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Sample records for reveal significant threshold

  1. Mouse models of cystathionine β-synthase deficiency reveal significant threshold effects of hyperhomocysteinemia

    PubMed Central

    Gupta, Sapna; Kühnisch, Jirko; Mustafa, Aladdin; Lhotak, Sarka; Schlachterman, Alexander; Slifker, Michael J.; Klein-Szanto, Andres; High, Katherine A.; Austin, Richard C.; Kruger, Warren D.

    2009-01-01

    Untreated cystathionine β-synthase (CBS) deficiency in humans is characterized by extremely elevated plasma total homocysteine (tHcy>200 μM), with thrombosis as the major cause of morbidity. Treatment with vitamins and diet leads to a dramatic reduction in thrombotic events, even though patients often still have severe elevations in tHcy (>80 μM). To understand the difference between extreme and severe hyperhomocysteinemia, we have examined two mouse models of CBS deficiency: Tg-hCBS Cbs−/− mice, with a mean serum tHcy of 169 μM, and Tg-I278T Cbs−/− mice, with a mean tHcy of 296 μM. Only Tg-I278T Cbs−/− animals exhibited strong biological phenotypes, including facial alopecia, osteoporosis, endoplasmic reticulum (ER) stress in the liver and kidney, and a 20% reduction in mean survival time. Metabolic profiling of serum and liver reveals that Tg-I278T Cbs−/− mice have significantly elevated levels of free oxidized homocysteine but not protein-bound homocysteine in serum and elevation of all forms of homocysteine and S-adenosylhomocysteine in the liver compared to Tg-hCBS Cbs−/− mice. RNA profiling of livers indicate that Tg-I278T Cbs−/− and Tg-hCBS Cbs−/− mice have unique gene signatures, with minimal overlap. Our results indicate that there is a clear pathogenic threshold effect for tHcy and bring into question the idea that mild elevations in tHcy are directly pathogenic. Gupta, S., Kühnisch, J., Mustafa, A., Lhotak, S., Schlachterman, A., Slifker, M. J., Klein-Szanto, A., High, K. A., Austin, R. C., Kruger, W. D. Mouse models of cystathionine β-synthase deficiency reveal significant threshold effects of hyperhomocysteinemia. PMID:18987302

  2. Statistical Significance of Clustering using Soft Thresholding

    PubMed Central

    Huang, Hanwen; Liu, Yufeng; Yuan, Ming; Marron, J. S.

    2015-01-01

    Clustering methods have led to a number of important discoveries in bioinformatics and beyond. A major challenge in their use is determining which clusters represent important underlying structure, as opposed to spurious sampling artifacts. This challenge is especially serious, and very few methods are available, when the data are very high in dimension. Statistical Significance of Clustering (SigClust) is a recently developed cluster evaluation tool for high dimensional low sample size data. An important component of the SigClust approach is the very definition of a single cluster as a subset of data sampled from a multivariate Gaussian distribution. The implementation of SigClust requires the estimation of the eigenvalues of the covariance matrix for the null multivariate Gaussian distribution. We show that the original eigenvalue estimation can lead to a test that suffers from severe inflation of type-I error, in the important case where there are a few very large eigenvalues. This paper addresses this critical challenge using a novel likelihood based soft thresholding approach to estimate these eigenvalues, which leads to a much improved SigClust. Major improvements in SigClust performance are shown by both mathematical analysis, based on the new notion of Theoretical Cluster Index, and extensive simulation studies. Applications to some cancer genomic data further demonstrate the usefulness of these improvements. PMID:26755893

  3. 77 FR 546 - Adjustment of Nationwide Significant Risk Threshold

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-05

    ... Federal Railroad Administration Adjustment of Nationwide Significant Risk Threshold AGENCY: Federal... nationwide significant risk threshold. SUMMARY: In accordance with Appendix D to Title 49 Code of Federal... Nationwide Significant Risk Threshold (NSRT). This action is needed to ensure that the public has the proper...

  4. 75 FR 82136 - Adjustment of Nationwide Significant Risk Threshold

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-29

    .... FRA-1999-6439, Notice No. 22] Adjustment of Nationwide Significant Risk Threshold AGENCY: Federal... Nationwide Significant Risk Threshold. SUMMARY: In accordance with Appendix D to Title 49 Code of Federal... Nationwide Significant Risk Threshold (NSRT). This action is needed to ensure that the public has the proper...

  5. 78 FR 70623 - Adjustment of Nationwide Significant Risk Threshold

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-26

    ...-6439, Notice No. 24] Adjustment of Nationwide Significant Risk Threshold AGENCY: Federal Railroad... Risk Threshold. SUMMARY: In accordance with appendix D to title 49 Code of Federal Regulations (CFR... Nationwide Significant Risk Threshold (NSRT). This action is needed to ensure that the public has the proper...

  6. Thresholds for significant decrease in hemodialysis access blood flow.

    PubMed

    Ram, Sunanda J; Nassar, Raja; Sharaf, Rashid; Magnasco, Alberto; Jones, Steven A; Paulson, William D

    2005-01-01

    During hemodialysis access surveillance, referral for evaluation and correction of stenosis is based upon determination that a significant decrease in blood flow (Q) has occurred. However, criteria for determining when a decrease is statistically significant have not yet been established. In this study we established such criteria by analyzing Q variation with the glucose pump test (GPT). We took nine Q measurements in each of 25 patients (18 grafts, 7 fistulas) during three dialysis sessions within a 2-week period (predialysis and during hours 1 and 3). We determined thresholds that define a significant percentage decrease in Q (deltaQ) for various p values. In order to confirm the general applicability of these thresholds, we computed the average within-patient Q variation during the three sessions (computed as a coefficient of variation and referred to as short-term variation). We then determined the relative influences of biological (true) variation and analytical error on short-term variation. We found that deltaQ must be > 33% to be significant at p < 0.05, whereas the threshold is > 17% for p < 0.20. Measuring Q at uniform versus different times during the sessions did not significantly reduce these thresholds. We also found that biological variation was nearly as large as short-term Q variation, whereas analytical error contributed minimally to short-term variation. In conclusion, this study defines thresholds for a significant deltaQ that have wide application in determining access referral for evaluation and correction of stenosis. Selection of a particular threshold should consider the relative importance of avoiding thrombosis versus avoiding unnecessary procedures. If avoiding unnecessary procedures is a priority, then we recommend a threshold of > 33%. These thresholds apply to other methods of measuring Q, provided analytical error is significantly less than biological variation.

  7. Estimation of significance thresholds for genomewide association scans

    PubMed Central

    Dudbridge, Frank; Gusnanto, Arief

    2008-01-01

    The question of what significance threshold is appropriate for genomewide association studies is somewhat unresolved. Previous theoretical suggestions have yet to be validated in practice, whereas permutation testing does not resolve a discrepancy between the genomewide multiplicity of the experiment and the subset of markers actually tested. We used genotypes from the Wellcome Trust Case-Control Consortium to estimate a genomewide significance threshold for the UK Caucasian population. We subsampled the genotypes at increasing densities, using permutation to estimate the nominal P-value for 5% family-wise error. By extrapolating to infinite density, we estimated the genomewide significance threshold to be about 7.2 × 10−8. To reduce the computation time, we considered Patterson's eigenvalue estimator of the effective number of tests, but found it to be an order of magnitude too low for multiplicity correction. However, by fitting a Beta distribution to the minimum P-value from permutation replicates, we showed that the effective number is a useful heuristic and suggest that its estimation in this context is an open problem. We conclude that permutation is still needed to obtain genomewide significance thresholds, but with subsampling, extrapolation and estimation of an effective number of tests, the threshold can be standardized for all studies of the same population. PMID:18300295

  8. Estimation of the geochemical threshold and its statistical significance

    USGS Publications Warehouse

    Miesch, A.T.

    1981-01-01

    A statistic is proposed for estimating the geochemical threshold and its statistical significance, or it may be used to identify a group of extreme values that can be tested for significance by other means. The statistic is the maximum gap between adjacent values in an ordered array after each gap has been adjusted for the expected frequency. The values in the ordered array are geochemical values transformed by either ln(?? - ??) or ln(?? - ??) and then standardized so that the mean is zero and the variance is unity. The expected frequency is taken from a fitted normal curve with unit area. The midpoint of an adjusted gap that exceeds the corresponding critical value may be taken as an estimate of the geochemical threshold, and the associated probability indicates the likelihood that the threshold separates two geochemical populations. The adjusted gap test may fail to identify threshold values if the variation tends to be continuous from background values to the higher values that reflect mineralized ground. However, the test will serve to identify other anomalies that may be too subtle to have been noted by other means. ?? 1981.

  9. The anaerobic threshold: definition, physiological significance and identification.

    PubMed

    Wasserman, K

    1986-01-01

    During exercise, the oxygen consumption above which aerobic energy production is supplemented by anaerobic mechanisms, causing a sustained increase in lactate and metabolic acidosis, is termed the anaerobic threshold (AT). The oxygen consumption at the AT depends on factors that affect oxygen delivery to the tissues. It is increased when oxygen flow is enhanced and decreased when oxygen flow is diminished. Its value is quite low in patients with heart disease. The AT is an important functional demarcation since the physiological responses to exercise are different above the AT compared to below the AT. Above the AT, in addition to the development of metabolic acidosis, exercise endurance is reduced, VO2 kinetics are slowed so that a steady state is delayed, and VE increases disproportionately to the metabolic requirement and a progressive tachypnea develops. The AT can be measured directly from the lactate concentration with precise threshold detection from a log-log transformation of lactate and VO2. This threshold also defines the VO2 above which the lactate/pyruvate ratio increases. As bicarbonate changes reciprocally with lactate, its measurement can also be used to estimate the lactate threshold. But most convenient are gas exchange measurements made during exercise testing which can be used to noninvasively detect the lactate or anaerobic threshold. These methods are based on the physical-chemical event of buffering lactic acid with bicarbonate, and the increased CO2 output which occurs in association with the acute development of a metabolic acidosis.

  10. Prevention of Significant Deterioration (PSD) Emission Thresholds for Fountain Foundry

    EPA Pesticide Factsheets

    This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  11. Bird colour vision: behavioural thresholds reveal receptor noise.

    PubMed

    Olsson, Peter; Lind, Olle; Kelber, Almut

    2015-01-15

    Birds have impressive physiological adaptations for colour vision, including tetrachromacy and coloured oil droplets, yet it is not clear exactly how well birds can discriminate the reflecting object colours that they encounter in nature. With behavioural experiments, we determined colour discrimination thresholds of chickens in bright and dim light. We performed the experiments with two colour series, orange and green, covering two parts of chicken colour space. These experiments allowed us to compare behavioural results with model expectations and determine how different noise types limit colour discrimination. At intensities ranging from bright light to those corresponding to early dusk (250-10 cd m(-2)), we describe thresholds accurately by assuming a constant signal-to-noise ratio, in agreement with an invariant Weber fraction of Weber's law. Below this intensity, signal-to-noise ratio decreases and Weber's law is violated because photon-shot noise limits colour discrimination. In very dim light (below 0.05 cd m(-2) for the orange series or 0.2 cd m(-2) for the green series) colour discrimination is possibly constrained by dark noise, and the lowest intensity at which chickens can discriminate colours is 0.025 and 0.08 cd m(-2) for the orange and green series, respectively. Our results suggest that chickens use spatial pooling of cone outputs to mitigate photon-shot noise. Surprisingly, we found no difference between colour discrimination of chickens and humans tested with the same test in bright light.

  12. Empirical estimation of genome-wide significance thresholds based on the 1000 Genomes Project data set

    PubMed Central

    Kanai, Masahiro; Tanaka, Toshihiro; Okada, Yukinori

    2016-01-01

    To assess the statistical significance of associations between variants and traits, genome-wide association studies (GWAS) should employ an appropriate threshold that accounts for the massive burden of multiple testing in the study. Although most studies in the current literature commonly set a genome-wide significance threshold at the level of P=5.0 × 10−8, the adequacy of this value for respective populations has not been fully investigated. To empirically estimate thresholds for different ancestral populations, we conducted GWAS simulations using the 1000 Genomes Phase 3 data set for Africans (AFR), Europeans (EUR), Admixed Americans (AMR), East Asians (EAS) and South Asians (SAS). The estimated empirical genome-wide significance thresholds were Psig=3.24 × 10−8 (AFR), 9.26 × 10−8 (EUR), 1.83 × 10−7 (AMR), 1.61 × 10−7 (EAS) and 9.46 × 10−8 (SAS). We additionally conducted trans-ethnic meta-analyses across all populations (ALL) and all populations except for AFR (ΔAFR), which yielded Psig=3.25 × 10−8 (ALL) and 4.20 × 10−8 (ΔAFR). Our results indicate that the current threshold (P=5.0 × 10−8) is overly stringent for all ancestral populations except for Africans; however, we should employ a more stringent threshold when conducting a meta-analysis, regardless of the presence of African samples. PMID:27305981

  13. Empirical estimation of genome-wide significance thresholds based on the 1000 Genomes Project data set.

    PubMed

    Kanai, Masahiro; Tanaka, Toshihiro; Okada, Yukinori

    2016-10-01

    To assess the statistical significance of associations between variants and traits, genome-wide association studies (GWAS) should employ an appropriate threshold that accounts for the massive burden of multiple testing in the study. Although most studies in the current literature commonly set a genome-wide significance threshold at the level of P=5.0 × 10(-8), the adequacy of this value for respective populations has not been fully investigated. To empirically estimate thresholds for different ancestral populations, we conducted GWAS simulations using the 1000 Genomes Phase 3 data set for Africans (AFR), Europeans (EUR), Admixed Americans (AMR), East Asians (EAS) and South Asians (SAS). The estimated empirical genome-wide significance thresholds were Psig=3.24 × 10(-8) (AFR), 9.26 × 10(-8) (EUR), 1.83 × 10(-7) (AMR), 1.61 × 10(-7) (EAS) and 9.46 × 10(-8) (SAS). We additionally conducted trans-ethnic meta-analyses across all populations (ALL) and all populations except for AFR (ΔAFR), which yielded Psig=3.25 × 10(-8) (ALL) and 4.20 × 10(-8) (ΔAFR). Our results indicate that the current threshold (P=5.0 × 10(-8)) is overly stringent for all ancestral populations except for Africans; however, we should employ a more stringent threshold when conducting a meta-analysis, regardless of the presence of African samples.

  14. Evaluation of different criteria for significant threshold shift in occupational hearing conservation programs. Final report

    SciTech Connect

    Royster, J.D.

    1992-12-09

    A comparison was undertaken of six different criteria for determinig significant hearing threshold shift. Each criterion was applied to the first eight audiograms for males participating in 15 different industrial hearing conservation programs. Of the different criteria used, the OSHA STS criterion produced the lowest overall percentage of employees tagged as having suffered a threshold shift. The 15-dB SHIFT and NIOSH SHIFT criteria produced the highest percentages. The mean percentages of employees tagged on an annual basis generally were small, less than 10 percent in referent data bases and 20 percent or less in the noncontrol data bases. The 15-dB SHIFT and NIOSH SHIFT criteria tagged 37 percent and 51 percent of employees in noncontrol data bases on the first test comparison and averaged 14 percent and 24 percent of employees even in referent data bases. The purpose of the significant threshold shift criterion was to tag employees with temporary threshold shifts (TTS) before they develop hearing loss. Therefore, the purpose of the threshold shift criterion selected was not to act as a recordable occupational illness but rather to reflect a significant amount of persistent hearing change.

  15. Ecogenomics of Zooplankton Community Reveals Ecological Threshold of Ammonia Nitrogen.

    PubMed

    Yang, Jianghua; Zhang, Xiaowei; Xie, Yuwei; Song, Chao; Sun, Jingying; Zhang, Yong; Giesy, John P; Yu, Hongxia

    2017-03-07

    Communities of zooplankton can be adversely affected by contamination resulting from human activities. Yet understanding the influence of water quality on zooplankton under field-conditions is hindered by traditional labor-intensive approaches that are prone to incomplete or uncertain taxonomic determinations. Here, for the first time, an eco-genomic approach, based on genetic diversity in the mitochondrial cytochrome c oxidase I (COI) region of DNA of zooplankton was used to develop a site-specific, water quality criterion (WQC) for ammonia (NH3). Ammonia has been recognized as a primary stressor in the catchment of the large, eutrophic Tai Lake, China. Nutrients, especially NH3 and nitrite (NO3(-)) had more significant effects on structure of the zooplankton community than did other environmental factors. Abundances of rotifers increased along a gradient of increasing concentrations of total ammonia nitrogen (TAN), while abundances of copepods and cladocera decreased. A novel, rapid, species sensitivity distribution (SSD) approach based on operational taxonomic units (OTUs) was established to develop a WQC for NH3. The WQC based on OTUs was consistent with the WQC based on the traditional morphology taxonomy approach. This genetics-based SSD approach could be a useful tool for monitoring for status and trends in species composition and deriving ecological criteria and an efficient biomonitoring tool to protect local aquatic ecosystems in virtually any aquatic ecosystem.

  16. A Multinomial Model for Identifying Significant Pure-Tone Threshold Shifts

    ERIC Educational Resources Information Center

    Schlauch, Robert S.; Carney, Edward

    2007-01-01

    Purpose: Significant threshold differences on retest for pure-tone audiometry are often evaluated by application of ad hoc rules, such as a shift in a pure-tone average or in 2 adjacent frequencies that exceeds a predefined amount. Rules that are so derived do not consider the probability of observing a particular audiogram. Methods: A general…

  17. Validation of hemolysis index thresholds optimizes detection of clinically significant hemolysis.

    PubMed

    Goyal, Tanu; Schmotzer, Christine L

    2015-04-01

    Automated hemolysis index (HI) measurement has standardized the identification and gradation of sample hemolysis. This study evaluates whether clinically significant changes in the concentration of intracellular analytes occur at manufacturer-recommended automated HI thresholds (HI ≥3, >25 mg/dL hemoglobin). Adult outpatient results for serum potassium (K+), magnesium (Mg), lactate dehydrogenase (LDH), and aspartate aminotransferase (AST) were analyzed. Mean ± SD analyte concentration and distribution within the reference interval (RI) were calculated for each HI group (1-7). Potassium results with an HI of 4 or more demonstrated clinically significant differences (≥0.5 mmol/L) in mean K+ concentration and RI classification compared with non-hemolyzed samples (HI = 1). LDH and AST showed clinically significant differences (+20%) for an HI of 3 or more. For Mg, only the group with an HI of 7 demonstrated a clinically significant difference (>25%); however, the number was low. Mean measured potassium concentrations are not clinically significantly affected by hemolysis at the manufacturer-recommended HI threshold, while AST and LDH are. Aligning reporting of sample hemolysis with clinically significant changes provides clinically meaningful alerts regarding this common pre-analytic error. Copyright© by the American Society for Clinical Pathology.

  18. Pattern Recognition Analysis Reveals Unique Contrast Sensitivity Isocontours Using Static Perimetry Thresholds Across the Visual Field

    PubMed Central

    Phu, Jack; Khuu, Sieu K.; Nivison-Smith, Lisa; Zangerl, Barbara; Choi, Agnes Yiu Jeung; Jones, Bryan W.; Pfeiffer, Rebecca L.; Marc, Robert E.; Kalloniatis, Michael

    2017-01-01

    Purpose To determine the locus of test locations that exhibit statistically similar age-related decline in sensitivity to light increments and age-corrected contrast sensitivity isocontours (CSIs) across the central visual field (VF). We compared these CSIs with test point clusters used by the Glaucoma Hemifield Test (GHT). Methods Sixty healthy observers underwent testing on the Humphrey Field Analyzer 30-2 test grid using Goldmann (G) stimulus sizes I-V. Age-correction factors for GI-V were determined using linear regression analysis. Pattern recognition analysis was used to cluster test locations across the VF exhibiting equal age-related sensitivity decline (age-related CSIs), and points of equal age-corrected sensitivity (age-corrected CSIs) for GI-V. Results There was a small but significant test size–dependent sensitivity decline with age, with smaller stimuli declining more rapidly. Age-related decline in sensitivity was more rapid in the periphery. A greater number of unique age-related CSIs was revealed when using smaller stimuli, particularly in the mid-periphery. Cluster analysis of age-corrected sensitivity thresholds revealed unique CSIs for GI-V, with smaller stimuli having a greater number of unique clusters. Zones examined by the GHT consisted of test locations that did not necessarily belong to the same CSI, particularly in the periphery. Conclusions Cluster analysis reveals statistically significant groups of test locations within the 30-2 test grid exhibiting the same age-related decline. CSIs facilitate pooling of sensitivities to reduce the variability of individual test locations. These CSIs could guide future structure-function and alternate hemifield asymmetry analyses by comparing matched areas of similar sensitivity signatures. PMID:28973333

  19. Carotid Artery Stenosis at MSCT: Is there a Threshold in Millimeters that Determines Clinical Significance?

    SciTech Connect

    Saba, Luca; Sanfilippo, Roberto; Montisci, Roberto; Mallarini, Giorgio

    2012-02-15

    Purpose: The purpose of this work was to determine whether it is possible to identify a reliable carotid stenosis threshold-measured in millimeters (mm)-that is associated with cerebrovascular symptoms. Methods: Written, informed consent was obtained for each patient; 149 consecutive patients (98 men; median age, 68 years) were studied for suspected pathology of the carotid arteries by using MDCTA. In each patient, carotid artery stenosis was quantified using the mm-method. Continuous data were described as the mean value {+-} standard deviation (SD), and they were compared by using the Student's t test. A ROC curve was calculated to test the study hypothesis and identify a specific mm-stenosis threshold. Logistic regression analysis was performed to include other MDCTA findings, such as plaque type and ulcerations. A P value < 0.05 was considered to indicate statistical significance. Results: Twenty-six patients were excluded. Of those remaining, 75 patients suffered cerebrovascular symptoms (61%). There was a statistically significant difference (P = 0.0046) in the mm-carotid stenosis between patients with symptoms (1.31 {+-} 0.64 mm SD) and without symptoms (1.68 {+-} 0.79 mm SD). Multiple logistic regression analysis confirmed that symptoms were associated with increased luminal stenosis (P = 0.013) and with the presence of fatty plaques (P = 0.0491). Moreover, the ROC curve (Az = 0.669; {+-}0.051 SD; P = 0.0009) indicated that a threshold of 1.6 mm stenosis was associated with a sensitivity to symptoms of 76%. Conclusions: The results of our study suggest an association between luminal stenosis (measure in mm) and the presence of cerebrovascular symptoms. Luminal stenosis of 1.6 mm is associated, with a sensitivity of 76%, with cerebrovascular symptoms.

  20. Critical storm thresholds for significant morphological changes and damage along the Emilia-Romagna coastline, Italy

    NASA Astrophysics Data System (ADS)

    Armaroli, Clara; Ciavola, Paolo; Perini, Luisa; Calabrese, Lorenzo; Lorito, Samantha; Valentini, Andrea; Masina, Marinella

    2012-03-01

    The definition of storm morphological thresholds along the coast of the Emilia-Romagna Region strictly depends on its configuration and variability. The region is located in northern Italy, facing the Adriatic Sea. The coastline is characterised by very different levels of economic development, ranging from natural zones with dunes to highly developed stretches protected by breakwaters and groynes. The Integrated Coastal Zone Management effort is mainly concentrated on preserving urban areas that generate significant income for the regional economy. Natural areas, while small in comparison to the urbanised zone, are important for environment preservation. Because of such a multiplicity of issues at stake, it was decided to produce two different thresholds: one for the morphological impact on natural sectors and another for inundation and damage to structures along urbanised zones. The "forcing" component of the threshold definition for natural areas was calculated by summing the effects of surge + tide + waves (run-up elevation) to find the Maximum Water Level (MWL) reached by the sea during one, ten and one-hundred year storm return periods. For urbanised zones, historical storm information was collected starting from the 1960s in order to identify the forcing conditions causing real damages. Each storm was classified in terms of wave height, period, direction and surge level. Morphological information were obtained from Lidar flights performed in 2003 and 2004 and from direct surveys undertaken in September 2008 and February 2009 as part of the monitoring programme for the MICORE Project. The computed MWL for each return period was then compared to beach elevations along natural areas in order to calculate the Dune Stability Factor (DSF), an index that accounts for the eroded sediment volume above the MWL during a storm. Based on analysis along 41 profile lines at a 500 m spacing, it was found that the 1-in-1 year return period wave height + 1-in-1 year return

  1. Thresholds for statistical and clinical significance in systematic reviews with meta-analytic methods.

    PubMed

    Jakobsen, Janus Christian; Wetterslev, Jørn; Winkel, Per; Lange, Theis; Gluud, Christian

    2014-11-21

    Thresholds for statistical significance when assessing meta-analysis results are being insufficiently demonstrated by traditional 95% confidence intervals and P-values. Assessment of intervention effects in systematic reviews with meta-analysis deserves greater rigour. Methodologies for assessing statistical and clinical significance of intervention effects in systematic reviews were considered. Balancing simplicity and comprehensiveness, an operational procedure was developed, based mainly on The Cochrane Collaboration methodology and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guidelines. We propose an eight-step procedure for better validation of meta-analytic results in systematic reviews (1) Obtain the 95% confidence intervals and the P-values from both fixed-effect and random-effects meta-analyses and report the most conservative results as the main results. (2) Explore the reasons behind substantial statistical heterogeneity using subgroup and sensitivity analyses (see step 6). (3) To take account of problems with multiplicity adjust the thresholds for significance according to the number of primary outcomes. (4) Calculate required information sizes (≈ the a priori required number of participants for a meta-analysis to be conclusive) for all outcomes and analyse each outcome with trial sequential analysis. Report whether the trial sequential monitoring boundaries for benefit, harm, or futility are crossed. (5) Calculate Bayes factors for all primary outcomes. (6) Use subgroup analyses and sensitivity analyses to assess the potential impact of bias on the review results. (7) Assess the risk of publication bias. (8) Assess the clinical significance of the statistically significant review results. If followed, the proposed eight-step procedure will increase the validity of assessments of intervention effects in systematic reviews of randomised clinical trials.

  2. A Model of Threshold Behavior Reveals Rescue Mechanisms of Bystander Proteins in Conformational Diseases

    PubMed Central

    Sandefur, Conner I.; Schnell, Santiago

    2011-01-01

    Conformational diseases result from the failure of a specific protein to fold into its correct functional state. The misfolded proteins can lead to the toxic aggregation of proteins. Protein misfolding in conformational diseases often displays a threshold behavior characterized by a sudden shift between nontoxic to toxic levels of misfolded proteins. In some conformational diseases, evidence suggests that misfolded proteins interact with bystander proteins (unfolded and native folded proteins), eliciting a misfolded phenotype. These bystander isomers would follow their normal physiological pathways in absence of misfolded proteins. In this article, we present a general mechanism of bystander and misfolded protein interaction which we have used to investigate how the threshold behavior in protein misfolding is triggered in conformational diseases. Using a continuous flow reactor model of the endoplasmic reticulum, we found that slight changes in the bystander protein residence time in the endoplasmic reticulum or the ratio of basal misfolded to bystander protein inflow rates can trigger the threshold behavior in protein misfolding. Our analysis reveals three mechanisms to rescue bystander proteins in conformational diseases. The results of our model can now help direct experiments to understand the threshold behavior and develop therapeutic strategies targeting the modulation of conformational diseases. PMID:21504722

  3. [The significance of quantitative temperature sense thresholds in diagnosis of small fibrous sensory neuropathy in patients with type 2 diabetes].

    PubMed

    Yin, Hou-min; Feng, Wei; Ding, Mei-ping

    2015-03-01

    To evaluate the small fiber function in patients with type 2 diabetes mellitus of the early stage by measuring the sensory threshold with the quantitative temperature testing technology. Twenty cases of patients with type 2 diabetes with no neurological deficit (DM group) and twenty age and sex-matched healthy controls underwent the detecting of cold sensory threshold (CST), warm sensory threshold (WST), cold pain threshold (CPT), heat pain threshold (HPT) in both inside of their hands. There was no significant difference in CST, WST, CPT and HPT between left and right inside of hand of the same sample among all the testers. But the four kinds of threshold showed significant difference in the right inside of hand between patients and healthy people ( P < 0.05). In addition, the CST and WST differed significantly in the left inside of hand between the patients and healthy controls while the CPT and HPT showed no significant difference in the left inside of hand between them. Patients group and control group with CST and WST on the left side of the comparison difference was statistically significant (P < 0.05). Quantitative analysis of temperature sense threshold can not only reflect increase of the pain threshold value, also can reflect its decrease, i. e. hyperalgesia, which may help to diagnose small fibrous peripheral neuropathy recognition, especially in early diabetic peripheral neuropathy.

  4. Integration of community structure data reveals observable effects below sediment guideline thresholds in a large estuary.

    PubMed

    Tremblay, Louis A; Clark, Dana; Sinner, Jim; Ellis, Joanne I

    2017-09-20

    The sustainable management of estuarine and coastal ecosystems requires robust frameworks due to the presence of multiple physical and chemical stressors. In this study, we assessed whether ecological health decline, based on community structure composition changes along a pollution gradient, occurred at levels below guideline threshold values for copper, zinc and lead. Canonical analysis of principal coordinates (CAP) was used to characterise benthic communities along a metal contamination gradient. The analysis revealed changes in benthic community distribution at levels below the individual guideline values for the three metals. These results suggest that field-based measures of ecological health analysed with multivariate tools can provide additional information to single metal guideline threshold values to monitor large systems exposed to multiple stressors.

  5. Quantitative gradient of subsidies reveals a threshold in community-level trophic cascades.

    PubMed

    Klemmer, Amanda J; Richardson, John S

    2013-09-01

    Evidence varies on how subsidies affect trophic cascades within recipient food webs. This could be due to complex nonlinearities being masked by single-level manipulations (presence/absence) of subsidies in past studies. We predicted that trophic cascade strength would increase nonlinearly across a gradient of subsidies. We set out to reveal these complex, nonlinear relationships through manipulating a quantitative gradient of detrital subsidies to lake benthic food webs along with the presence/absence of trout. Contrary to our prediction, we found that trophic cascades only occurred at low subsidy levels, disappearing as subsidies increased. This threshold in trophic cascade strength may be due to an increase in intermediate predators in the absence of top predators, as well as changes in the proportion of armored vs. un-armored primary consumers. Future studies on the effect of subsidies on trophic cascade strength need to incorporate naturally occurring gradients to reveal the complex direct and indirect interactions within food webs.

  6. Global Analysis of ATM Polymorphism Reveals Significant Functional Constraint

    PubMed Central

    Thorstenson, Yvonne R.; Shen, Peidong; Tusher, Virginia G.; Wayne, Tierney L.; Davis, Ronald W.; Chu, Gilbert; Oefner, Peter J.

    2001-01-01

    ATM, the gene that is mutated in ataxia-telangiectasia, is associated with cerebellar degeneration, abnormal proliferation of small blood vessels, and cancer. These clinically important manifestations have stimulated interest in defining the sequence variation in the ATM gene. Therefore, we undertook a comprehensive survey of sequence variation in ATM in diverse human populations. The protein-encoding exons of the gene (9,168 bp) and the adjacent intron and untranslated sequences (14,661 bp) were analyzed in 93 individuals from seven major human populations. In addition, the coding sequence was analyzed in one chimpanzee, one gorilla, one orangutan, and one Old World monkey. In human ATM, 88 variant sites were discovered by denaturing high-performance liquid chromatography, which is 96%–100% sensitive for detection of DNA sequence variation. ATM was compared to 14 other autosomal genes for nucleotide diversity. The noncoding regions of ATM had diversity values comparable to other genes, but the coding regions had very low diversity, especially in the last 29% of the protein sequence. A test of the neutral evolution hypothesis, through use of the Hudson/Kreitman/Aguadé statistic, revealed that this region of the human ATM gene was significantly constrained relative to that of the orangutan, the Old World monkey, and the mouse, but not relative to that of the chimpanzee or the gorilla. ATM displayed extensive linkage disequilibrium, consistent with suppression of meiotic recombination at this locus. Seven haplotypes were defined. Two haplotypes accounted for 82% of all chromosomes analyzed in all major populations; two others carrying the same D126E missense polymorphism accounted for 33% of chromosomes in Africa but were never observed outside of Africa. The high frequency of this polymorphism may be due either to a population expansion within Africa or to selective pressure. PMID:11443540

  7. Climatic thresholds for pedogenic iron oxides under aerobic conditions: Processes and their significance in paleoclimate reconstruction

    NASA Astrophysics Data System (ADS)

    Long, Xiaoyong; Ji, Junfeng; Barrón, Vidal; Torrent, José

    2016-10-01

    Iron oxides are widely distributed across the surface of the Earth as a result of the aerobic weathering of primary Fe-bearing minerals. Pedogenic iron oxides which consist mainly of hematite (Hm), goethite (Gt), maghemite (Mgh), are often concentrated synchronously in aerobic soils under low to moderate rainfall regimes. Magnetic susceptibility (χ) and redness, which respectively reflect the content of Mgh and Hm in soils, are considered reasonable pedogenic and climatic indicators in soil taxonomy and paleorainfall reconstruction. However, under high rainfall regimes, the grain growth of Mgh and transformation to Hm, combined with the prior formation of Gt under conditions of high relative humidity (RH), can result in magnetic reduction and dramatic yellowing of soils and sediments, which explains the existence of rainfall thresholds for Mgh and Hm at a large scale even before the pedogenic environment turns anaerobic. In order to capture the rainfall thresholds for Mgh and Hm occurring under aerobic conditions, we explored a tropical transect across a granitic region where the soil color turned from red to yellow under a wide rainfall range of 900-2200 mm/yr and a corresponding mean annual RH range of 77%-85%. We observed a lower rainfall threshold of ∼1500 mm/yr and a corresponding RH ∼80% for Mgh and Hm along this transect, as well as a higher rainfall threshold of ∼1700 mm/yr and a corresponding RH of ∼81% for Gt and total pedogenic iron oxides (citrate/bicarbonate/dithionite-extractable Fe, Fed). Cross-referencing with comparable studies in temperate and subtropical regions, we noted that the rainfall or RH thresholds for Fed and Hm or Mgh likewise increase with temperature. Moreover, the different thresholds for total and individual iron oxide phase indicates that a negative correlation between chemical weathering intensity and redness or χ in sediment sequences can occur under the prevalent climate regime just between their thresholds. Finally

  8. Testing significance relative to a fold-change threshold is a TREAT.

    PubMed

    McCarthy, Davis J; Smyth, Gordon K

    2009-03-15

    Statistical methods are used to test for the differential expression of genes in microarray experiments. The most widely used methods successfully test whether the true differential expression is different from zero, but give no assurance that the differences found are large enough to be biologically meaningful. We present a method, t-tests relative to a threshold (TREAT), that allows researchers to test formally the hypothesis (with associated p-values) that the differential expression in a microarray experiment is greater than a given (biologically meaningful) threshold. We have evaluated the method using simulated data, a dataset from a quality control experiment for microarrays and data from a biological experiment investigating histone deacetylase inhibitors. When the magnitude of differential expression is taken into account, TREAT improves upon the false discovery rate of existing methods and identifies more biologically relevant genes. R code implementing our methods is contributed to the software package limma available at http://www.bioconductor.org.

  9. Tests of English Language as Significant Thresholds for College-Bound Chinese and the Washback of Test-Preparation

    ERIC Educational Resources Information Center

    Matoush, Marylou M.; Fu, Danling

    2012-01-01

    Tests of English language mark significantly high thresholds for all college-bound students in the People's Republic of China. Many Chinese students hope to seek their fortunes at universities in the United States, or other English speaking countries. These students spend long hours, year after year, in test-preparation centres in order to develop…

  10. Alcohol significantly lowers the seizure threshold in mice when co-administered with bupropion hydrochloride

    PubMed Central

    Silverstone, Peter H; Williams, Robert; McMahon, Louis; Fleming, Rosanna; Fogarty, Siobhan

    2008-01-01

    Background Bupropion HCl is a widely used antidepressant that is known to cause seizures in a dose-dependent manner. Many patients taking antidepressants will consume alcohol, even when advised not to. Previous studies have not shown any interactions between bupropion HCl and alcohol. However, there have been no previous studies examining possible changes in seizure threshold induced by a combination of alcohol and bupropion HCl. Methods Experimentally naïve female Swiss albino mice (10 per group) received either single doses of bupropion HCl (ranging from 100 mg/kg to 120 mg/kg) or vehicle (0.9% NaCl) by intraperitoneal (IP) injection in a dose volume of 10 ml/kg, and single-dose ethanol alone (2.5 g/kg), or vehicle, 5 min prior to bupropion dosing. The presence or absence of seizures, the number of seizures, the onset, duration and the intensity of seizures were all recorded for 5 h following the administration of ethanol. Results The results show that administration of IP bupropion HCl alone induced seizures in mice in a dose-dependent manner, with the 120 mg/kg dose having the largest effect. The percentage of convulsing mice were 0%, 20%, 30% and 60% in the 0 (vehicle), 100, 110, and 120 mg/kg dose groups, respectively. Pretreatment with ethanol produced a larger bupropion HCl-induced convulsive effect at all the doses (70% each at 100, 110 and 120 mg/kg) and a 10% effect in the ethanol + vehicle only group. The convulsive dose of bupropion HCl required to induce seizures in 50% of mice (CD50), was 116.72 mg/kg for bupropion HCl alone (CI: 107.95, 126.20) and 89.40 mg/kg for ethanol/bupropion HCl (CI: 64.92, 123.10). Conclusion These results show that in mice alcohol lowers the seizure threshold for bupropion-induced seizures. Clinical implications are firstly that there may be an increased risk of seizures in patients consuming alcohol, and secondly that formulations that can release bupropion more readily in alcohol may present additional risks to patients

  11. The earth is flat (p > 0.05): significance thresholds and the crisis of unreplicable research.

    PubMed

    Amrhein, Valentin; Korner-Nievergelt, Fränzi; Roth, Tobias

    2017-01-01

    The widespread use of 'statistical significance' as a license for making a claim of a scientific finding leads to considerable distortion of the scientific process (according to the American Statistical Association). We review why degrading p-values into 'significant' and 'nonsignificant' contributes to making studies irreproducible, or to making them seem irreproducible. A major problem is that we tend to take small p-values at face value, but mistrust results with larger p-values. In either case, p-values tell little about reliability of research, because they are hardly replicable even if an alternative hypothesis is true. Also significance (p ≤ 0.05) is hardly replicable: at a good statistical power of 80%, two studies will be 'conflicting', meaning that one is significant and the other is not, in one third of the cases if there is a true effect. A replication can therefore not be interpreted as having failed only because it is nonsignificant. Many apparent replication failures may thus reflect faulty judgment based on significance thresholds rather than a crisis of unreplicable research. Reliable conclusions on replicability and practical importance of a finding can only be drawn using cumulative evidence from multiple independent studies. However, applying significance thresholds makes cumulative knowledge unreliable. One reason is that with anything but ideal statistical power, significant effect sizes will be biased upwards. Interpreting inflated significant results while ignoring nonsignificant results will thus lead to wrong conclusions. But current incentives to hunt for significance lead to selective reporting and to publication bias against nonsignificant findings. Data dredging, p-hacking, and publication bias should be addressed by removing fixed significance thresholds. Consistent with the recommendations of the late Ronald Fisher, p-values should be interpreted as graded measures of the strength of evidence against the null hypothesis. Also

  12. The Prevalence of Clinically Significant Prostate Cancer According to Commonly Used Histological Thresholds in Men Undergoing Template Prostate Mapping Biopsies.

    PubMed

    Valerio, M; Anele, C; Bott, S R J; Charman, S C; van der Meulen, J; El-Mahallawi, H; Emara, A M; Freeman, A; Jameson, C; Hindley, R G; Montgomery, B S I; Singh, P B; Ahmed, H U; Emberton, M

    2016-05-01

    Transrectal prostate biopsies are inaccurate and, thus, the prevalence of clinically significant prostate cancer in men undergoing biopsy is unknown. We determined the ability of different histological thresholds to denote clinically significant cancer in men undergoing a more accurate biopsy, that of transperineal template prostate mapping. In this multicenter, cross-sectional cohort of men who underwent template prostate mapping biopsies between May 2006 and January 2012, 4 different thresholds of significance combining tumor grade and burden were used to measure the consequent variation with respect to the prevalence of clinically significant disease. Of 1,203 men 17% (199) had no previous biopsy, 38% (455) had a prior negative transrectal ultrasound biopsy, 24% (289) were on active surveillance and 21% (260) were seeking risk stratification. Mean patient age was 63.5 years (SD 7.6) and median prostate specific antigen was 7.4 ng/ml (IQR 5.3-10.5). Overall 35% of the patients (424) had no cancer detected. The prevalence of clinically significant cancer varied between 14% and 83% according to the histological threshold used, in particular between 30% and 51% among men who had no previous biopsy, between 14% and 27% among men who had a prior negative biopsy, between 36% and 74% among men on active surveillance, and between 47% and 83% among men seeking risk stratification. According to template prostate mapping biopsy between 1 in 2 and 1 in 3 men have prostate cancer that is histologically defined as clinically significant. This suggests that the commonly used thresholds may be set too low. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  13. Lateralized Readiness Potentials Reveal Properties of a Neural Mechanism for Implementing a Decision Threshold

    PubMed Central

    van Vugt, Marieke K.; Simen, Patrick; Nystrom, Leigh; Holmes, Philip; Cohen, Jonathan D.

    2014-01-01

    Many perceptual decision making models posit that participants accumulate noisy evidence over time to improve the accuracy of their decisions, and that in free response tasks, participants respond when the accumulated evidence reaches a decision threshold. Research on the neural correlates of these models' components focuses primarily on evidence accumulation. Far less attention has been paid to the neural correlates of decision thresholds, reflecting the final commitment to a decision. Inspired by a model of bistable neural activity that implements a decision threshold, we reinterpret human lateralized readiness potentials (LRPs) as reflecting the crossing of a decision threshold. Interestingly, this threshold crossing preserves signatures of a drift-diffusion process of evidence accumulation that feeds in to the threshold mechanism. We show that, as our model predicts, LRP amplitudes and growth rates recorded while participants performed a motion discrimination task correlate with individual differences in behaviorally-estimated prior beliefs, decision thresholds and evidence accumulation rates. As such LRPs provide a useful measure to test dynamical models of both evidence accumulation and decision commitment processes non-invasively. PMID:24625827

  14. Source accuracy data reveal the thresholded nature of human episodic memory.

    PubMed

    Harlow, Iain M; Donaldson, David I

    2013-04-01

    Episodic recollection supports conscious retrieval of past events. It is unknown why recollected memories are often vivid, but at other times we struggle to remember. Such experiences might reflect a recollection threshold: Either the threshold is exceeded and information is retrieved, or recollection fails completely. Alternatively, retrieval failure could reflect weak memory: Recollection could behave as a continuous signal, always yielding some variable degree of information. Here we reconcile these views, using a novel source memory task that measures retrieval accuracy directly. We show that recollection is thresholded, such that retrieval sometimes simply fails. Our technique clarifies a fundamental property of memory and allows responses to be accurately measured, without recourse to subjective introspection. These findings raise new questions about how successful retrieval is determined and why it declines with age and disease.

  15. The earth is flat (p > 0.05): significance thresholds and the crisis of unreplicable research

    PubMed Central

    Korner-Nievergelt, Fränzi; Roth, Tobias

    2017-01-01

    The widespread use of ‘statistical significance’ as a license for making a claim of a scientific finding leads to considerable distortion of the scientific process (according to the American Statistical Association). We review why degrading p-values into ‘significant’ and ‘nonsignificant’ contributes to making studies irreproducible, or to making them seem irreproducible. A major problem is that we tend to take small p-values at face value, but mistrust results with larger p-values. In either case, p-values tell little about reliability of research, because they are hardly replicable even if an alternative hypothesis is true. Also significance (p ≤ 0.05) is hardly replicable: at a good statistical power of 80%, two studies will be ‘conflicting’, meaning that one is significant and the other is not, in one third of the cases if there is a true effect. A replication can therefore not be interpreted as having failed only because it is nonsignificant. Many apparent replication failures may thus reflect faulty judgment based on significance thresholds rather than a crisis of unreplicable research. Reliable conclusions on replicability and practical importance of a finding can only be drawn using cumulative evidence from multiple independent studies. However, applying significance thresholds makes cumulative knowledge unreliable. One reason is that with anything but ideal statistical power, significant effect sizes will be biased upwards. Interpreting inflated significant results while ignoring nonsignificant results will thus lead to wrong conclusions. But current incentives to hunt for significance lead to selective reporting and to publication bias against nonsignificant findings. Data dredging, p-hacking, and publication bias should be addressed by removing fixed significance thresholds. Consistent with the recommendations of the late Ronald Fisher, p-values should be interpreted as graded measures of the strength of evidence against the null

  16. Role of TRPV1 in high-threshold rat colonic splanchnic afferents is revealed by inflammation.

    PubMed

    Phillis, Benjamin D; Martin, Chris M; Kang, Daiwu; Larsson, Håkan; Lindström, Erik A; Martinez, Vicente; Blackshaw, L Ashley

    2009-08-07

    The vanilloid-1 receptor TRPV1 is known to play a role in extrinsic gastrointestinal afferent function. We investigated the role of TRPV1 in mechanosensitivity in afferents from normal and inflamed tissue. Colonic mechanosensitivity was determined in an in vitro rat colon preparation by recording from attached splanchnic nerves. Recordings were made from serosal/mesenteric afferents responding only at high thresholds to graded mechanical stimulation with von Frey probes. Colonic inflammation was induced by adding 5% dextran sulphate sodium (DSS) to the drinking water for 5 days, and was confirmed by histopathology. The selective TRPV1 antagonist, SB-750364 (10(-8) to 10(-6)M), was tested on mechanosensory stimulus response functions of afferents from normal and inflamed preparations (N=7 each). Mechanosensory responses had thresholds of 1-2g, and maximal responses were observed at 12 g. The stimulus response function was not affected by DSS-induced colitis. SB-750364 had no effect on stimulus response functions in normal preparations, but reduced (up to 60%) in a concentration-dependent manner those in inflammation (2-way ANOVA, p<0.05). Moreover, in inflamed tissue, spontaneous afferent activity showed a dose-dependent trend toward reduction with SB-750364. We conclude that mechanosensitivity of high-threshold serosal colonic splanchnic afferents to graded stimuli is unaffected during DSS colitis. However, there is a positive influence of TRPV1 in mechanosensitivity in inflammation, suggesting up-regulation of excitatory TRPV1-mediated mechanisms.

  17. Interactions between auditory 'what' and 'where' pathways revealed by enhanced near-threshold discrimination of frequency and position.

    PubMed

    Tardif, Eric; Spierer, Lucas; Clarke, Stephanie; Murray, Micah M

    2008-03-07

    Partially segregated neuronal pathways ("what" and "where" pathways, respectively) are thought to mediate sound recognition and localization. Less studied are interactions between these pathways. In two experiments, we investigated whether near-threshold pitch discrimination sensitivity (d') is altered by supra-threshold task-irrelevant position differences and likewise whether near-threshold position discrimination sensitivity is altered by supra-threshold task-irrelevant pitch differences. Each experiment followed a 2 x 2 within-subjects design regarding changes/no change in the task-relevant and task-irrelevant stimulus dimensions. In Experiment 1, subjects discriminated between 750 Hz and 752 Hz pure tones, and d' for this near-threshold pitch change significantly increased by a factor of 1.09 when accompanied by a task-irrelevant position change of 65 micros interaural time difference (ITD). No response bias was induced by the task-irrelevant position change. In Experiment 2, subjects discriminated between 385 micros and 431 micros ITDs, and d' for this near-threshold position change significantly increased by a factor of 0.73 when accompanied by task-irrelevant pitch changes (6 Hz). In contrast to Experiment 1, task-irrelevant pitch changes induced a response criterion bias toward responding that the two stimuli differed. The collective results are indicative of facilitative interactions between "what" and "where" pathways. By demonstrating how these pathways may cooperate under impoverished listening conditions, our results bear implications for possible neuro-rehabilitation strategies. We discuss our results in terms of the dual-pathway model of auditory processing.

  18. High-resolution tide projections reveal extinction threshold in response to sea-level rise.

    PubMed

    Field, Christopher R; Bayard, Trina S; Gjerdrum, Carina; Hill, Jason M; Meiman, Susan; Elphick, Chris S

    2017-05-01

    Sea-level rise will affect coastal species worldwide, but models that aim to predict these effects are typically based on simple measures of sea level that do not capture its inherent complexity, especially variation over timescales shorter than 1 year. Coastal species might be most affected, however, by floods that exceed a critical threshold. The frequency and duration of such floods may be more important to population dynamics than mean measures of sea level. In particular, the potential for changes in the frequency and duration of flooding events to result in nonlinear population responses or biological thresholds merits further research, but may require that models incorporate greater resolution in sea level than is typically used. We created population simulations for a threatened songbird, the saltmarsh sparrow (Ammodramus caudacutus), in a region where sea level is predictable with high accuracy and precision. We show that incorporating the timing of semidiurnal high tide events throughout the breeding season, including how this timing is affected by mean sea-level rise, predicts a reproductive threshold that is likely to cause a rapid demographic shift. This shift is likely to threaten the persistence of saltmarsh sparrows beyond 2060 and could cause extinction as soon as 2035. Neither extinction date nor the population trajectory was sensitive to the emissions scenarios underlying sea-level projections, as most of the population decline occurred before scenarios diverge. Our results suggest that the variation and complexity of climate-driven variables could be important for understanding the potential responses of coastal species to sea-level rise, especially for species that rely on coastal areas for reproduction.

  19. Exact coupling threshold for structural transition reveals diversified behaviors in interconnected networks

    NASA Astrophysics Data System (ADS)

    Darabi Sahneh, Faryad; Scoglio, Caterina; Van Mieghem, Piet

    2015-10-01

    An interconnected network features a structural transition between two regimes [F. Radicchi and A. Arenas, Nat. Phys. 9, 717 (2013), 10.1038/nphys2761]: one where the network components are structurally distinguishable and one where the interconnected network functions as a whole. Our exact solution for the coupling threshold uncovers network topologies with unexpected behaviors. Specifically, we show conditions that superdiffusion, introduced by Gómez et al. [Phys. Rev. Lett. 110, 028701 (2013), 10.1103/PhysRevLett.110.028701], can occur despite the network components functioning distinctly. Moreover, we find that components of certain interconnected network topologies are indistinguishable despite very weak coupling between them.

  20. Myeloid conditional deletion and transgenic models reveal a threshold for the neutrophil survival factor Serpinb1.

    PubMed

    Burgener, Sabrina S; Baumann, Mathias; Basilico, Paola; Remold-O'Donnell, Eileen; Touw, Ivo P; Benarafa, Charaf

    2016-09-01

    Serpinb1 is an inhibitor of neutrophil granule serine proteases cathepsin G, proteinase-3 and elastase. One of its core physiological functions is to protect neutrophils from granule protease-mediated cell death. Mice lacking Serpinb1a (Sb1a-/-), its mouse ortholog, have reduced bone marrow neutrophil numbers due to cell death mediated by cathepsin G and the mice show increased susceptibility to lung infections. Here, we show that conditional deletion of Serpinb1a using the Lyz2-cre and Cebpa-cre knock-in mice effectively leads to recombination-mediated deletion in neutrophils but protein-null neutrophils were only obtained using the latter recombinase-expressing strain. Absence of Serpinb1a protein in neutrophils caused neutropenia and increased granule permeabilization-induced cell death. We then generated transgenic mice expressing human Serpinb1 in neutrophils under the human MRP8 (S100A8) promoter. Serpinb1a expression levels in founder lines correlated positively with increased neutrophil survival when crossed with Sb1a-/- mice, which had their defective neutrophil phenotype rescued in the higher expressing transgenic line. Using new conditional and transgenic mouse models, our study demonstrates the presence of a relatively low Serpinb1a protein threshold in neutrophils that is required for sustained survival. These models will also be helpful in delineating recently described functions of Serpinb1 in metabolism and cancer.

  1. Auditory steady-state responses reveal amplitude modulation gap detection thresholds

    NASA Astrophysics Data System (ADS)

    Ross, Bernhard; Pantev, Christo

    2004-05-01

    Auditory evoked magnetic fields were recorded from the left hemisphere of healthy subjects using a 37-channel magnetometer while stimulating the right ear with 40-Hz amplitude modulated (AM) tone-bursts with 500-Hz carrier frequency in order to study the time-courses of amplitude and phase of auditory steady-state responses (ASSRs). The stimulus duration of 300 ms and the duration of the silent periods (3-300 ms) between succeeding stimuli were chosen to address the question whether the time-course of the ASSR can reflect both temporal integration and temporal resolution in the central auditory processing. Long lasting perturbations of the ASSR were found after gaps in the AM sound, even for gaps of short duration. These were interpreted as evidences for an auditory reset mechanism. Concomitant psycho-acoustical tests corroborated that gap durations perturbing the ASSR were in the same range as the threshold for AM gap detection. Magnetic source localizations estimated the ASSR sources in the primary auditory cortex, suggesting that the processing of temporal structures in the sound is performed at or below the cortical level.

  2. pH-dependent binding engineering reveals an FcRn affinity threshold that governs IgG recycling.

    PubMed

    Borrok, M Jack; Wu, Yanli; Beyaz, Nurten; Yu, Xiang-Qing; Oganesyan, Vaheh; Dall'Acqua, William F; Tsui, Ping

    2015-02-13

    The Fc domain of IgG has been the target of multiple mutational studies aimed at altering the pH-dependent IgG/FcRn interaction to modulate IgG pharmacokinetics. These studies have yielded antibody variants with disparate pharmacokinetic characteristics, ranging from extended in vivo half-life to those exhibiting extremely rapid clearance. To better understand pH-dependent binding parameters that govern these outcomes and limit FcRn-mediated half-life extension, we generated a panel of novel Fc variants with high affinity binding at acidic pH that vary in pH 7.4 affinities and assessed pharmacokinetic outcomes. Pharmacokinetic studies in human FcRn transgenic mice and cynomolgus monkeys showed that multiple variants with increased FcRn affinities at acidic pH exhibited extended serum half-lives relative to the parental IgG. Importantly, the results reveal an underappreciated affinity threshold of neutral pH binding that determines IgG recycling efficiency. Variants with pH 7.4 FcRn affinities below this threshold recycle efficiently and can exhibit increased serum persistence. Increasing neutral pH FcRn affinity beyond this threshold reduced serum persistence by offsetting the benefits of increased pH 6.0 binding. Ultra-high affinity binding to FcRn at both acidic and neutral pH leads to rapid serum clearance.

  3. Functional characterization of the guanine nucleotide exchange factor (GEF) motif of GIV protein reveals a threshold effect in signaling.

    PubMed

    Garcia-Marcos, Mikel; Kietrsunthorn, Patrick S; Pavlova, Yelena; Adia, Michelle A; Ghosh, Pradipta; Farquhar, Marilyn G

    2012-02-07

    Heterotrimeric G proteins are critical signal-transducing molecules controlled by a complex network of regulators. GIV (a.k.a. Girdin) is a unique component of this network and a nonreceptor guanine nucleotide exchange factor (GEF) that functions via a signature motif. GIV's GEF motif is involved in the regulation of critical biological processes such as phosphoinositide 3 kinase (PI3K)-Akt signaling, actin cytoskeleton remodeling, cell migration, and cancer metastasis. Here we investigated how the GEF function of GIV affects the wiring of its signaling pathway to shape different biological responses. Using a structure-guided approach, we designed a battery of GIV mutants with different Gαi-binding and -activating properties and used it to dissect the specific impact of changes in GIV's GEF activity on several cellular responses. In vivo signaling assays revealed a threshold effect of GEF activity for the activation of Akt by GIV in different cell lines and by different stimuli. Akt signaling is minimal at low GEF activity and is sharply increased to reach a maximum above a threshold of GEF activity, suggesting that GIV is a critical signal amplifier and that activation of Akt is ultrasensitive to changes in GIV's GEF activity. A similar threshold dependence was observed for other biological functions promoted by GIV such as remodeling of the actin cytoskeleton and cell migration. This functional characterization of GIV's GEF motif provides insights into the molecular interactions between nonreceptor GEFs and G proteins and the mechanisms that govern this signal transduction pathway.

  4. Application of thresholds of potential concern and limits of acceptable change in the condition assessment of a significant wetland.

    PubMed

    Rogers, Kerrylee; Saintilan, Neil; Colloff, Matthew J; Wen, Li

    2013-10-01

    We propose a framework in which thresholds of potential concern (TPCs) and limits of acceptable change (LACs) are used in concert in the assessment of wetland condition and vulnerability and apply the framework in a case study. The lower Murrumbidgee River floodplain (the 'Lowbidgee') is one of the most ecologically important wetlands in Australia and the focus of intense management intervention by State and Federal government agencies. We used a targeted management stakeholder workshop to identify key values that contribute to the ecological significance of the Lowbidgee floodplain, and identified LACs that, if crossed, would signify the loss of significance. We then used conceptual models linking the condition of these values (wetland vegetation communities, waterbirds, fish species and the endangered southern bell frog) to measurable threat indicators, for which we defined a management goal and a TPC. We applied this framework to data collected across 70 wetland storages', or eco-hydrological units, at the peak of a prolonged drought (2008) and following extensive re-flooding (2010). At the suggestion of water and wetland mangers, we neither aggregated nor integrated indices but reported separately in a series of chloropleth maps. The resulting assessment clearly identified the effect of rewetting in restoring indicators within TPC in most cases, for most storages. The scale of assessment was useful in informing the targeted and timely management intervention and provided a context for retaining and utilising monitoring information in an adaptive management context.

  5. Nano-cathodoluminescence reveals the effect of electron damage on the optical properties of nitride optoelectronics and the damage threshold

    NASA Astrophysics Data System (ADS)

    Griffiths, James T.; Zhang, Siyuan; Lhuillier, Jeremy; Zhu, Dandan; Fu, Wai Yuen; Howkins, Ashley; Boyd, Ian; Stowe, David; Wallis, David J.; Humphreys, Colin J.; Oliver, Rachel A.

    2016-10-01

    Nano-cathodoluminescence (Nano-CL) reveals optical emission from individual InGaN quantum wells for applications in optoelectronic devices. We show the luminescent intensity decays over time with exposure to the electron beam for energies between 80 and 200 keV. Measurements of the CL intensity over time show an exponential decline in intensity, which we propose is due to the formation of nitrogen Frenkel defects. The measured CL damage decreases with reductions in the electron accelerating voltage and we suggest that the electron induced structural damage may be suppressed below the proposed damage threshold. The electron beam induced damage leads to a non-radiative region that extends over the measured minority carrier diffusion length. Nano-CL may thus serve as a powerful technique to study III-nitride optoelectronics.

  6. 78 FR 55772 - Culturally Significant Object Imported for Exhibition Determinations: “Beauty Revealed: Images of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-11

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF STATE Culturally Significant Object Imported for Exhibition Determinations: ``Beauty Revealed: Images of Women in... April 15, 2003, I hereby determine that the object to be included in the exhibition ``Beauty...

  7. Adaptive Cellular Interactions in the Immune System: The Tunable Activation Threshold and the Significance of Subthreshold Responses

    NASA Astrophysics Data System (ADS)

    Grossman, Zvi; Paul, William E.

    1992-11-01

    A major challenge for immunologists is to explain how the immune system adjusts its responses to the microenvironmental context in which antigens are recognized. We propose that lymphocytes achieve this by tuning and updating their responsiveness to recurrent signals. In particular, cellular anergy in vivo is a dynamic state in which the threshold for a stereotypic mode of activation has been elevated. Anergy is associated with other forms of cellular activity, not paralysis. Cells engaged in such subthreshold interactions mediate functions such as maintenance of immunological memory and control of infections. In such interactions, patterns of signals are recognized and classified and evoke selective responses. The robust mechanism proposed for segregation of suprathreshold and subthreshold immune responses allows lymphocytes to use recognition of self-antigens in executing physiological functions. Autoreactivity is allowed where it is dissociated from uncontrolled aggression.

  8. Interactions among hydraulic conductivity distributions, subsurface topography, and transport thresholds revealed by a multitracer hillslope irrigation experiment

    DOE PAGES

    Jackson, C. Rhett; Du, Enhao; Klaus, Julian; ...

    2016-08-12

    Interactions among hydraulic conductivity distributions, subsurface topography, and lateral flow are poorly understood. We applied 407 mm of water and a suite of tracers over 51 h to a 12 by 16.5 m forested hillslope segment to determine interflow thresholds, preferential pathway pore velocities, large-scale conductivities, the time series of event water fractions, and the fate of dissolved nutrients. The 12% hillslope featured loamy sand A and E horizons overlying a sandy clay loam Bt at 1.25 m average depth. Interflow measured from two drains within an interception trench commenced after 131 and 208 mm of irrigation. Cumulative interflow equaledmore » 49% of applied water. Conservative tracer differences between the collection drains indicated differences in flow paths and storages within the plot. Event water fractions rose steadily throughout irrigation, peaking at 50% sixteen h after irrigation ceased. Data implied that tightly held water exchanged with event water throughout the experiment and a substantial portion of preevent water was released from the argillic layer. Surface-applied dye tracers bypassed the matrix, with peak concentrations measured shortly after flow commencement, indicating preferential network conductivities of 864–2240 mm/h, yet no macropore flow was observed. Near steady-state flow conditions indicated average conductivities of 460 mm/h and 2.5 mm/h for topsoils and the Bt horizon, respectively. Low ammonium and phosphorus concentrations in the interflow suggested rapid uptake or sorption, while higher nitrate concentrations suggested more conservative transport. Lastly, these results reveal how hydraulic conductivity variation and subsurface topographic complexity explain otherwise paradoxical solute and flow behaviors.« less

  9. Interactions among hydraulic conductivity distributions, subsurface topography, and transport thresholds revealed by a multitracer hillslope irrigation experiment

    SciTech Connect

    Jackson, C. Rhett; Du, Enhao; Klaus, Julian; Griffiths, Natalie A.; Bitew, Menberu; McDonnell, Jeffrey J.

    2016-08-12

    Interactions among hydraulic conductivity distributions, subsurface topography, and lateral flow are poorly understood. We applied 407 mm of water and a suite of tracers over 51 h to a 12 by 16.5 m forested hillslope segment to determine interflow thresholds, preferential pathway pore velocities, large-scale conductivities, the time series of event water fractions, and the fate of dissolved nutrients. The 12% hillslope featured loamy sand A and E horizons overlying a sandy clay loam Bt at 1.25 m average depth. Interflow measured from two drains within an interception trench commenced after 131 and 208 mm of irrigation. Cumulative interflow equaled 49% of applied water. Conservative tracer differences between the collection drains indicated differences in flow paths and storages within the plot. Event water fractions rose steadily throughout irrigation, peaking at 50% sixteen h after irrigation ceased. Data implied that tightly held water exchanged with event water throughout the experiment and a substantial portion of preevent water was released from the argillic layer. Surface-applied dye tracers bypassed the matrix, with peak concentrations measured shortly after flow commencement, indicating preferential network conductivities of 864–2240 mm/h, yet no macropore flow was observed. Near steady-state flow conditions indicated average conductivities of 460 mm/h and 2.5 mm/h for topsoils and the Bt horizon, respectively. Low ammonium and phosphorus concentrations in the interflow suggested rapid uptake or sorption, while higher nitrate concentrations suggested more conservative transport. Lastly, these results reveal how hydraulic conductivity variation and subsurface topographic complexity explain otherwise paradoxical solute and flow behaviors.

  10. Interactions among hydraulic conductivity distributions, subsurface topography, and transport thresholds revealed by a multitracer hillslope irrigation experiment

    SciTech Connect

    Jackson, C. Rhett; Du, Enhao; Klaus, Julian; Griffiths, Natalie A.; Bitew, Menberu; McDonnell, Jeffrey J.

    2016-08-12

    Interactions among hydraulic conductivity distributions, subsurface topography, and lateral flow are poorly understood. We applied 407 mm of water and a suite of tracers over 51 h to a 12 by 16.5 m forested hillslope segment to determine interflow thresholds, preferential pathway pore velocities, large-scale conductivities, the time series of event water fractions, and the fate of dissolved nutrients. The 12% hillslope featured loamy sand A and E horizons overlying a sandy clay loam Bt at 1.25 m average depth. Interflow measured from two drains within an interception trench commenced after 131 and 208 mm of irrigation. Cumulative interflow equaled 49% of applied water. Conservative tracer differences between the collection drains indicated differences in flow paths and storages within the plot. Event water fractions rose steadily throughout irrigation, peaking at 50% sixteen h after irrigation ceased. Data implied that tightly held water exchanged with event water throughout the experiment and a substantial portion of preevent water was released from the argillic layer. Surface-applied dye tracers bypassed the matrix, with peak concentrations measured shortly after flow commencement, indicating preferential network conductivities of 864–2240 mm/h, yet no macropore flow was observed. Near steady-state flow conditions indicated average conductivities of 460 mm/h and 2.5 mm/h for topsoils and the Bt horizon, respectively. Low ammonium and phosphorus concentrations in the interflow suggested rapid uptake or sorption, while higher nitrate concentrations suggested more conservative transport. Lastly, these results reveal how hydraulic conductivity variation and subsurface topographic complexity explain otherwise paradoxical solute and flow behaviors.

  11. Dissociation of internal energy-selected methyl bromide ion revealed from threshold photoelectron-photoion coincidence velocity imaging.

    PubMed

    Tang, Xiaofeng; Zhou, Xiaoguo; Sun, Zhongfa; Liu, Shilin; Liu, Fuyi; Sheng, Liusi; Yan, Bing

    2014-01-28

    Dissociative photoionization of methyl bromide (CH3Br) in an excitation energy range of 10.45-16.90 eV has been investigated by using threshold photoelectron-photoion coincidence (TPEPICO) velocity imaging. The coincident time-of-flight mass spectra indicate that the ground state X(2)E of CH3Br(+) is stable, and both A(2)A1 and B(2)E ionic excited states are fully dissociative to produce the unique fragment ion of CH3 (+). From TPEPICO 3D time-sliced velocity images of CH3 (+) dissociated from specific state-selected CH3Br(+) ion, kinetic energy release distribution (KERD) and angular distribution of CH3 (+) fragment ion are directly obtained. Both spin-orbit states of Br((2)P) atom can be clearly observed in fast dissociation of CH3Br(+)(A(2)A1) ion along C-Br rupture, while a KERD of Maxwell-Boltzmann profile is obtained in dissociation of CH3Br(+)(B(2)E) ion. With the aid of the re-calculated potential energy curves of CH3Br(+) including spin-orbit coupling, dissociation mechanisms of CH3Br(+) ion in A(2)A1 and B(2)E states along C-Br rupture are revealed. For CH3Br(+)(A(2)A1) ion, the CH3 (+) + Br((2)P1/2) channel is occurred via an adiabatic dissociation by vibration, while the Br((2)P3/2) formation is through vibronic coupling to the high vibrational level of X(2)E state followed by rapid dissociation. C-Br bond breaking of CH3Br(+)(B(2)E) ion can occur via slow internal conversion to the excited vibrational level of the lower electronic states and then dissociation.

  12. Redefining the Speed Limit of Phase Change Memory Revealed by Time-resolved Steep Threshold-Switching Dynamics of AgInSbTe Devices

    PubMed Central

    Shukla, Krishna Dayal; Saxena, Nishant; Durai, Suresh; Manivannan, Anbarasu

    2016-01-01

    Although phase-change memory (PCM) offers promising features for a ‘universal memory’ owing to high-speed and non-volatility, achieving fast electrical switching remains a key challenge. In this work, a correlation between the rate of applied voltage and the dynamics of threshold-switching is investigated at picosecond-timescale. A distinct characteristic feature of enabling a rapid threshold-switching at a critical voltage known as the threshold voltage as validated by an instantaneous response of steep current rise from an amorphous off to on state is achieved within 250 picoseconds and this is followed by a slower current rise leading to crystallization. Also, we demonstrate that the extraordinary nature of threshold-switching dynamics in AgInSbTe cells is independent to the rate of applied voltage unlike other chalcogenide-based phase change materials exhibiting the voltage dependent transient switching characteristics. Furthermore, numerical solutions of time-dependent conduction process validate the experimental results, which reveal the electronic nature of threshold-switching. These findings of steep threshold-switching of ‘sub-50 ps delay time’, opens up a new way for achieving high-speed non-volatile memory for mainstream computing. PMID:27886266

  13. Redefining the Speed Limit of Phase Change Memory Revealed by Time-resolved Steep Threshold-Switching Dynamics of AgInSbTe Devices

    NASA Astrophysics Data System (ADS)

    Shukla, Krishna Dayal; Saxena, Nishant; Durai, Suresh; Manivannan, Anbarasu

    2016-11-01

    Although phase-change memory (PCM) offers promising features for a ‘universal memory’ owing to high-speed and non-volatility, achieving fast electrical switching remains a key challenge. In this work, a correlation between the rate of applied voltage and the dynamics of threshold-switching is investigated at picosecond-timescale. A distinct characteristic feature of enabling a rapid threshold-switching at a critical voltage known as the threshold voltage as validated by an instantaneous response of steep current rise from an amorphous off to on state is achieved within 250 picoseconds and this is followed by a slower current rise leading to crystallization. Also, we demonstrate that the extraordinary nature of threshold-switching dynamics in AgInSbTe cells is independent to the rate of applied voltage unlike other chalcogenide-based phase change materials exhibiting the voltage dependent transient switching characteristics. Furthermore, numerical solutions of time-dependent conduction process validate the experimental results, which reveal the electronic nature of threshold-switching. These findings of steep threshold-switching of ‘sub-50 ps delay time’, opens up a new way for achieving high-speed non-volatile memory for mainstream computing.

  14. Metabolomics reveals significant variations in metabolites and correlations regarding the maturation of walnuts (Juglans regia L.)

    PubMed Central

    Rao, Guodong; Sui, Jinkai

    2016-01-01

    ABSTRACT The content of walnut metabolites is related to its nutritive value and physiological characteristics, however, comprehensive information concerning the metabolome of walnut kernels is limited. In this study we analyzed the metabolites of walnut kernels at five developmental stages from filling to ripening using GC-MS-based untargeted metabolomics; of a total 252 peaks identified, 85 metabolites were positively identified. Further statistical analysis revealed that these 85 metabolites covered different types of metabolism pathways. PCA scores revealed that the metabolic compositions of the embryo are different at each stage, while the metabolic composition of the endotesta could not be significantly separated into distinct groups. Additionally, 7225 metabolite-metabolite correlations were detected in walnut kernel by a Pearson correlation coefficient approach; during screening of the calculated correlations, 463 and 1047 were determined to be significant with r2≥0.49 and had a false discovery rate (FDR) ≤0.05 in endotesta and embryo, respectively. This work provides the first comprehensive metabolomic study of walnut kernels and reveals that most of the carbohydrate and protein-derived carbon was transferred into other compounds, such as fatty acids, during the maturation of walnuts, which may potentially provide the basis for further studies on walnut kernel metabolism. PMID:27215321

  15. Transcriptome sequencing revealed significant alteration of cortical promoter usage and splicing in schizophrenia.

    PubMed

    Wu, Jing Qin; Wang, Xi; Beveridge, Natalie J; Tooney, Paul A; Scott, Rodney J; Carr, Vaughan J; Cairns, Murray J

    2012-01-01

    While hybridization based analysis of the cortical transcriptome has provided important insight into the neuropathology of schizophrenia, it represents a restricted view of disease-associated gene activity based on predetermined probes. By contrast, sequencing technology can provide un-biased analysis of transcription at nucleotide resolution. Here we use this approach to investigate schizophrenia-associated cortical gene expression. The data was generated from 76 bp reads of RNA-Seq, aligned to the reference genome and assembled into transcripts for quantification of exons, splice variants and alternative promoters in postmortem superior temporal gyrus (STG/BA22) from 9 male subjects with schizophrenia and 9 matched non-psychiatric controls. Differentially expressed genes were then subjected to further sequence and functional group analysis. The output, amounting to more than 38 Gb of sequence, revealed significant alteration of gene expression including many previously shown to be associated with schizophrenia. Gene ontology enrichment analysis followed by functional map construction identified three functional clusters highly relevant to schizophrenia including neurotransmission related functions, synaptic vesicle trafficking, and neural development. Significantly, more than 2000 genes displayed schizophrenia-associated alternative promoter usage and more than 1000 genes showed differential splicing (FDR<0.05). Both types of transcriptional isoforms were exemplified by reads aligned to the neurodevelopmentally significant doublecortin-like kinase 1 (DCLK1) gene. This study provided the first deep and un-biased analysis of schizophrenia-associated transcriptional diversity within the STG, and revealed variants with important implications for the complex pathophysiology of schizophrenia.

  16. Metagenomic analysis reveals significant changes of microbial compositions and protective functions during drinking water treatment.

    PubMed

    Chao, Yuanqing; Ma, Liping; Yang, Ying; Ju, Feng; Zhang, Xu-Xiang; Wu, Wei-Min; Zhang, Tong

    2013-12-19

    The metagenomic approach was applied to characterize variations of microbial structure and functions in raw (RW) and treated water (TW) in a drinking water treatment plant (DWTP) at Pearl River Delta, China. Microbial structure was significantly influenced by the treatment processes, shifting from Gammaproteobacteria and Betaproteobacteria in RW to Alphaproteobacteria in TW. Further functional analysis indicated the basic metabolic functions of microorganisms in TW did not vary considerably. However, protective functions, i.e. glutathione synthesis genes in 'oxidative stress' and 'detoxification' subsystems, significantly increased, revealing the surviving bacteria may have higher chlorine resistance. Similar results were also found in glutathione metabolism pathway, which identified the major reaction for glutathione synthesis and supported more genes for glutathione metabolism existed in TW. This metagenomic study largely enhanced our knowledge about the influences of treatment processes, especially chlorination, on bacterial community structure and protective functions (e.g. glutathione metabolism) in ecosystems of DWTPs.

  17. Phylogeographic analysis reveals significant spatial genetic structure of Incarvillea sinensis as a product of mountain building

    PubMed Central

    2012-01-01

    Background Incarvillea sinensis is widely distributed from Southwest China to Northeast China and in the Russian Far East. The distribution of this species was thought to be influenced by the uplift of the Qinghai-Tibet Plateau and Quaternary glaciation. To reveal the imprints of geological events on the spatial genetic structure of Incarvillea sinensis, we examined two cpDNA segments ( trnH- psbA and trnS- trnfM) in 705 individuals from 47 localities. Results A total of 16 haplotypes was identified, and significant genetic differentiation was revealed (GST =0.843, NST = 0.975, P < 0.05). The survey detected two highly divergent cpDNA lineages connected by a deep gap with allopatric distributions: the southern lineage with higher genetic diversity and differentiation in the eastern Qinghai-Tibet Plateau, and the northern lineage in the region outside the Qinghai-Tibet Plateau. The divergence between these two lineages was estimated at 4.4 MYA. A correlation between the genetic and the geographic distances indicates that genetic drift was more influential than gene flow in the northern clade with lower diversity and divergence. However, a scenario of regional equilibrium between gene flow and drift was shown for the southern clade. The feature of spatial distribution of the genetic diversity of the southern lineage possibly indicated that allopatric fragmentation was dominant in the collections from the eastern Qinghai-Tibet Plateau. Conclusions The results revealed that the uplift of the Qinghai-Tibet Plateau likely resulted in the significant divergence between the lineage in the eastern Qinghai-Tibet Plateau and the other one outside this area. The diverse niches in the eastern Qinghai-Tibet Plateau created a wide spectrum of habitats to accumulate and accommodate new mutations. The features of genetic diversity of populations outside the eastern Qinghai-Tibet Plateau seemed to reveal the imprints of extinction during the Glacial and the interglacial and

  18. Transcriptome Sequencing Revealed Significant Alteration of Cortical Promoter Usage and Splicing in Schizophrenia

    PubMed Central

    Wu, Jing Qin; Wang, Xi; Beveridge, Natalie J.; Tooney, Paul A.; Scott, Rodney J.; Carr, Vaughan J.; Cairns, Murray J.

    2012-01-01

    Background While hybridization based analysis of the cortical transcriptome has provided important insight into the neuropathology of schizophrenia, it represents a restricted view of disease-associated gene activity based on predetermined probes. By contrast, sequencing technology can provide un-biased analysis of transcription at nucleotide resolution. Here we use this approach to investigate schizophrenia-associated cortical gene expression. Methodology/Principal Findings The data was generated from 76 bp reads of RNA-Seq, aligned to the reference genome and assembled into transcripts for quantification of exons, splice variants and alternative promoters in postmortem superior temporal gyrus (STG/BA22) from 9 male subjects with schizophrenia and 9 matched non-psychiatric controls. Differentially expressed genes were then subjected to further sequence and functional group analysis. The output, amounting to more than 38 Gb of sequence, revealed significant alteration of gene expression including many previously shown to be associated with schizophrenia. Gene ontology enrichment analysis followed by functional map construction identified three functional clusters highly relevant to schizophrenia including neurotransmission related functions, synaptic vesicle trafficking, and neural development. Significantly, more than 2000 genes displayed schizophrenia-associated alternative promoter usage and more than 1000 genes showed differential splicing (FDR<0.05). Both types of transcriptional isoforms were exemplified by reads aligned to the neurodevelopmentally significant doublecortin-like kinase 1 (DCLK1) gene. Conclusions This study provided the first deep and un-biased analysis of schizophrenia-associated transcriptional diversity within the STG, and revealed variants with important implications for the complex pathophysiology of schizophrenia. PMID:22558445

  19. β-Thalassemia Patients Revealed a Significant Change of Untargeted Metabolites in Comparison to Healthy Individuals

    PubMed Central

    Musharraf, Syed Ghulam; Iqbal, Ayesha; Ansari, Saqib Hussain; Parveen, Sadia; Khan, Ishtiaq Ahmad; Siddiqui, Amna Jabbar

    2017-01-01

    β-Thalassemia is one of the most prevalent forms of congenital blood disorders characterized by reduced hemoglobin levels with severe complications, affecting all dimensions of life. The mechanisms underlying the phenotypic heterogeneity of β-thalassemia are still poorly understood. We aimed to work over metabolite biomarkers to improve mechanistic understanding of phenotypic heterogeneity and hence better management of disorder at different levels. Untargeted serum metabolites were analyzed after protein precipitation and SPE (solid phase extraction) from 100 β-thalassemia patients and 61 healthy controls using GC-MS. 40 metabolites were identified having a significance difference between these two groups at probability of 0.05 and fold change >1.5. Out of these 40 metabolites, 17 were up-regulated while 23 were down-regulated. PCA and PLS-DA model was also created that revealed a fine separation with a sensitivity of 70% and specificity of 100% on external validation of samples. Metabolic pathway analysis revealed alteration in multiple pathways including glycolysis, pyruvate, propanoate, glycerophospholipid, galactose, fatty acid, starch and sucrose metabolism along with fatty acid elongation in mitochondria, glycerolipid, glyoxylate and dicarboxylate metabolism pointing towards the shift of metabolism in β-thalassemia patients in comparison to healthy individuals. PMID:28198811

  20. Seed metabolomic study reveals significant metabolite variations and correlations among different soybean cultivars.

    PubMed

    Lin, Hong; Rao, Jun; Shi, Jianxin; Hu, Chaoyang; Cheng, Fang; Wilson, Zoe A; Zhang, Dabing; Quan, Sheng

    2014-09-01

    Soybean [Glycine max (L.) Merr.] is one of the world's major crops, and soybean seeds are a rich and important resource for proteins and oils. While "omics" studies, such as genomics, transcriptomics, and proteomics, have been widely applied in soybean molecular research, fewer metabolomic studies have been conducted for large-scale detection of low molecular weight metabolites, especially in soybean seeds. In this study, we investigated the seed metabolomes of 29 common soybean cultivars through combined gas chromatography-mass spectrometry and ultra-performance liquid chromatography-tandem mass spectrometry. One hundred sixty-nine named metabolites were identified and subsequently used to construct a metabolic network of mature soybean seed. Among the 169 detected metabolites, 104 were found to be significantly variable in their levels across tested cultivars. Metabolite markers that could be used to distinguish genetically related soybean cultivars were also identified, and metabolite-metabolite correlation analysis revealed some significant associations within the same or among different metabolite groups. Findings from this work may potentially provide the basis for further studies on both soybean seed metabolism and metabolic engineering to improve soybean seed quality and yield.

  1. DNA entropy reveals a significant difference in complexity between housekeeping and tissue specific gene promoters.

    PubMed

    Thomas, David; Finan, Chris; Newport, Melanie J; Jones, Susan

    2015-10-01

    The complexity of DNA can be quantified using estimates of entropy. Variation in DNA complexity is expected between the promoters of genes with different transcriptional mechanisms; namely housekeeping (HK) and tissue specific (TS). The former are transcribed constitutively to maintain general cellular functions, and the latter are transcribed in restricted tissue and cells types for specific molecular events. It is known that promoter features in the human genome are related to tissue specificity, but this has been difficult to quantify on a genomic scale. If entropy effectively quantifies DNA complexity, calculating the entropies of HK and TS gene promoters as profiles may reveal significant differences. Entropy profiles were calculated for a total dataset of 12,003 human gene promoters and for 501 housekeeping (HK) and 587 tissue specific (TS) human gene promoters. The mean profiles show the TS promoters have a significantly lower entropy (p<2.2e-16) than HK gene promoters. The entropy distributions for the 3 datasets show that promoter entropies could be used to identify novel HK genes. Functional features comprise DNA sequence patterns that are non-random and hence they have lower entropies. The lower entropy of TS gene promoters can be explained by a higher density of positive and negative regulatory elements, required for genes with complex spatial and temporary expression. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Transcriptomic Analysis Reveals Significant B Lymphocyte Suppression in Corticosteroid-Treated Hosts with Pneumocystis Pneumonia.

    PubMed

    Hu, Yang; Wang, Dong; Zhai, Kan; Tong, Zhaohui

    2017-03-01

    Pneumocystis pneumonia (PCP) is an opportunistic, infectious disease that is prevalent in immunosuppressed hosts. Corticosteroid treatment is the most significant risk factor for patients with PCP who are human immunodeficiency virus negative, although little is known about how corticosteroids alter the host defense against Pneumocystis infection. In the present study, we used transcriptome analysis to examine the immune response in the lungs of corticosteroid-treated PCP mice. The results showed down-regulation in the genes related to both native immunity, such as antigen processing and presentation, inflammatory response, and phagocytosis, as well as B and T lymphocyte immunity. The repression of gene expression, corresponding to B cell immunity, including B cell signaling, homeostasis, and Ig production, was prominent. The finding was confirmed by quantitative PCR of mouse lungs and the peripheral blood of patients with PCP. Flow cytometry also revealed a significant depletion of B cells in corticosteroid-treated PCP mice. Our study has highlighted that corticosteroid treatment suppresses the B cell immunity in the PCP host, which is likely one of the main reasons that corticosteroid treatment may stimulate PCP development.

  3. Evaluating the effective numbers of independent tests and significant p-value thresholds in commercial genotyping arrays and public imputation reference datasets.

    PubMed

    Li, Miao-Xin; Yeung, Juilian M Y; Cherny, Stacey S; Sham, Pak C

    2012-05-01

    Current genome-wide association studies (GWAS) use commercial genotyping microarrays that can assay over a million single nucleotide polymorphisms (SNPs). The number of SNPs is further boosted by advanced statistical genotype-imputation algorithms and large SNP databases for reference human populations. The testing of a huge number of SNPs needs to be taken into account in the interpretation of statistical significance in such genome-wide studies, but this is complicated by the non-independence of SNPs because of linkage disequilibrium (LD). Several previous groups have proposed the use of the effective number of independent markers (M(e)) for the adjustment of multiple testing, but current methods of calculation for M(e) are limited in accuracy or computational speed. Here, we report a more robust and fast method to calculate M(e). Applying this efficient method [implemented in a free software tool named Genetic type 1 error calculator (GEC)], we systematically examined the M(e), and the corresponding p-value thresholds required to control the genome-wide type 1 error rate at 0.05, for 13 Illumina or Affymetrix genotyping arrays, as well as for HapMap Project and 1000 Genomes Project datasets which are widely used in genotype imputation as reference panels. Our results suggested the use of a p-value threshold of ~10(-7) as the criterion for genome-wide significance for early commercial genotyping arrays, but slightly more stringent p-value thresholds ~5 × 10(-8) for current or merged commercial genotyping arrays, ~10(-8) for all common SNPs in the 1000 Genomes Project dataset and ~5 × 10(-8) for the common SNPs only within genes.

  4. Young Mania Rating Scale: how to interpret the numbers? Determination of a severity threshold and of the minimal clinically significant difference in the EMBLEM cohort.

    PubMed

    Lukasiewicz, Michael; Gerard, Stephanie; Besnard, Adeline; Falissard, Bruno; Perrin, Elena; Sapin, Helene; Tohen, Mauricio; Reed, Catherine; Azorin, Jean-Michel

    2013-03-01

    The aim of this analysis was to identify Young Mania Rating Scale (YMRS) meaningful benchmarks for clinicians (severity threshold, minimal clinically significant difference [MCSD]) using the Clinical Global Impressions Bipolar (CGI-BP) mania scale, to provide a clinical perspective to randomized clinical trials (RCTs) results. We used the cohort of patients with acute manic/mixed state of bipolar disorders (N = 3459) included in the European Mania in Bipolar Longitudinal Evaluation of Medication (EMBLEM) study. A receiver-operating characteristic analysis was performed on randomly selected patients to determine the YMRS optimal severity threshold with CGI-BP mania score ≥ "Markedly ill" defining severity. The MCSD (clinically meaningful change in score relative to one point difference in CGI-BP mania for outcome measures) of YMRS, was assessed with a linear regression on baseline data. At baseline, YMRS mean score was 26.4 (±9.9), CGI-BP mania mean score was 4.8 (±1.0) and 61.7% of patients had a score ≥ 5. The optimal YMRS severity threshold of 25 (positive predictive value [PPV] = 83.0%; negative predictive value [NPV] = 66.0%) was determined. In this cohort, a YMRS score of 20 (typical cutoff for RCTs inclusion criteria) corresponds to a PPV of 74.6% and to a NPV of 77.6%, meaning that the majority of patients included would be classified as severely ill. The YMRS minimal clinically significant difference was 6.6 points.

  5. The thresholds for statistical and clinical significance – a five-step procedure for evaluation of intervention effects in randomised clinical trials

    PubMed Central

    2014-01-01

    Background Thresholds for statistical significance are insufficiently demonstrated by 95% confidence intervals or P-values when assessing results from randomised clinical trials. First, a P-value only shows the probability of getting a result assuming that the null hypothesis is true and does not reflect the probability of getting a result assuming an alternative hypothesis to the null hypothesis is true. Second, a confidence interval or a P-value showing significance may be caused by multiplicity. Third, statistical significance does not necessarily result in clinical significance. Therefore, assessment of intervention effects in randomised clinical trials deserves more rigour in order to become more valid. Methods Several methodologies for assessing the statistical and clinical significance of intervention effects in randomised clinical trials were considered. Balancing simplicity and comprehensiveness, a simple five-step procedure was developed. Results For a more valid assessment of results from a randomised clinical trial we propose the following five-steps: (1) report the confidence intervals and the exact P-values; (2) report Bayes factor for the primary outcome, being the ratio of the probability that a given trial result is compatible with a ‘null’ effect (corresponding to the P-value) divided by the probability that the trial result is compatible with the intervention effect hypothesised in the sample size calculation; (3) adjust the confidence intervals and the statistical significance threshold if the trial is stopped early or if interim analyses have been conducted; (4) adjust the confidence intervals and the P-values for multiplicity due to number of outcome comparisons; and (5) assess clinical significance of the trial results. Conclusions If the proposed five-step procedure is followed, this may increase the validity of assessments of intervention effects in randomised clinical trials. PMID:24588900

  6. Comparative Analysis of the Shadoo Gene between Cattle and Buffalo Reveals Significant Differences

    PubMed Central

    Du, Shou-Hui; Wang, Si-Qi; Zhang, Ya-Ping

    2012-01-01

    Background While prions play a central role in the pathogenesis of transmissible spongiform encephalopathies, the biology of these proteins and the pathophysiology of these diseases remain largely unknown. Since no case of bovine spongiform encephalopathy (BSE) has ever been reported in buffalo despite their phylogenetic proximity to cattle, genetic differences may be driving the different susceptibilities of these two species to BSE. We thus hypothesized that differences in expression of the most recently identified member of the prion family or Shadoo (SPRN) gene may relate to these species-specific differences. Principal Findings We first analyzed and compared the polymorphisms of the SPRN gene (∼4.4 kb), including the putative promoter, coding and 3′ regions, and further verified the entire ORF and putative promoter. This yielded a total of 117 fixed differences, remarkably: 1) a 12-bp insertion/deletion polymorphism in the hydrophobic domain of the cattle but not buffalo gene, introducing a four amino acid expansion/contraction in a series of 5 tandem Ala/Gly-containing repeats; 2) two fixed missense mutations (102Ser→Gly and 119Thr→Ala), and three missense mutations (92Pro>Thr/Met, 122Thr>Ile and 139Arg>Trp) in the coding region presenting different (P<0.05) genotypic and allelic frequency distributions between cattle and buffalo; and, 3) functional luciferase-reporter experiments for the predicted promoter region, consistent with a significantly higher activity in buffalo than cattle. Supporting these findings, immunoblotting revealed higher relative expression levels of Sho protein in cerebrum from buffalo than from cattle. In addition, for cattle, highest Sho expression was detected in obex, as compared to cerebrum or cerebellum. Significance Our findings support Sho as a non-PrP specific marker for prion infections, with obex as the best tissue source for the detection of Sho in TSE rapid tests. Moreover, these discoveries may prove advantageous

  7. Disease-aging network reveals significant roles of aging genes in connecting genetic diseases.

    PubMed

    Wang, Jiguang; Zhang, Shihua; Wang, Yong; Chen, Luonan; Zhang, Xiang-Sun

    2009-09-01

    One of the challenging problems in biology and medicine is exploring the underlying mechanisms of genetic diseases. Recent studies suggest that the relationship between genetic diseases and the aging process is important in understanding the molecular mechanisms of complex diseases. Although some intricate associations have been investigated for a long time, the studies are still in their early stages. In this paper, we construct a human disease-aging network to study the relationship among aging genes and genetic disease genes. Specifically, we integrate human protein-protein interactions (PPIs), disease-gene associations, aging-gene associations, and physiological system-based genetic disease classification information in a single graph-theoretic framework and find that (1) human disease genes are much closer to aging genes than expected by chance; and (2) diseases can be categorized into two types according to their relationships with aging. Type I diseases have their genes significantly close to aging genes, while type II diseases do not. Furthermore, we examine the topological characters of the disease-aging network from a systems perspective. Theoretical results reveal that the genes of type I diseases are in a central position of a PPI network while type II are not; (3) more importantly, we define an asymmetric closeness based on the PPI network to describe relationships between diseases, and find that aging genes make a significant contribution to associations among diseases, especially among type I diseases. In conclusion, the network-based study provides not only evidence for the intricate relationship between the aging process and genetic diseases, but also biological implications for prying into the nature of human diseases.

  8. PAG/Cbp suppression reveals a contribution of CTLA-4 to setting the activation threshold in T cells

    PubMed Central

    2013-01-01

    Background PAG/Cbp represents a ubiquitous mechanism for regulating Src family kinases by recruiting Csk to the plasma membrane, thereby controlling cellular activation. Since Src kinases are known oncogenes, we used RNA interference in primary human T cells to test whether the loss of PAG resulted in lymphocyte transformation. Results PAG-depletion enhanced Src kinase activity and augmented proximal T-cell receptor signaling; exactly the phenotype expected for loss of this negative regulator. Surprisingly, rather than becoming hyper-proliferative, PAG-suppressed T cells became unresponsive. This was mediated by a Fyn-dependent hyper-phosphorylation of the inhibitory receptor CTLA-4, which recruited the protein tyrosine phosphatase Shp-1 to lipid rafts. Co-suppression of CTLA-4 abrogates this inhibition and restores proliferation to T cells. Conclusion We have identified a fail-safe mechanism as well as a novel contribution of CTLA-4 to setting the activation threshold in T cells. PMID:23601194

  9. Genetic Analysis of Baker's Yeast Msh4-Msh5 Reveals a Threshold Crossover Level for Meiotic Viability

    PubMed Central

    Nishant, K. T.; Chen, Cheng; Shinohara, Miki; Shinohara, Akira; Alani, Eric

    2010-01-01

    During meiosis, the Msh4-Msh5 complex is thought to stabilize single-end invasion intermediates that form during early stages of recombination and subsequently bind to Holliday junctions to facilitate crossover formation. To analyze Msh4-Msh5 function, we mutagenized 57 residues in Saccharomyces cerevisiae Msh4 and Msh5 that are either conserved across all Msh4/5 family members or are specific to Msh4 and Msh5. The Msh5 subunit appeared more sensitive to mutagenesis. We identified msh4 and msh5 threshold (msh4/5-t) mutants that showed wild-type spore viability and crossover interference but displayed, compared to wild-type, up to a two-fold decrease in crossing over on large and medium sized chromosomes (XV, VII, VIII). Crossing over on a small chromosome, however, approached wild-type levels. The msh4/5-t mutants also displayed synaptonemal complex assembly defects. A triple mutant containing a msh4/5-t allele and mutations that decreased meiotic double-strand break levels (spo11-HA) and crossover interference (pch2Δ) showed synergistic defects in spore viability. Together these results indicate that the baker's yeast meiotic cell does not require the ∼90 crossovers maintained by crossover homeostasis to form viable spores. They also show that Pch2-mediated crossover interference is important to maintain meiotic viability when crossovers become limiting. PMID:20865162

  10. Identification of Threshold Prostate Specific Antigen Levels to Optimize the Detection of Clinically Significant Prostate Cancer by Magnetic Resonance Imaging/Ultrasound Fusion Guided Biopsy

    PubMed Central

    Shakir, Nabeel A.; George, Arvin K.; Siddiqui, M. Minhaj; Rothwax, Jason T.; Rais-Bahrami, Soroush; Stamatakis, Lambros; Su, Daniel; Okoro, Chinonyerem; Raskolnikov, Dima; Walton-Diaz, Annerleim; Simon, Richard; Turkbey, Baris; Choyke, Peter L.; Merino, Maria J.; Wood, Bradford J.; Pinto, Peter A.

    2015-01-01

    Purpose Prostate specific antigen sensitivity increases with lower threshold values but with a corresponding decrease in specificity. Magnetic resonance imaging/ultrasound targeted biopsy detects prostate cancer more efficiently and of higher grade than standard 12-core transrectal ultrasound biopsy but the optimal population for its use is not well defined. We evaluated the performance of magnetic resonance imaging/ultrasound targeted biopsy vs 12-core biopsy across a prostate specific antigen continuum. Materials and Methods We reviewed the records of all patients enrolled in a prospective trial who underwent 12-core transrectal ultrasound and magnetic resonance imaging/ultrasound targeted biopsies from August 2007 through February 2014. Patients were stratified by each of 4 prostate specific antigen cutoffs. The greatest Gleason score using either biopsy method was compared in and across groups as well as across the population prostate specific antigen range. Clinically significant prostate cancer was defined as Gleason 7 (4 + 3) or greater. Univariate and multivariate analyses were performed. Results A total of 1,003 targeted and 12-core transrectal ultrasound biopsies were performed, of which 564 diagnosed prostate cancer for a 56.2% detection rate. Targeted biopsy led to significantly more upgrading to clinically significant disease compared to 12-core biopsy. This trend increased more with increasing prostate specific antigen, specifically in patients with prostate specific antigen 4 to 10 and greater than 10 ng/ml. Prostate specific antigen 5.2 ng/ml or greater captured 90% of upgrading by targeted biopsy, corresponding to 64% of patients who underwent multiparametric magnetic resonance imaging and subsequent fusion biopsy. Conversely a greater proportion of clinically insignificant disease was detected by 12-core vs targeted biopsy overall. These differences persisted when controlling for potential confounders on multivariate analysis. Conclusions Prostate

  11. Dynamic metabolome profiling reveals significant metabolic changes during grain development of bread wheat (Triticum aestivum L.).

    PubMed

    Zhen, Shoumin; Dong, Kun; Deng, Xiong; Zhou, Jiaxing; Xu, Xuexin; Han, Caixia; Zhang, Wenying; Xu, Yanhao; Wang, Zhimin; Yan, Yueming

    2016-08-01

    Metabolites in wheat grains greatly influence nutritional values. Wheat provides proteins, minerals, B-group vitamins and dietary fiber to humans. These metabolites are important to human health. However, the metabolome of the grain during the development of bread wheat has not been studied so far. In this work the first dynamic metabolome of the developing grain of the elite Chinese bread wheat cultivar Zhongmai 175 was analyzed, using non-targeted gas chromatography/mass spectrometry (GC/MS) for metabolite profiling. In total, 74 metabolites were identified over the grain developmental stages. Metabolite-metabolite correlation analysis revealed that the metabolism of amino acids, carbohydrates, organic acids, amines and lipids was interrelated. An integrated metabolic map revealed a distinct regulatory profile. The results provide information that can be used by metabolic engineers and molecular breeders to improve wheat grain quality. The present metabolome approach identified dynamic changes in metabolite levels, and correlations among such levels, in developing seeds. The comprehensive metabolic map may be useful when breeding programs seek to improve grain quality. The work highlights the utility of GC/MS-based metabolomics, in conjunction with univariate and multivariate data analysis, when it is sought to understand metabolic changes in developing seeds. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

  12. Patient-Specific Simulations Reveal Significant Differences in Mechanical Stimuli in Venous and Arterial Coronary Grafts.

    PubMed

    Ramachandra, Abhay B; Kahn, Andrew M; Marsden, Alison L

    2016-08-01

    Mechanical stimuli are key to understanding disease progression and clinically observed differences in failure rates between arterial and venous grafts following coronary artery bypass graft surgery. We quantify biologically relevant mechanical stimuli, not available from standard imaging, in patient-specific simulations incorporating non-invasive clinical data. We couple CFD with closed-loop circulatory physiology models to quantify biologically relevant indices, including wall shear, oscillatory shear, and wall strain. We account for vessel-specific material properties in simulating vessel wall deformation. Wall shear was significantly lower (p = 0.014*) and atheroprone area significantly higher (p = 0.040*) in venous compared to arterial grafts. Wall strain in venous grafts was significantly lower (p = 0.003*) than in arterial grafts while no significant difference was observed in oscillatory shear index. Simulations demonstrate significant differences in mechanical stimuli acting on venous vs. arterial grafts, in line with clinically observed graft failure rates, offering a promising avenue for stratifying patients at risk for graft failure.

  13. Patient-Specific Simulations Reveal Significant Differences in Mechanical Stimuli in Venous and Arterial Coronary Grafts

    PubMed Central

    Ramachandra, Abhay B.; Kahn, Andrew M.

    2017-01-01

    Mechanical stimuli are key to understanding disease progression and clinically observed differences in failure rates between arterial and venous grafts following coronary artery bypass graft surgery. We quantify biologically relevant mechanical stimuli, not available from standard imaging, in patient-specific simulations incorporating non-invasive clinical data. We couple CFD with closed-loop circulatory physiology models to quantify biologically relevant indices, including wall shear, oscillatory shear, and wall strain. We account for vessel-specific material properties in simulating vessel wall deformation. Wall shear was significantly lower (p = 0.014*) and atheroprone area significantly higher (p = 0.040*) in venous compared to arterial grafts. Wall strain in venous grafts was significantly lower (p = 0.003*) than in arterial grafts while no significant difference was observed in oscillatory shear index. Simulations demonstrate significant differences in mechanical stimuli acting on venous vs. arterial grafts, in line with clinically observed graft failure rates, offering a promising avenue for stratifying patients at risk for graft failure. PMID:27447176

  14. Significant Locus and Metabolic Genetic Correlations Revealed in Genome-Wide Association Study of Anorexia Nervosa.

    PubMed

    Duncan, Laramie; Yilmaz, Zeynep; Gaspar, Helena; Walters, Raymond; Goldstein, Jackie; Anttila, Verneri; Bulik-Sullivan, Brendan; Ripke, Stephan; Thornton, Laura; Hinney, Anke; Daly, Mark; Sullivan, Patrick F; Zeggini, Eleftheria; Breen, Gerome; Bulik, Cynthia M

    2017-09-01

    The authors conducted a genome-wide association study of anorexia nervosa and calculated genetic correlations with a series of psychiatric, educational, and metabolic phenotypes. Following uniform quality control and imputation procedures using the 1000 Genomes Project (phase 3) in 12 case-control cohorts comprising 3,495 anorexia nervosa cases and 10,982 controls, the authors performed standard association analysis followed by a meta-analysis across cohorts. Linkage disequilibrium score regression was used to calculate genome-wide common variant heritability (single-nucleotide polymorphism [SNP]-based heritability [h(2)SNP]), partitioned heritability, and genetic correlations (rg) between anorexia nervosa and 159 other phenotypes. Results were obtained for 10,641,224 SNPs and insertion-deletion variants with minor allele frequencies >1% and imputation quality scores >0.6. The h(2)SNP of anorexia nervosa was 0.20 (SE=0.02), suggesting that a substantial fraction of the twin-based heritability arises from common genetic variation. The authors identified one genome-wide significant locus on chromosome 12 (rs4622308) in a region harboring a previously reported type 1 diabetes and autoimmune disorder locus. Significant positive genetic correlations were observed between anorexia nervosa and schizophrenia, neuroticism, educational attainment, and high-density lipoprotein cholesterol, and significant negative genetic correlations were observed between anorexia nervosa and body mass index, insulin, glucose, and lipid phenotypes. Anorexia nervosa is a complex heritable phenotype for which this study has uncovered the first genome-wide significant locus. Anorexia nervosa also has large and significant genetic correlations with both psychiatric phenotypes and metabolic traits. The study results encourage a reconceptualization of this frequently lethal disorder as one with both psychiatric and metabolic etiology.

  15. Genomes of three tomato pathogens within the Ralstonia solanacearum species complex reveal significant evolutionary divergence

    PubMed Central

    2010-01-01

    Background The Ralstonia solanacearum species complex includes thousands of strains pathogenic to an unusually wide range of plant species. These globally dispersed and heterogeneous strains cause bacterial wilt diseases, which have major socio-economic impacts. Pathogenicity is an ancestral trait in R. solanacearum and strains with high genetic variation can be subdivided into four phylotypes, correlating to isolates from Asia (phylotype I), the Americas (phylotype IIA and IIB), Africa (phylotype III) and Indonesia (phylotype IV). Comparison of genome sequences strains representative of this phylogenetic diversity can help determine which traits allow this bacterium to be such a pathogen of so many different plant species and how the bacteria survive in many different habitats. Results The genomes of three tomato bacterial wilt pathogens, CFBP2957 (phy. IIA), CMR15 (phy. III) and PSI07 (phy. IV) were sequenced and manually annotated. These genomes were compared with those of three previously sequenced R. solanacearum strains: GMI1000 (tomato, phy. I), IPO1609 (potato, phy. IIB), and Molk2 (banana, phy. IIB). The major genomic features (size, G+C content, number of genes) were conserved across all of the six sequenced strains. Despite relatively high genetic distances (calculated from average nucleotide identity) and many genomic rearrangements, more than 60% of the genes of the megaplasmid and 70% of those on the chromosome are syntenic. The three new genomic sequences revealed the presence of several previously unknown traits, probably acquired by horizontal transfers, within the genomes of R. solanacearum, including a type IV secretion system, a rhi-type anti-mitotic toxin and two small plasmids. Genes involved in virulence appear to be evolving at a faster rate than the genome as a whole. Conclusions Comparative analysis of genome sequences and gene content confirmed the differentiation of R. solanacearum species complex strains into four phylotypes. Genetic

  16. Genomes of three tomato pathogens within the Ralstonia solanacearum species complex reveal significant evolutionary divergence.

    PubMed

    Remenant, Benoît; Coupat-Goutaland, Bénédicte; Guidot, Alice; Cellier, Gilles; Wicker, Emmanuel; Allen, Caitilyn; Fegan, Mark; Pruvost, Olivier; Elbaz, Mounira; Calteau, Alexandra; Salvignol, Gregory; Mornico, Damien; Mangenot, Sophie; Barbe, Valérie; Médigue, Claudine; Prior, Philippe

    2010-06-15

    The Ralstonia solanacearum species complex includes thousands of strains pathogenic to an unusually wide range of plant species. These globally dispersed and heterogeneous strains cause bacterial wilt diseases, which have major socio-economic impacts. Pathogenicity is an ancestral trait in R. solanacearum and strains with high genetic variation can be subdivided into four phylotypes, correlating to isolates from Asia (phylotype I), the Americas (phylotype IIA and IIB), Africa (phylotype III) and Indonesia (phylotype IV). Comparison of genome sequences strains representative of this phylogenetic diversity can help determine which traits allow this bacterium to be such a pathogen of so many different plant species and how the bacteria survive in many different habitats. The genomes of three tomato bacterial wilt pathogens, CFBP2957 (phy. IIA), CMR15 (phy. III) and PSI07 (phy. IV) were sequenced and manually annotated. These genomes were compared with those of three previously sequenced R. solanacearum strains: GMI1000 (tomato, phy. I), IPO1609 (potato, phy. IIB), and Molk2 (banana, phy. IIB). The major genomic features (size, G+C content, number of genes) were conserved across all of the six sequenced strains. Despite relatively high genetic distances (calculated from average nucleotide identity) and many genomic rearrangements, more than 60% of the genes of the megaplasmid and 70% of those on the chromosome are syntenic. The three new genomic sequences revealed the presence of several previously unknown traits, probably acquired by horizontal transfers, within the genomes of R. solanacearum, including a type IV secretion system, a rhi-type anti-mitotic toxin and two small plasmids. Genes involved in virulence appear to be evolving at a faster rate than the genome as a whole. Comparative analysis of genome sequences and gene content confirmed the differentiation of R. solanacearum species complex strains into four phylotypes. Genetic distances between strains, in

  17. Growth behaviors of bacteria reveal the evolutionary significance of energy-efficiency

    NASA Astrophysics Data System (ADS)

    Maitra, Arijit; Dill, Ken

    2015-03-01

    Microorganisms have evolved a mosaic of gene expression changes to adapt their growth behaviors to changing environmental conditions. The subset of genes coding for the protein translation machineries, the ribosomes, however display robust linear activities with growth rates. Such patterns are considered to be the source of growth itself. There is another robust growth law, observed by Monod in the 1940s, in which bacteria are able to scale their growth with food concentration before plateauing off to a constant value. To interlink these observed growth laws we derive an analytical network model that leverages metabolic data to capture how the cell manages its exchange of energy to support costly gene expression. The model explores the limits of energy allocation for function and reveals evolutionary principles. Among others, we find, in glucose medium the fastest growing E. coli operate close to their maximum energy-efficiency. Optimization of energy efficiency provides a quantitative limit to how much energy is allocated for protein synthesis and it is determined by evolutionarily selected structural and biophysical constants. We conclude that energy efficiency has played a key role in bacterial evolution. Supported by the Laufer Center for Physical and Quantitative Biology, SBU.

  18. A Paleocene lowland macroflora from Patagonia reveals significantly greater richness than North American analogs

    NASA Astrophysics Data System (ADS)

    Iglesias, Ari; Wilf, Peter; Johnson, Kirk R.; Zamuner, Alba B.; Rubén Cúneo, N.; Matheos, Sergio D.; Singer, Bradley S.

    2007-10-01

    Few South American macrofloras of Paleocene age are known, and this limits our knowledge of diversity and composition between the end-Cretaceous event and the Eocene appearance of high floral diversity. We report new, unbiased collections of 2516 compression specimens from the Paleocene Salamanca Formation (ca. 61.7 Ma) from two localities in the Palacio de los Loros exposures in southern Chubut, Patagonia, Argentina. Our samples reveal considerably greater richness than was previously known from the Paleocene of Patagonia, including 36 species of angiosperm leaves as well as angiosperm fruits, flowers, and seeds; ferns; and conifer leaves, cones, and seeds. The floras, which are from siltstone and sandstone channel-fills deposited on low-relief floodplain landscapes in a humid, warm temperate climate, are climatically and paleoenvironmentally comparable to many quantitatively collected Paleocene floras from the Western Interior of North America. Adjusted for sample size, there are >50% more species at each Palacio de los Loros quarry than in any comparable U.S. Paleocene sample. These results indicate more vibrant terrestrial ecosystems in Patagonian than in North American floodplain environments ˜4 m.y. after the end-Cretaceous extinction, and they push back the time line 10 m.y. for the evolution of high floral diversity in South America. The cause of the dis parity is unknown but could involve reduced impact effects because of greater distance from the Chicxulub site, higher latest Cretaceous diversity, or faster recovery or immigration rates.

  19. Village energy survey reveals missing rural raw coal in northern China: Significance in science and policy.

    PubMed

    Zhi, Guorui; Zhang, Yayun; Sun, Jianzhong; Cheng, Miaomiao; Dang, Hongyan; Liu, Shijie; Yang, Junchao; Zhang, Yuzhe; Xue, Zhigang; Li, Shuyuan; Meng, Fan

    2017-04-01

    Burning coal for winter heating has been considered a major contributor to northern China's winter haze, with the district heating boilers holding the balance. However a decade of intensive efforts on district heating boilers brought few improvements to northern China's winter air quality, arousing a speculation that the household heating stoves mainly in rural area rather than the district heating boilers mainly in urban area dominate coal emissions in winter. This implies an extreme underestimation of rural household coal consumption by the China Energy Statistical Yearbooks (CESYs), although direct evidence supporting this speculation is lacking. A village energy survey campaign was launched to gather the firsthand information on household coal consumption in the rural areas of two cities, Baoding (in Hebei province) and Beijing (the capital of China). The survey data show that the rural raw coal consumption in Baoding (5.04 × 10(3) kt) was approximately 6.5 times the value listed in the official CESY 2013 and exceeded the rural total of whole Hebei Province (4668 kt), revealing a huge amount of raw coal missing from the current statistical system. More importantly, rural emissions of particulate matter (PM) and SO2 from raw coal, which had never been included in widely distributing environmental statistical reports, were found higher than those from industrial and urban household sectors in the two cities in 2013, which highlights the importance of rural coal burning in creating northern China's heavy haze and helps to explain why a number of modeling predictions on ambient pollutant concentrations based on normal emission inventories were more bias-prone in winter season than in other seasons. We therefore recommend placing greater emphasis on the "missing" rural raw coal to help China in its long-term ambition to achieve clean air in the context of rapid economic development.

  20. Melatonin Distribution Reveals Clues to Its Biological Significance in Basal Metazoans

    PubMed Central

    Roopin, Modi; Levy, Oren

    2012-01-01

    Although nearly ubiquitous in nature, the precise biological significance of endogenous melatonin is poorly understood in phylogenetically basal taxa. In the present work, we describe insights into the functional role of melatonin at the most “basal” level of metazoan evolution. Hitherto unknown morphological determinants of melatonin distribution were evaluated in Nematostella vectensis by detecting melatonin immunoreactivity and examining the spatial gene expression patterns of putative melatonin biosynthetic and receptor elements that are located at opposing ends of the melatonin signaling pathway. Immuno-melatonin profiling indicated an elaborate interaction with reproductive tissues, reinforcing previous conjectures of a melatonin-responsive component in anthozoan reproduction. In situ hybridization (ISH) to putative melatonin receptor elements highlighted the possibility that the bioregulatory effects of melatonin in anthozoan reproduction may be mediated by interactions with membrane receptors, as in higher vertebrates. Another intriguing finding of the present study pertains to the prevalence of melatonin in centralized nervous structures. This pattern may be of great significance given that it 1) identifies an ancestral association between melatonin and key neuronal components and 2) potentially implies that certain effects of melatonin in basal species may be spread widely by regionalized nerve centers. PMID:23300630

  1. Investigation of seasonal melting of Greenland using GPS records reveals significant ice mass loss in 2010

    NASA Astrophysics Data System (ADS)

    Yang, Q.; Dixon, T.; Wdowinski, S.

    2011-12-01

    Greenland has experienced significant ice mass loss in the past decade. High-precision global positioning system (GPS) data from sites on the rocky margin of Greenland enable measurement of vertical motion of the coastal area, which is an indicator of nearby mass loss. In this study, seasonal melting variation of the Greenland ice sheet (GrIS) is investigated using GPS vertical displacement data. Using a cubic spline fitting model, we retrieve three variables of the seasonal melting pattern for GrIS from 1996 to 2010: date of the beginning and end of melt season, length of melt season, and amount of uplift in the melt season. Data from three long -term sites on the periphery of Greenland show anomalously large uplift in 2010, implying significant melting in 2010. Preliminary results also show an early onset of melting in 2010, about 8 days earlier than the 1996-2009 average. In 2010, Greenland experienced a warmer and drier winter as well as a very warm summer, which presumably contributed to the anomalous ice mass loss of 2010.

  2. Diurnal sampling reveals significant variation in CO2 emission from a tropical productive lake.

    PubMed

    Reis, P C J; Barbosa, F A R

    2014-08-01

    It is well accepted in the literature that lakes are generally net heterotrophic and supersaturated with CO2 because they receive allochthonous carbon inputs. However, autotrophy and CO2 undersaturation may happen for at least part of the time, especially in productive lakes. Since diurnal scale is particularly important to tropical lakes dynamics, we evaluated diurnal changes in pCO2 and CO2 flux across the air-water interface in a tropical productive lake in southeastern Brazil (Lake Carioca) over two consecutive days. Both pCO2 and CO2 flux were significantly different between day (9:00 to 17:00) and night (21:00 to 5:00) confirming the importance of this scale for CO2 dynamics in tropical lakes. Net heterotrophy and CO2 outgassing from the lake were registered only at night, while significant CO2 emission did not happen during the day. Dissolved oxygen concentration and temperature trends over the diurnal cycle indicated the dependence of CO2 dynamics on lake metabolism (respiration and photosynthesis). This study indicates the importance of considering the diurnal scale when examining CO2 emissions from tropical lakes.

  3. Global gene expression profiles reveal significant nuclear reprogramming by the blastocyst stage after cloning.

    PubMed

    Smith, Sadie L; Everts, Robin E; Tian, X Cindy; Du, Fuliang; Sung, Li-Ying; Rodriguez-Zas, Sandra L; Jeong, Byeong-Seon; Renard, Jean-Paul; Lewin, Harris A; Yang, Xiangzhong

    2005-12-06

    Nuclear transfer (NT) has potential applications in agriculture and biomedicine, but the technology is hindered by low efficiency. Global gene expression analysis of clones is important for the comprehensive study of nuclear reprogramming. Here, we compared global gene expression profiles of individual bovine NT blastocysts with their somatic donor cells and fertilized control embryos using cDNA microarray technology. The NT embryos' gene expression profiles were drastically different from those of their donor cells and closely resembled those of the naturally fertilized embryos. Our findings demonstrate that the NT embryos have undergone significant nuclear reprogramming by the blastocyst stage; however, problems may occur during redifferentiation for tissue genesis and organogenesis, and small reprogramming errors may be magnified downstream in development.

  4. Vane blood-bathed technique reveals the significance of adrenergic reaction in myocardial infarction.

    PubMed

    Herbaczyńska-Cedro, Krystyna; Ceremuzyński, Leszek

    2010-01-01

    Using the blood-bathed technique of Vane we induced acute coronary occlusion in the dog and subsequently detected adrenaline release into the circulatory system, determined the rate of release and documented its significance for induction of cardiac arrhythmias. In the intact anesthetized dog, adrenaline excess of the magnitude released after coronary occlusion was sufficient to injure the healthy myocardium and to induce unfavorable metabolic systemic alterations. Subsequently, clinical research has documented that a serious clinical course of acute myocardial infarction is associated not only with enhanced excretion of catecholamines but also with augmentation of plasma renin activity and aldosterone levels. The positive therapeutic effect of aldosterone antagonists in acute myocardial infarction has been documented. The clinical value of our results, which were obtained in experimental and clinical studies, was later confirmed in multi-center trials.

  5. Seabird diving behaviour reveals the functional significance of shelf-sea fronts as foraging hotspots

    PubMed Central

    Miller, P. I.; Embling, C. B.; Bicknell, A. W. J.; Hosegood, P. J.; Morgan, G.; Ingram, S. N.

    2016-01-01

    Oceanic fronts are key habitats for a diverse range of marine predators, yet how they influence fine-scale foraging behaviour is poorly understood. Here, we investigated the dive behaviour of northern gannets Morus bassanus in relation to shelf-sea fronts. We GPS (global positioning system) tracked 53 breeding birds and examined the relationship between 1901 foraging dives (from time-depth recorders) and thermal fronts (identified via Earth Observation composite front mapping) in the Celtic Sea, Northeast Atlantic. We (i) used a habitat-use availability analysis to determine whether gannets preferentially dived at fronts, and (ii) compared dive characteristics in relation to fronts to investigate the functional significance of these oceanographic features. We found that relationships between gannet dive probabilities and fronts varied by frontal metric and sex. While both sexes were more likely to dive in the presence of seasonally persistent fronts, links to more ephemeral features were less clear. Here, males were positively correlated with distance to front and cross-front gradient strength, with the reverse for females. Both sexes performed two dive strategies: shallow V-shaped plunge dives with little or no active swim phase (92% of dives) and deeper U-shaped dives with an active pursuit phase of at least 3 s (8% of dives). When foraging around fronts, gannets were half as likely to engage in U-shaped dives compared with V-shaped dives, independent of sex. Moreover, V-shaped dive durations were significantly shortened around fronts. These behavioural responses support the assertion that fronts are important foraging habitats for marine predators, and suggest a possible mechanistic link between the two in terms of dive behaviour. This research also emphasizes the importance of cross-disciplinary research when attempting to understand marine ecosystems. PMID:27703698

  6. Seabird diving behaviour reveals the functional significance of shelf-sea fronts as foraging hotspots

    NASA Astrophysics Data System (ADS)

    Cox, S. L.; Miller, P. I.; Embling, C. B.; Scales, K. L.; Bicknell, A. W. J.; Hosegood, P. J.; Morgan, G.; Ingram, S. N.; Votier, S. C.

    2016-09-01

    Oceanic fronts are key habitats for a diverse range of marine predators, yet how they influence fine-scale foraging behaviour is poorly understood. Here, we investigated the dive behaviour of northern gannets Morus bassanus in relation to shelf-sea fronts. We GPS (global positioning system) tracked 53 breeding birds and examined the relationship between 1901 foraging dives (from time-depth recorders) and thermal fronts (identified via Earth Observation composite front mapping) in the Celtic Sea, Northeast Atlantic. We (i) used a habitat-use availability analysis to determine whether gannets preferentially dived at fronts, and (ii) compared dive characteristics in relation to fronts to investigate the functional significance of these oceanographic features. We found that relationships between gannet dive probabilities and fronts varied by frontal metric and sex. While both sexes were more likely to dive in the presence of seasonally persistent fronts, links to more ephemeral features were less clear. Here, males were positively correlated with distance to front and cross-front gradient strength, with the reverse for females. Both sexes performed two dive strategies: shallow V-shaped plunge dives with little or no active swim phase (92% of dives) and deeper U-shaped dives with an active pursuit phase of at least 3 s (8% of dives). When foraging around fronts, gannets were half as likely to engage in U-shaped dives compared with V-shaped dives, independent of sex. Moreover, V-shaped dive durations were significantly shortened around fronts. These behavioural responses support the assertion that fronts are important foraging habitats for marine predators, and suggest a possible mechanistic link between the two in terms of dive behaviour. This research also emphasizes the importance of cross-disciplinary research when attempting to understand marine ecosystems.

  7. Recent climatic changes in the Northern Extratropics with foci on extreme events and transitions through environmentally and socio-economically significant thresholds (Invited)

    NASA Astrophysics Data System (ADS)

    Groisman, P. Y.; Knight, R. W.; Karl, T. R.

    2009-12-01

    Contemporary climate models send several very different messages regarding changes in the energy and water cycle over northern extratropical land areas that are leading to climate extremes of different kinds. For the regions of the Northern Extratropics with a dense network of long-term time series of daily observations, we quantified several lines of evidence of contemporary changes that have lead to changes in the frequency (and intensity) of extreme events. Among these extreme events are very heavy rainfall events, prolonged no-rain intervals, indices that characterize severity of the “fire” weather, and timing and magnitude of peak streamflow. We paid a special attention to recent climatic changes in the Northern Extratropics characteristics of the seasonal cycle such as temperature transitions through environmentally and socio-economically significant thresholds (e.g., no-frost period, duration and “strength” of growing season and cold seasons, frequency and intensity of hot and cold spells) and energy accumulated indices that are proportional to the societal need to cope with seasonal weather (e.g., heating-degree and cooling degree days). These thresholds do not necessarily characterize extreme events, but rather changes in their dates, duration, totals, or distribution within the year which may affect society. In particular, our analyses for North America show increasing rates of changes in most of characteristics of the temperature seasonal cycle during the past few decades. Some of these changes can be considered as positive while others cause concern. In particular, in the area of the North American Monsoon (southwestern US) we observe strong warming that together with the precipitation deficit increases chances of detrimental weather conditions such as extremely hot nights that affect human health, prolonged no-rain periods, and higher values of the fire weather indices. Generally, the impact of hot nights on human health (a relative frequency

  8. Denaturation studies reveal significant differences between GFP and blue fluorescent protein.

    PubMed

    Saeed, Ibtesam A; Ashraf, S Salman

    2009-10-01

    Green fluorescent protein (GFP) is an unusually stable fluorescent protein that belongs to a family of related auto-fluorescent proteins (AFPs). These AFPs have been generated from jellyfish GFP by mutating the amino acids in the chromophore or its vicinity. Variants that emit light in the blue region (Blue Fluorescent Protein, BFP), red region, or yellow region are readily available and are widely used in diverse applications. Previously, we had used fluorescence spectroscopy to study the effect of pH on the denaturation of GFP with SDS, urea, and heat. Surprisingly, we found that SDS, urea or heat, did not have any significant effect on the fluorescence of GFP at pH 7.5 or 8.5, however, at pH 6.5, the protein lost all fluorescence within a very short period of time. These results suggested that GFP undergoes a structural/stability shift between pH 6.5 and 7.5, with the GFP structure at pH 6.5 being very sensitive to denaturation by SDS, urea, and heat. In the present study, we wanted to explore whether the stability or structure of the closely related BFP is also pH dependent. As expected, we found heat-induced denaturation and renaturation of BFP to be pH dependent, very much like GFP. However, when exposed to other denaturants like urea/heat or SDS we found BFP to behave very differently than GFP. Unlike GFP, which at pH 8.5 and 7.5 is very resistant to SDS-induced denaturation, BFP readily lost about 20% of its fluorescence at pH 8.5 and about 60% fluorescence at pH 7.5. Also, our denaturation and renaturation studies show that under certain conditions, BFP is more stable than GFP, such that under conditions where GFP is completely denatured, BFP still retained significant fluorescence. Taken together, our preliminary results show that despite being very similar in both amino acid sequences and overall structures, there may be subtle and important structural/conformational differences between BFP and GFP.

  9. Classification of microvascular patterns via cluster analysis reveals their prognostic significance in glioblastoma.

    PubMed

    Chen, Long; Lin, Zhi-Xiong; Lin, Guo-Shi; Zhou, Chang-Fu; Chen, Yu-Peng; Wang, Xing-Fu; Zheng, Zong-Qing

    2015-01-01

    There are limited researches focusing on microvascular patterns (MVPs) in human glioblastoma and their prognostic impact. We evaluated MVPs of 78 glioblastomas by CD34/periodic acid-Schiff dual staining and by cluster analysis of the percentage of microvascular area for distinct microvascular formations. The distribution of 5 types of basic microvascular formations, that is, microvascular sprouting (MS), vascular cluster (VC), vascular garland (VG), glomeruloid vascular proliferation (GVP), and vasculogenic mimicry (VM), was variable. Accordingly, cluster analysis classified MVPs into 2 types: type I MVP displayed prominent MSs and VCs, whereas type II MVP had numerous VGs, GVPs, and VMs. By analyzing the proportion of microvascular area for each type of formation, we determined that glioblastomas with few MSs and VCs had many GVPs and VMs, and vice versa. VG seemed to be a transitional type of formation. In case of type I MVP, expression of Ki-67 and p53 but not MGMT was significantly higher as compared with those of type II MVP (P < .05). Survival analysis showed that the type of MVPs presented as an independent prognostic factor of progression-free survival (PFS) and overall survival (OS) (both P < .001). Type II MVP had a more negative influence on PFS and OS than did type I MVP. We conclude that the heterogeneous MVPs in glioblastoma can be categorized properly by certain histopathologic and statistical analyses and may influence clinical outcome.

  10. Comparative genomics reveals genes significantly associated with woody hosts in the plant pathogen Pseudomonas syringae

    PubMed Central

    Laue, Bridget E.; Sharp, Paul M.; Green, Sarah

    2016-01-01

    Summary The diversification of lineages within Pseudomonas syringae has involved a number of adaptive shifts from herbaceous hosts onto various species of tree, resulting in the emergence of highly destructive diseases such as bacterial canker of kiwi and bleeding canker of horse chestnut. This diversification has involved a high level of gene gain and loss, and these processes are likely to play major roles in the adaptation of individual lineages onto their host plants. In order to better understand the evolution of P. syringae onto woody plants, we have generated de novo genome sequences for 26 strains from the P. syringae species complex that are pathogenic on a range of woody species, and have looked for statistically significant associations between gene presence and host type (i.e. woody or herbaceous) across a phylogeny of 64 strains. We have found evidence for a common set of genes associated with strains that are able to colonize woody plants, suggesting that divergent lineages have acquired similarities in genome composition that may form the genetic basis of their adaptation to woody hosts. We also describe in detail the gain, loss and rearrangement of specific loci that may be functionally important in facilitating this adaptive shift. Overall, our analyses allow for a greater understanding of how gene gain and loss may contribute to adaptation in P. syringae. PMID:27145446

  11. Introduction of e-learning in dental radiology reveals significantly improved results in final examination.

    PubMed

    Meckfessel, Sandra; Stühmer, Constantin; Bormann, Kai-Hendrik; Kupka, Thomas; Behrends, Marianne; Matthies, Herbert; Vaske, Bernhard; Stiesch, Meike; Gellrich, Nils-Claudius; Rücker, Martin

    2011-01-01

    Because a traditionally instructed dental radiology lecture course is very time-consuming and labour-intensive, online courseware, including an interactive-learning module, was implemented to support the lectures. The purpose of this study was to evaluate the perceptions of students who have worked with web-based courseware as well as the effect on their results in final examinations. Users (n(3+4)=138) had access to the e-program from any networked computer at any time. Two groups (n(3)=71, n(4)=67) had to pass a final exam after using the e-course. Results were compared with two groups (n(1)=42, n(2)=48) who had studied the same content by attending traditional lectures. In addition a survey of the students was statistically evaluated. Most of the respondents reported a positive attitude towards e-learning and would have appreciated more access to computer-assisted instruction. Two years after initiating the e-course the failure rate in the final examination dropped significantly, from 40% to less than 2%. The very positive response to the e-program and improved test scores demonstrated the effectiveness of our e-course as a learning aid. Interactive modules in step with clinical practice provided learning that is not achieved by traditional teaching methods alone. To what extent staff savings are possible is part of a further study. Copyright © 2010 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  12. Comparative Proteomics Reveals a Significant Bias Toward Alternative Protein Isoforms with Conserved Structure and Function

    PubMed Central

    Ezkurdia, Iakes; del Pozo, Angela; Frankish, Adam; Rodriguez, Jose Manuel; Harrow, Jennifer; Ashman, Keith; Valencia, Alfonso; Tress, Michael L.

    2012-01-01

    Advances in high-throughput mass spectrometry are making proteomics an increasingly important tool in genome annotation projects. Peptides detected in mass spectrometry experiments can be used to validate gene models and verify the translation of putative coding sequences (CDSs). Here, we have identified peptides that cover 35% of the genes annotated by the GENCODE consortium for the human genome as part of a comprehensive analysis of experimental spectra from two large publicly available mass spectrometry databases. We detected the translation to protein of “novel” and “putative” protein-coding transcripts as well as transcripts annotated as pseudogenes and nonsense-mediated decay targets. We provide a detailed overview of the population of alternatively spliced protein isoforms that are detectable by peptide identification methods. We found that 150 genes expressed multiple alternative protein isoforms. This constitutes the largest set of reliably confirmed alternatively spliced proteins yet discovered. Three groups of genes were highly overrepresented. We detected alternative isoforms for 10 of the 25 possible heterogeneous nuclear ribonucleoproteins, proteins with a key role in the splicing process. Alternative isoforms generated from interchangeable homologous exons and from short indels were also significantly enriched, both in human experiments and in parallel analyses of mouse and Drosophila proteomics experiments. Our results show that a surprisingly high proportion (almost 25%) of the detected alternative isoforms are only subtly different from their constitutive counterparts. Many of the alternative splicing events that give rise to these alternative isoforms are conserved in mouse. It was striking that very few of these conserved splicing events broke Pfam functional domains or would damage globular protein structures. This evidence of a strong bias toward subtle differences in CDS and likely conserved cellular function and structure is

  13. Comparative proteomics reveals a significant bias toward alternative protein isoforms with conserved structure and function.

    PubMed

    Ezkurdia, Iakes; del Pozo, Angela; Frankish, Adam; Rodriguez, Jose Manuel; Harrow, Jennifer; Ashman, Keith; Valencia, Alfonso; Tress, Michael L

    2012-09-01

    Advances in high-throughput mass spectrometry are making proteomics an increasingly important tool in genome annotation projects. Peptides detected in mass spectrometry experiments can be used to validate gene models and verify the translation of putative coding sequences (CDSs). Here, we have identified peptides that cover 35% of the genes annotated by the GENCODE consortium for the human genome as part of a comprehensive analysis of experimental spectra from two large publicly available mass spectrometry databases. We detected the translation to protein of "novel" and "putative" protein-coding transcripts as well as transcripts annotated as pseudogenes and nonsense-mediated decay targets. We provide a detailed overview of the population of alternatively spliced protein isoforms that are detectable by peptide identification methods. We found that 150 genes expressed multiple alternative protein isoforms. This constitutes the largest set of reliably confirmed alternatively spliced proteins yet discovered. Three groups of genes were highly overrepresented. We detected alternative isoforms for 10 of the 25 possible heterogeneous nuclear ribonucleoproteins, proteins with a key role in the splicing process. Alternative isoforms generated from interchangeable homologous exons and from short indels were also significantly enriched, both in human experiments and in parallel analyses of mouse and Drosophila proteomics experiments. Our results show that a surprisingly high proportion (almost 25%) of the detected alternative isoforms are only subtly different from their constitutive counterparts. Many of the alternative splicing events that give rise to these alternative isoforms are conserved in mouse. It was striking that very few of these conserved splicing events broke Pfam functional domains or would damage globular protein structures. This evidence of a strong bias toward subtle differences in CDS and likely conserved cellular function and structure is remarkable and

  14. Whole genome expression profiling reveals a significant role for immune function in human abdominal aortic aneurysms

    PubMed Central

    Lenk, Guy M; Tromp, Gerard; Weinsheimer, Shantel; Gatalica, Zoran; Berguer, Ramon; Kuivaniemi, Helena

    2007-01-01

    Background Abdominal aortic aneurysms are a common disorder with an incompletely understood etiology. We used Illumina and Affymetrix microarray platforms to generate global gene expression profiles for both aneurysmal (AAA) and non-aneurysmal abdominal aorta, and identified genes that were significantly differentially expressed between cases and controls. Results Affymetrix and Illumina arrays included 18,057 genes in common; 11,542 (64%) of these genes were considered to be expressed in either aneurysmal or normal abdominal aorta. There were 3,274 differentially expressed genes with a false discovery rate (FDR) ≤ 0.05. Many of these genes were not previously known to be involved in AAA, including SOST and RUNX3, which were confirmed using Q-RT-PCR (Pearson correlation coefficient for microarray and Q-RT-PCR data = 0.89; p-values for differences in expression between AAA and controls for SOST: 4.87 × 10-4 and for RUNX3: 4.33 × 10-5). Analysis of biological pathways, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), indicated extreme overrepresentation of immune related categories. The enriched categories included the GO category Immune Response (GO:0006955; FDR = 2.1 × 10-14), and the KEGG pathways natural killer cell mediated cytotoxicity (hsa04650; FDR = 5.9 × 10-6) and leukocyte transendothelial migration (hsa04670; FDR = 1.1 × 10-5). Conclusion Previous studies have provided evidence for the involvement of the immune system in AAA. The current expression analysis extends these findings by demonstrating broad coordinate gene expression in immunological pathways. A large number of genes involved in immune function were differentially expressed in AAA, and the pathway analysis gave these results a biological context. The data provide valuable insight for future studies to dissect the pathogenesis of human AAA. These pathways might also be used as targets for the development of therapeutic agents for AAA. PMID:17634102

  15. Palaeoceanographic significance of sedimentary features at the Argentine continental margin revealed by multichannel seismic reflection data

    NASA Astrophysics Data System (ADS)

    Gruetzner, Jens; Uenzelmann-Neben, Gabriele; Franke, Dieter

    2010-05-01

    The thermohaline circulation in the Argentine Basin today is characterized by the interaction of northward flowing Antarctic water masses (Antarctic Intermediate Water, AAIW; Circumpolar Deep Water, CDW; Antarctic Bottom Water, AABW) and southward flowing North Atlantic Deep Water (NADW). The transfer of heat and energy via both AABW and NADW constitutes an important component in maintaining the global conveyor belt. We aim at a better understanding of both paths and intensity of this current system in the past by investigating an extensive (> 11000 km) set of high quality seismic reflection profiles from the Argentine continental margin. The profiles show a significant contourite system containing both erosive and depositional features that formed through the evolution of water masses and their modifications (path, physical and chemical properties) due to plate tectonic events such as the opening of the Drake Passage or the extensive emplacement of volcanic flows at the Rio Grande Rise. Overall the depositional features indicate that along slope (contour current) transport dominates over down slope (turbiditic) processes at the southern Argentine margin south of 45° S. Further to the North down slope transport was more extensive as indicated by the presence of submarine canyons crossing the slope down to a depth of ~3500 m. Here we present preliminary results from the southern part of the continental margin (42°-50° S) where we focus on a set of ~50 km wide terraces on the slope and rise separated by contouritic channels. The terraces developed over time in alternating constructional (depositional) and erosive phases. An initial age frame was developed by mapping regional reflectors and seismic units known from previous studies. The sedimentary layer between regional reflectors AR 4 and AR 5 spanning roughly the time interval from the Eocene/Oligocene boundary to the early middle Miocene is thin (0.1 - 0.4 s TWT) below the Valentine Feilberg Terrace but

  16. Adaptive Thresholds

    SciTech Connect

    Bremer, P. -T.

    2014-08-26

    ADAPT is a topological analysis code that allow to compute local threshold, in particular relevance based thresholds for features defined in scalar fields. The initial target application is vortex detection but the software is more generally applicable to all threshold based feature definitions.

  17. Improving sensitivity of linear regression-based cell type-specific differential expression deconvolution with per-gene vs. global significance threshold.

    PubMed

    Glass, Edmund R; Dozmorov, Mikhail G

    2016-10-06

    The goal of many human disease-oriented studies is to detect molecular mechanisms different between healthy controls and patients. Yet, commonly used gene expression measurements from blood samples suffer from variability of cell composition. This variability hinders the detection of differentially expressed genes and is often ignored. Combined with cell counts, heterogeneous gene expression may provide deeper insights into the gene expression differences on the cell type-specific level. Published computational methods use linear regression to estimate cell type-specific differential expression, and a global cutoff to judge significance, such as False Discovery Rate (FDR). Yet, they do not consider many artifacts hidden in high-dimensional gene expression data that may negatively affect linear regression. In this paper we quantify the parameter space affecting the performance of linear regression (sensitivity of cell type-specific differential expression detection) on a per-gene basis. We evaluated the effect of sample sizes, cell type-specific proportion variability, and mean squared error on sensitivity of cell type-specific differential expression detection using linear regression. Each parameter affected variability of cell type-specific expression estimates and, subsequently, the sensitivity of differential expression detection. We provide the R package, LRCDE, which performs linear regression-based cell type-specific differential expression (deconvolution) detection on a gene-by-gene basis. Accounting for variability around cell type-specific gene expression estimates, it computes per-gene t-statistics of differential detection, p-values, t-statistic-based sensitivity, group-specific mean squared error, and several gene-specific diagnostic metrics. The sensitivity of linear regression-based cell type-specific differential expression detection differed for each gene as a function of mean squared error, per group sample sizes, and variability of the proportions

  18. Threshold Digraphs

    PubMed Central

    Cloteaux, Brian; LaMar, M. Drew; Moseman, Elizabeth; Shook, James

    2014-01-01

    A digraph whose degree sequence has a unique vertex labeled realization is called threshold. In this paper we present several characterizations of threshold digraphs and their degree sequences, and show these characterizations to be equivalent. Using this result, we obtain a new, short proof of the Fulkerson-Chen theorem on degree sequences of general digraphs. PMID:26601029

  19. An anti-hapten camelid antibody reveals a cryptic binding site with significant energetic contributions from a nonhypervariable loop

    SciTech Connect

    Fanning, Sean W.; Horn, James R.

    2014-03-05

    Conventional anti-hapten antibodies typically bind low-molecular weight compounds (haptens) in the crevice between the variable heavy and light chains. Conversely, heavy chain-only camelid antibodies, which lack a light chain, must rely entirely on a single variable domain to recognize haptens. While several anti-hapten VHHs have been generated, little is known regarding the underlying structural and thermodynamic basis for hapten recognition. Here, an anti-methotrexate VHH (anti-MTX VHH) was generated using grafting methods whereby the three complementarity determining regions (CDRs) were inserted onto an existing VHH framework. Thermodynamic analysis of the anti-MTX VHH CDR1-3 Graft revealed a micromolar binding affinity, while the crystal structure of the complex revealed a somewhat surprising noncanonical binding site which involved MTX tunneling under the CDR1 loop. Due to the close proximity of MTX to CDR4, a nonhypervariable loop, the CDR4 loop sequence was subsequently introduced into the CDR1-3 graft, which resulted in a dramatic 1000-fold increase in the binding affinity. Crystal structure analysis of both the free and complex anti-MTX CDR1-4 graft revealed CDR4 plays a significant role in both intermolecular contacts and binding site conformation that appear to contribute toward high affinity binding. Additionally, the anti-MTX VHH possessed relatively high specificity for MTX over closely related compounds aminopterin and folate, demonstrating that VHH domains are capable of binding low-molecular weight ligands with high affinity and specificity, despite their reduced interface.

  20. An anti-hapten camelid antibody reveals a cryptic binding site with significant energetic contributions from a nonhypervariable loop

    PubMed Central

    Fanning, Sean W; Horn, James R

    2011-01-01

    Conventional anti-hapten antibodies typically bind low-molecular weight compounds (haptens) in the crevice between the variable heavy and light chains. Conversely, heavy chain-only camelid antibodies, which lack a light chain, must rely entirely on a single variable domain to recognize haptens. While several anti-hapten VHHs have been generated, little is known regarding the underlying structural and thermodynamic basis for hapten recognition. Here, an anti-methotrexate VHH (anti-MTX VHH) was generated using grafting methods whereby the three complementarity determining regions (CDRs) were inserted onto an existing VHH framework. Thermodynamic analysis of the anti-MTX VHH CDR1-3 Graft revealed a micromolar binding affinity, while the crystal structure of the complex revealed a somewhat surprising noncanonical binding site which involved MTX tunneling under the CDR1 loop. Due to the close proximity of MTX to CDR4, a nonhypervariable loop, the CDR4 loop sequence was subsequently introduced into the CDR1-3 graft, which resulted in a dramatic 1000-fold increase in the binding affinity. Crystal structure analysis of both the free and complex anti-MTX CDR1-4 graft revealed CDR4 plays a significant role in both intermolecular contacts and binding site conformation that appear to contribute toward high affinity binding. Additionally, the anti-MTX VHH possessed relatively high specificity for MTX over closely related compounds aminopterin and folate, demonstrating that VHH domains are capable of binding low-molecular weight ligands with high affinity and specificity, despite their reduced interface. PMID:21557375

  1. Airway epithelial cell exposure to distinct e-cigarette liquid flavorings reveals toxicity thresholds and activation of CFTR by the chocolate flavoring 2,5-dimethypyrazine.

    PubMed

    Sherwood, Cara L; Boitano, Scott

    2016-05-17

    The potential for adverse respiratory effects following exposure to electronic (e-) cigarette liquid (e-liquid) flavorings remains largely unexplored. Given the multitude of flavor permutations on the market, identification of those flavor constituents that negatively impact the respiratory tract is a daunting task. In this study we examined the impact of common e-liquid flavoring chemicals on the airway epithelium, the cellular monolayer that provides the first line of defense against inhaled particulates, pathogens, and toxicants. We used the xCELLigence real-time cell analyzer (RTCA) as a primary high-capacity screening tool to assess cytotoxicity thresholds and physiological effects of common e-liquid flavoring chemicals on immortalized human bronchial epithelial cells (16HBE14o-). The RTCA was used secondarily to assess the capability of 16HBE14o- cells to respond to cellular signaling agonists following a 24 h exposure to select flavoring chemicals. Finally, we conducted biophysical measurements of well-differentiated primary mouse tracheal epithelial (MTE) cells with an Ussing chamber to measure the effects of e-cigarette flavoring constituents on barrier function and ion conductance. In our high-capacity screens five of the seven flavoring chemicals displayed changes in cellular impedance consistent with cell death at concentrations found in e-liquid. Vanillin and the chocolate flavoring 2,5-dimethylpyrazine caused alterations in cellular physiology indicative of a cellular signaling event. At subcytotoxic levels, 24 h exposure to 2,5-dimethylpyrazine compromised the ability of airway epithelial cells to respond to signaling agonists important in salt and water balance at the airway surface. Biophysical measurements of 2,5-dimethylpyrazine on primary MTE cells revealed alterations in ion conductance consistent with an efflux at the apical airway surface that was accompanied by a transient loss in transepithelial resistance. Mechanistic studies confirmed

  2. Quantitative superresolution microscopy reveals differences in nuclear DNA organization of multiple myeloma and monoclonal gammopathy of undetermined significance.

    PubMed

    Sathitruangsak, Chirawadee; Righolt, Christiaan H; Klewes, Ludger; Tammur, Pille; Ilus, Tiiu; Tamm, Anu; Punab, Mari; Olujohungbe, Adebayo; Mai, Sabine

    2015-05-01

    The mammalian nucleus has a distinct substructure that cannot be visualized directly by conventional microscopy. In this study, the organization of the DNA within the nucleus of multiple myeloma (MM) cells, their precursor cells (monoclonal gammopathy of undetermined significance; MGUS) and control lymphocytes of the representative patients is visualized and quantified by superresolution microscopy. Three-dimensional structured illumination microscopy (3D-SIM) increases the spatial resolution beyond the limits of conventional widefield fluorescence microscopy. 3D-SIM reveals new insights into the nuclear architecture of cancer as we show for the first time that it resolves organizational differences in intranuclear DNA organization of myeloma cells in MGUS and in MM patients. In addition, we report a significant increase in nuclear submicron DNA structure and structure of the DNA-free space in myeloma nuclei compared to normal lymphocyte nuclei. Our study provides previously unknown details of the nanoscopic DNA architecture of interphase nuclei of the normal lymphocytes, MGUS and MM cells. This study opens new avenues to understanding the disease progression from MGUS to MM.

  3. A genome scan revealed significant associations of growth traits with a major QTL and GHR2 in tilapia

    PubMed Central

    Liu, Feng; Sun, Fei; Xia, Jun Hong; Li, Jian; Fu, Gui Hong; Lin, Grace; Tu, Rong Jian; Wan, Zi Yi; Quek, Delia; Yue, Gen Hua

    2014-01-01

    Growth is an important trait in animal breeding. However, the genetic effects underpinning fish growth variability are still poorly understood. QTL mapping and analysis of candidate genes are effective methods to address this issue. We conducted a genome-wide QTL analysis for growth in tilapia. A total of 10, 7 and 8 significant QTLs were identified for body weight, total length and standard length at 140 dph, respectively. The majority of these QTLs were sex-specific. One major QTL for growth traits was identified in the sex-determining locus in LG1, explaining 71.7%, 67.2% and 64.9% of the phenotypic variation (PV) of body weight, total length and standard length, respectively. In addition, a candidate gene GHR2 in a QTL was significantly associated with body weight, explaining 13.1% of PV. Real-time qPCR revealed that different genotypes at the GHR2 locus influenced the IGF-1 expression level. The markers located in the major QTL for growth traits could be used in marker-assisted selection of tilapia. The associations between GHR2 variants and growth traits suggest that the GHR2 gene should be an important gene that explains the difference in growth among tilapia species. PMID:25435025

  4. The contribution of Islet1-expressing splanchnic mesoderm cells to distinct branchiomeric muscles reveals significant heterogeneity in head muscle development.

    PubMed

    Nathan, Elisha; Monovich, Amir; Tirosh-Finkel, Libbat; Harrelson, Zachary; Rousso, Tal; Rinon, Ariel; Harel, Itamar; Evans, Sylvia M; Tzahor, Eldad

    2008-02-01

    During embryogenesis, paraxial mesoderm cells contribute skeletal muscle progenitors, whereas cardiac progenitors originate in the lateral splanchnic mesoderm (SpM). Here we focus on a subset of the SpM that contributes to the anterior or secondary heart field (AHF/SHF), and lies adjacent to the cranial paraxial mesoderm (CPM), the precursors for the head musculature. Molecular analyses in chick embryos delineated the boundaries between the CPM, undifferentiated SpM progenitors of the AHF/SHF, and differentiating cardiac cells. We then revealed the regionalization of branchial arch mesoderm: CPM cells contribute to the proximal region of the myogenic core, which gives rise to the mandibular adductor muscle. SpM cells contribute to the myogenic cells in the distal region of the branchial arch that later form the intermandibular muscle. Gene expression analyses of these branchiomeric muscles in chick uncovered a distinct molecular signature for both CPM- and SpM-derived muscles. Islet1 (Isl1) is expressed in the SpM/AHF and branchial arch in both chick and mouse embryos. Lineage studies using Isl1-Cre mice revealed the significant contribution of Isl1(+) cells to ventral/distal branchiomeric (stylohyoid, mylohyoid and digastric) and laryngeal muscles. By contrast, the Isl1 lineage contributes to mastication muscles (masseter, pterygoid and temporalis) to a lesser extent, with virtually no contribution to intrinsic and extrinsic tongue muscles or extraocular muscles. In addition, in vivo activation of the Wnt/beta-catenin pathway in chick embryos resulted in marked inhibition of Isl1, whereas inhibition of this pathway increased Isl1 expression. Our findings demonstrate, for the first time, the contribution of Isl1(+) SpM cells to a subset of branchiomeric skeletal muscles.

  5. Ozone-Induced Dissociation of Conjugated Lipids Reveals Significant Reaction Rate Enhancements and Characteristic Odd-Electron Product Ions

    NASA Astrophysics Data System (ADS)

    Pham, Huong T.; Maccarone, Alan T.; Campbell, J. Larry; Mitchell, Todd W.; Blanksby, Stephen J.

    2013-02-01

    Ozone-induced dissociation (OzID) is an alternative ion activation method that relies on the gas phase ion-molecule reaction between a mass-selected target ion and ozone in an ion trap mass spectrometer. Herein, we evaluated the performance of OzID for both the structural elucidation and selective detection of conjugated carbon-carbon double bond motifs within lipids. The relative reactivity trends for [M + X]+ ions (where X = Li, Na, K) formed via electrospray ionization (ESI) of conjugated versus nonconjugated fatty acid methyl esters (FAMEs) were examined using two different OzID-enabled linear ion-trap mass spectrometers. Compared with nonconjugated analogues, FAMEs derived from conjugated linoleic acids were found to react up to 200 times faster and to yield characteristic radical cations. The significantly enhanced reactivity of conjugated isomers means that OzID product ions can be observed without invoking a reaction delay in the experimental sequence (i.e., trapping of ions in the presence of ozone is not required). This possibility has been exploited to undertake neutral-loss scans on a triple quadrupole mass spectrometer targeting characteristic OzID transitions. Such analyses reveal the presence of conjugated double bonds in lipids extracted from selected foodstuffs. Finally, by benchmarking of the absolute ozone concentration inside the ion trap, second order rate constants for the gas phase reactions between unsaturated organic ions and ozone were obtained. These results demonstrate a significant influence of the adducting metal on reaction rate constants in the fashion Li > Na > K.

  6. Interspecific rice hybrid of Oryza sativa x Oryza nivara reveals a significant increase in seed protein content.

    PubMed

    Mahmoud, Ahmed A; Sukumar, S; Krishnan, Hari B

    2008-01-23

    Wild species offer a potential reservoir of genetic variation for crop improvement. Besides the valuable genes for disease resistance that the wild species have provided for rice improvement, recent studies have shown that these wild species could also provide favorable alleles for the improvement of yield and yield-related traits. The present study reports yet another potential of wild relatives of rice, which involves the improvement of seed protein content. A significant increase in seed protein content was observed in an interspecific hybrid between Oryza sativa ssp. indica and the wild species Oryza nivara. The hybrid showed a protein content of 12.4%, which was 28 and 18.2% higher than those of the parents O. nivara and IR 64, respectively. The increase in protein content was dependent on the genetic background of the rice variety used in the hybridization. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of seed storage proteins demonstrated that a significant increase in prolamins and glutelins was mainly responsible for the elevated protein content of the hybrid. Amino acid analysis of seed proteins revealed that the hybrid had net gains of 19.5% in lysine and 19.4% in threonine over the O. nivara parent on a seed dry weight basis. Molecular analysis indicated that the increase in protein content of the hybrid was not a result of chromosomal rearrangements or transposable element activation, at least in the chromosomal regions containing seed storage protein genes. A preliminary genetic analysis of the F 2 segregating population showed that the inheritance of the increased protein content was polygenic in nature. The development of this interspecific hybrid offers a great potential for selecting new rice cultivars that combine the high yield and superior cooking quality of IR 64 with improved seed protein content.

  7. Significant genetic differentiation between Poland and Germany follows present-day political borders, as revealed by Y-chromosome analysis.

    PubMed

    Kayser, Manfred; Lao, Oscar; Anslinger, Katja; Augustin, Christa; Bargel, Grazyna; Edelmann, Jeanett; Elias, Sahar; Heinrich, Marielle; Henke, Jürgen; Henke, Lotte; Hohoff, Carsten; Illing, Anett; Jonkisz, Anna; Kuzniar, Piotr; Lebioda, Arleta; Lessig, Rüdiger; Lewicki, Slawomir; Maciejewska, Agnieszka; Monies, Dorota Marta; Pawłowski, Ryszard; Poetsch, Micaela; Schmid, Dagmar; Schmidt, Ulrike; Schneider, Peter M; Stradmann-Bellinghausen, Beate; Szibor, Reinhard; Wegener, Rudolf; Wozniak, Marcin; Zoledziewska, Magdalena; Roewer, Lutz; Dobosz, Tadeusz; Ploski, Rafal

    2005-09-01

    To test for human population substructure and to investigate human population history we have analysed Y-chromosome diversity using seven microsatellites (Y-STRs) and ten binary markers (Y-SNPs) in samples from eight regionally distributed populations from Poland (n = 913) and 11 from Germany (n = 1,215). Based on data from both Y-chromosome marker systems, which we found to be highly correlated (r = 0.96), and using spatial analysis of the molecular variance (SAMOVA), we revealed statistically significant support for two groups of populations: (1) all Polish populations and (2) all German populations. By means of analysis of the molecular variance (AMOVA) we observed a large and statistically significant proportion of 14% (for Y-SNPs) and 15% (for Y-STRs) of the respective total genetic variation being explained between both countries. The same population differentiation was detected using Monmonier's algorithm, with a resulting genetic border between Poland and Germany that closely resembles the course of the political border between both countries. The observed genetic differentiation was mainly, but not exclusively, due to the frequency distribution of two Y-SNP haplogroups and their associated Y-STR haplotypes: R1a1*, most frequent in Poland, and R1*(xR1a1), most frequent in Germany. We suggest here that the pronounced population differentiation between the two geographically neighbouring countries, Poland and Germany, is the consequence of very recent events in human population history, namely the forced human resettlement of many millions of Germans and Poles during and, especially, shortly after World War II. In addition, our findings have consequences for the forensic application of Y-chromosome markers, strongly supporting the implementation of population substructure into forensic Y chromosome databases, and also for genetic association studies.

  8. Color-Doppler sonographic tissue perfusion measurements reveal significantly diminished renal cortical perfusion in kidneys with vesicoureteral reflux

    PubMed Central

    Scholbach, T. M.; Sachse, C.

    2016-01-01

    Vesicoureteral reflux (VUR) and its sequelae may lead to reduced renal perfusion and loss of renal function. Methods to describe and monitor tissue perfusion are needed. We investigated dynamic tissue perfusion measurement (DTPM) with the PixelFlux-software to measure microvascular changes in the renal cortex in 35 children with VUR and 28 healthy children. DTPM of defined horizontal slices of the renal cortex was carried out. A kidney was assigned to the “low grade reflux”-group if the reflux grade of the voiding cystourethrogram was 1 to 3 and to the “high grade reflux”-group if the reflux grade was 4 to 5. Kidneys with VUR showed a significantly reduced cortical perfusion. Compared to healthy kidneys, this decline reached in low and high grade refluxes within the proximal 50% of the cortex: 3% and 12 %, in the distal 50% of the cortex: 21% and 44 % and in the most distal 20 % of the cortex 41% and 44%. DTPM reveals a perfusion loss in kidneys depending on the degree of VUR, which is most pronounced in the peripheral cortex. Thus, DTPM offers the tool to evaluate microvascular perfusion, to help planning treatment decisions in children with VUR. PMID:27051133

  9. Simultaneous Application of Heat, Drought, and Virus to Arabidopsis Plants Reveals Significant Shifts in Signaling Networks1[W][OPEN

    PubMed Central

    Prasch, Christian Maximilian; Sonnewald, Uwe

    2013-01-01

    Considering global climate change, the incidence of combined drought and heat stress is likely to increase in the future and will considerably influence plant-pathogen interactions. Until now, little has been known about plants exposed to simultaneously occurring abiotic and biotic stresses. To shed some light on molecular plant responses to multiple stress factors, a versatile multifactorial test system, allowing simultaneous application of heat, drought, and virus stress, was developed in Arabidopsis (Arabidopsis thaliana). Comparative analysis of single, double, and triple stress responses by transcriptome and metabolome analysis revealed that gene expression under multifactorial stress is not predictable from single stress treatments. Hierarchical cluster and principal component analyses identified heat as the major stress factor, clearly separating heat-stressed from non-heat-stressed plants. We identified 11 genes differentially regulated in all stress combinations as well as 23 genes specifically regulated under triple stress. Furthermore, we showed that virus-treated plants displayed enhanced expression of defense genes, which was abolished in plants additionally subjected to heat and drought stress. Triple stress also reduced the expression of genes involved in the R-mediated disease response and increased the cytoplasmic protein response, which was not seen under single stress conditions. These observations suggested that abiotic stress factors significantly altered turnip mosaic virus-specific signaling networks, which led to a deactivation of defense responses and a higher susceptibility of plants. Collectively, our transcriptome and metabolome data provide a powerful resource to study plant responses during multifactorial stress and allow identifying metabolic processes and functional networks involved in tripartite interactions of plants with their environment. PMID:23753177

  10. Significant Natural Product Biosynthetic Potential of Actinorhizal Symbionts of the Genus Frankia, as Revealed by Comparative Genomic and Proteomic Analyses▿

    PubMed Central

    Udwary, Daniel W.; Gontang, Erin A.; Jones, Adam C.; Jones, Carla S.; Schultz, Andrew W.; Winter, Jaclyn M.; Yang, Jane Y.; Beauchemin, Nicholas; Capson, Todd L.; Clark, Benjamin R.; Esquenazi, Eduardo; Eustáquio, Alessandra S.; Freel, Kelle; Gerwick, Lena; Gerwick, William H.; Gonzalez, David; Liu, Wei-Ting; Malloy, Karla L.; Maloney, Katherine N.; Nett, Markus; Nunnery, Joshawna K.; Penn, Kevin; Prieto-Davo, Alejandra; Simmons, Thomas L.; Weitz, Sara; Wilson, Micheal C.; Tisa, Louis S.; Dorrestein, Pieter C.; Moore, Bradley S.

    2011-01-01

    Bacteria of the genus Frankia are mycelium-forming actinomycetes that are found as nitrogen-fixing facultative symbionts of actinorhizal plants. Although soil-dwelling actinomycetes are well-known producers of bioactive compounds, the genus Frankia has largely gone uninvestigated for this potential. Bioinformatic analysis of the genome sequences of Frankia strains ACN14a, CcI3, and EAN1pec revealed an unexpected number of secondary metabolic biosynthesis gene clusters. Our analysis led to the identification of at least 65 biosynthetic gene clusters, the vast majority of which appear to be unique and for which products have not been observed or characterized. More than 25 secondary metabolite structures or structure fragments were predicted, and these are expected to include cyclic peptides, siderophores, pigments, signaling molecules, and specialized lipids. Outside the hopanoid gene locus, no cluster could be convincingly demonstrated to be responsible for the few secondary metabolites previously isolated from other Frankia strains. Few clusters were shared among the three species, demonstrating species-specific biosynthetic diversity. Proteomic analysis of Frankia sp. strains CcI3 and EAN1pec showed that significant and diverse secondary metabolic activity was expressed in laboratory cultures. In addition, several prominent signals in the mass range of peptide natural products were observed in Frankia sp. CcI3 by intact-cell matrix-assisted laser desorption-ionization mass spectrometry (MALDI-MS). This work supports the value of bioinformatic investigation in natural products biosynthesis using genomic information and presents a clear roadmap for natural products discovery in the Frankia genus. PMID:21498757

  11. Familial longevity study reveals a significant association of mitochondrial DNA copy number between centenarians and their offspring.

    PubMed

    He, Yong-Han; Chen, Xiao-Qiong; Yan, Dong-Jing; Xiao, Fu-Hui; Lin, Rong; Liao, Xiao-Ping; Liu, Yao-Wen; Pu, Shao-Yan; Yu, Qin; Sun, Hong-Peng; Jiang, Jian-Jun; Cai, Wang-Wei; Kong, Qing-Peng

    2016-11-01

    Reduced mitochondrial function is an important cause of aging and age-related diseases. We previously revealed a relatively higher level of mitochondrial DNA (mtDNA) content in centenarians. However, it is still unknown whether such an mtDNA content pattern of centenarians could be passed on to their offspring and how it was regulated. To address these issues, we recruited 60 longevity families consisting of 206 family members (cohort 1) and explored their mtDNA copy number. The results showed that the first generation of the offspring (F1 offspring) had a higher level of mtDNA copy number than their spouses (p < 0.05) independent of a gender effect. In addition, we found a positive association of mtDNA copy number in centenarians with that in F1 offspring (r = 0.54, p = 0.0008) but not with that in F1 spouses. These results were replicated in another independent cohort consisting of 153 subjects (cohort 2). RNA sequencing analysis suggests that the single-stranded DNA-binding protein 4 was significantly associated with mtDNA copy number and was highly expressed in centenarians as well as F1 offspring versus the F1 spouses, thus likely regulates the mtDNA copy number in the long-lived family members. In conclusion, our results suggest that the pattern of high mtDNA copy number is likely inheritable, which may act as a favorable factor to familial longevity through assuring adequate energy supply. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Relationships among oil density, gross composition, and thermal maturity indicators in northeastern Williston basin oils and their significance for expulsion thresholds and migration pathways

    SciTech Connect

    Osadetz, K.G.; Snowdon, L.R.; Brooks, P.W. )

    1991-06-01

    Oil density ({degree}API), gross composition, and biological market thermal maturity variations in northeastern Williston basin have stratigraphic and geographic significance controlled by migration pathways and source rock composition as it affects hydrocarbon generation and expulsion characteristics. When the depth and density of oil pools is compared to relationships predicted using the correlation between source rock thermal maturity and oil density, several different migration pathways can be inferred. Winnipegosis source oils indicate four paths. Most small pinnacle reef pools are sourced locally, but larger coalesced reefs contain oils migrated long distances through the Lower Member Winnipegosis Formation. Among oils that have migrated past Prairie salts, both locally sourced oils, like those on the flank of the Hummingbird Trough, and more mature, longer migrated oils in Saskatchewan Group reservoirs can be identified. Bakken oils have the longest migration pathways, controlled primarily by a lowstand shoreline sandstone on the eastern side of the basin. Lodgepole-sourced oils dominate Madison Group plays. Northwest of Steelman field, oil density increases primarily due to thermal maturity differences but also because of increasing biodegradation and water-washing that affect the western edge of the play trend. Along the margin of the Hummingbird Trough are a number of deep, medium-gravity pools whose oil compositions are entirely attributable to low thermal maturity and local migration pathways.

  13. Delaying discharge after the stimulus significantly decreases muscle activation thresholds with small impact on the selectivity: an in vivo study using TIME.

    PubMed

    Maciejasz, Paweł; Badia, Jordi; Boretius, Tim; Andreu, David; Stieglitz, Thomas; Jensen, Winnie; Navarro, Xavier; Guiraud, David

    2015-04-01

    The number of devices for electrical stimulation of nerve fibres implanted worldwide for medical applications is constantly increasing. Stimulation charge is one of the most important parameters of stimulation. High stimulation charge may cause tissue and electrode damage and also compromise the battery life of the electrical stimulators. Therefore, the objective of minimizing stimulation charge is an important issue. Delaying the second phase of biphasic stimulation waveform may decrease the charge required for fibre activation, but its impact on stimulation selectivity is not known. This information is particularly relevant when transverse intrafascicular multichannel electrode (TIME) is used, since it has been designed to provide for high selectivity. In this in vivo study, the rat sciatic nerve was electrically stimulated using monopolar and bipolar configurations with TIME. The results demonstrated that the inclusion of a 100-μs delay between the cathodic and the anodic phase of the stimulus allows to reduce charge requirements by around 30 %, while only slightly affecting stimulation selectivity. This study shows that adding a delay to the typical stimulation waveform significantly ([Formula: see text]) reduces the charge required for nerve fibres activation. Therefore, waveforms with the delayed discharge phase are more suitable for electrical stimulation of nerve fibres.

  14. Development of linear and threshold no significant risk levels for inhalation exposure to titanium dioxide using systematic review and mode of action considerations.

    PubMed

    Thompson, Chad M; Suh, Mina; Mittal, Liz; Wikoff, Daniele S; Welsh, Brian; Proctor, Deborah M

    2016-10-01

    Titanium dioxide (TiO2) has been characterized as a poorly soluble particulate (PSP) with low toxicity. It is well accepted that low toxicity PSPs such as TiO2 induce lung tumors in rats when deposition overwhelms particle clearance mechanisms. Despite the sensitivity of rats to PSPs and questionable relevance of PSP-induced tumors to humans, TiO2 is listed as a possible human carcinogen by some agencies and regulators. Thus, environmental toxicity criteria for TiO2 are needed for stakeholders to evaluate potential risks from environmental exposure and regulatory compliance. A systematic review of the literature was conducted to characterize the available data and identify candidate datasets upon which toxicity values could be derived. Key to this assessment, a survey of mechanistic data relevant for lung cancer was used to support quantitative inhalation risk assessment approaches. A total of 473 human studies were identified, 7 of which were epidemiological studies that met inclusion criteria to quantitatively characterize carcinogenic endpoints in humans. None of these studies supported derivation of toxicity criteria; therefore, animal data were used to derived safety values for TiO2 using different dose-metrics (regional deposited dose ratios, TiO2 particle surface area lung burden, and volumetric overload of alveolar macrophages), benchmark dose modeling, and different low-dose extrapolation approaches. Based on empirical evidence and mechanistic support for nonlinear mode of action involving particle overload, chronic inflammation and cell proliferation, a no significant risk level (NSRL) of 300 μg/day was derived. By comparison, low-dose linear extrapolation from tumor incidence in the rat lung resulted in an NSRL value of 44 μg/day. These toxicity values should be useful for stakeholders interested in assessing risks from environmental exposure to respirable TiO2. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Mitochondrial threshold effects.

    PubMed Central

    Rossignol, Rodrigue; Faustin, Benjamin; Rocher, Christophe; Malgat, Monique; Mazat, Jean-Pierre; Letellier, Thierry

    2003-01-01

    The study of mitochondrial diseases has revealed dramatic variability in the phenotypic presentation of mitochondrial genetic defects. To attempt to understand this variability, different authors have studied energy metabolism in transmitochondrial cell lines carrying different proportions of various pathogenic mutations in their mitochondrial DNA. The same kinds of experiments have been performed on isolated mitochondria and on tissue biopsies taken from patients with mitochondrial diseases. The results have shown that, in most cases, phenotypic manifestation of the genetic defect occurs only when a threshold level is exceeded, and this phenomenon has been named the 'phenotypic threshold effect'. Subsequently, several authors showed that it was possible to inhibit considerably the activity of a respiratory chain complex, up to a critical value, without affecting the rate of mitochondrial respiration or ATP synthesis. This phenomenon was called the 'biochemical threshold effect'. More recently, quantitative analysis of the effects of various mutations in mitochondrial DNA on the rate of mitochondrial protein synthesis has revealed the existence of a 'translational threshold effect'. In this review these different mitochondrial threshold effects are discussed, along with their molecular bases and the roles that they play in the presentation of mitochondrial diseases. PMID:12467494

  16. ChIP-on-chip significance analysis reveals large-scale binding and regulation by human transcription factor oncogenes.

    PubMed

    Margolin, Adam A; Palomero, Teresa; Sumazin, Pavel; Califano, Andrea; Ferrando, Adolfo A; Stolovitzky, Gustavo

    2009-01-06

    ChIP-on-chip has emerged as a powerful tool to dissect the complex network of regulatory interactions between transcription factors and their targets. However, most ChIP-on-chip analysis methods use conservative approaches aimed at minimizing false-positive transcription factor targets. We present a model with improved sensitivity in detecting binding events from ChIP-on-chip data. Its application to human T cells, followed by extensive biochemical validation, reveals that 3 oncogenic transcription factors, NOTCH1, MYC, and HES1, bind to several thousand target gene promoters, up to an order of magnitude increase over conventional analysis methods. Gene expression profiling upon NOTCH1 inhibition shows broad-scale functional regulation across the entire range of predicted target genes, establishing a closer link between occupancy and regulation. Finally, the increased sensitivity reveals a combinatorial regulatory program in which MYC cobinds to virtually all NOTCH1-bound promoters. Overall, these results suggest an unappreciated complexity of transcriptional regulatory networks and highlight the fundamental importance of genome-scale analysis to represent transcriptional programs.

  17. Genomic variants reveal differential evolutionary constraints on human transglutaminases and point towards unrecognized significance of transglutaminase 2

    PubMed Central

    Thangaraju, Kiruphagaran; Király, Róbert; Demény, Máté A.; András Mótyán, János; Fuxreiter, Mónika; Fésüs, László

    2017-01-01

    Transglutaminases (TGMs) catalyze Ca2+-dependent transamidation of proteins with specified roles in blood clotting (F13a) and in cornification (TGM1, TGM3). The ubiquitous TGM2 has well described enzymatic and non-enzymatic functions but in-spite of numerous studies its physiological function in humans has not been defined. We compared data on non-synonymous single nucleotide variations (nsSNVs) and loss-of-function variants on TGM1-7 and F13a from the Exome aggregation consortium dataset, and used computational and biochemical analysis to reveal the roles of damaging nsSNVs of TGM2. TGM2 and F13a display rarer damaging nsSNV sites than other TGMs and sequence of TGM2, F13a and TGM1 are evolutionary constrained. TGM2 nsSNVs are predicted to destabilize protein structure, influence Ca2+ and GTP regulation, and non-enzymatic interactions, but none coincide with conserved functional sites. We have experimentally characterized six TGM2 allelic variants detected so far in homozygous form, out of which only one, p.Arg222Gln, has decreased activities. Published exome sequencing data from various populations have not uncovered individuals with homozygous loss-of-function variants for TGM2, TGM3 and TGM7. Thus it can be concluded that human transglutaminases differ in harboring damaging variants and TGM2 is under purifying selection suggesting that it may have so far not revealed physiological functions. PMID:28248968

  18. The draft genome sequence of Corynebacterium diphtheriae bv. mitis NCTC 3529 reveals significant diversity between the primary disease-causing biovars.

    PubMed

    Sangal, Vartul; Tucker, Nicholas P; Burkovski, Andreas; Hoskisson, Paul A

    2012-06-01

    We report the draft genome of the human pathogen Corynebacterium diphtheriae bv. mitis NCTC 3529. This is the first C. diphtheriae bv. mitis strain to be sequenced and reveals significant differences from the other primary biovar, C. diphtheriae bv. gravis.

  19. Differential transcriptome analysis of diabetes-resistant and -sensitive mouse islets reveals significant overlap with human diabetes susceptibility genes.

    PubMed

    Kluth, Oliver; Matzke, Daniela; Schulze, Gunnar; Schwenk, Robert W; Joost, Hans-Georg; Schürmann, Annette

    2014-12-01

    Type 2 diabetes in humans and in obese mice is polygenic. In recent genome-wide association studies, genetic markers explaining a small portion of the genetic contribution to the disease were discovered. However, functional evidence linking these genes with the pathogenesis of diabetes is scarce. We performed RNA sequencing-based transcriptomics of islets from two obese mouse strains, a diabetes-susceptible (NZO) and a diabetes-resistant (B6-ob/ob) mouse, after a short glucose challenge and compared these results with human data. Alignment of 2,328 differentially expressed genes to 106 human diabetes candidate genes revealed an overlap of 20 genes, including TCF7L2, IGFBP2, CDKN2A, CDKN2B, GRB10, and PRC1. The data provide a functional validation of human diabetes candidate genes, including those involved in regulating islet cell recovery and proliferation, and identify additional candidates that could be involved in human β-cell failure. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  20. Multilocus phylogenetic analyses reveal unexpected abundant diversity and significant disjunct distribution pattern of the Hedgehog Mushrooms (Hydnum L.).

    PubMed

    Feng, Bang; Wang, Xiang-Hua; Ratkowsky, David; Gates, Genevieve; Lee, Su See; Grebenc, Tine; Yang, Zhu L

    2016-05-06

    Hydnum is a fungal genus proposed by Linnaeus in the early time of modern taxonomy. It contains several ectomycorrhizal species which are commonly consumed worldwide. However, Hydnum is one of the most understudied fungal genera, especially from a molecular phylogenetic view. In this study, we extensively gathered specimens of Hydnum from Asia, Europe, America and Australasia, and analyzed them by using sequences of four gene fragments (ITS, nrLSU, tef1α and rpb1). Our phylogenetic analyses recognized at least 31 phylogenetic species within Hydnum, 15 of which were reported for the first time. Most Australasian species were recognized as strongly divergent old relics, but recent migration between Australasia and the Northern Hemisphere was also detected. Within the Northern Hemisphere, frequent historical biota exchanges between the Old World and the New World via both the North Atlantic Land Bridge and the Bering Land Bridge could be elucidated. Our study also revealed that most Hydnum species found in subalpine areas of the Hengduan Mountains in southwestern China occur in northeastern/northern China and Europe, indicating that the composition of the mycobiota in the Hengduan Mountains reigion is more complicated than what we have known before.

  1. Multilocus phylogenetic analyses reveal unexpected abundant diversity and significant disjunct distribution pattern of the Hedgehog Mushrooms (Hydnum L.)

    PubMed Central

    Feng, Bang; Wang, Xiang-Hua; Ratkowsky, David; Gates, Genevieve; Lee, Su See; Grebenc, Tine; Yang, Zhu L.

    2016-01-01

    Hydnum is a fungal genus proposed by Linnaeus in the early time of modern taxonomy. It contains several ectomycorrhizal species which are commonly consumed worldwide. However, Hydnum is one of the most understudied fungal genera, especially from a molecular phylogenetic view. In this study, we extensively gathered specimens of Hydnum from Asia, Europe, America and Australasia, and analyzed them by using sequences of four gene fragments (ITS, nrLSU, tef1α and rpb1). Our phylogenetic analyses recognized at least 31 phylogenetic species within Hydnum, 15 of which were reported for the first time. Most Australasian species were recognized as strongly divergent old relics, but recent migration between Australasia and the Northern Hemisphere was also detected. Within the Northern Hemisphere, frequent historical biota exchanges between the Old World and the New World via both the North Atlantic Land Bridge and the Bering Land Bridge could be elucidated. Our study also revealed that most Hydnum species found in subalpine areas of the Hengduan Mountains in southwestern China occur in northeastern/northern China and Europe, indicating that the composition of the mycobiota in the Hengduan Mountains reigion is more complicated than what we have known before. PMID:27151256

  2. Characterization and phylogenetic analysis of α-gliadin gene sequences reveals significant genomic divergence in Triticeae species.

    PubMed

    Li, Guang-Rong; Lang, Tao; Yang, En-Nian; Liu, Cheng; Yang, Zu-Jun

    2014-12-01

    Although the unique properties of wheat α-gliadin gene family are well characterized, little is known about the evolution and genomic divergence of α-gliadin gene family within the Triticeae. We isolated a total of 203 α-gliadin gene sequences from 11 representative diploid and polyploid Triticeae species, and found 108 sequences putatively functional. Our results indicate that α-gliadin genes may have possibly originated from wild Secale species, where the sequences contain the shortest repetitive domains and display minimum variation. A miniature inverted-repeat transposable element insertion is reported for the first time in α-gliadin gene sequence of Thinopyrum intermedium in this study, indicating that the transposable element might have contributed to the diversification of α-gliadin genes family among Triticeae genomes. The phylogenetic analyses revealed that the α-gliadin gene sequences of Dasypyrum, Australopyrum, Lophopyrum, Eremopyrum and Pseudoroengeria species have amplified several times. A search for four typical toxic epitopes for celiac disease within the Triticeae α-gliadin gene sequences showed that the α-gliadins of wild Secale, Australopyrum and Agropyron genomes lack all four epitopes, while other Triticeae species have accumulated these epitopes, suggesting that the evolution of these toxic epitopes sequences occurred during the course of speciation, domestication or polyploidization of Triticeae.

  3. Light and Electron Microscopy of the European Beaver (Castor fiber) Stomach Reveal Unique Morphological Features with Possible General Biological Significance

    PubMed Central

    Petryński, Wojciech; Palkowska, Katarzyna; Prusik, Magdalena; Targońska, Krystyna; Giżejewski, Zygmunt; Przybylska-Gornowicz, Barbara

    2014-01-01

    Anatomical, histological, and ultrastructural studies of the European beaver stomach revealed several unique morphological features. The prominent attribute of its gross morphology was the cardiogastric gland (CGG), located near the oesophageal entrance. Light microscopy showed that the CGG was formed by invaginations of the mucosa into the submucosa, which contained densely packed proper gastric glands comprised primarily of parietal and chief cells. Mucous neck cells represented <0.1% of cells in the CGG gastric glands and 22–32% of cells in the proper gastric glands of the mucosa lining the stomach lumen. These data suggest that chief cells in the CGG develop from undifferentiated cells that migrate through the gastric gland neck rather than from mucous neck cells. Classical chief cell formation (i.e., arising from mucous neck cells) occurred in the mucosa lining the stomach lumen, however. The muscularis around the CGG consisted primarily of skeletal muscle tissue. The cardiac region was rudimentary while the fundus/corpus and pyloric regions were equally developed. Another unusual feature of the beaver stomach was the presence of specific mucus with a thickness up to 950 µm (in frozen, unfixed sections) that coated the mucosa. Our observations suggest that the formation of this mucus is complex and includes the secretory granule accumulation in the cytoplasm of pit cells, the granule aggregation inside cells, and the incorporation of degenerating cells into the mucus. PMID:24727802

  4. Light and electron microscopy of the European beaver (Castor fiber) stomach reveal unique morphological features with possible general biological significance.

    PubMed

    Ziółkowska, Natalia; Lewczuk, Bogdan; Petryński, Wojciech; Palkowska, Katarzyna; Prusik, Magdalena; Targońska, Krystyna; Giżejewski, Zygmunt; Przybylska-Gornowicz, Barbara

    2014-01-01

    Anatomical, histological, and ultrastructural studies of the European beaver stomach revealed several unique morphological features. The prominent attribute of its gross morphology was the cardiogastric gland (CGG), located near the oesophageal entrance. Light microscopy showed that the CGG was formed by invaginations of the mucosa into the submucosa, which contained densely packed proper gastric glands comprised primarily of parietal and chief cells. Mucous neck cells represented <0.1% of cells in the CGG gastric glands and 22-32% of cells in the proper gastric glands of the mucosa lining the stomach lumen. These data suggest that chief cells in the CGG develop from undifferentiated cells that migrate through the gastric gland neck rather than from mucous neck cells. Classical chief cell formation (i.e., arising from mucous neck cells) occurred in the mucosa lining the stomach lumen, however. The muscularis around the CGG consisted primarily of skeletal muscle tissue. The cardiac region was rudimentary while the fundus/corpus and pyloric regions were equally developed. Another unusual feature of the beaver stomach was the presence of specific mucus with a thickness up to 950 µm (in frozen, unfixed sections) that coated the mucosa. Our observations suggest that the formation of this mucus is complex and includes the secretory granule accumulation in the cytoplasm of pit cells, the granule aggregation inside cells, and the incorporation of degenerating cells into the mucus.

  5. The significance of the Golgi complex in envelopment of bovine herpesvirus 1 (BHV-1) as revealed by cryobased electron microscopy.

    PubMed

    Wild, Peter; Schraner, Elisabeth M; Cantieni, Daniel; Loepfe, Eva; Walther, Paul; Müller, Martin; Engels, Monika

    2002-01-01

    Nucleocapsids of herpesviruses originate in the nucleus of host cells and bud through the inner nuclear membrane acquiring tegument and envelope. The release of the enveloped virus particle from the perinuclear space is unknown. Cryobased electron microscopic imaging revealed enveloped virus particles within cisterns associated with the perinuclear space, a pre-Golgi compartment connecting Golgi cisterns to the perinuclear space, and enveloped virus particles in Golgi cisterns where they are packaged into transport vacuoles by membrane fission. To our knowledge, our images show for the first time the connectivity from the perinuclear space to Golgi cisterns. The data strongly indicate an intracisternal transport of enveloped virus particles from the budding site to the packaging site. Budding starts by condensation at the inner membrane. Condensation involving the viral envelope and peripheral tegument was persistent in virus particles within perinuclear space and associated cisterns. Virus particles within Golgi cisterns and transport vacuoles originating by Golgi membrane fission, however, lacked condensation. Instead, spikes were clearly evident. The phenomenon of condensation is considered likely to be responsible for preventing fusion of the viral envelope with cisternal membranes and/or for driving virions from the perinuclear space to Golgi cisterns. Glycoprotein K is discussed to likely play a role in the intracisternal transportation of virions. In addition to the pathway including intracisternal transport and packaging, there were clear indications for the well-known pathway involving wrapping of cytoplasmic nucleocapsids by Golgi membranes. The origin of the cytoplasmic nucleocapsids, however, remains obscure. Lack of evidence for release of nucleocapsids at the outer nuclear membrane suggests that the process is very rapid, or that nucleocapsids pass the nucleocytoplasmic barrier via an alternative route.

  6. Measuring microscale strain fields in articular cartilage during rapid impact reveals thresholds for chondrocyte death and a protective role for the superficial layer

    PubMed Central

    Bartell, Lena R.; Fortier, Lisa A.; Bonassar, Lawrence J.; Cohen, Itai

    2015-01-01

    Articular cartilage is a heterogeneous soft tissue that dissipates and distributes loads in mammalian joints. Though robust, cartilage is susceptible to damage from loading at high rates or magnitudes. Such injurious loads have been implicated in degenerative changes, including chronic osteoarthritis (OA), which remains a leading cause of disability in developed nations. Despite decades of research, mechanisms of OA initiation after trauma remain poorly understood. Indeed, although bulk cartilage mechanics are measurable during impact, current techniques cannot access microscale mechanics at those rapid time scales. We aimed to address this knowledge gap by imaging the microscale mechanics and corresponding acute biological changes of cartilage in response to rapid loading. In this study, we utilized fast-camera and confocal microscopy to achieve roughly 85 μm spatial resolution of the cartilage deformation during a rapid (~3 ms), localized impact and the chondrocyte death following impact. Our results showed that, at these high rates, strain and chondrocyte death were highly correlated (p<0.001) with a threshold of 8% microscale strain norm before any cell death occurred. Additionally, chondrocyte death had developed by two hours after impact, suggesting a time frame for clinical therapeutics. Moreover, when the superficial layer was removed, strain – and subsequently chondrocyte death – penetrated deeper into the samples (p<0.001), suggesting a protective role for the superficial layer of articular cartilage. Combined, these results provide insight regarding the detailed biomechanics that drive early chondrocyte damage after trauma and emphasize the importance of understanding cartilage and its mechanics on the microscale. PMID:26150096

  7. High-frequency thresholds: circumaural earphone versus insert earphone.

    PubMed

    Valente, M; Valente, M; Goebel, J

    1992-11-01

    Benefits of high-frequency audiometry in monitoring hearing sensitivity of patients administered ototoxic medications are well established. High-frequency thresholds have been reported to be variable, due in part to small differences in the placement of the earphone diaphragm over the opening of the ear canal. Reliability may be improved by using insert earphones (ER-2) when obtaining high-frequency thresholds. The purposes of this study were to determine high-frequency threshold test-retest reliability using Koss HV/1A+ and ER-2 earphones and to determine if significant differences are present between high-frequency thresholds obtained using these two earphones. Results obtained on 40 ears of 20 normal hearing adults revealed that differences between the test and retest thresholds for each earphone were not significant. Intrasubject threshold differences between the test and retest thresholds for each earphone were, for the most part, within +/- 10 dB at all test frequencies. Further, significantly greater intensity was required to measure threshold when using the ER-2 earphone when compared to the Koss HV/1A+ at all test frequencies.

  8. Octave-Band Thresholds for Modeled Reverberant Fields

    NASA Technical Reports Server (NTRS)

    Begault, Durand R.; Wenzel, Elizabeth M.; Tran, Laura L.; Anderson, Mark R.; Trejo, Leonard J. (Technical Monitor)

    1998-01-01

    Auditory thresholds for 10 subjects were obtained for speech stimuli reverberation. The reverberation was produced and manipulated by 3-D audio modeling based on an actual room. The independent variables were octave-band-filtering (bypassed, 0.25 - 2.0 kHz Fc) and reverberation time (0.2- 1.1 sec). An ANOVA revealed significant effects (threshold range: -19 to -35 dB re 60 dB SRL).

  9. Octave-Band Thresholds for Modeled Reverberant Fields

    NASA Technical Reports Server (NTRS)

    Begault, Durand R.; Wenzel, Elizabeth M.; Tran, Laura L.; Anderson, Mark R.; Trejo, Leonard J. (Technical Monitor)

    1998-01-01

    Auditory thresholds for 10 subjects were obtained for speech stimuli reverberation. The reverberation was produced and manipulated by 3-D audio modeling based on an actual room. The independent variables were octave-band-filtering (bypassed, 0.25 - 2.0 kHz Fc) and reverberation time (0.2- 1.1 sec). An ANOVA revealed significant effects (threshold range: -19 to -35 dB re 60 dB SRL).

  10. Life-table studies revealed significant effects of deforestation on the development and survivorship of Anopheles minimus larvae.

    PubMed

    Wang, Xiaoming; Zhou, Guofa; Zhong, Daibin; Wang, Xiaoling; Wang, Ying; Yang, Zhaoqing; Cui, Liwang; Yan, Guiyun

    2016-06-06

    Many developing countries are experiencing rapid ecological changes such as deforestation and shifting agricultural practices. These environmental changes may have an important consequence on malaria due to their impact on vector survival and reproduction. Despite intensive deforestation and malaria transmission in the China-Myanmar border area, the impact of deforestation on malaria vectors in the border area is unknown. We conducted life table studies on Anopheles minimus larvae to determine the pupation rate and development time in microcosms under deforested, banana plantation, and forested environments. The pupation rate of An. minimus was 3.8 % in the forested environment. It was significantly increased to 12.5 % in banana plantations and to 52.5 % in the deforested area. Deforestation reduced larval-to-pupal development time by 1.9-3.3 days. Food supplementation to aquatic habitats in forested environments and banana plantations significantly increased larval survival rate to a similar level as in the deforested environment. Deforestation enhanced the survival and development of An. minimus larvae, a major malaria vector in the China-Myanmar border area. Experimental determination of the life table parameters on mosquito larvae under a variety of environmental conditions is valuable to model malaria transmission dynamics and impact by climate and environmental changes.

  11. Metabolic and ventilatory thresholds assessment in front crawl swimming.

    PubMed

    Ribeiro, J; Figueiredo, P; Sousa, M; De Jesus, K; Keskinen, K; Vilas-Boas, J P; Fernandes, R J

    2015-01-01

    The purpose of this study was to assess and characterize the ventilatory anaerobic threshold in swimming, and to verify if the anaerobic metabolic threshold could be accurately estimated using ventilatory parameters. Twenty-eight national-level male swimmers performed a n x 200 m front crawl individualized intermittent incremental protocol, with 30 s rest intervals, until exhaustion. The ventilatory variables and heart rate were continuously measured using a telemetric portable gas analyser. The capillary blood samples for lactate concentration analysis were collected from the earlobe at rest, during rest intervals, and at the end of exercise. No significant differences were observed between the ventilatory and metabolic thresholds for lactate concentration, heart rate and velocity (P=0.62, 0.80 and 0.78, respectively). The Bland-Altman plot revealed higher agreement between both methods for heart rate and velocity values. Ventilatory anaerobic threshold occurred at a swimming velocity corresponding to 88% of maximal oxygen uptake and lactate concentration mean values at ventilatory and metabolic thresholds were lower than 3 mmol.L(-1). Swimming anaerobic metabolic threshold could be accurately estimated using ventilatory parameters. Moreover, ventilatory anaerobic threshold occurred at similar %VO2max than in other sports. The lactate concentration mean values at ventilatory and metabolic thresholds were lower than the reference value of 4 mmol.L(-1) evidencing that, in highly trained swimmers, individualized values of anaerobic threshold should be used instead of general references.

  12. Metabolomics reveals significant impairments in the immune system of the APP/PS1 transgenic mice of Alzheimer's disease.

    PubMed

    González-Domínguez, Raúl; García-Barrera, Tamara; Vitorica, Javier; Gómez-Ariza, José Luis

    2015-02-01

    Inflammatory processes and other failures related to the immune system are common features associated with Alzheimer's disease (AD), in both brain and the peripheral system. Thus, the study of the main organs of the immune system may have a great potential for the elucidation of pathological mechanisms underlying these abnormalities. This is the first metabolomic investigation performed in spleen and thymus from transgenic mice of AD. Tissues were fingerprinted using a metabolomic platform comprising GC-MS and ultra-HPLC-MS. Multivariate statistics demonstrated significant differences in numerous metabolites between the APP/PS1 mice and wild-type controls, and it was proven that multiple biochemical pathways are disturbed in these organs including abnormal metabolism of phospholipids, energy deficiencies, altered homeostasis of amino acids, oxidative stress, and others. Therefore, these findings highlight the importance of the proper metabolic functioning of peripheral immune system in the development of neurodegenerative disorders such as AD.

  13. Optical polarization tractography revealed significant fiber disarray in skeletal muscles of a mouse model for Duchenne muscular dystrophy.

    PubMed

    Wang, Y; Zhang, K; Wasala, N B; Duan, D; Yao, G

    2015-02-01

    Optical polarization tractography (OPT) was recently developed to visualize tissue fiber architecture with cellular-level resolution and accuracy. In this study, we explored the feasibility of using OPT to study muscle disease in the mdx4cv mouse model of Duchenne muscular dystrophy. The freshly dissected tibialis anterior muscles of mdx4cv and normal mice were imaged. A "fiber disarray index" (FDI) was developed to quantify the myofiber disorganization. In necrotic muscle regions of the mdx4cv mice, the FDI was significantly elevated and can be used to segment the 3D necrotic regions for assessing the overall muscle damage. These results demonstrated the OPT's capability for imaging microscopic fiber alternations in muscle research.

  14. Reticulate Structures Reveal the Significance of Cell Motility in the Morphogenesis of Complex Microbial Structures in Pavilion Lake, British Columbia

    NASA Astrophysics Data System (ADS)

    Shepard, R.

    2008-12-01

    Microbial communities are architects of incredibly complex and diverse morphological structures. Each morphology is a snapshot that reflects the complex interactions within the microbial community and between the community and its environment. Characterizing morphology as an emergent property of microbial communities is thus relevant to understanding the evolution of multicellularity and complexity in developmental systems, to the identification of biosignatures, and to furthering our understanding of modern and ancient microbial ecology. Recently discovered cyanobacterial mats in Pavilion Lake, British Columbia construct unusual complex architecture on the scale of decimeters that incorporates significant void space. Fundamental mesoscale morphological elements include terraces, arches, bridges, depressions, domes, and pillars. The mats themselves also exhibit several microscale morphologies, with reticulate structures being the dominant example. The reticulate structures exhibit a diverse spectrum of morphologies with endmembers characterized by either angular or curvilinear ridges. In laboratory studies, aggregation into reticulate structures occurs as a result of the random gliding and colliding among motile cyanobacterial filaments. Likewise, when Pavilion reticulate mats were sampled and brought to the surface, cyanobacteria invariably migrated out of the mat onto surrounding surfaces. Filaments were observed to move rapidly in clumps, preferentially following paths of previous filaments. The migrating filaments organized into new angular and ropey reticulate biofilms within hours of sampling, demonstrating that cell motility is responsible for the reticulate patterns. Because the morphogenesis of reticulate structures can be linked to motility behaviors of filamentous cyanobacteria, the Willow Point mats provide a unique natural laboratory in which to elucidate the connections between a specific microbial behavior and the construction of complex microbial

  15. Experimental passage of St. Louis encephalitis virus in vivo in mosquitoes and chickens reveals evolutionarily significant virus characteristics.

    PubMed

    Ciota, Alexander T; Jia, Yongqing; Payne, Anne F; Jerzak, Greta; Davis, Lauren J; Young, David S; Ehrbar, Dylan; Kramer, Laura D

    2009-11-17

    St. Louis encephalitis virus (SLEV; Flaviviridae, flavivirus) was the major cause of epidemic flaviviral encephalitis in the U.S. prior to the introduction of West Nile virus (WNV) in 1999. However, outbreaks of SLEV have been significantly more limited then WNV in terms of levels of activity and geographic dispersal. One possible explanation for these variable levels of activity is that differences in the potential for each virus to adapt to its host cycle exist. The need for arboviruses to replicate in disparate hosts is thought to result in constraints on both evolution and host-specific adaptation. If cycling is the cause of genetic stability observed in nature and arboviruses lack host specialization, then sequential passage should result in both the accumulation of mutations and specialized viruses better suited for replication in that host. Previous studies suggest that WNV and SLEV differ in capacity for both genetic change and host specialization, and in the costs each accrues from specializing. In an attempt to clarify how selective pressures contribute to epidemiological patterns of WNV and SLEV, we evaluated mutant spectra size, consensus genetic change, and phenotypic changes for SLEV in vivo following 20 sequential passages via inoculation in either Culex pipiens mosquitoes or chickens. Results demonstrate that the capacity for genetic change is large for SLEV and that the size of the mutant spectrum is host-dependent using our passage methodology. Despite this, a general lack of consensus change resulted from passage in either host, a result that contrasts with the idea that constraints on evolution in nature result from host cycling alone. Results also suggest that a high level of adaptation to both hosts already exists, despite host cycling. A strain significantly more infectious in chickens did emerge from one lineage of chicken passage, yet other lineages and all mosquito passage strains did not display measurable host-specific fitness gains. In

  16. Significant population genetic structure of the Cameroonian fresh water snail, Bulinus globosus, (Gastropoda: Planorbidae) revealed by nuclear microsatellite loci analysis.

    PubMed

    Djuikwo-Teukeng, F F; Da Silva, A; Njiokou, F; Kamgang, B; Ekobo, A Same; Dreyfuss, G

    2014-09-01

    In order to characterize the demographic traits and spatial structure of Cameroonians Bulinus globosus, intermediate host of Schistosoma haematobium, genetic structure of seven different populations, collected from the tropical zone, was studied using six polymorphic microsatellites. Intrapopulation genetic diversity ranged from 0.37 to 0.55. Interpopulation genetic diversity variation clearly illustrated their significant isolation due to distance with gene flow substantially limited to neighbouring populations. The effective population sizes (Ne) were relatively low (from 3.0 to 18.6), which supposes a high rate from which populations would lose their genetic diversity by drift. Analysis of genetic temporal variability indicated fluctuations of allelic frequencies (35 of 42 locus-population combinations, P<0.05) characteristic of stochastic demography, and this is reinforced by events of bottlenecks detected in all populations. These findings demonstrated that Cameroonian B. globosus were mixed-maters with some populations showing clear preference for outcrossing. These data also suggest that genetic drift and gene flow are the main factors shaping the genetic structure of studied populations.

  17. Multispectral images of flowers reveal the adaptive significance of using long-wavelength-sensitive receptors for edge detection in bees.

    PubMed

    Vasas, Vera; Hanley, Daniel; Kevan, Peter G; Chittka, Lars

    2017-03-17

    Many pollinating insects acquire their entire nutrition from visiting flowers, and they must therefore be efficient both at detecting flowers and at recognizing familiar rewarding flower types. A crucial first step in recognition is the identification of edges and the segmentation of the visual field into areas that belong together. Honeybees and bumblebees acquire visual information through three types of photoreceptors; however, they only use a single receptor type-the one sensitive to longer wavelengths-for edge detection and movement detection. Here, we show that these long-wavelength receptors (peak sensitivity at ~544 nm, i.e., green) provide the most consistent signals in response to natural objects. Using our multispectral image database of flowering plants, we found that long-wavelength receptor responses had, depending on the specific scenario, up to four times higher signal-to-noise ratios than the short- and medium-wavelength receptors. The reliability of the long-wavelength receptors emerges from an intricate interaction between flower coloration and the bee's visual system. This finding highlights the adaptive significance of bees using only long-wavelength receptors to locate flowers among leaves, before using information provided by all three receptors to distinguish the rewarding flower species through trichromatic color vision.

  18. Altered niche of an ecologically significant urchin species, Centrostephanus rodgersii, in its extended range revealed using an Autonomous Underwater Vehicle

    NASA Astrophysics Data System (ADS)

    Perkins, Nicholas R.; Hill, Nicole A.; Foster, Scott D.; Barrett, Neville S.

    2015-03-01

    Poleward range shifts of species as a result of global climate change are being increasingly documented. As species extend into new ranges their ecological impacts and the niches that they occupy may be unpredictable. We use benthic imagery obtained from the broad-scale deployment of an Autonomous Underwater Vehicle (AUV) to quantify the depth distribution of barrens habitat formed by a recent range extension of the sea urchin species, Centrostephanus rodgersii, a known ecosystem engineer. AUV transects covering similar depths from both the historical range of New South Wales, Australia, and from the range extension area of the east coast of Tasmania were examined for the presence of barrens. We find that C. rodgersii occupies a different realised niche in its extended range, with barrens habitat occurring significantly deeper in Tasmanian waters (16-58 m) compared to NSW waters (7-27 m). The expansion of barrens habitat has devastating impacts on biodiversity, with flow-on effects to ecosystem services and local fisheries, and in Tasmania this threat extends to deeper, invertebrate-dominated habitats. This finding has important management implications, in particular the need to incorporate deeper reef systems into planning, with increased barrens expected under future climate change predictions. One conservation management approach is the use of no-take Marine Protected Areas (MPAs) to prevent barren establishment in representative habitats by rebuilding viable populations of urchin predators. We also examine the correlation between MPA status and the occurrence of barrens within a small, no-take Tasmanian reserve and adjacent control sites. We find that there is suggestive, but inconclusive, evidence for fewer barrens in the MPA (p = 0.07). Our study highlights the utility of a novel technology for conducting large-scale benthic surveys and monitoring the impacts of range extending species.

  19. A deep sequencing reveals significant diversity among dominant variants and evolutionary dynamics of avian leukosis viruses in two infectious ecosystems.

    PubMed

    Meng, Fanfeng; Dong, Xuan; Hu, Tao; Chang, Shuang; Fan, Jianhua; Zhao, Peng; Cui, Zhizhong

    2016-12-19

    As a typical retrovirus, the evolution of Avian leukosis virus subgroup J (ALV-J) in different infectious ecosystems is not characterized, what we know is there are a cloud of diverse variants, namely quasispecies with considerable genetic diversity. This study is to explore the selection of infectious ecosystems on dominant variants and their evolutionary dynamics of ALV-J between DF1 cells and specific-pathogen-free (SPF) chickens. High-throughput sequencing platforms provide an approach for detecting quasispecies diversity more fully. An average of about 20,000 valid reads were obtained from two variable regions of gp85 gene and LTR-U3 region from each sample in different infectious ecosystems. The top 10 dominant variants among ALV-J from chicken plasmas, DF1 cells and liver tumor were completely different from each other. Also there was a difference of shannon entropy and global selection pressure values (ω) in different infectious ecosystems. In the plasmas of two chickens, a large portion of quasispecies contained a 3-peptides "LSD" repeat insertion that was only less than 0.01% in DF1 cell culture supernatants. In parallel studies, the LTR-U3 region of ALV-J from the chicken plasmas demonstrated more variants with mutations in their transcription regulatory elements than those from DF1 cells. Our data taken together suggest that the molecular epidemiology based on isolated ALV-J in cell culture may not represent the true evolution of virus in chicken flocks in the field. The biological significance of the "LSD" insert and mutations in LTR-U3 needs to be further studied.

  20. The Functional Significance of Posttranslational Modifications on Polo-Like Kinase 1 Revealed by Chemical Genetic Complementation

    PubMed Central

    Lasek, Amber L.; McPherson, Brittany M.; Trueman, Natalie G.; Burkard, Mark E.

    2016-01-01

    Mitosis is coordinated by carefully controlled phosphorylation and ubiquitin-mediated proteolysis. Polo-like kinase 1 (Plk1) plays a central role in regulating mitosis and cytokinesis by phosphorylating target proteins. Yet, Plk1 is itself a target for posttranslational modification by phosphorylation and ubiquitination. We developed a chemical-genetic complementation assay to evaluate the functional significance of 34 posttranslational modifications (PTMs) on human Plk1. To do this, we used human cells that solely express a modified analog-sensitive Plk1 (Plk1AS) and complemented with wildtype Plk1. The wildtype Plk1 provides cells with a functional Plk1 allele in the presence of 3-MB-PP1, a bulky ATP-analog inhibitor that specifically inhibits Plk1AS. Using this approach, we evaluated the ability of 34 singly non-modifiable Plk1 mutants to complement Plk1AS in the presence of 3-MB-PP1. Mutation of the T-loop activating residue T210 and adjacent T214 are lethal, but surprisingly individual mutation of the remaining 32 posttranslational modification sites did not disrupt the essential functions of Plk1. To evaluate redundancy, we simultaneously mutated all phosphorylation sites in the kinase domain except for T210 and T214 or all sites in the C-terminal polo-box domain (PBD). We discovered that redundant phosphorylation events within the kinase domain are required for accurate chromosome segregation in anaphase but those in the PBD are dispensable. We conclude that PTMs within the T-loop of Plk1 are essential and nonredundant, additional modifications in the kinase domain provide redundant control of Plk1 function, and those in the PBD are dispensable for essential mitotic functions of Plk1. This comprehensive evaluation of Plk1 modifications demonstrates that although phosphorylation and ubiquitination are important for mitotic progression, many individual PTMs detected in human tissue may have redundant, subtle, or dispensable roles in gene function. PMID

  1. Color difference thresholds in dentistry.

    PubMed

    Paravina, Rade D; Ghinea, Razvan; Herrera, Luis J; Bona, Alvaro D; Igiel, Christopher; Linninger, Mercedes; Sakai, Maiko; Takahashi, Hidekazu; Tashkandi, Esam; Perez, Maria del Mar

    2015-01-01

    The aim of this prospective multicenter study was to determine 50:50% perceptibility threshold (PT) and 50:50% acceptability threshold (AT) of dental ceramic under simulated clinical settings. The spectral radiance of 63 monochromatic ceramic specimens was determined using a non-contact spectroradiometer. A total of 60 specimen pairs, divided into 3 sets of 20 specimen pairs (medium to light shades, medium to dark shades, and dark shades), were selected for psychophysical experiment. The coordinating center and seven research sites obtained the Institutional Review Board (IRB) approvals prior the beginning of the experiment. Each research site had 25 observers, divided into five groups of five observers: dentists-D, dental students-S, dental auxiliaries-A, dental technicians-T, and lay persons-L. There were 35 observers per group (five observers per group at each site ×7 sites), for a total of 175 observers. Visual color comparisons were performed using a viewing booth. Takagi-Sugeno-Kang (TSK) fuzzy approximation was used for fitting the data points. The 50:50% PT and 50:50% AT were determined in CIELAB and CIEDE2000. The t-test was used to evaluate the statistical significance in thresholds differences. The CIELAB 50:50% PT was ΔEab  = 1.2, whereas 50:50% AT was ΔEab  = 2.7. Corresponding CIEDE2000 (ΔE00 ) values were 0.8 and 1.8, respectively. 50:50% PT by the observer group revealed differences among groups D, A, T, and L as compared with 50:50% PT for all observers. The 50:50% AT for all observers was statistically different than 50:50% AT in groups T and L. A 50:50% perceptibility and ATs were significantly different. The same is true for differences between two color difference formulas ΔE00 /ΔEab . Observer groups and sites showed high level of statistical difference in all thresholds. Visual color difference thresholds can serve as a quality control tool to guide the selection of esthetic dental materials, evaluate clinical performance, and

  2. Functional redundancy of the kinases MEK1 and MEK2: Rescue of the Mek1 mutant phenotype by Mek2 knock-in reveals a protein threshold effect.

    PubMed

    Aoidi, Rifdat; Maltais, Annie; Charron, Jean

    2016-01-26

    The mammalian genome contains two mitogen-activated protein kinase (MAPK) kinase (MEK)-encoding genes, Mek1 and Mek2. MEKs phosphorylate and activate the two extracellular signal-regulated kinase (ERK) isoforms ERK1 and ERK2. Mek1(-/-) embryos die due to placental defects, whereas Mek2(-/-) mice survive with a normal life span and fertility, suggesting that MEK1 has functions not shared by MEK2. However, most Mek1(+/-)Mek2(+/-) embryos also die from placental defects, indicating that both Mek genes contribute to placental development. To assess the functional specificity of the Mek1 and Mek2 genes, we produced a Mek1 knock-in allele in which the Mek2 coding sequences were placed under the control of Mek1 regulatory sequences (Mek1(2) allele). Mek1(2/2) mice were viable with no apparent phenotype, indicating rescue by MEK2 and functional redundancy between the two MEK proteins. However, Mek1(2/-) embryos with Mek2 in only one of the Mek1 alleles and the other Mek1 allele null died from abnormal placenta, suggesting a dosage effect. Analysis of mice from a Mek1 Mek2 allelic series revealed that the occurrence of the placenta phenotype correlated with the amount of MEK protein independently of which MEK isoform was produced. Thus, although MEK1 and MEK2 can substitute for each other, a minimum amount of MEK is critical for placenta development and embryo survival. Copyright © 2016, American Association for the Advancement of Science.

  3. Experimental and environmental factors affect spurious detection of ecological thresholds

    USGS Publications Warehouse

    Daily, Jonathan P.; Hitt, Nathaniel P.; Smith, David; Snyder, Craig D.

    2012-01-01

    Threshold detection methods are increasingly popular for assessing nonlinear responses to environmental change, but their statistical performance remains poorly understood. We simulated linear change in stream benthic macroinvertebrate communities and evaluated the performance of commonly used threshold detection methods based on model fitting (piecewise quantile regression [PQR]), data partitioning (nonparametric change point analysis [NCPA]), and a hybrid approach (significant zero crossings [SiZer]). We demonstrated that false detection of ecological thresholds (type I errors) and inferences on threshold locations are influenced by sample size, rate of linear change, and frequency of observations across the environmental gradient (i.e., sample-environment distribution, SED). However, the relative importance of these factors varied among statistical methods and between inference types. False detection rates were influenced primarily by user-selected parameters for PQR (τ) and SiZer (bandwidth) and secondarily by sample size (for PQR) and SED (for SiZer). In contrast, the location of reported thresholds was influenced primarily by SED. Bootstrapped confidence intervals for NCPA threshold locations revealed strong correspondence to SED. We conclude that the choice of statistical methods for threshold detection should be matched to experimental and environmental constraints to minimize false detection rates and avoid spurious inferences regarding threshold location.

  4. Threshold Graph Limits and Random Threshold Graphs

    PubMed Central

    Diaconis, Persi; Holmes, Susan; Janson, Svante

    2010-01-01

    We study the limit theory of large threshold graphs and apply this to a variety of models for random threshold graphs. The results give a nice set of examples for the emerging theory of graph limits. PMID:20811581

  5. Liquid chromatography-electrospray linear ion trap mass spectrometry analysis of targeted neuropeptides in Tac1(-/-) mouse spinal cords reveals significant lower concentration of opioid peptides.

    PubMed

    Saidi, Mouna; Beaudry, Francis

    2015-08-01

    Tachykinin and opioid peptides play a central role in pain transmission, modulation and inhibition. The treatment of pain is very important in medicine and many studies using NK1 receptor antagonists failed to show significant analgesic effects in humans. Recent investigations suggest that both pronociceptive tachykinins and the analgesic opioid systems are important for normal pain sensation. The analysis of opioid peptides in Tac1(-/-) spinal cord tissues offers a great opportunity to verify the influence of the tachykinin system on specific opioid peptides. The objectives of this study were to develop an HPLC-MS/MRM assay to quantify targeted peptides in spinal cord tissues. Secondly, we wanted to verify if the Tac1(-/-) mouse endogenous opioid system is hampered and therefore affects significantly the pain modulatory pathways. Targeted neuropeptides were analyzed by high performance liquid chromatography linear ion trap mass spectrometry. Our results reveal that EM-2, Leu-Enk and Dyn A were down-regulated in Tac1(-/-) spinal cord tissues. Interestingly, Dyn A was almost 3 fold down-regulated (p<0.0001). No significant concentration differences were observed in mouse Tac1(-/-) spinal cords for Met-Enk and CGRP. The analysis of Tac1(-/-) mouse spinal cords revealed noteworthy decreases of EM-2, Leu-Enk and Dyn A concentrations which strongly suggest a significant impact on the endogenous pain-relieving mechanisms. These observations may have insightful impact on future analgesic drug developments and therapeutic strategies.

  6. CARA Risk Assessment Thresholds

    NASA Technical Reports Server (NTRS)

    Hejduk, M. D.

    2016-01-01

    Warning remediation threshold (Red threshold): Pc level at which warnings are issued, and active remediation considered and usually executed. Analysis threshold (Green to Yellow threshold): Pc level at which analysis of event is indicated, including seeking additional information if warranted. Post-remediation threshold: Pc level to which remediation maneuvers are sized in order to achieve event remediation and obviate any need for immediate follow-up maneuvers. Maneuver screening threshold: Pc compliance level for routine maneuver screenings (more demanding than regular Red threshold due to additional maneuver uncertainty).

  7. Different continuous cropping spans significantly affect microbial community membership and structure in a vanilla-grown soil as revealed by deep pyrosequencing.

    PubMed

    Xiong, Wu; Zhao, Qingyun; Zhao, Jun; Xun, Weibing; Li, Rong; Zhang, Ruifu; Wu, Huasong; Shen, Qirong

    2015-07-01

    In the present study, soil bacterial and fungal communities across vanilla continuous cropping time-series fields were assessed through deep pyrosequencing of 16S ribosomal RNA (rRNA) genes and internal transcribed spacer (ITS) regions. The results demonstrated that the long-term monoculture of vanilla significantly altered soil microbial communities. Soil fungal diversity index increased with consecutive cropping years, whereas soil bacterial diversity was relatively stable. Bray-Curtis dissimilarity cluster and UniFrac-weighted principal coordinate analysis (PCoA) revealed that monoculture time was the major determinant for fungal community structure, but not for bacterial community structure. The relative abundances (RAs) of the Firmicutes, Actinobacteria, Bacteroidetes, and Basidiomycota phyla were depleted along the years of vanilla monoculture. Pearson correlations at the phyla level demonstrated that Actinobacteria, Armatimonadetes, Bacteroidetes, Verrucomicrobia, and Firmicutes had significant negative correlations with vanilla disease index (DI), while no significant correlation for fungal phyla was observed. In addition, the amount of the pathogen Fusarium oxysporum accumulated with increasing years and was significantly positively correlated with vanilla DI. By contrast, the abundance of beneficial bacteria, including Bradyrhizobium and Bacillus, significantly decreased over time. In sum, soil weakness and vanilla stem wilt disease after long-term continuous cropping can be attributed to the alteration of the soil microbial community membership and structure, i.e., the reduction of the beneficial microbes and the accumulation of the fungal pathogen.

  8. Targeted gene disruption of glycerol-3-phosphate dehydrogenase in Colletotrichum gloeosporioides reveals evidence that glycerol is a significant transferred nutrient from host plant to fungal pathogen.

    PubMed

    Wei, Yangdou; Shen, Wenyun; Dauk, Melanie; Wang, Feng; Selvaraj, Gopalan; Zou, Jitao

    2004-01-02

    Unidirectional transfer of nutrients from plant host to pathogen represents a most revealing aspect of the parasitic lifestyle of plant pathogens. Whereas much effort has been focused on sugars and amino acids, the identification of other significant metabolites is equally important for comprehensive characterization of metabolic interactions between plants and biotrophic fungal pathogens. Employing a strategy of targeted gene disruption, we generated a mutant strain (gpdhDelta) defective in glycerol-3-phosphate dehydrogenase in a hemibiotrophic plant pathogen, Colletotrichum gloeosporioides f.sp. malvae. The gpdhDelta strain had severe defects in carbon utilization as it could use neither glucose nor amino acids for sustained growth. Although the mutant mycelia were able to grow on potato dextrose agar medium, they displayed arrhythmicity in growth and failure to conidiate. The metabolic defect of gpdhDelta could be entirely ameliorated by glycerol in chemically defined minimal medium. Furthermore, glycerol was the one and only metabolite that could restore rhythmic growth and conidiation of gpdhDelta. Despite the profound defects in carbon source utilization, in planta the gpdhDelta strain exhibited normal pathogenicity, proceeded normally in its life cycle, and produced abundant conidia. Analysis of plant tissues at the peripheral zone of fungal infection sites revealed a time-dependent reduction in glycerol content. This study provides strong evidence for a role of glycerol as a significant transferred metabolite from plant to fungal pathogen.

  9. Vibration perception thresholds of human maxillary and mandibular central incisors.

    PubMed

    Robertson, Lee T; Levy, Jay H; Petrisor, Daniel; Lilly, David J; Dong, W K

    2003-04-01

    Tactile information from dental mechanoreceptors contributes to the perception of food bolus textures and the control of mastication. While numerous studies have measured the light-touch sensory thresholds of teeth, little information is available about the vibrotactile perception thresholds of teeth. This study uses an adaptive psychophysical procedure to determine thresholds of vibratory stimulation of maxillary and mandibular central incisors in 16 healthy human subjects. An electromechanical vibrator delivered labiolingual forces perpendicular to the long axis of the maxillary and mandibular incisors at 10 stimulation frequencies between 40 and 315 Hz. The median thresholds ranged between 44 and 104 mN. A linear regression analysis revealed a significant increase in the vibrotactile thresholds with increasing frequencies for stimulation of the maxillary and mandibular incisors. No significant differences were found between regression slopes of the thresholds of the maxillary and mandibular incisors. These results indicated that maxillary and mandibular incisors should be able to discriminate effectively among a variety of textures based on their ability to encode a wide range of vibration frequencies.

  10. Family-based association analyses of imputed genotypes reveal genome-wide significant association of Alzheimer's disease with OSBPL6, PTPRG, and PDCL3.

    PubMed

    Herold, C; Hooli, B V; Mullin, K; Liu, T; Roehr, J T; Mattheisen, M; Parrado, A R; Bertram, L; Lange, C; Tanzi, R E

    2016-11-01

    The genetic basis of Alzheimer's disease (AD) is complex and heterogeneous. Over 200 highly penetrant pathogenic variants in the genes APP, PSEN1, and PSEN2 cause a subset of early-onset familial AD. On the other hand, susceptibility to late-onset forms of AD (LOAD) is indisputably associated to the ɛ4 allele in the gene APOE, and more recently to variants in more than two-dozen additional genes identified in the large-scale genome-wide association studies (GWAS) and meta-analyses reports. Taken together however, although the heritability in AD is estimated to be as high as 80%, a large proportion of the underlying genetic factors still remain to be elucidated. In this study, we performed a systematic family-based genome-wide association and meta-analysis on close to 15 million imputed variants from three large collections of AD families (~3500 subjects from 1070 families). Using a multivariate phenotype combining affection status and onset age, meta-analysis of the association results revealed three single nucleotide polymorphisms (SNPs) that achieved genome-wide significance for association with AD risk: rs7609954 in the gene PTPRG (P-value=3.98 × 10(-8)), rs1347297 in the gene OSBPL6 (P-value=4.53 × 10(-8)), and rs1513625 near PDCL3 (P-value=4.28 × 10(-8)). In addition, rs72953347 in OSBPL6 (P-value=6.36 × 10(-7)) and two SNPs in the gene CDKAL1 showed marginally significant association with LOAD (rs10456232, P-value=4.76 × 10(-7); rs62400067, P-value=3.54 × 10(-7)). In summary, family-based GWAS meta-analysis of imputed SNPs revealed novel genomic variants in (or near) PTPRG, OSBPL6, and PDCL3 that influence risk for AD with genome-wide significance.

  11. Threshold Barrier of Carbon Nanotube Growth

    NASA Astrophysics Data System (ADS)

    Yuan, Qinghong; Hu, Hong; Ding, Feng

    2011-10-01

    A previously overlooked step of carbon nanotube (CNT) growth, incorporating C atoms into the CNT wall through the CNT-catalyst interface, is studied by density functional theory calculations. A significant barrier for incorporating C atoms into the CNT wall (˜2eV for most used catalysts, Fe, Co, and Ni) is revealed and the incorporation can be the threshold step of CNT growth in most experiments. In addition, the temperature dependent CNT growth rate is calculated and our calculation demonstrates that growing 0.1-1 m long CNTs in 1 h is theoretically possible.

  12. Threshold quantum cryptography

    SciTech Connect

    Tokunaga, Yuuki; Okamoto, Tatsuaki; Imoto, Nobuyuki

    2005-01-01

    We present the concept of threshold collaborative unitary transformation or threshold quantum cryptography, which is a kind of quantum version of threshold cryptography. Threshold quantum cryptography states that classical shared secrets are distributed to several parties and a subset of them, whose number is greater than a threshold, collaborates to compute a quantum cryptographic function, while keeping each share secretly inside each party. The shared secrets are reusable if no cheating is detected. As a concrete example of this concept, we show a distributed protocol (with threshold) of conjugate coding.

  13. Cochlear neuropathy and the coding of supra-threshold sound

    PubMed Central

    Bharadwaj, Hari M.; Verhulst, Sarah; Shaheen, Luke; Liberman, M. Charles; Shinn-Cunningham, Barbara G.

    2014-01-01

    Many listeners with hearing thresholds within the clinically normal range nonetheless complain of difficulty hearing in everyday settings and understanding speech in noise. Converging evidence from human and animal studies points to one potential source of such difficulties: differences in the fidelity with which supra-threshold sound is encoded in the early portions of the auditory pathway. Measures of auditory subcortical steady-state responses (SSSRs) in humans and animals support the idea that the temporal precision of the early auditory representation can be poor even when hearing thresholds are normal. In humans with normal hearing thresholds (NHTs), paradigms that require listeners to make use of the detailed spectro-temporal structure of supra-threshold sound, such as selective attention and discrimination of frequency modulation (FM), reveal individual differences that correlate with subcortical temporal coding precision. Animal studies show that noise exposure and aging can cause a loss of a large percentage of auditory nerve fibers (ANFs) without any significant change in measured audiograms. Here, we argue that cochlear neuropathy may reduce encoding precision of supra-threshold sound, and that this manifests both behaviorally and in SSSRs in humans. Furthermore, recent studies suggest that noise-induced neuropathy may be selective for higher-threshold, lower-spontaneous-rate nerve fibers. Based on our hypothesis, we suggest some approaches that may yield particularly sensitive, objective measures of supra-threshold coding deficits that arise due to neuropathy. Finally, we comment on the potential clinical significance of these ideas and identify areas for future investigation. PMID:24600357

  14. Pure versus combined Merkel cell carcinomas: immunohistochemical evaluation of cellular proteins (p53, Bcl-2, and c-kit) reveals significant overexpression of p53 in combined tumors.

    PubMed

    Lai, Jonathan H; Fleming, Kirsten E; Ly, Thai Yen; Pasternak, Sylvia; Godlewski, Marek; Doucette, Steve; Walsh, Noreen M

    2015-09-01

    Merkel cell polyomavirus is of oncogenic significance in approximately 80% of Merkel cell carcinomas. Morphological subcategories of the tumor differ in regard to viral status, the rare combined type being uniformly virus negative and the predominant pure type being mainly virus positive. Indications that different biological subsets of the tumor exist led us to explore this diversity. In an Eastern Canadian cohort of cases (75 patients; mean age, 76 years [range, 43-91]; male/female ratio, 43:32; 51 [68%] pure and 24 [34%] combined tumors), we semiquantitatively compared the immunohistochemical expression of 3 cellular proteins (p53, Bcl-2, and c-kit) in pure versus combined groups. Viral status was known in a subset of cases. The significant overexpression of p53 in the combined group (mean [SD], 153.8 [117.8] versus 121.6 [77.9]; P = .01) and the increased epidermal expression of this protein (p53 patches) in the same group lend credence to a primary etiologic role for sun damage in these cases. Expression of Bcl-2 and c-kit did not differ significantly between the 2 morphological groups. A relative increase in c-kit expression was significantly associated with a virus-negative status (median [interquartile range], 100 [60-115] versus 70 [0-100]; P = .03). Emerging data reveal divergent biological pathways in Merkel cell carcinoma, each with a characteristic immunohistochemical profile. Virus-positive tumors (all pure) exhibit high retinoblastoma protein and low p53 expression, whereas virus-negative cases (few pure and all combined) show high p53 and relatively high c-kit expression. The potential biological implications of this dichotomy call for consistent stratification of these tumors in future studies.

  15. Detectability thresholds of general modular graphs

    NASA Astrophysics Data System (ADS)

    Kawamoto, Tatsuro; Kabashima, Yoshiyuki

    2017-01-01

    We investigate the detectability thresholds of various modular structures in the stochastic block model. Our analysis reveals how the detectability threshold is related to the details of the modular pattern, including the hierarchy of the clusters. We show that certain planted structures are impossible to infer regardless of their fuzziness.

  16. Threshold Concepts in Biochemistry

    ERIC Educational Resources Information Center

    Loertscher, Jennifer

    2011-01-01

    Threshold concepts can be identified for any discipline and provide a framework for linking student learning to curricular design. Threshold concepts represent a transformed understanding of a discipline, without which the learner cannot progress and are therefore pivotal in learning in a discipline. Although threshold concepts have been…

  17. Threshold Concepts in Biochemistry

    ERIC Educational Resources Information Center

    Loertscher, Jennifer

    2011-01-01

    Threshold concepts can be identified for any discipline and provide a framework for linking student learning to curricular design. Threshold concepts represent a transformed understanding of a discipline, without which the learner cannot progress and are therefore pivotal in learning in a discipline. Although threshold concepts have been…

  18. Agreeable smellers and sensitive neurotics--correlations among personality traits and sensory thresholds.

    PubMed

    Croy, Ilona; Springborn, Maria; Lötsch, Jörn; Johnston, Amy N B; Hummel, Thomas

    2011-04-27

    Correlations between personality traits and a wide range of sensory thresholds were examined. Participants (N = 124) completed a personality inventory (NEO-FFI) and underwent assessment of olfactory, trigeminal, tactile and gustatory detection thresholds, as well as examination of trigeminal and tactile pain thresholds. Significantly enhanced odor sensitivity in socially agreeable people, significantly enhanced trigeminal sensitivity in neurotic subjects, and a tendency for enhanced pain tolerance in highly conscientious participants was revealed. It is postulated that varied sensory processing may influence an individual's perception of the environment; particularly their perception of socially relevant or potentially dangerous stimuli and thus, varied with personality.

  19. Agreeable Smellers and Sensitive Neurotics – Correlations among Personality Traits and Sensory Thresholds

    PubMed Central

    Croy, Ilona; Springborn, Maria; Lötsch, Jörn; Johnston, Amy N. B.; Hummel, Thomas

    2011-01-01

    Correlations between personality traits and a wide range of sensory thresholds were examined. Participants (N = 124) completed a personality inventory (NEO-FFI) and underwent assessment of olfactory, trigeminal, tactile and gustatory detection thresholds, as well as examination of trigeminal and tactile pain thresholds. Significantly enhanced odor sensitivity in socially agreeable people, significantly enhanced trigeminal sensitivity in neurotic subjects, and a tendency for enhanced pain tolerance in highly conscientious participants was revealed. It is postulated that varied sensory processing may influence an individual's perception of the environment; particularly their perception of socially relevant or potentially dangerous stimuli and thus, varied with personality. PMID:21556139

  20. Family-based Association Analyses of Imputed Genotypes Reveal Genome-Wide Significant Association of Alzheimer’s disease with OSBPL6, PTPRG and PDCL3

    PubMed Central

    Herold, Christine; Hooli, Basavaraj V.; Mullin, Kristina; Liu, Tian; Roehr, Johannes T; Mattheisen, Manuel; Parrado, Antonio R.; Bertram, Lars; Lange, Christoph; Tanzi, Rudolph E.

    2015-01-01

    The genetic basis of Alzheimer's disease (AD) is complex and heterogeneous. Over 200 highly penetrant pathogenic variants in the genes APP, PSEN1 and PSEN2 cause a subset of early-onset familial Alzheimer's disease (EOFAD). On the other hand, susceptibility to late-onset forms of AD (LOAD) is indisputably associated to the ε4 allele in the gene APOE, and more recently to variants in more than two-dozen additional genes identified in the large-scale genome-wide association studies (GWAS) and meta-analyses reports. Taken together however, although the heritability in AD is estimated to be as high as 80%, a large proportion of the underlying genetic factors still remain to be elucidated. In this study we performed a systematic family-based genome-wide association and meta-analysis on close to 15 million imputed variants from three large collections of AD families (~3,500 subjects from 1,070 families). Using a multivariate phenotype combining affection status and onset age, meta-analysis of the association results revealed three single nucleotide polymorphisms (SNPs) that achieved genome-wide significance for association with AD risk: rs7609954 in the gene PTPRG (P-value = 3.98·10−08), rs1347297 in the gene OSBPL6 (P-value = 4.53·10−08), and rs1513625 near PDCL3 (P-value = 4.28·10−08). In addition, rs72953347 in OSBPL6 (P-value = 6.36·10−07) and two SNPs in the gene CDKAL1 showed marginally significant association with LOAD (rs10456232, P-value: 4.76·10−07; rs62400067, P-value: 3.54·10−07). In summary, family-based GWAS meta-analysis of imputed SNPs revealed novel genomic variants in (or near) PTPRG, OSBPL6, and PDCL3 that influence risk for AD with genome-wide significance. PMID:26830138

  1. Threshold models in radiation carcinogenesis

    SciTech Connect

    Hoel, D.G.; Li, P.

    1998-09-01

    Cancer incidence and mortality data from the atomic bomb survivors cohort has been analyzed to allow for the possibility of a threshold dose response. The same dose-response models as used in the original papers were fit to the data. The estimated cancer incidence from the fitted models over-predicted the observed cancer incidence in the lowest exposure group. This is consistent with a threshold or nonlinear dose-response at low-doses. Thresholds were added to the dose-response models and the range of possible thresholds is shown for both solid tumor cancers as well as the different leukemia types. This analysis suggests that the A-bomb cancer incidence data agree more with a threshold or nonlinear dose-response model than a purely linear model although the linear model is statistically equivalent. This observation is not found with the mortality data. For both the incidence data and the mortality data the addition of a threshold term significantly improves the fit to the linear or linear-quadratic dose response for both total leukemias and also for the leukemia subtypes of ALL, AML, and CML.

  2. Recent fracture induced electromagnetic field measurements revealing an Earth system in second order phase transition before the occurrence of significant earthquakes

    NASA Astrophysics Data System (ADS)

    Potirakis, Stelios M.; Contoyiannis, Yiannis; Kopanas, John; Antonopoulos, George; Nomicos, Constantinos; Eftaxias, Konstantinos

    2015-04-01

    A crucial feature observed in the study of fracture induced electromagnetic emissions (EMEs) is the asynchronous appearance of MHz and kHz AE-EM precursors: the MHz EMEs precede the kHz ones: the strong avalanche-like kHz emissions are launched in the tail of pre-fracture emissions. Herein, we focus on the systematically observed precursory MHz EME. We show that both, the MHz EMEs recorded prior to recent significant earthquakes that occurred in Greece and the associated seismic activities came to critical condition a few days before the main shock occurrence. The analyses were performed my means of two independent statistical method, namely, the method of critical fluctuation and the natural time method, both revealing critical features. This results indicates the existence of a strong connection of the MHz EME with the corresponding earthquake preparation process. Accumulated laboratory, theoretical and numerical evidence supports the hypothesis that the MHz EME is emitted during the fracture of process of heterogeneous medium surrounding the family of strong entities (asperities) distributed along the fault sustaining the system. The kHz EME is attributed to the family of asperities themselves.

  3. Expression of progerin in aging mouse brains reveals structural nuclear abnormalities without detectible significant alterations in gene expression, hippocampal stem cells or behavior.

    PubMed

    Baek, Jean-Ha; Schmidt, Eva; Viceconte, Nikenza; Strandgren, Charlotte; Pernold, Karin; Richard, Thibaud J C; Van Leeuwen, Fred W; Dantuma, Nico P; Damberg, Peter; Hultenby, Kjell; Ulfhake, Brun; Mugnaini, Enrico; Rozell, Björn; Eriksson, Maria

    2015-03-01

    Hutchinson-Gilford progeria syndrome (HGPS) is a segmental progeroid syndrome with multiple features suggestive of premature accelerated aging. Accumulation of progerin is thought to underlie the pathophysiology of HGPS. However, despite ubiquitous expression of lamin A in all differentiated cells, the HGPS mutation results in organ-specific defects. For example, bone and skin are strongly affected by HGPS, while the brain appears to be unaffected. There are no definite explanations as to the variable sensitivity to progeria disease among different organs. In addition, low levels of progerin have also been found in several tissues from normal individuals, but it is not clear if low levels of progerin contribute to the aging of the brain. In an attempt to clarify the origin of this phenomenon, we have developed an inducible transgenic mouse model with expression of the most common HGPS mutation in brain, skin, bone and heart to investigate how the mutation affects these organs. Ultrastructural analysis of neuronal nuclei after 70 weeks of expression of the LMNA c.1824C>T mutation showed severe distortion with multiple lobulations and irregular extensions. Despite severe distortions in the nuclei of hippocampal neurons of HGPS animals, there were only negligible changes in gene expression after 63 weeks of transgenic expression. Behavioral analysis and neurogenesis assays, following long-term expression of the HGPS mutation, did not reveal significant pathology. Our results suggest that certain tissues are protected from functional deleterious effects of progerin.

  4. Expression of progerin in aging mouse brains reveals structural nuclear abnormalities without detectible significant alterations in gene expression, hippocampal stem cells or behavior

    PubMed Central

    Baek, Jean-Ha; Schmidt, Eva; Viceconte, Nikenza; Strandgren, Charlotte; Pernold, Karin; Richard, Thibaud J. C.; Van Leeuwen, Fred W.; Dantuma, Nico P.; Damberg, Peter; Hultenby, Kjell; Ulfhake, Brun; Mugnaini, Enrico; Rozell, Björn; Eriksson, Maria

    2015-01-01

    Hutchinson–Gilford progeria syndrome (HGPS) is a segmental progeroid syndrome with multiple features suggestive of premature accelerated aging. Accumulation of progerin is thought to underlie the pathophysiology of HGPS. However, despite ubiquitous expression of lamin A in all differentiated cells, the HGPS mutation results in organ-specific defects. For example, bone and skin are strongly affected by HGPS, while the brain appears to be unaffected. There are no definite explanations as to the variable sensitivity to progeria disease among different organs. In addition, low levels of progerin have also been found in several tissues from normal individuals, but it is not clear if low levels of progerin contribute to the aging of the brain. In an attempt to clarify the origin of this phenomenon, we have developed an inducible transgenic mouse model with expression of the most common HGPS mutation in brain, skin, bone and heart to investigate how the mutation affects these organs. Ultrastructural analysis of neuronal nuclei after 70 weeks of expression of the LMNA c.1824C>T mutation showed severe distortion with multiple lobulations and irregular extensions. Despite severe distortions in the nuclei of hippocampal neurons of HGPS animals, there were only negligible changes in gene expression after 63 weeks of transgenic expression. Behavioral analysis and neurogenesis assays, following long-term expression of the HGPS mutation, did not reveal significant pathology. Our results suggest that certain tissues are protected from functional deleterious effects of progerin. PMID:25343989

  5. Infrared Laser Spectroscopy of the n-PROPYL and i-PROPYL Radicals in Helium Droplets: Significant Bend-Stretch Coupling Revealed in the CH Stretch Region

    NASA Astrophysics Data System (ADS)

    Moradi, Christopher P.; Douberly, Gary E.; Tabor, Daniel P.; Sibert, Edwin

    2016-06-01

    The n-propyl and i-propyl radicals were generated in the gas phase via pyrolysis of n-butyl nitrite (CH3(CH2)3ONO) and i-butyl nitrite (CH3CH(CH3)CH2ONO) precursors, respectively. Nascent radicals were promptly solvated by a beam of He nanodroplets, and the infrared spectra of the radicals were recorded in the C-H stretching region. In addition to three vibrations of n-propyl previously measured in an Ar matrix, we observe many unreported bands between 2800 and 3150 wn, which we attribute to propyl radicals. The C-H stretching modes observed above 2960 wn for both radicals are in excellent agreement with anharmonic frequencies computed using VPT2. Between 2800 and 2960 wn, however, the spectra of n-propyl and i-propyl radicals become quite congested and difficult to assign due to the presence of multiple anharmonic resonances. Computations employing a local mode Hamiltonian reveal the origin of the spectral congestion to be strong coupling between the high frequency C-H stretching modes and the lower frequency bending/scissoring motions. The only significant local coupling is between stretches and bends on the same CH2/CH3 group.

  6. Physicochemical state of the nanotopographic surface of commercially pure titanium following anodization-hydrothermal treatment reveals significantly improved hydrophilicity and surface energy profiles.

    PubMed

    Takebe, Jun; Ito, Shigeki; Miura, Shingo; Miyata, Kyohei; Ishibashi, Kanji

    2012-01-01

    A method of coating commercially pure titanium (cpTi) implants with a highly crystalline, thin hydroxyapatite (HA) layer using discharge anodic oxidation followed by hydrothermal treatment (Spark discharged Anodic oxidation treatment ; SA-treated cpTi) has been reported for use in clinical dentistry. We hypothesized that a thin HA layer with high crystallinity and nanostructured anodic titanium oxide film on such SA-treated cpTi implant surfaces might be a crucial function of their surface-specific potential energy. To test this, we analyzed anodic oxide (AO) cpTi and SA-treated cpTi disks by SEM and AFM. Contact angles and surface free energy of each disk surface was measured using FAMAS software. High-magnification SEM and AFM revealed the nanotopographic structure of the anodic titanium oxide film on SA-treated cpTi; however, this was not observed on the AO cpTi surface. The contact angle and surface free energy measurements were also significantly different between AO cpTi and SA-treated cpTi surfaces (Tukey's, P<0.05). These data indicated that the change of physicochemical properties of an anodic titanium oxide film with HA crystals on an SA-treated cpTi surface may play a key role in the phenomenon of osteoconduction during the process of osseointegration.

  7. Genetic basis of heterosis for growth-related traits in Arabidopsis investigated by testcross progenies of near-isogenic lines reveals a significant role of epistasis.

    PubMed

    Melchinger, Albrecht E; Piepho, Hans-Peter; Utz, H Friedrich; Muminovic, Jasmina; Wegenast, Thilo; Törjék, Otto; Altmann, Thomas; Kusterer, Barbara

    2007-11-01

    Epistasis seems to play a significant role in the manifestation of heterosis. However, the power of detecting epistatic interactions among quantitative trait loci (QTL) in segregating populations is low. We studied heterosis in Arabidopsis thaliana hybrid C24 x Col-0 by testing near-isogenic lines (NILs) and their triple testcross (TTC) progenies. Our objectives were to (i) provide the theoretical basis for estimating different types of genetic effects with this experimental design, (ii) determine the extent of heterosis for seven growth-related traits, (iii) map the underlying QTL, and (iv) determine their gene action. Two substitution libraries, each consisting of 28 NILs and covering approximately 61 and 39% of the Arabidopsis genome, were assayed by 110 single-nucleotide polymorphism (SNP) markers. With our novel generation means approach 38 QTL were detected, many of which confirmed heterotic QTL detected previously in the same cross with TTC progenies of recombinant inbred lines. Furthermore, many of the QTL were common for different traits and in common with the 58 QTL detected by a method that compares triplets consisting of a NIL, its recurrent parent, and their F(1) cross. While the latter approach revealed mostly (75%) overdominant QTL, the former approach allowed separation of dominance and epistasis by analyzing all materials simultaneously and yielded substantial positive additive x additive effects besides directional dominance. Positive epistatic effects reduced heterosis for growth-related traits in our materials.

  8. Structural and functional analysis of aa3-type and cbb3-type cytochrome c oxidases of Paracoccus denitrificans reveals significant differences in proton-pump design.

    PubMed

    de Gier, J W; Schepper, M; Reijnders, W N; van Dyck, S J; Slotboom, D J; Warne, A; Saraste, M; Krab, K; Finel, M; Stouthamer, A H; van Spanning, R J; van der Oost, J

    1996-06-01

    In Paracoccus denitrificans the aa3-type cytochrome c oxidase and the bb3-type quinol oxidase have previously been characterized in detail, both biochemically and genetically. Here we report on the isolation of a genomic locus that harbours the gene cluster ccoNOOP, and demonstrate that it encodes an alternative cbb3-type cytochrome c oxidase. This oxidase has previously been shown to be specifically induced at low oxygen tensions, suggesting that its expression is controlled by an oxygen-sensing mechanism. This view is corroborated by the observation that the ccoNOOP gene cluster is preceded by a gene that encodes an FNR homologue and that its promoter region contains an FNR-binding motif. Biochemical and physiological analyses of a set of oxidase mutants revealed that, at least under the conditions tested, cytochromes aa3, bb3 and cbb3 make up the complete set of terminal oxidases in P. denitrificans. Proton-translocation measurements of these oxidase mutants indicate that all three oxidase types have the capacity to pump protons. Previously, however, we have reported decreased H+/e- coupling efficiencies of the cbb3-type oxidase under certain conditions. Sequence alignment suggests that many residues that have been proposed to constitute the chemical and pumped proton channels in cytochrome aa3 (and probably also in cytochrome bb3) are not conserved in cytochrome cbb3. It is concluded that the design of the proton pump in cytochrome cbb3 differs significantly from that in the other oxidase types.

  9. Embracing thresholds for better environmental management

    PubMed Central

    Kelly, Ryan P.; Erickson, Ashley L.; Mease, Lindley A.; Battista, Willow; Kittinger, John N.; Fujita, Rod

    2015-01-01

    Three decades of study have revealed dozens of examples in which natural systems have crossed biophysical thresholds (‘tipping points’)—nonlinear changes in ecosystem structure and function—as a result of human-induced stressors, dramatically altering ecosystem function and services. Environmental management that avoids such thresholds could prevent severe social, economic and environmental impacts. Here, we review management measures implemented in ecological systems that have thresholds. Using Ostrom's social–ecological systems framework, we analysed key biophysical and institutional factors associated with 51 social–ecological systems and associated management regimes, and related these to management success defined by ecological outcomes. We categorized cases as instances of prospective or retrospective management, based upon whether management aimed to avoid a threshold or to restore systems that have crossed a threshold. We find that smaller systems are more amenable to threshold-based management, that routine monitoring is associated with successful avoidance of thresholds and recovery after thresholds have been crossed, and that success is associated with the explicit threshold-based management. These findings are powerful evidence for the policy relevance of information on ecological thresholds across a wide range of ecosystems.

  10. Apolipoprotein A-I in Labeo rohita: Cloning and functional characterisation reveal its broad spectrum antimicrobial property, and indicate significant role during ectoparasitic infection.

    PubMed

    Mohapatra, Amruta; Karan, Sweta; Kar, Banya; Garg, L C; Dixit, A; Sahoo, P K

    2016-08-01

    Apolipoprotein A-I (ApoA-I) is the most abundant and multifunctional high-density lipoprotein (HDL) having a major role in lipid transport and potent antimicrobial activity against a wide range of microbes. In this study, a complete CDS of 771 bp of Labeo rohita (rohu) ApoA-I (LrApoA-I) encoding a protein of 256 amino acids was amplified, cloned and sequenced. Tissue specific transcription analysis of LrApoA-I revealed its expression in a wide range of tissues, with a very high level of expression in liver and spleen. Ontogenic study of LrApoA-I expression showed presence of transcripts in milt and 3 h post-fertilization onwards in the larvae. The expression kinetics of LrApoA-I was studied upon infection with three different types of pathogens to elucidate its functional significance. Its expression was found to be up-regulated in the anterior kidney of L. rohita post-infection with Aeromonas hydrophila. Similarly following poly I:C (poly inosinic:cytidylic) stimulation, the transcript levels increased in both the anterior kidney and liver tissues. Significant up-regulation of LrApoA-I expression was observed in skin, mucous, liver and anterior kidney of the fish challenged with the ectoparasite Argulus siamensis. Immunomodulatory effect of recombinant LrApoA-I (rApoA-I) produced in Escherichia coli was demonstrated against A. hydrophila challenge in vivo. L. rohita administered with rApoA-I at a dose of 100 μg exhibited significantly higher protection (∼55%) upon challenge with A. hydrophila 12 h post-administration of the protein, in comparison to that observed in control group, along with higher level of expression of immune-related genes. The heightened expression of ApoA-I observed post-infection reflected its involvement in immune responses against a wide range of infections including bacterial, viral as well as parasitic pathogens. Our results also suggest the possibility of using rApoA-I as an immunostimulant, particularly rendering protection

  11. Genome Wide Expression Profiling of Cancer Cell Lines Cultured in Microgravity Reveals Significant Dysregulation of Cell Cycle and MicroRNA Gene Networks

    PubMed Central

    Vidyasekar, Prasanna; Shyamsunder, Pavithra; Arun, Rajpranap; Santhakumar, Rajalakshmi; Kapadia, Nand Kishore; Kumar, Ravi; Verma, Rama Shanker

    2015-01-01

    Zero gravity causes several changes in metabolic and functional aspects of the human body and experiments in space flight have demonstrated alterations in cancer growth and progression. This study reports the genome wide expression profiling of a colorectal cancer cell line-DLD-1, and a lymphoblast leukemic cell line-MOLT-4, under simulated microgravity in an effort to understand central processes and cellular functions that are dysregulated among both cell lines. Altered cell morphology, reduced cell viability and an aberrant cell cycle profile in comparison to their static controls were observed in both cell lines under microgravity. The process of cell cycle in DLD-1 cells was markedly affected with reduced viability, reduced colony forming ability, an apoptotic population and dysregulation of cell cycle genes, oncogenes, and cancer progression and prognostic markers. DNA microarray analysis revealed 1801 (upregulated) and 2542 (downregulated) genes (>2 fold) in DLD-1 cultures under microgravity while MOLT-4 cultures differentially expressed 349 (upregulated) and 444 (downregulated) genes (>2 fold) under microgravity. The loss in cell proliferative capacity was corroborated with the downregulation of the cell cycle process as demonstrated by functional clustering of DNA microarray data using gene ontology terms. The genome wide expression profile also showed significant dysregulation of post transcriptional gene silencing machinery and multiple microRNA host genes that are potential tumor suppressors and proto-oncogenes including MIR22HG, MIR17HG and MIR21HG. The MIR22HG, a tumor-suppressor gene was one of the highest upregulated genes in the microarray data showing a 4.4 log fold upregulation under microgravity. Real time PCR validated the dysregulation in the host gene by demonstrating a 4.18 log fold upregulation of the miR-22 microRNA. Microarray data also showed dysregulation of direct targets of miR-22, SP1, CDK6 and CCNA2. PMID:26295583

  12. A novel method for RNA extraction from FFPE samples reveals significant differences in biomarker expression between orthotopic and subcutaneous pancreatic cancer patient-derived xenografts

    PubMed Central

    Brown, Mark; Maawy, Ali; Chang, Alexander; Lee, Jacqueline; Gharibi, Armen; Katz, Matthew H; Fleming, Jason; Hoffman, Robert M; Bouvet, Michael; Doebler, Robert; Kelber, Jonathan A

    2017-01-01

    Next-generation sequencing (NGS) can identify and validate new biomarkers of cancer onset, progression and therapy resistance. Substantial archives of formalin-fixed, paraffin-embedded (FFPE) cancer samples from patients represent a rich resource for linking molecular signatures to clinical data. However, performing NGS on FFPE samples is limited by poor RNA purification methods. To address this hurdle, we developed an improved methodology for extracting high-quality RNA from FFPE samples. By briefly integrating a newly-designed micro-homogenizing (mH) tool with commercially available FFPE RNA extraction protocols, RNA recovery is increased by approximately 3-fold while maintaining standard A260/A280 ratios and RNA quality index (RQI) values. Furthermore, we demonstrate that the mH-purified FFPE RNAs are longer and of higher integrity. Previous studies have suggested that pancreatic ductal adenocarcinoma (PDAC) gene expression signatures vary significantly under in vitro versus in vivo and in vivo subcutaneous versus orthotopic conditions. By using our improved mH-based method, we were able to preserve established expression patterns of KRas-dependency genes within these three unique microenvironments. Finally, expression analysis of novel biomarkers in KRas mutant PDAC samples revealed that PEAK1 decreases and MST1R increases by over 100-fold in orthotopic versus subcutaneous microenvironments. Interestingly, however, only PEAK1 levels remain elevated in orthotopically grown KRas wild-type PDAC cells. These results demonstrate the critical nature of the orthotopic tumor microenvironment when evaluating the clinical relevance of new biomarkers in cells or patient-derived samples. Furthermore, this new mH-based FFPE RNA extraction method has the potential to enhance and expand future FFPE-RNA-NGS cancer biomarker studies. PMID:27602776

  13. HRS Threshold Adjustment Test

    NASA Astrophysics Data System (ADS)

    Skapik, Joe

    1991-07-01

    This test will determine the optimal, non-standard discriminator thresholds for the few anomalous channels on each HRS detector. A 15 second flat field observation followed by a 210 second dark count is performed at each of 10 discriminator threshold values for each detector. The result of the test will be the optimal threshold values to be entered into the PDB. Edited 4/30/91 to add comments to disable/re-enable cross-talk tables.

  14. Overcoming the effects of false positives and threshold bias in graph theoretical analyses of neuroimaging data

    PubMed Central

    Drakesmith, M.; Caeyenberghs, K.; Dutt, A.; Lewis, G.; David, A.S.; Jones, D.K.

    2015-01-01

    Graph theory (GT) is a powerful framework for quantifying topological features of neuroimaging-derived functional and structural networks. However, false positive (FP) connections arise frequently and influence the inferred topology of networks. Thresholding is often used to overcome this problem, but an appropriate threshold often relies on a priori assumptions, which will alter inferred network topologies. Four common network metrics (global efficiency, mean clustering coefficient, mean betweenness and smallworldness) were tested using a model tractography dataset. It was found that all four network metrics were significantly affected even by just one FP. Results also show that thresholding effectively dampens the impact of FPs, but at the expense of adding significant bias to network metrics. In a larger number (n = 248) of tractography datasets, statistics were computed across random group permutations for a range of thresholds, revealing that statistics for network metrics varied significantly more than for non-network metrics (i.e., number of streamlines and number of edges). Varying degrees of network atrophy were introduced artificially to half the datasets, to test sensitivity to genuine group differences. For some network metrics, this atrophy was detected as significant (p < 0.05, determined using permutation testing) only across a limited range of thresholds. We propose a multi-threshold permutation correction (MTPC) method, based on the cluster-enhanced permutation correction approach, to identify sustained significant effects across clusters of thresholds. This approach minimises requirements to determine a single threshold a priori. We demonstrate improved sensitivity of MTPC-corrected metrics to genuine group effects compared to an existing approach and demonstrate the use of MTPC on a previously published network analysis of tractography data derived from a clinical population. In conclusion, we show that there are large biases and instability

  15. Bayesian Threshold Estimation

    ERIC Educational Resources Information Center

    Gustafson, S. C.; Costello, C. S.; Like, E. C.; Pierce, S. J.; Shenoy, K. N.

    2009-01-01

    Bayesian estimation of a threshold time (hereafter simply threshold) for the receipt of impulse signals is accomplished given the following: 1) data, consisting of the number of impulses received in a time interval from zero to one and the time of the largest time impulse; 2) a model, consisting of a uniform probability density of impulse time…

  16. Bayesian Threshold Estimation

    ERIC Educational Resources Information Center

    Gustafson, S. C.; Costello, C. S.; Like, E. C.; Pierce, S. J.; Shenoy, K. N.

    2009-01-01

    Bayesian estimation of a threshold time (hereafter simply threshold) for the receipt of impulse signals is accomplished given the following: 1) data, consisting of the number of impulses received in a time interval from zero to one and the time of the largest time impulse; 2) a model, consisting of a uniform probability density of impulse time…

  17. Threshold Concepts in Economics

    ERIC Educational Resources Information Center

    Shanahan, Martin

    2016-01-01

    Purpose: The purpose of this paper is to examine threshold concepts in the context of teaching and learning first-year university economics. It outlines some of the arguments for using threshold concepts and provides examples using opportunity cost as an exemplar in economics. Design/ Methodology/Approach: The paper provides an overview of the…

  18. Pausing at the Threshold

    ERIC Educational Resources Information Center

    Morgan, Patrick K.

    2015-01-01

    Since about 2003, the notion of threshold concepts--the central ideas in any field that change how learners think about other ideas--have become difficult to escape at library conferences and in general information literacy discourse. Their visibility will likely only increase because threshold concepts figure prominently in the Framework for…

  19. The perils of thresholding

    NASA Astrophysics Data System (ADS)

    Font-Clos, Francesc; Pruessner, Gunnar; Moloney, Nicholas R.; Deluca, Anna

    2015-04-01

    The thresholding of time series of activity or intensity is frequently used to define and differentiate events. This is either implicit, for example due to resolution limits, or explicit, in order to filter certain small scale physics from the supposed true asymptotic events. Thresholding the birth-death process, however, introduces a scaling region into the event size distribution, which is characterized by an exponent that is unrelated to the actual asymptote and is rather an artefact of thresholding. As a result, numerical fits of simulation data produce a range of exponents, with the true asymptote visible only in the tail of the distribution. This tail is increasingly difficult to sample as the threshold is increased. In the present case, the exponents and the spurious nature of the scaling region can be determined analytically, thus demonstrating the way in which thresholding conceals the true asymptote. The analysis also suggests a procedure for detecting the influence of the threshold by means of a data collapse involving the threshold-imposed scale.

  20. Threshold concepts in prosthetics.

    PubMed

    Hill, Sophie

    2016-11-24

    Curriculum documents identify key concepts within learning prosthetics. Threshold concepts provide an alternative way of viewing the curriculum, focussing on the ways of thinking and practicing within prosthetics. Threshold concepts can be described as an opening to a different way of viewing a concept. This article forms part of a larger study exploring what students and staff experience as difficult in learning about prosthetics. To explore possible threshold concepts within prosthetics. Qualitative, interpretative phenomenological analysis. Data from 18 students and 8 staff at two universities with undergraduate prosthetics and orthotics programmes were generated through interviews and questionnaires. The data were analysed using an interpretative phenomenological analysis approach. Three possible threshold concepts arose from the data: 'how we walk', 'learning to talk' and 'considering the person'. Three potential threshold concepts in prosthetics are suggested with possible implications for prosthetics education. These possible threshold concepts involve changes in both conceptual and ontological knowledge, integrating into the persona of the individual. This integration occurs through the development of memories associated with procedural concepts that combine with disciplinary concepts. Considering the prosthetics curriculum through the lens of threshold concepts enables a focus on how students learn to become prosthetists. This study provides new insights into how prosthetists learn. This has implications for curriculum design in prosthetics education. © The International Society for Prosthetics and Orthotics 2016.

  1. Double Photoionization Near Threshold

    NASA Technical Reports Server (NTRS)

    Wehlitz, Ralf

    2007-01-01

    The threshold region of the double-photoionization cross section is of particular interest because both ejected electrons move slowly in the Coulomb field of the residual ion. Near threshold both electrons have time to interact with each other and with the residual ion. Also, different theoretical models compete to describe the double-photoionization cross section in the threshold region. We have investigated that cross section for lithium and beryllium and have analyzed our data with respect to the latest results in the Coulomb-dipole theory. We find that our data support the idea of a Coulomb-dipole interaction.

  2. Life below the threshold.

    PubMed

    Castro, C

    1991-01-01

    This article explains that malnutrition, poor health, and limited educational opportunities plague Philippine children -- especially female children -- from families living below the poverty threshold. Nearly 70% of households in the Philippines do not meet the required daily level of nutritional intake. Because it is often -- and incorrectly -- assumed that women's nutritional requirements are lower than men's, women suffer higher rates of malnutrition and poor health. A 1987 study revealed that 11.7% of all elementary students were underweight and 13.9% had stunted growths. Among elementary-school girls, 17% were malnourished and 40% suffered from anemia (among lactating mothers, more than 1/2 are anemic). A 1988 Program for Decentralized Educational Development study showed that grade VI students learn only about 1/2 of what they are supposed to learn. 30% of the children enrolled in grade school drop out before they reach their senior year. The Department of Education, Culture and Sports estimates that some 2.56 million students dropped out of school in l989. That same year, some 3.7 million children were counted as part of the labor force. In Manila alone, some 60,000 children work the streets, whether doing odd jobs or begging, or turning to crime or prostitution. the article tells the story of a 12 year-old girl named Ging, a 4th grader at a public school and the oldest child in a poor family of 6 children. The undernourished Ging dreams of a good future for her family and sees education as a way out of poverty; unfortunately, her time after school is spend working in the streets or looking after her family. She considers herself luckier than many of the other children working in the streets, since she at least has a family.

  3. Financial networks with static and dynamic thresholds

    NASA Astrophysics Data System (ADS)

    Qiu, Tian; Zheng, Bo; Chen, Guang

    2010-04-01

    Based on the daily data of the American and Chinese stock markets, the dynamic behavior of a financial network with static and dynamic thresholds is investigated. Compared with the static threshold, the dynamic threshold suppresses the large fluctuation induced by the cross correlation of individual stock prices and leads to a stable topological structure in the dynamic evolution. Long-range time correlations are revealed for the average clustering coefficient, average degree and cross correlation of degrees. The dynamic network shows a two-peak behavior in the degree distribution.

  4. Efficient circular thresholding.

    PubMed

    Lai, Yu-Kun; Rosin, Paul L

    2014-03-01

    Otsu's algorithm for thresholding images is widely used, and the computational complexity of determining the threshold from the histogram is O(N) where N is the number of histogram bins. When the algorithm is adapted to circular rather than linear histograms then two thresholds are required for binary thresholding. We show that, surprisingly, it is still possible to determine the optimal threshold in O(N) time. The efficient optimal algorithm is over 300 times faster than traditional approaches for typical histograms and is thus particularly suitable for real-time applications. We further demonstrate the usefulness of circular thresholding using the adapted Otsu criterion for various applications, including analysis of optical flow data, indoor/outdoor image classification, and non-photorealistic rendering. In particular, by combining circular Otsu feature with other colour/texture features, a 96.9% correct rate is obtained for indoor/outdoor classification on the well known IITM-SCID2 data set, outperforming the state-of-the-art result by 4.3%.

  5. A MICROARRAY ANALYSIS OF GENE EXPRESSION IN THE EMBRYONIC FORELIMB OF THE C57BL/6J MOUSE REVEALS SIGNIFICANT ALTERATIONS METABOLIC AND DEVELOPMENTAL REGULATION FOLLOWING ETHANOL EXPOSURE.

    EPA Science Inventory

    The observation of transcriptional changes following embryonic ethanol exposure may provide significant insights into the biological response to ethanol exposure. In this study, we used microarray analysis to examine the transcriptional response of the developing limb to a dose ...

  6. A MICROARRAY ANALYSIS OF GENE EXPRESSION IN THE EMBRYONIC FORELIMB OF THE C57BL/6J MOUSE REVEALS SIGNIFICANT ALTERATIONS METABOLIC AND DEVELOPMENTAL REGULATION FOLLOWING ETHANOL EXPOSURE.

    EPA Science Inventory

    The observation of transcriptional changes following embryonic ethanol exposure may provide significant insights into the biological response to ethanol exposure. In this study, we used microarray analysis to examine the transcriptional response of the developing limb to a dose ...

  7. Genome of the Asian longhorned beetle, Anoplophora glabripennis), a globally significant invasive species, reveals key functional and evolutionary innovations at the beetle-plant interface

    USDA-ARS?s Scientific Manuscript database

    The Asian longhorned beetle (Anoplophora glabripennis; AGLAB) is a globally significant invasive species capable of inflicting severe feeding damage on many important orchard, ornamental and forest trees. Genome sequencing, annotation, gene expression assays, and functional and comparative genomic s...

  8. Ecohydrology on the Threshold?

    NASA Astrophysics Data System (ADS)

    Wainwright, John

    2013-04-01

    This presentation suggests that there are three major limitations to the development of ecohydrology as a coherent disciplinary area. One of the principal controls and feedbacks on patterns of plants and water in the environment is the form of the landscape and landscape-forming processes. Yet (eco)geomorphology is typically overlooked as a topic for ecohydrological investigation. Thus, the process domains used to explain patterns is typically overly restricted. As surface change controls the connectivity of other process, this restriction is significant. However, even when surface change is incorporated, there is often an emphasis on subdisciplinary areas, so that the investigation of patterns across process domains is not carried out in a holistic way. For example, studies of the feedbacks of vegetation on flow resistance are carried out significantly differently when considering wind and water flows (and indeed differently for water flows on hillslopes compared to in channels). Human action is the most important global control on ecohydrology, either from a top-down perspective through climate change, or from a bottom-up perspective through land use and land-use change. The actions of people on ecohydrological and ecogeomorphic processes, though, are typically considered in a static way. Techniques of agent-based modelling are being developed to overcome this limitation, but there need to be parallel developments in field techniques to address the data requirements and empirical underpinnings of such approaches. I argue that to cross the threshold into becoming a more mature discipline ecohydrology/ecogeomorphology needs to take on board the limitations of representations of process, pattern and people. Using examples from studies of land degradation in drylands, as well as from more temperate settings, I will suggest how progress may start to be made.

  9. Systems analysis of MVA-C induced immune response reveals its significance as a vaccine candidate against HIV/AIDS of clade C.

    PubMed

    Gómez, Carmen Elena; Perdiguero, Beatriz; Jiménez, Victoria; Filali-Mouhim, Abdelali; Ghneim, Khader; Haddad, Elias K; Quakkelaar, Esther D; Quakkerlaar, Esther D; Delaloye, Julie; Harari, Alexandre; Roger, Thierry; Duhen, Thomas; Dunhen, Thomas; Sékaly, Rafick P; Melief, Cornelis J M; Calandra, Thierry; Sallusto, Federica; Lanzavecchia, Antonio; Wagner, Ralf; Pantaleo, Giuseppe; Esteban, Mariano

    2012-01-01

    Based on the partial efficacy of the HIV/AIDS Thai trial (RV144) with a canarypox vector prime and protein boost, attenuated poxvirus recombinants expressing HIV-1 antigens are increasingly sought as vaccine candidates against HIV/AIDS. Here we describe using systems analysis the biological and immunological characteristics of the attenuated vaccinia virus Ankara strain expressing the HIV-1 antigens Env/Gag-Pol-Nef of HIV-1 of clade C (referred as MVA-C). MVA-C infection of human monocyte derived dendritic cells (moDCs) induced the expression of HIV-1 antigens at high levels from 2 to 8 hpi and triggered moDCs maturation as revealed by enhanced expression of HLA-DR, CD86, CD40, HLA-A2, and CD80 molecules. Infection ex vivo of purified mDC and pDC with MVA-C induced the expression of immunoregulatory pathways associated with antiviral responses, antigen presentation, T cell and B cell responses. Similarly, human whole blood or primary macrophages infected with MVA-C express high levels of proinflammatory cytokines and chemokines involved with T cell activation. The vector MVA-C has the ability to cross-present antigens to HIV-specific CD8 T cells in vitro and to increase CD8 T cell proliferation in a dose-dependent manner. The immunogenic profiling in mice after DNA-C prime/MVA-C boost combination revealed activation of HIV-1-specific CD4 and CD8 T cell memory responses that are polyfunctional and with effector memory phenotype. Env-specific IgG binding antibodies were also produced in animals receiving DNA-C prime/MVA-C boost. Our systems analysis of profiling immune response to MVA-C infection highlights the potential benefit of MVA-C as vaccine candidate against HIV/AIDS for clade C, the prevalent subtype virus in the most affected areas of the world.

  10. The influence of trait anxiety and illusory kinesthesia on pain threshold.

    PubMed

    Imai, Ryota; Osumi, Michihiro; Ishigaki, Tomoya; Morioka, Shu

    2017-07-01

    [Purpose] It has also been reported that decreased activity in the reward pathway causes a decrease in brain activity in the descending pain control system in people with high trait anxiety. Activation of this system is dependent on both the reward pathway and motor areas. Recently, studies have also shown that motor areas are activated by illusory kinesthesia. It was aimed to explore whether anxiety trait modulates the influence of illusory kinesthesia on pain threshold. [Subjects and Methods] The pain threshold and trait anxiety at rest before vibratory tendon stimulation (the task) were measured. After the task, the pain threshold, the illusory kinesthesia angle, and the intensity of illusory kinesthesia for patients with and without illusory kinesthesia were measured. A total of 35 healthy right-handed students participated, among whom 22 and 13 were included in the illusion and no-illusion groups, respectively. [Results] There was a significant increase in the pain threshold after task completion in both groups; however, there was no statistically significant difference between the two groups. Correlational analysis revealed that State-Trait Anxiety Inventory-trait score correlated negatively with the pain threshold in the no-illusion group, but there was no correlation in the illusion group. [Conclusion] The pain threshold improved regardless of the size of trait anxiety in the illusion group, but did not improve merely through sensory input by vibratory stimulation in the no-illusion group. Thus, illusory kinesthesia has effect of increasing the pain threshold.

  11. Hydrodynamics of sediment threshold

    NASA Astrophysics Data System (ADS)

    Ali, Sk Zeeshan; Dey, Subhasish

    2016-07-01

    A novel hydrodynamic model for the threshold of cohesionless sediment particle motion under a steady unidirectional streamflow is presented. The hydrodynamic forces (drag and lift) acting on a solitary sediment particle resting over a closely packed bed formed by the identical sediment particles are the primary motivating forces. The drag force comprises of the form drag and form induced drag. The lift force includes the Saffman lift, Magnus lift, centrifugal lift, and turbulent lift. The points of action of the force system are appropriately obtained, for the first time, from the basics of micro-mechanics. The sediment threshold is envisioned as the rolling mode, which is the plausible mode to initiate a particle motion on the bed. The moment balance of the force system on the solitary particle about the pivoting point of rolling yields the governing equation. The conditions of sediment threshold under the hydraulically smooth, transitional, and rough flow regimes are examined. The effects of velocity fluctuations are addressed by applying the statistical theory of turbulence. This study shows that for a hindrance coefficient of 0.3, the threshold curve (threshold Shields parameter versus shear Reynolds number) has an excellent agreement with the experimental data of uniform sediments. However, most of the experimental data are bounded by the upper and lower limiting threshold curves, corresponding to the hindrance coefficients of 0.2 and 0.4, respectively. The threshold curve of this study is compared with those of previous researchers. The present model also agrees satisfactorily with the experimental data of nonuniform sediments.

  12. The complete chloroplast genome sequence of Mahonia bealei (Berberidaceae) reveals a significant expansion of the inverted repeat and phylogenetic relationship with other angiosperms.

    PubMed

    Ma, Ji; Yang, Bingxian; Zhu, Wei; Sun, Lianli; Tian, Jingkui; Wang, Xumin

    2013-10-10

    Mahonia bealei (Berberidaceae) is a frequently-used traditional Chinese medicinal plant with efficient anti-inflammatory ability. This plant is one of the sources of berberine, a new cholesterol-lowering drug with anti-diabetic activity. We have sequenced the complete nucleotide sequence of the chloroplast (cp) genome of M. bealei. The complete cp genome of M. bealei is 164,792 bp in length, and has a typical structure with large (LSC 73,052 bp) and small (SSC 18,591 bp) single-copy regions separated by a pair of inverted repeats (IRs 36,501 bp) of large size. The Mahonia cp genome contains 111 unique genes and 39 genes are duplicated in the IR regions. The gene order and content of M. bealei are almost unarranged which is consistent with the hypothesis that large IRs stabilize cp genome and reduce gene loss-and-gain probabilities during evolutionary process. A large IR expansion of over 12 kb has occurred in M. bealei, 15 genes (rps19, rpl22, rps3, rpl16, rpl14, rps8, infA, rpl36, rps11, petD, petB, psbH, psbN, psbT and psbB) have expanded to have an additional copy in the IRs. The IR expansion rearrangement occurred via a double-strand DNA break and subsequence repair, which is different from the ordinary gene conversion mechanism. Repeat analysis identified 39 direct/inverted repeats 30 bp or longer with a sequence identity ≥ 90%. Analysis also revealed 75 simple sequence repeat (SSR) loci and almost all are composed of A or T, contributing to a distinct bias in base composition. Comparison of protein-coding sequences with ESTs reveals 9 putative RNA edits and 5 of them resulted in non-synonymous modifications in rpoC1, rps2, rps19 and ycf1. Phylogenetic analysis using maximum parsimony (MP) and maximum likelihood (ML) was performed on a dataset composed of 65 protein-coding genes from 25 taxa, which yields an identical tree topology as previous plastid-based trees, and provides strong support for the sister relationship between Ranunculaceae and Berberidaceae

  13. microTSS: accurate microRNA transcription start site identification reveals a significant number of divergent pri-miRNAs.

    PubMed

    Georgakilas, Georgios; Vlachos, Ioannis S; Paraskevopoulou, Maria D; Yang, Peter; Zhang, Yuhong; Economides, Aris N; Hatzigeorgiou, Artemis G

    2014-12-10

    A large fraction of microRNAs (miRNAs) are derived from intergenic non-coding loci and the identification of their promoters remains 'elusive'. Here, we present microTSS, a machine-learning algorithm that provides highly accurate, single-nucleotide resolution predictions for intergenic miRNA transcription start sites (TSSs). MicroTSS integrates high-resolution RNA-sequencing data with active transcription marks derived from chromatin immunoprecipitation and DNase-sequencing to enable the characterization of tissue-specific promoters. MicroTSS is validated with a specifically designed Drosha-null/conditional-null mouse model, generated using the conditional by inversion (COIN) methodology. Analyses of global run-on sequencing data revealed numerous pri-miRNAs in human and mouse either originating from divergent transcription at promoters of active genes or partially overlapping with annotated long non-coding RNAs. MicroTSS is readily applicable to any cell or tissue samples and constitutes the missing part towards integrating the regulation of miRNA transcription into the modelling of tissue-specific regulatory networks.

  14. Analysis of a triple testcross design with recombinant inbred lines reveals a significant role of epistasis in heterosis for biomass-related traits in Arabidopsis.

    PubMed

    Kusterer, Barbara; Muminovic, Jasmina; Utz, H Friedrich; Piepho, Hans-Peter; Barth, Susanne; Heckenberger, Martin; Meyer, Rhonda C; Altmann, Thomas; Melchinger, Albrecht E

    2007-04-01

    Primary causes of heterosis are still unknown. Our goal was to investigate the extent and underlying genetic causes of heterosis for five biomass-related traits in Arabidopsis thaliana. We (i) investigated the relative contribution of dominance and epistatic effects to heterosis in the hybrid C24 x Col-0 by generation means analysis and estimates of variance components based on a triple testcross (TTC) design with recombinant inbred lines (RILs), (ii) estimated the average degree of dominance, and (iii) examined the importance of reciprocal and maternal effects in this cross. In total, 234 RILs were crossed to parental lines and their F1's. Midparent heterosis (MPH) was high for rosette diameter at 22 days after sowing (DAS) and 29 DAS, growth rate (GR), and biomass yield (BY). Using the F2-metric, directional dominance prevailed for the majority of traits studied but reciprocal and maternal effects were not significant. Additive and dominance variances were significant for all traits. Additive x additive and dominance x dominance variances were significant for all traits but GR. We conclude that dominance as well as digenic and possibly higher-order epistatic effects play an important role in heterosis for biomass-related traits. Our results encourage the use of Arabidopsis hybrid C24 x Col-0 for identification and description of quantitative trait loci (QTL) for heterosis for biomass-related traits and further genomic studies.

  15. ISODATA: Thresholds for splitting clusters

    NASA Technical Reports Server (NTRS)

    Kan, E. P. F. (Principal Investigator)

    1972-01-01

    The author has identified the following significant results. The parameter AD (average distance) as used in the ISODATA program was critically examined. Thresholds of AD to decide on the splitting of clusters were obtained. For the univariate case, 0.84 was established as a sound choice, after examining several simple, as well as composite, distributions and also after investigating the probability of misclassification when points have to be reassigned to the newly identified clusters. For the multivariate case, the empirical threshold (N-0.16)/square root of N was extrapolated. A final criticism on AD was that AD would lose its effectiveness as a discriminative measure for the present purpose when N was large.

  16. Geometric morphometric analysis of Colombian Anopheles albimanus (Diptera: Culicidae) reveals significant effect of environmental factors on wing traits and presence of a metapopulation

    PubMed Central

    Gómez, Giovan F.; Márquez, Edna J.; Gutiérrez, Lina A.; Conn, Jan E.; Correa, Margarita M.

    2015-01-01

    Anopheles albimanus is a major malaria mosquito vector in Colombia. In the present study, wing variability (size and shape) in An. albimanus populations from Colombian Maracaibo and Chocó bio-geographical eco-regions and the relationship of these phenotypic traits with environmental factors were evaluated. Microsatellite and morphometric data facilitated a comparison of the genetic and phenetic structure of this species. Wing size was influenced by elevation and relative humidity, whereas wing shape was affected by these two variables and also by rainfall, latitude, temperature and eco-region. Significant differences in mean shape between populations and eco-regions were detected, but they were smaller than those at the intra-population level. Correct assignment based on wing shape was low at the population level (<58%) and only slightly higher (>70%) at the eco-regional level, supporting the low population structure inferred from microsatellite data. Wing size was similar among populations with no significant differences between eco-regions. Population relationships in the genetic tree did not agree with those from the morphometric data; however, both datasets consistently reinforced a panmictic population of An. albimanus. Overall, site-specific population differentiation is not strongly supported by wing traits or genotypic data. We hypothesize that the metapopulation structure of An. albimanus throughout these Colombian eco-regions is favoring plasticity in wing traits, a relevant characteristic of species living under variable environmental conditions and colonizing new habitats. PMID:24704285

  17. Geometric morphometric analysis of Colombian Anopheles albimanus (Diptera: Culicidae) reveals significant effect of environmental factors on wing traits and presence of a metapopulation.

    PubMed

    Gómez, Giovan F; Márquez, Edna J; Gutiérrez, Lina A; Conn, Jan E; Correa, Margarita M

    2014-07-01

    Anopheles albimanus is a major malaria mosquito vector in Colombia. In the present study, wing variability (size and shape) in An. albimanus populations from Colombian Maracaibo and Chocó bio-geographical eco-regions and the relationship of these phenotypic traits with environmental factors were evaluated. Microsatellite and morphometric data facilitated a comparison of the genetic and phenetic structure of this species. Wing size was influenced by elevation and relative humidity, whereas wing shape was affected by these two variables and also by rainfall, latitude, temperature and eco-region. Significant differences in mean shape between populations and eco-regions were detected, but they were smaller than those at the intra-population level. Correct assignment based on wing shape was low at the population level (<58%) and only slightly higher (>70%) at the eco-regional level, supporting the low population structure inferred from microsatellite data. Wing size was similar among populations with no significant differences between eco-regions. Population relationships in the genetic tree did not agree with those from the morphometric data; however, both datasets consistently reinforced a panmictic population of An. albimanus. Overall, site-specific population differentiation is not strongly supported by wing traits or genotypic data. We hypothesize that the metapopulation structure of An. albimanus throughout these Colombian eco-regions is favoring plasticity in wing traits, a relevant characteristic of species living under variable environmental conditions and colonizing new habitats.

  18. Genome-wide indel/SSR scanning reveals significant loci associated with excellent agronomic traits of a cabbage (Brassica oleracea) elite parental line ‘01–20’

    PubMed Central

    Lv, Honghao; Wang, Qingbiao; Han, Fengqing; Liu, Xing; Fang, Zhiyuan; Yang, Limei; Zhuang, Mu; Liu, Yumei; Li, Zhansheng; Zhang, Yangyong

    2017-01-01

    Elite parental lines are of great significance to crop breeding. To discover unique genomic loci associated with excellent economic traits in the elite cabbage inbred-line ‘01–20’, we performed comparisons of phenotypes as well as whole-genome insertion-deletion/simple sequence repeat loci between ‘01–20’ and each of its five sister lines. ‘01–20’ has a range of excellent agronomic traits, including early-maturing, and improvements in plant type and leaf colour. Eight unique loci were discovered for ‘01–20’ and ‘01-07-258’, another elite line similar to ‘01–20’ at the whole-genome level. In addition, two excellent double-haploid lines derived from a cross of ‘01–20’ also inherited these loci. Based on the quantitative trait locus association results, five of these loci were found to be associated with important agronomic traits, which could explain why the elite parent ‘01–20’ possesses greener outer leaves, a more compact and upright plant-type, rounder head, shorter core length, and better taste. Additionally, some of these loci have clustering effects for quantitative trait loci associated with different traits; therefore, important genes in these regions were analysed. The obtained results should enable marker-assisted multi-trait selection at the whole-genome level in cabbage breeding and provide insights into significant genome loci and their breeding effects. PMID:28164997

  19. Comparative genomic and transcriptional analyses of the carbohydrate-active enzymes and secretomes of phytopathogenic fungi reveal their significant roles during infection and development

    PubMed Central

    Lyu, Xueliang; Shen, Cuicui; Fu, Yanping; Xie, Jiatao; Jiang, Daohong; Li, Guoqing; Cheng, Jiasen

    2015-01-01

    Our comparative genomic analysis showed that the numbers of plant cell wall (PCW)- and fungal cell wall (FCW)-degradation-associated carbohydrate-active enzymes (CAZymes) in necrotrophic and hemibiotrophic fungi are significantly larger than that in most biotrophic fungi. However, our transcriptional analyses of CAZyme-encoding genes in Melampsora larici-populina, Puccinia graminis and Sclerotinia sclerotiorum showed that many genes encoding PCW- and FCW-degradation-associated CAZymes were significantly up-regulated during the infection of both necrotrophic fungi and biotrophic fungi, indicating an existence of a universal mechanism underlying PCW degradation and FCW reorganization or modification, which are both intimately involved in necrotrophic and biotrophic fungal infection. Furthermore, our results showed that the FCW reorganization or modification was also related to the fungal development. Additionally, our transcriptional analysis of the secretome of S. sclerotiorum showed that many secreted protein-encoding genes were dramatically induced during infection. Among them, a small, cysteine-rich protein SsCVNH was experimentally confirmed to be essential for the virulence and sclerotial development, indicating that the small secreted proteins might also play crucial roles as potential effectors in host-non-specific necrotrophic fungi. PMID:26531059

  20. Bovine Teat Microbiome Analysis Revealed Reduced Alpha Diversity and Significant Changes in Taxonomic Profiles in Quarters with a History of Mastitis

    PubMed Central

    Falentin, Hélène; Rault, Lucie; Nicolas, Aurélie; Bouchard, Damien S.; Lassalas, Jacques; Lamberton, Philippe; Aubry, Jean-Marc; Marnet, Pierre-Guy; Le Loir, Yves; Even, Sergine

    2016-01-01

    Mastitis is a mammary gland inflammatory disease often due to bacterial infections. Like many other infections, it used to be considered as a host-pathogen interaction driven by host and bacterial determinants. Until now, the involvement of the bovine mammary gland microbiota in the host-pathogen interaction has been poorly investigated, and mainly during the infectious episode. In this study, the bovine teat microbiome was investigated in 31 quarters corresponding to 27 animals, which were all free of inflammation at sampling time but which had different histories regarding mastitis: from no episode of mastitis on all the previous lactations (Healthy quarter, Hq) to one or several clinical mastitis events (Mastitic quarter, Mq). Several quarters whose status was unclear (possible history of subclinical mastitis) were classified as NDq. Total bacterial DNA was extracted from foremilk samples and swab samples of the teat canal. Taxonomic profiles were determined by pyrosequencing on 16s amplicons of the V3-4 region. Hq quarters showed a higher diversity compared to Mq ones (Shannon index: ~8 and 6, respectively). Clustering of the quarters based on their bacterial composition made it possible to separate Mq and Hq quarters into two separate clusters (C1 and C2, respectively). Discriminant analysis of taxonomic profiles between these clusters revealed several differences and allowed the identification of taxonomic markers in relation to mastitis history. C2 quarters were associated with a higher proportion of the Clostridia class (including genera such as Ruminococcus, Oscillospira, Roseburia, Dorea, etc.), the Bacteroidetes phylum (Prevotella, Bacteroides, Paludibacter, etc.), and the Bifidobacteriales order (Bifidobacterium), whereas C1 quarters showed a higher proportion of the Bacilli class (Staphylococcus) and Chlamydiia class. These results indicate that microbiota is altered in udders which have already developed mastitis, even far from the infectious episode

  1. Effects of contralateral acoustic stimulation on spontaneous otoacoustic emissions and hearing threshold fine structure.

    PubMed

    Dewey, James B; Lee, Jungmee; Dhar, Sumitrajit

    2014-12-01

    Medial olivocochlear (MOC) influence on cochlear mechanics can be noninvasively, albeit indirectly, explored via the effects of contralateral acoustic stimulation (CAS) on otoacoustic emissions. CAS-mediated effects are particularly pronounced for spontaneous otoacoustic emissions (SOAEs), which are typically reduced in amplitude and shifted upward in frequency by CAS. We investigated whether similar frequency shifts and magnitude reductions were observed behaviorally in the fine structure of pure-tone hearing thresholds, a phenomenon thought to share a common underlying mechanism with SOAEs. In normal-hearing listeners, fine-resolution thresholds were obtained over a narrow frequency range centered on the frequency of an SOAE, both in the absence and presence of 60-dB SPL broadband CAS. While CAS shifted threshold fine structure patterns and SOAEs upward in frequency by a comparable amount, little reduction in the presence or depth of fine structure was observed at frequencies near those of SOAEs. In fact, CAS typically improved thresholds, particularly at threshold minima, and increased fine structure depth when reductions in the amplitude of the associated SOAE were less than 10 dB. Additional measurements made at frequencies distant from SOAEs, or near SOAEs that were more dramatically reduced in amplitude by the CAS, revealed that CAS tended to elevate thresholds and reduce threshold fine structure depth. The results suggest that threshold fine structure is sensitive to MOC-mediated changes in cochlear gain, but that SOAEs complicate the interpretation of threshold measurements at nearby frequencies, perhaps due to masking or other interference effects. Both threshold fine structure and SOAEs may be significant sources of intersubject and intrasubject variability in psychoacoustic investigations of MOC function.

  2. Down-regulation of flavonoid 3'-hydroxylase gene expression by virus-induced gene silencing in soybean reveals the presence of a threshold mRNA level associated with pigmentation in pubescence.

    PubMed

    Nagamatsu, Atsushi; Masuta, Chikara; Matsuura, Hideyuki; Kitamura, Keisuke; Abe, Jun; Kanazawa, Akira

    2009-01-01

    Changes in flavonoid content are often manifested as altered pigmentation in plant tissues. Two loci have been identified as controlling pigmentation in soybean pubescence. Of these, the T locus appears to encode flavonoid 3'-hydroxylase (F3'H) protein: the T and t alleles are associated with tawny and gray colors, respectively, in pubescence. We previously down-regulated F3'H gene expression by virus-induced gene silencing (VIGS) in soybean. Despite this successful VIGS, the tawny pubescence pigmentation proved to be unchanged in greenhouse-grown plants. We hypothesized that the reduced mRNA level of the F3'H gene resulting from VIGS remained high enough to induce pigmentation. To verify this hypothesis, in the present study, we performed F3'H VIGS on plants grown under controlled conditions, in which the steady-state mRNA level of the F3'H gene was reduced to approximately 5% of that of greenhouse-grown plants. This VIGS treatment resulted in the loss of tawny pigmentation in pubescence, suggesting that the sf3'h1 gene is involved in the control of pigmentation in pubescence. We detected a marked decrease in target mRNA, an accumulation of short interfering RNAs (siRNAs), and a decrease in quercetin content relative to kaempferol in leaf tissues, indicating that sequence-specific mRNA degradation of the F3'H gene was induced. These results suggest that leaf tissues have a threshold mRNA level of the F3'H gene, which is associated with the occurrence of tawny pigmentation in pubescence. The estimated threshold mRNA level for pigmentation in pubescence was approximately 3% of the steady-state mRNA level of the F3'H gene in greenhouse-grown plants.

  3. Revealing the significance and polyphase tectonothermal evolution of a major metamorphic unit in an orogen: the central Sanandaj-Sirjan zone, Zagros Mts., Iran

    NASA Astrophysics Data System (ADS)

    Shakerardakani, Farzaneh; Neubauer, Franz; Genser, Johann; Liu, Xiaoming; Dong, Yunpeng; Monfaredi, Behzad; Benroider, Manfred; Finger, Fritz; Waitzinger, Michael

    2016-04-01

    The Dorud-Azna region in the central Sanandaj-Sirjan metamorphic belt plays a key role in promoting the tectonic evolution of Zagros orogen, within the frame of the Arabia-Eurasia collision zone. From footwall to hangingwall, structural data combined with the U-Pb zircon and extensive 40Ar-39Ar mineral dating survey demonstrate three metamorphosed tectonic units, which include: (1) The Triassic June complex is metamorphosed within greenschist facies conditions, overlain by (2) the amphibolite-grade metamorphic Galeh-Doz orthogneiss, which is intruded by mafic dykes, and (3) the Amphibolite-Metagabbro unit. To the east, these units were intruded by the Jurassic Darijune gabbro. We present U-Pb detrital zircon ages of a garnet-micaschist from the Amphibolite-Metagabbro unit, which yield six distinctive age groups, including a previously unrecognized Late Grenvillian age population at ~0.93 to 0.99 Ga. We speculate that this unique Late Grenvillian group coupled with biogeographic evidence suggests either relationship with the South China craton or to the "Gondwana superfan". The laser ablation ICP-MS U-Pb zircon ages of 608 ± 18 Ma and 588 ± 41 Ma of the granitic Galeh-Doz orthogneiss reveals a Panafrican basement same as known from the Yazd block of Central Iran. Geochemistry and Sr-Nd isotopes of alkaline and subalkaline mafic dykes within the Galeh-Doz orthogneiss show OIB-type to MORB-type and indicate involvement of both depleted and enriched sources for its genesis. The new 40Ar-39Ar amphibole age of ca. 322.2 ± 3.9 Ma from the alkaline mafic dyke implies Carboniferous cooling age after intrusion. The metagabbros (including the Dare-Hedavand metagabbro with a 206Pb/238U age of 314.6 ± 3.7 Ma) and amphibolites with E-MORB geochemical signature of the Amphibolite-Metagabbro unit represent an Upper Paleozoic rift. The geochemical composition of the Triassic greenschist facies metamorphosed June complex, implying formation in a same, but younger tectonic

  4. A new dinucleotide repeat polymorphism at the telomere of chromosome 21q reveals a significant difference between male and female rates of recombination

    SciTech Connect

    Blouin, J.L.; Gos, A.; Morris, M.A.

    1995-08-01

    We have used a half-YAC containing the human chromosome 21 long-arm telomere to clone, map, and characterize a new dinucleotide repeat polymorphism (D21S1575) close to 21qter. The marker is <120 kb from the telomeric (TTAGGG){sub n} sequences and is the most distal highly polymorphic marker on chromosome 21q. This marker has a heterozygosity of 71% because of a variable (TA){sub n} repeat embedded within a long interspersed element (LINE) element. Genotyping of the CEPH families and linkage analysis provided a more accurate determination of the full length of the chromosome 21 genetic map. A highly significant difference was detected between male and female recombination rates in the telomeric region: in the most telomeric 2.3 Mb of chromosome 21q, recombination was only observed in male meioses. 35 refs., 4 figs., 2 tabs.

  5. Conditional Deletion of the Glutamate Transporter GLT-1 Reveals That Astrocytic GLT-1 Protects against Fatal Epilepsy While Neuronal GLT-1 Contributes Significantly to Glutamate Uptake into Synaptosomes

    PubMed Central

    Petr, Geraldine T.; Sun, Yan; Frederick, Natalie M.; Zhou, Yun; Dhamne, Sameer C.; Hameed, Mustafa Q.; Miranda, Clive; Bedoya, Edward A.; Fischer, Kathryn D.; Armsen, Wencke; Wang, Jianlin; Danbolt, Niels C.; Rotenberg, Alexander; Aoki, Chiye J.

    2015-01-01

    GLT-1 (EAAT2; slc1a2) is the major glutamate transporter in the brain, and is predominantly expressed in astrocytes, but at lower levels also in excitatory terminals. We generated a conditional GLT-1 knock-out mouse to uncover cell-type-specific functional roles of GLT-1. Inactivation of the GLT-1 gene was achieved in either neurons or astrocytes by expression of synapsin-Cre or inducible human GFAP-CreERT2. Elimination of GLT-1 from astrocytes resulted in loss of ∼80% of GLT-1 protein and of glutamate uptake activity that could be solubilized and reconstituted in liposomes. This loss was accompanied by excess mortality, lower body weight, and seizures suggesting that astrocytic GLT-1 is of major importance. However, there was only a small (15%) reduction that did not reach significance of glutamate uptake into crude forebrain synaptosomes. In contrast, when GLT-1 was deleted in neurons, both the GLT-1 protein and glutamate uptake activity that could be solubilized and reconstituted in liposomes were virtually unaffected. These mice showed normal survival, weight gain, and no seizures. However, the synaptosomal glutamate uptake capacity (Vmax) was reduced significantly (40%). In conclusion, astrocytic GLT-1 performs critical functions required for normal weight gain, resistance to epilepsy, and survival. However, the contribution of astrocytic GLT-1 to glutamate uptake into synaptosomes is less than expected, and the contribution of neuronal GLT-1 to synaptosomal glutamate uptake is greater than expected based on their relative protein expression. These results have important implications for the interpretation of the many previous studies assessing glutamate uptake capacity by measuring synaptosomal uptake. PMID:25834045

  6. Functional (13)C-urea and glucose hydrogen/methane breath tests reveal significant association of small intestinal bacterial overgrowth in individuals with active Helicobacter pylori infection.

    PubMed

    Enko, Dietmar; Kriegshäuser, Gernot

    2017-01-01

    Helicobacter pylori infection is considered to alter the bacterial flora in the upper gastrointestinal tract. This study aimed at investigating the presence of small intestinal bacterial overgrowth (SIBO) in patients with active H. pylori infection assessed by functional breath testing. A total of 109 outpatients, who were referred for the H. pylori(13)C-urea breath test ((13)C-UBT) by general practitioners and specialists, were also tested for the presence of SIBO by the glucose hydrogen (H2)/methane (CH4) breath test (HMBT). A detailed anamnesis was carried out about the history of H. pylori infection, eradication therapies, proton pump inhibitor intake, and comorbidities. In total, 36/109 (33.0%) patients had a positive H. pylori(13)C-UBT, and 35/109 (32.1%) patients had a positive glucose HMBT, the latter being indicative of SIBO. Interestingly, individuals with a positive H. pylori(13)C-UBT were significantly more often associated with a positive glucose HMBT (p=0.002). Cohen's κ measuring agreement between the (13)C-UBT and the glucose HMBT was 0.31 (confidence intervals: 0.12-0.50) (p=0.001). Altogether, 19 of 54 (35.2%) patients, who had completed up to four eradication therapies, were diagnosed with SIBO by HMBT. H. pylori infection was found to be significantly associated with the presence of SIBO as determined by functional breath testing. In addition, SIBO rates appeared to have increased after completed eradication therapies. However, further longitudinal studies are warranted to fully elucidate the relationship and treatment modalities of coincident H. pylori infection and SIBO. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  7. Conditional deletion of the glutamate transporter GLT-1 reveals that astrocytic GLT-1 protects against fatal epilepsy while neuronal GLT-1 contributes significantly to glutamate uptake into synaptosomes.

    PubMed

    Petr, Geraldine T; Sun, Yan; Frederick, Natalie M; Zhou, Yun; Dhamne, Sameer C; Hameed, Mustafa Q; Miranda, Clive; Bedoya, Edward A; Fischer, Kathryn D; Armsen, Wencke; Wang, Jianlin; Danbolt, Niels C; Rotenberg, Alexander; Aoki, Chiye J; Rosenberg, Paul A

    2015-04-01

    GLT-1 (EAAT2; slc1a2) is the major glutamate transporter in the brain, and is predominantly expressed in astrocytes, but at lower levels also in excitatory terminals. We generated a conditional GLT-1 knock-out mouse to uncover cell-type-specific functional roles of GLT-1. Inactivation of the GLT-1 gene was achieved in either neurons or astrocytes by expression of synapsin-Cre or inducible human GFAP-CreERT2. Elimination of GLT-1 from astrocytes resulted in loss of ∼80% of GLT-1 protein and of glutamate uptake activity that could be solubilized and reconstituted in liposomes. This loss was accompanied by excess mortality, lower body weight, and seizures suggesting that astrocytic GLT-1 is of major importance. However, there was only a small (15%) reduction that did not reach significance of glutamate uptake into crude forebrain synaptosomes. In contrast, when GLT-1 was deleted in neurons, both the GLT-1 protein and glutamate uptake activity that could be solubilized and reconstituted in liposomes were virtually unaffected. These mice showed normal survival, weight gain, and no seizures. However, the synaptosomal glutamate uptake capacity (Vmax) was reduced significantly (40%). In conclusion, astrocytic GLT-1 performs critical functions required for normal weight gain, resistance to epilepsy, and survival. However, the contribution of astrocytic GLT-1 to glutamate uptake into synaptosomes is less than expected, and the contribution of neuronal GLT-1 to synaptosomal glutamate uptake is greater than expected based on their relative protein expression. These results have important implications for the interpretation of the many previous studies assessing glutamate uptake capacity by measuring synaptosomal uptake.

  8. Significant correlation between a set of genetic polymorphisms and a functional brain network revealed by feature selection and sparse Partial Least Squares.

    PubMed

    Le Floch, Edith; Guillemot, Vincent; Frouin, Vincent; Pinel, Philippe; Lalanne, Christophe; Trinchera, Laura; Tenenhaus, Arthur; Moreno, Antonio; Zilbovicius, Monica; Bourgeron, Thomas; Dehaene, Stanislas; Thirion, Bertrand; Poline, Jean-Baptiste; Duchesnay, Edouard

    2012-10-15

    Brain imaging is increasingly recognised as an intermediate phenotype to understand the complex path between genetics and behavioural or clinical phenotypes. In this context, a first goal is to propose methods to identify the part of genetic variability that explains some neuroimaging variability. Classical univariate approaches often ignore the potential joint effects that may exist between genes or the potential covariations between brain regions. In this paper, we propose instead to investigate an exploratory multivariate method in order to identify a set of Single Nucleotide Polymorphisms (SNPs) covarying with a set of neuroimaging phenotypes derived from functional Magnetic Resonance Imaging (fMRI). Recently, Partial Least Squares (PLS) regression or Canonical Correlation Analysis (CCA) have been proposed to analyse DNA and transcriptomics. Here, we propose to transpose this idea to the DNA vs. imaging context. However, in very high-dimensional settings like in imaging genetics studies, such multivariate methods may encounter overfitting issues. Thus we investigate the use of different strategies of regularisation and dimension reduction techniques combined with PLS or CCA to face the very high dimensionality of imaging genetics studies. We propose a comparison study of the different strategies on a simulated dataset first and then on a real dataset composed of 94 subjects, around 600,000 SNPs and 34 functional MRI lateralisation indexes computed from reading and speech comprehension contrast maps. We estimate the generalisability of the multivariate association with a cross-validation scheme and demonstrate the significance of this link, using a permutation procedure. Univariate selection appears to be necessary to reduce the dimensionality. However, the significant association uncovered by this two-step approach combining univariate filtering and L1-regularised PLS suggests that discovering meaningful genetic associations calls for a multivariate approach

  9. PCR reveals significantly higher rates of Trypanosoma cruzi infection than microscopy in the Chagas vector, Triatoma infestans: High rates found in Chuquisaca, Bolivia

    PubMed Central

    Pizarro, Juan Carlos; Lucero, David E; Stevens, Lori

    2007-01-01

    AGC GGA TAG TTC AGG – 3') primers. Amplicons were chromatographed on a 2% agarose gel with a 100 bp size standard, stained with ethidium bromide and viewed with UV fluorescence. For both the microscopy and PCR assays, we calculated sensitivity (number of positives by a method divided by the number of positives by either method) and discrepancy (one method was negative and the other was positive) at the locality, life stage and habitat level. The degree of agreement between PCR and microscopy was determined by calculating Kappa (k) values with 95% confidence intervals. Results We observed a high prevalence of T. cruzi infection in T. infestans (81.16% by PCR and 56.52% by microscopy) and discovered that PCR is significantly more sensitive than microscopic observation. The overall degree of agreement between the two methods was moderate (Kappa = 0.43 ± 0.07). The level of infection is significantly different among communities; however, prevalence was similar among habitats and life stages. Conclusion PCR was significantly more sensitive than microscopy in all habitats, developmental stages and localities in Chuquisaca, Bolivia. Overall we observed a high prevalence of T. cruzi infection in T. infestans in this area of Bolivia; however, microscopy underestimated infection at all levels examined. PMID:17597541

  10. Proton magnetic resonance spectroscopy reveals significant decline in the contents of N-acetylaspartylglutamate in the hippocampus of aged healthy subjects

    PubMed Central

    Chang, Ruiting; Zhu, Qingfeng; Song, Zhenhu; Wang, Ya

    2016-01-01

    Introduction To characterize the contents of choline (Cho), creatine (Cr) and N-acetylaspartylglutamate (NAA) in the hippocampus of healthy volunteers, we investigated the contents and their correlationship with age, gender and laterality. Material and methods Volunteers were grouped into a young, a middle and an old age. The Cho, Cr and NAA contents were determined with proton magnetic resonance spectroscopy (1H-MRS), and the correlationship was analyzed with Pearson correlation Results The concentration of NAA in the bilateral hippocampi was markedly lower in the old than in the young and the middle (LSD test, all p < 0.025). Furthermore, NAA/Cr in the bilateral hippocampi head (left: 1.10 ±0.40 vs. 1.54 ±0.49 or 1.43 ±0.49; right: 1.04 ±0.42 vs. 1.35 ±0.40 or 1.30 ±0.42), region 1 of the bilateral hippocampal body (left: 1.24 ±0.53 vs. 1.58 ±0.58 or 1.35 ±0.44; right: 1.30 ±0.43 vs. 1.54 ±0.51 or 1.35 ±0.51) and region 2 of the left hippocampal body (1.21 ±0.32 vs. 1.46 ±0.36 or 1.36 ±0.44) and the left hippocampal tail (1.11 ±0.40 vs. 1.36 ±0.47 or 1.15 ±0.32) was significantly higher in the old than in the young and the middle, respectively (all p < 0.026). The NAA content in the bilateral hippocampal head, body and tail negatively correlated with age. Moreover, the NAA, Cho and Cr contents in the hippocampal body and the tail were higher in the right than the left. Conclusions The NAA content of the hippocampal head, body and tail were significantly decreased in the old compared with younger persons, and it negatively correlates with age. The NAA, Cho and Cr contents exhibit laterality in the hippocampal body and tail. PMID:28144264

  11. Shotgun metagenomic data reveals significant abundance but low diversity of "Candidatus Scalindua" marine anammox bacteria in the Arabian Sea oxygen minimum zone.

    PubMed

    Villanueva, Laura; Speth, Daan R; van Alen, Theo; Hoischen, Alexander; Jetten, Mike S M

    2014-01-01

    Anaerobic ammonium oxidizing (anammox) bacteria are responsible for a significant portion of the loss of fixed nitrogen from the oceans, making them important players in the global nitrogen cycle. To date, marine anammox bacteria found in both water columns and sediments worldwide belong almost exclusively to "Candidatus Scalindua" species. Recently the genome assembly of a marine anammox enrichment culture dominated by "Candidatus Scalindua profunda" became available and can now be used as a template to study metagenome data obtained from various oxygen minimum zones (OMZs). Here, we sequenced genomic DNA from suspended particulate matter recovered at the upper (170 m deep) and center (600 m) area of the OMZ in the Arabian Sea by SOLiD and Ion Torrent technology. The genome of "Candidatus Scalindua profunda" served as a template to collect reads. Based on the mapped reads marine anammox Abundance was estimated to be at least 0.4% in the upper and 1.7% in the center area. Single nucleotide variation (SNV) analysis was performed to assess diversity of the "Candidatus Scalindua" populations. Most highly covered were the two diagnostic anammox genes hydrazine synthase (scal_01318c, hzsA) and hydrazine dehydrogenase (scal_03295, hdh), while other genes involved in anammox metabolism (narGH, nirS, amtB, focA, and ACS) had a lower coverage but could still be assembled and analyzed. The results show that "Candidatus Scalindua" is abundantly present in the Arabian Sea OMZ, but that the diversity within the ecosystem is relatively low.

  12. Hospital population screening reveals overrepresentation of CD5(-) monoclonal B-cell lymphocytosis and monoclonal gammopathy of undetermined significance of IgM type.

    PubMed

    Voigtlaender, Minna; Vogler, Birthe; Trepel, Martin; Panse, Jens; Jung, Roman; Bokemeyer, Carsten; Bacher, Ulrike; Binder, Mascha

    2015-09-01

    Monoclonal B-cell lymphocytosis (MBL) and monoclonal gammopathy of undetermined significance (MGUS) result from clonal expansions of mature B or plasma cells. Here, we set out to determine the immunophenotypic/monoclonal immunoglobulin (M protein) features and co-prevalence of MBL and MGUS in a hospital-based cohort of 1909 non-hematooncological patients. Of the evaluable cases, 3.8 % showed evidence for MBL by immunophenotyping, while 9.8 % were screened positive for M protein by immunofixation. With six concomitant cases (0.4 %), MBL and MGUS were not statistically associated. At least in two of these coincident cases, MBL and MGUS were of different clonal origin since both clones had divergent light chain restriction. CD5(-) MBL (57.1 %) and IgM+ MGUS (24.7 %) were strikingly overrepresented compared to population-based screenings and did not progress to overt lymphoma or myeloma during the observation period (mean follow-up of 117 weeks or 110 weeks, respectively). Prevalence and phenotypes suggest that a substantial proportion of incidental MBL and MGUS in hospitalized patients may be attributed to transiently expanded B-cell clones in the context of disease-related immune stimulation rather than reflecting veritable precursors of clonal B-cell malignancies.

  13. Marker-Based Estimates Reveal Significant Nonadditive Effects in Clonally Propagated Cassava (Manihot esculenta): Implications for the Prediction of Total Genetic Value and the Selection of Varieties

    PubMed Central

    Wolfe, Marnin D.; Kulakow, Peter; Rabbi, Ismail Y.; Jannink, Jean-Luc

    2016-01-01

    In clonally propagated crops, nonadditive genetic effects can be effectively exploited by the identification of superior genetic individuals as varieties. Cassava (Manihot esculenta Crantz) is a clonally propagated staple food crop that feeds hundreds of millions. We quantified the amount and nature of nonadditive genetic variation for three key traits in a breeding population of cassava from sub-Saharan Africa using additive and nonadditive genome-wide marker-based relationship matrices. We then assessed the accuracy of genomic prediction for total (additive plus nonadditive) genetic value. We confirmed previous findings based on diallel crosses that nonadditive genetic variation is significant for key cassava traits. Specifically, we found that dominance is particularly important for root yield and epistasis contributes strongly to variation in cassava mosaic disease (CMD) resistance. Further, we showed that total genetic value predicted observed phenotypes more accurately than additive only models for root yield but not for dry matter content, which is mostly additive or for CMD resistance, which has high narrow-sense heritability. We address the implication of these results for cassava breeding and put our work in the context of previous results in cassava, and other plant and animal species. PMID:27587297

  14. Label-free LC-MSMS analysis of vitreous from autoimmune uveitis reveals a significant decrease in secreted Wnt signalling inhibitors DKK3 and SFRP2.

    PubMed

    Hauck, Stefanie M; Hofmaier, Florian; Dietter, Johannes; Swadzba, Margarete E; Blindert, Marcel; Amann, Barbara; Behler, Jennifer; Kremmer, Elisabeth; Ueffing, Marius; Deeg, Cornelia A

    2012-07-19

    Equine recurrent uveitis is a severe and frequent blinding disease in horses which presents with auto-reactive invading T-cells, resulting in the destruction of the inner eye. Infiltration of inflammatory cells into the retina and vitreous is driven by currently unknown guidance cues, however surgical removal of the vitreous (vitrectomy) has proven therapeutically successful. Therefore, proteomic analyses of vitrectomy samples are likely to result in detection of proteins contributing to disease pathogenesis. Vitreous from healthy and ERU diseased horses were directly compared by quantitative mass spectrometry based on label-free quantification of peak intensities across samples. We found a significant upregulation of complement and coagulation cascades and downregulation of negative paracrine regulators of canonical Wnt signalling including the Wnt signalling inhibitors DKK3 and SFRP2. Based on immunohistochemistry, both proteins are expressed in equine retina and suggest localisation to retinal Müller glial cells (RMG), which may be the source cells for these proteins. Furthermore, retinal expression levels and patterns of DKK3 change in response to ERU. Since many other regulated proteins identified here are associated with RMG cells, these cells qualify as the prime responders to autoimmune triggers.

  15. 16S rRNA gene amplicon sequencing reveals significant changes in microbial compositions during cyanobacteria-laden drinking water sludge storage.

    PubMed

    Pei, Haiyan; Xu, Hangzhou; Wang, Jingjing; Jin, Yan; Xiao, Hong-Di; Ma, Chunxia; Sun, Jiongming; Li, Hongmin

    2017-10-10

    This is the first study to systematically investigate the microbial community structure in cyanobacteria-laden drinking water sludge generated by different types of coagulants (including AlCl3, FeCl3, and polymeric aluminium ferric chloride (PAFC)) using Illumina 16S rRNA gene MiSeq sequencing. Results show that Cyanobacteria, Proteobacteria, Firmicutes, Bacteroidetes, Verrucomicrobia, and Planctomycetes were the most dominant phyla in sludge, and because of the toxicity of high Al and Fe level in AlCl3 and FeCl3 sludges, respectively, the PAFC sludge exhibited greater microbial richness than that in AlCl3 and FeCl3 sludges. Due to lack of light and oxygen in sludge, relative abundance of the dominant genera Microcystis, Rhodobacter, Phenylobacterium, and Hydrogenophaga clearly decreased, especially after 4 d storage, and the amounts of extracellular microcystin and organic matter rose. As a result, the relative abundance of microcystin and organic degradation bacteria increased significantly, including pathogens such as Bacillus cereus, in particular after 4 d storage. Hence, sludge should be disposed of within 4 d to prevent massive growth of pathogens. In addition, because the increase of extracellular microcystins, organic matter, and pathogens in AlCl3 sludge was higher than that in FeCl3 and PAFC sludges, FeCl3 and PAFC may be ideal coagulants in drinking water treatment plants.

  16. Genome of the Asian longhorned beetle (Anoplophora glabripennis), a globally significant invasive species, reveals key functional and evolutionary innovations at the beetle-plant interface.

    PubMed

    McKenna, Duane D; Scully, Erin D; Pauchet, Yannick; Hoover, Kelli; Kirsch, Roy; Geib, Scott M; Mitchell, Robert F; Waterhouse, Robert M; Ahn, Seung-Joon; Arsala, Deanna; Benoit, Joshua B; Blackmon, Heath; Bledsoe, Tiffany; Bowsher, Julia H; Busch, André; Calla, Bernarda; Chao, Hsu; Childers, Anna K; Childers, Christopher; Clarke, Dave J; Cohen, Lorna; Demuth, Jeffery P; Dinh, Huyen; Doddapaneni, HarshaVardhan; Dolan, Amanda; Duan, Jian J; Dugan, Shannon; Friedrich, Markus; Glastad, Karl M; Goodisman, Michael A D; Haddad, Stephanie; Han, Yi; Hughes, Daniel S T; Ioannidis, Panagiotis; Johnston, J Spencer; Jones, Jeffery W; Kuhn, Leslie A; Lance, David R; Lee, Chien-Yueh; Lee, Sandra L; Lin, Han; Lynch, Jeremy A; Moczek, Armin P; Murali, Shwetha C; Muzny, Donna M; Nelson, David R; Palli, Subba R; Panfilio, Kristen A; Pers, Dan; Poelchau, Monica F; Quan, Honghu; Qu, Jiaxin; Ray, Ann M; Rinehart, Joseph P; Robertson, Hugh M; Roehrdanz, Richard; Rosendale, Andrew J; Shin, Seunggwan; Silva, Christian; Torson, Alex S; Jentzsch, Iris M Vargas; Werren, John H; Worley, Kim C; Yocum, George; Zdobnov, Evgeny M; Gibbs, Richard A; Richards, Stephen

    2016-11-11

    Relatively little is known about the genomic basis and evolution of wood-feeding in beetles. We undertook genome sequencing and annotation, gene expression assays, studies of plant cell wall degrading enzymes, and other functional and comparative studies of the Asian longhorned beetle, Anoplophora glabripennis, a globally significant invasive species capable of inflicting severe feeding damage on many important tree species. Complementary studies of genes encoding enzymes involved in digestion of woody plant tissues or detoxification of plant allelochemicals were undertaken with the genomes of 14 additional insects, including the newly sequenced emerald ash borer and bull-headed dung beetle. The Asian longhorned beetle genome encodes a uniquely diverse arsenal of enzymes that can degrade the main polysaccharide networks in plant cell walls, detoxify plant allelochemicals, and otherwise facilitate feeding on woody plants. It has the metabolic plasticity needed to feed on diverse plant species, contributing to its highly invasive nature. Large expansions of chemosensory genes involved in the reception of pheromones and plant kairomones are consistent with the complexity of chemical cues it uses to find host plants and mates. Amplification and functional divergence of genes associated with specialized feeding on plants, including genes originally obtained via horizontal gene transfer from fungi and bacteria, contributed to the addition, expansion, and enhancement of the metabolic repertoire of the Asian longhorned beetle, certain other phytophagous beetles, and to a lesser degree, other phytophagous insects. Our results thus begin to establish a genomic basis for the evolutionary success of beetles on plants.

  17. Thresholds for detection of constant rotary acceleration during vibratory rotary acceleration.

    PubMed

    Clark, B; Stewart, J D; Phillips, N H

    1980-06-01

    The effects of vibratory angular acceleration (aR) on detection thresholds for constant aR in a dynamic flight simulator are reported in three experiments. Detection thresholds were determined for 10 pilots and four nonpilots using a random, double-staircase procedure while the subjects sat erect in a device which rotated about an earth-vertical axis. Constant aRs were presented for 0.5 and 1.0 s with concurrent, vibratory aR at 1 and 5 Hz, and thresholds with no vibratory aR were established. The thresholds were obtained while the subjects observed a visual reference in the enclosed cockpit in two experiments and in total darkness in a third. The results confirmed earlier experiments showing an inverse relationship between the duration of constant aR and detection threshold and showed that the detection thresholds in darkness were higher than with a visual reference present. Two analyses of variance revealed no significant differences in thresholds across the three vibration conditions. These results indicate that vibratory aRs of fairly high levels can be present in a dynamic flight stimulator without masking the pilot's ability to detect either maneuver or disturbance motions.

  18. Comprehensive analysis of protein digestion using six trypsins reveals the origin of trypsin as a significant source of variability in proteomics1

    PubMed Central

    Walmsley, Scott J.; Rudnick, Paul A.; Liang, Yuxue; Dong, Qian; Stein, Stephen E.; Nesvizhskii, Alexey I.

    2014-01-01

    Trypsin is an endoprotease commonly used for sample preparation in proteomics experiments. Importantly, protein digestion is dependent on multiple factors, including the trypsin origin and digestion conditions. In-depth characterization of trypsin activity could lead to improved reliability of peptide detection and quantitation in both targeted and discovery proteomics studies. To this end, we assembled a data analysis pipeline and suite of visualization tools for quality control and comprehensive characterization of pre-analytical variability in proteomics experiments. Using these tools, we evaluated six available proteomics-grade trypsins and their digestion of a single purified protein, human serum albumin (HSA). HSA was aliquoted and then digested for 2 or 18 hours for each trypsin, and the resulting digests were desalted and analyzed in triplicate by reversed phase liquid chromatography - tandem mass spectrometry. Peptides were identified and quantified using the NIST MSQC pipeline and a comprehensive HSA mass spectral library. We performed a statistical analysis of peptide abundances from different digests, and further visualized the data using the principal component analysis and quantitative protein “sequence maps”. While the performance of individual trypsins across repeat digests was reproducible, significant differences were observed depending on the origin of the trypsin (i.e., bovine vs. porcine). Bovine trypsins produced a higher number of peptides containing missed cleavages, whereas porcine trypsins produced more semi-tryptic peptides. In addition, many cleavage sites showed variable digestion kinetics patterns, evident from the comparison of peptide abundances in 2 hour vs. 18 hour digests. Overall, this work illustrates effects of an often neglected source of variability in proteomics experiments: the origin of the trypsin. PMID:24116745

  19. Camelid Ig V genes reveal significant human homology not seen in therapeutic target genes, providing for a powerful therapeutic antibody platform

    PubMed Central

    Klarenbeek, Alex; Mazouari, Khalil El; Desmyter, Aline; Blanchetot, Christophe; Hultberg, Anna; de Jonge, Natalie; Roovers, Rob C; Cambillau, Christian; Spinelli, Sylvia; Del-Favero, Jurgen; Verrips, Theo; de Haard, Hans J; Achour, Ikbel

    2015-01-01

    Camelid immunoglobulin variable (IGV) regions were found homologous to their human counterparts; however, the germline V repertoires of camelid heavy and light chains are still incomplete and their therapeutic potential is only beginning to be appreciated. We therefore leveraged the publicly available HTG and WGS databases of Lama pacos and Camelus ferus to retrieve the germline repertoire of V genes using human IGV genes as reference. In addition, we amplified IGKV and IGLV genes to uncover the V germline repertoire of Lama glama and sequenced BAC clones covering part of the Lama pacos IGK and IGL loci. Our in silico analysis showed that camelid counterparts of all human IGKV and IGLV families and most IGHV families could be identified, based on canonical structure and sequence homology. Interestingly, this sequence homology seemed largely restricted to the Ig V genes and was far less apparent in other genes: 6 therapeutically relevant target genes differed significantly from their human orthologs. This contributed to efficient immunization of llamas with the human proteins CD70, MET, interleukin (IL)-1β and IL-6, resulting in large panels of functional antibodies. The in silico predicted human-homologous canonical folds of camelid-derived antibodies were confirmed by X-ray crystallography solving the structure of 2 selected camelid anti-CD70 and anti-MET antibodies. These antibodies showed identical fold combinations as found in the corresponding human germline V families, yielding binding site structures closely similar to those occurring in human antibodies. In conclusion, our results indicate that active immunization of camelids can be a powerful therapeutic antibody platform. PMID:26018625

  20. Modulation of ethylene responses by OsRTH1 overexpression reveals the biological significance of ethylene in rice seedling growth and development

    PubMed Central

    Zhang, Wei; Zhou, Xin; Wen, Chi-Kuang

    2012-01-01

    Overexpression of Arabidopsis Reversion-To-ethylene Sensitivity1 (RTE1) results in whole-plant ethylene insensitivity dependent on the ethylene receptor gene Ethylene Response1 (ETR1). However, overexpression of the tomato RTE1 homologue Green Ripe (GR) delays fruit ripening but does not confer whole-plant ethylene insensitivity. It was decided to investigate whether aspects of ethylene-induced growth and development of the monocotyledonous model plant rice could be modulated by rice RTE1 homologues (OsRTH genes). Results from a cross-species complementation test in Arabidopsis showed that OsRTH1 overexpression complemented the rte1-2 loss-of-function mutation and conferred whole-plant ethylene insensitivity in an ETR1-dependent manner. In contrast, OsRTH2 and OsRTH3 overexpression did not complement rte1-2 or confer ethylene insensitivity. In rice, OsRTH1 overexpression substantially prevented ethylene-induced alterations in growth and development, including leaf senescence, seedling leaf elongation and development, coleoptile elongation or curvature, and adventitious root development. Results of subcellular localizations of OsRTHs, each fused with the green fluorescent protein, in onion epidermal cells suggested that the three OsRTHs were predominantly localized to the Golgi. OsRTH1 may be an RTE1 orthologue of rice and modulate rice ethylene responses. The possible roles of auxins and gibberellins in the ethylene-induced alterations in growth were evaluated and the biological significance of ethylene in the early stage of rice seedling growth is discussed. PMID:22451723

  1. Modulation of ethylene responses by OsRTH1 overexpression reveals the biological significance of ethylene in rice seedling growth and development.

    PubMed

    Zhang, Wei; Zhou, Xin; Wen, Chi-Kuang

    2012-06-01

    Overexpression of Arabidopsis Reversion-To-ethylene Sensitivity1 (RTE1) results in whole-plant ethylene insensitivity dependent on the ethylene receptor gene Ethylene Response1 (ETR1). However, overexpression of the tomato RTE1 homologue Green Ripe (GR) delays fruit ripening but does not confer whole-plant ethylene insensitivity. It was decided to investigate whether aspects of ethylene-induced growth and development of the monocotyledonous model plant rice could be modulated by rice RTE1 homologues (OsRTH genes). Results from a cross-species complementation test in Arabidopsis showed that OsRTH1 overexpression complemented the rte1-2 loss-of-function mutation and conferred whole-plant ethylene insensitivity in an ETR1-dependent manner. In contrast, OsRTH2 and OsRTH3 overexpression did not complement rte1-2 or confer ethylene insensitivity. In rice, OsRTH1 overexpression substantially prevented ethylene-induced alterations in growth and development, including leaf senescence, seedling leaf elongation and development, coleoptile elongation or curvature, and adventitious root development. Results of subcellular localizations of OsRTHs, each fused with the green fluorescent protein, in onion epidermal cells suggested that the three OsRTHs were predominantly localized to the Golgi. OsRTH1 may be an RTE1 orthologue of rice and modulate rice ethylene responses. The possible roles of auxins and gibberellins in the ethylene-induced alterations in growth were evaluated and the biological significance of ethylene in the early stage of rice seedling growth is discussed.

  2. Comparative Proteomic Characterization of 4 Human Liver-Derived Single Cell Culture Models Reveals Significant Variation in the Capacity for Drug Disposition, Bioactivation, and Detoxication

    PubMed Central

    Sison-Young, Rowena L. C.; Mitsa, Dimitra; Jenkins, Rosalind E.; Mottram, David; Alexandre, Eliane; Richert, Lysiane; Aerts, Hélène; Weaver, Richard J.; Jones, Robert P.; Johann, Esther; Hewitt, Philip G.; Ingelman-Sundberg, Magnus; Goldring, Christopher E. P.; Kitteringham, Neil R.; Park, B. Kevin

    2015-01-01

    In vitro preclinical models for the assessment of drug-induced liver injury (DILI) are usually based on cryopreserved primary human hepatocytes (cPHH) or human hepatic tumor-derived cell lines; however, it is unclear how well such cell models reflect the normal function of liver cells. The physiological, pharmacological, and toxicological phenotyping of available cell-based systems is necessary in order to decide the testing purpose for which they are fit. We have therefore undertaken a global proteomic analysis of 3 human-derived hepatic cell lines (HepG2, Upcyte, and HepaRG) in comparison with cPHH with a focus on drug metabolizing enzymes and transport proteins (DMETs), as well as Nrf2-regulated proteins. In total, 4946 proteins were identified, of which 2722 proteins were common across all cell models, including 128 DMETs. Approximately 90% reduction in expression of cytochromes P450 was observed in HepG2 and Upcyte cells, and approximately 60% in HepaRG cells relative to cPHH. Drug transporter expression was also lower compared with cPHH with the exception of MRP3 and P-gp (MDR1) which appeared to be significantly expressed in HepaRG cells. In contrast, a high proportion of Nrf2-regulated proteins were more highly expressed in the cell lines compared with cPHH. The proteomic database derived here will provide a rational basis for the context-specific selection of the most appropriate ‘hepatocyte-like’ cell for the evaluation of particular cellular functions associated with DILI and, at the same time, assist in the construction of a testing paradigm which takes into account the in vivo disposition of a new drug. PMID:26160117

  3. Shotgun metagenomic data reveals significant abundance but low diversity of “Candidatus Scalindua” marine anammox bacteria in the Arabian Sea oxygen minimum zone

    PubMed Central

    Villanueva, Laura; Speth, Daan R.; van Alen, Theo; Hoischen, Alexander; Jetten, Mike S. M.

    2014-01-01

    Anaerobic ammonium oxidizing (anammox) bacteria are responsible for a significant portion of the loss of fixed nitrogen from the oceans, making them important players in the global nitrogen cycle. To date, marine anammox bacteria found in both water columns and sediments worldwide belong almost exclusively to “Candidatus Scalindua” species. Recently the genome assembly of a marine anammox enrichment culture dominated by “Candidatus Scalindua profunda” became available and can now be used as a template to study metagenome data obtained from various oxygen minimum zones (OMZs). Here, we sequenced genomic DNA from suspended particulate matter recovered at the upper (170 m deep) and center (600 m) area of the OMZ in the Arabian Sea by SOLiD and Ion Torrent technology. The genome of “Candidatus Scalindua profunda” served as a template to collect reads. Based on the mapped reads marine anammox Abundance was estimated to be at least 0.4% in the upper and 1.7% in the center area. Single nucleotide variation (SNV) analysis was performed to assess diversity of the “Candidatus Scalindua” populations. Most highly covered were the two diagnostic anammox genes hydrazine synthase (scal_01318c, hzsA) and hydrazine dehydrogenase (scal_03295, hdh), while other genes involved in anammox metabolism (narGH, nirS, amtB, focA, and ACS) had a lower coverage but could still be assembled and analyzed. The results show that “Candidatus Scalindua” is abundantly present in the Arabian Sea OMZ, but that the diversity within the ecosystem is relatively low. PMID:24550902

  4. Prognostic significance of infarct core pathology revealed by quantitative non-contrast in comparison with contrast cardiac magnetic resonance imaging in reperfused ST-elevation myocardial infarction survivors

    PubMed Central

    Carrick, David; Haig, Caroline; Rauhalammi, Sam; Ahmed, Nadeem; Mordi, Ify; McEntegart, Margaret; Petrie, Mark C.; Eteiba, Hany; Hood, Stuart; Watkins, Stuart; Lindsay, Mitchell; Mahrous, Ahmed; Ford, Ian; Tzemos, Niko; Sattar, Naveed; Welsh, Paul; Radjenovic, Aleksandra; Oldroyd, Keith G.; Berry, Colin

    2016-01-01

    Aims To assess the prognostic significance of infarct core tissue characteristics using cardiac magnetic resonance (CMR) imaging in survivors of acute ST-elevation myocardial infarction (STEMI). Methods and results We performed an observational prospective single centre cohort study in 300 reperfused STEMI patients (mean ± SD age 59 ± 12 years, 74% male) who underwent CMR 2 days and 6 months post-myocardial infarction (n = 267). Native T1 was measured in myocardial regions of interest (n = 288). Adverse remodelling was defined as an increase in left ventricular (LV) end-diastolic volume ≥20% at 6 months. All-cause death or first heart failure hospitalization was a pre-specified outcome that was assessed during follow-up (median duration 845 days). One hundred and sixty (56%) patients had a hypo-intense infarct core disclosed by native T1. In multivariable regression, infarct core native T1 was inversely associated with adverse remodelling [odds ratio (95% confidence interval (CI)] per 10 ms reduction in native T1: 0.91 (0.82, 0.00); P = 0.061). Thirty (10.4%) of 288 patients died or experienced a heart failure event and 13 of these events occurred post-discharge. Native T1 values (ms) within the hypo-intense infarct core (n = 160 STEMI patients) were inversely associated with the risk of all-cause death or first hospitalization for heart failure post-discharge (for a 10 ms increase in native T1: hazard ratio 0.730, 95% CI 0.617, 0.863; P < 0.001) including after adjustment for left ventricular ejection fraction, infarct core T2 and myocardial haemorrhage. The prognostic results for microvascular obstruction were similar. Conclusion Infarct core native T1 represents a novel non-contrast CMR biomarker with potential for infarct characterization and prognostication in STEMI survivors. Confirmatory studies are warranted. ClinicalTrials.gov identifier NCT02072850. PMID:26261290

  5. Significant Association between Sulfate-Reducing Bacteria and Uranium-Reducing Microbial Communities as Revealed by a Combined Massively Parallel Sequencing-Indicator Species Approach▿ †

    PubMed Central

    Cardenas, Erick; Wu, Wei-Min; Leigh, Mary Beth; Carley, Jack; Carroll, Sue; Gentry, Terry; Luo, Jian; Watson, David; Gu, Baohua; Ginder-Vogel, Matthew; Kitanidis, Peter K.; Jardine, Philip M.; Zhou, Jizhong; Criddle, Craig S.; Marsh, Terence L.; Tiedje, James M.

    2010-01-01

    Massively parallel sequencing has provided a more affordable and high-throughput method to study microbial communities, although it has mostly been used in an exploratory fashion. We combined pyrosequencing with a strict indicator species statistical analysis to test if bacteria specifically responded to ethanol injection that successfully promoted dissimilatory uranium(VI) reduction in the subsurface of a uranium contamination plume at the Oak Ridge Field Research Center in Tennessee. Remediation was achieved with a hydraulic flow control consisting of an inner loop, where ethanol was injected, and an outer loop for flow-field protection. This strategy reduced uranium concentrations in groundwater to levels below 0.126 μM and created geochemical gradients in electron donors from the inner-loop injection well toward the outer loop and downgradient flow path. Our analysis with 15 sediment samples from the entire test area found significant indicator species that showed a high degree of adaptation to the three different hydrochemical-created conditions. Castellaniella and Rhodanobacter characterized areas with low pH, heavy metals, and low bioactivity, while sulfate-, Fe(III)-, and U(VI)-reducing bacteria (Desulfovibrio, Anaeromyxobacter, and Desulfosporosinus) were indicators of areas where U(VI) reduction occurred. The abundance of these bacteria, as well as the Fe(III) and U(VI) reducer Geobacter, correlated with the hydraulic connectivity to the substrate injection site, suggesting that the selected populations were a direct response to electron donor addition by the groundwater flow path. A false-discovery-rate approach was implemented to discard false-positive results by chance, given the large amount of data compared. PMID:20729318

  6. Elaborating on Threshold Concepts

    ERIC Educational Resources Information Center

    Rountree, Janet; Robins, Anthony; Rountree, Nathan

    2013-01-01

    We propose an expanded definition of Threshold Concepts (TCs) that requires the successful acquisition and internalisation not only of knowledge, but also its practical elaboration in the domains of applied strategies and mental models. This richer definition allows us to clarify the relationship between TCs and Fundamental Ideas, and to account…

  7. Reading at the Threshold

    ERIC Educational Resources Information Center

    Gogan, Brian

    2013-01-01

    Recent considerations of threshold concepts in the rhetoric and writing studies discipline fail to consider the role that reading plays in the learning of student writers. This article reports results from a three-part, two-year, empirical study of seventy-five learners enrolled across four sections of a writing-intensive course. The course…

  8. Bedding material affects mechanical thresholds, heat thresholds and texture preference

    PubMed Central

    Moehring, Francie; O’Hara, Crystal L.; Stucky, Cheryl L.

    2015-01-01

    It has long been known that the bedding type animals are housed on can affect breeding behavior and cage environment. Yet little is known about its effects on evoked behavior responses or non-reflexive behaviors. C57BL/6 mice were housed for two weeks on one of five bedding types: Aspen Sani Chips® (standard bedding for our institute), ALPHA-Dri®, Cellu-Dri™, Pure-o’Cel™ or TEK-Fresh. Mice housed on Aspen exhibited the lowest (most sensitive) mechanical thresholds while those on TEK-Fresh exhibited 3-fold higher thresholds. While bedding type had no effect on responses to punctate or dynamic light touch stimuli, TEK-Fresh housed animals exhibited greater responsiveness in a noxious needle assay, than those housed on the other bedding types. Heat sensitivity was also affected by bedding as animals housed on Aspen exhibited the shortest (most sensitive) latencies to withdrawal whereas those housed on TEK-Fresh had the longest (least sensitive) latencies to response. Slight differences between bedding types were also seen in a moderate cold temperature preference assay. A modified tactile conditioned place preference chamber assay revealed that animals preferred TEK-Fresh to Aspen bedding. Bedding type had no effect in a non-reflexive wheel running assay. In both acute (two day) and chronic (5 week) inflammation induced by injection of Complete Freund’s Adjuvant in the hindpaw, mechanical thresholds were reduced in all groups regardless of bedding type, but TEK-Fresh and Pure-o’Cel™ groups exhibited a greater dynamic range between controls and inflamed cohorts than Aspen housed mice. PMID:26456764

  9. New near-threshold mesons

    NASA Astrophysics Data System (ADS)

    Cohen, Thomas D.; Gelman, Boris A.; Nussinov, Shmuel

    2004-01-01

    We show that under a number of rather plausible assumptions QCD spectrum may contain a number of mesons which have not been predicted or observed. Such states will have the quantum numbers of two existing mesons and masses very close to the dissociation threshold into the two mesons. Moreover, at least one of the two mesonic constituents itself must be very close to its dissociation threshold. In particular, one might expect the existence of loosely bound systems of D and D∗sJ(2317); similarly, K and f0(980), K¯ and f0(980), K and a0(980) and K¯ and a0(980) can be bound. The mechanism for binding in these cases is the S-wave kaon exchange. The nearness of one of the constituents to its decay threshold into a kaon plus a remainder, implies that the range of the kaon exchange force becomes abnormally long—significantly longer than 1/mK which greatly aids the binding.

  10. Elliptical polarization favors long quantum orbits in high-order above-threshold ionization of noble gases.

    PubMed

    Lai, XuanYang; Wang, ChuanLiang; Chen, YongJu; Hu, ZiLong; Quan, Wei; Liu, XiaoJun; Chen, Jing; Cheng, Ya; Xu, ZhiZhan; Becker, Wilhelm

    2013-01-25

    We demonstrate the significant role of long quantum orbits in strong-field atomic processes by investigating experimentally and theoretically the above-threshold ionization spectra of noble gases in intense elliptically polarized laser pulses. With increasing laser ellipticity, the yields of different energy regions of the measured electron spectrum in high-order above-threshold ionization drop at different rates. The experimental features can be reproduced by a theoretical simulation based on quantum-orbit theory, revealing that increasing ellipticity favors the contributions of the long quantum orbits in the high-order above-threshold ionization process.

  11. A Threshold Continuum for Aeolian Sand Transport

    NASA Astrophysics Data System (ADS)

    Swann, C.; Ewing, R. C.; Sherman, D. J.

    2015-12-01

    The threshold of motion for aeolian sand transport marks the initial entrainment of sand particles by the force of the wind. This is typically defined and modeled as a singular wind speed for a given grain size and is based on field and laboratory experimental data. However, the definition of threshold varies significantly between these empirical models, largely because the definition is based on visual-observations of initial grain movement. For example, in his seminal experiments, Bagnold defined threshold of motion when he observed that 100% of the bed was in motion. Others have used 50% and lesser values. Differences in threshold models, in turn, result is large errors in predicting the fluxes associated with sand and dust transport. Here we use a wind tunnel and novel sediment trap to capture the fractions of sand in creep, reptation and saltation at Earth and Mars pressures and show that the threshold of motion for aeolian sand transport is best defined as a continuum in which grains progress through stages defined by the proportion of grains in creep and saltation. We propose the use of scale dependent thresholds modeled by distinct probability distribution functions that differentiate the threshold based on micro to macro scale applications. For example, a geologic timescale application corresponds to a threshold when 100% of the bed in motion whereas a sub-second application corresponds to a threshold when a single particle is set in motion. We provide quantitative measurements (number and mode of particle movement) corresponding to visual observations, percent of bed in motion and degrees of transport intermittency for Earth and Mars. Understanding transport as a continuum provides a basis for revaluating sand transport thresholds on Earth, Mars and Titan.

  12. Hyper-arousal decreases human visual thresholds.

    PubMed

    Woods, Adam J; Philbeck, John W; Wirtz, Philip

    2013-01-01

    Arousal has long been known to influence behavior and serves as an underlying component of cognition and consciousness. However, the consequences of hyper-arousal for visual perception remain unclear. The present study evaluates the impact of hyper-arousal on two aspects of visual sensitivity: visual stereoacuity and contrast thresholds. Sixty-eight participants participated in two experiments. Thirty-four participants were randomly divided into two groups in each experiment: Arousal Stimulation or Sham Control. The Arousal Stimulation group underwent a 50-second cold pressor stimulation (immersing the foot in 0-2° C water), a technique known to increase arousal. In contrast, the Sham Control group immersed their foot in room temperature water. Stereoacuity thresholds (Experiment 1) and contrast thresholds (Experiment 2) were measured before and after stimulation. The Arousal Stimulation groups demonstrated significantly lower stereoacuity and contrast thresholds following cold pressor stimulation, whereas the Sham Control groups showed no difference in thresholds. These results provide the first evidence that hyper-arousal from sensory stimulation can lower visual thresholds. Hyper-arousal's ability to decrease visual thresholds has important implications for survival, sports, and everyday life.

  13. Thermoregulatory response thresholds during spinal anesthesia.

    PubMed

    Kurz, A; Sessler, D I; Schroeder, M; Kurz, M

    1993-10-01

    Reportedly, during spinal anesthesia, the shivering threshold is reduced approximately 1 degree C but the vasoconstriction threshold remains normal. Such divergence between the shivering and vasoconstriction thresholds is an unusual pattern of thermoregulatory impairment and suggests that the mechanisms of impairment during regional anesthesia may be especially complex. Accordingly, we sought to define the pattern of thermoregulatory impairment during spinal anesthesia by measuring response thresholds. Seven healthy women volunteered to participate on two study days. On one day, we evaluated thermoregulatory responses to hypothermia and hyperthermia during spinal anesthesia; on the other day, responses were evaluated without anesthesia. Upper body skin temperature was kept constant throughout the study. The volunteers were warmed via the lower body and cooled by central venous infusion of cold fluid. The core temperatures triggering a sweating rate of 40 g.m-2 x h-1, a finger flow of 0.1 mL/min, and a marked and sustained increase in oxygen consumption were considered the thermoregulatory thresholds for sweating, vasoconstriction, and shivering, respectively. Spinal anesthesia significantly decreased the thresholds for vasoconstriction and shivering, and the decrease in each was approximately 0.5 degree C. The range of temperatures not triggering thermoregulatory responses (those between sweating and vasoconstriction) was 0.9 +/- 0.6 degree C during spinal anesthesia. The synchronous decrease in the shivering and vasoconstriction thresholds during spinal anesthesia is consistent with thermoregulatory impairment resulting from altered afferent thermal input.

  14. Monocular and binocular depth discrimination thresholds.

    PubMed

    Kaye, S B; Siddiqui, A; Ward, A; Noonan, C; Fisher, A C; Green, J R; Brown, M C; Wareing, P A; Watt, P

    1999-11-01

    Measurement of stereoacuity at varying distances, by real or simulated depth stereoacuity tests, is helpful in the evaluation of patients with binocular imbalance or strabismus. Although the cue of binocular disparity underpins stereoacuity tests, there may be variable amounts of other binocular and monocular cues inherent in a stereoacuity test. In such circumstances, a combined monocular and binocular threshold of depth discrimination may be measured--stereoacuity conventionally referring to the situation where binocular disparity giving rise to retinal disparity is the only cue present. A child-friendly variable distance stereoacuity test (VDS) was developed, with a method for determining the binocular depth threshold from the combined monocular and binocular threshold of depth of discrimination (CT). Subjects with normal binocular function, reduced binocular function, and apparently absent binocularity were included. To measure the threshold of depth discrimination, subjects were required by means of a hand control to align two electronically controlled spheres at viewing distances of 1, 3, and 6m. Stereoacuity was also measured using the TNO, Frisby, and Titmus stereoacuity tests. BTs were calculated according to the function BT= arctan (1/tan alphaC - 1/tan alphaM)(-1), where alphaC and alphaM are the angles subtended at the nodal points by objects situated at the monocular threshold (alphaM) and the combined monocular-binocular threshold (alphaC) of discrimination. In subjects with good binocularity, BTs were similar to their combined thresholds, whereas subjects with reduced and apparently absent binocularity had binocular thresholds 4 and 10 times higher than their combined thresholds (CT). The VDS binocular thresholds showed significantly higher correlation and agreement with the TNO test and the binocular thresholds of the Frisby and Titmus tests, than the corresponding combined thresholds (p = 0.0019). The VDS was found to be an easy to use real depth

  15. Effects of ultrasound frequency and tissue stiffness on the histotripsy intrinsic threshold for cavitation.

    PubMed

    Vlaisavljevich, Eli; Lin, Kuang-Wei; Maxwell, Adam; Warnez, Matthew T; Mancia, Lauren; Singh, Rahul; Putnam, Andrew J; Fowlkes, Brian; Johnsen, Eric; Cain, Charles; Xu, Zhen

    2015-06-01

    Histotripsy is an ultrasound ablation method that depends on the initiation of a cavitation bubble cloud to fractionate soft tissue. Previous work has indicated that a cavitation cloud can be formed by a single pulse with one high-amplitude negative cycle, when the negative pressure amplitude directly exceeds a pressure threshold intrinsic to the medium. We hypothesize that the intrinsic threshold in water-based tissues is determined by the properties of the water inside the tissue, and changes in tissue stiffness or ultrasound frequency will have a minimal impact on the histotripsy intrinsic threshold. To test this hypothesis, the histotripsy intrinsic threshold was investigated both experimentally and theoretically. The probability of cavitation was measured by subjecting tissue phantoms with adjustable mechanical properties and ex vivo tissues to a histotripsy pulse of 1-2 cycles produced by 345-kHz, 500-kHz, 1.5-MHz and 3-MHz histotripsy transducers. Cavitation was detected and characterized by passive cavitation detection and high-speed photography, from which the probability of cavitation was measured versus pressure amplitude. The results revealed that the intrinsic threshold (the negative pressure at which probability = 0.5) is independent of stiffness for Young's moduli (E) <1 MPa, with only a small increase (∼2-3 MPa) in the intrinsic threshold for tendon (E = 380 MPa). Additionally, results for all samples revealed only a small increase of ∼2-3 MPa when the frequency was increased from 345 kHz to 3 MHz. The intrinsic threshold was measured to be between 24.7 and 30.6 MPa for all samples and frequencies tested in this study. Overall, the results of this study indicate that the intrinsic threshold to initiate a histotripsy bubble cloud is not significantly affected by tissue stiffness or ultrasound frequency in the hundreds of kilohertz to megahertz range.

  16. Elaborating on threshold concepts

    NASA Astrophysics Data System (ADS)

    Rountree, Janet; Robins, Anthony; Rountree, Nathan

    2013-09-01

    We propose an expanded definition of Threshold Concepts (TCs) that requires the successful acquisition and internalisation not only of knowledge, but also its practical elaboration in the domains of applied strategies and mental models. This richer definition allows us to clarify the relationship between TCs and Fundamental Ideas, and to account for both the important and the problematic characteristics of TCs in terms of the Knowledge/Strategies/Mental Models Framework defined in previous work.

  17. Network problem threshold

    NASA Technical Reports Server (NTRS)

    Gejji, Raghvendra, R.

    1992-01-01

    Network transmission errors such as collisions, CRC errors, misalignment, etc. are statistical in nature. Although errors can vary randomly, a high level of errors does indicate specific network problems, e.g. equipment failure. In this project, we have studied the random nature of collisions theoretically as well as by gathering statistics, and established a numerical threshold above which a network problem is indicated with high probability.

  18. Vision thresholds revisited

    NASA Astrophysics Data System (ADS)

    Garstang, R. H.

    1999-05-01

    During and just after World War II there was intense interest in the threshold for seeing faint sources against illuminated backgrounds. Knoll, Tousey and Hulburt (1946, 1948) determined the threshold for (effectively) point sources seen against backgrounds ranging in brightness from darkness to subdued daylight. Blackwell (1946) gave contrast ratios for sources of various sizes ranging from point sources up to circular disks of 6 degrees diameter, all seen against the same range of brightnesses, and determined by a very large number of visual observations made by a team of observers. I have combined the two sets of results, and represented them by an improvement on the theoretical formula for threshold illuminance as a function of background brightness which was suggested by Hecht (1934). My formula agrees very well with the observations, and is very suitable for incorporation into computer programs. Applications have been made to problems where the background brightness is caused by light pollution, and the source size is determined by the seeing. These include the optimum magnification and limiting magnitude of telescopes, and the analysis of visual limiting magnitudes determined by Bowen (1947) to determine the night sky brightness at Mount Wilson in 1947.

  19. Threshold Concepts in Research Education and Evidence of Threshold Crossing

    ERIC Educational Resources Information Center

    Kiley, Margaret; Wisker, Gina

    2009-01-01

    Most work on threshold concepts has hitherto related to discipline-specific undergraduate education, however, the idea of generic doctoral-level threshold concepts appeared to us to provide a strong and useful framework to support research learning and teaching at the graduate level. The early work regarding research-level threshold concepts is…

  20. Threshold Concepts in Research Education and Evidence of Threshold Crossing

    ERIC Educational Resources Information Center

    Kiley, Margaret; Wisker, Gina

    2009-01-01

    Most work on threshold concepts has hitherto related to discipline-specific undergraduate education, however, the idea of generic doctoral-level threshold concepts appeared to us to provide a strong and useful framework to support research learning and teaching at the graduate level. The early work regarding research-level threshold concepts is…

  1. Optical thresholding and Max Operation

    DTIC Science & Technology

    Thresholding and Max operations are essential elements in the implementation of neural networks. Although there have been several optical...implementations of neural networks, the thresholding functions are performed electronically. Optical thresholding and Max operations have the advantages of...we propose and study the properties of self-oscillation in nonlinear optical (NLO) four-wave mixing (FWM) and NLO resonators for parallel optical thresholding and Max operation.

  2. Vibration perception threshold for sight-threatening retinopathy screening in type 2 diabetic outpatients.

    PubMed

    Shen, Jing; Hu, Yanyun; Liu, Fang; Zeng, Hui; Li, Lianxi; Zhao, Jun; Zhao, Jungong; Zheng, Taishan; Lu, Huijuan; Lu, Fengdi; Bao, Yuqian; Jia, Weiping

    2013-10-01

    We investigated the relationship between vibration perception threshold and diabetic retinopathy and verified the screening value of vibration perception threshold for severe diabetic retinopathy. A total of 955 patients with type 2 diabetes were recruited and divided into three groups according to their fundus oculi photography results: no diabetic retinopathy (n = 654, 68.48%), non-sight-threatening diabetic retinopathy (n = 189, 19.79%) and sight-threatening diabetic retinopathy (n = 112, 11.73%). Their clinical and biochemical characteristics, vibration perception threshold and the diabetic retinopathy grades were detected and compared. There were significant differences in diabetes duration and blood glucose levels among three groups (all p < 0.05). The values of vibration perception threshold increased with the rising severity of retinopathy, and the vibration perception threshold level of sight-threatening diabetic retinopathy group was significantly higher than both non-sight-threatening diabetic retinopathy and no diabetic retinopathy groups (both p < 0.01). The prevalence of sight-threatening diabetic retinopathy in vibration perception threshold >25 V group was significantly higher than those in 16-24 V group (p < 0.01). The severity of diabetic retinopathy was positively associated with diabetes duration, blood glucose indexes and vibration perception threshold (all p < 0.01). Multiple stepwise regression analysis proved that glycosylated haemoglobin (β = 0.385, p = 0.000), diabetes duration (β = 0.275, p = 0.000) and vibration perception threshold (β = 0.180, p = 0.015) were independent risk factors for diabetic retinopathy. Receiver operating characteristic analysis further revealed that vibration perception threshold higher than 18 V was the optimal cut point for reflecting high risk of sight-threatening diabetic retinopathy (odds ratio = 4.20, 95% confidence interval = 2.67-6.59). There was a close association between vibration perception

  3. Laser threshold magnetometry

    NASA Astrophysics Data System (ADS)

    Jeske, Jan; Cole, Jared H.; Greentree, Andrew D.

    2016-01-01

    We propose a new type of sensor, which uses diamond containing the optically active nitrogen-vacancy (NV-) centres as a laser medium. The magnetometer can be operated at room-temperature and generates light that can be readily fibre coupled, thereby permitting use in industrial applications and remote sensing. By combining laser pumping with a radio-frequency Rabi-drive field, an external magnetic field changes the fluorescence of the NV- centres. We use this change in fluorescence level to push the laser above threshold, turning it on with an intensity controlled by the external magnetic field, which provides a coherent amplification of the readout signal with very high contrast. This mechanism is qualitatively different from conventional NV--based magnetometers which use fluorescence measurements, based on incoherent photon emission. We term our approach laser threshold magnetometer (LTM). We predict that an NV--based LTM with a volume of 1 mm3 can achieve shot-noise limited dc sensitivity of 1.86 fT /\\sqrt{{{Hz}}} and ac sensitivity of 3.97 fT /\\sqrt{{{Hz}}}.

  4. Coloring geographical threshold graphs

    SciTech Connect

    Bradonjic, Milan; Percus, Allon; Muller, Tobias

    2008-01-01

    We propose a coloring algorithm for sparse random graphs generated by the geographical threshold graph (GTG) model, a generalization of random geometric graphs (RGG). In a GTG, nodes are distributed in a Euclidean space, and edges are assigned according to a threshold function involving the distance between nodes as well as randomly chosen node weights. The motivation for analyzing this model is that many real networks (e.g., wireless networks, the Internet, etc.) need to be studied by using a 'richer' stochastic model (which in this case includes both a distance between nodes and weights on the nodes). Here, we analyze the GTG coloring algorithm together with the graph's clique number, showing formally that in spite of the differences in structure between GTG and RGG, the asymptotic behavior of the chromatic number is identical: {chi}1n 1n n / 1n n (1 + {omicron}(1)). Finally, we consider the leading corrections to this expression, again using the coloring algorithm and clique number to provide bounds on the chromatic number. We show that the gap between the lower and upper bound is within C 1n n / (1n 1n n){sup 2}, and specify the constant C.

  5. A Whole-Brain Voxel Based Measure of Intrinsic Connectivity Contrast Reveals Local Changes in Tissue Connectivity with Anesthetic without A Priori Assumptions on Thresholds or Regions of Interest

    PubMed Central

    Martuzzi, Roberto; Ramani, Ramachandran; Qiu, Maolin; Shen, Xilin; Papademetris, Xenophon; Constable, R. Todd

    2011-01-01

    The analysis of spontaneous fluctuations of functional magnetic resonance imaging (fMRI) signals has recently gained attention as a powerful tool for investigating brain circuits in a non-invasive manner. Correlation-based connectivity analysis investigates the correlations of spontaneous fluctuations of the fMRI signal either between a single seed region of interest (ROI) and the rest of the brain or between multiple ROIs. To do this, a priori knowledge is required for defining the ROI(s) and without such knowledge functional connectivity fMRI cannot be used as an exploratory tool for investigating the functional organization of the brain and its modulation under the different conditions. In this work we examine two indices that provide voxel based maps reflecting the intrinsic connectivity contrast (ICC) of individual tissue elements without the need for defining ROIs and hence require no a priori information or assumptions. These voxel based ICC measures can also be used to delineate regions of interest for further functional or network analyses. The indices were applied to the study of sevoflurane anesthesia-induced alterations in intrinsic connectivity. In concordance with previous studies, the results show that sevoflurane affects different brain circuits in a heterogeneous manner. In addition ICC analyses revealed changes in regions not previously identified using conventional ROI connectivity analyses, probably because of an inappropriate choice of the ROI in the earlier studies. This work highlights the importance of such voxel based connectivity methodology. PMID:21763437

  6. The nature of psychological thresholds.

    PubMed

    Rouder, Jeffrey N; Morey, Richard D

    2009-07-01

    Following G. T. Fechner (1966), thresholds have been conceptualized as the amount of intensity needed to transition between mental states, such as between states of unconsciousness and consciousness. With the advent of the theory of signal detection, however, discrete-state theory and the corresponding notion of threshold have been discounted. Consequently, phenomena such as subliminal priming and perception have a reduced theoretical basis. The authors propose a process-neutral definition of threshold that allows for graded perception and activation throughout the system. Thresholds correspond to maximum stimulus intensities such that the distribution of mental states does not differ from that when an appropriate baseline stimulus is presented. In practice, thresholds are maximum intensities such that the probability distribution on behavioral events does not differ from that from baseline. These thresholds, which the authors call task thresholds, may be estimated with modified item response psychometric measurement models. Copyright (c) 2009 APA, all rights reserved.

  7. Oscillatory threshold logic.

    PubMed

    Borresen, Jon; Lynch, Stephen

    2012-01-01

    In the 1940s, the first generation of modern computers used vacuum tube oscillators as their principle components, however, with the development of the transistor, such oscillator based computers quickly became obsolete. As the demand for faster and lower power computers continues, transistors are themselves approaching their theoretical limit and emerging technologies must eventually supersede them. With the development of optical oscillators and Josephson junction technology, we are again presented with the possibility of using oscillators as the basic components of computers, and it is possible that the next generation of computers will be composed almost entirely of oscillatory devices. Here, we demonstrate how coupled threshold oscillators may be used to perform binary logic in a manner entirely consistent with modern computer architectures. We describe a variety of computational circuitry and demonstrate working oscillator models of both computation and memory.

  8. Oscillatory Threshold Logic

    PubMed Central

    Borresen, Jon; Lynch, Stephen

    2012-01-01

    In the 1940s, the first generation of modern computers used vacuum tube oscillators as their principle components, however, with the development of the transistor, such oscillator based computers quickly became obsolete. As the demand for faster and lower power computers continues, transistors are themselves approaching their theoretical limit and emerging technologies must eventually supersede them. With the development of optical oscillators and Josephson junction technology, we are again presented with the possibility of using oscillators as the basic components of computers, and it is possible that the next generation of computers will be composed almost entirely of oscillatory devices. Here, we demonstrate how coupled threshold oscillators may be used to perform binary logic in a manner entirely consistent with modern computer architectures. We describe a variety of computational circuitry and demonstrate working oscillator models of both computation and memory. PMID:23173034

  9. Increment Threshold Functions in Retinopathy of Prematurity

    PubMed Central

    Hansen, Ronald M.; Moskowitz, Anne; Bush, Jennifer N.; Fulton, Anne B.

    2016-01-01

    Purpose To assess scotopic background adaptation in subjects with a history of preterm birth and retinopathy of prematurity (ROP). Retinopathy of prematurity is known to have long-term effects on rod photoreceptor and rod mediated postreceptor retinal function. Methods Rod-mediated thresholds for detection of 3° diameter, 50 ms stimuli presented 20° from fixation were measured using a spatial forced choice method in 36 subjects (aged 9–17 years) with a history of preterm birth and 11 age similar term-born subjects. Thresholds were measured first in the dark-adapted condition and then in the presence of 6 steady background lights (−2.8 to +2.0 log scot td). A model of the increment threshold function was fit to each subject's thresholds to estimate the dark-adapted threshold (TDA) and the Eigengrau (A0, the background that elevates threshold 0.3 log unit above TDA). Results In subjects with a history of severe ROP, both TDA and A0 were significantly elevated relative to those in former preterms who never had ROP and term-born control subjects. Subjects who had mild ROP had normal TDA but elevated A0. Neither TDA nor A0 differed significantly between former preterms who never had ROP and term-born controls. Conclusions The results suggest that in severe ROP, threshold is affected at a preadaptation site, possibly the rod outer segment. In mild ROP, changes in the Eigengrau may reflect increased intrinsic noise in the photoreceptor or postreceptor circuitry or both. PMID:27145476

  10. Optimising threshold levels for information transmission in binary threshold networks: Independent multiplicative noise on each threshold

    NASA Astrophysics Data System (ADS)

    Zhou, Bingchang; McDonnell, Mark D.

    2015-02-01

    The problem of optimising the threshold levels in multilevel threshold system subject to multiplicative Gaussian and uniform noise is considered. Similar to previous results for additive noise, we find a bifurcation phenomenon in the optimal threshold values, as the noise intensity changes. This occurs when the number of threshold units is greater than one. We also study the optimal thresholds for combined additive and multiplicative Gaussian noise, and find that all threshold levels need to be identical to optimise the system when the additive noise intensity is a constant. However, this identical value is not equal to the signal mean, unlike the case of additive noise. When the multiplicative noise intensity is instead held constant, the optimal threshold levels are not all identical for small additive noise intensity but are all equal to zero for large additive noise intensity. The model and our results are potentially relevant for sensor network design and understanding neurobiological sensory neurons such as in the peripheral auditory system.

  11. The threshold hypothesis: evidence from less developed Latin American countries, 1950 to 1980.

    PubMed

    Cutright, P; Hargens, L

    1984-11-01

    Historical research among European countries finds large differences in the level of social, economic or demographic development among countries, or regions within countries at the time marital fertility rates began their decline from traditional high levels. This research tests a threshold hypothesis which holds that fertility will decline from traditional high levels if threshold levels of life expectancy and literacy are surpassed. Using a pooled regression analysis of 1950, 1960, 1970 and 1980 crude births rates (CBRs) in 20 less developed Latin American countries, in conjunction with 10-year lagged measures of social, economic and family planning program development, analyses reveal statistically significant effects of passing Beaver's (1975) threshold levels of 1950 literacy, or 1950 life expectancy, that are independent of levels of lagged literacy (or lagged life expectancy), economic and family planning program development, as well as measures that control period effects.

  12. Threshold of soil water content for ecosystem carbon fluxes and their response to climate warming in an alpine meadow

    NASA Astrophysics Data System (ADS)

    Quan, Quan

    2017-04-01

    1. Soil water content (SWC) has been recognized to largely regulate ecosystem carbon (C) fluxes and their responses to climate change. However, it remains unclear whether there exists a SWC threshold for ecosystem C fluxes and their responses to climate warming. 2. Based on a field warming experiment in an alpine meadow on the Qinghai-Tibet Plateau (QTP), we examined how SWC regulates ecosystem C fluxes in response to experimental warming. 3. We first detected a SWC threshold of 27.3 ± 5.2% for all the C flux variables except root respiration. This threshold did not change over years in 2014 or 2015 across all the warming or clipping treatments. C fluxes increased with SWC below the threshold but significantly decreased with SWC above it. Warming effects on C fluxes varied with seasons and years due to the changes in SWC. Experimental warming stimulated C fluxes when SWC was above the threshold but depressed C fluxes when SWC was below the threshold. C fluxes were always positively correlated with soil temperature when SWC was above its threshold. When SWC was below its threshold, net ecosystem exchange (NEE) and gross ecosystem production (GEP) decreased but root respiration, soil respiration, and ecosystem respiration increased with soil temperature. 4. This study provided field evidence on the traditionally speculated concept of SWC threshold and revealed how SWC threshold regulates responses of different ecosystem C fluxes to climate warming. The findings offer mechanistic explanations for ecosystem C fluxes in response to climate warming under varying SWC status and changing precipitation regimes.

  13. Assessing the regional and temporal variability of the topographic threshold for ephemeral gully initiation using quantile regression in Wallonia (Belgium)

    NASA Astrophysics Data System (ADS)

    Maugnard, A.; Van Dyck, S.; Bielders, C. L.

    2014-02-01

    Ephemeral gully erosion is responsible for large losses of soil on cropland and causes serious off-site damages. Understanding and predicting the occurrence of ephemeral gully erosion are therefore major concerns for land users, decision makers or alike. In order to explain and predict the initiation of gully erosion, numerous studies have focused on the concept of topographic threshold which relies on the slope and contributing area at the gully head. Different approaches have been used so far for defining this threshold. However, these approaches may be questioned because they are partly subjective, not always statistically-based or based on the statistical weight of all data points rather than on the data points at the threshold. To cope with these deficiencies, quantile regression is proposed as an alternative for determining the threshold line. It is applied to assess the regional and temporal variability of gully initiation in Wallonia (Belgium) and compared to previous thresholding approaches. A database of gullies was created from aerial photographs for three agro-pedological areas. The areas differed considerably in terms of number (102-282), mean length (84-151 m) and type of gullies. Most gullies were located on land with summer crops and more than 70% were restricted to a single plot. Significant differences in the topographical threshold were observed across areas, but these regional differences were not consistent across the various thresholding methods. Only 12-18% of gullies were recurrent over time, yet the topographic threshold determined by quantile regression seemed to be stable in spite of annual differences in land use and climate. The results reveal the need for greater standardization of thresholding methods. Quantile regression should be preferred over other previous approaches as it is more consistent with the concept of threshold and appears more robust.

  14. Automated threshold detection for auditory brainstem responses: comparison with visual estimation in a stem cell transplantation study.

    PubMed

    Bogaerts, Sofie; Clements, John D; Sullivan, Jeremy M; Oleskevich, Sharon

    2009-08-26

    Auditory brainstem responses (ABRs) are used to study auditory acuity in animal-based medical research. ABRs are evoked by acoustic stimuli, and consist of an electrical signal resulting from summated activity in the auditory nerve and brainstem nuclei. ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Traditionally, threshold has been assessed by visual estimation of a series of ABRs evoked by different sound intensities. Here we develop an automated threshold detection method that eliminates the variability and subjectivity associated with visual estimation. The automated method is a robust computational procedure that detects the sound level at which the peak amplitude of the evoked ABR signal first exceeds four times the standard deviation of the baseline noise. Implementation of the procedure was achieved by evoking ABRs in response to click and tone stimuli, under normal and experimental conditions (adult stem cell transplantation into cochlea). Automated detection revealed that the threshold shift from pre- to post-surgery hearing levels was similar in mice receiving stem cell transplantation or sham injection for click and tone stimuli. Visual estimation by independent observers corroborated these results but revealed variability in ABR threshold shifts and significance levels for stem cell-transplanted and sham-injected animals. In summary, the automated detection method avoids the subjectivity of visual analysis and offers a rapid, easily accessible http://axograph.com/source/abr.html approach to measure hearing threshold levels in auditory brainstem response.

  15. Probabilistic Threshold Criterion

    SciTech Connect

    Gresshoff, M; Hrousis, C A

    2010-03-09

    The Probabilistic Shock Threshold Criterion (PSTC) Project at LLNL develops phenomenological criteria for estimating safety or performance margin on high explosive (HE) initiation in the shock initiation regime, creating tools for safety assessment and design of initiation systems and HE trains in general. Until recently, there has been little foundation for probabilistic assessment of HE initiation scenarios. This work attempts to use probabilistic information that is available from both historic and ongoing tests to develop a basis for such assessment. Current PSTC approaches start with the functional form of the James Initiation Criterion as a backbone, and generalize to include varying areas of initiation and provide a probabilistic response based on test data for 1.8 g/cc (Ultrafine) 1,3,5-triamino-2,4,6-trinitrobenzene (TATB) and LX-17 (92.5% TATB, 7.5% Kel-F 800 binder). Application of the PSTC methodology is presented investigating the safety and performance of a flying plate detonator and the margin of an Ultrafine TATB booster initiating LX-17.

  16. Photoproduction of the phi (1020) near threshold

    SciTech Connect

    D.J. Tedeschi; M. Huertas

    2000-05-12

    Photoproduction of phi mesons at photon energies below 2 GeV were measured at the CLAS detector in Hall B of Thomas Jefferson National Accelerator Facility. Preliminary differential cross sections are reported from the proton near threshold. The measurement are extended to the region in the variable t where production mechanisms beyond that of diffraction are expected to become significant.

  17. Simulated Critical Differences for Speech Reception Thresholds

    ERIC Educational Resources Information Center

    Pedersen, Ellen Raben; Juhl, Peter Møller

    2017-01-01

    Purpose: Critical differences state by how much 2 test results have to differ in order to be significantly different. Critical differences for discrimination scores have been available for several decades, but they do not exist for speech reception thresholds (SRTs). This study presents and discusses how critical differences for SRTs can be…

  18. Acupuncture modulates facial warm sensory thresholds.

    PubMed

    Benoliel, Rafael; Zaidan, Shadya; Eliav, Eli

    2011-01-01

    To assess the effects of four- and six-point acupuncture on facial sensory detection thresholds to thermal and electrical stimuli. Ten healthy volunteers underwent four-point acupuncture at ST6 and LI4 bilaterally for 15 minutes. A further 10 subjects underwent six-point acupuncture by adding needling at ST2 bilaterally. Sensory testing to thermal and electrical stimuli applied to mental and infraorbital nerve dermatomes was performed at baseline, 10 minutes, 1 hour, and 1 day after needling. In the mental and infraorbital nerve dermatomes, six-point acupuncture significantly increased warm threshold by a peak mean of 1.1°C to 1.4°C (repeated measures ANOVA P = .001) and this effect was significant at all time points relative to baseline (P < .05). No significant effects were observed by the four-point acupuncture on warm thresholds, and neither four- nor six-point acupuncture significantly altered electrical detection thresholds. A dose effect, related to the number of points employed, may be present when employing acupuncture.

  19. Learning foraging thresholds for lizards

    SciTech Connect

    Goldberg, L.A.; Hart, W.E.; Wilson, D.B.

    1996-01-12

    This work gives a proof of convergence for a randomized learning algorithm that describes how anoles (lizards found in the Carribean) learn a foraging threshold distance. This model assumes that an anole will pursue a prey if and only if it is within this threshold of the anole`s perch. This learning algorithm was proposed by the biologist Roughgarden and his colleagues. They experimentally confirmed that this algorithm quickly converges to the foraging threshold that is predicted by optimal foraging theory our analysis provides an analytic confirmation that the learning algorithm converses to this optimal foraging threshold with high probability.

  20. Threshold phenomena in soft matter

    NASA Astrophysics Data System (ADS)

    Huang, Zhibin

    Although two different fields are covered, this thesis is mainly focused on some threshold behaviors in both liquid crystal field and fluid dynamic systems. A method of rubbed polyimide is used to obtain pretilt. Sufficiently strong rubbing of a polyimide (SE-1211) results in a large polar pretilt of liquid crystal director with respect to the homeotropic orientation. There exists a threshold rubbing strength required to induce nonzero pretilt. For the homologous liquid crystal series alkyl-cyanobyphenyl, we found that the threshold rubbing strength is a monotonic function of the number of methylene units. A dual easy axis model is then used to explain the results. Freedericksz transition measurements have been used to determine the quadratical and quartic coefficients associated with the molecules' tilt with respect to the layer normal in surface-induced smectic layers in the nematic phase above the smectic-A-nematic phase transition temperature. Both the quadratic and quartic coefficients are consistent with the scaling relationship as predicted in theory, and their ratio is approximately constant. A Rayleigh-Taylor instability experiment is performed by using a magnetic field gradient to draw down a low density but highly paramagnetic fluid below a more dense fluid in a Hele-Shaw cell. When turning off the magnetic field, the RT instability occurs in situ and the growth of the most unstable wavevector is measured as a function of time. The wavelength of the RT instability along with the growth rate was measured as a function of capillary number (which is related to the density difference and interfacial tension between two fluids). A theory for the instability that permits different viscosities for two immiscible fluids was developed, and good agreement was found with the experimental results. The technique of magnetic levitation promises to broaden significantly the accessible parameter space of gravitational interfacial instability experiments. A method is

  1. Threshold concepts in finance: student perspectives

    NASA Astrophysics Data System (ADS)

    Hoadley, Susan; Kyng, Tim; Tickle, Leonie; Wood, Leigh N.

    2015-10-01

    Finance threshold concepts are the essential conceptual knowledge that underpin well-developed financial capabilities and are central to the mastery of finance. In this paper we investigate threshold concepts in finance from the point of view of students, by establishing the extent to which students are aware of threshold concepts identified by finance academics. In addition, we investigate the potential of a framework of different types of knowledge to differentiate the delivery of the finance curriculum and the role of modelling in finance. Our purpose is to identify ways to improve curriculum design and delivery, leading to better student outcomes. Whilst we find that there is significant overlap between what students identify as important in finance and the threshold concepts identified by academics, much of this overlap is expressed by indirect reference to the concepts. Further, whilst different types of knowledge are apparent in the student data, there is evidence that students do not necessarily distinguish conceptual from other types of knowledge. As well as investigating the finance curriculum, the research demonstrates the use of threshold concepts to compare and contrast student and academic perceptions of a discipline and, as such, is of interest to researchers in education and other disciplines.

  2. Hypnotic relaxation results in elevated thresholds of sensory detection but not of pain detection.

    PubMed

    Kramer, Sybille; Zims, Rolf; Simang, Michael; Rüger, Linda; Irnich, Dominik

    2014-12-15

    Many studies show an effectiveness of hypnotic analgesia. It has been discussed whether the analgesic effect is mainly caused by the relaxation that is concomitant to hypnosis. This study was designed to evaluate the effects of hypnotic relaxation suggestion on different somatosensory detection and pain thresholds. Quantitative sensory testing (QST) measurements were performed before and during hypnosis in twenty-three healthy subjects on the dorsum of the right hand. Paired t-test was used to compare threshold changes. The influence of hypnotic susceptibility was evaluated by calculating correlation coefficients for threshold changes and hypnotic susceptibility (Harvard group scale). During hypnosis significantly changed somatosensory thresholds (reduced function) were observed for the following sensory detection thresholds: Cold Detection Threshold (CDT), Warm Detection Threshold (WDT), Thermal Sensory Limen (TSL) and Mechanical Detection Threshold (MDT). The only unchanged sensory detection threshold was Vibration Detection Threshold (VDT). No significant changes were observed for the determined pain detection thresholds (Cold Pain Thresholds, Heat Pain Thresholds, Mechanical Pain Sensitivity, Dynamic Mechanical Allodynia, Wind-up Ratio and Pressure Pain Threshold). No correlation of hypnotic susceptibility and threshold changes were detected. Hypnotic relaxation without a specific analgesic suggestion results in thermal and mechanical detection, but not pain threshold changes. We thus conclude that a relaxation suggestion has no genuine effect on sensory pain thresholds. ClinicalTrials.gov, Identifier: NCT02261155 (9th October 2014).

  3. Factors Affecting Perceptual Threshold in Argus II Retinal Prosthesis Subjects

    PubMed Central

    Ahuja, A. K.; Yeoh, J.; Dorn, J. D.; Caspi, A.; Wuyyuru, V.; McMahon, M. J.; Humayun, M. S.; Greenberg, R. J.; daCruz, L.

    2013-01-01

    Purpose The Argus II epiretinal prosthesis has been developed to provide partial restoration of vision to subjects blinded from outer retinal degenerative disease. Participants were surgically implanted with the system in the United States and Europe in a single arm, prospective, multicenter clinical trial. The purpose of this investigation was to determine which factors affect electrical thresholds in order to inform surgical placement of the device. Methods Electrode–retina and electrode–fovea distances were determined using SD-OCT and fundus photography, respectively. Perceptual threshold to electrical stimulation of electrodes was measured using custom developed software, in which current amplitude was varied until the threshold was found. Full field stimulus light threshold was measured using the Espion D-FST test. Relationships between electrical threshold and these three explanatory variables (electrode–retina distance, electrode–fovea distance, and monocular light threshold) were quantified using regression. Results Regression analysis showed a significant correlation between electrical threshold and electrode–retina distance (R2 = 0.50, P = 0.0002; n = 703 electrodes). 90.3% of electrodes in contact with the macula (n = 207) elicited percepts at charge densities less than 1 mC/cm2/phase. These threshold data also correlated well with ganglion cell density profile (P = 0.03). A weaker, but still significant, inverse correlation was found between light threshold and electrical threshold (R2 < 0.52, P = 0.01). Multivariate modeling indicated that electrode–retina distance and light threshold are highly predictive of electrode threshold (R2 = 0.87; P < 0.0005). Conclusions Taken together, these results suggest that while light threshold should be used to inform patient selection, macular contact of the array is paramount. Translational Relevance Reported Argus II clinical study results are in good agreement with prior in vitro and in vivo studies

  4. Factors Affecting Perceptual Threshold in Argus II Retinal Prosthesis Subjects.

    PubMed

    Ahuja, A K; Yeoh, J; Dorn, J D; Caspi, A; Wuyyuru, V; McMahon, M J; Humayun, M S; Greenberg, R J; Dacruz, L

    2013-04-01

    The Argus II epiretinal prosthesis has been developed to provide partial restoration of vision to subjects blinded from outer retinal degenerative disease. Participants were surgically implanted with the system in the United States and Europe in a single arm, prospective, multicenter clinical trial. The purpose of this investigation was to determine which factors affect electrical thresholds in order to inform surgical placement of the device. Electrode-retina and electrode-fovea distances were determined using SD-OCT and fundus photography, respectively. Perceptual threshold to electrical stimulation of electrodes was measured using custom developed software, in which current amplitude was varied until the threshold was found. Full field stimulus light threshold was measured using the Espion D-FST test. Relationships between electrical threshold and these three explanatory variables (electrode-retina distance, electrode-fovea distance, and monocular light threshold) were quantified using regression. Regression analysis showed a significant correlation between electrical threshold and electrode-retina distance (R(2) = 0.50, P = 0.0002; n = 703 electrodes). 90.3% of electrodes in contact with the macula (n = 207) elicited percepts at charge densities less than 1 mC/cm(2)/phase. These threshold data also correlated well with ganglion cell density profile (P = 0.03). A weaker, but still significant, inverse correlation was found between light threshold and electrical threshold (R(2) < 0.52, P = 0.01). Multivariate modeling indicated that electrode-retina distance and light threshold are highly predictive of electrode threshold (R(2) = 0.87; P < 0.0005). Taken together, these results suggest that while light threshold should be used to inform patient selection, macular contact of the array is paramount. Reported Argus II clinical study results are in good agreement with prior in vitro and in vivo studies, and support the development of higher-density systems that

  5. Immune impairment thresholds in HIV infection.

    PubMed

    Iwami, Shingo; Nakaoka, Shinji; Takeuchi, Yasuhiro; Miura, Yoshiharu; Miura, Tomoyuki

    2009-04-27

    Longitudinal studies of patients infected with HIV-1 reveal a long and variable length of asymptomatic phase between infection and development of AIDS. Some HIV infected patients are still asymptomatic after 15 or more years of infection but some patients develop AIDS within 2 years. The mechanistic basis of the disease progression has remained obscure but many researchers have been trying to explain it. For example, the possible importance of viral diversity for the disease progression and the development of AIDS has been very well worked out in the early-1990s, especially by some important works of Martin A. Nowak. These studies can give an elegant explanation for a variability of asymptomatic phase. Here, a simple mathematical model was used to propose a new explanation for a variable length of asymptomatic phase. The main idea is that the immune impairment rate increases over the HIV infection. Our model suggested the existence of so-called "Risky threshold" and "Immunodeficiency threshold" on the impairment rate. The former implies that immune system may collapse when the impairment rate of HIV exceeds the threshold value. The latter implies that immune system always collapses when the impairment rate exceeds the value. We found that the length of asymptomatic phase is determined stochastically between these threshold values depending on the virological and immunological states. Furthermore, we investigated a distribution of the length of asymptomatic phase and a survival rate of the immune responses in one HIV patient.

  6. Thresholds in Xeric Hydrology and Biogeochemistry

    NASA Astrophysics Data System (ADS)

    Meixner, T.; Brooks, P. D.; Simpson, S. C.; Soto, C. D.; Yuan, F.; Turner, D.; Richter, H.

    2011-12-01

    Due to water limitation, thresholds in hydrologic and biogeochemical processes are common in arid and semi-arid systems. Some of these thresholds such as those focused on rainfall runoff relationships have been well studied. However to gain a full picture of the role that thresholds play in driving the hydrology and biogeochemistry of xeric systems a full view of the entire array of processes at work is needed. Here a walk through the landscape of xeric systems will be conducted illustrating the powerful role of hydrologic thresholds on xeric system biogeochemistry. To understand xeric hydro-biogeochemistry two key ideas need to be focused on. First, it is important to start from a framework of reaction and transport. Second an understanding of the temporal and spatial components of thresholds that have a large impact on hydrologic and biogeochemical fluxes needs to be offered. In the uplands themselves episodic rewetting and drying of soils permits accelerated biogeochemical processing but also more gradual drainage of water through the subsurface than expected in simple conceptions of biogeochemical processes. Hydrologic thresholds (water content above hygroscopic) results in a stop start nutrient spiral of material across the landscape since runoff connecting uplands to xeric perennial riparian is episodic and often only transports materials a short distance (100's of m). This episodic movement results in important and counter-intuitive nutrient inputs to riparian zones but also significant processing and uptake of nutrients. The floods that transport these biogeochemicals also result in significant input to riparian groundwater and may be key to sustaining these critical ecosystems. Importantly the flood driven recharge process itself is a threshold process dependent on flood characteristics (floods greater than 100 cubic meters per second) and antecedent conditions (losing to near neutral gradients). Floods also appear to influence where arid and semi

  7. Multiple runoff processes and multiple thresholds control agricultural runoff generation

    NASA Astrophysics Data System (ADS)

    Saffarpour, Shabnam; Western, Andrew W.; Adams, Russell; McDonnell, Jeffrey J.

    2016-11-01

    Thresholds and hydrologic connectivity associated with runoff processes are a critical concept for understanding catchment hydrologic response at the event timescale. To date, most attention has focused on single runoff response types, and the role of multiple thresholds and flow path connectivities has not been made explicit. Here we first summarise existing knowledge on the interplay between thresholds, connectivity and runoff processes at the hillslope-small catchment scale into a single figure and use it in examining how runoff response and the catchment threshold response to rainfall affect a suite of runoff generation mechanisms in a small agricultural catchment. A 1.37 ha catchment in the Lang Lang River catchment, Victoria, Australia, was instrumented and hourly data of rainfall, runoff, shallow groundwater level and isotope water samples were collected. The rainfall, runoff and antecedent soil moisture data together with water levels at several shallow piezometers are used to identify runoff processes in the study site. We use isotope and major ion results to further support the findings of the hydrometric data. We analyse 60 rainfall events that produced 38 runoff events over two runoff seasons. Our results show that the catchment hydrologic response was typically controlled by the Antecedent Soil Moisture Index and rainfall characteristics. There was a strong seasonal effect in the antecedent moisture conditions that led to marked seasonal-scale changes in runoff response. Analysis of shallow well data revealed that streamflows early in the runoff season were dominated primarily by saturation excess overland flow from the riparian area. As the runoff season progressed, the catchment soil water storage increased and the hillslopes connected to the riparian area. The hillslopes transferred a significant amount of water to the riparian zone during and following events. Then, during a particularly wet period, this connectivity to the riparian zone, and

  8. Threshold Hypothesis: Fact or Artifact?

    ERIC Educational Resources Information Center

    Karwowski, Maciej; Gralewski, Jacek

    2013-01-01

    The threshold hypothesis (TH) assumes the existence of complex relations between creative abilities and intelligence: linear associations below 120 points of IQ and weaker or lack of associations above the threshold. However, diverse results have been obtained over the last six decades--some confirmed the hypothesis and some rejected it. In this…

  9. Threshold Hypothesis: Fact or Artifact?

    ERIC Educational Resources Information Center

    Karwowski, Maciej; Gralewski, Jacek

    2013-01-01

    The threshold hypothesis (TH) assumes the existence of complex relations between creative abilities and intelligence: linear associations below 120 points of IQ and weaker or lack of associations above the threshold. However, diverse results have been obtained over the last six decades--some confirmed the hypothesis and some rejected it. In this…

  10. Threshold Concepts and Information Literacy

    ERIC Educational Resources Information Center

    Townsend, Lori; Brunetti, Korey; Hofer, Amy R.

    2011-01-01

    What do we teach when we teach information literacy in higher education? This paper describes a pedagogical approach to information literacy that helps instructors focus content around transformative learning thresholds. The threshold concept framework holds promise for librarians because it grounds the instructor in the big ideas and underlying…

  11. The Nature of Psychological Thresholds

    ERIC Educational Resources Information Center

    Rouder, Jeffrey N.; Morey, Richard D.

    2009-01-01

    Following G. T. Fechner (1966), thresholds have been conceptualized as the amount of intensity needed to transition between mental states, such as between a states of unconsciousness and consciousness. With the advent of the theory of signal detection, however, discrete-state theory and the corresponding notion of threshold have been discounted.…

  12. The Nature of Psychological Thresholds

    ERIC Educational Resources Information Center

    Rouder, Jeffrey N.; Morey, Richard D.

    2009-01-01

    Following G. T. Fechner (1966), thresholds have been conceptualized as the amount of intensity needed to transition between mental states, such as between a states of unconsciousness and consciousness. With the advent of the theory of signal detection, however, discrete-state theory and the corresponding notion of threshold have been discounted.…

  13. Comparison of two stimulus-delivery systems for measurement of nasal pungency thresholds.

    PubMed

    Cometto-Muñiz, J E; Cain, W S; Hiraishi, T; Abraham, M H; Gola, J M

    2000-06-01

    Using representative members of each of three homologous series of chemicals-ketones, acetates and alcohols-we measured nasal pungency thresholds in anosmics via two stimulus-delivery systems. The first system consists of the fairly commonly used 270 ml, plastic 'squeeze bottles'. The second system consists of 1900 ml, glass vessels with Teflon tubing and nose-pieces. Although bulkier and more susceptible to mechanical breakage, the glass vessels possess advantages that can allow them to provide 'environmentally realistic' chemosensory thresholds, i.e. thresholds closer in absolute values to those that might be obtained under whole-body exposures. Such advantages include a larger volume of the vapor-source to accommodate whole sniffs, and a tight nose-nose-piece connection to avoid stimulus dilution. The outcome revealed that, for every chemical, the glass vessels provided nasal pungency thresholds significantly lower than those provided by the squeeze bottles. The difference amounted, on average, to a factor of 4.6, though the relative potency of the compounds remained the same under both systems. Additionally, when tested with the highest homologues used here, namely, octyl acetate and 1-octanol, anosmics using the glass vessels had little or no difficulty achieving the criterion for threshold whereas they did have difficulty when using the squeeze bottles.

  14. Psychologic factors are related to some sensory pain thresholds but not nociceptive flexion reflex threshold in chronic whiplash.

    PubMed

    Sterling, Michele; Hodkinson, Emily; Pettiford, Catherine; Souvlis, Tina; Curatolo, Michele

    2008-02-01

    Sensory hypersensitivity, central hyperexcitability [lowered nociceptive flexion reflex (NFR) thresholds], and psychologic distress are features of chronic whiplash. However, relationships between these substrates are not clear. This study tested the hypothesis that psychologic distress and catastrophization are correlated with sensory hypersensitivity and NFR responses in chronic whiplash. Pressure and thermal pain thresholds (mean values across 3 body sites), NFR threshold, and pain at threshold Visual Analog Scale were measured in 30 participants with chronic whiplash and 30 asymptomatic controls. Pain and disability levels Neck Disability Index, psychologic distress (GHQ-28), and catastrophization (PCS) were also measured in the whiplash group. Whiplash injured participants demonstrated lowered pain thresholds to pressure and cold (P<0.05); lowered NFR thresholds (P=0.003), and demonstrated above threshold levels of psychologic distress (GHQ-28) and levels of catastrophization comparable with other musculoskeletal conditions. There were no group differences for heat pain thresholds or pain at NFR threshold. In the whiplash group, PCS scores correlated moderately with cold pain threshold (r=0.51, P=0.01). In contrast, there were no significant correlations between GHQ-28 scores and pain threshold measures or between psychologic factors and NFR responses in whiplash participants. There were no significant correlations between psychologic factors and pain thresholds or NFR responses in controls. We have demonstrated that psychologic factors have some association with sensory hypersensitivity (cold pain threshold measures) in chronic whiplash but do not seem to influence spinal cord excitability. This suggests that psychologic disorders are important, but not the only, determinants of central hypersensitivity in whiplash patients.

  15. Eszopiclone increases the respiratory arousal threshold and lowers the apnoea/hypopnoea index in obstructive sleep apnoea patients with a low arousal threshold.

    PubMed

    Eckert, Danny J; Owens, Robert L; Kehlmann, Geoffrey B; Wellman, Andrew; Rahangdale, Shilpa; Yim-Yeh, Susie; White, David P; Malhotra, Atul

    2011-06-01

    Recent insights into sleep apnoea pathogenesis reveal that a low respiratory arousal threshold (awaken easily) is important for many patients. As most patients experience stable breathing periods mediated by upper-airway dilator muscle activation via accumulation of respiratory stimuli, premature awakening may prevent respiratory stimuli build up as well as the resulting stabilization of sleep and breathing. The aim of the present physiological study was to determine the effects of a non-benzodiazepine sedative, eszopiclone, on the arousal threshold and the AHI (apnoea/hypopnoea index) in obstructive sleep apnoea patients. We hypothesized that eszopiclone would increase the arousal threshold and lower the AHI in patients with a low arousal threshold (0 to -15 cm H(2)O). Following a baseline overnight polysomnogram with an epiglottic pressure catheter to quantify the arousal threshold, 17 obstructive sleep apnoea patients, without major hypoxaemia [nadir SaO(2) (arterial blood oxygen saturation) >70%], returned on two additional nights and received 3 mg of eszopiclone or placebo immediately prior to each study. Compared with placebo, eszopiclone significantly increased the arousal threshold [-14.0 (-19.9 to -10.9) compared with -18.0 (-22.2 to -15.1) cm H(2)O; P<0.01], and sleep duration, improved sleep quality and lowered the AHI without respiratory event prolongation or worsening hypoxaemia. Among the eight patients identified as having a low arousal threshold, reductions in the AHI occurred invariably and were most pronounced (25±6 compared with 14±4 events/h of sleep; P<0.01). In conclusion, eszopiclone increases the arousal threshold and lowers the AHI in obstructive sleep apnoea patients that do not have marked overnight hypoxaemia. The greatest reductions in the AHI occurred in those with a low arousal threshold. The results of this single night physiological study suggest that certain sedatives may be of therapeutic benefit for a definable subgroup of

  16. Effects of pulse duration on magnetostimulation thresholds

    SciTech Connect

    Saritas, Emine U.; Goodwill, Patrick W.; Conolly, Steven M.

    2015-06-15

    . Results: The magnetostimulation limits decreased with increasing pulse duration (T{sub pulse}). For T{sub pulse} < 18 ms, the thresholds were significantly higher than at the longest pulse durations (p < 0.01, paired Wilcoxon signed-rank test). The normalized magnetostimulation threshold (B{sub Norm}) vs duration curve at all three frequencies agreed almost identically, indicating that the observed effect is independent of the operating frequency. At the shortest pulse duration (T{sub pulse} ≈ 2 ms), the thresholds were approximately 24% higher than at the asymptotes. The thresholds decreased to within 4% of their asymptotic values for T{sub pulse} > 20 ms. These trends were well characterized (R{sup 2} = 0.78) by a stretched exponential function given by B{sub Norm}=1+αe{sup −(T{sub p}{sub u}{sub l}{sub s}{sub e}/β){sup γ}}, where the fitted parameters were α = 0.44, β = 4.32, and γ = 0.60. Conclusions: This work shows for the first time that the magnetostimulation thresholds decrease with increasing pulse duration, and that this effect is independent of the operating frequency. Normalized threshold vs duration trends are almost identical for a 20-fold range of frequencies: the thresholds are significantly higher at short pulse durations and settle to within 4% of their asymptotic values for durations longer than 20 ms. These results emphasize the importance of matching the human-subject experiments to the imaging conditions of a particular setup. Knowing the dependence of the safety limits to all contributing factors is critical for increasing the time-efficiency of imaging systems that utilize time-varying magnetic fields.

  17. On the definition of threshold voltage for tunnel FETs

    NASA Astrophysics Data System (ADS)

    Mori, Yoshiaki; Sato, Shingo; Omura, Yasuhisa; Chattopadhyay, Avik; Mallik, Abhijit

    2017-07-01

    This paper proposes how to experimentally define the threshold voltage for various TFETs based on the theoretical point of view. We propose that the gate voltage defined corresponding to the peak of normalized transconductance is effectively the threshold voltage of TFETs. We also demonstrate that this definition is valid for different structures of TFET. In addition, we address the short-channel effect with such definition of threshold voltage for lateral TFET. It is shown that the short-channel effect significantly increased the off-current and the threshold voltage due to the extension of the drain potential and degradation of gate-field integrity in TFETs.

  18. Metabolomics using GC-TOF-MS followed by subsequent GC-FID and HILIC-MS/MS analysis revealed significantly altered fatty acid and phospholipid species profiles in plasma of smokers.

    PubMed

    Müller, Daniel C; Degen, Christian; Scherer, Gerhard; Jahreis, Gerhard; Niessner, Reinhard; Scherer, Max

    2014-09-01

    Mass spectrometry is an ideal tool for investigations of the metabolome in human plasma. To investigate the impact of smoking on the human metabolome, we performed an untargeted metabolic fingerprinting using GC-TOF-MS with EDTA-plasma samples from 25 smokers and 25 non-smokers. The observed elevated levels in the monounsaturated fatty acids (MUFAs) in smokers were verified by a targeted analysis using GC-FID, which revealed also significantly alterations in saturated and polyunsaturated fatty acids in smokers (p<0.05, Mann-Whitney U test). Since the main fraction of fatty acids in plasma is esterified to phospholipids, we analyzed phosphatidylcholine (PC) and phosphatidylethanolamine (PE) species composition in the plasma samples of the same subjects. The profiles of 39 PC and 40 PE species were analyzed with a newly developed and validated HILIC-ESI-MS/MS method. We were able to baseline separate the two lipid classes (PC from PE) by maintaining co-elution of individual lipid species of each class. The method shows a linear range from 0.5μM to 2000μM and an inter- and intraday coefficient of variation (CV)<20% across all analytes. Application of the validated method to the plasma samples of smokers and non-smokers, derived from a diet-controlled smoking study, revealed significantly elevated levels of PC and PE species containing MUFAs in smokers. In summary, we could demonstrate that there is a significantly altered total fatty acid profile, with increased MUFAs, in the plasma of smokers compared to non-smokers. Results obtained with the new HILIC-MS/MS method indicate that the altered fatty acid profile is also reflected in the PC and PE profile of smokers.

  19. Should we expect population thresholds for wildlife disease?

    USGS Publications Warehouse

    Lloyd-Smith, J. O.; Cross, P.C.; Briggs, C.J.; Daugherty, M.; Getz, W.M.; Latto, J.; Sanchez, M.; Smith, A.; Swei, A.

    2005-01-01

    Host population thresholds for invasion or persistence of infectious disease are core concepts of disease ecology, and underlie on-going and controversial disease control policies based on culling and vaccination. Empirical evidence for these thresholds in wildlife populations has been sparse, however, though recent studies have narrowed this gap. Here we review the theoretical bases for population thresholds for disease, revealing why they are difficult to measure and sometimes are not even expected, and identifying important facets of wildlife ecology left out of current theories. We discuss strengths and weaknesses of selected empirical studies that have reported disease thresholds for wildlife, identify recurring obstacles, and discuss implications of our imperfect understanding of wildlife thresholds for disease control policy.

  20. Learning Portals: Analyzing Threshold Concept Theory for LIS Education

    ERIC Educational Resources Information Center

    Tucker, Virginia M.; Weedman, Judith; Bruce, Christine S.; Edwards, Sylvia L.

    2014-01-01

    This paper explores the theoretical framework of threshold concepts and its potential for LIS education. Threshold concepts are key ideas, often troublesome and counterintuitive, that are critical to profound understanding of a domain. Once understood, they allow mastery of significant aspects of the domain, opening up new, previously inaccessible…

  1. Bayesian estimation of dose thresholds

    NASA Technical Reports Server (NTRS)

    Groer, P. G.; Carnes, B. A.

    2003-01-01

    An example is described of Bayesian estimation of radiation absorbed dose thresholds (subsequently simply referred to as dose thresholds) using a specific parametric model applied to a data set on mice exposed to 60Co gamma rays and fission neutrons. A Weibull based relative risk model with a dose threshold parameter was used to analyse, as an example, lung cancer mortality and determine the posterior density for the threshold dose after single exposures to 60Co gamma rays or fission neutrons from the JANUS reactor at Argonne National Laboratory. The data consisted of survival, censoring times and cause of death information for male B6CF1 unexposed and exposed mice. The 60Co gamma whole-body doses for the two exposed groups were 0.86 and 1.37 Gy. The neutron whole-body doses were 0.19 and 0.38 Gy. Marginal posterior densities for the dose thresholds for neutron and gamma radiation were calculated with numerical integration and found to have quite different shapes. The density of the threshold for 60Co is unimodal with a mode at about 0.50 Gy. The threshold density for fission neutrons declines monotonically from a maximum value at zero with increasing doses. The posterior densities for all other parameters were similar for the two radiation types.

  2. The effect of signal onset/offset envelope on underwater detection thresholds of a harbor seal (Phoca vitulina).

    PubMed

    Turnbull, S D; Terhune, J M

    1995-07-01

    The effects of signal onset/offset envelope on the underwater hearing thresholds of a harbor seal (Phoca vitulina) were measured. Pure-tone, 540-ms pulses at 2, 4, 8, and 16 kHz were presented as test signals. An ANOVA revealed that there were no significant differences between repeated threshold measures for abrupt onset/offset signal envelopes versus slow onset/offset signal envelopes [F = 4.380, d.f. = (1,18), p > 0.05]. Seal vocalizations which have an abrupt onset/offset may be serving a short-range communicative function by helping the listener determine the direction of a nearby sender.

  3. Threshold for superconductivity in ultrathin amorphous gallium films

    SciTech Connect

    Jaeger, H.M.; Haviland, D.B.; Goldman, A.M.; Orr, B.G.

    1986-10-01

    Systematic studies of the onset of superconductivity in ultrathin amorphous Ga films have revealed the existence of a threshold dependent only on the normal-state sheet resistance. Global superconductivity, or zero resistance, develops only when the normal-state sheet resistance falls below 6000 ..cap omega../D'Alembertian. This result agrees with previous observations on crystalline Sn films and further supports the notion of a universal resistance threshold.

  4. Identifying Thresholds for Ecosystem-Based Management

    PubMed Central

    Samhouri, Jameal F.; Levin, Phillip S.; Ainsworth, Cameron H.

    2010-01-01

    Background One of the greatest obstacles to moving ecosystem-based management (EBM) from concept to practice is the lack of a systematic approach to defining ecosystem-level decision criteria, or reference points that trigger management action. Methodology/Principal Findings To assist resource managers and policymakers in developing EBM decision criteria, we introduce a quantitative, transferable method for identifying utility thresholds. A utility threshold is the level of human-induced pressure (e.g., pollution) at which small changes produce substantial improvements toward the EBM goal of protecting an ecosystem's structural (e.g., diversity) and functional (e.g., resilience) attributes. The analytical approach is based on the detection of nonlinearities in relationships between ecosystem attributes and pressures. We illustrate the method with a hypothetical case study of (1) fishing and (2) nearshore habitat pressure using an empirically-validated marine ecosystem model for British Columbia, Canada, and derive numerical threshold values in terms of the density of two empirically-tractable indicator groups, sablefish and jellyfish. We also describe how to incorporate uncertainty into the estimation of utility thresholds and highlight their value in the context of understanding EBM trade-offs. Conclusions/Significance For any policy scenario, an understanding of utility thresholds provides insight into the amount and type of management intervention required to make significant progress toward improved ecosystem structure and function. The approach outlined in this paper can be applied in the context of single or multiple human-induced pressures, to any marine, freshwater, or terrestrial ecosystem, and should facilitate more effective management. PMID:20126647

  5. The gradual nature of threshold switching

    NASA Astrophysics Data System (ADS)

    Wimmer, M.; Salinga, M.

    2014-11-01

    The recent commercialization of electronic memories based on phase change materials proved the usability of this peculiar family of materials for application purposes. More advanced data storage and computing concepts, however, demand a deeper understanding especially of the electrical properties of the amorphous phase and the switching behaviour. In this work, we investigate the temporal evolution of the current through the amorphous state of the prototypical phase change material, Ge2Sb2Te5, under constant voltage. A custom-made electrical tester allows the measurement of delay times over five orders of magnitude, as well as the transient states of electrical excitation prior to the actual threshold switching. We recognize a continuous current increase over time prior to the actual threshold-switching event to be a good measure for the electrical excitation. A clear correlation between a significant rise in pre-switching-current and the later occurrence of threshold switching can be observed. This way, we found experimental evidence for the existence of an absolute minimum for the threshold voltage (or electric field respectively) holding also for time scales far beyond the measurement range.

  6. Efficient adaptive thresholding with image masks

    NASA Astrophysics Data System (ADS)

    Oh, Young-Taek; Hwang, Youngkyoo; Kim, Jung-Bae; Bang, Won-Chul

    2014-03-01

    Adaptive thresholding is a useful technique for document analysis. In medical image processing, it is also helpful for segmenting structures, such as diaphragms or blood vessels. This technique sets a threshold using local information around a pixel, then binarizes the pixel according to the value. Although this technique is robust to changes in illumination, it takes a significant amount of time to compute thresholds because it requires adding all of the neighboring pixels. Integral images can alleviate this overhead; however, medical images, such as ultrasound, often come with image masks, and ordinary algorithms often cause artifacts. The main problem is that the shape of the summing area is not rectangular near the boundaries of the image mask. For example, the threshold at the boundary of the mask is incorrect because pixels on the mask image are also counted. Our key idea to cope with this problem is computing the integral image for the image mask to count the valid number of pixels. Our method is implemented on a GPU using CUDA, and experimental results show that our algorithm is 164 times faster than a naïve CPU algorithm for averaging.

  7. Audiometric Thresholds: Stimulus Considerations in Sound Field and Under Earphones.

    PubMed

    Norrix, Linda W; Anderson, Alora

    2015-12-01

    This study evaluates a new stimulus, FREquency Specific Hearing assessment (FRESH) noise, to obtain hearing thresholds and reviews the potential pitfalls of using narrow band noise. Twelve adults with simulated gradually sloping hearing loss and 12 adults with steeply sloping hearing loss participated. Hearing thresholds were measured in sound field and under a supraaural earphone for FRESH noise, warbled tones, and narrowband noise. Pure-tone thresholds were also measured under the supraaural earphone. FRESH noise thresholds were similar to pure-tone and warbled-tone thresholds regardless of audiometric configuration. For the group with gradually sloping hearing loss, thresholds obtained with narrowband noise were approximately 4 dB better than those obtained with the other test stimuli. For the group with steeply sloping hearing loss, narrowband noise significantly underestimated hearing thresholds-the steeper the hearing loss, the greater the underestimation. When hearing loss is suspected, FRESH noise is appropriate for accurately determining audiometric thresholds in sound field and under earphones. A wider band, attention-getting stimulus such as narrowband noise can result in thresholds that are inaccurate. Clinical decision making regarding choice of test stimulus is discussed.

  8. Relationship between left atrium catheter contact force and pacing threshold.

    PubMed

    Barrio-López, Teresa; Ortiz, Mercedes; Castellanos, Eduardo; Lázaro, Carla; Salas, Jefferson; Madero, Sergio; Almendral, Jesús

    2017-08-01

    The purpose of this study is to analyze the relationship between contact force (CF) and pacing threshold in left atrium (LA). Six to ten LA sites were studied in 28 consecutive patients with atrial fibrillation undergoing pulmonary vein isolation. Median CF, bipolar and unipolar electrogram voltage, impedance, and bipolar and unipolar thresholds for consistent constant capture and for consistent intermittent capture were measured at each site. Pacing threshold measurements were performed at 188 LA sites. Both unipolar and bipolar pacing thresholds correlated significantly with median CF; however, unipolar pacing threshold correlated better (unipolar: Pearson R -0.45; p < 0.001; Spearman Rho -0.62; p < 0.001, bipolar: Pearson R -0.39; p < 0.001; Spearman Rho -0.52; p < 0.001). Consistent constant capture threshold had better correlation with median CF than consistent intermittent capture threshold for both unipolar and bipolar pacing (Pearson R -0.45; p < 0.001 and Spearman Rho -0.62; p < 0.001 vs. Pearson R -0.35; p < 0.001; Spearman Rho -0.52; p < 0.001). The best pacing threshold cutoff point to detect a good CF (>10 g) was 3.25 mA for unipolar pacing with 69% specificity and 73% sensitivity. Both increased to 80% specificity and 74% sensitivity for sites with normal bipolar voltage and a pacing threshold cutoff value of 2.85 mA. Pacing thresholds correlate with CF in human not previously ablated LA. Since the combination of a normal bipolar voltage and a unipolar pacing threshold <2.85 mA provide reasonable parameters of validity, pacing threshold could be of interest as a surrogate for CF in LA.

  9. Threshold photodissociation of Cr+2

    NASA Astrophysics Data System (ADS)

    Lessen, D. E.; Asher, R. L.; Brucat, P. J.

    1991-08-01

    A one-photon photodissociation threshold for supersonically cooled Cr+2 is determined to be 2.13 eV. This threshold provides a strict upper limit to the adiabatic binding energy of the ground state of chromium dimer cation if the initial internal energy of the parent ion may be neglected. From the difference in the IPs of chromium atom and dimer, an upper limit to the dissociation of Cr2 is placed at 1.77 eV.

  10. Influence of vowel selection on determination of phonation threshold pressure.

    PubMed

    Plexico, Laura W; Sandage, Mary J

    2012-09-01

    Phonation threshold pressure values reported in the literature have largely been determined with use of one of three consonant-vowel sequences, /pi/, /pae/, and /pa/; however, it is not currently known if vowel choice influences phonation threshold pressure values. Based on the evidence that describes velopharyngeal closure variations between vowels, this research effort hypothesized that phonation threshold pressure values measured from the consonant-vowel sequence /pi/ would be significantly lower than the /pae/ and /pa/ sequences. Twelve female participants aged between 20 and 27 years produced five-syllable trains of /pi/, /pae/, and /pa/ at low, modal, and high pitches. A within-subject repeated measures approach was conducted to compare phonation threshold pressure value differences between the three consonant-vowel sequences for three different pitches while controlling for other task elicitation variables that may also influence phonation threshold pressure values. Repeated measures analysis of the data indicated that there was no significant difference (P<0.05) in phonation threshold pressure values between the three consonant-vowel sequences at any frequency assessed. Further, for all three consonant-vowel sequences measured, significant differences of phonation threshold pressure magnitude were observed when comparing the high frequency versus the low and modal frequencies, a finding consistent with previous publications. The vowel selected for task elicitation for phonation threshold pressure determination does not appear to significantly affect phonation threshold values, indicating flexibility of the vowel aspect of this measure for clinical use of phonation threshold pressure. Copyright © 2012 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

  11. Visual discrimination thresholds for time to arrival.

    PubMed

    Landwehr, Klaus; Baurès, Robin; Oberfeld, Daniel; Hecht, Heiko

    2013-10-01

    In a seminal article, Todd (Journal of Experimental Psychology: Human Perception and Performance 7:795-810, 1981) reported a difference threshold of about 50 ms to discriminate the times of arrival of two differently sized objects that simultaneously approached head-on at constant but different velocities. Subsequent investigators, however, have often found much higher thresholds. We did one complete replication of Todd's experiment, and then modified his stimuli and experimental regime, which we hypothesized may have been responsible for some of the discrepancies reported in the literature. Unlike Todd and most other researchers, we exclusively used untrained observers. Several of our participants performed almost as well as the trained observers used by Todd and others, but the performance of most of our participants fell short of this standard. Furthermore, thresholds were affected by the experimental regimes, with large differences between objects' sizes and speeds compromising performance. Analyses of the response patterns revealed that the responses were driven mainly by the objects' relative apparent sizes.

  12. Threshold foraging behavior of baleen whales

    USGS Publications Warehouse

    Piatt, John F.; Methven, David A.

    1992-01-01

    We conducted hydroacoustic surveys for capelin Mallotus villosus in Witless Bay, Newfoundland, Canada, on 61 days during the summers of 1983 to 1985. On 32 of those days in whlch capelin surveys were conducted, we observed a total of 129 baleen whales - Including 93 humpback Megaptera novaeangliae, 31 minke Balaenoptera acutorostrata and 5 fin whales B. phvsalus. Although a few whales were observed when capelin schools were scarce, the majority (96%) of whales were observed when mean daily capelin densities exceeded 5 schools per linear km surveyed (range of means over 3 yr: 0.0 to 14.0 schools km-1). Plots of daily whale abundance (no. h-1 surveyed) vs daily capelin school density (mean no. schools km-1 surveyed) in each summer revealed that baleen whales have a threshold foraging response to capelin density. Thresholds were estimated using a simple itterative step-function model. Foraging thresholds of baleen whales (7.3, 5.0, and 5.8 schools km-1) varied between years in relation to the overall abundance of capelin schools in the study area during summer (means of 7.2, 3.3, and 5.3 schools km-1, respectively).

  13. Lowering the threshold for the diagnosis of gestational diabetes.

    PubMed

    Rust, O A; Bofill, J A; Andrew, M E; Kincaid, T A; Stubbs, T M; Miller, E H; Morrison, J C

    1996-10-01

    Our purpose was to determine whether lowering the diagnostic threshold for gestational diabetes mellitus on 3-hour 100 gm oral glucose tolerance testing will select a population at risk for adverse perinatal outcome. In this retrospective study 434 patients with an abnormal 50 gm glucose screen result (> or = 140 mg/dl) underwent a standardized 3-hour oral glucose tolerance test. The results were stratified according to maternal weight and the criteria recommended by Sacks or Carpenter. Birth weight and rate of macrosomia were the primary perinatal outcome variables analyzed. Analysis of the data set stratified according to the Sacks criteria revealed results very similar to the Carpenter criteria data set. Patients who would have been newly diagnosed with gestational diabetes mellitus only if the lowered criteria were used (group 2) were older and heavier. No other variable comparisons achieved statistical significance. When the same patients were stratified according to prepregnancy weight, overweight patients were older, gained less weight during the third trimester, underwent cesarean section more often, and had higher cumulative maternal morbidity. Regression analysis showed that the degree of hyperglycemia did not predict macrosomia or influence birth weight, but prepregnant maternal body mass index was associated with macrosomia. Fetal macrosomia is influenced by maternal prepregnant body mass index. Lowering the glucose tolerance test threshold would result in overdiagnosis of gestational diabetes mellitus without improving perinatal outcome.

  14. Quantitative measurement of odor detection thresholds using an air dilution olfactometer, and association with genetic variants in a sample of diverse ancestry

    PubMed Central

    Cook, Gillian R.; Krithika, S; Edwards, Melissa; Kavanagh, Paula

    2014-01-01

    Genetic association studies require a quantitative and reliable method for odor threshold assessment in order to examine the contribution of genetic variants to complex olfactory phenotypes. Our main goal was to assess the feasibility of a portable Scentroid air dilution olfactometer for use in such studies. Using the Scentroid SM110C and the SK5 n-butanol Sensitivity Kit (IDES Canada Inc.), n-butanol odor thresholds were determined for 182 individuals of diverse ancestry (mean age: 20.4 ± 2.5 years; n = 128 female; n = 54 male). Threshold scores from repeat participants were used to calculate a test–retest reliability coefficient, which was statistically significant (r = 0.754, p < 0.001, n = 29), indicating that the Scentroid provides reliable estimates of odor thresholds. In addition, we performed a preliminary genetic analysis evaluating the potential association of n-butanol odor thresholds to six single-nucleotide polymorphisms (SNPs) putatively involved in general olfactory sensitivity (GOS). The results of multiple linear regression analysis revealed no significant association between the SNPs tested and threshold scores. However, our sample size was relatively small, and our study was only powered to identify genetic markers with strong effects on olfactory sensitivity. Overall, we find that the Scentroid provides reliable quantitative measures of odor detection threshold and is well suited for genetic studies of olfactory sensitivity. PMID:25392755

  15. Quantitative measurement of odor detection thresholds using an air dilution olfactometer, and association with genetic variants in a sample of diverse ancestry.

    PubMed

    Cook, Gillian R; Krithika, S; Edwards, Melissa; Kavanagh, Paula; Parra, Esteban J

    2014-01-01

    Genetic association studies require a quantitative and reliable method for odor threshold assessment in order to examine the contribution of genetic variants to complex olfactory phenotypes. Our main goal was to assess the feasibility of a portable Scentroid air dilution olfactometer for use in such studies. Using the Scentroid SM110C and the SK5 n-butanol Sensitivity Kit (IDES Canada Inc.), n-butanol odor thresholds were determined for 182 individuals of diverse ancestry (mean age: 20.4 ± 2.5 years; n = 128 female; n = 54 male). Threshold scores from repeat participants were used to calculate a test-retest reliability coefficient, which was statistically significant (r = 0.754, p < 0.001, n = 29), indicating that the Scentroid provides reliable estimates of odor thresholds. In addition, we performed a preliminary genetic analysis evaluating the potential association of n-butanol odor thresholds to six single-nucleotide polymorphisms (SNPs) putatively involved in general olfactory sensitivity (GOS). The results of multiple linear regression analysis revealed no significant association between the SNPs tested and threshold scores. However, our sample size was relatively small, and our study was only powered to identify genetic markers with strong effects on olfactory sensitivity. Overall, we find that the Scentroid provides reliable quantitative measures of odor detection threshold and is well suited for genetic studies of olfactory sensitivity.

  16. High-frequency (8 to 16 kHz) reference thresholds and intrasubject threshold variability relative to ototoxicity criteria using a Sennheiser HDA 200 earphone.

    PubMed

    Frank, T

    2001-04-01

    The first purpose of this study was to determine high-frequency (8 to 16 kHz) thresholds for standardizing reference equivalent threshold sound pressure levels (RETSPLs) for a Sennheiser HDA 200 earphone. The second and perhaps more important purpose of this study was to determine whether repeated high-frequency thresholds using a Sennheiser HDA 200 earphone had a lower intrasubject threshold variability than the ASHA 1994 significant threshold shift criteria for ototoxicity. High-frequency thresholds (8 to 16 kHz) were obtained for 100 (50 male, 50 female) normally hearing (0.25 to 8 kHz) young adults (mean age of 21.2 yr) in four separate test sessions using a Sennheiser HDA 200 earphone. The mean and median high-frequency thresholds were similar for each test session and increased as frequency increased. At each frequency, the high-frequency thresholds were not significantly (p > 0.05) different for gender, test ear, or test session. The median thresholds at each frequency were similar to the 1998 interim ISO RETSPLs; however, large standard deviations and wide threshold distributions indicated very high intersubject threshold variability, especially at 14 and 16 kHz. Threshold repeatability was determined by finding the threshold differences between each possible test session comparison (N = 6). About 98% of all of the threshold differences were within a clinically acceptable range of +/-10 dB from 8 to 14 kHz. The threshold differences between each subject's second, third, and fourth minus their first test session were also found to determine whether intrasubject threshold variability was less than the ASHA 1994 criteria for determining a significant threshold shift due to ototoxicity. The results indicated a false-positive rate of 0% for a threshold shift > or = 20 dB at any frequency and a false-positive rate of 2% for a threshold shift >10 dB at two consecutive frequencies. This study verified that the output of high-frequency audiometers at 0 dB HL using

  17. Unstable particles near threshold

    NASA Astrophysics Data System (ADS)

    Chway, Dongjin; Jung, Tae Hyun; Kim, Hyung Do

    2016-07-01

    We explore the physics of unstable particles when the mother particle's mass is approximately the sum of the masses of its daughter particles. In this case, the conventional wave function renormalization factor used for the narrow width approximation is ill-defined. We propose a simple resolution of the problem that allows the use of the narrow width approximation by defining the wave function renormalization factor and the branching ratio in terms of the spectral density. We test new definitions by calculating the cross section in the Higgs portal model and a significant improvement is obtained. Meanwhile, no single decay width can be assigned to the unstable particles and non-exponential decay occurs at all time scales.

  18. Femtosecond damage threshold of multilayer metal films

    NASA Astrophysics Data System (ADS)

    Ibrahim, Wael M. G.; Elsayed-Ali, Hani E.; Shinn, Michelle D.; Bonner, Carl E.

    2003-05-01

    With the availability of terawatt laser systems with subpicosecond pulses, laser damage to optical components has become the limiting factor for further increases in the output peak power. Evaluation of different material structures in accordance to their suitability for high-power laser systems is essential. Multi-shot damage experiments, using 110 fs laser pulses at 800 nm, on polycrystalline single layer gold films and multi-layer (gold-vanadium, and gold-titanium) films were conducted. The laser incident fluence was varied, in both cases, from 0.1 to 0.6 J/cm2. No evidence of surface damage was apparent in the gold sample up to a fluence of 0.3 J/cm2. The multilayer sample experienced the onset of surface damage at the lowest fluence value used of 0.1 J/cm2. Damage results are in contrast with the time resolved ultrafast thermoreflectivity measurements that revealed a reduction of the thermoreflectivity signal for the multilayer films. This decrease in the thermoreflectivity signal signifies a reduction in the surface electron temperature that should translate in a lower lattice temperature at the later stage. Hence, one should expect a higher damage threshold for the multilayer samples. Comparison of the experimental results with the predictions of the Two-Temperature Model (TTM) is presented. The damage threshold of the single layer gold film corresponds to the melting threshold predicted by the model. In contrast to the single layer gold film, the multi-layer sample damaged at almost one third the damage threshold predicted by the TTM model. Possible damage mechanisms leading to the early onset of damage for the multilayer films are discussed.

  19. Vestibular Evoked Myogenic Potential (VEMP) Testing: Normative Threshold Response Curves and Effects of Age

    PubMed Central

    Janky, Kristen L.; Shepard, Neil

    2009-01-01

    Background Vestibular Evoked Myogenic Potential (VEMP) testing has gained increased interest in the diagnosis of a variety of vestibular etiologies. Comparisons of P13 / N23 latency, amplitude and threshold response curves have been used to compare pathologic groups to normal controls. Appropriate characterization of these etiologies requires normative data across the frequency spectrum and age range. Purpose The objective of the current study was to test the hypothesis that significant changes in VEMP responses occur as a function of increased age across all test stimuli as well as characterize the VEMP threshold response curve across age. Research Design This project incorporated a prospective study design using a sample of convenience. Openly recruited subjects were assigned to groups according to age. Study Sample Forty-six normal controls ranging between 20 and 76 years of age participated in the study. Participants were separated by decade into 5 age categories from 20 to 60 plus years. Normal participants were characterized by having normal hearing sensitivity, no history of neurologic or balance/dizziness involvement and negative results on a direct office vestibular examination. Intervention VEMP responses were measured at threshold to click and 250, 500, 750, and 1000 Hz tone burst stimuli and at a suprathreshold level to 500 Hz toneburst stimuli at123 dBSPL. Data Collection and Analysis A mixed group factorial ANOVA and linear regression were performed to examine the effects of VEMP characteristics upon age. Results There were no significant differences between ears for any of the test parameters. There were no significant differences between age groups for n23 latency or amplitude in response to any of the stimuli. Significant mean differences did exist between age groups for p13 latency (250, 750, and 1000 Hz) and threshold (500 and 750 Hz). Age was significantly correlated with VEMP parameters. VEMP threshold was positively correlated (250, 500, 750

  20. Electrocardiogram signal denoising based on a new improved wavelet thresholding

    NASA Astrophysics Data System (ADS)

    Han, Guoqiang; Xu, Zhijun

    2016-08-01

    Good quality electrocardiogram (ECG) is utilized by physicians for the interpretation and identification of physiological and pathological phenomena. In general, ECG signals may mix various noises such as baseline wander, power line interference, and electromagnetic interference in gathering and recording process. As ECG signals are non-stationary physiological signals, wavelet transform is investigated to be an effective tool to discard noises from corrupted signals. A new compromising threshold function called sigmoid function-based thresholding scheme is adopted in processing ECG signals. Compared with other methods such as hard/soft thresholding or other existing thresholding functions, the new algorithm has many advantages in the noise reduction of ECG signals. It perfectly overcomes the discontinuity at ±T of hard thresholding and reduces the fixed deviation of soft thresholding. The improved wavelet thresholding denoising can be proved to be more efficient than existing algorithms in ECG signal denoising. The signal to noise ratio, mean square error, and percent root mean square difference are calculated to verify the denoising performance as quantitative tools. The experimental results reveal that the waves including P, Q, R, and S waves of ECG signals after denoising coincide with the original ECG signals by employing the new proposed method.

  1. Threshold concepts in dental education.

    PubMed

    Kinchin, I M; Cabot, L B; Kobus, M; Woolford, M

    2011-11-01

    The paper presents a conceptual framework to inform dental education. Drawing from a vast body of research into student learning, the simple model presented here has an explanatory value in describing what is currently observed to happen and a predictive value in guiding future teaching practices. We introduce to dental education the application of threshold concepts that have a transformative role in offering a new vision of the curriculum that helps to move away from the medieval transmission model of higher education towards a dual processing model that better reflects the way in which professionals operate within the discipline. Threshold concepts give a role for the student voice in offering a novice perspective which is paradoxically something that is out of reach of the subject expert. Finally, the application of threshold concepts highlights some of the weaknesses in the competency-based training model of clinical teaching. 2011 John Wiley & Sons A/S.

  2. Ku-band radar threshold analysis

    NASA Technical Reports Server (NTRS)

    Weber, C. L.; Polydoros, A.

    1979-01-01

    The statistics of the CFAR threshold for the Ku-band radar was determined. Exact analytical results were developed for both the mean and standard deviations in the designated search mode. The mean value is compared to the results of a previously reported simulation. The analytical results are more optimistic than the simulation results, for which no explanation is offered. The normalized standard deviation is shown to be very sensitive to signal-to-noise ratio and very insensitive to the noise correlation present in the range gates of the designated search mode. The substantial variation in the CFAR threshold is dominant at large values of SNR where the normalized standard deviation is greater than 0.3. Whether or not this significantly affects the resulting probability of detection is a matter which deserves additional attention.

  3. Behavioral pure tone threshold shifts caused by tympanic membrane electrodes

    PubMed Central

    Smith, SB; Lichtenhan, JT; Cone, B

    2016-01-01

    Objective To determine if tympanic membrane (TM) electrodes induce behavioral pure tone threshold shifts. Design Pure tone thresholds (250–8000 Hz) were measured twice in test (n=18) and control (n=10) groups. TM electrodes were placed between first and second threshold measurements in the test group, whereas the control group did not receive electrodes. Pure tone threshold shifts were compared between groups. The effect of TM electrode contact location on threshold shifts was evaluated in the test group. Results TM electrodes significantly increased average low-frequency thresholds, 7.5 dB at 250 Hz and 4.2 dB at 500 Hz, and shifts were as large as 25 dB in individual ears. Also, threshold shifts did not appear to vary at any frequency with TM electrode contact location. Conclusions Low-frequency threshold shifts occur when using TM electrodes and insert earphones. These findings are relevant to interpreting electrocochleographic responses to low-frequency stimuli. PMID:26845670

  4. A Novel Psychovisual Threshold on Large DCT for Image Compression

    PubMed Central

    2015-01-01

    A psychovisual experiment prescribes the quantization values in image compression. The quantization process is used as a threshold of the human visual system tolerance to reduce the amount of encoded transform coefficients. It is very challenging to generate an optimal quantization value based on the contribution of the transform coefficient at each frequency order. The psychovisual threshold represents the sensitivity of the human visual perception at each frequency order to the image reconstruction. An ideal contribution of the transform at each frequency order will be the primitive of the psychovisual threshold in image compression. This research study proposes a psychovisual threshold on the large discrete cosine transform (DCT) image block which will be used to automatically generate the much needed quantization tables. The proposed psychovisual threshold will be used to prescribe the quantization values at each frequency order. The psychovisual threshold on the large image block provides significant improvement in the quality of output images. The experimental results on large quantization tables from psychovisual threshold produce largely free artifacts in the visual output image. Besides, the experimental results show that the concept of psychovisual threshold produces better quality image at the higher compression rate than JPEG image compression. PMID:25874257

  5. Predictive information speeds up visual awareness in an individuation task by modulating threshold setting, not processing efficiency.

    PubMed

    De Loof, Esther; Van Opstal, Filip; Verguts, Tom

    2016-04-01

    Theories on visual awareness claim that predicted stimuli reach awareness faster than unpredicted ones. In the current study, we disentangle whether prior information about the upcoming stimulus affects visual awareness of stimulus location (i.e., individuation) by modulating processing efficiency or threshold setting. Analogous research on stimulus identification revealed that prior information modulates threshold setting. However, as identification and individuation are two functionally and neurally distinct processes, the mechanisms underlying identification cannot simply be extrapolated directly to individuation. The goal of this study was therefore to investigate how individuation is influenced by prior information about the upcoming stimulus. To do so, a drift diffusion model was fitted to estimate the processing efficiency and threshold setting for predicted versus unpredicted stimuli in a cued individuation paradigm. Participants were asked to locate a picture, following a cue that was congruent, incongruent or neutral with respect to the picture's identity. Pictures were individuated faster in the congruent and neutral condition compared to the incongruent condition. In the diffusion model analysis, the processing efficiency was not significantly different across conditions. However, the threshold setting was significantly higher following an incongruent cue compared to both congruent and neutral cues. Our results indicate that predictive information about the upcoming stimulus influences visual awareness by shifting the threshold for individuation rather than by enhancing processing efficiency.

  6. Thresholds in chemical respiratory sensitisation.

    PubMed

    Cochrane, Stella A; Arts, Josje H E; Ehnes, Colin; Hindle, Stuart; Hollnagel, Heli M; Poole, Alan; Suto, Hidenori; Kimber, Ian

    2015-07-03

    There is a continuing interest in determining whether it is possible to identify thresholds for chemical allergy. Here allergic sensitisation of the respiratory tract by chemicals is considered in this context. This is an important occupational health problem, being associated with rhinitis and asthma, and in addition provides toxicologists and risk assessors with a number of challenges. In common with all forms of allergic disease chemical respiratory allergy develops in two phases. In the first (induction) phase exposure to a chemical allergen (by an appropriate route of exposure) causes immunological priming and sensitisation of the respiratory tract. The second (elicitation) phase is triggered if a sensitised subject is exposed subsequently to the same chemical allergen via inhalation. A secondary immune response will be provoked in the respiratory tract resulting in inflammation and the signs and symptoms of a respiratory hypersensitivity reaction. In this article attention has focused on the identification of threshold values during the acquisition of sensitisation. Current mechanistic understanding of allergy is such that it can be assumed that the development of sensitisation (and also the elicitation of an allergic reaction) is a threshold phenomenon; there will be levels of exposure below which sensitisation will not be acquired. That is, all immune responses, including allergic sensitisation, have threshold requirement for the availability of antigen/allergen, below which a response will fail to develop. The issue addressed here is whether there are methods available or clinical/epidemiological data that permit the identification of such thresholds. This document reviews briefly relevant human studies of occupational asthma, and experimental models that have been developed (or are being developed) for the identification and characterisation of chemical respiratory allergens. The main conclusion drawn is that although there is evidence that the

  7. On computational Gestalt detection thresholds.

    PubMed

    Grompone von Gioi, Rafael; Jakubowicz, Jérémie

    2009-01-01

    The aim of this paper is to show some recent developments of computational Gestalt theory, as pioneered by Desolneux, Moisan and Morel. The new results allow to predict much more accurately the detection thresholds. This step is unavoidable if one wants to analyze visual detection thresholds in the light of computational Gestalt theory. The paper first recalls the main elements of computational Gestalt theory. It points out a precision issue in this theory, essentially due to the use of discrete probability distributions. It then proposes to overcome this issue by using continuous probability distributions and illustrates it on the meaningful alignment detector of Desolneux et al.

  8. Low Threshold Quantum Dot Lasers.

    PubMed

    Iyer, Veena Hariharan; Mahadevu, Rekha; Pandey, Anshu

    2016-04-07

    Semiconductor quantum dots have replaced conventional inorganic phosphors in numerous applications. Despite their overall successes as emitters, their impact as laser materials has been severely limited. Eliciting stimulated emission from quantum dots requires excitation by intense short pulses of light typically generated using other lasers. In this Letter, we develop a new class of quantum dots that exhibit gain under conditions of extremely low levels of continuous wave illumination. We observe thresholds as low as 74 mW/cm(2) in lasers made from these materials. Due to their strong optical absorption as well as low lasing threshold, these materials could possibly convert light from diffuse, polychromatic sources into a laser beam.

  9. Evaluating tactile sensitivity adaptation by measuring the differential threshold of archers.

    PubMed

    Kotani, Kentaro; Ito, Seiji; Miura, Toshihiro; Horii, Ken

    2007-03-01

    This study investigated the relationship between the force applied to a finger and the differential threshold of the force. Further, it presented an improvement function for tactile perception in archers by adapting to circumstances in which enhanced tactile perception and finger dexterity are required to practice archery on a daily basis. For this purpose, a tactile display using an air jet was developed. The air was aimed at the center of the fingertip of the index finger. The inner diameter of the nozzle was set to 3 mm. In this study, a psychophysical experiment was conducted to obtain the differential threshold from two subject groups-an archery athlete group and a control group. A total of six levels of standard stimuli ranging from 2.0 gf to 7.0 gf was obtained. As a result, the differential threshold of the archery group was significantly higher than that of the control group. The Weber ratio of the archery group remained around 0.13 and that of control group was 0.10. The experiment also revealed that the differential threshold for archers exhibited less fluctuation between the trials and between the days, which implied that the tactile perception of archery athletes may be more stable than that of non-experienced subjects. This may be a plasticity property of tactile perception.

  10. Methodology for determination of two new sensory thresholds: Compromised acceptance threshold and rejection threshold.

    PubMed

    Lima Filho, Tarcísio; Minim, Valéria Paula Rodrigues; Silva, Rita de Cássia Dos Santos Navarro da; Della Lucia, Suzana Maria; Minim, Luis Antônio

    2015-10-01

    The existing methodologies for determining thresholds generate unreliable estimates of the point at which the intensity of a stimulus begins to compromise acceptance or result in sensory rejection of a product. Thus, a new methodology was proposed for determination of two new sensory thresholds: the compromised acceptance threshold (CAT) and the rejection threshold (RT). In this new methodology, increasing or decreasing series of stimulus intensity are measured together with a standard stimulus (control sample) by means of acceptance tests. In the present study, the CAT and RT were determined for sucrose concentrations in grape nectar, demonstrating that when reducing the sucrose concentration of grape nectar form 9.00% (w/v) to 6.87% there begins to occur impairment of product acceptance (CAT), and when reducing the sucrose concentration from 9.00% to 3.83% there begins to occur sensory rejection (RT) of the product. When compared to existing threshold determination methodologies, the proposed methodology permitted for calculating, with greater reliability, the points at which compromise of acceptance (CAT) and sensory rejection (RT) of the product begin to occur. In addition to the case study presented, the proposed methodology has a wide range of applications in science and in the food, cosmetic and pharmaceutical industries. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. In Vivo Imaging Reveals Significant Tumor Vascular Dysfunction and Increased Tumor Hypoxia-Inducible Factor-1α Expression Induced by High Single-Dose Irradiation in a Pancreatic Tumor Model.

    PubMed

    Maeda, Azusa; Chen, Yonghong; Bu, Jiachuan; Mujcic, Hilda; Wouters, Bradly G; DaCosta, Ralph S

    2017-01-01

    To investigate the effect of high-dose irradiation on pancreatic tumor vasculature and microenvironment using in vivo imaging techniques. A BxPC3 pancreatic tumor xenograft was established in a dorsal skinfold window chamber model and a subcutaneous hind leg model. Tumors were irradiated with a single dose of 4, 12, or 24 Gy. The dorsal skinfold window chamber model was used to assess tumor response, vascular function and permeability, platelet and leukocyte adhesion to the vascular endothelium, and tumor hypoxia for up to 14 days after 24-Gy irradiation. The hind leg model was used to monitor tumor size, hypoxia, and vascularity for up to 65 days after 24-Gy irradiation. Tumors were assessed histologically to validate in vivo observations. In vivo fluorescence imaging revealed temporary vascular dysfunction in tumors irradiated with a single dose of 4 to 24 Gy, but most significantly with a single dose of 24 Gy. Vascular functional recovery was observed by 14 days after irradiation in a dose-dependent manner. Furthermore, irradiation with 24 Gy caused platelet and leukocyte adhesion to the vascular endothelium within hours to days after irradiation. Vascular permeability was significantly higher in irradiated tumors compared with nonirradiated controls 14 days after irradiation. This observation corresponded with increased expression of hypoxia-inducible factor-1α in irradiated tumors. In the hind leg model, irradiation with a single dose of 24 Gy led to tumor growth delay, followed by tumor regrowth. Irradiation of the BxPC3 tumors with a single dose of 24 Gy caused transient vascular dysfunction and increased expression of hypoxia-inducible factor-1α. Such biological changes may impact tumor response to high single-dose and hypofractionated irradiation, and further investigations are needed to better understand the clinical outcomes of stereotactic body radiation therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Runoff generation on semi-arid, low-angled terrain: A long-term data set showing non-stable threshold response

    NASA Astrophysics Data System (ADS)

    Coles, A.; McDonnell, J. J.; McConkey, B.; Appels, W.

    2013-12-01

    Runoff generation on the semi-arid, low-angled terrain of the Canadian prairies is complex and poorly understood. Threshold activation of overland flow has been reported at the catchment scale during periods of snowmelt onto frozen ground and during summer rainstorms (where approximately 7% of rainstorms generate runoff). However, the threshold-runoff behavior is temporally and spatially non-stable. As yet, the interactions of precipitation, soil and other factors that drive threshold-like overland flow in this environment are not well described. This has significant implications for predicting water quality and flood generation under a rapidly changing northern climate. Here we present results from statistical analysis of a 51-year (1962-present) prairie rainfall, runoff, soil moisture and snowpack data set from the Semiarid Prairie Agricultural Research Centre in southern Saskatchewan. We focus on runoff response thresholds in flow on three separate 5 ha plots to precipitation inputs, including 125 snowmelt-runoff events and 122 rainfall-runoff events. We have found, from previous analysis of this data set, that precipitation amount (snow water equivalent or storm rainfall) is not the sole driver of runoff, and that a combination of fall soil moisture and winter precipitation better accounts for snowmelt runoff in the spring. Here, we explore the multi-dimensional characterization of thresholds in state space to more accurately determine the catchment and climatic conditions driving the position and strength of a threshold, thereby revealing the dominant mechanisms underlying multi-driver, variable runoff thresholds.

  13. Multimodal Distribution of Human Cold Pain Thresholds

    PubMed Central

    Lötsch, Jörn; Dimova, Violeta; Lieb, Isabel; Zimmermann, Michael; Oertel, Bruno G.; Ultsch, Alfred

    2015-01-01

    Background It is assumed that different pain phenotypes are based on varying molecular pathomechanisms. Distinct ion channels seem to be associated with the perception of cold pain, in particular TRPM8 and TRPA1 have been highlighted previously. The present study analyzed the distribution of cold pain thresholds with focus at describing the multimodality based on the hypothesis that it reflects a contribution of distinct ion channels. Methods Cold pain thresholds (CPT) were available from 329 healthy volunteers (aged 18 – 37 years; 159 men) enrolled in previous studies. The distribution of the pooled and log-transformed threshold data was described using a kernel density estimation (Pareto Density Estimation (PDE)) and subsequently, the log data was modeled as a mixture of Gaussian distributions using the expectation maximization (EM) algorithm to optimize the fit. Results CPTs were clearly multi-modally distributed. Fitting a Gaussian Mixture Model (GMM) to the log-transformed threshold data revealed that the best fit is obtained when applying a three-model distribution pattern. The modes of the identified three Gaussian distributions, retransformed from the log domain to the mean stimulation temperatures at which the subjects had indicated pain thresholds, were obtained at 23.7 °C, 13.2 °C and 1.5 °C for Gaussian #1, #2 and #3, respectively. Conclusions The localization of the first and second Gaussians was interpreted as reflecting the contribution of two different cold sensors. From the calculated localization of the modes of the first two Gaussians, the hypothesis of an involvement of TRPM8, sensing temperatures from 25 – 24 °C, and TRPA1, sensing cold from 17 °C can be derived. In that case, subjects belonging to either Gaussian would possess a dominance of the one or the other receptor at the skin area where the cold stimuli had been applied. The findings therefore support a suitability of complex analytical approaches to detect mechanistically

  14. Crossing Thresholds in Academic Reading

    ERIC Educational Resources Information Center

    Abbott, Rob

    2013-01-01

    This paper looks at the conceptual thresholds in relation to academic reading which might be crossed by undergraduate English Literature students. It is part of a wider study following 16 students through three years of undergraduate study. It uses theoretical ideas from Bakhtin and Foucault to analyse interviews with English lecturers. It…

  15. Threshold Concepts and Pedagogic Representation

    ERIC Educational Resources Information Center

    Meyer, Jan H. F.

    2016-01-01

    Purpose: The purpose of this paper is to present a brief exposure to the development of the threshold concepts framework (TCF), the intention being to illuminate for interested readers a broader landscape of research activity than that perhaps conveyed by the individual contributions to this special edition. Design/Methodology/Approach: There is…

  16. Quantifying ecological thresholds from response surfaces

    Treesearch

    Heather E. Lintz; Bruce McCune; Andrew N. Gray; Katherine A. McCulloh

    2011-01-01

    Ecological thresholds are abrupt changes of ecological state. While an ecological threshold is a widely accepted concept, most empirical methods detect them in time or across geographic space. Although useful, these approaches do not quantify the direct drivers of threshold response. Causal understanding of thresholds detected empirically requires their investigation...

  17. Chemical sensing thresholds for mine detection dogs

    NASA Astrophysics Data System (ADS)

    Phelan, James M.; Barnett, James L.

    2002-08-01

    Mine detection dogs have been found to be an effective method to locate buried landmines. The capabilities of the canine olfaction method are from a complex combination of training and inherent capacity of the dog for odor detection. The purpose of this effort was to explore the detection thresholds of a limited group of dogs that were trained specifically for landmine detection. Soils were contaminated with TNT and 2,4-DNT to develop chemical vapor standards to present to the dogs. Soils contained ultra trace levels of TNT and DNT, which produce extremely low vapor levels. Three groups of dogs were presented the headspace vapors from the contaminated soils in work environments for each dog group. One positive sample was placed among several that contained clean soils and, the location and vapor source (strength, type) was frequently changed. The detection thresholds for the dogs were determined from measured and extrapolated dilution of soil chemical residues and, estimated soil vapor values using phase partitioning relationships. The results showed significant variances in dog sensing thresholds, where some dogs could sense the lowest levels and others had trouble with even the highest source. The remarkable ultra-trace levels detectable by the dogs are consistent with the ultra-trace chemical residues derived from buried landmines; however, poor performance may go unnoticed without periodic challenge tests at levels consistent with performance requirements.

  18. Anaerobic threshold measurements of elite oarsmen.

    PubMed

    Mickelson, T C; Hagerman, F C

    1982-01-01

    Anaerobic threshold (AT) and Vo2max were determined by automated analysis for 25 members of the 1980 U.S. Olympic Rowing Team during a progressive rowing ergometer exercise to exhaustion. Heart rates and power outputs were also measured to gauge severity of the exercise and to compare with metabolic data. Power increments of 27 W each min were achieved by progressively increasing the brake weight resistance on the ergometer while maintaining a stroke rate of 28-32 strokes/min and spinning the ergometer flywheel at 550 rpm. Anaerobic threshold measurements were determined by observing the onset of the non-linear relationship between Vo2 and VE-Vco2; plots of delta FEO2 and FECO2 were also utilized to confirm recorded AT's. A mean AT of 83% of Vo2max attests to the high aerobic capacity of oarsmen and supports previous research conducted with these subjects. Power output data indicated that 72% of total power is generated at AT; this substantiates previous energy cost data recorded during simulated rowing during which work was 70% aerobic and 30% anaerobic. High levels of anaerobic thresholds among oarsmen are attributed to the specific nature of training regimens that increase oxidative capacity of muscle fibers and significantly improve the cardiorespiratory transport system. Measurement of heart rate at AT has provided coaches and athletes an objective method of determining the intensity of training sessions.

  19. Bacteriopheophorbide esters: photosensitizers without "threshold dose"?

    NASA Astrophysics Data System (ADS)

    Moser, Joerg G.; Ostrowsky, Andreas; Guemuesdagli, Maria; Kleiber, Beate

    1994-03-01

    Uptake and phototoxicity of the methyl-, ethyl-, n-propyl, and 2-propyl esters of 132- hydroxy bacteriopheophorbide a were studied in OAT 75 SCLC cells and 3 different amelanotic melanoma cell lines. (A 375, Melur SP 18, SkAMel 25). Specific phototoxicity did not substantially differ for the different esters. Most surprisingly, these photosensitizers did not show any significant threshold behavior: even at 25 (mu) W/cm2 (775 nm, diode laser) cancer cell suspensions were killed in a time-dependent logarithmic fashion. Furthermore, phototoxicity is enhanced at low power densities if compared with the effects at 1 - 10 mW/cm2. This can be related only in part to a lack of oxygen at higher power densities. Complementary experiments confirmed that threshold is power but not dose dependent. Thus, threshold power density should be included into a prospective list of criteria characterizing photosensitizers suitable for photodynamic cancer therapy. The obvious lack of a limiting power density in bacteriopheophobide a esters make these sensitizers a prospective tool for tumor therapy in considerable tissue depth.

  20. Behavioral and Molecular Genetics of Reading-Related AM and FM Detection Thresholds.

    PubMed

    Bruni, Matthew; Flax, Judy F; Buyske, Steven; Shindhelm, Amber D; Witton, Caroline; Brzustowicz, Linda M; Bartlett, Christopher W

    2017-03-01

    Auditory detection thresholds for certain frequencies of both amplitude modulated (AM) and frequency modulated (FM) dynamic auditory stimuli are associated with reading in typically developing and dyslexic readers. We present the first behavioral and molecular genetic characterization of these two auditory traits. Two extant extended family datasets were given reading tasks and psychoacoustic tasks to determine FM 2 Hz and AM 20 Hz sensitivity thresholds. Univariate heritabilities were significant for both AM (h (2)  = 0.20) and FM (h (2)  = 0.29). Bayesian posterior probability of linkage (PPL) analysis found loci for AM (12q, PPL = 81 %) and FM (10p, PPL = 32 %; 20q, PPL = 65 %). Bivariate heritability analyses revealed that FM is genetically correlated with reading, while AM was not. Bivariate PPL analysis indicates that FM loci (10p, 20q) are not also associated with reading.

  1. Inverted Perceptual Judgment of Nociceptive Stimuli at Threshold Level following Inconsistent Cues

    PubMed Central

    Walter, Carmen; Dimova, Violeta; Bu, Julia; Parnham, Michael J.; Oertel, Bruno G.; Lötsch, Jörn

    2015-01-01

    Objective The perception of pain is susceptible to modulation by psychological and contextual factors. It has been shown that subjects judge noxious stimuli as more painful in a respective suggestive context, which disappears when the modifying context is resolved. However, a context in which subjects judge the painfulness of a nociceptive stimulus in exactly the opposite direction to that of the cues has never been shown so far. Methods Nociceptive stimuli (300 ms intranasal gaseous CO2) at the individual pain threshold level were applied after a visual cue announcing the stimulus as either “no pain”, merely a “stimulus”, or “pain”. Among the stimuli at threshold level, other CO2 stimuli that were clearly below or above pain threshold were randomly interspersed. These were announced beforehand in 12 subjects randomly with correct or incorrect cues, i.e., clearly painful or clearly non-painful stimuli were announced equally often as not painful or painful. By contrast, in a subsequent group of another 12 subjects, the stimuli were always announced correctly with respect to the evoked pain. Results The random and often incorrect announcement of stimuli clearly below or above pain threshold caused the subjects to rate the stimuli at pain-threshold level in the opposite direction of the cue, i.e., when the stimuli were announced as “pain” significantly more often than as non-painful and vice versa (p < 10-4). By contrast, in the absence of incongruence between announcement and perception of the far-from-threshold stimuli, stimuli at pain threshold were rated in the cued direction. Conclusions The present study revealed the induction of associations incongruent with a given message in the perception of pain. We created a context of unreliable cues whereby subjects perceived the stimulus opposite to that suggested by a prior cue, i.e., potentially nociceptive stimuli at pain threshold level that were announced as painful were judged as non-painful and

  2. Faster magnet sorting with a threshold acceptance algorithm

    NASA Astrophysics Data System (ADS)

    Lidia, Steve; Carr, Roger

    1995-02-01

    We introduce here a new technique for sorting magnets to minimize the field errors in permanent magnet insertion devices. Simulated annealing has been used in this role, but we find the technique of threshold acceptance produces results of equal quality in less computer time. Threshold accepting would be of special value in designing very long insertion devices, such as long free electron lasers (FELs). Our application of threshold acceptance to magnet sorting showed that it converged to equivalently low values of the cost function, but that it converged significantly faster. We present typical cases showing time to convergence for various error tolerances, magnet numbers, and temperature schedules.

  3. Faster magnet sorting with a threshold acceptance algorithm

    NASA Astrophysics Data System (ADS)

    Lidia, S.; Carr, R.

    1994-08-01

    The authors introduce here a new technique for sorting magnets to minimize the field errors in permanent magnet insertion devices. Simulated annealing has been used in this role, but they find the technique of threshold acceptance produces results of equal quality in less computer time. Threshold accepting would be of special value in designing very long insertion devices, such as long FEL's. Their application of threshold acceptance to magnet sorting showed that it converged to equivalently low values of the cost function, but that it converged significantly faster. They present typical cases showing time to convergence for various error tolerances, magnet numbers, and temperature schedules.

  4. High-frequency threshold measurements using insert earphones.

    PubMed

    Tang, H; Letowski, T

    1992-10-01

    Several recent studies have reported large intersubject variability of high-frequency thresholds measured with circumaural earphones. In the present study, high-frequency thresholds of 10 subjects were measured with circumaural (Sennheiser HD-250) and insert (Etymotic ER-1) earphones at 10, 12, 14, and 16 kHz. Overall results show significantly smaller variability of the threshold data obtained with insert earphones than with circumaural earphones. The above data indicate that insert earphones may be more suitable for high-frequency testing than circumaural earphones.

  5. Factors affecting mechanical (nociceptive) thresholds in piglets

    PubMed Central

    Janczak, Andrew M; Ranheim, Birgit; Fosse, Torunn K; Hild, Sophie; Nordgreen, Janicke; Moe, Randi O; Zanella, Adroaldo J

    2012-01-01

    Objective To evaluate the stability and repeatability of measures of mechanical (nociceptive) thresholds in piglets and to examine potentially confounding factors when using a hand held algometer. Study design Descriptive, prospective cohort. Animals Forty-four piglets from four litters, weighing 4.6 ± 1.0 kg (mean ± SD) at 2 weeks of age. Methods Mechanical thresholds were measured twice on each of 2 days during the first and second week of life. Data were analyzed using a repeated measures design to test the effects of behavior prior to testing, sex, week, day within week, and repetition within day. The effect of body weight and the interaction between piglet weight and behaviour were also tested. Piglet was entered into the model as a random effect as an additional test of repeatability. The effect of repeated testing was used to test the stability of measures. Pearson correlations between repeated measures were used to test the repeatability of measures. Variance component analysis was used to describe the variability in the data. Results Variance component analysis indicated that piglet explained only 17% of the variance in the data. All variables in the model (behaviour prior to testing, sex, week, day within week, repetition within day, body weight, the interaction between body weight and behaviour, piglet identity) except sex had a significant effect (p < 0.04 for all). Correlations between repeated measures increased from the first to the second week. Conclusions and Clinical relevance Repeatability was acceptable only during the second week of testing and measures changed with repeated testing and increased with increasing piglet weight, indicating that time (age) and animal body weight should be taken into account when measuring mechanical (nociceptive) thresholds in piglets. Mechanical (nociceptive) thresholds can be used both for testing the efficacy of anaesthetics and analgesics, and for assessing hyperalgesia in chronic pain states in research and

  6. Monolayer semiconductor nanocavity lasers with ultralow thresholds

    DOE PAGES

    Wu, Sanfeng; Buckley, Sonia; Schaibley, John R.; ...

    2015-03-16

    Engineering the electromagnetic environment of a nanoscale light emitter by a photonic cavity can significantly enhance its spontaneous emission rate through cavity quantum electrodynamics in the Purcell regime. This effect can greatly reduce the lasing threshold of the emitter1–5, providing the ultimate low-threshold laser system with small footprint, low power consumption and ultrafast modulation. A state-of-the-art ultra-low threshold nanolaser has been successfully developed though embedding quantum dots into photonic crystal cavity (PhCC)6–8. However, several core challenges impede the practical applications of this architecture, including the random positions and compositional fluctuations of the dots7, extreme difficulty in current injection8, and lackmore » of compatibility with electronic circuits7,8. Here, we report a new strategy to lase, where atomically thin crystalline semiconductor, i.e., a tungsten-diselenide (WSe2) monolayer, is nondestructively and deterministically introduced as a gain medium at the surface of a pre-fabricated PhCC. A new type of continuous-wave nanolaser operating in the visible regime is achieved with an optical pumping threshold as low as 27 nW at 130 K, similar to the value achieved in quantum dot PhCC lasers7. The key to the lasing action lies in the monolayer nature of the gain medium, which confines direct-gap excitons to within 1 nm of the PhCC surface. The surface-gain geometry allows unprecedented accessibilities to multi-functionalize the gain, enabling electrically pumped operation. Our scheme is scalable and compatible with integrated photonics for on-chip optical communication technologies.« less

  7. Monolayer semiconductor nanocavity lasers with ultralow thresholds

    SciTech Connect

    Wu, Sanfeng; Buckley, Sonia; Schaibley, John R.; Feng, Liefeng; Yan, Jiaqiang; Mandrus, David G.; Hatami, Fariba; Yao, Wang; Vučković, Jelena; Majumdar, Arka; Xu, Xiaodong

    2015-03-16

    Engineering the electromagnetic environment of a nanoscale light emitter by a photonic cavity can significantly enhance its spontaneous emission rate through cavity quantum electrodynamics in the Purcell regime. This effect can greatly reduce the lasing threshold of the emitter1–5, providing the ultimate low-threshold laser system with small footprint, low power consumption and ultrafast modulation. A state-of-the-art ultra-low threshold nanolaser has been successfully developed though embedding quantum dots into photonic crystal cavity (PhCC)6–8. However, several core challenges impede the practical applications of this architecture, including the random positions and compositional fluctuations of the dots7, extreme difficulty in current injection8, and lack of compatibility with electronic circuits7,8. Here, we report a new strategy to lase, where atomically thin crystalline semiconductor, i.e., a tungsten-diselenide (WSe2) monolayer, is nondestructively and deterministically introduced as a gain medium at the surface of a pre-fabricated PhCC. A new type of continuous-wave nanolaser operating in the visible regime is achieved with an optical pumping threshold as low as 27 nW at 130 K, similar to the value achieved in quantum dot PhCC lasers7. The key to the lasing action lies in the monolayer nature of the gain medium, which confines direct-gap excitons to within 1 nm of the PhCC surface. The surface-gain geometry allows unprecedented accessibilities to multi-functionalize the gain, enabling electrically pumped operation. Our scheme is scalable and compatible with integrated photonics for on-chip optical communication technologies.

  8. Monolayer semiconductor nanocavity lasers with ultralow thresholds.

    PubMed

    Wu, Sanfeng; Buckley, Sonia; Schaibley, John R; Feng, Liefeng; Yan, Jiaqiang; Mandrus, David G; Hatami, Fariba; Yao, Wang; Vučković, Jelena; Majumdar, Arka; Xu, Xiaodong

    2015-04-02

    Engineering the electromagnetic environment of a nanometre-scale light emitter by use of a photonic cavity can significantly enhance its spontaneous emission rate, through cavity quantum electrodynamics in the Purcell regime. This effect can greatly reduce the lasing threshold of the emitter, providing a low-threshold laser system with small footprint, low power consumption and ultrafast modulation. An ultralow-threshold nanoscale laser has been successfully developed by embedding quantum dots into a photonic crystal cavity (PCC). However, several challenges impede the practical application of this architecture, including the random positions and compositional fluctuations of the dots, extreme difficulty in current injection, and lack of compatibility with electronic circuits. Here we report a new lasing strategy: an atomically thin crystalline semiconductor--that is, a tungsten diselenide monolayer--is non-destructively and deterministically introduced as a gain medium at the surface of a pre-fabricated PCC. A continuous-wave nanolaser operating in the visible regime is thereby achieved with an optical pumping threshold as low as 27 nanowatts at 130 kelvin, similar to the value achieved in quantum-dot PCC lasers. The key to the lasing action lies in the monolayer nature of the gain medium, which confines direct-gap excitons to within one nanometre of the PCC surface. The surface-gain geometry gives unprecedented accessibility and hence the ability to tailor gain properties via external controls such as electrostatic gating and current injection, enabling electrically pumped operation. Our scheme is scalable and compatible with integrated photonics for on-chip optical communication technologies.

  9. ECG signal compression by multi-iteration EZW coding for different wavelets and thresholds.

    PubMed

    Tohumoglu, Gülay; Sezgin, K Erbil

    2007-02-01

    The modified embedded zero-tree wavelet (MEZW) compression algorithm for the one-dimensional signal was originally derived for image compression based on Shapiro's EZW algorithm. It is revealed that the proposed codec is significantly more efficient in compression and in computation than previously proposed ECG compression schemes. The coder also attains exact bit rate control and generates a bit stream progressive in quality or rate. The EZW and MEZW algorithms apply the chosen threshold values or the expressions in order to specify that the significant transformed coefficients are greatly significant. Thus, two different threshold definitions, namely percentage and dyadic thresholds, are used, and they are applied for different wavelet types in biorthogonal and orthogonal classes. In detail, the MEZW and EZW algorithms results are quantitatively compared in terms of the compression ratio (CR) and percentage root mean square difference (PRD). Experiments are carried out on the selected records from the MIT-BIH arrhythmia database and an original ECG signal. It is observed that the MEZW algorithm shows a clear advantage in the CR achieved for a given PRD over the traditional EZW, and it gives better results for the biorthogonal wavelets than the orthogonal wavelets.

  10. Determination of the taste threshold of copper in water.

    PubMed

    Zacarías, I; Yáñez, C G; Araya, M; Oraka, C; Olivares, M; Uauy, R

    2001-01-01

    Copper effects on human health represent a relevant issue in modern nutrition. One of the difficulties in assessing the early, acute effects of copper ingested via drinking water is that the taste of copper may influence the response and the capacity to taste copper in different waters is unknown. The purpose of the study was to determine the taste threshold of copper in different types of water, using soluble and insoluble salts (copper sulfate and copper chloride). Copper-containing solutions (range 1.0-8.0 mg/l Cu) were prepared in tap water, distilled deionized water and uncarbonated mineral water. Sixty-one healthy volunteers (17-50 years of age), with no previous training for sensory evaluation, participated in the study. A modified triangle test was used to define the taste threshold value. The threshold was defined as the lowest copper concentration detected by 50% of the subjects assessed. To evaluate the olfactory input in the threshold value obtained, 15 of 61 subjects underwent a second set of triangle tests with the nose open and clamped, using distilled water with copper sulfate at a concentration corresponding to the individual's threshold. The taste threshold in tap water was 2.6 mg/l Cu for both copper sulfate and copper chloride. The corresponding values for distilled deionized water were 2.4 and 2.5 mg/l Cu for copper sulfate and copper chloride, respectively. In uncarbonated mineral water the threshold values were slightly higher, 3.5 and 3.8 mg/l Cu for copper sulfate and for copper chloride, respectively, which are significantly higher than those observed in tap and distilled waters (P < 0.01, Kruskal-Wallis test). The taste threshold did not change significantly when the nose was clamped. In conclusion, the median values for copper taste threshold were low, ranging between 2.4 and 3.8 mg/l Cu, depending on the type of water.

  11. "Structural Transformation" as a Threshold Concept in University Teaching

    ERIC Educational Resources Information Center

    Kinchin, Ian M.; Miller, Norma L.

    2012-01-01

    In an attempt to reveal potential threshold concepts in the field of higher education pedagogy, groups of university teachers (in the UK and in Panama) were encouraged to develop personal reflection upon their conceptions of teaching. This was initiated through concept mapping activities. It was hoped that this would help participants to address…

  12. "Structural Transformation" as a Threshold Concept in University Teaching

    ERIC Educational Resources Information Center

    Kinchin, Ian M.; Miller, Norma L.

    2012-01-01

    In an attempt to reveal potential threshold concepts in the field of higher education pedagogy, groups of university teachers (in the UK and in Panama) were encouraged to develop personal reflection upon their conceptions of teaching. This was initiated through concept mapping activities. It was hoped that this would help participants to address…

  13. Influence of taekwondo as security martial arts training on anaerobic threshold, cardiorespiratory fitness, and blood lactate recovery.

    PubMed

    Kim, Dae-Young; Seo, Byoung-Do; Choi, Pan-Am

    2014-04-01

    [Purpose] This study was conducted to determine the influence of Taekwondo as security martial arts training on anaerobic threshold, cardiorespiratory fitness, and blood lactate recovery. [Subjects and Methods] Fourteen healthy university students were recruited and divided into an exercise group and a control group (n = 7 in each group). The subjects who participated in the experiment were subjected to an exercise loading test in which anaerobic threshold, value of ventilation, oxygen uptake, maximal oxygen uptake, heart rate, and maximal values of ventilation / heart rate were measured during the exercise, immediately after maximum exercise loading, and at 1, 3, 5, 10, and 15 min of recovery. [Results] At the anaerobic threshold time point, the exercise group showed a significantly longer time to reach anaerobic threshold. The exercise group showed significantly higher values for the time to reach VO2max, maximal values of ventilation, maximal oxygen uptake and maximal values of ventilation / heart rate. Significant changes were observed in the value of ventilation volumes at the 1- and 5-min recovery time points within the exercise group; oxygen uptake and maximal oxygen uptake were significantly different at the 5- and 10-min time points; heart rate was significantly different at the 1- and 3-min time points; and maximal values of ventilation / heart rate was significantly different at the 5-min time point. The exercise group showed significant decreases in blood lactate levels at the 15- and 30-min recovery time points. [Conclusion] The study results revealed that Taekwondo as a security martial arts training increases the maximal oxygen uptake and anaerobic threshold and accelerates an individual's recovery to the normal state of cardiorespiratory fitness and blood lactate level. These results are expected to contribute to the execution of more effective security services in emergencies in which violence can occur.

  14. Estimating ecological thresholds for phosphorus in the Everglades.

    PubMed

    Richardson, Curtis J; King, Ryan S; Qian, Song S; Vaithiyanathan, Panchabi; Qualls, Robert G; Stow, Craig A

    2007-12-01

    The Florida Everglades, a wetland of international importance, has been undergoing a significant shift in its native flora and fauna due to excessive total phosphorus (TP) loadings (an average of 147 t per annum from 1995to 2004) and an elevated mean TP concentration (69 microg L(-1) of TP in 2004) from agricultural runoff and Lake Okeechobee outflow despite the use of 16000 ha of stormwater treatment areas. Here, we present a Bayesian changepoint analysis of long-term experimental research and show that exceeding a surface water geometric mean TP threshold concentration of 15 microg L(-1) causes an ecological imbalance in algal, macrophyte, and macroinvertebrate assemblages as well as slough community structure. A phosphorus threshold for all trophic levels may be more realistic and protective when presented as a threshold zone (12-15 microg L(-1)) because estimates of uncertainty must be utilized to accurately define TP thresholds, which change with seasons and water depths. Most interior areas of the Everglades are currently at or below this threshold zone, but the exterior areas near inflow structures (except for the Everglades National Park) are presently receiving double or triple the proposed threshold. Our Bayesian approach, used hereto address ecological imbalance along nutrient gradients, is applicable to determining thresholds and stable states in other aquatic ecosystems.

  15. Sustained Focal Cortical Compression Reduces Electrically-Induced Seizure Threshold

    PubMed Central

    Ding, Ming-Chieh; Lo, Eng H.; Stanley, Garrett B.

    2008-01-01

    Brain injury can often result in the subsequent appearance of seizures, suggesting an alteration in neural excitability associated with the balance between neuronal excitation and inhibition. The process by which this occurs has yet to be fully elucidated. The specific nature of the changes in excitation and inhibition is still unclear, as is the process by which the seizures appear following injury. In this study, we investigated the effects of focal cortical compression on electrically-induced localized seizure threshold in rats. Male Long Evans rats were implanted with stimulating screw electrodes in their motor cortices above the regions controlling forelimb movement. Initial seizure threshold was determined in the animals using a ramped electrical stimulation procedure prior to any compression. Following initial threshold determination, animals underwent sustained cortical compression and then following a 24 hour recovery period had their seizure thresholds tested again with electrical stimulation. Reliability of threshold measurements was confirmed through repeated measurements of seizure threshold. Localized seizure threshold was significantly lowered following sustained cortical compression as compared to control cases. Taken together, the results here suggest a change in global brain excitability following localized, focal compression. PMID:18495350

  16. Universal formulas for percolation thresholds

    NASA Astrophysics Data System (ADS)

    Galam, Serge; Mauger, Alain

    1996-03-01

    A power law is postulated for both site and bond percolation thresholds. The formula is pc=p0[(d-1)(q-1)]-adb, where d is the space dimension and q the coordination number. All thresholds up to d-->∞ are found to belong to only three universality classes. For two classes b=0 for site dilution while b=a for bond dilution. The remaining class associated with high dimensions is characterized by b=2a-1 for both sites and bonds. Classes are defined by a set of value for \\{p0;a\\}. Deviations from available numerical estimates at d<=7 are within +/-0.008 and +/-0.0004 for high dimensional hypercubic expansions at d>=8. The formula is found to be also valid for Ising critical temperatures.

  17. Scaling behavior of threshold epidemics

    NASA Astrophysics Data System (ADS)

    Ben-Naim, E.; Krapivsky, P. L.

    2012-05-01

    We study the classic Susceptible-Infected-Recovered (SIR) model for the spread of an infectious disease. In this stochastic process, there are two competing mechanism: infection and recovery. Susceptible individuals may contract the disease from infected individuals, while infected ones recover from the disease at a constant rate and are never infected again. Our focus is the behavior at the epidemic threshold where the rates of the infection and recovery processes balance. In the infinite population limit, we establish analytically scaling rules for the time-dependent distribution functions that characterize the sizes of the infected and the recovered sub-populations. Using heuristic arguments, we also obtain scaling laws for the size and duration of the epidemic outbreaks as a function of the total population. We perform numerical simulations to verify the scaling predictions and discuss the consequences of these scaling laws for near-threshold epidemic outbreaks.

  18. Threshold electrodisintegration of 3He

    NASA Astrophysics Data System (ADS)

    Hicks, R. S.; Hotta, A.; Churchwell, S.; Jiang, X.; Peterson, G. A.; Shaw, J.; Asavapibhop, B.; Berisso, M. C.; Bosted, P. E.; Burchesky, K.; Miskimen, R. A.; Rock, S. E.; Nakagawa, I.; Tamae, T.; Suda, T.; Golak, J.; Skibiński, R.; Witała, H.; Casagrande, F.; Turchinetz, W.; Cichocki, A.; Wang, K.; Glöckle, W.; Kamada, H.; Kobayashi, T.; Nogga, A.

    2003-06-01

    Cross sections were measured for the near-threshold electrodisintegration of 3He at momentum transfer values of q=2.4, 4.4, and 4.7 fm-1. From these and prior measurements the transverse and longitudinal response functions RT and RL were deduced. Comparisons are made against previously published and new nonrelativistic A=3 calculations using the best available nucleon-nucleon NN potentials. In general, for q<2 fm-1 these calculations accurately predict the threshold electrodisintegration of 3He. Agreement at increasing q demands consideration of two-body terms, but discrepancies still appear at the highest momentum transfers probed, perhaps due to the neglect of relativistic dynamics, or to the underestimation of high-momentum wave-function components.

  19. Roots at the Percolation Threshold

    NASA Astrophysics Data System (ADS)

    Kroener, E.; Ahmed, M. A.; Kaestner, A.; Vontobel, P.; Zarebanadkouki, M.; Carminati, A.

    2014-12-01

    Much of the carbon assimilated by plants during photosynthesis is lost to the soil via rhizodepositions. One component of rhizopdeposition is mucilage, a hydrogel that dramatically alters the soil physical properties. Mucilage was assumed to explain unexpectedly low rhizosphere rewetting rates during irrigation (Carminati et al. 2010) and temporarily water repellency in the rhizosphere after severe drying (Moradi et al. 2012).Here, we present an experimental and theoretical study for the rewetting behaviour of a soil mixed with mucilage, which was used as an analogue of the rhizosphere. Our samples were made of two layers of untreated soils separated by a thin layer (ca. 1 mm) of soil treated with mucilage. We prepared soil columns of varying particle size, mucilage concentration and height of the middle layer above the water table. The dry soil columns were re-wetted by capillary rise from the bottom.The rewetting of the middle layer showed a distinct dual behavior. For mucilage concentrations lower than a certain threshold, water could cross the thin layer almost immediately after rewetting of bulk soil. At slightly higher mucilage concentrations, the thin layer was almost impermeable. The mucilage concentration at the threshold strongly depended on particle size: the smaller the particle size the larger the soil specific surface and the more mucilage was needed to cover the entire particle surface and to induce water repellency.We applied a classic pore network model to simulate the experimental observations. In the model a certain fraction of nodes were randomly disconnected to reproduce the effect of mucilage in temporarily blocking the flow. The percolation model could qualitatively reproduce well the threshold characteristics of the experiments. Our experiments, together with former observations of water dynamics in the rhizosphere, suggest that the rhizosphere is near the percolation threshold, where small variations in mucilage concentration sensitively

  20. Superlinear threshold detectors in quantum cryptography

    SciTech Connect

    Lydersen, Lars; Maroey, Oystein; Skaar, Johannes; Makarov, Vadim; Jain, Nitin; Wittmann, Christoffer; Marquardt, Christoph; Leuchs, Gerd

    2011-09-15

    We introduce the concept of a superlinear threshold detector, a detector that has a higher probability to detect multiple photons if it receives them simultaneously rather than at separate times. Highly superlinear threshold detectors in quantum key distribution systems allow eavesdropping the full secret key without being revealed. Here, we generalize the detector control attack, and analyze how it performs against quantum key distribution systems with moderately superlinear detectors. We quantify the superlinearity in superconducting single-photon detectors based on earlier published data, and gated avalanche photodiode detectors based on our own measurements. The analysis shows that quantum key distribution systems using detector(s) of either type can be vulnerable to eavesdropping. The avalanche photodiode detector becomes superlinear toward the end of the gate. For systems expecting substantial loss, or for systems not monitoring loss, this would allow eavesdropping using trigger pulses containing less than 120 photons per pulse. Such an attack would be virtually impossible to catch with an optical power meter at the receiver entrance.

  1. Acute effects of vibration on thermal perception thresholds.

    PubMed

    Burström, Lage; Lundström, Ronnie; Sjödin, Fredrik; Lindmark, Asta; Lindkvist, Markus; Hagberg, Mats; Nilsson, Tohr

    2008-04-01

    This study focuses on the acute effects of vibration and how vibrations influence the measures of the thermal perception thresholds during different vibration magnitudes, frequencies, and durations. The fingers of ten healthy subjects, five males and five females, were exposed to vibration under 16 conditions with a combination of different frequency, intensity and exposure time. The vibration frequency was 31.5 and 125 Hz and exposure lasted between 2 and 16 min. The energy-equivalent frequency weighted acceleration, according to ISO 5349-1, for the experimental time of 16 min was 2.5 or 5.0 m/s(2) (r.m.s.), corresponding to a 8-h equivalent acceleration, A(8) of 0.46 and 0.92 m/s(2), respectively. A measure of the thermal perception of cold and warmth was conducted before the different exposures to vibration. Immediately after the vibration exposure the acute effect was measured continuously on the exposed index finger for the first 75 s, followed by 30 s of measures at every minute for a maximum of 10 min. If the subject's thermal thresholds had not recovered, the measures continued for a maximum of 30 min with measurements taken every 5 min. For all experimental conditions and 30 s after exposure, the mean changes of the thresholds compared with the pre-test were found to be 0.05 and -0.67 degrees C for the warmth and cold thresholds, respectively. The effect of the vibration exposure was only significant on the cold threshold and only for the first minute after exposure when the threshold was decreased. The warmth threshold was not significantly affected at all. The frequency and the exposure time of the vibration stimuli had no significant influence on the perception thresholds for the sensation of cold or warmth. Increased equivalent frequency weighted acceleration resulted in a significant decrease of the subjects' cold threshold, not the warmth. The thresholds were unaffected when changes in the vibration magnitude were expressed as the frequency weighted

  2. Wafer plane inspection with soft resist thresholding

    NASA Astrophysics Data System (ADS)

    Hess, Carl; Shi, Rui-fang; Wihl, Mark; Xiong, Yalin; Pang, Song

    2008-10-01

    Wafer Plane Inspection (WPI) is an inspection mode on the KLA-Tencor TeraScaTM platform that uses the high signalto- noise ratio images from the high numerical aperture microscope, and then models the entire lithographic process to enable defect detection on the wafer plane[1]. This technology meets the needs of some advanced mask manufacturers to identify the lithographically-significant defects while ignoring the other non-lithographically-significant defects. WPI accomplishes this goal by performing defect detection based on a modeled image of how the mask features would actually print in the photoresist. There are several advantages to this approach: (1) the high fidelity of the images provide a sensitivity advantage over competing approaches; (2) the ability to perform defect detection on the wafer plane allows one to only see those defects that have a printing impact on the wafer; (3) the use of modeling on the lithographic portion of the flow enables unprecedented flexibility to support arbitrary illumination profiles, process-window inspection in unit time, and combination modes to find both printing and non-printing defects. WPI is proving to be a valuable addition to the KLA-Tencor detection algorithm suite. The modeling portion of WPI uses a single resist threshold as the final step in the processing. This has been shown to be adequate on several advanced customer layers, but is not ideal for all layers. Actual resist chemistry has complicated processes including acid and base-diffusion and quench that are not consistently well-modeled with a single resist threshold. We have considered the use of an advanced resist model for WPI, but rejected it because the burdensome requirements for the calibration of the model were not practical for reticle inspection. This paper describes an alternative approach that allows for a "soft" resist threshold to be applied that provides a more robust solution for the most challenging processes. This approach is just

  3. Pain Threshold Tests in Patients With Heel Pain Syndrome.

    PubMed

    Saban, Bernice; Masharawi, Youssef

    2016-07-01

    Pressure pain threshold (PPT) is a useful tool for evaluating mechanical sensitivity in patients suffering from various musculoskeletal disorders. However, no previous study has investigated PPT in the heel of patients experiencing plantar heel pain syndrome (PHPS). The aim of this study was to compare PPT levels and topographic presentation of sensitivity in the heel of patients with PHPS and in healthy controls. The reliability of PPT testing in patients with PHPS was assessed for intra- and interrater recordings. The PPT levels of 40 feet in each group were then assessed on 5 predetermined sites in the heel using a standardized measurement protocol. Patient functional status (FS) as measured by the Foot & Ankle Computerized Adaptive Test was employed as an external reference. Multivariate analysis of covariance revealed no group differences for PPTs at all sites (P = .406). Age (P = .099) or BMI (P = .510) did not affect PPT values, although there was an effect on gender (P = .006). The analysis revealed significant differences between sites (P < .001) demonstrating a diverse topographic distribution. In the PHPS group, PPT levels at the anterior/medial, posterior/medial and central sites were significantly lower than at the posterior/lateral and anterior/lateral sites (P < .05). For the control group, PPT levels at the anterior/medial site were significantly lower than all other sites (P < .001). No significant differences were found between PPT of the PHPS patients and controls, therefore, PPT cannot be recommended as an assessment tool for these patients. The topographic distribution indicated low PPT levels at the anterior/medial area of the heel in patients with PHPS and controls. Level II, comparative study. © The Author(s) 2016.

  4. Corporate influence on threshold limit values

    SciTech Connect

    Castleman, B.I.; Ziem, G.E.

    1988-01-01

    Investigations into the historical development of specific Threshold Limit Values (TLVs) for many substances have revealed serious shortcomings in the process followed by the American Conference of Governmental Industrial Hygienists. Unpublished corporate communications were important in developing TLVs for 104 substances; for 15 of these, the TLV documentation was based solely on such information. Efforts to obtain written copies of this unpublished material were mostly unsuccessful. Case studies on the TLV Committee's handling of lead and seven carcinogens illustrate various aspects of corporate influence and interaction with the committee. Corporate representatives listed officially as consultants since 1970 were given primary responsibility for developing TLVs on proprietary chemicals of the companies that employed them (Dow, DuPont). It is concluded that an ongoing international effort is needed to develop scientifically based guidelines to replace the TLVs in a climate of openness and without manipulation by vested interests.

  5. Vibrationally assisted below-threshold ionization

    NASA Astrophysics Data System (ADS)

    Horton, Spencer L.; Liu, Yusong; Chakraborty, Pratip; Matsika, Spiridoula; Weinacht, Thomas

    2017-06-01

    We perform time-resolved UV pump (4.77 eV) and VUV probe (7.94 eV) measurements of internal conversion of 1,3-cyclohexadiene (CHD). Our measurements reveal a substantial ionization of the "hot" ground state following internal conversion despite the fact that our probe photon energy is below the ionization potential (8.21 eV). With the aid of electronic structure calculations, we interpret our results in terms of vibrationally assisted below-threshold ionization, where vibrational energy is converted to electronic energy. The effect relies on both having vibrational modes which allow for this vibrational-electronic coupling and exciting these modes during the internal conversion. We contrast our measurements in CHD with another similar molecule, cis,cis-1,3-cyclooctadiene (cis,cis-COD), for which we do not see the effect.

  6. Language and motor function thresholds during pediatric extra-operative electrical cortical stimulation brain mapping.

    PubMed

    Zea Vera, Alonso; Aungaroon, Gewalin; Horn, Paul S; Byars, Anna W; Greiner, Hansel M; Tenney, Jeffrey R; Arthur, Todd M; Crone, Nathan E; Holland, Katherine D; Mangano, Francesco T; Arya, Ravindra

    2017-10-01

    To examine current thresholds and their determinants for language and motor mapping with extra-operative electrical cortical stimulation (ECS). ECS electrocorticograph recordings were reviewed to determine functional thresholds. Predictors of functional thresholds were found with multivariable analyses. In 122 patients (age 11.9±5.4years), average minimum, frontal, and temporal language thresholds were 7.4 (± 3.0), 7.8 (± 3.0), and 7.4 (± 3.1) mA respectively. Average minimum, face, upper and lower extremity motor thresholds were 5.4 (± 2.8), 6.1 (± 2.8), 4.9 (± 2.3), and 5.3 (± 3.3) mA respectively. Functional and after-discharge (AD)/seizure thresholds were significantly related. Minimum, frontal, and temporal language thresholds were higher than AD thresholds at all ages. Minimum motor threshold was higher than minimum AD threshold up to 8.0years of age, face motor threshold was higher than frontal AD threshold up to 11.8years age, and lower subsequently. UE motor thresholds remained below frontal AD thresholds throughout the age range. Functional thresholds are frequently above AD thresholds in younger children. These findings raise concerns about safety and neurophysiologic validity of ECS mapping. Functional and AD/seizure thresholds relationships suggest individual differences in cortical excitability which cannot be explained by clinical variables. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  7. Blood lactate and ventilatory thresholds in wheelchair athletes with tetraplegia and paraplegia.

    PubMed

    Leicht, C A; Griggs, K E; Lavin, J; Tolfrey, K; Goosey-Tolfrey, V L

    2014-08-01

    The purpose of this study was to analyse the influence of spinal cord injury level on blood lactate (BLa) and ventilatory thresholds. Ten athletes with tetraplegia (TETRA) and nine athletes with paraplegia (PARA) performed a graded wheelchair propulsion treadmill exercise step test to exhaustion. The aerobic and anaerobic BLa thresholds, the ventilatory threshold and the respiratory compensation point (RCP) were determined. The BLa thresholds were determined in 34 of 38 cases, ventilatory thresholds and RCPs in 31 of 38 cases. The anaerobic BLa threshold (76 ± 7 % [Formula: see text]) and the RCP (77 ± 8 % [Formula: see text]) did not differ significantly from each other (P = 0.92), with a coefficient of variation of 4.8 ± 3.4 % between thresholds. All other thresholds differed significantly from each other (P < 0.05). Thresholds expressed as the percentage of peak oxygen uptake did not differ between TETRA and PARA (P > 0.05) despite altered breathing in TETRA, which included a higher ventilatory equivalent for oxygen and a lower tidal volume. Measuring BLa leads to a higher threshold determination rate compared with ventilatory data and the anaerobic BLa threshold can be used to predict the RCP. The altered breathing in TETRA does not seem to have a pronounced effect on the ventilatory threshold or the RCP.

  8. Above-threshold ionization by chirped laser pulses

    SciTech Connect

    Nakajima, Takashi

    2007-05-15

    We theoretically investigate above-threshold ionization by chirped laser pulses. By comparing the photoelectron energy spectra and the photoelectron angular distributions of Na for the laser pulses with different chirp rates but with the identical spectral profile, we find that the ionization processes have a clear dependence on the chirp rate. Further calculations without excited bound states during the time propagation of the wave function reveal practically no chirp dependence, which is clear evidence that the origin of the chirp dependence in above-threshold ionization is the excited bound states.

  9. Threshold condition for nonlinear tearing modes in tokamaks

    SciTech Connect

    Zabiego, M.F.; Callen, J.D.

    1996-03-01

    Low-mode-number tearing, mode nonlinear evolution is analyzed emphasizing the need for a threshold condition, to account for observations in tokamaks. The discussion is illustrated by two models recently introduced in the literature. The models can be compared with the available data and/or serve as a basis for planning some experiments in order to either test theory (by means of beta-limit scaling laws, as proposed in this paper) or attempt to control undesirable tearing modes. Introducing a threshold condition in the tearing mode stability analysis is found to reveal some bifurcation points and thus domains of intrinsic stability in the island dynamics operational space.

  10. Comparison of electrically evoked compound action potential thresholds and loudness estimates for the stimuli used to program the Advanced Bionics cochlear implant.

    PubMed

    Jeon, Eun Kyung; Brown, Carolyn J; Etler, Christine P; O'Brien, Sara; Chiou, Li-Kuei; Abbas, Paul J

    2010-01-01

    the individual data revealed considerable discrepancy between the contour of ECAP threshold versus electrode function and the behavioral loudness estimates used for programming. ECAP thresholds recorded from Advanced Bionics cochlear implant users always indicated levels where the programming stimulus was audible for the listener. However, the correlation between ECAP thresholds and M-levels (the primary metric used to program the speech processor of the Advanced Bionics CI), while statistically significant, was quite modest. If programming levels are to be determined on the basis of ECAP thresholds, care should be taken to ensure that stimulation is not uncomfortably loud, particularly on the basal electrodes in the array.

  11. Pain tolerance in children and adolescents: sex differences and psychosocial influences on pain threshold and endurance.

    PubMed

    Schmitz, A-K; Vierhaus, M; Lohaus, A

    2013-01-01

    Laboratory studies with children and adolescents revealed inconsistent findings regarding sex differences in pain tolerance, although lower pain tolerance is commonly reported for adult women. Besides biological mechanisms, several socio-cognitive variables are discussed which may influence pain tolerance in regard to sex differences. The purpose of the present study was to investigate the pain tolerance of children and adolescents using the cold pressor task (CPT) and to analyse influences of pain-coping and pain-related self-efficacy. About 1021 children and adolescents aged 9-17 participated in the study. Pain tolerance was defined as the length of time a participant's hand remains under water during the CPT. Two phases of pain tolerance were differentiated: the time until pain is reported (pain threshold) and the time from the threshold until the pain increases to a level resulting in the hand being withdrawn (pain endurance). Pain-coping and pain-related self-efficacy were assessed by self-report questionnaires. We revealed an obvious effect of sex on pain threshold, which increased with age, a small effect on pain tolerance and no significant effect on endurance. Independent of sex, pain endurance was influenced by pain-related self-efficacy and positive self-instruction. Our results support the assumption that female and male adolescents develop in different directions regarding their pain tolerance when reaching puberty. This seems mainly attributable to a decrease of pain threshold in girls. In contrast, boys and girls are able to endure pain to an equal extent influenced, however, by self-efficacy and coping variables. © 2012 European Federation of International Association for the Study of Pain Chapters.

  12. Transient threshold shift after gunshot noise exposure.

    PubMed

    Saedi, B; Ghasemi, M; Motiee, M; Mojtahed, M; Safavi, A

    2013-01-01

    Many people, such as soldiers, are routinely exposed to gunshot noise during target practice. It is suspected that this high-intensity noise may affect audition through repeated Transient Threshold Shifts (TTS); it can also mechanically alter auditory components such as waves. This study investigates the scope of gunshot noise from the AK-47 rifle (Kalashnikov) and the impact on the shooters' audition. Forty soldiers (80 ears) were recruited in this study. They were all young and being exposed to gunshot noise for the first time. Gunshot characteristics were measured before exposure. The soldiers underwent auditory evaluation with Pure Tone Audiometry (PTA) and Oto-Acoustic Emission (OAE) once before exposure and immediately (less than one hour) after exposure. The AK-47 gunshot noise pressure level varied between L(AIm) = 73.7 dBA to L(AIm) = 111.4 dBA. Fourteen participants had subclinical hearing impairment in their pre-exposure evaluation; this number increased to 16 after the exposure. Six months post-exposure and later, the number of cases with impairment had fallen to eight (improvement in 50%). Both pre- and post-exposure OAE results were within normal values, while PTA results indicated a significant threshold alteration only at 6 kHz. The results of this study confirm that exposure to gunshot noise with no ear protection can represent a significant hazard for auditory function, especially at higher frequencies.

  13. 40 CFR 98.361 - Reporting threshold.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...) MANDATORY GREENHOUSE GAS REPORTING Manure Management § 98.361 Reporting threshold. Livestock facilities must report GHG emissions under this subpart if the facility meets the reporting threshold as defined in 98...

  14. 40 CFR 98.361 - Reporting threshold.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...) MANDATORY GREENHOUSE GAS REPORTING Manure Management § 98.361 Reporting threshold. Livestock facilities must report GHG emissions under this subpart if the facility meets the reporting threshold as defined in 98...

  15. USE OF THRESHOLDS IN LANDSCAPE ASSESSMENTS

    EPA Science Inventory

    Identification and use of thresholds are potentially important additions to interpretations of ecological monitoring data. However, there are a number of issues related to defining and using thresholds in interpreting ecological data. Most of these issues center around the pauc...

  16. Androstadienone odor thresholds in adolescents.

    PubMed

    Hummel, Thomas; Krone, Franziska; Lundström, Johan N; Bartsch, Oliver

    2005-03-01

    A sex-related difference in olfactory sensitivity to androstenone has been reported to occur during adolescence. More males than females exhibited anosmia to androstenone, or an increase in androstenone threshold with age. The current study addressed the question whether similar, sexually dimorphic effects of aging over puberty can also be found for androstadienone. A total of 102 subjects participated (36 females, 66 males). Similar to previous investigations, subjects were divided into a group of 47 individuals with a mean age of 13.3 years, defined as pre/peri-pubertal, and a group of 55 subjects with a mean age of 17.1 years, defined as post-pubertal. All subjects underwent tests for verbal abilities, general olfactory function, and measurements of androstadienone thresholds. The study provided the following major results: (1) Male subjects exhibited higher androstadienone sensitivity in the pre/peri-pubertal group as compared to the post-pubertal group. This difference was not observed in female subjects. Correspondingly, a negative correlation between age and androstadienone sensitivity was found for male subjects, but not for female subjects. (2) In contrast to this sex-specific change of the androstadienone odor threshold, verbal skills and odor identification abilities increased with age in all subjects regardless of their sex. In conclusion, the present observations confirm previous research on sex-differentiated effects of aging during puberty on sensitivity towards odorous steroids. While the underlying causes are unknown, it may be hypothesized that the decreased sensitivity could result from the increased endogenous levels of androstadienone in male subjects. Future studies should include both steroid and non-steroid odorants to further explore these age-related changes.

  17. Thresholds for impaired species recovery

    PubMed Central

    Hutchings, Jeffrey A.

    2015-01-01

    Studies on small and declining populations dominate research in conservation biology. This emphasis reflects two overarching frameworks: the small-population paradigm focuses on correlates of increased extinction probability; the declining-population paradigm directs attention to the causes and consequences of depletion. Neither, however, particularly informs research on the determinants, rate or uncertainty of population increase. By contrast, Allee effects (positive associations between population size and realized per capita population growth rate, rrealized, a metric of average individual fitness) offer a theoretical and empirical basis for identifying numerical and temporal thresholds at which recovery is unlikely or uncertain. Following a critique of studies on Allee effects, I quantify population-size minima and subsequent trajectories of marine fishes that have and have not recovered following threat mitigation. The data suggest that threat amelioration, albeit necessary, can be insufficient to effect recovery for populations depleted to less than 10% of maximum abundance (Nmax), especially when they remain depleted for lengthy periods of time. Comparing terrestrial and aquatic vertebrates, life-history analyses suggest that population-size thresholds for impaired recovery are likely to be comparatively low for marine fishes but high for marine mammals. Articulation of a ‘recovering population paradigm’ would seem warranted. It might stimulate concerted efforts to identify generic impaired recovery thresholds across species. It might also serve to reduce the confusion of terminology, and the conflation of causes and consequences with patterns currently evident in the literature on Allee effects, thus strengthening communication among researchers and enhancing the practical utility of recovery-oriented research to conservation practitioners and resource managers. PMID:26213739

  18. Clinical testing of otolith function: perceptual thresholds and myogenic potentials.

    PubMed

    Agrawal, Yuri; Bremova, Tatiana; Kremmyda, Olympia; Strupp, Michael; MacNeilage, Paul R

    2013-12-01

    Cervical and ocular vestibular-evoked myogenic potential (cVEMP/oVEMP) tests are widely used clinical tests of otolith function. However, VEMP testing may not be the ideal measure of otolith function given the significant inter-individual variability in responses and given that the stimuli used to elicit VEMPs are not physiological. We therefore evaluated linear motion perceptual threshold testing compared with cVEMP and oVEMP testing as measures of saccular and utricular function, respectively. A multi-axis motion platform was used to measure horizontal (along the inter-aural and naso-occipital axes) and vertical motion perceptual thresholds. These findings were compared with the vibration-evoked oVEMP as a measure of utricular function and sound-evoked cVEMP as a measure of saccular function. We also considered how perceptual threshold and cVEMP/oVEMP testing are each associated with Dizziness Handicap Inventory (DHI) scores. We enrolled 33 patients with bilateral vestibulopathy of different severities and 42 controls to have sufficient variability in otolith function. Subjects with abnormal oVEMP amplitudes had significantly higher (poorer) perceptual thresholds in the inter-aural and naso-occipital axes in age-adjusted analyses; no significant associations were observed for vertical perceptual thresholds and cVEMP amplitudes. Both oVEMP amplitudes and naso-occipital axis perceptual thresholds were significantly associated with DHI scores. These data suggest that horizontal perceptual thresholds and oVEMPs may estimate the same underlying physiological construct: utricular function.

  19. Ultra-low threshold polariton condensation

    NASA Astrophysics Data System (ADS)

    Steger, Mark; Fluegel, Brian; Alberi, Kirstin; Snoke, David W.; Pfeiffer, Loren N.; West, Ken; Mascarenhas, Angelo

    2017-03-01

    We demonstrate condensation of microcavity polaritons with a very sharp threshold occuring at two orders of magnitude lower pump intensity than previous demonstrations of condensation. The long cavity-lifetime and trapping and pumping geometries are crucial to the realization of this low threshold. Polariton condensation, or "polariton lasing" has long been proposed as a promising source of coherent light at lower threshold than traditional lasing, and these results suggest methods to bring this threshold even lower.

  20. Ultra-low threshold polariton condensation.

    PubMed

    Steger, Mark; Fluegel, Brian; Alberi, Kirstin; Snoke, David W; Pfeiffer, Loren N; West, Ken; Mascarenhas, Angelo

    2017-03-15

    We demonstrate the condensation of microcavity polaritons with a very sharp threshold occurring at a two orders of magnitude pump intensity lower than previous demonstrations of condensation. The long cavity lifetime and trapping and pumping geometries are crucial to the realization of this low threshold. Polariton condensation, or "polariton lasing" has long been proposed as a promising source of coherent light at a lower threshold than traditional lasing, and these results indicate some considerations for optimizing designs for lower thresholds.

  1. Ultra-low threshold polariton condensation

    DOE PAGES

    Steger, Mark; Fluegel, Brian; Alberi, Kirstin; ...

    2017-03-13

    Here, we demonstrate the condensation of microcavity polaritons with a very sharp threshold occurring at a two orders of magnitude pump intensity lower than previous demonstrations of condensation. The long cavity lifetime and trapping and pumping geometries are crucial to the realization of this low threshold. Polariton condensation, or 'polariton lasing' has long been proposed as a promising source of coherent light at a lower threshold than traditional lasing, and these results indicate some considerations for optimizing designs for lower thresholds.

  2. The Electromyographic Threshold in Girls and Women.

    PubMed

    Long, Devon; Dotan, Raffy; Pitt, Brynlynn; McKinlay, Brandon; O'Brien, Thomas D; Tokuno, Craig; Falk, Bareket

    2017-02-01

    The electromyographic threshold (EMGTh) is thought to reflect increased high-threshold/type-II motor-unit (MU) recruitment and was shown higher in boys than in men. Women differ from men in muscular function. Establish whether females' EMGTh and girls-women differences are different than males'. Nineteen women (22.9 ± 3.3yrs) and 20 girls (10.3 ± 1.1yrs) had surface EMG recorded from the right and left vastus lateralis muscles during ramped cycle-ergometry to exhaustion. EMG root-mean-squares were averaged per pedal revolution. EMGTh was determined as the least residual sum of squares for any two regression-line data divisions, if the trace rose ≥ 3SD above its regression line. EMGTh was expressed as % final power-output (%Pmax) and %VO2pk power (%PVO2pk). EMGTh was detected in 13 (68%) of women, but only 9 (45%) of girls (p < .005) and tended to be higher in the girls (%Pmax= 88.6 ± 7.0 vs. 83.0 ± 6.9%, p = .080; %PVO2pk= (101.6 ± 17.6 vs. 90.6 ± 7.8%, p = .063). When EMGTh was undetected it was assumed to occur at 100%Pmax or beyond. Consequently, EMGTh values turned significantly higher in girls than in women (94.8 ± 7.4 vs. 88.4 ± 9.9%Pmax, p = .026; and 103.2 ± 11.7 vs. 95.2 ± 9.9%PVO2pk, p = .028). During progressive exercise, girls appear to rely less on higher-threshold/type-II MUs than do women, suggesting differential muscle activation strategy.

  3. Tissue damage thresholds during therapeutic electrical stimulation

    PubMed Central

    Cogan, Stuart F; Ludwig, Kip A; Welle, Cristin G; Takmakov, Pavel

    2017-01-01

    Objective Recent initiatives in bioelectronic modulation of the nervous system by the NIH (SPARC), DARPA (ElectRx, SUBNETS) and the GlaxoSmithKline Bioelectronic Medicines effort are ushering in a new era of therapeutic electrical stimulation. These novel therapies are prompting a re-evaluation of established electrical thresholds for stimulation-induced tissue damage. Approach In this review, we explore what is known and unknown in published literature regarding tissue damage from electrical stimulation. Main results For macroelectrodes, the potential for tissue damage is often assessed by comparing the intensity of stimulation, characterized by the charge density and charge per phase of a stimulus pulse, with a damage threshold identified through histological evidence from in vivo experiments as described by the Shannon equation. While the Shannon equation has proved useful in assessing the likely occurrence of tissue damage, the analysis is limited by the experimental parameters of the original studies. Tissue damage is influenced by factors not explicitly incorporated into the Shannon equation, including pulse frequency, duty cycle, current density, and electrode size. Microelectrodes in particular do not follow the charge per phase and charge density co-dependence reflected in the Shannon equation. The relevance of these factors to tissue damage is framed in the context of available reports from modeling and in vivo studies. Significance It is apparent that emerging applications, especially with microelectrodes, will require clinical charge densities that exceed traditional damage thresholds. Experimental data show that stimulation at higher charge densities can be achieved without causing tissue damage, suggesting that safety parameters for microelectrodes might be distinct from those defined for macroelectrodes. However, these increased charge densities may need to be justified by bench, non-clinical or clinical testing to provide evidence of device safety

  4. Tissue damage thresholds during therapeutic electrical stimulation

    NASA Astrophysics Data System (ADS)

    Cogan, Stuart F.; Ludwig, Kip A.; Welle, Cristin G.; Takmakov, Pavel

    2016-04-01

    Objective. Recent initiatives in bioelectronic modulation of the nervous system by the NIH (SPARC), DARPA (ElectRx, SUBNETS) and the GlaxoSmithKline Bioelectronic Medicines effort are ushering in a new era of therapeutic electrical stimulation. These novel therapies are prompting a re-evaluation of established electrical thresholds for stimulation-induced tissue damage. Approach. In this review, we explore what is known and unknown in published literature regarding tissue damage from electrical stimulation. Main results. For macroelectrodes, the potential for tissue damage is often assessed by comparing the intensity of stimulation, characterized by the charge density and charge per phase of a stimulus pulse, with a damage threshold identified through histological evidence from in vivo experiments as described by the Shannon equation. While the Shannon equation has proved useful in assessing the likely occurrence of tissue damage, the analysis is limited by the experimental parameters of the original studies. Tissue damage is influenced by factors not explicitly incorporated into the Shannon equation, including pulse frequency, duty cycle, current density, and electrode size. Microelectrodes in particular do not follow the charge per phase and charge density co-dependence reflected in the Shannon equation. The relevance of these factors to tissue damage is framed in the context of available reports from modeling and in vivo studies. Significance. It is apparent that emerging applications, especially with microelectrodes, will require clinical charge densities that exceed traditional damage thresholds. Experimental data show that stimulation at higher charge densities can be achieved without causing tissue damage, suggesting that safety parameters for microelectrodes might be distinct from those defined for macroelectrodes. However, these increased charge densities may need to be justified by bench, non-clinical or clinical testing to provide evidence of device

  5. Optimal threshold estimation for binary classifiers using game theory

    PubMed Central

    Sanchez, Ignacio Enrique

    2017-01-01

    Many bioinformatics algorithms can be understood as binary classifiers. They are usually compared using the area under the receiver operating characteristic ( ROC) curve. On the other hand, choosing the best threshold for practical use is a complex task, due to uncertain and context-dependent skews in the abundance of positives in nature and in the yields/costs for correct/incorrect classification. We argue that considering a classifier as a player in a zero-sum game allows us to use the minimax principle from game theory to determine the optimal operating point. The proposed classifier threshold corresponds to the intersection between the ROC curve and the descending diagonal in ROC space and yields a minimax accuracy of 1-FPR. Our proposal can be readily implemented in practice, and reveals that the empirical condition for threshold estimation of “specificity equals sensitivity” maximizes robustness against uncertainties in the abundance of positives in nature and classification costs. PMID:28003875

  6. Sex and Age Differences in the Risk Threshold for Delinquency

    PubMed Central

    Loeber, Rolf; Slotboom, Anne-Marie; Bijleveld, Catrien C. J. H.; Hipwell, Alison E.; Stepp, Stephanie D.; Koot, Hans M.

    2015-01-01

    This study examines sex differences in the risk threshold for adolescent delinquency. Analyses were based on longitudinal data from the Pittsburgh Youth Study (n = 503) and the Pittsburgh Girls Study (n = 856). The study identified risk factors, promotive factors, and accumulated levels of risks as predictors of delinquency and nondelinquency, respectively. The risk thresholds for boys and girls were established at two developmental stages (late childhood: ages 10–12 years, and adolescence: ages 13–16 years) and compared between boys and girls. Sex similarities as well as differences existed in risk and promotive factors for delinquency. ROC analyses revealed only small sex differences in delinquency thresholds, that varied by age. Accumulative risk level had a linear relationship with boys’ delinquency and a quadratic relationship with girls’ delinquency, indicating stronger effects for girls at higher levels of risk. PMID:23183920

  7. Optimal threshold estimation for binary classifiers using game theory.

    PubMed

    Sanchez, Ignacio Enrique

    2016-01-01

    Many bioinformatics algorithms can be understood as binary classifiers. They are usually compared using the area under the receiver operating characteristic ( ROC) curve. On the other hand, choosing the best threshold for practical use is a complex task, due to uncertain and context-dependent skews in the abundance of positives in nature and in the yields/costs for correct/incorrect classification. We argue that considering a classifier as a player in a zero-sum game allows us to use the minimax principle from game theory to determine the optimal operating point. The proposed classifier threshold corresponds to the intersection between the ROC curve and the descending diagonal in ROC space and yields a minimax accuracy of 1-FPR. Our proposal can be readily implemented in practice, and reveals that the empirical condition for threshold estimation of "specificity equals sensitivity" maximizes robustness against uncertainties in the abundance of positives in nature and classification costs.

  8. Normalized pulsed energy thresholding in a nonlinear optical loop mirror.

    PubMed

    Nahmias, M A; Shastri, B J; Tait, A N; Eder, M; Rafidi, Nicole; Tian, Yue; Prucnal, P R

    2015-04-10

    We demonstrate for the first time, to the best of our knowledge, that a Sagnac interferometer can threshold the energies of pulses. Pulses below a given threshold T are suppressed, while those above this threshold are normalized. The device contains an in-loop tunable isolator and 10.4 m of a highly doped silica fiber. We derive an analytical model of the nonlinear optical loop mirror's pulse energy transfer function and show that its energy transfer function approximates a step function for very high phase shifts (>π). We reveal some limitations of this approach, showing that a step-function transfer function necessarily results in pulse distortion in fast, nonresonant all-optical devices.

  9. Threshold Concepts in Finance: Student Perspectives

    ERIC Educational Resources Information Center

    Hoadley, Susan; Kyng, Tim; Tickle, Leonie; Wood, Leigh N.

    2015-01-01

    Finance threshold concepts are the essential conceptual knowledge that underpin well-developed financial capabilities and are central to the mastery of finance. In this paper we investigate threshold concepts in finance from the point of view of students, by establishing the extent to which students are aware of threshold concepts identified by…

  10. Threshold Concepts in Finance: Student Perspectives

    ERIC Educational Resources Information Center

    Hoadley, Susan; Kyng, Tim; Tickle, Leonie; Wood, Leigh N.

    2015-01-01

    Finance threshold concepts are the essential conceptual knowledge that underpin well-developed financial capabilities and are central to the mastery of finance. In this paper we investigate threshold concepts in finance from the point of view of students, by establishing the extent to which students are aware of threshold concepts identified by…

  11. Compositional threshold for Nuclear Waste Glass Durability

    SciTech Connect

    Kruger, Albert A.; Farooqi, Rahmatullah; Hrma, Pavel R.

    2013-04-24

    Within the composition space of glasses, a distinct threshold appears to exist that separates "good" glasses, i.e., those which are sufficiently durable, from "bad" glasses of a low durability. The objective of our research is to clarify the origin of this threshold by exploring the relationship between glass composition, glass structure and chemical durability around the threshold region.

  12. Comparison studies on the percolation thresholds of binary mixture tablets containing excipients of plastic/brittle and plastic/plastic deformation properties.

    PubMed

    Amin, Mohd C I; Fell, John T

    2004-01-01

    Percolation theory has been used with great interest in understanding the design and characterization of dosage forms. In this study, work has been carried out to investigate the behavior of binary mixture tablets containing excipients of similar and different deformation properties. The binary mixture tablets were prepared by direct compression using lactose, polyvinyl chloride (PVC), Eudragit RS 100, and microcrystalline cellulose (MCC). The application of percolation theory on the relationships between compactibility, Pmax, or compression susceptibility (compressibility), gamma, and mixture compositions reveals the presence of percolation thresholds even for mixtures of similar deformation properties. The results showed that all mixture compositions exhibited at least one discreet change in the slope, which was referred to as the percolation threshold. The PVC/Eudragit RS100 mixture compositions showed significant percolation threshold at 80% (w/w) PVC loading. Two percolation thresholds were observed from a series of binary mixtures containing similar plastic deformation materials (PVC/MCC). The percolation thresholds were determined at 20% (w/w) and 80% (w/w) PVC loading. These are areas where one of the components percolates throughout the system and the properties of the tablets are expected to experience a sudden change. Experimental results, however, showed that total disruption of the tablet physical properties at the specified percolation thresholds can be observed for PVC/lactose mixtures at 20-30% (w/w) loading while only minor changes in the tablets' strength for PVC/MCC or PVC/Eudragit RS 100 mixtures were observed.

  13. Slow passage through thresholds in quantum dot lasers.

    PubMed

    Viktorov, E A; Erneux, T; Kolykhalova, E D; Dudelev, V V; Danckaert, J; Soboleva, K K; Deryagin, A G; Novikov, I I; Maximov, M V; Zhukov, A E; Ustinov, V M; Kuchinskii, V I; Sibbett, W; Rafailov, E U; Sokolovskii, G S

    2016-11-01

    A turn on of a quantum dot (QD) semiconductor laser simultaneously operating at the ground state (GS) and excited state (ES) is investigated both experimentally and theoretically. We find experimentally that the slow passage through the two successive laser thresholds may lead to significant delays in the GS and ES turn ons. The difference between the turn-on times is measured as a function of the pump rate of change ɛ and reveals no clear power law. This has motivated a detailed analysis of rate equations appropriate for two-state lasing QD lasers. We find that the effective time of the GS turn on follows an ɛ^{-1/2} power law provided that the rate of change is not too small. The effective time of the ES transition follows an ɛ^{-1} power law, but its first order correction in ln(ɛ) is numerically significant. The two turn ons result from different physical mechanisms. The delay of the GS transition strongly depends on the slow growth of the dot population, whereas the ES transition only depends on the time needed to leave a repellent steady state.

  14. Slow passage through thresholds in quantum dot lasers

    NASA Astrophysics Data System (ADS)

    Viktorov, E. A.; Erneux, T.; Kolykhalova, E. D.; Dudelev, V. V.; Danckaert, J.; Soboleva, K. K.; Deryagin, A. G.; Novikov, I. I.; Maximov, M. V.; Zhukov, A. E.; Ustinov, V. M.; Kuchinskii, V. I.; Sibbett, W.; Rafailov, E. U.; Sokolovskii, G. S.

    2016-11-01

    A turn on of a quantum dot (QD) semiconductor laser simultaneously operating at the ground state (GS) and excited state (ES) is investigated both experimentally and theoretically. We find experimentally that the slow passage through the two successive laser thresholds may lead to significant delays in the GS and ES turn ons. The difference between the turn-on times is measured as a function of the pump rate of change ɛ and reveals no clear power law. This has motivated a detailed analysis of rate equations appropriate for two-state lasing QD lasers. We find that the effective time of the GS turn on follows an ɛ-1 /2 power law provided that the rate of change is not too small. The effective time of the ES transition follows an ɛ-1 power law, but its first order correction in ln(ɛ ) is numerically significant. The two turn ons result from different physical mechanisms. The delay of the GS transition strongly depends on the slow growth of the dot population, whereas the ES transition only depends on the time needed to leave a repellent steady state.

  15. Wavelet detection of weak far-magnetic signal based on adaptive ARMA model threshold

    NASA Astrophysics Data System (ADS)

    Zhang, Ning; Lin, Chun-sheng; Fang, Shi

    2009-10-01

    Based on Mallat algorithm, a de-noising algorithm of adaptive wavelet threshold is applied for weak magnetic signal detection of far moving target in complex magnetic environment. The choice of threshold is the key problem. With the spectrum analysis of the magnetic field target, a threshold algorithm on the basis of adaptive ARMA model filter is brought forward to improve the wavelet filtering performance. The simulation of this algorithm on measured data is carried out. Compared to Donoho threshold algorithm, it shows that adaptive ARMA model threshold algorithm significantly improved the capability of weak magnetic signal detection in complex magnetic environment.

  16. Epidemic threshold in directed networks.

    PubMed

    Li, Cong; Wang, Huijuan; Van Mieghem, Piet

    2013-12-01

    Epidemics have so far been mostly studied in undirected networks. However, many real-world networks, such as the online social network Twitter and the world wide web, on which information, emotion, or malware spreads, are directed networks, composed of both unidirectional links and bidirectional links. We define the directionality ξ as the percentage of unidirectional links. The epidemic threshold τ(c) for the susceptible-infected-susceptible (SIS) epidemic is lower bounded by 1/λ(1) in directed networks, where λ(1), also called the spectral radius, is the largest eigenvalue of the adjacency matrix. In this work, we propose two algorithms to generate directed networks with a given directionality ξ. The effect of ξ on the spectral radius λ(1), principal eigenvector x(1), spectral gap (λ(1)-|λ(2)|), and algebraic connectivity μ(N-1) is studied. Important findings are that the spectral radius λ(1) decreases with the directionality ξ, whereas the spectral gap and the algebraic connectivity increase with the directionality ξ. The extent of the decrease of the spectral radius depends on both the degree distribution and the degree-degree correlation ρ(D). Hence, in directed networks, the epidemic threshold is larger and a random walk converges to its steady state faster than that in undirected networks with the same degree distribution.

  17. Epidemic threshold in directed networks

    NASA Astrophysics Data System (ADS)

    Li, Cong; Wang, Huijuan; Van Mieghem, Piet

    2013-12-01

    Epidemics have so far been mostly studied in undirected networks. However, many real-world networks, such as the online social network Twitter and the world wide web, on which information, emotion, or malware spreads, are directed networks, composed of both unidirectional links and bidirectional links. We define the directionality ξ as the percentage of unidirectional links. The epidemic threshold τc for the susceptible-infected-susceptible (SIS) epidemic is lower bounded by 1/λ1 in directed networks, where λ1, also called the spectral radius, is the largest eigenvalue of the adjacency matrix. In this work, we propose two algorithms to generate directed networks with a given directionality ξ. The effect of ξ on the spectral radius λ1, principal eigenvector x1, spectral gap (λ1-λ2), and algebraic connectivity μN-1 is studied. Important findings are that the spectral radius λ1 decreases with the directionality ξ, whereas the spectral gap and the algebraic connectivity increase with the directionality ξ. The extent of the decrease of the spectral radius depends on both the degree distribution and the degree-degree correlation ρD. Hence, in directed networks, the epidemic threshold is larger and a random walk converges to its steady state faster than that in undirected networks with the same degree distribution.

  18. Computational gestalts and perception thresholds.

    PubMed

    Desolneux, Agnès; Moisan, Lionel; Morel, Jean-Michel

    2003-01-01

    In 1923, Max Wertheimer proposed a research programme and method in visual perception. He conjectured the existence of a small set of geometric grouping laws governing the perceptual synthesis of phenomenal objects, or "gestalt" from the atomic retina input. In this paper, we review this set of geometric grouping laws, using the works of Metzger, Kanizsa and their schools. In continuation, we explain why the Gestalt theory research programme can be translated into a Computer Vision programme. This translation is not straightforward, since Gestalt theory never addressed two fundamental matters: image sampling and image information measurements. Using these advances, we shall show that gestalt grouping laws can be translated into quantitative laws allowing the automatic computation of gestalts in digital images. From the psychophysical viewpoint, a main issue is raised: the computer vision gestalt detection methods deliver predictable perception thresholds. Thus, we are set in a position where we can build artificial images and check whether some kind of agreement can be found between the computationally predicted thresholds and the psychophysical ones. We describe and discuss two preliminary sets of experiments, where we compared the gestalt detection performance of several subjects with the predictable detection curve. In our opinion, the results of this experimental comparison support the idea of a much more systematic interaction between computational predictions in Computer Vision and psychophysical experiments.

  19. Lowering the CUORE energy threshold

    NASA Astrophysics Data System (ADS)

    Copello, S.; Alduino, C.; Alfonso, K.; Artusa, D. R.; Avignone, F. T., III.; Azzolini, O.; Banks, T. I.; Bari, G.; Beeman, J. W.; Bellini, F.; Bersani, A.; Biassoni, M.; Branca, A.; Brofferio, C.; Bucci, C.; Camacho, A.; Caminata, A.; Canonica, L.; Cao, X. G.; Capelli, S.; Cappelli, L.; Carbone, L.; Cardani, L.; Carniti, P.; Casali, N.; Cassina, L.; Chiesa, D.; Chott, N.; Clemenza, M.; Cosmelli, C.; Cremonesi, O.; Creswick, R. J.; Cushman, J. S.; D’Addabbo, A.; Dafinei, I.; Davis, C. J.; Dell’Oro, S.; Deninno, M. M.; Di Domizio, S.; Di Vacri, M. L.; Drobizhev, A.; Fang, D. Q.; Faverzani, M.; Fernandes, G.; Ferri, E.; Ferroni, F.; Fiorini, E.; Franceschi, M. A.; Freedman, S. J.; Fujikawa, B. K.; Giachero, A.; Gironi, L.; Giuliani, A.; Gladstone, L.; Gorla, P.; Gotti, C.; Gutierrez, T. D.; Haller, E. E.; Han, K.; Hansen, E.; Heeger, K. M.; Hennings-Yeomans, R.; Hickerson, K. P.; Huang, H. Z.; Kadel, R.; Keppel, G.; Kolomensky, Yu. G.; Leder, A.; Ligi, C.; Lim, K. E.; Liu, X.; Ma, Y. G.; Maino, M.; Marini, L.; Martinez, M.; Maruyama, R. H.; Mei, Y.; Moggi, N.; Morganti, S.; Mosteiro, P. J.; Napolitano, T.; Nones, C.; Norman, E. B.; Nucciotti, A.; O’Donnell, T.; Orio, F.; Ouellet, J. L.; Pagliarone, C. E.; Pallavicini, M.; Palmieri, V.; Pattavina, L.; Pavan, M.; Pessina, G.; Pettinacci, V.; Piperno, G.; Pira, c. C.; Pirro, S.; Pozzi, S.; Previtali, E.; Rosenfeld, C.; Rusconi, C.; Sangiorgio, S.; Santone, D.; Scielzo, N. D.; Singh, V.; Sisti, M.; Smith, A. R.; Taffarello, L.; Tenconi, M.; Terranova, F.; Tomei, C.; Trentalange, S.; Vignati, M.; Wagaarachchi, S. L.; Wang, B. S.; Wang, H. W.; Wilson, J.; Winslow, L. A.; Wise, T.; Woodcraft, A.; Zanotti, L.; Zhang, G. Q.; Zhu, B. X.; Zimmermann, S.; Zucchelli, S.

    2017-09-01

    The Cryogenic Underground Observatory for Rare Events (CUORE) is a ton-scale double beta decay experiment based on TeO2 cryogenic bolometers and is currently in the last construction stage at the Gran Sasso National Laboratory (LNGS). Its primary goal is to observe neutrino-less double beta decay of 130Te, however thanks to the ultra-low background and large projected exposure it could also be suitable for other rare event searches, as the detection of solar axions, neutrinos from type II supernovae or direct detection of dark matter. The sensitivity for these searches will depend on the performance achieved at the low energy threshold. For this reason a trigger algorithm based on continuous data filtering has been developed which will allow lowering the threshold down to the few keV region. The new trigger has been tested in CUORE-0, a single-tower CUORE prototype consisting of 52 TeO2 bolometers and recently concluded, and here we present the results in terms of trigger efficiency, data selection and low-energy calibration.

  20. Threshold-avoiding proteomics pipeline.

    PubMed

    Suits, Frank; Hoekman, Berend; Rosenling, Therese; Bischoff, Rainer; Horvatovich, Peter

    2011-10-15

    We present a new proteomics analysis pipeline focused on maximizing the dynamic range of detected molecules in liquid chromatography-mass spectrometry (LC-MS) data and accurately quantifying low-abundance peaks to identify those with biological relevance. Although there has been much work to improve the quality of data derived from LC-MS instruments, the goal of this study was to extend the dynamic range of analyzed compounds by making full use of the information available within each data set and across multiple related chromatograms in an experiment. Our aim was to distinguish low-abundance signal peaks from noise by noting their coherent behavior across multiple data sets, and central to this is the need to delay the culling of noise peaks until the final peak-matching stage of the pipeline, when peaks from a single sample appear in the context of all others. The application of thresholds that might discard signal peaks early is thereby avoided, hence the name TAPP: threshold-avoiding proteomics pipeline. TAPP focuses on quantitative low-level processing of raw LC-MS data and includes novel preprocessing, peak detection, time alignment, and cluster-based matching. We demonstrate the performance of TAPP on biologically relevant sample data consisting of porcine cerebrospinal fluid spiked over a wide range of concentrations with horse heart cytochrome c.

  1. Threshold temperature optical fibre sensors

    NASA Astrophysics Data System (ADS)

    Stasiewicz, K. A.; Musial, J. E.

    2016-12-01

    This paper presents a new approach to manufacture a threshold temperature sensor based on a biconical optical fibre taper. The presented sensor employs the influence of variable state of concentration of some isotropic materials like wax or paraffin. Application of the above- mentioned materials is an attempt to prove that there is a possibility to obtain a low-cost, repeatable and smart sensor working as an in-line element. Optical fibre taper was obtained from a standard single mode fibre (SMF28®) by using a low pressure gas burner technique. The diameter of the manufactured tapers was 6.0 ± 0.5 μm with the length of elongation equal to 30.50 ± 0.16 mm. The applied technology allowed to produce tapers with the losses of 0.183 ± 0.015 dB. Application of materials with different temperature transition points made it possible to obtain the threshold work at the temperatures connected directly with their conversion temperature. External materials at the temperatures above their melting points do not influence the propagation losses. For each of them two types of the protection area and position of the optical fibre taper were applied.

  2. Extracellular voltage threshold settings can be tuned for optimal encoding of movement and stimulus parameters

    NASA Astrophysics Data System (ADS)

    Oby, Emily R.; Perel, Sagi; Sadtler, Patrick T.; Ruff, Douglas A.; Mischel, Jessica L.; Montez, David F.; Cohen, Marlene R.; Batista, Aaron P.; Chase, Steven M.

    2016-06-01

    Objective. A traditional goal of neural recording with extracellular electrodes is to isolate action potential waveforms of an individual neuron. Recently, in brain-computer interfaces (BCIs), it has been recognized that threshold crossing events of the voltage waveform also convey rich information. To date, the threshold for detecting threshold crossings has been selected to preserve single-neuron isolation. However, the optimal threshold for single-neuron identification is not necessarily the optimal threshold for information extraction. Here we introduce a procedure to determine the best threshold for extracting information from extracellular recordings. We apply this procedure in two distinct contexts: the encoding of kinematic parameters from neural activity in primary motor cortex (M1), and visual stimulus parameters from neural activity in primary visual cortex (V1). Approach. We record extracellularly from multi-electrode arrays implanted in M1 or V1 in monkeys. Then, we systematically sweep the voltage detection threshold and quantify the information conveyed by the corresponding threshold crossings. Main Results. The optimal threshold depends on the desired information. In M1, velocity is optimally encoded at higher thresholds than speed; in both cases the optimal thresholds are lower than are typically used in BCI applications. In V1, information about the orientation of a visual stimulus is optimally encoded at higher thresholds than is visual contrast. A conceptual model explains these results as a consequence of cortical topography. Significance. How neural signals are processed impacts the information that can be extracted from them. Both the type and quality of information contained in threshold crossings depend on the threshold setting. There is more information available in these signals than is typically extracted. Adjusting the detection threshold to the parameter of interest in a BCI context should improve our ability to decode motor intent

  3. Revealing Rembrandt

    PubMed Central

    Parker, Andrew J.

    2014-01-01

    The power and significance of artwork in shaping human cognition is self-evident. The starting point for our empirical investigations is the view that the task of neuroscience is to integrate itself with other forms of knowledge, rather than to seek to supplant them. In our recent work, we examined a particular aspect of the appreciation of artwork using present-day functional magnetic resonance imaging (fMRI). Our results emphasized the continuity between viewing artwork and other human cognitive activities. We also showed that appreciation of a particular aspect of artwork, namely authenticity, depends upon the co-ordinated activity between the brain regions involved in multiple decision making and those responsible for processing visual information. The findings about brain function probably have no specific consequences for understanding how people respond to the art of Rembrandt in comparison with their response to other artworks. However, the use of images of Rembrandt's portraits, his most intimate and personal works, clearly had a significant impact upon our viewers, even though they have been spatially confined to the interior of an MRI scanner at the time of viewing. Neuroscientific studies of humans viewing artwork have the capacity to reveal the diversity of human cognitive responses that may be induced by external advice or context as people view artwork in a variety of frameworks and settings. PMID:24795552

  4. Effects of stimulation parameters and electrode location on thresholds for epidural stimulation of cat motor cortex

    NASA Astrophysics Data System (ADS)

    Wongsarnpigoon, Amorn; Grill, Warren M.

    2011-12-01

    Epidural electrical stimulation (ECS) of the motor cortex is a developing therapy for neurological disorders. Both placement and programming of ECS systems may affect the therapeutic outcome, but the treatment parameters that will maximize therapeutic outcomes and minimize side effects are not known. We delivered ECS to the motor cortex of anesthetized cats and investigated the effects of electrode placement and stimulation parameters on thresholds for evoking motor responses in the contralateral forelimb. Thresholds were inversely related to stimulation frequency and the number of pulses per stimulus train. Thresholds were lower over the forelimb representation in motor cortex (primary site) than surrounding sites (secondary sites), and thresholds at sites <4 mm away from the primary site were significantly lower than at sites >4 mm away. Electrode location and montage influenced the effects of polarity on thresholds: monopolar anodic and cathodic thresholds were not significantly different over the primary site, cathodic thresholds were significantly lower than anodic thresholds over secondary sites and bipolar thresholds were significantly lower with the anode over the primary site than with the cathode over the primary site. A majority of bipolar thresholds were either between or equal to the respective monopolar thresholds, but several bipolar thresholds were greater than or less than the monopolar thresholds of both the anode and cathode. During bipolar stimulation, thresholds were influenced by both electric field superposition and indirect, synaptically mediated interactions. These results demonstrate the influence of stimulation parameters and electrode location during cortical stimulation, and these effects should be considered during the programming of systems for therapeutic cortical stimulation.

  5. The Influence of Humidity on Assessing Irritation Threshold of Ammonia.

    PubMed

    Monsé, Christian; Sucker, Kirsten; Hoffmeyer, Frank; Jettkant, Birger; Berresheim, Hans; Bünger, Jürgen; Brüning, Thomas

    2016-01-01

    A large number of occupational exposure limit values (OELs) are based on avoiding of sensory irritation of the eyes and the upper respiratory tract. In order to investigate the chemosensory effect range of a chemical, odor and sensory irritation thresholds (lateralization thresholds, LTs) can be assessed. Humidity affects olfactory function and thus influences odor thresholds; however, a similar effect has not been shown for sensory irritation thresholds. The purpose of the present study was to explore whether LTs for ammonia vapor vary depending on the water vapor content of the inspired stimulus. Eight healthy nonsmoking volunteers were simultaneously exposed to ammonia vapor through one nostril and clean air through the other and were asked to determine which nostril received the chemical. Within experimental runs, ascending ammonia concentrations (60-350 ppm) that were either dry or humidified were administered at fixed time intervals. Geometric mean LTs obtained at wet (181 ppm) or dry (172 ppm) conditions did not differ significantly (P = 0.19) and were within the range of those reported by previous studies. These results suggest that humidity is not a critical factor in determining sensory irritation thresholds for ammonia, and future studies will examine if these findings are transferable to sensory irritation thresholds for other chemicals.

  6. The Influence of Humidity on Assessing Irritation Threshold of Ammonia

    PubMed Central

    Sucker, Kirsten; Jettkant, Birger; Berresheim, Hans; Brüning, Thomas

    2016-01-01

    A large number of occupational exposure limit values (OELs) are based on avoiding of sensory irritation of the eyes and the upper respiratory tract. In order to investigate the chemosensory effect range of a chemical, odor and sensory irritation thresholds (lateralization thresholds, LTs) can be assessed. Humidity affects olfactory function and thus influences odor thresholds; however, a similar effect has not been shown for sensory irritation thresholds. The purpose of the present study was to explore whether LTs for ammonia vapor vary depending on the water vapor content of the inspired stimulus. Eight healthy nonsmoking volunteers were simultaneously exposed to ammonia vapor through one nostril and clean air through the other and were asked to determine which nostril received the chemical. Within experimental runs, ascending ammonia concentrations (60–350 ppm) that were either dry or humidified were administered at fixed time intervals. Geometric mean LTs obtained at wet (181 ppm) or dry (172 ppm) conditions did not differ significantly (P = 0.19) and were within the range of those reported by previous studies. These results suggest that humidity is not a critical factor in determining sensory irritation thresholds for ammonia, and future studies will examine if these findings are transferable to sensory irritation thresholds for other chemicals. PMID:27379250

  7. Novel Threshold Changeable Secret Sharing Schemes Based on Polynomial Interpolation.

    PubMed

    Yuan, Lifeng; Li, Mingchu; Guo, Cheng; Choo, Kim-Kwang Raymond; Ren, Yizhi

    2016-01-01

    After any distribution of secret sharing shadows in a threshold changeable secret sharing scheme, the threshold may need to be adjusted to deal with changes in the security policy and adversary structure. For example, when employees leave the organization, it is not realistic to expect departing employees to ensure the security of their secret shadows. Therefore, in 2012, Zhang et al. proposed (t → t', n) and ({t1, t2,⋯, tN}, n) threshold changeable secret sharing schemes. However, their schemes suffer from a number of limitations such as strict limit on the threshold values, large storage space requirement for secret shadows, and significant computation for constructing and recovering polynomials. To address these limitations, we propose two improved dealer-free threshold changeable secret sharing schemes. In our schemes, we construct polynomials to update secret shadows, and use two-variable one-way function to resist collusion attacks and secure the information stored by the combiner. We then demonstrate our schemes can adjust the threshold safely.

  8. Novel Threshold Changeable Secret Sharing Schemes Based on Polynomial Interpolation

    PubMed Central

    Li, Mingchu; Guo, Cheng; Choo, Kim-Kwang Raymond; Ren, Yizhi

    2016-01-01

    After any distribution of secret sharing shadows in a threshold changeable secret sharing scheme, the threshold may need to be adjusted to deal with changes in the security policy and adversary structure. For example, when employees leave the organization, it is not realistic to expect departing employees to ensure the security of their secret shadows. Therefore, in 2012, Zhang et al. proposed (t → t′, n) and ({t1, t2,⋯, tN}, n) threshold changeable secret sharing schemes. However, their schemes suffer from a number of limitations such as strict limit on the threshold values, large storage space requirement for secret shadows, and significant computation for constructing and recovering polynomials. To address these limitations, we propose two improved dealer-free threshold changeable secret sharing schemes. In our schemes, we construct polynomials to update secret shadows, and use two-variable one-way function to resist collusion attacks and secure the information stored by the combiner. We then demonstrate our schemes can adjust the threshold safely. PMID:27792784

  9. Vestibular Perceptual Thresholds Increase above the Age of 40.

    PubMed

    Bermúdez Rey, María Carolina; Clark, Torin K; Wang, Wei; Leeder, Tania; Bian, Yong; Merfeld, Daniel M

    2016-01-01

    We measured vestibular perceptual thresholds in 105 healthy humans (54F/51M) ranging from 18 to 80 years of age. Direction-recognition thresholds were measured using standard methods. The motion consisted of single cycles of sinusoidal acceleration at 0.2 Hz for roll tilt and 1.0 Hz for yaw rotation about an earth-vertical axis, inter-aural earth-horizontal translation (y-translation), inferior-superior earth-vertical translation (z-translation), and roll tilt. A large subset of this population (99 of 105) also performed a modified Romberg test of standing balance. Despite the relatively large population (54F/51M), we found no difference between thresholds of male and female subjects. After pooling across sex, we found that thresholds increased above the age of 40 for all five motion directions investigated. The data were best modeled by a two-segment age model that yielded a constant baseline below an age cutoff of about 40 and a threshold increase above the age cutoff. For all subjects who passed all conditions of the balance test, the baseline thresholds were 0.97°/s for yaw rotation, 0.66°/s for 1-Hz roll tilt, 0.35°/s for 0.2-Hz roll tilt, 0.58 cm/s for y-translation, and 1.24 cm/s for z-translation. As a percentage of the baseline, the fitted slopes (indicating the threshold increase each decade above the age cutoff) were 83% for z-translation, 56% for 1-Hz roll tilt, 46% for y-translation, 32% for 0.2-Hz roll tilt, and 15% for yaw rotation. Even taking age and other factors into consideration, we found a significant correlation of balance test failures with increasing roll-tilt thresholds.

  10. Vestibular Perceptual Thresholds Increase above the Age of 40

    PubMed Central

    Bermúdez Rey, María Carolina; Clark, Torin K.; Wang, Wei; Leeder, Tania; Bian, Yong; Merfeld, Daniel M.

    2016-01-01

    We measured vestibular perceptual thresholds in 105 healthy humans (54F/51M) ranging from 18 to 80 years of age. Direction-recognition thresholds were measured using standard methods. The motion consisted of single cycles of sinusoidal acceleration at 0.2 Hz for roll tilt and 1.0 Hz for yaw rotation about an earth-vertical axis, inter-aural earth-horizontal translation (y-translation), inferior–superior earth-vertical translation (z-translation), and roll tilt. A large subset of this population (99 of 105) also performed a modified Romberg test of standing balance. Despite the relatively large population (54F/51M), we found no difference between thresholds of male and female subjects. After pooling across sex, we found that thresholds increased above the age of 40 for all five motion directions investigated. The data were best modeled by a two-segment age model that yielded a constant baseline below an age cutoff of about 40 and a threshold increase above the age cutoff. For all subjects who passed all conditions of the balance test, the baseline thresholds were 0.97°/s for yaw rotation, 0.66°/s for 1-Hz roll tilt, 0.35°/s for 0.2-Hz roll tilt, 0.58 cm/s for y-translation, and 1.24 cm/s for z-translation. As a percentage of the baseline, the fitted slopes (indicating the threshold increase each decade above the age cutoff) were 83% for z-translation, 56% for 1-Hz roll tilt, 46% for y-translation, 32% for 0.2-Hz roll tilt, and 15% for yaw rotation. Even taking age and other factors into consideration, we found a significant correlation of balance test failures with increasing roll-tilt thresholds. PMID:27752252

  11. Factors affecting perceptual thresholds in a suprachoroidal retinal prosthesis.

    PubMed

    Shivdasani, Mohit N; Sinclair, Nicholas C; Dimitrov, Peter N; Varsamidis, Mary; Ayton, Lauren N; Luu, Chi D; Perera, Thushara; McDermott, Hugh J; Blamey, Peter J

    2014-09-09

    The suprachoroidal location for a retinal prosthesis provides advantages over other locations in terms of a simplified surgical procedure and a potentially more stable electrode-neural interface. The aim of this study was to assess the factors affecting perceptual thresholds, and to optimize stimulus parameters to achieve the lowest thresholds in patients implanted with a suprachoroidal retinal prosthesis. Three patients with profound vision loss from retinitis pigmentosa were implanted with a suprachoroidal array. Perceptual thresholds measured on individual electrodes were analyzed as a function of stimulus (return configuration, pulse polarity, pulse width, interphase gap, and rate), electrode (area and number of ganged electrodes), and clinical (retinal thickness and electrode-retina distance) parameters. A total of 92.8% of 904 measurements made up to 680 days post implantation yielded thresholds (range, 44-436 nanocoulombs [nC]) below the safe charge limit. Thresholds were found to vary between individuals and to depend significantly on electrode-retina distance, negligibly on retinal thickness, and not on electrode area or the number of ganged electrodes. Lowest thresholds were achieved when using a monopolar return, anodic-first polarity, short pulse widths (100 μs) combined with long interphase gaps (500 μs), and high stimulation rates (≥400 pulses per second [pps]). With suprachoroidal stimulation, anodic-first pulses with a monopolar return are most efficacious. To enable high rates, an appropriate combination of pulse width and interphase gap must be chosen to ensure low thresholds and electrode voltages. Electrode-retina distance needs to be monitored carefully owing to its influence on thresholds. These results inform implantable stimulator specifications for a suprachoroidal retinal prosthesis. (ClinicalTrials.gov number, NCT01603576.). Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  12. The Global Spike: Conserved Dendritic Properties Enable Unique Ca2+ Spike Generation in Low-Threshold Spiking Neurons

    PubMed Central

    Connelly, William M.; Crunelli, Vincenzo

    2015-01-01

    Low-threshold Ca2+ spikes (LTS) are an indispensible signaling mechanism for neurons in areas including the cortex, cerebellum, basal ganglia, and thalamus. They have critical physiological roles and have been strongly associated with disorders including epilepsy, Parkinson's disease, and schizophrenia. However, although dendritic T-type Ca2+ channels have been implicated in LTS generation, because the properties of low-threshold spiking neuron dendrites are unknown, the precise mechanism has remained elusive. Here, combining data from fluorescence-targeted dendritic recordings and Ca2+ imaging from low-threshold spiking cells in rat brain slices with computational modeling, the cellular mechanism responsible for LTS generation is established. Our data demonstrate that key somatodendritic electrical conduction properties are highly conserved between glutamatergic thalamocortical neurons and GABAergic thalamic reticular nucleus neurons and that these properties are critical for LTS generation. In particular, the efficiency of soma to dendrite voltage transfer is highly asymmetric in low-threshold spiking cells, and in the somatofugal direction, these neurons are particularly electrotonically compact. Our data demonstrate that LTS have remarkably similar amplitudes and occur synchronously throughout the dendritic tree. In fact, these Ca2+ spikes cannot occur locally in any part of the cell, and hence we reveal that LTS are generated by a unique whole-cell mechanism that means they always occur as spatially global spikes. This all-or-none, global electrical and biochemical signaling mechanism clearly distinguishes LTS from other signals, including backpropagating action potentials and dendritic Ca2+/NMDA spikes, and has important consequences for dendritic function in low-threshold spiking neurons. SIGNIFICANCE STATEMENT Low-threshold Ca2+ spikes (LTS) are critical for important physiological processes, including generation of sleep-related oscillations, and are

  13. Low-energy structure of above-threshold-ionization electron spectra: Role of the Coulomb threshold effect

    NASA Astrophysics Data System (ADS)

    Telnov, Dmitry A.; Chu, Shih-I.

    2011-06-01

    Recent experimental observations of above-threshold ionization of rare gas atoms and diatomic molecules by midinfrared laser fields [C. I. Blaga , Nat. Phys.PRLTAO1745-247310.1038/nphys1228 5, 335 (2009); W. Quan , Phys. Rev. Lett.PRLTAO0031-900710.1103/PhysRevLett.103.093001 103, 093001 (2009)] revealed a prominent maximum in the electron energy spectrum very close to the ionization threshold which is not reproduced by widely used Keldysh-Faisal-Reiss theories. We have performed fully ab initio theoretical analysis and precision calculations to explore the quantum origin of the low-energy structure (LES) observed in the experiments. Our study shows that an important role in shaping of LES is played by the effect of Coulomb attraction in the final electron state and the Coulomb threshold effect.

  14. Effects of Temperature on the Histotripsy Intrinsic Threshold for Cavitation.

    PubMed

    Vlaisavljevich, Eli; Xu, Zhen; Maxwell, Adam; Mancia, Lauren; Zhang, Xi; Lin, Kuang-Wei; Duryea, Alexander; Sukovich, Jonathan; Hall, Tim; Johnsen, Eric; Cain, Charles

    2016-05-10

    Histotripsy is an ultrasound ablation method that depends on the initiation of a dense cavitation bubble cloud to fractionate soft tissue. Previous work has demonstrated that a cavitation cloud can be formed by a single acoustic pulse with one high amplitude negative cycle, when the negative pressure amplitude exceeds a threshold intrinsic to the medium. The intrinsic thresholds in soft tissues and tissue phantoms that are water-based are similar to the intrinsic threshold of water over an experimentally verified frequency range of 0.3-3 MHz. Previous work studying the histotripsy intrinsic threshold has been limited to experiments performed at room temperature (~20°C). In this study, we investigate the effects of temperature on the histotripsy intrinsic threshold in water, which is essential to accurately predict the intrinsic thresholds expected over the full range of in vivo therapeutic temperatures. Based on previous work studying the histotripsy intrinsic threshold and classical nucleation theory, we hypothesize that the intrinsic threshold will decrease with increasing temperature. To test this hypothesis, the intrinsic threshold in water was investigated both experimentally and theoretically. The probability of generating cavitation bubbles was measured by applying a single pulse with one high amplitude negative cycle at 1 MHz to distilled, degassed water at temperatures ranging from 10°C-90°C. Cavitation was detected and characterized by passive cavitation detection and high-speed photography, from which the probability of cavitation was measured vs. pressure amplitude. The results indicate that the intrinsic threshold (the negative pressure at which the cavitation probability=0.5) significantly decreases with increasing temperature, showing a nearly linear decreasing trend from 29.8±0.4 MPa at 10˚C to 14.9±1.4 MPa at 90˚C. Overall, the results of this study support our hypothesis that the intrinsic threshold is highly dependent upon the temperature

  15. NaCl Taste Thresholds in 13 Inbred Mouse Strains

    PubMed Central

    Ishiwatari, Yutaka

    2012-01-01

    Molecular mechanisms of salty taste in mammals are not completely understood. We use genetic approaches to study these mechanisms. Previously, we developed a high-throughput procedure to measure NaCl taste thresholds, which involves conditioning mice to avoid LiCl and then examining avoidance of NaCl solutions presented in 48-h 2-bottle preference tests. Using this procedure, we measured NaCl taste thresholds of mice from 13 genealogically divergent inbred stains: 129P3/J, A/J, BALB/cByJ, C3H/HeJ, C57BL/6ByJ, C57BL/6J, CBA/J, CE/J, DBA/2J, FVB/NJ, NZB/BlNJ, PWK/PhJ, and SJL/J. We found substantial strain variation in NaCl taste thresholds: mice from the A/J and 129P3/J strains had high thresholds (were less sensitive), whereas mice from the BALB/cByJ, C57BL/6J, C57BL/6ByJ, CE/J, DBA/2J, NZB/BINJ, and SJL/J had low thresholds (were more sensitive). NaCl taste thresholds measured in this study did not significantly correlate with NaCl preferences or amiloride sensitivity of chorda tympani nerve responses to NaCl determined in the same strains in other studies. To examine whether strain differences in NaCl taste thresholds could have been affected by variation in learning ability or sensitivity to toxic effects of LiCl, we used the same method to measure citric acid taste thresholds in 4 inbred strains with large differences in NaCl taste thresholds but similar acid sensitivity in preference tests (129P3/J, A/J, C57BL/6J, and DBA/2J). Citric acid taste thresholds were similar in these 4 strains. This suggests that our technique measures taste quality–specific thresholds that are likely to represent differences in peripheral taste responsiveness. The strain differences in NaCl taste sensitivity found in this study provide a basis for genetic analysis of this phenotype. PMID:22293936

  16. Odor detection thresholds in a population of older adults.

    PubMed

    Schubert, Carla R; Fischer, Mary E; Pinto, A Alex; Klein, Barbara E K; Klein, Ronald; Cruickshanks, Karen J

    2017-06-01

    To measure odor detection thresholds and associated nasal and behavioral factors in an older adult population. Cross-sectional cohort study. Odor detection thresholds were obtained using an automated olfactometer on 832 participants, aged 68 to 99 (mean age = 77) years in the 21-year (2013-2016) follow-up visit of the Epidemiology of Hearing Loss Study. The mean odor detection threshold (ODT) score was 8.2 (range = 1-13; standard deviation = 2.54), corresponding to an n-butanol concentration of slightly less than 0.03%. Older participants were significantly more likely to have lower (worse) ODT scores than younger participants (P < .001). There were no significant differences in mean ODT scores between men and women. Older age was significantly associated with worse performance in multivariable regression models, and exercising at least once per week was associated with reduced odds of having a low (≤5) ODT score. Cognitive impairment was also associated with poor performance, whereas a history of allergies or a deviated septum was associated with better performance. Odor detection threshold scores were worse in older age groups but similar between men and women in this large population of older adults. Regular exercise was associated with better odor detection thresholds, adding to the evidence that decline in olfactory function with age may be partly preventable. 3b. Laryngoscope, 127:1257-1262, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  17. Granular motions near the threshold of entrainment

    NASA Astrophysics Data System (ADS)

    Valyrakis, Manousos; Alexakis, athanasios-Theodosios

    2016-04-01

    Our society is continuously impacted by significant weather events many times resulting in catastrophes that interrupt our normal way of life. In the context of climate change and increasing urbanisation these "extreme" hydrologic events are intensified both in magnitude and frequency, inducing costs of the order of billions of pounds. The vast majority of such costs and impacts (even more to developed societies) are due to water related catastrophes such as the geomorphic action of flowing water (including scouring of critical infrastructure, bed and bank destabilisation) and flooding. New tools and radically novel concepts are in need, to enable our society becoming more resilient. This presentation, emphasises the utility of inertial sensors in gaining new insights on the interaction of flow hydrodynamics with the granular surface at the particle scale and for near threshold flow conditions. In particular, new designs of the "smart-sphere" device are discussed with focus on the purpose specific sets of flume experiments, designed to identify the exact response of the particle resting at the bed surface for various below, near and above threshold flow conditions. New sets of measurements are presented for particle entrainment from a Lagrangian viewpoint. Further to finding direct application in addressing real world challenges in the water sector, it is shown that such novel sensor systems can also help the research community (both experimentalists and computational modellers) gain a better insight on the underlying processes governing granular dynamics.

  18. Depression Storage Thresholds in Prairie Hydrology

    NASA Astrophysics Data System (ADS)

    Martz, L. W.

    2012-12-01

    An initial and essential step in hydrologic modeling is to decompose a watershed into its constituent channel and catchment segments and to measure the geometric andenvironmental properties of those segments. TOPAZ (Topographic Parameterization) is a widely used software system that processes digital elevation models todelineate channel and catchment segments and to measure their geometric properties. TOPAZ and similar software are now widely used in meso-scale hydrologic modeling. TOPAZ and similar software assume that surface depressions are errors in the digital elevation data and apply various techniques to fill those depressions and direct flow across the resulting surface. However, it is the case in many low-relief areas of the earth's surface that depressions are real features that function as significant storage reservoirs. These depressions are typically strung together by connecting channels and the filling of depressions represents major thresholds in changing the contributing area of streams. This paper examines some recent advances in digital terrain analysis for hydrologic model parameterization that address the role of depression storage thresholds in producing step-wise and major changes in watershed contributing areas.

  19. Peaks Over Threshold (POT): A methodology for automatic threshold estimation using goodness of fit p-value

    NASA Astrophysics Data System (ADS)

    Solari, Sebastián.; Egüen, Marta; Polo, María. José; Losada, Miguel A.

    2017-04-01

    Threshold estimation in the Peaks Over Threshold (POT) method and the impact of the estimation method on the calculation of high return period quantiles and their uncertainty (or confidence intervals) are issues that are still unresolved. In the past, methods based on goodness of fit tests and EDF-statistics have yielded satisfactory results, but their use has not yet been systematized. This paper proposes a methodology for automatic threshold estimation, based on the Anderson-Darling EDF-statistic and goodness of fit test. When combined with bootstrapping techniques, this methodology can be used to quantify both the uncertainty of threshold estimation and its impact on the uncertainty of high return period quantiles. This methodology was applied to several simulated series and to four precipitation/river flow data series. The results obtained confirmed its robustness. For the measured series, the estimated thresholds corresponded to those obtained by nonautomatic methods. Moreover, even though the uncertainty of the threshold estimation was high, this did not have a significant effect on the width of the confidence intervals of high return period quantiles.

  20. High-throughput method for comparative analysis of denaturing gradient gel electrophoresis profiles from human fecal samples reveals significant increases in two bifidobacterial species after inulin-type prebiotic intake.

    PubMed

    Joossens, Marie; Huys, Geert; Van Steen, Kristel; Cnockaert, Margo; Vermeire, Séverine; Rutgeerts, Paul; Verbeke, Kristin; Vandamme, Peter; De Preter, Vicky

    2011-02-01

    Denaturing gradient gel electrophoresis (DGGE) is one of the most commonly used molecular tools to study complex microbial communities. Despite its widespread use, meaningful interpretative analysis remains a major drawback of this method. We evaluated the combination of computer-assisted band-matching with nonparametric statistics for comparative analysis of DGGE banding patterns. Fecal samples from 17 healthy volunteers who consumed 20 g of the prebiotic compound oligofructose-enriched inulin (OF-IN) for 4 weeks were analyzed before and after treatment. DGGE fingerprinting profiles were analyzed using bionumerics software version 4.6., which resulted in a data matrix that was used for statistical analysis. When comparing DGGE profiles before and after OF-IN intake with a Wilcoxon nonparametric test for paired data, two band-classes increased significantly after OF-IN intake (P<0.003 and <0.02). These two band-classes could be assigned to the species Bifidobacterium longum and Bifidobacterium adolescentis by band-sequencing analysis, and their significant increase was quantitatively confirmed with real-time PCR using species-specific primers (respectively P<0.012 and <0.010). Therefore, the nonparametric analysis of a data matrix obtained by computer-assisted band-matching of complex profiles facilitated the interpretative analysis of these profiles and provided an objective and high-throughput method for the detection of significant taxonomic differences in larger numbers of complex profiles.

  1. Epidemic thresholds for bipartite networks

    NASA Astrophysics Data System (ADS)

    Hernández, D. G.; Risau-Gusman, S.

    2013-11-01

    It is well known that sexually transmitted diseases (STD) spread across a network of human sexual contacts. This network is most often bipartite, as most STD are transmitted between men and women. Even though network models in epidemiology have quite a long history now, there are few general results about bipartite networks. One of them is the simple dependence, predicted using the mean field approximation, between the epidemic threshold and the average and variance of the degree distribution of the network. Here we show that going beyond this approximation can lead to qualitatively different results that are supported by numerical simulations. One of the new features, that can be relevant for applications, is the existence of a critical value for the infectivity of each population, below which no epidemics can arise, regardless of the value of the infectivity of the other population.

  2. Threshold effect under nonlinear limitation of the intensity of high-power light

    SciTech Connect

    Tereshchenko, S A; Podgaetskii, V M; Gerasimenko, A Yu; Savel'ev, M S

    2015-04-30

    A model is proposed to describe the properties of limiters of high-power laser radiation, which takes into account the threshold character of nonlinear interaction of radiation with the working medium of the limiter. The generally accepted non-threshold model is a particular case of the threshold model if the threshold radiation intensity is zero. Experimental z-scan data are used to determine the nonlinear optical characteristics of media with carbon nanotubes, polymethine and pyran dyes, zinc selenide, porphyrin-graphene and fullerene-graphene. A threshold effect of nonlinear interaction between laser radiation and some of investigated working media of limiters is revealed. It is shown that the threshold model more adequately describes experimental z-scan data. (nonlinear optical phenomena)

  3. Sesame allergy threshold dose distribution.

    PubMed

    Dano, D; Remington, B C; Astier, C; Baumert, J L; Kruizinga, A G; Bihain, B E; Taylor, S L; Kanny, G

    2015-09-01

    Sesame is a relevant food allergen in France. Compared to other allergens there is a lack of food challenge data and more data could help sesame allergy risk management. The aim of this study is to collect more sesame challenge data and investigate the most efficient food challenge method for future studies. Records of patients at University Hospital in Nancy (France) with objective symptoms to sesame challenges were collected and combined with previously published data. An estimation of the sesame allergy population threshold was calculated based on individual NOAELs and LOAELs. Clinical dosing schemes at Nancy were investigated to see if the optimal protocol for sesame is currently used. Fourteen patients (10 M/4 F, 22 ± 14.85 years old) with objective symptoms were added to previously published data making a total of 35 sesame allergic patients. The most sensitive patient reacted to the first dose at challenge of 1.02 mg sesame protein. The ED05 ranges between 1.2 and 4.0 mg of sesame protein (Log-Normal, Log-Logistic, and Weibull models) and the ED10 between 4.2 and 6.2 mg. The optimal food challenge dosing scheme for sesame follows semi-log dose increases from 0.3 to 3000 mg protein. This article provides a valuable update to the existing clinical literature regarding sesame NOAELs and LOAELs. Establishment of a population threshold for sesame could help in increasing the credibility of precautionary labelling and decrease the costs associated with unexpected allergic reactions. Also, the use of an optimal dosing scheme would decrease time spent on diagnostic and thereafter on the economic burden of sesame allergy diagnosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Comparative Genomics of Two Closely Related Unicellular Thermo-Acidophilic Red Algae, Galdieria sulphuraria and Cyanidioschyzon merolae, Reveals the Molecular Basis of the Metabolic Flexibility of Galdieria sulphuraria and Significant Differences in Carbohydrate Metabolism of Both Algae1

    PubMed Central

    Barbier, Guillaume; Oesterhelt, Christine; Larson, Matthew D.; Halgren, Robert G.; Wilkerson, Curtis; Garavito, R. Michael; Benning, Christoph; Weber, Andreas P.M.

    2005-01-01

    Unicellular algae serve as models for the study and discovery of metabolic pathways, for the functional dissection of cell biological processes such as organellar division and cell motility, and for the identification of novel genes and gene functions. The recent completion of several algal genome sequences and expressed sequence tag collections and the establishment of nuclear and organellar transformation methods has opened the way for functional genomics approaches using algal model systems. The thermo-acidophilic unicellular red alga Galdieria sulphuraria represents a particularly interesting species for a genomics approach owing to its extraordinary metabolic versatility such as heterotrophic and mixotrophic growth on more than 50 different carbon sources and its adaptation to hot acidic environments. However, the ab initio prediction of genes required for unknown metabolic pathways from genome sequences is not trivial. A compelling strategy for gene identification is the comparison of similarly sized genomes of related organisms with different physiologies. Using this approach, candidate genes were identified that are critical to the metabolic versatility of Galdieria. Expressed sequence tags and high-throughput genomic sequence reads covering >70% of the G. sulphuraria genome were compared to the genome of the unicellular, obligate photoautotrophic red alga Cyanidioschyzon merolae. More than 30% of the Galdieria sequences did not relate to any of the Cyanidioschyzon genes. A closer inspection of these sequences revealed a large number of membrane transporters and enzymes of carbohydrate metabolism that are unique to Galdieria. Based on these data, it is proposed that genes involved in the uptake of reduced carbon compounds and enzymes involved in their metabolism are crucial to the metabolic flexibility of G. sulphuraria. PMID:15710685

  5. Do Optimal Prognostic Thresholds in Continuous Physiological Variables Really Exist? Analysis of Origin of Apparent Thresholds, with Systematic Review for Peak Oxygen Consumption, Ejection Fraction and BNP

    PubMed Central

    Leong, Tora; Rehman, Michaela B.; Pastormerlo, Luigi Emilio; Harrell, Frank E.; Coats, Andrew J. S.; Francis, Darrel P.

    2014-01-01

    Background Clinicians are sometimes advised to make decisions using thresholds in measured variables, derived from prognostic studies. Objectives We studied why there are conflicting apparently-optimal prognostic thresholds, for example in exercise peak oxygen uptake (pVO2), ejection fraction (EF), and Brain Natriuretic Peptide (BNP) in heart failure (HF). Data Sources and Eligibility Criteria Studies testing pVO2, EF or BNP prognostic thresholds in heart failure, published between 1990 and 2010, listed on Pubmed. Methods First, we examined studies testing pVO2, EF or BNP prognostic thresholds. Second, we created repeated simulations of 1500 patients to identify whether an apparently-optimal prognostic threshold indicates step change in risk. Results 33 studies (8946 patients) tested a pVO2 threshold. 18 found it prognostically significant: the actual reported threshold ranged widely (10–18 ml/kg/min) but was overwhelmingly controlled by the individual study population's mean pVO2 (r = 0.86, p<0.00001). In contrast, the 15 negative publications were testing thresholds 199% further from their means (p = 0.0001). Likewise, of 35 EF studies (10220 patients), the thresholds in the 22 positive reports were strongly determined by study means (r = 0.90, p<0.0001). Similarly, in the 19 positives of 20 BNP studies (9725 patients): r = 0.86 (p<0.0001). Second, survival simulations always discovered a “most significant” threshold, even when there was definitely no step change in mortality. With linear increase in risk, the apparently-optimal threshold was always near the sample mean (r = 0.99, p<0.001). Limitations This study cannot report the best threshold for any of these variables; instead it explains how common clinical research procedures routinely produce false thresholds. Key Findings First, shifting (and/or disappearance) of an apparently-optimal prognostic threshold is strongly determined by studies' average pVO2, EF or BNP. Second

  6. Sweet taste and menthol increase cough reflex thresholds.

    PubMed

    Wise, Paul M; Breslin, Paul A S; Dalton, Pamela

    2012-06-01

    Cough is a vital protective reflex that is triggered by both mechanical and chemical stimuli. The current experiments explored how chemosensory stimuli modulate this important reflex. Cough thresholds were measured using a single-inhalation capsaicin challenge. Experiment 1 examined the impact of sweet taste: Cough thresholds were measured after rinsing the mouth with a sucrose solution (sweet) or with water (control). Experiment 2 examined the impact of menthol: Cough thresholds were measured after inhaling headspace above a menthol solution (menthol vapor) or headspace above the mineral oil solvent (control). Experiment 3 examined the impact of rinsing the mouth with a (bitter) sucrose octaacetate solution. Rinsing with sucrose and inhaling menthol vapor significantly increased measured cough thresholds. Rinsing with sucrose octaacete caused a non-significant decrease in cough thresholds, an important demonstration of specificity. Decreases in cough reflex sensitivity from sucrose or menthol could help explain why cough syrups without pharmacologically active ingredients are often almost as effective as formulations with an added drug. Further, the results support the idea that adding menthol to cigarettes might make tobacco smoke more tolerable for beginning smokers, at least in part, by reducing the sensitivity of an important airway defense mechanism. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Phosphate control of phoA, phoC and phoD gene expression in Streptomyces coelicolor reveals significant differences in binding of PhoP to their promoter regions.

    PubMed

    Apel, Alexander K; Sola-Landa, Alberto; Rodríguez-García, Antonio; Martín, Juan F

    2007-10-01

    Three putative alkaline phosphatase genes, phoA, phoC and phoD, were identified in the genome of Streptomyces coelicolor by homology with the amino acid sequence obtained from the PhoA protein of Streptomyces griseus. PhoA and PhoC correspond to broad-spectrum alkaline phosphatases whereas PhoD is similar to a Ca(2+)-dependent phospholipase D of Streptomyces chromofuscus. The phoA and phoD genes were efficiently expressed in R5 medium under phosphate-limited conditions, as shown by studies using the xylE reporter gene, whereas phoC was poorly transcribed under the same conditions. Expression of phoA was clearly PhoP-dependent since it was not transcribed in the S. coelicolor DeltaphoP mutant and was strongly activated under low phosphate concentrations. Similarly, expression of phoD was PhoP-dependent and highly sensitive to phosphate availability. By contrast, expression of phoC was not PhoP-dependent. Electrophoretic mobility shift assays showed that PhoP binds to the phoA and phoD promoters, but not to that of phoC. Footprinting studies with GST-PhoP revealed the presence of a PHO box (two direct 11 nt repeats) in the phoA promoter and two PHO boxes in the promoter of phoD. The transcription start points of the three promoters were identified by primer extension. The transcription start point of phoD coincides with the G of its translation start codon, indicating that this gene is transcribed as a leaderless mRNA. The deduced -10 and -35 regions of phoD (but not those of phoA) overlapped with the PHO boxes in this promoter, suggesting that an excess of PhoP interferes with binding of the RNA polymerase to this promoter. In summary, the three promoters showed clear differences in the modulation of their expression by PhoP.

  8. Shape discrimination thresholds among subjects with emmetropia and corrected myopia.

    PubMed

    Rajeev, Narayanan; Tan, Eddie; Liyana, Raja; Metha, Andrew

    2015-07-01

    Myopia is highly prevalent in some Asian countries yet the ability of subjects with myopia to discriminate shapes using radial frequency (RF) patterns—circular patterns that are defined by sinusoidal modulation of the radius in polar coordinates—is not well documented. In this psychophysical study, we explore the relative ability of subjects with corrected myopia to discriminate shapes using radial frequency patterns. Specifically, the aims were to find if there are any differences in modulation detection thresholds among subjects with emmetropia and corrected myopia and to establish thresholds as a function of myopic refractive error. Shape discrimination thresholds were measured for subjects with emmetropia (n = 20) and corrected myopia (n = 20) using circular D4 (fourth derivative of Gaussian) radial frequency patterns. A total of five radial frequency patterns (RF1 to RF16) with peak spatial frequencies of 2, 4, 6 and 8 (SF2 to SF8) cycles per degree were studied. The radial frequency suffix determines the number of deformation cycles present around the circumference, while the peak spatial frequency is related to the thickness of the circular contour. Overall, shape discrimination thresholds were not significantly different (p > 0.05) between subjects with emmetropia and corrected myopia. Similarly, there was no significant correlation (p > 0.05) in thresholds with the magnitude of corrected myopia. Shape discrimination performance was best for RF8 patterns, with thresholds ranging from nine to 12 seconds of arc for SF2 to SF6 patterns and from 20 to 22 seconds of arc for SF8 patterns. Thresholds were significantly higher (p < 0.05) for SF8 patterns compared to the other spatial frequency patterns (SF2 to SF6) for all radial frequency patterns. The average thresholds increased by about 1 to 1.5 log units from RF1 to RF4 and RF8. Across all patterns studied here, shape discrimination thresholds remain at hyperacuity levels and are not degraded in subjects

  9. Improved Culture Medium (TiKa) for Mycobacterium avium Subspecies Paratuberculosis (MAP) Matches qPCR Sensitivity and Reveals Significant Proportions of Non-viable MAP in Lymphoid Tissue of Vaccinated MAP Challenged Animals

    PubMed Central

    Bull, Tim J.; Munshi, Tulika; Mikkelsen, Heidi; Hartmann, Sofie B.; Sørensen, Maria R.; Garcia, Joanna S.; Lopez-Perez, Paula M.; Hofmann, Sven; Hilpert, Kai; Jungersen, Gregers

    2017-01-01

    The quantitative detection of viable pathogen load is an important tool in determining the degree of infection in animals and contamination of foodstuffs. Current conventional culture methods are limited in their ability to determine these levels in Mycobacterium avium subspecies paratuberculosis (MAP) due to slow growth, clumping and low recoverability issues. The principle goal of this study was to evaluate a novel culturing process (TiKa) with unique ability to stimulate MAP growth from low sample loads and dilutions. We demonstrate it was able to stimulate a mean 29-fold increase in recoverability and an improved sensitivity of up to three logs when compared with conventional culture. Using TiKa culture, MAP clumping was minimal and produced visible colonies in half the time required by standard culture methods. Parallel quantitative evaluation of the TiKa culture approach and qPCR on MAP loads in tissue and gut mucosal samples from a MAP vaccine-challenge study, showed good correlations between colony counts (cfu) and qPCR derived genome equivalents (Geq) over a large range of loads with a 30% greater sensitivity for TiKa culture approach at low loads (two logs). Furthermore, the relative fold changes in Geq and cfu from the TiKa culture approach suggests that non-mucosal tissue loads from MAP infected animals contained a reduced proportion of non-viable MAP (mean 19-fold) which was reduced significantly further (mean 190-fold) in vaccinated “reactor” calves. This study shows TiKa culture equates well with qPCR and provides important evidence that accuracy in estimating viable MAP load using DNA tests alone may vary significantly between samples of mucosal and lymphatic origin. PMID:28101082

  10. Improved Culture Medium (TiKa) for Mycobacterium avium Subspecies Paratuberculosis (MAP) Matches qPCR Sensitivity and Reveals Significant Proportions of Non-viable MAP in Lymphoid Tissue of Vaccinated MAP Challenged Animals.

    PubMed

    Bull, Tim J; Munshi, Tulika; Mikkelsen, Heidi; Hartmann, Sofie B; Sørensen, Maria R; Garcia, Joanna S; Lopez-Perez, Paula M; Hofmann, Sven; Hilpert, Kai; Jungersen, Gregers

    2016-01-01

    The quantitative detection of viable pathogen load is an important tool in determining the degree of infection in animals and contamination of foodstuffs. Current conventional culture methods are limited in their ability to determine these levels in Mycobacterium avium subspecies paratuberculosis (MAP) due to slow growth, clumping and low recoverability issues. The principle goal of this study was to evaluate a novel culturing process (TiKa) with unique ability to stimulate MAP growth from low sample loads and dilutions. We demonstrate it was able to stimulate a mean 29-fold increase in recoverability and an improved sensitivity of up to three logs when compared with conventional culture. Using TiKa culture, MAP clumping was minimal and produced visible colonies in half the time required by standard culture methods. Parallel quantitative evaluation of the TiKa culture approach and qPCR on MAP loads in tissue and gut mucosal samples from a MAP vaccine-challenge study, showed good correlations between colony counts (cfu) and qPCR derived genome equivalents (Geq) over a large range of loads with a 30% greater sensitivity for TiKa culture approach at low loads (two logs). Furthermore, the relative fold changes in Geq and cfu from the TiKa culture approach suggests that non-mucosal tissue loads from MAP infected animals contained a reduced proportion of non-viable MAP (mean 19-fold) which was reduced significantly further (mean 190-fold) in vaccinated "reactor" calves. This study shows TiKa culture equates well with qPCR and provides important evidence that accuracy in estimating viable MAP load using DNA tests alone may vary significantly between samples of mucosal and lymphatic origin.

  11. Quasi-two-dimensional threshold voltage model for junctionless cylindrical surrounding gate metal-oxide-semiconductor field-effect transistor with dual-material gate

    NASA Astrophysics Data System (ADS)

    Li, Cong; Zhuang, Yi-Qi; Zhang, Li; Jin, Gang

    2014-01-01

    Based on the quasi-two-dimensional (2D) solution of Poisson's equation in two continuous channel regions, an analytical threshold voltage model for short-channel junctionless dual-material cylindrical surrounding-gate (JLDMCSG) metal-oxide-semiconductor field-effect transistor (MOSFET) is developed. Using the derived model, channel potential distribution, horizontal electrical field distribution, and threshold voltage roll-off of JLDMCSG MOSFET are investigated. Compared with junctionless single-material CSG (JLSGCSG) MOSFET, JLDMCSG MOSFET can effectively suppress short-channel effects and simultaneously improve carrier transport efficiency. It is also revealed that threshold voltage roll-off of JLDMCSG can be significantly reduced by adopting both a small oxide thickness and a small silicon channel radius. The model is verified by comparing its calculated results with that obtained from three-dimensional (3D) numerical device simulator ISE.

  12. Thresholds of allergenic proteins in foods

    SciTech Connect

    Hourihane, Jonathan O'B. . E-mail: J.Hourihane@soton.ac.uk; Knulst, Andre C.

    2005-09-01

    Threshold doses or Estimated Eliciting Doses (EEDs) represent an important new field of research in food allergy. Clinicians and regulators have embraced some toxicological concepts such as LOAEL and NOAEL and applied them to an area of significant clinical uncertainty and interest. The impact of intrinsic human factors (e.g., asthma and exercise) and extrinsic event factors (e.g., season, location and especially dose of allergen) on a future allergic reaction in the community needs to be considered carefully when interpreting results of clinical and research low-dose food challenges. The ongoing cooperation of food allergy research groups in medicine, food science and government will surely deliver results of the highest importance to the wider communities of allergology, food science and technology and the increasing number of allergic consumers.

  13. Is heart rate variability a feasible method to determine anaerobic threshold in progressive resistance exercise in coronary artery disease?

    PubMed

    Sperling, Milena P R; Simões, Rodrigo P; Caruso, Flávia C R; Mendes, Renata G; Arena, Ross; Borghi-Silva, Audrey

    2016-01-01

    Recent studies have shown that the magnitude of the metabolic and autonomic responses during progressive resistance exercise (PRE) is associated with the determination of the anaerobic threshold (AT). AT is an important parameter to determine intensity in dynamic exercise. To investigate the metabolic and cardiac autonomic responses during dynamic resistance exercise in patients with Coronary Artery Disease (CAD). Twenty men (age = 63±7 years) with CAD [Left Ventricular Ejection Fraction (LVEF) = 60±10%] underwent a PRE protocol on a leg press until maximal exertion. The protocol began at 10% of One Repetition Maximum Test (1-RM), with subsequent increases of 10% until maximal exhaustion. Heart Rate Variability (HRV) indices from Poincaré plots (SD1, SD2, SD1/SD2) and time domain (rMSSD and RMSM), and blood lactate were determined at rest and during PRE. Significant alterations in HRV and blood lactate were observed starting at 30% of 1-RM (p<0.05). Bland-Altman plots revealed a consistent agreement between blood lactate threshold (LT) and rMSSD threshold (rMSSDT) and between LT and SD1 threshold (SD1T). Relative values of 1-RM in all LT, rMSSDT and SD1T did not differ (29%±5 vs 28%±5 vs 29%±5 Kg, respectively). HRV during PRE could be a feasible noninvasive method of determining AT in CAD patients to plan intensities during cardiac rehabilitation.

  14. Is heart rate variability a feasible method to determine anaerobic threshold in progressive resistance exercise in coronary artery disease?

    PubMed Central

    Sperling, Milena P. R.; Simões, Rodrigo P.; Caruso, Flávia C. R.; Mendes, Renata G.; Arena, Ross; Borghi-Silva, Audrey

    2016-01-01

    ABSTRACT Background Recent studies have shown that the magnitude of the metabolic and autonomic responses during progressive resistance exercise (PRE) is associated with the determination of the anaerobic threshold (AT). AT is an important parameter to determine intensity in dynamic exercise. Objectives To investigate the metabolic and cardiac autonomic responses during dynamic resistance exercise in patients with Coronary Artery Disease (CAD). Method Twenty men (age = 63±7 years) with CAD [Left Ventricular Ejection Fraction (LVEF) = 60±10%] underwent a PRE protocol on a leg press until maximal exertion. The protocol began at 10% of One Repetition Maximum Test (1-RM), with subsequent increases of 10% until maximal exhaustion. Heart Rate Variability (HRV) indices from Poincaré plots (SD1, SD2, SD1/SD2) and time domain (rMSSD and RMSM), and blood lactate were determined at rest and during PRE. Results Significant alterations in HRV and blood lactate were observed starting at 30% of 1-RM (p<0.05). Bland-Altman plots revealed a consistent agreement between blood lactate threshold (LT) and rMSSD threshold (rMSSDT) and between LT and SD1 threshold (SD1T). Relative values of 1-RM in all LT, rMSSDT and SD1T did not differ (29%±5 vs 28%±5 vs 29%±5 Kg, respectively). Conclusion HRV during PRE could be a feasible noninvasive method of determining AT in CAD patients to plan intensities during cardiac rehabilitation. PMID:27556384

  15. Experimental pain thresholds and plasma beta-endorphin levels during exercise.

    PubMed

    Droste, C; Greenlee, M W; Schreck, M; Roskamm, H

    1991-03-01

    Experimental pain thresholds (electrical intracutaneous finger and dental pulp stimulation) and plasma hormone levels (beta-endorphin, cortisol, and catecholamines) were measured in ten healthy sportive men before, during, and after progressively more strenuous physical exercise. In a double-blind study conducted on two different days, 20 mg of the opioid-antagonist naloxone or placebo was administered prior to exercise. A significant pain threshold elevation was found during exercise for finger (ANOVA, P less than 0.004) and dental pulp stimulation (P less than 0.01). Pain threshold elevation was most pronounced during maximal exertion, at which time the subjects reported the greatest subjective fatigue. Thresholds remained elevated 10-15 min after the end of exercise, and, 60 min after exercise, thresholds returned to baseline values. The subjective magnitude estimation of suprathreshold stimuli was significantly reduced (P less than 0.0001) 5-10 min after exercise. Plasma beta-endorphin, cortisol, and catecholamines increased significantly (P less than 0.0005, all values) during exercise. Plasma beta-endorphin levels did not correlate significantly with pain thresholds (r = -0.37, NS). Naloxone failed to affect pain thresholds, although beta-endorphin and cortisol increased significantly more (P less than 0.02) during exercise after naloxone. It is concluded that short-term, exhaustive physical exercise can evoke a transient elevation in pain thresholds. This exercise-induced elevation in pain threshold does not, however, appear to be directly related to plasma endorphin levels.

  16. Regulatory criteria: Legal or ecological thresholds?

    SciTech Connect

    Cook, J.M.; Skorupa, J.P.; Schwarzbach, S.E.

    1994-12-31

    Selenium-laden irrigation drainwater has been identified as a significant threat to breeding waterfowl and shorebirds in terminal sink environments throughout the western United States. Due to historic wetland habitat losses, irrigation drainwater disposal ponds represent virtually all the available breeding habitat for waterbirds in the southern San Joaquin Valley of California. Egg selenium residues from birds breeding at these ponds have been monitored by the US Fish and Wildlife Service since 1987, and physiological risk thresholds for individual and population-level hatchability and teratogenesis have been determined from these studies. For Blacknecked stilt populations, egg selenium below 3 ppm may be considered a safe level, hatchability is significantly depressed at mean egg selenium concentrations above 8 ppm, and induction of teratogenesis is virtually certain at egg selenium levels above 18 ppm (p < 0.05). Egg samples collected in 1993 from these ponds showed concentrations as high as 160 ppm. Despite the high degree of statistical confidence in these effects thresholds, and the incidence of selenium-induced bird death and deformity at these ponds, regulation of evaporation ponds has been problematic. Existing civil statutes regarding water quality are dependent on risk-based criteria, but irrigation drainwater is exempted from these regulations. The only applicable law is the Migratory Bird Treaty Act, a criminal statute with no risk-based guidelines, and consequently no wildlife safety factors. The authors present data from the San Joaquin Valley in the context of these regulatory and legal limitations. Evaluation of acute and chronic models for ambient water quality indicate that this approach may not provide adequate protection for breeding birds. Based on the inadequacy of these models, the authors consider the development of regulatory criteria for egg selenium, a standard which is ecologically relevant.

  17. DNA repair by MGMT, but not AAG, causes a threshold in alkylation-induced colorectal carcinogenesis.

    PubMed

    Fahrer, Jörg; Frisch, Janina; Nagel, Georg; Kraus, Alexander; Dörsam, Bastian; Thomas, Adam D; Reißig, Sonja; Waisman, Ari; Kaina, Bernd

    2015-10-01

    Epidemiological studies indicate that N-nitroso compounds (NOC) are causally linked to colorectal cancer (CRC). NOC induce DNA alkylations, including O (6)-methylguanine (O (6)-MeG) and N-methylated purines, which are repaired by O (6)-MeG-DNA methyltransferase (MGMT) and N-alkyladenine-DNA glycosylase (AAG)-initiated base excision repair, respectively. In view of recent evidence of nonlinear mutagenicity for NOC-like compounds, the question arises as to the existence of threshold doses in CRC formation. Here, we set out to determine the impact of DNA repair on the dose-response of alkylation-induced CRC. DNA repair proficient (WT) and deficient (Mgmt (-/-), Aag (-/-) and Mgmt (-/-)/Aag (-/-)) mice were treated with azoxymethane (AOM) and dextran sodium sulfate to trigger CRC. Tumors were quantified by non-invasive mini-endoscopy. A non-linear increase in CRC formation was observed in WT and Aag (-/-) mice. In contrast, a linear dose-dependent increase in tumor frequency was found in Mgmt (-/-) and Mgmt (-/-)/Aag (-/-) mice. The data were corroborated by hockey stick modeling, yielding similar carcinogenic thresholds for WT and Aag (-/-) and no threshold for MGMT lacking mice. O (6)-MeG levels and depletion of MGMT correlated well with the observed dose-response in CRC formation. AOM induced dose-dependently DNA double-strand breaks in colon crypts including Lgr5-positive colon stem cells, which coincided with ATR-Chk1-p53 signaling. Intriguingly, Mgmt (-/-) mice displayed significantly enhanced levels of γ-H2AX, suggesting the usefulness of γ-H2AX as an early genotoxicity marker in the colorectum. This study demonstrates for the first time a non-linear dose-response for alkylation-induced colorectal carcinogenesis and reveals DNA repair by MGMT, but not AAG, as a key node in determining a carcinogenic threshold.

  18. Marker-Based Estimates Reveal Significant Non-additive Effects in Clonally Propagated Cassava (Manihot esculenta): Implications for the Prediction of Total Genetic Value and the Selection of Varieties.

    PubMed

    Wolfe, Marnin D; Kulakow, Peter; Rabbi, Ismail Y; Jannink, Jean-Luc

    2016-08-31

    In clonally propagated crops, non-additive genetic effects can be effectively exploited by the identification of superior genetic individuals as varieties. Cassava (Manihot esculenta Crantz) is a clonally propagated staple food crop that feeds hundreds of millions. We quantified the amount and nature of non-additive genetic variation for three key traits in a breeding population of cassava from sub-Saharan Africa using additive and non-additive genome-wide marker-based relationship matrices. We then assessed the accuracy of genomic prediction for total (additive plus non-additive) genetic value. We confirmed previous findings based on diallel populations, that non-additive genetic variation is significant for key cassava traits. Specifically, we found that dominance is particularly important for root yield and epistasis contributes strongly to variation in CMD resistance. Further, we showed that total genetic value predicted observed phenotypes more accurately than additive only models for root yield but not for dry matter content, which is mostly additive or for CMD resistance, which has high narrow-sense heritability. We address the implication of these results for cassava breeding and put our work in the context of previous results in cassava, and other plant and animal species.

  19. A new iterative triclass thresholding technique in image segmentation.

    PubMed

    Cai, Hongmin; Yang, Zhong; Cao, Xinhua; Xia, Weiming; Xu, Xiaoyin

    2014-03-01

    We present a new method in image segmentation that is based on Otsu's method but iteratively searches for subregions of the image for segmentation, instead of treating the full image as a whole region for processing. The iterative method starts with Otsu's threshold and computes the mean values of the two classes as separated by the threshold. Based on the Otsu's threshold and the two mean values, the method separates the image into three classes instead of two as the standard Otsu's method does. The first two classes are determined as the foreground and background and they will not be processed further. The third class is denoted as a to-be-determined (TBD) region that is processed at next iteration. At the succeeding iteration, Otsu's method is applied on the TBD region to calculate a new threshold and two class means and the TBD region is again separated into three classes, namely, foreground, background, and a new TBD region, which by definition is smaller than the previous TBD regions. Then, the new TBD region is processed in the similar manner. The process stops when the Otsu's thresholds calculated between two iterations is less than a preset threshold. Then, all the intermediate foreground and background regions are, respectively, combined to create the final segmentation result. Tests on synthetic and real images showed that the new iterative method can achieve better performance than the standard Otsu's method in many challenging cases, such as identifying weak objects and revealing fine structures of complex objects while the added computational cost is minimal.

  20. Speech evoked auditory brainstem response and gap detection threshold in middle-aged individual.

    PubMed

    Sanju, Himanshu Kumar; Bohra, Vaishnavi; Sinha, Sujeet Kumar

    2017-04-01

    This study aimed at characterizing the gap detection threshold (GDT) and speech evoked ABR (SABR) in younger and middle-aged individuals. Two groups of subjects were participated in the study which includes 15 young adults in the age range of 15-25 years and 15 middle-aged individuals in the age range of 40-60 years. SABR with stimulus/da/of 40 ms and GDT were investigated on both groups. For SABR, Mann-Whitney U test revealed that ageing has significantly adverse effect on the encoding of F1 and F2 at brainstem level. However, no significant effect of ageing (till middle age) on the encoding of F0 was observed in present study. Mann-Whitney U test also showed significant longer latency of wave V in middle-aged individuals compared to younger adults. Furthermore, GDT was significantly better in younger adults compared to middle-aged individuals according to Mann-Whitney U test. This study also revealed no significant correlation between GDT and F0, F1, F2 for younger as well as middle-aged individuals. The findings of this study showed poor encoding of certain aspects of speech at brainstem level in middle-aged individuals compared to younger adults. This study also revealed deterioration of auditory processes in middle-aged individuals.

  1. Thresholds for Cenozoic bipolar glaciation.

    PubMed

    Deconto, Robert M; Pollard, David; Wilson, Paul A; Pälike, Heiko; Lear, Caroline H; Pagani, Mark

    2008-10-02

    The long-standing view of Earth's Cenozoic glacial history calls for the first continental-scale glaciation of Antarctica in the earliest Oligocene epoch ( approximately 33.6 million years ago), followed by the onset of northern-hemispheric glacial cycles in the late Pliocene epoch, about 31 million years later. The pivotal early Oligocene event is characterized by a rapid shift of 1.5 parts per thousand in deep-sea benthic oxygen-isotope values (Oi-1) within a few hundred thousand years, reflecting a combination of terrestrial ice growth and deep-sea cooling. The apparent absence of contemporaneous cooling in deep-sea Mg/Ca records, however, has been argued to reflect the growth of more ice than can be accommodated on Antarctica; this, combined with new evidence of continental cooling and ice-rafted debris in the Northern Hemisphere during this period, raises the possibility that Oi-1 represents a precursory bipolar glaciation. Here we test this hypothesis using an isotope-capable global climate/ice-sheet model that accommodates both the long-term decline of Cenozoic atmospheric CO(2) levels and the effects of orbital forcing. We show that the CO(2) threshold below which glaciation occurs in the Northern Hemisphere ( approximately 280 p.p.m.v.) is much lower than that for Antarctica ( approximately 750 p.p.m.v.). Therefore, the growth of ice sheets in the Northern Hemisphere immediately following Antarctic glaciation would have required rapid CO(2) drawdown within the Oi-1 timeframe, to levels lower than those estimated by geochemical proxies and carbon-cycle models. Instead of bipolar glaciation, we find that Oi-1 is best explained by Antarctic glaciation alone, combined with deep-sea cooling of up to 4 degrees C and Antarctic ice that is less isotopically depleted (-30 to -35 per thousand) than previously suggested. Proxy CO(2) estimates remain above our model's northern-hemispheric glaciation threshold of approximately 280 p.p.m.v. until approximately 25 Myr

  2. Study of the improvement in bone conduction threshold after stapedectomy.

    PubMed

    García-Iza, Leire; Navarro, Juan José; Goiburu, Miren; Pérez, Nuria; Altuna, Xabier

    2016-01-01

    Bone conduction threshold depression is not always a result of inner ear and cochlear nerve pathology. In fact, middle ear pathologies may be responsible for such threshold depression, as occurs in otosclerosis. The aims of this study were to evaluate the improvement of bone conduction threshold in patients with otosclerosis that underwent stapedectomy and to study the postoperative audiological results. This was a retrospective study on 95 patients (116 ears) diagnosed with otosclerosis having conductive or mixed hearing loss that received surgery (stapedectomy and complete removal of the footplate) consecutively. Audiometry was performed on all patients pre- and postoperatively (one month and one year after surgery). Bone and air conduction thresholds were measured at 4 frequencies (500, 1000, 2000 and 4000Hz). The air-bone gap was closed, with a residual air-bone gap below 10dB in 92.2% of the patients and below 5dB in 79.3% of the cases. The air conduction threshold improved an average of 25dB. The patients that had an affected bone conduction threshold preoperatively improved bone conduction postoperatively at the frequencies of 1000 and 2000Hz (6 and 12dB, respectively). Consequently, the Carhart notch disappeared on the audiogram. These results were maintained at one year of follow up. We found a significant improvement in the bone conduction threshold at the frequencies of 1000 and 2000Hz and a disappearance of the Carhart notch in the audiogram after stapedectomy and total footplate removal in patients diagnosed with otosclerosis having mixed hearing loss. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. All rights reserved.

  3. Noxious heat threshold temperature and pronociceptive effects of allyl isothiocyanate (mustard oil) in TRPV1 or TRPA1 gene-deleted mice.

    PubMed

    Tékus, Valéria; Horváth, Ádám; Hajna, Zsófia; Borbély, Éva; Bölcskei, Kata; Boros, Melinda; Pintér, Erika; Helyes, Zsuzsanna; Pethő, Gábor; Szolcsányi, János

    2016-06-01

    To investigate the roles of TRPV1 and TRPA1 channels in baseline and allyl isothiocyanate (AITC)-evoked nociceptive responses by comparing wild-type and gene-deficient mice. In contrast to conventional methods of thermonociception measuring reflex latencies, we used our novel methods to determine the noxious heat threshold. It was revealed that the heat threshold of the tail measured by an increasing-temperature water bath is significantly higher in TRPV1(-/-), but not TRPA1(-/-), mice compared to respective wild-types. There was no difference between the noxious heat thresholds of the hind paw as measured by an increasing-temperature hot plate in TRPV1(-/-), TRPA1(-/-) and the corresponding wild-type mice. The withdrawal latency of the tail from 0°C water was prolonged in TRPA1(-/-), but not TRPV1(-/-), mice compared to respective wild-types. In wild-type animals, dipping the tail or paw into 1% AITC induced an 8-14°C drop of the noxious heat threshold (heat allodynia) of both the tail and paw, and 40-50% drop of the mechanonociceptive threshold (mechanical allodynia) of the paw measured by dynamic plantar esthesiometry. These AITC-evoked responses were diminished in TRPV1(-/-), but not TRPA1(-/-), mice. Tail withdrawal latency to 1% AITC was significantly prolonged in both gene-deleted strains. Different heat sensors determine the noxious heat threshold in distinct areas: a pivotal role for TRPV1 on the tail is contrasted with no involvement of either TRPV1 or TRPA1 on the hind paw. Noxious heat threshold measurement appears appropriate for preclinical screening of TRP channel ligands as novel analgesics. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Solvation properties of N-substituted cis and trans amides are not identical: significant enthalpy and entropy changes are revealed by the use of variable temperature 1H NMR in aqueous and chloroform solutions and ab initio calculations.

    PubMed

    Troganis, Anastassios N; Sicilia, Emilia; Barbarossou, Klimentini; Gerothanassis, Ioannis P; Russo, Nino

    2005-12-29

    The cis/trans conformational equilibrium of N-methyl formamide (NMF) and the sterically hindered tert-butylformamide (TBF) was investigated by the use of variable temperature gradient 1H NMR in aqueous solution and in the low dielectric constant and solvation ability solvent CDCl3 and various levels of first principles calculations. The trans isomer of NMF in aqueous solution is enthalpically favored relative to the cis (deltaH(o) = -5.79 +/- 0.18 kJ mol(-1)) with entropy differences at 298 K (298 x deltaS(o) = -0.23 +/- 0.17 kJ mol(-1)) playing a minor role. The experimental value of the enthalpy difference strongly decreases (deltaH(o) = -1.72 +/- 0.06 kJ mol(-1)), and the contribution of entropy at 298 K (298 x deltaS(o) = -1.87 +/- 0.06 kJ mol(-1)) increases in the case of the sterically hindered tert-butylformamide. The trans isomer of NMF in CDCl3 solution is enthalpically favored relative to the cis (deltaH(o) = -3.71 +/- 0.17 kJ mol(-1)) with entropy differences at 298 K (298 x deltaS(o) = 1.02 +/- 0.19 kJ mol(-1)) playing a minor role. In the sterically hindered tert-butylformamide, the trans isomer is enthalpically disfavored (deltaH(o) = 1.60 +/- 0.09 kJ mol(-1)) but is entropically favored (298 x deltaS(o) = 1.71 +/- 0.10 kJ mol(-1)). The results are compared with literature data of model peptides. It is concluded that, in amide bonds at 298 K and in the absence of strongly stabilizing sequence-specific inter-residue interactions involving side chains, the free energy difference of the cis/trans isomers and both the enthalpy and entropy contributions are strongly dependent on the N-alkyl substitution and the solvent. The significant decreasing enthalpic benefit of the trans isomer in CDCl3 compared to that in H2O, in the case of NMF and TBF, is partially offset by an adverse entropy contribution. This is in agreement with the general phenomenon of enthalpy versus entropy compensation. B3LY/6-311++G** and MP2/6-311++G** quantum chemical calculations

  5. Genome-scale co-expression network comparison across Escherichia coli and Salmonella enterica serovar Typhimurium reveals significant conservation at the regulon level of local regulators despite their dissimilar lifestyles.

    PubMed

    Zarrineh, Peyman; Sánchez-Rodríguez, Aminael; Hosseinkhan, Nazanin; Narimani, Zahra; Marchal, Kathleen; Masoudi-Nejad, Ali

    2014-01-01

    Availability of genome-wide gene expression datasets provides the opportunity to study gene expression across different organisms under a plethora of experimental conditions. In our previous work, we developed an algorithm called COMODO (COnserved MODules across Organisms) that identifies conserved expression modules between two species. In the present study, we expanded COMODO to detect the co-expression conservation across three organisms by adapting the statistics behind it. We applied COMODO to study expression conservation/divergence between Escherichia coli, Salmonella enterica, and Bacillus subtilis. We observed that some parts of the regulatory interaction networks were conserved between E. coli and S. enterica especially in the regulon of local regulators. However, such conservation was not observed between the regulatory interaction networks of B. subtilis and the two other species. We found co-expression conservation on a number of genes involved in quorum sensing, but almost no conservation for genes involved in pathogenicity across E. coli and S. enterica which could partially explain their different lifestyles. We concluded that despite their different lifestyles, no significant rewiring have occurred at the level of local regulons involved for instance, and notable conservation can be detected in signaling pathways and stress sensing in the phylogenetically close species S. enterica and E. coli. Moreover, conservation of local regulons seems to depend on the evolutionary time of divergence across species disappearing at larger distances as shown by the comparison with B. subtilis. Global regulons follow a different trend and show major rewiring even at the limited evolutionary distance that separates E. coli and S. enterica.

  6. Genome-Scale Co-Expression Network Comparison across Escherichia coli and Salmonella enterica Serovar Typhimurium Reveals Significant Conservation at the Regulon Level of Local Regulators Despite Their Dissimilar Lifestyles

    PubMed Central

    Zarrineh, Peyman; Sánchez-Rodríguez, Aminael; Hosseinkhan, Nazanin; Narimani, Zahra; Marchal, Kathleen; Masoudi-Nejad, Ali

    2014-01-01

    Availability of genome-wide gene expression datasets provides the opportunity to study gene expression across different organisms under a plethora of experimental conditions. In our previous work, we developed an algorithm called COMODO (COnserved MODules across Organisms) that identifies conserved expression modules between two species. In the present study, we expanded COMODO to detect the co-expression conservation across three organisms by adapting the statistics behind it. We applied COMODO to study expression conservation/divergence between Escherichia coli, Salmonella enterica, and Bacillus subtilis. We observed that some parts of the regulatory interaction networks were conserved between E. coli and S. enterica especially in the regulon of local regulators. However, such conservation was not observed between the regulatory interaction networks of B. subtilis and the two other species. We found co-expression conservation on a number of genes involved in quorum sensing, but almost no conservation for genes involved in pathogenicity across E. coli and S. enterica which could partially explain their different lifestyles. We concluded that despite their different lifestyles, no significant rewiring have occurred at the level of local regulons involved for instance, and notable conservation can be detected in signaling pathways and stress sensing in the phylogenetically close species S. enterica and E. coli. Moreover, conservation of local regulons seems to depend on the evolutionary time of divergence across species disappearing at larger distances as shown by the comparison with B. subtilis. Global regulons follow a different trend and show major rewiring even at the limited evolutionary distance that separates E. coli and S. enterica. PMID:25101984

  7. A Large Study on Immunological Response to a Whole-Cell Killed Oral Cholera Vaccine Reveals That There Are Significant Geographical Differences in Response and That O Blood Group Individuals Do Not Elicit a Higher Response▿ †

    PubMed Central

    Ramamurthy, T.; Wagener, Diane; Chowdhury, Goutam; Majumder, Partha P.

    2010-01-01

    The ABO blood group system has been implicated in susceptibility to cholera or in explaining variability in the immune response to a cholera vaccine. O blood group individuals were found to be more susceptible to cholera and elicited lower vibriocidal antibody response to cholera toxin B subunit-killed oral vaccine. Based on the observations that O blood group individuals were more susceptible to cholera and that high mortality was associated with cholera, an evolutionary explanation was provided for the extremely low prevalence of the O blood group in the Gangetic Delta (West Bengal, India, and Bangladesh). However, conflicting results were reported from a later study conducted in Indonesia using a live attenuated oral cholera vaccine; O blood group individuals showed a higher vibriocidal antibody response. In a study conducted in a region of India where cholera is endemic (Kolkata, West Bengal) that comprised 992 individuals vaccinated by a killed whole-cell oral cholera vaccine, we found no statistically significant difference between O and non-O individuals either in the frequency distributions of the fold increase or in the postvaccination increase in geometric mean titer compared to the baseline. Further, in contrast to the earlier observation that the O allele frequency is extremely low in the Gangetic Delta, we have noted that the O allele frequency exceeds 0.5 in the vast majority of ethnic groups of this region. In addition, we have found large differences in response to the vaccine among residents of an area where cholera is not endemic compared to an area where cholera is endemic to The percentages of vaccinees who seroconverted in an area where cholera is not endemic (Son La province of Vietnam) was >90% compared to ∼50% in Kolkata, India, an area where cholera is endemic. PMID:20554804

  8. GHRS Side 2 Threshold Adjustment - 4

    NASA Astrophysics Data System (ADS)

    Skapik, Joe

    1994-01-01

    This test will determine the optimal, non-standard discriminator thresholds for the few anomalous channels on HRS detector 2. A 15 second flat field observation followed by a 210 second dark count is performed at each of 10 discriminator threshold values for each detector. The result of the test will be the optimal threshold values to be entered into the PDB. Edited 4/30/91 to add comments to disable/re-enable cross-talk tables.

  9. GHRS Side 1 Threshold Adjustment - 4

    NASA Astrophysics Data System (ADS)

    Skapik, Joe

    1994-01-01

    This test will determine the optimal, non-standard discriminator thresholds for the few anomalous channels on HRS detector 1. A 15 second flat field observation followed by a 210 second dark count is performed at each of 10 discriminator threshold values for each detector. The result of the test will be the optimal threshold values to be entered into the PDB. Edited 4/30/91 to add comments to disable/re-enable cross-talk tables.

  10. Required thermal thresholds during transport of animals.

    PubMed

    Schrama, J W; van der Hel, W; Gorssen, J; Henken, A M; Verstegen, M W; Noordhuizen, J P

    1996-09-01

    Conditions (total complex of stressors) during the transport of animals vary strongly between and within transports. Adverse climatic conditions are stressors that animals have to face during transport. The thermoregulation of animals id discussed with respect to threshold values for optimal climatic conditions. These thermal thresholds depend on animal related factors and environmental conditions. The specific impact of transport conditions, such as food and water deprivation, high stocking density, high humidity and high air velocity, on thermal thresholds are described.

  11. Meta-analysis Reveals Genome-Wide Significance at 15q13 for Nonsyndromic Clefting of Both the Lip and the Palate, and Functional Analyses Implicate GREM1 As a Plausible Causative Gene.

    PubMed

    Ludwig, Kerstin U; Ahmed, Syeda Tasnim; Böhmer, Anne C; Sangani, Nasim Bahram; Varghese, Sheryil; Klamt, Johanna; Schuenke, Hannah; Gültepe, Pinar; Hofmann, Andrea; Rubini, Michele; Aldhorae, Khalid Ahmed; Steegers-Theunissen, Regine P; Rojas-Martinez, Augusto; Reiter, Rudolf; Borck, Guntram; Knapp, Michael; Nakatomi, Mitsushiro; Graf, Daniel; Mangold, Elisabeth; Peters, Heiko

    2016-03-01

    Nonsyndromic orofacial clefts are common birth defects with multifactorial etiology. The most common type is cleft lip, which occurs with or without cleft palate (nsCLP and nsCLO, respectively). Although genetic components play an important role in nsCLP, the genetic factors that predispose to palate involvement are largely unknown. In this study, we carried out a meta-analysis on genetic and clinical data from three large cohorts and identified strong association between a region on chromosome 15q13 and nsCLP (P = 8.13 × 10(-14) for rs1258763; relative risk (RR): 1.46, 95% confidence interval (CI): 1.32-1.61)) but not nsCLO (P = 0.27; RR: 1.09 (0.94-1.27)). The 5 kb region of strongest association maps downstream of Gremlin-1 (GREM1), which encodes a secreted antagonist of the BMP4 pathway. We show during mouse embryogenesis, Grem1 is expressed in the developing lip and soft palate but not in the hard palate. This is consistent with genotype-phenotype correlations between rs1258763 and a specific nsCLP subphenotype, since a more than two-fold increase in risk was observed in patients displaying clefts of both the lip and soft palate but who had an intact hard palate (RR: 3.76, CI: 1.47-9.61, Pdiff<0.05). While we did not find lip or palate defects in Grem1-deficient mice, wild type embryonic palatal shelves developed divergent shapes when cultured in the presence of ectopic Grem1 protein (P = 0.0014). The present study identified a non-coding region at 15q13 as the second, genome-wide significant locus specific for nsCLP, after 13q31. Moreover, our data suggest that the closely located GREM1 gene contributes to a rare clinical nsCLP entity. This entity specifically involves abnormalities of the lip and soft palate, which develop at different time-points and in separate anatomical regions.

  12. Meta-analysis Reveals Genome-Wide Significance at 15q13 for Nonsyndromic Clefting of Both the Lip and the Palate, and Functional Analyses Implicate GREM1 As a Plausible Causative Gene

    PubMed Central

    Ludwig, Kerstin U.; Ahmed, Syeda Tasnim; Böhmer, Anne C.; Sangani, Nasim Bahram; Varghese, Sheryil; Klamt, Johanna; Schuenke, Hannah; Gültepe, Pinar; Hofmann, Andrea; Rubini, Michele; Aldhorae, Khalid Ahmed; Steegers-Theunissen, Regine P.; Rojas-Martinez, Augusto; Reiter, Rudolf; Borck, Guntram; Knapp, Michael; Nakatomi, Mitsushiro; Graf, Daniel; Mangold, Elisabeth; Peters, Heiko

    2016-01-01

    Nonsyndromic orofacial clefts are common birth defects with multifactorial etiology. The most common type is cleft lip, which occurs with or without cleft palate (nsCLP and nsCLO, respectively). Although genetic components play an important role in nsCLP, the genetic factors that predispose to palate involvement are largely unknown. In this study, we carried out a meta-analysis on genetic and clinical data from three large cohorts and identified strong association between a region on chromosome 15q13 and nsCLP (P = 8.13×10−14 for rs1258763; relative risk (RR): 1.46, 95% confidence interval (CI): 1.32–1.61)) but not nsCLO (P = 0.27; RR: 1.09 (0.94–1.27)). The 5 kb region of strongest association maps downstream of Gremlin-1 (GREM1), which encodes a secreted antagonist of the BMP4 pathway. We show during mouse embryogenesis, Grem1 is expressed in the developing lip and soft palate but not in the hard palate. This is consistent with genotype-phenotype correlations between rs1258763 and a specific nsCLP subphenotype, since a more than two-fold increase in risk was observed in patients displaying clefts of both the lip and soft palate but who had an intact hard palate (RR: 3.76, CI: 1.47–9.61, Pdiff<0.05). While we did not find lip or palate defects in Grem1-deficient mice, wild type embryonic palatal shelves developed divergent shapes when cultured in the presence of ectopic Grem1 protein (P = 0.0014). The present study identified a non-coding region at 15q13 as the second, genome-wide significant locus specific for nsCLP, after 13q31. Moreover, our data suggest that the closely located GREM1 gene contributes to a rare clinical nsCLP entity. This entity specifically involves abnormalities of the lip and soft palate, which develop at different time-points and in separate anatomical regions. PMID:26968009

  13. Co-clinical Analysis of a Genetically Engineered Mouse Model and Human Prostate Cancer Reveals Significance of NKX3.1 Expression for Response to 5α-reductase Inhibition.

    PubMed

    Dutta, Aditya; Panja, Sukanya; Virk, Renu K; Kim, Jaime Yeji; Zott, Roseann; Cremers, Serge; Golombos, David M; Liu, Deli; Mosquera, Juan Miguel; Mostaghel, Elahe A; Barbieri, Christopher E; Mitrofanova, Antonina; Abate-Shen, Cory

    2017-10-01

    Although men on active surveillance for prostate cancer (PCa) may benefit from intervention with 5α-reductase inhibitors (5-ARIs), it has not been resolved whether 5-ARIs are effective for delaying disease progression and, if so, whether specific patients are more likely to benefit. To identify molecular features predictive of patient response to 5-ARIs. Nkx3.1 mutant mice, a model of early-stage PCa, were treated with the 5-ARI finasteride, and histopathological and molecular analyses were performed. Cross-species computational analyses were used to compare expression profiles for treated mice with those of patients who had received 5-ARIs before prostatectomy. Finasteride administered to Nkx3.1 mutant mice. 5-ARI-treated patient specimens obtained retrospectively. Endpoints in mice included histopathology, immunohistochemistry, and molecular profiling. GraphPad Prism software, R-studio, and Matlab were used for statistical and data analyses. Finasteride treatment of Nkx3.1 mutant mice resulted in a significant reduction in prostatic intraepithelial neoplasia (PIN), as evident from histopathological and expression profiling analyses. Cross-species computational analysis comparing finasteride-treated mice with two independent 5-ARI-treated patient cohorts showed that reduced NKX3.1 expression is predictive of response to 5-ARI. A limitation of the study is that these retrospective human cohorts have relatively few patients with limited clinical outcome data. Future prospective clinical trials are needed to validate whether stratifying patients on the basis of NKX3.1 expression improves the benefit of 5-ARIs during active surveillance. This co-clinical study implicates NKX3.1 status as a predictor of response to 5-ARIs, and suggests that molecular features, including NKX3.1 expression, may help to identify PCa patients most likely to benefit from 5-ARIs during active surveillance. The aim of precision cancer prevention is to tailor interventions on the basis of

  14. Array comparative genomic hybridization analyses of all blastomeres of a cohort of embryos from young IVF patients revealed significant contribution of mitotic errors to embryo mosaicism at the cleavage stage.

    PubMed

    Chow, Judy F C; Yeung, William S B; Lau, Estella Y L; Lee, Vivian C Y; Ng, Ernest H Y; Ho, Pak-Chung

    2014-11-24

    Embryos produced by in vitro fertilization (IVF) have a high level of aneuploidy, which is believed to be a major factor affecting the success of human assisted reproduction treatment. The aneuploidy rate of cleavage stage embryos based on 1-2 biopsied blastomeres has been well-reported, however, the true aneuploidy rate of whole embryos remain unclear because of embryo mosaicism. To study the prevalence of mosaicism in top quality IVF embryos, surplus embryos donated from young patients (aged 28-32) in the assisted reproduction program at Queen Mary Hospital, Hong Kong were used. Thirty-six good quality day 2 embryos were thawed. Out of the 135 blastomeres in these embryos, 121 (89.6%) survived thawing. Twelve of these embryos without lysed blastomeres and which cleaved to at least seven cells after a 24-h culture were dissembled into individual blastomeres, which were analysed by array comparative genomic hybridization and microsatellite marker analysis by fluorescent PCR. Out of 12 day-3 embryos, 2 (16.7%) were normal, 3 (25%) were diploid/aneuploidy with <38% abnormality, 4 (33.3%) were diploid/aneuploidy mosaic with > =38% abnormality, and three (25%) were mosaic aneuploids. Conclusive chromosomal data were obtained from a high percentage of blastomeres (92.8%, 90/97). Microsatellite marker analysis performed on blastomeres in aneuploid embryos enabled us to reconstruct the chromosomal status of the blastomeres in each cleavage division. The results showed the occurrence of meiotic errors in 3 (25%) of the studied embryos. There were 16 mitotic errors (18.8%, 16/85) in the 85 mitotic divisions undertaken by the studied embryos. The observed mitotic errors were mainly contributed by endoreduplication (31.3%, 5/16), non-disjunction (25%, 4/16) and anaphase lagging (25%, 4/16). Chromosome breakages occurred in 6 divisions (7.1%, 6/85). Mosaicism occurs in a high percentage of good-quality cleavage stage embryos and mitotic errors contribute significantly to

  15. Exhaustive Thresholds and Resistance Checkpoints

    NASA Technical Reports Server (NTRS)

    Easton, Charles; Khuzadi, Mbuyi

    2008-01-01

    Once deployed, all intricate systems that operate for a long time (such as an airplane or chemical processing plant) experience degraded performance during operational lifetime. These can result from losses of integrity in subsystems and parts that generally do not materially impact the operation of the vehicle (e.g., the light behind the button that opens the sliding door of the minivan). Or it can result from loss of more critical parts or subsystems. Such losses need to be handled quickly in order to avoid loss of personnel, mission, or part of the system itself. In order to manage degraded systems, knowledge of its potential problem areas and the means by which these problems are detected should be developed during the initial development of the system. Once determined, a web of sensors is employed and their outputs are monitored with other system parameters while the system is in preparation or operation. Just gathering the data is only part of the story. The interpretation of the data itself and the response of the system must be carefully developed as well to avoid a mishap. Typically, systems use a test-threshold-response paradigm to process potential system faults. However, such processing sub-systems can suffer from errors and oversights of a consistent type, causing system aberrant behavior instead of expected system and recovery operations. In our study, we developed a complete checklist for determining the completeness of a fault system and its robustness to common processing and response difficulties.

  16. Roots at the percolation threshold

    NASA Astrophysics Data System (ADS)

    Kroener, Eva; Ahmed, Mutez Ali; Carminati, Andrea

    2015-04-01

    The rhizosphere is the layer of soil around the roots where complex and dynamic interactions between plants and soil affect the capacity of plants to take up water. The physical properties of the rhizosphere are affected by mucilage, a gel exuded by roots. Mucilage can absorb large volumes of water, but it becomes hydrophobic after drying. We use a percolation model to describe the rewetting of dry rhizosphere. We find that at a critical mucilage concentration the rhizosphere becomes impermeable. The critical mucilage concentration depends on the radius of the soil particle size. Capillary rise experiments with neutron radiography prove that for concentrations below the critical mucilage concentration water could easily cross the rhizosphere, while above the critical concentration water could no longer percolate through it. Our studies, together with former observations of water dynamics in the rhizosphere, suggest that the rhizosphere is near the percolation threshold, where small variations in mucilage concentration sensitively alter the soil hydraulic conductivity. Is mucilage exudation a plant mechanism to efficiently control the rhizosphere conductivity and the access to water?

  17. Roots at the percolation threshold.

    PubMed

    Kroener, Eva; Ahmed, Mutez Ali; Carminati, Andrea

    2015-04-01

    The rhizosphere is the layer of soil around the roots where complex and dynamic interactions between plants and soil affect the capacity of plants to take up water. The physical properties of the rhizosphere are affected by mucilage, a gel exuded by roots. Mucilage can absorb large volumes of water, but it becomes hydrophobic after drying. We use a percolation model to describe the rewetting of dry rhizosphere. We find that at a critical mucilage concentration the rhizosphere becomes impermeable. The critical mucilage concentration depends on the radius of the soil particle size. Capillary rise experiments with neutron radiography prove that for concentrations below the critical mucilage concentration water could easily cross the rhizosphere, while above the critical concentration water could no longer percolate through it. Our studies, together with former observations of water dynamics in the rhizosphere, suggest that the rhizosphere is near the percolation threshold, where small variations in mucilage concentration sensitively alter the soil hydraulic conductivity. Is mucilage exudation a plant mechanism to efficiently control the rhizosphere conductivity and the access to water?

  18. Percolation Threshold in Polycarbonate Nanocomposites

    NASA Astrophysics Data System (ADS)

    Ahuja, Suresh

    2014-03-01

    Nanocomposites have unique mechanical, electrical, magnetic, optical and thermal properties. Many methods could be applied to prepare polymer-inorganic nanocomposites, such as sol-gel processing, in-situ polymerization, particle in-situ formation, blending, and radiation synthesis. The analytical composite models that have been put forth include Voigt and Reuss bounds, Polymer nanocomposites offer the possibility of substantial improvements in material properties such as shear and bulk modulus, yield strength, toughness, film scratch resistance, optical properties, electrical conductivity, gas and solvent transport, with only very small amounts of nanoparticles Experimental results are compared against composite models of Hashin and Shtrikman bounds, Halpin-Tsai model, Cox model, and various Mori and Tanaka models. Examples of numerical modeling are molecular dynamics modeling and finite element modeling of reduced modulus and hardness that takes into account the modulus of the components and the effect of the interface between the hard filler and relatively soft polymer, polycarbonate. Higher nanoparticle concentration results in poor dispersion and adhesion to polymer matrix which results in lower modulus and hardness and departure from the existing composite models. As the level of silica increases beyond a threshold level, aggregates form which results in weakening of the structure. Polymer silica interface is found to be weak as silica is non-interacting promoting interfacial slip at silica-matrix junctions. Our experimental results compare favorably with those of nanocomposites of polyesters where the effect of nanoclay on composite hardness and modulus depended on dispersion of nanoclay in polyester.

  19. Exhaustive Thresholds and Resistance Checkpoints

    NASA Technical Reports Server (NTRS)

    Easton, Charles; Khuzadi, Mbuyi

    2008-01-01

    Once deployed, all intricate systems that operate for a long time (such as an airplane or chemical processing plant) experience degraded performance during operational lifetime. These can result from losses of integrity in subsystems and parts that generally do not materially impact the operation of the vehicle (e.g., the light behind the button that opens the sliding door of the minivan). Or it can result from loss of more critical parts or subsystems. Such losses need to be handled quickly in order to avoid loss of personnel, mission, or part of the system itself. In order to manage degraded systems, knowledge of its potential problem areas and the means by which these problems are detected should be developed during the initial development of the system. Once determined, a web of sensors is employed and their outputs are monitored with other system parameters while the system is in preparation or operation. Just gathering the data is only part of the story. The interpretation of the data itself and the response of the system must be carefully developed as well to avoid a mishap. Typically, systems use a test-threshold-response paradigm to process potential system faults. However, such processing sub-systems can suffer from errors and oversights of a consistent type, causing system aberrant behavior instead of expected system and recovery operations. In our study, we developed a complete checklist for determining the completeness of a fault system and its robustness to common processing and response difficulties.

  20. A study of FM threshold extension techniques

    NASA Technical Reports Server (NTRS)

    Arndt, G. D.; Loch, F. J.

    1972-01-01

    The characteristics of three postdetection threshold extension techniques are evaluated with respect to the ability of such techniques to improve the performance of a phase lock loop demodulator. These techniques include impulse-noise elimination, signal correlation for the detection of impulse noise, and delta modulation signal processing. Experimental results from signal to noise ratio data and bit error rate data indicate that a 2- to 3-decibel threshold extension is readily achievable by using the various techniques. This threshold improvement is in addition to the threshold extension that is usually achieved through the use of a phase lock loop demodulator.

  1. Automatic threshold selection using histogram quantization

    NASA Astrophysics Data System (ADS)

    Wang, Yue; Adali, Tulay; Lo, Shih-Chung B.

    1997-04-01

    An automatic threshold selection method is proposed for biomedical image analysis based on a histogram coding scheme. The threshold values can be determined based on the well-known Lloyd-Max scalar quantization rule, which is optimal in the sense of achieving minimum mean-square-error distortion. An iterative self-organizing learning rule is derived to determine the threshold levels. The rule does not require any prior information about the histogram, hence is fully automatic. Experimental results show that this new approach is easy to implement yet is highly efficient, robust with respect to noise, and yields reliable estimates of the threshold levels.

  2. Individual differences reveal correlates of hidden hearing deficits.

    PubMed

    Bharadwaj, Hari M; Masud, Salwa; Mehraei, Golbarg; Verhulst, Sarah; Shinn-Cunningham, Barbara G

    2015-02-04

    Clinical audiometry has long focused on determining the detection thresholds for pure tones, which depend on intact cochlear mechanics and hair cell function. Yet many listeners with normal hearing thresholds complain of communication difficulties, and the causes for such problems are not well understood. Here, we explore whether normal-hearing listeners exhibit such suprathreshold deficits, affecting the fidelity with which subcortical areas encode the temporal structure of clearly audible sound. Using an array of measures, we evaluated a cohort of young adults with thresholds in the normal range to assess both cochlear mechanical function and temporal coding of suprathreshold sounds. Listeners differed widely in both electrophysiological and behavioral measures of temporal coding fidelity. These measures correlated significantly with each other. Conversely, these differences were unrelated to the modest variation in otoacoustic emissions, cochlear tuning, or the residual differences in hearing threshold present in our cohort. Electroencephalography revealed that listeners with poor subcortical encoding had poor cortical sensitivity to changes in interaural time differences, which are critical for localizing sound sources and analyzing complex scenes. These listeners also performed poorly when asked to direct selective attention to one of two competing speech streams, a task that mimics the challenges of many everyday listening environments. Together with previous animal and computational models, our results suggest that hidden hearing deficits, likely originating at the level of the cochlear nerve, are part of "normal hearing." Copyright © 2015 the authors 0270-6474/15/352161-12$15.00/0.

  3. Exploitation of a single species by a threshold management policy.

    PubMed

    Meza, Magno Enrique Mendoza; Costa, Michel Iskin da Silveira

    2011-11-01

    Continuous time models of single exploited populations usually generate outcomes expressing a dependence of yield and economic items on harvest intensity. In this work it is shown that a known threshold policy is able to generate yield and related economic items that do not depend on harvest intensity, but rather on the values of the population threshold itself and the species intrinsic parameters. It is argued that since this result can be carried over to other models of single species dynamics, it may have significant implications in the management and conservation of exploited populations.

  4. Near-Threshold Production of ϕ Mesons in pp Collisions

    NASA Astrophysics Data System (ADS)

    Hartmann, M.; Maeda, Y.; Keshelashvili, I.; Koch, H. R.; Mikirtytchiants, S.; Barsov, S.; Borgs, W.; Büscher, M.; Dimitrov, V. I.; Dymov, S.; Hejny, V.; Kleber, V.; Koptev, V.; Kulessa, P.; Mersmann, T.; Merzliakov, S.; Mussgiller, A.; Nekipelov, M.; Nioradze, M.; Ohm, H.; Pysz, K.; Schleichert, R.; Stein, H. J.; Ströher, H.; Watzlawik, K.-H.; Wüstner, P.

    2006-06-01

    The pp→ppϕ reaction has been studied at the Cooler Synchrotron COSY-Jülich, using the internal beam and ANKE facility. Total cross sections have been determined at three excess energies γ near the production threshold. The differential cross section closest to threshold at γ=18.5MeV exhibits a clear S wave dominance as well as a noticeable effect due to the proton-proton final-state interaction. Taken together with data for ppω production, a significant enhancement of the ϕ/ω ratio of a factor 8 is found compared to predictions based on the Okubo-Zweig-Iizuka rule.

  5. Near-threshold production of phi mesons in pp collisions.

    PubMed

    Hartmann, M; Maeda, Y; Keshelashvili, I; Koch, H R; Mikirtytchiants, S; Barsov, S; Borgs, W; Büscher, M; Dimitrov, V I; Dymov, S; Hejny, V; Kleber, V; Koptev, V; Kulessa, P; Mersmann, T; Merzliakov, S; Mussgiller, A; Nekipelov, M; Nioradze, M; Ohm, H; Pysz, K; Schleichert, R; Stein, H J; Ströher, H; Watzlawik, K-H; Wüstner, P

    2006-06-23

    The pp-->ppphi reaction has been studied at the Cooler Synchrotron COSY-Jülich, using the internal beam and ANKE facility. Total cross sections have been determined at three excess energies epsilon near the production threshold. The differential cross section closest to threshold at epsilon=18.5 MeV exhibits a clear S wave dominance as well as a noticeable effect due to the proton-proton final-state interaction. Taken together with data for ppomega production, a significant enhancement of the phi/omega ratio of a factor 8 is found compared to predictions based on the Okubo-Zweig-Iizuka rule.

  6. [Temporary hearing threshold shift in policemen after firearm training].

    PubMed

    Cassano, F; Montesano, Roberta; Bobbio, Elena; Borraccia, V; Volpe, C; Bavaro, P; Quaranta, N

    2012-01-01

    The paper involves exposure to noise of the State Police officers connected with the use of firearms. The noise generated by these weapons is of short duration and high intensity. The research was carried out during the sessions of firearm training of State Police officers to assess exposure to noise. The values of the various investigations, both audiometric and phonometric, carried out made it possible to demonstrate a significant exposure and a temporary increase in the threshold, above the frequency of 6000 Hz. Even taking account of the abatement from use of headphones, an exposure was demonstrated that was above the statutory limits, as was confirmed by the temporary hearing threshold shift.

  7. Hemispheric lateralization of motor thresholds in relation to stuttering.

    PubMed

    Alm, Per A; Karlsson, Ragnhild; Sundberg, Madeleine; Axelson, Hans W

    2013-01-01

    Stuttering is a complex speech disorder. Previous studies indicate a tendency towards elevated motor threshold for the left hemisphere, as measured using transcranial magnetic stimulation (TMS). This may reflect a monohemispheric motor system impairment. The purpose of the study was to investigate the relative side-to-side difference (asymmetry) and the absolute levels of motor threshold for the hand area, using TMS in adults who stutter (n = 15) and in controls (n = 15). In accordance with the hypothesis, the groups differed significantly regarding the relative side-to-side difference of finger motor threshold (p = 0.0026), with the stuttering group showing higher motor threshold of the left hemisphere in relation to the right. Also the absolute level of the finger motor threshold for the left hemisphere differed between the groups (p = 0.049). The obtained results, together with previous investigations, provide support for the hypothesis that stuttering tends to be related to left hemisphere motor impairment, and possibly to a dysfunctional state of bilateral speech motor control.

  8. Hard decoding algorithm for optimizing thresholds under general Markovian noise

    NASA Astrophysics Data System (ADS)

    Chamberland, Christopher; Wallman, Joel; Beale, Stefanie; Laflamme, Raymond

    2017-04-01

    Quantum error correction is instrumental in protecting quantum systems from noise in quantum computing and communication settings. Pauli channels can be efficiently simulated and threshold values for Pauli error rates under a variety of error-correcting codes have been obtained. However, realistic quantum systems can undergo noise processes that differ significantly from Pauli noise. In this paper, we present an efficient hard decoding algorithm for optimizing thresholds and lowering failure rates of an error-correcting code under general completely positive and trace-preserving (i.e., Markovian) noise. We use our hard decoding algorithm to study the performance of several error-correcting codes under various non-Pauli noise models by computing threshold values and failure rates for these codes. We compare the performance of our hard decoding algorithm to decoders optimized for depolarizing noise and show improvements in thresholds and reductions in failure rates by several orders of magnitude. Our hard decoding algorithm can also be adapted to take advantage of a code's non-Pauli transversal gates to further suppress noise. For example, we show that using the transversal gates of the 5-qubit code allows arbitrary rotations around certain axes to be perfectly corrected. Furthermore, we show that Pauli twirling can increase or decrease the threshold depending upon the code properties. Lastly, we show that even if the physical noise model differs slightly from the hypothesized noise model used to determine an optimized decoder, failure rates can still be reduced by applying our hard decoding algorithm.

  9. Hemispheric Lateralization of Motor Thresholds in Relation to Stuttering

    PubMed Central

    Alm, Per A.; Karlsson, Ragnhild; Sundberg, Madeleine; Axelson, Hans W.

    2013-01-01

    Stuttering is a complex speech disorder. Previous studies indicate a tendency towards elevated motor threshold for the left hemisphere, as measured using transcranial magnetic stimulation (TMS). This may reflect a monohemispheric motor system impairment. The purpose of the study was to investigate the relative side-to-side difference (asymmetry) and the absolute levels of motor threshold for the hand area, using TMS in adults who stutter (n = 15) and in controls (n = 15). In accordance with the hypothesis, the groups differed significantly regarding the relative side-to-side difference of finger motor threshold (p = 0.0026), with the stuttering group showing higher motor threshold of the left hemisphere in relation to the right. Also the absolute level of the finger motor threshold for the left hemisphere differed between the groups (p = 0.049). The obtained results, together with previous investigations, provide support for the hypothesis that stuttering tends to be related to left hemisphere motor impairment, and possibly to a dysfunctional state of bilateral speech motor control. PMID:24146930

  10. Threshold-limited spreading in social networks with multiple initiators

    NASA Astrophysics Data System (ADS)

    Singh, P.; Sreenivasan, S.; Szymanski, B. K.; Korniss, G.

    2013-07-01

    A classical model for social-influence-driven opinion change is the threshold model. Here we study cascades of opinion change driven by threshold model dynamics in the case where multiple initiators trigger the cascade, and where all nodes possess the same adoption threshold ϕ. Specifically, using empirical and stylized models of social networks, we study cascade size as a function of the initiator fraction p. We find that even for arbitrarily high value of ϕ, there exists a critical initiator fraction pc(ϕ) beyond which the cascade becomes global. Network structure, in particular clustering, plays a significant role in this scenario. Similarly to the case of single-node or single-clique initiators studied previously, we observe that community structure within the network facilitates opinion spread to a larger extent than a homogeneous random network. Finally, we study the efficacy of different initiator selection strategies on the size of the cascade and the cascade window.

  11. Anaerobic threshold determination with analysis of salivary amylase.

    PubMed

    Calvo, F; Chicharro, J L; Bandrés, F; Lucía, A; Pérez, M; Alvarez, J; Mojares, L L; Vaquero, A F; Legido, J C

    1997-12-01

    The purpose of this study was to determine the anaerobic threshold from analysis of amylase concentration in total saliva during a laboratory exercise test. Each of 20 healthy young men performed both a submaximal and a maximal test on a treadmill. During the submaximal test, capillary blood and total saliva samples were collected for determination of anaerobic threshold (AT) and saliva threshold (Tsa), respectively. Tsa was defined as the point at which the first continuous increase in amylase concentration occurred during exercise. The results showed no significant difference between values of AT and Tsa when both were expressed either as running velocity or as heart rate. In addition, there existed a high correlation between AT and Tsa (r = .93, p < .001). It was therefore concluded that the analysis of amylase concentration in total saliva during exercise might be used as a valid new method for determining AT.

  12. Improved bat algorithm applied to multilevel image thresholding.

    PubMed

    Alihodzic, Adis; Tuba, Milan

    2014-01-01

    Multilevel image thresholding is a very important image processing technique that is used as a basis for image segmentation and further higher level processing. However, the required computational time for exhaustive search grows exponentially with the number of desired thresholds. Swarm intelligence metaheuristics are well known as successful and efficient optimization methods for intractable problems. In this paper, we adjusted one of the latest swarm intelligence algorithms, the bat algorithm, for the multilevel image thresholding problem. The results of testing on standard benchmark images show that the bat algorithm is comparable with other state-of-the-art algorithms. We improved standard bat algorithm, where our modifications add some elements from the differential evolution and from the artificial bee colony algorithm. Our new proposed improved bat algorithm proved to be better than five other state-of-the-art algorithms, improving quality of results in all cases and significantly improving convergence speed.

  13. Improved Bat Algorithm Applied to Multilevel Image Thresholding

    PubMed Central

    2014-01-01

    Multilevel image thresholding is a very important image processing technique that is used as a basis for image segmentation and further higher level processing. However, the required computational time for exhaustive search grows exponentially with the number of desired thresholds. Swarm intelligence metaheuristics are well known as successful and efficient optimization methods for intractable problems. In this paper, we adjusted one of the latest swarm intelligence algorithms, the bat algorithm, for the multilevel image thresholding problem. The results of testing on standard benchmark images show that the bat algorithm is comparable with other state-of-the-art algorithms. We improved standard bat algorithm, where our modifications add some elements from the differential evolution and from the artificial bee colony algorithm. Our new proposed improved bat algorithm proved to be better than five other state-of-the-art algorithms, improving quality of results in all cases and significantly improving convergence speed. PMID:25165733

  14. Threshold-limited spreading in social networks with multiple initiators

    PubMed Central

    Singh, P.; Sreenivasan, S.; Szymanski, B. K.; Korniss, G.

    2013-01-01

    A classical model for social-influence-driven opinion change is the threshold model. Here we study cascades of opinion change driven by threshold model dynamics in the case where multiple initiators trigger the cascade, and where all nodes possess the same adoption threshold ϕ. Specifically, using empirical and stylized models of social networks, we study cascade size as a function of the initiator fraction p. We find that even for arbitrarily high value of ϕ, there exists a critical initiator fraction pc(ϕ) beyond which the cascade becomes global. Network structure, in particular clustering, plays a significant role in this scenario. Similarly to the case of single-node or single-clique initiators studied previously, we observe that community structure within the network facilitates opinion spread to a larger extent than a homogeneous random network. Finally, we study the efficacy of different initiator selection strategies on the size of the cascade and the cascade window. PMID:23900230

  15. Rainfall thresholds for the initiation of debris flows at La Honda, California

    USGS Publications Warehouse

    Wilson, R.C.; Wieczorek, G.F.

    1995-01-01

    A simple numerical model, based on the physical analogy of a leaky barrel, can simulate significant features of the interaction between rainfall and shallow-hillslope pore pressures. The leaky-barrel-model threshold is consistent with, but slightly higher than, an earlier, purely empirical, threshold. The number of debris flows triggered by a storm can be related to the time and amount by which the leaky-barrel-model response exceeded the threshold during the storm. -from Authors

  16. Thresholds in marsh resilience to the Deepwater Horizon oil spill

    NASA Astrophysics Data System (ADS)

    Silliman, Brian R.; Dixon, Philip M.; Wobus, Cameron; He, Qiang; Daleo, Pedro; Hughes, Brent B.; Rissing, Matthew; Willis, Jonathan M.; Hester, Mark W.

    2016-09-01

    Ecosystem boundary retreat due to human-induced pressure is a generally observed phenomenon. However, studies that document thresholds beyond which internal resistance mechanisms are overwhelmed are uncommon. Following the Deepwater Horizon (DWH) oil spill, field studies from a few sites suggested that oiling of salt marshes could lead to a biogeomorphic feedback where plant death resulted in increased marsh erosion. We tested for spatial generality of and thresholds in this effect across 103 salt marsh sites spanning ~430 kilometers of shoreline in coastal Louisiana, Alabama, and Mississippi, using data collected as part of the natural resource damage assessment (NRDA). Our analyses revealed a threshold for oil impacts on marsh edge erosion, with higher erosion rates occurring for ~1-2 years after the spill at sites with the highest amounts of plant stem oiling (90-100%). These results provide compelling evidence showing large-scale ecosystem loss following the Deepwater Horizon oil spill. More broadly, these findings provide rare empirical evidence identifying a geomorphologic threshold in the resistance of an ecosystem to increasing intensity of human-induced disturbance.

  17. Thresholds in marsh resilience to the Deepwater Horizon oil spill

    PubMed Central

    Silliman, Brian R.; Dixon, Philip M.; Wobus, Cameron; He, Qiang; Daleo, Pedro; Hughes, Brent B.; Rissing, Matthew; Willis, Jonathan M.; Hester, Mark W.

    2016-01-01

    Ecosystem boundary retreat due to human-induced pressure is a generally observed phenomenon. However, studies that document thresholds beyond which internal resistance mechanisms are overwhelmed are uncommon. Following the Deepwater Horizon (DWH) oil spill, field studies from a few sites suggested that oiling of salt marshes could lead to a biogeomorphic feedback where plant death resulted in increased marsh erosion. We tested for spatial generality of and thresholds in this effect across 103 salt marsh sites spanning ~430 kilometers of shoreline in coastal Louisiana, Alabama, and Mississippi, using data collected as part of the natural resource damage assessment (NRDA). Our analyses revealed a threshold for oil impacts on marsh edge erosion, with higher erosion rates occurring for ~1–2 years after the spill at sites with the highest amounts of plant stem oiling (90–100%). These results provide compelling evidence showing large-scale ecosystem loss following the Deepwater Horizon oil spill. More broadly, these findings provide rare empirical evidence identifying a geomorphologic threshold in the resistance of an ecosystem to increasing intensity of human-induced disturbance. PMID:27679956

  18. Fundamental frequency effects on thresholds for vowel formant discrimination.

    PubMed

    Kewley-Port, D; Li, X; Zheng, Y; Neel, A T

    1996-10-01

    The present experiments examined the effect of fundamental frequency (F0) on thresholds for the discrimination of formant frequency for male vowels. Thresholds for formant-frequency discrimination were obtained for six vowels with two fundamental frequencies: normal F0 (126 Hz) and low F0 (101 Hz). Four well-trained subjects performed an adaptive tracking task under low stimulus uncertainty. Comparisons between the normal-F0 and the low-F0 conditions showed that formants were resolved more accurately for low F0. These thresholds for male vowels were compared to thresholds for female vowels previously reported by Kewley-Port and Watson [J. Acoust. Soc. Am. 95, 485-496 (1994)]. Analyses of the F0 sets demonstrated that formant thresholds were significantly degraded for increases both in formant frequency and in F0. A piece-wise linear function was fit to each of the three sets of delta F thresholds as a function of formant frequency. The shape of the three parallel functions was similar such that delta F was constant in the F1 region and increased with formant frequency in the F2 region. The capability for humans to discriminate formant frequency may therefore be described as uniform in the F1 region (< 800 Hz) when represented as delta F and also uniform in the F2 region when represented as a ratio of delta F/F. A model of formant discrimination is proposed in which the effects of formant frequency are represented by the shape of an underlying piece-wise linear function. Increases in F0 significantly degrade overall discrimination independently from formant frequency.

  19. Electric Field Model of Transcranial Electric Stimulation in Nonhuman Primates: Correspondence to Individual Motor Threshold

    PubMed Central

    Lee, Won Hee; Lisanby, Sarah H.; Laine, Andrew F.

    2015-01-01

    Objective To develop a pipeline for realistic head models of nonhuman primates (NHPs) for simulations of noninvasive brain stimulation, and use these models together with empirical threshold measurements to demonstrate that the models capture individual anatomical variability. Methods Based on structural MRI data, we created models of the electric field (E-field) induced by right unilateral (RUL) electroconvulsive therapy (ECT) in four rhesus macaques. Individual motor threshold (MT) was measured with transcranial electric stimulation (TES) administered through the RUL electrodes in the same subjects. Results The interindividual anatomical differences resulted in 57% variation in median E-field strength in the brain at fixed stimulus current amplitude. Individualization of the stimulus current by MT reduced the E-field variation in the target motor area by 27%. There was significant correlation between the measured MT and the ratio of simulated electrode current and E-field strength (r2 = 0.95, p = 0.026). Exploratory analysis revealed significant correlations of this ratio with anatomical parameters including of the superior electrode-to-cortex distance, vertex-to-cortex distance, and brain volume (r2 > 0.96, p < 0.02). The neural activation threshold was estimated to be 0.45 ± 0.07 V/cm for 0.2 ms stimulus pulse width. Conclusion These results suggest that our individual-specific NHP E-field models appropriately capture individual anatomical variability relevant to the dosing of TES/ECT. These findings are exploratory due to the small number of subjects. Significance This work can contribute insight in NHP studies of ECT and other brain stimulation interventions, help link the results to clinical studies, and ultimately lead to more rational brain stimulation dosing paradigms. PMID:25910001

  20. The asymmetry of U.S. monetary policy: Evidence from a threshold Taylor rule with time-varying threshold values

    NASA Astrophysics Data System (ADS)

    Zhu, Yanli; Chen, Haiqiang

    2017-05-01

    In this paper, we revisit the issue whether U.S. monetary policy is asymmetric by estimating a forward-looking threshold Taylor rule with quarterly data from 1955 to 2015. In order to capture the potential heterogeneity for regime shift mechanism under different economic conditions, we modify the threshold model by assuming the threshold value as a latent variable following an autoregressive (AR) dynamic process. We use the unemployment rate as the threshold variable and separate the sample into two periods: expansion periods and recession periods. Our findings support that the U.S. monetary policy operations are asymmetric in these two regimes. More precisely, the monetary authority tends to implement an active Taylor rule with a weaker response to the inflation gap (the deviation of inflation from its target) and a stronger response to the output gap (the deviation of output from its potential level) in recession periods. The threshold value, interpreted as the targeted unemployment rate of monetary authorities, exhibits significant time-varying properties, confirming the conjecture that policy makers may adjust their reference point for the unemployment rate accordingly to reflect their attitude on the health of general economy.