furthermore, SDS gel fractionation can resolve different molecular weight forms of targeted proteins with potential diagnostic value. Because fractionation is at the protein level, consistency of peptide quantitation profiles across fractions permits rapid detection of quantitation problems for specific peptides from a given protein. Despite the lack of internal standards, the entire workflow can be highly reproducible, and long-term reproducibility of relative protein abundance can be obtained using different mass spectrometers and LC methods with external reference standards. Quantitation down to ~200 pg/mL could be achieved using this workflow. Hence, the label-free GeLC-MRM workflow enables rapid, sensitive, and economical initial screening of large numbers of candidate biomarkers prior to setting up SID-MRM assays or immunoassays for the most promising candidate biomarkers. PMID:21726088

  14. Rapid verification of candidate serological biomarkers using gel-based, label-free multiple reaction monitoring.

    PubMed

    Tang, Hsin-Yao; Beer, Lynn A; Barnhart, Kurt T; Speicher, David W

    2011-09-02

    Stable isotope dilution-multiple reaction monitoring-mass spectrometry (SID-MRM-MS) has emerged as a promising platform for verification of serological candidate biomarkers. However, cost and time needed to synthesize and evaluate stable isotope peptides, optimize spike-in assays, and generate standard curves quickly becomes unattractive when testing many candidate biomarkers. In this study, we demonstrate that label-free multiplexed MRM-MS coupled with major protein depletion and 1D gel separation is a time-efficient, cost-effective initial biomarker verification strategy requiring less than 100 μL of serum. Furthermore, SDS gel fractionation can resolve different molecular weight forms of targeted proteins with potential diagnostic value. Because fractionation is at the protein level, consistency of peptide quantitation profiles across fractions permits rapid detection of quantitation problems for specific peptides from a given protein. Despite the lack of internal standards, the entire workflow can be highly reproducible, and long-term reproducibility of relative protein abundance can be obtained using different mass spectrometers and LC methods with external reference standards. Quantitation down to ~200 pg/mL could be achieved using this workflow. Hence, the label-free GeLC-MRM workflow enables rapid, sensitive, and economical initial screening of large numbers of candidate biomarkers prior to setting up SID-MRM assays or immunoassays for the most promising candidate biomarkers.

  15. Genotypic variability enhances the reproducibility of an ecological study.

    PubMed

    Milcu, Alexandru; Puga-Freitas, Ruben; Ellison, Aaron M; Blouin, Manuel; Scheu, Stefan; Freschet, Grégoire T; Rose, Laura; Barot, Sebastien; Cesarz, Simone; Eisenhauer, Nico; Girin, Thomas; Assandri, Davide; Bonkowski, Michael; Buchmann, Nina; Butenschoen, Olaf; Devidal, Sebastien; Gleixner, Gerd; Gessler, Arthur; Gigon, Agnès; Greiner, Anna; Grignani, Carlo; Hansart, Amandine; Kayler, Zachary; Lange, Markus; Lata, Jean-Christophe; Le Galliard, Jean-François; Lukac, Martin; Mannerheim, Neringa; Müller, Marina E H; Pando, Anne; Rotter, Paula; Scherer-Lorenzen, Michael; Seyhun, Rahme; Urban-Mead, Katherine; Weigelt, Alexandra; Zavattaro, Laura; Roy, Jacques

    2018-02-01

    Many scientific disciplines are currently experiencing a 'reproducibility crisis' because numerous scientific findings cannot be repeated consistently. A novel but controversial hypothesis postulates that stringent levels of environmental and biotic standardization in experimental studies reduce reproducibility by amplifying the impacts of laboratory-specific environmental factors not accounted for in study designs. A corollary to this hypothesis is that a deliberate introduction of controlled systematic variability (CSV) in experimental designs may lead to increased reproducibility. To test this hypothesis, we had 14 European laboratories run a simple microcosm experiment using grass (Brachypodium distachyon L.) monocultures and grass and legume (Medicago truncatula Gaertn.) mixtures. Each laboratory introduced environmental and genotypic CSV within and among replicated microcosms established in either growth chambers (with stringent control of environmental conditions) or glasshouses (with more variable environmental conditions). The introduction of genotypic CSV led to 18% lower among-laboratory variability in growth chambers, indicating increased reproducibility, but had no significant effect in glasshouses where reproducibility was generally lower. Environmental CSV had little effect on reproducibility. Although there are multiple causes for the 'reproducibility crisis', deliberately including genetic variability may be a simple solution for increasing the reproducibility of ecological studies performed under stringently controlled environmental conditions.

  16. Evaluation of TaqMan qPCR System Integrating Two Identically Labelled Hydrolysis Probes in Single Assay

    PubMed Central

    Nagy, Alexander; Vitásková, Eliška; Černíková, Lenka; Křivda, Vlastimil; Jiřincová, Helena; Sedlák, Kamil; Horníčková, Jitka; Havlíčková, Martina

    2017-01-01

    Ongoing evolution of viral pathogens is a significant issue in diagnostic virology employing TaqMan qPCR/RT-qPCR. Specific concerns are related to false negativity due to probe binding failure. One option for compensating for such deficiency is to integrate a second identically labelled probe in the assay. However, how this alteration influences the reaction parameters has not been comprehensively demonstrated. In the present study, we evaluate a TaqMan protocol using two identically labelled hydrolysis probes (simple, LNA (locked-nucleic-acid)) and MGB (minor-groove-binder) modified probes and combinations thereof in a single assay. Our results based on a synthetic amplicon suggest that the second probe does not compromise the TaqMan qPCR/RT-qPCR parameters, which repeatedly and reproducibly remained comparable to those of the corresponding single-probe assays, irrespective of the relative probe orientation, whether opposite or tandem, and probe modifications or combinations thereof. On the other hand, the second probe additively contributed to the overall fluorescence signal. The utility of the dual-probe approach was demonstrated on practical examples by using field specimens. We hope that the present study might serve as a theoretical basis for the development or improvement of TaqMan qPCR/RT-qPCR assays for the detection of highly variable nucleic acid templates. PMID:28120891

  17. Gold Nanoparticle Labels Amplify Ellipsometric Signals

    NASA Technical Reports Server (NTRS)

    Venkatasubbarao, Srivatsa

    2008-01-01

    The ellipsometric method reported in the immediately preceding article was developed in conjunction with a method of using gold nanoparticles as labels on biomolecules that one seeks to detect. The purpose of the labeling is to exploit the optical properties of the gold nanoparticles in order to amplify the measurable ellipsometric effects and thereby to enable ultrasensitive detection of the labeled biomolecules without need to develop more-complex ellipsometric instrumentation. The colorimetric, polarization, light-scattering, and other optical properties of nanoparticles depend on their sizes and shapes. In the present method, these size-and-shape-dependent properties are used to magnify the polarization of scattered light and the diattenuation and retardance of signals derived from ellipsometry. The size-and-shape-dependent optical properties of the nanoparticles make it possible to interrogate the nanoparticles by use of light of various wavelengths, as appropriate, to optimally detect particles of a specific type at high sensitivity. Hence, by incorporating gold nanoparticles bound to biomolecules as primary or secondary labels, the performance of ellipsometry as a means of detecting the biomolecules can be improved. The use of gold nanoparticles as labels in ellipsometry has been found to afford sensitivity that equals or exceeds the sensitivity achieved by use of fluorescence-based methods. Potential applications for ellipsometric detection of gold nanoparticle-labeled biomolecules include monitoring molecules of interest in biological samples, in-vitro diagnostics, process monitoring, general environmental monitoring, and detection of biohazards.

  18. Reading the Small Print – Labelling Recommendations for Orthopaedic Implants

    PubMed Central

    Haene, Roger A; Sandhu, Ranbir S; Baxandall, Richard

    2009-01-01

    INTRODUCTION There exist, currently, no clear guidelines regarding standards for surgical implant labelling. Dimensions of the laminar flow canopies in orthopaedic use fixes the distance at which implant labels can be read. Mistakes when reading the label on an implant box can pose health risks for patients, and financial consequences for medical institutions. SUBJECTS AND METHODS Using scientifically validated tools such as the Snellen Chart Formula, a theoretical minimum standard for text on implant labels was reached. This theoretical standard was then tested under real operating conditions. After discovering a minimum practical standard for implant labels, the authors then audited current labels in use on a wide range of orthopaedic implant packages. Furthermore, other non-text-related labelling problems were also noted. RESULTS There is a definite minimum standard which should be observed when implant labels are manufactured. Implants in current use bear labels on the packaging that are of an insufficient standard to ensure patient safety in theatre. CONCLUSIONS The authors have established text parameters that will increase the legibility of implant labels. In the interests of improving risk management in theatre, therefore, the authors propose a standard for orthopaedic implant labelling, and believe this will provide a useful foundation for further discussion between the orthopaedic community and implant manufacturers. PMID:19686615

  19. Food Labels

    MedlinePlus

    ... Staying Safe Videos for Educators Search English Español Food Labels KidsHealth / For Teens / Food Labels What's in ... to have at least 95% organic ingredients. Making Food Labels Work for You The first step in ...

  20. Label Review Training: Module 1: Label Basics, Page 25

    EPA Pesticide Factsheets

    This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review: clarity, accuracy, consistency with EPA policy, and enforceability.

  1. Label Review Training: Module 1: Label Basics, Page 29

    EPA Pesticide Factsheets

    This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. This page is a quiz on Module 1.

  2. Reproducibility of the anti-Factor Xa and anti-Factor IIa assays applied to enoxaparin solution.

    PubMed

    Martinez, Céline; Savadogo, Adama; Agut, Christophe; Anger, Pascal

    2013-01-01

    Enoxaparin is a widely used subcutaneously administered antithrombotic agent comprising a complex mixture of glycosaminoglycan chains. Owing to this complexity, its antithrombotic potency cannot be defined by physicochemical methods and is therefore evaluated using an enzymatic assay of anti-Xa and anti-IIa activity. Maintaining consistent anti-Xa activity in the final medicinal product allows physicians to ensure administration of the appropriate dosage to their patients. Bioassays are usually complex and display poorer reproducibility than physicochemical tests such as HPLC assays. Here, we describe the implementation of a common robotic platform and standard release potency testing procedures for enoxaparin sodium injection (Lovenox, Sanofi, Paris, France) products at seven quality control sites within Sanofi. Qualification and analytical procedures, as well as data handling, were optimized and harmonized to improve assay reproducibility. An inter-laboratory study was performed in routine-release conditions. The coefficients of variation for repeatability and reproducibility in assessments of anti-Xa activity were 1.0% and 1.2%, respectively. The tolerance interval in reproducibility precision conditions, expressed as percentage potency, was 96.8-103.2% of the drug product target of 10,000 IU/ml, comparing favorably with the United States of America Pharmacopeia specification (90-110%). The maximum difference between assays in two different laboratories is expected to be 4.1%. The reproducibility characteristics of anti-IIa activity assessments were found to be similar. These results demonstrate the effectiveness of the standardization process established and allow for further improvements to quality control in Lovenox manufacture. This process guarantees closeness between actual and target potencies, as exemplified by the results of release assays obtained during a three-year period. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Assessing Cognitive Performance in Badminton Players: A Reproducibility and Validity Study

    PubMed Central

    van de Water, Tanja; Faber, Irene; Elferink-Gemser, Marije

    2017-01-01

    Abstract Fast reaction and good inhibitory control are associated with elite sports performance. To evaluate the reproducibility and validity of a newly developed Badminton Reaction Inhibition Test (BRIT), fifteen elite (25 ± 4 years) and nine non-elite (24 ± 4 years) Dutch male badminton players participated in the study. The BRIT measured four components: domain-general reaction time, badminton-specific reaction time, domain-general inhibitory control and badminton-specific inhibitory control. Five participants were retested within three weeks on the badminton-specific components. Reproducibility was acceptable for badminton-specific reaction time (ICC = 0.626, CV = 6%) and for badminton-specific inhibitory control (ICC = 0.317, CV = 13%). Good construct validity was shown for badminton-specific reaction time discriminating between elite and non-elite players (F = 6.650, p < 0.05). Elite players did not outscore non-elite players on domain-general reaction time nor on both components of inhibitory control (p > 0.05). Concurrent validity for domain-general reaction time was good, as it was associated with a national ranking for elite (p = 0.70, p < 0.01) and non-elite (p = 0.70, p < 0.05) players. No relationship was found between the national ranking and badminton-specific reaction time, nor both components of inhibitory control (p > 0.05). In conclusion, reproducibility and validity of inhibitory control assessment was not confirmed, however, the BRIT appears a reproducible and valid measure of reaction time in badminton players. Reaction time measured with the BRIT may provide input for training programs aiming to improve badminton players’ performance. PMID:28210347

  4. Assessing Cognitive Performance in Badminton Players: A Reproducibility and Validity Study.

    PubMed

    van de Water, Tanja; Huijgen, Barbara; Faber, Irene; Elferink-Gemser, Marije

    2017-01-01

    Fast reaction and good inhibitory control are associated with elite sports performance. To evaluate the reproducibility and validity of a newly developed Badminton Reaction Inhibition Test (BRIT), fifteen elite (25 ± 4 years) and nine non-elite (24 ± 4 years) Dutch male badminton players participated in the study. The BRIT measured four components: domain-general reaction time, badminton-specific reaction time, domain-general inhibitory control and badminton-specific inhibitory control. Five participants were retested within three weeks on the badminton-specific components. Reproducibility was acceptable for badminton-specific reaction time (ICC = 0.626, CV = 6%) and for badminton-specific inhibitory control (ICC = 0.317, CV = 13%). Good construct validity was shown for badminton-specific reaction time discriminating between elite and non-elite players (F = 6.650, p < 0.05). Elite players did not outscore non-elite players on domain-general reaction time nor on both components of inhibitory control (p > 0.05). Concurrent validity for domain-general reaction time was good, as it was associated with a national ranking for elite (p = 0.70, p < 0.01) and non-elite (p = 0.70, p < 0.05) players. No relationship was found between the national ranking and badminton-specific reaction time, nor both components of inhibitory control (p > 0.05). In conclusion, reproducibility and validity of inhibitory control assessment was not confirmed, however, the BRIT appears a reproducible and valid measure of reaction time in badminton players. Reaction time measured with the BRIT may provide input for training programs aiming to improve badminton players' performance.

  5. Appearance of acute gouty arthritis on indium-111-labeled leukocyte scintigraphy

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

    Palestro, C.J.; Vega, A.; Kim, C.K.

    1990-05-01

    Indium-111-labeled leukocyte scintigraphy was performed on a 66-yr-old male with polyarticular acute gouty arthritis. Images revealed intense labeled leukocyte accumulation in a pattern indistinguishable from septic arthritis, in both knees and ankles, and the metatarsophalangeal joint of both great toes, all of which were involved in the acute gouty attack. Joint aspirate as well as blood cultures were reported as no growth; the patient was treated with intravenous colchicine and ACTH for 10 days with dramatic improvement noted. Labeled leukocyte imaging, repeated 12 days after the initial study, revealed near total resolution of joint abnormalities, concordant with the patient's clinicalmore » improvement. This case demonstrates that while acute gouty arthritis is a potential pitfall in labeled leukocyte imaging, in the presence of known gout, it may provide a simple, objective, noninvasive method of evaluating patient response to therapy.« less

  6. Can we improve accuracy and reliability of MRI interpretation in children with optic pathway glioma? Proposal for a reproducible imaging classification.

    PubMed

    Lambron, Julien; Rakotonjanahary, Josué; Loisel, Didier; Frampas, Eric; De Carli, Emilie; Delion, Matthieu; Rialland, Xavier; Toulgoat, Frédérique

    2016-02-01

    Magnetic resonance (MR) images from children with optic pathway glioma (OPG) are complex. We initiated this study to evaluate the accuracy of MR imaging (MRI) interpretation and to propose a simple and reproducible imaging classification for MRI. We randomly selected 140 MRIs from among 510 MRIs performed on 104 children diagnosed with OPG in France from 1990 to 2004. These images were reviewed independently by three radiologists (F.T., 15 years of experience in neuroradiology; D.L., 25 years of experience in pediatric radiology; and J.L., 3 years of experience in radiology) using a classification derived from the Dodge and modified Dodge classifications. Intra- and interobserver reliabilities were assessed using the Bland-Altman method and the kappa coefficient. These reviews allowed the definition of reliable criteria for MRI interpretation. The reviews showed intraobserver variability and large discrepancies among the three radiologists (kappa coefficient varying from 0.11 to 1). These variabilities were too large for the interpretation to be considered reproducible over time or among observers. A consensual analysis, taking into account all observed variabilities, allowed the development of a definitive interpretation protocol. Using this revised protocol, we observed consistent intra- and interobserver results (kappa coefficient varying from 0.56 to 1). The mean interobserver difference for the solid portion of the tumor with contrast enhancement was 0.8 cm(3) (limits of agreement = -16 to 17). We propose simple and precise rules for improving the accuracy and reliability of MRI interpretation for children with OPG. Further studies will be necessary to investigate the possible prognostic value of this approach.

  7. Cyberinfrastructure to Support Collaborative and Reproducible Computational Hydrologic Modeling

    NASA Astrophysics Data System (ADS)

    Goodall, J. L.; Castronova, A. M.; Bandaragoda, C.; Morsy, M. M.; Sadler, J. M.; Essawy, B.; Tarboton, D. G.; Malik, T.; Nijssen, B.; Clark, M. P.; Liu, Y.; Wang, S. W.

    2017-12-01

    Creating cyberinfrastructure to support reproducibility of computational hydrologic models is an important research challenge. Addressing this challenge requires open and reusable code and data with machine and human readable metadata, organized in ways that allow others to replicate results and verify published findings. Specific digital objects that must be tracked for reproducible computational hydrologic modeling include (1) raw initial datasets, (2) data processing scripts used to clean and organize the data, (3) processed model inputs, (4) model results, and (5) the model code with an itemization of all software dependencies and computational requirements. HydroShare is a cyberinfrastructure under active development designed to help users store, share, and publish digital research products in order to improve reproducibility in computational hydrology, with an architecture supporting hydrologic-specific resource metadata. Researchers can upload data required for modeling, add hydrology-specific metadata to these resources, and use the data directly within HydroShare.org for collaborative modeling using tools like CyberGIS, Sciunit-CLI, and JupyterHub that have been integrated with HydroShare to run models using notebooks, Docker containers, and cloud resources. Current research aims to implement the Structure For Unifying Multiple Modeling Alternatives (SUMMA) hydrologic model within HydroShare to support hypothesis-driven hydrologic modeling while also taking advantage of the HydroShare cyberinfrastructure. The goal of this integration is to create the cyberinfrastructure that supports hypothesis-driven model experimentation, education, and training efforts by lowering barriers to entry, reducing the time spent on informatics technology and software development, and supporting collaborative research within and across research groups.

  8. Less label, more free: approaches in label-free quantitative mass spectrometry.

    PubMed

    Neilson, Karlie A; Ali, Naveid A; Muralidharan, Sridevi; Mirzaei, Mehdi; Mariani, Michael; Assadourian, Gariné; Lee, Albert; van Sluyter, Steven C; Haynes, Paul A

    2011-02-01

    In this review we examine techniques, software, and statistical analyses used in label-free quantitative proteomics studies for area under the curve and spectral counting approaches. Recent advances in the field are discussed in an order that reflects a logical workflow design. Examples of studies that follow this design are presented to highlight the requirement for statistical assessment and further experiments to validate results from label-free quantitation. Limitations of label-free approaches are considered, label-free approaches are compared with labelling techniques, and forward-looking applications for label-free quantitative data are presented. We conclude that label-free quantitative proteomics is a reliable, versatile, and cost-effective alternative to labelled quantitation. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. The effect of illustrations on patient comprehension of medication instruction labels.

    PubMed

    Hwang, Stephen W; Tram, Carolyn Q N; Knarr, Nadia

    2005-06-16

    Labels with special instructions regarding how a prescription medication should be taken or its possible side effects are often applied to pill bottles. The goal of this study was to determine whether the addition of illustrations to these labels affects patient comprehension. Study participants (N = 130) were enrolled by approaching patients at three family practice clinics in Toronto, Canada. Participants were asked to interpret two sets of medication instruction labels, the first with text only and the second with the same text accompanied by illustrations. Two investigators coded participants' responses as incorrect, partially correct, or completely correct. Health literacy levels of participants were measured using a validated instrument, the REALM test. All participants gave a completely correct interpretation for three out of five instruction labels, regardless of whether illustrations were present or not. For the two most complex labels, only 34-55% of interpretations of the text-only version were completely correct. The addition of illustrations was associated with improved performance in 5-7% of subjects and worsened performance in 7-9% of subjects. The commonly-used illustrations on the medication labels used in this study were of little or no use in improving patients' comprehension of the accompanying written instructions.

  10. The effect of illustrations on patient comprehension of medication instruction labels

    PubMed Central

    Hwang, Stephen W; Tram, Carolyn QN; Knarr, Nadia

    2005-01-01

    Background Labels with special instructions regarding how a prescription medication should be taken or its possible side effects are often applied to pill bottles. The goal of this study was to determine whether the addition of illustrations to these labels affects patient comprehension. Methods Study participants (N = 130) were enrolled by approaching patients at three family practice clinics in Toronto, Canada. Participants were asked to interpret two sets of medication instruction labels, the first with text only and the second with the same text accompanied by illustrations. Two investigators coded participants' responses as incorrect, partially correct, or completely correct. Health literacy levels of participants were measured using a validated instrument, the REALM test. Results All participants gave a completely correct interpretation for three out of five instruction labels, regardless of whether illustrations were present or not. For the two most complex labels, only 34–55% of interpretations of the text-only version were completely correct. The addition of illustrations was associated with improved performance in 5–7% of subjects and worsened performance in 7–9% of subjects. Conclusion The commonly-used illustrations on the medication labels used in this study were of little or no use in improving patients' comprehension of the accompanying written instructions. PMID:15960849

  11. Reproducibility and quantitation of amplicon sequencing-based detection

    PubMed Central

    Zhou, Jizhong; Wu, Liyou; Deng, Ye; Zhi, Xiaoyang; Jiang, Yi-Huei; Tu, Qichao; Xie, Jianping; Van Nostrand, Joy D; He, Zhili; Yang, Yunfeng

    2011-01-01

    To determine the reproducibility and quantitation of the amplicon sequencing-based detection approach for analyzing microbial community structure, a total of 24 microbial communities from a long-term global change experimental site were examined. Genomic DNA obtained from each community was used to amplify 16S rRNA genes with two or three barcode tags as technical replicates in the presence of a small quantity (0.1% wt/wt) of genomic DNA from Shewanella oneidensis MR-1 as the control. The technical reproducibility of the amplicon sequencing-based detection approach is quite low, with an average operational taxonomic unit (OTU) overlap of 17.2%±2.3% between two technical replicates, and 8.2%±2.3% among three technical replicates, which is most likely due to problems associated with random sampling processes. Such variations in technical replicates could have substantial effects on estimating β-diversity but less on α-diversity. A high variation was also observed in the control across different samples (for example, 66.7-fold for the forward primer), suggesting that the amplicon sequencing-based detection approach could not be quantitative. In addition, various strategies were examined to improve the comparability of amplicon sequencing data, such as increasing biological replicates, and removing singleton sequences and less-representative OTUs across biological replicates. Finally, as expected, various statistical analyses with preprocessed experimental data revealed clear differences in the composition and structure of microbial communities between warming and non-warming, or between clipping and non-clipping. Taken together, these results suggest that amplicon sequencing-based detection is useful in analyzing microbial community structure even though it is not reproducible and quantitative. However, great caution should be taken in experimental design and data interpretation when the amplicon sequencing-based detection approach is used for quantitative

  12. 10 CFR 1016.35 - Authority to reproduce Restricted Data.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Authority to reproduce Restricted Data. 1016.35 Section 1016.35 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) SAFEGUARDING OF RESTRICTED DATA Control of Information § 1016.35 Authority to reproduce Restricted Data. Secret Restricted Data will not be reproduced...

  13. 10 CFR 1016.35 - Authority to reproduce Restricted Data.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Authority to reproduce Restricted Data. 1016.35 Section 1016.35 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) SAFEGUARDING OF RESTRICTED DATA Control of Information § 1016.35 Authority to reproduce Restricted Data. Secret Restricted Data will not be reproduced...

  14. Tunable coating of gold nanostars: tailoring robust SERS labels for cell imaging

    NASA Astrophysics Data System (ADS)

    Bassi, B.; Taglietti, A.; Galinetto, P.; Marchesi, N.; Pascale, A.; Cabrini, E.; Pallavicini, P.; Dacarro, G.

    2016-07-01

    Surface modification of noble metal nanoparticles with mixed molecular monolayers is one of the most powerful tools in nanotechnology, and is used to impart and tune new complex surface properties. In imaging techniques based on surface enhanced Raman spectroscopy (SERS), precise and controllable surface modifications are needed to carefully design reproducible, robust and adjustable SERS nanoprobes. We report here the attainment of SERS labels based on gold nanostars (GNSs) coated with a mixed monolayer composed of a poly ethylene glycol (PEG) thiol (neutral or negatively charged) that ensure stability in biological environments, and of a signalling unit 7-Mercapto-4-methylcoumarin as a Raman reporter molecule. The composition of the coating mixture is precisely controlled using an original method, allowing the modulation of the SERS intensity and ensuring overall nanoprobe stability. The further addition of a positively charged layer of poly (allylamine hydrocloride) on the surface of negatively charged SERS labels does not change the SERS response, but it promotes the penetration of GNSs in SH-SY5Y neuroblastoma cells. As an example of an application of such an approach, we demonstrate here the internalization of these new labels by means of visualization of cell morphology obtained with SERS mapping.

  15. Nutrition-Labeling Regulation Impacts on Restaurant Environments

    PubMed Central

    Saelens, Brian E.; Chan, Nadine; Krieger, James; Nelson, Young; Boles, Myde; Colburn, Trina; Glanz, Karen; Ta, Myduc; Bruemmer, Barbara

    2012-01-01

    Background Recent attempts to improve the healthfulness of away-from-home eating include regulations requiring restaurants to post nutrition information. The impact of such regulations on restaurant environments is unknown. Purpose To examine changes in restaurant environments from before to after nutrition-labeling regulation in a newly regulated county versus a nonregulated county. Methods Using the Nutrition Environment Measures Surveys–Restaurant version audit, environments within the same quick-service chain restaurants were evaluated in King County (regulated) before and 6 and 18 months after regulation enforcement and in Multnomah County (nonregulated) restaurants over a 6-month period. Data were collected in 2008–2010 and analyses conducted in 2011. Results Overall availability of healthy options and facilitation of healthy eating did not differentially increase in King County versus Multnomah County restaurants aside from the substantial increase in onsite nutrition information posting in King County restaurants required by the new regulation. Barriers to healthful eating decreased in King County relative to Multnomah County restaurants, particularly in food-oriented establishments. King County restaurants demonstrated modest increases in signage that promotes healthy eating, although the frequency of such promotion remained low, and the availability of reduced portions decreased in these restaurants. The healthfulness of children’s menus improved modestly over time, but not differentially by county. Conclusions A restaurant nutrition-labeling regulation was accompanied by some, but not uniform, improvements in other aspects of restaurant environments in the regulated compared to the nonregulated county. Additional opportunities exist for improving the healthfulness of awayfrom- home eating beyond menu labeling. PMID:23079173

  16. Making Early Modern Medicine: Reproducing Swedish Bitters.

    PubMed

    Ahnfelt, Nils-Otto; Fors, Hjalmar

    2016-05-01

    Historians of science and medicine have rarely applied themselves to reproducing the experiments and practices of medicine and pharmacy. This paper delineates our efforts to reproduce "Swedish Bitters," an early modern composite medicine in wide European use from the 1730s to the present. In its original formulation, it was made from seven medicinal simples: aloe, rhubarb, saffron, myrrh, gentian, zedoary and agarikon. These were mixed in alcohol together with some theriac, a composite medicine of classical origin. The paper delineates the compositional history of Swedish Bitters and the medical rationale underlying its composition. It also describes how we go about to reproduce the medicine in a laboratory using early modern pharmaceutical methods, and analyse it using contemporary methods of pharmaceutical chemistry. Our aim is twofold: first, to show how reproducing medicines may provide a path towards a deeper understanding of the role of sensual and practical knowledge in the wider context of early modern medical culture; and second, how it may yield interesting results from the point of view of contemporary pharmaceutical science.

  17. The construction of a two-dimensional reproducing kernel function and its application in a biomedical model.

    PubMed

    Guo, Qi; Shen, Shu-Ting

    2016-04-29

    There are two major classes of cardiac tissue models: the ionic model and the FitzHugh-Nagumo model. During computer simulation, each model entails solving a system of complex ordinary differential equations and a partial differential equation with non-flux boundary conditions. The reproducing kernel method possesses significant applications in solving partial differential equations. The derivative of the reproducing kernel function is a wavelet function, which has local properties and sensitivities to singularity. Therefore, study on the application of reproducing kernel would be advantageous. Applying new mathematical theory to the numerical solution of the ventricular muscle model so as to improve its precision in comparison with other methods at present. A two-dimensional reproducing kernel function inspace is constructed and applied in computing the solution of two-dimensional cardiac tissue model by means of the difference method through time and the reproducing kernel method through space. Compared with other methods, this method holds several advantages such as high accuracy in computing solutions, insensitivity to different time steps and a slow propagation speed of error. It is suitable for disorderly scattered node systems without meshing, and can arbitrarily change the location and density of the solution on different time layers. The reproducing kernel method has higher solution accuracy and stability in the solutions of the two-dimensional cardiac tissue model.

  18. Mindtagger: A Demonstration of Data Labeling in Knowledge Base Construction.

    PubMed

    Shin, Jaeho; Ré, Christopher; Cafarella, Michael

    2015-08-01

    End-to-end knowledge base construction systems using statistical inference are enabling more people to automatically extract high-quality domain-specific information from unstructured data. As a result of deploying DeepDive framework across several domains, we found new challenges in debugging and improving such end-to-end systems to construct high-quality knowledge bases. DeepDive has an iterative development cycle in which users improve the data. To help our users, we needed to develop principles for analyzing the system's error as well as provide tooling for inspecting and labeling various data products of the system. We created guidelines for error analysis modeled after our colleagues' best practices, in which data labeling plays a critical role in every step of the analysis. To enable more productive and systematic data labeling, we created Mindtagger, a versatile tool that can be configured to support a wide range of tasks. In this demonstration, we show in detail what data labeling tasks are modeled in our error analysis guidelines and how each of them is performed using Mindtagger.

  19. Photoaffinity Labeling of Ras Converting Enzyme using Peptide Substrates that Incorporate Benzoylphenylalanine (Bpa) Residues: Improved Labeling and Structural Implications

    PubMed Central

    Kyro, Kelly; Manandhar, Surya P.; Mullen, Daniel; Schmidt, Walter K.; Distefano, Mark D.

    2012-01-01

    Rce1p catalyzes the proteolytic trimming of C-terminal tripeptides from isoprenylated proteins containing CAAX-box sequences. Because Rce1p processing is a necessary component in the Ras pathway of oncogenic signal transduction, Rce1p holds promise as a potential target for therapeutic intervention. However, its mechanism of proteolysis and active site have yet to be defined. Here, we describe synthetic peptide analogues that mimic the natural lipidated Rce1p substrate and incorporate photolabile groups for photoaffinity-labeling applications. These photoactive peptides are designed to crosslink to residues in or near the Rce1p active site. By incorporating the photoactive group via p-benzoyl-L-phenylalanine (Bpa) residues directly into the peptide substrate sequence, the labeling efficiency was substantially increased relative to a previously-synthesized compound. Incorporation of biotin on the N-terminus of the peptides permitted photolabeled Rce1p to be isolated via streptavidin affinity capture. Our findings further suggest that residues outside the CAAX-box sequence are in contact with Rce1p, which has implications for future inhibitor design. PMID:22079863

  20. Reproducibility of HTS-SQUID magnetocardiography in an unshielded clinical environment.

    PubMed

    Leder, U; Schrey, F; Haueisen, J; Dörrer, L; Schreiber, J; Liehr, M; Schwarz, G; Solbrig, O; Figulla, H R; Seidel, P

    2001-07-01

    A new technology has been developed which measures the magnetic field of the human heart (magnetocardiogram, MCG) by using high temperature superconducting (HTS) sensors. These sensors can be operated at the temperature of liquid nitrogen without electromagnetic shielding. We tested the reproducibility of HTS-MCG measurements in healthy volunteers. Unshielded HTS-MCG measurements were performed in 18 healthy volunteers in left precordial position in two separate sessions in a clinical environment. The heart cycles of 10 min were averaged, smoothed, the baselines were adjusted, and the data were standardized to the respective areas under the curves (AUC) of the absolute values of the QRST amplitudes. The QRS complexes and the ST-T intervals were used to assess the reproducibility of the two measurements. Ratios (R(QRS), R(STT)) were calculated by dividing the AUC of the first measurement by the ones of the second measurement. The linear correlation coefficients (CORR(QRS), CORR(STT)) of the time intervals of the two measurements were calculated, too. The HTS-MCG signal was completely concealed by the high noise level in the raw data. The averaging and smoothing algorithms unmasked the QRS complex and the ST segment. A high reproducibility was found for the QRS complex (R(QRS)=1.2+/-0.3, CORR(QRS)=0.96+/-0.06). Similarly to the shape of the ECG it was characterized by three bends, the Q, R, and S waves. In the ST-T interval, the reproducibility was considerably lower (R(STT)=0.9+/-0.2, CORR(STT)=0.66+/-0.28). In contrast to the shape of the ECG, a baseline deflection after the T wave which may belong to U wave activity was found in a number of volunteers. HTS-MCG devices can be operated in a clinical environment without shielding. Whereas the reproducibility was found to be high for the depolarization interval, it was considerably lower for the ST segment and for the T wave. Therefore, before clinically applying HTS-MCG systems to the detection of repolarization

  1. In Silico Labeling: Predicting Fluorescent Labels in Unlabeled Images.

    PubMed

    Christiansen, Eric M; Yang, Samuel J; Ando, D Michael; Javaherian, Ashkan; Skibinski, Gaia; Lipnick, Scott; Mount, Elliot; O'Neil, Alison; Shah, Kevan; Lee, Alicia K; Goyal, Piyush; Fedus, William; Poplin, Ryan; Esteva, Andre; Berndl, Marc; Rubin, Lee L; Nelson, Philip; Finkbeiner, Steven

    2018-04-19

    Microscopy is a central method in life sciences. Many popular methods, such as antibody labeling, are used to add physical fluorescent labels to specific cellular constituents. However, these approaches have significant drawbacks, including inconsistency; limitations in the number of simultaneous labels because of spectral overlap; and necessary perturbations of the experiment, such as fixing the cells, to generate the measurement. Here, we show that a computational machine-learning approach, which we call "in silico labeling" (ISL), reliably predicts some fluorescent labels from transmitted-light images of unlabeled fixed or live biological samples. ISL predicts a range of labels, such as those for nuclei, cell type (e.g., neural), and cell state (e.g., cell death). Because prediction happens in silico, the method is consistent, is not limited by spectral overlap, and does not disturb the experiment. ISL generates biological measurements that would otherwise be problematic or impossible to acquire. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. Food label use and its relation to dietary intake among US adults.

    PubMed

    Ollberding, Nicholas Jay; Wolf, Randi L; Contento, Isobel

    2010-08-01

    Rates of diet-related chronic disease combined with the lack of current data on patterns of food label use by the US population warrant re-examination of the use and potential influence of this public health tool. The purpose of this study was to describe the prevalence of food label use and the association between food label use and nutrient intake in a nationally representative sample of US adults who participated in the 2005-2006 National Health and Nutrition Examination Survey. Data on food label use were collected during the interview portion of the survey, and nutrient intake was estimated using the average of two 24-hour dietary recalls. In this sample, 61.6% of participants reported using the Nutrition Facts panel, 51.6% looked at the list of ingredients, 47.2% looked at serving size, and 43.8% reviewed health claims at least sometimes when deciding to purchase a food product. There were significant differences (P<0.05) in food label use across all demographic characteristics examined. Significant differences (P<0.05) in mean nutrient intake of total energy, total fat, saturated fat, cholesterol, sodium, dietary fiber, and sugars were observed between food label users and non-users with label users reporting healthier nutrient consumption. The greatest differences observed were for total energy and fat and for use of specific nutrient information on the food label. Despite food label use being associated with improved dietary factors, label use alone is not expected to be sufficient in modifying behavior ultimately leading to improved health outcomes. 2010 American Dietetic Association. Published by Elsevier Inc. All rights reserved.

  3. Effectiveness of offering healthy labelled meals in improving the nutritional quality of lunch meals eaten in a worksite canteen.

    PubMed

    Lassen, A D; Beck, A; Leedo, E; Andersen, E W; Christensen, T; Mejborn, H; Thorsen, A V; Tetens, I

    2014-04-01

    Healthier meal selections at restaurants and canteens are often limited and not actively promoted. In this Danish study the effectiveness of a healthy labelling certification program in improving dietary intake and influencing edible plate waste was evaluated in a quasi-experimental study design. Employees from an intervention worksite canteen and a matched control canteen were included in the study at baseline (February 2012), after completing the certification process (end-point) and six month from end-point (follow-up) (total n=270). In order to estimate nutrient composition of the consumed lunch meals and plate waste a validated digital photographic method was used combining estimation of food intake with food nutrient composition data. Food satisfaction was rated by participants using a questionnaire. Several significant positive nutritional effects were observed at the intervention canteen including a mean decrease in energy density in the consumed meals from 561kJ/100g at baseline to 368 and 407kJ/100g at end-point and follow-up, respectively (P<0.001). No significant changes were seen with regard to food satisfaction and plate waste. In the control canteen no positive nutritional effects were observed. The results of the study highlight the potential of using healthy labelling certification programs as a possible driver for increasing both the availability and awareness of healthy meal choices, thereby improving dietary intake when eating out. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Long-term reproducibility of phantom signal intensities in nonuniformity corrected STIR-MRI examinations of skeletal muscle.

    PubMed

    Viddeleer, Alain R; Sijens, Paul E; van Ooijen, Peter M A; Kuypers, Paul D L; Hovius, Steven E R; Oudkerk, Matthijs

    2009-08-01

    Nerve regeneration could be monitored by comparing MRI image intensities in time, as denervated muscles display increased signal intensity in STIR sequences. In this study long-term reproducibility of STIR image intensity was assessed under clinical conditions and the required image intensity nonuniformity correction was improved by using phantom scans obtained at multiple positions. Three-dimensional image intensity nonuniformity was investigated in phantom scans. Next, over a three-year period, 190 clinical STIR hand scans were obtained using a standardized acquisition protocol, and corrected for intensity nonuniformity by using the results of phantom scanning. The results of correction with 1, 3, and 11 phantom scans were compared. The image intensities in calibration tubes close to the hands were measured every time to determine the reproducibility of our method. With calibration, the reproducibility of STIR image intensity improved from 7.8 to 6.4%. Image intensity nonuniformity correction with 11 phantom scans gave significantly better results than correction with 1 or 3 scans. The image intensities in clinical STIR images acquired at different times can be compared directly, provided that the acquisition protocol is standardized and that nonuniformity correction is applied. Nonuniformity correction is preferably based on multiple phantom scans.

  5. Legislation--Impact and Trends in Nutrition Labeling: A Global Overview.

    PubMed

    Kasapila, William; Shaarani, Sharifudin Md

    2016-01-01

    The need for accurate nutrition labeling on food products has never been greater. Obesity has assumed near-epidemic levels in both industrialized and emerging nations in recent years, and governments and consumer groups around the world are looking for ways to improve the nutritional choices for their citizenry while simultaneously balancing their freedom of choice through the use of nutrition labeling. Despite increasingly aggressive efforts by government and industry organizations to raise consumer awareness, though, many consumers either do not consult nutrition labels or they are not in a position to interpret the information on these labels accurately. To gain some fresh insights into nutrition labeling practices worldwide, this paper provides a review of the relevant peer-reviewed, scholarly, and government literature to describe regulations enacted to date, evolving and future trends, and the likely impact of food product labels. In this regard, the paper highlights similarities and discrepancies that exist, identifies gaps, and gives directions for the future.

  6. A Novel Method for Relative Quantitation of N-Glycans by Isotopic Labeling Using 18O-Water

    PubMed Central

    Tao, Shujuan; Orlando, Ron

    2014-01-01

    Quantitation is an essential aspect of comprehensive glycomics study. Here, a novel isotopic-labeling method is described for N-glycan quantitation using 18O-water. The incorporation of the 18O-labeling into the reducing end of N-glycans is simply and efficiently achieved during peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase F release. This process provides a 2-Da mass difference compared with the N-glycans released in 16O-water. A mathematical calculation method was also developed to determine the 18O/16O ratios from isotopic peaks. Application of this method to several standard glycoprotein mixtures and human serum demonstrated that this method can facilitate the relative quantitation of N-glycans over a linear dynamic range of two orders, with high accuracy and reproducibility. PMID:25365792

  7. Do nutrition labels influence healthier food choices? Analysis of label viewing behaviour and subsequent food purchases in a labelling intervention trial.

    PubMed

    Ni Mhurchu, Cliona; Eyles, Helen; Jiang, Yannan; Blakely, Tony

    2018-02-01

    There are few objective data on how nutrition labels are used in real-world shopping situations, or how they affect dietary choices and patterns. The Starlight study was a four-week randomised, controlled trial of the effects of three different types of nutrition labels on consumer food purchases: Traffic Light Labels, Health Star Rating labels, or Nutrition Information Panels (control). Smartphone technology allowed participants to scan barcodes of packaged foods and receive randomly allocated labels on their phone screen, and to record their food purchases. The study app therefore provided objectively recorded data on label viewing behaviour and food purchases over a four-week period. A post-hoc analysis of trial data was undertaken to assess frequency of label use, label use by food group, and association between label use and the healthiness of packaged food products purchased. Over the four-week intervention, study participants (n = 1255) viewed nutrition labels for and/or purchased 66,915 barcoded packaged products. Labels were viewed for 23% of all purchased products, with decreasing frequency over time. Shoppers were most likely to view labels for convenience foods, cereals, snack foods, bread and bakery products, and oils. They were least likely to view labels for sugar and honey products, eggs, fish, fruit and vegetables, and meat. Products for which participants viewed the label and subsequently purchased the product during the same shopping episode were significantly healthier than products where labels were viewed but the product was not subsequently purchased: mean difference in nutrient profile score -0.90 (95% CI -1.54 to -0.26). In a secondary analysis of a nutrition labelling intervention trial, there was a significant association between label use and the healthiness of products purchased. Nutrition label use may therefore lead to healthier food purchases. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. Participant Nonnaiveté and the reproducibility of cognitive psychology.

    PubMed

    Zwaan, Rolf A; Pecher, Diane; Paolacci, Gabriele; Bouwmeester, Samantha; Verkoeijen, Peter; Dijkstra, Katinka; Zeelenberg, René

    2017-07-25

    Many argue that there is a reproducibility crisis in psychology. We investigated nine well-known effects from the cognitive psychology literature-three each from the domains of perception/action, memory, and language, respectively-and found that they are highly reproducible. Not only can they be reproduced in online environments, but they also can be reproduced with nonnaïve participants with no reduction of effect size. Apparently, some cognitive tasks are so constraining that they encapsulate behavior from external influences, such as testing situation and prior recent experience with the experiment to yield highly robust effects.

  9. Improvements in Irritability with Open-Label Methylphenidate Treatment in Youth with Comorbid Attention Deficit/Hyperactivity Disorder and Disruptive Mood Dysregulation Disorder.

    PubMed

    Winters, Drew E; Fukui, Sadaaki; Leibenluft, Ellen; Hulvershorn, Leslie A

    2018-06-01

    The purpose of this open-label study was to examine the effects of long-acting methylphenidate (MPH) treatment on irritability and related emotional symptoms associated with disruptive mood dysregulation disorder (DMDD) in youth with comorbid attention-deficit/hyperactivity disorder (ADHD). The sample included 22 medication-free male and female subjects (ages 9-15) who met criteria for both DMDD and ADHD. Participants underwent a 4-week trial of long-acting MPH treatment (Concerta ® ), with weekly dosing increases until a therapeutic dose was reached. Repeated measures t-tests were used to compare pre- and posttreatment ratings of primary and secondary measures. The primary outcome was self-report irritability. Secondary outcomes included parent and child ratings of emotional frequency, emotional lability, and negative affect (NA). Multiple regression was used to examine the impact baseline hyperactivity, age, gender, race, socioeconomic status, or comorbid diagnosis had on treatment outcomes. Significant improvements (medium to large effect sizes) in child-rated irritability as well as parent and child ratings of emotional lability, NA, and anger were found. As anticipated, ADHD symptoms also improved. While a majority of the sample saw improvement in child-rated irritability (71%), symptoms worsened a small proportion (19%), and an even smaller portion experienced no change (10%). No demographics, psychiatric comorbidities, or severity of ADHD symptoms influenced treatment outcomes. Study findings suggest that MPH treatment significantly improved mood and emotional symptoms associated with DMDD comorbid with ADHD. These findings, coupled with good tolerability in this open-label pilot study supports further research into the use of MPH as a first-line treatment for DMDD. Future work examining MPH treatment of youth with DMDD with and without comorbid ADHD is needed.

  10. Statistical label fusion with hierarchical performance models

    PubMed Central

    Asman, Andrew J.; Dagley, Alexander S.; Landman, Bennett A.

    2014-01-01

    Label fusion is a critical step in many image segmentation frameworks (e.g., multi-atlas segmentation) as it provides a mechanism for generalizing a collection of labeled examples into a single estimate of the underlying segmentation. In the multi-label case, typical label fusion algorithms treat all labels equally – fully neglecting the known, yet complex, anatomical relationships exhibited in the data. To address this problem, we propose a generalized statistical fusion framework using hierarchical models of rater performance. Building on the seminal work in statistical fusion, we reformulate the traditional rater performance model from a multi-tiered hierarchical perspective. This new approach provides a natural framework for leveraging known anatomical relationships and accurately modeling the types of errors that raters (or atlases) make within a hierarchically consistent formulation. Herein, we describe several contributions. First, we derive a theoretical advancement to the statistical fusion framework that enables the simultaneous estimation of multiple (hierarchical) performance models within the statistical fusion context. Second, we demonstrate that the proposed hierarchical formulation is highly amenable to the state-of-the-art advancements that have been made to the statistical fusion framework. Lastly, in an empirical whole-brain segmentation task we demonstrate substantial qualitative and significant quantitative improvement in overall segmentation accuracy. PMID:24817809

  11. Response to Comment on "Estimating the reproducibility of psychological science".

    PubMed

    Anderson, Christopher J; Bahník, Štěpán; Barnett-Cowan, Michael; Bosco, Frank A; Chandler, Jesse; Chartier, Christopher R; Cheung, Felix; Christopherson, Cody D; Cordes, Andreas; Cremata, Edward J; Della Penna, Nicolas; Estel, Vivien; Fedor, Anna; Fitneva, Stanka A; Frank, Michael C; Grange, James A; Hartshorne, Joshua K; Hasselman, Fred; Henninger, Felix; van der Hulst, Marije; Jonas, Kai J; Lai, Calvin K; Levitan, Carmel A; Miller, Jeremy K; Moore, Katherine S; Meixner, Johannes M; Munafò, Marcus R; Neijenhuijs, Koen I; Nilsonne, Gustav; Nosek, Brian A; Plessow, Franziska; Prenoveau, Jason M; Ricker, Ashley A; Schmidt, Kathleen; Spies, Jeffrey R; Stieger, Stefan; Strohminger, Nina; Sullivan, Gavin B; van Aert, Robbie C M; van Assen, Marcel A L M; Vanpaemel, Wolf; Vianello, Michelangelo; Voracek, Martin; Zuni, Kellylynn

    2016-03-04

    Gilbert et al. conclude that evidence from the Open Science Collaboration's Reproducibility Project: Psychology indicates high reproducibility, given the study methodology. Their very optimistic assessment is limited by statistical misconceptions and by causal inferences from selectively interpreted, correlational data. Using the Reproducibility Project: Psychology data, both optimistic and pessimistic conclusions about reproducibility are possible, and neither are yet warranted. Copyright © 2016, American Association for the Advancement of Science.

  12. OpenMS - A platform for reproducible analysis of mass spectrometry data.

    PubMed

    Pfeuffer, Julianus; Sachsenberg, Timo; Alka, Oliver; Walzer, Mathias; Fillbrunn, Alexander; Nilse, Lars; Schilling, Oliver; Reinert, Knut; Kohlbacher, Oliver

    2017-11-10

    In recent years, several mass spectrometry-based omics technologies emerged to investigate qualitative and quantitative changes within thousands of biologically active components such as proteins, lipids and metabolites. The research enabled through these methods potentially contributes to the diagnosis and pathophysiology of human diseases as well as to the clarification of structures and interactions between biomolecules. Simultaneously, technological advances in the field of mass spectrometry leading to an ever increasing amount of data, demand high standards in efficiency, accuracy and reproducibility of potential analysis software. This article presents the current state and ongoing developments in OpenMS, a versatile open-source framework aimed at enabling reproducible analyses of high-throughput mass spectrometry data. It provides implementations of frequently occurring processing operations on MS data through a clean application programming interface in C++ and Python. A collection of 185 tools and ready-made workflows for typical MS-based experiments enable convenient analyses for non-developers and facilitate reproducible research without losing flexibility. OpenMS will continue to increase its ease of use for developers as well as users with improved continuous integration/deployment strategies, regular trainings with updated training materials and multiple sources of support. The active developer community ensures the incorporation of new features to support state of the art research. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  13. Diagnostic labels of NANDA-I in a southern region of Spain

    PubMed Central

    González-Rodríguez, Rafael; Martelo-Baro, María de los Ángeles; Bas-Sarmiento, Pilar

    2017-01-01

    ABSTRACT Objective: to determine the incidence of NANDA-I diagnostic labels (North American Nursing Diagnosis Association-International) and to establish the distribution of cases of assistance and the associated labels, according to sociodemographic variables (age and sex). Method: descriptive, cross-sectional epidemiological study of labels of NANDA-I, under ecological design. The distribution of labels was analyzed according to sex and age; the corresponding frequencies were calculated and for each label the incidence were calculated rates with aggregate data from the attended cases. Results: the total number of cases of care under study was 9,928 (41.65% men and 58.35% women). The identified labels were 16,456 (7,084 men and 9,372 women); average of 1.7 labels per case of care; Out of 216 labels proposed by NANDA-I, in its 2012-14 classification, 152 were used, representing 70.4%. The labels with the highest incidence rates per thousand inhabitants were: Anxiety, Willingness to Improve Knowledge and Risk of Infection. Conclusions: the study allowed detecting, through NANDA-I, the answers to the health problems of greater incidence in the users attended. PMID:28614433

  14. Improvements in metabolic flux analysis using carbon bond labeling experiments: bondomer balancing and Boolean function mapping.

    PubMed

    Sriram, Ganesh; Shanks, Jacqueline V

    2004-04-01

    The biosynthetically directed fractional (13)C labeling method for metabolic flux evaluation relies on performing a 2-D [(13)C, (1)H] NMR experiment on extracts from organisms cultured on a uniformly labeled carbon substrate. This article focuses on improvements in the interpretation of data obtained from such an experiment by employing the concept of bondomers. Bondomers take into account the natural abundance of (13)C; therefore many bondomers in a real network are zero, and can be precluded a priori--thus resulting in fewer balances. Using this method, we obtained a set of linear equations which can be solved to obtain analytical formulas for NMR-measurable quantities in terms of fluxes in glycolysis and the pentose phosphate pathways. For a specific case of this network with four degrees of freedom, a priori identifiability of the fluxes was shown possible for any set of fluxes. For a more general case with five degrees of freedom, the fluxes were shown identifiable for a representative set of fluxes. Minimal sets of measurements which best identify the fluxes are listed. Furthermore, we have delineated Boolean function mapping, a new method to iteratively simulate bondomer abundances or efficiently convert carbon skeleton rearrangement information to mapping matrices. The efficiency of this method is expected to be valuable while analyzing metabolic networks which are not completely known (such as in plant metabolism) or while implementing iterative bondomer balancing methods.

  15. Pushing the limits for amplifying BrdU-labeled DNA encoding 16S rRNA: DNA polymerase as the determining factor.

    PubMed

    Roux-Michollet, Dad D; Schimel, Joshua P; Holden, Patricia A

    2010-12-01

    Identifying microorganisms that are active under specific conditions in ecosystems is a challenge in microbial ecology. Recently, the bromodeoxyuridine (BrdU) technique was developed to label actively growing cells. BrdU, a thymidine analog, is incorporated into newly synthesized DNA, and the BrdU-labeled DNA is then isolated from total extractable DNA by immunocapture using a BrdU-specific antibody. Analyzing the BrdU-labeled DNA allows for assessing the actively growing community, which can then be compared to the unlabeled DNA that represents the total community. However, applying the BrdU approach to study soils has been problematic due to low DNA amounts and soil contaminants. To address these challenges, we developed a protocol, optimizing specificity and reproducibility, to amplify BrdU-labeled gene fragments encoding 16S rRNA. We found that the determining factor was the DNA polymerase: among the 13 different polymerases we tested, only 3 provided adequate yields with minimal contamination, and only two of those three produced similar amplification patterns of community DNA. Copyright © 2010 Elsevier B.V. All rights reserved.

  16. Nutrition-labeling regulation impacts on restaurant environments.

    PubMed

    Saelens, Brian E; Chan, Nadine L; Krieger, James; Nelson, Young; Boles, Myde; Colburn, Trina A; Glanz, Karen; Ta, Myduc L; Bruemmer, Barbara

    2012-11-01

    Recent attempts to improve the healthfulness of away-from-home eating include regulations requiring restaurants to post nutrition information. The impact of such regulations on restaurant environments is unknown. To examine changes in restaurant environments from before to after nutrition-labeling regulation in a newly regulated county versus a nonregulated county. Using the Nutrition Environment Measures Survey-Restaurant version audit, environments within the same quick-service chain restaurants were evaluated in King County (regulated) before and 6 and 18 months after regulation enforcement and in Multnomah County (nonregulated) restaurants over a 6-month period. Data were collected in 2008-2010 and analyses conducted in 2011. Overall availability of healthy options and facilitation of healthy eating did not increase differentially in King County versus Multnomah County restaurants aside from the substantial increase in onsite nutrition information posting in King County restaurants required by the new regulation. Barriers to healthful eating decreased in King County relative to Multnomah County restaurants, particularly in food-oriented establishments. King County restaurants demonstrated modest increases in signage that promotes healthy eating, although the frequency of such promotion remained low, and the availability of reduced portions decreased in these restaurants. The healthfulness of children's menus improved modestly over time, but not differentially by county. A restaurant nutrition-labeling regulation was accompanied by some, but not uniform, improvements in other aspects of restaurant environments in the regulated compared to the nonregulated county. Additional opportunities exist for improving the healthfulness of away-from-home eating beyond menu labeling. Copyright © 2012 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  17. Fab fragment labeled with ICG-derivative for detecting digestive tract cancer.

    PubMed

    Yano, Hiromi; Muguruma, Naoki; Ito, Susumu; Aoyagi, Eriko; Kimura, Tetsuo; Imoto, Yoshitaka; Cao, Jianxin; Inoue, Shohei; Sano, Shigeki; Nagao, Yoshimitsu; Kido, Hiroshi

    2006-09-01

    In previous studies, we generated infrared ray fluorescence-labeled monoclonal antibodies and developed an infrared ray fluorescence endoscope capable of detecting the monoclonal antibodies to establish a novel diagnostic technique for gastrointestinal cancer. Although the whole IgG molecule has commonly been used for preparation of labeled antibodies, labeled IgG displays insufficient sensitivity and specificity, probably resulting from non-specific binding of the Fc fragment to target cells or interference between fluorochromes on the identical labeled antibody, which might be caused by molecular structure. In this in vitro study, we characterized an Fc-free fluorescence-labeled Fab fragment, which was expected to yield more specific binding to target cells than the whole IgG molecule. An anti-mucin antibody and ICG-ATT, an ICG derivative, were used as the labeled antibody and labeling compound, respectively. Paraffin sections of excised gastric cancer tissues were subjected to staining. The labeled whole IgG molecule (ICG-ATT-labeled IgG) and the labeled Fab fragment (ICG-ATT-labeled Fab) were prepared according to a previous report, and the fluorescence properties, antibody activities, and features of fluorescence microscope images obtained from paraffin sections were compared. Both ICG-ATT-labeled Fab and ICG-ATT-labeled IgG were excited by a near infrared ray of 766nm, and maximum emission occurred at 804nm. Antibody activities of ICG-ATT-labeled Fab were shown to be similar to those of unlabeled anti-MUC1 antibody. The fluorescence intensity obtained from paraffin sections of excised gastric cancer tissues revealed a tendency to be greater with ICG-ATT-labeled Fab than with ICG-ATT-labeled IgG. The infrared ray fluorescence-labeled Fab fragment was likely to be more specific than the conventionally labeled antibodies. Fragmentation of antibodies is considered to contribute to improved sensitivity and specificity of labeled antibodies for detection of micro

  18. Dynamic map labeling.

    PubMed

    Been, Ken; Daiches, Eli; Yap, Chee

    2006-01-01

    We address the problem of filtering, selecting and placing labels on a dynamic map, which is characterized by continuous zooming and panning capabilities. This consists of two interrelated issues. The first is to avoid label popping and other artifacts that cause confusion and interrupt navigation, and the second is to label at interactive speed. In most formulations the static map labeling problem is NP-hard, and a fast approximation might have O(nlogn) complexity. Even this is too slow during interaction, when the number of labels shown can be several orders of magnitude less than the number in the map. In this paper we introduce a set of desiderata for "consistent" dynamic map labeling, which has qualities desirable for navigation. We develop a new framework for dynamic labeling that achieves the desiderata and allows for fast interactive display by moving all of the selection and placement decisions into the preprocessing phase. This framework is general enough to accommodate a variety of selection and placement algorithms. It does not appear possible to achieve our desiderata using previous frameworks. Prior to this paper, there were no formal models of dynamic maps or of dynamic labels; our paper introduces both. We formulate a general optimization problem for dynamic map labeling and give a solution to a simple version of the problem. The simple version is based on label priorities and a versatile and intuitive class of dynamic label placements we call "invariant point placements". Despite these restrictions, our approach gives a useful and practical solution. Our implementation is incorporated into the G-Vis system which is a full-detail dynamic map of the continental USA. This demo is available through any browser.

  19. Perceptions of New Zealand nutrition labels by Māori, Pacific and low-income shoppers.

    PubMed

    Signal, Louise; Lanumata, Tolotea; Robinson, Jo-Ani; Tavila, Aliitasi; Wilton, Jenny; Ni Mhurchu, Cliona

    2008-07-01

    In New Zealand the burden of nutrition-related disease is greatest among Māori, Pacific and low-income peoples. Nutrition labels have the potential to promote healthy food choices and eating behaviours. To date, there has been a noticeable lack of research among indigenous peoples, ethnic minorities and low-income populations regarding their perceptions, use and understanding of nutrition labels. Our aim was to evaluate perceptions of New Zealand nutrition labels by Māori, Pacific and low-income peoples and to explore improvements or alternatives to current labelling systems. Māori, Samoan and Tongan researchers recruited participants who were regular food shoppers. Six focus groups were conducted which involved 158 people in total: one Māori group, one Samoan, one Tongan, and three low-income groups. Māori, Pacific and low-income New Zealanders rarely use nutrition labels to assist them with their food purchases for a number of reasons, including lack of time to read labels, lack of understanding, shopping habits and relative absence of simple nutrition labels on the low-cost foods they purchase. Current New Zealand nutrition labels are not meeting the needs of those who need them most. Possible improvements include targeted social marketing and education campaigns, increasing the number of low-cost foods with voluntary nutrition labels, a reduction in the price of 'healthy' food, and consideration of an alternative mandatory nutrition labelling system that uses simple imagery like traffic lights.

  20. Improved 18F Labeling of Peptides with a Fluoride-Aluminum-Chelate Complex

    PubMed Central

    McBride, William J.; D’Souza, Christopher A.; Sharkey, Robert M.; Karacay, Habibe; Rossi, Edmund A.; Chang, Chien-Hsing; Goldenberg, David M.

    2010-01-01

    We reported previously the feasibility to radiolabel peptides with fluorine-18 (18F) using a rapid, one-pot, method that first mixes 18F− with Al3+, and then binds the (Al18F)2+ complex to a NOTA ligand on the peptide. In this report, we examined several new NOTA ligands and determined how temperature, reaction time, and reagent concentration affected the radiolabeling yield. Four structural variations of the NOTA ligand had isolated radiolabeling yields ranging from 5.8% to 87% under similar reaction conditions. All of the Al18F NOTA complexes were stable in vitro in human serum and those that were tested in vivo also were stable. The radiolabeling reactions were performed at 100°C and the peptides could be labeled in as little as five minutes. The IMP467 peptide could be labeled up to 115 GBq/μmol (3100 Ci/mmol), with a total reaction and purification time of 30 min without chromatographic purification. PMID:20540570

  1. 13C metabolic flux analysis: optimal design of isotopic labeling experiments.

    PubMed

    Antoniewicz, Maciek R

    2013-12-01

    Measuring fluxes by 13C metabolic flux analysis (13C-MFA) has become a key activity in chemical and pharmaceutical biotechnology. Optimal design of isotopic labeling experiments is of central importance to 13C-MFA as it determines the precision with which fluxes can be estimated. Traditional methods for selecting isotopic tracers and labeling measurements did not fully utilize the power of 13C-MFA. Recently, new approaches were developed for optimal design of isotopic labeling experiments based on parallel labeling experiments and algorithms for rational selection of tracers. In addition, advanced isotopic labeling measurements were developed based on tandem mass spectrometry. Combined, these approaches can dramatically improve the quality of 13C-MFA results with important applications in metabolic engineering and biotechnology. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Looking at the label and beyond: the effects of calorie labels, health consciousness, and demographics on caloric intake in restaurants.

    PubMed

    Ellison, Brenna; Lusk, Jayson L; Davis, David

    2013-02-08

    Recent legislation has required calorie labels on restaurant menus as a means of improving Americans' health. Despite the growing research in this area, no consensus has been reached on the effectiveness of menu labels. This suggests the possibility of heterogeneity in responses to caloric labels across people with different attitudes and demographics. The purpose of this study was to explore the potential relationships between caloric intake and diners' socio-economic characteristics and attitudes in a restaurant field experiment that systematically varied the caloric information printed on the menus. We conducted a field experiment in a full service restaurant where patrons were randomly assigned to one of three menu treatments which varied the amount of caloric information printed on the menus (none, numeric, or symbolic calorie label). At the conclusion of their meals, diners were asked to complete a brief survey regarding their socio-economic characteristics, attitudes, and meal selections. Using regression analysis, we estimated the number of entrée and extra calories ordered by diners as a function of demographic and attitudinal variables. Additionally, irrespective of the menu treatment to which a subject was assigned, our study identified which types of people are likely to be low-, medium-, and high-calorie diners. Results showed that calorie labels have the greatest impact on those who are least health conscious. Additionally, using a symbolic calorie label can further reduce the caloric intake of even the most health conscious patrons. Finally, calorie labels were more likely to influence the selection of the main entrée as opposed to supplemental items such as drinks and desserts. If numeric calorie labels are implemented (as currently proposed), they are most likely to influence consumers who are less health conscious - probably one of the key targets of this legislation. Unfortunately, numeric labels did little for those consumers who were already

  3. Looking at the label and beyond: the effects of calorie labels, health consciousness, and demographics on caloric intake in restaurants

    PubMed Central

    2013-01-01

    Background Recent legislation has required calorie labels on restaurant menus as a means of improving Americans’ health. Despite the growing research in this area, no consensus has been reached on the effectiveness of menu labels. This suggests the possibility of heterogeneity in responses to caloric labels across people with different attitudes and demographics. The purpose of this study was to explore the potential relationships between caloric intake and diners’ socio-economic characteristics and attitudes in a restaurant field experiment that systematically varied the caloric information printed on the menus. Methods We conducted a field experiment in a full service restaurant where patrons were randomly assigned to one of three menu treatments which varied the amount of caloric information printed on the menus (none, numeric, or symbolic calorie label). At the conclusion of their meals, diners were asked to complete a brief survey regarding their socio-economic characteristics, attitudes, and meal selections. Using regression analysis, we estimated the number of entrée and extra calories ordered by diners as a function of demographic and attitudinal variables. Additionally, irrespective of the menu treatment to which a subject was assigned, our study identified which types of people are likely to be low-, medium-, and high-calorie diners. Results Results showed that calorie labels have the greatest impact on those who are least health conscious. Additionally, using a symbolic calorie label can further reduce the caloric intake of even the most health conscious patrons. Finally, calorie labels were more likely to influence the selection of the main entrée as opposed to supplemental items such as drinks and desserts. Conclusions If numeric calorie labels are implemented (as currently proposed), they are most likely to influence consumers who are less health conscious – probably one of the key targets of this legislation. Unfortunately, numeric labels did

  4. Graphic warning labels in cigarette advertisements: recall and viewing patterns.

    PubMed

    Strasser, Andrew A; Tang, Kathy Z; Romer, Daniel; Jepson, Christopher; Cappella, Joseph N

    2012-07-01

    The Family Smoking Prevention and Control Act gave the U.S. Food and Drug Administration (FDA) legal authority to mandate graphic warning labels on cigarette advertising and packaging. The FDA requires that these graphic warning labels be embedded into cigarette advertising and packaging by September 2012. The aim of this study was to examine differences in recall and viewing patterns of text-only versus graphic cigarette warning labels and the association between viewing patterns and recall. Participants (current daily smokers; N=200) were randomized to view a cigarette advertisement with either text-only or graphic warning labels. Viewing patterns were measured using eye-tracking, and recall was later assessed. Sessions were conducted between November 2008 and November 2009. Data analysis was conducted between March 2011 and July 2011. There was a significant difference in percentage correct recall of the warning label between those in the text-only versus graphic warning label condition, 50% vs 83% (χ(2)=23.74, p=0.0001). Time to first viewing of the graphic warning label text and dwell time duration (i.e., time spent looking) on the graphic image were significantly associated with correct recall. Warning labels that drew attention more quickly and resulted in longer dwell times were associated with better recall. Graphic warning labels improve smokers' recall of warning and health risks; these labels do so by drawing and holding attention. Copyright © 2012 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  5. A novel methodology to reproduce previously recorded six-degree of freedom kinematics on the same diarthrodial joint.

    PubMed

    Moore, Susan M; Thomas, Maribeth; Woo, Savio L-Y; Gabriel, Mary T; Kilger, Robert; Debski, Richard E

    2006-01-01

    The objective of this study was to develop a novel method to more accurately reproduce previously recorded 6-DOF kinematics of the tibia with respect to the femur using robotic technology. Furthermore, the effect of performing only a single or multiple registrations and the effect of robot joint configuration were investigated. A single registration consisted of registering the tibia and femur with respect to the robot at full extension and reproducing all kinematics while multiple registrations consisted of registering the bones at each flexion angle and reproducing only the kinematics of the corresponding flexion angle. Kinematics of the knee in response to an anterior (134 N) and combined internal/external (+/-10 N m) and varus/valgus (+/-5 N m) loads were collected at 0 degrees , 15 degrees , 30 degrees , 60 degrees , and 90 degrees of flexion. A six axes, serial-articulated robotic manipulator (PUMA Model 762) was calibrated and the working volume was reduced to improve the robot's accuracy. The effect of the robot joint configuration was determined by performing single and multiple registrations for three selected configurations. For each robot joint configuration, the accuracy in position of the reproduced kinematics improved after multiple registrations (0.7+/-0.3, 1.2+/-0.5, and 0.9+/-0.2 mm, respectively) when compared to only a single registration (1.3+/-0.9, 2.0+/-1.0, and 1.5+/-0.7 mm, respectively) (p<0.05). The accuracy in position of each robot joint configuration was unique as significant differences were detected between each of the configurations. These data demonstrate that the number of registrations and the robot joint configuration both affect the accuracy of the reproduced kinematics. Therefore, when using robotic technology to reproduce previously recorded kinematics, it may be necessary to perform these analyses for each individual robotic system and for each diarthrodial joint, as different joints will require the robot to be placed in

  6. PRN 87-1: Label Improvement Program for Pesticides Applied through Irrigation Systems (Chemigation)

    EPA Pesticide Factsheets

    This Notice requires registrants of pesticide products registered under FIFRA and applied through irrigation systems to revise the labeling for such products to include additional use directions and other statements described in this Notice.

  7. Understanding Food Labels

    MedlinePlus

    ... Healthy eating for girls Understanding food labels Understanding food labels There is lots of info on food ... need to avoid because of food allergies. Other food label terms top In addition to the Nutrition ...

  8. An improved label propagation algorithm based on node importance and random walk for community detection

    NASA Astrophysics Data System (ADS)

    Ma, Tianren; Xia, Zhengyou

    2017-05-01

    Currently, with the rapid development of information technology, the electronic media for social communication is becoming more and more popular. Discovery of communities is a very effective way to understand the properties of complex networks. However, traditional community detection algorithms consider the structural characteristics of a social organization only, with more information about nodes and edges wasted. In the meanwhile, these algorithms do not consider each node on its merits. Label propagation algorithm (LPA) is a near linear time algorithm which aims to find the community in the network. It attracts many scholars owing to its high efficiency. In recent years, there are more improved algorithms that were put forward based on LPA. In this paper, an improved LPA based on random walk and node importance (NILPA) is proposed. Firstly, a list of node importance is obtained through calculation. The nodes in the network are sorted in descending order of importance. On the basis of random walk, a matrix is constructed to measure the similarity of nodes and it avoids the random choice in the LPA. Secondly, a new metric IAS (importance and similarity) is calculated by node importance and similarity matrix, which we can use to avoid the random selection in the original LPA and improve the algorithm stability. Finally, a test in real-world and synthetic networks is given. The result shows that this algorithm has better performance than existing methods in finding community structure.

  9. 78 FR 66826 - Prior Label Approval System: Generic Label Approval

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-07

    ... container of a misleading form or size.\\1\\ FSIS has interpreted these provisions as requiring that the...-evaluating-labeling . Labels submitted as an extraordinary circumstance are given the highest priority for... submissions to FSIS headquarters, thus increasing the availability of FSIS labeling staff. Upon publication of...

  10. Reproducibility in Computational Neuroscience Models and Simulations

    PubMed Central

    McDougal, Robert A.; Bulanova, Anna S.; Lytton, William W.

    2016-01-01

    Objective Like all scientific research, computational neuroscience research must be reproducible. Big data science, including simulation research, cannot depend exclusively on journal articles as the method to provide the sharing and transparency required for reproducibility. Methods Ensuring model reproducibility requires the use of multiple standard software practices and tools, including version control, strong commenting and documentation, and code modularity. Results Building on these standard practices, model sharing sites and tools have been developed that fit into several categories: 1. standardized neural simulators, 2. shared computational resources, 3. declarative model descriptors, ontologies and standardized annotations; 4. model sharing repositories and sharing standards. Conclusion A number of complementary innovations have been proposed to enhance sharing, transparency and reproducibility. The individual user can be encouraged to make use of version control, commenting, documentation and modularity in development of models. The community can help by requiring model sharing as a condition of publication and funding. Significance Model management will become increasingly important as multiscale models become larger, more detailed and correspondingly more difficult to manage by any single investigator or single laboratory. Additional big data management complexity will come as the models become more useful in interpreting experiments, thus increasing the need to ensure clear alignment between modeling data, both parameters and results, and experiment. PMID:27046845

  11. Intravenous Administration of Stable-Labeled N-Acetylcysteine Demonstrates an Indirect Mechanism for Boosting Glutathione and Improving Redox Status.

    PubMed

    Zhou, Jie; Coles, Lisa D; Kartha, Reena V; Nash, Nardina; Mishra, Usha; Lund, Troy C; Cloyd, James C

    2015-08-01

    There is an increasing interest in using N-acetylcysteine (NAC) as a treatment for neurodegenerative disorders to increase glutathione (GSH) levels and its redox status. The purpose of this study was to characterize the biosynthesis of NAC to GSH using a novel stable isotope-labeled technique, and investigate the pharmacodynamics of NAC in vivo. Female wild-type mice were given a single intravenous bolus dose of 150 mg kg(-1) stable-labeled NAC. Plasma, red blood cells (RBC), and brain tissues were collected at predesignated time points. Stable-labeled NAC and its metabolite GSH (both labeled and unlabeled forms) were quantified in blood and brain samples. Molar ratios of the reduced and oxidized forms of GSH (GSH divided by glutathione disulfide, redox ratio) were also determined. The elimination phase half-life of NAC was approximately 34 min. Both labeled and unlabeled GSH in RBC were found to increase; however, the area under the curve above baseline (AUCb0-280 ) of labeled GSH was only 1% of the unlabeled form. These data indicate that NAC is not a direct precursor of GSH. In addition, NAC has prolonged effects in brain even when the drug has been eliminated from systemic circulation. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  12. Improved Reproducibility for Perovskite Solar Cells with 1 cm2 Active Area by a Modified Two-Step Process.

    PubMed

    Shen, Heping; Wu, Yiliang; Peng, Jun; Duong, The; Fu, Xiao; Barugkin, Chog; White, Thomas P; Weber, Klaus; Catchpole, Kylie R

    2017-02-22

    With rapid progress in recent years, organohalide perovskite solar cells (PSC) are promising candidates for a new generation of highly efficient thin-film photovoltaic technologies, for which up-scaling is an essential step toward commercialization. In this work, we propose a modified two-step method to deposit the CH 3 NH 3 PbI 3 (MAPbI 3 ) perovskite film that improves the uniformity, photovoltaic performance, and repeatability of large-area perovskite solar cells. This method is based on the commonly used two-step method, with one additional process involving treating the perovskite film with concentrated methylammonium iodide (MAI) solution. This additional treatment is proved to be helpful for tailoring the residual PbI 2 level to an optimal range that is favorable for both optical absorption and inhibition of recombination. Scanning electron microscopy and photoluminescence image analysis further reveal that, compared to the standard two-step and one-step methods, this method is very robust for achieving uniform and pinhole-free large-area films. This is validated by the photovoltaic performance of the prototype devices with an active area of 1 cm 2 , where we achieved the champion efficiency of ∼14.5% and an average efficiency of ∼13.5%, with excellent reproducibility.

  13. Reproducibility and responsiveness of quality of life assessment and six minute walk test in elderly heart failure patients.

    PubMed

    O'Keeffe, S T; Lye, M; Donnellan, C; Carmichael, D N

    1998-10-01

    To examine the reproducibility and responsiveness to change of a six minute walk test and a quality of life measure in elderly patients with heart failure. Longitudinal within patient study. 60 patients with heart failure (mean age 82 years) attending a geriatric outpatient clinic, 45 of whom underwent a repeat assessment three to eight weeks later. Subjects underwent a standardised six minute walk test and completed the chronic heart failure questionnaire (CHQ), a heart failure specific quality of life questionnaire. Intraclass correlation coefficients (ICC) were calculated using a random effects one way analysis of variance as a measure of reproducibility. Guyatt's responsiveness coefficient and effect sizes were calculated as measures of responsiveness to change. 24 patients reported no major change in cardiac status, while seven had deteriorated and 14 had improved between the two clinic visits. Reproducibility was satisfactory (ICC > 0.75) for the six minute walk test, for the total CHQ score, and for the dyspnoea, fatigue, and emotion domains of the CHQ. Effect sizes for all measures were large (> 0.8), and responsiveness coefficients were very satisfactory (> 0.7). Effect sizes for detecting deterioration were greater than those for detecting improvement. Quality of life assessment and a six minute walk test are reproducible and responsive measures of cardiac status in frail, very elderly patients with heart failure.

  14. Abandoning a label doesn’t make it disappear: The perseverance of labeling effects

    PubMed Central

    Foroni, Francesco; Rothbart, Myron

    2012-01-01

    Labels exert strong influence on perception and judgment. The present experiment examines the possibility that such effects may persist even when labels are abandoned. Participants judged the similarity of pairs of silhouette drawings of female body types, ordered on a continuum from very thin to very heavy, under conditions where category labels were, and were not, superimposed on the ordered stimuli. Consistent with earlier research, labels had strong effects on perceived similarity, with silhouettes sharing the same label judged as more similar than those having different labels. Moreover, when the labels were removed and no longer present, the effect of the labels, although diminished, persisted. It did not make any difference whether the labels were simply abandoned or, in addition, had their validity challenged. The results are important for our understanding of categorization and labeling processes. The potential theoretical and practical implications of these results for social processes are discussed. PMID:23105148

  15. Improving transparency and reproducibility through registration: The status of intervention trials published in clinical psychology journals.

    PubMed

    Cybulski, Lukasz; Mayo-Wilson, Evan; Grant, Sean

    2016-09-01

    Prospective registration increases the validity of randomized controlled trials (RCTs). In the United States, registration is a legal requirement for drugs and devices regulated by the Food and Drug Administration (FDA), and many biomedical journals refuse to publish trials that are not registered. Trials in clinical psychology have not been subject to these requirements; it is unknown to what extent they are registered. We searched the 25 highest-impact clinical psychology journals that published at least 1 RCT of a health-related psychological intervention in 2013. For included trials, we evaluated their registration status (prospective, retrospective, not registered) and the completeness of their outcome definitions. We identified 163 articles that reported 165 RCTs; 73 (44%) RCTs were registered, of which only 25 (15%) were registered prospectively. Of registered RCTs, only 42 (58%) indicated their registration status in the publication. Only 2 (1% of all trials) were registered prospectively and defined their primary outcomes completely. For the primary outcome(s), 72 (99%) of all registrations defined the domain, 67 (92%) the time frame, and 48 (66%) the specific measurements. Only 19 (26%) and 5 (7%) defined the specific metric and method of aggregation, respectively, for all primary outcomes. Very few reports of RCTs published in clinical psychology journals were registered prospectively and completely. Clinical psychology journals could improve transparency and reproducibility, as well as reduce bias, by requiring complete prospective trial registration for publication and by including trial registration numbers in all reports of RCTs. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  16. The Effect of Labeling on Preschool Children's Performance in the Dimensional Change Card Sort Task

    ERIC Educational Resources Information Center

    Muller, Ulrich; Zelazo, Philip D.; Lurye, Leah E.; Liebermann, Dana P.

    2008-01-01

    Previous research suggests that experimenter-induced labeling of test cards improves preschoolers' performance on the Dimensional Change Card Sort Task (DCCS), a measure of flexible rule use. Three experiments attempted to further clarify how labeling aids performance on the DCCS. Experiment 1 examined the nature of the labeling effect but failed…

  17. GigaDB: promoting data dissemination and reproducibility

    PubMed Central

    Sneddon, Tam P.; Si Zhe, Xiao; Edmunds, Scott C.; Li, Peter; Goodman, Laurie; Hunter, Christopher I.

    2014-01-01

    Often papers are published where the underlying data supporting the research are not made available because of the limitations of making such large data sets publicly and permanently accessible. Even if the raw data are deposited in public archives, the essential analysis intermediaries, scripts or software are frequently not made available, meaning the science is not reproducible. The GigaScience journal is attempting to address this issue with the associated data storage and dissemination portal, the GigaScience database (GigaDB). Here we present the current version of GigaDB and reveal plans for the next generation of improvements. However, most importantly, we are soliciting responses from you, the users, to ensure that future developments are focused on the data storage and dissemination issues that still need resolving. Database URL: http://www.gigadb.org PMID:24622612

  18. Development of a facile and sensitive HPLC-FLD method via fluorescence labeling for triterpenic acid bioavailability investigation.

    PubMed

    You, Jinmao; Wu, Di; Zhao, Mei; Li, Guoliang; Gong, Peiwei; Wu, Yueyue; Guo, Yu; Chen, Guang; Zhao, Xianen; Sun, Zhiwei; Xia, Lian; Wu, Yongning

    2017-06-01

    Triterpenic acids are widely distributed in many fruits and are known for their medicinal benefits. The study of bioavailability has been an important task for a better understanding of the triterpenic acids. Although many methods based on fluorescence labeling for triterpenic acid determination have been established, these reported methods needed anhydrous conditions, which are not suitable for the convenient study of triterpenic acid bioavailability. Inspired by that, a versatile method, which overcomes the difficulty of the reported methods, has been first developed in this study. The novel method using 2-[12-benzo[b]acridin-5- (12H)-yl]-acetohydrazide (BAAH) as the fluorescence labeling reagent coupled with high-performance liquid chromatography with fluorescence detection was first developed for the study of triterpenic acid bioavailability. Furthermore, the labeling conditions have been optimized in order to achieve the best fluorescence labeling yield. Under the optimal conditions, the quantitative linear range of analytes was 2-1000 ng mL -1 , and the correlation coefficients were >0.9998. The detection limits for all triterpenic acid derivatives were achieved within the range of 0.28-0.29 ng mL -1 . The proposed method was successfully applied to the study of triterpenic acid bioavailability with excellent applicability and good reproducibility. Copyright © 2016 John Wiley & Sons, Ltd.

  19. Introduction to Pesticide Labels

    EPA Pesticide Factsheets

    Pesticide product labels provide critical information about how to safely and legally handle and use pesticide products. Unlike most other types of product labels, pesticide labels are legally enforceable. Learn about pesticide product labels.

  20. How to Write a Reproducible Paper

    NASA Astrophysics Data System (ADS)

    Irving, D. B.

    2016-12-01

    The geosciences have undergone a computational revolution in recent decades, to the point where almost all modern research relies heavily on software and code. Despite this profound change in the research methods employed by geoscientists, the reporting of computational results has changed very little in academic journals. This lag has led to something of a reproducibility crisis, whereby it is impossible to replicate and verify most of today's published computational results. While it is tempting to decry the slow response of journals and funding agencies in the face of this crisis, there are very few examples of reproducible research upon which to base new communication standards. In an attempt to address this deficiency, this presentation will describe a procedure for reporting computational results that was employed in a recent Journal of Climate paper. The procedure was developed to be consistent with recommended computational best practices and seeks to minimize the time burden on authors, which has been identified as the most important barrier to publishing code. It should provide a starting point for geoscientists looking to publish reproducible research, and could be adopted by journals as a formal minimum communication standard.

  1. Tools and techniques for computational reproducibility.

    PubMed

    Piccolo, Stephen R; Frampton, Michael B

    2016-07-11

    When reporting research findings, scientists document the steps they followed so that others can verify and build upon the research. When those steps have been described in sufficient detail that others can retrace the steps and obtain similar results, the research is said to be reproducible. Computers play a vital role in many research disciplines and present both opportunities and challenges for reproducibility. Computers can be programmed to execute analysis tasks, and those programs can be repeated and shared with others. The deterministic nature of most computer programs means that the same analysis tasks, applied to the same data, will often produce the same outputs. However, in practice, computational findings often cannot be reproduced because of complexities in how software is packaged, installed, and executed-and because of limitations associated with how scientists document analysis steps. Many tools and techniques are available to help overcome these challenges; here we describe seven such strategies. With a broad scientific audience in mind, we describe the strengths and limitations of each approach, as well as the circumstances under which each might be applied. No single strategy is sufficient for every scenario; thus we emphasize that it is often useful to combine approaches.

  2. Graphic Warning Labels in Cigarette Advertisements: Recall and Viewing Patterns

    PubMed Central

    Strasser, Andrew A.; Tang, Kathy Z.; Romer, Daniel; Jepson, Chris; Cappella, Joseph N.

    2012-01-01

    Background The Family Smoking Prevention and Control Act gave the U.S. Food and Drug Administration (FDA) legal authority to mandate graphic warning labels on cigarette advertising and packaging. The FDA requires that these graphic warning labels be embedded into cigarette advertising and packaging by September 2012. Purpose The aim of this study was to examine differences in recall and viewing patterns of text-only versus graphic cigarette warning labels; and, the association between viewing patterns and recall. Methods Participants (current daily smokers; N=200) were randomized to view a cigarette advertisement with either text-only or graphic warning labels. Viewing patterns were measured using eye-tracking, and recall was later assessed. Sessions were conducted between November 2008 and November 2009. Data analysis was conducted between March 2011 and July 2011. Results There was a significant difference in percentage correct recall of the warning label between those in the text-only versus graphic warning label condition, 50% versus 83% (χ2 =23.74, p=0.0001). Time to first view of the graphic warning label text, and dwell time duration (i.e., time spent looking) on the graphic image were significantly associated with correct recall. Warning labels that drew attention more quickly and resulted in longer dwell times were associated with better recall. Conclusions Graphic warning labels improve smokers’ recall of warning and health risks; they do so by drawing and holding attention. PMID:22704744

  3. Gold/silver/gold trilayer films on nanostructured polycarbonate substrates for direct and label-free nanoplasmonic biosensing.

    PubMed

    López-Muñoz, Gerardo A; Estévez, M-Carmen; Vázquez-García, Marc; Berenguel-Alonso, Miguel; Alonso-Chamarro, Julián; Homs-Corbera, Antoni; Lechuga, Laura M

    2018-05-01

    Ultrasmooth gold/silver/gold trilayer nanostructured plasmonic sensors were obtained using commercial Blu-ray optical discs as nanoslits-based flexible polymer substrates. A thin gold film was used as an adhesion and nucleation layer to improve the chemical stability and reduce the surface roughness of the overlying silver film, without increasing ohmic plasmon losses. The structures were physically and optically characterized and compared with nanostructures of single gold layer. Ultrasmooth and chemically stable trilayer nanostructures with a surface roughness <0.5 nm were obtained following a simple and reproducible fabrication process. They showed a figure of merit (FOM) value up to 69.2 RIU -1 which is significantly higher (more than 95%) than the gold monolayer counterpart. Their potential for biosensing was demonstrated by employing the trilayer sensor for the direct and refractometric (label-free) detection of C-reactive protein (CRP) biomarker in undiluted urine achieving a Limit of Detection (LOD) in the pM order. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Person Perception and Verbal Labeling: The Development of Social Labels.

    ERIC Educational Resources Information Center

    Brooks-Gunn, Jeanne; Lewis, Michael

    This study examined the social labels which are first used by infants, social differentiation on the basis of labeling behavior, and overgeneralization of social labels. Subjects were 81 infants from 9 to 36 months of age. The 9- to 24-month-olds were shown slides of themselves, their mothers, their fathers, and unfamiliar children, babies, and…

  5. 3D GRASE PROPELLER: Improved Image Acquisition Technique for Arterial Spin Labeling Perfusion Imaging

    PubMed Central

    Tan, Huan; Hoge, W. Scott; Hamilton, Craig A.; Günther, Matthias; Kraft, Robert A.

    2014-01-01

    Arterial spin labeling (ASL) is a non-invasive technique that can quantitatively measure cerebral blood flow (CBF). While traditionally ASL employs 2D EPI or spiral acquisition trajectories, single-shot 3D GRASE is gaining popularity in ASL due to inherent SNR advantage and spatial coverage. However, a major limitation of 3D GRASE is through-plane blurring caused by T2 decay. A novel technique combining 3D GRASE and a PROPELLER trajectory (3DGP) is presented to minimize through-plane blurring without sacrificing perfusion sensitivity or increasing total scan time. Full brain perfusion images were acquired at a 3×3×5mm3 nominal voxel size with Q2TIPS-FAIR as the ASL preparation sequence. Data from 5 healthy subjects was acquired on a GE 1.5T scanner in less than 4 minutes per subject. While showing good agreement in CBF quantification with 3D GRASE, 3DGP demonstrated reduced through-plane blurring, improved anatomical details, high repeatability and robustness against motion, making it suitable for routine clinical use. PMID:21254211

  6. Development of High-Performance Chemical Isotope Labeling LC-MS for Profiling the Carbonyl Submetabolome.

    PubMed

    Zhao, Shuang; Dawe, Margot; Guo, Kevin; Li, Liang

    2017-06-20

    Metabolites containing a carbonyl group represent several important classes of molecules including various forms of ketones and aldehydes such as steroids and sugars. We report a high-performance chemical isotope labeling (CIL) LC-MS method for profiling the carbonyl submetabolome with high coverage and high accuracy and precision of relative quantification. This method is based on the use of dansylhydrazine (DnsHz) labeling of carbonyl metabolites to change their chemical and physical properties to such an extent that the labeled metabolites can be efficiently separated by reversed phase LC and ionized by electrospray ionization MS. In the analysis of six standards representing different carbonyl classes, acetaldehyde could be ionized only after labeling and MS signals were significantly increased for other 5 standards with an enhancement factor ranging from ∼15-fold for androsterone to ∼940-fold for 2-butanone. Differential 12 C- and 13 C-DnsHz labeling was developed for quantifying metabolic differences in comparative samples where individual samples were separately labeled with 12 C-labeling and spiked with a 13 C-labeled pooled sample, followed by LC-MS analysis, peak pair picking, and peak intensity ratio measurement. In the replicate analysis of a 1:1 12 C-/ 13 C-labeled human urine mixture (n = 6), an average of 2030 ± 39 pairs per run were detected with 1737 pairs in common, indicating the possibility of detecting a large number of carbonyl metabolites as well as high reproducibility of peak pair detection. The average RSD of the peak pair ratios was 7.6%, and 95.6% of the pairs had a RSD value of less than 20%, demonstrating high precision for peak ratio measurement. In addition, the ratios of most peak pairs were close to the expected value of 1.0 (e.g., 95.5% of them had ratios of between 0.67 and 1.5), showing the high accuracy of the method. For metabolite identification, a library of DnsHz-labeled standards was constructed, including 78 carbonyl

  7. The Influence of Sugar-Sweetened Beverage Health Warning Labels on Parents' Choices.

    PubMed

    Roberto, Christina A; Wong, Diandra; Musicus, Aviva; Hammond, David

    2016-02-01

    US states have introduced bills requiring sugar-sweetened beverages (SSBs) to display health warning labels. This study examined how such labels may influence parents and which labels are most impactful. In this study, 2381 demographically and educationally diverse parents participated in an online survey. Parents were randomly assigned to 1 of 6 conditions: (1) no warning label (control); (2) calorie label; or (3-6) 1 of 4 text versions of a warning label (eg, Safety Warning: Drinking beverages with added sugar[s] contributes to obesity, diabetes, and tooth decay). Parents chose a beverage for their child in a vending machine choice task, rated perceptions of different beverages, and indicated interest in receiving beverage coupons. Regression analyses controlling for frequency of beverage purchases were used to compare the no warning label group, calorie label group, and all warning label groups combined. Significantly fewer parents chose an SSB for their child in the warning label condition (40%) versus the no label (60%) and calorie label conditions (53%). Parents in the warning label condition also chose significantly fewer SSB coupons, believed that SSBs were less healthy for their child, and were less likely to intend to purchase SSBs. All P values <.05 after correcting for multiple comparisons. There were no consistent differences among different versions of the warning labels. Health warning labels on SSBs improved parents' understanding of health harms associated with overconsumption of such beverages and may reduce parents' purchase of SSBs for their children. Copyright © 2016 by the American Academy of Pediatrics.

  8. The Discovery of Novel Biomarkers Improves Breast Cancer Intrinsic Subtype Prediction and Reconciles the Labels in the METABRIC Data Set

    PubMed Central

    Milioli, Heloisa Helena; Vimieiro, Renato; Riveros, Carlos; Tishchenko, Inna; Berretta, Regina; Moscato, Pablo

    2015-01-01

    Background The prediction of breast cancer intrinsic subtypes has been introduced as a valuable strategy to determine patient diagnosis and prognosis, and therapy response. The PAM50 method, based on the expression levels of 50 genes, uses a single sample predictor model to assign subtype labels to samples. Intrinsic errors reported within this assay demonstrate the challenge of identifying and understanding the breast cancer groups. In this study, we aim to: a) identify novel biomarkers for subtype individuation by exploring the competence of a newly proposed method named CM1 score, and b) apply an ensemble learning, as opposed to the use of a single classifier, for sample subtype assignment. The overarching objective is to improve class prediction. Methods and Findings The microarray transcriptome data sets used in this study are: the METABRIC breast cancer data recorded for over 2000 patients, and the public integrated source from ROCK database with 1570 samples. We first computed the CM1 score to identify the probes with highly discriminative patterns of expression across samples of each intrinsic subtype. We further assessed the ability of 42 selected probes on assigning correct subtype labels using 24 different classifiers from the Weka software suite. For comparison, the same method was applied on the list of 50 genes from the PAM50 method. Conclusions The CM1 score portrayed 30 novel biomarkers for predicting breast cancer subtypes, with the confirmation of the role of 12 well-established genes. Intrinsic subtypes assigned using the CM1 list and the ensemble of classifiers are more consistent and homogeneous than the original PAM50 labels. The new subtypes show accurate distributions of current clinical markers ER, PR and HER2, and survival curves in the METABRIC and ROCK data sets. Remarkably, the paradoxical attribution of the original labels reinforces the limitations of employing a single sample classifiers to predict breast cancer intrinsic subtypes

  9. MO-FG-CAMPUS-JeP3-02: A Novel Setup Approach to Improve C-Spine Curvature Reproducibility for Head and Neck Radiotherapy Using Optical Surface Imaging with Two Regions of Interest

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

    Ryan, K; Gil, M; Li, G

    Purpose: To develop a novel approach to improve cervical spine (c-spine) curvature reproducibility for head and neck (HN) patients using optical surface imaging (OSI) with two regions of interests (ROIs). Methods: The OSI-guided, two-step setup procedure requires two ROIs: ROI-1 of the shoulders and ROI-2 of the face. The neck can be stretched or squeezed in superior-inferior (SI) direction using a specially-designed sliding head support. We hypothesize that when these two ROIs are aligned, the c-spine should fall into a naturally reproducible position under same setup conditions. An anthropomorphous phantom test was performed to examine neck pitch angles comparing withmore » the calculated angles. Three volunteers participated in the experiments, which start with conventional HN setup using skin markers and room lasers. An OSI image and lateral photo-picture were acquired as the references. In each of the three replicate tests, conventional setup was first applied after volunteers got on the couch. ROI-1 was aligned by moving the body, followed by ROI-2 alignment via adjusting head position and orientation under real-time OSI guidance. A final static OSI image and lateral picture were taken to evaluate both anterior and posterior surface alignments. Three degrees of freedom can be adjusted if an open-face mask was applied, including head SI shift using the sliding head support and pitch-and-roll rotations using a commercial couch extension. Surface alignment was analyzed comparing with conventional setup. Results: The neck pitch angle measured by OSI is consistent with the calculated (0.2±0.6°). Volunteer study illustrated improved c-spine setup reproducibility using OSI comparing with conventional setup. ROI alignments with 2mm/1° tolerance are achieved within 3 minutes. Identical knee support is important to achieve ROI-1 pitch alignment. Conclusion: The feasibility of this novel approach has been demonstrated for c-spine curvature setup reproducibility

  10. Impact of brand or generic labeling on medication effectiveness and side effects.

    PubMed

    Faasse, Kate; Martin, Leslie R; Grey, Andrew; Gamble, Greg; Petrie, Keith J

    2016-02-01

    Branding medication with a known pharmaceutical company name or product name bestows on the drug an added assurance of authenticity and effectiveness compared to a generic preparation. This study examined the impact of brand name and generic labeling on medication effectiveness and side effects. 87 undergraduate students with frequent headaches took part in the study. Using a within-subjects counterbalanced design, each participant took tablets labeled either as brand name "Nurofen" or "Generic Ibuprofen" to treat each of 4 headaches. In reality, half of the tablets were placebos, and half were active ibuprofen (400 mg). Participants recorded their headache pain on a verbal descriptor and visual analogue scale prior to taking the tablets, and again 1 hour afterward. Medication side effects were also reported. Pain reduction following the use of brand name labeled tablets was similar in active ibuprofen or a placebo. However, if the tablets had a generic label, placebo tablets were significantly less effective compared to active ibuprofen. Fewer side effects were attributed to placebo tablets with brand name labeling compared to the same placebo tablets with a generic label. Branding of a tablet appears to have conferred a treatment benefit in the absence of an active ingredient, while generic labeled tablets were substantially less effective if they contained no active ingredient. Branding is also associated with reduced attribution of side effects to placebo tablets. Future interventions to improve perceptions of generics may have utility in improving treatment outcomes from generic drugs. (c) 2016 APA, all rights reserved).

  11. Does semi-automatic bone-fragment segmentation improve the reproducibility of the Letournel acetabular fracture classification?

    PubMed

    Boudissa, M; Orfeuvre, B; Chabanas, M; Tonetti, J

    2017-09-01

    The Letournel classification of acetabular fracture shows poor reproducibility in inexperienced observers, despite the introduction of 3D imaging. We therefore developed a method of semi-automatic segmentation based on CT data. The present prospective study aimed to assess: (1) whether semi-automatic bone-fragment segmentation increased the rate of correct classification; (2) if so, in which fracture types; and (3) feasibility using the open-source itksnap 3.0 software package without incurring extra cost for users. Semi-automatic segmentation of acetabular fractures significantly increases the rate of correct classification by orthopedic surgery residents. Twelve orthopedic surgery residents classified 23 acetabular fractures. Six used conventional 3D reconstructions provided by the center's radiology department (conventional group) and 6 others used reconstructions obtained by semi-automatic segmentation using the open-source itksnap 3.0 software package (segmentation group). Bone fragments were identified by specific colors. Correct classification rates were compared between groups on Chi 2 test. Assessment was repeated 2 weeks later, to determine intra-observer reproducibility. Correct classification rates were significantly higher in the "segmentation" group: 114/138 (83%) versus 71/138 (52%); P<0.0001. The difference was greater for simple (36/36 (100%) versus 17/36 (47%); P<0.0001) than complex fractures (79/102 (77%) versus 54/102 (53%); P=0.0004). Mean segmentation time per fracture was 27±3min [range, 21-35min]. The segmentation group showed excellent intra-observer correlation coefficients, overall (ICC=0.88), and for simple (ICC=0.92) and complex fractures (ICC=0.84). Semi-automatic segmentation, identifying the various bone fragments, was effective in increasing the rate of correct acetabular fracture classification on the Letournel system by orthopedic surgery residents. It may be considered for routine use in education and training. III: prospective

  12. Reproducibility of ECG-gated ultrasound diameter assessment of small abdominal aortic aneurysms.

    PubMed

    Bredahl, K; Eldrup, N; Meyer, C; Eiberg, J E; Sillesen, H

    2013-03-01

    No standardised ultrasound procedure to obtain reliable growth estimates for abdominal aortic aneurysms (AAA) is currently available. We investigated the feasibility and reproducibility of a novel approach controlling for a combination of vessel wall delineation and cardiac cycle variation. Prospective comparative study. Consecutive patients (N = 27) with an AAA, attending their 6-month control as part of a medical treatment trial, were scanned twice by two ultrasound operators. Then, all ultrasound recordings were transferred to a core facility and analysed by a third person. The AAA diameter was determined in four different ways: from the leading edge of adventitia on the anterior wall to either the leading edge of the adventitia (method A) or leading edge of the intima (method B) on the posterior wall, with both measurements performed in systole and diastole. Inter-operator reproducibility was ± 3 mm for all methods applied. There was no difference in outcome between methods A and B; likewise, end-diastolic measurement did not improve reproducibility in preference to peak-systolic measurement. The use of a standardised ultrasound protocol including ECG-gating and subsequent off-line reading with minute calliper placement reduces variability. This may be of use in developing protocols to better detect even small AAA growth rates during clinical trials. Copyright © 2012 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

  13. Reproducible Bioinformatics Research for Biologists

    USDA-ARS?s Scientific Manuscript database

    This book chapter describes the current Big Data problem in Bioinformatics and the resulting issues with performing reproducible computational research. The core of the chapter provides guidelines and summaries of current tools/techniques that a noncomputational researcher would need to learn to pe...

  14. Vitamin E supplement improves erythrocyte membrane fluidity of thalassemia: an ESR spin labeling study.

    PubMed

    Sutipornpalangkul, Werasak; Morales, Noppawan Phumala; Unchern, Supeenun; Sanvarinda, Yupin; Chantharaksri, Udom; Fucharoen, Suthat

    2012-01-01

    Beta-thalassemia/Hemoglobin E (beta-thal/Hb E) is prevalent in Thailand. The imbalance of globin chains in red blood cells is the primary cause of this anemic disease. The excess alpha-globin in beta-thal/Hb E causes typical damage(s) to membrane of erythroblasts and erythrocytes. By using three paramagnetic labeled compounds (5-, 12-, and 16-spin labeled stearic acids, SLS), the changes of the molecular motion in the lipid bilayer of thalassemic RBCs that have structural modification can be detected. to investigate erythrocyte membrane fluidity and the effect of vitamin E treatment in beta-thalassemia/Hemoglobin E patients by using spin labeling techniques. The erythrocyte membrane fluidity was investigated in nine splenectomized and five non-splenectomized beta-thalassemia/hemoglobin E (beta-thal/Hb E) patients using EPR spin labeling techniques. To determine the effect of vitamin E on erythrocyte membrane fluidity, only the splenectomized patients were enrolled. Patients were divided into two groups. The first group received 350 mg vitamin E daily for a period of 1 month (n = 5) and the second group received placebo for an equal period (n = 4). Three paramagnetic fatty acid, 5-, 12-, and 16-doxyl stearic acids, (5-, 12- and 16-DS) were used to label phospholipids layer near both the surface (5-DS) and the deeper hydrophobic region of membrane (12-and 16-DS). Lipid peroxidation (TBARs) was measured using a colorimetric method. Vitamin E was measured with high performance liquid chromatography (HPLC). Significantly higher values of erythrocyte membrane fluidity were revealed with 12-, 16-DS in splenectomized patients, as compared with non-splenectomized patients and normal subjects. In 3-thal/Hb E patients, fluidity values, both outer hyperfine splitting (2T(//)) and order parameter (S) of 12-DS showed inverse correlation with serum TBARs. There was no significant difference between the fluidity values measured with 5-DS. After vitamin E supplementation, the

  15. Shear wave elastography for breast masses is highly reproducible.

    PubMed

    Cosgrove, David O; Berg, Wendie A; Doré, Caroline J; Skyba, Danny M; Henry, Jean-Pierre; Gay, Joel; Cohen-Bacrie, Claude

    2012-05-01

    To evaluate intra- and interobserver reproducibility of shear wave elastography (SWE) for breast masses. For intraobserver reproducibility, each observer obtained three consecutive SWE images of 758 masses that were visible on ultrasound. 144 (19%) were malignant. Weighted kappa was used to assess the agreement of qualitative elastographic features; the reliability of quantitative measurements was assessed by intraclass correlation coefficients (ICC). For the interobserver reproducibility, a blinded observer reviewed images and agreement on features was determined. Mean age was 50 years; mean mass size was 13 mm. Qualitatively, SWE images were at least reasonably similar for 666/758 (87.9%). Intraclass correlation for SWE diameter, area and perimeter was almost perfect (ICC ≥ 0.94). Intraobserver reliability for maximum and mean elasticity was almost perfect (ICC = 0.84 and 0.87) and was substantial for the ratio of mass-to-fat elasticity (ICC = 0.77). Interobserver agreement was moderate for SWE homogeneity (κ = 0.57), substantial for qualitative colour assessment of maximum elasticity (κ = 0.66), fair for SWE shape (κ = 0.40), fair for B-mode mass margins (κ = 0.38), and moderate for B-mode mass shape (κ = 0.58), orientation (κ = 0.53) and BI-RADS assessment (κ = 0.59). SWE is highly reproducible for assessing elastographic features of breast masses within and across observers. SWE interpretation is at least as consistent as that of BI-RADS ultrasound B-mode features. • Shear wave ultrasound elastography can measure the stiffness of breast tissue • It provides a qualitatively and quantitatively interpretable colour-coded map of tissue stiffness • Intraobserver reproducibility of SWE is almost perfect while intraobserver reproducibility of SWE proved to be moderate to substantial • The most reproducible SWE features between observers were SWE image homogeneity and maximum elasticity.

  16. Accuracy of femoral templating in reproducing anatomical femoral offset in total hip replacement.

    PubMed

    Davies, H; Foote, J; Spencer, R F

    2007-01-01

    Restoration of hip biomechanics is a crucial component of successful total hip replacement. Preoperative templating is recommended to ensure that the size and orientation of implants is optimised. We studied how closely natural femoral offset could be reproduced using the manufacturers' templates for 10 femoral stems in common use in the UK. A series of 23 consecutive preoperative radiographs from patients who had undergone unilateral total hip replacement for unilateral osteoarthritis of the hip was employed. The change in offset between the templated position of the best-fitting template and the anatomical centre of the hip was measured. The templates were then ranked according to their ability to reproduce the normal anatomical offset. The most accurate was the CPS-Plus (Root Mean Square Error 2.0 mm) followed in rank order by: C stem (2.16), CPT (2.40), Exeter (3.23), Stanmore (3.28), Charnley (3.65), Corail (3.72), ABG II (4.30), Furlong HAC (5.08) and Furlong modular (7.14). A similar pattern of results was achieved when the standard error of variability of offset was analysed. We observed a wide variation in the ability of the femoral prosthesis templates to reproduce normal femoral offset. This variation was independent of the seniority of the observer. The templates of modern polished tapered stems with high modularity were best able to reproduce femoral offset. The current move towards digitisation of X-rays may offer manufacturers an opportunity to improve template designs in certain instances, and to develop appropriate computer software.

  17. A study on the consumer's perception of front-of-pack nutrition labeling

    PubMed Central

    Kim, Woo Kyoung

    2009-01-01

    The goal of this research is to investigate the present situation for front of pack labeling in Korea and the perception of consumers for the new system of labeling, front of pack labeling, based on the consumer survey. We investigated the number of processed foods with front of pack labeling in one retailer in Youngin-si. And we also surveyed 1,019 participants nationwide whose ages were from 20 to 49; the knowledge of nutrition labeling, the knowledge of 'front of pack labeling', and the opinion about the labeling system. The data were analyzed using SAS statistics program. The results were as follows: 13.4% of processed foods had front of pack labeling, and 16.8% of the consumers always checked the nutrition labeling, while 32.7% of the consumers seldom checked it. In addition, 44.3% of the consumers think that 'front of pack labeling' is necessary, and 58.3% of the consumers think it is important to show the percentage of daily value as a way of 'front of pack labeling'. However, 32% of the consumer think the possibility of 'front of pack labeling' is slim. Meanwhile, 58.3% of the consumers think that it is important to have the color difference according to contents. The number of favorite nutrients in the front of pack was four or five. It seems that the recognition of current nutrition labeling has the influence on the willingness of using the future 'front of pack labeling'. Along with our study, the policy for 'front of pack labeling' has to be updated and improved constantly since 'front of pack labeling' helps consumer understand nutrition facts. PMID:20098583

  18. Datathons and Software to Promote Reproducible Research.

    PubMed

    Celi, Leo Anthony; Lokhandwala, Sharukh; Montgomery, Robert; Moses, Christopher; Naumann, Tristan; Pollard, Tom; Spitz, Daniel; Stretch, Robert

    2016-08-24

    Datathons facilitate collaboration between clinicians, statisticians, and data scientists in order to answer important clinical questions. Previous datathons have resulted in numerous publications of interest to the critical care community and serve as a viable model for interdisciplinary collaboration. We report on an open-source software called Chatto that was created by members of our group, in the context of the second international Critical Care Datathon, held in September 2015. Datathon participants formed teams to discuss potential research questions and the methods required to address them. They were provided with the Chatto suite of tools to facilitate their teamwork. Each multidisciplinary team spent the next 2 days with clinicians working alongside data scientists to write code, extract and analyze data, and reformulate their queries in real time as needed. All projects were then presented on the last day of the datathon to a panel of judges that consisted of clinicians and scientists. Use of Chatto was particularly effective in the datathon setting, enabling teams to reduce the time spent configuring their research environments to just a few minutes-a process that would normally take hours to days. Chatto continued to serve as a useful research tool after the conclusion of the datathon. This suite of tools fulfills two purposes: (1) facilitation of interdisciplinary teamwork through archiving and version control of datasets, analytical code, and team discussions, and (2) advancement of research reproducibility by functioning postpublication as an online environment in which independent investigators can rerun or modify analyses with relative ease. With the introduction of Chatto, we hope to solve a variety of challenges presented by collaborative data mining projects while improving research reproducibility.

  19. Extending the scope of eco-labelling in the food industry to drive change beyond sustainable agriculture practices.

    PubMed

    Miranda-Ackerman, Marco A; Azzaro-Pantel, Catherine

    2017-12-15

    New consumer awareness is shifting industry towards more sustainable practices, creating a virtuous cycle between producers and consumers enabled by eco-labelling. Eco-labelling informs consumers of specific characteristics of products and has been used to market greener products. Eco-labelling in the food industry has yet been mostly focused on promoting organic farming, limiting the scope to the agricultural stage of the supply chain, while carbon labelling informs on the carbon footprint throughout the life cycle of the product. These labelling strategies help value products in the eyes of the consumer. Because of this, decision makers are motivated to adopt more sustainable models. In the food industry, this has led to important environmental impact improvements at the agricultural stage, while most other stages in the Food Supply Chain (FSC) have continued to be designed inefficiently. The objective of this work is to define a framework showing how carbon labelling can be integrated into the design process of the FSC. For this purpose, the concept of Green Supply Chain Network Design (GSCND) focusing on the strategic decision making for location and allocation of resources and production capacity is developed considering operational, financial and environmental (CO 2 emissions) issues along key stages in the product life cycle. A multi-objective optimization strategy implemented by use of a genetic algorithm is applied to a case study on orange juice production. The results show that the consideration of CO 2 emission minimization as an objective function during the GSCND process together with techno-economic criteria produces improved FSC environmental performance compared to both organic and conventional orange juice production. Typical results thus highlight the importance that carbon emissions optimization and labelling may have to improve FSC beyond organic labelling. Finally, CO 2 emission-oriented labelling could be an important tool to improve the

  20. Selected reaction monitoring (SRM) mass spectrometry without isotope labeling can be used for rapid protein quantification

    PubMed Central

    Zhi, Wenbo; Wang, Meiyao

    2014-01-01

    The validation of putative biomarker candidates has become the major bottle-neck in protein biomarker development. Conventional immunoaffinity methods are limited by the availability of antibodies and kits. Here we demonstrated the feasibility of using the selected reaction monitoring (SRM) without isotope labeling to achieve fast and reproducible quantification of serum proteins. The SRM/MRM assays for three standard serum proteins, including ceruloplasmin (CP), serum aymloid A (SAA) and sex hormone binding globulin (SHBG) have good linear ranges, generally 103 – 104. There are almost perfect correlations between SRM intensities and the loaded peptide amounts (R2 is usually ~0.99). Our data suggest that SRM/MRM is able to quantify proteins at 0.2 – 2 fmol level, which are comparable to the commercial ELISA/LUMINEX kits for these proteins. Excellent correlations between SRM/MRM and ELISA/LUMINEX assays were observed for SAA and SHBG (R2 = 0.928 and 0.851 respectively). The correlation between SRM/MRM and ELISA for CP is less desirable (R2 = 0.565). The reproducibility for SRM/MRM assays is generally very good but may depend on the proteins/peptides (R2 = 0.931 and 0.882 for SAA and SHBG, and 0.723 for CP). SRM/MRM assay without isotope labeling is a rapid and useful method for protein biomarker validation in a modest number of samples and is especially useful when other assays such as ELISA or Luminex beads are not available. PMID:21594933

  1. Efficient Site-Specific Labeling of Proteins via Cysteines

    PubMed Central

    Kim, Younggyu; Ho, Sam O.; Gassman, Natalie R.; Korlann, You; Landorf, Elizabeth V.; Collart, Frank R.; Weiss, Shimon

    2011-01-01

    Methods for chemical modifications of proteins have been crucial for the advancement of proteomics. In particular, site-specific covalent labeling of proteins with fluorophores and other moieties has permitted the development of a multitude of assays for proteome analysis. A common approach for such a modification is solvent-accessible cysteine labeling using thiol-reactive dyes. Cysteine is very attractive for site-specific conjugation due to its relative rarity throughout the proteome and the ease of its introduction into a specific site along the protein's amino acid chain. This is achieved by site-directed mutagenesis, most often without perturbing the protein's function. Bottlenecks in this reaction, however, include the maintenance of reactive thiol groups without oxidation before the reaction, and the effective removal of unreacted molecules prior to fluorescence studies. Here, we describe an efficient, specific, and rapid procedure for cysteine labeling starting from well-reduced proteins in the solid state. The efficacy and specificity of the improved procedure are estimated using a variety of single-cysteine proteins and thiol-reactive dyes. Based on UV/vis absorbance spectra, coupling efficiencies are typically in the range 70–90%, and specificities are better than ~95%. The labeled proteins are evaluated using fluorescence assays, proving that the covalent modification does not alter their function. In addition to maleimide-based conjugation, this improved procedure may be used for other thiol-reactive conjugations such as haloacetyl, alkyl halide, and disulfide interchange derivatives. This facile and rapid procedure is well suited for high throughput proteome analysis. PMID:18275130

  2. Efficient site-specific labeling of proteins via cysteines.

    PubMed

    Kim, Younggyu; Ho, Sam O; Gassman, Natalie R; Korlann, You; Landorf, Elizabeth V; Collart, Frank R; Weiss, Shimon

    2008-03-01

    Methods for chemical modifications of proteins have been crucial for the advancement of proteomics. In particular, site-specific covalent labeling of proteins with fluorophores and other moieties has permitted the development of a multitude of assays for proteome analysis. A common approach for such a modification is solvent-accessible cysteine labeling using thiol-reactive dyes. Cysteine is very attractive for site-specific conjugation due to its relative rarity throughout the proteome and the ease of its introduction into a specific site along the protein's amino acid chain. This is achieved by site-directed mutagenesis, most often without perturbing the protein's function. Bottlenecks in this reaction, however, include the maintenance of reactive thiol groups without oxidation before the reaction, and the effective removal of unreacted molecules prior to fluorescence studies. Here, we describe an efficient, specific, and rapid procedure for cysteine labeling starting from well-reduced proteins in the solid state. The efficacy and specificity of the improved procedure are estimated using a variety of single-cysteine proteins and thiol-reactive dyes. Based on UV/vis absorbance spectra, coupling efficiencies are typically in the range 70-90%, and specificities are better than approximately 95%. The labeled proteins are evaluated using fluorescence assays, proving that the covalent modification does not alter their function. In addition to maleimide-based conjugation, this improved procedure may be used for other thiol-reactive conjugations such as haloacetyl, alkyl halide, and disulfide interchange derivatives. This facile and rapid procedure is well suited for high throughput proteome analysis.

  3. Impedance analysis of GPCR-mediated changes in endothelial barrier function: overview, and fundamental considerations for stable and reproducible measurements

    PubMed Central

    Stolwijk, Judith A.; Matrougui, Khalid; Renken, Christian W.; Trebak, Mohamed

    2014-01-01

    The past 20 years have seen significant growth in using impedance-based assays to understand the molecular underpinning of endothelial and epithelial barrier function in response to physiological agonists, pharmacological and toxicological compounds. Most studies on barrier function use G protein coupled receptor (GPCR) agonists which couple to fast and transient changes in barrier properties. The power of impedance based techniques such as Electric Cell-Substrate Impedance Sensing (ECIS) reside in its ability to detect minute changes in cell layer integrity label-free and in real-time ranging from seconds to days. We provide a comprehensive overview of the biophysical principles, applications and recent developments in impedance-based methodologies. Despite extensive application of impedance analysis in endothelial barrier research little attention has been paid to data analysis and critical experimental variables, which are both essential for signal stability and reproducibility. We describe the rationale behind common ECIS data presentation and interpretation and illustrate practical guidelines to improve signal intensity by adapting technical parameters such as electrode layout, monitoring frequency or parameter (resistance versus impedance magnitude). Moreover, we discuss the impact of experimental parameters, including cell source, liquid handling and agonist preparation on signal intensity and kinetics. Our discussions are supported by experimental data obtained from human microvascular endothelial cells challenged with three GPCR agonists, thrombin, histamine and Sphingosine-1-Phosphate. PMID:25537398

  4. Impedance analysis of GPCR-mediated changes in endothelial barrier function: overview and fundamental considerations for stable and reproducible measurements.

    PubMed

    Stolwijk, Judith A; Matrougui, Khalid; Renken, Christian W; Trebak, Mohamed

    2015-10-01

    The past 20 years has seen significant growth in using impedance-based assays to understand the molecular underpinning of endothelial and epithelial barrier function in response to physiological agonists and pharmacological and toxicological compounds. Most studies on barrier function use G protein-coupled receptor (GPCR) agonists which couple to fast and transient changes in barrier properties. The power of impedance-based techniques such as electric cell-substrate impedance sensing (ECIS) resides in its ability to detect minute changes in cell layer integrity label-free and in real-time ranging from seconds to days. We provide a comprehensive overview of the biophysical principles, applications, and recent developments in impedance-based methodologies. Despite extensive application of impedance analysis in endothelial barrier research, little attention has been paid to data analysis and critical experimental variables, which are both essential for signal stability and reproducibility. We describe the rationale behind common ECIS data presentation and interpretation and illustrate practical guidelines to improve signal intensity by adapting technical parameters such as electrode layout, monitoring frequency, or parameter (resistance versus impedance magnitude). Moreover, we discuss the impact of experimental parameters, including cell source, liquid handling, and agonist preparation on signal intensity and kinetics. Our discussions are supported by experimental data obtained from human microvascular endothelial cells challenged with three GPCR agonists, thrombin, histamine, and sphingosine-1-phosphate.

  5. Gold@silver bimetal nanoparticles/pyramidal silicon 3D substrate with high reproducibility for high-performance SERS

    NASA Astrophysics Data System (ADS)

    Zhang, Chao; Jiang, Shou Zhen; Yang, Cheng; Li, Chong Hui; Huo, Yan Yan; Liu, Xiao Yun; Liu, Ai Hua; Wei, Qin; Gao, Sai Sai; Gao, Xing Guo; Man, Bao Yuan

    2016-05-01

    A novel and efficient surface enhanced Raman scattering (SERS) substrate has been presented based on Gold@silver/pyramidal silicon 3D substrate (Au@Ag/3D-Si). By combining the SERS activity of Ag, the chemical stability of Au and the large field enhancement of 3D-Si, the Au@Ag/3D-Si substrate possesses perfect sensitivity, homogeneity, reproducibility and chemical stability. Using R6G as probe molecule, the SERS results imply that the Au@Ag/3D-Si substrate is superior to the 3D-Si, Ag/3D-Si and Au/3D-Si substrate. We also confirmed these excellent behaviors in theory via a commercial COMSOL software. The corresponding experimental and theoretical results indicate that our proposed Au@Ag/3D-Si substrate is expected to develop new opportunities for label-free SERS detections in biological sensors, biomedical diagnostics and food safety.

  6. [The reproducibility of multifocal ERG recordings].

    PubMed

    Meigen, T; Friedrich, A

    2002-09-01

    Multifocal electroretinogram recordings (mfERG) can be used to detect a local dysfunction of the retina. In this study we tested both the intrasessional and inter-sessional reproducibility of mfERG amplitudes. MfERGs from 6 eyes of 6 normal subjects were recorded on two different days using DTL electrodes. The relative coefficient of variation ( RCV) was used to quantify the amplitude reproducibility. We tested the effect of (a) session (inter- vs. intrasessional), (b) recording duration (7.3 vs. 3.6 min), (c) trace type (hexagon traces vs. ring averages), and (d) amplitude definition (peak-trough analysis vs. scalar product) on RCV. RCV was 6.5+/-0.4% (Mean+/-SEM, n=96) when averaged across all recording conditions and all subjects. The ANOVA showed a significant difference ( p=0.018) between hexagon traces and ring averages. Another significant effect ( p=0.016) occurred for the interaction of (a) and (b). MfERGs can be recorded with a high degree of reproducibility even for short recording durations and single hexagon traces. As the factor (a) did not show a significant effect, the new placement of the DTL electrode in the second session does not necessarily increase the retest variability compared to a second recording within the same session.

  7. Is advising food allergic patients to avoid food with precautionary allergen labelling out of date?

    PubMed

    Zurzolo, Giovanni A; de Courten, Maximilian; Koplin, Jennifer; Mathai, Michael L; Allen, Katrina J

    2016-06-01

    Precautionary allergen labelling (PAL) continues to be used by the food manufacturing industry to alert the food allergic consumer that cross-contact may have occurred during the supply chain for ingredients or the manufacturing process. This review will summarize recent evidence regarding use and interpretation of precautionary labels by industry, healthcare professionals, and food allergic consumers. Consumers find precautionary labels difficult to interpret and often distrust them as disclaimers of product liability. It is unclear from a clinician's perspective how healthcare professionals should advise their patients regarding these statements. Recent studies suggest that consumers do not always read food labels and that these labels are difficult to interpret and are often distrusted by consumers as disclaimers of liability. There is evidence to suggest that this behaviour occurs in all countries assessed that use PAL. The healthcare professional remains confused about the interpretation and value of the current PAL system as it is unclear whether foods that contain no advisory labels are safe to consume. There is a need for improvement in the value and use of precautionary labelling for allergen risk assessment for allergic consumers. New studies have shown the confusion that currently exists in regard to PAL for the healthcare professional and the consumer alike. The studies have also highlighted certain gaps in the literature that, once addressed, will improve the uniformity of PAL and provide the healthcare professional with appropriate advice which they can in turn relay to the allergic consumer. Because of the global supply of food products there is a need for an international approach in improving PAL.

  8. Overview of Single-Molecule Speckle (SiMS) Microscopy and Its Electroporation-Based Version with Efficient Labeling and Improved Spatiotemporal Resolution.

    PubMed

    Yamashiro, Sawako; Watanabe, Naoki

    2017-07-06

    Live-cell single-molecule imaging was introduced more than a decade ago, and has provided critical information on remodeling of the actin cytoskeleton, the motion of plasma membrane proteins, and dynamics of molecular motor proteins. Actin remodeling has been the best target for this approach because actin and its associated proteins stop diffusing when assembled, allowing visualization of single-molecules of fluorescently-labeled proteins in a state specific manner. The approach based on this simple principle is called Single-Molecule Speckle (SiMS) microscopy. For instance, spatiotemporal regulation of actin polymerization and lifetime distribution of actin filaments can be monitored directly by tracking actin SiMS. In combination with fluorescently labeled probes of various actin regulators, SiMS microscopy has contributed to clarifying the processes underlying recycling, motion and remodeling of the live-cell actin network. Recently, we introduced an electroporation-based method called eSiMS microscopy, with high efficiency, easiness and improved spatiotemporal precision. In this review, we describe the application of live-cell single-molecule imaging to cellular actin dynamics and discuss the advantages of eSiMS microscopy over previous SiMS microscopy.

  9. Label Review Training: Module 1: Label Basics, Page 7

    EPA Pesticide Factsheets

    Page 7, Label Training, Pesticide labels translate results of our extensive evaluations of pesticide products into conditions, directions and precautions that define parameters for use of a pesticide with the goal of ensuring protection of human he

  10. Reproducible nucleation sites for flux dendrites in MgB 2

    NASA Astrophysics Data System (ADS)

    Johansen, T. H.; Shantsev, D. V.; Olsen, Å. A. F.; Roussel, M.; Pan, A. V.; Dou, S. X.

    2007-12-01

    Magneto-optical imaging was used to study dendritic flux penetration in films of MgB 2. By repeating experiments under the same external conditions, reproducible features were seen in the pattern formation; dendrites tend to nucleate from fixed locations along the edge. However, their detailed structure deeper inside the film is never reproduced. The reproducibility in nucleation sites is explained as a result of edge roughness causing field hot spots.

  11. Challenges and Path Forward on Mandatory Allergen Labeling and Voluntary Precautionary Allergen Labeling for a Global Company.

    PubMed

    Yeung, Jupiter; Robert, Marie-Claude

    2018-01-01

    For food manufacturers, the label on a food package is a tool meant to alert consumers to the presence of specific allergens, allowing consumers to make informed decisions and not unnecessarily limit their food choices. Mandatory allergen labeling is used when the allergen is an intentionally added ingredient, whereas voluntary allergen labeling is used when the presence of the allergen is unintentional and may be in the finished product as a result of cross-contact. In a globalized economy, ensuring food safety is a growing challenge for manufacturers. When ingredients and technologies are sourced worldwide from multiple business partners, complexity rises, which can increase the chance for errors, leading to potential harm. Threshold science, Voluntary Incidental Trace Allergen Labelling (VITAL) reference doses, fit-for-purpose analytical technology, and common sense enable us to optimize allergen management for the benefit of allergic consumers. This is a good strategy because all stakeholders share the common goal of making foods safe and wholesome for all. Herein, we recommend that (1) senior management make science-based thresholds a priority for both regulatory authorities and the food industry; (2) VITAL 2.0 be adopted as a risk assessment and risk management tool for precautionary allergen labeling (PAL); (3) a standardized message for PAL, i.e., "may contain x," be used to make it easily understandable to allergic consumers so they can make informed food choices; and (4) validated fit-for-purpose allergen methods be used to meet analytical needs. This is an opportunity for us to speak with one voice and demonstrate that food safety is not a competitive issue, but a shared responsibility. This approach could significantly improve allergic consumers' lives.

  12. An improved immobilized enzyme reactor-mass spectrometry-based label free assay for butyrylcholinesterase ligand screening.

    PubMed

    Vilela, Adriana Ferreira Lopes; Seidl, Cláudia; Lima, Juliana Maria; Cardoso, Carmen Lúcia

    2018-05-15

    Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are key cholinesterase enzymes responsible for the hydrolysis of acetylcholine into choline and acetic acid, an essential process for the restoration of the cholinergic neuron. The loss of cholinergic function in the central nervous system contributes to the cognitive decline associated with advanced age and Alzheimer's disease (AD). Inhibitions assays represent a significant role in the drug discovery process. Herein, we describe an improved label free method to screen and characterize new BChE ligands. The liquid chromatography system uses an immobilized capillary enzyme reactor (ICER) as a low affinity and high selectivity column coupled to a mass spectrometer (MS). The enzyme activity was evaluated by monitoring the choline's precursor ion [M + H] + m/z 104 for a brief period. The method was validated using two known cholinesterase inhibitors tacrine and galanthamine. The IC 50 values were 0.03 ± 0.006 μM and 0.88 ± 0.2 for tacrine and galanthamine respectively, and Ki was 0.11 ± 0.2 for galanthamine. The efficient combination of the huBChE-ICER with sensitive enzymatic assay detection such as MS, improved the reliable, fast identification of new ligands. Moreover, specific direct quantitation of the product contributes to the reduction of false positive and negative results. Copyright © 2018. Published by Elsevier Inc.

  13. Development and evaluation of an automatic labeling technique for spring small grains

    NASA Technical Reports Server (NTRS)

    Crist, E. P.; Malila, W. A. (Principal Investigator)

    1981-01-01

    A labeling technique is described which seeks to associate a sampling entity with a particular crop or crop group based on similarity of growing season and temporal-spectral patterns of development. Human analyst provide contextual information, after which labeling decisions are made automatically. Results of a test of the technique on a large, multi-year data set are reported. Grain labeling accuracies are similar to those achieved by human analysis techniques, while non-grain accuracies are lower. Recommendations for improvments and implications of the test results are discussed.

  14. An efficient and reproducible method for improving growth of a soil alga (Chlorococcum infusionum) for toxicity assays.

    PubMed

    Nam, Sun-Hwa; An, Youn-Joo

    2015-12-01

    This study evaluated five methods of soil inoculation using the soil alga Chlorococcum infusionum to determine the most efficient and reproducible method for promoting the growth of soil algae for toxicity testing. The five techniques included application of C. infusionum in a circle on top of the soil, to a central spot on top of the soil, to a central spot in the subsoil, to one side on top of the soil, and application divided between a circle and a central spot on top of the soil. Of these, the first method generated the greatest amount of chlorophyll fluorescence and was the method with the best reproducibility. We evaluated the applicability of this method in an assessment of the toxicity of copper and nickel to C. infusionum in two representative standard soils. Copper (20-75 mg/kg for OECD soil and 20-60 mg/kg Lufa 2.2 soil) and nickel (400-500 mg/kg for OECD soil and 60-100 mg/kg Lufa 2.2 soil) reduced the chlorophyll fluorescence of C. infusionum when the inoculation was delivered in a circle on top of both soil types. To our knowledge, this is the first study to assess the suitability of different soil algal inoculation methods for terrestrial toxicity testing. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Revisiting the scientific method to improve rigor and reproducibility of immunohistochemistry in reproductive science.

    PubMed

    Manuel, Sharrón L; Johnson, Brian W; Frevert, Charles W; Duncan, Francesca E

    2018-04-21

    Immunohistochemistry (IHC) is a robust scientific tool whereby cellular components are visualized within a tissue, and this method has been and continues to be a mainstay for many reproductive biologists. IHC is highly informative if performed and interpreted correctly, but studies have shown that the general use and reporting of appropriate controls in IHC experiments is low. This omission of the scientific method can result in data that lacks rigor and reproducibility. In this editorial, we highlight key concepts in IHC controls and describe an opportunity for our field to partner with the Histochemical Society to adopt their IHC guidelines broadly as researchers, authors, ad hoc reviewers, editorial board members, and editors-in-chief. Such cross-professional society interactions will ensure that we produce the highest quality data as new technologies emerge that still rely upon the foundations of classic histological and immunohistochemical principles.

  16. Handgrip force steadiness in young and older adults: a reproducibility study.

    PubMed

    Blomkvist, Andreas W; Eika, Fredrik; de Bruin, Eling D; Andersen, Stig; Jorgensen, Martin

    2018-04-02

    Force steadiness is a quantitative measure of the ability to control muscle tonus. It is an independent predictor of functional performance and has shown to correlate well with different degrees of motor impairment following stroke. Despite being clinically relevant, few studies have assessed the validity of measuring force steadiness. The aim of this study was to explore the reproducibility of handgrip force steadiness, and to assess age difference in steadiness. Intrarater reproducibility (the degree to which a rating gives consistent result on separate occasions) was investigated in a test-retest design with seven days between sessions. Ten young and thirty older adults were recruited and handgrip steadiness was tested at 5%, 10% and 25% of maximum voluntary contraction (MVC) using Nintendo Wii Balance Board (WBB). Coefficients of variation were calculated from the mean force produced (CVM) and the target force (CVT). Area between the force curve and the target force line (Area) was also calculated. For the older adults we explored reliability using intraclass correlation coefficient (ICC) and agreement using standard error of measurement (SEM), limits of agreement (LOA) and smallest real difference (SRD). A systematic improvement in handgrip steadiness was found between sessions for all measures (CVM, CVT, Area). CVM and CVT at 5% of MVC showed good to high reliability, while Area had poor reliability for all percentages of MVC. Averaged ICC for CVM, CVT and Area was 0.815, 0.806 and 0.464, respectively. Averaged ICC on 5%, 10%, and 25% of MVC was 0.751, 0.667 and 0.668, respectively. Measures of agreement showed similar trends with better results for CVM and CVT than for Area. Young adults had better handgrip steadiness than older adults across all measures. The CVM and CVT measures demonstrated good reproducibility at lower percentages of MVC using the WBB, and could become relevant measures in the clinical setting. The Area measure had poor reproducibility

  17. Labelling fashion magazine advertisements: Effectiveness of different label formats on social comparison and body dissatisfaction.

    PubMed

    Tiggemann, Marika; Brown, Zoe

    2018-06-01

    The experiment investigated the impact on women's body dissatisfaction of different forms of label added to fashion magazine advertisements. Participants were 340 female undergraduate students who viewed 15 fashion advertisements containing a thin and attractive model. They were randomly allocated to one of five label conditions: no label, generic disclaimer label (indicating image had been digitally altered), consequence label (indicating that viewing images might make women feel bad about themselves), informational label (indicating the model in the advertisement was underweight), or a graphic label (picture of a paint brush). Although exposure to the fashion advertisements resulted in increased body dissatisfaction, there was no significant effect of label type on body dissatisfaction; no form of label demonstrated any ameliorating effect. In addition, the consequence and informational labels resulted in increased perceived realism and state appearance comparison. Yet more extensive research is required before the effective implementation of any form of label. Copyright © 2018 Elsevier Ltd. All rights reserved.

  18. Bar Code Labels

    NASA Technical Reports Server (NTRS)

    1988-01-01

    American Bar Codes, Inc. developed special bar code labels for inventory control of space shuttle parts and other space system components. ABC labels are made in a company-developed anodizing aluminum process and consecutively marketed with bar code symbology and human readable numbers. They offer extreme abrasion resistance and indefinite resistance to ultraviolet radiation, capable of withstanding 700 degree temperatures without deterioration and up to 1400 degrees with special designs. They offer high resistance to salt spray, cleaning fluids and mild acids. ABC is now producing these bar code labels commercially or industrial customers who also need labels to resist harsh environments.

  19. Metaresearch for Evaluating Reproducibility in Ecology and Evolution.

    PubMed

    Fidler, Fiona; Chee, Yung En; Wintle, Bonnie C; Burgman, Mark A; McCarthy, Michael A; Gordon, Ascelin

    2017-03-01

    Recent replication projects in other disciplines have uncovered disturbingly low levels of reproducibility, suggesting that those research literatures may contain unverifiable claims. The conditions contributing to irreproducibility in other disciplines are also present in ecology. These include a large discrepancy between the proportion of "positive" or "significant" results and the average statistical power of empirical research, incomplete reporting of sampling stopping rules and results, journal policies that discourage replication studies, and a prevailing publish-or-perish research culture that encourages questionable research practices. We argue that these conditions constitute sufficient reason to systematically evaluate the reproducibility of the evidence base in ecology and evolution. In some cases, the direct replication of ecological research is difficult because of strong temporal and spatial dependencies, so here, we propose metaresearch projects that will provide proxy measures of reproducibility.

  20. 21 CFR 1302.04 - Location and size of symbol on label and labeling.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Location and size of symbol on label and labeling. 1302.04 Section 1302.04 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE LABELING AND PACKAGING REQUIREMENTS FOR CONTROLLED SUBSTANCES § 1302.04 Location and size of symbol on label...

  1. 21 CFR 1302.04 - Location and size of symbol on label and labeling.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 9 2011-04-01 2011-04-01 false Location and size of symbol on label and labeling. 1302.04 Section 1302.04 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE LABELING AND PACKAGING REQUIREMENTS FOR CONTROLLED SUBSTANCES § 1302.04 Location and size of symbol on label...

  2. 21 CFR 1302.04 - Location and size of symbol on label and labeling.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 9 2012-04-01 2012-04-01 false Location and size of symbol on label and labeling. 1302.04 Section 1302.04 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE LABELING AND PACKAGING REQUIREMENTS FOR CONTROLLED SUBSTANCES § 1302.04 Location and size of symbol on label...

  3. 40 CFR 60.536 - Permanent label, temporary label, and owner's manual.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Performance for New Residential Wood Heaters § 60.536 Permanent label, temporary label, and owner's manual. (a... section. (2) Except for wood heaters subject to § 60.530 (e), (f), or (g), the permanent label shall... material expected to last the lifetime of the wood heater, (iv) Present required information in a manner so...

  4. 40 CFR 60.536 - Permanent label, temporary label, and owner's manual.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Performance for New Residential Wood Heaters § 60.536 Permanent label, temporary label, and owner's manual. (a... section. (2) Except for wood heaters subject to § 60.530 (e), (f), or (g), the permanent label shall... material expected to last the lifetime of the wood heater, (iv) Present required information in a manner so...

  5. 40 CFR 60.536 - Permanent label, temporary label, and owner's manual.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Performance for New Residential Wood Heaters § 60.536 Permanent label, temporary label, and owner's manual. (a... section. (2) Except for wood heaters subject to § 60.530 (e), (f), or (g), the permanent label shall... material expected to last the lifetime of the wood heater, (iv) Present required information in a manner so...

  6. 40 CFR 60.536 - Permanent label, temporary label, and owner's manual.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Performance for New Residential Wood Heaters § 60.536 Permanent label, temporary label, and owner's manual. (a... section. (2) Except for wood heaters subject to § 60.530 (e), (f), or (g), the permanent label shall... material expected to last the lifetime of the wood heater, (iv) Present required information in a manner so...

  7. 40 CFR 60.536 - Permanent label, temporary label, and owner's manual.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Performance for New Residential Wood Heaters § 60.536 Permanent label, temporary label, and owner's manual. (a... section. (2) Except for wood heaters subject to § 60.530 (e), (f), or (g), the permanent label shall... material expected to last the lifetime of the wood heater, (iv) Present required information in a manner so...

  8. A Framework for Reproducible Latent Fingerprint Enhancements.

    PubMed

    Carasso, Alfred S

    2014-01-01

    Photoshop processing of latent fingerprints is the preferred methodology among law enforcement forensic experts, but that appproach is not fully reproducible and may lead to questionable enhancements. Alternative, independent, fully reproducible enhancements, using IDL Histogram Equalization and IDL Adaptive Histogram Equalization, can produce better-defined ridge structures, along with considerable background information. Applying a systematic slow motion smoothing procedure to such IDL enhancements, based on the rapid FFT solution of a Lévy stable fractional diffusion equation, can attenuate background detail while preserving ridge information. The resulting smoothed latent print enhancements are comparable to, but distinct from, forensic Photoshop images suitable for input into automated fingerprint identification systems, (AFIS). In addition, this progressive smoothing procedure can be reexamined by displaying the suite of progressively smoother IDL images. That suite can be stored, providing an audit trail that allows monitoring for possible loss of useful information, in transit to the user-selected optimal image. Such independent and fully reproducible enhancements provide a valuable frame of reference that may be helpful in informing, complementing, and possibly validating the forensic Photoshop methodology.

  9. A Framework for Reproducible Latent Fingerprint Enhancements

    PubMed Central

    Carasso, Alfred S.

    2014-01-01

    Photoshop processing1 of latent fingerprints is the preferred methodology among law enforcement forensic experts, but that appproach is not fully reproducible and may lead to questionable enhancements. Alternative, independent, fully reproducible enhancements, using IDL Histogram Equalization and IDL Adaptive Histogram Equalization, can produce better-defined ridge structures, along with considerable background information. Applying a systematic slow motion smoothing procedure to such IDL enhancements, based on the rapid FFT solution of a Lévy stable fractional diffusion equation, can attenuate background detail while preserving ridge information. The resulting smoothed latent print enhancements are comparable to, but distinct from, forensic Photoshop images suitable for input into automated fingerprint identification systems, (AFIS). In addition, this progressive smoothing procedure can be reexamined by displaying the suite of progressively smoother IDL images. That suite can be stored, providing an audit trail that allows monitoring for possible loss of useful information, in transit to the user-selected optimal image. Such independent and fully reproducible enhancements provide a valuable frame of reference that may be helpful in informing, complementing, and possibly validating the forensic Photoshop methodology. PMID:26601028

  10. Improving classification with forced labeling of other related classes: application to prediction of upstaged ductal carcinoma in situ using mammographic features

    NASA Astrophysics Data System (ADS)

    Hou, Rui; Shi, Bibo; Grimm, Lars J.; Mazurowski, Maciej A.; Marks, Jeffrey R.; King, Lorraine M.; Maley, Carlo C.; Hwang, E. Shelley; Lo, Joseph Y.

    2018-02-01

    Predicting whether ductal carcinoma in situ (DCIS) identified at core biopsy contains occult invasive disease is an import task since these "upstaged" cases will affect further treatment planning. Therefore, a prediction model that better classifies pure DCIS and upstaged DCIS can help avoid overtreatment and overdiagnosis. In this work, we propose to improve this classification performance with the aid of two other related classes: Atypical Ductal Hyperplasia (ADH) and Invasive Ductal Carcinoma (IDC). Our data set contains mammograms for 230 cases. Specifically, 66 of them are ADH cases; 99 of them are biopsy-proven DCIS cases, of whom 25 were found to contain invasive disease at the time of definitive surgery. The remaining 65 cases were diagnosed with IDC at core biopsy. Our hypothesis is that knowledge can be transferred from training with the easier and more readily available cases of benign but suspicious ADH versus IDC that is already apparent at initial biopsy. Thus, embedding both ADH and IDC cases to the classifier will improve the performance of distinguishing upstaged DCIS from pure DCIS. We extracted 113 mammographic features based on a radiologist's annotation of clusters.Our method then added both ADH and IDC cases during training, where ADH were "force labeled" or treated by the classifier as pure DCIS (negative) cases, and IDC were labeled as upstaged DCIS (positive) cases. A logistic regression classifier was built based on the designed training dataset to perform a prediction of whether biopsy-proven DCIS cases contain invasive cancer. The performance was assessed by repeated 5-fold CrossValidation and Receiver Operating Characteristic(ROC) curve analysis. While prediction performance with only training on DCIS dataset had an average AUC of 0.607(%95CI, 0.479-0.721). By adding both ADH and IDC cases for training, we improved the performance to 0.691(95%CI, 0.581-0.801).

  11. Direct synthesis of ESBO derivatives-¹⁸O labelled with dioxirane.

    PubMed

    La Tegola, Stefano; Annese, Cosimo; Suman, Michele; Tommasi, Immacolata; Fusco, Caterina; D'Accolti, Lucia

    2013-01-01

    This work addresses a new approach developed in our laboratory, consisting in the application of isolated dimethyldioxirane (DDO, 1a) labelled with ¹⁸O for synthesis of epoxidized glyceryl linoleate (Gly-LLL, 2). We expect that this work could contribute in improving analytical methods for the determination of epoxidized soybean oil (ESBO) in complex food matrices by adopting an ¹⁸O-labelled-epoxidized triacylglycerol as an internal standard.

  12. An assessment of pharmacists' readiness for paperless labeling: a national survey.

    PubMed

    Ho, Yun-Xian; Chen, Qingxia; Nian, Hui; Johnson, Kevin B

    2014-01-01

    To assess the state of readiness for the adoption of paperless labeling among a nationally representative sample of pharmacies, including chain pharmacies, independent retail pharmacies, hospitals, and other rural or urban dispensing sites. Both quantitative and qualitative analyses were used to analyze responses to a cross-sectional survey disseminated to American Pharmacists Association pharmacists nationwide. The survey assessed factors related to pharmacists' attitudinal readiness (ie, perceptions of impact) and pharmacies' structural readiness (eg, availability of electronic resources, internet access) for the paperless labeling initiative. We received a total of 436 survey responses (6% response rate) from pharmacists representing 44 US states and territories. Across the spectrum of settings we studied, pharmacists had work access to computers, printers, fax machines and access to the internet or intranet. Approximately 79% of respondents believed that the initiative would improve the adequacy of drug information available in their work site and 95% believed it would either not change (33%) or would improve (62%) communication to patients. Overall, respondents' comments supported advancing the initiative; however, some comments revealed reservations regarding corporate or pharmacy buy-in, success of implementation, and ease of adoption. This is the first nationwide study to report about pharmacists' perspectives on paperless labeling. In general, pharmacists believe they are ready and that their pharmacies are well equipped for the transition to paperless labeling. Further exploration of perspectives from product label manufacturers and corporate pharmacy offices is needed to understand fully what will be necessary to complete this transition.

  13. Synthesis of γ-Phosphate-Labeled and Doubly Labeled Adenosine Triphosphate Analogs.

    PubMed

    Hacker, Stephan M; Welter, Moritz; Marx, Andreas

    2015-03-09

    This unit describes the synthesis of γ-phosphate-labeled and doubly labeled adenosine triphosphate (ATP) analogs and their characterization using the phosphodiesterase I from Crotalus adamanteus (snake venom phosphodiesterase; SVPD). In the key step of the synthesis, ATP or an ATP analog, bearing a linker containing a trifluoroacetamide group attached to the nucleoside, are modified with an azide-containing linker at the terminal phosphate using an alkylation reaction. Subsequently, different labels are introduced to the linkers by transformation of one functional group to an amine and coupling to an N-hydroxysuccinimide ester. Specifically, the Staudinger reaction of the azide is employed as a straightforward means to obtain an amine in the presence of various labels. Furthermore, the fluorescence characteristics of a fluorogenic, doubly labeled ATP analog are investigated following enzymatic cleavage by SVPD. Copyright © 2015 John Wiley & Sons, Inc.

  14. Style-independent document labeling: design and performance evaluation

    NASA Astrophysics Data System (ADS)

    Mao, Song; Kim, Jong Woo; Thoma, George R.

    2003-12-01

    The Medical Article Records System or MARS has been developed at the U.S. National Library of Medicine (NLM) for automated data entry of bibliographical information from medical journals into MEDLINE, the premier bibliographic citation database at NLM. Currently, a rule-based algorithm (called ZoneCzar) is used for labeling important bibliographical fields (title, author, affiliation, and abstract) on medical journal article page images. While rules have been created for medical journals with regular layout types, new rules have to be manually created for any input journals with arbitrary or new layout types. Therefore, it is of interest to label any journal articles independent of their layout styles. In this paper, we first describe a system (called ZoneMatch) for automated generation of crucial geometric and non-geometric features of important bibliographical fields based on string-matching and clustering techniques. The rule based algorithm is then modified to use these features to perform style-independent labeling. We then describe a performance evaluation method for quantitatively evaluating our algorithm and characterizing its error distributions. Experimental results show that the labeling performance of the rule-based algorithm is significantly improved when the generated features are used.

  15. Central Corneal Thickness Reproducibility among Ten Different Instruments.

    PubMed

    Pierro, Luisa; Iuliano, Lorenzo; Gagliardi, Marco; Ambrosi, Alessandro; Rama, Paolo; Bandello, Francesco

    2016-11-01

    To assess agreement between one ultrasonic (US) and nine optical instruments for the measurement of central corneal thickness (CCT), and to evaluate intra- and inter-operator reproducibility. In this observational cross-sectional study, two masked operators measured CCT thickness twice in 28 healthy eyes. We used seven spectral-domain optical coherence tomography (SD-OCT) devices, one time-domain OCT, one Scheimpflug camera, and one US-based instrument. Inter- and intra-operator reproducibility was evaluated by intraclass correlation coefficient (ICC), coefficient of variation (CV), and Bland-Altman test analysis. Instrument-to-instrument reproducibility was determined by ANOVA for repeated measurements. We also tested how the devices disagreed regarding systemic bias and random error using a structural equation model. Mean CCT of all instruments ranged from 536 ± 42 μm to 577 ± 40 μm. An instrument-to-instrument correlation test showed high values among the 10 investigated devices (correlation coefficient range 0.852-0.995; p values <0.0001 in all cases). The highest correlation coefficient values were registered between 3D OCT-2000 Topcon-Spectral OCT/SLO Opko (0.995) and Cirrus HD-OCT Zeiss-RS-3000 Nidek (0.995), whereas the lowest were seen between SS-1000 CASIA and Spectral OCT/SLO Opko (0.852). ICC and CV showed excellent inter- and intra-operator reproducibility for all optic-based devices, except for the US-based device. Bland-Altman analysis demonstrated low mean biases between operators. Despite highlighting good intra- and inter-operator reproducibility, we found that a scale bias between instruments might interfere with thorough CCT monitoring. We suggest that optimal monitoring is achieved with the same operator and the same device.

  16. Reproducibility of ZrO2-based freeze casting for biomaterials.

    PubMed

    Naleway, Steven E; Fickas, Kate C; Maker, Yajur N; Meyers, Marc A; McKittrick, Joanna

    2016-04-01

    The processing technique of freeze casting has been intensely researched for its potential to create porous scaffold and infiltrated composite materials for biomedical implants and structural materials. However, in order for this technique to be employed medically or commercially, it must be able to reliably produce materials in great quantities with similar microstructures and properties. Here we investigate the reproducibility of the freeze casting process by independently fabricating three sets of eight ZrO2-epoxy composite scaffolds with the same processing conditions but varying solid loading (10, 15 and 20 vol.%). Statistical analyses (One-way ANOVA and Tukey's HSD tests) run upon measurements of the microstructural dimensions of these composite scaffold sets show that, while the majority of microstructures are similar, in all cases the composite scaffolds display statistically significant variability. In addition, composite scaffolds where mechanically compressed and statistically analyzed. Similar to the microstructures, almost all of their resultant properties displayed significant variability though most composite scaffolds were similar. These results suggest that additional research to improve control of the freeze casting technique is required before scaffolds and composite scaffolds can reliably be reproduced for commercial or medical applications. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. 78 FR 24211 - Draft Guidance for Industry on Safety Considerations for Container Labels and Carton Labeling...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-24

    ... container labels and carton labeling design, is the second in a series of three planned guidance documents...] Draft Guidance for Industry on Safety Considerations for Container Labels and Carton Labeling Design To... entitled ``Safety Considerations for Container Labels and Carton Labeling Design to Minimize Medication...

  18. Magnetic Resonance Imaging of Iron Oxide-Labeled Human Embryonic Stem Cell-Derived Cardiac Progenitors.

    PubMed

    Skelton, Rhys J P; Khoja, Suhail; Almeida, Shone; Rapacchi, Stanislas; Han, Fei; Engel, James; Zhao, Peng; Hu, Peng; Stanley, Edouard G; Elefanty, Andrew G; Kwon, Murray; Elliott, David A; Ardehali, Reza

    2016-01-01

    Given the limited regenerative capacity of the heart, cellular therapy with stem cell-derived cardiac cells could be a potential treatment for patients with heart disease. However, reliable imaging techniques to longitudinally assess engraftment of the transplanted cells are scant. To address this issue, we used ferumoxytol as a labeling agent of human embryonic stem cell-derived cardiac progenitor cells (hESC-CPCs) to facilitate tracking by magnetic resonance imaging (MRI) in a large animal model. Differentiating hESCs were exposed to ferumoxytol at different time points and varying concentrations. We determined that treatment with ferumoxytol at 300 μg/ml on day 0 of cardiac differentiation offered adequate cell viability and signal intensity for MRI detection without compromising further differentiation into definitive cardiac lineages. Labeled hESC-CPCs were transplanted by open surgical methods into the left ventricular free wall of uninjured pig hearts and imaged both ex vivo and in vivo. Comprehensive T2*-weighted images were obtained immediately after transplantation and 40 days later before termination. The localization and dispersion of labeled cells could be effectively imaged and tracked at days 0 and 40 by MRI. Thus, under the described conditions, ferumoxytol can be used as a long-term, differentiation-neutral cell-labeling agent to track transplanted hESC-CPCs in vivo using MRI. The development of a safe and reproducible in vivo imaging technique to track the fate of transplanted human embryonic stem cell-derived cardiac progenitor cells (hESC-CPCs) is a necessary step to clinical translation. An iron oxide nanoparticle (ferumoxytol)-based approach was used for cell labeling and subsequent in vivo magnetic resonance imaging monitoring of hESC-CPCs transplanted into uninjured pig hearts. The present results demonstrate the use of ferumoxytol labeling and imaging techniques in tracking the location and dispersion of cell grafts, highlighting its

  19. Differential protein expression analysis using stable isotope labeling and PQD linear ion trap MS technology.

    PubMed

    Armenta, Jenny M; Hoeschele, Ina; Lazar, Iulia M

    2009-07-01

    An isotope tags for relative and absolute quantitation (iTRAQ)-based reversed-phase liquid chromatography (RPLC)-tandem mass spectrometry (MS/MS) method was developed for differential protein expression profiling in complex cellular extracts. The estrogen positive MCF-7 cell line, cultured in the presence of 17beta-estradiol (E2) and tamoxifen (Tam), was used as a model system. MS analysis was performed with a linear trap quadrupole (LTQ) instrument operated by using pulsed Q dissociation (PQD) detection. Optimization experiments were conducted to maximize the iTRAQ labeling efficiency and the number of quantified proteins. MS data filtering criteria were chosen to result in a false positive identification rate of <4%. The reproducibility of protein identifications was approximately 60%-67% between duplicate, and approximately 50% among triplicate LC-MS/MS runs, respectively. The run-to-run reproducibility, in terms of relative standard deviations (RSD) of global mean iTRAQ ratios, was better than 10%. The quantitation accuracy improved with the number of peptides used for protein identification. From a total of 530 identified proteins (P < 0.001) in the E2/Tam treated MCF-7 cells, a list of 255 proteins (quantified by at least two peptides) was generated for differential expression analysis. A method was developed for the selection, normalization, and statistical evaluation of such datasets. An approximate approximately 2-fold change in protein expression levels was necessary for a protein to be selected as a biomarker candidate. According to this data processing strategy, approximately 16 proteins involved in biological processes such as apoptosis, RNA processing/metabolism, DNA replication/transcription/repair, cell proliferation and metastasis, were found to be up- or down-regulated.

  20. Metaresearch for Evaluating Reproducibility in Ecology and Evolution

    PubMed Central

    Fidler, Fiona; Chee, Yung En; Wintle, Bonnie C.; Burgman, Mark A.; McCarthy, Michael A.; Gordon, Ascelin

    2017-01-01

    Abstract Recent replication projects in other disciplines have uncovered disturbingly low levels of reproducibility, suggesting that those research literatures may contain unverifiable claims. The conditions contributing to irreproducibility in other disciplines are also present in ecology. These include a large discrepancy between the proportion of “positive” or “significant” results and the average statistical power of empirical research, incomplete reporting of sampling stopping rules and results, journal policies that discourage replication studies, and a prevailing publish-or-perish research culture that encourages questionable research practices. We argue that these conditions constitute sufficient reason to systematically evaluate the reproducibility of the evidence base in ecology and evolution. In some cases, the direct replication of ecological research is difficult because of strong temporal and spatial dependencies, so here, we propose metaresearch projects that will provide proxy measures of reproducibility. PMID:28596617

  1. Rationale and design of a randomized trial to evaluate an evidence-based prescription drug label on actual medication use.

    PubMed

    Shrank, William H; Parker, Ruth; Davis, Terry; Pandit, Anjali U; Knox, Joann P; Moraras, Pear; Rademaker, Alfred; Wolf, Michael S

    2010-11-01

    Medication errors are an important public health concern, and poor understanding of medication labels are a root cause. Research shows that labels are variable, of poor quality, and not patient-centered. No real-world trials have evaluated whether improved medication labels can affect appropriate medication use, adherence or health outcomes. We developed an evidence-based prescription label that addresses both content and format. The enhanced label includes a universal medication schedule (UMS) that standardizes the directions for use incorporating 1) standard time periods for administration (morning, noon, evening, and bedtime), 2) numeric vs. alpha characters, 3) 'carriage returns' to separate daily dose and 4) a graphic aid to visually depict dose and frequency. We will evaluate the effect of providing this label to randomly sampled patients who receive their care from free clinics, mobile vans and federally qualified health centers (FQHCs) in Northern Virginia. We will recruit patients with diabetes or hypertension; these patients will be randomly assigned to receive all of their medications with improved labels or to receive prescriptions with standard labels. The primary outcome will be the patient's ability to correctly demonstrate dosing instructions. Other outcomes include adherence, error rates and health outcomes. To our knowledge, this trial is the first to evaluate the effect of prescription label improvement on understanding, medication use and outcomes in a clinical setting. If successful, these findings could be implemented broadly to promote safe and appropriate medication use and to support evidence-based standards in the development of labels. Copyright © 2010 Elsevier Inc. All rights reserved.

  2. An International Ki67 Reproducibility Study

    PubMed Central

    2013-01-01

    Background In breast cancer, immunohistochemical assessment of proliferation using the marker Ki67 has potential use in both research and clinical management. However, lack of consistency across laboratories has limited Ki67’s value. A working group was assembled to devise a strategy to harmonize Ki67 analysis and increase scoring concordance. Toward that goal, we conducted a Ki67 reproducibility study. Methods Eight laboratories received 100 breast cancer cases arranged into 1-mm core tissue microarrays—one set stained by the participating laboratory and one set stained by the central laboratory, both using antibody MIB-1. Each laboratory scored Ki67 as percentage of positively stained invasive tumor cells using its own method. Six laboratories repeated scoring of 50 locally stained cases on 3 different days. Sources of variation were analyzed using random effects models with log2-transformed measurements. Reproducibility was quantified by intraclass correlation coefficient (ICC), and the approximate two-sided 95% confidence intervals (CIs) for the true intraclass correlation coefficients in these experiments were provided. Results Intralaboratory reproducibility was high (ICC = 0.94; 95% CI = 0.93 to 0.97). Interlaboratory reproducibility was only moderate (central staining: ICC = 0.71, 95% CI = 0.47 to 0.78; local staining: ICC = 0.59, 95% CI = 0.37 to 0.68). Geometric mean of Ki67 values for each laboratory across the 100 cases ranged 7.1% to 23.9% with central staining and 6.1% to 30.1% with local staining. Factors contributing to interlaboratory discordance included tumor region selection, counting method, and subjective assessment of staining positivity. Formal counting methods gave more consistent results than visual estimation. Conclusions Substantial variability in Ki67 scoring was observed among some of the world’s most experienced laboratories. Ki67 values and cutoffs for clinical decision-making cannot be transferred between laboratories without

  3. Off-Label Drug Use

    MedlinePlus

    ... their drugs for off-label uses. Off-label marketing is very different from off-label use. Why ... at a higher risk for medication errors, side effects, and unwanted drug reactions. It’s important that the ...

  4. Pesticide Label Review Training

    EPA Pesticide Factsheets

    This training will help ensure that reviewers evaluate labels according to four core principles. It also will help pesticide registrants developing labels understand what EPA expects of pesticide labels, and what the Agency generally finds acceptable.

  5. The US FDA pregnancy lactation and labeling rule - Implications for maternal immunization.

    PubMed

    Gruber, Marion F

    2015-11-25

    The FDA has responsibility for ensuring that prescription drug and biological products including vaccines are accompanied by labeling that summarizes scientific information concerning their safe and effective use. As part of a broader effort to improve the content and format of prescription drug labeling FDA published a final rule, the Content and Format of Labeling for Human Prescription Drug and Biological Products; Requirements for Pregnancy and Lactation Labeling, referred to as the "Pregnancy and Lactation Labeling Rule (PLLR)." The most significant change to be implemented by this Rule is the removal of the letter risk categories A, B, C, D and X from all labeling, replacing them with a narrative summary of the risks of using a drug or biological product including vaccines during pregnancy. The PLLR requires an evaluation of available information about a product's use in pregnancy and provides an opportunity to update labeling when new information about use of a vaccine in pregnancy becomes available. Implementation of the provisions articulated in the PLLR, as they apply to vaccine product labeling, will require close collaboration between FDA and the vaccine manufacturer for both currently licensed vaccines and those in development. Copyright © 2015 The Author. Published by Elsevier Ltd.. All rights reserved.

  6. 46 CFR 56.80-10 - Forming (reproduces 129.2).

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Forming (reproduces 129.2). 56.80-10 Section 56.80-10 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PIPING SYSTEMS AND APPURTENANCES Bending and Forming § 56.80-10 Forming (reproduces 129.2). (a) Piping components may be formed...

  7. 46 CFR 56.80-10 - Forming (reproduces 129.2).

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 2 2011-10-01 2011-10-01 false Forming (reproduces 129.2). 56.80-10 Section 56.80-10 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PIPING SYSTEMS AND APPURTENANCES Bending and Forming § 56.80-10 Forming (reproduces 129.2). (a) Piping components may be formed...

  8. Reproducibility of tumor motion probability distribution function in stereotactic body radiation therapy of lung cancer.

    PubMed

    Zhang, Fan; Hu, Jing; Kelsey, Chris R; Yoo, David; Yin, Fang-Fang; Cai, Jing

    2012-11-01

    To evaluate the reproducibility of tumor motion probability distribution function (PDF) in stereotactic body radiation therapy (SBRT) of lung cancer using cine megavoltage (MV) images. Cine MV images of 20 patients acquired during three-dimensional conformal (6-11 beams) SBRT treatments were retrospectively analyzed to extract tumor motion trajectories. For each patient, tumor motion PDFs were generated per fraction (PDF(n)) using three selected "usable" beams. Patients without at least three usable beams were excluded from the study. Fractional PDF reproducibility (R(n)) was calculated as the Dice similarity coefficient between PDF(n) to a "ground-truth" PDF (PDF(g)), which was generated using the selected beams of all fractions. The mean of R(n), labeled as R(m), was calculated for each patient and correlated to the patient's mean tumor motion rang (A(m)). Change of R(m) during the course of SBRT treatments was also evaluated. Intra- and intersubject coefficient of variation (CV) of R(m) and A(m) were determined. Thirteen patients had at least three usable beams and were analyzed. The mean of R(m) was 0.87 (range, 0.84-0.95). The mean of A(m) was 3.18 mm (range, 0.46-7.80 mm). R(m) was found to decrease as A(m) increases following an equation of R(m) = 0.17e(-0.9Am) + 0.84. R(m) also decreased slightly throughout the course of treatments. Intersubject CV of R(m) (0.05) was comparable to intrasubject CV of R(m) (range, 0.02-0.09); intersubject CV of A(m) (0.73) was significantly greater than intrasubject CV of A(m) (range, 0.09-0.24). Tumor motion PDF can be determined using cine MV images acquired during the treatments. The reproducibility of lung tumor motion PDF decreased exponentially as the tumor motion range increased and decreased slightly throughout the course of the treatments. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Composting in small laboratory pilots: Performance and reproducibility

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

    Lashermes, G.; Barriuso, E.; Le Villio-Poitrenaud, M.

    2012-02-15

    Highlights: Black-Right-Pointing-Pointer We design an innovative small-scale composting device including six 4-l reactors. Black-Right-Pointing-Pointer We investigate the performance and reproducibility of composting on a small scale. Black-Right-Pointing-Pointer Thermophilic conditions are established by self-heating in all replicates. Black-Right-Pointing-Pointer Biochemical transformations, organic matter losses and stabilisation are realistic. Black-Right-Pointing-Pointer The organic matter evolution exhibits good reproducibility for all six replicates. - Abstract: Small-scale reactors (<10 l) have been employed in composting research, but few attempts have assessed the performance of composting considering the transformations of organic matter. Moreover, composting at small scales is often performed by imposing a fixed temperature, thus creatingmore » artificial conditions, and the reproducibility of composting has rarely been reported. The objectives of this study are to design an innovative small-scale composting device safeguarding self-heating to drive the composting process and to assess the performance and reproducibility of composting in small-scale pilots. The experimental setup included six 4-l reactors used for composting a mixture of sewage sludge and green wastes. The performance of the process was assessed by monitoring the temperature, O{sub 2} consumption and CO{sub 2} emissions, and characterising the biochemical evolution of organic matter. A good reproducibility was found for the six replicates with coefficients of variation for all parameters generally lower than 19%. An intense self-heating ensured the existence of a spontaneous thermophilic phase in all reactors. The average loss of total organic matter (TOM) was 46% of the initial content. Compared to the initial mixture, the hot water soluble fraction decreased by 62%, the hemicellulose-like fraction by 68%, the cellulose-like fraction by 50% and the lignin-like fractions by 12% in the

  10. Reproducible Tissue Homogenization and Protein Extraction for Quantitative Proteomics Using MicroPestle-Assisted Pressure-Cycling Technology.

    PubMed

    Shao, Shiying; Guo, Tiannan; Gross, Vera; Lazarev, Alexander; Koh, Ching Chiek; Gillessen, Silke; Joerger, Markus; Jochum, Wolfram; Aebersold, Ruedi

    2016-06-03

    The reproducible and efficient extraction of proteins from biopsy samples for quantitative analysis is a critical step in biomarker and translational research. Recently, we described a method consisting of pressure-cycling technology (PCT) and sequential windowed acquisition of all theoretical fragment ions-mass spectrometry (SWATH-MS) for the rapid quantification of thousands of proteins from biopsy-size tissue samples. As an improvement of the method, we have incorporated the PCT-MicroPestle into the PCT-SWATH workflow. The PCT-MicroPestle is a novel, miniaturized, disposable mechanical tissue homogenizer that fits directly into the microTube sample container. We optimized the pressure-cycling conditions for tissue lysis with the PCT-MicroPestle and benchmarked the performance of the system against the conventional PCT-MicroCap method using mouse liver, heart, brain, and human kidney tissues as test samples. The data indicate that the digestion of the PCT-MicroPestle-extracted proteins yielded 20-40% more MS-ready peptide mass from all tissues tested with a comparable reproducibility when compared to the conventional PCT method. Subsequent SWATH-MS analysis identified a higher number of biologically informative proteins from a given sample. In conclusion, we have developed a new device that can be seamlessly integrated into the PCT-SWATH workflow, leading to increased sample throughput and improved reproducibility at both the protein extraction and proteomic analysis levels when applied to the quantitative proteomic analysis of biopsy-level samples.

  11. Reproducibility of Search Strategies Is Poor in Systematic Reviews Published in High-Impact Pediatrics, Cardiology and Surgery Journals: A Cross-Sectional Study

    PubMed Central

    2016-01-01

    Background A high-quality search strategy is considered an essential component of systematic reviews but many do not contain reproducible search strategies. It is unclear if low reproducibility spans medical disciplines, is affected by librarian/search specialist involvement or has improved with increased awareness of reporting guidelines. Objectives To examine the reporting of search strategies in systematic reviews published in Pediatrics, Surgery or Cardiology journals in 2012 and determine rates and predictors of including a reproducible search strategy. Methods We identified all systematic reviews published in 2012 in the ten highest impact factor journals in Pediatrics, Surgery and Cardiology. Each search strategy was coded to indicate what elements were reported and whether the overall search was reproducible. Reporting and reproducibility rates were compared across disciplines and we measured the influence of librarian/search specialist involvement, discipline or endorsement of a reporting guideline on search reproducibility. Results 272 articles from 25 journals were included. Reporting of search elements ranged widely from 91% of articles naming search terms to 33% providing a full search strategy and 22% indicating the date the search was executed. Only 22% of articles provided at least one reproducible search strategy and 13% provided a reproducible strategy for all databases searched in the article. Librarians or search specialists were reported as involved in 17% of articles. There were strong disciplinary differences on the reporting of search elements. In the multivariable analysis, only discipline (Pediatrics) was a significant predictor of the inclusion of a reproducible search strategy. Conclusions Despite recommendations to report full, reproducible search strategies, many articles still do not. In addition, authors often report a single strategy as covering all databases searched, further decreasing reproducibility. Further research is needed

  12. Towards the Geometry of Reproducing Kernels

    NASA Astrophysics Data System (ADS)

    Galé, J. E.

    2010-11-01

    It is shown here how one is naturally led to consider a category whose objects are reproducing kernels of Hilbert spaces, and how in this way a differential geometry for such kernels may be settled down.

  13. Comment on "Estimating the reproducibility of psychological science".

    PubMed

    Gilbert, Daniel T; King, Gary; Pettigrew, Stephen; Wilson, Timothy D

    2016-03-04

    A paper from the Open Science Collaboration (Research Articles, 28 August 2015, aac4716) attempting to replicate 100 published studies suggests that the reproducibility of psychological science is surprisingly low. We show that this article contains three statistical errors and provides no support for such a conclusion. Indeed, the data are consistent with the opposite conclusion, namely, that the reproducibility of psychological science is quite high. Copyright © 2016, American Association for the Advancement of Science.

  14. Prognostic Value and Reproducibility of Pretreatment CT Texture Features in Stage III Non-Small Cell Lung Cancer

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

    Fried, David V.; Graduate School of Biomedical Sciences, The University of Texas Health Science Center at Houston, Houston, Texas; Tucker, Susan L.

    2014-11-15

    Purpose: To determine whether pretreatment CT texture features can improve patient risk stratification beyond conventional prognostic factors (CPFs) in stage III non-small cell lung cancer (NSCLC). Methods and Materials: We retrospectively reviewed 91 cases with stage III NSCLC treated with definitive chemoradiation therapy. All patients underwent pretreatment diagnostic contrast enhanced computed tomography (CE-CT) followed by 4-dimensional CT (4D-CT) for treatment simulation. We used the average-CT and expiratory (T50-CT) images from the 4D-CT along with the CE-CT for texture extraction. Histogram, gradient, co-occurrence, gray tone difference, and filtration-based techniques were used for texture feature extraction. Penalized Cox regression implementing cross-validation wasmore » used for covariate selection and modeling. Models incorporating texture features from the 33 image types and CPFs were compared to those with models incorporating CPFs alone for overall survival (OS), local-regional control (LRC), and freedom from distant metastases (FFDM). Predictive Kaplan-Meier curves were generated using leave-one-out cross-validation. Patients were stratified based on whether their predicted outcome was above or below the median. Reproducibility of texture features was evaluated using test-retest scans from independent patients and quantified using concordance correlation coefficients (CCC). We compared models incorporating the reproducibility seen on test-retest scans to our original models and determined the classification reproducibility. Results: Models incorporating both texture features and CPFs demonstrated a significant improvement in risk stratification compared to models using CPFs alone for OS (P=.046), LRC (P=.01), and FFDM (P=.005). The average CCCs were 0.89, 0.91, and 0.67 for texture features extracted from the average-CT, T50-CT, and CE-CT, respectively. Incorporating reproducibility within our models yielded 80.4% (±3.7% SD), 78.3% (±4.0% SD

  15. Determination of N-glycans by high performance liquid chromatography using 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate as the glycosylamine labeling reagent.

    PubMed

    Wu, Yike; Sha, Qiuyue; Du, Juan; Wang, Chang; Zhang, Liang; Liu, Bi-Feng; Lin, Yawei; Liu, Xin

    2018-02-02

    Robust, efficient identification and accurate quantification of N-glycans are of great significance in N-glycomics analysis. Here, a simple and rapid derivatization method, based on the combination of microwave-assisted deglycosylation and 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) labeling, was developed for the analysis of N-glycan by high performance liquid chromatography with fluorescence detection (HPLC-FLD). After optimizing various parameters affecting deglycosylation and derivatization by RNase B, the time for N-glycan labeling was shortened to 50 min with ∼10-fold enhancement in detection sensitivity comparing to conventional 2-aminobenzoic acid (2-AA) labeling method. Additionally, the method showed good linearity (correlation coefficients > 0.991) and reproducibility (RSD < 8.7%). These advantages of the proposed method were further validated by the analysis of complex samples, including fetuin and human serum. Investigation of serum N-glycome for preliminary diagnosis of human lung cancer was conducted, where significant changes of several N-glycans corresponding to core-fucosylated, mono- and disialylated glycans have been evidenced by a series of statistical analysis. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. Data Identifiers and Citations Enable Reproducible Science

    NASA Astrophysics Data System (ADS)

    Tilmes, C.

    2011-12-01

    Modern science often involves data processing with tremendous volumes of data. Keeping track of that data has been a growing challenge for data center. Researchers who access and use that data don't always reference and cite their data sources adequately for consumers of their research to follow their methodology or reproduce their analyses or experiments. Recent research has led to recommendations for good identifiers and citations that can help address this problem. This paper will describe some of the best practices in data identifiers, reference and citation. Using a simplified example scenario based on a long term remote sensing satellite mission, it will explore issues in identifying dynamic data sets and the importance of good data citations for reproducibility. It will describe the difference between granule and collection level identifiers, using UUIDs and DOIs to illustrate some recommendations for developing identifiers and assigning them during data processing. As data processors create data products, the provenance of the input products and precise steps that led to their creation are recorded and published for users of the data to see. As researchers access the data from an archive, they can use the provenance to help understand the genesis of the data, which could have effects on their usage of the data. By citing the data on publishing their research, others can retrieve the precise data used in their research and reproduce the analyses and experiments to confirm the results. Describing the experiment to a sufficient extent to reproduce the research enforces a formal approach that lends credibility to the results, and ultimately, to the policies of decision makers depending on that research.

  17. Repeatability and Reproducibility of Virtual Subjective Refraction.

    PubMed

    Perches, Sara; Collados, M Victoria; Ares, Jorge

    2016-10-01

    To establish the repeatability and reproducibility of a virtual refraction process using simulated retinal images. With simulation software, aberrated images corresponding with each step of the refraction process were calculated following the typical protocol of conventional subjective refraction. Fifty external examiners judged simulated retinal images until the best sphero-cylindrical refraction and the best visual acuity were achieved starting from the aberrometry data of three patients. Data analyses were performed to assess repeatability and reproducibility of the virtual refraction as a function of pupil size and aberrometric profile of different patients. SD values achieved in three components of refraction (M, J0, and J45) are lower than 0.25D in repeatability analysis. Regarding reproducibility, we found SD values lower than 0.25D in the most cases. When the results of virtual refraction with different pupil diameters (4 and 6 mm) were compared, the mean of differences (MoD) obtained were not clinically significant (less than 0.25D). Only one of the aberrometry profiles with high uncorrected astigmatism shows poor results for the M component in reproducibility and pupil size dependence analysis. In all cases, vision achieved was better than 0 logMAR. A comparison between the compensation obtained with virtual and conventional subjective refraction was made as an example of this application, showing good quality retinal images in both processes. The present study shows that virtual refraction has similar levels of precision as conventional subjective refraction. Moreover, virtual refraction has also shown that when high low order astigmatism is present, the refraction result is less precise and highly dependent on pupil size.

  18. Stable isotope labelling methods in mass spectrometry-based quantitative proteomics.

    PubMed

    Chahrour, Osama; Cobice, Diego; Malone, John

    2015-09-10

    Mass-spectrometry based proteomics has evolved as a promising technology over the last decade and is undergoing a dramatic development in a number of different areas, such as; mass spectrometric instrumentation, peptide identification algorithms and bioinformatic computational data analysis. The improved methodology allows quantitative measurement of relative or absolute protein amounts, which is essential for gaining insights into their functions and dynamics in biological systems. Several different strategies involving stable isotopes label (ICAT, ICPL, IDBEST, iTRAQ, TMT, IPTL, SILAC), label-free statistical assessment approaches (MRM, SWATH) and absolute quantification methods (AQUA) are possible, each having specific strengths and weaknesses. Inductively coupled plasma mass spectrometry (ICP-MS), which is still widely recognised as elemental detector, has recently emerged as a complementary technique to the previous methods. The new application area for ICP-MS is targeting the fast growing field of proteomics related research, allowing absolute protein quantification using suitable elemental based tags. This document describes the different stable isotope labelling methods which incorporate metabolic labelling in live cells, ICP-MS based detection and post-harvest chemical label tagging for protein quantification, in addition to summarising their pros and cons. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. A new approach of light microscopic immunohistochemical triple-staining: combination of Fos labeling with diaminobenzidine-nickel and neuropeptides labeled with Alexa488 and Alexa555 fluorescent dyes.

    PubMed

    Majercikova, Z; Weering, H van; Scsukova, S; Mikkelsen, J D; Kiss, A

    2012-10-01

    neuropeptides labeled with Alexa488 and Alexa555 on cryo-processed 35-40 µm thick free-floating brain sections is an excellent approach providing further advantages for quick and reproducible triple immuno-staining enabling to compare the activity of at least two phenotypes of neurons on the same section. Alexa488 and Alexa555 fluorescent dyes, Fos, hypocretin, melanin-concentrating hormone, cryostat sections, triple labeling immunohistochemistry, rat.

  20. Decoding DNA labels by melting curve analysis using real-time PCR.

    PubMed

    Balog, József A; Fehér, Liliána Z; Puskás, László G

    2017-12-01

    Synthetic DNA has been used as an authentication code for a diverse number of applications. However, existing decoding approaches are based on either DNA sequencing or the determination of DNA length variations. Here, we present a simple alternative protocol for labeling different objects using a small number of short DNA sequences that differ in their melting points. Code amplification and decoding can be done in two steps using quantitative PCR (qPCR). To obtain a DNA barcode with high complexity, we defined 8 template groups, each having 4 different DNA templates, yielding 158 (>2.5 billion) combinations of different individual melting temperature (Tm) values and corresponding ID codes. The reproducibility and specificity of the decoding was confirmed by using the most complex template mixture, which had 32 different products in 8 groups with different Tm values. The industrial applicability of our protocol was also demonstrated by labeling a drone with an oil-based paint containing a predefined DNA code, which was then successfully decoded. The method presented here consists of a simple code system based on a small number of synthetic DNA sequences and a cost-effective, rapid decoding protocol using a few qPCR reactions, enabling a wide range of authentication applications.

  1. Opinion: Is science really facing a reproducibility crisis, and do we need it to?

    PubMed Central

    Fanelli, Daniele

    2018-01-01

    Efforts to improve the reproducibility and integrity of science are typically justified by a narrative of crisis, according to which most published results are unreliable due to growing problems with research and publication practices. This article provides an overview of recent evidence suggesting that this narrative is mistaken, and argues that a narrative of epochal changes and empowerment of scientists would be more accurate, inspiring, and compelling. PMID:29531051

  2. Chemical biology-based approaches on fluorescent labeling of proteins in live cells.

    PubMed

    Jung, Deokho; Min, Kyoungmi; Jung, Juyeon; Jang, Wonhee; Kwon, Youngeun

    2013-05-01

    Recently, significant advances have been made in live cell imaging owing to the rapid development of selective labeling of proteins in vivo. Green fluorescent protein (GFP) was the first example of fluorescent reporters genetically introduced to protein of interest (POI). While GFP and various types of engineered fluorescent proteins (FPs) have been actively used for live cell imaging for many years, the size and the limited windows of fluorescent spectra of GFP and its variants set limits on possible applications. In order to complement FP-based labeling methods, alternative approaches that allow incorporation of synthetic fluorescent probes to target POIs were developed. Synthetic fluorescent probes are smaller than fluorescent proteins, often have improved photochemical properties, and offer a larger variety of colors. These synthetic probes can be introduced to POIs selectively by numerous approaches that can be largely categorized into chemical recognition-based labeling, which utilizes metal-chelating peptide tags and fluorophore-carrying metal complexes, and biological recognition-based labeling, such as (1) specific non-covalent binding between an enzyme tag and its fluorophore-carrying substrate, (2) self-modification of protein tags using substrate variants conjugated to fluorophores, (3) enzymatic reaction to generate a covalent binding between a small molecule substrate and a peptide tag, and (4) split-intein-based C-terminal labeling of target proteins. The chemical recognition-based labeling reaction often suffers from compromised selectivity of metal-ligand interaction in the cytosolic environment, consequently producing high background signals. Use of protein-substrate interactions or enzyme-mediated reactions generally shows improved specificity but each method has its limitations. Some examples are the presence of large linker protein, restriction on the choice of introducible probes due to the substrate specificity of enzymes, and competitive

  3. GeoTrust Hub: A Platform For Sharing And Reproducing Geoscience Applications

    NASA Astrophysics Data System (ADS)

    Malik, T.; Tarboton, D. G.; Goodall, J. L.; Choi, E.; Bhatt, A.; Peckham, S. D.; Foster, I.; Ton That, D. H.; Essawy, B.; Yuan, Z.; Dash, P. K.; Fils, G.; Gan, T.; Fadugba, O. I.; Saxena, A.; Valentic, T. A.

    2017-12-01

    Recent requirements of scholarly communication emphasize the reproducibility of scientific claims. Text-based research papers are considered poor mediums to establish reproducibility. Papers must be accompanied by "research objects", aggregation of digital artifacts that together with the paper provide an authoritative record of a piece of research. We will present GeoTrust Hub (http://geotrusthub.org), a platform for creating, sharing, and reproducing reusable research objects. GeoTrust Hub provides tools for scientists to create `geounits'--reusable research objects. Geounits are self-contained, annotated, and versioned containers that describe and package computational experiments in an efficient and light-weight manner. Geounits can be shared on public repositories such as HydroShare and FigShare, and also using their respective APIs reproduced on provisioned clouds. The latter feature enables science applications to have a lifetime beyond sharing, wherein they can be independently verified and trust be established as they are repeatedly reused. Through research use cases from several geoscience laboratories across the United States, we will demonstrate how tools provided from GeoTrust Hub along with Hydroshare as its public repository for geounits is advancing the state of reproducible research in the geosciences. For each use case, we will address different computational reproducibility requirements. Our first use case will be an example of setup reproducibility which enables a scientist to set up and reproduce an output from a model with complex configuration and development environments. Our second use case will be an example of algorithm/data reproducibility, where in a shared data science model/dataset can be substituted with an alternate one to verify model output results, and finally an example of interactive reproducibility, in which an experiment is dependent on specific versions of data to produce the result. Toward this we will use software and data

  4. Self-reference and random sampling approach for label-free identification of DNA composition using plasmonic nanomaterials.

    PubMed

    Freeman, Lindsay M; Pang, Lin; Fainman, Yeshaiahu

    2018-05-09

    The analysis of DNA has led to revolutionary advancements in the fields of medical diagnostics, genomics, prenatal screening, and forensic science, with the global DNA testing market expected to reach revenues of USD 10.04 billion per year by 2020. However, the current methods for DNA analysis remain dependent on the necessity for fluorophores or conjugated proteins, leading to high costs associated with consumable materials and manual labor. Here, we demonstrate a potential label-free DNA composition detection method using surface-enhanced Raman spectroscopy (SERS) in which we identify the composition of cytosine and adenine within single strands of DNA. This approach depends on the fact that there is one phosphate backbone per nucleotide, which we use as a reference to compensate for systematic measurement variations. We utilize plasmonic nanomaterials with random Raman sampling to perform label-free detection of the nucleotide composition within DNA strands, generating a calibration curve from standard samples of DNA and demonstrating the capability of resolving the nucleotide composition. The work represents an innovative way for detection of the DNA composition within DNA strands without the necessity of attached labels, offering a highly sensitive and reproducible method that factors in random sampling to minimize error.

  5. Repeatability and reproducibility of ribotyping and its computer interpretation.

    PubMed

    Lefresne, Gwénola; Latrille, Eric; Irlinger, Françoise; Grimont, Patrick A D

    2004-04-01

    Many molecular typing methods are difficult to interpret because their repeatability (within-laboratory variance) and reproducibility (between-laboratory variance) have not been thoroughly studied. In the present work, ribotyping of coryneform bacteria was the basis of a study involving within-gel and between-gel repeatability and between-laboratory reproducibility (two laboratories involved). The effect of different technical protocols, different algorithms, and different software for fragment size determination was studied. Analysis of variance (ANOVA) showed, within a laboratory, that there was no significant added variance between gels. However, between-laboratory variance was significantly higher than within-laboratory variance. This may be due to the use of different protocols. An experimental function was calculated to transform the data and make them compatible (i.e., erase the between-laboratory variance). The use of different interpolation algorithms (spline, Schaffer and Sederoff) was a significant source of variation in one laboratory only. The use of either Taxotron (Institut Pasteur) or GelCompar (Applied Maths) was not a significant source of added variation when the same algorithm (spline) was used. However, the use of Bio-Gene (Vilber Lourmat) dramatically increased the error (within laboratory, within gel) in one laboratory, while decreasing the error in the other laboratory; this might be due to automatic normalization attempts. These results were taken into account for building a database and performing automatic pattern identification using Taxotron. Conversion of the data considerably improved the identification of patterns irrespective of the laboratory in which the data were obtained.

  6. Multi-label literature classification based on the Gene Ontology graph.

    PubMed

    Jin, Bo; Muller, Brian; Zhai, Chengxiang; Lu, Xinghua

    2008-12-08

    The Gene Ontology is a controlled vocabulary for representing knowledge related to genes and proteins in a computable form. The current effort of manually annotating proteins with the Gene Ontology is outpaced by the rate of accumulation of biomedical knowledge in literature, which urges the development of text mining approaches to facilitate the process by automatically extracting the Gene Ontology annotation from literature. The task is usually cast as a text classification problem, and contemporary methods are confronted with unbalanced training data and the difficulties associated with multi-label classification. In this research, we investigated the methods of enhancing automatic multi-label classification of biomedical literature by utilizing the structure of the Gene Ontology graph. We have studied three graph-based multi-label classification algorithms, including a novel stochastic algorithm and two top-down hierarchical classification methods for multi-label literature classification. We systematically evaluated and compared these graph-based classification algorithms to a conventional flat multi-label algorithm. The results indicate that, through utilizing the information from the structure of the Gene Ontology graph, the graph-based multi-label classification methods can significantly improve predictions of the Gene Ontology terms implied by the analyzed text. Furthermore, the graph-based multi-label classifiers are capable of suggesting Gene Ontology annotations (to curators) that are closely related to the true annotations even if they fail to predict the true ones directly. A software package implementing the studied algorithms is available for the research community. Through utilizing the information from the structure of the Gene Ontology graph, the graph-based multi-label classification methods have better potential than the conventional flat multi-label classification approach to facilitate protein annotation based on the literature.

  7. Effects of thermochemical treatment on CuSbS 2 photovoltaic absorber quality and solar cell reproducibility

    DOE PAGES

    de Souza Lucas, Francisco Willian; Welch, Adam W.; Baranowski, Lauryn L.; ...

    2016-08-01

    CuSbS 2 is a promising nontoxic and earth-abundant photovoltaic absorber that is chemically simpler than the widely studied Cu 2ZnSnS 4. However, CuSbS 2 photovoltaic (PV) devices currently have relatively low efficiency and poor reproducibility, often due to suboptimal material quality and insufficient optoelectronic properties. To address these issues, here we develop a thermochemical treatment (TT) for CuSbS 2 thin films, which consists of annealing in Sb 2S 3 vapor followed by a selective KOH surface chemical etch. The annealed CuSbS 2 films show improved structural quality and optoelectronic properties, such as stronger band-edge photoluminescence and longer photoexcited carrier lifetime.more » These improvements also lead to more reproducible CuSbS 2 PV devices, with performance currently limited by a large cliff-type interface band offset with CdS contact. Altogether, these results point to the potential avenues to further increase the performance of CuSbS 2 thin film solar cell, and the findings can be transferred to other thin film photovoltaic technologies.« less

  8. An assessment of pharmacists’ readiness for paperless labeling: a national survey

    PubMed Central

    Ho, Yun-Xian; Chen, Qingxia; Nian, Hui; Johnson, Kevin B

    2014-01-01

    Objective To assess the state of readiness for the adoption of paperless labeling among a nationally representative sample of pharmacies, including chain pharmacies, independent retail pharmacies, hospitals, and other rural or urban dispensing sites. Methods Both quantitative and qualitative analyses were used to analyze responses to a cross-sectional survey disseminated to American Pharmacists Association pharmacists nationwide. The survey assessed factors related to pharmacists’ attitudinal readiness (ie, perceptions of impact) and pharmacies’ structural readiness (eg, availability of electronic resources, internet access) for the paperless labeling initiative. Results We received a total of 436 survey responses (6% response rate) from pharmacists representing 44 US states and territories. Across the spectrum of settings we studied, pharmacists had work access to computers, printers, fax machines and access to the internet or intranet. Approximately 79% of respondents believed that the initiative would improve the adequacy of drug information available in their work site and 95% believed it would either not change (33%) or would improve (62%) communication to patients. Overall, respondents’ comments supported advancing the initiative; however, some comments revealed reservations regarding corporate or pharmacy buy-in, success of implementation, and ease of adoption. Conclusions This is the first nationwide study to report about pharmacists’ perspectives on paperless labeling. In general, pharmacists believe they are ready and that their pharmacies are well equipped for the transition to paperless labeling. Further exploration of perspectives from product label manufacturers and corporate pharmacy offices is needed to understand fully what will be necessary to complete this transition. PMID:23523874

  9. Reproducible research in vadose zone sciences

    USDA-ARS?s Scientific Manuscript database

    A significant portion of present-day soil and Earth science research is computational, involving complex data analysis pipelines, advanced mathematical and statistical models, and sophisticated computer codes. Opportunities for scientific progress are greatly diminished if reproducing and building o...

  10. An Open Science and Reproducible Research Primer for Landscape Ecologists

    EPA Science Inventory

    In recent years many funding agencies, some publishers, and even the United States government have enacted policies that encourage open science and strive for reproducibility; however, the knowledge and skills to implement open science and enable reproducible research are not yet...

  11. A novel electrochemical immunosensor using β-cyclodextrins functionalized silver supported adamantine-modified glucose oxidase as labels for ultrasensitive detection of alpha-fetoprotein.

    PubMed

    Gao, Jian; Ma, Hongmin; Lv, Xiaohui; Yan, Tao; Li, Na; Cao, Wei; Wei, Qin

    2015-09-17

    In this work, a novel sandwich-type electrochemical immunosensor based on host-guest interaction was fabricated for the detection of alpha-fetoprotein (AFP). Due to the large specific surface area of multiwalled carbon nanotubes and the unique supramolecular recognition ability of β-cyclodextrins, ferrocenecarboxylic acid (Fc) was incorporated into this sensor platform by host-guest interaction to generate an electrochemical signal. And β-cyclodextrins functionalized silver supported adamantine-modified glucose oxidase (GOD-CD-Ag), was used as a label to improve the analytical performance of the immunosensor by the dual amplification strategy. The obtained GOD-CD-Ag conjugates could convert glucose into gluconic acid with the formation of hydrogen peroxide (H2O2). And then silver nanoparticles could in situ catalyze the reduction of the generated H2O2, dramatically improving the oxidation reaction of Fc. The developed immunosensor shows a wide linear calibration range from 0.001 to 5.0 ng/mL with a low detection limit (0.2 pg/mL) for the detection of AFP. The method, with ideal reproducibility and selectivity, has a wide application prospect in clinical research. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Consumer knowledge and attitudes to salt intake and labelled salt information.

    PubMed

    Grimes, Carley A; Riddell, Lynn J; Nowson, Caryl A

    2009-10-01

    The objective of this study was to investigate consumers' knowledge of health risks of high salt intake and frequency of use and understanding of labelled salt information. We conducted a cross-sectional survey in shopping centres within Metropolitan Melbourne. A sample of 493 subjects was recruited. The questionnaire assessed salt related shopping behaviours, attitudes to salt intake and health and their ability to interpret labelled sodium information. Four hundred and seventy four valid surveys were collected (65% female, 64% being the main shopper). Most participants knew of the relationship between salt intake and high blood pressure (88%). Sixty five percent of participants were unable to correctly identify the relationship between salt and sodium. Sixty nine percent reported reading the salt content of food products when shopping. Salt label usage was significantly related to shoppers concern about the amount of salt in their diet and the belief that their health could improve by lowering salt intake. Approximately half of the sample was unable to accurately use labelled sodium information to pick low salt options. Raising consumer awareness of the health risks associated with high salt consumption may increase salt label usage and purchases of low salt foods. However, for food labels to be effective in helping consumers select low salt foods a more 'user friendly' labelling format is needed.

  13. Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study.

    PubMed

    Kang, Dae-Wook; Adams, James B; Gregory, Ann C; Borody, Thomas; Chittick, Lauren; Fasano, Alessio; Khoruts, Alexander; Geis, Elizabeth; Maldonado, Juan; McDonough-Means, Sharon; Pollard, Elena L; Roux, Simon; Sadowsky, Michael J; Lipson, Karen Schwarzberg; Sullivan, Matthew B; Caporaso, J Gregory; Krajmalnik-Brown, Rosa

    2017-01-23

    Autism spectrum disorders (ASD) are complex neurobiological disorders that impair social interactions and communication and lead to restricted, repetitive, and stereotyped patterns of behavior, interests, and activities. The causes of these disorders remain poorly understood, but gut microbiota, the 10 13 bacteria in the human intestines, have been implicated because children with ASD often suffer gastrointestinal (GI) problems that correlate with ASD severity. Several previous studies have reported abnormal gut bacteria in children with ASD. The gut microbiome-ASD connection has been tested in a mouse model of ASD, where the microbiome was mechanistically linked to abnormal metabolites and behavior. Similarly, a study of children with ASD found that oral non-absorbable antibiotic treatment improved GI and ASD symptoms, albeit temporarily. Here, a small open-label clinical trial evaluated the impact of Microbiota Transfer Therapy (MTT) on gut microbiota composition and GI and ASD symptoms of 18 ASD-diagnosed children. MTT involved a 2-week antibiotic treatment, a bowel cleanse, and then an extended fecal microbiota transplant (FMT) using a high initial dose followed by daily and lower maintenance doses for 7-8 weeks. The Gastrointestinal Symptom Rating Scale revealed an approximately 80% reduction of GI symptoms at the end of treatment, including significant improvements in symptoms of constipation, diarrhea, indigestion, and abdominal pain. Improvements persisted 8 weeks after treatment. Similarly, clinical assessments showed that behavioral ASD symptoms improved significantly and remained improved 8 weeks after treatment ended. Bacterial and phagedeep sequencing analyses revealed successful partial engraftment of donor microbiota and beneficial changes in the gut environment. Specifically, overall bacterial diversity and the abundance of Bifidobacterium, Prevotella, and Desulfovibrio among other taxa increased following MTT, and these changes persisted after

  14. Hyperplex-MRM: a hybrid multiple reaction monitoring method using mTRAQ/iTRAQ labeling for multiplex absolute quantification of human colorectal cancer biomarker.

    PubMed

    Yin, Hong-Rui; Zhang, Lei; Xie, Li-Qi; Huang, Li-Yong; Xu, Ye; Cai, San-Jun; Yang, Peng-Yuan; Lu, Hao-Jie

    2013-09-06

    Novel biomarker verification assays are urgently required to improve the efficiency of biomarker development. Benefitting from lower development costs, multiple reaction monitoring (MRM) has been used for biomarker verification as an alternative to immunoassay. However, in general MRM analysis, only one sample can be quantified in a single experiment, which restricts its application. Here, a Hyperplex-MRM quantification approach, which combined mTRAQ for absolute quantification and iTRAQ for relative quantification, was developed to increase the throughput of biomarker verification. In this strategy, equal amounts of internal standard peptides were labeled with mTRAQ reagents Δ0 and Δ8, respectively, as double references, while 4-plex iTRAQ reagents were used to label four different samples as an alternative to mTRAQ Δ4. From the MRM trace and MS/MS spectrum, total amounts and relative ratios of target proteins/peptides of four samples could be acquired simultaneously. Accordingly, absolute amounts of target proteins/peptides in four different samples could be achieved in a single run. In addition, double references were used to increase the reliability of the quantification results. Using this approach, three biomarker candidates, ademosylhomocysteinase (AHCY), cathepsin D (CTSD), and lysozyme C (LYZ), were successfully quantified in colorectal cancer (CRC) tissue specimens of different stages with high accuracy, sensitivity, and reproducibility. To summarize, we demonstrated a promising quantification method for high-throughput verification of biomarker candidates.

  15. Reproducing an extreme flood with uncertain post-event information

    NASA Astrophysics Data System (ADS)

    Fuentes-Andino, Diana; Beven, Keith; Halldin, Sven; Xu, Chong-Yu; Reynolds, José Eduardo; Di Baldassarre, Giuliano

    2017-07-01

    Studies for the prevention and mitigation of floods require information on discharge and extent of inundation, commonly unavailable or uncertain, especially during extreme events. This study was initiated by the devastating flood in Tegucigalpa, the capital of Honduras, when Hurricane Mitch struck the city. In this study we hypothesized that it is possible to estimate, in a trustworthy way considering large data uncertainties, this extreme 1998 flood discharge and the extent of the inundations that followed from a combination of models and post-event measured data. Post-event data collected in 2000 and 2001 were used to estimate discharge peaks, times of peak, and high-water marks. These data were used in combination with rain data from two gauges to drive and constrain a combination of well-known modelling tools: TOPMODEL, Muskingum-Cunge-Todini routing, and the LISFLOOD-FP hydraulic model. Simulations were performed within the generalized likelihood uncertainty estimation (GLUE) uncertainty-analysis framework. The model combination predicted peak discharge, times of peaks, and more than 90 % of the observed high-water marks within the uncertainty bounds of the evaluation data. This allowed an inundation likelihood map to be produced. Observed high-water marks could not be reproduced at a few locations on the floodplain. Identifications of these locations are useful to improve model set-up, model structure, or post-event data-estimation methods. Rainfall data were of central importance in simulating the times of peak and results would be improved by a better spatial assessment of rainfall, e.g. from radar data or a denser rain-gauge network. Our study demonstrated that it was possible, considering the uncertainty in the post-event data, to reasonably reproduce the extreme Mitch flood in Tegucigalpa in spite of no hydrometric gauging during the event. The method proposed here can be part of a Bayesian framework in which more events can be added into the analysis as

  16. Label-Free Electrical Immunosensor for Highly Sensitive and Specific Detection of Microcystin-LR in Water Samples.

    PubMed

    Tan, Feng; Saucedo, Nuvia Maria; Ramnani, Pankaj; Mulchandani, Ashok

    2015-08-04

    Microcystin-LR (MCLR) is one of the most commonly detected and toxic cyclic heptapeptide cyanotoxins released by cyanobacterial blooms in surface waters, for which sensitive and specific detection methods are necessary to carry out its recognition and quantification. Here, we present a single-walled carbon nanotube (SWCNTs)-based label-free chemiresistive immunosensor for highly sensitive and specific detection of MCLR in different source waters. MCLR was initially immobilized on SWCNTs modified interdigitated electrode, followed by incubation with monoclonal anti-MCLR antibody. The competitive binding of MCLR in sample solutions induced departure of the antibody from the antibody-antigen complexes formed on SWCNTs, resulting in change in the conductivity between source and drain of the sensor. The displacement assay greatly improved the sensitivity of the sensor compared with direct immunoassay on the same device. The immunosensor exhibited a wide linear response to log value of MCLR concentration ranging from 1 to 1000 ng/L, with a detection limit of 0.6 ng/L. This method showed good reproducibility, stability and recovery. The proposed method provides a powerful tool for rapid and sensitive monitoring of MCLR in environmental samples.

  17. ROCS: a Reproducibility Index and Confidence Score for Interaction Proteomics Studies

    PubMed Central

    2012-01-01

    published AP-MS experiments, each containing well characterized protein interactions, allowing for systematic benchmarking of ROCS. We show that our method may be used on its own to make accurate identification of specific, biologically relevant protein-protein interactions, or in combination with other AP-MS scoring methods to significantly improve inferences. Conclusions Our method addresses important issues encountered in AP-MS datasets, making ROCS a very promising tool for this purpose, either on its own or in conjunction with other methods. We anticipate that our methodology may be used more generally in proteomics studies and databases, where experimental reproducibility issues arise. The method is implemented in the R language, and is available as an R package called “ROCS”, freely available from the CRAN repository http://cran.r-project.org/. PMID:22682516

  18. Inter-labeler and intra-labeler variability of condition severity classification models using active and passive learning methods.

    PubMed

    Nissim, Nir; Shahar, Yuval; Elovici, Yuval; Hripcsak, George; Moskovitch, Robert

    2017-09-01

    Labeling instances by domain experts for classification is often time consuming and expensive. To reduce such labeling efforts, we had proposed the application of active learning (AL) methods, introduced our CAESAR-ALE framework for classifying the severity of clinical conditions, and shown its significant reduction of labeling efforts. The use of any of three AL methods (one well known [SVM-Margin], and two that we introduced [Exploitation and Combination_XA]) significantly reduced (by 48% to 64%) condition labeling efforts, compared to standard passive (random instance-selection) SVM learning. Furthermore, our new AL methods achieved maximal accuracy using 12% fewer labeled cases than the SVM-Margin AL method. However, because labelers have varying levels of expertise, a major issue associated with learning methods, and AL methods in particular, is how to best to use the labeling provided by a committee of labelers. First, we wanted to know, based on the labelers' learning curves, whether using AL methods (versus standard passive learning methods) has an effect on the Intra-labeler variability (within the learning curve of each labeler) and inter-labeler variability (among the learning curves of different labelers). Then, we wanted to examine the effect of learning (either passively or actively) from the labels created by the majority consensus of a group of labelers. We used our CAESAR-ALE framework for classifying the severity of clinical conditions, the three AL methods and the passive learning method, as mentioned above, to induce the classifications models. We used a dataset of 516 clinical conditions and their severity labeling, represented by features aggregated from the medical records of 1.9 million patients treated at Columbia University Medical Center. We analyzed the variance of the classification performance within (intra-labeler), and especially among (inter-labeler) the classification models that were induced by using the labels provided by seven

  19. Detecting RNA/DNA hybridization using double-labeled donor probes with enhanced fluorescence resonance energy transfer signals.

    PubMed

    Okamura, Yukio; Watanabe, Yuichiro

    2006-01-01

    Fluorescence resonance energy transfer (FRET) occurs when two fluorophores are in close proximity, and the emission energy of a donor fluorophore is transferred to excite an acceptor fluorophore. Using such fluorescently labeled oligonucleotides as FRET probes, makes possible specific detection of RNA molecules even if similar sequences are present in the environment. A higher ratio of signal to background fluorescence is required for more sensitive probe detection. We found that double-labeled donor probes labeled with BODIPY dye resulted in a remarkable increase in fluorescence intensity compared to single-labeled donor probes used in conventional FRET. Application of this double-labeled donor system can improve a variety of FRET techniques.

  20. How reproducible is cutaneous electrogastrography? An in-depth evidence-based study.

    PubMed

    Jonderko, K; Kasicka-Jonderko, A; Krusiec-Swidergoł, B; Dzielicki, M; Strój, L; Doliński, M; Doliński, K; Błońska-Fajfrowska, B

    2005-12-01

    To check on reproducibility of parameters of the cutaneous electrogastrogram registered at a close or a distant time span. Twenty-two volunteers recruited by an advertisement (11 females and 11 males, median age 25 years, range: 18-35) underwent three surface electrogastrography examinations of which two were taken on consecutive days and the third one was accomplished at least 2 weeks before or after the two other sessions. The examination involved a 30-min fasted recording, followed by a 90-min postprandial registration after intake of a 394-kcal mixed solid-liquid test meal. Parameters of the electrogastrogram pertaining to the frequency of the gastric slow waves exhibited good to moderate reproducibility, whereas fair reproducibility characterized parameters expected to describe the power of gastric slow waves. With the exception of the difference fed minus fasted power (DeltaDP), in no instance was the medium term reproducibility any worse than the short term one. Categorical data analysis revealed that the relative time share of normogastria postprandially exhibited a better reproducibility than in the fasted period. The Cohen's kappa-value of 0.459 for the DeltaDP for the medium term reproducibility placed this parameter within the range of moderate agreement between repeat examinations. Of the two two-parameter combinations considered, the alliance of the fasted and fed normogastria performed worse than any of those parameters considered alone, whereas a combination of the DeltaDP with the fed-state normogastria revealed a kappa-value amounting to 0.510 for the medium term reproducibility. The feasibility of some electrogastrographic parameters to convey clinically useful information may be hampered by their fair reproducibility. Recoding of parameters of the cutaneous electrogastrogram from primary continuous to secondary categorical may help achieve a better agreement between repeat examinations.

  1. To label or not to label: applications of quantitative proteomics in neuroscience research.

    PubMed

    Filiou, Michaela D; Martins-de-Souza, Daniel; Guest, Paul C; Bahn, Sabine; Turck, Christoph W

    2012-02-01

    Proteomics has provided researchers with a sophisticated toolbox of labeling-based and label-free quantitative methods. These are now being applied in neuroscience research where they have already contributed to the elucidation of fundamental mechanisms and the discovery of candidate biomarkers. In this review, we evaluate and compare labeling-based and label-free quantitative proteomic techniques for applications in neuroscience research. We discuss the considerations required for the analysis of brain and central nervous system specimens, the experimental design of quantitative proteomic workflows as well as the feasibility, advantages, and disadvantages of the available techniques for neuroscience-oriented questions. Furthermore, we assess the use of labeled standards as internal controls for comparative studies in humans and review applications of labeling-based and label-free mass spectrometry approaches in relevant model organisms and human subjects. Providing a comprehensive guide of feasible and meaningful quantitative proteomic methodologies for neuroscience research is crucial not only for overcoming current limitations but also for gaining useful insights into brain function and translating proteomics from bench to bedside. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Status of the Local Enforcement of Energy Efficiency Standards and Labeling Program in China

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

    Zhou, Nan; Zheng, Nina; Fino-Chen, Cecilia

    2011-09-26

    As part of its commitment to promoting and improving the local enforcement of appliance energy efficiency standards and labeling, the China National Institute of Standardization (CNIS) launched the National and Local Enforcement of Energy Efficiency Standards and Labeling project on August 14, 2009. The project’s short-term goal is to expand the effort to improve enforcement of standards and labeling requirements to the entire country within three years, with a long-term goal of perfecting overall enforcement. For this project, Jiangsu, Shandong, Sichuan and Shanghai were selected as pilot locations. This report provides information on the local enforcement project’s recent background, activitiesmore » and results as well as comparison to previous rounds of check-testing in 2006 and 2007. In addition, the report also offers evaluation on the achievement and weaknesses in the local enforcement scheme and recommendations. The results demonstrate both improvement and some backsliding. Enforcement schemes are in place in all target cities and applicable national standards and regulations were followed as the basis for local check testing. Check testing results show in general high labeling compliance across regions with 100% compliance for five products, including full compliance for all three products tested in Jiangsu province and two out of three products tested in Shandong province. Program results also identified key weaknesses in labeling compliance in Sichuan as well as in the efficiency standards compliance levels for small and medium three-phase asynchronous motors and self-ballasted fluorescent lamps. For example, compliance for the same product ranged from as low as 40% to 100% with mixed results for products that had been tested in previous rounds. For refrigerators, in particular, the efficiency standards compliance rate exhibited a wider range of 50% to 100%, and the average rate across all tested models also dropped from 96% in 2007 to 63

  3. Three-dimensional reproducibility of natural head position.

    PubMed

    Weber, Diana W; Fallis, Drew W; Packer, Mark D

    2013-05-01

    Although natural head position has proven to be reliable in the sagittal plane, with an increasing interest in 3-dimensional craniofacial analysis, a determination of its reproducibility in the coronal and axial planes is essential. This study was designed to evaluate the reproducibility of natural head position over time in the sagittal, coronal, and axial planes of space with 3-dimensional imaging. Three-dimensional photographs were taken of 28 adult volunteers (ages, 18-40 years) in natural head position at 5 times: baseline, 4 hours, 8 hours, 24 hours, and 1 week. Using the true vertical and horizontal laser lines projected in an iCAT cone-beam computed tomography machine (Imaging Sciences International, Hatfield, Pa) for orientation, we recorded references for natural head position on the patient's face with semipermanent markers. By using a 3-dimensional camera system, photographs were taken at each time point to capture the orientation of the reference points. By superimposing each of the 5 photographs on stable anatomic surfaces, changes in the position of the markers were recorded and assessed for parallelism by using 3dMDvultus (3dMD, Atlanta, Ga) and software (Dolphin Imaging & Management Solutions, Chatsworth, Calif). No statistically significant differences were observed between the 5 time points in any of the 3 planes of space. However, a statistically significant difference was observed between the mean angular deviations of 3 reference planes, with a hierarchy of natural head position reproducibility established as coronal > axial > sagittal. Within the parameters of this study, natural head position was found to be reproducible in the sagittal, coronal, and axial planes of space. The coronal plane had the least variation over time, followed by the axial and sagittal planes. Copyright © 2013 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  4. Measures of low back function: a review of reproducibility studies.

    PubMed

    Essendrop, Morten; Maul, Irina; Läubli, Thomas; Riihimäki, Hilkka; Schibye, Bente

    2002-05-01

    The objective of the present study was to make a systematic literature review with preset quality criteria concerning reproducibility of the tests of the low back regarding strength, endurance and range of motion. Literature in Medline and local databases was reviewed for articles concerning the reproducibility of strength, endurance, and range of motion measurements. Measures of low back function are widely used, and are important for both clinical and research purposes in relation to low back problems. A review of the reproducibility of these tests has not previously been made. After extensive discussion among all the authors, general evaluation parameters were defined for the quality assessment. Every study was graded from 0 to 2 for each parameter. Parameters evaluated were: number of subjects, subject description, method description, test/retest interval, description of results, and statistics. The literature search revealed a total of 79 studies. Most studies suffered from methodological weaknesses and only eleven studies received ten or more quality points (maximum 14). The results from the highest graded studies are highlighted. It may be concluded that there is a considerable lack of information about the reproducibility of functional measures for the low back, and therefore a recommendation for consensus is difficult. However, most tests performed in the sagittal plane are reliable for use on groups. Measures of low back function are thought to be of great importance for clinicians, and low back researchers in general. A review of reproducibility will be helpful both as a survey of tests, and to provide information on the usefulness in relation to the level of reproducibility.

  5. Benchmarking contactless acquisition sensor reproducibility for latent fingerprint trace evidence

    NASA Astrophysics Data System (ADS)

    Hildebrandt, Mario; Dittmann, Jana

    2015-03-01

    Optical, nano-meter range, contactless, non-destructive sensor devices are promising acquisition techniques in crime scene trace forensics, e.g. for digitizing latent fingerprint traces. Before new approaches are introduced in crime investigations, innovations need to be positively tested and quality ensured. In this paper we investigate sensor reproducibility by studying different scans from four sensors: two chromatic white light sensors (CWL600/CWL1mm), one confocal laser scanning microscope, and one NIR/VIS/UV reflection spectrometer. Firstly, we perform an intra-sensor reproducibility testing for CWL600 with a privacy conform test set of artificial-sweat printed, computer generated fingerprints. We use 24 different fingerprint patterns as original samples (printing samples/templates) for printing with artificial sweat (physical trace samples) and their acquisition with contactless sensory resulting in 96 sensor images, called scan or acquired samples. The second test set for inter-sensor reproducibility assessment consists of the first three patterns from the first test set, acquired in two consecutive scans using each device. We suggest using a simple feature space set in spatial and frequency domain known from signal processing and test its suitability for six different classifiers classifying scan data into small differences (reproducible) and large differences (non-reproducible). Furthermore, we suggest comparing the classification results with biometric verification scores (calculated with NBIS, with threshold of 40) as biometric reproducibility score. The Bagging classifier is nearly for all cases the most reliable classifier in our experiments and the results are also confirmed with the biometric matching rates.

  6. Genetically Modified Food Labeling in China: In Pursuit of a Rational Path.

    PubMed

    Zhu, Xiao; Roberts, Michael T; Wu, Kaijie

    2016-08-01

    Facing a tension between the increasing use of genetically engineered or modified food and consumer concerns over the risks associated with GMOs, China has established a GM food labeling regime through regulations-known as Agro-GMO regulations-to protect consumers' right to know. However, the design and enforcement of this GM food labeling regime is problematic. As a result, the labeling regime is ineffective and inconsistent, leaving consumers' rights unprotected. As the recently amended Food Safety Law in China requires GM food labeling for the first time, this article argues that China should replace the current Agro-GMO food labeling scheme with a special regulatory scheme. A comparative analysis of the GM food labeling systems in the European Union and United States, coupled with a rigorous examination of the problems and barriers of GM food labeling in China, sets a solid foundation by which to propose changes to incorporate into a special regulatory scheme. To this end, this article engages in such an analysis and recommends practical steps to guide the enactment of a special regulatory scheme. The recommendations comport with China's unique legal and political culture, but also could be used by other national regulatory regimes who permit use of GM food while also being committed to improving consumers' right to know.

  7. Quantitative proteome analysis using isobaric peptide termini labeling (IPTL).

    PubMed

    Arntzen, Magnus O; Koehler, Christian J; Treumann, Achim; Thiede, Bernd

    2011-01-01

    The quantitative comparison of proteome level changes across biological samples has become an essential feature in proteomics that remains challenging. We have recently introduced isobaric peptide termini labeling (IPTL), a novel strategy for isobaric quantification based on the derivatization of peptide termini with complementary isotopically labeled reagents. Unlike non-isobaric quantification methods, sample complexity at the MS level is not increased, providing improved sensitivity and protein coverage. The distinguishing feature of IPTL when comparing it to more established isobaric labeling methods (iTRAQ and TMT) is the presence of quantification signatures in all sequence-determining ions in MS/MS spectra, not only in the low mass reporter ion region. This makes IPTL a quantification method that is accessible to mass spectrometers with limited capabilities in the low mass range. Also, the presence of several quantification points in each MS/MS spectrum increases the robustness of the quantification procedure.

  8. Extraction and labeling high-resolution images from PDF documents

    NASA Astrophysics Data System (ADS)

    Chachra, Suchet K.; Xue, Zhiyun; Antani, Sameer; Demner-Fushman, Dina; Thoma, George R.

    2013-12-01

    Accuracy of content-based image retrieval is affected by image resolution among other factors. Higher resolution images enable extraction of image features that more accurately represent the image content. In order to improve the relevance of search results for our biomedical image search engine, Open-I, we have developed techniques to extract and label high-resolution versions of figures from biomedical articles supplied in the PDF format. Open-I uses the open-access subset of biomedical articles from the PubMed Central repository hosted by the National Library of Medicine. Articles are available in XML and in publisher supplied PDF formats. As these PDF documents contain little or no meta-data to identify the embedded images, the task includes labeling images according to their figure number in the article after they have been successfully extracted. For this purpose we use the labeled small size images provided with the XML web version of the article. This paper describes the image extraction process and two alternative approaches to perform image labeling that measure the similarity between two images based upon the image intensity projection on the coordinate axes and similarity based upon the normalized cross-correlation between the intensities of two images. Using image identification based on image intensity projection, we were able to achieve a precision of 92.84% and a recall of 82.18% in labeling of the extracted images.

  9. Selective disulfide reduction for labeling and enhancement of Fab antibody fragments

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

    Kirley, Terence L., E-mail: terry.kirley@uc.edu; Greis, Kenneth D.; Norman, Andrew B.

    Many methods have been developed for chemical labeling and enhancement of the properties of antibodies and their common fragments, including the Fab and F(ab’){sub 2} fragments. Somewhat selective reduction of some antibody disulfide bonds has been previously achieved, yielding antibodies and antibody fragments that can be labeled at defined sites, enhancing their utility and properties. Selective reduction of the two hinge disulfide bonds present in F(ab’){sub 2} fragments using mild reduction has been useful. However, such reduction is often not quantitative and results in the reduction of multiple disulfide bonds, and therefore subsequent multiple labeling or conjugation sites are neithermore » homogenous nor stoichiometric. Here, a simple and efficient selective reduction of the single disulfide bond linking the partial heavy chain and the intact light chain which compose the Fab fragment is accomplished utilizing tris(2-carboxyethyl)phosphine (TCEP) immobilized on agarose beads. The resultant reduced cysteine residues were labeled with several cysteine-selective fluorescent reagents, as well as by cysteine-directed PEGylation. These two cysteine residues can also be re-ligated by means of a bifunctional cysteine cross-linking agent, dibromobimane, thereby both restoring a covalent linkage between the heavy and light chains at this site, far removed from the antigen binding site, and also introducing a fluorescent probe. There are many other research and clinical uses for these selectively partially reduced Fab fragments, including biotinylation, toxin and drug conjugation, and incorporation of radioisotopes, and this technique enables simple generation of very useful Fab fragment derivatives with many potential applications. - Highlights: • TCEP agarose is effective for selective reduction of a single Fab disulfide bond. • This disulfide is solvent accessible and distant from the antigen binding site. • A variety of buffers of varying pHs can be

  10. Inter-Labeler and Intra-Labeler Variability of Condition Severity Classification Models Using Active and Passive Learning Methods

    PubMed Central

    Nissim, Nir; Shahar, Yuval; Boland, Mary Regina; Tatonetti, Nicholas P; Elovici, Yuval; Hripcsak, George; Moskovitch, Robert

    2018-01-01

    Background and Objectives Labeling instances by domain experts for classification is often time consuming and expensive. To reduce such labeling efforts, we had proposed the application of active learning (AL) methods, introduced our CAESAR-ALE framework for classifying the severity of clinical conditions, and shown its significant reduction of labeling efforts. The use of any of three AL methods (one well known [SVM-Margin], and two that we introduced [Exploitation and Combination_XA]) significantly reduced (by 48% to 64%) condition labeling efforts, compared to standard passive (random instance-selection) SVM learning. Furthermore, our new AL methods achieved maximal accuracy using 12% fewer labeled cases than the SVM-Margin AL method. However, because labelers have varying levels of expertise, a major issue associated with learning methods, and AL methods in particular, is how to best to use the labeling provided by a committee of labelers. First, we wanted to know, based on the labelers’ learning curves, whether using AL methods (versus standard passive learning methods) has an effect on the Intra-labeler variability (within the learning curve of each labeler) and inter-labeler variability (among the learning curves of different labelers). Then, we wanted to examine the effect of learning (either passively or actively) from the labels created by the majority consensus of a group of labelers. Methods We used our CAESAR-ALE framework for classifying the severity of clinical conditions, the three AL methods and the passive learning method, as mentioned above, to induce the classifications models. We used a dataset of 516 clinical conditions and their severity labeling, represented by features aggregated from the medical records of 1.9 million patients treated at Columbia University Medical Center. We analyzed the variance of the classification performance within (intra-labeler), and especially among (inter-labeler) the classification models that were induced by

  11. Capacitive label reader

    DOEpatents

    Arlowe, H. Duane

    1985-01-01

    A capacitive label reader includes an outer ring transmitting portion, an inner ring transmitting portion, and a plurality of insulated receiving portions. A label is the mirror-image of the reader except that identifying portions corresponding to the receiving portions are insulated from only one of two coupling elements. Positive and negative pulses applied, respectively, to the two transmitting rings biased a CMOS shift register positively to either a 1 or 0 condition. The output of the CMOS may be read as an indication of the label.

  12. Capacitive label reader

    DOEpatents

    Arlowe, H.D.

    1983-07-15

    A capacitive label reader includes an outer ring transmitting portion, an inner ring transmitting portion, and a plurality of insulated receiving portions. A label is the mirror-image of the reader except that identifying portions corresponding to the receiving portions are insulated from only one of two coupling elements. Positive and negative pulses applied, respectively, to the two transmitting rings biased a CMOS shift register positively to either a 1 or 0 condition. The output of the CMOS may be read as an indication of the label.

  13. Using prediction markets to estimate the reproducibility of scientific research.

    PubMed

    Dreber, Anna; Pfeiffer, Thomas; Almenberg, Johan; Isaksson, Siri; Wilson, Brad; Chen, Yiling; Nosek, Brian A; Johannesson, Magnus

    2015-12-15

    Concerns about a lack of reproducibility of statistically significant results have recently been raised in many fields, and it has been argued that this lack comes at substantial economic costs. We here report the results from prediction markets set up to quantify the reproducibility of 44 studies published in prominent psychology journals and replicated in the Reproducibility Project: Psychology. The prediction markets predict the outcomes of the replications well and outperform a survey of market participants' individual forecasts. This shows that prediction markets are a promising tool for assessing the reproducibility of published scientific results. The prediction markets also allow us to estimate probabilities for the hypotheses being true at different testing stages, which provides valuable information regarding the temporal dynamics of scientific discovery. We find that the hypotheses being tested in psychology typically have low prior probabilities of being true (median, 9%) and that a "statistically significant" finding needs to be confirmed in a well-powered replication to have a high probability of being true. We argue that prediction markets could be used to obtain speedy information about reproducibility at low cost and could potentially even be used to determine which studies to replicate to optimally allocate limited resources into replications.

  14. Using prediction markets to estimate the reproducibility of scientific research

    PubMed Central

    Dreber, Anna; Pfeiffer, Thomas; Almenberg, Johan; Isaksson, Siri; Wilson, Brad; Chen, Yiling; Nosek, Brian A.; Johannesson, Magnus

    2015-01-01

    Concerns about a lack of reproducibility of statistically significant results have recently been raised in many fields, and it has been argued that this lack comes at substantial economic costs. We here report the results from prediction markets set up to quantify the reproducibility of 44 studies published in prominent psychology journals and replicated in the Reproducibility Project: Psychology. The prediction markets predict the outcomes of the replications well and outperform a survey of market participants’ individual forecasts. This shows that prediction markets are a promising tool for assessing the reproducibility of published scientific results. The prediction markets also allow us to estimate probabilities for the hypotheses being true at different testing stages, which provides valuable information regarding the temporal dynamics of scientific discovery. We find that the hypotheses being tested in psychology typically have low prior probabilities of being true (median, 9%) and that a “statistically significant” finding needs to be confirmed in a well-powered replication to have a high probability of being true. We argue that prediction markets could be used to obtain speedy information about reproducibility at low cost and could potentially even be used to determine which studies to replicate to optimally allocate limited resources into replications. PMID:26553988

  15. Reproducibility of dynamically represented acoustic lung images from healthy individuals

    PubMed Central

    Maher, T M; Gat, M; Allen, D; Devaraj, A; Wells, A U; Geddes, D M

    2008-01-01

    Background and aim: Acoustic lung imaging offers a unique method for visualising the lung. This study was designed to demonstrate reproducibility of acoustic lung images recorded from healthy individuals at different time points and to assess intra- and inter-rater agreement in the assessment of dynamically represented acoustic lung images. Methods: Recordings from 29 healthy volunteers were made on three separate occasions using vibration response imaging. Reproducibility was measured using quantitative, computerised assessment of vibration energy. Dynamically represented acoustic lung images were scored by six blinded raters. Results: Quantitative measurement of acoustic recordings was highly reproducible with an intraclass correlation score of 0.86 (very good agreement). Intraclass correlations for inter-rater agreement and reproducibility were 0.61 (good agreement) and 0.86 (very good agreement), respectively. There was no significant difference found between the six raters at any time point. Raters ranged from 88% to 95% in their ability to identically evaluate the different features of the same image presented to them blinded on two separate occasions. Conclusion: Acoustic lung imaging is reproducible in healthy individuals. Graphic representation of lung images can be interpreted with a high degree of accuracy by the same and by different reviewers. PMID:18024534

  16. 16 CFR 460.12 - Labels.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Practices FEDERAL TRADE COMMISSION TRADE REGULATION RULES LABELING AND ADVERTISING OF HOME INSULATION § 460.12 Labels. If you are a manufacturer, you must label all packages of your insulation. The labels must contain: (a) The type of insulation. (b) A chart showing these items: (1) For batts and blankets of any...

  17. 16 CFR 460.12 - Labels.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Practices FEDERAL TRADE COMMISSION TRADE REGULATION RULES LABELING AND ADVERTISING OF HOME INSULATION § 460.12 Labels. If you are a manufacturer, you must label all packages of your insulation. The labels must contain: (a) The type of insulation. (b) A chart showing these items: (1) For batts and blankets of any...

  18. 16 CFR 460.12 - Labels.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Practices FEDERAL TRADE COMMISSION TRADE REGULATION RULES LABELING AND ADVERTISING OF HOME INSULATION § 460.12 Labels. If you are a manufacturer, you must label all packages of your insulation. The labels must contain: (a) The type of insulation. (b) A chart showing these items: (1) For batts and blankets of any...

  19. 16 CFR 460.12 - Labels.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Practices FEDERAL TRADE COMMISSION TRADE REGULATION RULES LABELING AND ADVERTISING OF HOME INSULATION § 460.12 Labels. If you are a manufacturer, you must label all packages of your insulation. The labels must contain: (a) The type of insulation. (b) A chart showing these items: (1) For batts and blankets of any...

  20. 16 CFR 460.12 - Labels.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Practices FEDERAL TRADE COMMISSION TRADE REGULATION RULES LABELING AND ADVERTISING OF HOME INSULATION § 460.12 Labels. If you are a manufacturer, you must label all packages of your insulation. The labels must contain: (a) The type of insulation. (b) A chart showing these items: (1) For batts and blankets of any...

  1. 21 CFR 895.25 - Labeling.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... eliminated by labeling or a change in labeling, or change in advertising if the device is a restricted device... person(s) responsible for the labeling or advertising of the device specifying: (1) The deception or risk... labeling, or change in advertising if the device is a restricted device, necessary to correct the deception...

  2. Sharing meanings: developing interoperable semantic technologies to enhance reproducibility in earth and environmental science research

    NASA Astrophysics Data System (ADS)

    Schildhauer, M.

    2015-12-01

    Earth and environmental scientists are familiar with the entities, processes, and theories germane to their field of study, and comfortable collecting and analyzing data in their area of interest. Yet, while there appears to be consistency and agreement as to the scientific "terms" used to describe features in their data and analyses, aside from a few fundamental physical characteristics—such as mass or velocity-- there can be broad tolerances, if not considerable ambiguity, in how many earth science "terms" map to the underlying "concepts" that they actually represent. This ambiguity in meanings, or "semantics", creates major problems for scientific reproducibility. It greatly impedes the ability to replicate results—by making it difficult to determine the specifics of the intended meanings of terms such as deforestation or carbon flux -- as to scope, composition, magnitude, etc. In addition, semantic ambiguity complicates assemblage of comparable data for reproducing results, due to ambiguous or idiosyncratic labels for measurements, such as percent cover of forest, where the term "forest" is undefined; or where a reported output of "total carbon-emissions" might just include CO2 emissions, but not methane emissions. In this talk, we describe how the NSF-funded DataONE repository for earth and environmental science data (http://dataone.org), is using W3C-standard languages (RDF/OWL) to build an ontology for clarifying concepts embodied in heterogeneous data and model outputs. With an initial focus on carbon cycling concepts using terrestrial biospheric model outputs and LTER productivity data, we describe how we are achieving interoperability with "semantic vocabularies" (or ontologies) from aligned earth and life science domains, including OBO-foundry ontologies such as ENVO and BCO; the ISO/OGC O&M; and the NSF Earthcube GeoLink project. Our talk will also discuss best practices that may be helpful for other groups interested in constructing their own

  3. Reproducibility of Tumor Motion Probability Distribution Function in Stereotactic Body Radiation Therapy of Lung Cancer

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

    Zhang Fan; Medical Physics Graduate Program, Duke University, Durham, North Carolina; Hu Jing

    2012-11-01

    Purpose: To evaluate the reproducibility of tumor motion probability distribution function (PDF) in stereotactic body radiation therapy (SBRT) of lung cancer using cine megavoltage (MV) images. Methods and Materials: Cine MV images of 20 patients acquired during three-dimensional conformal (6-11 beams) SBRT treatments were retrospectively analyzed to extract tumor motion trajectories. For each patient, tumor motion PDFs were generated per fraction (PDF{sub n}) using three selected 'usable' beams. Patients without at least three usable beams were excluded from the study. Fractional PDF reproducibility (R{sub n}) was calculated as the Dice similarity coefficient between PDF{sub n} to a 'ground-truth' PDF (PDF{submore » g}), which was generated using the selected beams of all fractions. The mean of R{sub n}, labeled as R{sub m}, was calculated for each patient and correlated to the patient's mean tumor motion rang (A{sub m}). Change of R{sub m} during the course of SBRT treatments was also evaluated. Intra- and intersubject coefficient of variation (CV) of R{sub m} and A{sub m} were determined. Results: Thirteen patients had at least three usable beams and were analyzed. The mean of R{sub m} was 0.87 (range, 0.84-0.95). The mean of A{sub m} was 3.18 mm (range, 0.46-7.80 mm). R{sub m} was found to decrease as A{sub m} increases following an equation of R{sub m} = 0.17e{sup -0.9Am} + 0.84. R{sub m} also decreased slightly throughout the course of treatments. Intersubject CV of R{sub m} (0.05) was comparable to intrasubject CV of R{sub m} (range, 0.02-0.09); intersubject CV of A{sub m} (0.73) was significantly greater than intrasubject CV of A{sub m} (range, 0.09-0.24). Conclusions: Tumor motion PDF can be determined using cine MV images acquired during the treatments. The reproducibility of lung tumor motion PDF decreased exponentially as the tumor motion range increased and decreased slightly throughout the course of the treatments.« less

  4. 40 CFR 168.65 - Pesticide export label and labeling requirements.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... toxic pesticides. If the pesticide, device or active ingredient is highly toxic to humans, the skull and... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Pesticide export label and labeling...) PESTICIDE PROGRAMS STATEMENTS OF ENFORCEMENT POLICIES AND INTERPRETATIONS Export Policy and Procedures for...

  5. 40 CFR 168.65 - Pesticide export label and labeling requirements.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... toxic pesticides. If the pesticide, device or active ingredient is highly toxic to humans, the skull and... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Pesticide export label and labeling...) PESTICIDE PROGRAMS STATEMENTS OF ENFORCEMENT POLICIES AND INTERPRETATIONS Export Policy and Procedures for...

  6. 40 CFR 168.65 - Pesticide export label and labeling requirements.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... toxic pesticides. If the pesticide, device or active ingredient is highly toxic to humans, the skull and... 40 Protection of Environment 25 2012-07-01 2012-07-01 false Pesticide export label and labeling...) PESTICIDE PROGRAMS STATEMENTS OF ENFORCEMENT POLICIES AND INTERPRETATIONS Export Policy and Procedures for...

  7. Dual-process theory and consumer response to front-of-package nutrition label formats.

    PubMed

    Sanjari, S Setareh; Jahn, Steffen; Boztug, Yasemin

    2017-11-01

    Nutrition labeling literature yields fragmented results about the effect of front-of-package (FOP) nutrition label formats on healthy food choice. Specifically, it is unclear which type of nutrition label format is effective across different shopping situations. To address this gap, the present review investigates the available nutrition labeling literature through the prism of dual-process theory, which posits that decisions are made either quickly and automatically (system 1) or slowly and deliberately (system 2). A systematically performed review of nutrition labeling literature returned 59 papers that provide findings that can be explained according to dual-process theory. The findings of these studies suggest that the effectiveness of nutrition label formats is influenced by the consumer's dominant processing system, which is a function of specific contexts and personal variables (eg, motivation, nutrition knowledge, time pressure, and depletion). Examination of reported findings through a situational processing perspective reveals that consumers might prefer different FOP nutrition label formats in different situations and can exhibit varying responses to the same label format across situations. This review offers several suggestions for policy makers and researchers to help improve current FOP nutrition label formats. © The Author(s) 2017. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  8. Noncharged and Charged Monodendronised Perylene Bisimides as Highly Fluorescent Labels and their Bioconjugates.

    PubMed

    Huth, Katharina; Heek, Timm; Achazi, Katharina; Kühne, Christian; Urner, Leonhard H; Pagel, Kevin; Dernedde, Jens; Haag, Rainer

    2017-04-06

    A series of water-soluble, hydroxylated and sulphated, polyglycerol (PG) dendronised, monofunctional perylene bisimides (PBIs) were synthesised in three generations. Their photophysical properties were determined by absorption and emission spectroscopy and their suitability as potential biolabels examined by biological in vitro studies after bioconjugation. It could be shown that the photophysical properties of the PBI labels can be improved by increasing the sterical demand and ionic charge of the attached dendron. Thereby, charged labels show superior suppression of aggregation over charge neutral labels owing to electrostatic repulsion forces on the PG-dendron. The ionic charges also enabled a reduction in dendron generation while retaining the labels' outstanding fluorescence quantum yields (FQYs) up to 100 %. These core-unsubstituted perylene derivatives were successfully applied as fluorescent labels upon bioconjugation to the therapeutic antibody cetuximab. The dye-antibody conjugates showed a strongly enhanced aggregation tendency compared to the corresponding free dyes. Biological evaluation by receptor-binding, cellular uptake, and cytotoxicity studies revealed that labelling did not affect the antibody's function, which renders the noncharged and charged dendronised PBIs suitable candidates as fluorescent labels in biological imaging. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. 13C labeling analysis of sugars by high resolution-mass spectrometry for metabolic flux analysis.

    PubMed

    Acket, Sébastien; Degournay, Anthony; Merlier, Franck; Thomasset, Brigitte

    2017-06-15

    Metabolic flux analysis is particularly complex in plant cells because of highly compartmented metabolism. Analysis of free sugars is interesting because it provides data to define fluxes around hexose, pentose, and triose phosphate pools in different compartment. In this work, we present a method to analyze the isotopomer distribution of free sugars labeled with carbon 13 using a liquid chromatography-high resolution mass spectrometry, without derivatized procedure, adapted for Metabolic flux analysis. Our results showed a good sensitivity, reproducibility and better accuracy to determine isotopic enrichments of free sugars compared to our previous methods [5, 6]. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. 78 FR 47154 - Food Labeling; Gluten-Free Labeling of Foods

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-05

    ...The Food and Drug Administration (FDA or we) is issuing a final rule to define the term ``gluten-free'' for voluntary use in the labeling of foods. The final rule defines the term ``gluten-free'' to mean that the food bearing the claim does not contain an ingredient that is a gluten-containing grain (e.g., spelt wheat); an ingredient that is derived from a gluten-containing grain and that has not been processed to remove gluten (e.g., wheat flour); or an ingredient that is derived from a gluten-containing grain and that has been processed to remove gluten (e.g., wheat starch), if the use of that ingredient results in the presence of 20 parts per million (ppm) or more gluten in the food (i.e., 20 milligrams (mg) or more gluten per kilogram (kg) of food); or inherently does not contain gluten; and that any unavoidable presence of gluten in the food is below 20 ppm gluten (i.e., below 20 mg gluten per kg of food). A food that bears the claim ``no gluten,'' ``free of gluten,'' or ``without gluten'' in its labeling and fails to meet the requirements for a ``gluten-free'' claim will be deemed to be misbranded. In addition, a food whose labeling includes the term ``wheat'' in the ingredient list or in a separate ``Contains wheat'' statement as required by a section of the Federal Food, Drug, and Cosmetic Act (the FD&C Act) and also bears the claim ``gluten-free'' will be deemed to be misbranded unless its labeling also bears additional language clarifying that the wheat has been processed to allow the food to meet FDA requirements for a ``gluten-free'' claim. Establishing a definition of the term ``gluten-free'' and uniform conditions for its use in food labeling will help ensure that individuals with celiac disease are not misled and are provided with truthful and accurate information with respect to foods so labeled. We are issuing the final rule under the Food Allergen Labeling and Consumer Protection Act of 2004 (FALCPA).

  11. Collaborative labeling of malignant glioma with WebMILL: a first look

    NASA Astrophysics Data System (ADS)

    Singh, Eesha; Asman, Andrew J.; Xu, Zhoubing; Chambless, Lola; Thompson, Reid; Landman, Bennett A.

    2012-02-01

    Malignant gliomas are the most common form of primary neoplasm in the central nervous system, and one of the most rapidly fatal of all human malignancies. They are treated by maximal surgical resection followed by radiation and chemotherapy. Herein, we seek to improve the methods available to quantify the extent of tumors using newly presented, collaborative labeling techniques on magnetic resonance imaging. Traditionally, labeling medical images has entailed that expert raters operate on one image at a time, which is resource intensive and not practical for very large datasets. Using many, minimally trained raters to label images has the possibility of minimizing laboratory requirements and allowing high degrees of parallelism. A successful effort also has the possibility of reducing overall cost. This potentially transformative technology presents a new set of problems, because one must pose the labeling challenge in a manner accessible to people with little or no background in labeling medical images and raters cannot be expected to read detailed instructions. Hence, a different training method has to be employed. The training must appeal to all types of learners and have the same concepts presented in multiple ways to ensure that all the subjects understand the basics of labeling. Our overall objective is to demonstrate the feasibility of studying malignant glioma morphometry through statistical analysis of the collaborative efforts of many, minimally-trained raters. This study presents preliminary results on optimization of the WebMILL framework for neoplasm labeling and investigates the initial contributions of 78 raters labeling 98 whole-brain datasets.

  12. Diagnostic and Treatment Reproducibility of Cervical Intraepithelial Neoplasia / Squamous Intraepithelial Lesion and Factors Affecting the Diagnosis.

    PubMed

    Sağlam, Arzu; Usubütün, Alp; Dolgun, Anıl; Mutter, George L; Salman, M Coşkun; Kurtulan, Olcay; Akyol, Aytekin; Özkan, Eylem Akar; Baykara, Sema; Bülbül, Dilek; Calay, Zerrin; Eren, Funda; Gümürdülü, Derya; Haberal, Nihan; Ilvan, Şennur; Karaveli, Şeyda; Koyuncuoğlu, Meral; Müezzinoğlu, Bahar; Müftüoğlu, Kamil Hakan; Özen, Özlem; Özdemir, Necmettin; Peştereli, Elif; Ulukuş, Çağnur; Zekioğlu, Osman

    2017-01-01

    Inter-observer differences in the diagnosis of HPV related cervical lesions are problematic and response of gynecologists to these diagnostic entities is non-standardized. This study evaluated the diagnostic reproducibility of "cervical intraepithelial neoplasia" (CIN) and "squamous intraepithelial lesion" (SIL) diagnoses. 19 pathologists evaluated 66 cases once using H&E slides and once with immunohistochemical studies (p16, Ki-67 and Pro-ExC). Management response to diagnoses was evaluated amongst 12 gynecologists. Pathologists and gynecologists were also given a questionnaire about how additional information like smear results and age modify diagnosis and management. We show moderate interobserver diagnostic reproducibility amongst pathologists. The overall kappa value was 0.50 and 0.59 using the CIN and SIL classifications respectively. Impact of immunohistochemical evaluation on interpretation of cases differed and there was lack of statistically significant improvement of interobserver diagnostic reproducibility with the addition of immunohistochemistry. We saw that choice of treatment methods amongst gynecologists varied and overall concordance was only fair to moderate. The CIN2 diagnostic category was seen to have the lowest percentage agreement amongst both pathologists and gynecologists. We showed that pathologists had diagnostic "styles" and gynecologists had management "styles". In summary each pathologist had different diagnostic tendencies which were affected not only by histopathology and marker studies, but also by the patient management tendencies of the gynecologist that the pathologist worked with. The two-tiered modified Bethesda system improved diagnostic agreement. We concluded that immunohistochemistry should be used only to resolve problems in select cases and not for every case.

  13. A simple hand‐held magnet array for efficient and reproducible SABRE hyperpolarisation using manual sample shaking

    PubMed Central

    Richardson, Peter M.; Jackson, Scott; Parrott, Andrew J.; Nordon, Alison; Duckett, Simon B.

    2018-01-01

    Signal amplification by reversible exchange (SABRE) is a hyperpolarisation technique that catalytically transfers nuclear polarisation from parahydrogen, the singlet nuclear isomer of H2, to a substrate in solution. The SABRE exchange reaction is carried out in a polarisation transfer field (PTF) of tens of gauss before transfer to a stronger magnetic field for nuclear magnetic resonance (NMR) detection. In the simplest implementation, polarisation transfer is achieved by shaking the sample in the stray field of a superconducting NMR magnet. Although convenient, this method suffers from limited reproducibility and cannot be used with NMR spectrometers that do not have appreciable stray fields, such as benchtop instruments. Here, we use a simple hand‐held permanent magnet array to provide the necessary PTF during sample shaking. We find that the use of this array provides a 25% increase in SABRE enhancement over the stray field approach, while also providing improved reproducibility. Arrays with a range of PTFs were tested, and the PTF‐dependent SABRE enhancements were found to be in excellent agreement with comparable experiments carried out using an automated flow system where an electromagnet is used to generate the PTF. We anticipate that this approach will improve the efficiency and reproducibility of SABRE experiments carried out using manual shaking and will be particularly useful for benchtop NMR, where a suitable stray field is not readily accessible. The ability to construct arrays with a range of PTFs will also enable the rapid optimisation of SABRE enhancement as function of PTF for new substrate and catalyst systems. PMID:29193324

  14. Like your labels?

    PubMed

    Field, Michele

    2010-01-01

    The descriptive “conventions” used on food labels are always evolving. Today, however, the changes are so complicated (partly driven by legislation requiring disclosures about environmental impacts, health issues, and geographical provenance) that these labels more often baffle buyers than enlighten them. In a light-handed manner, the article points to how sometimes reading label language can be like deciphering runes—and how if we are familiar with the technical terms, we can find a literal meaning, but still not see the implications. The article could be ten times longer because food labels vary according to cultures—but all food-exporting cultures now take advantage of our short attention-span when faced with these texts. The question is whether less is more—and if so, in this contest for our attention, what “contestant” is voted off.

  15. Improved fluorescent labeling of chitin oligomers: Chitinolytic properties of acidic mammalian chitinase under somatic tissue pH conditions.

    PubMed

    Wakita, Satoshi; Kimura, Masahiro; Kato, Naoki; Kashimura, Akinori; Kobayashi, Shunsuke; Kanayama, Naoto; Ohno, Misa; Honda, Shotaro; Sakaguchi, Masayoshi; Sugahara, Yasusato; Bauer, Peter O; Oyama, Fumitaka

    2017-05-15

    Acidic mammalian chitinase (AMCase) has been implicated in various pathophysiological conditions including asthma, allergic inflammation and food processing. AMCase is most active at pH 2.0, and its activity gradually decreases to up to pH 8. Here we analyzed chitin degradation by AMCase in weak acidic to neutral conditions by fluorophore-assisted carbohydrate electrophoresis established originally for oligosaccharides analysis. We found that specific fragments with slower-than-expected mobility as defined by chitin oligosaccharide markers were generated at pH 5.0∼8.0 as by-products of the reaction. We established an improved method for chitin oligosaccharides suppressing this side reaction by pre-acidification of the fluorophore-labeling reaction mixture. Our improved method specifically detects chitin oligosaccharides and warrants quantification of up to 50nmol of the material. Using this strategy, we found that AMCase produced dimer of N-acetyl-d-glucosamine (GlcNAc) at strong acidic to neutral condition. Moreover, we found that AMCase generates (GlcNAc) 2 as well as (GlcNAc) 3 under physiological conditions. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. Capacitive label reader

    DOEpatents

    Arlowe, H.D.

    1985-11-12

    A capacitive label reader includes an outer ring transmitting portion, an inner ring transmitting portion, and a plurality of insulated receiving portions. A label is the mirror-image of the reader except that identifying portions corresponding to the receiving portions are insulated from only one of two coupling elements. Positive and negative pulses applied, respectively, to the two transmitting rings biased a CMOS shift register positively to either a 1 or 0 condition. The output of the CMOS may be read as an indication of the label. 5 figs.

  17. Rapid protein concentration, efficient fluorescence labeling and purification on a micro/nanofluidics chip.

    PubMed

    Wang, Chen; Ouyang, Jun; Ye, De-Kai; Xu, Jing-Juan; Chen, Hong-Yuan; Xia, Xing-Hua

    2012-08-07

    Fluorescence analysis has proved to be a powerful detection technique for achieving single molecule analysis. However, it usually requires the labeling of targets with bright fluorescent tags since most chemicals and biomolecules lack fluorescence. Conventional fluorescence labeling methods require a considerable quantity of biomolecule samples, long reaction times and extensive chromatographic purification procedures. Herein, a micro/nanofluidics device integrating a nanochannel in a microfluidics chip has been designed and fabricated, which achieves rapid protein concentration, fluorescence labeling, and efficient purification of product in a miniaturized and continuous manner. As a demonstration, labeling of the proteins bovine serum albumin (BSA) and IgG with fluorescein isothiocyanate (FITC) is presented. Compared to conventional methods, the present micro/nanofluidics device performs about 10(4)-10(6) times faster BSA labeling with 1.6 times higher yields due to the efficient nanoconfinement effect, improved mass, and heat transfer in the chip device. The results demonstrate that the present micro/nanofluidics device promises rapid and facile fluorescence labeling of small amount of reagents such as proteins, nucleic acids and other biomolecules with high efficiency.

  18. Correlates of nutrition label use among college students and young adults: a review.

    PubMed

    Christoph, Mary J; An, Ruopeng; Ellison, Brenna

    2016-08-01

    Nutrition labels are an essential source for consumers to obtain nutrition-related information on food products and serve as a population-level intervention with unparalleled reach. The present study systematically reviewed existing evidence on the correlates of nutrition label use among college students and young adults. Keyword and reference searches were conducted in PubMed, EBSCO, PsycInfo, Cochrane Library and Web of Science. Inclusion criteria included: study design (randomized controlled trial, cohort study, pre-post study or cross-sectional study); population (college students and young adults 18-30 years old); main outcome (nutrition label use); article type (peer-reviewed publication); and language (English). College/university. College students and young adults. Sixteen studies based on data from college surveys in four countries (USA, UK, Canada, South Korea) were identified from keyword and reference search. Reported prevalence of nutrition label use varied substantially across studies; a weighted average calculation showed 36·5 % of college students and young adults reported using labels always or often. Females were more likely to use nutrition labels than males. Nutrition label use was found to be associated with attitudes towards healthy diet, beliefs on the importance of nutrition labels in guiding food selection, self-efficacy, and nutrition knowledge and education. The impact of nutrition labelling on food purchase and intake could differ by population subgroups. Nutrition awareness campaigns and education programmes may be important mechanisms for promoting nutrition label use among college students and young adults. Future research is warranted to assess the role of label use on improved dietary decisions.

  19. Hydrological Modeling Reproducibility Through Data Management and Adaptors for Model Interoperability

    NASA Astrophysics Data System (ADS)

    Turner, M. A.

    2015-12-01

    Because of a lack of centralized planning and no widely-adopted standards among hydrological modeling research groups, research communities, and the data management teams meant to support research, there is chaos when it comes to data formats, spatio-temporal resolutions, ontologies, and data availability. All this makes true scientific reproducibility and collaborative integrated modeling impossible without some glue to piece it all together. Our Virtual Watershed Integrated Modeling System provides the tools and modeling framework hydrologists need to accelerate and fortify new scientific investigations by tracking provenance and providing adaptors for integrated, collaborative hydrologic modeling and data management. Under global warming trends where water resources are under increasing stress, reproducible hydrological modeling will be increasingly important to improve transparency and understanding of the scientific facts revealed through modeling. The Virtual Watershed Data Engine is capable of ingesting a wide variety of heterogeneous model inputs, outputs, model configurations, and metadata. We will demonstrate one example, starting from real-time raw weather station data packaged with station metadata. Our integrated modeling system will then create gridded input data via geostatistical methods along with error and uncertainty estimates. These gridded data are then used as input to hydrological models, all of which are available as web services wherever feasible. Models may be integrated in a data-centric way where the outputs too are tracked and used as inputs to "downstream" models. This work is part of an ongoing collaborative Tri-state (New Mexico, Nevada, Idaho) NSF EPSCoR Project, WC-WAVE, comprised of researchers from multiple universities in each of the three states. The tools produced and presented here have been developed collaboratively alongside watershed scientists to address specific modeling problems with an eye on the bigger picture of

  20. Quantification of atrial dynamics using cardiovascular magnetic resonance: inter-study reproducibility.

    PubMed

    Kowallick, Johannes T; Morton, Geraint; Lamata, Pablo; Jogiya, Roy; Kutty, Shelby; Hasenfuß, Gerd; Lotz, Joachim; Nagel, Eike; Chiribiri, Amedeo; Schuster, Andreas

    2015-05-17

    Cardiovascular magnetic resonance (CMR) offers quantification of phasic atrial functions based on volumetric assessment and more recently, on CMR feature tracking (CMR-FT) quantitative strain and strain rate (SR) deformation imaging. Inter-study reproducibility is a key requirement for longitudinal studies but has not been defined for CMR-based quantification of left atrial (LA) and right atrial (RA) dynamics. Long-axis 2- and 4-chamber cine images were acquired at 9:00 (Exam A), 9:30 (Exam B) and 14:00 (Exam C) in 16 healthy volunteers. LA and RA reservoir, conduit and contractile booster pump functions were quantified by volumetric indexes as derived from fractional volume changes and by strain and SR as derived from CMR-FT. Exam A and B were compared to assess the inter-study reproducibility. Morning and afternoon scans were compared to address possible diurnal variation of atrial function. Inter-study reproducibility was within acceptable limits for all LA and RA volumetric, strain and SR parameters. Inter-study reproducibility was better for volumetric indexes and strain than for SR parameters and better for LA than for RA dynamics. For the LA, reservoir function showed the best reproducibility (intraclass correlation coefficient (ICC) 0.94-0.97, coefficient of variation (CoV) 4.5-8.2%), followed by conduit (ICC 0.78-0.97, CoV 8.2-18.5%) and booster pump function (ICC 0.71-0.95, CoV 18.3-22.7). Similarly, for the RA, reproducibility was best for reservoir function (ICC 0.76-0.96, CoV 7.5-24.0%) followed by conduit (ICC 0.67-0.91, CoV 13.9-35.9) and booster pump function (ICC 0.73-0.90, CoV 19.4-32.3). Atrial dynamics were not measurably affected by diurnal variation between morning and afternoon scans. Inter-study reproducibility for CMR-based derivation of LA and RA functions is acceptable using either volumetric, strain or SR parameters with LA function showing higher reproducibility than RA function assessment. Amongst the different functional components