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Sample records for transcriptional variation reproduced

  1. Does systematic variation improve the reproducibility of animal experiments?

    NARCIS (Netherlands)

    Jonker, R.M.; Guenther, A.; Engqvist, L.; Schmoll, T.

    2013-01-01

    Reproducibility of results is a fundamental tenet of science. In this journal, Richter et al.1 tested whether systematic variation in experimental conditions (heterogenization) affects the reproducibility of results. Comparing this approach with the current standard of ensuring reproducibility

  2. Regulatory hotspots in the malaria parasite genome dictate transcriptional variation.

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    Joseph M Gonzales

    2008-09-01

    Full Text Available The determinants of transcriptional regulation in malaria parasites remain elusive. The presence of a well-characterized gene expression cascade shared by different Plasmodium falciparum strains could imply that transcriptional regulation and its natural variation do not contribute significantly to the evolution of parasite drug resistance. To clarify the role of transcriptional variation as a source of stain-specific diversity in the most deadly malaria species and to find genetic loci that dictate variations in gene expression, we examined genome-wide expression level polymorphisms (ELPs in a genetic cross between phenotypically distinct parasite clones. Significant variation in gene expression is observed through direct co-hybridizations of RNA from different P. falciparum clones. Nearly 18% of genes were regulated by a significant expression quantitative trait locus. The genetic determinants of most of these ELPs resided in hotspots that are physically distant from their targets. The most prominent regulatory locus, influencing 269 transcripts, coincided with a Chromosome 5 amplification event carrying the drug resistance gene, pfmdr1, and 13 other genes. Drug selection pressure in the Dd2 parental clone lineage led not only to a copy number change in the pfmdr1 gene but also to an increased copy number of putative neighboring regulatory factors that, in turn, broadly influence the transcriptional network. Previously unrecognized transcriptional variation, controlled by polymorphic regulatory genes and possibly master regulators within large copy number variants, contributes to sweeping phenotypic evolution in drug-resistant malaria parasites.

  3. Determinants, reproducibility, and seasonal variation of ergosterol levels in house dust.

    Science.gov (United States)

    Leppänen, H K; Nevalainen, A; Vepsäläinen, A; Roponen, M; Täubel, M; Laine, O; Rantakokko, P; von Mutius, E; Pekkanen, J; Hyvärinen, A

    2014-06-01

    This study aimed to clarify the determinants that affect the concentrations of ergosterol and viable fungi in house dust and to examine the seasonal variation and reproducibility of ergosterol concentrations indoors. In studying the determinants, dust samples from living room floors and vacuum cleaner dust bags were collected from 107 farming and 105 non-farming homes. Ergosterol levels were determined with gas chromatography-mass spectrometry,and the dust bag dust was cultivated for enumeration of fungal genera. Lifestyle and environmental factors, for example using of the fireplace, and visible mold observations in homes, explained 20–26% of the variation of fungal concentrations. For the reproducibility study, samples were collected from five urban homes in four different seasons. The reproducibility of ergosterol determinations within a sample was excellent (ICC = 89.8) for floor dust and moderate (ICC = 63.8) for dust bag dust, but poor when sampling the same home throughout a year (ICC = 31.3 and 12.6, respectively) due to large temporal variation in ergosterol concentrations. In conclusion, environmental characteristics only partially predicted the variation of fungal concentrations. Based on these studies, we recommend repeated sampling of dust over time if one seeks to adequately describe overall fungal levels and exposure in a home. This study shows that levels of ergosterol and viable fungi in house dust are related to visible mold observations. Only 20% of the variation in fungal levels can be explained with questionnaires, and therefore, environmental samples need to be taken in addition. Reproducibility of ergosterol determination was excellent for floor dust, and thus, ergosterol measurements from floor dust samples could be suitable for assessing the fungal load in building investigations. The temporal variation needs to be taken into account when describing the ergosterol concentration of urban homes.

  4. DNA template dependent accuracy variation of nucleotide selection in transcription.

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    Harriet Mellenius

    Full Text Available It has been commonly assumed that the effect of erroneous transcription of DNA genes into messenger RNAs on peptide sequence errors are masked by much more frequent errors of mRNA translation to protein. We present a theoretical model of transcriptional accuracy. It uses experimentally estimated standard free energies of double-stranded DNA and RNA/DNA hybrids and predicts a DNA template dependent transcriptional accuracy variation spanning several orders of magnitude. The model also identifies high-error as well a high-accuracy transcription motifs. The source of the large accuracy span is the context dependent variation of the stacking free energy of pairs of correct and incorrect base pairs in the ever moving transcription bubble. Our model predictions have direct experimental support from recent single molecule based identifications of transcriptional errors in the C. elegans transcriptome. Our conclusions challenge the general view that amino acid substitution errors in proteins are mainly caused by translational errors. It suggests instead that transcriptional error hotspots are the dominating source of peptide sequence errors in some DNA template contexts, while mRNA translation is the major cause of protein errors in other contexts.

  5. In silico detection of sequence variations modifying transcriptional regulation.

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    Malin C Andersen

    2008-01-01

    Full Text Available Identification of functional genetic variation associated with increased susceptibility to complex diseases can elucidate genes and underlying biochemical mechanisms linked to disease onset and progression. For genes linked to genetic diseases, most identified causal mutations alter an encoded protein sequence. Technological advances for measuring RNA abundance suggest that a significant number of undiscovered causal mutations may alter the regulation of gene transcription. However, it remains a challenge to separate causal genetic variations from linked neutral variations. Here we present an in silico driven approach to identify possible genetic variation in regulatory sequences. The approach combines phylogenetic footprinting and transcription factor binding site prediction to identify variation in candidate cis-regulatory elements. The bioinformatics approach has been tested on a set of SNPs that are reported to have a regulatory function, as well as background SNPs. In the absence of additional information about an analyzed gene, the poor specificity of binding site prediction is prohibitive to its application. However, when additional data is available that can give guidance on which transcription factor is involved in the regulation of the gene, the in silico binding site prediction improves the selection of candidate regulatory polymorphisms for further analyses. The bioinformatics software generated for the analysis has been implemented as a Web-based application system entitled RAVEN (regulatory analysis of variation in enhancers. The RAVEN system is available at http://www.cisreg.ca for all researchers interested in the detection and characterization of regulatory sequence variation.

  6. In Silico Detection of Sequence Variations Modifying Transcriptional Regulation

    Science.gov (United States)

    Andersen, Malin C; Engström, Pär G; Lithwick, Stuart; Arenillas, David; Eriksson, Per; Lenhard, Boris; Wasserman, Wyeth W; Odeberg, Jacob

    2008-01-01

    Identification of functional genetic variation associated with increased susceptibility to complex diseases can elucidate genes and underlying biochemical mechanisms linked to disease onset and progression. For genes linked to genetic diseases, most identified causal mutations alter an encoded protein sequence. Technological advances for measuring RNA abundance suggest that a significant number of undiscovered causal mutations may alter the regulation of gene transcription. However, it remains a challenge to separate causal genetic variations from linked neutral variations. Here we present an in silico driven approach to identify possible genetic variation in regulatory sequences. The approach combines phylogenetic footprinting and transcription factor binding site prediction to identify variation in candidate cis-regulatory elements. The bioinformatics approach has been tested on a set of SNPs that are reported to have a regulatory function, as well as background SNPs. In the absence of additional information about an analyzed gene, the poor specificity of binding site prediction is prohibitive to its application. However, when additional data is available that can give guidance on which transcription factor is involved in the regulation of the gene, the in silico binding site prediction improves the selection of candidate regulatory polymorphisms for further analyses. The bioinformatics software generated for the analysis has been implemented as a Web-based application system entitled RAVEN (regulatory analysis of variation in enhancers). The RAVEN system is available at http://www.cisreg.ca for all researchers interested in the detection and characterization of regulatory sequence variation. PMID:18208319

  7. Investigation of dimensional variation in parts manufactured by fused deposition modeling using Gauge Repeatability and Reproducibility

    Science.gov (United States)

    Mohamed, Omar Ahmed; Hasan Masood, Syed; Lal Bhowmik, Jahar

    2018-02-01

    In the additive manufacturing (AM) market, the question is raised by industry and AM users on how reproducible and repeatable the fused deposition modeling (FDM) process is in providing good dimensional accuracy. This paper aims to investigate and evaluate the repeatability and reproducibility of the FDM process through a systematic approach to answer this frequently asked question. A case study based on the statistical gage repeatability and reproducibility (gage R&R) technique is proposed to investigate the dimensional variations in the printed parts of the FDM process. After running the simulation and analysis of the data, the FDM process capability is evaluated, which would help the industry for better understanding the performance of FDM technology.

  8. Reproducibility of blood pressure variation in older ambulatory and bedridden subjects.

    Science.gov (United States)

    Tsuchihashi, Takuya; Kawakami, Yasunobu; Imamura, Tsuyoshi; Abe, Isao

    2002-06-01

    We investigated the influence of ambulation on the reproducibility of circadian blood pressure variation in older nursing home residents. Ambulatory blood pressure monitoring was performed twice in 37 older nursing home residents. Nursing home in Japan. Subjects included 18 ambulatory nursing home residents who had no limitation on physical activity and 19 bedridden residents who did not participate in physical activity. Twenty-four-hour, daytime, and nighttime blood pressure levels and their variability. The 24-hour and daytime variability of systolic blood pressure (SBP) was significantly greater in ambulatory than in bedridden subjects, whereas nighttime variability was similar. Significant correlations in SBP averaged for the whole day, daytime, and nighttime were observed between the two examinations in ambulatory (r =.80-.83) and bedridden (r =.83-.91) subjects, but the variabilities of SBP for the whole day and during the daytime of the first measurement were correlated with those of the second measurement in bedridden (r =.67 and r =.47, respectively) but not in ambulatory (r =.39 and r =.28, respectively) subjects. Significant correlations were found between the nocturnal SBP changes at two occasions in both ambulatory (r =.50) and bedridden (r =.51) subjects, but the dipper versus nondipper profiles, defined as reduction in SBP of greater than 10% versus not, showed low reproducibility in ambulatory subjects; five ambulatory (28%) and one bedridden (5%) subjects showed divergent profiles between the two examinations. The reproducibility of blood pressure variation in nursing home residents is influenced by ambulation.

  9. Mate-finding as an overlooked critical determinant of dispersal variation in sexually-reproducing animals.

    Science.gov (United States)

    Gilroy, James J; Lockwood, Julie L

    2012-01-01

    Dispersal is a critically important process in ecology, but robust predictive models of animal dispersal remain elusive. We identify a potentially ubiquitous component of variation in animal dispersal that has been largely overlooked until now: the influence of mate encounters on settlement probability. We use an individual-based model to simulate dispersal in sexually-reproducing organisms that follow a simple set of movement rules based on conspecific encounters, within an environment lacking spatial habitat heterogeneity. We show that dispersal distances vary dramatically with fluctuations in population density in such a model, even in the absence of variation in dispersive traits between individuals. In a simple random-walk model with promiscuous mating, dispersal distributions become increasingly 'fat-tailed' at low population densities due to the increasing scarcity of mates. Similar variation arises in models incorporating territoriality. In a model with polygynous mating, we show that patterns of sex-biased dispersal can even be reversed across a gradient of population density, despite underlying dispersal mechanisms remaining unchanged. We show that some widespread dispersal patterns found in nature (e.g. fat tailed distributions) can arise as a result of demographic variability in the absence of heterogeneity in dispersive traits across the population. This implies that models in which individual dispersal distances are considered to be fixed traits might be unrealistic, as dispersal distances vary widely under a single dispersal mechanism when settlement is influenced by mate encounters. Mechanistic models offer a promising means of advancing our understanding of dispersal in sexually-reproducing organisms.

  10. Normal variation and long-term reproducibility of image-selected in vivo brain MR spectroscopy

    International Nuclear Information System (INIS)

    Smith, M.A.; Porter, D.; Lowry, M.; Ayton, V.; Twelves, C.J.; Richards, M.A.; Garlick, P.; Maisey, M.N.

    1988-01-01

    MR spectroscopy of P-31 in the brain was performed with a 1.5-T MR imaging and spectroscopy system using ISIS with a 5-cm cube. A standardized spectral processing routine was adopted, and the ratios of peak areas were measured. Localized brain spectra were obtained from 17 healthy subjects, of whom ten had undergone repeated investigations after a delay of at least 1 month. The variation among healthy subjects, expressed as the mean +- standard deviation, and the long-term reproducibility, expressed as the coefficient of variation, were as follows: for peak areas phosphocreatine (PCr) Pi 2.46 +- 0.72, 21.3%, for PCr/PME, 1.97 +- 0.62, 16.8%, for PCr/PDE, 0.51 +- 0.07, 8.1%; for PCr/Υ-adenosine triphosphate (ATP), 1.13 + 0.15, 6.3%; for PCr/α-ATP, 1.09 +- 0.21, 10.3%, for PCr/β-ATP, 1.66 +- .027, 10.4%; and for pH, 7.00 +- 0.05, 0.8%

  11. Variation in the transcriptional response of threatened coral larvae to elevated temperatures.

    Science.gov (United States)

    Polato, Nicholas R; Altman, Naomi S; Baums, Iliana B

    2013-03-01

    Coral populations have declined worldwide largely due to increased sea surface temperatures. Recovery of coral populations depends in part upon larval recruitment. Many corals reproduce during the warmest time of year when further increases in temperature can lead to low fertilization rates of eggs and high larval mortality. Microarray experiments were designed to capture and assess variability in the thermal stress responses of Acropora palmata larvae from Puerto Rico. Transcription profiles showed a striking acceleration of normal developmental gene expression patterns with increased temperature. The transcriptional response to heat suggested rapid depletion of larval energy stores via peroxisomal lipid oxidation and included key enzymes that indicated the activation of the glyoxylate cycle. High temperature also resulted in expression differences in key developmental signalling genes including the conserved WNT pathway that is critical for pattern formation and tissue differentiation in developing embryos. Expression of these and other important developmental and thermal stress genes such as ferritin, heat shock proteins, cytoskeletal components, cell adhesion and autophagy proteins also varied among larvae derived from different parent colonies. Disruption of normal developmental and metabolic processes will have negative impacts on larval survival and dispersal as temperatures rise. However, it appears that variation in larval response to high temperature remains despite the dramatic population declines. Further research is needed to determine whether this variation is heritable or attributable to maternal effects. © 2013 Blackwell Publishing Ltd.

  12. Genetic variation shapes protein networks mainly through non-transcriptional mechanisms.

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    Eric J Foss

    2011-09-01

    Full Text Available Networks of co-regulated transcripts in genetically diverse populations have been studied extensively, but little is known about the degree to which these networks cause similar co-variation at the protein level. We quantified 354 proteins in a genetically diverse population of yeast segregants, which allowed for the first time construction of a coherent protein co-variation matrix. We identified tightly co-regulated groups of 36 and 93 proteins that were made up predominantly of genes involved in ribosome biogenesis and amino acid metabolism, respectively. Even though the ribosomal genes were tightly co-regulated at both the protein and transcript levels, genetic regulation of proteins was entirely distinct from that of transcripts, and almost no genes in this network showed a significant correlation between protein and transcript levels. This result calls into question the widely held belief that in yeast, as opposed to higher eukaryotes, ribosomal protein levels are regulated primarily by regulating transcript levels. Furthermore, although genetic regulation of the amino acid network was more similar for proteins and transcripts, regression analysis demonstrated that even here, proteins vary predominantly as a result of non-transcriptional variation. We also found that cis regulation, which is common in the transcriptome, is rare at the level of the proteome. We conclude that most inter-individual variation in levels of these particular high abundance proteins in this genetically diverse population is not caused by variation of their underlying transcripts.

  13. Thickness of patellofemoral articular cartilage as measured on MR imaging: sequence comparison of accuracy, reproducibility, and interobserver variation

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    Van Leersum, M.D. [Dept. of Radiology, Thomas Jefferson Univ. Hospital, Philadelphia, PA (United States); Schweitzer, M.E. [Dept. of Radiology, Thomas Jefferson Univ. Hospital, Philadelphia, PA (United States); Gannon, F. [Dept. of Pathology, Thomas Jefferson Univ. Hospital, Philadelphia, PA (United States); Vinitski, S. [Dept. of Radiology, Thomas Jefferson Univ. Hospital, Philadelphia, PA (United States); Finkel, G. [Dept. of Pathology, Thomas Jefferson Univ. Hospital, Philadelphia, PA (United States); Mitchell, D.G. [Dept. of Radiology, Thomas Jefferson Univ. Hospital, Philadelphia, PA (United States)

    1995-08-01

    This study was undertaken to assess the accuracy, precision, and reliability of magnetic resonance (MR) measurements of articular cartilage. Fifteen cadaveric patellas were imaged in the axial plane at 1.5 T. Gradient echo and fat-suppressed FSE, T2-weighted, proton density, and T1-weighted sequences were performed. We measured each 5-mm section separately at three standardized positions, giving a total of 900 measurements. These findings were correlated with independently performed measurements of the corresponding anatomic sections. A hundred random measurements were also evaluated for reproducibility and interobserver variation. Although all sequences were highly accurate, the T1-weighted images were the most accurate, with a mean difference of 0.25 mm and a correlation coefficient of 0.85. All sequences were also highly reproducible with little inter-observer variation. In an attempt to improve the accuracy of the MR measurements further, we retrospectively evaluated all measurements with discrepancies greater than 1 mm from the specimen. All these differences were attributable to focal defects causing exaggeration of the thickness on MR imaging. (orig.)

  14. Thickness of patellofemoral articular cartilage as measured on MR imaging: sequence comparison of accuracy, reproducibility, and interobserver variation

    International Nuclear Information System (INIS)

    Van Leersum, M.D.; Schweitzer, M.E.; Gannon, F.; Vinitski, S.; Finkel, G.; Mitchell, D.G.

    1995-01-01

    This study was undertaken to assess the accuracy, precision, and reliability of magnetic resonance (MR) measurements of articular cartilage. Fifteen cadaveric patellas were imaged in the axial plane at 1.5 T. Gradient echo and fat-suppressed FSE, T2-weighted, proton density, and T1-weighted sequences were performed. We measured each 5-mm section separately at three standardized positions, giving a total of 900 measurements. These findings were correlated with independently performed measurements of the corresponding anatomic sections. A hundred random measurements were also evaluated for reproducibility and interobserver variation. Although all sequences were highly accurate, the T1-weighted images were the most accurate, with a mean difference of 0.25 mm and a correlation coefficient of 0.85. All sequences were also highly reproducible with little inter-observer variation. In an attempt to improve the accuracy of the MR measurements further, we retrospectively evaluated all measurements with discrepancies greater than 1 mm from the specimen. All these differences were attributable to focal defects causing exaggeration of the thickness on MR imaging. (orig.)

  15. Axially perpendicular offset Raman scheme for reproducible measurement of housed samples in a noncircular container under variation of container orientation.

    Science.gov (United States)

    Duy, Pham K; Chang, Kyeol; Sriphong, Lawan; Chung, Hoeil

    2015-03-17

    An axially perpendicular offset (APO) scheme that is able to directly acquire reproducible Raman spectra of samples contained in an oval container under variation of container orientation has been demonstrated. This scheme utilized an axially perpendicular geometry between the laser illumination and the Raman photon detection, namely, irradiation through a sidewall of the container and gathering of the Raman photon just beneath the container. In the case of either backscattering or transmission measurements, Raman sampling volumes for an internal sample vary when the orientation of an oval container changes; therefore, the Raman intensities of acquired spectra are inconsistent. The generated Raman photons traverse the same bottom of the container in the APO scheme; the Raman sampling volumes can be relatively more consistent under the same situation. For evaluation, the backscattering, transmission, and APO schemes were simultaneously employed to measure alcohol gel samples contained in an oval polypropylene container at five different orientations and then the accuracies of the determination of the alcohol concentrations were compared. The APO scheme provided the most reproducible spectra, yielding the best accuracy when the axial offset distance was 10 mm. Monte Carlo simulations were performed to study the characteristics of photon propagation in the APO scheme and to explain the origin of the optimal offset distance that was observed. In addition, the utility of the APO scheme was further demonstrated by analyzing samples in a circular glass container.

  16. A sensitive, reproducible, and economic real-time reverse transcription PCR detecting avian metapneumovirus subtypes A and B.

    Science.gov (United States)

    Franzo, G; Drigo, M; Lupini, C; Catelli, E; Laconi, A; Listorti, V; Bonci, M; Naylor, C J; Martini, M; Cecchinato, M

    2014-06-01

    Use of real-time PCR is increasing in the diagnosis of infectious disease due to its sensitivity, specificity, and speed of detection. These characteristics make it particularly suited for the diagnosis of viral infections, like avian metapneumovirus (AMPV), for which effective control benefits from continuously updated knowledge of the epidemiological situation. Other real-time reverse transcription (RT)-PCRs have been published based on highly specific fluorescent dye-labeled probes, but they have high initial cost, complex validation, and a marked susceptibility to the genetic variability of their target sequence. With this in mind, we developed and validated a SYBR Green I-based quantitative RT-PCR for the detection of the two most prevalent AMPV subtypes (i.e., subtypes A and B). The assay demonstrated an analytical sensitivity comparable with that of a previously published real-time RT-PCR and the ability to detect RNA equivalent to approximately 0.5 infectious doses for both A and B subtypes. The high efficiency and linearity between viral titer and crossing point displayed for both subtypes make it suited for viral quantification. Optimization of reaction conditions and the implementation of melting curve analysis guaranteed the high specificity of the assay. The stable melting temperature difference between the two subtypes indicated the possibility of subtyping through melting temperature analysis. These characteristics make our assay a sensitive, specific, and rapid tool, enabling contemporaneous detection, quantification, and discrimination of AMPV subtype A and B.

  17. Post-transcriptional Mechanisms Contribute Little to Phenotypic Variation in Snake Venoms.

    Science.gov (United States)

    Rokyta, Darin R; Margres, Mark J; Calvin, Kate

    2015-09-09

    Protein expression is a major link in the genotype-phenotype relationship, and processes affecting protein abundances, such as rates of transcription and translation, could contribute to phenotypic evolution if they generate heritable variation. Recent work has suggested that mRNA abundances do not accurately predict final protein abundances, which would imply that post-transcriptional regulatory processes contribute significantly to phenotypes. Post-transcriptional processes also appear to buffer changes in transcriptional patterns as species diverge, suggesting that the transcriptional changes have little or no effect on the phenotypes undergoing study. We tested for concordance between mRNA and protein expression levels in snake venoms by means of mRNA-seq and quantitative mass spectrometry for 11 snakes representing 10 species, six genera, and three families. In contrast to most previous work, we found high correlations between venom gland transcriptomes and venom proteomes for 10 of our 11 comparisons. We tested for protein-level buffering of transcriptional changes during species divergence by comparing the difference between transcript abundance and protein abundance for three pairs of species and one intraspecific pair. We found no evidence for buffering during divergence of our three species pairs but did find evidence for protein-level buffering for our single intraspecific comparison, suggesting that buffering, if present, was a transient phenomenon in venom divergence. Our results demonstrated that post-transcriptional mechanisms did not contribute significantly to phenotypic evolution in venoms and suggest a more prominent and direct role for cis-regulatory evolution in phenotypic variation, particularly for snake venoms. Copyright © 2015 Rokyta et al.

  18. Deciphering molecular circuits from genetic variation underlying transcriptional responsiveness to stimuli.

    Science.gov (United States)

    Gat-Viks, Irit; Chevrier, Nicolas; Wilentzik, Roni; Eisenhaure, Thomas; Raychowdhury, Raktima; Steuerman, Yael; Shalek, Alex K; Hacohen, Nir; Amit, Ido; Regev, Aviv

    2013-04-01

    Individual genetic variation affects gene responsiveness to stimuli, often by influencing complex molecular circuits. Here we combine genomic and intermediate-scale transcriptional profiling with computational methods to identify variants that affect the responsiveness of genes to stimuli (responsiveness quantitative trait loci or reQTLs) and to position these variants in molecular circuit diagrams. We apply this approach to study variation in transcriptional responsiveness to pathogen components in dendritic cells from recombinant inbred mouse strains. We identify reQTLs that correlate with particular stimuli and position them in known pathways. For example, in response to a virus-like stimulus, a trans-acting variant responds as an activator of the antiviral response; using RNA interference, we identify Rgs16 as the likely causal gene. Our approach charts an experimental and analytic path to decipher the mechanisms underlying genetic variation in circuits that control responses to stimuli.

  19. Molecular measurement of BCR-ABL transcript variations in chronic myeloid leukemia patients in cytogenetic remission

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    Costa Juliana

    2010-11-01

    Full Text Available Abstract Background The monitoring of BCR-ABL transcript levels by real-time quantitative polymerase chain reaction (RT-qPCR has become important to assess minimal residual disease (MRD and standard of care in the treatment of chronic myeloid leukemia (CML. In this study, we performed a prospective, sequential analysis using RT-qPCR monitoring of BCR-ABL gene rearrangements in blood samples from 91 CML patients in chronic phase (CP who achieved complete cytogenetic remission (CCyR and major molecular remission (MMR throughout imatinib treatment. Methods The absolute level of BCR-ABL transcript from peripheral blood was serially measured every 4 to 12 weeks by RT-qPCR. Only level variations > 0.5%, according to the international scale, was considered positive. Sequential cytogenetic analysis was also performed in bone marrow samples from all patients using standard protocols. Results Based on sequential analysis of BCR-ABL transcripts, the 91 patients were divided into three categories: (A 57 (62.6% had no variation on sequential analysis; (B 30 (32.9% had a single positive variation result obtained in a single sample; and (C 4 (4.39% had variations of BCR-ABL transcripts in at least two consecutive samples. Of the 34 patients who had elevated levels of transcripts (group B and C, 19 (55.8% had a BCR-ABL/BCR ratio, 13 (38.2% patients had a 1% to 10% increase and 2 patients had a >10% increase of RT-qPCR. The last two patients had lost a CCyR, and none of them showed mutations in the ABL gene. Transient cytogenetic alterations in Ph-negative cells were observed in five (5.5% patients, and none of whom lost CCyR. Conclusions Despite an increase levels of BCR-ABL/BCR ratio variations by RT-qPCR, the majority of CML patients with MMR remained in CCyR. Thus, such single variations should neither be considered predictive of subsequent failure and nor an indication for altering imatinib dose or switching to second generation therapy. Changing of

  20. Study of the variation of the nuclear transcriptional map during de initial development of Drosophyla melanogaster embryos

    International Nuclear Information System (INIS)

    Alonso, C.E.V.

    1987-01-01

    The variation of nuclear transcriptional map during the initial development of Drosophyla melanogaster embryos were studied. Thermic treatment, chromatographic techniques and liquid scintilation in embryos inoculated with radioactive uridine were used. (L.J.C.)

  1. Distinct Contributions of Replication and Transcription to Mutation Rate Variation of Human Genomes

    KAUST Repository

    Cui, Peng; Ding, Feng; Lin, Qiang; Zhang, Lingfang; Li, Ang; Zhang, Zhang; Hu, Songnian; Yu, Jun

    2012-01-01

    Here, we evaluate the contribution of two major biological processes—DNA replication and transcription—to mutation rate variation in human genomes. Based on analysis of the public human tissue transcriptomics data, high-resolution replicating map of Hela cells and dbSNP data, we present significant correlations between expression breadth, replication time in local regions and SNP density. SNP density of tissue-specific (TS) genes is significantly higher than that of housekeeping (HK) genes. TS genes tend to locate in late-replicating genomic regions and genes in such regions have a higher SNP density compared to those in early-replication regions. In addition, SNP density is found to be positively correlated with expression level among HK genes. We conclude that the process of DNA replication generates stronger mutational pressure than transcription-associated biological processes do, resulting in an increase of mutation rate in TS genes while having weaker effects on HK genes. In contrast, transcription-associated processes are mainly responsible for the accumulation of mutations in highly-expressed HK genes.

  2. Distinct Contributions of Replication and Transcription to Mutation Rate Variation of Human Genomes

    KAUST Repository

    Cui, Peng

    2012-03-23

    Here, we evaluate the contribution of two major biological processes—DNA replication and transcription—to mutation rate variation in human genomes. Based on analysis of the public human tissue transcriptomics data, high-resolution replicating map of Hela cells and dbSNP data, we present significant correlations between expression breadth, replication time in local regions and SNP density. SNP density of tissue-specific (TS) genes is significantly higher than that of housekeeping (HK) genes. TS genes tend to locate in late-replicating genomic regions and genes in such regions have a higher SNP density compared to those in early-replication regions. In addition, SNP density is found to be positively correlated with expression level among HK genes. We conclude that the process of DNA replication generates stronger mutational pressure than transcription-associated biological processes do, resulting in an increase of mutation rate in TS genes while having weaker effects on HK genes. In contrast, transcription-associated processes are mainly responsible for the accumulation of mutations in highly-expressed HK genes.

  3. Understanding gene sequence variation in the context of transcription regulation in yeast.

    Directory of Open Access Journals (Sweden)

    Irit Gat-Viks

    2010-01-01

    Full Text Available DNA sequence polymorphism in a regulatory protein can have a widespread transcriptional effect. Here we present a computational approach for analyzing modules of genes with a common regulation that are affected by specific DNA polymorphisms. We identify such regulatory-linkage modules by integrating genotypic and expression data for individuals in a segregating population with complementary expression data of strains mutated in a variety of regulatory proteins. Our procedure searches simultaneously for groups of co-expressed genes, for their common underlying linkage interval, and for their shared regulatory proteins. We applied the method to a cross between laboratory and wild strains of S. cerevisiae, demonstrating its ability to correctly suggest modules and to outperform extant approaches. Our results suggest that middle sporulation genes are under the control of polymorphism in the sporulation-specific tertiary complex Sum1p/Rfm1p/Hst1p. In another example, our analysis reveals novel inter-relations between Swi3 and two mitochondrial inner membrane proteins underlying variation in a module of aerobic cellular respiration genes. Overall, our findings demonstrate that this approach provides a useful framework for the systematic mapping of quantitative trait loci and their role in gene expression variation.

  4. Diffusion weighted imaging of the normal breast: reproducibility of apparent diffusion coefficient measurements and variation with menstrual cycle and menopausal status

    International Nuclear Information System (INIS)

    O'Flynn, Elizabeth A.M.; Morgan, Veronica A.; Giles, Sharon L.; de Souza, Nandita M.

    2012-01-01

    To establish the reproducibility of apparent diffusion coefficient (ADC) measurements in normal fibroglandular breast tissue and to assess variation in ADC values with phase of the menstrual cycle and menopausal status. Thirty-one volunteers (13 premenopausal, 18 postmenopausal) underwent magnetic resonance twice (interval 11-22 days) using diffusion-weighted MRI. ADC total and a perfusion-insensitive ADC high (omitting b = 0) were calculated. Reproducibility and inter-observer variability of mean ADC values were assessed. The difference in mean ADC values between the two phases of the menstrual cycle and the postmenopausal breast were evaluated. ADC total and ADC high showed good reproducibility (r% = 17.6, 22.4). ADC high showed very good inter-observer agreement (kappa = 0.83). The intraclass correlation coefficients (ICC) were 0.93 and 0.91. Mean ADC values were significantly lower in the postmenopausal breast (ADC total 1.46 ± 0.3 x 10 -3 mm 2 /s, ADC high 1.33 ± 0.3 x 10 -3 mm 2 /s) compared with the premenopausal breast (ADC total 1.84 ± 0.26 x 10 -3 mm 2 /s, ADC high 1.77 ± 0.26 x 10 -3 mm 2 /s; both P total P = 0.2, ADC high P = 0.24) or between postmenopausal women taking or not taking oestrogen supplements (ADC total P = 0.6, ADC high P = 0.46). ADC values in fibroglandular breast tissue are reproducible. Lower ADC values within the postmenopausal breast may reduce diffusion-weighted contrast and have implications for accurately detecting tumours. (orig.)

  5. Diffusion weighted imaging of the normal breast: reproducibility of apparent diffusion coefficient measurements and variation with menstrual cycle and menopausal status

    Energy Technology Data Exchange (ETDEWEB)

    O' Flynn, Elizabeth A.M.; Morgan, Veronica A.; Giles, Sharon L. [Cancer Research UK and ESPSRC Cancer Imaging Centre, Clinical Magnetic Resonance Group, Surrey (United Kingdom); deSouza, Nandita M. [Royal Marsden NHS Foundation Trust, Clinical Magnetic Resonance Group, Institute of Cancer Research, Surrey (United Kingdom)

    2012-07-15

    To establish the reproducibility of apparent diffusion coefficient (ADC) measurements in normal fibroglandular breast tissue and to assess variation in ADC values with phase of the menstrual cycle and menopausal status. Thirty-one volunteers (13 premenopausal, 18 postmenopausal) underwent magnetic resonance twice (interval 11-22 days) using diffusion-weighted MRI. ADC{sub total} and a perfusion-insensitive ADC{sub high} (omitting b = 0) were calculated. Reproducibility and inter-observer variability of mean ADC values were assessed. The difference in mean ADC values between the two phases of the menstrual cycle and the postmenopausal breast were evaluated. ADC{sub total} and ADC{sub high} showed good reproducibility (r% = 17.6, 22.4). ADC{sub high} showed very good inter-observer agreement (kappa = 0.83). The intraclass correlation coefficients (ICC) were 0.93 and 0.91. Mean ADC values were significantly lower in the postmenopausal breast (ADC{sub total} 1.46 {+-} 0.3 x 10{sup -3} mm{sup 2}/s, ADC{sub high} 1.33 {+-} 0.3 x 10{sup -3} mm{sup 2}/s) compared with the premenopausal breast (ADC{sub total} 1.84 {+-} 0.26 x 10{sup -3} mm{sup 2}/s, ADC{sub high} 1.77 {+-} 0.26 x 10{sup -3} mm{sup 2}/s; both P < 0.001). No significant difference was seen in ADC values in relation to menstrual cycle (ADC{sub total} P = 0.2, ADC{sub high} P = 0.24) or between postmenopausal women taking or not taking oestrogen supplements (ADC{sub total} P = 0.6, ADC{sub high} P = 0.46). ADC values in fibroglandular breast tissue are reproducible. Lower ADC values within the postmenopausal breast may reduce diffusion-weighted contrast and have implications for accurately detecting tumours. (orig.)

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

    Science.gov (United States)

    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.

  7. Diffusion-weighted MR imaging of the normal pancreas: reproducibility and variations of apparent diffusion coefficient measurement at 1.5- and 3.0-Tesla.

    Science.gov (United States)

    Barral, M; Soyer, P; Ben Hassen, W; Gayat, E; Aout, M; Chiaradia, M; Rahmouni, A; Luciani, A

    2013-04-01

    To evaluate reproducibility and variations in apparent diffusion coefficient (ADC) measurement in normal pancreatic parenchyma at 1.5- and 3.0-Tesla and determine if differences may exist between the four pancreatic segments. Diffusion-weighted MR imaging of the pancreas was performed at 1.5-Tesla in 20 patients and at 3.0-Tesla in other 20 patients strictly matched for gender and age using the same b values (0, 400 and 800s/mm(2)). Two independent observers placed regions of interest within the four pancreatic segments to measure ADC at both fields. Intra- and inter-observer agreement in ADC measurement was assessed using Bland-Altman analysis and comparison between ADC values obtained at both fields using non-parametrical tests. There were no significant differences in ADC between repeated measurements and between ADC obtained at 1.5-Tesla and those at 3.0-Tesla. The 95% limits of intra-observer agreement between ADC were 2.3%-22.7% at 1.5-Tesla and 1%-24.2% at 3.0-Tesla and those for inter-observer agreement between 1.9%-14% at 1.5-Tesla and 8%-25% at 3.0-Tesla. ADC values were similar in all pancreatic segments at 3.0-T whereas the tail had lower ADC at 1.5-Tesla. ADC measurement conveys high degrees of intra- and inter-observer reproducibility. ADC have homogeneous distribution among the four pancreatic segments at 3.0-Tesla. Copyright © 2012 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.

  8. Loss of variation of state detected in soybean metabolic and human myelomonocytic leukaemia cell transcriptional networks under external stimuli

    KAUST Repository

    Sakata, Katsumi

    2016-10-24

    Soybean (Glycine max) is sensitive to flooding stress, and flood damage at the seedling stage is a barrier to growth. We constructed two mathematical models of the soybean metabolic network, a control model and a flooded model, from metabolic profiles in soybean plants. We simulated the metabolic profiles with perturbations before and after the flooding stimulus using the two models. We measured the variation of state that the system could maintain from a state–space description of the simulated profiles. The results showed a loss of variation of state during the flooding response in the soybean plants. Loss of variation of state was also observed in a human myelomonocytic leukaemia cell transcriptional network in response to a phorbol-ester stimulus. Thus, we detected a loss of variation of state under external stimuli in two biological systems, regardless of the regulation and stimulus types. Our results suggest that a loss of robustness may occur concurrently with the loss of variation of state in biological systems. We describe the possible applications of the quantity of variation of state in plant genetic engineering and cell biology. Finally, we present a hypothetical “external stimulus-induced information loss” model of biological systems.

  9. Loss of variation of state detected in soybean metabolic and human myelomonocytic leukaemia cell transcriptional networks under external stimuli

    KAUST Repository

    Sakata, Katsumi; Saito, Toshiyuki; Ohyanagi, Hajime; Okumura, Jun; Ishige, Kentaro; Suzuki, Harukazu; Nakamura, Takuji; Komatsu, Setsuko

    2016-01-01

    Soybean (Glycine max) is sensitive to flooding stress, and flood damage at the seedling stage is a barrier to growth. We constructed two mathematical models of the soybean metabolic network, a control model and a flooded model, from metabolic profiles in soybean plants. We simulated the metabolic profiles with perturbations before and after the flooding stimulus using the two models. We measured the variation of state that the system could maintain from a state–space description of the simulated profiles. The results showed a loss of variation of state during the flooding response in the soybean plants. Loss of variation of state was also observed in a human myelomonocytic leukaemia cell transcriptional network in response to a phorbol-ester stimulus. Thus, we detected a loss of variation of state under external stimuli in two biological systems, regardless of the regulation and stimulus types. Our results suggest that a loss of robustness may occur concurrently with the loss of variation of state in biological systems. We describe the possible applications of the quantity of variation of state in plant genetic engineering and cell biology. Finally, we present a hypothetical “external stimulus-induced information loss” model of biological systems.

  10. Aluminum resistance transcription factor 1 (ART1) contributes to natural variation in rice aluminum resistance

    Science.gov (United States)

    Transcription factors (TFs) mediate stress resistance indirectly via physiological mechanisms driven by the array of genes they regulate. Therefore, when studying TF-mediated stress resistance, it is important to understand how TFs interact with different genetic backgrounds. Here, we fine-mapped th...

  11. Genetic variations in GPSM3 associated with protection from rheumatoid arthritis affect its transcript abundance.

    Science.gov (United States)

    Gall, B J; Wilson, A; Schroer, A B; Gross, J D; Stoilov, P; Setola, V; Watkins, C M; Siderovski, D P

    2016-03-01

    G protein signaling modulator 3 (GPSM3) is a regulator of G protein-coupled receptor signaling, with expression restricted to leukocytes and lymphoid organs. Previous genome-wide association studies have highlighted single-nucleotide polymorphisms (SNPs; rs204989 and rs204991) in a region upstream of the GPSM3 transcription start site as being inversely correlated to the prevalence of rheumatoid arthritis (RA)-this association is supported by the protection afforded to Gpsm3-deficient mice in models of inflammatory arthritis. Here, we assessed the functional consequences of these polymorphisms. We collected biospecimens from 50 volunteers with RA diagnoses, 50 RA-free volunteers matched to the aforementioned group and 100 unmatched healthy young volunteers. We genotyped these individuals for GPSM3 (rs204989, rs204991), CCL21 (rs2812378) and HLA gene region (rs6457620) polymorphisms, and found no significant differences in minor allele frequencies between the RA and disease-free cohorts. However, we identified that individuals homozygous for SNPs rs204989 and rs204991 had decreased GPSM3 transcript abundance relative to individuals homozygous for the major allele. In vitro promoter activity studies suggest that SNP rs204989 is the primary cause of this decrease in transcript levels. Knockdown of GPSM3 in THP-1 cells, a human monocytic cell line, was found to disrupt ex vivo migration to the chemokine MCP-1.

  12. Transcription factor 7-like 2 (TCF7L2) variations associated with ...

    Indian Academy of Sciences (India)

    2012-08-13

    Aug 13, 2012 ... ... variations associated with earlier age-onset of type 2 diabetes in Thai patients ... Genomewide linkage analysis has revealed that a region on chromosome ..... 2003 Meta-analysis and a large association study confirm a role ...

  13. Transcription through the eye of a needle: daily and annual cyclic gene expression variation in Douglas-fir needles.

    Science.gov (United States)

    Cronn, Richard; Dolan, Peter C; Jogdeo, Sanjuro; Wegrzyn, Jill L; Neale, David B; St Clair, J Bradley; Denver, Dee R

    2017-07-24

    Perennial growth in plants is the product of interdependent cycles of daily and annual stimuli that induce cycles of growth and dormancy. In conifers, needles are the key perennial organ that integrates daily and seasonal signals from light, temperature, and water availability. To understand the relationship between seasonal cycles and seasonal gene expression responses in conifers, we examined diurnal and circannual needle mRNA accumulation in Douglas-fir (Pseudotsuga menziesii) needles at diurnal and circannual scales. Using mRNA sequencing, we sampled 6.1 × 10 9 reads from 19 trees and constructed a de novo pan-transcriptome reference that includes 173,882 tree-derived transcripts. Using this reference, we mapped RNA-Seq reads from 179 samples that capture daily and annual variation. We identified 12,042 diurnally-cyclic transcripts, 9299 of which showed homology to annotated genes from other plant genomes, including angiosperm core clock genes. Annual analysis revealed 21,225 circannual transcripts, 17,335 of which showed homology to annotated genes from other plant genomes. The timing of maximum gene expression is associated with light intensity at diurnal scales and photoperiod at annual scales, with approximately half of transcripts reaching maximum expression +/- 2 h from sunrise and sunset, and +/- 20 days from winter and summer solstices. Comparisons with published studies from other conifers shows congruent behavior in clock genes with Japanese cedar (Cryptomeria), and a significant preservation of gene expression patterns for 2278 putative orthologs from Douglas-fir during the summer growing season, and 760 putative orthologs from spruce (Picea) during the transition from fall to winter. Our study highlight the extensive diurnal and circannual transcriptome variability demonstrated in conifer needles. At these temporal scales, 29% of expressed transcripts show a significant diurnal cycle, and 58.7% show a significant circannual cycle. Remarkably

  14. Transcriptional Profiling of Saccharomyces cerevisiae Reveals the Impact of Variation of a Single Transcription Factor on Differential Gene Expression in 4NQO, Fermentable, and Nonfermentable Carbon Sources

    Directory of Open Access Journals (Sweden)

    Xiaoqing Rong-Mullins

    2018-02-01

    . Hence, the complement to 4NQO resistance was poor growth on nonfermentable carbon sources, which in turn varied depending on the allele of Yrr1 expressed in the isogenic yeast. The oxidation state of the yeast affected the 4NQO toxicity by altering the reactive oxygen species (ROS generated by cellular metabolism. The integration of RNA-Seq and ChIP-Seq elucidated how Yrr1 regulates global gene transcription in response to 4NQO and how various Yrr1 alleles confer differential resistance to 4NQO. This study provides guidance for further investigation into how Yrr1 regulates cellular responses to 4NQO, as well as transcriptomic resources for further analysis of transcription factor variation on carbon source utilization.

  15. Associations of GBP2 gene copy number variations with growth traits and transcriptional expression in Chinese cattle.

    Science.gov (United States)

    Zhang, Gui-Min; Zheng, Li; He, Hua; Song, Cheng-Chuang; Zhang, Zi-Jing; Cao, Xiu-Kai; Lei, Chu-Zhao; Lan, Xian-Yong; Qi, Xing-Lei; Chen, Hong; Huang, Yong-Zhen

    2018-03-20

    Copy number variations (CNVs) recently have been recognized as another important genetic variability followed single nucleotide polymorphisms (SNPs). The guanylate binding protein 2 (GBP2) gene plays an important role in cell proliferation. This study was performed to determine the presence of GBP2 CNV (relative to Angus cattle) in 466 individuals representing six main cattle breeds from China, identify its relationship with growth, and explore the biological effects of gene expression. There were two CNV regions in the GBP2 gene, for three types, CNV1 loss type (relative to Angus cattle) was more frequent in XN than other breeds, and CNV2 loss type (relative to Angus cattle) was more frequent in XN and CDM than other breeds. Though the GBP2 gene copy number presented no correlation with the transcriptional expression of JX (P > .05), but the transcriptional expression in heart is higher than other tissues, and the copy number in muscles and fat of JX is higher than others breeds. Statistical analysis revealed that the GBP2 gene CNV1 and CNV2 were significantly associated with growth traits (P cattle breeds, and our results suggested that the CNVs in GBP2 gene may be considered markers for the molecular breeding of Chinese beef cattle. Copyright © 2018. Published by Elsevier B.V.

  16. Molecular Evolution and Genetic Variation of G2-Like Transcription Factor Genes in Maize.

    Directory of Open Access Journals (Sweden)

    Fang Liu

    Full Text Available The productivity of maize (Zea mays L. depends on the development of chloroplasts, and G2-like transcription factors play a central role in regulating chloroplast development. In this study, we identified 59 G2-like genes in the B73 maize genome and systematically analyzed these genes at the molecular and evolutionary levels. Based on gene structure character, motif compositions and phylogenetic analysis, maize G2-like genes (ZmG1- ZmG59 were divided into seven groups (I-VII. By synteny analysis, 18 collinear gene pairs and strongly conserved microsyntny among regions hosting G2-like genes across maize and sorghum were found. Here, we showed that the vast majority of ZmG gene duplications resulted from whole genome duplication events rather than tandem duplications. After gene duplication events, some ZmG genes were silenced. The functions of G2-like genes were multifarious and most genes that are expressed in green tissues may relate to maize photosynthesis. The qRT-PCR showed that the expression of these genes was sensitive to low temperature and drought. Furthermore, we analyzed differences of ZmGs specific to cultivars in temperate and tropical regions at the population level. Interestingly, the single nucleotide polymorphism (SNP analysis revealed that nucleotide polymorphism associated with different temperature zones. Above all, G2-like genes were highly conserved during evolution, but polymorphism could be caused due to a different geographical location. Moreover, G2-like genes might be related to cold and drought stresses.

  17. Genetic variation in metallothionein and metal-regulatory transcription factor 1 in relation to urinary cadmium, copper, and zinc

    International Nuclear Information System (INIS)

    Adams, Scott V.; Barrick, Brian; Christopher, Emily P.; Shafer, Martin M.; Makar, Karen W.; Song, Xiaoling; Lampe, Johanna W.; Vilchis, Hugo; Ulery, April; Newcomb, Polly A.

    2015-01-01

    Background: Metallothionein (MT) proteins play critical roles in the physiological handling of both essential (Cu and Zn) and toxic (Cd) metals. MT expression is regulated by metal-regulatory transcription factor 1 (MTF1). Hence, genetic variation in the MT gene family and MTF1 might influence excretion of these metals. Methods: 321 women were recruited in Seattle, WA and Las Cruces, NM and provided demographic information, urine samples for measurement of metal concentrations by mass spectrometry and creatinine, and blood or saliva for extraction of DNA. Forty-one single nucleotide polymorphisms (SNPs) within the MTF1 gene region and the region of chromosome 16 encoding the MT gene family were selected for genotyping in addition to an ancestry informative marker panel. Linear regression was used to estimate the association of SNPs with urinary Cd, Cu, and Zn, adjusted for age, urinary creatinine, smoking history, study site, and ancestry. Results: Minor alleles of rs28366003 and rs10636 near the MT2A gene were associated with lower urinary Cd, Cu, and Zn. Minor alleles of rs8044719 and rs1599823, near MT1A and MT1B, were associated with lower urinary Cd and Zn, respectively. Minor alleles of rs4653329 in MTF1 were associated with lower urinary Cd. Conclusions: These results suggest that genetic variation in the MT gene region and MTF1 influences urinary Cd, Cu, and Zn excretion. - Highlights: • Genetic variation in metallothionein (MT) genes was assessed in two diverse populations. • Single nucleotide polymorphisms (SNPs) in MT genes were associated with mean urinary Cd, Cu and Zn. • Genetic variation may influence biomarkers of exposure, and associations of exposure with health.

  18. Genetic variation in metallothionein and metal-regulatory transcription factor 1 in relation to urinary cadmium, copper, and zinc

    Energy Technology Data Exchange (ETDEWEB)

    Adams, Scott V., E-mail: sadams@fhcrc.org [Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109 (United States); Barrick, Brian [Department of Plant and Environmental Sciences, New Mexico State University, Box 30003 MSC 3Q, Las Cruces, NM 88003 (United States); Christopher, Emily P. [Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109 (United States); Shafer, Martin M. [Environmental Chemistry and Technology, Wisconsin State Laboratory of Hygiene, University of Wisconsin, 2601 Agriculture Dr., Madison, WI 53718 (United States); Makar, Karen W.; Song, Xiaoling [Public Health Science Biomarker Laboratory, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109 (United States); Lampe, Johanna W. [Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109 (United States); Vilchis, Hugo [Border Epidemiology and Environmental Health Center, New Mexico State University, Box 30001 MSC 3BEC, Las Cruces, NM 88003 (United States); Ulery, April [Department of Plant and Environmental Sciences, New Mexico State University, Box 30003 MSC 3Q, Las Cruces, NM 88003 (United States); Newcomb, Polly A. [Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109 (United States)

    2015-12-15

    Background: Metallothionein (MT) proteins play critical roles in the physiological handling of both essential (Cu and Zn) and toxic (Cd) metals. MT expression is regulated by metal-regulatory transcription factor 1 (MTF1). Hence, genetic variation in the MT gene family and MTF1 might influence excretion of these metals. Methods: 321 women were recruited in Seattle, WA and Las Cruces, NM and provided demographic information, urine samples for measurement of metal concentrations by mass spectrometry and creatinine, and blood or saliva for extraction of DNA. Forty-one single nucleotide polymorphisms (SNPs) within the MTF1 gene region and the region of chromosome 16 encoding the MT gene family were selected for genotyping in addition to an ancestry informative marker panel. Linear regression was used to estimate the association of SNPs with urinary Cd, Cu, and Zn, adjusted for age, urinary creatinine, smoking history, study site, and ancestry. Results: Minor alleles of rs28366003 and rs10636 near the MT2A gene were associated with lower urinary Cd, Cu, and Zn. Minor alleles of rs8044719 and rs1599823, near MT1A and MT1B, were associated with lower urinary Cd and Zn, respectively. Minor alleles of rs4653329 in MTF1 were associated with lower urinary Cd. Conclusions: These results suggest that genetic variation in the MT gene region and MTF1 influences urinary Cd, Cu, and Zn excretion. - Highlights: • Genetic variation in metallothionein (MT) genes was assessed in two diverse populations. • Single nucleotide polymorphisms (SNPs) in MT genes were associated with mean urinary Cd, Cu and Zn. • Genetic variation may influence biomarkers of exposure, and associations of exposure with health.

  19. Natural variation in monoterpene synthesis in kiwifruit: transcriptional regulation of terpene synthases by NAC and ETHYLENE-INSENSITIVE3-like transcription factors.

    Science.gov (United States)

    Nieuwenhuizen, Niels J; Chen, Xiuyin; Wang, Mindy Y; Matich, Adam J; Perez, Ramon Lopez; Allan, Andrew C; Green, Sol A; Atkinson, Ross G

    2015-04-01

    Two kiwifruit (Actinidia) species with contrasting terpene profiles were compared to understand the regulation of fruit monoterpene production. High rates of terpinolene production in ripe Actinidia arguta fruit were correlated with increasing gene and protein expression of A. arguta terpene synthase1 (AaTPS1) and correlated with an increase in transcript levels of the 2-C-methyl-D-erythritol 4-phosphate pathway enzyme 1-deoxy-D-xylulose-5-phosphate synthase (DXS). Actinidia chinensis terpene synthase1 (AcTPS1) was identified as part of an array of eight tandemly duplicated genes, and AcTPS1 expression and terpene production were observed only at low levels in developing fruit. Transient overexpression of DXS in Nicotiana benthamiana leaves elevated monoterpene synthesis by AaTPS1 more than 100-fold, indicating that DXS is likely to be the key step in regulating 2-C-methyl-D-erythritol 4-phosphate substrate flux in kiwifruit. Comparative promoter analysis identified potential NAC (for no apical meristem [NAM], Arabidopsis transcription activation factor [ATAF], and cup-shaped cotyledon [CUC])-domain transcription factor) and ETHYLENE-INSENSITIVE3-like transcription factor (TF) binding sites in the AaTPS1 promoter, and cloned members of both TF classes were able to activate the AaTPS1 promoter in transient assays. Electrophoretic mobility shift assays showed that AaNAC2, AaNAC3, and AaNAC4 bind a 28-bp fragment of the proximal NAC binding site in the AaTPS1 promoter but not the A. chinensis AcTPS1 promoter, where the NAC binding site was mutated. Activation could be restored by reintroducing multiple repeats of the 12-bp NAC core-binding motif. The absence of NAC transcriptional activation in ripe A. chinensis fruit can account for the low accumulation of AcTPS1 transcript, protein, and monoterpene volatiles in this species. These results indicate the importance of NAC TFs in controlling monoterpene production and other traits in ripening fruits. © 2015 American

  20. Natural Variation in Monoterpene Synthesis in Kiwifruit: Transcriptional Regulation of Terpene Synthases by NAC and ETHYLENE-INSENSITIVE3-Like Transcription Factors1

    Science.gov (United States)

    Nieuwenhuizen, Niels J.; Chen, Xiuyin; Wang, Mindy Y.; Matich, Adam J.; Perez, Ramon Lopez; Allan, Andrew C.; Green, Sol A.; Atkinson, Ross G.

    2015-01-01

    Two kiwifruit (Actinidia) species with contrasting terpene profiles were compared to understand the regulation of fruit monoterpene production. High rates of terpinolene production in ripe Actinidia arguta fruit were correlated with increasing gene and protein expression of A. arguta terpene synthase1 (AaTPS1) and correlated with an increase in transcript levels of the 2-C-methyl-d-erythritol 4-phosphate pathway enzyme 1-deoxy-d-xylulose-5-phosphate synthase (DXS). Actinidia chinensis terpene synthase1 (AcTPS1) was identified as part of an array of eight tandemly duplicated genes, and AcTPS1 expression and terpene production were observed only at low levels in developing fruit. Transient overexpression of DXS in Nicotiana benthamiana leaves elevated monoterpene synthesis by AaTPS1 more than 100-fold, indicating that DXS is likely to be the key step in regulating 2-C-methyl-d-erythritol 4-phosphate substrate flux in kiwifruit. Comparative promoter analysis identified potential NAC (for no apical meristem [NAM], Arabidopsis transcription activation factor [ATAF], and cup-shaped cotyledon [CUC])-domain transcription factor) and ETHYLENE-INSENSITIVE3-like transcription factor (TF) binding sites in the AaTPS1 promoter, and cloned members of both TF classes were able to activate the AaTPS1 promoter in transient assays. Electrophoretic mobility shift assays showed that AaNAC2, AaNAC3, and AaNAC4 bind a 28-bp fragment of the proximal NAC binding site in the AaTPS1 promoter but not the A. chinensis AcTPS1 promoter, where the NAC binding site was mutated. Activation could be restored by reintroducing multiple repeats of the 12-bp NAC core-binding motif. The absence of NAC transcriptional activation in ripe A. chinensis fruit can account for the low accumulation of AcTPS1 transcript, protein, and monoterpene volatiles in this species. These results indicate the importance of NAC TFs in controlling monoterpene production and other traits in ripening fruits. PMID:25649633

  1. Gravitational and magnetic field variations synergize to cause subtle variations in the global transcriptional state of Arabidopsis in vitro callus cultures

    Directory of Open Access Journals (Sweden)

    Manzano Ana I

    2012-03-01

    Full Text Available Abstract Background Biological systems respond to changes in both the Earth's magnetic and gravitational fields, but as experiments in space are expensive and infrequent, Earth-based simulation techniques are required. A high gradient magnetic field can be used to levitate biological material, thereby simulating microgravity and can also create environments with a reduced or an enhanced level of gravity (g, although special attention should be paid to the possible effects of the magnetic field (B itself. Results Using diamagnetic levitation, we exposed Arabidopsis thaliana in vitro callus cultures to five environments with different levels of effective gravity and magnetic field strengths. The environments included levitation, i.e. simulated μg* (close to 0 g* at B = 10.1 T, intermediate g* (0.1 g* at B = 14.7 T and enhanced gravity levels (1.9 g* at B = 14.7 T and 2 g* at B = 10.1 T plus an internal 1 g* control (B = 16.5 T. The asterisk denotes the presence of the background magnetic field, as opposed to the effective gravity environments in the absence of an applied magnetic field, created using a Random Position Machine (simulated μg and a Large Diameter Centrifuge (2 g. Microarray analysis indicates that changes in the overall gene expression of cultured cells exposed to these unusual environments barely reach significance using an FDR algorithm. However, it was found that gravitational and magnetic fields produce synergistic variations in the steady state of the transcriptional profile of plants. Transcriptomic results confirm that high gradient magnetic fields (i.e. to create μg* and 2 g* conditions have a significant effect, mainly on structural, abiotic stress genes and secondary metabolism genes, but these subtle gravitational effects are only observable using clustering methodologies. Conclusions A detailed microarray dataset analysis, based on clustering of similarly expressed genes (GEDI software, can detect underlying global

  2. Reliability versus reproducibility

    International Nuclear Information System (INIS)

    Lautzenheiser, C.E.

    1976-01-01

    Defect detection and reproducibility of results are two separate but closely related subjects. It is axiomatic that a defect must be detected from examination to examination or reproducibility of results is very poor. On the other hand, a defect can be detected on each of subsequent examinations for higher reliability and still have poor reproducibility of results

  3. The Need for Reproducibility

    Energy Technology Data Exchange (ETDEWEB)

    Robey, Robert W. [Los Alamos National Laboratory

    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?

  4. Testing Reproducibility in Earth Sciences

    Science.gov (United States)

    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

  5. Genotypic variation in the sulfur assimilation and metabolism of onion (Allium cepa L.) I. Plant composition and transcript accumulation

    KAUST Repository

    McCallum, John A.

    2011-06-01

    Organosulfur compounds are major sinks for assimilated sulfate in onion (Allium cepa L.) and accumulation varies widely due to plant genotype and sulfur nutrition. In order to better characterise sulfur metabolism phenotypes and identify potential control points we compared plant composition and transcript accumulation of the primary sulfur assimilation pathway in the high pungency genotype \\'W202A\\' and the low pungency genotype \\'Texas Grano 438\\' grown hydroponically under S deficient (S-) and S-sufficient (S+) conditions. Accumulation of total S and alk(en)yl cysteine sulfoxide flavour precursors was significantly higher under S+ conditions and in \\'W202A\\' in agreement with previous studies. Leaf sulfate and cysteine levels were significantly higher in \\'W202A\\' and under S+. Glutathione levels were reduced by S- treatment but were not affected by genotype, suggesting that thiol pool sizes are regulated differently in mild and pungent onions. The only significant treatment effect observed on transcript accumulation in leaves was an elevated accumulation of O-acetyl serine thiol-lyase under S-. By contrast, transcript accumulation of all genes in roots was influenced by one or more treatments. APS reductase transcript level was not affected by genotype but was strongly increased by S-. Significant genotype × S treatment effects were observed in a root high affinity-sulfur transporter and ferredoxin-sulfite reductase. ATP sulfurylase transcript levels were significantly higher under S+ and in \\'W202A\\'. © 2011 Elsevier Ltd. All rights reserved.

  6. Epigenetic variation in asexually reproducing organisms

    NARCIS (Netherlands)

    Verhoeven, K.J.F.; Preite, V.

    2014-01-01

    The role that epigenetic inheritance can play in adaptation may differ between sexuals and asexuals because (1) the dynamics of adaptation differ under sexual and asexual reproduction and the opportunities offered by epigenetic inheritance may affect these dynamics differently; and (2) in asexual

  7. Magni Reproducibility Example

    DEFF Research Database (Denmark)

    2016-01-01

    An example of how to use the magni.reproducibility package for storing metadata along with results from a computational experiment. The example is based on simulating the Mandelbrot set.......An example of how to use the magni.reproducibility package for storing metadata along with results from a computational experiment. The example is based on simulating the Mandelbrot set....

  8. Variations of transcript profiles between sea otters Enhydra lutris from Prince William Sound, Alaska, and clinically normal reference otters

    Science.gov (United States)

    Miles, A. Keith; Bowen, Lizabeth; Ballachey, Brenda E.; Bodkin, James L.; Murray, M.; Estes, J.L.; Keister, Robin A.; Stott, J.L.

    2012-01-01

    Development of blood leukocyte gene transcript profiles has the potential to expand condition assessments beyond those currently available to evaluate wildlife health, including sea otters Enhydra lutris, both individually and as populations. The 10 genes targeted in our study represent multiple physiological systems that play a role in immuno-modulation, inflammation, cell protection, tumor suppression, cellular stress-response, xenobiotic metabolizing enzymes, and antioxidant enzymes. These genes can be modified by biological, physical, or anthropogenic impacts and consequently provide information on the general type of stressors present in a given environment. We compared gene transcript profiles of sea otters sampled in 2008 among areas within Prince William Sound impacted to varying degrees by the 1989 ‘Exxon Valdez’ oil spill with those of captive and wild reference sea otters. Profiles of sea otters from Prince William Sound showed elevated transcription in genes associated with tumor formation, cell death, organic exposure, inflammation, and viral exposure when compared to the reference sea otter group, indicating possible recent and chronic exposure to organic contaminants. Sea otters from historically designated oiled areas within Prince William Sound 19 yr after the oil spill had higher transcription of genes associated with tumor formation, cell death, heat shock, and inflammation than those from areas designated as less impacted by the spill.

  9. Differential transcript abundance and genotypic variation of four putative allergen-encoding gene families in melting peach

    NARCIS (Netherlands)

    Yang, Z.; Ma, Y.; Chen, L.; Xie, R.; Zhang, X.; Zhang, B.; Lu, M.; Wu, S.; Gilissen, L.J.W.J.; Ree, van R.; Gao, Z.

    2011-01-01

    We analysed the temporal and spatial transcript expression of the panel of 18 putative isoallergens from four gene families (Pru p 1–4) in the peach fruit, anther and leaf of two melting cultivars, to gain insight into their expression profiles and to identify the key family members. Genotypic

  10. The Effect of Common Inversion Polymorphisms In(2L)t and In(3R)Mo on Patterns of Transcriptional Variation in Drosophila melanogaster.

    Science.gov (United States)

    Lavington, Erik; Kern, Andrew D

    2017-11-06

    Chromosomal inversions are a ubiquitous feature of genetic variation. Theoretical models describe several mechanisms by which inversions can drive adaptation and be maintained as polymorphisms. While inversions have been shown previously to be under selection, or contain genetic variation under selection, the specific phenotypic consequences of inversions leading to their maintenance remain unclear. Here we use genomic sequence and expression data from the Drosophila Genetic Reference Panel (DGRP) to explore the effects of two cosmopolitan inversions, In ( 2L ) t and In ( 3R ) Mo , on patterns of transcriptional variation. We demonstrate that each inversion has a significant effect on transcript abundance for hundreds of genes across the genome. Inversion-affected loci (IAL) appear both within inversions as well as on unlinked chromosomes. Importantly, IAL do not appear to be influenced by the previously reported genome-wide expression correlation structure. We found that five genes involved with sterol uptake, four of which are Niemann-Pick Type 2 orthologs, are upregulated in flies with In ( 3R ) Mo but do not have SNPs in linkage disequilibrium (LD) with the inversion. We speculate that this upregulation is driven by genetic variation in mod ( mdg4 ) that is in LD with In ( 3R ) Mo We find that there is little evidence for a regional or position effect of inversions on gene expression at the chromosomal level, but do find evidence for the distal breakpoint of In ( 3R ) Mo interrupting one gene and possibly disassociating the two flanking genes from regulatory elements. Copyright © 2017 Lavington and Kern.

  11. Annual variation in the levels of transcripts of sex-specific genes in the mantle of the common mussel, Mytilus edulis.

    Directory of Open Access Journals (Sweden)

    Sandhya Anantharaman

    Full Text Available Mytilus species are used as sentinels for the assessment of environmental health but sex or stage in the reproduction cycle is rarely considered even though both parameters are likely to influence responses to pollution. We have validated the use of a qPCR assay for sex identification and related the levels of transcripts to the reproductive cycle. A temporal study of mantle of Mytilus edulis found transcripts of male-specific vitelline coat lysin (VCL and female-specific vitelline envelope receptor for lysin (VERL could identify sex over a complete year. The levels of VCL/VERL were proportional to the numbers of sperm/ova and are indicative of the stage of the reproductive cycle. Maximal levels of VCL and VERL were found in February 2009 declining to minima between July - August before increasing and re-attaining a peak in February 2010. Water temperature may influence these transitions since they coincide with minimal water temperature in February and maximal temperature in August. An identical pattern of variation was found for a cryptic female-specific transcript (H5 but a very different pattern was observed for oestrogen receptor 2 (ER2. ER2 varied in a sex-specific way with male > female for most of the cycle, with a female maxima in July and a male maxima in December. Using artificially spawned animals, the transcripts for VCL, VERL and H5 were shown to be present in gametes and thus their disappearance from mantle is indicative of spawning. VCL and VERL are present at equivalent levels in February and July-August but during gametogenesis (August to January and spawning (March to June VCL is present at lower relative amounts than VERL. This may indicate sex-specific control mechanisms for these processes and highlight a potential pressure point leading to reduced reproductive output if environmental factors cause asynchrony to gamete maturation or release.

  12. MHC class II genes in the European badger (Meles meles) : Characterization, patterns of variation, and transcription analysis

    NARCIS (Netherlands)

    Sin, Yung Wa; Dugdale, Hannah L.; Newman, Chris; Macdonald, David W.; Burke, Terry

    The major histocompatibility complex (MHC) comprises many genes, some of which are polymorphic with numerous alleles. Sequence variation among alleles is most pronounced in exon 2 of the class II genes, which encodes the alpha 1 and beta 1 domains that form the antigen-binding site (ABS) for the

  13. Comparative analysis of behavioral and transcriptional variation underlying CO2 sensory neuron function and development in Drosophila.

    Science.gov (United States)

    Pan, Jia Wern; McLaughlin, Joi; Yang, Haining; Leo, Charles; Rambarat, Paula; Okuwa, Sumie; Monroy-Eklund, Anaïs; Clark, Sabrina; Jones, Corbin D; Volkan, Pelin Cayirlioglu

    2017-10-02

    Carbon dioxide is an important environmental cue for many insects, regulating many behaviors including some that have direct human impacts. To further improve our understanding of how this system varies among closely related insect species, we examined both the behavioral response to CO 2 as well as the transcriptional profile of key developmental regulators of CO 2 sensory neurons in the olfactory system across the Drosophila genus. We found that CO 2 generally evokes repulsive behavior across most of the Drosophilids we examined, but this behavior has been lost or reduced in several lineages. Comparisons of transcriptional profiles from the developing and adult antennae for subset these species suggest that behavioral differences in some species may be due to differences in the expression of the CO 2 co-receptor Gr63a. Furthermore, these differences in Gr63a expression are correlated with changes in the expression of a few genes known to be involved in the development of the CO 2 circuit, namely dac, an important regulator of sensilla fate for sensilla that house CO 2 ORNs, and mip120, a member of the MMB/dREAM epigenetic regulatory complex that regulates CO 2 receptor expression. In contrast, most of the other known structural, molecular, and developmental components of the peripheral Drosophila CO 2 olfactory system seem to be well-conserved across all examined lineages. These findings suggest that certain components of CO 2 sensory ORN development may be more evolutionarily labile, and may contribute to differences in CO 2 -evoked behavioral responses across species.

  14. Preserve specimens for reproducibility

    Czech Academy of Sciences Publication Activity Database

    Krell, F.-T.; Klimeš, Petr; Rocha, L. A.; Fikáček, M.; Miller, S. E.

    2016-01-01

    Roč. 539, č. 7628 (2016), s. 168 ISSN 0028-0836 Institutional support: RVO:60077344 Keywords : reproducibility * specimen * biodiversity Subject RIV: EH - Ecology, Behaviour Impact factor: 40.137, year: 2016 http://www.nature.com/nature/journal/v539/n7628/full/539168b.html

  15. Reproducibility of ultrasonic testing

    International Nuclear Information System (INIS)

    Lecomte, J.-C.; Thomas, Andre; Launay, J.-P.; Martin, Pierre

    The reproducibility of amplitude quotations for both artificial and natural reflectors was studied for several combinations of instrument/search unit, all being of the same type. This study shows that in industrial inspection if a range of standardized equipment is used, a margin of error of about 6 decibels has to be taken into account (confidence interval of 95%). This margin is about 4 to 5 dB for natural or artificial defects located in the central area and about 6 to 7 dB for artificial defects located on the back surface. This lack of reproducibility seems to be attributable first to the search unit and then to the instrument and operator. These results were confirmed by analysis of calibration data obtained from 250 tests performed by 25 operators under shop conditions. The margin of error was higher than the 6 dB obtained in the study [fr

  16. Magnet stability and reproducibility

    CERN Document Server

    Marks, N

    2010-01-01

    Magnet stability and reproducibility have become increasingly important as greater precision and beams with smaller dimension are required for research, medical and other purpose. The observed causes of mechanical and electrical instability are introduced and the engineering arrangements needed to minimize these problems discussed; the resulting performance of a state-of-the-art synchrotron source (Diamond) is then presented. The need for orbit feedback to obtain best possible beam stability is briefly introduced, but omitting any details of the necessary technical equipment, which is outside the scope of the presentation.

  17. Reproducible research in palaeomagnetism

    Science.gov (United States)

    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

  18. Light-induced Variation in Phenolic Compounds in Cabernet Sauvignon Grapes (Vitis vinifera L.) Involves Extensive Transcriptome Reprogramming of Biosynthetic Enzymes, Transcription Factors, and Phytohormonal Regulators.

    Science.gov (United States)

    Sun, Run-Ze; Cheng, Guo; Li, Qiang; He, Yan-Nan; Wang, Yu; Lan, Yi-Bin; Li, Si-Yu; Zhu, Yan-Rong; Song, Wen-Feng; Zhang, Xue; Cui, Xiao-Di; Chen, Wu; Wang, Jun

    2017-01-01

    Light environments have long been known to influence grape ( Vitis vinifera L.) berry development and biosynthesis of phenolic compounds, and ultimately affect wine quality. Here, the accumulation and compositional changes of hydroxycinnamic acids (HCAs) and flavonoids, as well as global gene expression were analyzed in Cabernet Sauvignon grape berries under sunlight exposure treatments at different phenological stages. Sunlight exposure did not consistently affect the accumulation of berry skin flavan-3-ol or anthocyanin among different seasons due to climatic variations, but increased HCA content significantly at véraison and harvest, and enhanced flavonol accumulation dramatically with its timing and severity degree trend. As in sunlight exposed berries, a highly significant correlation was observed between the expression of genes coding phenylalanine ammonia-lyase, 4-coumarate: CoA ligase, flavanone 3-hydroxylase and flavonol synthase family members and corresponding metabolite accumulation in the phenolic biosynthesis pathway, which may positively or negatively be regulated by MYB, bHLH, WRKY, AP2/EREBP, C2C2, NAC, and C2H2 transcription factors (TFs). Furthermore, some candidate genes required for auxin, ethylene and abscisic acid signal transductions were also identified which are probably involved in berry development and flavonoid biosynthesis in response to enhanced sunlight irradiation. Taken together, this study provides a valuable overview of the light-induced phenolic metabolism and transcriptome changes, especially the dynamic responses of TFs and signaling components of phytohormones, and contributes to the further understanding of sunlight-responsive phenolic biosynthesis regulation in grape berries.

  19. Light-induced Variation in Phenolic Compounds in Cabernet Sauvignon Grapes (Vitis vinifera L.) Involves Extensive Transcriptome Reprogramming of Biosynthetic Enzymes, Transcription Factors, and Phytohormonal Regulators

    Science.gov (United States)

    Sun, Run-Ze; Cheng, Guo; Li, Qiang; He, Yan-Nan; Wang, Yu; Lan, Yi-Bin; Li, Si-Yu; Zhu, Yan-Rong; Song, Wen-Feng; Zhang, Xue; Cui, Xiao-Di; Chen, Wu; Wang, Jun

    2017-01-01

    Light environments have long been known to influence grape (Vitis vinifera L.) berry development and biosynthesis of phenolic compounds, and ultimately affect wine quality. Here, the accumulation and compositional changes of hydroxycinnamic acids (HCAs) and flavonoids, as well as global gene expression were analyzed in Cabernet Sauvignon grape berries under sunlight exposure treatments at different phenological stages. Sunlight exposure did not consistently affect the accumulation of berry skin flavan-3-ol or anthocyanin among different seasons due to climatic variations, but increased HCA content significantly at véraison and harvest, and enhanced flavonol accumulation dramatically with its timing and severity degree trend. As in sunlight exposed berries, a highly significant correlation was observed between the expression of genes coding phenylalanine ammonia-lyase, 4-coumarate: CoA ligase, flavanone 3-hydroxylase and flavonol synthase family members and corresponding metabolite accumulation in the phenolic biosynthesis pathway, which may positively or negatively be regulated by MYB, bHLH, WRKY, AP2/EREBP, C2C2, NAC, and C2H2 transcription factors (TFs). Furthermore, some candidate genes required for auxin, ethylene and abscisic acid signal transductions were also identified which are probably involved in berry development and flavonoid biosynthesis in response to enhanced sunlight irradiation. Taken together, this study provides a valuable overview of the light-induced phenolic metabolism and transcriptome changes, especially the dynamic responses of TFs and signaling components of phytohormones, and contributes to the further understanding of sunlight-responsive phenolic biosynthesis regulation in grape berries. PMID:28469625

  20. Allelic Variations at Four Major Maturity E Genes and Transcriptional Abundance of the E1 Gene Are Associated with Flowering Time and Maturity of Soybean Cultivars

    Science.gov (United States)

    Wang, Yueqiang; Chen, Xin; Ren, Haixiang; Yang, Jiayin; Cheng, Wen; Zong, Chunmei; Gu, Heping; Qiu, Hongmei; Wu, Hongyan; Zhang, Xingzheng; Cui, Tingting; Xia, Zhengjun

    2014-01-01

    The time to flowering and maturity are ecologically and agronomically important traits for soybean landrace and cultivar adaptation. As a typical short-day crop, long day conditions in the high-latitude regions require soybean cultivars with photoperiod insensitivity that can mature before frost. Although the molecular basis of four major E loci (E1 to E4) have been deciphered, it is not quite clear whether, or to what degree, genetic variation and the expression level of the four E genes are associated with the time to flowering and maturity of soybean cultivars. In this study, we genotyped 180 cultivars at E1 to E4 genes, meanwhile, the time to flowering and maturity of those cultivars were investigated at six geographic locations in China from 2011 to 2012 and further confirmed in 2013. The percentages of recessive alleles at E1, E2, E3 and E4 loci were 38.34%, 84.45%, 36.33%, and 7.20%, respectively. Statistical analysis showed that allelic variations at each of four loci had a significant effect on flowering time as well as maturity. We classified the 180 cultivars into eight genotypic groups based on allelic variations of the four major E loci. The genetic group of e1-nf representing dysfunctional alleles at the E1 locus flowered earliest in all the geographic locations. In contrast, cultivars in the E1E2E3E4 group originated from the southern areas flowered very late or did not flower before frost at high latitude locations. The transcriptional abundance of functional E1 gene was significantly associated with flowering time. However, the ranges of time to flowering and maturity were quite large within some genotypic groups, implying the presence of some other unknown genetic factors that are involved in control of flowering time or maturity. Known genes (e.g. E3 and E4) and other unknown factors may function, at least partially, through regulation of the expression of the E1 gene. PMID:24830458

  1. Reproducibility of central lumbar vertebral BMD

    International Nuclear Information System (INIS)

    Chan, F.; Pocock, N.; Griffiths, M.; Majerovic, Y.; Freund, J.

    1997-01-01

    Full text: Lumbar vertebral bone mineral density (BMD) using dual X-ray absorptiometry (DXA) has generally been calculated from a region of interest which includes the entire vertebral body. Although this region excludes part of the transverse processes, it does include the outer cortical shell of the vertebra. Recent software has been devised to calculate BMD in a central vertebral region of interest which excludes the outer cortical envelope. Theoretically this area may be more sensitive to detecting osteoporosis which affects trabecular bone to a greater extent than cortical bone. Apart from the sensitivity of BMD estimation, the reproducibility of any measurement is important owing to the slow rate of change of bone mass. We have evaluated the reproducibility of this new vertebral region of interest in 23 women who had duplicate lumbar spine DXA scans performed on the same day. The patients were repositioned between each measurement. Central vertebral analysis was performed for L2-L4 and the reproducibility of area, bone mineral content (BMC) and BMD calculated as the coefficient of variation; these values were compared with those from conventional analysis. Thus we have shown that the reproducibility of the central BMD is comparable to the conventional analysis which is essential if this technique is to provide any additional clinical data. The reasons for the decrease in reproducibility of the area and hence BMC requires further investigation

  2. Light-induced Variation in Phenolic Compounds in Cabernet Sauvignon Grapes (Vitis vinifera L. Involves Extensive Transcriptome Reprogramming of Biosynthetic Enzymes, Transcription Factors, and Phytohormonal Regulators

    Directory of Open Access Journals (Sweden)

    Jun Wang

    2017-04-01

    Full Text Available Light environments have long been known to influence grape (Vitis vinifera L. berry development and biosynthesis of phenolic compounds, and ultimately affect wine quality. Here, the accumulation and compositional changes of hydroxycinnamic acids (HCAs and flavonoids, as well as global gene expression were analyzed in Cabernet Sauvignon grape berries under sunlight exposure treatments at different phenological stages. Sunlight exposure did not consistently affect the accumulation of berry skin flavan-3-ol or anthocyanin among different seasons due to climatic variations, but increased HCA content significantly at véraison and harvest, and enhanced flavonol accumulation dramatically with its timing and severity degree trend. As in sunlight exposed berries, a highly significant correlation was observed between the expression of genes coding phenylalanine ammonia-lyase, 4-coumarate: CoA ligase, flavanone 3-hydroxylase and flavonol synthase family members and corresponding metabolite accumulation in the phenolic biosynthesis pathway, which may positively or negatively be regulated by MYB, bHLH, WRKY, AP2/EREBP, C2C2, NAC, and C2H2 transcription factors (TFs. Furthermore, some candidate genes required for auxin, ethylene and abscisic acid signal transductions were also identified which are probably involved in berry development and flavonoid biosynthesis in response to enhanced sunlight irradiation. Taken together, this study provides a valuable overview of the light-induced phenolic metabolism and transcriptome changes, especially the dynamic responses of TFs and signaling components of phytohormones, and contributes to the further understanding of sunlight-responsive phenolic biosynthesis regulation in grape berries.

  3. Reproducibility in a multiprocessor system

    Science.gov (United States)

    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.

  4. Contextual sensitivity in scientific reproducibility.

    Science.gov (United States)

    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.

  5. Reproducibility of the chamber scarification test

    DEFF Research Database (Denmark)

    Andersen, Klaus Ejner

    1996-01-01

    The chamber scarification test is a predictive human skin irritation test developed to rank the irritation potential of products and ingredients meant for repeated use on normal and diseased skin. 12 products or ingredients can be tested simultaneously on the forearm skin of each volunteer....... The test combines with the procedure scratching of the skin at each test site and subsequent closed patch tests with the products, repeated daily for 3 days. The test is performed on groups of human volunteers: a skin irritant substance or products is included in each test as a positive control...... high reproducibility of the test. Further, intra-individual variation in skin reaction to the 2 control products in 26 volunteers, who participated 2x, is shown, which supports the conclusion that the chamber scarification test is a useful short-term human skin irritation test with high reproducibility....

  6. Causes and consequences of chromatin variation between inbred mice.

    Directory of Open Access Journals (Sweden)

    Mona Hosseini

    2013-06-01

    Full Text Available Variation at regulatory elements, identified through hypersensitivity to digestion by DNase I, is believed to contribute to variation in complex traits, but the extent and consequences of this variation are poorly characterized. Analysis of terminally differentiated erythroblasts in eight inbred strains of mice identified reproducible variation at approximately 6% of DNase I hypersensitive sites (DHS. Only 30% of such variable DHS contain a sequence variant predictive of site variation. Nevertheless, sequence variants within variable DHS are more likely to be associated with complex traits than those in non-variant DHS, and variants associated with complex traits preferentially occur in variable DHS. Changes at a small proportion (less than 10% of variable DHS are associated with changes in nearby transcriptional activity. Our results show that whilst DNA sequence variation is not the major determinant of variation in open chromatin, where such variants exist they are likely to be causal for complex traits.

  7. Reproducibility of esophageal scintigraphy using semi-solid yoghurt

    Energy Technology Data Exchange (ETDEWEB)

    Imai, Yukinori; Kinoshita, Manabu; Asakura, Yasushi; Kakinuma, Tohru; Shimoji, Katsunori; Fujiwara, Kenji; Suzuki, Kenji; Miyamae, Tatsuya [Saitama Medical School, Moroyama (Japan)

    1999-10-01

    Esophageal scintigraphy is a non-invasive method which evaluate esophageal function quantitatively. We applied new technique using semi-solid yoghurt, which can evaluate esophageal function in a sitting position. To evaluate the reproducibility of this method, scintigraphy were performed in 16 healthy volunteers. From the result of four swallows except the first one, the mean coefficients of variation in esophageal transit time and esophageal emptying time were 12.8% and 13.4% respectively (interday variation). As regards the interday variation, this method had also good reproducibility from the result on the 2 separate days. (author)

  8. Contextual sensitivity in scientific reproducibility

    Science.gov (United States)

    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

  9. Relevant principal factors affecting the reproducibility of insect primary culture.

    Science.gov (United States)

    Ogata, Norichika; Iwabuchi, Kikuo

    2017-06-01

    The primary culture of insect cells often suffers from problems with poor reproducibility in the quality of the final cell preparations. The cellular composition of the explants (cell number and cell types), surgical methods (surgical duration and surgical isolation), and physiological and genetic differences between donors may be critical factors affecting the reproducibility of culture. However, little is known about where biological variation (interindividual differences between donors) ends and technical variation (variance in replication of culture conditions) begins. In this study, we cultured larval fat bodies from the Japanese rhinoceros beetle, Allomyrina dichotoma, and evaluated, using linear mixed models, the effect of interindividual variation between donors on the reproducibility of the culture. We also performed transcriptome analysis of the hemocyte-like cells mainly seen in the cultures using RNA sequencing and ultrastructural analyses of hemocytes using a transmission electron microscope, revealing that the cultured cells have many characteristics of insect hemocytes.

  10. Reproducible Bioinformatics Research for Biologists

    Science.gov (United States)

    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...

  11. Reproducibility of brain ADC histograms

    International Nuclear Information System (INIS)

    Steens, S.C.A.; Buchem, M.A. van; Admiraal-Behloul, F.; Schaap, J.A.; Hoogenraad, F.G.C.; Wheeler-Kingshott, C.A.M.; Tofts, P.S.; Cessie, S. le

    2004-01-01

    The aim of this study was to assess the effect of differences in acquisition technique on whole-brain apparent diffusion coefficient (ADC) histogram parameters, as well as to assess scan-rescan reproducibility. Diffusion-weighted imaging (DWI) was performed in 7 healthy subjects with b-values 0-800, 0-1000, and 0-1500 s/mm 2 and fluid-attenuated inversion recovery (FLAIR) DWI with b-values 0-1000 s/mm 2 . All sequences were repeated with and without repositioning. The peak location, peak height, and mean ADC of the ADC histograms and mean ADC of a region of interest (ROI) in the white matter were compared using paired-sample t tests. Scan-rescan reproducibility was assessed using paired-sample t tests, and repeatability coefficients were reported. With increasing maximum b-values, ADC histograms shifted to lower values, with an increase in peak height (p<0.01). With FLAIR DWI, the ADC histogram shifted to lower values with a significantly higher, narrower peak (p<0.01), although the ROI mean ADC showed no significant differences. For scan-rescan reproducibility, no significant differences were observed. Different DWI pulse sequences give rise to different ADC histograms. With a given pulse sequence, however, ADC histogram analysis is a robust and reproducible technique. Using FLAIR DWI, the partial-voluming effect of cerebrospinal fluid, and thus its confounding effect on histogram analyses, can be reduced

  12. Short- and long-term reproducibility of radioisotopic examination of gastric emptying

    Energy Technology Data Exchange (ETDEWEB)

    Jonderko, K. (Silesian School of Medicine, Katowice (Poland). Dept. of Gastroenterology)

    1990-01-01

    Reproducibility of gastric emptying (GE) of a radiolabelled solid meal was assessed. The short-term reproducibility was evaluated on the basis of 12 paired GE examinations performed 1-3 days apart. Twelve paired GE examinations taken 3-8 months apart enabled long-term reproducibility assessment. Reproducibility of GE parameters was expressed in terms of the coefficient of variation, CV. No significant between-day variation of solid GE was found either regarding the short-term or the long-term reproducibility. Although slightly higher CV values characterized the long-term reproducibility of the GE parameters considered, the variations of the differences between repeated GE examinations did not differ significantly between short- and long-term GE reproducibility. The results obtained justify the use of radioisotopic GE measurement for the assessment of early and late results of pharmacologic or surgical management. (author).

  13. Reproducibility of a reaming test

    DEFF Research Database (Denmark)

    Pilny, Lukas; Müller, Pavel; De Chiffre, Leonardo

    2012-01-01

    The reproducibility of a reaming test was analysed to document its applicability as a performance test for cutting fluids. Reaming tests were carried out on a drilling machine using HSS reamers. Workpiece material was an austenitic stainless steel, machined using 4.75 m∙min-1 cutting speed and 0......). Process reproducibility was assessed as the ability of different operators to ensure a consistent rating of individual lubricants. Absolute average values as well as experimental standard deviations of the evaluation parameters were calculated, and uncertainty budgeting was performed. Results document...... a built-up edge occurrence hindering a robust evaluation of cutting fluid performance, if the data evaluation is based on surface finish only. Measurements of hole geometry provide documentation to recognize systematic error distorting the performance test....

  14. Reproducibility of a reaming test

    DEFF Research Database (Denmark)

    Pilny, Lukas; Müller, Pavel; De Chiffre, Leonardo

    2014-01-01

    The reproducibility of a reaming test was analysed to document its applicability as a performance test for cutting fluids. Reaming tests were carried out on a drilling machine using HSS reamers. Workpiece material was an austenitic stainless steel, machined using 4.75 m•min−1 cutting speed and 0......). Process reproducibility was assessed as the ability of different operators to ensure a consistent rating of individual lubricants. Absolute average values as well as experimental standard deviations of the evaluation parameters were calculated, and uncertainty budgeting was performed. Results document...... a built–up edge occurrence hindering a robust evaluation of cutting fluid performance, if the data evaluation is based on surface finish only. Measurements of hole geometry provide documentation to recognise systematic error distorting the performance test....

  15. Towards Reproducibility in Computational Hydrology

    Science.gov (United States)

    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

  16. Modeling reproducibility of porescale multiphase flow experiments

    Science.gov (United States)

    Ling, B.; Tartakovsky, A. M.; Bao, J.; Oostrom, M.; Battiato, I.

    2017-12-01

    Multi-phase flow in porous media is widely encountered in geological systems. Understanding immiscible fluid displacement is crucial for processes including, but not limited to, CO2 sequestration, non-aqueous phase liquid contamination and oil recovery. Microfluidic devices and porescale numerical models are commonly used to study multiphase flow in biological, geological, and engineered porous materials. In this work, we perform a set of drainage and imbibition experiments in six identical microfluidic cells to study the reproducibility of multiphase flow experiments. We observe significant variations in the experimental results, which are smaller during the drainage stage and larger during the imbibition stage. We demonstrate that these variations are due to sub-porescale geometry differences in microcells (because of manufacturing defects) and variations in the boundary condition (i.e.,fluctuations in the injection rate inherent to syringe pumps). Computational simulations are conducted using commercial software STAR-CCM+, both with constant and randomly varying injection rate. Stochastic simulations are able to capture variability in the experiments associated with the varying pump injection rate.

  17. Measurement System Analyses - Gauge Repeatability and Reproducibility Methods

    Science.gov (United States)

    Cepova, Lenka; Kovacikova, Andrea; Cep, Robert; Klaput, Pavel; Mizera, Ondrej

    2018-02-01

    The submitted article focuses on a detailed explanation of the average and range method (Automotive Industry Action Group, Measurement System Analysis approach) and of the honest Gauge Repeatability and Reproducibility method (Evaluating the Measurement Process approach). The measured data (thickness of plastic parts) were evaluated by both methods and their results were compared on the basis of numerical evaluation. Both methods were additionally compared and their advantages and disadvantages were discussed. One difference between both methods is the calculation of variation components. The AIAG method calculates the variation components based on standard deviation (then a sum of variation components does not give 100 %) and the honest GRR study calculates the variation components based on variance, where the sum of all variation components (part to part variation, EV & AV) gives the total variation of 100 %. Acceptance of both methods among the professional society, future use, and acceptance by manufacturing industry were also discussed. Nowadays, the AIAG is the leading method in the industry.

  18. Reproducibility of isotope ratio measurements

    International Nuclear Information System (INIS)

    Elmore, D.

    1981-01-01

    The use of an accelerator as part of a mass spectrometer has improved the sensitivity for measuring low levels of long-lived radionuclides by several orders of magnitude. However, the complexity of a large tandem accelerator and beam transport system has made it difficult to match the precision of low energy mass spectrometry. Although uncertainties for accelerator measured isotope ratios as low as 1% have been obtained under favorable conditions, most errors quoted in the literature for natural samples are in the 5 to 20% range. These errors are dominated by statistics and generally the reproducibility is unknown since the samples are only measured once

  19. Evaluation of multichannel reproduced sound

    DEFF Research Database (Denmark)

    Choisel, Sylvain; Wickelmaier, Florian Maria

    2007-01-01

    A study was conducted with the goal of quantifying auditory attributes which underlie listener preference for multichannel reproduced sound. Short musical excerpts were presented in mono, stereo and several multichannel formats to a panel of forty selected listeners. Scaling of auditory attributes......, as well as overall preference, was based on consistency tests of binary paired-comparison judgments and on modeling the choice frequencies using probabilistic choice models. As a result, the preferences of non-expert listeners could be measured reliably at a ratio scale level. Principal components derived...

  20. Variation in Bluetongue virus real-time reverse transcription polymerase chain reaction assay results in blood samples of sheep, cattle, and alpaca.

    Science.gov (United States)

    Brito, Barbara P; Gardner, Ian A; Hietala, Sharon K; Crossley, Beate M

    2011-07-01

    Bluetongue is a vector-borne viral disease that affects domestic and wild ruminants. The epidemiology of this disease has recently changed, with occurrence in new geographic areas. Various real-time quantitative reverse transcription polymerase chain reaction (real-time qRT-PCR) assays are used to detect Bluetongue virus (BTV); however, the impact of biologic differences between New World camelids and domestic ruminant samples on PCR efficiency, for which the BTV real-time qRT-PCR was initially validated are unknown. New world camelids are known to have important biologic differences in whole blood composition, including hemoglobin concentration, which can alter PCR performance. In the present study, sheep, cattle, and alpaca blood were spiked with BTV serotypes 10, 11, 13, and 17 and analyzed in 10-fold dilutions by real-time qRT-PCR to determine if species affected nucleic acid recovery and assay performance. A separate experiment was performed using spiked alpaca blood subsequently diluted in 10-fold series in sheep blood to assess the influence of alpaca blood on performance efficiency of the BTV real-time qRT-PCR assay. Results showed that BTV-specific nucleic acid detection from alpaca blood was consistently 1-2 logs lower than from sheep and cattle blood, and results were similar for each of the 4 BTV serotypes analyzed.

  1. The Reproducibility of Nuclear Morphometric Measurements in Invasive Breast Carcinoma

    Directory of Open Access Journals (Sweden)

    Pauliina Kronqvist

    1997-01-01

    Full Text Available The intraobserver and interobserver reproducibility of computerized nuclear morphometry was determined in repeated measurements of 212 samples of invasive breast cancer. The influence of biological variation and the selection of the measurement area was also tested. Morphometrically determined mean nuclear profile area (Pearson’s r 0.89, grading efficiency (GE 0.95 and standard deviation (SD of nuclear profile area (Pearson’s r 0.84, GE 0.89 showed high reproducibility. In this respect, nuclear morphometry equals with other established methods of quantitative pathology and exceeds the results of subjective grading of nuclear atypia in invasive breast cancer. A training period of eight days was sufficient to produce clear improvement in consistency of nuclear morphometry results. By estimating the sources of variation it could be shown that the variation associated with the measurement procedure itself is small. Instead, sample associated variation is responsible for the majority of variation in the measurements (82.9% in mean nuclear profile area and 65.9% in SD of nuclear profile area. This study points out that when standardized methods are applied computerized morphometry is a reproducible and reliable method of assessing nuclear atypia in invasive breast cancer. For further improvement special emphasize should be put on sampling rules of selecting the microscope fields and measurement areas.

  2. Systematic heterogenization for better reproducibility in animal experimentation.

    Science.gov (United States)

    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.

  3. Variation in the Abundance of OsHAK1 Transcript Underlies the Differential Salinity Tolerance of an indica and a japonica Rice Cultivar

    Directory of Open Access Journals (Sweden)

    Guang Chen

    2018-01-01

    Full Text Available Salinity imposes a major constraint over the productivity of rice. A set of chromosome segment substitution lines (CSSLs, derived from a cross between the japonica type cultivar (cv. Nipponbare (salinity sensitive and the indica type cv. 9311 (moderately tolerant, was scored using a hydroponics system for their salinity tolerance at the seedling stage. Two of the CSSLs, which share a ∼1.2 Mbp stretch of chromosome 4 derived from cv. Nipponbare, were as sensitive to the stress as cv. Nipponbare itself. Fine mapping based on an F2 population bred from a backcross between one of these CSSLs and cv. 9311 narrowed this region to 95 Kbp, within which only one gene (OsHAK1 exhibited a differential (lower transcript abundance in cv. Nipponbare and the two CSSLs compared to in cv. 9311. The gene was up-regulated by exposure to salinity stress both in the root and the shoot, while a knockout mutant proved to be more salinity sensitive than its wild type with respect to its growth at both the vegetative and reproductive stages. Seedlings over-expressing OsHAK1 were more tolerant than wild type, displaying a superior photosynthetic rate, a higher leaf chlorophyll content, an enhanced accumulation of proline and a reduced level of lipid peroxidation. At the transcriptome level, the over-expression of OsHAK1 stimulated a number of stress-responsive genes as well as four genes known to be involved in Na+ homeostasis and the salinity response (OsHKT1;5, OsSOS1, OsLti6a and OsLti6b. When the stress was applied at booting through to maturity, the OsHAK1 over-expressors out-yielded wild type by 25%, and no negative pleiotropic effects were expressed in plants gown under non-saline conditions. The level of expression of OsHAK1 was correlated with Na+/K+ homeostasis, which implies that the gene should be explored a target for molecular approaches to the improvement of salinity tolerance in rice.

  4. Structure and stability of genetic variance-covariance matrices: A Bayesian sparse factor analysis of transcriptional variation in the three-spined stickleback.

    Science.gov (United States)

    Siren, J; Ovaskainen, O; Merilä, J

    2017-10-01

    The genetic variance-covariance matrix (G) is a quantity of central importance in evolutionary biology due to its influence on the rate and direction of multivariate evolution. However, the predictive power of empirically estimated G-matrices is limited for two reasons. First, phenotypes are high-dimensional, whereas traditional statistical methods are tuned to estimate and analyse low-dimensional matrices. Second, the stability of G to environmental effects and over time remains poorly understood. Using Bayesian sparse factor analysis (BSFG) designed to estimate high-dimensional G-matrices, we analysed levels variation and covariation in 10,527 expressed genes in a large (n = 563) half-sib breeding design of three-spined sticklebacks subject to two temperature treatments. We found significant differences in the structure of G between the treatments: heritabilities and evolvabilities were higher in the warm than in the low-temperature treatment, suggesting more and faster opportunity to evolve in warm (stressful) conditions. Furthermore, comparison of G and its phenotypic equivalent P revealed the latter is a poor substitute of the former. Most strikingly, the results suggest that the expected impact of G on evolvability-as well as the similarity among G-matrices-may depend strongly on the number of traits included into analyses. In our results, the inclusion of only few traits in the analyses leads to underestimation in the differences between the G-matrices and their predicted impacts on evolution. While the results highlight the challenges involved in estimating G, they also illustrate that by enabling the estimation of large G-matrices, the BSFG method can improve predicted evolutionary responses to selection. © 2017 John Wiley & Sons Ltd.

  5. Reproducible research: a minority opinion

    Science.gov (United States)

    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.

  6. Reproducibility of ultrasonography for assessing abdominal fat distribution in a population at high risk of diabetes

    DEFF Research Database (Denmark)

    Philipsen, A; Carstensen, Bendix; Sandbæk, Annelli

    2013-01-01

    the reproducibility of this method have been published.Objective:The aim of this study was to investigate the reproducibility of ultrasonography in the assessment of abdominal fat distribution in a population at high risk of type 2 diabetes.Design and Methods:Ultrasonography was used to estimate visceral......- and interobserver variation, and Bland-Altman plots were drawn for all three substudies.Results:Coefficients of variation for intra- and interobserver variation were in the range 3.4-6.1%, except for interobserver variation for subcutaneous fat (9.5%). Short-term variation over a median of 35 days had a coefficient...

  7. Obesity has an interactive effect with genetic variation in the activating transcription factor 6 gene on the risk of pre-diabetes in individuals of Chinese Han descent.

    Science.gov (United States)

    Gu, Nan; Ma, Xiaowei; Zhang, Junqing; Dong, Aimei; Jin, Mengmeng; Feng, Nan; Zhang, Hong; Guo, Xiaohui

    2014-01-01

    Endoplasmic reticulum (ER) stress is one of the contributing factors to the development of β-cell failure in type 2 diabetes. ER stress response through ATF6 has been shown to play an important role in insulin resistance and pancreatic β-cell function. We investigated whether genetic polymorphisms in ATF6 were associated with the risk of pre-diabetes in a Chinese Han population, and whether they had a synergistic effect with obesity. Our samples included 828 individuals who were diagnosed as pre-diabetic, and 620 controls. The minor allele A at rs2340721 was associated with increased risk for pre-diabetes(p = 0.013), and this association was still significant after adjusting for gender, age, body mass index (BMI), and waist-hip ratio(p' = 0.011). BMI, treated as a continuous variable, and rs2340721 had an interactive effect on pre-diabetic risk(p for interaction = 0.003, β = 0.106). Carriers of GG at rs7522210 were also at a higher risk compared to non-carriers (OR = 1.390, 95%CI:1.206-1.818, p = 0.013, adjusted OR' = 1.516, 95%CI:1.101-2.006, p' = 0.006). GG homozygotes had increased fasting blood glucose (FBG) levels(GG vs CX: 5.6 ± 0.52 vs 5.5 ± 0.57 mmol/L, p = 0.016), lower insulin levels (0,30,120 minutes after glucose load) (p < 0.05), and reduced areas under the insulin curve than non-carriers(GG vs CX:67.3(44.2-102.3) vs 73.1(49.4-111.4), p = 0.014). rs10918270 was associated with FBG, and rs4657103 with 2 hour glucose levels after a 75 g glucose load. We also identified a haplotype of TTAG composed of rs4657103, rs2134697, rs2340721, and rs12079579, which was associated with pre-diabetes. The genetic variation in ATF6 is associated with pre-diabetes and has interactive effects with BMI on pre-diabetes in the Chinese Han population.

  8. Obesity has an interactive effect with genetic variation in the activating transcription factor 6 gene on the risk of pre-diabetes in individuals of Chinese Han descent.

    Directory of Open Access Journals (Sweden)

    Nan Gu

    Full Text Available Endoplasmic reticulum (ER stress is one of the contributing factors to the development of β-cell failure in type 2 diabetes. ER stress response through ATF6 has been shown to play an important role in insulin resistance and pancreatic β-cell function. We investigated whether genetic polymorphisms in ATF6 were associated with the risk of pre-diabetes in a Chinese Han population, and whether they had a synergistic effect with obesity. Our samples included 828 individuals who were diagnosed as pre-diabetic, and 620 controls. The minor allele A at rs2340721 was associated with increased risk for pre-diabetes(p = 0.013, and this association was still significant after adjusting for gender, age, body mass index (BMI, and waist-hip ratio(p' = 0.011. BMI, treated as a continuous variable, and rs2340721 had an interactive effect on pre-diabetic risk(p for interaction = 0.003, β = 0.106. Carriers of GG at rs7522210 were also at a higher risk compared to non-carriers (OR = 1.390, 95%CI:1.206-1.818, p = 0.013, adjusted OR' = 1.516, 95%CI:1.101-2.006, p' = 0.006. GG homozygotes had increased fasting blood glucose (FBG levels(GG vs CX: 5.6 ± 0.52 vs 5.5 ± 0.57 mmol/L, p = 0.016, lower insulin levels (0,30,120 minutes after glucose load (p < 0.05, and reduced areas under the insulin curve than non-carriers(GG vs CX:67.3(44.2-102.3 vs 73.1(49.4-111.4, p = 0.014. rs10918270 was associated with FBG, and rs4657103 with 2 hour glucose levels after a 75 g glucose load. We also identified a haplotype of TTAG composed of rs4657103, rs2134697, rs2340721, and rs12079579, which was associated with pre-diabetes. The genetic variation in ATF6 is associated with pre-diabetes and has interactive effects with BMI on pre-diabetes in the Chinese Han population.

  9. Reproducibility of morphometric X-ray absorptiometry

    International Nuclear Information System (INIS)

    Culton, N.; Pocock, N.

    1999-01-01

    Full text: Morphometric X-ray absorptiometry (MXA) using DXA is potentially a useful clinical tool which may provide additional vertebral fracture information with low radiation exposure. While morphometric analysis is semi-automated, operator intervention is crucial for the accurate positioning of the six data points quantifying the vertebral heights at the anterior, middle and posterior positions. Our study evaluated intra-operator reproducibility of MXA in an elderly patient population and assessed the effect of training and experience on vertebral height precision. Ten patients, with a mean lumbar T score of - 2.07, were studied. Images were processed by a trained operator who had initially only limited morphometric experience. The analysis of the data files were repeated at 2 and 6 weeks, during which time the operator had obtained further experience and training. The intra-operator precision of vertebral height measurements was calculated using the three separate combinations of paired analyses, and expressed as the coefficient of variation. This study confirms the importance of adequate training and attention to detail in MXA analysis. The data indicate that the precision of MXA is adequate for its use in the diagnosis of vertebral fractures, based on a 20% deformity criteria. Use of MXA for monitoring would require approximately an 8% change in vertebral heights to achieve statistical significance

  10. Reproducibility of ECG-gated Ultrasound Diameter Assessment of Small Abdominal Aortic Aneurysms

    DEFF Research Database (Denmark)

    Bredahl, K; Eldrup, N; Meyer, C

    2013-01-01

    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....

  11. Audiovisual biofeedback improves diaphragm motion reproducibility in MRI

    Science.gov (United States)

    Kim, Taeho; Pollock, Sean; Lee, Danny; O’Brien, Ricky; Keall, Paul

    2012-01-01

    Purpose: In lung radiotherapy, variations in cycle-to-cycle breathing results in four-dimensional computed tomography imaging artifacts, leading to inaccurate beam coverage and tumor targeting. In previous studies, the effect of audiovisual (AV) biofeedback on the external respiratory signal reproducibility has been investigated but the internal anatomy motion has not been fully studied. The aim of this study is to test the hypothesis that AV biofeedback improves diaphragm motion reproducibility of internal anatomy using magnetic resonance imaging (MRI). Methods: To test the hypothesis 15 healthy human subjects were enrolled in an ethics-approved AV biofeedback study consisting of two imaging sessions spaced ∼1 week apart. Within each session MR images were acquired under free breathing and AV biofeedback conditions. The respiratory signal to the AV biofeedback system utilized optical monitoring of an external marker placed on the abdomen. Synchronously, serial thoracic 2D MR images were obtained to measure the diaphragm motion using a fast gradient-recalled-echo MR pulse sequence in both coronal and sagittal planes. The improvement in the diaphragm motion reproducibility using the AV biofeedback system was quantified by comparing cycle-to-cycle variability in displacement, respiratory period, and baseline drift. Additionally, the variation in improvement between the two sessions was also quantified. Results: The average root mean square error (RMSE) of diaphragm cycle-to-cycle displacement was reduced from 2.6 mm with free breathing to 1.6 mm (38% reduction) with the implementation of AV biofeedback (p-value biofeedback (p-value biofeedback (p-value = 0.012). The diaphragm motion reproducibility improvements with AV biofeedback were consistent with the abdominal motion reproducibility that was observed from the external marker motion variation. Conclusions: This study was the first to investigate the potential of AV biofeedback to improve the motion

  12. Theory of reproducing kernels and applications

    CERN Document Server

    Saitoh, Saburou

    2016-01-01

    This book provides a large extension of the general theory of reproducing kernels published by N. Aronszajn in 1950, with many concrete applications. In Chapter 1, many concrete reproducing kernels are first introduced with detailed information. Chapter 2 presents a general and global theory of reproducing kernels with basic applications in a self-contained way. Many fundamental operations among reproducing kernel Hilbert spaces are dealt with. Chapter 2 is the heart of this book. Chapter 3 is devoted to the Tikhonov regularization using the theory of reproducing kernels with applications to numerical and practical solutions of bounded linear operator equations. In Chapter 4, the numerical real inversion formulas of the Laplace transform are presented by applying the Tikhonov regularization, where the reproducing kernels play a key role in the results. Chapter 5 deals with ordinary differential equations; Chapter 6 includes many concrete results for various fundamental partial differential equations. In Chapt...

  13. Reproducibility of gene expression across generations of Affymetrix microarrays

    Directory of Open Access Journals (Sweden)

    Haslett Judith N

    2003-06-01

    Full Text Available Abstract Background The development of large-scale gene expression profiling technologies is rapidly changing the norms of biological investigation. But the rapid pace of change itself presents challenges. Commercial microarrays are regularly modified to incorporate new genes and improved target sequences. Although the ability to compare datasets across generations is crucial for any long-term research project, to date no means to allow such comparisons have been developed. In this study the reproducibility of gene expression levels across two generations of Affymetrix GeneChips® (HuGeneFL and HG-U95A was measured. Results Correlation coefficients were computed for gene expression values across chip generations based on different measures of similarity. Comparing the absolute calls assigned to the individual probe sets across the generations found them to be largely unchanged. Conclusion We show that experimental replicates are highly reproducible, but that reproducibility across generations depends on the degree of similarity of the probe sets and the expression level of the corresponding transcript.

  14. Reproducibility of surface roughness in reaming

    DEFF Research Database (Denmark)

    Müller, Pavel; De Chiffre, Leonardo

    An investigation on the reproducibility of surface roughness in reaming was performed to document the applicability of this approach for testing cutting fluids. Austenitic stainless steel was used as a workpiece material and HSS reamers as cutting tools. Reproducibility of the results was evaluat...

  15. Reproducibility principles, problems, practices, and prospects

    CERN Document Server

    Maasen, Sabine

    2016-01-01

    Featuring peer-reviewed contributions from noted experts in their fields of research, Reproducibility: Principles, Problems, Practices, and Prospects presents state-of-the-art approaches to reproducibility, the gold standard sound science, from multi- and interdisciplinary perspectives. Including comprehensive coverage for implementing and reflecting the norm of reproducibility in various pertinent fields of research, the book focuses on how the reproducibility of results is applied, how it may be limited, and how such limitations can be understood or even controlled in the natural sciences, computational sciences, life sciences, social sciences, and studies of science and technology. The book presents many chapters devoted to a variety of methods and techniques, as well as their epistemic and ontological underpinnings, which have been developed to safeguard reproducible research and curtail deficits and failures. The book also investigates the political, historical, and social practices that underlie repro...

  16. Composting in small laboratory pilots: Performance and reproducibility

    International Nuclear Information System (INIS)

    Lashermes, G.; Barriuso, E.; Le Villio-Poitrenaud, M.; Houot, S.

    2012-01-01

    Highlights: ► We design an innovative small-scale composting device including six 4-l reactors. ► We investigate the performance and reproducibility of composting on a small scale. ► Thermophilic conditions are established by self-heating in all replicates. ► Biochemical transformations, organic matter losses and stabilisation are realistic. ► The organic matter evolution exhibits good reproducibility for all six replicates. - Abstract: Small-scale reactors ( 2 consumption and CO 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 final compost. The TOM losses, compost stabilisation and evolution of the biochemical fractions were similar to observed in large reactors or on-site experiments, excluding the lignin degradation, which was less important than in full-scale systems. The reproducibility of the process and the quality of the final compost make it possible to propose the use of this experimental device for research requiring a mass reduction of the initial composted waste mixtures.

  17. Reproducibility of Mammography Units, Film Processing and Quality Imaging

    International Nuclear Information System (INIS)

    Gaona, Enrique

    2003-01-01

    The purpose of this study was to carry out an exploratory survey of the problems of quality control in mammography and processors units as a diagnosis of the current situation of mammography facilities. Measurements of reproducibility, optical density, optical difference and gamma index are included. Breast cancer is the most frequently diagnosed cancer and is the second leading cause of cancer death among women in the Mexican Republic. Mammography is a radiographic examination specially designed for detecting breast pathology. We found that the problems of reproducibility of AEC are smaller than the problems of processors units because almost all processors fall outside of the acceptable variation limits and they can affect the mammography quality image and the dose to breast. Only four mammography units agree with the minimum score established by ACR and FDA for the phantom image

  18. Reproducibility of CT bone dosimetry: Operator versus automated ROI definition

    International Nuclear Information System (INIS)

    Louis, O.; Luypaert, R.; Osteaux, M.; Kalender, W.

    1988-01-01

    Intrasubject reproducibility with repeated determination of vertebral mineral density from a given set of CT images was investigated. The region of interest (ROI) in 10 patient scans was selected by four independent operators either manually or with an automated procedure separating cortical and spongeous bone, the operators being requested to interact in ROI selection. The mean intrasubject variation was found to be much lower with the automated process (0.3 to 0.6%) than with the conventional method (2.5 to 5.2%). In a second study, 10 patients were examined twice to determine the reproducibility of CT slice selection by the operator. The errors were of the same order of magnitude as in ROI selection. (orig.)

  19. Learning Reproducibility with a Yearly Networking Contest

    KAUST Repository

    Canini, Marco

    2017-08-10

    Better reproducibility of networking research results is currently a major goal that the academic community is striving towards. This position paper makes the case that improving the extent and pervasiveness of reproducible research can be greatly fostered by organizing a yearly international contest. We argue that holding a contest undertaken by a plurality of students will have benefits that are two-fold. First, it will promote hands-on learning of skills that are helpful in producing artifacts at the replicable-research level. Second, it will advance the best practices regarding environments, testbeds, and tools that will aid the tasks of reproducibility evaluation committees by and large.

  20. The Economics of Reproducibility in Preclinical Research.

    Directory of Open Access Journals (Sweden)

    Leonard P Freedman

    2015-06-01

    Full Text Available Low reproducibility rates within life science research undermine cumulative knowledge production and contribute to both delays and costs of therapeutic drug development. An analysis of past studies indicates that the cumulative (total prevalence of irreproducible preclinical research exceeds 50%, resulting in approximately US$28,000,000,000 (US$28B/year spent on preclinical research that is not reproducible-in the United States alone. We outline a framework for solutions and a plan for long-term improvements in reproducibility rates that will help to accelerate the discovery of life-saving therapies and cures.

  1. Thou Shalt Be Reproducible! A Technology Perspective

    Directory of Open Access Journals (Sweden)

    Patrick Mair

    2016-07-01

    Full Text Available This article elaborates on reproducibility in psychology from a technological viewpoint. Modernopen source computational environments are shown and explained that foster reproducibilitythroughout the whole research life cycle, and to which emerging psychology researchers shouldbe sensitized, are shown and explained. First, data archiving platforms that make datasets publiclyavailable are presented. Second, R is advocated as the data-analytic lingua franca in psychologyfor achieving reproducible statistical analysis. Third, dynamic report generation environments forwriting reproducible manuscripts that integrate text, data analysis, and statistical outputs such asfigures and tables in a single document are described. Supplementary materials are provided inorder to get the reader started with these technologies.

  2. Examination of reproducibility in microbiological degredation experiments

    DEFF Research Database (Denmark)

    Sommer, Helle Mølgaard; Spliid, Henrik; Holst, Helle

    1998-01-01

    Experimental data indicate that certain microbiological degradation experiments have a limited reproducibility. Nine identical batch experiments were carried out on 3 different days to examine reproducibility. A pure culture, isolated from soil, grew with toluene as the only carbon and energy...... source. Toluene was degraded under aerobic conditions at a constant temperature of 28 degreesC. The experiments were modelled by a Monod model - extended to meet the air/liquid system, and the parameter values were estimated using a statistical nonlinear estimation procedure. Model reduction analysis...... resulted in a simpler model without the biomass decay term. In order to test for model reduction and reproducibility of parameter estimates, a likelihood ratio test was employed. The limited reproducibility for these experiments implied that all 9 batch experiments could not be described by the same set...

  3. Archiving Reproducible Research with R and Dataverse

    DEFF Research Database (Denmark)

    Leeper, Thomas

    2014-01-01

    Reproducible research and data archiving are increasingly important issues in research involving statistical analyses of quantitative data. This article introduces the dvn package, which allows R users to publicly archive datasets, analysis files, codebooks, and associated metadata in Dataverse...

  4. Reproducing Epidemiologic Research and Ensuring Transparency.

    Science.gov (United States)

    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.

  5. Enacting the International/Reproducing Eurocentrism

    Directory of Open Access Journals (Sweden)

    Zeynep Gülşah Çapan

    Full Text Available Abstract This article focuses on the way in which Eurocentric conceptualisations of the ‘international’ are reproduced in different geopolitical contexts. Even though the Eurocentrism of International Relations has received growing attention, it has predominantly been concerned with unearthing the Eurocentrism of the ‘centre’, overlooking its varied manifestations in other geopolitical contexts. The article seeks to contribute to discussions about Eurocentrism by examining how different conceptualisations of the international are at work at a particular moment, and how these conceptualisations continue to reproduce Eurocentrism. It will focus on the way in which Eurocentric designations of spatial and temporal hierarchies were reproduced in the context of Turkey through a reading of how the ‘Gezi Park protests’ of 2013 and ‘Turkey’ itself were written into the story of the international.

  6. Reproducibility, controllability, and optimization of LENR experiments

    Energy Technology Data Exchange (ETDEWEB)

    Nagel, David J. [The George Washington University, Washington DC 20052 (United States)

    2006-07-01

    Low-energy nuclear reaction (LENR) measurements are significantly, and increasingly reproducible. Practical control of the production of energy or materials by LENR has yet to be demonstrated. Minimization of costly inputs and maximization of desired outputs of LENR remain for future developments. The paper concludes by underlying that it is now clearly that demands for reproducible experiments in the early years of LENR experiments were premature. In fact, one can argue that irreproducibility should be expected for early experiments in a complex new field. As emphasized in the paper and as often happened in the history of science, experimental and theoretical progress can take even decades. It is likely to be many years before investments in LENR experiments will yield significant returns, even for successful research programs. However, it is clearly that a fundamental understanding of the anomalous effects observed in numerous experiments will significantly increase reproducibility, improve controllability, enable optimization of processes, and accelerate the economic viability of LENR.

  7. Reproducibility, controllability, and optimization of LENR experiments

    International Nuclear Information System (INIS)

    Nagel, David J.

    2006-01-01

    Low-energy nuclear reaction (LENR) measurements are significantly, and increasingly reproducible. Practical control of the production of energy or materials by LENR has yet to be demonstrated. Minimization of costly inputs and maximization of desired outputs of LENR remain for future developments. The paper concludes by underlying that it is now clearly that demands for reproducible experiments in the early years of LENR experiments were premature. In fact, one can argue that irreproducibility should be expected for early experiments in a complex new field. As emphasized in the paper and as often happened in the history of science, experimental and theoretical progress can take even decades. It is likely to be many years before investments in LENR experiments will yield significant returns, even for successful research programs. However, it is clearly that a fundamental understanding of the anomalous effects observed in numerous experiments will significantly increase reproducibility, improve controllability, enable optimization of processes, and accelerate the economic viability of LENR

  8. Undefined cellulase formulations hinder scientific reproducibility.

    Science.gov (United States)

    Himmel, Michael E; Abbas, Charles A; Baker, John O; Bayer, Edward A; Bomble, Yannick J; Brunecky, Roman; Chen, Xiaowen; Felby, Claus; Jeoh, Tina; Kumar, Rajeev; McCleary, Barry V; Pletschke, Brett I; Tucker, Melvin P; Wyman, Charles E; Decker, Stephen R

    2017-01-01

    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 preparations 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.

  9. Reproducibility of somatosensory spatial perceptual maps.

    Science.gov (United States)

    Steenbergen, Peter; Buitenweg, Jan R; Trojan, Jörg; Veltink, Peter H

    2013-02-01

    Various studies have shown subjects to mislocalize cutaneous stimuli in an idiosyncratic manner. Spatial properties of individual localization behavior can be represented in the form of perceptual maps. Individual differences in these maps may reflect properties of internal body representations, and perceptual maps may therefore be a useful method for studying these representations. For this to be the case, individual perceptual maps need to be reproducible, which has not yet been demonstrated. We assessed the reproducibility of localizations measured twice on subsequent days. Ten subjects participated in the experiments. Non-painful electrocutaneous stimuli were applied at seven sites on the lower arm. Subjects localized the stimuli on a photograph of their own arm, which was presented on a tablet screen overlaying the real arm. Reproducibility was assessed by calculating intraclass correlation coefficients (ICC) for the mean localizations of each electrode site and the slope and offset of regression models of the localizations, which represent scaling and displacement of perceptual maps relative to the stimulated sites. The ICCs of the mean localizations ranged from 0.68 to 0.93; the ICCs of the regression parameters were 0.88 for the intercept and 0.92 for the slope. These results indicate a high degree of reproducibility. We conclude that localization patterns of non-painful electrocutaneous stimuli on the arm are reproducible on subsequent days. Reproducibility is a necessary property of perceptual maps for these to reflect properties of a subject's internal body representations. Perceptual maps are therefore a promising method for studying body representations.

  10. [Natural head position's reproducibility on photographs].

    Science.gov (United States)

    Eddo, Marie-Line; El Hayeck, Émilie; Hoyeck, Maha; Khoury, Élie; Ghoubril, Joseph

    2017-12-01

    The purpose of this study is to evaluate the reproducibility of natural head position with time on profile photographs. Our sample is composed of 96 students (20-30 years old) at the department of dentistry of Saint Joseph University in Beirut. Two profile photographs were taken in natural head position about a week apart. No significant differences were found between T0 and T1 (E = 1.065°). Many studies confirmed this reproducibility with time. Natural head position can be adopted as an orientation for profile photographs in orthodontics. © EDP Sciences, SFODF, 2017.

  11. Highly reproducible polyol synthesis for silver nanocubes

    Science.gov (United States)

    Han, Hye Ji; Yu, Taekyung; Kim, Woo-Sik; Im, Sang Hyuk

    2017-07-01

    We could synthesize the Ag nanocubes highly reproducibly by conducting the polyol synthesis using HCl etchant in dark condition because the photodecomposition/photoreduction of AgCl nanoparticles formed at initial reaction stage were greatly depressed and consequently the selective self-nucleation of Ag single crystals and their selective growth reaction could be promoted. Whereas the reproducibility of the formation of Ag nanocubes were very poor when we synthesize the Ag nanocubes in light condition due to the photoreduction of AgCl to Ag.

  12. Reproducible statistical analysis with multiple languages

    DEFF Research Database (Denmark)

    Lenth, Russell; Højsgaard, Søren

    2011-01-01

    This paper describes the system for making reproducible statistical analyses. differs from other systems for reproducible analysis in several ways. The two main differences are: (1) Several statistics programs can be in used in the same document. (2) Documents can be prepared using OpenOffice or ......Office or \\LaTeX. The main part of this paper is an example showing how to use and together in an OpenOffice text document. The paper also contains some practical considerations on the use of literate programming in statistics....

  13. The reproducibility of single photon absorptiometry in a clinical setting

    International Nuclear Information System (INIS)

    Valkema, R.; Blokland, J.A.K.; Pauwels, E.K.J.; Papapoulos, S.E.; Bijvoet, O.L.M.

    1989-01-01

    The reproducibility of single photon absorptiometry (SPA) results for detection of changes in bone mineral content (BMC) was evaluated in a clinical setting. During a period of 18 months with 4 different sources, the calibration scans of an aluminium standard had a variation of less than 1% unless the activity of the 125 I source was low. The calibration procedure was performed weekly and this was sufficient to correct for drift of the system. The short term reproducibility in patients was assessed with 119 duplicate measurements made in direct succession. The best reproducibility (CV=1.35%) was found for fat corrected BMC results expressed in g/cm, obtained at the site proximal to the 8 mm space between the radius and ulna. Analysis of all SPA scans made during 1 year (487 scans) showed a failure of the automatic procedure to detect the space of 8 mm between the forearm bones in 19 scans (3.9%). A space adjacent to the ulnar styloid was taken as the site for the first scan in these examinations. This problem may be recognized and corrected relatively easy. A significant correlation was found between BMC at the lower arm and BMC of the lumbar spine assessed with dual photon absorptiometry. However, the error of estimation of proximal BMC (SEE=20%) and distal BMC (SEE=19.4%) made these measurements of little value to predict BMC at the lumbar spine in individuals. The short term reproducibility in patients combined with long term stability of the equipment in our clinical setting showed that SPA is a reliable technique to assess changes in bone mass at the lower arm of 4% between 2 measurements with a confidence level of 95%. (orig.)

  14. The transcriptional landscape

    DEFF Research Database (Denmark)

    Nielsen, Henrik

    2011-01-01

    The application of new and less biased methods to study the transcriptional output from genomes, such as tiling arrays and deep sequencing, has revealed that most of the genome is transcribed and that there is substantial overlap of transcripts derived from the two strands of DNA. In protein coding...... regions, the map of transcripts is very complex due to small transcripts from the flanking ends of the transcription unit, the use of multiple start and stop sites for the main transcript, production of multiple functional RNA molecules from the same primary transcript, and RNA molecules made...... by independent transcription from within the unit. In genomic regions separating those that encode proteins or highly abundant RNA molecules with known function, transcripts are generally of low abundance and short-lived. In most of these cases, it is unclear to what extent a function is related to transcription...

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

    Science.gov (United States)

    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.

  16. Reproducibility of an aerobic endurance test for nonexpert swimmers.

    Science.gov (United States)

    Veronese da Costa, Adalberto; Costa, Manoel da Cunha; Carlos, Daniel Medeiros; Guerra, Luis Marcos de Medeiros; Silva, Antônio José; Barbosa, Tiago Manoel Cabral Dos Santos

    2012-01-01

    This study aimed to verify the reproduction of an aerobic test to determine nonexpert swimmers' resistance. The sample consisted of 24 male swimmers (age: 22.79 ± 3.90 years; weight: 74.72 ± 11.44 kg; height: 172.58 ± 4.99 cm; and fat percentage: 15.19% ± 3.21%), who swim for 1 hour three times a week. A new instrument was used in this study (a Progressive Swim Test): the swimmer wore an underwater MP3 player and increased their swimming speed on hearing a beep after every 25 meters. Each swimmer's heart rate was recorded before the test (BHR) and again after the test (AHR). The rate of perceived exertion (RPE) and the number of laps performed (NLP) were also recorded. The sample size was estimated using G*Power software (v 3.0.10; Franz Faul, Kiel University, Kiel, Germany). The descriptive values were expressed as mean and standard deviation. After confirming the normality of the data using both the Shapiro-Wilk and Levene tests, a paired t-test was performed to compare the data. The Pearson's linear correlation (r) and intraclass coefficient correlation (ICC) tests were used to determine relative reproducibility. The standard error of measurement (SEM) and the coefficient of variation (CV) were used to determine absolute reproducibility. The limits of agreement and the bias of the absolute and relative values between days were determined by Bland-Altman plots. All values had a significance level of P 0.50 and ICC > 0.66. The SEM had a variation of ±2% and the CV was 0.90; SEM swimmers. The Progressive Swim Test for nonexpert swimmers produces comparable results for noncompetitive swimmers with a favorable degree of reproducibility, thus presenting possible applications for researching the physiological performance of nonexpert swimmers.

  17. Reproducing kernel Hilbert spaces of Gaussian priors

    NARCIS (Netherlands)

    Vaart, van der A.W.; Zanten, van J.H.; Clarke, B.; Ghosal, S.

    2008-01-01

    We review definitions and properties of reproducing kernel Hilbert spaces attached to Gaussian variables and processes, with a view to applications in nonparametric Bayesian statistics using Gaussian priors. The rate of contraction of posterior distributions based on Gaussian priors can be described

  18. Reproducibility of the results in ultrasonic testing

    International Nuclear Information System (INIS)

    Chalaye, M.; Launay, J.P.; Thomas, A.

    1980-12-01

    This memorandum reports on the conclusions of the tests carried out in order to evaluate the reproducibility of ultrasonic tests made on welded joints. FRAMATOME have started a study to assess the dispersion of results afforded by the test line and to characterize its behaviour. The tests covered sensors and ultrasonic generators said to be identical to each other (same commercial batch) [fr

  19. Reproducibility in Computational Neuroscience Models and Simulations

    Science.gov (United States)

    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

  20. Estimating the reproducibility of psychological science

    NARCIS (Netherlands)

    Aarts, Alexander A.; Anderson, Joanna E.; Anderson, Christopher J.; Attridge, Peter R.; Attwood, Angela; Axt, Jordan; Babel, Molly; Bahnik, Stepan; Baranski, Erica; Barnett-Cowan, Michael; Bartmess, Elizabeth; Beer, Jennifer; Bell, Raoul; Bentley, Heather; Beyan, Leah; Binion, Grace; Borsboom, Denny; Bosch, Annick; Bosco, Frank A.; Bowman, Sara D.; Brandt, Mark J.; Braswell, Erin; Brohmer, Hilmar; Brown, Benjamin T.; Brown, Kristina; Bruening, Jovita; Calhoun-Sauls, Ann; Chagnon, Elizabeth; Callahan, Shannon P.; Chandler, Jesse; Chartier, Christopher R.; Cheung, Felix; Cillessen, Linda; Christopherson, Cody D.; Clay, Russ; Cleary, Hayley; Cloud, Mark D.; Cohn, Michael; Cohoon, Johanna; Columbus, Simon; Cordes, Andreas; Costantini, Giulio; Hartgerink, Chris; Krijnen, Job; Nuijten, Michele B.; van 't Veer, Anna E.; Van Aert, Robbie; van Assen, M.A.L.M.; Wissink, Joeri; Zeelenberg, Marcel

    2015-01-01

    INTRODUCTION Reproducibility is a defining feature of science, but the extent to which it characterizes current research is unknown. Scientific claims should not gain credence because of the status or authority of their originator but by the replicability of their supporting evidence. Even research

  1. Reproducibility, Controllability, and Optimization of Lenr Experiments

    Science.gov (United States)

    Nagel, David J.

    2006-02-01

    Low-energy nuclear reaction (LENR) measurements are significantly and increasingly reproducible. Practical control of the production of energy or materials by LENR has yet to be demonstrated. Minimization of costly inputs and maximization of desired outputs of LENR remain for future developments.

  2. Estimating the reproducibility of psychological science

    NARCIS (Netherlands)

    Anderson, Joanna E.; Aarts, Alexander A.; Anderson, Christopher J.; Attridge, Peter R.; Attwood, Angela; Axt, Jordan; Babel, Molly; Bahník, Štěpán; Baranski, Erica; Barnett-Cowan, Michael; Bartmess, Elizabeth; Beer, Jennifer; Bell, Raoul; Bentley, Heather; Beyan, Leah; Binion, Grace; Borsboom, Denny; Bosch, Annick; Bosco, Frank A.; Bowman, Sara D.; Brandt, Mark J.; Braswell, Erin; Brohmer, Hilmar; Brown, Benjamin T.; Brown, Kristina; Brüning, Jovita; Calhoun-Sauls, Ann; Callahan, Shannon P.; Chagnon, Elizabeth; Chandler, Jesse; Chartier, Christopher R.; Cheung, Felix; Christopherson, Cody D.; Cillessen, Linda; Clay, Russ; Cleary, Hayley; Cloud, Mark D.; Conn, Michael; Cohoon, Johanna; Columbus, Simon; Cordes, Andreas; Costantini, Giulio; Alvarez, Leslie D Cramblet; Cremata, Ed; Crusius, Jan; DeCoster, Jamie; DeGaetano, Michelle A.; Penna, Nicolás Delia; Den Bezemer, Bobby; Deserno, Marie K.; Devitt, Olivia; Dewitte, Laura; Dobolyi, David G.; Dodson, Geneva T.; Donnellan, M. Brent; Donohue, Ryan; Dore, Rebecca A.; Dorrough, Angela; Dreber, Anna; Dugas, Michelle; Dunn, Elizabeth W.; Easey, Kayleigh; Eboigbe, Sylvia; Eggleston, Casey; Embley, Jo; Epskamp, Sacha; Errington, Timothy M.; Estel, Vivien; Farach, Frank J.; Feather, Jenelle; Fedor, Anna; Fernández-Castilla, Belén; Fiedler, Susann; Field, James G.; Fitneva, Stanka A.; Flagan, Taru; Forest, Amanda L.; Forsell, Eskil; Foster, Joshua D.; Frank, Michael C.; Frazier, Rebecca S.; Fuchs, Heather; Gable, Philip; Galak, Jeff; Galliani, Elisa Maria; Gampa, Anup; Garcia, Sara; Gazarian, Douglas; Gilbert, Elizabeth; Giner-Sorolla, Roger; Glöckner, Andreas; Goellner, Lars; Goh, Jin X.; Goldberg, Rebecca; Goodbourn, Patrick T.; Gordon-McKeon, Shauna; Gorges, Bryan; Gorges, Jessie; Goss, Justin; Graham, Jesse; Grange, James A.; Gray, Jeremy; Hartgerink, Chris; Hartshorne, Joshua; Hasselman, Fred; Hayes, Timothy; Heikensten, Emma; Henninger, Felix; Hodsoll, John; Holubar, Taylor; Hoogendoorn, Gea; Humphries, Denise J.; Hung, Cathy O Y; Immelman, Nathali; Irsik, Vanessa C.; Jahn, Georg; Jäkel, Frank; Jekel, Marc; Johannesson, Magnus; Johnson, Larissa G.; Johnson, David J.; Johnson, Kate M.; Johnston, William J.; Jonas, Kai; Joy-Gaba, Jennifer A.; Kappes, Heather Barry; Kelso, Kim; Kidwell, Mallory C.; Kim, Seung Kyung; Kirkhart, Matthew; Kleinberg, Bennett; Knežević, Goran; Kolorz, Franziska Maria; Kossakowski, Jolanda J.; Krause, Robert Wilhelm; Krijnen, Job; Kuhlmann, Tim; Kunkels, Yoram K.; Kyc, Megan M.; Lai, Calvin K.; Laique, Aamir; Lakens, Daniël|info:eu-repo/dai/nl/298811855; Lane, Kristin A.; Lassetter, Bethany; Lazarević, Ljiljana B.; Le Bel, Etienne P.; Lee, Key Jung; Lee, Minha; Lemm, Kristi; Levitan, Carmel A.; Lewis, Melissa; Lin, Lin; Lin, Stephanie; Lippold, Matthias; Loureiro, Darren; Luteijn, Ilse; MacKinnon, Sean; Mainard, Heather N.; Marigold, Denise C.; Martin, Daniel P.; Martinez, Tylar; Masicampo, E. J.; Matacotta, Josh; Mathur, Maya; May, Michael; Mechin, Nicole; Mehta, Pranjal; Meixner, Johannes; Melinger, Alissa; Miller, Jeremy K.; Miller, Mallorie; Moore, Katherine; Möschl, Marcus; Motyl, Matt; Müller, Stephanie M.; Munafo, Marcus; Neijenhuijs, Koen I.; Nervi, Taylor; Nicolas, Gandalf; Nilsonne, Gustav; Nosek, Brian A.; Nuijten, Michèle B.; Olsson, Catherine; Osborne, Colleen; Ostkamp, Lutz; Pavel, Misha; Penton-Voak, Ian S.; Perna, Olivia; Pernet, Cyril; Perugini, Marco; Pipitone, R. Nathan; Pitts, Michael; Plessow, Franziska; Prenoveau, Jason M.; Rahal, Rima Maria; Ratliff, Kate A.; Reinhard, David; Renkewitz, Frank; Ricker, Ashley A.; Rigney, Anastasia; Rivers, Andrew M.; Roebke, Mark; Rutchick, Abraham M.; Ryan, Robert S.; Sahin, Onur; Saide, Anondah; Sandstrom, Gillian M.; Santos, David; Saxe, Rebecca; Schlegelmilch, René; Schmidt, Kathleen; Scholz, Sabine; Seibel, Larissa; Selterman, Dylan Faulkner; Shaki, Samuel; Simpson, William B.; Sinclair, H. Colleen; Skorinko, Jeanine L M; Slowik, Agnieszka; Snyder, Joel S.; Soderberg, Courtney; Sonnleitner, Carina; Spencer, Nick; Spies, Jeffrey R.; Steegen, Sara; Stieger, Stefan; Strohminger, Nina; Sullivan, Gavin B.; Talhelm, Thomas; Tapia, Megan; Te Dorsthorst, Anniek; Thomae, Manuela; Thomas, Sarah L.; Tio, Pia; Traets, Frits; Tsang, Steve; Tuerlinckx, Francis; Turchan, Paul; Valášek, Milan; Van't Veer, Anna E.; Van Aert, Robbie; Van Assen, Marcel|info:eu-repo/dai/nl/407629971; Van Bork, Riet; Van De Ven, Mathijs; Van Den Bergh, Don; Van Der Hulst, Marije; Van Dooren, Roel; Van Doorn, Johnny; Van Renswoude, Daan R.; Van Rijn, Hedderik; Vanpaemel, Wolf; Echeverría, Alejandro Vásquez; Vazquez, Melissa; Velez, Natalia; Vermue, Marieke; Verschoor, Mark; Vianello, Michelangelo; Voracek, Martin; Vuu, Gina; Wagenmakers, Eric Jan; Weerdmeester, Joanneke; Welsh, Ashlee; Westgate, Erin C.; Wissink, Joeri; Wood, Michael; Woods, Andy; Wright, Emily; Wu, Sining; Zeelenberg, Marcel; Zuni, Kellylynn

    2015-01-01

    Reproducibility is a defining feature of science, but the extent to which it characterizes current research is unknown. We conducted replications of 100 experimental and correlational studies published in three psychology journals using high-powered designs and original materials when available.

  3. Reproducibility of heart rate variability, blood pressure variability and baroreceptor sensitivity during rest and head-up tilt

    DEFF Research Database (Denmark)

    Højgaard, Michael V; Agner, Erik; Kanters, Jørgen K

    2005-01-01

    OBJECTIVE: Previous studies have indicated moderate-to-poor reproducibility of heart rate variability (HRV) but the reproducibility of blood pressure variability (BPV) and spectral measures of baroreceptor sensitivity (BRS) are not well established. METHODS: We measured normal-to-normal heart beat...... pressures were extracted for the assessment of day-to-day and short-term reproducibility. Power spectrum analysis (Fourier) and transfer function analysis was performed. Reproducibility was assessed using the coefficient of variation (CV). The reproducibility of the mean RR interval, mean systolic......, diastolic and mean blood pressure was good (CVspectral parameters of HRV (CV range 18-36%) and BPV (16-44%) and moderate reproducibility of BRS (14-20%). CONCLUSION: Spectral estimates of BRS had only moderate reproducibility although...

  4. ITK: Enabling Reproducible Research and Open Science

    Directory of Open Access Journals (Sweden)

    Matthew Michael McCormick

    2014-02-01

    Full Text Available 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.

  5. A PHYSICAL ACTIVITY QUESTIONNAIRE: REPRODUCIBILITY AND VALIDITY

    Directory of Open Access Journals (Sweden)

    Nicolas Barbosa

    2007-12-01

    Full Text Available This study evaluates the Quantification de L'Activite Physique en Altitude chez les Enfants (QAPACE supervised self-administered questionnaire reproducibility and validity on the estimation of the mean daily energy expenditure (DEE on Bogotá's schoolchildren. The comprehension was assessed on 324 students, whereas the reproducibility was studied on a different random sample of 162 who were exposed twice to it. Reproducibility was assessed using both the Bland-Altman plot and the intra-class correlation coefficient (ICC. The validity was studied in a sample of 18 girls and 18 boys randomly selected, which completed the test - re-test study. The DEE derived from the questionnaire was compared with the laboratory measurement results of the peak oxygen uptake (Peak VO2 from ergo-spirometry and Leger Test. The reproducibility ICC was 0.96 (95% C.I. 0.95-0.97; by age categories 8-10, 0.94 (0.89-0. 97; 11-13, 0.98 (0.96- 0.99; 14-16, 0.95 (0.91-0.98. The ICC between mean TEE as estimated by the questionnaire and the direct and indirect Peak VO2 was 0.76 (0.66 (p<0.01; by age categories, 8-10, 11-13, and 14-16 were 0.89 (0.87, 0.76 (0.78 and 0.88 (0.80 respectively. The QAPACE questionnaire is reproducible and valid for estimating PA and showed a high correlation with the Peak VO2 uptake

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

    Science.gov (United States)

    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.

  7. Reproducibility of scoring emphysema by HRCT

    International Nuclear Information System (INIS)

    Malinen, A.; Partanen, K.; Rytkoenen, H.; Vanninen, R.; Erkinjuntti-Pekkanen, R.

    2002-01-01

    Purpose: We evaluated the reproducibility of three visual scoring methods of emphysema and compared these methods with pulmonary function tests (VC, DLCO, FEV1 and FEV%) among farmer's lung patients and farmers. Material and Methods: Three radiologists examined high-resolution CT images of farmer's lung patients and their matched controls (n=70) for chronic interstitial lung diseases. Intraobserver reproducibility and interobserver variability were assessed for three methods: severity, Sanders' (extent) and Sakai. Pulmonary function tests as spirometry and diffusing capacity were measured. Results: Intraobserver -values for all three methods were good (0.51-0.74). Interobserver varied from 0.35 to 0.72. The Sanders' and the severity methods correlated strongly with pulmonary function tests, especially DLCO and FEV1. Conclusion: The Sanders' method proved to be reliable in evaluating emphysema, in terms of good consistency of interpretation and good correlation with pulmonary function tests

  8. Reproducibility of scoring emphysema by HRCT

    Energy Technology Data Exchange (ETDEWEB)

    Malinen, A.; Partanen, K.; Rytkoenen, H.; Vanninen, R. [Kuopio Univ. Hospital (Finland). Dept. of Clinical Radiology; Erkinjuntti-Pekkanen, R. [Kuopio Univ. Hospital (Finland). Dept. of Pulmonary Diseases

    2002-04-01

    Purpose: We evaluated the reproducibility of three visual scoring methods of emphysema and compared these methods with pulmonary function tests (VC, DLCO, FEV1 and FEV%) among farmer's lung patients and farmers. Material and Methods: Three radiologists examined high-resolution CT images of farmer's lung patients and their matched controls (n=70) for chronic interstitial lung diseases. Intraobserver reproducibility and interobserver variability were assessed for three methods: severity, Sanders' (extent) and Sakai. Pulmonary function tests as spirometry and diffusing capacity were measured. Results: Intraobserver -values for all three methods were good (0.51-0.74). Interobserver varied from 0.35 to 0.72. The Sanders' and the severity methods correlated strongly with pulmonary function tests, especially DLCO and FEV1. Conclusion: The Sanders' method proved to be reliable in evaluating emphysema, in terms of good consistency of interpretation and good correlation with pulmonary function tests.

  9. Additive Manufacturing: Reproducibility of Metallic Parts

    Directory of Open Access Journals (Sweden)

    Konda Gokuldoss Prashanth

    2017-02-01

    Full Text Available The present study deals with the properties of five different metals/alloys (Al-12Si, Cu-10Sn and 316L—face centered cubic structure, CoCrMo and commercially pure Ti (CP-Ti—hexagonal closed packed structure fabricated by selective laser melting. The room temperature tensile properties of Al-12Si samples show good consistency in results within the experimental errors. Similar reproducible results were observed for sliding wear and corrosion experiments. The other metal/alloy systems also show repeatable tensile properties, with the tensile curves overlapping until the yield point. The curves may then follow the same path or show a marginal deviation (~10 MPa until they reach the ultimate tensile strength and a negligible difference in ductility levels (of ~0.3% is observed between the samples. The results show that selective laser melting is a reliable fabrication method to produce metallic materials with consistent and reproducible properties.

  10. Reproducibility in cyclostratigraphy: initiating an intercomparison project

    Science.gov (United States)

    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

  11. A how to guide to reproducible research

    OpenAIRE

    Whitaker, Kirstie

    2018-01-01

    This talk will discuss the perceived and actual barriers experienced by researchers attempting to do reproducible research, and give practical guidance on how they can be overcome. It will include suggestions on how to make your code and data available and usable for others (including a strong suggestion to document both clearly so you don't have to reply to lots of email questions from future users). Specifically it will include a brief guide to version control, collaboration and disseminati...

  12. Bad Behavior: Improving Reproducibility in Behavior Testing.

    Science.gov (United States)

    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.

  13. A Framework for Reproducible Latent Fingerprint Enhancements.

    Science.gov (United States)

    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.

  14. Reproducibility of 201Tl myocardial imaging

    International Nuclear Information System (INIS)

    McLaughlin, P.R.; Martin, R.P.; Doherty, P.; Daspit, S.; Goris, M.; Haskell, W.; Lewis, S.; Kriss, J.P.; Harrison, D.C.

    1977-01-01

    Seventy-six thallium-201 myocardial perfusion studies were performed on twenty-five patients to assess their reproducibility and the effect of varying the level of exercise on the results of imaging. Each patient had a thallium-201 study at rest. Fourteen patients had studies on two occasions at maximum exercise, and twelve patients had studies both at light and at maximum exercise. Of 70 segments in the 14 patients assessed on each of two maximum exercise tests, 64 (91 percent) were reproducible. Only 53 percent (16/30) of the ischemic defects present at maximum exercise were seen in the light exercise study in the 12 patients assessed at two levels of exercise. Correlation of perfusion defects with arteriographically proven significant coronary stenosis was good for the left anterior descending and right coronary arteries, but not as good for circumflex artery disease. Thallium-201 myocardial imaging at maximum exercise is reproducible within acceptable limits, but careful attention to exercise technique is essential for valid comparative studies

  15. Standing Together for Reproducibility in Large-Scale Computing: Report on reproducibility@XSEDE

    OpenAIRE

    James, Doug; Wilkins-Diehr, Nancy; Stodden, Victoria; Colbry, Dirk; Rosales, Carlos; Fahey, Mark; Shi, Justin; Silva, Rafael F.; Lee, Kyo; Roskies, Ralph; Loewe, Laurence; Lindsey, Susan; Kooper, Rob; Barba, Lorena; Bailey, David

    2014-01-01

    This is the final report on reproducibility@xsede, a one-day workshop held in conjunction with XSEDE14, the annual conference of the Extreme Science and Engineering Discovery Environment (XSEDE). The workshop's discussion-oriented agenda focused on reproducibility in large-scale computational research. Two important themes capture the spirit of the workshop submissions and discussions: (1) organizational stakeholders, especially supercomputer centers, are in a unique position to promote, enab...

  16. Reproducibility with the Keeler Pulsair 2000 non-contact tonometer.

    Science.gov (United States)

    Vernon, S A

    1995-06-01

    The IOP variation on repeated testing with the recently introduced Keeler Pulsair 2000 instrument was investigated. One hundred normal individuals (50 male and 50 female) new to the instrument had three sets of IOP recordings within a 15 minute time period. The mean of the first set of IOPs from both right and left eyes was significantly higher than those from subsequent sets (p < 0.0001 for right eyes and p = 0.01 and < 0.0002 for left eyes). This tendency increased significantly with increasing IOP. Second and third IOP sets were, however, similar indicating stabilisation of IOP measurements. The coefficient of repeatability of the instrument between second and third sets was 4.2 mm Hg for right eyes and 3.6 mm Hg for left eyes. The Pulsair 2000 passes the British standard for reproducibility of a standard test method.

  17. Repeatability and reproducibility of ribotyping and its computer interpretation.

    Science.gov (United States)

    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.

  18. Convergence of macrostates under reproducible processes

    International Nuclear Information System (INIS)

    Rau, Jochen

    2010-01-01

    I show that whenever a system undergoes a reproducible macroscopic process the mutual distinguishability of macrostates, as measured by their relative entropy, diminishes. This extends the second law which regards only ordinary entropies, and hence only the distinguishability between macrostates and one specific reference state (equidistribution). The new result holds regardless of whether the process is linear or nonlinear. Its proof hinges on the monotonicity of quantum relative entropy under arbitrary coarse grainings, even those that cannot be represented by trace-preserving completely positive maps.

  19. Open and reproducible global land use classification

    Science.gov (United States)

    Nüst, Daniel; Václavík, Tomáš; Pross, Benjamin

    2015-04-01

    Researchers led by the Helmholtz Centre for Environmental research (UFZ) developed a new world map of land use systems based on over 30 diverse indicators (http://geoportal.glues.geo.tu-dresden.de/stories/landsystemarchetypes.html) of land use intensity, climate and environmental and socioeconomic factors. They identified twelve land system archetypes (LSA) using a data-driven classification algorithm (self-organizing maps) to assess global impacts of land use on the environment, and found unexpected similarities across global regions. We present how the algorithm behind this analysis can be published as an executable web process using 52°North WPS4R (https://wiki.52north.org/bin/view/Geostatistics/WPS4R) within the GLUES project (http://modul-a.nachhaltiges-landmanagement.de/en/scientific-coordination-glues/). WPS4R is an open source collaboration platform for researchers, analysts and software developers to publish R scripts (http://www.r-project.org/) as a geo-enabled OGC Web Processing Service (WPS) process. The interoperable interface to call the geoprocess allows both reproducibility of the analysis and integration of user data without knowledge about web services or classification algorithms. The open platform allows everybody to replicate the analysis in their own environments. The LSA WPS process has several input parameters, which can be changed via a simple web interface. The input parameters are used to configure both the WPS environment and the LSA algorithm itself. The encapsulation as a web process allows integration of non-public datasets, while at the same time the publication requires a well-defined documentation of the analysis. We demonstrate this platform specifically to domain scientists and show how reproducibility and open source publication of analyses can be enhanced. We also discuss future extensions of the reproducible land use classification, such as the possibility for users to enter their own areas of interest to the system and

  20. Reproducibility in Research: Systems, Infrastructure, Culture

    Directory of Open Access Journals (Sweden)

    Tom Crick

    2017-11-01

    Full Text Available The reproduction and replication of research results has become a major issue for a number of scientific disciplines. In computer science and related computational disciplines such as systems biology, the challenges closely revolve around the ability to implement (and exploit novel algorithms and models. Taking a new approach from the literature and applying it to a new codebase frequently requires local knowledge missing from the published manuscripts and transient project websites. Alongside this issue, benchmarking, and the lack of open, transparent and fair benchmark sets present another barrier to the verification and validation of claimed results. In this paper, we outline several recommendations to address these issues, driven by specific examples from a range of scientific domains. Based on these recommendations, we propose a high-level prototype open automated platform for scientific software development which effectively abstracts specific dependencies from the individual researcher and their workstation, allowing easy sharing and reproduction of results. This new e-infrastructure for reproducible computational science offers the potential to incentivise a culture change and drive the adoption of new techniques to improve the quality and efficiency – and thus reproducibility – of scientific exploration.

  1. Coevolution within a transcriptional network by compensatory trans and cis mutations

    KAUST Repository

    Kuo, D.; Licon, K.; Bandyopadhyay, S.; Chuang, R.; Luo, C.; Catalana, J.; Ravasi, Timothy; Tan, K.; Ideker, T.

    2010-01-01

    Transcriptional networks have been shown to evolve very rapidly, prompting questions as to how such changes arise and are tolerated. Recent comparisons of transcriptional networks across species have implicated variations in the cis-acting DNA

  2. Transcriptional regulation by competing transcription factor modules.

    Directory of Open Access Journals (Sweden)

    Rutger Hermsen

    2006-12-01

    Full Text Available Gene regulatory networks lie at the heart of cellular computation. In these networks, intracellular and extracellular signals are integrated by transcription factors, which control the expression of transcription units by binding to cis-regulatory regions on the DNA. The designs of both eukaryotic and prokaryotic cis-regulatory regions are usually highly complex. They frequently consist of both repetitive and overlapping transcription factor binding sites. To unravel the design principles of these promoter architectures, we have designed in silico prokaryotic transcriptional logic gates with predefined input-output relations using an evolutionary algorithm. The resulting cis-regulatory designs are often composed of modules that consist of tandem arrays of binding sites to which the transcription factors bind cooperatively. Moreover, these modules often overlap with each other, leading to competition between them. Our analysis thus identifies a new signal integration motif that is based upon the interplay between intramodular cooperativity and intermodular competition. We show that this signal integration mechanism drastically enhances the capacity of cis-regulatory domains to integrate signals. Our results provide a possible explanation for the complexity of promoter architectures and could be used for the rational design of synthetic gene circuits.

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

    Science.gov (United States)

    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

  4. PSYCHOLOGY. Estimating the reproducibility of psychological science.

    Science.gov (United States)

    2015-08-28

    Reproducibility is a defining feature of science, but the extent to which it characterizes current research is unknown. We conducted replications of 100 experimental and correlational studies published in three psychology journals using high-powered designs and original materials when available. Replication effects were half the magnitude of original effects, representing a substantial decline. Ninety-seven percent of original studies had statistically significant results. Thirty-six percent of replications had statistically significant results; 47% of original effect sizes were in the 95% confidence interval of the replication effect size; 39% of effects were subjectively rated to have replicated the original result; and if no bias in original results is assumed, combining original and replication results left 68% with statistically significant effects. Correlational tests suggest that replication success was better predicted by the strength of original evidence than by characteristics of the original and replication teams. Copyright © 2015, American Association for the Advancement of Science.

  5. Reproducibility of artificial multiple scattering media

    NARCIS (Netherlands)

    Marakis, Evangelos; van Harten, Wouter; Uppu, Ravitej; Pinkse, Pepijn Willemszoon Harry

    2016-01-01

    State of the art authentication systems depend on physical unclonable functions (PUF) [1], physical keys that are assumed unclonable due to technological constraints. Random scattering media, dielectric materials with rapid and random refractive index variations, are considered as ideal optical PUFs

  6. WRKY transcription factors

    Science.gov (United States)

    Bakshi, Madhunita; Oelmüller, Ralf

    2014-01-01

    WRKY transcription factors are one of the largest families of transcriptional regulators found exclusively in plants. They have diverse biological functions in plant disease resistance, abiotic stress responses, nutrient deprivation, senescence, seed and trichome development, embryogenesis, as well as additional developmental and hormone-controlled processes. WRKYs can act as transcriptional activators or repressors, in various homo- and heterodimer combinations. Here we review recent progress on the function of WRKY transcription factors in Arabidopsis and other plant species such as rice, potato, and parsley, with a special focus on abiotic, developmental, and hormone-regulated processes. PMID:24492469

  7. Induction of neutral trehalase Nth1 by heat and osmotic stress is controlled by STRE elements and Msn2/Msn4 transcription factors: variations of PKA effect during stress and growth.

    Science.gov (United States)

    Zähringer, H; Thevelein, J M; Nwaka, S

    2000-01-01

    Saccharomyces cerevisiae neutral trehalase, encoded by NTH1, controls trehalose hydrolysis in response to multiple stress conditions, including nutrient limitation. The presence of three stress responsive elements (STREs, CCCCT) in the NTH1 promoter suggested that the transcriptional activator proteins Msn2 and Msn4, as well as the cAMP-dependent protein kinase (PKA), control the stress-induced expression of Nth1. Here, we give direct evidence that Msn2/Msn4 and the STREs control the heat-, osmotic stress- and diauxic shift-dependent induction of Nth1. Disruption of MSN2 and MSN4 abolishes or significantly reduces the heat- and NaCl-induced increases in Nth1 activity and transcription. Stress-induced increases in activity of a lacZ reporter gene put under control of the NTH1 promoter is nearly absent in the double mutant. In all instances, basal expression is also reduced by about 50%. The trehalose concentration in the msn2 msn4 double mutant increases less during heat stress and drops more slowly during recovery than in wild-type cells. This shows that Msn2/Msn4-controlled expression of enzymes of trehalose synthesis and hydrolysis help to maintain trehalose concentration during stress. However, the Msn2/Msn4-independent mechanism exists for heat control of trehalose metabolism. Site-directed mutagenesis of the three STREs (CCCCT changed to CATCT) in NTH1 promoter fused to a reporter gene indicates that the relative proximity of STREs to each other is important for the function of NTH1. Elimination of the three STREs abolishes the stress-induced responses and reduces basal expression by 30%. Contrary to most STRE-regulated genes, the PKA effect on the induction of NTH1 by heat and sodium chloride is variable. During diauxic growth, NTH1 promoter-controlled reporter activity strongly increases, as opposed to the previously observed decrease in Nth1 activity, suggesting a tight but opposite control of the enzyme at the transcriptional and post-translational levels

  8. Empirical evaluation of cross-site reproducibility in radiomic features for characterizing prostate MRI

    Science.gov (United States)

    Chirra, Prathyush; Leo, Patrick; Yim, Michael; Bloch, B. Nicolas; Rastinehad, Ardeshir R.; Purysko, Andrei; Rosen, Mark; Madabhushi, Anant; Viswanath, Satish

    2018-02-01

    The recent advent of radiomics has enabled the development of prognostic and predictive tools which use routine imaging, but a key question that still remains is how reproducible these features may be across multiple sites and scanners. This is especially relevant in the context of MRI data, where signal intensity values lack tissue specific, quantitative meaning, as well as being dependent on acquisition parameters (magnetic field strength, image resolution, type of receiver coil). In this paper we present the first empirical study of the reproducibility of 5 different radiomic feature families in a multi-site setting; specifically, for characterizing prostate MRI appearance. Our cohort comprised 147 patient T2w MRI datasets from 4 different sites, all of which were first pre-processed to correct acquisition-related for artifacts such as bias field, differing voxel resolutions, as well as intensity drift (non-standardness). 406 3D voxel wise radiomic features were extracted and evaluated in a cross-site setting to determine how reproducible they were within a relatively homogeneous non-tumor tissue region; using 2 different measures of reproducibility: Multivariate Coefficient of Variation and Instability Score. Our results demonstrated that Haralick features were most reproducible between all 4 sites. By comparison, Laws features were among the least reproducible between sites, as well as performing highly variably across their entire parameter space. Similarly, the Gabor feature family demonstrated good cross-site reproducibility, but for certain parameter combinations alone. These trends indicate that despite extensive pre-processing, only a subset of radiomic features and associated parameters may be reproducible enough for use within radiomics-based machine learning classifier schemes.

  9. Navicular bone position determined by positional MRI: a reproducibility study

    Energy Technology Data Exchange (ETDEWEB)

    Hansen, Philip; Nybing, Janus D. [Copenhagen University Hospital Frederiksberg and Bispebjerg, Department of Radiology, Frederiksberg (Denmark); Johannsen, Finn E.; Stallknecht, Sandra E. [Copenhagen University Hospital Bispebjerg, Institute of Sports Medicine Copenhagen, Copenhagen, NV (Denmark); Hangaard, Stine; Hansen, Bjarke B. [Copenhagen University Hospital Frederiksberg, Parker Institute, Department of Rheumatology, Frederiksberg (Denmark); Boesen, Mikael [Copenhagen University Hospital Frederiksberg and Bispebjerg, Department of Radiology, Frederiksberg (Denmark); Copenhagen University Hospital Frederiksberg, Parker Institute, Department of Rheumatology, Frederiksberg (Denmark)

    2016-02-15

    To examine intraobserver, interobserver and between-day reproducibility of positional MRI for evaluation of navicular bone height (NVH) and medial navicular position (MNP). Positional MRI (pMRI) of the foot was performed on ten healthy participants (0.25 T G-scanner). Scanning was performed in supine and standing position, respectively. Two radiologists evaluated the images in a blinded manner. Reliability and agreement were assessed by calculation of intraclass correlation coefficient (ICC) and 95 % limits of agreement as a percentage of the mean (LOA%). Intraobserver and interobserver reliability was ''substantial'' in both supine and standing position (ICC 0.86-0.98) and showed good agreement (LOA% 4.9-14.7 %). Between-day reliability of navicular height and medial navicular position in standing position remained substantial (ICC 0.85-0.92) with adequate agreement (LOA% 8.3-19.8 %). In supine position between-day reliability was ''moderate'' for NVH (ICC 0.72) and ''slight'' for MNP (ICC 0.39). Agreement remained adequate between-days for MNP in supine position (LOA% 17.7 %), but it was less than adequate for NVH in supine position (LOA% 24.2 %). Navicular height and medial navicular position can be measured by pMRI in a very reproducible manner within and between observers. Increased measurement variation is observed between-days in supine position, which may be due to small positional differences or other unknown biomechanical factors. (orig.)

  10. Navicular bone position determined by positional MRI: a reproducibility study

    International Nuclear Information System (INIS)

    Hansen, Philip; Nybing, Janus D.; Johannsen, Finn E.; Stallknecht, Sandra E.; Hangaard, Stine; Hansen, Bjarke B.; Boesen, Mikael

    2016-01-01

    To examine intraobserver, interobserver and between-day reproducibility of positional MRI for evaluation of navicular bone height (NVH) and medial navicular position (MNP). Positional MRI (pMRI) of the foot was performed on ten healthy participants (0.25 T G-scanner). Scanning was performed in supine and standing position, respectively. Two radiologists evaluated the images in a blinded manner. Reliability and agreement were assessed by calculation of intraclass correlation coefficient (ICC) and 95 % limits of agreement as a percentage of the mean (LOA%). Intraobserver and interobserver reliability was ''substantial'' in both supine and standing position (ICC 0.86-0.98) and showed good agreement (LOA% 4.9-14.7 %). Between-day reliability of navicular height and medial navicular position in standing position remained substantial (ICC 0.85-0.92) with adequate agreement (LOA% 8.3-19.8 %). In supine position between-day reliability was ''moderate'' for NVH (ICC 0.72) and ''slight'' for MNP (ICC 0.39). Agreement remained adequate between-days for MNP in supine position (LOA% 17.7 %), but it was less than adequate for NVH in supine position (LOA% 24.2 %). Navicular height and medial navicular position can be measured by pMRI in a very reproducible manner within and between observers. Increased measurement variation is observed between-days in supine position, which may be due to small positional differences or other unknown biomechanical factors. (orig.)

  11. Reproducibility of neuroimaging analyses across operating systems.

    Science.gov (United States)

    Glatard, Tristan; Lewis, Lindsay B; Ferreira da Silva, Rafael; Adalat, Reza; Beck, Natacha; Lepage, Claude; Rioux, Pierre; Rousseau, Marc-Etienne; Sherif, Tarek; Deelman, Ewa; Khalili-Mahani, Najmeh; Evans, Alan C

    2015-01-01

    Neuroimaging pipelines are known to generate different results depending on the computing platform where they are compiled and executed. We quantify these differences for brain tissue classification, fMRI analysis, and cortical thickness (CT) extraction, using three of the main neuroimaging packages (FSL, Freesurfer and CIVET) and different versions of GNU/Linux. We also identify some causes of these differences using library and system call interception. We find that these packages use mathematical functions based on single-precision floating-point arithmetic whose implementations in operating systems continue to evolve. While these differences have little or no impact on simple analysis pipelines such as brain extraction and cortical tissue classification, their accumulation creates important differences in longer pipelines such as subcortical tissue classification, fMRI analysis, and cortical thickness extraction. With FSL, most Dice coefficients between subcortical classifications obtained on different operating systems remain above 0.9, but values as low as 0.59 are observed. Independent component analyses (ICA) of fMRI data differ between operating systems in one third of the tested subjects, due to differences in motion correction. With Freesurfer and CIVET, in some brain regions we find an effect of build or operating system on cortical thickness. A first step to correct these reproducibility issues would be to use more precise representations of floating-point numbers in the critical sections of the pipelines. The numerical stability of pipelines should also be reviewed.

  12. Environment and industrial economy: Challenge of reproducibility

    International Nuclear Information System (INIS)

    Rullani, E.

    1992-01-01

    Historically and methodologically counterposed until now, the environmentalist and the economic approach to environmental problems need to be integrated in a new approach that considers, from one side, the relevance of the ecological equilibria for the economic systems and, from the other side, the economic dimension (in terms of investments and transformations in the production system) of any attempt to achieve a better environment. In order to achieve this integration, both approaches are compelled to give up some cultural habits that have characterized them, and have contributed to over-emphasize the opposition between them. The article shows that both approaches can converge into a new one, in which environment is no longer only an holistic, not bargainable, natural external limit to human activity (as in the environmentalist approach), nor simply a scarce and exhaustible resource (as economics tends to consider it); environment should instead become part of the reproducibility sphere, or, in other words, it must be regarded as part of the output that the economic system provides. This new approach, due to scientific and technological advances, is made possible for an increasing class of environmental problems. In order to do this, an evolution is required, that could be able to convert environmental goals into investment and technological innovation goals, and communicate to the firms the value society assigns to environmental resources. This value, the author suggests, should correspond to the reproduction cost. Various examples of this new approach are analyzed and discussed

  13. NetBenchmark: a bioconductor package for reproducible benchmarks of gene regulatory network inference.

    Science.gov (United States)

    Bellot, Pau; Olsen, Catharina; Salembier, Philippe; Oliveras-Vergés, Albert; Meyer, Patrick E

    2015-09-29

    In the last decade, a great number of methods for reconstructing gene regulatory networks from expression data have been proposed. However, very few tools and datasets allow to evaluate accurately and reproducibly those methods. Hence, we propose here a new tool, able to perform a systematic, yet fully reproducible, evaluation of transcriptional network inference methods. Our open-source and freely available Bioconductor package aggregates a large set of tools to assess the robustness of network inference algorithms against different simulators, topologies, sample sizes and noise intensities. The benchmarking framework that uses various datasets highlights the specialization of some methods toward network types and data. As a result, it is possible to identify the techniques that have broad overall performances.

  14. Liquid scintigraphic gastric emptying - is it reproducible?

    International Nuclear Information System (INIS)

    Cooper, R.G.; Shuter, B.; Leach, M.; Roach, P.J.

    1999-01-01

    Full text: Radioisotope gastric emptying (GE) studies have been used as a non-invasive technique for motility assessment for many years. In a recent study investigating the correlation of mesenteric vascular changes with GE, six subjects had a repeat study 2-4 months later. Repeat studies were required due to minor technical problems (5 subjects) and a very slow GE (I subject) on the original study. Subjects drank 275 ml of 'Ensure Plus' mixed with 8 MBq 67 Ga-DTPA and were imaged for 2 h while lying supine. GE time-activity curves for each subject were generated and time to half emptying (T l/2 ) calculated. Five of the six subjects had more rapid GE on the second study. Three of the subjects had T l/2 values on their second study which were within ± 15 min of their original T l/2 . The other three subjects had T l/2 values on their second study which were 36 min, 55 min and 280 min (subject K.H.) less than their original T l/2 . Statistical analysis (t-test) was performed on paired T l/2 values. The average T l/2 value was greater in the first study than in the second (149 ± 121 and 86 ± 18 min respectively), although the difference was not statistically significant (P ∼ 0.1). Subjects' anxiety levels were not quantitated during the GE study; however, several major equipment faults occurred during the original study of subject K.H., who became visibly stressed. These results suggest that the reproducibility of GE studies may be influenced by psychological factors

  15. Is my network module preserved and reproducible?

    Directory of Open Access Journals (Sweden)

    Peter Langfelder

    2011-01-01

    Full Text Available In many applications, one is interested in determining which of the properties of a network module change across conditions. For example, to validate the existence of a module, it is desirable to show that it is reproducible (or preserved in an independent test network. Here we study several types of network preservation statistics that do not require a module assignment in the test network. We distinguish network preservation statistics by the type of the underlying network. Some preservation statistics are defined for a general network (defined by an adjacency matrix while others are only defined for a correlation network (constructed on the basis of pairwise correlations between numeric variables. Our applications show that the correlation structure facilitates the definition of particularly powerful module preservation statistics. We illustrate that evaluating module preservation is in general different from evaluating cluster preservation. We find that it is advantageous to aggregate multiple preservation statistics into summary preservation statistics. We illustrate the use of these methods in six gene co-expression network applications including 1 preservation of cholesterol biosynthesis pathway in mouse tissues, 2 comparison of human and chimpanzee brain networks, 3 preservation of selected KEGG pathways between human and chimpanzee brain networks, 4 sex differences in human cortical networks, 5 sex differences in mouse liver networks. While we find no evidence for sex specific modules in human cortical networks, we find that several human cortical modules are less preserved in chimpanzees. In particular, apoptosis genes are differentially co-expressed between humans and chimpanzees. Our simulation studies and applications show that module preservation statistics are useful for studying differences between the modular structure of networks. Data, R software and accompanying tutorials can be downloaded from the following webpage: http

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

    Science.gov (United States)

    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.

  17. Reproducibility of an aerobic endurance test for nonexpert swimmers

    Directory of Open Access Journals (Sweden)

    Veronese da Costa A

    2012-09-01

    Full Text Available Adalberto Veronese da Costa,1,2 Manoel da Cunha Costa,3 Daniel Medeiros Carlos,1 Luis Marcos de Medeiros Guerra,1,2 Antônio José Silva,2 Tiago Manoel Cabral dos Santos Barbosa2,41Department of Physical Education, Bioscience Laboratory of Human Kinetics, Rio Grande do Norte State University, Mossoró, Brazil; 2Sport Sciences Trás-os-Montes e Alto Douro University, Research Center in Sport, Health and Human Development, Vila Real, Portugal; 3Superior School of Physical Education, Human Performance Laboratory, Pernambuco State University, Recife, Brazil; 4National Institute of Education, Nanyang Technological University, SingaporeBackground: This study aimed to verify the reproduction of an aerobic test to determine nonexpert swimmers' resistance.Methods: The sample consisted of 24 male swimmers (age: 22.79 ± 3.90 years; weight: 74.72 ± 11.44 kg; height: 172.58 ± 4.99 cm; and fat percentage: 15.19% ± 3.21%, who swim for 1 hour three times a week. A new instrument was used in this study (a Progressive Swim Test: the swimmer wore an underwater MP3 player and increased their swimming speed on hearing a beep after every 25 meters. Each swimmer's heart rate was recorded before the test (BHR and again after the test (AHR. The rate of perceived exertion (RPE and the number of laps performed (NLP were also recorded. The sample size was estimated using G*Power software (v 3.0.10; Franz Faul, Kiel University, Kiel, Germany. The descriptive values were expressed as mean and standard deviation. After confirming the normality of the data using both the Shapiro–Wilk and Levene tests, a paired t-test was performed to compare the data. The Pearson's linear correlation (r and intraclass coefficient correlation (ICC tests were used to determine relative reproducibility. The standard error of measurement (SEM and the coefficient of variation (CV were used to determine absolute reproducibility. The limits of agreement and the bias of the absolute and relative

  18. High Reproducibility of ELISPOT Counts from Nine Different Laboratories

    Directory of Open Access Journals (Sweden)

    Srividya Sundararaman

    2015-01-01

    Full Text Available The primary goal of immune monitoring with ELISPOT is to measure the number of T cells, specific for any antigen, accurately and reproducibly between different laboratories. In ELISPOT assays, antigen-specific T cells secrete cytokines, forming spots of different sizes on a membrane with variable background intensities. Due to the subjective nature of judging maximal and minimal spot sizes, different investigators come up with different numbers. This study aims to determine whether statistics-based, automated size-gating can harmonize the number of spot counts calculated between different laboratories. We plated PBMC at four different concentrations, 24 replicates each, in an IFN-γ ELISPOT assay with HCMV pp65 antigen. The ELISPOT plate, and an image file of the plate was counted in nine different laboratories using ImmunoSpot® Analyzers by (A Basic Count™ relying on subjective counting parameters set by the respective investigators and (B SmartCount™, an automated counting protocol by the ImmunoSpot® Software that uses statistics-based spot size auto-gating with spot intensity auto-thresholding. The average coefficient of variation (CV for the mean values between independent laboratories was 26.7% when counting with Basic Count™, and 6.7% when counting with SmartCount™. Our data indicates that SmartCount™ allows harmonization of counting ELISPOT results between different laboratories and investigators.

  19. Precision and reproducibility in AMS radiocarbon measurements.

    Energy Technology Data Exchange (ETDEWEB)

    Hotchkis, M A; Fink, D; Hua, Q; Jacobsen, G E; Lawson, E M; Smith, A M; Tuniz, C [Australian Nuclear Science and Technology Organisation, Lucas Heights, NSW (Australia)

    1997-12-31

    Accelerator Mass Spectrometry (AMS) is a technique by which rare radioisotopes such as {sup 14}C can be measured at environmental levels with high efficiency. Instead of detecting radioactivity, which is very weak for long-lived environmental radioisotopes, atoms are counted directly. The sample is placed in an ion source, from which a negative ion beam of the atoms of interest is extracted, mass analysed, and injected into a tandem accelerator. After stripping to positive charge states in the accelerator HV terminal, the ions are further accelerated, analysed with magnetic and electrostatic devices and counted in a detector. An isotopic ratio is derived from the number of radioisotope atoms counted in a given time and the beam current of a stable isotope of the same element, measured after the accelerator. For radiocarbon, {sup 14}C/{sup 13}C ratios are usually measured, and the ratio of an unknown sample is compared to that of a standard. The achievable precision for such ratio measurements is limited primarily by {sup 14}C counting statistics and also by a variety of factors related to accelerator and ion source stability. At the ANTARES AMS facility at Lucas Heights Research Laboratories we are currently able to measure {sup 14}C with 0.5% precision. In the two years since becoming operational, more than 1000 {sup 14}C samples have been measured. Recent improvements in precision for {sup 14}C have been achieved with the commissioning of a 59 sample ion source. The measurement system, from sample changing to data acquisition, is under common computer control. These developments have allowed a new regime of automated multi-sample processing which has impacted both on the system throughput and the measurement precision. We have developed data evaluation methods at ANTARES which cross-check the self-consistency of the statistical analysis of our data. Rigorous data evaluation is invaluable in assessing the true reproducibility of the measurement system and aids in

  20. Precision and reproducibility in AMS radiocarbon measurements.

    Energy Technology Data Exchange (ETDEWEB)

    Hotchkis, M.A.; Fink, D.; Hua, Q.; Jacobsen, G.E.; Lawson, E. M.; Smith, A.M.; Tuniz, C. [Australian Nuclear Science and Technology Organisation, Lucas Heights, NSW (Australia)

    1996-12-31

    Accelerator Mass Spectrometry (AMS) is a technique by which rare radioisotopes such as {sup 14}C can be measured at environmental levels with high efficiency. Instead of detecting radioactivity, which is very weak for long-lived environmental radioisotopes, atoms are counted directly. The sample is placed in an ion source, from which a negative ion beam of the atoms of interest is extracted, mass analysed, and injected into a tandem accelerator. After stripping to positive charge states in the accelerator HV terminal, the ions are further accelerated, analysed with magnetic and electrostatic devices and counted in a detector. An isotopic ratio is derived from the number of radioisotope atoms counted in a given time and the beam current of a stable isotope of the same element, measured after the accelerator. For radiocarbon, {sup 14}C/{sup 13}C ratios are usually measured, and the ratio of an unknown sample is compared to that of a standard. The achievable precision for such ratio measurements is limited primarily by {sup 14}C counting statistics and also by a variety of factors related to accelerator and ion source stability. At the ANTARES AMS facility at Lucas Heights Research Laboratories we are currently able to measure {sup 14}C with 0.5% precision. In the two years since becoming operational, more than 1000 {sup 14}C samples have been measured. Recent improvements in precision for {sup 14}C have been achieved with the commissioning of a 59 sample ion source. The measurement system, from sample changing to data acquisition, is under common computer control. These developments have allowed a new regime of automated multi-sample processing which has impacted both on the system throughput and the measurement precision. We have developed data evaluation methods at ANTARES which cross-check the self-consistency of the statistical analysis of our data. Rigorous data evaluation is invaluable in assessing the true reproducibility of the measurement system and aids in

  1. Parameter optimization for reproducible cardiac 1 H-MR spectroscopy at 3 Tesla.

    Science.gov (United States)

    de Heer, Paul; Bizino, Maurice B; Lamb, Hildo J; Webb, Andrew G

    2016-11-01

    To optimize data acquisition parameters in cardiac proton MR spectroscopy, and to evaluate the intra- and intersession variability in myocardial triglyceride content. Data acquisition parameters at 3 Tesla (T) were optimized and reproducibility measured using, in total, 49 healthy subjects. The signal-to-noise-ratio (SNR) and the variance in metabolite amplitude between averages were measured for: (i) global versus local power optimization; (ii) static magnetic field (B 0 ) shimming performed during free-breathing or within breathholds; (iii) post R-wave peak measurement times between 50 and 900 ms; (iv) without respiratory compensation, with breathholds and with navigator triggering; and (v) frequency selective excitation, Chemical Shift Selective (CHESS) and Multiply Optimized Insensitive Suppression Train (MOIST) water suppression techniques. Using the optimized parameters intra- and intersession myocardial triglyceride content reproducibility was measured. Two cardiac proton spectra were acquired with the same parameters and compared (intrasession reproducibility) after which the subject was removed from the scanner and placed back in the scanner and a third spectrum was acquired which was compared with the first measurement (intersession reproducibility). Local power optimization increased SNR on average by 22% compared with global power optimization (P = 0.0002). The average linewidth was not significantly different for pencil beam B 0 shimming using free-breathing or breathholds (19.1 Hz versus 17.5 Hz; P = 0.15). The highest signal stability occurred at a cardiac trigger delay around 240 ms. The mean amplitude variation was significantly lower for breathholds versus free-breathing (P = 0.03) and for navigator triggering versus free-breathing (P = 0.03) as well as for navigator triggering versus breathhold (P = 0.02). The mean residual water signal using CHESS (1.1%, P = 0.01) or MOIST (0.7%, P = 0.01) water suppression was significantly lower than using

  2. Reproducibility of non-invasive assessment of skin endothelial function using laser Doppler flowmetry and laser speckle contrast imaging.

    Directory of Open Access Journals (Sweden)

    Cyril Puissant

    Full Text Available Endothelial dysfunction precedes atherosclerosis. Vasodilation induced by acetylcholine (ACh is a specific test of endothelial function. Reproducibility of laser techniques such as laser-Doppler-flowmetry (LDF and Laser-speckle-contrast-imaging (LSCI to detect ACh vasodilation is debated and results expressions lack standardization. We aimed to study at a 7-day interval (i the inter-subject reproducibility, (ii the intra-subjects reproducibility, and (iii the effect of the results expressions over variability.Using LDF and LSCI simultaneously, we performed two different ACh-iontophoresis protocols. The maximal ACh vasodilation (peak-ACh was expressed as absolute or normalized flow or conductance values. Inter-subject reproducibility was expressed as coefficient of variation (inter-CV,%. Intra-subject reproducibility was expressed as within subject coefficients of variation (intra-CV,%, and intra-class correlation coefficients (ICC. Fifteen healthy subjects were included. The inter-subject reproducibility of peak-ACh depended upon the expression of the results and ranged from 55% to 162% for LDF and from 17% to 83% for LSCI. The intra-subject reproducibility (intra-CV/ICC of peak-ACh was reduced when assessed with LSCI compared to LDF no matter how the results were expressed and whatever the protocol used. The highest intra-subject reproducibility was found using LSCI. It was 18.7%/0.87 for a single current stimulation (expressed as cutaneous vascular conductance and 11.4%/0.61 for multiple current stimulations (expressed as absolute value.ACh-iontophoresis coupled with LSCI is a promising test to assess endothelial function because it is reproducible, safe, and non-invasive. N°: NCT01664572.

  3. Guidelines for Reproducibly Building and Simulating Systems Biology Models.

    Science.gov (United States)

    Medley, J Kyle; Goldberg, Arthur P; Karr, Jonathan R

    2016-10-01

    Reproducibility is the cornerstone of the scientific method. However, currently, many systems biology models cannot easily be reproduced. This paper presents methods that address this problem. We analyzed the recent Mycoplasma genitalium whole-cell (WC) model to determine the requirements for reproducible modeling. We determined that reproducible modeling requires both repeatable model building and repeatable simulation. New standards and simulation software tools are needed to enhance and verify the reproducibility of modeling. New standards are needed to explicitly document every data source and assumption, and new deterministic parallel simulation tools are needed to quickly simulate large, complex models. We anticipate that these new standards and software will enable researchers to reproducibly build and simulate more complex models, including WC models.

  4. Towards reproducible descriptions of neuronal network models.

    Directory of Open Access Journals (Sweden)

    Eilen Nordlie

    2009-08-01

    Full Text Available Progress in science depends on the effective exchange of ideas among scientists. New ideas can be assessed and criticized in a meaningful manner only if they are formulated precisely. This applies to simulation studies as well as to experiments and theories. But after more than 50 years of neuronal network simulations, we still lack a clear and common understanding of the role of computational models in neuroscience as well as established practices for describing network models in publications. This hinders the critical evaluation of network models as well as their re-use. We analyze here 14 research papers proposing neuronal network models of different complexity and find widely varying approaches to model descriptions, with regard to both the means of description and the ordering and placement of material. We further observe great variation in the graphical representation of networks and the notation used in equations. Based on our observations, we propose a good model description practice, composed of guidelines for the organization of publications, a checklist for model descriptions, templates for tables presenting model structure, and guidelines for diagrams of networks. The main purpose of this good practice is to trigger a debate about the communication of neuronal network models in a manner comprehensible to humans, as opposed to machine-readable model description languages. We believe that the good model description practice proposed here, together with a number of other recent initiatives on data-, model-, and software-sharing, may lead to a deeper and more fruitful exchange of ideas among computational neuroscientists in years to come. We further hope that work on standardized ways of describing--and thinking about--complex neuronal networks will lead the scientific community to a clearer understanding of high-level concepts in network dynamics, and will thus lead to deeper insights into the function of the brain.

  5. Participant Nonnaiveté and the reproducibility of cognitive psychology.

    Science.gov (United States)

    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.

  6. Transcription and chromatin determinants of de novo DNA methylation timing in oocytes.

    Science.gov (United States)

    Gahurova, Lenka; Tomizawa, Shin-Ichi; Smallwood, Sébastien A; Stewart-Morgan, Kathleen R; Saadeh, Heba; Kim, Jeesun; Andrews, Simon R; Chen, Taiping; Kelsey, Gavin

    2017-01-01

    Gametogenesis in mammals entails profound re-patterning of the epigenome. In the female germline, DNA methylation is acquired late in oogenesis from an essentially unmethylated baseline and is established largely as a consequence of transcription events. Molecular and functional studies have shown that imprinted genes become methylated at different times during oocyte growth; however, little is known about the kinetics of methylation gain genome wide and the reasons for asynchrony in methylation at imprinted loci. Given the predominant role of transcription, we sought to investigate whether transcription timing is rate limiting for de novo methylation and determines the asynchrony of methylation events. Therefore, we generated genome-wide methylation and transcriptome maps of size-selected, growing oocytes to capture the onset and progression of methylation. We find that most sequence elements, including most classes of transposable elements, acquire methylation at similar rates overall. However, methylation of CpG islands (CGIs) is delayed compared with the genome average and there are reproducible differences amongst CGIs in onset of methylation. Although more highly transcribed genes acquire methylation earlier, the major transitions in the oocyte transcriptome occur well before the de novo methylation phase, indicating that transcription is generally not rate limiting in conferring permissiveness to DNA methylation. Instead, CGI methylation timing negatively correlates with enrichment for histone 3 lysine 4 (H3K4) methylation and dependence on the H3K4 demethylases KDM1A and KDM1B, implicating chromatin remodelling as a major determinant of methylation timing. We also identified differential enrichment of transcription factor binding motifs in CGIs acquiring methylation early or late in oocyte growth. By combining these parameters into multiple regression models, we were able to account for about a fifth of the variation in methylation timing of CGIs. Finally

  7. Longitudinal in vivo reproducibility of cartilage volume and surface in osteoarthritis of the knee

    Energy Technology Data Exchange (ETDEWEB)

    Brem, M.H. [Harvard Medical School, Brigham and Women' s Hospital, Musculoskeletal Division, Department of Radiology, ASB-1, L-1, Room 003E, Boston, MA (United States); University of Erlangen-Nuremberg, Division of Trauma Surgery and Orthopaedic Surgery, Department of Surgery, Erlangen (Germany); Pauser, J.; Yoshioka, H.; Stratmann, J.; Kikinis, R.; Duryea, J.; Lang, P. [Harvard Medical School, Brigham and Women' s Hospital, Musculoskeletal Division, Department of Radiology, ASB-1, L-1, Room 003E, Boston, MA (United States); Brenning, A. [University of Erlangen-Nuremberg, Department of Medical Informatics, Biometry and Epidemiology, Erlangen (Germany); Hennig, F.F. [University of Erlangen-Nuremberg, Division of Trauma Surgery and Orthopaedic Surgery, Department of Surgery, Erlangen (Germany); Winalski, C.S. [Harvard Medical School, Brigham and Women' s Hospital, Musculoskeletal Division, Department of Radiology, ASB-1, L-1, Room 003E, Boston, MA (United States); Cleveland Clinic Foundation, Division of Radiology, Cleveland, OH (United States)

    2007-04-15

    The aim of this study was to evaluate the longitudinal reproducibility of cartilage volume and surface area measurements in moderate osteoarthritis (OA) of the knee. We analysed 5 MRI (GE 1.5T, sagittal 3D SPGR) data sets of patients with osteoarthritis (OA) of the knee (Kellgren Lawrence grade I-II). Two scans were performed: one baseline scan and one follow-up scan 3 months later (96 {+-} 10 days). For segmentation, 3D Slicer 2.5 software was used. Two segmentations were performed by two readers independently who were blinded to the scan dates. Tibial and femoral cartilage volume and surface were determined. Longitudinal and cross-sectional precision errors were calculated using the standard deviation (SD) and coefficient of variation (CV%=100 x [SD/mean]) from the repeated measurements in each patient. The in vivo reproducibility was then calculated as the root mean square of these individual reproducibility errors. The cross-sectional root mean squared coefficient of variation (RMSE-CV) was 1.2, 2.2 and 2.4% for surface area measurements (femur, medial and lateral tibia respectively) and 1.4, 1.8 and 1.3% for the corresponding cartilage volumes. Longitudinal RMSE-CV was 3.3, 3.1 and 3.7% for the surface area measurements (femur, medial and lateral tibia respectively) and 2.3, 3.3 and 2.4% for femur, medial and lateral tibia cartilage volumes. The longitudinal in vivo reproducibility of cartilage surface and volume measurements in the knee using this segmentation method is excellent. To the best of our knowledge we measured, for the first time, the longitudinal reproducibility of cartilage volume and surface area in participants with mild to moderate OA. (orig.)

  8. Longitudinal in vivo reproducibility of cartilage volume and surface in osteoarthritis of the knee

    International Nuclear Information System (INIS)

    Brem, M.H.; Pauser, J.; Yoshioka, H.; Stratmann, J.; Kikinis, R.; Duryea, J.; Lang, P.; Brenning, A.; Hennig, F.F.; Winalski, C.S.

    2007-01-01

    The aim of this study was to evaluate the longitudinal reproducibility of cartilage volume and surface area measurements in moderate osteoarthritis (OA) of the knee. We analysed 5 MRI (GE 1.5T, sagittal 3D SPGR) data sets of patients with osteoarthritis (OA) of the knee (Kellgren Lawrence grade I-II). Two scans were performed: one baseline scan and one follow-up scan 3 months later (96 ± 10 days). For segmentation, 3D Slicer 2.5 software was used. Two segmentations were performed by two readers independently who were blinded to the scan dates. Tibial and femoral cartilage volume and surface were determined. Longitudinal and cross-sectional precision errors were calculated using the standard deviation (SD) and coefficient of variation (CV%=100 x [SD/mean]) from the repeated measurements in each patient. The in vivo reproducibility was then calculated as the root mean square of these individual reproducibility errors. The cross-sectional root mean squared coefficient of variation (RMSE-CV) was 1.2, 2.2 and 2.4% for surface area measurements (femur, medial and lateral tibia respectively) and 1.4, 1.8 and 1.3% for the corresponding cartilage volumes. Longitudinal RMSE-CV was 3.3, 3.1 and 3.7% for the surface area measurements (femur, medial and lateral tibia respectively) and 2.3, 3.3 and 2.4% for femur, medial and lateral tibia cartilage volumes. The longitudinal in vivo reproducibility of cartilage surface and volume measurements in the knee using this segmentation method is excellent. To the best of our knowledge we measured, for the first time, the longitudinal reproducibility of cartilage volume and surface area in participants with mild to moderate OA. (orig.)

  9. Dynamic analysis of stochastic transcription cycles.

    Directory of Open Access Journals (Sweden)

    Claire V Harper

    2011-04-01

    Full Text Available In individual mammalian cells the expression of some genes such as prolactin is highly variable over time and has been suggested to occur in stochastic pulses. To investigate the origins of this behavior and to understand its functional relevance, we quantitatively analyzed this variability using new mathematical tools that allowed us to reconstruct dynamic transcription rates of different reporter genes controlled by identical promoters in the same living cell. Quantitative microscopic analysis of two reporter genes, firefly luciferase and destabilized EGFP, was used to analyze the dynamics of prolactin promoter-directed gene expression in living individual clonal and primary pituitary cells over periods of up to 25 h. We quantified the time-dependence and cyclicity of the transcription pulses and estimated the length and variation of active and inactive transcription phases. We showed an average cycle period of approximately 11 h and demonstrated that while the measured time distribution of active phases agreed with commonly accepted models of transcription, the inactive phases were differently distributed and showed strong memory, with a refractory period of transcriptional inactivation close to 3 h. Cycles in transcription occurred at two distinct prolactin-promoter controlled reporter genes in the same individual clonal or primary cells. However, the timing of the cycles was independent and out-of-phase. For the first time, we have analyzed transcription dynamics from two equivalent loci in real-time in single cells. In unstimulated conditions, cells showed independent transcription dynamics at each locus. A key result from these analyses was the evidence for a minimum refractory period in the inactive-phase of transcription. The response to acute signals and the result of manipulation of histone acetylation was consistent with the hypothesis that this refractory period corresponded to a phase of chromatin remodeling which significantly

  10. The Transcription Factor Encyclopedia

    DEFF Research Database (Denmark)

    Yusuf, Dimas; Butland, Stefanie L; Swanson, Magdalena I

    2012-01-01

    mini review articles on pertinent human, mouse and rat TFs. Notable features of the TFe website include a high-quality PDF generator and web API for programmatic data retrieval. TFe aims to rapidly educate scientists about the TFs they encounter through the delivery of succinct summaries written......ABSTRACT: Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini review articles on transcription factors (TFs) that is founded on the principles of open access and collaboration. Our consortium of over 100 researchers has collectively contributed over 130...

  11. A Transcription and Translation Protocol for Sensitive Cross-Cultural Team Research.

    Science.gov (United States)

    Clark, Lauren; Birkhead, Ana Sanchez; Fernandez, Cecilia; Egger, Marlene J

    2017-10-01

    Assurance of transcript accuracy and quality in interview-based qualitative research is foundational for data accuracy and study validity. Based on our experience in a cross-cultural ethnographic study of women's pelvic organ prolapse, we provide practical guidance to set up step-by-step interview transcription and translation protocols for team-based research on sensitive topics. Beginning with team decisions about level of detail in transcription, completeness, and accuracy, we operationalize the process of securing vendors to deliver the required quality of transcription and translation. We also share rubrics for assessing transcript quality and the team protocol for managing transcripts (assuring consistency of format, insertion of metadata, anonymization, and file labeling conventions) and procuring an acceptable initial translation of Spanish-language interviews. Accurate, complete, and systematically constructed transcripts in both source and target languages respond to the call for more transparency and reproducibility of scientific methods.

  12. Reproducible diagnosis of Chronic Lymphocytic Leukemia by flow cytometry

    DEFF Research Database (Denmark)

    Rawstron, Andy C; Kreuzer, Karl-Anton; Soosapilla, Asha

    2018-01-01

    The diagnostic criteria for CLL rely on morphology and immunophenotype. Current approaches have limitations affecting reproducibility and there is no consensus on the role of new markers. The aim of this project was to identify reproducible criteria and consensus on markers recommended for the di...

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

    Science.gov (United States)

    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.

  14. Participant Nonnaiveté and the reproducibility of cognitive psychology

    NARCIS (Netherlands)

    R.A. Zwaan (Rolf); D. Pecher (Diane); G. Paolacci (Gabriele); S. Bouwmeester (Samantha); P.P.J.L. Verkoeijen (Peter); K. Dijkstra (Katinka); R. Zeelenberg (René)

    2017-01-01

    textabstractMany 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

  15. Reproducing Kernels and Coherent States on Julia Sets

    Energy Technology Data Exchange (ETDEWEB)

    Thirulogasanthar, K., E-mail: santhar@cs.concordia.ca; Krzyzak, A. [Concordia University, Department of Computer Science and Software Engineering (Canada)], E-mail: krzyzak@cs.concordia.ca; Honnouvo, G. [Concordia University, Department of Mathematics and Statistics (Canada)], E-mail: g_honnouvo@yahoo.fr

    2007-11-15

    We construct classes of coherent states on domains arising from dynamical systems. An orthonormal family of vectors associated to the generating transformation of a Julia set is found as a family of square integrable vectors, and, thereby, reproducing kernels and reproducing kernel Hilbert spaces are associated to Julia sets. We also present analogous results on domains arising from iterated function systems.

  16. Reproducing Kernels and Coherent States on Julia Sets

    International Nuclear Information System (INIS)

    Thirulogasanthar, K.; Krzyzak, A.; Honnouvo, G.

    2007-01-01

    We construct classes of coherent states on domains arising from dynamical systems. An orthonormal family of vectors associated to the generating transformation of a Julia set is found as a family of square integrable vectors, and, thereby, reproducing kernels and reproducing kernel Hilbert spaces are associated to Julia sets. We also present analogous results on domains arising from iterated function systems

  17. Completely reproducible description of digital sound data with cellular automata

    International Nuclear Information System (INIS)

    Wada, Masato; Kuroiwa, Jousuke; Nara, Shigetoshi

    2002-01-01

    A novel method of compressive and completely reproducible description of digital sound data by means of rule dynamics of CA (cellular automata) is proposed. The digital data of spoken words and music recorded with the standard format of a compact disk are reproduced completely by this method with use of only two rules in a one-dimensional CA without loss of information

  18. Basal transcription machinery

    Indian Academy of Sciences (India)

    2007-03-29

    Mar 29, 2007 ... The holoenzyme of prokaryotic RNA polymerase consists of the core enzyme, made of two , , ' and subunits, which lacks promoter selectivity and a sigma () subunit which enables the core enzyme to initiate transcription in a promoter dependent fashion. A stress sigma factor s, in prokaryotes ...

  19. Machine Dictation and Transcription.

    Science.gov (United States)

    Harvey, Evelyn; And Others

    This instructional package contains both an instructor's manual and a student's manual for a course in machine dictation and transcription. The instructor's manual contains an overview with tips on teaching the course, letters for dictation, and a key to the letters. The student's manual contains an overview of the course and of the skills needed…

  20. Transcriptional Regulation in Haematopoiesis:

    DEFF Research Database (Denmark)

    Lauridsen, Felicia K B

    with the capacity to both self-renew and differentiate. This thesis is built upon two studies, which investigate two different aspects of the haematopoietic system; heterogeneity within the HSC compartment (presented in manuscript I), and the interplay between transcription factors controlling granulocyte/ monocyte...

  1. The reproducibility of 31-phosphorus MRS measures of muscle energetics at 3 Tesla in trained men.

    Directory of Open Access Journals (Sweden)

    Lindsay M Edwards

    Full Text Available OBJECTIVE: Magnetic resonance spectroscopy (MRS provides an exceptional opportunity for the study of in vivo metabolism. MRS is widely used to measure phosphorus metabolites in trained muscle, although there are no published data regarding its reproducibility in this specialized cohort. Thus, the aim of this study was to assess the reproducibility of (31P-MRS in trained skeletal muscle. METHODS: We recruited fifteen trained men (VO(2peak = 4.7±0.8 L min(-1/58±8 mL kg(-1 min(-1 and performed duplicate MR experiments during plantar flexion exercise, three weeks apart. RESULTS: Measures of resting phosphorus metabolites were reproducible, with 1.7 mM the smallest detectable difference in phosphocreatine (PCr. Measures of metabolites during exercise were less reliable: exercising PCr had a coefficient of variation (CV of 27% during exercise, compared with 8% at rest. Estimates of mitochondrial function were variable, but experimentally useful. The CV of PCr(1/2t was 40%, yet much of this variance was inter-subject such that differences of <20% were detectable with n = 15, given a significance threshold of p<0.05. CONCLUSIONS: 31-phosphorus MRS provides reproducible and experimentally useful measures of phosphorus metabolites and mitochondrial function in trained human skeletal muscle.

  2. Reproducibility of myelin content-based human habenula segmentation at 3 Tesla.

    Science.gov (United States)

    Kim, Joo-Won; Naidich, Thomas P; Joseph, Joshmi; Nair, Divya; Glasser, Matthew F; O'halloran, Rafael; Doucet, Gaelle E; Lee, Won Hee; Krinsky, Hannah; Paulino, Alejandro; Glahn, David C; Anticevic, Alan; Frangou, Sophia; Xu, Junqian

    2018-03-26

    In vivo morphological study of the human habenula, a pair of small epithalamic nuclei adjacent to the dorsomedial thalamus, has recently gained significant interest for its role in reward and aversion processing. However, segmenting the habenula from in vivo magnetic resonance imaging (MRI) is challenging due to the habenula's small size and low anatomical contrast. Although manual and semi-automated habenula segmentation methods have been reported, the test-retest reproducibility of the segmented habenula volume and the consistency of the boundaries of habenula segmentation have not been investigated. In this study, we evaluated the intra- and inter-site reproducibility of in vivo human habenula segmentation from 3T MRI (0.7-0.8 mm isotropic resolution) using our previously proposed semi-automated myelin contrast-based method and its fully-automated version, as well as a previously published manual geometry-based method. The habenula segmentation using our semi-automated method showed consistent boundary definition (high Dice coefficient, low mean distance, and moderate Hausdorff distance) and reproducible volume measurement (low coefficient of variation). Furthermore, the habenula boundary in our semi-automated segmentation from 3T MRI agreed well with that in the manual segmentation from 7T MRI (0.5 mm isotropic resolution) of the same subjects. Overall, our proposed semi-automated habenula segmentation showed reliable and reproducible habenula localization, while its fully-automated version offers an efficient way for large sample analysis. © 2018 Wiley Periodicals, Inc.

  3. Repeatability and Reproducibility of Intraocular Pressure and Dynamic Corneal Response Parameters Assessed by the Corvis ST

    Directory of Open Access Journals (Sweden)

    Bernardo T. Lopes

    2017-01-01

    Full Text Available Purpose. To assess the repeatability and reproducibility of dynamic corneal response parameters measured by the Corvis ST (Oculus, Wetzlar, Germany. Methods. One eye randomly selected from 32 healthy volunteers was examined by the Corvis ST. Three different devices were used in an alternated random order for taking three measurements at each device in each subject. Standard intraocular pressure (IOP, the biomechanical-compensated IOP (bIOP, and DCR parameters were evaluated. The within-subject standard deviation (ζw and coefficient of variation (CV were assessed. Results. Regarding pressure indices, the ζw was below 1 mmHg for repeatability (0.98 for IOP and 0.89 for bIOP and the CV was 6.6% for IOP and 6.1% for bIOP. For reproducibility, the ζw was around 1 mmHg (1.12 for IOP and 1.05 for bIOP and the CV was 7.6% for IOP and 7.1% for bIOP. Most of DCR indices presented CV for repeatability below 4%. For reproducibility, the CV of most of the indices were below 6%. The deformation amplitude (DA ratio in 1 mm and integrated radius were below 4% (1.2% and 3.8%, resp.. Conclusions. The Corvis ST showed good precision (repeatability and reproducibility for IOP measurements and for DCR in healthy eyes.

  4. Reproducibility of retinal nerve fiber layer thickness measures using eye tracking in children with nonglaucomatous optic neuropathy.

    Science.gov (United States)

    Rajjoub, Raneem D; Trimboli-Heidler, Carmelina; Packer, Roger J; Avery, Robert A

    2015-01-01

    To determine the intra- and intervisit reproducibility of circumpapillary retinal nerve fiber layer (RNFL) thickness measures using eye tracking-assisted spectral-domain optical coherence tomography (SD OCT) in children with nonglaucomatous optic neuropathy. Prospective longitudinal study. Circumpapillary RNFL thickness measures were acquired with SD OCT using the eye-tracking feature at 2 separate study visits. Children with normal and abnormal vision (visual acuity ≥ 0.2 logMAR above normal and/or visual field loss) who demonstrated clinical and radiographic stability were enrolled. Intra- and intervisit reproducibility was calculated for the global average and 9 anatomic sectors by calculating the coefficient of variation and intraclass correlation coefficient. Forty-two subjects (median age 8.6 years, range 3.9-18.2 years) met inclusion criteria and contributed 62 study eyes. Both the abnormal and normal vision cohort demonstrated the lowest intravisit coefficient of variation for the global RNFL thickness. Intervisit reproducibility remained good for those with normal and abnormal vision, although small but statistically significant increases in the coefficient of variation were observed for multiple anatomic sectors in both cohorts. The magnitude of visual acuity loss was significantly associated with the global (ß = 0.026, P < .01) and temporal sector coefficient of variation (ß = 0.099, P < .01). SD OCT with eye tracking demonstrates highly reproducible RNFL thickness measures. Subjects with vision loss demonstrate greater intra- and intervisit variability than those with normal vision. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Reproducibility of intrarenal kinetics of Gd-DOTA with rabbits with dynamic MRI

    International Nuclear Information System (INIS)

    Grenier, N.; Broussin, J.; Barat, J.L.; Ducassou, D.

    1989-01-01

    Ten normal rabbits and seven rabbits with experimental acute renal failure by tubular necrosis were studied with dynamic MR to evaluate the reproducibility of intrarenal kinetics of Gd-DOTA. Sequential spin-echo sequences with short TR (200 msec)/TE (26 msec) were used yielding a 29 sec acquisition time. A usual semi-quantitative analysis of intrarenal contrast demonstrated the reproducilibity of some phases of the dynamic sequence in particular a drop in the signal within inner medulla between the third and the fourth minute after infusion. This effect, related to a high concentration of Gd-DOTA within the tubules was observed in 9 over 10 normal rabbits and in none of the rabbits with acute renal failure. The quantitative analysis calculation was based on relative signal intensity and contrast-to-noise ratio from the absolute signal intensity measure on regions-of-interest (ROI) on the cortex, outer medulla and inner medulla. No reproducibility of the variations with time of these parameters could be assessed. A gread number of factors of variations or error, mainly during the measurements of signal intensity with ROI, could explain this lack of reproducibility. At the present, dynamic MR is therefore not able to quantitatively evaluate the renal function. Only a semi-quantitative estimation of tubular concentration can be deduced [fr

  6. Effect of Initial Conditions on Reproducibility of Scientific Research

    Science.gov (United States)

    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

  7. Using the mouse to model human disease: increasing validity and reproducibility

    Directory of Open Access Journals (Sweden)

    Monica J. Justice

    2016-02-01

    Full Text Available Experiments that use the mouse as a model for disease have recently come under scrutiny because of the repeated failure of data, particularly derived from preclinical studies, to be replicated or translated to humans. The usefulness of mouse models has been questioned because of irreproducibility and poor recapitulation of human conditions. Newer studies, however, point to bias in reporting results and improper data analysis as key factors that limit reproducibility and validity of preclinical mouse research. Inaccurate and incomplete descriptions of experimental conditions also contribute. Here, we provide guidance on best practice in mouse experimentation, focusing on appropriate selection and validation of the model, sources of variation and their influence on phenotypic outcomes, minimum requirements for control sets, and the importance of rigorous statistics. Our goal is to raise the standards in mouse disease modeling to enhance reproducibility, reliability and clinical translation of findings.

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

    Energy Technology Data Exchange (ETDEWEB)

    Sakai, Yasuo; Nakajima, Mitsuo; Horioka, Kazuhiko [Department of Energy Sciences, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-ku, Yokohama 226-8502 (Japan)

    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.

  9. DNA Topoisomerases in Transcription

    DEFF Research Database (Denmark)

    Rødgaard, Morten Terpager

    2015-01-01

    This Ph.D. thesis summarizes the main results of my studies on the interplay between DNA topoisomerases and transcription. The work was performed from 2011 to 2015 at Aarhus University in the Laboratory of Genome Research, and was supervised by associate professor Anni H. Andersen. Most of the ex......This Ph.D. thesis summarizes the main results of my studies on the interplay between DNA topoisomerases and transcription. The work was performed from 2011 to 2015 at Aarhus University in the Laboratory of Genome Research, and was supervised by associate professor Anni H. Andersen. Most...... topoisomerase-DNA cleavage complex. The second study is an investigation of how topoisomerases influence gene regulation by keeping the genome in an optimal topological state....

  10. Deciphering Transcriptional Regulation

    DEFF Research Database (Denmark)

    Valen, Eivind

    The myriad of cells in the human body are all made from the same blueprint: the human genome. At the heart of this diversity lies the concept of gene regulation, the process in which it is decided which genes are used where and when. Genes do not function as on/off buttons, but more like a volume...... mostly near the start of the gene known as the promoter. This region contains patterns scattered in the DNA that the TFs can recognize and bind to. Such binding can prompt the assembly of the pre-initiation complex which ultimately leads to transcription of the gene. In order to achieve the regulation...... on what characterizes a hippocampus promoter. Pairing CAGE with TF binding site prediction we identi¿ed a likely key regulator of hippocampus. Finally, we developed a method for CAGE exploration. While the DeepCAGE library characterized a full 1.4 million transcription initiation events it did not capture...

  11. Reproducibility of corticospinal diffusion tensor tractography in normal subjects and hemiparetic stroke patients

    International Nuclear Information System (INIS)

    Lin, Chao-Chun; Tsai, Miao-Yu; Lo, Yu-Chien; Liu, Yi-Jui; Tsai, Po-Pang; Wu, Chiao-Ying; Lin, Chia-Wei; Shen, Wu-Chung; Chung, Hsiao-Wen

    2013-01-01

    Purpose: The reproducibility of corticospinal diffusion tensor tractography (DTT) for a guideline is important before longitudinal monitoring of the therapy effects in stroke patients. This study aimed to establish the reproducibility of corticospinal DTT indices in healthy subjects and chronic hemiparetic stroke patients. Materials and methods: Written informed consents were obtained from 10 healthy subjects (mean age 25.8 ± 6.8 years), who underwent two scans in one session plus the third scan one week later, and from 15 patients (mean age 47.5 ± 9.1 years, 6–60 months after the onset of stroke, NIHSS scores between 9 and 20) who were scanned thrice on separate days within one month. Diffusion-tensor imaging was performed at 3 T with 25 diffusion directions. Corticospinal tracts were reconstructed using fiber assignment by continuous tracking without and with motion/eddy-current corrections. Intra- and inter-rater as well as intra- and inter-session variations of the DTT derived indices (fiber number, apparent diffusion coefficient (ADC), and fractional anisotropy (FA)) were assessed. Results: Intra-session and inter-session coefficients of variations (CVs) are small for FA (1.13–2.09%) and ADC (0.45–1.64%), but much larger for fiber number (8.05–22.4%). Inter-session CVs in the stroke side of patients (22.4%) are higher than those in the normal sides (18.0%) and in the normal subjects (14.7%). Motion/eddy-current correction improved inter-session reproducibility only for the fiber number of the infarcted corticospinal tract (CV reduced from 22.4% to 14.1%). Conclusion: The fiber number derived from corticospinal DTT shows substantially lower precision than ADC and FA, with infarcted tracts showing lower reproducibility than the healthy tissues

  12. Identification and reproducibility of dietary patterns in a Danish cohort: the Inter99 study.

    Science.gov (United States)

    Lau, Cathrine; Glümer, Charlotte; Toft, Ulla; Tetens, Inge; Carstensen, Bendix; Jørgensen, Torben; Borch-Johnsen, Knut

    2008-05-01

    We aimed to identify dietary patterns in a Danish adult population and assess the reproducibility of the dietary patterns identified. Baseline data of 3,372 women and 3,191 men (30-60 years old) from the population-based survey Inter99 was used. Food intake, assessed by a FFQ, was aggregated into thirty-four separate food groups. Dietary patterns were identified by principal component analysis. Confirmatory factor analysis and Bland Altman plots were used to assess the reproducibility of the dietary patterns identified. The Bland Altman plots were used as an alternative and new method. Two factors were retained for both women and men, which accounted for 15.1-17.4 % of the total variation. The 'Traditional' pattern was characterised by high loadings ( > or = 0.40) on paté or high-fat meat for sandwiches, mayonnaise salads, red meat, potatoes, butter and lard, low-fat fish, low-fat meat for sandwiches, and sauces. The 'Modern' pattern was characterised by high loadings on vegetables, fruit, mixed vegetable dishes, vegetable oil and vinegar dressing, poultry, and pasta, rice and wheat kernels. Small differences were observed between patterns identified for women and men. The root mean square error approximation from the confirmatory factor analysis was 0.08. The variation observed from the Bland Altman plots of factors from explorative v. confirmative analyses and explorative analyses from two sub-samples was between 18.8 and 47.7 %. Pearson's correlation was >0.89 (P < 0.0001). The reproducibility was better for women than for men. We conclude that the 'Traditional' and 'Modern' dietary patterns identified were reproducible.

  13. The MARS for squat, countermovement, and standing long jump performance analyses: are measures reproducible?

    Science.gov (United States)

    Hébert-Losier, Kim; Beaven, C Martyn

    2014-07-01

    Jump tests are often used to assess the effect of interventions because their outcomes are reported valid indicators of functional performance. In this study, we examined the reproducibility of performance parameters from 3 common jump tests obtained using the commercially available Kistler Measurement, Analysis and Reporting Software (MARS). On 2 separate days, 32 men performed 3 squat jumps (SJs), 3 countermovement jumps (CMJs), and 3 standing long jumps (LJs) on a Kistler force-plate. On both days, the performance measures from the best jump of each series were extracted using the MARS. Changes in the mean scores, intraclass correlation coefficients (ICCs), and coefficients of variations (CVs) were computed to quantify the between-day reproducibility of each parameter. Moreover, the reproducibility quantifiers specific to the 3 separate jumps were compared using nonparametric tests. Overall, an acceptable between-day reproducibility (mean ± SD, ICC, and CV) of SJ (0.88 ± 0.06 and 7.1 ± 3.8%), CMJ (0.84 ± 0.17 and 5.9 ± 4.1%), and LJ (0.80 ± 0.13 and 8.1 ± 4.1%) measures was found using the MARS, except for parameters directly relating to the rate of force development (i.e., time to maximal force) and change in momentum during countermovement (i.e., negative force impulse) where reproducibility was lower. A greater proportion of the performance measures from the standing LJs had low ICCs and/or high CVs values most likely owing to the complex nature of the LJ test. Practitioners and researchers can use most of the jump test parameters from the MARS with confidence to quantify changes in the functional ability of individuals over time, except for those relating to the rate of force development or change in momentum during countermovement phases of jumps.

  14. In utero diffusion tensor imaging of the fetal brain: A reproducibility study.

    Science.gov (United States)

    Jakab, András; Tuura, Ruth; Kellenberger, Christian; Scheer, Ianina

    2017-01-01

    Our purpose was to evaluate the within-subject reproducibility of in utero diffusion tensor imaging (DTI) metrics and the visibility of major white matter structures. Images for 30 fetuses (20-33. postmenstrual weeks, normal neurodevelopment: 6 cases, cerebral pathology: 24 cases) were acquired on 1.5 T or 3.0 T MRI. DTI with 15 diffusion-weighting directions was repeated three times for each case, TR/TE: 2200/63 ms, voxel size: 1 ∗ 1 mm, slice thickness: 3-5 mm, b-factor: 700 s/mm 2 . Reproducibility was evaluated from structure detectability, variability of DTI measures using the coefficient of variation (CV), image correlation and structural similarity across repeated scans for six selected structures. The effect of age, scanner type, presence of pathology was determined using Wilcoxon rank sum test. White matter structures were detectable in the following percentage of fetuses in at least two of the three repeated scans: corpus callosum genu 76%, splenium 64%, internal capsule, posterior limb 60%, brainstem fibers 40% and temporooccipital association pathways 60%. The mean CV of DTI metrics ranged between 3% and 14.6% and we measured higher reproducibility in fetuses with normal brain development. Head motion was negatively correlated with reproducibility, this effect was partially ameliorated by motion-correction algorithm using image registration. Structures on 3.0 T had higher variability both with- and without motion correction. Fetal DTI is reproducible for projection and commissural bundles during mid-gestation, however, in 16-30% of the cases, data were corrupted by artifacts, resulting in impaired detection of white matter structures. To achieve robust results for the quantitative analysis of diffusivity and anisotropy values, fetal-specific image processing is recommended and repeated DTI is needed to ensure the detectability of fiber pathways.

  15. Reproducibility of corneal, macular and retinal nerve fiber layer ...

    African Journals Online (AJOL)

    side the limits of a consulting room.5. Reproducibility of ... examination, intraocular pressure and corneal thickness ... All OCT measurements were taken between 2 and 5 pm ..... CAS-OCT, Slit-lamp OCT, RTVue-100) have shown ICC.

  16. Beyond Bundles - Reproducible Software Environments with GNU Guix

    CERN Multimedia

    CERN. Geneva; Wurmus, Ricardo

    2018-01-01

    Building reproducible data analysis pipelines and numerical experiments is a key challenge for reproducible science, in which tools to reproduce software environments play a critical role. The advent of “container-based” deployment tools such as Docker and Singularity has made it easier to replicate software environments. These tools are very much about bundling the bits of software binaries in a convenient way, not so much about describing how software is composed. Science is not just about replicating, though—it demands the ability to inspect and to experiment. In this talk we will present GNU Guix, a software management toolkit. Guix departs from container-based solutions in that it enables declarative composition of software environments. It is comparable to “package managers” like apt or yum, but with a significant difference: Guix provides accurate provenance tracking of build artifacts, and bit-reproducible software. We will illustrate the many ways in which Guix can improve how software en...

  17. The reproducibility of random amplified polymorphic DNA (RAPD ...

    African Journals Online (AJOL)

    RAPD) profiles of Streptococcus thermophilus strains by using the polymerase chain reaction (PCR). Several factors can cause the amplification of false and non reproducible bands in the RAPD profiles. We tested three primers, OPI-02 MOD, ...

  18. Transcriptional networks controlling adipocyte differentiation

    DEFF Research Database (Denmark)

    Siersbæk, R; Mandrup, Susanne

    2011-01-01

    " of the transcription factor networks operating at specific time points during adipogenesis. Using such global "snapshots," we have demonstrated that dramatic remodeling of the chromatin template occurs within the first few hours following adipogenic stimulation and that many of the early transcription factors bind...... in a cooperative fashion to transcription factor hotspots. Such hotspots are likely to represent key chromatin nodes, where many adipogenic signaling pathways converge to drive the adipogenic transcriptional reprogramming....

  19. Reproducibility of oligonucleotide microarray transcriptome analyses - An interlaboratory comparison using chemostat cultures of Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Piper, M.D.W.; Daran-Lapujade, P.; Bro, Christoffer

    2002-01-01

    . In each of the laboratories, three independent replicate cultures were grown aerobically as well as anaerobically. Although variations introduced by in vitro handling steps were small and unbiased, greater variation from replicate cultures underscored that, to obtain reliable information, experimental...... replication is essential. Under aerobic conditions, 86% of the most highly expressed yeast genes showed an average intra-laboratory coefficient of variation of 0.23. This is significantly lower than previously reported for shake-flask-culture transcriptome analyses and probably reflects the strict control...... of growth conditions in chemostats. Using the triplicate data sets and appropriate statistical analysis, the change calls from anaerobic versus aerobic comparisons yielded an over 95% agreement between the laboratories for transcripts that changed by over 2-fold, leaving only a small fraction of genes...

  20. Identification, variation and transcription of pneumococcal repeat sequences

    Science.gov (United States)

    2011-01-01

    Background Small interspersed repeats are commonly found in many bacterial chromosomes. Two families of repeats (BOX and RUP) have previously been identified in the genome of Streptococcus pneumoniae, a nasopharyngeal commensal and respiratory pathogen of humans. However, little is known about the role they play in pneumococcal genetics. Results Analysis of the genome of S. pneumoniae ATCC 700669 revealed the presence of a third repeat family, which we have named SPRITE. All three repeats are present at a reduced density in the genome of the closely related species S. mitis. However, they are almost entirely absent from all other streptococci, although a set of elements related to the pneumococcal BOX repeat was identified in the zoonotic pathogen S. suis. In conjunction with information regarding their distribution within the pneumococcal chromosome, this suggests that it is unlikely that these repeats are specialised sequences performing a particular role for the host, but rather that they constitute parasitic elements. However, comparing insertion sites between pneumococcal sequences indicates that they appear to transpose at a much lower rate than IS elements. Some large BOX elements in S. pneumoniae were found to encode open reading frames on both strands of the genome, whilst another was found to form a composite RNA structure with two T box riboswitches. In multiple cases, such BOX elements were demonstrated as being expressed using directional RNA-seq and RT-PCR. Conclusions BOX, RUP and SPRITE repeats appear to have proliferated extensively throughout the pneumococcal chromosome during the species' past, but novel insertions are currently occurring at a relatively slow rate. Through their extensive secondary structures, they seem likely to affect the expression of genes with which they are co-transcribed. Software for annotation of these repeats is freely available from ftp://ftp.sanger.ac.uk/pub/pathogens/strep_repeats/. PMID:21333003

  1. Assay reproducibility in clinical studies of plasma miRNA.

    Directory of Open Access Journals (Sweden)

    Jonathan Rice

    Full Text Available There are increasing reports of plasma miRNAs as biomarkers of human disease but few standards in methodologic reporting, leading to inconsistent data. We systematically reviewed plasma miRNA studies published between July 2013-June 2014 to assess methodology. Six parameters were investigated: time to plasma extraction, methods of RNA extraction, type of miRNA, quantification, cycle threshold (Ct setting, and methods of statistical analysis. We compared these data with a proposed standard methodologic technique. Beginning with initial screening for 380 miRNAs using microfluidic array technology and validation in an additional cohort of patients, we compared 11 miRNAs that exhibited differential expression between 16 patients with benign colorectal neoplasms (advanced adenomas and 16 patients without any neoplasm (controls. Plasma was isolated immediately, 12, 24, 48, or 72 h following phlebotomy. miRNA was extracted using two different techniques (Trizol LS with pre-amplification or modified miRNeasy. We performed Taqman-based RT-PCR assays for the 11 miRNAs with subsequent analyses using a variable Ct setting or a fixed Ct set at 0.01, 0.03, 0.05, or 0.5. Assays were performed in duplicate by two different operators. RNU6 was the internal reference. Systematic review yielded 74 manuscripts meeting inclusion criteria. One manuscript (1.4% documented all 6 methodological parameters, while < 5% of studies listed Ct setting. In our proposed standard technique, plasma extraction ≤12 h provided consistent ΔCt. miRNeasy extraction yielded higher miRNA concentrations and fewer non-expressed miRNAs compared to Trizol LS (1/704 miRNAs [0.14%] vs 109/704 miRNAs [15%], not expressed, respectively. A fixed Ct bar setting of 0.03 yielded the most reproducible data, provided that <10% miRNA were non-expressed. There was no significant intra-operator variability. There was significant inter-operator variation using Trizol LS extraction, while this was

  2. Reproducibility of retinal circulation measurements obtained using laser speckle flowgraphy-NAVI in patients with glaucoma

    Directory of Open Access Journals (Sweden)

    Nakamura M

    2011-08-01

    Full Text Available Naoko Aizawa, Yu Yokoyama, Naoki Chiba, Kazuko Omodaka, Masayuki Yasuda, Takaaki Otomo, Masahiko Nakamura, Nobuo Fuse, Toru NakazawaDepartment of Ophthalmology, Tohoku University Graduate School of Medicine Sendai, Miyagi, JapanBackground: Laser speckle flowgraphy (LSFG enables noninvasive quantification of the retinal circulation in glaucoma patients. In this study, we tested the intrasession reproducibility of LSFG-NAVI, a modified LSFG technique.Methods: Sixty-five eyes from 33 subjects (male (M:female (F = 17:16 with a mean age of 49.4 ± 11.2 years were examined in this study. Two parameters indicating reproducibility – the coefficient of variation (COV and the intraclass correlation coefficient (ICC – were analyzed three times on the same day that mean blur rate (MBR was measured using LSFG-NAVI. The sites analyzed were the retinal artery and vein, the optic disk, and the choroid. Following classification according to the Glaucoma Hemifield Test (GHT; SITA-Standard 30-2 program, the COV and ICC were examined in patients with (GHT+; 38 eyes, M:F = 20:18, average age 48.9 ± 12.8 years and without (GHT-; 27 eyes, M:F = 13:14, average age 50.1 ± 8.7 years abnormal glaucomatous visual fields.Results: For all subjects, the intrasession reproducibility of MBR in the optic disk (COV: 3.4 ± 2.0; ICC: 0.95 and choroid (COV: 4.7 ± 3.4; ICC: 0.98 was excellent. The reproducibility for the retinal vein (COV: 8.4 ± 5.6, ICC: 0.90 and retinal artery (COV: 10.9 ± 9.9, ICC: 0.9 was moderate. MBRs in the optic disk had good reproducibility in both the GHT+ group (COV: 3.8 ± 2.0; ICC: 0.97 and the GHT− group (COV: 2.9 ± 2.1; ICC: 0.95. Local assessment of the optic disk in normal or glaucoma patients showed that the COVs of the quadrant optic disk areas were best in the temporal area of MBR (3.4%, 4.2%, respectively.Conclusion: LSFG-NAVI showed favorable reproducibility in evaluation of retinal circulation of glaucoma patients, particularly in

  3. Shear wave elastography for breast masses is highly reproducible.

    Science.gov (United States)

    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.

  4. Reproducibility of computer-aided detection system in digital mammograms

    International Nuclear Information System (INIS)

    Kim, Seung Ja; Cho, Nariya; Cha, Joo Hee; Chung, Hye Kyung; Lee, Sin Ho; Cho, Kyung Soo; Kim, Sun Mi; Moon, Woo Kyung

    2005-01-01

    To evaluate the reproducibility of the computer-aided detection (CAD) system for digital mammograms. We applied the CAD system (ImageChecker M1000-DM, version 3.1; R2 Technology) to full field digital mammograms. These mammograms were taken twice at an interval of 10-45 days (mean:25 days) for 34 preoperative patients (breast cancer n=27, benign disease n=7, age range:20-66 years, mean age:47.9 years). On the mammograms, lesions were visible in 19 patients and these were depicted as 15 masses and 12 calcification clusters. We analyzed the sensitivity, the false positive rate (FPR) and the reproducibility of the CAD marks. The broader sensitivities of the CAD system were 80% (12 of 15), 67%(10 of 15) for masses and those for calcification clusters were 100% (12 of 12). The strict sensitivities were 50% (15 of 30) and 50% (15 of 30) for masses and 92% (22 of 24) and 79% (19 of 24) for the clusters. The FPR for the masses was 0.21-0.22/image, the FPR for the clusters was 0.03-0.04/image and the total FPR was 0.24-0.26/image. Among 132 mammography images, the identical images regardless of the existence of CAD marks were 59% (78 of 132), and the identical images with CAD marks were 22% (15 of 69). The reproducibility of the CAD marks for the true positive mass was 67% (12 of 18) and 71% (17 of 24) for the true positive cluster. The reproducibility of CAD marks for the false positive mass was 8% (4 of 53), and the reproducibility of CAD marks for the false positive clusters was 14% (1 of 7). The reproducibility of the total mass marks was 23% (16 of 71), and the reproducibility of the total cluster marks was 58% (18 of 31). CAD system showed higher sensitivity and reproducibility of CAD marks for the calcification clusters which are related to breast cancer. Yet the overall reproducibility of CAD marks was low; therefore, the CAD system must be applied considering this limitation

  5. Using prediction markets to estimate the reproducibility of scientific research

    Science.gov (United States)

    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

  6. Validation and reproducibility of an Australian caffeine food frequency questionnaire.

    Science.gov (United States)

    Watson, E J; Kohler, M; Banks, S; Coates, A M

    2017-08-01

    The aim of this study was to measure validity and reproducibility of a caffeine food frequency questionnaire (C-FFQ) developed for the Australian population. The C-FFQ was designed to assess average daily caffeine consumption using four categories of food and beverages including; energy drinks; soft drinks/soda; coffee and tea and chocolate (food and drink). Participants completed a seven-day food diary immediately followed by the C-FFQ on two consecutive days. The questionnaire was first piloted in 20 adults, and then, a validity/reproducibility study was conducted (n = 90 adults). The C-FFQ showed moderate correlations (r = .60), fair agreement (mean difference 63 mg) and reasonable quintile rankings indicating fair to moderate agreement with the seven-day food diary. To test reproducibility, the C-FFQ was compared to itself and showed strong correlations (r = .90), good quintile rankings and strong kappa values (κ = 0.65), indicating strong reproducibility. The C-FFQ shows adequate validity and reproducibility and will aid researchers in Australia to quantify caffeine consumption.

  7. Using prediction markets to estimate the reproducibility of scientific research.

    Science.gov (United States)

    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.

  8. Reproducibility of Ultrasound and Magnetic Resonance Imaging Measurements of Tendon Size

    International Nuclear Information System (INIS)

    Brushoej, C.; Henriksen, B.M.; Albrecht-Beste, E.; Hoelmich, P.; Larsen, K.; Bachmann Nielsen, M.

    2006-01-01

    Purpose: To investigate the intra- and inter-tester reproducibility of measurements of the Achilles tendon, tibialis anterior tendon, and the tibialis posterior tendon in football players using ultrasound (US) and magnetic resonance imaging (MRI). Material and Methods: Eleven asymptomatic football players were examined. Using a standardized US scanning protocol, the tendons were examined by two observers with US for thickness, width, and cross-sectional area. One observer conducted the procedure twice. The subjects also underwent an MRI examination, and the assessment of tendon size was conducted twice by two observers. Results: The best reproducibility judged by coefficient of variation (CV) and 95% confidence interval was determined for the Achilles tendon on both US and MRI. The variability of US on measurements on the tibialis anterior and tibialis posterior tendons was less than that when using MRI. In 12 out of 18 measurements, there were systematic differences between observers as judged by one-sided F-test. Conclusion: The reproducibility of the three tendons was limited. Precaution should be taken when looking for minor quantitative changes, i.e., training-induced hypertrophy, and when doing so, the Achilles tendon should be used

  9. Characterization and reproducibility of HepG2 hanging drop spheroids toxicology in vitro.

    Science.gov (United States)

    Hurrell, Tracey; Ellero, Andrea Antonio; Masso, Zelie Flavienne; Cromarty, Allan Duncan

    2018-02-21

    Hepatotoxicity remains a major challenge in drug development despite preclinical toxicity screening using hepatocytes of human origin. To overcome some limitations of reproducing the hepatic phenotype, more structurally and functionally authentic cultures in vitro can be introduced by growing cells in 3D spheroid cultures. Characterisation and reproducibility of HepG2 spheroid cultures using a high-throughput hanging drop technique was performed and features contributing to potential phenotypic variation highlighted. Cultured HepG2 cells were seeded into Perfecta 3D® 96-well hanging drop plates and assessed over time for morphology, viability, cell cycle distribution, protein content and protein-mass profiles. Divergent aspects which were assessed included cell stocks, seeding density, volume of culture medium and use of extracellular matrix additives. Hanging drops are advantageous due to no complex culture matrix being present, enabling background free extractions for downstream experimentation. Varying characteristics were observed across cell stocks and batches, seeding density, culture medium volume and extracellular matrix when using immortalized HepG2 cells. These factors contribute to wide-ranging cellular responses and highlights concerns with respect to generating a reproducible phenotype in HepG2 hanging drop spheroids. Copyright © 2018 Elsevier Ltd. All rights reserved.

  10. Repeatability and Reproducibility of Compression Strength Measurements Conducted According to ASTM E9

    Science.gov (United States)

    Luecke, William E.; Ma, Li; Graham, Stephen M.; Adler, Matthew A.

    2010-01-01

    Ten commercial laboratories participated in an interlaboratory study to establish the repeatability and reproducibility of compression strength tests conducted according to ASTM International Standard Test Method E9. The test employed a cylindrical aluminum AA2024-T351 test specimen. Participants measured elastic modulus and 0.2 % offset yield strength, YS(0.2 % offset), using an extensometer attached to the specimen. The repeatability and reproducibility of the yield strength measurement, expressed as coefficient of variations were cv(sub r)= 0.011 and cv(sub R)= 0.020 The reproducibility of the test across the laboratories was among the best that has been reported for uniaxial tests. The reported data indicated that using diametrically opposed extensometers, instead of a single extensometer doubled the precision of the test method. Laboratories that did not lubricate the ends of the specimen measured yield stresses and elastic moduli that were smaller than those measured in laboratories that lubricated the specimen ends. A finite element analysis of the test specimen deformation for frictionless and perfect friction could not explain the discrepancy, however. The modulus measured from stress-strain data were reanalyzed using a technique that finds the optimal fit range, and applies several quality checks to the data. The error in modulus measurements from stress-strain curves generally increased as the fit range decreased to less than 40 % of the stress range.

  11. Transcript structure and domain display: a customizable transcript visualization tool.

    Science.gov (United States)

    Watanabe, Kenneth A; Ma, Kaiwang; Homayouni, Arielle; Rushton, Paul J; Shen, Qingxi J

    2016-07-01

    Transcript Structure and Domain Display (TSDD) is a publicly available, web-based program that provides publication quality images of transcript structures and domains. TSDD is capable of producing transcript structures from GFF/GFF3 and BED files. Alternatively, the GFF files of several model organisms have been pre-loaded so that users only needs to enter the locus IDs of the transcripts to be displayed. Visualization of transcripts provides many benefits to researchers, ranging from evolutionary analysis of DNA-binding domains to predictive function modeling. TSDD is freely available for non-commercial users at http://shenlab.sols.unlv.edu/shenlab/software/TSD/transcript_display.html : jeffery.shen@unlv.nevada.edu. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  12. Effect of food and activity on the reproducibility of isotopic GFR estimation

    International Nuclear Information System (INIS)

    Wilkinson, J.; Fleming, J.S.; Waller, D.G.

    1990-01-01

    The reproducibility of the plasma clearance of 99 Tc m DTPA was studied in 26 patients under standardized conditions with the subject fasting and at rest. The coefficient of variation of duplicate measurements in patients with glomerular filtration rates (GRFs) ranging from 11-103 ml min -1 was 8%. Mean GFR following a breakfast containing 670 kcal and 31 g protein was increased significantly from 40.7±28.1 ml min -1 to 43.6±30.8 ml min -1 . When fasted but permitted free exercise there was no consistent trend in GFR but the coefficient of variation of duplicate estimates increased significantly to 12.1%. It is recommended that routine GFR measurement should be carried out fasting or following a light diet with restricted activity. (author)

  13. Reproducibility of pulse-wave analysis and pulse-wave velocity determination in chronic kidney disease

    DEFF Research Database (Denmark)

    Frimodt-Møller, Marie; Nielsen, Arne Høj; Kamper, Anne-Lise

    2008-01-01

    are highly reproducible in pre-dialysis patients with CKD with the day-to-day variation being in accordance with the intra- and inter-observer variation. Thus, applanation tonometry using the SphygmoCor system is a simple, non-invasive method to assess central haemodynamics in clinical trials in patients......BACKGROUND: Indices of central arterial stiffness, derived by use of applanation tonometry, have shown to be strong independent predictors of cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD). The objective of this study was to evaluate the intra- and inter...... performed under standardized conditions in 19 CKD patients with a mean GFR 25.3 ml/min/1.73 m(2) (range 9.9-42.2) by two trained observers and repeated by one of the observers within a week. RESULTS: The mean inter-observer and day-to-day differences (+/-2 SD) for the augmentation index (AIx) were 0...

  14. Reproducible isolation of lymph node stromal cells reveals site-dependent differences in fibroblastic reticular cells

    Directory of Open Access Journals (Sweden)

    Anne L Fletcher

    2011-09-01

    Full Text Available Within lymph nodes, non-hematopoietic stromal cells organize and interact with leukocytes in an immunologically important manner. In addition to organizing T and B cell segregation and expressing lymphocyte survival factors, several recent studies have shown that lymph node stromal cells shape the naïve T cell repertoire, expressing self-antigens which delete self-reactive T cells in a unique and non-redundant fashion. A fundamental role in peripheral tolerance, in addition to an otherwise extensive functional portfolio, necessitates closer study of lymph node stromal cell subsets using modern immunological techniques; however this has not routinely been possible in the field, due to difficulties reproducibly isolating these rare subsets. Techniques were therefore developed for successful ex vivo and in vitro manipulation and characterization of lymph node stroma. Here we discuss and validate these techniques in mice and humans, and apply them to address several unanswered questions regarding lymph node composition. We explored the steady-state stromal composition of lymph nodes isolated from mice and humans, and found that marginal reticular cells and lymphatic endothelial cells required lymphocytes for their normal maturation in mice. We also report alterations in the proportion and number of fibroblastic reticular cells (FRCs between skin-draining and mesenteric lymph nodes. Similarly, transcriptional profiling of FRCs revealed changes in cytokine production from these sites. Together, these methods permit highly reproducible stromal cell isolation, sorting, and culture.

  15. Reproducible isolation of lymph node stromal cells reveals site-dependent differences in fibroblastic reticular cells.

    Science.gov (United States)

    Fletcher, Anne L; Malhotra, Deepali; Acton, Sophie E; Lukacs-Kornek, Veronika; Bellemare-Pelletier, Angelique; Curry, Mark; Armant, Myriam; Turley, Shannon J

    2011-01-01

    Within lymph nodes, non-hematopoietic stromal cells organize and interact with leukocytes in an immunologically important manner. In addition to organizing T and B cell segregation and expressing lymphocyte survival factors, several recent studies have shown that lymph node stromal cells shape the naïve T cell repertoire, expressing self-antigens which delete self-reactive T cells in a unique and non-redundant fashion. A fundamental role in peripheral tolerance, in addition to an otherwise extensive functional portfolio, necessitates closer study of lymph node stromal cell subsets using modern immunological techniques; however this has not routinely been possible in the field, due to difficulties reproducibly isolating these rare subsets. Techniques were therefore developed for successful ex vivo and in vitro manipulation and characterization of lymph node stroma. Here we discuss and validate these techniques in mice and humans, and apply them to address several unanswered questions regarding lymph node composition. We explored the steady-state stromal composition of lymph nodes isolated from mice and humans, and found that marginal reticular cells and lymphatic endothelial cells required lymphocytes for their normal maturation in mice. We also report alterations in the proportion and number of fibroblastic reticular cells (FRCs) between skin-draining and mesenteric lymph nodes. Similarly, transcriptional profiling of FRCs revealed changes in cytokine production from these sites. Together, these methods permit highly reproducible stromal cell isolation, sorting, and culture.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  18. Reproducibility of clinical research in critical care: a scoping review.

    Science.gov (United States)

    Niven, Daniel J; McCormick, T Jared; Straus, Sharon E; Hemmelgarn, Brenda R; Jeffs, Lianne; Barnes, Tavish R M; Stelfox, Henry T

    2018-02-21

    The ability to reproduce experiments is a defining principle of science. Reproducibility of clinical research has received relatively little scientific attention. However, it is important as it may inform clinical practice, research agendas, and the design of future studies. We used scoping review methods to examine reproducibility within a cohort of randomized trials examining clinical critical care research and published in the top general medical and critical care journals. To identify relevant clinical practices, we searched the New England Journal of Medicine, The Lancet, and JAMA for randomized trials published up to April 2016. To identify a comprehensive set of studies for these practices, included articles informed secondary searches within other high-impact medical and specialty journals. We included late-phase randomized controlled trials examining therapeutic clinical practices in adults admitted to general medical-surgical or specialty intensive care units (ICUs). Included articles were classified using a reproducibility framework. An original study was the first to evaluate a clinical practice. A reproduction attempt re-evaluated that practice in a new set of participants. Overall, 158 practices were examined in 275 included articles. A reproduction attempt was identified for 66 practices (42%, 95% CI 33-50%). Original studies reported larger effects than reproduction attempts (primary endpoint, risk difference 16.0%, 95% CI 11.6-20.5% vs. 8.4%, 95% CI 6.0-10.8%, P = 0.003). More than half of clinical practices with a reproduction attempt demonstrated effects that were inconsistent with the original study (56%, 95% CI 42-68%), among which a large number were reported to be efficacious in the original study and to lack efficacy in the reproduction attempt (34%, 95% CI 19-52%). Two practices reported to be efficacious in the original study were found to be harmful in the reproduction attempt. A minority of critical care practices with research published

  19. Reproducibility of graph metrics in fMRI networks

    Directory of Open Access Journals (Sweden)

    Qawi K Telesford

    2010-12-01

    Full Text Available The reliability of graph metrics calculated in network analysis is essential to the interpretation of complex network organization. These graph metrics are used to deduce the small-world properties in networks. In this study, we investigated the test-retest reliability of graph metrics from functional magnetic resonance imaging (fMRI data collected for two runs in 45 healthy older adults. Graph metrics were calculated on data for both runs and compared using intraclass correlation coefficient (ICC statistics and Bland-Altman (BA plots. ICC scores describe the level of absolute agreement between two measurements and provide a measure of reproducibility. For mean graph metrics, ICC scores were high for clustering coefficient (ICC=0.86, global efficiency (ICC=0.83, path length (ICC=0.79, and local efficiency (ICC=0.75; the ICC score for degree was found to be low (ICC=0.29. ICC scores were also used to generate reproducibility maps in brain space to test voxel-wise reproducibility for unsmoothed and smoothed data. Reproducibility was uniform across the brain for global efficiency and path length, but was only high in network hubs for clustering coefficient, local efficiency and degree. BA plots were used to test the measurement repeatability of all graph metrics. All graph metrics fell within the limits for repeatability. Together, these results suggest that with exception of degree, mean graph metrics are reproducible and suitable for clinical studies. Further exploration is warranted to better understand reproducibility across the brain on a voxel-wise basis.

  20. Effective Form of Reproducing the Total Financial Potential of Ukraine

    Directory of Open Access Journals (Sweden)

    Portna Oksana V.

    2015-03-01

    Full Text Available Development of scientific principles of reproducing the total financial potential of the country and its effective form is an urgent problem both in theoretical and practical aspects of the study, the solution of which is intended to ensure the active mobilization and effective use of the total financial potential of Ukraine, and as a result — its expanded reproduction as well, which would contribute to realization of the internal capacities for stabilization of the national economy. The purpose of the article is disclosing the essence of the effective form of reproducing the total financial potential of the country, analyzing the results of reproducing the total financial potential of Ukraine. It has been proved that the basis for the effective form of reproducing the total financial potential of the country is the volume and flow of resources, which are associated with the «real» economy, affect the dynamics of GDP and define it, i.e. resource and process forms of reproducing the total financial potential of Ukraine (which precede the effective one. The analysis of reproducing the total financial potential of Ukraine has shown that in the analyzed period there was an increase in the financial possibilities of the country, but steady dynamics of reduction of the total financial potential was observed. If we consider the amount of resources involved in production, creating a net value added and GDP, it occurs on a restricted basis. Growth of the total financial potential of Ukraine is connected only with extensive quantitative factors rather than intensive qualitative changes.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  3. Normalization with Corresponding Naïve Tissue Minimizes Bias Caused by Commercial Reverse Transcription Kits on Quantitative Real-Time PCR Results.

    Directory of Open Access Journals (Sweden)

    Andreas Garcia-Bardon

    Full Text Available Real-time reverse transcription polymerase chain reaction (PCR is the gold standard for expression analysis. Designed to improve reproducibility and sensitivity, commercial kits are commonly used for the critical step of cDNA synthesis. The present study was designed to determine the impact of these kits. mRNA from mouse brains were pooled to create serial dilutions ranging from 0.0625 μg to 2 μg, which were transcribed into cDNA using four different commercial reverse-transcription kits. Next, we transcribed mRNA from brain tissue after acute brain injury and naïve mice into cDNA for qPCR. Depending on tested genes, some kits failed to show linear results in dilution series and revealed strong variations in cDNA yield. Absolute expression data in naïve and trauma settings varied substantially between these kits. Normalization with a housekeeping gene failed to reduce kit-dependent variations, whereas normalization eliminated differences when naïve samples from the same region were used. The study shows strong evidence that choice of commercial cDNA synthesis kit has a major impact on PCR results and, consequently, on comparability between studies. Additionally, it provides a solution to overcome this limitation by normalization with data from naïve samples. This simple step helps to compare mRNA expression data between different studies and groups.

  4. Expression microarray reproducibility is improved by optimising purification steps in RNA amplification and labelling

    Directory of Open Access Journals (Sweden)

    Brenton James D

    2004-01-01

    Full Text Available Abstract Background Expression microarrays have evolved into a powerful tool with great potential for clinical application and therefore reliability of data is essential. RNA amplification is used when the amount of starting material is scarce, as is frequently the case with clinical samples. Purification steps are critical in RNA amplification and labelling protocols, and there is a lack of sufficient data to validate and optimise the process. Results Here the purification steps involved in the protocol for indirect labelling of amplified RNA are evaluated and the experimentally determined best method for each step with respect to yield, purity, size distribution of the transcripts, and dye coupling is used to generate targets tested in replicate hybridisations. DNase treatment of diluted total RNA samples followed by phenol extraction is the optimal way to remove genomic DNA contamination. Purification of double-stranded cDNA is best achieved by phenol extraction followed by isopropanol precipitation at room temperature. Extraction with guanidinium-phenol and Lithium Chloride precipitation are the optimal methods for purification of amplified RNA and labelled aRNA respectively. Conclusion This protocol provides targets that generate highly reproducible microarray data with good representation of transcripts across the size spectrum and a coefficient of repeatability significantly better than that reported previously.

  5. Reproducibility problems of in-service ultrasonic testing results

    International Nuclear Information System (INIS)

    Honcu, E.

    1974-01-01

    The reproducibility of the results of ultrasonic testing is the basic precondition for its successful application in in-service inspection of changes in the quality of components of nuclear power installations. The results of periodic ultrasonic inspections are not satisfactory from the point of view of reproducibility. Regardless, the ultrasonic pulse-type method is suitable for evaluating the quality of most components of nuclear installations and often the sole method which may be recommended for inspection with regard to its technical and economic aspects. (J.B.)

  6. Reproducing Kernel Method for Solving Nonlinear Differential-Difference Equations

    Directory of Open Access Journals (Sweden)

    Reza Mokhtari

    2012-01-01

    Full Text Available On the basis of reproducing kernel Hilbert spaces theory, an iterative algorithm for solving some nonlinear differential-difference equations (NDDEs is presented. The analytical solution is shown in a series form in a reproducing kernel space, and the approximate solution , is constructed by truncating the series to terms. The convergence of , to the analytical solution is also proved. Results obtained by the proposed method imply that it can be considered as a simple and accurate method for solving such differential-difference problems.

  7. Reproducibility of biomarkers in induced sputum and in serum from chronic smokers.

    Science.gov (United States)

    Zuiker, Rob G J A; Kamerling, Ingrid M C; Morelli, Nicoletta; Calderon, Cesar; Boot, J Diderik; de Kam, Marieke; Diamant, Zuzana; Burggraaf, Jacobus; Cohen, Adam F

    2015-08-01

    Soluble inflammatory markers obtained from non-invasive airway sampling such as induced sputum may be useful biomarkers for targeted pharmaceutical interventions. However, before these soluble markers can be used as potential targets, their variability and reproducibility need to be established in distinct study populations. This study aimed to assess the reproducibility of biomarkers obtained from induced sputum and serum in chronic smokers and non-smokers. Sputum and serum samples were obtained from 16 healthy non-smokers and 16 asymptomatic chronic smokers (for both groups: 8M/8F, 30-52 years, FEV1 ≥80% pred.; ≥10 pack years for the smokers) on 2 separate visits 4-10 days apart. Soluble markers in serum and sputum were analysed by ELISA. The differences between smokers vs non-smokers were analysed with a t-test and variability was assessed on log-transformed data by a mixed model ANOVA. Analysable sputum samples could be obtained from all 32 subjects. In both study populations neutrophils and macrophages were the predominant cell types. Serum Pulmonary Surfactant Associated Protein D had favourable reproducibility criteria for reliability ratio (0.99), intra-subject coefficient of variation (11.2%) and the Bland Altman limits of agreement. Furthermore, chronic smokers, compared to non-smokers, had significantly higher sputum concentrations of IL-8 (1094.6 pg/mL vs 460.8 pg/mL, p = 0.006)), and higher serum concentrations of Pulmonary Surfactant Associated Protein D (110.9 pg/mL vs 64.7 pg/mL, p = 0.019), and lower concentrations of Serum Amyloid A (1352.4 pg/mL vs 2297.5 pg/mL, p = 0.022). Serum Pulmonary Surfactant Associated Protein D proved to be a biomarker that fulfilled the criteria for reproducibility in both study groups. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Repeatability and Reproducibility in Proteomic Identifications by Liquid Chromatography—Tandem Mass Spectrometry

    Science.gov (United States)

    Tabb, David L.; Vega-Montoto, Lorenzo; Rudnick, Paul A.; Variyath, Asokan Mulayath; Ham, Amy-Joan L.; Bunk, David M.; Kilpatrick, Lisa E.; Billheimer, Dean D.; Blackman, Ronald K.; Cardasis, Helene L.; Carr, Steven A.; Clauser, Karl R.; Jaffe, Jacob D.; Kowalski, Kevin A.; Neubert, Thomas A.; Regnier, Fred E.; Schilling, Birgit; Tegeler, Tony J.; Wang, Mu; Wang, Pei; Whiteaker, Jeffrey R.; Zimmerman, Lisa J.; Fisher, Susan J.; Gibson, Bradford W.; Kinsinger, Christopher R.; Mesri, Mehdi; Rodriguez, Henry; Stein, Steven E.; Tempst, Paul; Paulovich, Amanda G.; Liebler, Daniel C.; Spiegelman, Cliff

    2009-01-01

    The complexity of proteomic instrumentation for LC-MS/MS introduces many possible sources of variability. Data-dependent sampling of peptides constitutes a stochastic element at the heart of discovery proteomics. Although this variation impacts the identification of peptides, proteomic identifications are far from completely random. In this study, we analyzed interlaboratory data sets from the NCI Clinical Proteomic Technology Assessment for Cancer to examine repeatability and reproducibility in peptide and protein identifications. Included data spanned 144 LC-MS/MS experiments on four Thermo LTQ and four Orbitrap instruments. Samples included yeast lysate, the NCI-20 defined dynamic range protein mix, and the Sigma UPS 1 defined equimolar protein mix. Some of our findings reinforced conventional wisdom, such as repeatability and reproducibility being higher for proteins than for peptides. Most lessons from the data, however, were more subtle. Orbitraps proved capable of higher repeatability and reproducibility, but aberrant performance occasionally erased these gains. Even the simplest protein digestions yielded more peptide ions than LC-MS/MS could identify during a single experiment. We observed that peptide lists from pairs of technical replicates overlapped by 35–60%, giving a range for peptide-level repeatability in these experiments. Sample complexity did not appear to affect peptide identification repeatability, even as numbers of identified spectra changed by an order of magnitude. Statistical analysis of protein spectral counts revealed greater stability across technical replicates for Orbitraps, making them superior to LTQ instruments for biomarker candidate discovery. The most repeatable peptides were those corresponding to conventional tryptic cleavage sites, those that produced intense MS signals, and those that resulted from proteins generating many distinct peptides. Reproducibility among different instruments of the same type lagged behind

  9. Handgrip force steadiness in young and older adults: a reproducibility study.

    Science.gov (United States)

    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

  10. Reproducibility of the Internal Load and Performance-Based Responses to Simulated Amateur Boxing.

    Science.gov (United States)

    Thomson, Edward D; Lamb, Kevin L

    2017-12-01

    Thomson, ED and Lamb, KL. Reproducibility of the internal load and performance-based responses to simulated amateur boxing. J Strength Cond Res 31(12): 3396-3402, 2017-The aim of this study was to examine the reproducibility of the internal load and performance-based responses to repeated bouts of a three-round amateur boxing simulation protocol (boxing conditioning and fitness test [BOXFIT]). Twenty-eight amateur boxers completed 2 familiarization trials before performing 2 complete trials of the BOXFIT, separated by 4-7 days. To characterize the internal load, mean (HRmean) and peak (HRpeak) heart rate, breath-by-breath oxygen uptake (V[Combining Dot Above]O2), aerobic energy expenditure, excess carbon dioxide production (CO2excess), and ratings of perceived exertion were recorded throughout each round, and blood lactate determined post-BOXFIT. Additionally, an indication of the performance-based demands of the BOXFIT was provided by a measure of acceleration of the punches thrown in each round. Analyses revealed there were no significant differences (p > 0.05) between repeated trials in any round for all dependent measures. The typical error (coefficient variation %) for all but 1 marker of internal load (CO2excess) was 1.2-16.5% and reflected a consistency that was sufficient for the detection of moderate changes in variables owing to an intervention. The reproducibility of the punch accelerations was high (coefficient of variance % range = 2.1-2.7%). In general, these findings suggest that the internal load and performance-based efforts recorded during the BOXFIT are reproducible and, thereby, offer practitioners a method by which meaningful changes impacting on performance could be identified.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Christopher M Walker

    Full Text Available 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.

  13. Urethral pressure reflectometry in women with pelvic organ prolapse: a study of reproducibility.

    Science.gov (United States)

    Khayyami, Yasmine; Lose, Gunnar; Klarskov, Niels

    2017-05-01

    The mechanism of continence in women with pelvic organ prolapse (POP) before and after surgery remains unknown. Urethral pressure reflectometry (UPR) separates women with stress urinary incontinence (SUI) from continent women by measuring urethral opening pressure at an abdominal pressure of 50 cmH 2 O (P O-Abd 50 ). UPR can help identify women with POP at risk of postoperative de novo SUI. The aim of this study was to investigate the reproducibility of UPR in women with POP. Women with anterior or posterior vaginal wall prolapse were recruited for this prospective, observational study from our outpatient clinic. The women were examined with UPR on two occasions. Measurements were done at rest, and during squeezing and straining. Statistical analyses were performed using SAS 9.4. A Bland-Altman analysis with limits of agreement and coefficients of variation was used to determine the level of agreement between measurements. Paired t tests were used to estimate the difference; a two-tailed P value of rest or during squeezing or in the values of P O-Abd 50 . P O-Abd 50 showed limits of agreement of 15.3 cmH 2 O and a coefficient of variation of 9.9 %. UPR was found to be a highly reproducible method in women with POP. UPR may be used in future studies to help reveal urodynamic features predictive of postoperative de novo SUI in women with POP.

  14. Potency Evaluation of Recombinant Human Erythropoietin in Brazil: Assessment of Reproducibility Using a Practical Approach

    Directory of Open Access Journals (Sweden)

    Michele Cardoso do Nascimento

    2015-08-01

    Full Text Available In this study, we compared the results of potency determination of recombinant human erythropoietin (rhEPO obtained between 2010 and 2012 by the National Institute of Quality Control in Health (INCQS/Fiocruz, i.e., the National Control Laboratory (NCL, and by a manufacturer of rhEPO. In total, 47 different batches of commercially prepared rhEPO (alpha isoform were analyzed. All results, including those of the control and warning limits, remained within the limits recommended by European Pharmacopoeia (Ph. Eur.. All relative error (RE values were less than ± 30%, wh ereas most were approximately ± 20%. Applying the Bland-Altman plot, only two of 47 values remained outside the limits of agreement (LA. In addition, agreement of potency determination between INCQS and the manufacturer coefficient of variation of reproducibility (% CVR was considered satisfactory. Taken together, our results demonstrate (i. the potency assay of rhEPO performed at INCQS, is standardized and controlled, (ii. the comparison of our results with those of the manufacturer, revealed an adequate inter-laboratory variation, and (iii. the critical appraisal proposed here appears to be a feasible tool to assess the reproducibility of biological activity, providing additional information regarding monitoring and production consistency to manufacturers and NCLs.

  15. Nucleocytoplasmic shuttling of transcription factors

    DEFF Research Database (Denmark)

    Cartwright, P; Helin, K

    2000-01-01

    To elicit the transcriptional response following intra- or extracellular stimuli, the signals need to be transmitted to their site of action within the nucleus. The nucleocytoplasmic shuttling of transcription factors is a mechanism mediating this process. The activation and inactivation...... of the transcriptional response is essential for cells to progress through the cell cycle in a normal manner. The involvement of cytoplasmic and nuclear accessory molecules, and the general nuclear membrane transport components, are essential for this process. Although nuclear import and export for different...... transcription factor families are regulated by similar mechanisms, there are several differences that allow for the specific activation of each transcription factor. This review discusses the general import and export pathways found to be common amongst many different transcription factors, and highlights...

  16. Transcriptional Silencing of Retroviral Vectors

    DEFF Research Database (Denmark)

    Lund, Anders Henrik; Duch, M.; Pedersen, F.S.

    1996-01-01

    . Extinction of long-term vector expression has been observed after implantation of transduced hematopoietic cells as well as fibroblasts, myoblasts and hepatocytes. Here we review the influence of vector structure, integration site and cell type on transcriptional silencing. While down-regulation of proviral...... transcription is known from a number of cellular and animal models, major insight has been gained from studies in the germ line and embryonal cells of the mouse. Key elements for the transfer and expression of retroviral vectors, such as the viral transcriptional enhancer and the binding site for the t......RNA primer for reverse transcription may have a major influence on transcriptional silencing. Alterations of these elements of the vector backbone as well as the use of internal promoter elements from housekeeping genes may contribute to reduce transcriptional silencing. The use of cell culture and animal...

  17. DNA topology and transcription

    Science.gov (United States)

    Kouzine, Fedor; Levens, David; Baranello, Laura

    2014-01-01

    Chromatin is a complex assembly that compacts DNA inside the nucleus while providing the necessary level of accessibility to regulatory factors conscripted by cellular signaling systems. In this superstructure, DNA is the subject of mechanical forces applied by variety of molecular motors. Rather than being a rigid stick, DNA possesses dynamic structural variability that could be harnessed during critical steps of genome functioning. The strong relationship between DNA structure and key genomic processes necessitates the study of physical constrains acting on the double helix. Here we provide insight into the source, dynamics, and biology of DNA topological domains in the eukaryotic cells and summarize their possible involvement in gene transcription. We emphasize recent studies that might inspire and impact future experiments on the involvement of DNA topology in cellular functions. PMID:24755522

  18. Eukaryotic transcription factors

    DEFF Research Database (Denmark)

    Staby, Lasse; O'Shea, Charlotte; Willemoës, Martin

    2017-01-01

    Gene-specific transcription factors (TFs) are key regulatory components of signaling pathways, controlling, for example, cell growth, development, and stress responses. Their biological functions are determined by their molecular structures, as exemplified by their structured DNA-binding domains...... regions with function-related, short sequence motifs and molecular recognition features with structural propensities. This review focuses on molecular aspects of TFs, which represent paradigms of ID-related features. Through specific examples, we review how the ID-associated flexibility of TFs enables....... It is furthermore emphasized how classic biochemical concepts like allostery, conformational selection, induced fit, and feedback regulation are undergoing a revival with the appreciation of ID. The review also describes the most recent advances based on computational simulations of ID-based interaction mechanisms...

  19. Transcription of tandemly repetitive DNA: functional roles.

    Science.gov (United States)

    Biscotti, Maria Assunta; Canapa, Adriana; Forconi, Mariko; Olmo, Ettore; Barucca, Marco

    2015-09-01

    A considerable fraction of the eukaryotic genome is made up of satellite DNA constituted of tandemly repeated sequences. These elements are mainly located at centromeres, pericentromeres, and telomeres and are major components of constitutive heterochromatin. Although originally satellite DNA was thought silent and inert, an increasing number of studies are providing evidence on its transcriptional activity supporting, on the contrary, an unexpected dynamicity. This review summarizes the multiple structural roles of satellite noncoding RNAs at chromosome level. Indeed, satellite noncoding RNAs play a role in the establishment of a heterochromatic state at centromere and telomere. These highly condensed structures are indispensable to preserve chromosome integrity and genome stability, preventing recombination events, and ensuring the correct chromosome pairing and segregation. Moreover, these RNA molecules seem to be involved also in maintaining centromere identity and in elongation, capping, and replication of telomere. Finally, the abnormal variation of centromeric and pericentromeric DNA transcription across major eukaryotic lineages in stress condition and disease has evidenced the critical role that these transcripts may play and the potentially dire consequences for the organism.

  20. Multichannel electrogastrography under a magnifying glass--an in-depth study on reproducibility of fed state electrogastrograms.

    Science.gov (United States)

    Krusiec-Swidergoł, B; Jonderko, K

    2008-06-01

    We checked on reproducibility of parameters of a multichannel electrogastrogram in adults after intake of typical, applied in electrogastrography, test meals. Recordings of multichannel electrogastrograms were accomplished in four blocks comprising 18 subjects (nine healthy volunteers and nine patients with functional GI disorders) each. Every subject had two examinations taken 1-2 days apart, and a third one was accomplished at least 2 weeks before or after the two other sessions. The registration involved a 30-min fasted and a 2-h postprandial period after one of the meal stimuli tested within a given block: 400 mL water, 400 g yoghurt (378 kcal), a scrambled eggs sandwich (370 kcal), a pancake (355 kcal). From among the parameters reflecting the propagation of the gastric slow waves, the average percentage of slow wave coupling (APSWC) exhibited a good (coefficient of variation for paired examinations CV(p) < or = 10%) to moderate (10 < CV(p) < or = 30%) reproducibility. On the other hand, the reproducibility of the maximum dominant frequency difference and the spatial dominant power difference was found to be unsatisfactory. The reproducibility of the multichannel electrogastrographic parameters did not differ between healthy volunteers and patients with functional GI disorders. Gender or the kind of a test meal did not affect the reproducibility of the electrogastrographic parameters either. The medium-term reproducibility was not any worse than the short-term one. From among the parameters of a multichannel electrogastrogram intended to quantify the propagation of slow waves, only the APSWC offers a reproducibility potentially good enough for clinical applications.

  1. A multiparametric automatic method to monitor long-term reproducibility in digital mammography: results from a regional screening programme.

    Science.gov (United States)

    Gennaro, G; Ballaminut, A; Contento, G

    2017-09-01

    This study aims to illustrate a multiparametric automatic method for monitoring long-term reproducibility of digital mammography systems, and its application on a large scale. Twenty-five digital mammography systems employed within a regional screening programme were controlled weekly using the same type of phantom, whose images were analysed by an automatic software tool. To assess system reproducibility levels, 15 image quality indices (IQIs) were extracted and compared with the corresponding indices previously determined by a baseline procedure. The coefficients of variation (COVs) of the IQIs were used to assess the overall variability. A total of 2553 phantom images were collected from the 25 digital mammography systems from March 2013 to December 2014. Most of the systems showed excellent image quality reproducibility over the surveillance interval, with mean variability below 5%. Variability of each IQI was 5%, with the exception of one index associated with the smallest phantom objects (0.25 mm), which was below 10%. The method applied for reproducibility tests-multi-detail phantoms, cloud automatic software tool to measure multiple image quality indices and statistical process control-was proven to be effective and applicable on a large scale and to any type of digital mammography system. • Reproducibility of mammography image quality should be monitored by appropriate quality controls. • Use of automatic software tools allows image quality evaluation by multiple indices. • System reproducibility can be assessed comparing current index value with baseline data. • Overall system reproducibility of modern digital mammography systems is excellent. • The method proposed and applied is cost-effective and easily scalable.

  2. Reproducible and expedient rice regeneration system using in vitro ...

    African Journals Online (AJOL)

    Inevitable prerequisite for expedient regeneration in rice is the selection of totipotent explant and developing an apposite combination of growth hormones. Here, we reported a reproducible regeneration protocol in which basal segments of the stem of the in vitro grown rice plants were used as ex-plant. Using the protocol ...

  3. Intercenter reproducibility of binary typing for Staphylococcus aureus

    NARCIS (Netherlands)

    van Leeuwen, Willem B.; Snoeijers, Sandor; van der Werken-Libregts, Christel; Tuip, Anita; van der Zee, Anneke; Egberink, Diane; de Proost, Monique; Bik, Elisabeth; Lunter, Bjorn; Kluytmans, Jan; Gits, Etty; van Duyn, Inge; Heck, Max; van der Zwaluw, Kim; Wannet, Wim; Noordhoek, Gerda T.; Mulder, Sije; Renders, Nicole; Boers, Miranda; Zaat, Sebastiaan; van der Riet, Daniëlle; Kooistra, Mirjam; Talens, Adriaan; Dijkshoorn, Lenie; van der Reyden, Tanny; Veenendaal, Dick; Bakker, Nancy; Cookson, Barry; Lynch, Alisson; Witte, Wolfgang; Cuny, Christa; Blanc, Dominique; Vernez, Isabelle; Hryniewicz, Waleria; Fiett, Janusz; Struelens, Marc; Deplano, Ariane; Landegent, Jim; Verbrugh, Henri A.; van Belkum, Alex

    2002-01-01

    The reproducibility of the binary typing (BT) protocol developed for epidemiological typing of Staphylococcus aureus was analyzed in a biphasic multicenter study. In a Dutch multicenter pilot study, 10 genetically unique isolates of methicillin-resistant S. aureus (MRSA) were characterized by the BT

  4. Reproducibility of Tactile Assessments for Children with Unilateral Cerebral Palsy

    Science.gov (United States)

    Auld, Megan Louise; Ware, Robert S.; Boyd, Roslyn Nancy; Moseley, G. Lorimer; Johnston, Leanne Marie

    2012-01-01

    A systematic review identified tactile assessments used in children with cerebral palsy (CP), but their reproducibility is unknown. Sixteen children with unilateral CP and 31 typically developing children (TDC) were assessed 2-4 weeks apart. Test-retest percent agreements within one point for children with unilateral CP (and TDC) were…

  5. Modeling and evaluating repeatability and reproducibility of ordinal classifications

    NARCIS (Netherlands)

    de Mast, J.; van Wieringen, W.N.

    2010-01-01

    This paper argues that currently available methods for the assessment of the repeatability and reproducibility of ordinal classifications are not satisfactory. The paper aims to study whether we can modify a class of models from Item Response Theory, well established for the study of the reliability

  6. ReproPhylo: An Environment for Reproducible Phylogenomics.

    Directory of Open Access Journals (Sweden)

    Amir Szitenberg

    2015-09-01

    Full Text Available The reproducibility of experiments is key to the scientific process, and particularly necessary for accurate reporting of analyses in data-rich fields such as phylogenomics. We present ReproPhylo, a phylogenomic analysis environment developed to ensure experimental reproducibility, to facilitate the handling of large-scale data, and to assist methodological experimentation. Reproducibility, and instantaneous repeatability, is built in to the ReproPhylo system and does not require user intervention or configuration because it stores the experimental workflow as a single, serialized Python object containing explicit provenance and environment information. This 'single file' approach ensures the persistence of provenance across iterations of the analysis, with changes automatically managed by the version control program Git. This file, along with a Git repository, are the primary reproducibility outputs of the program. In addition, ReproPhylo produces an extensive human-readable report and generates a comprehensive experimental archive file, both of which are suitable for submission with publications. The system facilitates thorough experimental exploration of both parameters and data. ReproPhylo is a platform independent CC0 Python module and is easily installed as a Docker image or a WinPython self-sufficient package, with a Jupyter Notebook GUI, or as a slimmer version in a Galaxy distribution.

  7. Reproducibility of abdominal fat assessment by ultrasound and computed tomography.

    Science.gov (United States)

    Mauad, Fernando Marum; Chagas-Neto, Francisco Abaeté; Benedeti, Augusto César Garcia Saab; Nogueira-Barbosa, Marcello Henrique; Muglia, Valdair Francisco; Carneiro, Antonio Adilton Oliveira; Muller, Enrico Mattana; Elias Junior, Jorge

    2017-01-01

    To test the accuracy and reproducibility of ultrasound and computed tomography (CT) for the quantification of abdominal fat in correlation with the anthropometric, clinical, and biochemical assessments. Using ultrasound and CT, we determined the thickness of subcutaneous and intra-abdominal fat in 101 subjects-of whom 39 (38.6%) were men and 62 (61.4%) were women-with a mean age of 66.3 years (60-80 years). The ultrasound data were correlated with the anthropometric, clinical, and biochemical parameters, as well as with the areas measured by abdominal CT. Intra-abdominal thickness was the variable for which the correlation with the areas of abdominal fat was strongest (i.e., the correlation coefficient was highest). We also tested the reproducibility of ultrasound and CT for the assessment of abdominal fat and found that CT measurements of abdominal fat showed greater reproducibility, having higher intraobserver and interobserver reliability than had the ultrasound measurements. There was a significant correlation between ultrasound and CT, with a correlation coefficient of 0.71. In the assessment of abdominal fat, the intraobserver and interobserver reliability were greater for CT than for ultrasound, although both methods showed high accuracy and good reproducibility.

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

    Science.gov (United States)

    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.

  9. Reproducibility of contrast-enhanced transrectal ultrasound of the prostate

    NARCIS (Netherlands)

    Sedelaar, J. P.; Goossen, T. E.; Wijkstra, H.; de la Rosette, J. J.

    2001-01-01

    Transrectal three-dimensional (3-D) contrast-enhanced power Doppler ultrasound (US) is a novel technique for studying possible prostate malignancy. Before studies can be performed to investigate the clinical validity of the technique, reproducibility of the contrast US studies must be proven.

  10. Reproducibility in the assessment of acute pancreatitis with computed tomography

    International Nuclear Information System (INIS)

    Freire Filho, Edison de Oliveira; Vieira, Renata La Rocca; Yamada, Andre Fukunishi; Shigueoka, David Carlos; Bekhor, Daniel; Freire, Maxime Figueiredo de Oliveira; Ajzen, Sergio; D'Ippolito, Giuseppe

    2007-01-01

    Objective: To evaluate the reproducibility of unenhanced and contrast-enhanced computed tomography in the assessment of patients with acute pancreatitis. Materials and methods: Fifty-one unenhanced and contrast-enhanced abdominal computed tomography studies of patients with acute pancreatitis were blindly reviewed by two radiologists (observers 1 and 2). The morphological index was separately calculated for unenhanced and contrast-enhanced computed tomography and the disease severity index was established. Intraobserver and interobserver reproducibility of computed tomography was measured by means of the kappa index (κ). Results: Interobserver agreement was κ 0.666, 0.705, 0.648, 0.547 and 0.631, respectively for unenhanced and contrast-enhanced morphological index, presence of pancreatic necrosis, pancreatic necrosis extension, and disease severity index. Intraobserver agreement (observers 1 and 2, respectively) was κ = 0.796 and 0.732 for unenhanced morphological index; κ 0.725 and 0.802 for contrast- enhanced morphological index; κ = 0.674 and 0.849 for presence of pancreatic necrosis; κ = 0.606 and 0.770 for pancreatic necrosis extension; and κ = 0.801 and 0.687 for disease severity index at computed tomography. Conclusion: Computed tomography for determination of morphological index and disease severity index in the staging of acute pancreatitis is a quite reproducible method. The absence of contrast- enhancement does not affect the computed tomography morphological index reproducibility. (author)

  11. Reproducible positioning in chest X-ray radiography

    International Nuclear Information System (INIS)

    1974-01-01

    A device is described that can be used to ensure reproducibility in the positioning of the patient during X-ray radiography of the thorax. Signals are taken from an electrocardiographic monitor and from a device recording the respiratory cycle. Radiography is performed only when two preselected signals coincide

  12. Reproducibility of Manual Platelet Estimation Following Automated Low Platelet Counts

    Directory of Open Access Journals (Sweden)

    Zainab S Al-Hosni

    2016-11-01

    Full Text Available Objectives: Manual platelet estimation is one of the methods used when automated platelet estimates are very low. However, the reproducibility of manual platelet estimation has not been adequately studied. We sought to assess the reproducibility of manual platelet estimation following automated low platelet counts and to evaluate the impact of the level of experience of the person counting on the reproducibility of manual platelet estimates. Methods: In this cross-sectional study, peripheral blood films of patients with platelet counts less than 100 × 109/L were retrieved and given to four raters to perform manual platelet estimation independently using a predefined method (average of platelet counts in 10 fields using 100× objective multiplied by 20. Data were analyzed using intraclass correlation coefficient (ICC as a method of reproducibility assessment. Results: The ICC across the four raters was 0.840, indicating excellent agreement. The median difference of the two most experienced raters was 0 (range: -64 to 78. The level of platelet estimate by the least-experienced rater predicted the disagreement (p = 0.037. When assessing the difference between pairs of raters, there was no significant difference in the ICC (p = 0.420. Conclusions: The agreement between different raters using manual platelet estimation was excellent. Further confirmation is necessary, with a prospective study using a gold standard method of platelet counts.

  13. Reproducibility of Quantitative Structural and Physiological MRI Measurements

    Science.gov (United States)

    2017-08-09

    project.org/) and SPSS (IBM Corp., Armonk, NY) for data analysis. Mean and confidence inter- vals for each measure are found in Tables 1–7. To assess...visits, and was calculated using a two- way mixed model in SPSS MCV and MRD values closer to 0 are considered to be the most reproducible, and ICC

  14. Reproducibility of abdominal fat assessment by ultrasound and computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Mauad, Fernando Marum; Chagas-Neto, Francisco Abaete; Benedeti, Augusto Cesar Garcia Saab; Nogueira-Barbosa, Marcello Henrique; Muglia, Valdair Francisco; Carneiro, Antonio Adilton Oliveira; Muller, Enrico Mattana; Elias Junior, Jorge, E-mail: fernando@fatesa.edu.br [Faculdade de Tecnologia em Saude (FATESA), Ribeirao Preto, SP (Brazil); Universidade de Fortaleza (UNIFOR), Fortaleza, CE (Brazil). Departmento de Radiologia; Universidade de Sao Paulo (FMRP/USP), Ribeirao Preto, SP (Brazil). Faculdade de Medicina. Departmento de Medicina Clinica; Universidade de Sao Paulo (FFCLRP/USP), Ribeirao Preto, SP (Brazil). Faculdade de Filosofia, Ciencias e Letras; Hospital Mae de Deus, Porto Alegre, RS (Brazil)

    2017-05-15

    Objective: To test the accuracy and reproducibility of ultrasound and computed tomography (CT) for the quantification of abdominal fat in correlation with the anthropometric, clinical, and biochemical assessments. Materials and Methods: Using ultrasound and CT, we determined the thickness of subcutaneous and intra-abdominal fat in 101 subjects-of whom 39 (38.6%) were men and 62 (61.4%) were women-with a mean age of 66.3 years (60-80 years). The ultrasound data were correlated with the anthropometric, clinical, and biochemical parameters, as well as with the areas measured by abdominal CT. Results: Intra-abdominal thickness was the variable for which the correlation with the areas of abdominal fat was strongest (i.e., the correlation coefficient was highest). We also tested the reproducibility of ultrasound and CT for the assessment of abdominal fat and found that CT measurements of abdominal fat showed greater reproducibility, having higher intraobserver and interobserver reliability than had the ultrasound measurements. There was a significant correlation between ultrasound and CT, with a correlation coefficient of 0.71. Conclusion: In the assessment of abdominal fat, the intraobserver and interobserver reliability were greater for CT than for ultrasound, although both methods showed high accuracy and good reproducibility. (author)

  15. High Reproducibility of ELISPOT Counts from Nine Different Laboratories

    DEFF Research Database (Denmark)

    Sundararaman, Srividya; Karulin, Alexey Y; Ansari, Tameem

    2015-01-01

    The primary goal of immune monitoring with ELISPOT is to measure the number of T cells, specific for any antigen, accurately and reproducibly between different laboratories. In ELISPOT assays, antigen-specific T cells secrete cytokines, forming spots of different sizes on a membrane with variable...

  16. Reproducibility of the Pleth Variability Index in premature infants

    NARCIS (Netherlands)

    Den Boogert, W.J. (Wilhelmina J.); H.A. van Elteren (Hugo); T.G. Goos (Tom); I.K.M. Reiss (Irwin); R.C.J. de Jonge (Rogier); V.J. van den Berg (Victor J.)

    2017-01-01

    textabstractThe aim was to assess the reproducibility of the Pleth Variability Index (PVI), developed for non-invasive monitoring of peripheral perfusion, in preterm neonates below 32 weeks of gestational age. Three PVI measurements were consecutively performed in stable, comfortable preterm

  17. Reproducibility of the Pleth Variability Index in premature infants

    NARCIS (Netherlands)

    Den Boogert, Wilhelmina J.; Van Elteren, Hugo A.; Goos, T.G.; Reiss, Irwin K.M.; De Jonge, Rogier C.J.; van Den Berg, Victor J.

    2017-01-01

    The aim was to assess the reproducibility of the Pleth Variability Index (PVI), developed for non-invasive monitoring of peripheral perfusion, in preterm neonates below 32 weeks of gestational age. Three PVI measurements were consecutively performed in stable, comfortable preterm neonates in the

  18. Annotating with Propp's Morphology of the Folktale: Reproducibility and Trainability

    NARCIS (Netherlands)

    Fisseni, B.; Kurji, A.; Löwe, B.

    2014-01-01

    We continue the study of the reproducibility of Propp’s annotations from Bod et al. (2012). We present four experiments in which test subjects were taught Propp’s annotation system; we conclude that Propp’s system needs a significant amount of training, but that with sufficient time investment, it

  19. Exploring the Coming Repositories of Reproducible Experiments: Challenges and Opportunities

    DEFF Research Database (Denmark)

    Freire, Juliana; Bonnet, Philippe; Shasha, Dennis

    2011-01-01

    Computational reproducibility efforts in many communities will soon give rise to validated software and data repositories of high quality. A scientist in a field may want to query the components of such repositories to build new software workflows, perhaps after adding the scientist’s own algorithms...

  20. Reproducibility and consistency of proteomic experiments on natural populations of a non-model aquatic insect.

    Science.gov (United States)

    Hidalgo-Galiana, Amparo; Monge, Marta; Biron, David G; Canals, Francesc; Ribera, Ignacio; Cieslak, Alexandra

    2014-01-01

    Population proteomics has a great potential to address evolutionary and ecological questions, but its use in wild populations of non-model organisms is hampered by uncontrolled sources of variation. Here we compare the response to temperature extremes of two geographically distant populations of a diving beetle species (Agabus ramblae) using 2-D DIGE. After one week of acclimation in the laboratory under standard conditions, a third of the specimens of each population were placed at either 4 or 27°C for 12 h, with another third left as a control. We then compared the protein expression level of three replicated samples of 2-3 specimens for each treatment. Within each population, variation between replicated samples of the same treatment was always lower than variation between treatments, except for some control samples that retained a wider range of expression levels. The two populations had a similar response, without significant differences in the number of protein spots over- or under-expressed in the pairwise comparisons between treatments. We identified exemplary proteins among those differently expressed between treatments, which proved to be proteins known to be related to thermal response or stress. Overall, our results indicate that specimens collected in the wild are suitable for proteomic analyses, as the additional sources of variation were not enough to mask the consistency and reproducibility of the response to the temperature treatments.

  1. Reproducibility of airway luminal size in asthma measured by HRCT.

    Science.gov (United States)

    Brown, Robert H; Henderson, Robert J; Sugar, Elizabeth A; Holbrook, Janet T; Wise, Robert A

    2017-10-01

    Brown RH, Henderson RJ, Sugar EA, Holbrook JT, Wise RA, on behalf of the American Lung Association Airways Clinical Research Centers. Reproducibility of airway luminal size in asthma measured by HRCT. J Appl Physiol 123: 876-883, 2017. First published July 13, 2017; doi:10.1152/japplphysiol.00307.2017.-High-resolution CT (HRCT) is a well-established imaging technology used to measure lung and airway morphology in vivo. However, there is a surprising lack of studies examining HRCT reproducibility. The CPAP Trial was a multicenter, randomized, three-parallel-arm, sham-controlled 12-wk clinical trial to assess the use of a nocturnal continuous positive airway pressure (CPAP) device on airway reactivity to methacholine. The lack of a treatment effect of CPAP on clinical or HRCT measures provided an opportunity for the current analysis. We assessed the reproducibility of HRCT imaging over 12 wk. Intraclass correlation coefficients (ICCs) were calculated for individual airway segments, individual lung lobes, both lungs, and air trapping. The ICC [95% confidence interval (CI)] for airway luminal size at total lung capacity ranged from 0.95 (0.91, 0.97) to 0.47 (0.27, 0.69). The ICC (95% CI) for airway luminal size at functional residual capacity ranged from 0.91 (0.85, 0.95) to 0.32 (0.11, 0.65). The ICC measurements for airway distensibility index and wall thickness were lower, ranging from poor (0.08) to moderate (0.63) agreement. The ICC for air trapping at functional residual capacity was 0.89 (0.81, 0.94) and varied only modestly by lobe from 0.76 (0.61, 0.87) to 0.95 (0.92, 0.97). In stable well-controlled asthmatic subjects, it is possible to reproducibly image unstimulated airway luminal areas over time, by region, and by size at total lung capacity throughout the lungs. Therefore, any changes in luminal size on repeat CT imaging are more likely due to changes in disease state and less likely due to normal variability. NEW & NOTEWORTHY There is a surprising lack

  2. Microarray analysis of gender- and parasite-specific gene transcription in Strongyloides ratti

    NARCIS (Netherlands)

    Evans, Helen; Mello, Luciane V.; Fang, Yongxiang; Wit, Ernst; Thompson, Fiona J.; Viney, Mark E.; Paterson, Steve

    2008-01-01

    The molecular mechanisms by which parasitic nematodes reproduce and have adapted to life within a host are unclear. In the present study, microarray analysis was used to explore differential transcription among the different stages and sexes of Strongyloides ratti, a parasitic nematode of brown

  3. Variational principles

    CERN Document Server

    Moiseiwitsch, B L

    2004-01-01

    This graduate-level text's primary objective is to demonstrate the expression of the equations of the various branches of mathematical physics in the succinct and elegant form of variational principles (and thereby illuminate their interrelationship). Its related intentions are to show how variational principles may be employed to determine the discrete eigenvalues for stationary state problems and to illustrate how to find the values of quantities (such as the phase shifts) that arise in the theory of scattering. Chapter-by-chapter treatment consists of analytical dynamics; optics, wave mecha

  4. Review: The transcripts associated with organ allograft rejection.

    Science.gov (United States)

    Halloran, Philip F; Venner, Jeffery M; Madill-Thomsen, Katelynn S; Einecke, Gunilla; Parkes, Michael D; Hidalgo, Luis G; Famulski, Konrad S

    2018-04-01

    The molecular mechanisms operating in human organ transplant rejection are best inferred from the mRNAs expressed in biopsies because the corresponding proteins often have low expression and short half-lives, while small non-coding RNAs lack specificity. Associations should be characterized in a population that rigorously identifies T cell-mediated (TCMR) and antibody-mediated rejection (ABMR). This is best achieved in kidney transplant biopsies, but the results are generalizable to heart, lung, or liver transplants. Associations can be universal (all rejection), TCMR-selective, or ABMR-selective, with universal being strongest and ABMR-selective weakest. Top universal transcripts are IFNG-inducible (eg, CXCL11 IDO1, WARS) or shared by effector T cells (ETCs) and NK cells (eg, KLRD1, CCL4). TCMR-selective transcripts are expressed in activated ETCs (eg, CTLA4, IFNG), activated (eg, ADAMDEC1), or IFNG-induced macrophages (eg, ANKRD22). ABMR-selective transcripts are expressed in NK cells (eg, FGFBP2, GNLY) and endothelial cells (eg, ROBO4, DARC). Transcript associations are highly reproducible between biopsy sets when the same rejection definitions, case mix, algorithm, and technology are applied, but exact ranks will vary. Previously published rejection-associated transcripts resemble universal and TCMR-selective transcripts due to incomplete representation of ABMR. Rejection-associated transcripts are never completely rejection-specific because they are shared with the stereotyped response-to-injury and innate immunity. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

  5. Variation in RNA-Seq transcriptome profiles of peripheral whole blood from healthy individuals with and without globin depletion.

    Directory of Open Access Journals (Sweden)

    Heesun Shin

    Full Text Available BACKGROUND: The molecular profile of circulating blood can reflect physiological and pathological events occurring in other tissues and organs of the body and delivers a comprehensive view of the status of the immune system. Blood has been useful in studying the pathobiology of many diseases. It is accessible and easily collected making it ideally suited to the development of diagnostic biomarker tests. The blood transcriptome has a high complement of globin RNA that could potentially saturate next-generation sequencing platforms, masking lower abundance transcripts. Methods to deplete globin mRNA are available, but their effect has not been comprehensively studied in peripheral whole blood RNA-Seq data. In this study we aimed to assess technical variability associated with globin depletion in addition to assessing general technical variability in RNA-Seq from whole blood derived samples. RESULTS: We compared technical and biological replicates having undergone globin depletion or not and found that the experimental globin depletion protocol employed removed approximately 80% of globin transcripts, improved the correlation of technical replicates, allowed for reliable detection of thousands of additional transcripts and generally increased transcript abundance measures. Differential expression analysis revealed thousands of genes significantly up-regulated as a result of globin depletion. In addition, globin depletion resulted in the down-regulation of genes involved in both iron and zinc metal ion bonding. CONCLUSIONS: Globin depletion appears to meaningfully improve the quality of peripheral whole blood RNA-Seq data, and may improve our ability to detect true biological variation. Some concerns remain, however. Key amongst them the significant reduction in RNA yields following globin depletion. More generally, our investigation of technical and biological variation with and without globin depletion finds that high-throughput sequencing by RNA

  6. Shot-to-shot reproducibility of a self-magnetically insulated ion diode

    International Nuclear Information System (INIS)

    Pushkarev, A. I.; Isakova, Yu. I.; Khailov, I. P.

    2012-01-01

    In this paper we present the analysis of shot to shot reproducibility of the ion beam which is formed by a self-magnetically insulated ion diode with an explosive emission graphite cathode. The experiments were carried out with the TEMP-4M accelerator operating in double-pulse mode: the first pulse is of negative polarity (300–500 ns, 100–150 kV), and this is followed by a second pulse of positive polarity (150 ns, 250–300 kV). The ion current density was 10–70 A/cm 2 depending on the diode geometry. The beam was composed from carbon ions (80%–85%) and protons. It was found that shot to shot variation in the ion current density was about 35%–40%, whilst the diode voltage and current were comparatively stable with the variation limited to no more than 10%. It was shown that focusing of the ion beam can improve the stability of the ion current generation and reduces the variation to 18%–20%. In order to find out the reason for the shot-to-shot variation in ion current density we examined the statistical correlation between the current density of the accelerated beam and other measured characteristics of the diode, such as the accelerating voltage, total current, and first pulse duration. The correlation between the ion current density measured simultaneously at different positions within the cross-section of the beam was also investigated. It was shown that the shot-to-shot variation in ion current density is mainly attributed to the variation in the density of electrons diffusing from the drift region into the A-K gap.

  7. An inter-laboratory comparison of urinary 3-hydroxypropylmercapturic acid measurement demonstrates good reproducibility between laboratories

    Directory of Open Access Journals (Sweden)

    Bailey Brian

    2011-10-01

    Full Text Available Abstract Background Biomarkers have been used extensively in clinical studies to assess toxicant exposure in smokers and non-smokers and have recently been used in the evaluation of novel tobacco products. The urinary metabolite 3-HPMA, a metabolite of the major tobacco smoke toxicity contributor acrolein, is one example of a biomarker used to measure exposure to tobacco smoke. A number of laboratories have developed liquid chromatography with tandem mass spectrometry (LC-MS/MS based methods to measure urinary 3-HPMA; however, it is unclear to what extent the data obtained by these different laboratories are comparable. Findings This report describes an inter-laboratory comparison carried out to evaluate the comparability of 3-HPMA measurement between four laboratories. A common set of spiked and authentic smoker and non-smoker urine samples were used. Each laboratory used their in-house LC-MS/MS method and a common internal standard. A comparison of the repeatability ('r', reproducibility ('R', and coefficient of variation for 3-HPMA demonstrated that within-laboratory variation was consistently lower than between-laboratory variation. The average inter-laboratory coefficient of variation was 7% for fortified urine samples and 16.2% for authentic urine samples. Together, this represents an inter-laboratory variation of 12.2%. Conclusion The results from this first inter-laboratory comparison for the measurement of 3-HPMA in urine demonstrate a reasonably good consensus between laboratories. However, some consistent measurement biases were still observed between laboratories, suggesting that additional work may be required to further reduce the inter-laboratory coefficient of variation.

  8. Properties of the reverse transcription reaction in mRNA quantification

    DEFF Research Database (Denmark)

    Ståhlberg, Anders; Håkansson, Joakim; Xian, Xiaojie

    2004-01-01

    BACKGROUND: In most measurements of gene expression, mRNA is first reverse-transcribed into cDNA. We studied the reverse transcription reaction and its consequences for quantitative measurements of gene expression. METHODS: We used SYBR green I-based quantitative real-time PCR (QPCR) to measure...... the properties of reverse transcription reaction for the beta-tubulin, glyceraldehyde-3-phosphate dehydrogenase, Glut2, CaV1D, and insulin II genes, using random hexamers, oligo(dT), and gene-specific reverse transcription primers. RESULTS: Experimental variation in reverse transcription-QPCR (RT......-QPCR) was mainly attributable to the reverse transcription step. Reverse transcription efficiency depended on priming strategy, and the dependence was different for the five genes studied. Reverse transcription yields also depended on total RNA concentration. CONCLUSIONS: RT-QPCR gene expression measurements...

  9. Extensive Variation in Chromatin States Across Humans

    KAUST Repository

    Kasowski, M.

    2013-10-17

    The majority of disease-associated variants lie outside protein-coding regions, suggesting a link between variation in regulatory regions and disease predisposition. We studied differences in chromatin states using five histone modifications, cohesin, and CTCF in lymphoblastoid lines from 19 individuals of diverse ancestry. We found extensive signal variation in regulatory regions, which often switch between active and repressed states across individuals. Enhancer activity is particularly diverse among individuals, whereas gene expression remains relatively stable. Chromatin variability shows genetic inheritance in trios, correlates with genetic variation and population divergence, and is associated with disruptions of transcription factor binding motifs. Overall, our results provide insights into chromatin variation among humans.

  10. Extensive Variation in Chromatin States Across Humans

    KAUST Repository

    Kasowski, M.; Kyriazopoulou-Panagiotopoulou, S.; Grubert, F.; Zaugg, J. B.; Kundaje, A.; Liu, Y.; Boyle, A. P.; Zhang, Q. C.; Zakharia, F.; Spacek, D. V.; Li, J.; Xie, D.; Olarerin-George, A.; Steinmetz, L. M.; Hogenesch, J. B.; Kellis, M.; Batzoglou, S.; Snyder, M.

    2013-01-01

    The majority of disease-associated variants lie outside protein-coding regions, suggesting a link between variation in regulatory regions and disease predisposition. We studied differences in chromatin states using five histone modifications, cohesin, and CTCF in lymphoblastoid lines from 19 individuals of diverse ancestry. We found extensive signal variation in regulatory regions, which often switch between active and repressed states across individuals. Enhancer activity is particularly diverse among individuals, whereas gene expression remains relatively stable. Chromatin variability shows genetic inheritance in trios, correlates with genetic variation and population divergence, and is associated with disruptions of transcription factor binding motifs. Overall, our results provide insights into chromatin variation among humans.

  11. Detection of HCV-RNA by Reverse Transcription Polymerase Chain Reaction Using Biotinylated and Radioiodinated Primers

    International Nuclear Information System (INIS)

    Ryu, Jin Sook; Moon, Dae Hyuk; Cheon, Jun Hong; Chung, Yoon Young; Park, Hung Dong; Chung, Young Hwa; Lee, Young Sang

    1994-01-01

    This study was performed to evaluate the clinical applicability of the reverse transcription polymerase chain reaction (RT-PCR) kit of HCV-RNA using biotinylated and radioiodinated primers. Study subjects were 118 patients with positive anti-HCV. HCV-RNA in patients serum was extracted by guanidium thiocyanate method. After first amplification, the product was reamplified by primers labelled with biotin and I-125. The final amplification product was detected by counting the radioactivity after incubation in avidin coated tubes. In 51 samples, the test was repeated for evaluation of reproducibility. This new method was also compared with conventional RT-PCR methods in 34 samples from patients with chronic liver disease. The results were as follows, 1) HCV-RNA was positive in 85(97%)of 88 patients with chronic liver disease, and in 23 (73%) of 30 patients with normal liver function. 2) In comparison with conventional method, HCV-RNA was detected in 32(94%) of 34 patients with new method, whereas in 27(79% ) of the same group with conventional method 3) Repeated test with new method in 52 samples demonstrated 82% of concordant result. In conclusion, new method with biotinylated and radioiodinated primers was more sensitive than conventional method. However, great care must be taken for quality control because there were considerable interassay variation and possibility of false positivity and false negativity.

  12. Detection of HCV-RNA by Reverse Transcription Polymerase Chain Reaction Using Biotinylated and Radioiodinated Primers

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Jin Sook; Moon, Dae Hyuk; Cheon, Jun Hong; Chung, Yoon Young; Park, Hung Dong; Chung, Young Hwa; Lee, Young Sang [Asan Medical Center, University of Ulsan, Seoul (Korea, Republic of)

    1994-07-15

    This study was performed to evaluate the clinical applicability of the reverse transcription polymerase chain reaction (RT-PCR) kit of HCV-RNA using biotinylated and radioiodinated primers. Study subjects were 118 patients with positive anti-HCV. HCV-RNA in patients serum was extracted by guanidium thiocyanate method. After first amplification, the product was reamplified by primers labelled with biotin and I-125. The final amplification product was detected by counting the radioactivity after incubation in avidin coated tubes. In 51 samples, the test was repeated for evaluation of reproducibility. This new method was also compared with conventional RT-PCR methods in 34 samples from patients with chronic liver disease. The results were as follows, 1) HCV-RNA was positive in 85(97%)of 88 patients with chronic liver disease, and in 23 (73%) of 30 patients with normal liver function. 2) In comparison with conventional method, HCV-RNA was detected in 32(94%) of 34 patients with new method, whereas in 27(79% ) of the same group with conventional method 3) Repeated test with new method in 52 samples demonstrated 82% of concordant result. In conclusion, new method with biotinylated and radioiodinated primers was more sensitive than conventional method. However, great care must be taken for quality control because there were considerable interassay variation and possibility of false positivity and false negativity.

  13. Evaluation of the reproducibility of amplicon sequencing with Illumina MiSeq platform.

    Science.gov (United States)

    Wen, Chongqing; Wu, Liyou; Qin, Yujia; Van Nostrand, Joy D; Ning, Daliang; Sun, Bo; Xue, Kai; Liu, Feifei; Deng, Ye; Liang, Yuting; Zhou, Jizhong

    2017-01-01

    Illumina's MiSeq has become the dominant platform for gene amplicon sequencing in microbial ecology studies; however, various technical concerns, such as reproducibility, still exist. To assess reproducibility, 16S rRNA gene amplicons from 18 soil samples of a reciprocal transplantation experiment were sequenced on an Illumina MiSeq. The V4 region of 16S rRNA gene from each sample was sequenced in triplicate with each replicate having a unique barcode. The average OTU overlap, without considering sequence abundance, at a rarefaction level of 10,323 sequences was 33.4±2.1% and 20.2±1.7% between two and among three technical replicates, respectively. When OTU sequence abundance was considered, the average sequence abundance weighted OTU overlap was 85.6±1.6% and 81.2±2.1% for two and three replicates, respectively. Removing singletons significantly increased the overlap for both (~1-3%, pdeep sequencing increased OTU overlap both when sequence abundance was considered (95%) and when not (44%). However, if singletons were not removed the overlap between two technical replicates (not considering sequence abundance) plateaus at 39% with 30,000 sequences. Diversity measures were not affected by the low overlap as α-diversities were similar among technical replicates while β-diversities (Bray-Curtis) were much smaller among technical replicates than among treatment replicates (e.g., 0.269 vs. 0.374). Higher diversity coverage, but lower OTU overlap, was observed when replicates were sequenced in separate runs. Detrended correspondence analysis indicated that while there was considerable variation among technical replicates, the reproducibility was sufficient for detecting treatment effects for the samples examined. These results suggest that although there is variation among technical replicates, amplicon sequencing on MiSeq is useful for analyzing microbial community structure if used appropriately and with caution. For example, including technical replicates

  14. Reproducibility of in-vivo diffusion tensor cardiovascular magnetic resonance in hypertrophic cardiomyopathy

    Directory of Open Access Journals (Sweden)

    McGill Laura-Ann

    2012-12-01

    Full Text Available Abstract Background Myocardial disarray is an important histological feature of hypertrophic cardiomyopathy (HCM which has been studied post-mortem, but its in-vivo prevalence and extent is unknown. Cardiac Diffusion Tensor Imaging (cDTI provides information on mean intravoxel myocyte orientation and potentially myocardial disarray. Recent technical advances have improved in-vivo cDTI, and the aim of this study was to assess the interstudy reproducibility of quantitative in-vivo cDTI in patients with HCM. Methods and results A stimulated-echo single-shot-EPI sequence with zonal excitation and parallel imaging was implemented. Ten patients with HCM were each scanned on 2 different days. For each scan 3 short axis mid-ventricular slices were acquired with cDTI at end systole. Fractional anisotropy (FA, mean diffusivity (MD, and helix angle (HA maps were created using a cDTI post-processing platform developed in-house. The mean ± SD global FA was 0.613 ± 0.044, MD was 0.750 ± 0.154 × 10-3 mm2/s and HA was epicardium −34.3 ± 7.6°, mesocardium 3.5 ± 6.9° and endocardium 38.9 ± 8.1°. Comparison of initial and repeat studies showed global interstudy reproducibility for FA (SD = ± 0.045, Coefficient of Variation (CoV = 7.2%, MD (SD = ± 0.135 × 10-3 mm2/s, CoV = 18.6% and HA (epicardium SD = ± 4.8°; mesocardium SD = ± 3.4°; endocardium SD = ± 2.9°. Reproducibility of FA was superior to MD (p = 0.003. Global MD was significantly higher in the septum than the reference lateral wall (0.784 ± 0.188 vs 0.750 ± 0.154 x10-3 mm2/s, p  Conclusions To the best of our knowledge, this is the first study to assess the interstudy reproducibility of DTI in the human HCM heart in-vivo and the largest cDTI study in HCM to date. Our results show good reproducibility of FA, MD and HA which indicates that current technology yields robust in-vivo measurements that have potential clinical value. The

  15. Reproducible analyses of microbial food for advanced life support systems

    Science.gov (United States)

    Petersen, Gene R.

    1988-01-01

    The use of yeasts in controlled ecological life support systems (CELSS) for microbial food regeneration in space required the accurate and reproducible analysis of intracellular carbohydrate and protein levels. The reproducible analysis of glycogen was a key element in estimating overall content of edibles in candidate yeast strains. Typical analytical methods for estimating glycogen in Saccharomyces were not found to be entirely aplicable to other candidate strains. Rigorous cell lysis coupled with acid/base fractionation followed by specific enzymatic glycogen analyses were required to obtain accurate results in two strains of Candida. A profile of edible fractions of these strains was then determined. The suitability of yeasts as food sources in CELSS food production processes is discussed.

  16. Tools for Reproducibility and Extensibility in Scientific Research

    CERN Multimedia

    CERN. Geneva

    2018-01-01

    Open inquiry through reproducing results is fundamental to the scientific process. Contemporary research relies on software engineering pipelines to collect, process, and analyze data. The open source projects within Project Jupyter facilitate these objectives by bringing software engineering within the context of scientific communication. We will highlight specific projects that are computational building blocks for scientific communication, starting with the Jupyter Notebook. We will also explore applications of projects that build off of the Notebook such as Binder, JupyterHub, and repo2docker. We will discuss how these projects can individually and jointly improve reproducibility in scientific communication. Finally, we will demonstrate applications of Jupyter software that allow researchers to build upon the code of other scientists, both to extend their work and the work of others.    There will be a follow-up demo session in the afternoon, hosted by iML. Details can be foun...

  17. MASSIVE DATA, THE DIGITIZATION OF SCIENCE, AND REPRODUCIBILITY OF RESULTS

    CERN Multimedia

    CERN. Geneva

    2010-01-01

    As the scientific enterprise becomes increasingly computational and data-driven, the nature of the information communicated must change. Without inclusion of the code and data with published computational results, we are engendering a credibility crisis in science. Controversies such as ClimateGate, the microarray-based drug sensitivity clinical trials under investigation at Duke University, and retractions from prominent journals due to unverified code suggest the need for greater transparency in our computational science. In this talk I argue that the scientific method be restored to (1) a focus on error control as central to scientific communication and (2) complete communication of the underlying methodology producing the results, ie. reproducibility. I outline barriers to these goals based on recent survey work (Stodden 2010), and suggest solutions such as the “Reproducible Research Standard” (Stodden 2009), giving open licensing options designed to create an intellectual property framework for scien...

  18. Timbral aspects of reproduced sound in small rooms. I

    DEFF Research Database (Denmark)

    Bech, Søren

    1995-01-01

    , has been simulated using an electroacoustic setup. The model included the direct sound, 17 individual reflections, and the reverberant field. The threshold of detection and just-noticeable differences for an increase in level were measured for individual reflections using eight subjects for noise......This paper reports some of the influences of individual reflections on the timbre of reproduced sound. A single loudspeaker with frequency-independent directivity characteristics, positioned in a listening room of normal size with frequency-independent absorption coefficients of the room surfaces...... and speech. The results have shown that the first-order floor and ceiling reflections are likely to individually contribute to the timbre of reproduced speech. For a noise signal, additional reflections from the left sidewall will contribute individually. The level of the reverberant field has been found...

  19. Transition questions in clinical practice - validity and reproducibility

    DEFF Research Database (Denmark)

    Lauridsen, Henrik Hein

    2008-01-01

    Transition questions in CLINICAL practice - validity and reproducibility Lauridsen HH1, Manniche C3, Grunnet-Nilsson N1, Hartvigsen J1,2 1   Clinical Locomotion Science, Institute of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense, Denmark. e-mail: hlauridsen......@health.sdu.dk 2   Nordic Institute of Chiropractic and Clinical Biomechanics, Part of Clinical Locomotion Science, Odense, Denmark 3   Backcenter Funen, Part of Clinical Locomotion Science, Ringe, Denmark   Abstract  Understanding a change score is indispensable for interpretation of results from clinical studies...... are reproducible in patients with low back pain and/or leg pain. Despite critique of several biases, our results have reinforced the construct validity of TQ’s as an outcome measure since only 1 hypothesis was rejected. On the basis of our findings we have outlined a proposal for a standardised use of transition...

  20. Properties of galaxies reproduced by a hydrodynamic simulation

    Science.gov (United States)

    Vogelsberger, M.; Genel, S.; Springel, V.; Torrey, P.; Sijacki, D.; Xu, D.; Snyder, G.; Bird, S.; Nelson, D.; Hernquist, L.

    2014-05-01

    Previous simulations of the growth of cosmic structures have broadly reproduced the `cosmic web' of galaxies that we see in the Universe, but failed to create a mixed population of elliptical and spiral galaxies, because of numerical inaccuracies and incomplete physical models. Moreover, they were unable to track the small-scale evolution of gas and stars to the present epoch within a representative portion of the Universe. Here we report a simulation that starts 12 million years after the Big Bang, and traces 13 billion years of cosmic evolution with 12 billion resolution elements in a cube of 106.5 megaparsecs a side. It yields a reasonable population of ellipticals and spirals, reproduces the observed distribution of galaxies in clusters and characteristics of hydrogen on large scales, and at the same time matches the `metal' and hydrogen content of galaxies on small scales.

  1. LHC Orbit Correction Reproducibility and Related Machine Protection

    CERN Document Server

    Baer, T; Schmidt, R; Wenninger, J

    2012-01-01

    The Large Hadron Collider (LHC) has an unprecedented nominal stored beam energy of up to 362 MJ per beam. In order to ensure an adequate machine protection by the collimation system, a high reproducibility of the beam position at collimators and special elements like the final focus quadrupoles is essential. This is realized by a combination of manual orbit corrections, feed forward and real time feedback. In order to protect the LHC against inconsistent orbit corrections, which could put the machine in a vulnerable state, a novel software-based interlock system for orbit corrector currents was developed. In this paper, the principle of the new interlock system is described and the reproducibility of the LHC orbit correction is discussed against the background of this system.

  2. Towards reproducibility of research by reuse of IT best practices

    CERN Multimedia

    CERN. Geneva

    2013-01-01

    Reproducibility of any research gives much higher credibility both to research results and to the researchers. This is true for any kind of research including computer science, where a lot of tools and approaches have been developed to ensure reproducibility. In this talk I will focus on basic and seemingly simple principles, which sometimes look too obvious to follow, but help researchers build beautiful and reliable systems that produce consistent, measurable results. My talk will cover, among other things, the problem of embedding machine learning techniques into analysis strategy. I will also speak about the most common pitfalls in this process and how to avoid them. In addition, I will demonstrate the research environment based on the principles that I will have outlined. About the speaker Andrey Ustyuzhanin (36) is Head of CERN partnership program at Yandex. He is involved in the development of event indexing and event filtering services which Yandex has been providing for the LHCb experiment sinc...

  3. Reproducibility of Computer-Aided Detection Marks in Digital Mammography

    International Nuclear Information System (INIS)

    Kim, Seung Ja; Moon, Woo Kyung; Cho, Nariya; Kim, Sun Mi; Im, Jung Gi; Cha, Joo Hee

    2007-01-01

    To evaluate the performance and reproducibility of a computeraided detection (CAD) system in mediolateral oblique (MLO) digital mammograms taken serially, without release of breast compression. A CAD system was applied preoperatively to the fulfilled digital mammograms of two MLO views taken without release of breast compression in 82 patients (age range: 33 83 years; mean age: 49 years) with previously diagnosed breast cancers. The total number of visible lesion components in 82 patients was 101: 66 masses and 35 microcalcifications. We analyzed the sensitivity and reproducibility of the CAD marks. The sensitivity of the CAD system for first MLO views was 71% (47/66) for masses and 80% (28/35) for microcalcifications. The sensitivity of the CAD system for second MLO views was 68% (45/66) for masses and 17% (6/35) for microcalcifications. In 84 ipsilateral serial MLO image sets (two patients had bilateral cancers), identical images, regardless of the existence of CAD marks, were obtained for 35% (29/84) and identical images with CAD marks were obtained for 29% (23/78). Identical images, regardless of the existence of CAD marks, for contralateral MLO images were 65% (52/80) and identical images with CAD marks were obtained for 28% (11/39). The reproducibility of CAD marks for the true positive masses in serial MLO views was 84% (42/50) and that for the true positive microcalcifications was 0% (0/34). The CAD system in digital mammograms showed a high sensitivity for detecting masses and microcalcifications. However, reproducibility of microcalcification marks was very low in MLO views taken serially without release of breast compression. Minute positional change and patient movement can alter the images and result in a significant effect on the algorithm utilized by the CAD for detecting microcalcifications

  4. Automated Generation of Technical Documentation and Provenance for Reproducible Research

    Science.gov (United States)

    Jolly, B.; Medyckyj-Scott, D.; Spiekermann, R.; Ausseil, A. G.

    2017-12-01

    Data provenance and detailed technical documentation are essential components of high-quality reproducible research, however are often only partially addressed during a research project. Recording and maintaining this information during the course of a project can be a difficult task to get right as it is a time consuming and often boring process for the researchers involved. As a result, provenance records and technical documentation provided alongside research results can be incomplete or may not be completely consistent with the actual processes followed. While providing access to the data and code used by the original researchers goes some way toward enabling reproducibility, this does not count as, or replace, data provenance. Additionally, this can be a poor substitute for good technical documentation and is often more difficult for a third-party to understand - particularly if they do not understand the programming language(s) used. We present and discuss a tool built from the ground up for the production of well-documented and reproducible spatial datasets that are created by applying a series of classification rules to a number of input layers. The internal model of the classification rules required by the tool to process the input data is exploited to also produce technical documentation and provenance records with minimal additional user input. Available provenance records that accompany input datasets are incorporated into those that describe the current process. As a result, each time a new iteration of the analysis is performed the documentation and provenance records are re-generated to provide an accurate description of the exact process followed. The generic nature of this tool, and the lessons learned during its creation, have wider application to other fields where the production of derivative datasets must be done in an open, defensible, and reproducible way.

  5. Towards reproducible MSMS data preprocessing, quality control and quantification

    OpenAIRE

    Gatto, Laurent; Lilley, Kathryn S.

    2010-01-01

    The development of MSnbase aims at providing researchers dealing with labelled quantitative proteomics data with a transparent, portable, extensible and open-source collaborative framework to easily manipulate and analyse MS2-level raw tandem mass spectrometry data. The implementation in R gives users and developers a great variety of powerful tools to be used in a controlled and reproducible way. Furthermore, MSnbase has been developed following an object-oriented programming paradigm: all i...

  6. Cuban strategy for reproducing, preserving and developing nuclear knowledge

    International Nuclear Information System (INIS)

    Elias Hardy, L.L.; Guzman Martinez, F.; Rodriguez Hoyos, O.E.; Lopez Nunez, A.F.

    2006-01-01

    One of the problems in the changing world is the preservation of knowledge for the next human generation, and nuclear knowledge is not an exception. Cuba has worked for reproducing, preserving, developing and capturing nuclear knowledge, mainly through a higher education centre, the Higher Institute of Nuclear Sciences and Technologies. This institute is a component of a national network in the preparation of manpower not only for nuclear activities but also for environmental and managerial activities too. (author)

  7. Regulating Ultrasound Cavitation in order to Induce Reproducible Sonoporation

    Science.gov (United States)

    Mestas, J.-L.; Alberti, L.; El Maalouf, J.; Béra, J.-C.; Gilles, B.

    2010-03-01

    Sonoporation would be linked to cavitation, which generally appears to be a non reproducible and unstationary phenomenon. In order to obtain an acceptable trade-off between cell mortality and transfection, a regulated cavitation generator based on an acoustical cavitation measurement was developed and tested. The medium to be sonicated is placed in a sample tray. This tray is immersed in in degassed water and positioned above the face of a flat ultrasonic transducer (frequency: 445 kHz; intensity range: 0.08-1.09 W/cm2). This technical configuration was admitted to be conducive to standing-wave generation through reflection at the air/medium interface in the well thus enhancing the cavitation phenomenon. Laterally to the transducer, a homemade hydrophone was oriented to receive the acoustical signal from the bubbles. From this spectral signal recorded at intervals of 5 ms, a cavitation index was calculated as the mean of the cavitation spectrum integration in a logarithmic scale, and the excitation power is automatically corrected. The device generates stable and reproducible cavitation level for a wide range of cavitation setpoint from stable cavitation condition up to full-developed inertial cavitation. For the ultrasound intensity range used, the time delay of the response is lower than 200 ms. The cavitation regulation device was evaluated in terms of chemical bubble collapse effect. Hydroxyl radical production was measured on terephthalic acid solutions. In open loop, the results present a great variability whatever the excitation power. On the contrary the closed loop allows a great reproducibility. This device was implemented for study of sonodynamic effect. The regulation provides more reproducible results independent of cell medium and experimental conditions (temperature, pressure). Other applications of this regulated cavitation device concern internalization of different particles (Quantum Dot) molecules (SiRNA) or plasmids (GFP, DsRed) into different

  8. Serous tubal intraepithelial carcinoma: diagnostic reproducibility and its implications.

    Science.gov (United States)

    Carlson, Joseph W; Jarboe, Elke A; Kindelberger, David; Nucci, Marisa R; Hirsch, Michelle S; Crum, Christopher P

    2010-07-01

    Serous tubal intraepithelial carcinoma (STIC) is detected in between 5% and 7% of women undergoing risk-reduction salpingooophorectomy for mutations in the BRCA1 or 2 genes (BRCA+), and seems to play a role in the pathogenesis of many ovarian and "primary peritoneal" serous carcinomas. The recognition of STIC is germane to the management of BRCA+ women; however, the diagnostic reproducibility of STIC is unknown. Twenty-one cases were selected and classified as STIC or benign, using both hematoxylin and eosin and immunohistochemical stains for p53 and MIB-1. Digital images of 30 hematoxylin and eosin-stained STICs (n=14) or benign tubal epithelium (n=16) were photographed and randomized for blind digital review in a Powerpoint format by 6 experienced gynecologic pathologists and 6 pathology trainees. A generalized kappa statistic for multiple raters was calculated for all groups. For all reviewers, the kappa was 0.333, indicating poor reproducibility; kappa was 0.453 for the experienced gynecologic pathologists (fair-to-good reproducibility), and kappa=0.253 for the pathology residents (poor reproducibility). In the experienced group, 3 of 14 STICs were diagnosed by all 6 reviewers, and 9 of 14 by a majority of the reviewers. These results show that interobserver concordance in the recognition of STIC in high-quality digital images is at best fair-to-good for even experienced gynecologic pathologists, and a proportion cannot be consistently identified even among experienced observers. In view of these findings, a diagnosis of STIC should be corroborated by a second pathologist, if feasible.

  9. Adaptive Learning in Cartesian Product of Reproducing Kernel Hilbert Spaces

    OpenAIRE

    Yukawa, Masahiro

    2014-01-01

    We propose a novel adaptive learning algorithm based on iterative orthogonal projections in the Cartesian product of multiple reproducing kernel Hilbert spaces (RKHSs). The task is estimating/tracking nonlinear functions which are supposed to contain multiple components such as (i) linear and nonlinear components, (ii) high- and low- frequency components etc. In this case, the use of multiple RKHSs permits a compact representation of multicomponent functions. The proposed algorithm is where t...

  10. Reproducibility Test for Thermoluminescence Dosimeter (TLD) Using TLD Radpro

    International Nuclear Information System (INIS)

    Nur Khairunisa Zahidi; Ahmad Bazlie Abdul Kadir; Faizal Azrin Abdul Razalim

    2016-01-01

    Thermoluminescence dosimeters (TLD) as one type of dosimeter which are often used to substitute the film badge. Like a film badge, it is worn for a period of time and then must be processed to determine the dose received. This study was to test the reproducibility of TLD using Radpro reader. This study aimed to determine the dose obtained by TLD-100 chips when irradiated with Co-60 gamma source and to test the effectiveness of TLD Radpro reader as a machine to analyse the TLD. Ten chips of TLD -100 were irradiated using Eldorado machine with Co-60 source at a distance of 5 meters from the source with 2 mSv dose exposure. After the irradiation process, TLD-100 chips were read using the TLD Radpro reader. These steps will be repeated for nine times to obtain reproducibility coefficient, r i . The readings of dose obtained from experiment was almost equivalent to the actual dose. Results shows that the average value obtained for reproducibility coefficient, r i is 6.39 % which is less than 10 %. As conclusion, the dose obtained from experiment considered accurate because its value were almost equivalent to the actual dose and TLD Radpro was verified as a good reader to analyse the TLD. (author)

  11. Reproducibility of the Portuguese version of the PEDro Scale

    Directory of Open Access Journals (Sweden)

    Silvia Regina Shiwa

    2011-10-01

    Full Text Available The objective of this study was to test the inter-rater reproducibility of the Portuguese version of the PEDro Scale. Seven physiotherapists rated the methodological quality of 50 reports of randomized controlled trials written in Portuguese indexed on the PEDro database. Each report was also rated using the English version of the PEDro Scale. Reproducibility was evaluated by comparing two separate ratings of reports written in Portuguese and comparing the Portuguese PEDro score with the English version of the scale. Kappa coefficients ranged from 0.53 to 1.00 for individual item and an intraclass correlation coefficient (ICC of 0.82 for the total PEDro score was observed. The standard error of the measurement of the scale was 0.58. The Portuguese version of the scale was comparable with the English version, with an ICC of 0.78. The inter-rater reproducibility of the Brazilian Portuguese PEDro Scale is adequate and similar to the original English version.

  12. Can cancer researchers accurately judge whether preclinical reports will reproduce?

    Directory of Open Access Journals (Sweden)

    Daniel Benjamin

    2017-06-01

    Full Text Available There is vigorous debate about the reproducibility of research findings in cancer biology. Whether scientists can accurately assess which experiments will reproduce original findings is important to determining the pace at which science self-corrects. We collected forecasts from basic and preclinical cancer researchers on the first 6 replication studies conducted by the Reproducibility Project: Cancer Biology (RP:CB to assess the accuracy of expert judgments on specific replication outcomes. On average, researchers forecasted a 75% probability of replicating the statistical significance and a 50% probability of replicating the effect size, yet none of these studies successfully replicated on either criterion (for the 5 studies with results reported. Accuracy was related to expertise: experts with higher h-indices were more accurate, whereas experts with more topic-specific expertise were less accurate. Our findings suggest that experts, especially those with specialized knowledge, were overconfident about the RP:CB replicating individual experiments within published reports; researcher optimism likely reflects a combination of overestimating the validity of original studies and underestimating the difficulties of repeating their methodologies.

  13. On the origin of reproducible sequential activity in neural circuits

    Science.gov (United States)

    Afraimovich, V. S.; Zhigulin, V. P.; Rabinovich, M. I.

    2004-12-01

    Robustness and reproducibility of sequential spatio-temporal responses is an essential feature of many neural circuits in sensory and motor systems of animals. The most common mathematical images of dynamical regimes in neural systems are fixed points, limit cycles, chaotic attractors, and continuous attractors (attractive manifolds of neutrally stable fixed points). These are not suitable for the description of reproducible transient sequential neural dynamics. In this paper we present the concept of a stable heteroclinic sequence (SHS), which is not an attractor. SHS opens the way for understanding and modeling of transient sequential activity in neural circuits. We show that this new mathematical object can be used to describe robust and reproducible sequential neural dynamics. Using the framework of a generalized high-dimensional Lotka-Volterra model, that describes the dynamics of firing rates in an inhibitory network, we present analytical results on the existence of the SHS in the phase space of the network. With the help of numerical simulations we confirm its robustness in presence of noise in spite of the transient nature of the corresponding trajectories. Finally, by referring to several recent neurobiological experiments, we discuss possible applications of this new concept to several problems in neuroscience.

  14. Aveiro method in reproducing kernel Hilbert spaces under complete dictionary

    Science.gov (United States)

    Mai, Weixiong; Qian, Tao

    2017-12-01

    Aveiro Method is a sparse representation method in reproducing kernel Hilbert spaces (RKHS) that gives orthogonal projections in linear combinations of reproducing kernels over uniqueness sets. It, however, suffers from determination of uniqueness sets in the underlying RKHS. In fact, in general spaces, uniqueness sets are not easy to be identified, let alone the convergence speed aspect with Aveiro Method. To avoid those difficulties we propose an anew Aveiro Method based on a dictionary and the matching pursuit idea. What we do, in fact, are more: The new Aveiro method will be in relation to the recently proposed, the so called Pre-Orthogonal Greedy Algorithm (P-OGA) involving completion of a given dictionary. The new method is called Aveiro Method Under Complete Dictionary (AMUCD). The complete dictionary consists of all directional derivatives of the underlying reproducing kernels. We show that, under the boundary vanishing condition, bring available for the classical Hardy and Paley-Wiener spaces, the complete dictionary enables an efficient expansion of any given element in the Hilbert space. The proposed method reveals new and advanced aspects in both the Aveiro Method and the greedy algorithm.

  15. Validity and reproducibility of a Spanish dietary history.

    Directory of Open Access Journals (Sweden)

    Pilar Guallar-Castillón

    Full Text Available To assess the validity and reproducibility of food and nutrient intake estimated with the electronic diet history of ENRICA (DH-E, which collects information on numerous aspects of the Spanish diet.The validity of food and nutrient intake was estimated using Pearson correlation coefficients between the DH-E and the mean of seven 24-hour recalls collected every 2 months over the previous year. The reproducibility was estimated using intraclass correlation coefficients between two DH-E made one year apart.The correlations coefficients between the DH-E and the mean of seven 24-hour recalls for the main food groups were cereals (r = 0.66, meat (r = 0.66, fish (r = 0.42, vegetables (r = 0.62 and fruits (r = 0.44. The mean correlation coefficient for all 15 food groups considered was 0.53. The correlations for macronutrients were: energy (r = 0.76, proteins (r= 0.58, lipids (r = 0.73, saturated fat (r = 0.73, monounsaturated fat (r = 0.59, polyunsaturated fat (r = 0.57, and carbohydrates (r = 0.66. The mean correlation coefficient for all 41 nutrients studied was 0.55. The intraclass correlation coefficient between the two DH-E was greater than 0.40 for most foods and nutrients.The DH-E shows good validity and reproducibility for estimating usual intake of foods and nutrients.

  16. In vivo quantification of intracerebral GABA by single-voxel {sup 1}H-MRS-How reproducible are the results?

    Energy Technology Data Exchange (ETDEWEB)

    Bogner, W. [MR Centre of Excellence, Department of Radiology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria)], E-mail: wolfgang@nmr.at; Gruber, S. [MR Centre of Excellence, Department of Radiology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria)], E-mail: stephan@nmr.at; Doelken, M. [Department of Neuroradiology, University of Erlangen-Nuremberg, Schwabachanlage 6, D-91054 Erlangen (Austria)], E-mail: marc.doelken@uk-erlangen.de; Stadlbauer, A. [Department of Neurosurgery, University of Erlangen-Nuremberg, Schwabachanlage 6, D-91054 Erlangen (Austria)], E-mail: andi@nmr.at; Ganslandt, O. [Department of Neurosurgery, University of Erlangen-Nuremberg, Schwabachanlage 6, D-91054 Erlangen (Austria)], E-mail: oliver.ganslandt@uk-erlangen.de; Boettcher, U. [Siemens Medical Solution, Karl-Schall Str. 6, D-91052 Erlangen (Germany)], E-mail: uwe.boettcher@siemens.com; Trattnig, S. [MR Centre of Excellence, Department of Radiology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria)], E-mail: siegfried.trattnig@meduniwien.ac.at; Doerfler, A. [Department of Neuroradiology, University of Erlangen-Nuremberg, Schwabachanlage 6, D-91054 Erlangen (Austria)], E-mail: a.doerfler@nrad.imed.uni-erlangen.de; Stefan, H. [Center Epilepsy Erlangen (ZEE), Department of Neurology, University of Erlangen-Nuremberg, Schwabachanlage 6, D-91054 Erlangen (Germany)], E-mail: Hermann.Stefan@uk-erlangen.de; Hammen, T. [Center Epilepsy Erlangen (ZEE), Department of Neurology, University of Erlangen-Nuremberg, Schwabachanlage 6, D-91054 Erlangen (Germany)], E-mail: thilo.hammen@uk-erlangen.de

    2010-03-15

    Gamma aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the human brain. It plays a decisive role in a variety of nervous system disorders, such as anxiety disorders, epilepsy, schizophrenia, insomnia, and many others. The reproducibility of GABA quantification results obtained with a single-voxel spectroscopy J-difference editing sequence with Point Resolved Spectroscopy localization (MEGA-PRESS) was determined on a 3.0 Tesla MR scanner in healthy adults. Eleven volunteers were measured in long- and short-term intervals. Intra- and inter-subject reproducibility were evaluated. Internal referencing of GABA+ to total creatine (tCr) and water (H{sub 2}O), as well as two different post-processing methods for the evaluation (signal integration and time-domain fitting) were compared. In all subjects lower coefficient of variation and therefore higher reproducibility can be observed for fitting compared to integration. The GABA+/tCr ratio performs better than the GABA+/H{sub 2}O ratio or GABA+ without internal referencing for both fitting and integration (GABA+/tCr: 13.3% and 17.0%; GABA+/H{sub 2}O: 15.0% and 17.8%; GABA+: 19.2% and 21.7%). Four-day measurements on three subjects showed higher intra- than inter-subject reproducibility (GABA+/tCr {approx}10-12%). With a coefficient of variation of about 13% for inter-subject and 10-12% for intra-subject variability of GABA+/tCr, this technique seems to be a precise tool that can detect GABA confidently. The results of this study show the reproducibility limitations of GABA quantification in vivo, which are necessary for further clinical studies.

  17. In vivo quantification of intracerebral GABA by single-voxel 1H-MRS-How reproducible are the results?

    International Nuclear Information System (INIS)

    Bogner, W.; Gruber, S.; Doelken, M.; Stadlbauer, A.; Ganslandt, O.; Boettcher, U.; Trattnig, S.; Doerfler, A.; Stefan, H.; Hammen, T.

    2010-01-01

    Gamma aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the human brain. It plays a decisive role in a variety of nervous system disorders, such as anxiety disorders, epilepsy, schizophrenia, insomnia, and many others. The reproducibility of GABA quantification results obtained with a single-voxel spectroscopy J-difference editing sequence with Point Resolved Spectroscopy localization (MEGA-PRESS) was determined on a 3.0 Tesla MR scanner in healthy adults. Eleven volunteers were measured in long- and short-term intervals. Intra- and inter-subject reproducibility were evaluated. Internal referencing of GABA+ to total creatine (tCr) and water (H 2 O), as well as two different post-processing methods for the evaluation (signal integration and time-domain fitting) were compared. In all subjects lower coefficient of variation and therefore higher reproducibility can be observed for fitting compared to integration. The GABA+/tCr ratio performs better than the GABA+/H 2 O ratio or GABA+ without internal referencing for both fitting and integration (GABA+/tCr: 13.3% and 17.0%; GABA+/H 2 O: 15.0% and 17.8%; GABA+: 19.2% and 21.7%). Four-day measurements on three subjects showed higher intra- than inter-subject reproducibility (GABA+/tCr ∼10-12%). With a coefficient of variation of about 13% for inter-subject and 10-12% for intra-subject variability of GABA+/tCr, this technique seems to be a precise tool that can detect GABA confidently. The results of this study show the reproducibility limitations of GABA quantification in vivo, which are necessary for further clinical studies.

  18. Coordinated Evolution of Transcriptional and Post-Transcriptional Regulation for Mitochondrial Functions in Yeast Strains.

    Directory of Open Access Journals (Sweden)

    Xuepeng Sun

    Full Text Available Evolution of gene regulation has been proposed to play an important role in environmental adaptation. Exploring mechanisms underlying coordinated evolutionary changes at various levels of gene regulation could shed new light on how organism adapt in nature. In this study, we focused on regulatory differences between a laboratory Saccharomyces cerevisiae strain BY4742 and a pathogenic S. cerevisiae strain, YJM789. The two strains diverge in many features, including growth rate, morphology, high temperature tolerance, and pathogenicity. Our RNA-Seq and ribosomal footprint profiling data showed that gene expression differences are pervasive, and genes functioning in mitochondria are mostly divergent between the two strains at both transcriptional and translational levels. Combining functional genomics data from other yeast strains, we further demonstrated that significant divergence of expression for genes functioning in the electron transport chain (ETC was likely caused by differential expression of a transcriptional factor, HAP4, and that post-transcriptional regulation mediated by an RNA-binding protein, PUF3, likely led to expression divergence for genes involved in mitochondrial translation. We also explored mito-nuclear interactions via mitochondrial DNA replacement between strains. Although the two mitochondrial genomes harbor substantial sequence divergence, neither growth nor gene expression were affected by mitochondrial DNA replacement in both fermentative and respiratory growth media, indicating compatible mitochondrial and nuclear genomes between these two strains in the tested conditions. Collectively, we used mitochondrial functions as an example to demonstrate for the first time that evolution at both transcriptional and post-transcriptional levels could lead to coordinated regulatory changes underlying strain specific functional variations.

  19. Identification and reproducibility of diagnostic DNA markers for tuber starch and yield optimization in a novel association mapping population of potato (Solanum tuberosum L.).

    Science.gov (United States)

    Schönhals, E M; Ortega, F; Barandalla, L; Aragones, A; Ruiz de Galarreta, J I; Liao, J-C; Sanetomo, R; Walkemeier, B; Tacke, E; Ritter, E; Gebhardt, C

    2016-04-01

    SNPs in candidate genes Pain - 1, InvCD141 (invertases), SSIV (starch synthase), StCDF1 (transcription factor), LapN (leucine aminopeptidase), and cytoplasm type are associated with potato tuber yield, starch content and/or starch yield. Tuber yield (TY), starch content (TSC), and starch yield (TSY) are complex characters of high importance for the potato crop in general and for industrial starch production in particular. DNA markers associated with superior alleles of genes that control the natural variation of TY, TSC, and TSY could increase precision and speed of breeding new cultivars optimized for potato starch production. Diagnostic DNA markers are identified by association mapping in populations of tetraploid potato varieties and advanced breeding clones. A novel association mapping population of 282 genotypes including varieties, breeding clones and Andean landraces was assembled and field evaluated in Northern Spain for TY, TSC, TSY, tuber number (TN) and tuber weight (TW). The landraces had lower mean values of TY, TW, TN, and TSY. The population was genotyped for 183 microsatellite alleles, 221 single nucleotide polymorphisms (SNPs) in fourteen candidate genes and eight known diagnostic markers for TSC and TSY. Association test statistics including kinship and population structure reproduced five known marker-trait associations of candidate genes and discovered new ones, particularly for tuber yield and starch yield. The inclusion of landraces increased the number of detected marker-trait associations. Integration of the present association mapping results with previous QTL linkage mapping studies for TY, TSC, TSY, TW, TN, and tuberization revealed some hot spots of QTL for these traits in the potato genome. The genomic positions of markers linked or associated with QTL for complex tuber traits suggest high multiplicity and genome wide distribution of the underlying genes.

  20. Reverse Transcription Errors and RNA-DNA Differences at Short Tandem Repeats.

    Science.gov (United States)

    Fungtammasan, Arkarachai; Tomaszkiewicz, Marta; Campos-Sánchez, Rebeca; Eckert, Kristin A; DeGiorgio, Michael; Makova, Kateryna D

    2016-10-01

    Transcript variation has important implications for organismal function in health and disease. Most transcriptome studies focus on assessing variation in gene expression levels and isoform representation. Variation at the level of transcript sequence is caused by RNA editing and transcription errors, and leads to nongenetically encoded transcript variants, or RNA-DNA differences (RDDs). Such variation has been understudied, in part because its detection is obscured by reverse transcription (RT) and sequencing errors. It has only been evaluated for intertranscript base substitution differences. Here, we investigated transcript sequence variation for short tandem repeats (STRs). We developed the first maximum-likelihood estimator (MLE) to infer RT error and RDD rates, taking next generation sequencing error rates into account. Using the MLE, we empirically evaluated RT error and RDD rates for STRs in a large-scale DNA and RNA replicated sequencing experiment conducted in a primate species. The RT error rates increased exponentially with STR length and were biased toward expansions. The RDD rates were approximately 1 order of magnitude lower than the RT error rates. The RT error rates estimated with the MLE from a primate data set were concordant with those estimated with an independent method, barcoded RNA sequencing, from a Caenorhabditis elegans data set. Our results have important implications for medical genomics, as STR allelic variation is associated with >40 diseases. STR nonallelic transcript variation can also contribute to disease phenotype. The MLE and empirical rates presented here can be used to evaluate the probability of disease-associated transcripts arising due to RDD. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  1. Is gene transcription involved in seed dry after-ripening?

    Directory of Open Access Journals (Sweden)

    Patrice Meimoun

    Full Text Available Orthodox seeds are living organisms that survive anhydrobiosis and may display dormancy, an inability to germinate at harvest. Seed germination potential can be acquired during a prolonged period of dry storage called after-ripening. The aim of this work was to determine if gene transcription is an underlying regulatory mechanism for dormancy alleviation during after-ripening. To identify changes in gene transcription strictly associated with the acquisition of germination potential but not with storage, we used seed storage at low relative humidity that maintains dormancy as control. Transcriptome profiling was performed using DNA microarray to compare change in gene transcript abundance between dormant (D, after-ripened non-dormant (ND and after-ripened dormant seeds (control, C. Quantitative real-time polymerase chain reaction (qPCR was used to confirm gene expression. Comparison between D and ND showed the differential expression of 115 probesets at cut-off values of two-fold change (p<0.05. Comparisons between both D and C with ND in transcript abundance showed that only 13 transcripts, among 115, could be specific to dormancy alleviation. qPCR confirms the expression pattern of these transcripts but without significant variation between conditions. Here we show that sunflower seed dormancy alleviation in the dry state is not related to regulated changes in gene expression.

  2. Inter-examiner reproducibility of tests for lumbar motor control

    Directory of Open Access Journals (Sweden)

    Elkjaer Arne

    2011-05-01

    Full Text Available Abstract Background Many studies show a relation between reduced lumbar motor control (LMC and low back pain (LBP. However, test circumstances vary and during test performance, subjects may change position. In other words, the reliability - i.e. reproducibility and validity - of tests for LMC should be based on quantitative data. This has not been considered before. The aim was to analyse the reproducibility of five different quantitative tests for LMC commonly used in daily clinical practice. Methods The five tests for LMC were: repositioning (RPS, sitting forward lean (SFL, sitting knee extension (SKE, and bent knee fall out (BKFO, all measured in cm, and leg lowering (LL, measured in mm Hg. A total of 40 subjects (14 males, 26 females 25 with and 15 without LBP, with a mean age of 46.5 years (SD 14.8, were examined independently and in random order by two examiners on the same day. LBP subjects were recruited from three physiotherapy clinics with a connection to the clinic's gym or back-school. Non-LBP subjects were recruited from the clinic's staff acquaintances, and from patients without LBP. Results The means and standard deviations for each of the tests were 0.36 (0.27 cm for RPS, 1.01 (0.62 cm for SFL, 0.40 (0.29 cm for SKE, 1.07 (0.52 cm for BKFO, and 32.9 (7.1 mm Hg for LL. All five tests for LMC had reproducibility with the following ICCs: 0.90 for RPS, 0.96 for SFL, 0.96 for SKE, 0.94 for BKFO, and 0.98 for LL. Bland and Altman plots showed that most of the differences between examiners A and B were less than 0.20 cm. Conclusion These five tests for LMC displayed excellent reproducibility. However, the diagnostic accuracy of these tests needs to be addressed in larger cohorts of subjects, establishing values for the normal population. Also cut-points between subjects with and without LBP must be determined, taking into account age, level of activity, degree of impairment and participation in sports. Whether reproducibility of these

  3. Cervical vertebrae maturation method morphologic criteria: poor reproducibility.

    Science.gov (United States)

    Nestman, Trenton S; Marshall, Steven D; Qian, Fang; Holton, Nathan; Franciscus, Robert G; Southard, Thomas E

    2011-08-01

    The cervical vertebrae maturation (CVM) method has been advocated as a predictor of peak mandibular growth. A careful review of the literature showed potential methodologic errors that might influence the high reported reproducibility of the CVM method, and we recently established that the reproducibility of the CVM method was poor when these potential errors were eliminated. The purpose of this study was to further investigate the reproducibility of the individual vertebral patterns. In other words, the purpose was to determine which of the individual CVM vertebral patterns could be classified reliably and which could not. Ten practicing orthodontists, trained in the CVM method, evaluated the morphology of cervical vertebrae C2 through C4 from 30 cephalometric radiographs using questions based on the CVM method. The Fleiss kappa statistic was used to assess interobserver agreement when evaluating each cervical vertebrae morphology question for each subject. The Kendall coefficient of concordance was used to assess the level of interobserver agreement when determining a "derived CVM stage" for each subject. Interobserver agreement was high for assessment of the lower borders of C2, C3, and C4 that were either flat or curved in the CVM method, but interobserver agreement was low for assessment of the vertebral bodies of C3 and C4 when they were either trapezoidal, rectangular horizontal, square, or rectangular vertical; this led to the overall poor reproducibility of the CVM method. These findings were reflected in the Fleiss kappa statistic. Furthermore, nearly 30% of the time, individual morphologic criteria could not be combined to generate a final CVM stage because of incompatible responses to the 5 questions. Intraobserver agreement in this study was only 62%, on average, when the inconclusive stagings were excluded as disagreements. Intraobserver agreement was worse (44%) when the inconclusive stagings were included as disagreements. For the group of subjects

  4. Reproducibility of trabecular bone score with different scan modes using dual-energy X-ray absorptiometry: a phantom study

    Energy Technology Data Exchange (ETDEWEB)

    Bandirali, Michele; Messina, Carmelo [Universita degli Studi di Milano, Scuola di Specializzazione in Radiodiagnostica, Milano (Italy); Di Leo, Giovanni [Unita di Radiologia, IRCCS Policlinico San Donato, San Donato Milanese (Italy); Pastor Lopez, Maria Juana; Ulivieri, Fabio M. [Servizio di Medicina Nucleare, Ospedale Maggiore, Mineralometria Ossea Computerizzata e Ambulatorio Malattie Metabolismo Minerale e Osseo, Milano (Italy); Mai, Alessandro [Universita degli Studi di Milano, Tecniche di Radiologia Medica, per Immagini e Radioterapia, Milano (Italy); Sardanelli, Francesco [Unita di Radiologia, IRCCS Policlinico San Donato, San Donato Milanese (Italy); Universita degli Studi di Milano, Dipartimento di Scienze Biomediche per la Salute, San Donato Milanese (Italy)

    2014-08-12

    The trabecular bone score (TBS) accounts for the bone microarchitecture and is calculated on dual-energy X-ray absorptiometry (DXA). We estimated the reproducibility of the TBS using different scan modes compared to the reproducibility bone mineral density (BMD). A spine phantom was used with a Hologic QDR-Discovery A densitometer. For each scan mode [fast array, array, high definition (HD)], 25 scans were automatically performed without phantom repositioning; a further 25 scans were performed with phantom repositioning. For each scan, the TBS was obtained. The coefficient of variation (CoV) was calculated as the ratio between standard deviation and mean; percent least significant change (LSC%) as 2.8 x CoV; reproducibility as the complement to 100 % of LSC%. Differences among scan modes were assessed using ANOVA. Without phantom repositioning, the mean TBS (mm{sup -1}) was: 1.352 (fast array), 1.321 (array), and 1.360 (HD); with phantom repositioning, it was 1.345, 1.332, and 1.362, respectively. Reproducibility of the TBS without phantom repositioning was 97.7 % (fast array), 98.3 % (array), and 98.2 % (HD); with phantom repositioning, it was 97.9 %, 98.7 %, and 98.4 %, respectively. LSC% was ≤2.26 %. Differences among scan modes were all statistically significant (p ≤ 0.019). Reproducibility of BMD was 99.1 % with all scan modes, while LSC% was from 0.86 % to 0.91 %. Reproducibility error of the TBS was 2-3-fold higher than that of BMD. Although statistically significant, differences in TBS among scan modes were within the highest LSC%. Thus, the three scan modes can be considered interchangeable. (orig.)

  5. Reproducibility of the serum lipid response to coffee oil in healthy volunteers

    Directory of Open Access Journals (Sweden)

    Katan Martijn B

    2003-10-01

    Full Text Available Abstract Background Humans and animals show a certain consistency in the response of their serum lipids to fat-modified diets. This may indicate a genetic basis underlying this response. Coffee oil might be used as a model substance to investigate which genes determine differences in the serum lipid response. Before carrying out such studies our objective was to investigate to what extent the effect of coffee oil on serum lipid concentrations is reproducible within subjects. Methods The serum lipid response of 32 healthy volunteers was measured twice in separate five-week periods in which coffee oil was administered (69 mg cafestol / day. Results Total cholesterol levels increased by 24% in period 1 (range:0;52% and 18% in period 2 (1;48%, LDL cholesterol by 29 % (-9;71% and 20% (-12;57%, triglycerides by 66% (16;175% and 58% (-13;202%, and HDL cholesterol did not change significantly: The range of the HDL response was -19;25% in period 1 and -20;33% in period 2. The correlation between the two responses was 0.20 (95%CI -0.16, 0.51 for total cholesterol, 0.16 (95%CI -0.20, 0.48 for LDL, 0.67 (95%CI 0.42, 0.83 for HDL, and 0.77 (95%CI 0.56, 0.88 for triglycerides. Conclusions The responses of total and LDL cholesterol to coffee oil were poorly reproducible within subjects. The responses of HDL and triglycerides, however, appeared to be highly reproducible. Therefore, investigating the genetic sources of the variation in the serum-lipid response to coffee oil is more promising for HDL and triglycerides.

  6. Stochastic model for gene transcription on Drosophila melanogaster embryos

    Science.gov (United States)

    Prata, Guilherme N.; Hornos, José Eduardo M.; Ramos, Alexandre F.

    2016-02-01

    We examine immunostaining experimental data for the formation of stripe 2 of even-skipped (eve) transcripts on D. melanogaster embryos. An estimate of the factor converting immunofluorescence intensity units into molecular numbers is given. The analysis of the eve dynamics at the region of stripe 2 suggests that the promoter site of the gene has two distinct regimes: an earlier phase when it is predominantly activated until a critical time when it becomes mainly repressed. That suggests proposing a stochastic binary model for gene transcription on D. melanogaster embryos. Our model has two random variables: the transcripts number and the state of the source of mRNAs given as active or repressed. We are able to reproduce available experimental data for the average number of transcripts. An analysis of the random fluctuations on the number of eves and their consequences on the spatial precision of stripe 2 is presented. We show that the position of the anterior or posterior borders fluctuate around their average position by ˜1 % of the embryo length, which is similar to what is found experimentally. The fitting of data by such a simple model suggests that it can be useful to understand the functions of randomness during developmental processes.

  7. Pairwise comparisons of ten porcine tissues identify differential transcriptional regulation at the gene, isoform, promoter and transcription start site level

    International Nuclear Information System (INIS)

    Farajzadeh, Leila; Hornshøj, Henrik; Momeni, Jamal; Thomsen, Bo; Larsen, Knud; Hedegaard, Jakob; Bendixen, Christian; Madsen, Lone Bruhn

    2013-01-01

    Highlights: •Transcriptome sequencing yielded 223 mill porcine RNA-seq reads, and 59,000 transcribed locations. •Establishment of unique transcription profiles for ten porcine tissues including four brain tissues. •Comparison of transcription profiles at gene, isoform, promoter and transcription start site level. •Highlights a high level of regulation of neuro-related genes at both gene, isoform, and TSS level. •Our results emphasize the pig as a valuable animal model with respect to human biological issues. -- Abstract: The transcriptome is the absolute set of transcripts in a tissue or cell at the time of sampling. In this study RNA-Seq is employed to enable the differential analysis of the transcriptome profile for ten porcine tissues in order to evaluate differences between the tissues at the gene and isoform expression level, together with an analysis of variation in transcription start sites, promoter usage, and splicing. Totally, 223 million RNA fragments were sequenced leading to the identification of 59,930 transcribed gene locations and 290,936 transcript variants using Cufflinks with similarity to approximately 13,899 annotated human genes. Pairwise analysis of tissues for differential expression at the gene level showed that the smallest differences were between tissues originating from the porcine brain. Interestingly, the relative level of differential expression at the isoform level did generally not vary between tissue contrasts. Furthermore, analysis of differential promoter usage between tissues, revealed a proportionally higher variation between cerebellum (CBE) versus frontal cortex and cerebellum versus hypothalamus (HYP) than in the remaining comparisons. In addition, the comparison of differential transcription start sites showed that the number of these sites is generally increased in comparisons including hypothalamus in contrast to other pairwise assessments. A comprehensive analysis of one of the tissue contrasts, i

  8. Comparative transcriptional and genomic analysis of Plasmodium falciparum field isolates.

    Directory of Open Access Journals (Sweden)

    Margaret J Mackinnon

    2009-10-01

    Full Text Available Mechanisms for differential regulation of gene expression may underlie much of the phenotypic variation and adaptability of malaria parasites. Here we describe transcriptional variation among culture-adapted field isolates of Plasmodium falciparum, the species responsible for most malarial disease. It was found that genes coding for parasite protein export into the red cell cytosol and onto its surface, and genes coding for sexual stage proteins involved in parasite transmission are up-regulated in field isolates compared with long-term laboratory isolates. Much of this variability was associated with the loss of small or large chromosomal segments, or other forms of gene copy number variation that are prevalent in the P. falciparum genome (copy number variants, CNVs. Expression levels of genes inside these segments were correlated to that of genes outside and adjacent to the segment boundaries, and this association declined with distance from the CNV boundary. This observation could not be explained by copy number variation in these adjacent genes. This suggests a local-acting regulatory role for CNVs in transcription of neighboring genes and helps explain the chromosomal clustering that we observed here. Transcriptional co-regulation of physical clusters of adaptive genes may provide a way for the parasite to readily adapt to its highly heterogeneous and strongly selective environment.

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

    Science.gov (United States)

    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.

  10. Submicroscopic malaria parasite carriage: how reproducible are polymerase chain reaction-based methods?

    Directory of Open Access Journals (Sweden)

    Daniela Camargos Costa

    2014-02-01

    Full Text Available The polymerase chain reaction (PCR-based methods for the diagnosis of malaria infection are expected to accurately identify submicroscopic parasite carriers. Although a significant number of PCR protocols have been described, few studies have addressed the performance of PCR amplification in cases of field samples with submicroscopic malaria infection. Here, the reproducibility of two well-established PCR protocols (nested-PCR and real-time PCR for the Plasmodium 18 small subunit rRNA gene were evaluated in a panel of 34 blood field samples from individuals that are potential reservoirs of malaria infection, but were negative for malaria by optical microscopy. Regardless of the PCR protocol, a large variation between the PCR replicates was observed, leading to alternating positive and negative results in 38% (13 out of 34 of the samples. These findings were quite different from those obtained from the microscopy-positive patients or the unexposed individuals; the diagnosis of these individuals could be confirmed based on the high reproducibility and specificity of the PCR-based protocols. The limitation of PCR amplification was restricted to the field samples with very low levels of parasitaemia because titrations of the DNA templates were able to detect < 3 parasites/µL in the blood. In conclusion, conventional PCR protocols require careful interpretation in cases of submicroscopic malaria infection, as inconsistent and false-negative results can occur.

  11. [Reproducibility of Fuhrman nuclear grade: advantages of a two-grade system].

    Science.gov (United States)

    Letourneux, Hervé; Lindner, Véronique; Lang, Hervé; Massfelder, Thierry; Meyer, Nicolas; Saussine, Christian; Jacqmin, Didier

    2006-06-01

    The Fuhrman nuclear grade is the reference histoprognostic grading system routinely used all over the world for renal cell carcinoma. Studies measuring the inter-observer and intra-observer concordance of Fuhrman grade show poor results in terms of reproducibility and repeatability. These variations are due to a certain degree of subjectivity of the pathologist in application of the definition of tumour grade, particularly nuclear grade. Elements able to account for this subjectivity in renal cell carcinoma are identified from a review of the literature. To improve the reliability of nuclear grade, the territory occupied by the highest grade must be specified and the grades should probably be combined. At the present time, regrouping of grade 1 and 2 tumours as low grade and grade 3 and 4 tumours as high grade would achieve better reproducibility, while preserving the prognostic: value for overall survival. The development of new treatment modalities and their use in adjuvant situations will imply the use of reliable histoprognostic factors to specify, indications.

  12. The Development of Reproducible and Selective Uric Acid Biosensor by Using Electrodeposited Polytyramine as Matrix Polymer

    Directory of Open Access Journals (Sweden)

    Manihar Situmorang

    2017-11-01

    Full Text Available A versatile method for the construction of reproducible and high selective uric acid biosensor is explained. Electrodeposited polytyramine is used as biosensor matrixes due to its compatibility to immobilize enzyme uric oxidase in the membrane electrode. The precise control over the charge passed during deposition of polytyramine allows concomitant control over the thickness of the deposited enzyme layers onto the surface of the electrode. The uric acid biosensor showed a sensitive response to uric acid with a linear calibration curve lies in the concentration range of 0.1–2.5 mM, slope 0.066 µA mM-1, and the limit detection was 0.01 mM uric acid (S/N = 3. The biosensor shown excellent reproducibility, the variation between response curves for uric acid lies between RSD 1% at low concentrations and up to RSD 6% at saturation concentration. Uric acid biosensor is free from normal interference. The biosensor showed good stability and to be applicable to determine uric acid in real samples. Analysis of uric acid in the reference standard serum samples by the biosensor method are all agreed with the real value from supplier. Standard samples were also analyzed independently by two methods: the present biosensor method and the standard UV-Vis spectrophotometry method, gave a correlation coefficient of 0.994. This result confirms that the biosensor method meets the rigid demands expected for uric acid in real samples.

  13. FAST TRACK COMMUNICATION: Reproducible room temperature giant magnetocaloric effect in Fe-Rh

    Science.gov (United States)

    Manekar, Meghmalhar; Roy, S. B.

    2008-10-01

    We present the results of magnetocaloric effect (MCE) studies in polycrystalline Fe-Rh alloy over a temperature range of 250-345 K across the first order antiferromagnetic to ferromagnetic transition. By measuring the MCE under various thermomagnetic histories, contrary to the long held belief, we show here explicitly that the giant MCE in Fe-Rh near room temperature does not vanish after the first field cycle. In spite of the fact that the virgin magnetization curve is lost after the first field cycle near room temperature, reproducibility in the MCE under multiple field cycles can be achieved by properly choosing a combination of isothermal and adiabatic field variation cycles in the field-temperature phase space. This reproducible MCE leads to a large effective refrigerant capacity of 324.42 J kg-1, which is larger than that of the well-known magnetocaloric material Gd5Si2Ge2. This information could be important as Fe-Rh has the advantage of having a working temperature of around 300 K, which can be used for room temperature magnetic refrigeration.

  14. Automated analysis of phantom images for the evaluation of long-term reproducibility in digital mammography

    International Nuclear Information System (INIS)

    Gennaro, G; Ferro, F; Contento, G; Fornasin, F; Di Maggio, C

    2007-01-01

    The performance of an automatic software package was evaluated with phantom images acquired by a full-field digital mammography unit. After the validation, the software was used, together with a Leeds TORMAS test object, to model the image acquisition process. Process modelling results were used to evaluate the sensitivity of the method in detecting changes of exposure parameters from routine image quality measurements in digital mammography, which is the ultimate purpose of long-term reproducibility tests. Image quality indices measured by the software included the mean pixel value and standard deviation of circular details and surrounding background, contrast-to-noise ratio and relative contrast; detail counts were also collected. The validation procedure demonstrated that the software localizes the phantom details correctly and the difference between automatic and manual measurements was within few grey levels. Quantitative analysis showed sufficient sensitivity to relate fluctuations in exposure parameters (kV p or mAs) to variations in image quality indices. In comparison, detail counts were found less sensitive in detecting image quality changes, even when limitations due to observer subjectivity were overcome by automatic analysis. In conclusion, long-term reproducibility tests provided by the Leeds TORMAS phantom with quantitative analysis of multiple IQ indices have been demonstrated to be effective in predicting causes of deviation from standard operating conditions and can be used to monitor stability in full-field digital mammography

  15. Metaleptic Variations

    OpenAIRE

    Pernot, Dominique

    2014-01-01

    Les derniers romans de Gabriel Josipovici offrent beaucoup de variété, allant de la parodie, de la fiction comique légère, dans Only Joking et Making Mistakes, à des sujets plus graves, plus personnels, ontologiques. Dans un court roman, Everything Passes, et dans un roman majeur, Goldberg: Variations, le lecteur est amené à se poser des questions sur la nature mystérieuse de la réalité, qui est, trop souvent, acceptée sans conteste par de nombreux roma...

  16. RNA-guided transcriptional regulation

    Science.gov (United States)

    Church, George M.; Mali, Prashant G.; Esvelt, Kevin M.

    2016-02-23

    Methods of modulating expression of a target nucleic acid in a cell are provided including introducing into the cell a first foreign nucleic acid encoding one or more RNAs complementary to DNA, wherein the DNA includes the target nucleic acid, introducing into the cell a second foreign nucleic acid encoding a nuclease-null Cas9 protein that binds to the DNA and is guided by the one or more RNAs, introducing into the cell a third foreign nucleic acid encoding a transcriptional regulator protein or domain, wherein the one or more RNAs, the nuclease-null Cas9 protein, and the transcriptional regulator protein or domain are expressed, wherein the one or more RNAs, the nuclease-null Cas9 protein and the transcriptional regulator protein or domain co-localize to the DNA and wherein the transcriptional regulator protein or domain regulates expression of the target nucleic acid.

  17. Transcriptional control of megakaryocyte development.

    Science.gov (United States)

    Goldfarb, A N

    2007-10-15

    Megakaryocytes are highly specialized cells that arise from a bipotent megakaryocytic-erythroid progenitor (MEP). This developmental leap requires coordinated activation of megakaryocyte-specific genes, radical changes in cell cycle properties, and active prevention of erythroid differentiation. These programs result from upregulation of megakaryocyte-selective transcription factors, downregulation of erythroid-selective transcription factors and ongoing mediation of common erythro-megakaryocytic transcription factors. Unlike most developmental programs, no single lineage-unique family of master regulators exerts executive control over the megakaryocytic plan. Rather, an assemblage of non-unique factors and signals converge to determine lineage and differentiation. In human megakaryopoiesis, hereditary disorders of platelet production have confirmed contributions from three distinct transcription factor families. Murine models have extended this repertoire to include multiple additional factors. At a mechanistic level, the means by which these non-unique factors collaborate in the establishment of a perfectly unique cell type remains a central question.

  18. Gene expression differences between PAXgene and Tempus blood RNA tubes are highly reproducible between independent samples and biobanks.

    Science.gov (United States)

    Skogholt, Anne Heidi; Ryeng, Einar; Erlandsen, Sten Even; Skorpen, Frank; Schønberg, Svanhild A; Sætrom, Pål

    2017-03-23

    Gene expression profiling from blood is sensitive to technology choices. For example, the main blood RNA collection systems-the PAXgene and Tempus tubes-differently influence RNA expression signatures. The aim of this study was to establish a common RNA isolation protocol for these two systems and investigate if it could reduce the differences in gene expression between them. We collected identical blood samples on the PAXgene and Tempus systems and retrieved blood samples from two independent biobanks-NOWAC and HUNT3-which are based on PAXgene and Tempus, respectively. High-quality RNA was extracted from both sampling systems by using their original protocols and our common modified protocol, and were profiled on Illumina microarrays. Regardless of the protocol used, we found most of the measured transcripts to be differently affected by the two sampling systems. However, our modified protocol reduced the number of transcripts that were significantly differentially expressed between PAXgene and Tempus by approximately 50%. Expression differences between PAXgene and Tempus were highly reproducible both between protocols and between different independent sample sets (Pearson correlation 0.563-0.854 across 47323 probes). Moreover, the modified protocol increased the microRNA output of the system with lowest microRNA yield, the PAXgene system. Most transcripts are affected by the choice of sampling system, but these effects are highly reproducible between independent samples. We propose that by running a control experiment with samples on both systems in parallel with biologically relevant samples, researchers may adjust for technical differences between the sampling systems.

  19. Peripheral nerve MRI: precision and reproducibility of T2*-derived measurements at 3.0-T. A feasibility study

    Energy Technology Data Exchange (ETDEWEB)

    Tagliafico, Alberto [University of Genoa, Institute of Anatomy, Department of Experimental Medicine, Genoa (Italy); Bignotti, Bianca; Martinoli, Carlo [University of Genoa, Radiology Department, Genoa, Genova (Italy); Tagliafico, Giulio [CNR-IMATI, Consiglio Nazionale delle Ricerche, Istituto di Matematica Applicata e Tecnologie Informatiche, Genova (Italy)

    2015-05-01

    To prospectively evaluate the precision and reproducibility of T2*-derived measurements of the peripheral nerves. The study was approved by the local ethics committee and written informed consent was obtained. Bilateral upper and lower limb MRI examination was performed in 40 healthy subjects on a 3.0-T scanner. MRI protocol included T1-turbo spin-echo, T2-turbo spin-echo with fat suppression, and multiecho gradient recalled echo. Measurements of T2* times on T2* maps at different anatomical levels were performed. Three authors measured independently and in different sessions at baseline and after 4 weeks. Non-parametric tests and Bland-Altman statistics were used. Minimum and maximum percentage variability were 10 % and 19 % for T2* (84-91 % of reproducibility). Maximum values of minimum detectable differences between limbs was 16 % (with 95 % CI: 2-37). Intra- and inter-observer agreement of the three radiologists for T2* was considered good. Evaluating the combined influence of the observer and of the repeated measurements the reproducibility was 87-98 %. T2* measurement of the peripheral nerves is precise and reproducible. The healthy contralateral side can be used as an internal control. Variations in T2* values up to 16 % have to be considered. (orig.)

  20. Dynamic Contrast-enhanced MR Imaging in Renal Cell Carcinoma: Reproducibility of Histogram Analysis on Pharmacokinetic Parameters

    Science.gov (United States)

    Wang, Hai-yi; Su, Zi-hua; Xu, Xiao; Sun, Zhi-peng; Duan, Fei-xue; Song, Yuan-yuan; Li, Lu; Wang, Ying-wei; Ma, Xin; Guo, Ai-tao; Ma, Lin; Ye, Hui-yi

    2016-01-01

    Pharmacokinetic parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) have been increasingly used to evaluate the permeability of tumor vessel. Histogram metrics are a recognized promising method of quantitative MR imaging that has been recently introduced in analysis of DCE-MRI pharmacokinetic parameters in oncology due to tumor heterogeneity. In this study, 21 patients with renal cell carcinoma (RCC) underwent paired DCE-MRI studies on a 3.0 T MR system. Extended Tofts model and population-based arterial input function were used to calculate kinetic parameters of RCC tumors. Mean value and histogram metrics (Mode, Skewness and Kurtosis) of each pharmacokinetic parameter were generated automatically using ImageJ software. Intra- and inter-observer reproducibility and scan–rescan reproducibility were evaluated using intra-class correlation coefficients (ICCs) and coefficient of variation (CoV). Our results demonstrated that the histogram method (Mode, Skewness and Kurtosis) was not superior to the conventional Mean value method in reproducibility evaluation on DCE-MRI pharmacokinetic parameters (K trans & Ve) in renal cell carcinoma, especially for Skewness and Kurtosis which showed lower intra-, inter-observer and scan-rescan reproducibility than Mean value. Our findings suggest that additional studies are necessary before wide incorporation of histogram metrics in quantitative analysis of DCE-MRI pharmacokinetic parameters. PMID:27380733

  1. Assessment of precision and reproducibility of a new myograph

    Directory of Open Access Journals (Sweden)

    Piepenbrock Siegfried

    2007-12-01

    Full Text Available Abstract Background The physiological characteristics of muscle activity and the assessment of muscle strength represent important diagnostic information. There are many devices that measure muscle force in humans, but some require voluntary contractions, which are difficult to assess in weak or unconscious patients who are unable to complete a full range of voluntary force assessment tasks. Other devices, which obtain standard muscle contractions by electric stimulations, do not have the technology required to induce and measure reproducible valid contractions at the optimum muscle length. Methods In our study we used a newly developed diagnostic device which measures accurately the reproducibility and time-changed-variability of the muscle force in an individual muscle. A total of 500 in-vivo measurements of supra-maximal isometric single twitch contractions were carried out on the musculus adductor pollicis of 5 test subjects over 10 sessions, with ten repetitions per session. The same protocol was performed on 405 test subjects with two repetitions each to determine a reference-interval on healthy subjects. Results Using our test setting, we found a high reproducibility of the muscle contractions of each test subject. The precision of the measurements performed with our device was 98.74%. Only two consecutive measurements are needed in order to assess a real, representative individual value of muscle force. The mean value of the force of contraction was 9.51 N and the 95% reference interval was 4.77–14.25 N. Conclusion The new myograph is a highly reliable measuring device with which the adductor pollicis can be investigated at the optimum length. It has the potential to become a reliable and valid tool for diagnostic in the clinical setting and for monitoring neuromuscular diseases.

  2. Efficient and reproducible mammalian cell bioprocesses without probes and controllers?

    Science.gov (United States)

    Tissot, Stéphanie; Oberbek, Agata; Reclari, Martino; Dreyer, Matthieu; Hacker, David L; Baldi, Lucia; Farhat, Mohamed; Wurm, Florian M

    2011-07-01

    Bioprocesses for recombinant protein production with mammalian cells are typically controlled for several physicochemical parameters including the pH and dissolved oxygen concentration (DO) of the culture medium. Here we studied whether these controls are necessary for efficient and reproducible bioprocesses in an orbitally shaken bioreactor (OSR). Mixing, gas transfer, and volumetric power consumption (P(V)) were determined in both a 5-L OSR and a 3-L stirred-tank bioreactor (STR). The two cultivation systems had a similar mixing intensity, but the STR had a lower volumetric mass transfer coefficient of oxygen (k(L)a) and a higher P(V) than the OSR. Recombinant CHO cell lines expressing either tumor necrosis factor receptor as an Fc fusion protein (TNFR:Fc) or an anti-RhesusD monoclonal antibody were cultivated in the two systems. The 5-L OSR was operated in an incubator shaker with 5% CO(2) in the gas environment but without pH and DO control whereas the STR was operated with or without pH and DO control. Higher cell densities and recombinant protein titers were obtained in the OSR as compared to both the controlled and the non-controlled STRs. To test the reproducibility of a bioprocess in a non-controlled OSR, the two CHO cell lines were each cultivated in parallel in six 5-L OSRs. Similar cell densities, cell viabilities, and recombinant protein titers along with similar pH and DO profiles were achieved in each group of replicates. Our study demonstrated that bioprocesses can be performed in OSRs without pH or DO control in a highly reproducible manner, at least at the scale of operation studied here. Copyright © 2011 Elsevier B.V. All rights reserved.

  3. REPRODUCIBILITY OF MASKED HYPERTENSION AMONG ADULTS 30 YEARS AND OLDER

    Science.gov (United States)

    Viera, Anthony J.; Lin, Feng-Chang; Tuttle, Laura A.; Olsson, Emily; Stankevitz, Kristin; Girdler, Susan S.; Klein, J. Larry; Hinderliter, Alan L.

    2015-01-01

    Objective Masked hypertension (MH) refers to non-elevated office blood pressure (BP) with elevated out-of-office BP, but its reproducibility has not been conclusively established. We examined one-week reproducibility of MH by home BP monitoring (HBPM) and ambulatory BP monitoring (ABPM). Methods We recruited 420 adults not on BP-lowering medication with recent clinic BP between 120/80 and 149/95 mm Hg. For main comparisons, participants with office average ABPM average was ≥135/85 mm Hg; they were considered to have MH by HBPM if the average was ≥135/85 mm Hg. Percent agreements were quantified using kappa. We also examined prevalence of MH defined as office average ABPM average ≥130/80 mm Hg. We conducted sensitivity analyses using different threshold BP levels for ABPM-office pairings and HBPM-office pairings for defining MH. Results Prevalence rates of MH based on office-awake ABPM pairings were 44% and 43%, with agreement of 71% (kappa=0.40; 95% CI 0.31–0.49). MH was less prevalent (15% and 17%) using HBPM-office pairings, with agreement of 82% (kappa=0.30; 95% CI 0.16–0.44), and more prevalent when considering 24-hour average (50% and 48%). MH was also less prevalent when more stringent diagnostic criteria were applied. Office-HBPM pairings and office-awake ABPM pairings had fair agreement on MH classification on both occasions, with kappas of 0.36 and 0.30. Conclusions MH has fair short-term reproducibility, providing further evidence that for some people, out-of-office BP is systematically higher than when measured in the office setting. PMID:24842491

  4. Reproducibility and Transparency in Ocean-Climate Modeling

    Science.gov (United States)

    Hannah, N.; Adcroft, A.; Hallberg, R.; Griffies, S. M.

    2015-12-01

    Reproducibility is a cornerstone of the scientific method. Within geophysical modeling and simulation achieving reproducibility can be difficult, especially given the complexity of numerical codes, enormous and disparate data sets, and variety of supercomputing technology. We have made progress on this problem in the context of a large project - the development of new ocean and sea ice models, MOM6 and SIS2. Here we present useful techniques and experience.We use version control not only for code but the entire experiment working directory, including configuration (run-time parameters, component versions), input data and checksums on experiment output. This allows us to document when the solutions to experiments change, whether due to code updates or changes in input data. To avoid distributing large input datasets we provide the tools for generating these from the sources, rather than provide raw input data.Bugs can be a source of non-determinism and hence irreproducibility, e.g. reading from or branching on uninitialized memory. To expose these we routinely run system tests, using a memory debugger, multiple compilers and different machines. Additional confidence in the code comes from specialised tests, for example automated dimensional analysis and domain transformations. This has entailed adopting a code style where we deliberately restrict what a compiler can do when re-arranging mathematical expressions.In the spirit of open science, all development is in the public domain. This leads to a positive feedback, where increased transparency and reproducibility makes using the model easier for external collaborators, who in turn provide valuable contributions. To facilitate users installing and running the model we provide (version controlled) digital notebooks that illustrate and record analysis of output. This has the dual role of providing a gross, platform-independent, testing capability and a means to documents model output and analysis.

  5. Reproducibility of gallbladder ejection fraction measured by fatty meal cholescintigraphy

    International Nuclear Information System (INIS)

    Al-Muqbel, Kusai M.; Hani, M. N. Hani; Elheis, M. A.; Al-Omari, M. H.

    2010-01-01

    There are conflicting data in the literature regarding the reproducibility of the gallbladder ejection fraction (GBEF) measured by fatty meal cholescintigraphy (CS). We aimed to test the reproducibility of GBEF measured by fatty meal CS. Thirty-five subjects (25 healthy volunteers and 10 patients with chronic abdominal pain) underwent fatty meal CS twice in order to measure GBEF1 and GBEF2. The healthy volunteers underwent a repeat scan within 1-13 months from the first scan. The patients underwent a repeat scan within 1-4 years from the first scan and were not found to have chronic acalculous cholecystitis (CAC). Our standard fatty meal was composed of a 60-g Snickers chocolate bar and 200 ml full-fat yogurt. The mean ± SD values for GBEF1 and GBEF2 were 52±17% and 52±16%, respectively. There was a direct linear correlation between the values of GBEF1 and GBEF2 for the subjects, with a correlation coefficient of 0.509 (p=0.002). Subgroup data analysis of the volunteer group showed that there was significant linear correlation between volunteer values of GBEF1 and GBEF2, with a correlation coefficient of 0.473 (p=0.017). Subgroup data analysis of the non-CAC patient group showed no significant correlation between patient values of GBEF1 and GBEF2, likely due to limited sample size. This study showed that fatty meal CS is a reliable test in gallbladder motility evaluation and that GBEF measured by fatty meal CS is reproducible

  6. Reproducibility of gallbladder ejection fraction measured by fatty meal cholescintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Al-Muqbel, Kusai M.; Hani, M. N. Hani; Elheis, M. A.; Al-Omari, M. H. [School of Medicine, Jordan University of Science and Technology, Irbid (Jordan)

    2010-12-15

    There are conflicting data in the literature regarding the reproducibility of the gallbladder ejection fraction (GBEF) measured by fatty meal cholescintigraphy (CS). We aimed to test the reproducibility of GBEF measured by fatty meal CS. Thirty-five subjects (25 healthy volunteers and 10 patients with chronic abdominal pain) underwent fatty meal CS twice in order to measure GBEF1 and GBEF2. The healthy volunteers underwent a repeat scan within 1-13 months from the first scan. The patients underwent a repeat scan within 1-4 years from the first scan and were not found to have chronic acalculous cholecystitis (CAC). Our standard fatty meal was composed of a 60-g Snickers chocolate bar and 200 ml full-fat yogurt. The mean {+-} SD values for GBEF1 and GBEF2 were 52{+-}17% and 52{+-}16%, respectively. There was a direct linear correlation between the values of GBEF1 and GBEF2 for the subjects, with a correlation coefficient of 0.509 (p=0.002). Subgroup data analysis of the volunteer group showed that there was significant linear correlation between volunteer values of GBEF1 and GBEF2, with a correlation coefficient of 0.473 (p=0.017). Subgroup data analysis of the non-CAC patient group showed no significant correlation between patient values of GBEF1 and GBEF2, likely due to limited sample size. This study showed that fatty meal CS is a reliable test in gallbladder motility evaluation and that GBEF measured by fatty meal CS is reproducible

  7. Repeatability and reproducibility of decisions by latent fingerprint examiners.

    Directory of Open Access Journals (Sweden)

    Bradford T Ulery

    Full Text Available The interpretation of forensic fingerprint evidence relies on the expertise of latent print examiners. We tested latent print examiners on the extent to which they reached consistent decisions. This study assessed intra-examiner repeatability by retesting 72 examiners on comparisons of latent and exemplar fingerprints, after an interval of approximately seven months; each examiner was reassigned 25 image pairs for comparison, out of total pool of 744 image pairs. We compare these repeatability results with reproducibility (inter-examiner results derived from our previous study. Examiners repeated 89.1% of their individualization decisions, and 90.1% of their exclusion decisions; most of the changed decisions resulted in inconclusive decisions. Repeatability of comparison decisions (individualization, exclusion, inconclusive was 90.0% for mated pairs, and 85.9% for nonmated pairs. Repeatability and reproducibility were notably lower for comparisons assessed by the examiners as "difficult" than for "easy" or "moderate" comparisons, indicating that examiners' assessments of difficulty may be useful for quality assurance. No false positive errors were repeated (n = 4; 30% of false negative errors were repeated. One percent of latent value decisions were completely reversed (no value even for exclusion vs. of value for individualization. Most of the inter- and intra-examiner variability concerned whether the examiners considered the information available to be sufficient to reach a conclusion; this variability was concentrated on specific image pairs such that repeatability and reproducibility were very high on some comparisons and very low on others. Much of the variability appears to be due to making categorical decisions in borderline cases.

  8. Repeat: a framework to assess empirical reproducibility in biomedical research

    Directory of Open Access Journals (Sweden)

    Leslie D. McIntosh

    2017-09-01

    Full Text Available Abstract Background The reproducibility of research is essential to rigorous science, yet significant concerns of the reliability and verifiability of biomedical research have been recently highlighted. Ongoing efforts across several domains of science and policy are working to clarify the fundamental characteristics of reproducibility and to enhance the transparency and accessibility of research. Methods The aim of the proceeding work is to develop an assessment tool operationalizing key concepts of research transparency in the biomedical domain, specifically for secondary biomedical data research using electronic health record data. The tool (RepeAT was developed through a multi-phase process that involved coding and extracting recommendations and practices for improving reproducibility from publications and reports across the biomedical and statistical sciences, field testing the instrument, and refining variables. Results RepeAT includes 119 unique variables grouped into five categories (research design and aim, database and data collection methods, data mining and data cleaning, data analysis, data sharing and documentation. Preliminary results in manually processing 40 scientific manuscripts indicate components of the proposed framework with strong inter-rater reliability, as well as directions for further research and refinement of RepeAT. Conclusions The use of RepeAT may allow the biomedical community to have a better understanding of the current practices of research transparency and accessibility among principal investigators. Common adoption of RepeAT may improve reporting of research practices and the availability of research outputs. Additionally, use of RepeAT will facilitate comparisons of research transparency and accessibility across domains and institutions.

  9. Cyberinfrastructure to Support Collaborative and Reproducible Computational Hydrologic Modeling

    Science.gov (United States)

    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.

  10. National Capital Planning Commission Meeting Transcripts

    Data.gov (United States)

    National Capital Planning Commission — Transcripts of the monthly (with the exception of August) National Capital Planning Commission meeting transcripts are provided for research to confirm actions taken...

  11. Reproducibility and Reliability of Repeated Quantitative Fluorescence Angiography

    DEFF Research Database (Denmark)

    Nerup, Nikolaj; Knudsen, Kristine Bach Korsholm; Ambrus, Rikard

    2017-01-01

    INTRODUCTION: When using fluorescence angiography (FA) in perioperative perfusion assessment, repeated measures with re-injections of fluorescent dye (ICG) may be required. However, repeated injections may cause saturation of dye in the tissue, exceeding the limit of fluorescence intensity...... that the camera can detect. As the emission of fluorescence is dependent of the excitatory light intensity, reduction of this may solve the problem. The aim of the present study was to investigate the reproducibility and reliability of repeated quantitative FA during a reduction of excitatory light....

  12. On weights which admit the reproducing kernel of Bergman type

    Directory of Open Access Journals (Sweden)

    Zbigniew Pasternak-Winiarski

    1992-01-01

    Full Text Available In this paper we consider (1 the weights of integration for which the reproducing kernel of the Bergman type can be defined, i.e., the admissible weights, and (2 the kernels defined by such weights. It is verified that the weighted Bergman kernel has the analogous properties as the classical one. We prove several sufficient conditions and necessary and sufficient conditions for a weight to be an admissible weight. We give also an example of a weight which is not of this class. As a positive example we consider the weight μ(z=(Imz2 defined on the unit disk in ℂ.

  13. Ratio-scaling of listener preference of multichannel reproduced sound

    DEFF Research Database (Denmark)

    Choisel, Sylvain; Wickelmaier, Florian

    2005-01-01

    -trivial assumption in the case of complex spatial sounds. In the present study the Bradley-Terry-Luce (BTL) model was employed to investigate the unidimensionality of preference judgments made by 40 listeners on multichannel reproduced sound. Short musical excerpts played back in eight reproduction modes (mono...... music). As a main result, the BTL model was found to predict the choice frequencies well. This implies that listeners were able to integrate the complex nature of the sounds into a unidimensional preference judgment. It further implies the existence of a preference scale on which the reproduction modes...

  14. INFRARED IMAGING OF CARBON AND CERAMIC COMPOSITES: DATA REPRODUCIBILITY

    International Nuclear Information System (INIS)

    Knight, B.; Howard, D. R.; Ringermacher, H. I.; Hudson, L. D.

    2010-01-01

    Infrared NDE techniques have proven to be superior for imaging of flaws in ceramic matrix composites (CMC) and carbon silicon carbide composites (C/SiC). Not only can one obtain accurate depth gauging of flaws such as delaminations and layered porosity in complex-shaped components such as airfoils and other aeronautical components, but also excellent reproducibility of image data is obtainable using the STTOF (Synthetic Thermal Time-of-Flight) methodology. The imaging of large complex shapes is fast and reliable. This methodology as applied to large C/SiC flight components at the NASA Dryden Flight Research Center will be described.

  15. Towards interoperable and reproducible QSAR analyses: Exchange of datasets.

    Science.gov (United States)

    Spjuth, Ola; Willighagen, Egon L; Guha, Rajarshi; Eklund, Martin; Wikberg, Jarl Es

    2010-06-30

    QSAR is a widely used method to relate chemical structures to responses or properties based on experimental observations. Much effort has been made to evaluate and validate the statistical modeling in QSAR, but these analyses treat the dataset as fixed. An overlooked but highly important issue is the validation of the setup of the dataset, which comprises addition of chemical structures as well as selection of descriptors and software implementations prior to calculations. This process is hampered by the lack of standards and exchange formats in the field, making it virtually impossible to reproduce and validate analyses and drastically constrain collaborations and re-use of data. We present a step towards standardizing QSAR analyses by defining interoperable and reproducible QSAR datasets, consisting of an open XML format (QSAR-ML) which builds on an open and extensible descriptor ontology. The ontology provides an extensible way of uniquely defining descriptors for use in QSAR experiments, and the exchange format supports multiple versioned implementations of these descriptors. Hence, a dataset described by QSAR-ML makes its setup completely reproducible. We also provide a reference implementation as a set of plugins for Bioclipse which simplifies setup of QSAR datasets, and allows for exporting in QSAR-ML as well as old-fashioned CSV formats. The implementation facilitates addition of new descriptor implementations from locally installed software and remote Web services; the latter is demonstrated with REST and XMPP Web services. Standardized QSAR datasets open up new ways to store, query, and exchange data for subsequent analyses. QSAR-ML supports completely reproducible creation of datasets, solving the problems of defining which software components were used and their versions, and the descriptor ontology eliminates confusions regarding descriptors by defining them crisply. This makes is easy to join, extend, combine datasets and hence work collectively, but

  16. Towards interoperable and reproducible QSAR analyses: Exchange of datasets

    Directory of Open Access Journals (Sweden)

    Spjuth Ola

    2010-06-01

    Full Text Available Abstract Background QSAR is a widely used method to relate chemical structures to responses or properties based on experimental observations. Much effort has been made to evaluate and validate the statistical modeling in QSAR, but these analyses treat the dataset as fixed. An overlooked but highly important issue is the validation of the setup of the dataset, which comprises addition of chemical structures as well as selection of descriptors and software implementations prior to calculations. This process is hampered by the lack of standards and exchange formats in the field, making it virtually impossible to reproduce and validate analyses and drastically constrain collaborations and re-use of data. Results We present a step towards standardizing QSAR analyses by defining interoperable and reproducible QSAR datasets, consisting of an open XML format (QSAR-ML which builds on an open and extensible descriptor ontology. The ontology provides an extensible way of uniquely defining descriptors for use in QSAR experiments, and the exchange format supports multiple versioned implementations of these descriptors. Hence, a dataset described by QSAR-ML makes its setup completely reproducible. We also provide a reference implementation as a set of plugins for Bioclipse which simplifies setup of QSAR datasets, and allows for exporting in QSAR-ML as well as old-fashioned CSV formats. The implementation facilitates addition of new descriptor implementations from locally installed software and remote Web services; the latter is demonstrated with REST and XMPP Web services. Conclusions Standardized QSAR datasets open up new ways to store, query, and exchange data for subsequent analyses. QSAR-ML supports completely reproducible creation of datasets, solving the problems of defining which software components were used and their versions, and the descriptor ontology eliminates confusions regarding descriptors by defining them crisply. This makes is easy to join

  17. Infrared Imaging of Carbon and Ceramic Composites: Data Reproducibility

    Science.gov (United States)

    Knight, B.; Howard, D. R.; Ringermacher, H. I.; Hudson, L. D.

    2010-02-01

    Infrared NDE techniques have proven to be superior for imaging of flaws in ceramic matrix composites (CMC) and carbon silicon carbide composites (C/SiC). Not only can one obtain accurate depth gauging of flaws such as delaminations and layered porosity in complex-shaped components such as airfoils and other aeronautical components, but also excellent reproducibility of image data is obtainable using the STTOF (Synthetic Thermal Time-of-Flight) methodology. The imaging of large complex shapes is fast and reliable. This methodology as applied to large C/SiC flight components at the NASA Dryden Flight Research Center will be described.

  18. Explicit signal to noise ratio in reproducing kernel Hilbert spaces

    DEFF Research Database (Denmark)

    Gomez-Chova, Luis; Nielsen, Allan Aasbjerg; Camps-Valls, Gustavo

    2011-01-01

    This paper introduces a nonlinear feature extraction method based on kernels for remote sensing data analysis. The proposed approach is based on the minimum noise fraction (MNF) transform, which maximizes the signal variance while also minimizing the estimated noise variance. We here propose...... an alternative kernel MNF (KMNF) in which the noise is explicitly estimated in the reproducing kernel Hilbert space. This enables KMNF dealing with non-linear relations between the noise and the signal features jointly. Results show that the proposed KMNF provides the most noise-free features when confronted...

  19. T2 relaxation time in patellar cartilage - global and regional reproducibility at 1.5 Tesla and 3 Tesla

    International Nuclear Information System (INIS)

    Glaser, C.; Horng, A.; Mendlik, T.; Weckbach, S.; Hoffmann, R.T.; Wagner, S.; Raya, J.G.; Reiser, M.; Horger, W.

    2007-01-01

    Purpose: Evaluation of the global and regional reproducibility of T2 relaxation time in patellar cartilage at 1.5 T and 3 T. Materials and Methods: 6 left patellae of 6 healthy volunteers (aged 25-30, 3 female, 3 male) were examined using a fat-saturated multiecho sequence and a T1-w 3D-FLASH sequence with water excitation at 1.5 Tesla and 3 Tesla. Three consecutive data sets were acquired within one MRI session with the examined knee being repositioned in the coil and scanner between each data set. The segmented cartilage (FLASH sequence) was overlaid on the multiecho data and T2 values were calculated for the total cartilage, 3 horizontal layers consisting of a superficial, intermedial and deep layer, 3 facets consisting of a medial, median (ridge) and lateral facet (global T2 values) and 27 ROIs/MRI slices (regional T2 value). The reproducibility (precision error) was calculated as the root mean square average of the individual standard deviations [ms] and coefficients of variation (COV) [%]. Results: The mean global reproducibility error for T2 was 3.53% (±0.38%) at 1.5 Tesla and 3.25% (±0.61%) at 3 Tesla. The mean regional reproducibility error for T2 was 8.62% (±2.61%) at 1.5 Tesla and 9.66% (±3.37%) at 3 Tesla. There was no significant difference with respect to absolute reproducibility errors between 1.5 Tesla and 3 Tesla at a constant spatial resolution. However, different reproducibility errors were found between the cartilage layers. One third of the data variability could be attributed to the influence of the different cartilage layers, and another 10% to the influence of the separate MRI slices. Conclusion: Our data provides an estimation of the global and regional reproducibility errors of T2 in healthy cartilage. In the analysis of small subregions, an increase in the regional reproducibility error must be accepted. The data may serve as a basis for sample size calculations of study populations and may contribute to the decision regarding the

  20. SU-E-T-676: Reproducibility and Consistency of Two SunNuclear 3D Scanning Tanks

    International Nuclear Information System (INIS)

    Hessler, J; DiCostanzo, D; Grzetic, S; Ayan, A; Gupta, N; Woollard, J

    2015-01-01

    Purpose: To determine if two Sun Nuclear 3D Scanning (SNC 3DS) tanks collect reproducible and consistent data and test the precision of the SNC Dosimetry auto-setup. Methods: Percent depth doses (PDDs) and profiles were collected on two SNC 3DS tanks with a Varian TrueBeam linear accelerator. SNC Dosimetry auto-setup application was used with CC13 ionization chambers. After auto-setup, collimator light field was checked manually against the position of the chamber. Comparing measured data for repeated measurements with tank 1 allowed evaluation of SNC-3DS auto-setup and tank reproducibility. Comparing measured data between tanks 1 and 2 allowed evaluation of consistency between tanks. Results: Preliminary results showed reproducibility of depth of maximum dose (Dmax) of 0.38mm for a 10cmx10cm field and 0.67mm for 30cmx30cm on a single tank. PDD values at 5cm, 10cm, and 20cm depths were reproducible within 0.26%. Consistency of Dmax between tanks was 0.17mm for a 10cmx10cm field and 0.44mm for 30cmx30cm. PDD values at 5cm, 10cm, and 20cmwere consistent within 0.06%. Profiles showed reproducibility in field width within 0.4mm for a 10cmx10cm field and 0.7mm for a 30cmx30cm field. Profiles showed consistency in field width within 0.2mm for 10cmx10cm and 30cmx30cm field sizes. Penumbra width was reproducible and consistent to under 0.5mm except for 30cmx30cm field size at 30cm depth where the reproducibility was 2.2mm and the consistency was 2.6mm. Conclusion: In conclusion, the SNC 3DS tank shows good reproducibility in measured data. Since the tank to tank variation in measured data is within the uncertainty of repeated single tank measurements the tanks also perform consistently

  1. Transcription profiles of mitochondrial genes correlate with mitochondrial DNA haplotypes in a natural population of Silene vulgaris

    Directory of Open Access Journals (Sweden)

    Olson Matthew S

    2010-01-01

    Full Text Available Abstract Background Although rapid changes in copy number and gene order are common within plant mitochondrial genomes, associated patterns of gene transcription are underinvestigated. Previous studies have shown that the gynodioecious plant species Silene vulgaris exhibits high mitochondrial diversity and occasional paternal inheritance of mitochondrial markers. Here we address whether variation in DNA molecular markers is correlated with variation in transcription of mitochondrial genes in S. vulgaris collected from natural populations. Results We analyzed RFLP variation in two mitochondrial genes, cox1 and atp1, in offspring of ten plants from a natural population of S. vulgaris in Central Europe. We also investigated transcription profiles of the atp1 and cox1 genes. Most DNA haplotypes and transcription profiles were maternally inherited; for these, transcription profiles were associated with specific mitochondrial DNA haplotypes. One individual exhibited a pattern consistent with paternal inheritance of mitochondrial DNA; this individual exhibited a transcription profile suggestive of paternal but inconsistent with maternal inheritance. We found no associations between gender and transcript profiles. Conclusions Specific transcription profiles of mitochondrial genes were associated with specific mitochondrial DNA haplotypes in a natural population of a gynodioecious species S. vulgaris. Our findings suggest the potential for a causal association between rearrangements in the plant mt genome and transcription product variation.

  2. SU-F-T-55: Reproducibility of Interstitial HDR Brachytherapy Plans

    Energy Technology Data Exchange (ETDEWEB)

    Lee, S; Ellis, R; Traughber, B; Podder, T [University Hospitals Case Medical Center, Cleveland, OH (United States)

    2016-06-15

    Purpose: Treating gynecological cancers with interstitial high-dose-rate (HDR) brachytherapy requires precise reconstruction of catheter positions to obtain accurate dosimetric plans. In this study, we investigated the degree of reproducibility of dosimetric plans for Syed HDR brachytherapy. Methods: We randomly selected five patients having cervix-vaginal cancer who were recently treated in our clinic with interstitial HDR brachytherapy with a prescription dose of 25–30 Gy in five fractions. Interstitial needles/catheters were placed under fluoroscopic guidance and intra-operative 3T MRI scan was performed to confirm the desired catheter placement for adequate target volume coverage. A CT scan was performed and fused with the MRI for delineating high-risk CTV (HR-CTV), intermediate-risk CTV (IR-CTV) and OARs. HDR treatment plans were generated using Oncentra planning software. A single plan was used for all five fractions of treatment for each patient. For this study, we took the original clinical plan and removed all the reconstructed catheters from the plan keeping the original contours unchanged. Then, we manually reconstructed all the catheters and entered the same dwell time from the first original clinical plan. The dosimetric parameters studied were: D90 for HR-CTV and IR-CV, and D2cc for bladder, rectum, sigmoid and bowel. Results: The mean of absolute differences in dosimetric coverage (D90) were (range): 1.3% (1.0–2.0%) and 2.0% (0.9–3.6%) for HR-CTV and IR-CTV, respectively. In case of OARs, the mean of absolute variations in D2cc were (range): 4.7% (0.7–8.9%) for bladder, 1.60% (0.3–3.2%) for rectum, 1.6% (0–3.9%) for sigmoid, and 1.8% (0–5.1%) for bowel. Conclusion: Overall, the reproducibility of interstitial HDR plans was within clinically acceptable limit. Observed maximum variation in D2cc for bladder. If number of catchers and dwell points were relatively low or any one catheter was heavily loaded, then reproducibility of the plan

  3. Method for pulse to pulse dose reproducibility applied to electron linear accelerators

    International Nuclear Information System (INIS)

    Ighigeanu, D.; Martin, D.; Oproiu, C.; Cirstea, E.; Craciun, G.

    2002-01-01

    An original method for obtaining programmed beam single shots and pulse trains with programmed pulse number, pulse repetition frequency, pulse duration and pulse dose is presented. It is particularly useful for automatic control of absorbed dose rate level, irradiation process control as well as in pulse radiolysis studies, single pulse dose measurement or for research experiments where pulse-to-pulse dose reproducibility is required. This method is applied to the electron linear accelerators, ALIN-10 of 6.23 MeV and 82 W and ALID-7, of 5.5 MeV and 670 W, built in NILPRP. In order to implement this method, the accelerator triggering system (ATS) consists of two branches: the gun branch and the magnetron branch. ATS, which synchronizes all the system units, delivers trigger pulses at a programmed repetition rate (up to 250 pulses/s) to the gun (80 kV, 10 A and 4 ms) and magnetron (45 kV, 100 A, and 4 ms).The accelerated electron beam existence is determined by the electron gun and magnetron pulses overlapping. The method consists in controlling the overlapping of pulses in order to deliver the beam in the desired sequence. This control is implemented by a discrete pulse position modulation of gun and/or magnetron pulses. The instabilities of the gun and magnetron transient regimes are avoided by operating the accelerator with no accelerated beam for a certain time. At the operator 'beam start' command, the ATS controls electron gun and magnetron pulses overlapping and the linac beam is generated. The pulse-to-pulse absorbed dose variation is thus considerably reduced. Programmed absorbed dose, irradiation time, beam pulse number or other external events may interrupt the coincidence between the gun and magnetron pulses. Slow absorbed dose variation is compensated by the control of the pulse duration and repetition frequency. Two methods are reported in the electron linear accelerators' development for obtaining the pulse to pulse dose reproducibility: the method

  4. Experiencing variation

    DEFF Research Database (Denmark)

    Kobayashi, Sofie; Berge, Maria; Grout, Brian William Wilson

    2017-01-01

    This study contributes towards a better understanding of learning dynamics in doctoral supervision by analysing how learning opportunities are created in the interaction between supervisors and PhD students, using the notion of experiencing variation as a key to learning. Empirically, we have based...... the study on four video-recorded sessions, with four different PhD students and their supervisors, all from life sciences. Our analysis revealed that learning opportunities in the supervision sessions concerned either the content matter of research (for instance, understanding soil structure......), or the research methods— more specifically how to produce valid results. Our results illustrate how supervisors and PhD students create a space of learning together in their particular discipline by varying critical aspects of their research in their discussions. Situations where more openended research issues...

  5. Highly Efficient and Reproducible Nonfullerene Solar Cells from Hydrocarbon Solvents

    KAUST Repository

    Wadsworth, Andrew; Ashraf, Raja; Abdelsamie, Maged; Pont, Sebastian; Little, Mark; Moser, Maximilian; Hamid, Zeinab; Neophytou, Marios; Zhang, Weimin; Amassian, Aram; Durrant, James R.; Baran, Derya; McCulloch, Iain

    2017-01-01

    With chlorinated solvents unlikely to be permitted for use in solution-processed organic solar cells in industry, there must be a focus on developing nonchlorinated solvent systems. Here we report high-efficiency devices utilizing a low-bandgap donor polymer (PffBT4T-2DT) and a nonfullerene acceptor (EH-IDTBR) from hydrocarbon solvents and without using additives. When mesitylene was used as the solvent, rather than chlorobenzene, an improved power conversion efficiency (11.1%) was achieved without the need for pre- or post-treatments. Despite altering the processing conditions to environmentally friendly solvents and room-temperature coating, grazing incident X-ray measurements confirmed that active layers processed from hydrocarbon solvents retained the robust nanomorphology obtained with hot-processed chlorinated solvents. The main advantages of hydrocarbon solvent-processed devices, besides the improved efficiencies, were the reproducibility and storage lifetime of devices. Mesitylene devices showed better reproducibility and shelf life up to 4000 h with PCE dropping by only 8% of its initial value.

  6. Everware toolkit. Supporting reproducible science and challenge-driven education.

    Science.gov (United States)

    Ustyuzhanin, A.; Head, T.; Babuschkin, I.; Tiunov, A.

    2017-10-01

    Modern science clearly demands for a higher level of reproducibility and collaboration. To make research fully reproducible one has to take care of several aspects: research protocol description, data access, environment preservation, workflow pipeline, and analysis script preservation. Version control systems like git help with the workflow and analysis scripts part. Virtualization techniques like Docker or Vagrant can help deal with environments. Jupyter notebooks are a powerful platform for conducting research in a collaborative manner. We present project Everware that seamlessly integrates git repository management systems such as Github or Gitlab, Docker and Jupyter helping with a) sharing results of real research and b) boosts education activities. With the help of Everware one can not only share the final artifacts of research but all the depth of the research process. This been shown to be extremely helpful during organization of several data analysis hackathons and machine learning schools. Using Everware participants could start from an existing solution instead of starting from scratch. They could start contributing immediately. Everware allows its users to make use of their own computational resources to run the workflows they are interested in, which leads to higher scalability of the toolkit.

  7. Size Control of Sessile Microbubbles for Reproducibly Driven Acoustic Streaming

    Science.gov (United States)

    Volk, Andreas; Kähler, Christian J.

    2018-05-01

    Acoustically actuated bubbles are receiving growing interest in microfluidic applications, as they induce a streaming field that can be used for particle sorting and fluid mixing. An essential but often unspoken challenge in such applications is to maintain a constant bubble size to achieve reproducible conditions. We present an automatized system for the size control of a cylindrical bubble that is formed at a blind side pit of a polydimethylsiloxane microchannel. Using a pressure control system, we adapt the protrusion depth of the bubble into the microchannel to a precision of approximately 0.5 μ m on a timescale of seconds. By comparing the streaming field generated by bubbles of width 80 μ m with a protrusion depth between -12 and 60 μ m , we find that the mean velocity of the induced streaming fields varies by more than a factor of 4. We also find a qualitative change of the topology of the streaming field. Both observations confirm the importance of the bubble size control system in order to achieve reproducible and reliable bubble-driven streaming experiments.

  8. Fluctuation-Driven Neural Dynamics Reproduce Drosophila Locomotor Patterns.

    Directory of Open Access Journals (Sweden)

    Andrea Maesani

    2015-11-01

    Full Text Available The neural mechanisms determining the timing of even simple actions, such as when to walk or rest, are largely mysterious. One intriguing, but untested, hypothesis posits a role for ongoing activity fluctuations in neurons of central action selection circuits that drive animal behavior from moment to moment. To examine how fluctuating activity can contribute to action timing, we paired high-resolution measurements of freely walking Drosophila melanogaster with data-driven neural network modeling and dynamical systems analysis. We generated fluctuation-driven network models whose outputs-locomotor bouts-matched those measured from sensory-deprived Drosophila. From these models, we identified those that could also reproduce a second, unrelated dataset: the complex time-course of odor-evoked walking for genetically diverse Drosophila strains. Dynamical models that best reproduced both Drosophila basal and odor-evoked locomotor patterns exhibited specific characteristics. First, ongoing fluctuations were required. In a stochastic resonance-like manner, these fluctuations allowed neural activity to escape stable equilibria and to exceed a threshold for locomotion. Second, odor-induced shifts of equilibria in these models caused a depression in locomotor frequency following olfactory stimulation. Our models predict that activity fluctuations in action selection circuits cause behavioral output to more closely match sensory drive and may therefore enhance navigation in complex sensory environments. Together these data reveal how simple neural dynamics, when coupled with activity fluctuations, can give rise to complex patterns of animal behavior.

  9. Reproducibility of suppression of Pythium wilt of cucumber by compost

    Directory of Open Access Journals (Sweden)

    Mauritz Vilhelm Vestberg

    2014-10-01

    Full Text Available There is increasing global interest in using compost to suppress soil-borne fungal and bacterial diseases and nematodes. We studied the reproducibility of compost suppressive capacity (SC against Pythium wilt of cucumber using nine composts produced by the same composting plant in 2008 and 2009. A bioassay was set up in a greenhouse using cucumber inoculated with two strains of Pythium. The composts were used as 20% mixtures (v:v of a basic steam-sterilized light Sphagnum peat and sand (3:1, v:v. Shoot height was measured weekly during the 5-week experiment. At harvest, the SC was calculated as the % difference in shoot dry weight (DW between non-inoculated and inoculated cucumbers. The SC was not affected by year of production (2008 or 2009, indicating reproducibility of SC when the raw materials and the composting method are not changed. Differences in shoot height were not as pronounced as those for shoot DW. The results were encouraging, but further studies are still needed for producing compost with guaranteed suppressiveness properties.

  10. Reproducibility of tomographic evaluation of posterolateral lumbar arthrodesis consolidation

    Directory of Open Access Journals (Sweden)

    Marcelo Italo Risso Neto

    2015-06-01

    Full Text Available OBJECTIVE: To evaluate interobserver agreement of Glassman classification for posterolateral lumbar spine arthrodesis.METHODS: One hundred and thirty-four CT scans from patients who underwent posterolateral arthrodesis of the lumbar and lumbosacral spine were evaluated by four observers, namely two orthopedic surgeons experienced in spine surgery and two in training in this area. Using the reconstructed tomographic images at oblique coronal plane, 299 operated levels were systematically analyzed looking for arthrodesis signals. The appearance of bone healing in each operated level was classified in five categories as proposed by Glassman to the posterolateral arthrodesis: 1 bilateral solid arthrodesis; 2 unilateral solid arthrodesis; 3 bilateral partial arthrodesis; 4 unilateral partial arthrodesis; 5 absence of arthrodesis. In a second step, the evaluation of each operated level was divided into two categories: fusion (including type 1, 2, 3, and 4 and non fusion (type 5. Statistical analysis was performed by calculating the Kappa coefficient considering the paired analysis between the two experienced observers and between the two observers in training.RESULTS: The interobserver reproducibility by the kappa coefficient for arthrodesis consolidation analysis for the classification proposed, divided into 5 types, was 0.729 for both experienced surgeons and training surgeons. Considering only two categories kappa coefficient was 0.745 between experienced surgeons and 0.795 between training surgeons. In all analyzes, we obtained high concordance power.CONCLUSION: Interobserver reproducibility was observed with high concordance in the classification proposed by Glassman for posterolateral arthrodesis of the lumbar and lumbosacral spine.

  11. Reproducibility of P-31 spectroscopic imaging of normal human myocardium

    International Nuclear Information System (INIS)

    Tavares, N.J.; Chew, W.; Auffermann, W.; Higgins, C.B.

    1988-01-01

    To assess reproducibility of P-31 MR spectroscopy of human myocardium, ten normal male volunteers were studied on two separate occasions. Spectra were acquired on a clinical 1.5-T MR imaging unit (Signa, General Electric) using a one-dimensional gated spectroscopic imaging sequence (matrix size, 32 X 256) over 20 minutes. Peaks in the adenosine triphosphate (ATP) region, phosphocreatine (PCR), phosphodiesters (PD), and peaks attributable to 2,3 diphosphoglycerate from blood were observed. Interindividual and intraindividual variability expressed as standard errors of the mean (mean +- SEM) were 1.54 +- 0.04 (variability among subjects) and 0.04 (variability between first and second studies) for PCR/β ATP; 0.97 +- 0.18 and 0.06 for PD/β ATP; and 0.62 +- 0.10 and 0.05 for PD/PCR, respectively. In conclusion, P-31 MR spectroscopy yields consistent and reproducible myocardial spectra that might be useful in the future for the evaluation and monitoring of cardiac disease

  12. Highly Efficient and Reproducible Nonfullerene Solar Cells from Hydrocarbon Solvents

    KAUST Repository

    Wadsworth, Andrew

    2017-06-01

    With chlorinated solvents unlikely to be permitted for use in solution-processed organic solar cells in industry, there must be a focus on developing nonchlorinated solvent systems. Here we report high-efficiency devices utilizing a low-bandgap donor polymer (PffBT4T-2DT) and a nonfullerene acceptor (EH-IDTBR) from hydrocarbon solvents and without using additives. When mesitylene was used as the solvent, rather than chlorobenzene, an improved power conversion efficiency (11.1%) was achieved without the need for pre- or post-treatments. Despite altering the processing conditions to environmentally friendly solvents and room-temperature coating, grazing incident X-ray measurements confirmed that active layers processed from hydrocarbon solvents retained the robust nanomorphology obtained with hot-processed chlorinated solvents. The main advantages of hydrocarbon solvent-processed devices, besides the improved efficiencies, were the reproducibility and storage lifetime of devices. Mesitylene devices showed better reproducibility and shelf life up to 4000 h with PCE dropping by only 8% of its initial value.

  13. A Bayesian Perspective on the Reproducibility Project: Psychology.

    Science.gov (United States)

    Etz, Alexander; Vandekerckhove, Joachim

    2016-01-01

    We revisit the results of the recent Reproducibility Project: Psychology by the Open Science Collaboration. We compute Bayes factors-a quantity that can be used to express comparative evidence for an hypothesis but also for the null hypothesis-for a large subset (N = 72) of the original papers and their corresponding replication attempts. In our computation, we take into account the likely scenario that publication bias had distorted the originally published results. Overall, 75% of studies gave qualitatively similar results in terms of the amount of evidence provided. However, the evidence was often weak (i.e., Bayes factor studies (64%) did not provide strong evidence for either the null or the alternative hypothesis in either the original or the replication, and no replication attempts provided strong evidence in favor of the null. In all cases where the original paper provided strong evidence but the replication did not (15%), the sample size in the replication was smaller than the original. Where the replication provided strong evidence but the original did not (10%), the replication sample size was larger. We conclude that the apparent failure of the Reproducibility Project to replicate many target effects can be adequately explained by overestimation of effect sizes (or overestimation of evidence against the null hypothesis) due to small sample sizes and publication bias in the psychological literature. We further conclude that traditional sample sizes are insufficient and that a more widespread adoption of Bayesian methods is desirable.

  14. Automation of cDNA Synthesis and Labelling Improves Reproducibility

    Directory of Open Access Journals (Sweden)

    Daniel Klevebring

    2009-01-01

    Full Text Available Background. Several technologies, such as in-depth sequencing and microarrays, enable large-scale interrogation of genomes and transcriptomes. In this study, we asses reproducibility and throughput by moving all laboratory procedures to a robotic workstation, capable of handling superparamagnetic beads. Here, we describe a fully automated procedure for cDNA synthesis and labelling for microarrays, where the purification steps prior to and after labelling are based on precipitation of DNA on carboxylic acid-coated paramagnetic beads. Results. The fully automated procedure allows for samples arrayed on a microtiter plate to be processed in parallel without manual intervention and ensuring high reproducibility. We compare our results to a manual sample preparation procedure and, in addition, use a comprehensive reference dataset to show that the protocol described performs better than similar manual procedures. Conclusions. We demonstrate, in an automated gene expression microarray experiment, a reduced variance between replicates, resulting in an increase in the statistical power to detect differentially expressed genes, thus allowing smaller differences between samples to be identified. This protocol can with minor modifications be used to create cDNA libraries for other applications such as in-depth analysis using next-generation sequencing technologies.

  15. Reproducibility of temporomandibular joint tomography. Influence of shifted X-ray beam and tomographic focal plane on reproducibility

    International Nuclear Information System (INIS)

    Saito, Masashi

    1999-01-01

    Proper tomographic focal plane and x-ray beam direction are the most important factors to obtain accurate images of the temporomandibular joint (TMJ). In this study, to clarify the magnitude of effect of these two factors on the image quality. We evaluated the reproducibility of tomograms by measuring the distortion when the x-ray beam was shifted from the correct center of the object. The effects of the deviation of the tomographic focal plane on image quality were evaluated by the MTF (Modulation Transfer Function). Two types of tomograms, one the plane type, the other the rotational type were used in this study. A TMJ model was made from Teflon for the purpose of evaluation by shifting the x-ray beam. The x-ray images were obtained by tilting the model from 0 to 10 degrees 2-degree increments. These x-ray images were processed for computer image analysis, and then the distance between condyle and the joint space was measured. To evaluate the influence of the shifted tomographic focal plane on image sharpness, the x-ray images from each setting were analyzed by MTF. To obtain the MTF, ''knife-edge'' made from Pb was used. The images were scanned with a microdensitometer at the central focal plane, and 0, 0.5, 1 mm away respectively. The density curves were analyzed by Fourier analysis and the MTF was calculated. The reproducibility of images became worse by shifting the x-ray beam. This tendency was similar for both tomograms. Object characteristics such as anterior and posterior portion of the joint space affected the deterioration of reproducibility of the tomography. The deviation of the tomographic focal plane also decreased the reproducibility of the x-ray images. The rotational type showed a better MTF, but it became seriously unfavorable with slight changes of the tomographic focal plane. Contrarily, the plane type showed a lower MTF, but the image was stable with shifting of the tomographic focal plane. (author)

  16. Optimizing the fMRI data-processing pipeline using prediction and reproducibility performance metrics: I. A preliminary group analysis

    DEFF Research Database (Denmark)

    Strother, Stephen C.; Conte, Stephen La; Hansen, Lars Kai

    2004-01-01

    We argue that published results demonstrate that new insights into human brain function may be obscured by poor and/or limited choices in the data-processing pipeline, and review the work on performance metrics for optimizing pipelines: prediction, reproducibility, and related empirical Receiver......, temporal detrending, and between-subject alignment) in a group analysis of BOLD-fMRI scans from 16 subjects performing a block-design, parametric-static-force task. Large-scale brain networks were detected using a multivariate linear discriminant analysis (canonical variates analysis, CVA) that was tuned...... of baseline scans have constant, equal means, and this assumption was assessed with prediction metrics. Higher-order polynomial warps compared to affine alignment had only a minor impact on the performance metrics. We found that both prediction and reproducibility metrics were required for optimizing...

  17. Transcriptional responses in honey bee larvae infected with chalkbrood fungus.

    Science.gov (United States)

    Aronstein, Katherine A; Murray, Keith D; Saldivar, Eduardo

    2010-06-21

    Diseases and other stress factors working synergistically weaken honey bee health and may play a major role in the losses of bee populations in recent years. Among a large number of bee diseases, chalkbrood has been on the rise. We present here the experimental identification of honey bee genes that are differentially expressed in response to infection of honey bee larvae with the chalkbrood fungus, Ascosphaera apis. We used cDNA-AFLP Technology to profile transcripts in infected and uninfected bee larvae. From 64 primer combinations, over 7,400 transcriptionally-derived fragments were obtained A total of 98 reproducible polymorphic cDNA-AFLP fragments were excised and sequenced, followed by quantitative real-time RT-PCR (qRT-PCR) analysis of these and additional samples.We have identified a number of differentially-regulated transcripts that are implicated in general mechanisms of stress adaptation, including energy metabolism and protein transport. One of the most interesting differentially-regulated transcripts is for a chitinase-like enzyme that may be linked to anti-fungal activities in the honey bee larvae, similarly to gut and fat-body specific chitinases found in mosquitoes and the red flour beetle. Surprisingly, we did not find many components of the well-characterized NF-kappaB intracellular signaling pathways to be differentially-regulated using the cDNA-AFLP approach. Therefore, utilizing qRT-PCR, we probed some of the immune related genes to determine whether the lack of up-regulation of their transcripts in our analysis can be attributed to lack of immune activation or to limitations of the cDNA-AFLP approach. Using a combination of cDNA-AFLP and qRT-PCR analyses, we were able to determine several key transcriptional events that constitute the overall effort in the honey bee larvae to fight natural fungal infection. Honey bee transcripts identified in this study are involved in critical functions related to transcriptional regulation, apoptotic

  18. Paleomagnetic analysis of curved thrust belts reproduced by physical models

    Science.gov (United States)

    Costa, Elisabetta; Speranza, Fabio

    2003-12-01

    This paper presents a new methodology for studying the evolution of curved mountain belts by means of paleomagnetic analyses performed on analogue models. Eleven models were designed aimed at reproducing various tectonic settings in thin-skinned tectonics. Our models analyze in particular those features reported in the literature as possible causes for peculiar rotational patterns in the outermost as well as in the more internal fronts. In all the models the sedimentary cover was reproduced by frictional low-cohesion materials (sand and glass micro-beads), which detached either on frictional or on viscous layers. These latter were reproduced in the models by silicone. The sand forming the models has been previously mixed with magnetite-dominated powder. Before deformation, the models were magnetized by means of two permanent magnets generating within each model a quasi-linear magnetic field of intensity variable between 20 and 100 mT. After deformation, the models were cut into closely spaced vertical sections and sampled by means of 1×1-cm Plexiglas cylinders at several locations along curved fronts. Care was taken to collect paleomagnetic samples only within virtually undeformed thrust sheets, avoiding zones affected by pervasive shear. Afterwards, the natural remanent magnetization of these samples was measured, and alternating field demagnetization was used to isolate the principal components. The characteristic components of magnetization isolated were used to estimate the vertical-axis rotations occurring during model deformation. We find that indenters pushing into deforming belts from behind form non-rotational curved outer fronts. The more internal fronts show oroclinal-type rotations of a smaller magnitude than that expected for a perfect orocline. Lateral symmetrical obstacles in the foreland colliding with forward propagating belts produce non-rotational outer curved fronts as well, whereas in between and inside the obstacles a perfect orocline forms

  19. Epigenetics regulates transcription and pathogenesis in the parasite Trichomonas vaginalis.

    Science.gov (United States)

    Pachano, Tomas; Nievas, Yesica R; Lizarraga, Ayelen; Johnson, Patricia J; Strobl-Mazzulla, Pablo H; de Miguel, Natalia

    2017-06-01

    Trichomonas vaginalis is a common sexually transmitted parasite that colonizes the human urogenital tract. Infections range from asymptomatic to highly inflammatory, depending on the host and the parasite strain. Different T. vaginalis strains vary greatly in their adherence and cytolytic capacities. These phenotypic differences might be attributed to differentially expressed genes as a consequence of extra-genetic variation, such as epigenetic modifications. In this study, we explored the role of histone acetylation in regulating gene transcription and pathogenesis in T. vaginalis. Here, we show that histone 3 lysine acetylation (H3KAc) is enriched in nucleosomes positioned around the transcription start site of active genes (BAP1 and BAP2) in a highly adherent parasite strain; compared with the low acetylation abundance in contrast to that observed in a less-adherent strain that expresses these genes at low levels. Additionally, exposition of less-adherent strain with a specific histone deacetylases inhibitor, trichostatin A, upregulated the transcription of BAP1 and BAP2 genes in concomitance with an increase in H3KAc abundance and chromatin accessibility around their transcription start sites. Moreover, we demonstrated that the binding of initiator binding protein, the transcription factor responsible for the initiation of transcription of ~75% of known T. vaginalis genes, depends on the histone acetylation state around the metazoan-like initiator to which initiator binding protein binds. Finally, we found that trichostatin A treatment increased parasite aggregation and adherence to host cells. Our data demonstrated for the first time that H3KAc is a permissive histone modification that functions to mediate both transcription and pathogenesis of the parasite T. vaginalis. © 2017 John Wiley & Sons Ltd.

  20. Identification and characterization of transcript polymorphisms in soybean lines varying in oil composition and content.

    Science.gov (United States)

    Goettel, Wolfgang; Xia, Eric; Upchurch, Robert; Wang, Ming-Li; Chen, Pengyin; An, Yong-Qiang Charles

    2014-04-23

    Variation in seed oil composition and content among soybean varieties is largely attributed to differences in transcript sequences and/or transcript accumulation of oil production related genes in seeds. Discovery and analysis of sequence and expression variations in these genes will accelerate soybean oil quality improvement. In an effort to identify these variations, we sequenced the transcriptomes of soybean seeds from nine lines varying in oil composition and/or total oil content. Our results showed that 69,338 distinct transcripts from 32,885 annotated genes were expressed in seeds. A total of 8,037 transcript expression polymorphisms and 50,485 transcript sequence polymorphisms (48,792 SNPs and 1,693 small Indels) were identified among the lines. Effects of the transcript polymorphisms on their encoded protein sequences and functions were predicted. The studies also provided independent evidence that the lack of FAD2-1A gene activity and a non-synonymous SNP in the coding sequence of FAB2C caused elevated oleic acid and stearic acid levels in soybean lines M23 and FAM94-41, respectively. As a proof-of-concept, we developed an integrated RNA-seq and bioinformatics approach to identify and functionally annotate transcript polymorphisms, and demonstrated its high effectiveness for discovery of genetic and transcript variations that result in altered oil quality traits. The collection of transcript polymorphisms coupled with their predicted functional effects will be a valuable asset for further discovery of genes, gene variants, and functional markers to improve soybean oil quality.

  1. OneD: increasing reproducibility of Hi-C samples with abnormal karyotypes.

    Science.gov (United States)

    Vidal, Enrique; le Dily, François; Quilez, Javier; Stadhouders, Ralph; Cuartero, Yasmina; Graf, Thomas; Marti-Renom, Marc A; Beato, Miguel; Filion, Guillaume J

    2018-05-04

    The three-dimensional conformation of genomes is an essential component of their biological activity. The advent of the Hi-C technology enabled an unprecedented progress in our understanding of genome structures. However, Hi-C is subject to systematic biases that can compromise downstream analyses. Several strategies have been proposed to remove those biases, but the issue of abnormal karyotypes received little attention. Many experiments are performed in cancer cell lines, which typically harbor large-scale copy number variations that create visible defects on the raw Hi-C maps. The consequences of these widespread artifacts on the normalized maps are mostly unexplored. We observed that current normalization methods are not robust to the presence of large-scale copy number variations, potentially obscuring biological differences and enhancing batch effects. To address this issue, we developed an alternative approach designed to take into account chromosomal abnormalities. The method, called OneD, increases reproducibility among replicates of Hi-C samples with abnormal karyotype, outperforming previous methods significantly. On normal karyotypes, OneD fared equally well as state-of-the-art methods, making it a safe choice for Hi-C normalization. OneD is fast and scales well in terms of computing resources for resolutions up to 5 kb.

  2. Reproducibility in light microscopy: Maintenance, standards and SOPs.

    Science.gov (United States)

    Deagle, Rebecca C; Wee, Tse-Luen Erika; Brown, Claire M

    2017-08-01

    Light microscopy has grown to be a valuable asset in both the physical and life sciences. It is a highly quantitative method available in individual research laboratories and often centralized in core facilities. However, although quantitative microscopy is becoming a customary tool in research, it is rarely standardized. To achieve accurate quantitative microscopy data and reproducible results, three levels of standardization must be considered: (1) aspects of the microscope, (2) the sample, and (3) the detector. The accuracy of the data is only as reliable as the imaging system itself, thereby imposing the need for routine standard performance testing. Depending on the task some maintenance procedures should be performed once a month, some before each imaging session, while others conducted annually. This text should be implemented as a resource for researchers to integrate with their own standard operating procedures to ensure the highest quality quantitative microscopy data. Copyright © 2017. Published by Elsevier Ltd.

  3. Reproducibility and signal response linearity of Alanine gel dosimeter

    International Nuclear Information System (INIS)

    Silva, Cleber Feijo Silva; Campos, Leticia Lucente

    2008-01-01

    Gel Dosimetry has been studied mainly for medical applications, because it presents signal response in the dose range used in radiotherapy treatments and it can be applied for three dimensional dosimetry. Alanine gel dosimeter is a new gel material developed at IPEN that presents significant improvement on previous alanine systems developed by Costa (1994). The DL-Alanine (C 3 H 7 NO 2 ) is an amino acid tissue equivalent that improves the production of ferric ions in the solution. These ferric ions concentration can be measured by spectrophotometry technique. This work aims to study the reproducibility of the alanine gel solutions and the signal response as a function of gamma radiation dose, considering that these two properties are very important for characterizing and standardizing any dosimeter. (author)

  4. Reproducibility of Automated Voice Range Profiles, a Systematic Literature Review

    DEFF Research Database (Denmark)

    Printz, Trine; Rosenberg, Tine; Godballe, Christian

    2018-01-01

    literature on test-retest accuracy of the automated voice range profile assessment. Study design: Systematic review. Data sources: PubMed, Scopus, Cochrane Library, ComDisDome, Embase, and CINAHL (EBSCO). Methods: We conducted a systematic literature search of six databases from 1983 to 2016. The following......Objective: Reliable voice range profiles are of great importance when measuring effects and side effects from surgery affecting voice capacity. Automated recording systems are increasingly used, but the reproducibility of results is uncertain. Our objective was to identify and review the existing...... keywords were used: phonetogram, voice range profile, and acoustic voice analysis. Inclusion criteria were automated recording procedure, healthy voices, and no intervention between test and retest. Test-retest values concerning fundamental frequency and voice intensity were reviewed. Results: Of 483...

  5. Novel burn device for rapid, reproducible burn wound generation.

    Science.gov (United States)

    Kim, J Y; Dunham, D M; Supp, D M; Sen, C K; Powell, H M

    2016-03-01

    Scarring following full thickness burns leads to significant reductions in range of motion and quality of life for burn patients. To effectively study scar development and the efficacy of anti-scarring treatments in a large animal model (female red Duroc pigs), reproducible, uniform, full-thickness, burn wounds are needed to reduce variability in observed results that occur with burn depth. Prior studies have proposed that initial temperature of the burner, contact time with skin, thermal capacity of burner material, and the amount of pressure applied to the skin need to be strictly controlled to ensure reproducibility. The purpose of this study was to develop a new burner that enables temperature and pressure to be digitally controlled and monitored in real-time throughout burn wound creation and compare it to a standard burn device. A custom burn device was manufactured with an electrically heated burn stylus and a temperature control feedback loop via an electronic microstat. Pressure monitoring was controlled by incorporation of a digital scale into the device, which measured downward force. The standard device was comprised of a heat resistant handle with a long rod connected to the burn stylus, which was heated using a hot plate. To quantify skin surface temperature and internal stylus temperature as a function of contact time, the burners were heated to the target temperature (200±5°C) and pressed into the skin for 40s to create the thermal injuries. Time to reach target temperature and elapsed time between burns were recorded. In addition, each unit was evaluated for reproducibility within and across three independent users by generating burn wounds at contact times spanning from 5 to 40s at a constant pressure and at pressures of 1 or 3lbs with a constant contact time of 40s. Biopsies were collected for histological analysis and burn depth quantification using digital image analysis (ImageJ). The custom burn device maintained both its internal

  6. The Web system of visualization and analysis equipped with reproducibility

    International Nuclear Information System (INIS)

    Ueshima, Yutaka; Saito, Kanji; Takeda, Yasuhiro; Nakai, Youichi; Hayashi, Sachiko

    2005-01-01

    In the advanced photon experimental research, real-time visualization and steering system is thought as desirable method of data analysis. This approach is valid only in the fixed analysis at one time or in the easily reproducible experiment. But, in the research for an unknown problem like the advanced photon experimental research, it is necessary that the observation data can be analyzed many times because profitable analysis is difficult at the first time. Consequently, output data should be filed to refer and analyze at any time. To support the research, we need the followed automatic functions, transporting data files from data generator to data storage, analyzing data, tracking history of data handling, and so on. The supporting system will be integrated database system with several functional servers distributed on the network. (author)

  7. Quark/gluon jet discrimination: a reproducible analysis using R

    CERN Multimedia

    CERN. Geneva

    2017-01-01

    The power to discriminate between light-quark jets and gluon jets would have a huge impact on many searches for new physics at CERN and beyond. This talk will present a walk-through of the development of a prototype machine learning classifier for differentiating between quark and gluon jets at experiments like those at the Large Hadron Collider at CERN. A new fast feature selection method that combines information theory and graph analytics will be outlined. This method has found new variables that promise significant improvements in discrimination power. The prototype jet tagger is simple, interpretable, parsimonious, and computationally extremely cheap, and therefore might be suitable for use in trigger systems for real-time data processing. Nested stratified k-fold cross validation was used to generate robust estimates of model performance. The data analysis was performed entirely in the R statistical programming language, and is fully reproducible. The entire analysis workflow is data-driven, automated a...

  8. Enhancing Scientific Foundations to Ensure Reproducibility: A New Paradigm.

    Science.gov (United States)

    Hsieh, Terry; Vaickus, Max H; Remick, Daniel G

    2018-01-01

    Progress in science is dependent on a strong foundation of reliable results. The publish or perish paradigm in research, coupled with an increase in retracted articles from the peer-reviewed literature, is beginning to erode the trust of both the scientific community and the public. The NIH is combating errors by requiring investigators to follow new guidelines addressing scientific premise, experimental design, biological variables, and authentication of reagents. Herein, we discuss how implementation of NIH guidelines will help investigators proactively address pitfalls of experimental design and methods. Careful consideration of the variables contributing to reproducibility helps ensure robust results. The NIH, investigators, and journals must collaborate to ensure that quality science is funded, explored, and published. Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  9. Towards Reproducible Research Data Analyses in LHC Particle Physics

    CERN Document Server

    Simko, Tibor

    2017-01-01

    The reproducibility of the research data analysis requires having access not only to the original datasets, but also to the computing environment, the analysis software and the workflow used to produce the original results. We present the nascent CERN Analysis Preservation platform with a set of tools developed to support particle physics researchers in preserving the knowledge around analyses so that capturing, sharing, reusing and reinterpreting data becomes easier. The presentation will focus on three pillars: (i) capturing structured knowledge information about data analysis processes; (ii) capturing the computing environment, the software code, the datasets, the configuration and other information assets used in data analyses; (iii) re-instantiating of preserved analyses on a containerised computing cloud for the purposes of re-validation and re-interpretation.

  10. Timbral aspects of reproduced sound in small rooms. II

    DEFF Research Database (Denmark)

    Bech, Søren

    1996-01-01

    A single loudspeaker with frequency-dependent directivity characteristics, positioned in a room of normal size with frequency-dependent absorption coefficients of the room surfaces, has been simulated using an electroacoustic setup. The model included the direct sound, seventeen individual...... reflections and the reverberant field. The threshold of detection, and just-noticeable differences for an increase in level were measured for individual reflections. The results have confirmed that the first-order floor reflection is likely to contribute individually to the timbre of reproduced noise. However......, for a speech signal none of the investigated reflections will contribute individually to the timbre. It is suggested that the threshold of detection is determined by the spectral changes in the dominant frequency range of 500 Hz to 2 kHz. For increases in the level of individual reflections, the most likely...

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

    Science.gov (United States)

    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.

  12. Efficient and reproducible identification of mismatch repair deficient colon cancer

    DEFF Research Database (Denmark)

    Joost, Patrick; Bendahl, Pär-Ola; Halvarsson, Britta

    2013-01-01

    BACKGROUND: The identification of mismatch-repair (MMR) defective colon cancer is clinically relevant for diagnostic, prognostic and potentially also for treatment predictive purposes. Preselection of tumors for MMR analysis can be obtained with predictive models, which need to demonstrate ease...... of application and favorable reproducibility. METHODS: We validated the MMR index for the identification of prognostically favorable MMR deficient colon cancers and compared performance to 5 other prediction models. In total, 474 colon cancers diagnosed ≥ age 50 were evaluated with correlation between...... clinicopathologic variables and immunohistochemical MMR protein expression. RESULTS: Female sex, age ≥60 years, proximal tumor location, expanding growth pattern, lack of dirty necrosis, mucinous differentiation and presence of tumor-infiltrating lymphocytes significantly correlated with MMR deficiency. Presence...

  13. Numerical optimization of alignment reproducibility for customizable surgical guides.

    Science.gov (United States)

    Kroes, Thomas; Valstar, Edward; Eisemann, Elmar

    2015-10-01

    Computer-assisted orthopedic surgery aims at minimizing invasiveness, postoperative pain, and morbidity with computer-assisted preoperative planning and intra-operative guidance techniques, of which camera-based navigation and patient-specific templates (PST) are the most common. PSTs are one-time templates that guide the surgeon initially in cutting slits or drilling holes. This method can be extended to reusable and customizable surgical guides (CSG), which can be adapted to the patients' bone. Determining the right set of CSG input parameters by hand is a challenging task, given the vast amount of input parameter combinations and the complex physical interaction between the PST/CSG and the bone. This paper introduces a novel algorithm to solve the problem of choosing the right set of input parameters. Our approach predicts how well a CSG instance is able to reproduce the planned alignment based on a physical simulation and uses a genetic optimization algorithm to determine optimal configurations. We validate our technique with a prototype of a pin-based CSG and nine rapid prototyped distal femora. The proposed optimization technique has been compared to manual optimization by experts, as well as participants with domain experience. Using the optimization technique, the alignment errors remained within practical boundaries of 1.2 mm translation and [Formula: see text] rotation error. In all cases, the proposed method outperformed manual optimization. Manually optimizing CSG parameters turns out to be a counterintuitive task. Even after training, subjects with and without anatomical background fail in choosing appropriate CSG configurations. Our optimization algorithm ensures that the CSG is configured correctly, and we could demonstrate that the intended alignment of the CSG is accurately reproduced on all tested bone geometries.

  14. Illusory Motion Reproduced by Deep Neural Networks Trained for Prediction.

    Science.gov (United States)

    Watanabe, Eiji; Kitaoka, Akiyoshi; Sakamoto, Kiwako; Yasugi, Masaki; Tanaka, Kenta

    2018-01-01

    The cerebral cortex predicts visual motion to adapt human behavior to surrounding objects moving in real time. Although the underlying mechanisms are still unknown, predictive coding is one of the leading theories. Predictive coding assumes that the brain's internal models (which are acquired through learning) predict the visual world at all times and that errors between the prediction and the actual sensory input further refine the internal models. In the past year, deep neural networks based on predictive coding were reported for a video prediction machine called PredNet. If the theory substantially reproduces the visual information processing of the cerebral cortex, then PredNet can be expected to represent the human visual perception of motion. In this study, PredNet was trained with natural scene videos of the self-motion of the viewer, and the motion prediction ability of the obtained computer model was verified using unlearned videos. We found that the computer model accurately predicted the magnitude and direction of motion of a rotating propeller in unlearned videos. Surprisingly, it also represented the rotational motion for illusion images that were not moving physically, much like human visual perception. While the trained network accurately reproduced the direction of illusory rotation, it did not detect motion components in negative control pictures wherein people do not perceive illusory motion. This research supports the exciting idea that the mechanism assumed by the predictive coding theory is one of basis of motion illusion generation. Using sensory illusions as indicators of human perception, deep neural networks are expected to contribute significantly to the development of brain research.

  15. Reproducibility in Psychological Science: When Do Psychological Phenomena Exist?

    Directory of Open Access Journals (Sweden)

    Seppo E. Iso-Ahola

    2017-06-01

    Full Text Available Scientific evidence has recently been used to assert that certain psychological phenomena do not exist. Such claims, however, cannot be made because (1 scientific method itself is seriously limited (i.e., it can never prove a negative; (2 non-existence of phenomena would require a complete absence of both logical (theoretical and empirical support; even if empirical support is weak, logical and theoretical support can be strong; (3 statistical data are only one piece of evidence and cannot be used to reduce psychological phenomena to statistical phenomena; and (4 psychological phenomena vary across time, situations and persons. The human mind is unreproducible from one situation to another. Psychological phenomena are not particles that can decisively be tested and discovered. Therefore, a declaration that a phenomenon is not real is not only theoretically and empirically unjustified but runs counter to the propositional and provisional nature of scientific knowledge. There are only “temporary winners” and no “final truths” in scientific knowledge. Psychology is a science of subtleties in human affect, cognition and behavior. Its phenomena fluctuate with conditions and may sometimes be difficult to detect and reproduce empirically. When strictly applied, reproducibility is an overstated and even questionable concept in psychological science. Furthermore, statistical measures (e.g., effect size are poor indicators of the theoretical importance and relevance of phenomena (cf. “deliberate practice” vs. “talent” in expert performance, not to mention whether phenomena are real or unreal. To better understand psychological phenomena, their theoretical and empirical properties should be examined via multiple parameters and criteria. Ten such parameters are suggested.

  16. Reproducibility in Psychological Science: When Do Psychological Phenomena Exist?

    Science.gov (United States)

    Iso-Ahola, Seppo E.

    2017-01-01

    Scientific evidence has recently been used to assert that certain psychological phenomena do not exist. Such claims, however, cannot be made because (1) scientific method itself is seriously limited (i.e., it can never prove a negative); (2) non-existence of phenomena would require a complete absence of both logical (theoretical) and empirical support; even if empirical support is weak, logical and theoretical support can be strong; (3) statistical data are only one piece of evidence and cannot be used to reduce psychological phenomena to statistical phenomena; and (4) psychological phenomena vary across time, situations and persons. The human mind is unreproducible from one situation to another. Psychological phenomena are not particles that can decisively be tested and discovered. Therefore, a declaration that a phenomenon is not real is not only theoretically and empirically unjustified but runs counter to the propositional and provisional nature of scientific knowledge. There are only “temporary winners” and no “final truths” in scientific knowledge. Psychology is a science of subtleties in human affect, cognition and behavior. Its phenomena fluctuate with conditions and may sometimes be difficult to detect and reproduce empirically. When strictly applied, reproducibility is an overstated and even questionable concept in psychological science. Furthermore, statistical measures (e.g., effect size) are poor indicators of the theoretical importance and relevance of phenomena (cf. “deliberate practice” vs. “talent” in expert performance), not to mention whether phenomena are real or unreal. To better understand psychological phenomena, their theoretical and empirical properties should be examined via multiple parameters and criteria. Ten such parameters are suggested. PMID:28626435

  17. Reproducible gene targeting in recalcitrant Escherichia coli isolates

    Directory of Open Access Journals (Sweden)

    De Greve Henri

    2011-06-01

    Full Text Available Abstract Background A number of allele replacement methods can be used to mutate bacterial genes. For instance, the Red recombinase system of phage Lambda has been used very efficiently to inactivate chromosomal genes in E. coli K-12, through recombination between regions of homology. However, this method does not work reproducibly in some clinical E. coli isolates. Findings The procedure was modified by using longer homologous regions (85 bp and 500-600 bp, to inactivate genes in the uropathogenic E. coli strain UTI89. An lrhA regulator mutant, and deletions of the lac operon as well as the complete type 1 fimbrial gene cluster, were obtained reproducibly. The modified method is also functional in other recalcitrant E. coli, like the avian pathogenic E. coli strain APEC1. The lrhA regulator and lac operon deletion mutants of APEC1 were successfully constructed in the same way as the UTI89 mutants. In other avian pathogenic E. coli strains (APEC3E, APEC11A and APEC16A it was very difficult or impossible to construct these mutants, with the original Red recombinase-based method, with a Red recombinase-based method using longer (85 bp homologous regions or with our modified protocol, using 500 - 600 bp homologous regions. Conclusions The method using 500-600 bp homologous regions can be used reliably in some clinical isolates, to delete single genes or entire operons by homologous recombination. However, it does not invariably show a greater efficiency in obtaining mutants, when compared to the original Red-mediated gene targeting method or to the gene targeting method with 85 bp homologous regions. Therefore the length of the homology regions is not the only limiting factor for the construction of mutants in these recalcitrant strains.

  18. Psychometric Evaluation of the Brachial Assessment Tool Part 1: Reproducibility.

    Science.gov (United States)

    Hill, Bridget; Williams, Gavin; Olver, John; Ferris, Scott; Bialocerkowski, Andrea

    2018-04-01

    To evaluate reproducibility (reliability and agreement) of the Brachial Assessment Tool (BrAT), a new patient-reported outcome measure for adults with traumatic brachial plexus injury (BPI). Prospective repeated-measure design. Outpatient clinics. Adults with confirmed traumatic BPI (N=43; age range, 19-82y). People with BPI completed the 31-item 4-response BrAT twice, 2 weeks apart. Results for the 3 subscales and summed score were compared at time 1 and time 2 to determine reliability, including systematic differences using paired t tests, test retest using intraclass correlation coefficient model 1,1 (ICC 1,1 ), and internal consistency using Cronbach α. Agreement parameters included standard error of measurement, minimal detectable change, and limits of agreement. BrAT. Test-retest reliability was excellent (ICC 1,1 =.90-.97). Internal consistency was high (Cronbach α=.90-.98). Measurement error was relatively low (standard error of measurement range, 3.1-8.8). A change of >4 for subscale 1, >6 for subscale 2, >4 for subscale 3, and >10 for the summed score is indicative of change over and above measurement error. Limits of agreement ranged from ±4.4 (subscale 3) to 11.61 (summed score). These findings support the use of the BrAT as a reproducible patient-reported outcome measure for adults with traumatic BPI with evidence of appropriate reliability and agreement for both individual and group comparisons. Further psychometric testing is required to establish the construct validity and responsiveness of the BrAT. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  19. Illusory Motion Reproduced by Deep Neural Networks Trained for Prediction

    Directory of Open Access Journals (Sweden)

    Eiji Watanabe

    2018-03-01

    Full Text Available The cerebral cortex predicts visual motion to adapt human behavior to surrounding objects moving in real time. Although the underlying mechanisms are still unknown, predictive coding is one of the leading theories. Predictive coding assumes that the brain's internal models (which are acquired through learning predict the visual world at all times and that errors between the prediction and the actual sensory input further refine the internal models. In the past year, deep neural networks based on predictive coding were reported for a video prediction machine called PredNet. If the theory substantially reproduces the visual information processing of the cerebral cortex, then PredNet can be expected to represent the human visual perception of motion. In this study, PredNet was trained with natural scene videos of the self-motion of the viewer, and the motion prediction ability of the obtained computer model was verified using unlearned videos. We found that the computer model accurately predicted the magnitude and direction of motion of a rotating propeller in unlearned videos. Surprisingly, it also represented the rotational motion for illusion images that were not moving physically, much like human visual perception. While the trained network accurately reproduced the direction of illusory rotation, it did not detect motion components in negative control pictures wherein people do not perceive illusory motion. This research supports the exciting idea that the mechanism assumed by the predictive coding theory is one of basis of motion illusion generation. Using sensory illusions as indicators of human perception, deep neural networks are expected to contribute significantly to the development of brain research.

  20. Repeatability and reproducibility of an automated gas production technique

    NARCIS (Netherlands)

    Laar, van H.; Straalen, van W.M.; Gelder, van A.H.; Boever, de J.L.; heer, D' B.; Vedder, H.; Kroes, R.; Bot, de P.; Hees, van J.; Cone, J.W.

    2006-01-01

    Two ring tests with five and three laboratories, respectively, were conducted to quantify variation within and among laboratories in an automated gas production technique. Single batches of the feeds soya bean meal (SBM), wheat grain (WG), grass silage (GS) and maize gluten meal (MG) were divided

  1. Using network component analysis to dissect regulatory networks mediated by transcription factors in yeast.

    Directory of Open Access Journals (Sweden)

    Chun Ye

    2009-03-01

    Full Text Available Understanding the relationship between genetic variation and gene expression is a central question in genetics. With the availability of data from high-throughput technologies such as ChIP-Chip, expression, and genotyping arrays, we can begin to not only identify associations but to understand how genetic variations perturb the underlying transcription regulatory networks to induce differential gene expression. In this study, we describe a simple model of transcription regulation where the expression of a gene is completely characterized by two properties: the concentrations and promoter affinities of active transcription factors. We devise a method that extends Network Component Analysis (NCA to determine how genetic variations in the form of single nucleotide polymorphisms (SNPs perturb these two properties. Applying our method to a segregating population of Saccharomyces cerevisiae, we found statistically significant examples of trans-acting SNPs located in regulatory hotspots that perturb transcription factor concentrations and affinities for target promoters to cause global differential expression and cis-acting genetic variations that perturb the promoter affinities of transcription factors on a single gene to cause local differential expression. Although many genetic variations linked to gene expressions have been identified, it is not clear how they perturb the underlying regulatory networks that govern gene expression. Our work begins to fill this void by showing that many genetic variations affect the concentrations of active transcription factors in a cell and their affinities for target promoters. Understanding the effects of these perturbations can help us to paint a more complete picture of the complex landscape of transcription regulation. The software package implementing the algorithms discussed in this work is available as a MATLAB package upon request.

  2. Geographical localisation of the geomagnetic secular variation

    DEFF Research Database (Denmark)

    Aubert, Julien; Finlay, Chris; Olsen, Nils

    2013-01-01

    the model and geomagnetic data previously processed in the same way. Our results suggest that conservation of angular momentum and heterogeneous thermochemical boundary control in the coupled inner core / outer core / mantle system are central to understanding how Earth’s magnetic field currently evolves......., westward moving, magnetic flux patches at the core surface. Despite its successes in explaining the main morphological properties of Earth’s magnetic field, self-consistent numerical modelling of the geodynamo has so far failed to reproduce this field variation pattern. Furthermore its magnetohydrodynamic...... control from either, or both, the inner-core boundary and the core-mantle boundary. In addition to presenting an Earth-like magnetic field morphology, these new numerical models also reproduce the morphology and localization of geomagnetic secular variation. In our models, the conservation of the angular...

  3. Variability and reproducibility of rubidium-82 kinetic parameters in the myocardium of the anesthetized canine

    International Nuclear Information System (INIS)

    Coxson, P.G.; Brennan, K.M.; Huesman, R.H.

    1995-01-01

    Kinetic analysis of 82 Rb (I) dynamic PET data produces quantitative measures which could be used to evaluate ischemic heart disease. These measures have the potential to generate objective comparisons of different patients or the same patient at different times. To achieve this potential, it is essential to determine the variability and reproducibility of the kinetic parameters. A total of 48 I dynamic PET datasets were acquired from two pure bred beagles. Each animal underwent eight I PET studies with essentially the same protocol for three successive weeks. Data were acquired with the Donner 600-Crystal Positron Tomograph (PET600). In each week, single-slice dynamic I PET datasets were collected with the animal at rest at three different gantry positions separated by 5 mm. Additional dataset were collected after dipyridamole infusion and after administration of aminophylline to induce a return to rest. A two-compartment kinetic model with correction for myocardial vasculature and spillover from the left ventricular blood pool was used to analyze the dynamic datasets. Model parameters for uptake (k 1 ), washout (k 2 ) and vascular fraction (f v ) were estimated in 11-14 myocardial regions of interest (ROIs) using a weighted least-squares criterion. Statistical fluctuation due to the PET acquisition process was minimized by using a relatively high I dose (about 30 mCi) to take advantage of the high count rate capacity of the PET600. The variation in mean k 1 , where the mean is taken over the myocardial ROIs was 10%-20% (Dog 1) and 15%-50% (Dog 2) among the rest studies conducted on the same data. Similar variation was evident in comparing studies in the same animal for different weeks. Spatial and temporal variation in estimates of the uptake rate (k 1 ) of I in the resting myocardium of the anesthetized canine are small in relation to the functional increase in k 1 , following dipyridamole stress. 17 refs., 14 figs

  4. Transcriptional regulation of hepatic lipogenesis.

    Science.gov (United States)

    Wang, Yuhui; Viscarra, Jose; Kim, Sun-Joong; Sul, Hei Sook

    2015-11-01

    Fatty acid and fat synthesis in the liver is a highly regulated metabolic pathway that is important for very low-density lipoprotein (VLDL) production and thus energy distribution to other tissues. Having common features at their promoter regions, lipogenic genes are coordinately regulated at the transcriptional level. Transcription factors, such as upstream stimulatory factors (USFs), sterol regulatory element-binding protein 1C (SREBP1C), liver X receptors (LXRs) and carbohydrate-responsive element-binding protein (ChREBP) have crucial roles in this process. Recently, insights have been gained into the signalling pathways that regulate these transcription factors. After feeding, high blood glucose and insulin levels activate lipogenic genes through several pathways, including the DNA-dependent protein kinase (DNA-PK), atypical protein kinase C (aPKC) and AKT-mTOR pathways. These pathways control the post-translational modifications of transcription factors and co-regulators, such as phosphorylation, acetylation or ubiquitylation, that affect their function, stability and/or localization. Dysregulation of lipogenesis can contribute to hepatosteatosis, which is associated with obesity and insulin resistance.

  5. Structural insights into transcription complexes

    NARCIS (Netherlands)

    Berger, I.; Blanco, A.G.; Boelens, R.; Cavarelli, J.; Coll, M.; Folkers, G.E.; Nie, Y.; Pogenberg, V.; Schultz, P.; Wilmanns, M.; Moras, D.; Poterszman, A.

    2011-01-01

    Control of transcription allows the regulation of cell activity in response to external stimuli and research in the field has greatly benefited from efforts in structural biology. In this review, based on specific examples from the European SPINE2-COMPLEXES initiative, we illustrate the impact of

  6. Transcription factor-based biosensor

    Science.gov (United States)

    Dietrich, Jeffrey A; Keasling, Jay D

    2013-10-08

    The present invention provides for a system comprising a BmoR transcription factor, a .sigma..sup.54-RNA polymerase, and a pBMO promoter operatively linked to a reporter gene, wherein the pBMO promoter is capable of expression of the reporter gene with an activated form of the BmoR and the .sigma..sup.54-RNA polymerase.

  7. Magnetic resonance elastography of the kidneys: feasibility and reproducibility in young healthy adults.

    Science.gov (United States)

    Rouvière, Olivier; Souchon, Rémi; Pagnoux, Gaële; Ménager, Jean-Michel; Chapelon, Jean-Yves

    2011-10-01

    To evaluate the feasibility and reproducibility of renal magnetic resonance elastography (MRE) in young healthy volunteers. Ten volunteers underwent renal MRE twice at a 4-5 week interval. The vibrations (45 and 76 Hz) were generated by a speaker positioned beneath the volunteers' back and centered on their left kidney. For each frequency, three sagittal slices were acquired (eight phase offsets per cycle, motion-encoding gradients successively positioned along the three directions of space). Shear velocity images were reconstructed using the curl operator combined with the local frequency estimation (LFE) algorithm. The mean shear velocities measured in the renal parenchyma during the two examinations were not significantly different and exhibited a mean variation of 6% at 45 Hz and 76 Hz. The mean shear velocities in renal parenchyma were 2.21 ± 0.14 m/s at 45 Hz (shear modulus of 4.9 ± 0.5 kPa) and 3.07 ± 0.17 m/s at 76 Hz (9.4 ± 0.8 kPa, P < 0.01). The mean shear velocities in the renal cortex and medulla were respectively 2.19 ± 0.13 m/s and 2.32 ± 0.16 m/s at 45 Hz (P = 0.002) and 3.06 ± 0.16 m/s and 3.10 ± 0.22 m/s at 76 Hz (P = 0.13). Renal MRE was feasible and reproducible. Two independent measurements of shear velocities in the renal parenchyma of the same subjects showed an average variability of 6%. Copyright © 2011 Wiley-Liss, Inc.

  8. Reproducibility of duplex ultrasonography and air plethysmography used for the evaluation of chronic venous insufficiency.

    Science.gov (United States)

    Asbeutah, Akram Mahmoud; Riha, Andrea Zdena; Cameron, James Donald; McGrath, Barry Patrick

    2005-04-01

    The purpose of this study was to determine the reproducibility of measurements on duplex ultrasonography (DU) and air plethysmography (APG) in subjects with post-thrombotic syndrome. Duplex ultrasonography and APG were used to measure indices of lower limb venous reflux in 15 limbs with a history of deep vein thrombosis and evidence of venous insufficiency as diagnosed by ultrasonography. Three limbs were in class 0; 4 were in classes 1 to 3; and 8 were in classes 4 to 6, according to clinical, etiologic, anatomic, and pathophysiologic clinical classification. Duplex ultrasonography was performed 3 times on the same day, and venous diameter, area, peak reflux velocity, reflux flow volume, and reflux duration measurements were obtained. Air plethysmography was performed on 2 days, 7 to 10 days apart, with 1 measurement on the first day and 2 measurements on the second day. Values obtained from APG included outflow fraction, venous filling index, ejection fraction, and residual volume fraction. The measurements were performed by a vascular technologist blinded to the previous test results. One-way analysis of variance, the Student paired t test, and Bland-Altman plots were used to examine the statistical differences of the DU and APG parameters for all measurements. The mean coefficient of variation for within-subject measurements of all DU and APG parameters measured was less than 10%. Bland-Altman plots showed that there were no apparent trends with increasing values over a wide range for any of the DU parameters, nor were there any for the APG parameters. Under ideal conditions, when measured by a highly trained technologist, both DU and APG showed satisfactory reproducibility.

  9. Social smile reproducibility using 3-D stereophotogrammetry and reverse engineering technology.

    Science.gov (United States)

    Dindaroğlu, Furkan; Duran, Gökhan Serhat; Görgülü, Serkan; Yetkiner, Enver

    2016-05-01

    To assess the range of social smile reproducibility using 3-D stereophotogrammetry and reverse engineering technology. Social smile images of white adolescents (N  =  15, mean age  =  15.4 ±1.5 years; range  =  14-17 years) were obtained using 3dMDFlex (3dMD, Atlanta, Ga). Each participant was asked to produce 16 social smiles at 3-minute intervals. All images were obtained in natural head position. Alignment of images, segmentation of smile area, and 3-D deviation analysis were carried out using Geomagic Control software (3D Systems Inc, Cary, NC). A single image was taken as a reference, and the remaining 15 images were compared with the reference image to evaluate positive and negative deviations. The differences between the mean deviation limits of participants with the highest and the lowest deviations and the total mean deviations were evaluated using Bland-Altman Plots. Minimum and maximum deviations of a single image from the reference image were 0.34 and 2.69 mm, respectively. Lowest deviation between two images was within 0.5 mm and 1.54 mm among all participants (mean, 0.96 ± 0.21 mm), and the highest deviation was between 0.41 mm and 2.69 mm (mean, 1.53 ± 0.46 mm). For a single patient, when all alignments were considered together, the mean deviation was between 0.32 ± 0.10 mm and 0.59 ± 0.24 mm. Mean deviation for one image was between 0.14 and 1.21 mm. The range of reproducibility of the social smile presented individual variability, but this variation was not clinically significant or detectable under routine clinical observation.

  10. Laboratory synthesis of an independently reproducing vertebrate species

    OpenAIRE

    Lutes, Aracely A.; Baumann, Diana P.; Neaves, William B.; Baumann, Peter

    2011-01-01

    Speciation in animals commonly involves an extrinsic barrier to genetic exchange followed by the accumulation of sufficient genetic variation to impede subsequent productive interbreeding. All-female species of whiptail lizards, which originated by interspecific hybridization between sexual progenitors, are an exception to this rule. Here, the arising species instantaneously acquires a novel genotype combining distinctive alleles from two different species, and reproduction by parthenogenesis...

  11. Reproducibility between conventional and digital periapical radiography for bone height measurement

    Directory of Open Access Journals (Sweden)

    Miguel Simancas Pallares

    2015-10-01

    Conclusions. Reproducibility between methods was considered poor, including subgroup analysis, therefore, reproducibility between methods is minimal. Usage of these methods in periodontics should be made implementing the whole knowledge of the technical features and the advantages of these systems.

  12. Interobserver reproducibility of radiographic evaluation of lumbar spine instability.

    Science.gov (United States)

    Segundo, Saulo de Tarso de Sá Pereira; Valesin, Edgar Santiago; Lenza, Mario; Santos, Durval do Carmo Barros; Rosemberg, Laercio Alberto; Ferretti, Mario

    2016-01-01

    To measure the interobserver reproducibility of the radiographic evaluation of lumbar spine instability. Measurements of the dynamic radiographs of the lumbar spine in lateral view were performed, evaluating the anterior translation and the angulation among the vertebral bodies. The tests were evaluated at workstations of the organization, through the Carestream Health Vue RIS (PACS), version 11.0.12.14 Inc. 2009© system. Agreement in detecting cases of radiographic instability among the observers varied from 88.1 to 94.4%, and the agreement coefficients AC1 were all above 0.8, indicating excellent agreement. The interobserver analysis performed among orthopedic surgeons with different levels of training in dynamic radiographs of the spine obtained high reproducibility and agreement. However, some factors, such as the manual method of measurement and the presence of vertebral osteophytes, might have generated a few less accurate results in this comparative evaluation of measurements. Mensurar a reprodutibilidade interobservadores da avaliação radiográfica da instabilidade da coluna lombar. Foram realizadas mensurações das radiografias dinâmicas de coluna lombar na incidência em perfil, avaliando-se a translação anterior e a angulação entre os corpos vertebrais. Os exames foram avaliados em workstations da própria instituição, por meio do sistema Vue RIS (PACS) da Carestream Health, versão 11.0.12.14 Inc. 2009©. A proporção de concordância em detecção de casos de instabilidade radiográfica entre os observadores variou de 88,1 a 94,4%, e os coeficientes de concordância AC1 estiveram todos acima de 0,8, indicando concordância excelente. A análise interobservadores realizada entre médicos ortopedistas com diferentes níveis de treinamento em radiografias dinâmicas da coluna vertebral obteve elevada reprodutibilidade e concordância. No entanto, alguns fatores, como método manual de aferição e a presença de osteófitos vertebrais, podem

  13. Reproducing an extreme flood with uncertain post-event information

    Directory of Open Access Journals (Sweden)

    D. Fuentes-Andino

    2017-07-01

    Full Text Available 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

  14. Reproducibility of up-flow column percolation tests for contaminated soils.

    Directory of Open Access Journals (Sweden)

    Tetsuo Yasutaka

    Full Text Available Up-flow column percolation tests are used at laboratory scale to assess the leaching behavior of hazardous substance from contaminated soils in a specific condition as a function of time. Monitoring the quality of these test results inter or within laboratory is crucial, especially if used for Environment-related legal policy or for routine testing purposes. We tested three different sandy loam type soils (Soils I, II and III to determine the reproducibility (variability inter laboratory of test results and to evaluate the difference in the test results within laboratory. Up-flow column percolation tests were performed following the procedure described in the ISO/TS 21268-3. This procedure consists of percolating solution (calcium chloride 1 mM from bottom to top at a flow rate of 12 mL/h through softly compacted soil contained in a column of 5 cm diameter and 30 ± 5 cm height. Eluate samples were collected at liquid-to-solid ratio of 0.1, 0.2, 0.5, 1, 2, 5 and 10 L/kg and analyzed for quantification of the target elements (Cu, As, Se, Cl, Ca, F, Mg, DOC and B in this research. For Soil I, 17 institutions in Japan joined this validation test. The up-flow column experiments were conducted in duplicate, after 48 h of equilibration time and at a flow rate of 12 mL/h. Column percolation test results from Soils II and III were used to evaluate the difference in test results from the experiments conducted in duplicate in a single laboratory, after 16 h of equilibration time and at a flow rate of 36 mL/h. Overall results showed good reproducibility (expressed in terms of the coefficient of variation, CV, calculated by dividing the standard deviation by the mean, as the CV was lower than 30% in more than 90% of the test results associated with Soil I. Moreover, low variability (expressed in terms of difference between the two test results divided by the mean was observed in the test results related to Soils II and III, with a variability lower than 30

  15. Range resolution and reproducibility of a dedicated phantom for proton PBS daily quality assurance.

    Science.gov (United States)

    Placidi, Lorenzo; Togno, Michele; Weber, Damien C; Lomax, Antony J; Hrbacek, Jan

    2018-03-13

    Wedge phantoms coupled with a CCD camera are suggested as a simple means to improve the efficiency of quality assurance for pencil beam scanning (PBS) proton therapy, in particular to verify energy/range consistency on a daily basis. The method is based on the analysis of an integral image created by a pencil beam (PB) pattern delivered through a wedge. We have investigated the reproducibility of this method and its dependence on setup and positional beam errors for a commercially available phantom (Sphinx ® , IBA Dosimetry) and CCD camera (Lynx ® , IBA Dosimetry) system. The phantom includes 4 wedges of different thickness, allowing verification of the range for 4 energies within one integral image. Each wedge was irradiated with a line pattern of clinical energies (120, 150, 180 and 230MeV). The equipment was aligned to the isocenter using lasers, and the delivery was repeated for 5 consecutive days, 4 times each day. Range was computed using the myQA software (IBA Dosimetry) and inter- and intra-setup uncertainty were calculated. Dependence of range on energy was investigated delivering the same pencil beam pattern but with energy variations in steps of ±0.2MeV for all the nominal energies, up to ±1.0MeV. Possible range uncertainties, caused by setup and positional errors, were then simulated including inclination of the phantom, pencil beam and couch shifts. Intra position setup (based on in-room laser system) shows a maximum in plane difference within 1.5mm. Range reproducibility (standard deviation) was less than 0.14mm. Setup and beam errors did not affect significantly the results, except for a vertical shift of 10mm which leads to an error in the range computation. Taking into account different day-to-day setup and beam errors, day-to-day determination of range has been shown to be reproducible using the proposed system. Copyright © 2018. Published by Elsevier GmbH.

  16. Reproducibility of thoracic kyphosis measurements in patients with adolescent idiopathic scoliosis.

    Science.gov (United States)

    Ohrt-Nissen, Søren; Cheung, Jason Pui Yin; Hallager, Dennis Winge; Gehrchen, Martin; Kwan, Kenny; Dahl, Benny; Cheung, Kenneth M C; Samartzis, Dino

    2017-01-01

    Current surgical treatment for adolescent idiopathic scoliosis (AIS) involves correction in both the coronal and sagittal plane, and thorough assessment of these parameters is essential for evaluation of surgical results. However, various definitions of thoracic kyphosis (TK) have been proposed, and the intra- and inter-rater reproducibility of these measures has not been determined. As such, the purpose of the current study was to determine the intra- and inter-rater reproducibility of several TK measurements used in the assessment of AIS. Twenty patients (90% females) surgically treated for AIS with alternate-level pedicle screw fixation were included in the study. Three raters independently evaluated pre- and postoperative standing lateral plain radiographs. For each radiograph, several definitions of TK were measured as well as L1-S1 and nonfixed lumbar lordosis. All variables were measured twice 14 days apart, and a mixed effects model was used to determine the repeatability coefficient (RC), which is a measure of the agreement between repeated measurements. Also, the intra- and inter-rater intra-class correlation coefficient (ICC) was determined as a measure of reliability. Preoperative median Cobb angle was 58° (range 41°-86°), and median surgical curve correction was 68% (range 49-87%). Overall intra-rater RC was highest for T2-T12 and nonfixed TK (11°) and lowest for T4-T12 and T5-T12 (8°). Inter-rater RC was highest for T1-T12, T1-nonfixed, and nonfixed TK (13°) and lowest for T5-T12 (9°). Agreement varied substantially between pre- and postoperative radiographs. Inter-rater ICC was highest for T4-T12 (0.92; 95% CI 0.88-0.95) and T5-T12 (0.92; 95% CI 0.88-0.95) and lowest for T1-nonfixed (0.80; 95% CI 0.72-0.88). Considerable variation for all TK measurements was noted. Intra- and inter-rater reproducibility was best for T4-T12 and T5-T12. Future studies should consider adopting a relevant minimum difference as a limit for true change in TK.

  17. Experiments in order to reproduce cold fusion results

    International Nuclear Information System (INIS)

    Bimbot, R.; Blain, G.; Boureau, G.; Cieur, M.

    1989-01-01

    Three experiments have been performed in order to try and reproduce the cold fusion experiments reported by FLEISCHMANN and PONS (D 2 O electrolysis) and by the Frascati Group (D 2 absorption in Ti at liquid nitrogen temperature). In the two electrolysis experiments, a Pd cathode was used together with a Pt anode and a Pd (D 2 ) reference electrode, in acid and basic media. The electrolysis cell was surrounded by four neutron counters filled with an organic scintillator (NE213). The electronics made it possible to discriminate neutrons from gamma rays. The global efficiency for neutron detection was 20%, and the detection threshold was equal to 1 neutron/s/4π. A germanium detector (efficiency 70%) and a NaI crystal were used to record gamma ray spectra. In one of the experiments, tritium was measured in the solution before and after electrolysis. None of the two experiments showed neutron, gamma, or tritium production above background. In the third experiment, deuterium was absorbed in titanium by cooling at liquid nitrogen temperature, and desorbed by warming up at room temperature; both neutron and gamma emissions were recorded during these operations. The results of this experiment were also negative [fr

  18. Reproducible microtechnique for measuring stimulation of human lymphocytes by phytohemagglutinin

    International Nuclear Information System (INIS)

    Willard, K.E.; Lloyd, E.L.

    1977-01-01

    Methods based on tritiated thymidine incorporation were used for studies on the blastogenic transformation of human lymphocytes by phytohemagglutinin (PHA) in vitro. A stimulation index was calculated as the ratio of the radioactivity measured in lymphocytes to which PHA had been added to that in similar samples from which PHA was omitted. The stimulation indices have been shown to be reproducible to within 10 percent for the same individuals sampled at different times. The maximum mitotic indices for normal control subjects varied from 249 to 340. Seven to 11 different concentrations of PHA were used with each blood sample tested. The maximum index occurred, for most samples, at concentrations of PHA between 0.0625 μl and 1.0 μl/well. A systematic decrease in the maximum mitotic indices was found with increasing age in the range tested (19 to 58 years). Measurements of the single radium case 03 to 416, aged 70, with a residual body burden of 1.0 μCi 226 Ra gave a maximum value for the mitotic index of 44 at a concentration of 0.25 μl/well. This was a factor of 5 less than the value expected from our normal control subjects

  19. The rapid reproducers paradox: population control and individual procreative rights.

    Science.gov (United States)

    Wissenburg, M

    1998-01-01

    This article argues that population policies need to be evaluated from macro and micro perspectives and to consider individual rights. Ecological arguments that are stringent conditions of liberal democracy are assessed against a moral standard. The moral standard is applied to a series of reasons for limiting procreative rights in the cause of sustainability. The focus is directly on legally enforced antinatalist measures and not on indirect policies with incentives and disincentives. The explicit assumption is that population policy violates the fairness to individuals for societal gain and that population policies are incompatible with stringent conditions of liberal democracy. The author identifies the individual-societal tradeoff as the "rapid reproducers paradox." The perfect sustainable population level is either not possible or is a repugnant alternative. 12 ecological arguments are presented, and none are found compatible with notions of a liberal democracy. Three alternative antinatalist options are the acceptance of less rigid and still coercive policies, amendments to the conception of liberal democracy, or loss of hope and choice of noncoercive solutions to sustainability, none of which is found viable. If voluntary abstinence and distributive solutions fail, then frugal demand options and technological supply options both will be necessary.

  20. Virtual Raters for Reproducible and Objective Assessments in Radiology

    Science.gov (United States)

    Kleesiek, Jens; Petersen, Jens; Döring, Markus; Maier-Hein, Klaus; Köthe, Ullrich; Wick, Wolfgang; Hamprecht, Fred A.; Bendszus, Martin; Biller, Armin

    2016-04-01

    Volumetric measurements in radiologic images are important for monitoring tumor growth and treatment response. To make these more reproducible and objective we introduce the concept of virtual raters (VRs). A virtual rater is obtained by combining knowledge of machine-learning algorithms trained with past annotations of multiple human raters with the instantaneous rating of one human expert. Thus, he is virtually guided by several experts. To evaluate the approach we perform experiments with multi-channel magnetic resonance imaging (MRI) data sets. Next to gross tumor volume (GTV) we also investigate subcategories like edema, contrast-enhancing and non-enhancing tumor. The first data set consists of N = 71 longitudinal follow-up scans of 15 patients suffering from glioblastoma (GB). The second data set comprises N = 30 scans of low- and high-grade gliomas. For comparison we computed Pearson Correlation, Intra-class Correlation Coefficient (ICC) and Dice score. Virtual raters always lead to an improvement w.r.t. inter- and intra-rater agreement. Comparing the 2D Response Assessment in Neuro-Oncology (RANO) measurements to the volumetric measurements of the virtual raters results in one-third of the cases in a deviating rating. Hence, we believe that our approach will have an impact on the evaluation of clinical studies as well as on routine imaging diagnostics.

  1. Diet rapidly and reproducibly alters the human gut microbiome

    Science.gov (United States)

    David, Lawrence A.; Maurice, Corinne F.; Carmody, Rachel N.; Gootenberg, David B.; Button, Julie E.; Wolfe, Benjamin E.; Ling, Alisha V.; Devlin, A. Sloan; Varma, Yug; Fischbach, Michael A.; Biddinger, Sudha B.; Dutton, Rachel J.; Turnbaugh, Peter J.

    2013-01-01

    Long-term diet influences the structure and activity of the trillions of microorganisms residing in the human gut1–5, but it remains unclear how rapidly and reproducibly the human gut microbiome responds to short-term macronutrient change. Here, we show that the short-term consumption of diets composed entirely of animal or plant products alters microbial community structure and overwhelms inter-individual differences in microbial gene expression. The animal-based diet increased the abundance of bile-tolerant microorganisms (Alistipes, Bilophila, and Bacteroides) and decreased the levels of Firmicutes that metabolize dietary plant polysaccharides (Roseburia, Eubacterium rectale, and Ruminococcus bromii). Microbial activity mirrored differences between herbivorous and carnivorous mammals2, reflecting trade-offs between carbohydrate and protein fermentation. Foodborne microbes from both diets transiently colonized the gut, including bacteria, fungi, and even viruses. Finally, increases in the abundance and activity of Bilophila wadsworthia on the animal-based diet support a link between dietary fat, bile acids, and the outgrowth of microorganisms capable of triggering inflammatory bowel disease6. In concert, these results demonstrate that the gut microbiome can rapidly respond to altered diet, potentially facilitating the diversity of human dietary lifestyles. PMID:24336217

  2. Histopathologic reproducibility of thyroid disease in an epidemiologic study

    International Nuclear Information System (INIS)

    Ron, E.; Griffel, B.; Liban, E.; Modan, B.

    1986-01-01

    An investigation of the long-term effects of childhood scalp irradiation demonstrated a significantly increased risk of thyroid tumors in the irradiated population. Because of the complexity of thyroid cancer diagnosis, a histopathologic slide review of 59 of the 68 patients (irradiated and nonirradiated) with thyroid disease was undertaken. The review revealed 90% agreement (kappa = +0.85, P less than 0.01) between the original and review diagnosis. Four of 27 cases previously diagnosed as malignant were reclassified as benign, yielding a cancer misdiagnosis rate of 14.8%. All four of the misdiagnosed cancers were of follicular or mixed papillary-follicular type. As a result of the histologic review, the ratio of malignant to benign tumors decreased from 2.55 to 1.75. Since disagreement in diagnosis was similar in the irradiated and nonirradiated groups, the relative risk of radiation-associated neoplasms did not change substantially. The histopathologic review shows that although there were some problems in diagnostic reproducibility, they were not statistically significant and did not alter our previous conclusions regarding radiation exposure. However, a 15% reduction in the number of malignancies might affect epidemiologic studies with an external comparison as well as geographic or temporal comparisons

  3. Finding reproducible cluster partitions for the k-means algorithm.

    Science.gov (United States)

    Lisboa, Paulo J G; Etchells, Terence A; Jarman, Ian H; Chambers, Simon J

    2013-01-01

    K-means clustering is widely used for exploratory data analysis. While its dependence on initialisation is well-known, it is common practice to assume that the partition with lowest sum-of-squares (SSQ) total i.e. within cluster variance, is both reproducible under repeated initialisations and also the closest that k-means can provide to true structure, when applied to synthetic data. We show that this is generally the case for small numbers of clusters, but for values of k that are still of theoretical and practical interest, similar values of SSQ can correspond to markedly different cluster partitions. This paper extends stability measures previously presented in the context of finding optimal values of cluster number, into a component of a 2-d map of the local minima found by the k-means algorithm, from which not only can values of k be identified for further analysis but, more importantly, it is made clear whether the best SSQ is a suitable solution or whether obtaining a consistently good partition requires further application of the stability index. The proposed method is illustrated by application to five synthetic datasets replicating a real world breast cancer dataset with varying data density, and a large bioinformatics dataset.

  4. A Kepler Workflow Tool for Reproducible AMBER GPU Molecular Dynamics.

    Science.gov (United States)

    Purawat, Shweta; Ieong, Pek U; Malmstrom, Robert D; Chan, Garrett J; Yeung, Alan K; Walker, Ross C; Altintas, Ilkay; Amaro, Rommie E

    2017-06-20

    With the drive toward high throughput molecular dynamics (MD) simulations involving ever-greater numbers of simulation replicates run for longer, biologically relevant timescales (microseconds), the need for improved computational methods that facilitate fully automated MD workflows gains more importance. Here we report the development of an automated workflow tool to perform AMBER GPU MD simulations. Our workflow tool capitalizes on the capabilities of the Kepler platform to deliver a flexible, intuitive, and user-friendly environment and the AMBER GPU code for a robust and high-performance simulation engine. Additionally, the workflow tool reduces user input time by automating repetitive processes and facilitates access to GPU clusters, whose high-performance processing power makes simulations of large numerical scale possible. The presented workflow tool facilitates the management and deployment of large sets of MD simulations on heterogeneous computing resources. The workflow tool also performs systematic analysis on the simulation outputs and enhances simulation reproducibility, execution scalability, and MD method development including benchmarking and validation. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  5. A reproducible brain tumour model established from human glioblastoma biopsies

    International Nuclear Information System (INIS)

    Wang, Jian; Chekenya, Martha; Bjerkvig, Rolf; Enger, Per Ø; Miletic, Hrvoje; Sakariassen, Per Ø; Huszthy, Peter C; Jacobsen, Hege; Brekkå, Narve; Li, Xingang; Zhao, Peng; Mørk, Sverre

    2009-01-01

    Establishing clinically relevant animal models of glioblastoma multiforme (GBM) remains a challenge, and many commonly used cell line-based models do not recapitulate the invasive growth patterns of patient GBMs. Previously, we have reported the formation of highly invasive tumour xenografts in nude rats from human GBMs. However, implementing tumour models based on primary tissue requires that these models can be sufficiently standardised with consistently high take rates. In this work, we collected data on growth kinetics from a material of 29 biopsies xenografted in nude rats, and characterised this model with an emphasis on neuropathological and radiological features. The tumour take rate for xenografted GBM biopsies were 96% and remained close to 100% at subsequent passages in vivo, whereas only one of four lower grade tumours engrafted. Average time from transplantation to the onset of symptoms was 125 days ± 11.5 SEM. Histologically, the primary xenografts recapitulated the invasive features of the parent tumours while endothelial cell proliferations and necrosis were mostly absent. After 4-5 in vivo passages, the tumours became more vascular with necrotic areas, but also appeared more circumscribed. MRI typically revealed changes related to tumour growth, several months prior to the onset of symptoms. In vivo passaging of patient GBM biopsies produced tumours representative of the patient tumours, with high take rates and a reproducible disease course. The model provides combinations of angiogenic and invasive phenotypes and represents a good alternative to in vitro propagated cell lines for dissecting mechanisms of brain tumour progression

  6. Can a coupled meteorology–chemistry model reproduce the ...

    Science.gov (United States)

    The ability of a coupled meteorology–chemistry model, i.e., Weather Research and Forecast and Community Multiscale Air Quality (WRF-CMAQ), to reproduce the historical trend in aerosol optical depth (AOD) and clear-sky shortwave radiation (SWR) over the Northern Hemisphere has been evaluated through a comparison of 21-year simulated results with observation-derived records from 1990 to 2010. Six satellite-retrieved AOD products including AVHRR, TOMS, SeaWiFS, MISR, MODIS-Terra and MODIS-Aqua as well as long-term historical records from 11 AERONET sites were used for the comparison of AOD trends. Clear-sky SWR products derived by CERES at both the top of atmosphere (TOA) and surface as well as surface SWR data derived from seven SURFRAD sites were used for the comparison of trends in SWR. The model successfully captured increasing AOD trends along with the corresponding increased TOA SWR (upwelling) and decreased surface SWR (downwelling) in both eastern China and the northern Pacific. The model also captured declining AOD trends along with the corresponding decreased TOA SWR (upwelling) and increased surface SWR (downwelling) in the eastern US, Europe and the northern Atlantic for the period of 2000–2010. However, the model underestimated the AOD over regions with substantial natural dust aerosol contributions, such as the Sahara Desert, Arabian Desert, central Atlantic and northern Indian Ocean. Estimates of the aerosol direct radiative effect (DRE) at TOA a

  7. From alginate impressions to digital virtual models: accuracy and reproducibility.

    Science.gov (United States)

    Dalstra, Michel; Melsen, Birte

    2009-03-01

    To compare the accuracy and reproducibility of measurements performed on digital virtual models with those taken on plaster casts from models poured immediately after the impression was taken, the 'gold standard', and from plaster models poured following a 3-5 day shipping procedure of the alginate impression. Direct comparison of two measuring techniques. The study was conducted at the Department of Orthodontics, School of Dentistry, University of Aarhus, Denmark in 2006/2007. Twelve randomly selected orthodontic graduate students with informed consent. Three sets of alginate impressions were taken from the participants within 1 hour. Plaster models were poured immediately from two of the sets, while the third set was kept in transit in the mail for 3-5 days. Upon return a plaster model was poured as well. Finally digital models were made from the plaster models. A number of measurements were performed on the plaster casts with a digital calliper and on the corresponding digital models using the virtual measuring tool of the accompanying software. Afterwards these measurements were compared statistically. No statistical differences were found between the three sets of plaster models. The intra- and inter-observer variability are smaller for the measurements performed on the digital models. Sending alginate impressions by mail does not affect the quality and accuracy of plaster casts poured from them afterwards. Virtual measurements performed on digital models display less variability than the corresponding measurements performed with a calliper on the actual models.

  8. Reproducibility of 3.0 Tesla Magnetic Resonance Spectroscopy for Measuring Hepatic Fat Content

    NARCIS (Netherlands)

    van Werven, Jochem R.; Hoogduin, Johannes M.; Nederveen, Aart J.; van Vliet, Andre A.; Wajs, Ewa; Vandenberk, Petra; Stroes, Erik S. G.; Stoker, Jaap

    Purpose: To investigate reproducibility of proton magnetic resonance spectroscopy (H-1-MRS) to measure hepatic triglyceride content (HTGC). Materials and Methods: In 24 subjects, HTGC was evaluated using H-1-MRS at 3.0 Tesla. We studied "between-weeks" reproducibility and reproducibility of H-1-MRS

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

    Energy Technology Data Exchange (ETDEWEB)

    Cutajar, Marica; Hales, Patrick W.; Clark, Christopher A.; Gordon, Isky [UCL Institute of Child Health, Imaging and Biophysics Unit, London (United Kingdom); Thomas, David L. [UCL Institute of Neurology, Department of Brain Repair and Rehabilitation, London (United Kingdom); Banks, T. [Great Ormond Street Hospital, Department of Radiology, London (United Kingdom)

    2014-06-15

    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{sup -1} [100 ml tissue]{sup -1}, and using DCE MRI was 287 ± 70 ml min{sup -1} [100 ml tissue]{sup -1}. The group coefficient of variation (CV{sub g}) was 18 % for ASL and 28 % for DCE-MRI. Repeatability studies showed that ASL was more reproducible than DCE with CV{sub g}s 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. (orig.)

  10. A multicenter reproducibility study of single-voxel {sup 1}H-MRS of the medial temporal lobe

    Energy Technology Data Exchange (ETDEWEB)

    Traeber, Frank; Block, Wolfgang; Guer, Okan; Schild, Hans H. [University of Bonn, Department of Radiology, Bonn (Germany); Freymann, Nikolaus; Heun, Reinhard; Jessen, Frank [University of Bonn, Department of Psychiatry, Bonn (Germany); Kucinski, Thomas [University of Hamburg, Department of Neuroradiology, Hamburg (Germany); Hammen, Thilo [University of Erlangen, Department of Psychiatry, Erlangen (Germany); Ende, Gabriele [Central Institute of Mental Health, NMR Research in Psychiatry, Mannheim (Germany); Pilatus, Ulrich [University of Frankfurt, Department of Neuroradiology, Frankfurt (Germany); Hampel, Harald [University of Munich, Department of Psychiatry, Munich (Germany)

    2006-05-15

    Proton magnetic resonance spectroscopy ({sup 1}H-MRS) has provided evidence for a reduction of N-acetyl-aspartate (NAA) in the medial temporal lobe (MTL) in cerebral disorders such as Alzheimer's Disease. Within the {sup 1}H-MRS study of the German Research Network on Dementia, we determined the multicenter reproducibility of single-voxel {sup 1}H-MRS of the MTL. At five sites with 1.5T MR systems, single-voxel {sup 1}H spectra from the MTL of an identical healthy subject were measured. The same subject was also examined at one of the sites five times to assess intracenter stability. The protocol included water-suppressed spectra with TE 272 ms and TE 30 ms and unsuppressed spectra for absolute quantification of metabolite concentrations. The intracenter reproducibility of absolute NAA concentration, expressed as coefficient of variation (CV), was 1.8%. CV for the concentrations of creatine (Cr), choline (Cho), and myoinositol (MI) and for the ratios NAA/Cr, NAA/Cho, and MI/NAA varied by 11-16%. Intercenter CV was 3.9% for NAA and were below 10% for all other metabolites and metabolic ratios. Our study demonstrates that quantitative assessment of NAA with single-voxel MRS can be performed with high intercenter reproducibility. This is the basis for applying {sup 1}H-MRS in large-scale early recognition and treatment studies in MTL affecting disorders. (orig.)

  11. Validity and reproducibility of the ErgomoPro power meter compared with the SRM and Powertap power meters.

    Science.gov (United States)

    Duc, Sebastien; Villerius, Vincent; Bertucci, William; Grappe, Frederic

    2007-09-01

    The ErgomoPro (EP) is a power meter that measures power output (PO) during outdoor and indoor cycling via 2 optoelectronic sensors located in the bottom bracket axis. The aim of this study was to determine the validity and the reproducibility of the EP compared with the SRM crank set and Powertap hub (PT). The validity of the EP was tested in the laboratory during 8 submaximal incremental tests (PO: 100 to 400 W), eight 30-min submaximal constant-power tests (PO = 180 W), and 8 sprint tests (PO > 750 W) and in the field during 8 training sessions (time: 181 +/- 73 min; PO: approximately 140 to 160 W). The reproducibility was assessed by calculating the coefficient of PO variation (CV) during the submaximal incremental and constant tests. The EP provided a significantly higher PO than the SRM and PT during the submaximal incremental test: The mean PO differences were +6.3% +/- 2.5% and +11.1% +/- 2.1% respectively. The difference was greater during field training sessions (+12.0% +/- 5.7% and +16.5% +/- 5.9%) but lower during sprint tests (+1.6% +/- 2.5% and +3.2% +/- 2.7%). The reproducibility of the EP is lower than those of the SRM and PT (CV = 4.1% +/- 1.8%, 1.9% +/- 0.4%, and 2.1% +/- 0.8%, respectively). The EP power meter appears less valid and reliable than the SRM and PT systems.

  12. Reproducibility of task activation using the Addenbrooke's cognitive examination in healthy controls: A functional Transcranial Doppler ultrasonography study.

    Science.gov (United States)

    Beishon, L; Williams, C A L; Panerai, R B; Robinson, T G; Haunton, V J

    2017-11-01

    Cerebral blood flow velocity (CBFv) changes occurring with cognitive stimulation can be measured by Transcranial Doppler ultrasonography (TCD). The aim of this study was to assess the reproducibility of CBFv changes to the Addenbrooke's cognitive examination (ACE-III). 13 volunteers underwent bilateral TCD (middle cerebral artery), continuous heart rate (HR, 3-lead ECG, Finometer), beat-to-beat mean arterial pressure (MAP, Finometer), and end-tidal CO 2 (ETCO 2 , capnography). After 5min baseline, all ACE-III tasks were performed in 3 domains (A/B/C). Data presented are population CBFv peak normalised changes and area under the curve (AUC). Statistical analysis was by 2-way repeated measures (ANOVA), intra-class correlation coefficient (ICC), standard error of measurement (SEM) and coefficient of variation (CV). 12 bilateral data sets were obtained (10 right hand dominant, 6 female). Baseline parameters (MAP, HR, ETCO 2 ) did not differ between visits. All tasks increased CBFv. Only domain A on AUC analysis differed significantly on ANOVA, and one task on post hoc testing (p examine reproducibility of CBFv changes to a complete cognitive assessment tool. Reproducibility of CBFv measurements to the ACE-III was variable. AUC may provide more reliable estimates than peak CBFv responses. These data need validating in patient populations. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Measurement of Trabecular Bone Parameters in Porcine Vertebral Bodies Using Multidetector CT: Evaluation of Reproducibility of 3-Dimensional CT Histomorphometry

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Sung Hwan; Goo, Jin Mo [Dept. of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul (Korea, Republic of); Moon Kyung Chul [Dept. of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul (Korea, Republic of); An, Sang Bu [Dept. of radiology, National Cancer Center, Goyang (Korea, Republic of); Kim, Kwang Gi [Dept. of Biomedical Engineering, Division of Basic and Applied Sciences, National Cancer Center, Goyang (Korea, Republic of)

    2011-05-15

    To evaluate the reproducibility of 3-dimensional histomorphometry for the microarchitecture analysis of trabecular bone parameters using multidetector computed tomography (MDCT). Thirty-six specimens from porcine vertebral bodies were imaged five times with a 64- detector row MDCT system using the same scan protocols. Locations of the specimens were nearly identical through the scans. Three-dimensional structural parameters of trabecular bone were derived from the five data sets using image analyzing software. The features measured by the analysis programs were trabecular bone volume, trabecular bone volume/tissue volume, trabecular thickness, trabecular separation, trabecular number, trabecular bone pattern factor, structural model index. The structural trabecular parameters showed excellent reproducibility through repeated scanning. Intraclass correlation coefficients of all seven structural parameters were in the range of 0.998 to 1.000. Coefficients of variation of the six structural parameters, excluding structural model index, were not over 1.6%. The measurement of the trabecular structural parameters using multidetector CT and three-dimensional histomophometry analysis program was validated and showed excellent reproducibility. This method could be used as a noninvasive and easily available test in a clinical setting.

  14. A multicenter reproducibility study of single-voxel 1H-MRS of the medial temporal lobe

    International Nuclear Information System (INIS)

    Traeber, Frank; Block, Wolfgang; Guer, Okan; Schild, Hans H.; Freymann, Nikolaus; Heun, Reinhard; Jessen, Frank; Kucinski, Thomas; Hammen, Thilo; Ende, Gabriele; Pilatus, Ulrich; Hampel, Harald

    2006-01-01

    Proton magnetic resonance spectroscopy ( 1 H-MRS) has provided evidence for a reduction of N-acetyl-aspartate (NAA) in the medial temporal lobe (MTL) in cerebral disorders such as Alzheimer's Disease. Within the 1 H-MRS study of the German Research Network on Dementia, we determined the multicenter reproducibility of single-voxel 1 H-MRS of the MTL. At five sites with 1.5T MR systems, single-voxel 1 H spectra from the MTL of an identical healthy subject were measured. The same subject was also examined at one of the sites five times to assess intracenter stability. The protocol included water-suppressed spectra with TE 272 ms and TE 30 ms and unsuppressed spectra for absolute quantification of metabolite concentrations. The intracenter reproducibility of absolute NAA concentration, expressed as coefficient of variation (CV), was 1.8%. CV for the concentrations of creatine (Cr), choline (Cho), and myoinositol (MI) and for the ratios NAA/Cr, NAA/Cho, and MI/NAA varied by 11-16%. Intercenter CV was 3.9% for NAA and were below 10% for all other metabolites and metabolic ratios. Our study demonstrates that quantitative assessment of NAA with single-voxel MRS can be performed with high intercenter reproducibility. This is the basis for applying 1 H-MRS in large-scale early recognition and treatment studies in MTL affecting disorders. (orig.)

  15. Intra- and inter-observer reproducibility of global and regional magnetic resonance feature tracking derived strain parameters of the left and right ventricle

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, Björn, E-mail: bjoernschmidt1989@gmx.de [Department of Radiology, University Hospital of Cologne, Kerpener Str. 62, D-50937, Cologne (Germany); Dick, Anastasia, E-mail: anastasia-dick@web.de [Department of Radiology, University Hospital of Cologne, Kerpener Str. 62, D-50937, Cologne (Germany); Treutlein, Melanie, E-mail: melanie-treutlein@web.de [Department of Radiology, University Hospital of Cologne, Kerpener Str. 62, D-50937, Cologne (Germany); Schiller, Petra, E-mail: petra.schiller@uni-koeln.de [Institute of Medical Statistics, Informatics and Epidemiology, University of Cologne, Kerpener Str. 62, D-50937, Cologne (Germany); Bunck, Alexander C., E-mail: alexander.bunck@uk-koeln.de [Department of Radiology, University Hospital of Cologne, Kerpener Str. 62, D-50937, Cologne (Germany); Maintz, David, E-mail: david.maintz@uk-koeln.de [Department of Radiology, University Hospital of Cologne, Kerpener Str. 62, D-50937, Cologne (Germany); Baeßler, Bettina, E-mail: bettina.baessler@uk-koeln.de [Department of Radiology, University Hospital of Cologne, Kerpener Str. 62, D-50937, Cologne (Germany)

    2017-04-15

    Highlights: • Left and right ventricular CMR feature tracking is highly reproducible. • The only exception is radial strain and strain rate. • Sample size estimations are presented as a practical reference for future studies. - Abstract: Objectives: To investigate the reproducibility of regional and global strain and strain rate (SR) parameters of both ventricles and to determine sample sizes for all investigated strain and SR parameters in order to generate a practical reference for future studies. Materials and methods: The study population consisted of 20 healthy individuals and 20 patients with acute myocarditis. Cine sequences in three horizontal long axis views and a stack of short axis views covering the entire left and right ventricle (LV, RV) were retrospectively analysed using a dedicated feature tracking (FT) software algorithm (TOMTEC). For intra-observer analysis, one observer analysed CMR images of all patients and volunteers twice. For inter-observer analysis, three additional blinded observers analysed the same datasets once. Intra- and inter-observer reproducibility were tested in all patients and controls using Bland-Altman analyses, intra-class correlation coefficients (ICCs) and coefficients of variation. Results: Intra-observer reproducibility of global LV strain and SR parameters was excellent (range of ICCs: 0.81–1.00), the only exception being global radial SR with a poor reproducibility (ICC 0.23). On a regional level, basal and midventricular strain and SR parameters were more reproducible when compared to apical parameters. Inter-observer reproducibility of all LV parameters was slightly lower than intra-observer reproducibility, yet still good to excellent for all global and regional longitudinal and circumferential strain and SR parameters (range of ICCs: 0.66–0.93). Similar to the LV, all global RV longitudinal and circumferential strain and SR parameters showed an excellent reproducibility, (range of ICCs: 0.75–0

  16. Intra- and inter-observer reproducibility of global and regional magnetic resonance feature tracking derived strain parameters of the left and right ventricle

    International Nuclear Information System (INIS)

    Schmidt, Björn; Dick, Anastasia; Treutlein, Melanie; Schiller, Petra; Bunck, Alexander C.; Maintz, David; Baeßler, Bettina

    2017-01-01

    Highlights: • Left and right ventricular CMR feature tracking is highly reproducible. • The only exception is radial strain and strain rate. • Sample size estimations are presented as a practical reference for future studies. - Abstract: Objectives: To investigate the reproducibility of regional and global strain and strain rate (SR) parameters of both ventricles and to determine sample sizes for all investigated strain and SR parameters in order to generate a practical reference for future studies. Materials and methods: The study population consisted of 20 healthy individuals and 20 patients with acute myocarditis. Cine sequences in three horizontal long axis views and a stack of short axis views covering the entire left and right ventricle (LV, RV) were retrospectively analysed using a dedicated feature tracking (FT) software algorithm (TOMTEC). For intra-observer analysis, one observer analysed CMR images of all patients and volunteers twice. For inter-observer analysis, three additional blinded observers analysed the same datasets once. Intra- and inter-observer reproducibility were tested in all patients and controls using Bland-Altman analyses, intra-class correlation coefficients (ICCs) and coefficients of variation. Results: Intra-observer reproducibility of global LV strain and SR parameters was excellent (range of ICCs: 0.81–1.00), the only exception being global radial SR with a poor reproducibility (ICC 0.23). On a regional level, basal and midventricular strain and SR parameters were more reproducible when compared to apical parameters. Inter-observer reproducibility of all LV parameters was slightly lower than intra-observer reproducibility, yet still good to excellent for all global and regional longitudinal and circumferential strain and SR parameters (range of ICCs: 0.66–0.93). Similar to the LV, all global RV longitudinal and circumferential strain and SR parameters showed an excellent reproducibility, (range of ICCs: 0.75–0

  17. Role of gauge invariance in a variational and mean-field calculation

    International Nuclear Information System (INIS)

    Masperi, L.; Omero, C.

    1981-08-01

    We show that the implementation of gauge invariance is essential for a variational treatment to correctly reproduce all the features of the phase diagram for the Z(2) lattice gauge theory with matter field. (author)

  18. Alternative staffing services. Contract transcription.

    Science.gov (United States)

    Tessier, C

    1992-03-01

    Contract medical transcription services can be of great assistance in meeting the demands for transcription, without jeopardizing patient, physician, or institutional confidentiality. You simply must require the contract service to provide at least the same degree of protection and preservation of confidentiality that you should require inhouse. To achieve this you must make these requirements explicit, comprehensive, comprehensible, believable, and enforceable. Discuss the requirements with prospective contractors. Review them at least annually with existing contractors and when contracts are due for renewal. Be sure to specify the consequence of breaching confidentiality, and if there are breaches, enforce the terms of the contract. Consult your institution's legal counsel both in developing the contract and in enforcing its provisions. Take into consideration your department's and institution's policies, AHIMA's statement on confidentiality, as well as local, state, and federal laws. Above all, never lose sight of the patient. Ultimately, it is not patient information that you are obligated to protect. It is the patient.

  19. The post-transcriptional operon

    DEFF Research Database (Denmark)

    Tenenbaum, Scott A.; Christiansen, Jan; Nielsen, Henrik

    2011-01-01

    model (PTO) is used to describe data from an assortment of methods (e.g. RIP-Chip, CLIP-Chip, miRNA profiling, ribosome profiling) that globally address the functionality of mRNA. Several examples of post-transcriptional operons have been documented in the literature and demonstrate the usefulness...... of the model in identifying new participants in cellular pathways as well as in deepening our understanding of cellular responses....

  20. Static and Dynamic Handgrip Strength Endurance: Test-Retest Reproducibility.

    Science.gov (United States)

    Gerodimos, Vassilis; Karatrantou, Konstantina; Psychou, Dimitra; Vasilopoulou, Theodora; Zafeiridis, Andreas

    2017-03-01

    This study investigated the reliability of static and dynamic handgrip strength endurance using different protocols and indicators for the assessment of strength endurance. Forty young, healthy men and women (age, 18-22 years) performed 2 handgrip strength endurance protocols: a static protocol (sustained submaximal contraction at 50% of maximal voluntary contraction) and a dynamic one (8, 10, and 12 maximal repetitions). The participants executed each protocol twice to assess the test-retest reproducibility. Total work and total time were used as indicators of strength endurance in the static protocol; the strength recorded at each maximal repetition, the percentage change, and fatigue index were used as indicators of strength endurance in the dynamic protocol. The static protocol showed high reliability irrespective of sex and hand for total time and work. The 12-repetition dynamic protocol exhibited moderate-high reliability for repeated maximal repetitions and percentage change; the 8- and 10-repetition protocols demonstrated lower reliability irrespective of sex and hand. The fatigue index was not a reliable indicator for the assessment of dynamic handgrip endurance. Static handgrip endurance can be measured reliably using the total time and total work as indicators of strength endurance. For the evaluation of dynamic handgrip endurance, the 12-repetition protocol is recommended, using the repeated maximal repetitions and percentage change as indicators of strength endurance. Practitioners should consider the static (50% maximal voluntary contraction) and dynamic (12 repeated maximal repetitions) protocols as reliable for the assessment of handgrip strength endurance. The evaluation of static endurance in conjunction with dynamic endurance would provide more complete information about hand function. Copyright © 2017 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

  1. Development of a Consistent and Reproducible Porcine Scald Burn Model

    Science.gov (United States)

    Kempf, Margit; Kimble, Roy; Cuttle, Leila

    2016-01-01

    There are very few porcine burn models that replicate scald injuries similar to those encountered by children. We have developed a robust porcine burn model capable of creating reproducible scald burns for a wide range of burn conditions. The study was conducted with juvenile Large White pigs, creating replicates of burn combinations; 50°C for 1, 2, 5 and 10 minutes and 60°C, 70°C, 80°C and 90°C for 5 seconds. Visual wound examination, biopsies and Laser Doppler Imaging were performed at 1, 24 hours and at 3 and 7 days post-burn. A consistent water temperature was maintained within the scald device for long durations (49.8 ± 0.1°C when set at 50°C). The macroscopic and histologic appearance was consistent between replicates of burn conditions. For 50°C water, 10 minute duration burns showed significantly deeper tissue injury than all shorter durations at 24 hours post-burn (p ≤ 0.0001), with damage seen to increase until day 3 post-burn. For 5 second duration burns, by day 7 post-burn the 80°C and 90°C scalds had damage detected significantly deeper in the tissue than the 70°C scalds (p ≤ 0.001). A reliable and safe model of porcine scald burn injury has been successfully developed. The novel apparatus with continually refreshed water improves consistency of scald creation for long exposure times. This model allows the pathophysiology of scald burn wound creation and progression to be examined. PMID:27612153

  2. Reproducing American Sign Language Sentences: Cognitive Scaffolding in Working Memory

    Directory of Open Access Journals (Sweden)

    Ted eSupalla

    2014-08-01

    Full Text Available The American Sign Language Sentence Reproduction Test (ASL-SRT requires the precise reproduction of a series of ASL sentences increasing in complexity and length. Error analyses of such tasks provides insight into working memory and scaffolding processes. Data was collected from three groups expected to differ in fluency: deaf children, deaf adults and hearing adults, all users of ASL. Quantitative (correct/incorrect recall and qualitative error analyses were performed. Percent correct on the reproduction task supports its sensitivity to fluency as test performance clearly differed across the three groups studied. A linguistic analysis of errors further documented differing strategies and bias across groups. Subjects’ recall projected the affordance and constraints of deep linguistic representations to differing degrees, with subjects resorting to alternate processing strategies in the absence of linguistic knowledge. A qualitative error analysis allows us to capture generalizations about the relationship between error pattern and the cognitive scaffolding, which governs the sentence reproduction process. Highly fluent signers and less-fluent signers share common chokepoints on particular words in sentences. However, they diverge in heuristic strategy. Fluent signers, when they make an error, tend to preserve semantic details while altering morpho-syntactic domains. They produce syntactically correct sentences with equivalent meaning to the to-be-reproduced one, but these are not verbatim reproductions of the original sentence. In contrast, less-fluent signers tend to use a more linear strategy, preserving lexical status and word ordering while omitting local inflections, and occasionally resorting to visuo-motoric imitation. Thus, whereas fluent signers readily use top-down scaffolding in their working memory, less fluent signers fail to do so. Implications for current models of working memory across spoken and signed modalities are

  3. Finite-rank potential that reproduces the Pade approximant

    International Nuclear Information System (INIS)

    Tani, S.

    1979-01-01

    If a scattering potential is of a finite rank, say N, the exact solution of the problem can be obtained from the Born series, if the potential strength is within the radius of convergence; the exact solution can be obtained from the analytical continuation of the formal Born series outside the radius of convergence. Beyond the first 2N terms of the Born series, an individual term of the Born series depends on the first 2N terms, and the [N/N] Pade approximant and the exact solution agree with each other. The above-mentioned features of a finite-rank problem are relevant to scattering theory in general, because most scattering problems may be handled as an extension of the rank-N problem, in which the rank N tends to infinity. The foregoing aspects of scattering theory will be studied in depth in the present paper, and in so doing we proceed in the opposite direction. Namely, given a potential, we calculate the first 2N terms of the Born series for the K matrix and the first N terms of the Born series for the wave function. Using these data, a special rank-N potential is constructed in such a way that it reproduces the [N/N] Pade approximant of the K matrix of the original scattering problem. One great advantage of obtaining such a rank-N potential is that the wave function of the system may be approximated in the same spirit as done for the K matrix; hence, we can introduce a new approximation method for dealing with an off-shell T matrix. A part of the mathematical work is incomplete, but the physical aspects are thoroughly discussed

  4. Modelling soil erosion at European scale: towards harmonization and reproducibility

    Science.gov (United States)

    Bosco, C.; de Rigo, D.; Dewitte, O.; Poesen, J.; Panagos, P.

    2015-02-01

    Soil erosion by water is one of the most widespread forms of soil degradation. The loss of soil as a result of erosion can lead to decline in organic matter and nutrient contents, breakdown of soil structure and reduction of the water-holding capacity. Measuring soil loss across the whole landscape is impractical and thus research is needed to improve methods of estimating soil erosion with computational modelling, upon which integrated assessment and mitigation strategies may be based. Despite the efforts, the prediction value of existing models is still limited, especially at regional and continental scale, because a systematic knowledge of local climatological and soil parameters is often unavailable. A new approach for modelling soil erosion at regional scale is here proposed. It is based on the joint use of low-data-demanding models and innovative techniques for better estimating model inputs. The proposed modelling architecture has at its basis the semantic array programming paradigm and a strong effort towards computational reproducibility. An extended version of the Revised Universal Soil Loss Equation (RUSLE) has been implemented merging different empirical rainfall-erosivity equations within a climatic ensemble model and adding a new factor for a better consideration of soil stoniness within the model. Pan-European soil erosion rates by water have been estimated through the use of publicly available data sets and locally reliable empirical relationships. The accuracy of the results is corroborated by a visual plausibility check (63% of a random sample of grid cells are accurate, 83% at least moderately accurate, bootstrap p ≤ 0.05). A comparison with country-level statistics of pre-existing European soil erosion maps is also provided.

  5. A reproducible brain tumour model established from human glioblastoma biopsies

    Directory of Open Access Journals (Sweden)

    Li Xingang

    2009-12-01

    Full Text Available Abstract Background Establishing clinically relevant animal models of glioblastoma multiforme (GBM remains a challenge, and many commonly used cell line-based models do not recapitulate the invasive growth patterns of patient GBMs. Previously, we have reported the formation of highly invasive tumour xenografts in nude rats from human GBMs. However, implementing tumour models based on primary tissue requires that these models can be sufficiently standardised with consistently high take rates. Methods In this work, we collected data on growth kinetics from a material of 29 biopsies xenografted in nude rats, and characterised this model with an emphasis on neuropathological and radiological features. Results The tumour take rate for xenografted GBM biopsies were 96% and remained close to 100% at subsequent passages in vivo, whereas only one of four lower grade tumours engrafted. Average time from transplantation to the onset of symptoms was 125 days ± 11.5 SEM. Histologically, the primary xenografts recapitulated the invasive features of the parent tumours while endothelial cell proliferations and necrosis were mostly absent. After 4-5 in vivo passages, the tumours became more vascular with necrotic areas, but also appeared more circumscribed. MRI typically revealed changes related to tumour growth, several months prior to the onset of symptoms. Conclusions In vivo passaging of patient GBM biopsies produced tumours representative of the patient tumours, with high take rates and a reproducible disease course. The model provides combinations of angiogenic and invasive phenotypes and represents a good alternative to in vitro propagated cell lines for dissecting mechanisms of brain tumour progression.

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

    Science.gov (United States)

    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. Reproducibility and quantitativity of oblique-angle reconstruction in single photon emission computed tomography using Tl-201 myocardial phantom

    International Nuclear Information System (INIS)

    Bunko, Hisashi; Nanbu, Ichiro; Seki, Hiroyasu

    1984-01-01

    This study was carried out in order to evaluate reproducibility and quantitativity of oblique-angle reconstruction of myocardial phantom SPECT. Myocardial phantom with transmural and subendcardial defects, and off-axis phantom with wall thickness changing continuously from 0 to 23 mm were used. Sixty projection data in every 6 0 were aquired using dual-camera (ZLC) with high resolution collimators connected to Scintipac-2400 computer system. Oblique-angle reconstructed images were obtained by indicating the long axis of the phantom manually in the transaxial and vertical long axial tomograms. Reproducibility and quantitativity were evaluated by creating circumferential profile (CFP) of the finally reconstructed short axial images. Inter- and intra-operater reproducibility of relative counting ratio were less than 6.7% (C.V.) and 3.3% (C.V.), respectively. Both inter- and intraoperater reproducibility of absolute counts were better than that of counting ratio (less than 5.1% (C.V.) and 2.9% (C.V.), respectively). Variation of defect location in the reconstructed image and between the slices were less than 1 sampling interval of CFP (6 0 ) and 0.6 slice, respectively. Quantitativity of counts in the reconstructed images was poor in the transmulal defect, but was fair in the subendocardial defect. Counting ratio was greatly affected by wall thickness. Temporal quantitatibity or linearity of the counts in sequential SPECTs was good in non-defect area, especially when wall thickness was greater than 70% (16 mm) of maximum. In conclusion, three-dimensional oblique-angle reconstruction in Tl-201 myocardial SPECT could be applicable to relative and temporal quantitation of local myocardial activity other than defect area for the quantitative evaluation of Tl-201 myocardial wash-out. (J.P.N.)

  8. Evaluation of Oceanic Surface Observation for Reproducing the Upper Ocean Structure in ECHAM5/MPI-OM

    Science.gov (United States)

    Luo, Hao; Zheng, Fei; Zhu, Jiang

    2017-12-01

    Better constraints of initial conditions from data assimilation are necessary for climate simulations and predictions, and they are particularly important for the ocean due to its long climate memory; as such, ocean data assimilation (ODA) is regarded as an effective tool for seasonal to decadal predictions. In this work, an ODA system is established for a coupled climate model (ECHAM5/MPI-OM), which can assimilate all available oceanic observations using an ensemble optimal interpolation approach. To validate and isolate the performance of different surface observations in reproducing air-sea climate variations in the model, a set of observing system simulation experiments (OSSEs) was performed over 150 model years. Generally, assimilating sea surface temperature, sea surface salinity, and sea surface height (SSH) can reasonably reproduce the climate variability and vertical structure of the upper ocean, and assimilating SSH achieves the best results compared to the true states. For the El Niño-Southern Oscillation (ENSO), assimilating different surface observations captures true aspects of ENSO well, but assimilating SSH can further enhance the accuracy of ENSO-related feedback processes in the coupled model, leading to a more reasonable ENSO evolution and air-sea interaction over the tropical Pacific. For ocean heat content, there are still limitations in reproducing the long time-scale variability in the North Atlantic, even if SSH has been taken into consideration. These results demonstrate the effectiveness of assimilating surface observations in capturing the interannual signal and, to some extent, the decadal signal but still highlight the necessity of assimilating profile data to reproduce specific decadal variability.

  9. SEASTAR: systematic evaluation of alternative transcription start sites in RNA.

    Science.gov (United States)

    Qin, Zhiyi; Stoilov, Peter; Zhang, Xuegong; Xing, Yi

    2018-05-04

    Alternative first exons diversify the transcriptomes of eukaryotes by producing variants of the 5' Untranslated Regions (5'UTRs) and N-terminal coding sequences. Accurate transcriptome-wide detection of alternative first exons typically requires specialized experimental approaches that are designed to identify the 5' ends of transcripts. We developed a computational pipeline SEASTAR that identifies first exons from RNA-seq data alone then quantifies and compares alternative first exon usage across multiple biological conditions. The exons inferred by SEASTAR coincide with transcription start sites identified directly by CAGE experiments and bear epigenetic hallmarks of active promoters. To determine if differential usage of alternative first exons can yield insights into the mechanism controlling gene expression, we applied SEASTAR to an RNA-seq dataset that tracked the reprogramming of mouse fibroblasts into induced pluripotent stem cells. We observed dynamic temporal changes in the usage of alternative first exons, along with correlated changes in transcription factor expression. Using a combined sequence motif and gene set enrichment analysis we identified N-Myc as a regulator of alternative first exon usage in the pluripotent state. Our results demonstrate that SEASTAR can leverage the available RNA-seq data to gain insights into the control of gene expression and alternative transcript variation in eukaryotic transcriptomes.

  10. A computational model for histone mark propagation reproduces the distribution of heterochromatin in different human cell types.

    Science.gov (United States)

    Schwämmle, Veit; Jensen, Ole Nørregaard

    2013-01-01

    Chromatin is a highly compact and dynamic nuclear structure that consists of DNA and associated proteins. The main organizational unit is the nucleosome, which consists of a histone octamer with DNA wrapped around it. Histone proteins are implicated in the regulation of eukaryote genes and they carry numerous reversible post-translational modifications that control DNA-protein interactions and the recruitment of chromatin binding proteins. Heterochromatin, the transcriptionally inactive part of the genome, is densely packed and contains histone H3 that is methylated at Lys 9 (H3K9me). The propagation of H3K9me in nucleosomes along the DNA in chromatin is antagonizing by methylation of H3 Lysine 4 (H3K4me) and acetylations of several lysines, which is related to euchromatin and active genes. We show that the related histone modifications form antagonized domains on a coarse scale. These histone marks are assumed to be initiated within distinct nucleation sites in the DNA and to propagate bi-directionally. We propose a simple computer model that simulates the distribution of heterochromatin in human chromosomes. The simulations are in agreement with previously reported experimental observations from two different human cell lines. We reproduced different types of barriers between heterochromatin and euchromatin providing a unified model for their function. The effect of changes in the nucleation site distribution and of propagation rates were studied. The former occurs mainly with the aim of (de-)activation of single genes or gene groups and the latter has the power of controlling the transcriptional programs of entire chromosomes. Generally, the regulatory program of gene transcription is controlled by the distribution of nucleation sites along the DNA string.

  11. Production of the 2400 kb Duchenne muscular dystrophy (DMD) gene transcript; transcription time and cotranscriptional splicing

    Energy Technology Data Exchange (ETDEWEB)

    Tennyson, C.N.; Worton, R.G. [Univ. of Toronto and the Hospital for Sick Children, Ontario (Canada)

    1994-09-01

    The largest known gene in any organism is the human DMD gene which has 79 exons that span 2400 kb. The extreme nature of the DMD gene raises questions concerning the time required for transcription and whether splicing begins before transcription is complete. DMD gene transcription is induced as cultured human myoblasts differentiate to form multinucleated myotubes, providing a system for studying the kinetics of transcription and splicing. Using quantitative RT-PCR, transcript accumulation was monitored from four different regions within the gene following induction of expression. By comparing the accumulation of transcripts from the 5{prime} and 3{prime} ends of the gene we have shown that approximately 12 hours are required to transcribe 1770 kb of the gene, extrapolating to a time of 16 hours for the transcription unit expressed in muscle. Comparison of accumulation profiles for spliced and total transcript demonstrated that transcripts are spliced at the 5{prime} end before transcription is complete, providing strong evidence for cotranscriptional splicing of DMD gene transcripts. Finally, the rate of transcript accumulation was reduced at the 3{prime} end of the gene relative to the 5{prime} end, perhaps due to premature termination of transcription complexes as they traverse this enormous transcription unit. The lag between transcription initiation and the appearance of complete transcripts could be important in limiting transcript production in dividing cells and to the timing of mRNA appearance in differentiating muscle.

  12. Mutual interdependence of splicing and transcription elongation.

    Science.gov (United States)

    Brzyżek, Grzegorz; Świeżewski, Szymon

    2015-01-01

    Transcription and splicing are intrinsically linked, as splicing needs a pre-mRNA substrate to commence. The more nuanced view is that the rate of transcription contributes to splicing regulation. On the other hand there is accumulating evidence that splicing has an active role in controlling transcription elongation by DNA-dependent RNA polymerase II (RNAP II). We briefly review those mechanisms and propose a unifying model where splicing controls transcription elongation to provide an optimal timing for successive rounds of splicing.

  13. Interplay between DNA supercoiling and transcription elongation.

    Science.gov (United States)

    Ma, Jie; Wang, Michelle

    2014-01-01

    Transcription-coupled DNA supercoiling has been shown to be an important regulator of transcription that is broadly present in the cell. Here we review experimental work which shows that RNA polymerase is a powerful torsional motor that can alter DNA topology and structure, and DNA supercoiling in turn directly affects transcription elongation.

  14. Reproducibility over a 1-month period of 1H-MR spectroscopic imaging NAA/Cr ratios in clinically stable multiple sclerosis patients.

    Science.gov (United States)

    Mostert, J P; Blaauw, Y; Koch, M W; Kuiper, A J; Hoogduin, J M; De Keyser, J

    2008-08-01

    N-acetylaspartate/creatine (NAA/Cr) ratios, assessed with proton magnetic resonance spectroscopy, are increasingly used as a surrogate marker for axonal dysfunction and degeneration in multiple sclerosis (MS). The purpose of this study was to test short-time reproducibility of NAA/Cr ratios in patients with clinically stable MS. In 35 MS patients we analysed NAA/Cr ratios obtained with (1)H-MR spectroscopic imaging at the centrum semiovale either with lateral ventricles partially included (group 1; n=15) or more cranially with no ventricles included (group 2; n=20). To test short-term reproducibility of the NAA/Cr measurements, patients were scanned twice 4 weeks apart. We determined mean NAA/Cr and Cho/Cr ratios of 12 grey matter and 24 white matter voxels. Mean NAA/Cr ratios of both the white and grey matter did not change after 4 weeks. Overall 4-week reproducibility of the NAA/Cr ratio, expressed as coefficient of variation, was 4.8% for grey matter and 3.5% for white matter. Reproducibility of cranial scanning of the ventricles was slightly better than with cerebrospinal fluid included. Our study shows good short-term reproducibility of NAA/Cr ratio measurements in the centrum semiovale, which supports the reliability of this technique for longitudinal studies.

  15. Highly Reproducible Automated Proteomics Sample Preparation Workflow for Quantitative Mass Spectrometry.

    Science.gov (United States)

    Fu, Qin; Kowalski, Michael P; Mastali, Mitra; Parker, Sarah J; Sobhani, Kimia; van den Broek, Irene; Hunter, Christie L; Van Eyk, Jennifer E

    2018-01-05

    Sample preparation for protein quantification by mass spectrometry requires multiple processing steps including denaturation, reduction, alkylation, protease digestion, and peptide cleanup. Scaling these procedures for the analysis of numerous complex biological samples can be tedious and time-consuming, as there are many liquid transfer steps and timed reactions where technical variations can be introduced and propagated. We established an automated sample preparation workflow with a total processing time for 96 samples of 5 h, including a 2 h incubation with trypsin. Peptide cleanup is accomplished by online diversion during the LC/MS/MS analysis. In a selected reaction monitoring (SRM) assay targeting 6 plasma biomarkers and spiked β-galactosidase, mean intraday and interday cyclic voltammograms (CVs) for 5 serum and 5 plasma samples over 5 days were samples repeated on 3 separate days had total CVs below 20%. Similar results were obtained when the workflow was transferred to a second site: 93% of peptides had CVs below 20%. An automated trypsin digestion workflow yields uniformly processed samples in less than 5 h. Reproducible quantification of peptides was observed across replicates, days, instruments, and laboratory sites, demonstrating the broad applicability of this approach.

  16. High-throughput miniaturized bioreactors for cell culture process development: reproducibility, scalability, and control.

    Science.gov (United States)

    Rameez, Shahid; Mostafa, Sigma S; Miller, Christopher; Shukla, Abhinav A

    2014-01-01

    Decreasing the timeframe for cell culture process development has been a key goal toward accelerating biopharmaceutical development. Advanced Microscale Bioreactors (ambr™) is an automated micro-bioreactor system with miniature single-use bioreactors with a 10-15 mL working volume controlled by an automated workstation. This system was compared to conventional bioreactor systems in terms of its performance for the production of a monoclonal antibody in a recombinant Chinese Hamster Ovary cell line. The miniaturized bioreactor system was found to produce cell culture profiles that matched across scales to 3 L, 15 L, and 200 L stirred tank bioreactors. The processes used in this article involve complex feed formulations, perturbations, and strict process control within the design space, which are in-line with processes used for commercial scale manufacturing of biopharmaceuticals. Changes to important process parameters in ambr™ resulted in predictable cell growth, viability and titer changes, which were in good agreement to data from the conventional larger scale bioreactors. ambr™ was found to successfully reproduce variations in temperature, dissolved oxygen (DO), and pH conditions similar to the larger bioreactor systems. Additionally, the miniature bioreactors were found to react well to perturbations in pH and DO through adjustments to the Proportional and Integral control loop. The data presented here demonstrates the utility of the ambr™ system as a high throughput system for cell culture process development. © 2014 American Institute of Chemical Engineers.

  17. SiGe epitaxial memory for neuromorphic computing with reproducible high performance based on engineered dislocations

    Science.gov (United States)

    Choi, Shinhyun; Tan, Scott H.; Li, Zefan; Kim, Yunjo; Choi, Chanyeol; Chen, Pai-Yu; Yeon, Hanwool; Yu, Shimeng; Kim, Jeehwan

    2018-01-01

    Although several types of architecture combining memory cells and transistors have been used to demonstrate artificial synaptic arrays, they usually present limited scalability and high power consumption. Transistor-free analog switching devices may overcome these limitations, yet the typical switching process they rely on—formation of filaments in an amorphous medium—is not easily controlled and hence hampers the spatial and temporal reproducibility of the performance. Here, we demonstrate analog resistive switching devices that possess desired characteristics for neuromorphic computing networks with minimal performance variations using a single-crystalline SiGe layer epitaxially grown on Si as a switching medium. Such epitaxial random access memories utilize threading dislocations in SiGe to confine metal filaments in a defined, one-dimensional channel. This confinement results in drastically enhanced switching uniformity and long retention/high endurance with a high analog on/off ratio. Simulations using the MNIST handwritten recognition data set prove that epitaxial random access memories can operate with an online learning accuracy of 95.1%.

  18. Reliable Mechanochemistry: Protocols for Reproducible Outcomes of Neat and Liquid Assisted Ball-mill Grinding Experiments.

    Science.gov (United States)

    Belenguer, Ana M; Lampronti, Giulio I; Sanders, Jeremy K M

    2018-01-23

    The equilibrium outcomes of ball mill grinding can dramatically change as a function of even tiny variations in the experimental conditions such as the presence of very small amounts of added solvent. To reproducibly and accurately capture this sensitivity, the experimentalist needs to carefully consider every single factor that can affect the ball mill grinding reaction under investigation, from ensuring the grinding jars are clean and dry before use, to accurately adding the stoichiometry of the starting materials, to validating that the delivery of solvent volume is accurate, to ensuring that the interaction between the solvent and the powder is well understood and, if necessary, a specific soaking time is added to the procedure. Preliminary kinetic studies are essential to determine the necessary milling time to achieve equilibrium. Only then can exquisite phase composition curves be obtained as a function of the solvent concentration under ball mill liquid assisted grinding (LAG). By using strict and careful procedures analogous to the ones here presented, such milling equilibrium curves can be obtained for virtually all milling systems. The system we use to demonstrate these procedures is a disulfide exchange reaction starting from the equimolar mixture of two homodimers to obtain at equilibrium quantitative heterodimer. The latter is formed by ball mill grinding as two different polymorphs, Form A and Form B. The ratio R = [Form B] / ([Form A] + [Form B]) at milling equilibrium depends on the nature and concentration of the solvent in the milling jar.

  19. Reproducibility of the Lauge-Hansen, Danis-Weber, and AO classifications for ankle fractures

    Directory of Open Access Journals (Sweden)

    Lucas Lopes da Fonseca

    Full Text Available ABSTRACT Objective: This study evaluated the reproducibility of the three main classifications of ankle fractures most commonly used in emergency clinical practice: Lauge-Hansen, Danis-Weber, and AO-OTA. The secondary objective was to assess whether the level of professional experience influenced the interobserver agreement for the classification of this pathology. Methods: The study included 83 digitized preoperative radiographic images of ankle fractures, in anteroposterior and lateral views, of different adults that had occurred between January and December 2013. For sample calculation, the estimated accuracy was approximately 15%, with a sampling error of 5% and a sampling power of 80%. The images were analyzed and classified by six different observers: two foot and ankle surgeons, two general orthopedic surgeons, and two-second-year residents in orthopedics and traumatology. The Kappa statistical method of multiple variances was used to assess the variations. Results: The Danis-Weber classification indicated that 40% of the agreements among all observers were good or excellent, whereas only 20% of good and excellent agreements were obtained using the AO and Lauge Hansen classifications. The Kappa index was 0.49 for the Danis-Weber classification, 0.32 for Lauge Hansen, and 0.38 for AO. Conclusion: The Hansen-Lauge classification presented the poorest interobserver agreement among the three systems. The AO classification demonstrated a moderate agreement and the Danis-Weber classification presented an excellent interobserver agreement index, regardless of professional experience.

  20. Reproducible simulation of respiratory motion in porcine lung explants

    Energy Technology Data Exchange (ETDEWEB)

    Biederer, J. [Dept. of Diagnostic Radiology, Univ. Hospital Schleswig-Holstein, Campus Kiel (Germany); Dept. of Radiology, German Cancer Research Center, Heidelberg (Germany); Plathow, C. [Dept. of Diagnostic Radiology, Eberhard-Karls-Univ. Tuebingen (Germany); Dept. of Radiology, German Cancer Research Center, Heidelberg (Germany); Schoebinger, M.; Meinzer, H.P. [Dept. of Medical and Biological Informatics, German Cancer Research Center, Heidelberg (Germany); Tetzlaff, R.; Puderbach, M.; Zaporozhan, J.; Kauczor, H.U. [Dept. of Radiology, German Cancer Research Center, Heidelberg (Germany); Bolte, H.; Heller, M. [Dept. of Diagnostic Radiology, Univ. Hospital Schleswig-Holstein, Campus Kiel (Germany)

    2006-11-15

    Purpose: To develop a model for exactly reproducible respiration motion simulations of animal lung explants inside an MR-compatible chest phantom. Materials and Methods: The materials included a piston pump and a flexible silicone reconstruction of a porcine diaphragm and were used in combination with an established MR-compatible chest phantom for porcine heart-lung preparations. The rhythmic inflation and deflation of the diaphragm at the bottom of the artificial thorax with water (1-1.5 L) induced lung tissue displacement resembling diaphragmatic breathing. This system was tested on five porcine heart-lung preparations using 1.5T MRI with transverse and coronal 3D-GRE (TR/TE=3.63/1.58, 256 x 256 matrix, 350 mm FOV, 4 mm slices) and half Fourier T2-FSE (TR/TE=545/29, 256 x 192, 350 mm, 6 mm) as well as multiple row detector CT (16 x 1 mm collimation, pitch 1.5, FOV 400 mm, 120 mAs) acquired at five fixed inspiration levels. Dynamic CT scans and coronal MRI with dynamic 2D-GRE and 2D-SS-GRE sequences (image frequencies of 10/sec and 3/sec, respectively) were acquired during continuous 'breathing' (7/minute). The position of the piston pump was visually correlated with the respiratory motion visible through the transparent wall of the phantom and with dynamic displays of CT and MR images. An elastic body splines analysis of the respiratory motion was performed using CT data. Results: Visual evaluation of MRI and CT showed three-dimensional movement of the lung tissue throughout the respiration cycle. Local tissue displacement inside the lung explants was documented with motion maps calculated from CT. The maximum displacement at the top of the diaphragm (mean 26.26 [SD 1.9] mm on CT and 27.16 [SD 1.5] mm on MRI, respectively [p=0.25; Wilcoxon test]) was in the range of tidal breathing in human patients. Conclusion: The chest phantom with a diaphragmatic pump is a promising platform for multi-modality imaging studies of the effects of respiratory lung

  1. Reproducible simulation of respiratory motion in porcine lung explants

    International Nuclear Information System (INIS)

    Biederer, J.; Plathow, C.; Schoebinger, M.; Meinzer, H.P.; Tetzlaff, R.; Puderbach, M.; Zaporozhan, J.; Kauczor, H.U.; Bolte, H.; Heller, M.

    2006-01-01

    Purpose: To develop a model for exactly reproducible respiration motion simulations of animal lung explants inside an MR-compatible chest phantom. Materials and Methods: The materials included a piston pump and a flexible silicone reconstruction of a porcine diaphragm and were used in combination with an established MR-compatible chest phantom for porcine heart-lung preparations. The rhythmic inflation and deflation of the diaphragm at the bottom of the artificial thorax with water (1-1.5 L) induced lung tissue displacement resembling diaphragmatic breathing. This system was tested on five porcine heart-lung preparations using 1.5T MRI with transverse and coronal 3D-GRE (TR/TE=3.63/1.58, 256 x 256 matrix, 350 mm FOV, 4 mm slices) and half Fourier T2-FSE (TR/TE=545/29, 256 x 192, 350 mm, 6 mm) as well as multiple row detector CT (16 x 1 mm collimation, pitch 1.5, FOV 400 mm, 120 mAs) acquired at five fixed inspiration levels. Dynamic CT scans and coronal MRI with dynamic 2D-GRE and 2D-SS-GRE sequences (image frequencies of 10/sec and 3/sec, respectively) were acquired during continuous 'breathing' (7/minute). The position of the piston pump was visually correlated with the respiratory motion visible through the transparent wall of the phantom and with dynamic displays of CT and MR images. An elastic body splines analysis of the respiratory motion was performed using CT data. Results: Visual evaluation of MRI and CT showed three-dimensional movement of the lung tissue throughout the respiration cycle. Local tissue displacement inside the lung explants was documented with motion maps calculated from CT. The maximum displacement at the top of the diaphragm (mean 26.26 [SD 1.9] mm on CT and 27.16 [SD 1.5] mm on MRI, respectively [p=0.25; Wilcoxon test]) was in the range of tidal breathing in human patients. Conclusion: The chest phantom with a diaphragmatic pump is a promising platform for multi-modality imaging studies of the effects of respiratory lung motion. (orig.)

  2. Evaluation of mammographic density patterns: reproducibility and concordance among scales

    Directory of Open Access Journals (Sweden)

    Garrido-Estepa Macarena

    2010-09-01

    .32% respectively, while this percentage was lower for the quantitative scales (21.89% for BI-RADS and 21.86% for Boyd. Conclusions Visual scales of mammographic density show a high reproducibility when appropriate training is provided. Their ability to distinguish between high and low risk render them useful for routine use by breast cancer screening programs. Quantitative-based scales are more specific than pattern-based scales in classifying populations in the high-risk group.

  3. Establishment of reproducible osteosarcoma rat model using orthotopic implantation technique.

    Science.gov (United States)

    Yu, Zhe; Sun, Honghui; Fan, Qingyu; Long, Hua; Yang, Tongtao; Ma, Bao'an

    2009-05-01

    osteosarcoma model was shown to be feasible: the take rate was high, surgical mortality was negligible and the procedure was simple to perform and easily reproduced. It may be a useful tool in the investigation of antiangiogenic and anticancer therapeutics. Ultrasound was found to be a highly accurate tool for tumor diagnosis, localization and measurement and may be recommended for monitoring tumor growth in this model.

  4. Experimentally Reproducing Thermal Breakdown of Rock at Earth's Surface

    Science.gov (United States)

    Eppes, M. C.; Griffiths, L.; Heap, M. J.; Keanini, R.; Baud, P.

    2016-12-01

    Thermal stressing induces microcrack growth in rock in part due to thermal expansion mismatch between different minerals, mineral phases, or crystalline axes and/or thermal gradients in the entire rock mass. This knowledge is largely derived from experimental studies of thermal microcracking, typically under conditions of very high temperatures (hundreds of °C). Thermal stressing at lower temperatures has received significantly less attention despite the fact that it may play an important role in rock breakdown at and near Earth's surface (Aldred et al., 2015; Collins and Stock, 2016). In particular, Eppes et al. (2016) attribute recorded Acoustic Emissions (AE) from a highly instrumented granite boulder sitting on the ground in natural conditions to subcritical crack growth driven by thermal stresses arising from a combination of solar- and weather-induced temperature changes; however the maximum temperature the boulder experienced was just 65 °C. In order to better understand these results without complicating factors of a natural environment, we conducted controlled laboratory experiments on cylindrical samples (40 mm length and 20 mm diameter) cored from the same granite as the Eppes et al. (2016) experiment, subjecting them to temperature fluctuations that reproduced the field measurements. We used a novel experimental configuration whereby two high temperature piezo-transducers are each in contact with an opposing face of the sample. The servo-controlled uniaxial press compensates for the thermal expansion and contraction of the pistons and the sample, keeping the coupling between the transducers and the sample, and the axial force acting on the sample, constant throughout. The system records AE, as well as P-wave velocity, both independent proxies for microfracture, as well as strain and temperature. Preliminary tests, heating and cooling granite at a rate of 1 °C/min, show that a large amount of AE occurs at temperatures as low as 100 °C. Ultimately, by

  5. La transcription phonétique du dictionnaire Franqus

    Directory of Open Access Journals (Sweden)

    Denis Dumas

    2006-12-01

    Full Text Available Abstract The phonetic transcription in the Franqus dictionary will obey two principles: first realism, to warrant its own representativity and social legitimacy; second, economy, to assure its consistency and to avoid unnecessary redundancy. Will be included all distinctive traits (e.g. the historical long vowels /E:, A/, and will be excluded all automatic variations such as dental assibilation. Also included are traits that, while nondistinctive, are invariable, such as intramorphemic prevocalic glides (e.g. the always monosyllabic words pied, puis, fouine, etc.. Morphology will be implied, particularly in the realization of schwa (according to suffixes such as -ment or in the behaviour of certain prefixes (dis-, . . . o- final prefixes. Special attention will be given to “paradoxical” schwas (which should or could be deleted but never are as well as to the local adaptation of anglicisms. In sum, the transcriptions will integrate overall structural facts pertaining to the phonology, morphology and lexicon specific to this language variety

  6. Directing traffic on DNA-How transcription factors relieve or induce transcriptional interference.

    Science.gov (United States)

    Hao, Nan; Palmer, Adam C; Dodd, Ian B; Shearwin, Keith E

    2017-03-15

    Transcriptional interference (TI) is increasingly recognized as a widespread mechanism of gene control, particularly given the pervasive nature of transcription, both sense and antisense, across all kingdoms of life. Here, we discuss how transcription factor binding kinetics strongly influence the ability of a transcription factor to relieve or induce TI.

  7. Errors in data interpretation from genetic variation of human analytes

    OpenAIRE

    Howie, Heather L.; Delaney, Meghan; Wang, Xiaohong; Er, Lay See; Kapp, Linda; Lebedev, Jenna N.; Zimring, James C.

    2017-01-01

    In recent years, the extent of our vulnerability to misinterpretation due to poorly characterized reagents has become an issue of great concern. Antibody reagents have been identified as a major source of error, contributing to the ?reproducibility crisis.? In the current report, we define an additional dimension of the crisis; in particular, we define variation of the targets being analyzed. We report that natural variation in the immunoglobulin ?constant? region alters the reactivity with c...

  8. The Journey of a Transcription Factor

    DEFF Research Database (Denmark)

    Pireyre, Marie

    Plants have developed astonishing networks regulating their metabolism to adapt to their environment. The complexity of these networks is illustrated by the expansion of families of regulators such as transcription factors in the plant kingdom. Transcription factors specifically impact...... transcriptional networks by integrating exogenous and endogenous stimuli and regulating gene expression accordingly. Regulation of transcription factors and their activation is thus highly important to modulate the transcriptional programs and increase fitness of the plant in a given environment. Plant metabolism....... The biosynthetic machinery of GLS is governed by interplay of six MYB and three bHLH transcription factors. MYB28, MYB29 and MYB76 regulate methionine-derived GLS, and MYB51, MYB34 and MYB122 regulate tryptophan-derived GLS. The three bHLH transcription factors MYC2, MYC3 and MYC4 physically interact with all six...

  9. Repression of Meiotic Genes by Antisense Transcription and by Fkh2 Transcription Factor in Schizosaccharomyces pombe

    OpenAIRE

    Chen, Huei-Mei; Rosebrock, Adam P.; Khan, Sohail R.; Futcher, Bruce; Leatherwood, Janet K.

    2012-01-01

    In S. pombe, about 5% of genes are meiosis-specific and accumulate little or no mRNA during vegetative growth. Here we use Affymetrix tiling arrays to characterize transcripts in vegetative and meiotic cells. In vegetative cells, many meiotic genes, especially those induced in mid-meiosis, have abundant antisense transcripts. Disruption of the antisense transcription of three of these mid-meiotic genes allowed vegetative sense transcription. These results suggest that antisense transcription ...

  10. SU-E-J-252: Reproducibility of Radiogenomic Image Features: Comparison of Two Semi-Automated Segmentation Methods

    Energy Technology Data Exchange (ETDEWEB)

    Lee, M; Woo, B; Kim, J [Seoul National University, Seoul (Korea, Republic of); Jamshidi, N; Kuo, M [UCLA School of Medicine, Los Angeles, CA (United States)

    2015-06-15

    Purpose: Objective and reliable quantification of imaging phenotype is an essential part of radiogenomic studies. We compared the reproducibility of two semi-automatic segmentation methods for quantitative image phenotyping in magnetic resonance imaging (MRI) of glioblastoma multiforme (GBM). Methods: MRI examinations with T1 post-gadolinium and FLAIR sequences of 10 GBM patients were downloaded from the Cancer Image Archive site. Two semi-automatic segmentation tools with different algorithms (deformable model and grow cut method) were used to segment contrast enhancement, necrosis and edema regions by two independent observers. A total of 21 imaging features consisting of area and edge groups were extracted automatically from the segmented tumor. The inter-observer variability and coefficient of variation (COV) were calculated to evaluate the reproducibility. Results: Inter-observer correlations and coefficient of variation of imaging features with the deformable model ranged from 0.953 to 0.999 and 2.1% to 9.2%, respectively, and the grow cut method ranged from 0.799 to 0.976 and 3.5% to 26.6%, respectively. Coefficient of variation for especially important features which were previously reported as predictive of patient survival were: 3.4% with deformable model and 7.4% with grow cut method for the proportion of contrast enhanced tumor region; 5.5% with deformable model and 25.7% with grow cut method for the proportion of necrosis; and 2.1% with deformable model and 4.4% with grow cut method for edge sharpness of tumor on CE-T1W1. Conclusion: Comparison of two semi-automated tumor segmentation techniques shows reliable image feature extraction for radiogenomic analysis of GBM patients with multiparametric Brain MRI.

  11. Reproducibility of a semi-automatic method for 6-point vertebral morphometry in a multi-centre trial

    International Nuclear Information System (INIS)

    Guglielmi, Giuseppe; Stoppino, Luca Pio; Placentino, Maria Grazia; D'Errico, Francesco; Palmieri, Francesco

    2009-01-01

    Purpose: To evaluate the reproducibility of a semi-automated system for vertebral morphometry (MorphoXpress) in a large multi-centre trial. Materials and methods: The study involved 132 clinicians (no radiologist) with different levels of experience across 20 osteo-centres in Italy. All have received training in using MorphoXpress. An expert radiologist was also involved providing data used as standard of reference. The test image originate from normal clinical activity and represent a variety of normal, under and over exposed films, indicating both normal anatomy and vertebral deformities. The image was represented twice to the clinicians in a random order. Using the software, the clinicians initially marked the midpoints of the upper and lower vertebrae to include as many of the vertebrae (T5-L4) as practical within each given image. MorphoXpress performs the localisation of all morphometric points based on statistical model-based vision system. Intra-operator as well inter-operator measurement of agreement was calculated using the coefficient of variation and the mean and standard deviation of the difference of two measurements to check their agreement. Results: The overall intra-operator mean differences in vertebral heights is 1.61 ± 4.27% (1 S.D.). The overall intra-operator coefficient of variation is 3.95%. The overall inter-operator mean differences in vertebral heights is 2.93 ± 5.38% (1 S.D.). The overall inter-operator coefficient of variation is 6.89%. Conclusions: The technology tested here can facilitate reproducible quantitative morphometry suitable for large studies of vertebral deformities

  12. SU-E-J-252: Reproducibility of Radiogenomic Image Features: Comparison of Two Semi-Automated Segmentation Methods

    International Nuclear Information System (INIS)

    Lee, M; Woo, B; Kim, J; Jamshidi, N; Kuo, M

    2015-01-01

    Purpose: Objective and reliable quantification of imaging phenotype is an essential part of radiogenomic studies. We compared the reproducibility of two semi-automatic segmentation methods for quantitative image phenotyping in magnetic resonance imaging (MRI) of glioblastoma multiforme (GBM). Methods: MRI examinations with T1 post-gadolinium and FLAIR sequences of 10 GBM patients were downloaded from the Cancer Image Archive site. Two semi-automatic segmentation tools with different algorithms (deformable model and grow cut method) were used to segment contrast enhancement, necrosis and edema regions by two independent observers. A total of 21 imaging features consisting of area and edge groups were extracted automatically from the segmented tumor. The inter-observer variability and coefficient of variation (COV) were calculated to evaluate the reproducibility. Results: Inter-observer correlations and coefficient of variation of imaging features with the deformable model ranged from 0.953 to 0.999 and 2.1% to 9.2%, respectively, and the grow cut method ranged from 0.799 to 0.976 and 3.5% to 26.6%, respectively. Coefficient of variation for especially important features which were previously reported as predictive of patient survival were: 3.4% with deformable model and 7.4% with grow cut method for the proportion of contrast enhanced tumor region; 5.5% with deformable model and 25.7% with grow cut method for the proportion of necrosis; and 2.1% with deformable model and 4.4% with grow cut method for edge sharpness of tumor on CE-T1W1. Conclusion: Comparison of two semi-automated tumor segmentation techniques shows reliable image feature extraction for radiogenomic analysis of GBM patients with multiparametric Brain MRI

  13. Laboratory synthesis of an independently reproducing vertebrate species.

    Science.gov (United States)

    Lutes, Aracely A; Baumann, Diana P; Neaves, William B; Baumann, Peter

    2011-06-14

    Speciation in animals commonly involves an extrinsic barrier to genetic exchange followed by the accumulation of sufficient genetic variation to impede subsequent productive interbreeding. All-female species of whiptail lizards, which originated by interspecific hybridization between sexual progenitors, are an exception to this rule. Here, the arising species instantaneously acquires a novel genotype combining distinctive alleles from two different species, and reproduction by parthenogenesis constitutes an effective intrinsic barrier to genetic exchange. Fertilization of diploid parthenogenetic females by males of sexual species has produced several triploid species, but these instantaneous speciation events have neither been observed in nature nor have they been reconstituted in the laboratory. Here we report the generation of four self-sustaining clonal lineages of a tetraploid species resulting from fertilization of triploid oocytes from a parthenogenetic Aspidoscelis exsanguis with haploid sperm from Aspidoscelis inornata. Molecular and cytological analysis confirmed the genetic identity of the hybrids and revealed that the females retain the capability of parthenogenetic reproduction characteristic of their triploid mothers. The tetraploid females have established self-perpetuating clonal lineages which are now in the third generation. Our results confirm the hypothesis that secondary hybridization events can lead to asexual lineages of increased ploidy when favorable combinations of parental genomes are assembled. We anticipate that these animals will be a critical tool in understanding the mechanisms underlying the origin and subsequent evolution of asexual amniotes.

  14. SU-E-J-227: Breathing Pattern Consistency and Reproducibility: Comparative Analysis for Supine and Prone Body Positioning

    International Nuclear Information System (INIS)

    Laugeman, E; Weiss, E; Chen, S; Hugo, G; Rosu, M

    2014-01-01

    Purpose: Evaluate and compare the cycle-to-cycle consistency of breathing patterns and their reproducibility over the course of treatment, for supine and prone positioning. Methods: Respiratory traces from 25 patients were recorded for sequential supine/prone 4DCT scans acquired prior to treatment, and during the course of the treatment (weekly or bi-weekly). For each breathing cycle, the average(AVE), end-of-exhale(EoE) and end-of-inhale( EoI) locations were identified using in-house developed software. In addition, the mean values and variations for the above quantities were computed for each breathing trace. F-tests were used to compare the cycle-to-cycle consistency of all pairs of sequential supine and prone scans. Analysis of variances was also performed using population means for AVE, EoE and EoI to quantify differences between the reproducibility of prone and supine respiration traces over the treatment course. Results: Consistency: Cycle-to-cycle variations are less in prone than supine in the pre-treatment and during-treatment scans for AVE, EoE and EoI points, for the majority of patients (differences significant at p<0.05). The few cases where the respiratory pattern had more variability in prone appeared to be random events. Reproducibility: The reproducibility of breathing patterns (supine and prone) improved as treatment progressed, perhaps due to patients becoming more comfortable with the procedure. However, variability in supine position continued to remain significantly larger than in prone (p<0.05), as indicated by the variance analysis of population means for the pretreatment and subsequent during-treatment scans. Conclusions: Prone positioning stabilizes breathing patterns in most subjects investigated in this study. Importantly, a parallel analysis of the same group of patients revealed a tendency towards increasing motion amplitude of tumor targets in prone position regardless of their size or location; thus, the choice for body positioning

  15. Semi-automated scoring of pulmonary emphysema from X-ray CT: Trainee reproducibility and accuracy

    Energy Technology Data Exchange (ETDEWEB)

    Owrangi, Amir M., E-mail: aowrangi@robarts.ca [Imaging Research Laboratories, Robarts Research Institute, London (Canada); Entwistle, Brandon, E-mail: Brandon.Entwistle@londonhospitals.ca; Lu, Andrew, E-mail: Andrew.Lu@londonhospitals.ca; Chiu, Jack, E-mail: Jack.Chiu@londonhospitals.ca; Hussain, Nabil, E-mail: Nabil.Hussain@londonhospitals.ca; Etemad-Rezai, Roya, E-mail: Roya.EtemadRezai@lhsc.on.ca; Parraga, Grace, E-mail: gparraga@robarts.ca [Imaging Research Laboratories, Robarts Research Institute, London (Canada); Graduate Program in Biomedical Engineering, Department of Medical Imaging, Department of Medical Biophysics, The University of Western Ontario, London (Canada)

    2013-11-01

    Objective: We developed a semi-automated tool to quantify emphysema from thoracic X-ray multi-detector (64-slice) computed tomography (CT) for training purposes and multi-reader studies. Materials and Methods: Thoracic X-ray CT was acquired in 93 ex-smokers, who were evaluated by six trainees with little or no expertise (trainees) and a single experienced thoracic radiologist (expert). A graphic user interface (GUI) was developed for emphysema quantification based on the percentile of lung where a score of 0 = no abnormalities, 1 = 1–25%, 2 = 26–50%, 3 = 51–75% and 4 = 76–100% for each lung side/slice. Trainees blinded to subject characteristics scored randomized images twice; accuracy was determined by comparison to expert scores, density histogram 15th percentile (HU{sub 15}), relative area at −950 HU (RA{sub 950}), low attenuation clusters at −950 HU (LAC{sub 950}), −856 HU (LAC{sub 856}) and the diffusing capacity for carbon monoxide (DL{sub CO%pred}). Intra- and inter-observer reproducibility was evaluated using coefficients-of-variation (COV), intra-class (ICC) and Pearson correlations. Results: Trainee–expert correlations were significant (r = 0.85–0.97, p < 0.0001) and a significant trainee bias (0.15 ± 0.22) was observed. Emphysema score was correlated with RA{sub 950} (r = 0.88, p < 0.0001), HU{sub 15} (r = −0.77, p < 0.0001), LAC{sub 950} (r = 0.76, p < 0.0001), LAC{sub 856} (r = 0.74, p = 0.0001) and DL{sub CO%pred} (r = −0.71, p < 0.0001). Intra-observer reproducibility (COV = 4–27%; ICC = 0.75–0.94) was moderate to high for trainees; intra- and inter-observer COV were negatively and non-linearly correlated with emphysema score. Conclusion: We developed a GUI for rapid and interactive emphysema scoring that allows for comparison of multiple readers with clinical and radiological standards.

  16. Evaluation of MidIR fibre optic reflectance: Detection limit, reproducibility and binary mixture discrimination

    Science.gov (United States)

    Sessa, Clarimma; Bagán, Héctor; García, José Francisco

    2013-11-01

    MidIR fibre optic reflectance (MidIR-FORS) is a promising analytical technique in the field of science conservation, especially because it is non-destructive. Another advantage of MidIR-FORS is that the obtained information is representative, as a large amount of spectral data can be collected. Although the technique has a high potential and is almost routinely applied, its quality parameters have not been thoroughly studied in the specific application of analysis of artistic materials. The objective of this study is to evaluate the instrumental capabilities of MidIR-FORS for the analysis of artwork materials in terms of detection limit, reproducibility, and mixture characterisation. The study has been focused on oil easel painting and several paints of known composition have been analysed. Paint layers include blue pigments not only because of their important role along art history, but also because their physical and spectroscopic characteristics allow a better evaluation of the MidIR-FORS capabilities. The results of the analysis indicate that MidIR-FORS supplies a signal affected by different factors, such as the optical, morphological and physical properties of the surface, in addition to the composition of materials analysed. Consequently, the detection limits established are relatively high for artistic objects (Prussian blue - PB 2.1-6.5%; Phthalocyanine blue - Pht 6.3-10.2%; synthetic Ultramarine blue - UM 12.1%) and may therefore lead to an incomplete description of the artwork. Reproducibility of the technique over time and across surface has been determined. The results show that the major sources of dispersion are the heterogeneity of the pigments distribution, physical features, and band shape distortions. The total dispersion is around 4% for the most intense bands (oil) and increases up to 26% when weak or overlapped bands are considered (PB, Pht, UM). The application of different pre-treatments (cutoff of fibres absorption, Savizky-Golay smoothing

  17. The intra-observer reproducibility of cardiovascular magnetic resonance myocardial feature tracking strain assessment is independent of field strength

    International Nuclear Information System (INIS)

    Schuster, Andreas; Morton, Geraint; Hussain, Shazia T.

    2013-01-01

    Background: Cardiovascular magnetic resonance myocardial feature tracking (CMR-FT) is a promising novel method for quantification of myocardial wall mechanics from standard steady-state free precession (SSFP) images. We sought to determine whether magnetic field strength affects the intra-observer reproducibility of CMR-FT strain analysis. Methods: We studied 2 groups, each consisting of 10 healthy subjects, at 1.5 T or 3 T Analysis was performed at baseline and after 4 weeks using dedicated CMR-FT prototype software (Tomtec, Germany) to analyze standard SSFP cine images. Right ventricular (RV) and left ventricular (LV) longitudinal strain (Ell RV and Ell LV ) and LV long-axis radial strain (Err LAX ) were derived from the 4-chamber cine, and LV short-axis circumferential and radial strains (Ecc SAX , Err SAX ) from the short-axis orientation. Strain parameters were assessed together with LV ejection fraction (EF) and volumes. Intra-observer reproducibility was determined by comparing the first and the second analysis in both groups. Results: In all volunteers resting strain parameters were successfully derived from the SSFP images. There was no difference in strain parameters, volumes and EF between field strengths (p > 0.05). In general Ecc SAX was the most reproducible strain parameter as determined by the coefficient of variation (CV) at 1.5 T (CV 13.3% and 46% global and segmental respectively) and 3 T (CV 17.2% and 31.1% global and segmental respectively). The least reproducible parameter was Ell RV (CV 1.5 T 28.7% and 53.2%; 3 T 43.5% and 63.3% global and segmental respectively). Conclusions: CMR-FT results are similar with reasonable intra-observer reproducibility in different groups of volunteers at 1.5 T and 3 T. CMR-FT is a promising novel technique and our data indicate that results might be transferable between field strengths. However there is a considerable amount of segmental variability indicating that further refinements are needed before CMR

  18. Short- and long-term quantitation reproducibility of brain metabolites in the medial wall using proton echo planar spectroscopic imaging.

    Science.gov (United States)

    Tsai, Shang-Yueh; Lin, Yi-Ru; Wang, Woan-Chyi; Niddam, David M

    2012-11-15

    Proton echo planar spectroscopic imaging (PEPSI) is a fast magnetic resonance spectroscopic imaging (MRSI) technique that allows mapping spatial metabolite distributions in the brain. Although the medial wall of the cortex is involved in a wide range of pathological conditions, previous MRSI studies have not focused on this region. To decide the magnitude of metabolic changes to be considered significant in this region, the reproducibility of the method needs to be established. The study aims were to establish the short- and long-term reproducibility of metabolites in the right medial wall and to compare regional differences using a constant short-echo time (TE30) and TE averaging (TEavg) optimized to yield glutamatergic information. 2D sagittal PEPSI was implemented at 3T using a 32 channel head coil. Acquisitions were repeated immediately and after approximately 2 weeks to assess the coefficients of variation (COV). COVs were obtained from eight regions-of-interest (ROIs) of varying size and location. TE30 resulted in better spectral quality and similar or lower quantitation uncertainty for all metabolites except glutamate (Glu). When Glu and glutamine (Gln) were quantified together (Glx) reduced quantitation uncertainty and increased reproducibility was observed for TE30. TEavg resulted in lowered quantitation uncertainty for Glu but in less reliable quantification of several other metabolites. TEavg did not result in a systematically improved short- or long-term reproducibility for Glu. The ROI volume was a major factor influencing reproducibility. For both short- and long-term repetitions, the Glu COVs obtained with TEavg were 5-8% for the large ROIs, 12-17% for the medium sized ROIs and 16-26% for the smaller cingulate ROIs. COVs obtained with TE30 for the less specific Glx were 3-5%, 8-10% and 10-15%. COVs for N-acetyl aspartate, creatine and choline using TE30 with long-term repetition were between 2-10%. Our results show that the cost of more specific

  19. Variational principles for locally variational forms

    International Nuclear Information System (INIS)

    Brajercik, J.; Krupka, D.

    2005-01-01

    We present the theory of higher order local variational principles in fibered manifolds, in which the fundamental global concept is a locally variational dynamical form. Any two Lepage forms, defining a local variational principle for this form, differ on intersection of their domains, by a variationally trivial form. In this sense, but in a different geometric setting, the local variational principles satisfy analogous properties as the variational functionals of the Chern-Simons type. The resulting theory of extremals and symmetries extends the first order theories of the Lagrange-Souriau form, presented by Grigore and Popp, and closed equivalents of the first order Euler-Lagrange forms of Hakova and Krupkova. Conceptually, our approach differs from Prieto, who uses the Poincare-Cartan forms, which do not have higher order global analogues

  20. Transcriptional Regulation and the Diversification of Metabolism in Wine Yeast Strains

    Science.gov (United States)

    Rossouw, Debra; Jacobson, Dan; Bauer, Florian F.

    2012-01-01

    Transcription factors and their binding sites have been proposed as primary targets of evolutionary adaptation because changes to single transcription factors can lead to far-reaching changes in gene expression patterns. Nevertheless, there is very little concrete evidence for such evolutionary changes. Industrial wine yeast strains, of the species Saccharomyces cerevisiae, are a geno- and phenotypically diverse group of organisms that have adapted to the ecological niches of industrial winemaking environments and have been selected to produce specific styles of wine. Variation in transcriptional regulation among wine yeast strains may be responsible for many of the observed differences and specific adaptations to different fermentative conditions in the context of commercial winemaking. We analyzed gene expression profiles of wine yeast strains to assess the impact of transcription factor expression on metabolic networks. The data provide new insights into the molecular basis of variations in gene expression in industrial strains and their consequent effects on metabolic networks important to wine fermentation. We show that the metabolic phenotype of a strain can be shifted in a relatively predictable manner by changing expression levels of individual transcription factors, opening opportunities to modify transcription networks to achieve desirable outcomes. PMID:22042577

  1. Variation and Mathematics Pedagogy

    Science.gov (United States)

    Leung, Allen

    2012-01-01

    This discussion paper put forwards variation as a theme to structure mathematical experience and mathematics pedagogy. Patterns of variation from Marton's Theory of Variation are understood and developed as types of variation interaction that enhance mathematical understanding. An idea of a discernment unit comprising mutually supporting variation…

  2. Quantum theory as the most robust description of reproducible experiments

    Science.gov (United States)

    De Raedt, Hans; Katsnelson, Mikhail I.; Michielsen, Kristel

    2014-08-01

    knowledge always starts from the middle, that is, from the world of macroscopic objects. According to Bohr, the quantum theoretical description crucially depends on the existence of macroscopic objects which can be used as measuring devices. For an extensive analysis of the quantum measurement process from a dynamical point of view see Ref. [51]. Most importantly, the description of the macroscopic level is robust, that is, essentially independent of the underlying "more fundamental" picture [2]. As will be seen later, formalizing the notion of "robustness" is key to derive the basic equations of quantum theory from the general framework of logical inference.Key assumptions of the deductive approach are that the mathematical description is a complete description of the experiment under consideration and that there is no uncertainty about the conditions under which the experiment is carried out. If the theory does not fully account for all the relevant aspects of the phenomenon that we wish to describe, the general rules by which we deduce whether a proposition is true or false can no longer be used. However, in these circumstances, we can still resort to logical inference [37-41] to find useful answers to unambiguous questions. Of course, in general it will no longer be possible to say whether a proposition is true or false, hence there will always remain a residue of doubt. However, as will be shown, the description obtained through logical inference may also be unambiguous and independent of the individual.In the present paper, we demonstrate that the basic equations of quantum theory directly follow from logical inference applied to experiments in which there is uncertainty about individual events, the stringent condition that certain properties of the collection of events are reproducible, meaning that they are robust with respect to small changes in the conditions under which the experiments are carried out.

  3. Calculus of variations

    CERN Document Server

    Elsgolc, L E; Stark, M

    1961-01-01

    Calculus of Variations aims to provide an understanding of the basic notions and standard methods of the calculus of variations, including the direct methods of solution of the variational problems. The wide variety of applications of variational methods to different fields of mechanics and technology has made it essential for engineers to learn the fundamentals of the calculus of variations. The book begins with a discussion of the method of variation in problems with fixed boundaries. Subsequent chapters cover variational problems with movable boundaries and some other problems; sufficiency

  4. Mitotic Transcriptional Activation: Clearance of Actively Engaged Pol II via Transcriptional Elongation Control in Mitosis.

    Science.gov (United States)

    Liang, Kaiwei; Woodfin, Ashley R; Slaughter, Brian D; Unruh, Jay R; Box, Andrew C; Rickels, Ryan A; Gao, Xin; Haug, Jeffrey S; Jaspersen, Sue L; Shilatifard, Ali

    2015-11-05

    Although it is established that some general transcription factors are inactivated at mitosis, many details of mitotic transcription inhibition (MTI) and its underlying mechanisms are largely unknown. We have identified mitotic transcriptional activation (MTA) as a key regulatory step to control transcription in mitosis for genes with transcriptionally engaged RNA polymerase II (Pol II) to activate and transcribe until the end of the gene to clear Pol II from mitotic chromatin, followed by global impairment of transcription reinitiation through MTI. Global nascent RNA sequencing and RNA fluorescence in situ hybridization demonstrate the existence of transcriptionally engaged Pol II in early mitosis. Both genetic and chemical inhibition of P-TEFb in mitosis lead to delays in the progression of cell division. Together, our study reveals a mechanism for MTA and MTI whereby transcriptionally engaged Pol II can progress into productive elongation and finish transcription to allow proper cellular division. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. SU-G-JeP3-15: Is the Reproducibility with Respect to Bone of Tumor Position at Simulation for Breath Hold CT Scans Correlated to the Reproducibility for Multiple Breath Hold CBCTs at Treatment in SBRT Thoracic Patients?

    Energy Technology Data Exchange (ETDEWEB)

    Pollard, J; Prajapati, S; Gao, S; Nitsch, P; Sadagopan, R; Wang, X; Balter, P [UT MD Anderson Cancer Center, Houston, TX (United States)

    2016-06-15

    Purpose: To evaluate correlation between the reproducibility of tumor position under feedback guided voluntary deep inspiration breath hold gating at simulation and at treatment. Methods: All patients treated with breath hold (BH) have 3-6 BH CTs taken at simulation (sim). In addition, if the relationship between the tumor and nearby bony anatomy on treatment BH CT(or CBCT) is found to be greater than 5 mm different at treatment than it was at sim, a repeat BH CT is taken before treatment. We retrospectively analyzed the sim CTs for 19 patients who received BH SBRT lung treatments and had repeat BH CT on treatment. We evaluated the reproducibility of the tumor position during the simulation CTs and compared this to the reproducibility of the tumor position on the repeat treatment CT with our in-house CT alignment software (CT-Assisted Targeting for Radiotherapy). Results: Comparing the tumor position for multiple simulation BH CTs, we calculated: maximum difference (max) = 0.69cm; average difference (x) = 0.28cm; standard deviation (σ) = 0.18cm. Comparing the repeat BH CBCTs on treatment days we calculated: max = 0.44cm; x = 0.16cm; σ = 0.22cm. We also found that for 95% of our BH cases, the absolute variation in tumor position within the same imaging day was within 5mm of the range at the time of simulation and treatment. We found that 75% of the BH cases had less residual tumor motion on treatment days than at simulation. Conclusion: This suggests that a GTV contour based upon the residual tumor motion in multiple BH datasets plus 2 mm margin should be sufficient to cover the full range of residual tumor motion on treatment days.

  6. Promoter proximal polyadenylation sites reduce transcription activity

    DEFF Research Database (Denmark)

    Andersen, Pia Kjølhede; Lykke-Andersen, Søren; Jensen, Torben Heick

    2012-01-01

    Gene expression relies on the functional communication between mRNA processing and transcription. We previously described the negative impact of a point-mutated splice donor (SD) site on transcription. Here we demonstrate that this mutation activates an upstream cryptic polyadenylation (CpA) site......, which in turn causes reduced transcription. Functional depletion of U1 snRNP in the context of the wild-type SD triggers the same CpA event accompanied by decreased RNA levels. Thus, in accordance with recent findings, U1 snRNP can shield premature pA sites. The negative impact of unshielded pA sites...... on transcription requires promoter proximity, as demonstrated using artificial constructs and supported by a genome-wide data set. Importantly, transcription down-regulation can be recapitulated in a gene context devoid of splice sites by placing a functional bona fide pA site/transcription terminator within ∼500...

  7. Transcription and recombination: when RNA meets DNA.

    Science.gov (United States)

    Aguilera, Andrés; Gaillard, Hélène

    2014-08-01

    A particularly relevant phenomenon in cell physiology and proliferation is the fact that spontaneous mitotic recombination is strongly enhanced by transcription. The most accepted view is that transcription increases the occurrence of double-strand breaks and/or single-stranded DNA gaps that are repaired by recombination. Most breaks would arise as a consequence of the impact that transcription has on replication fork progression, provoking its stalling and/or breakage. Here, we discuss the mechanisms responsible for the cross talk between transcription and recombination, with emphasis on (1) the transcription-replication conflicts as the main source of recombinogenic DNA breaks, and (2) the formation of cotranscriptional R-loops as a major cause of such breaks. The new emerging questions and perspectives are discussed on the basis of the interference between transcription and replication, as well as the way RNA influences genome dynamics. Copyright © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.

  8. Specificity and robustness in transcription control networks.

    Science.gov (United States)

    Sengupta, Anirvan M; Djordjevic, Marko; Shraiman, Boris I

    2002-02-19

    Recognition by transcription factors of the regulatory DNA elements upstream of genes is the fundamental step in controlling gene expression. How does the necessity to provide stability with respect to mutation constrain the organization of transcription control networks? We examine the mutation load of a transcription factor interacting with a set of n regulatory response elements as a function of the factor/DNA binding specificity and conclude on theoretical grounds that the optimal specificity decreases with n. The predicted correlation between variability of binding sites (for a given transcription factor) and their number is supported by the genomic data for Escherichia coli. The analysis of E. coli genomic data was carried out using an algorithm suggested by the biophysical model of transcription factor/DNA binding. Complete results of the search for candidate transcription factor binding sites are available at http://www.physics.rockefeller.edu/~boris/public/search_ecoli.

  9. Glucose levels and genetic variants across transcriptional pathways: interaction effects with BMI

    NARCIS (Netherlands)

    Povel, C.M.; Feskens, E.J.M.; Imholz, S.; Blaak, E.E.; Boer, J.M.A.; Dollé, M.E.T.

    2010-01-01

    Objective: Much of the genetic variation in glucose levels remains to be discovered. Especially, research on gene–environment interactions is scarce. Overweight is one of the main risk factors for hyperglycemia. As transcriptional regulation is important for both weight maintenance and glucose

  10. Scan-rescan reproducibility of segmental aortic wall shear stress as assessed by phase-specific segmentation with 4D flow MRI in healthy volunteers.

    Science.gov (United States)

    van der Palen, Roel L F; Roest, Arno A W; van den Boogaard, Pieter J; de Roos, Albert; Blom, Nico A; Westenberg, Jos J M

    2018-05-26

    The aim was to investigate scan-rescan reproducibility and observer variability of segmental aortic 3D systolic wall shear stress (WSS) by phase-specific segmentation with 4D flow MRI in healthy volunteers. Ten healthy volunteers (age 26.5 ± 2.6 years) underwent aortic 4D flow MRI twice. Maximum 3D systolic WSS (WSSmax) and mean 3D systolic WSS (WSSmean) for five thoracic aortic segments over five systolic cardiac phases by phase-specific segmentations were calculated. Scan-rescan analysis and observer reproducibility analysis were performed. Scan-rescan data showed overall good reproducibility for WSSmean (coefficient of variation, COV 10-15%) with moderate-to-strong intraclass correlation coefficient (ICC 0.63-0.89). The variability in WSSmax was high (COV 16-31%) with moderate-to-good ICC (0.55-0.79) for different aortic segments. Intra- and interobserver reproducibility was good-to-excellent for regional aortic WSSmax (ICC ≥ 0.78; COV ≤ 17%) and strong-to-excellent for WSSmean (ICC ≥ 0.86; COV ≤ 11%). In general, ascending aortic segments showed more WSSmax/WSSmean variability compared to aortic arch or descending aortic segments for scan-rescan, intraobserver and interobserver comparison. Scan-rescan reproducibility was good for WSSmean and moderate for WSSmax for all thoracic aortic segments over multiple systolic phases in healthy volunteers. Intra/interobserver reproducibility for segmental WSS assessment was good-to-excellent. Variability of WSSmax is higher and should be taken into account in case of individual follow-up or in comparative rest-stress studies to avoid misinterpretation.

  11. Reproducibility of “The bethesda system for reporting thyroid cytopathology:” A retrospective analysis of 107 patients

    Directory of Open Access Journals (Sweden)

    Pragati Awasthi

    2018-01-01

    Full Text Available Objectives: Fine-needle aspiration cytology (FNAC has emerged as an indispensable tool to discriminate thyroid lesions into benign or malignant for appropriate management. The need for simplicity of communication and standardization of terminology for thyroid FNAC reporting led to introduction of “The Bethesda system for reporting Thyroid Cytopathology” (TBSRTC in a conference held at the National Cancer Institute in 2007. This study aims at establishing the reproducibility of TBSRTC for diagnosing thyroid lesions. Materials and Methods: The present study comprised thyroid FNAC from 107 patients retrospectively over a period of 1.5 year (June 2013 to December 2014, which were reviewed by two trained cytopathologists and re-categorized according to TBSRTC. The interobserver variation and reproducibility of the reporting system was statistically assessed using Cohen's kappa. Results: The cytopathologists were in agreement in 98 out of 107 cases (91.5%. Maximum concordance was noted in benign category (91 of 96 cases; 92.85%, followed by 2 cases each in nondiagnostic/unsatisfactory (ND/US and follicular neoplasm/suspicious for follicular neoplasm (FN/SFN category (2.04% each and 1 case each in atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS, suspicious for malignancy (SUS, and malignant category (1.02% each. The highest diagnostic disagreement was noted among ND/US and benign and benign and FN/SFN categories. Conclusion: The utilization of TBSRTC for reporting thyroid cytology should be promoted in our country because it provides a homogeneous, standardized, and unanimous terminology for cytological diagnosis of thyroid lesions. The present study could substantiate the diagnostic reproducibility of this system.

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

    Science.gov (United States)

    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.

  13. Reproducibility of MRI renal artery blood flow and BOLD measurements in patients with chronic kidney disease and healthy controls.

    Science.gov (United States)

    Khatir, Dinah S; Pedersen, Michael; Jespersen, Bente; Buus, Niels H

    2014-11-01

    Determine the reproducibility of renal artery blood flow (RABF) and blood-oxygenation level dependent (R2 *) in patients with chronic kidney disease (CKD) and healthy controls. RABF and R2 * were measured in 11 CKD patients and 9 controls twice with 1- to 2-week interval. R2 * in the cortex and medulla were determined after breathing atmospheric air and 100% oxygen. Reproducibility was evaluated by coefficients of variation (CV), limits of agreements and intra-class coefficient calculated by variance components by maximum likelihood modeling. Single-kidney RABF (mL/min) for patients was: 170 ± 130 and 186 ± 137, and for controls: 365 ± 119 and 361 ± 107 (P Renal cortical R2 * was: 13.6 ± 0.9 and 13.5 ± 1.2 in patients (CV = 8.0%), and 13.8 ± 1.6 and 14.0 ± 1.5 in controls (CV = 5.6%), while medullary R2 *(s(-1) ) was: 26.9 ± 2.0 and 27.0 ± 4.0 (CV = 8.0%) in patients, and 26.0 ± 2.4 and 26.1 ± 2.1 (CV = 3.6%) in controls, for first and second scans, respectively. In both groups R2 * in medulla decreased after breathing 100% oxygen. The reproducibility was high for both RABF and R2 * in patients and controls, particularly in the cortex. Inhalation of 100% oxygen reduced medullary R2 *. © 2013 Wiley Periodicals, Inc.

  14. [Reproducibility and accuracy in the morphometric and mechanical quantification of trabecular bone from 3 Tesla magnetic resonance images].

    Science.gov (United States)

    Alberich-Bayarri, A; Martí-Bonmatí, L; Sanz-Requena, R; Sánchez-González, J; Hervás Briz, V; García-Martí, G; Pérez, M Á

    2014-01-01

    We used an animal model to analyze the reproducibility and accuracy of certain biomarkers of bone image quality in comparison to a gold standard of computed microtomography (μCT). We used magnetic resonance (MR) imaging and μCT to study the metaphyses of 5 sheep tibiae. The MR images (3 Teslas) were acquired with a T1-weighted gradient echo sequence and an isotropic spatial resolution of 180μm. The μCT images were acquired using a scanner with a spatial resolution of 7.5μm isotropic voxels. In the preparation of the images, we applied equalization, interpolation, and thresholding algorithms. In the quantitative analysis, we calculated the percentage of bone volume (BV/TV), the trabecular thickness (Tb.Th), the trabecular separation (Tb.Sp), the trabecular index (Tb.N), the 2D fractal dimension (D(2D)), the 3D fractal dimension (D(3D)), and the elastic module in the three spatial directions (Ex, Ey and Ez). The morphometric and mechanical quantification of trabecular bone by MR was very reproducible, with percentages of variation below 9% for all the parameters. Its accuracy compared to the gold standard (μCT) was high, with errors less than 15% for BV/TV, D(2D), D(3D), and E(app)x, E(app)y and E(app)z. Our experimental results in animals confirm that the parameters of BV/TV, D(2D), D(3D), and E(app)x, E(app)y and E(app)z obtained by MR have excellent reproducibility and accuracy and can be used as imaging biomarkers for the quality of trabecular bone. Copyright © 2013 SERAM. Published by Elsevier Espana. All rights reserved.

  15. Measuring stone surface area from a radiographic image is accurate and reproducible with the help of an imaging program.

    Science.gov (United States)

    Kurien, Abraham; Ganpule, Arvind; Muthu, V; Sabnis, R B; Desai, Mahesh

    2009-01-01

    The surface area of the stone from a radiographic image is one of the more suitable parameters defining stone bulk. The widely accepted method of measuring stone surface area is to count the number of square millimeters enclosed within a tracing of the stone outline on graph paper. This method is time consuming and cumbersome with potential for human error, especially when multiple measurements are needed. The purpose of this study was to evaluate the accuracy, efficiency, and reproducibility of a commercially available imaging program, Adobe Photoshop 7.0 for the measurement of stone surface area. The instructions to calculate area using the software are simple and easy in a Windows-based format. The accuracy of the imaging software was estimated by measuring surface areas of shapes of known mathematical areas. The efficiency and reproducibility were then evaluated from radiographs of 20 persons with radiopaque upper-tract urinary stones. The surface areas of stone images were measured using both graph paper and imaging software. Measurements were repeated after 10 days to assess the reproducibility of the techniques. The time taken to measure the area by the two methods was also assessed separately. The accuracy of the imaging software was estimated to be 98.7%. The correlation coefficient between the two methods was R(2) = 0.97. The mean percentage variation using the imaging software was 0.68%, while it was 6.36% with the graph paper. The mean time taken to measure using the image analyzer and graph paper was 1.9 +/- 0.8 minutes and 4.5 +/- 1.08 minutes, respectively (P stone surface area from radiographs compared with manual measurements using graph paper.

  16. Reproducibility of the assessment of myocardial function using gated Tc-99m-MIBI SPECT and quantitative software

    International Nuclear Information System (INIS)

    Lee, Dong Soo; Cheon, Gi Jeong; Ahn, Ji Young; Jeong, Joon Ki; Lee, Myung Chul

    1998-01-01

    We investigated reproducibility of the quantification of left ventricular volume and ejection fraction, and grading of myocardial wall motion and systolic thickening when we used gated myocardial SPECT and Cedars quantification software. We performed gated myocardial SPECT in 33 consecutive patients twice in the same position after Tc-99m-MIBI SPECT. We used 16 frames per cycle for the gating of sequential Tc-99m-MIBI SPECT. After reconstruction, we used Cedars quantitative gated SPECT and calculated ventricular volume and ejection fraction (EF). Wall motion was graded using 5 point score. Wall thickening was graded using 4 point score. Coefficient of variation for re-examination of volume and fraction were calculated. Kappa values (k-value) for assessing reproducibility of wall motion or wall thickening were calculated. Enddiastolic volumes (EDV) ranged from 58 ml to 248 ml (122 ml +/-42 ml), endsystolic volumes (ESV) from 20 ml to 174 ml (65 ml+/-39 ml), and EF from 20% to 68% (51%+/-14%). Geometric mean of standard deviations of 33 patients was 5.0 ml for EDV, 3.9 ml for ESV and 1.9% for EF. Their average differences were not different from zero (p>0.05). k-value for wall motion using 2 consecutive images was 0.76 (confidence interval: 0.71-0.81). k-value was 0.87 (confidence interval: 0.83-0.90) for assessment of wall thickening. We concluded that quantification of functional indices, assessment of wall motion and wall thickening using gated Tc-99m MIBI SPECT was reproducible and we could use this method for the evaluation of short-acting drug effect

  17. V(D)J recombination on minichromosomes is not affected by transcription.

    Science.gov (United States)

    Hsieh, C L; McCloskey, R P; Lieber, M R

    1992-08-05

    It has been shown previously by others that transcription is temporally correlated with the onset of V(D)J recombination at the endogenous antigen receptor loci. We have been interested in determining whether this temporal correlation indicates a causal connection between these two processes. We have compared V(D)J recombination minichromosome substrates that have transcripts running through the recombination zone with substrates that do not in a transient transfection assay. In this system, the substrates acquire a minichromosome conformation within the first several hours after transfection. We find that the substrates recombine equally well over a 100-fold range in transcriptional variation. In additional studies, we have taken substrates that have low levels of transcription and inhibited transcription further by methylating the substrate DNA or by treating the cells with a general transcription inhibitor (alpha-amanitin). Although these treatments decrease the level of expression an additional 10-100-fold, there is still no observable effect on V(D)J recombination. Based on these results, we conclude that transcription is not necessary for the V(D)J reaction mechanism and does not alter substrate structure at the DNA level or at the simplest levels of chromatin structure in a way that affects the reaction.

  18. Reproducibility and influencing factors of 31P MR spectroscopy in rabbit liver with two-dimensional chemical shift imaging

    International Nuclear Information System (INIS)

    Yu Risheng; Sun Jianzhong; Ding Wenhong; Xu Xiufang; Wang Zhikang

    2009-01-01

    Objective: To investigate the reproducibility and influencing factors of relative quantification of phosphorus metabolites with two-dimensional chemical shift imaging (2D CSI) in rabbit liver. Methods: Using 2D CSI MRS, 500 ml phosphate (NaH 2 PO 4 ) solution phantom with 0.05 mol/L concentration and one healthy rabbit were scanned 30 times respectively in one day and rescanned 30 times in the next day, and the stability of MR scanner and reproducibility of within-run and between-days in the same individual were analyzed. Each of thirty rabbits was scanned and rescanned one time respectively in different days, and the reproducibility of between-days in one group was analyzed. The data were statistically analyzed with t tests. Results: (1) Phosphate solution phantom had a good reproducibility of within-run with the coefficient variation (CV) of 4.92% and 5.12% respectively in different two days. No significant change of phosphorus metabolites was detected in between-days, which was 16.68±0.82 and 16.56± 0.85 respectively (t=0.665, P>0.05). (2) The CV of metabolites in one healthy rabbit ranged from 8.04% to 34.13%. Among the metabolites, β-ATP had the best reproducibility with the CV less than 10%. PME was 0.88±0.28 and 0.88±0.30, PDE was 4.35±0.66 and 4.35±0.66, Pi was 0.95±0.30 and 0.97±0.28, α-ATP was 5.58±0.60 and 5.61±0.61, β-ATP was 2.70±0.22 and 2.71± 0.22, γ-ATP was 2.20±0.63 and 2.18±0.44 respectively, no significant changes of metabolites were detected in between-days (P>0.05). (3) The CV of metabolites in 30 healthy rabbits ranged from 8.48% to 36.21%. Among the metabolites, β-ATP had the best reproducibility with CV less than 10%. PME was 0.84±0.30 and 0.79±0.28, PDE was 4.29±0.72 and 3.94±0.84, Pi was 0.91±0.28 and 0.92± 0.31, α-ATP was 5.65±0.66 and 5.36±0.60, β-ATP was 2.71±0.23 and 2.66±0.25, γ-ATP was 2.07±0.29 and 1.99±0.37 respectively, no significant changes of metabolites were detected in between-days (P>0

  19. Transcriptional networks and chromatin remodeling controlling adipogenesis

    DEFF Research Database (Denmark)

    Siersbæk, Rasmus; Nielsen, Ronni; Mandrup, Susanne

    2012-01-01

    Adipocyte differentiation is tightly controlled by a transcriptional cascade, which directs the extensive reprogramming of gene expression required to convert fibroblast-like precursor cells into mature lipid-laden adipocytes. Recent global analyses of transcription factor binding and chromatin...... remodeling have revealed 'snapshots' of this cascade and the chromatin landscape at specific time-points of differentiation. These studies demonstrate that multiple adipogenic transcription factors co-occupy hotspots characterized by an open chromatin structure and specific epigenetic modifications....... Such transcription factor hotspots are likely to represent key signaling nodes which integrate multiple adipogenic signals at specific chromatin sites, thereby facilitating coordinated action on gene expression....

  20. Validation of a method for accurate and highly reproducible quantification of brain dopamine transporter SPECT studies