Science.gov

Sample records for reveal significant threshold

  1. Guidelines for Auditory Threshold Measurement for Significant Threshold Shift.

    PubMed

    Campbell, Kathleen; Hammill, Tanisha; Hoffer, Michael; Kil, Jonathan; Le Prell, Colleen

    2016-09-01

    The purpose of this article is to provide guidelines for determining a Significant Noise-Induced Threshold Shift in clinical trials involving human populations. The article reviews recommendations for the standards to be referenced for human subjects, equipment, test environment, and personnel. Additional guidelines for military populations are provided. Guidelines for the calibration of audiometers, sound booth noise levels, and immitance equipment are provided. In addition the guidance provides specific suggestions for the subjects history before study onset, and otoscopy.Test frequencies for threshold determination and methods of threshold determination are reviewed for both air conduction and bone conduction for both baseline testing and later determination of either a temporary (TTS) or permanent threshold shift (PTS). Once a Significant Noise-Induced Threshold Shift has been determined, subjects should be retested, conductive component should be ruled out or addressed, and the subject should be counseled or referred for additional medical evaluation. Guidance for reporting procedures and the computerized study database are described. Finally, experimental designs suggested for noise-induced otoprotection clinical trials are described. PMID:27518134

  2. Defining the threshold for significant versus insignificant prostate cancer.

    PubMed

    Van der Kwast, Theo H; Roobol, Monique J

    2013-08-01

    Autopsy studies have shown the presence of a large reservoir of latent prostate cancers in adult men. Serum PSA testing of asymptomatic men leads to the detection of a proportion of these latent prostate cancers. The unequivocal demonstration of a substantial (30-50%) risk of overdiagnosis by the two largest randomized population-based screening trials has led to a growing awareness of this unwanted effect. Unsurprisingly, active surveillance is now becoming the favoured strategy for deferring active treatment in men diagnosed with low-risk prostate cancer and reducing their risk of overtreatment. Almost all eligibility criteria for active surveillance refer to a strict pathological definition of insignificant prostate cancer, based on two landmark studies published about 20 years ago. However, current epidemiological data suggest that this original pathological definition of insignificant prostate cancer is too restrictive. In addition, the International Society of Urological Pathology (ISUP) 2005 modification to the Gleason grading system might have resulted in a marked upgrading of biopsy-diagnosed prostate cancers, reducing the number of men eligible for active surveillance. An updated definition of insignificant prostate cancer should reflect the optimal trade-off between reducing the risk of underestimating a significant prostate cancer and including as many men as possible in active surveillance programmes. PMID:23712205

  3. An improved method to set significance thresholds for β diversity testing in microbial community comparisons.

    PubMed

    Gülay, Arda; Smets, Barth F

    2015-09-01

    Exploring the variation in microbial community diversity between locations (β diversity) is a central topic in microbial ecology. Currently, there is no consensus on how to set the significance threshold for β diversity. Here, we describe and quantify the technical components of β diversity, including those associated with the process of subsampling. These components exist for any proposed β diversity measurement procedure. Further, we introduce a strategy to set significance thresholds for β diversity of any group of microbial samples using rarefaction, invoking the notion of a meta-community. The proposed technique was applied to several in silico generated operational taxonomic unit (OTU) libraries and experimental 16S rRNA pyrosequencing libraries. The latter represented microbial communities from different biological rapid sand filters at a full-scale waterworks. We observe that β diversity, after subsampling, is inflated by intra-sample differences; this inflation is avoided in the proposed method. In addition, microbial community evenness (Gini > 0.08) strongly affects all β diversity estimations due to bias associated with rarefaction. Where published methods to test β significance often fail, the proposed meta-community-based estimator is more successful at rejecting insignificant β diversity values. Applying our approach, we reveal the heterogeneous microbial structure of biological rapid sand filters both within and across filters. PMID:25534614

  4. 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. PMID:25609782

  5. [Thresholds of continuously approaching sound sources with rhythmic structures typical for biologically significant signals].

    PubMed

    Andreeva, I G; Gvozdeva, A P

    2015-01-01

    Localization of biologically significant moving rhythmic sources with different pulse/pause ratio has been practically not investigated. The issue of the perception thresholds of continuously approaching sound sources is addressed in the present study. The illusion of approaching sound courses was created by noise pulse sequences linearly increasing in amplitude and emitted by a loudspeaker placed at the level of the subject's head, 1.1 m away, under free field conditions. The sequences were formed by short (5 and 10 ms) or long (70 and 100 ms) pulses. The continuous movement thresholds were evaluated by the pauses between noise pulses varying from 10 to 150 ms. For the short pulse sequences the thresholds were 49 and 41 ms, while for the long ones they decreased to 21 and 16 ms, respectively. A progressive decay of the continuous movement perception threshold in pausing between noise pulses with increasing width over the whole pulse-width range studied was observed. The thresholds for the short noise pulse sequences were 54 and 51 ms did not differ significantly, while for the long noise pulse sequences they were almost twice as long, 91 and 115 ms. For the structures representing the short (up to 10 ms) pulse sequences, the thresholds were highly variable in magnitude that is indicative of a probabilistic evaluation of movement in case of insufficient information. For the long (tens of ms) pulse sequences, the threshold evaluation was stabilized. The continuous movement thresholds and the effective masking time for sound pulse sequences coincided suggesting critical role of non-simultaneous masking for the evaluation of movement continuity. PMID:25859603

  6. 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.

  7. 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…

  8. 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.

  9. 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

  10. Factors influencing the outcome of intrauterine insemination (IUI): age, clinical variables and significant thresholds.

    PubMed

    Speyer, B E; Abramov, B; Saab, W; Doshi, A; Sarna, U; Harper, J C; Serhal, P

    2013-10-01

    The aim was to investigate the influence of various biological factors upon the outcome of intrauterine insemination (IUI). The total IUI history (856 cycles) of 352 couples was studied. Live-birth showed a strong negative correlation with female age but no correlation with male age. Antimüllerian hormone (AMH) and antral follicle count (AFC) correlated negatively with female age, and follicle stimulating hormone (FSH) correlated positively. Significant thresholds were found for all three variables, and also for total motile count (TMC) in the prepared sperm. Calculating pregnancy losses per positive pregnancy showed a strong correlation with increasing female age. This was highly significant for biochemical losses but not for fetal heart miscarriages. Male age had no effect on rate of pregnancy loss. In conclusion, female age, FSH, AMH and TMC are good predictive factors for live-birth and therefore relate to essential in vivo steps in the reproductive process. PMID:24127958

  11. Ribavirin reveals a lethal threshold of allowable mutation frequency for Hantaan virus.

    PubMed

    Chung, Dong-Hoon; Sun, Yanjie; Parker, William B; Arterburn, Jeffrey B; Bartolucci, Al; Jonsson, Colleen B

    2007-11-01

    The broad spectrum of antiviral activity of ribavirin (RBV) lies in its ability to inhibit IMP dehydrogenase, which lowers cellular GTP. However, RBV can act as a potent mutagen for some RNA viruses. Previously we have shown a lack of correlation between antiviral activity and GTP repression for Hantaan virus (HTNV) and evidence for RBV's ability to promote error-prone replication. To further explore the mechanism of RBV, GTP levels, specific infectivity, and/or mutation frequency was measured in the presence of RBV, mycophenolic acid (MPA), selenazofurin, or tiazofurin. While all four drugs resulted in a decrease in the GTP levels and infectious virus, only RBV increased the mutation frequency of viral RNA (vRNA). MPA, however, could enhance RBV's mutagenic effect, which suggests distinct mechanisms of action for each. Therefore, a simple drop in GTP levels does not drive the observed error-prone replication. To further explore RBV's mechanism of action, we made a comprehensive analysis of the mutation frequency over several RBV concentrations. Of importance, we observed that the viral population reached a threshold after which mutation frequency did not correlate with a dose-dependent decrease in the level of vRNA, PFU, or [RTP]/[GTP] (where RTP is ribavirin-5'-triphosphate) over these same concentrations of RBV. Modeling of the relationship of mutation frequency and drug concentration showed an asymptotic relationship at this point. After this threshold, approximately 57% of the viral cDNA population was identical to the wild type. These studies revealed a lethal threshold, after which we did not observe a complete loss of the quasispecies structure of the wild-type genome, although we observed extinction of HTNV. PMID:17699579

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

    PubMed Central

    McCarthy, Davis J.; Smyth, Gordon K.

    2009-01-01

    Motivation: 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. Results: 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. Availability: R code implementing our methods is contributed to the software package limma available at http://www.bioconductor.org. Contact: smyth@wehi.edu.au PMID:19176553

  13. Lateralized readiness potentials reveal properties of a neural mechanism for implementing a decision threshold.

    PubMed

    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. On the necessity and biological significance of threshold-free regulon prediction outputs.

    PubMed

    Rigali, Sébastien; Nivelle, Renaud; Tocquin, Pierre

    2015-02-01

    The in silico prediction of cis-acting elements in a genome is an efficient way to quickly obtain an overview of the biological processes controlled by a trans-acting factor, and connections between regulatory networks. Several regulon prediction web tools are available, designed to identify DNA motifs predicted to be bound by transcription factors using position weight matrix-based algorithms. In this paper we expose and discuss the conflicting objectives of software creators (bioinformaticians) and software users (biologists), who aim for reliable and exhaustive prediction outputs, respectively. Software makers, concerned with providing tools that minimise the number of false positive hits, often impose a stringent threshold score for a sequence to be included in the list of the putative cis-acting sites. This rigidity eventually results in the identification of strongly reliable but largely straightforward sites, i.e. those associated with genes already anticipated to be targeted by the studied transcription factor. Importantly, this biased identification of strongly bound sequences contrasts with the biological reality where, in many circumstances, a weak DNA-protein interaction is required for the appropriate gene's expression. We show here a series of transcriptionally controlled systems involving weakly bound cis-acting elements that could never have been discovered because of the policy of preventing software users from modifying the screening parameters. Proposing only trustworthy prediction outputs thus prevents biologists from fully utilising their knowledge background and deciding to analyse statistically irrelevant hits that could nonetheless be potentially involved in subtle, unexpected, though essential cis-trans relationships. PMID:25387521

  15. 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. PMID:23192370

  16. 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

    2008-03-01

    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. PMID:18191423

  17. 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.

  18. 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. PMID:27107834

  19. 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...: Images of Women in Qing Dynasty Chinese Painting,'' imported from abroad for temporary exhibition...

  20. The Significance of Accounting Order for Evapotranspiration and Recharge in Monthly and Daily Threshold-Type Water Budgets

    USGS Publications Warehouse

    Oki, Delwyn S.

    2008-01-01

    Most threshold-type water-budget models account for the loss of water by evapotranspiration before accounting for recharge. Recharge estimates can differ substantially, depending on whether recharge is counted before or after evapotranspiration in the water budget. This disparity is the source of uncertainty and is most pronounced for areas where soil-moisture storage capacity is small or for water budgets computed using a large time interval (such as monthly). Water budgets that account for recharge before evapotranspiration provide higher estimates of recharge and lower estimates of evapotranspiration relative to water budgets that account for evapotranspiration before recharge. The choice of accounting method is less significant for a daily computation interval than for a monthly computation interval. In general, uncertainty in recharge estimates is least for water budgets computed using the shortest computation interval that the data allow and that is consistent with the physical processes being represented. If the data only allow for long (weekly or monthly) computation intervals, then selecting the appropriate accounting order for the study area may be critical. For monthly water budgets, accounting for recharge before evapotranspiration is most appropriate in areas where rainfall occurs infrequently, whereas accounting for evapotranspiration before recharge is most appropriate where rainfall occurs relatively uniformly throughout the month.

  1. Increasing the oscillation frequency of strong magnetic fields above 101 kHz significantly raises peripheral nerve excitation thresholds

    PubMed Central

    Weinberg, Irving N.; Stepanov, Pavel Y.; Fricke, Stanley T.; Probst, Roland; Urdaneta, Mario; Warnow, Daniel; Sanders, Howard; Glidden, Steven C.; McMillan, Alan; Starewicz, Piotr M.; Reilly, J. Patrick

    2012-01-01

    Purpose: A time-varying magnetic field can cause unpleasant peripheral nerve stimulation (PNS) when the maximum excursion of the magnetic field (ΔB) is above a frequency-dependent threshold level [P. Mansfield and P. R. Harvey, Magn. Reson. Med. 29, 746–758 (1993)]. Clinical and research magnetic resonance imaging (MRI) gradient systems have been designed to avoid such bioeffects by adhering to regulations and guidelines established on the basis of clinical trials. Those trials, generally employing sinusoidal waveforms, tested human responses to magnetic fields at frequencies between 0.5 and 10 kHz [W. Irnich and F. Schmitt, Magn. Reson. Med. 33, 619–623 (1995), T. F. Budinger et al., J. Comput. Assist. Tomogr. 15, 909–914 (1991), and D. J. Schaefer et al., J. Magn. Reson. Imaging 12, 20–29 (2000)]. PNS thresholds for frequencies higher than 10 kHz had been extrapolated, using physiological models [J. P. Reilly et al., IEEE Trans. Biomed. Eng. BME-32(12), 1001–1011 (1985)]. The present study provides experimental data on human PNS thresholds to oscillating magnetic field stimulation from 2 to 183 kHz. Sinusoidal waveforms were employed for several reasons: (1) to facilitate comparison with earlier reports that used sine waves, (2) because prior designers of fast gradient hardware for generalized waveforms (e.g., including trapezoidal pulses) have employed quarter-sine-wave resonant circuits to reduce the rise- and fall-times of pulse waveforms, and (3) because sinusoids are often used in fast pulse sequences (e.g., spiral scans) [S. Nowak, U.S. patent 5,245,287 (14 September 1993) and K. F. King and D. J. Schaefer, J. Magn. Reson. Imaging 12, 164–170 (2000)]. Methods: An IRB-approved prospective clinical trial was performed, involving 26 adults, in which one wrist was exposed to decaying sinusoidal magnetic field pulses at frequencies from 2 to 183 kHz and amplitudes up to 0.4 T. Sham exposures (i.e., with no magnetic fields) were applied to all

  2. 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

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

    PubMed

    Rao, Guodong; Sui, Jinkai; Zhang, Jianguo

    2016-01-01

    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 r(2)≥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

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

    NASA Astrophysics Data System (ADS)

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

    2014-01-01

    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 X2E of CH3Br+ is stable, and both A2A1 and B2E 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(2P) atom can be clearly observed in fast dissociation of CH3Br+(A2A1) ion along C-Br rupture, while a KERD of Maxwell-Boltzmann profile is obtained in dissociation of CH3Br+(B2E) ion. With the aid of the re-calculated potential energy curves of CH3Br+ including spin-orbit coupling, dissociation mechanisms of CH3Br+ ion in A2A1 and B2E states along C-Br rupture are revealed. For CH3Br+(A2A1) ion, the CH3+ + Br(2P1/2) channel is occurred via an adiabatic dissociation by vibration, while the Br(2P3/2) formation is through vibronic coupling to the high vibrational level of X2E state followed by rapid dissociation. C-Br bond breaking of CH3Br+(B2E) ion can occur via slow internal conversion to the excited vibrational level of the lower electronic states and then dissociation.

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

    NASA Astrophysics Data System (ADS)

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

    2013-12-01

    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.

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

    SciTech Connect

    Tang, Xiaofeng; Zhou, Xiaoguo E-mail: yanbing@jlu.edu.cn; Liu, Shilin; Sun, Zhongfa; Liu, Fuyi; Sheng, Liusi; Yan, Bing E-mail: yanbing@jlu.edu.cn

    2014-01-28

    Dissociative photoionization of methyl bromide (CH{sub 3}Br) 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{sup 2}E of CH{sub 3}Br{sup +} is stable, and both A{sup 2}A{sub 1} and B{sup 2}E ionic excited states are fully dissociative to produce the unique fragment ion of CH{sub 3}{sup +}. From TPEPICO 3D time-sliced velocity images of CH{sub 3}{sup +} dissociated from specific state-selected CH{sub 3}Br{sup +} ion, kinetic energy release distribution (KERD) and angular distribution of CH{sub 3}{sup +} fragment ion are directly obtained. Both spin-orbit states of Br({sup 2}P) atom can be clearly observed in fast dissociation of CH{sub 3}Br{sup +}(A{sup 2}A{sub 1}) ion along C–Br rupture, while a KERD of Maxwell-Boltzmann profile is obtained in dissociation of CH{sub 3}Br{sup +}(B{sup 2}E) ion. With the aid of the re-calculated potential energy curves of CH{sub 3}Br{sup +} including spin-orbit coupling, dissociation mechanisms of CH{sub 3}Br{sup +} ion in A{sup 2}A{sub 1} and B{sup 2}E states along C–Br rupture are revealed. For CH{sub 3}Br{sup +}(A{sup 2}A{sub 1}) ion, the CH{sub 3}{sup +} + Br({sup 2}P{sub 1/2}) channel is occurred via an adiabatic dissociation by vibration, while the Br({sup 2}P{sub 3/2}) formation is through vibronic coupling to the high vibrational level of X{sup 2}E state followed by rapid dissociation. C–Br bond breaking of CH{sub 3}Br{sup +}(B{sup 2}E) ion can occur via slow internal conversion to the excited vibrational level of the lower electronic states and then dissociation.

  7. 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. PMID:24942044

  8. Thresholds and criteria for evaluating and communicating impact significance in environmental statements: 'See no evil, hear no evil, speak no evil'?

    SciTech Connect

    Wood, Graham

    2008-01-15

    The evaluation and communication of the significance of environmental effects remains a critical yet poorly understood component of EIA theory and practice. Following a conceptual overview of the generic dimensions of impact significance in EIA, this paper reports upon the findings of an empirical study of recent environmental impact statements that considers the treatment of significance for impacts concerning landscape ('see no evil') and noise ('hear no evil'), focussing specifically upon the evaluation and communication of impact significance ('speak no evil') in UK practice. Particular attention is given to the use of significance criteria and thresholds, including the development of a typology of approaches applied within the context of noise and landscape/visual impacts. Following a broader discussion of issues surrounding the formulation, application and interpretation of significance criteria, conclusions and recommendations relevant to wider EIA practice are suggested.

  9. A spontaneous metastasis model reveals the significance of claudin-9 overexpression in lung cancer metastasis.

    PubMed

    Sharma, Rajesh K; Chheda, Zinal S; Das Purkayastha, Biswa Pratim; Gomez-Gutierrez, Jorge G; Jala, Venkatakrishna R; Haribabu, Bodduluri

    2016-03-01

    Metastasis causes most cancer related mortality but the mechanisms governing metastatic dissemination are poorly defined. Metastasis involves egression of cancer cells from the primary tumors, their survival in circulation and colonization at the secondary sites. Cancer cell egression from the primary tumor is the least defined process of metastasis as experimental metastasis models directly seed cancer cells in circulation, thus bypassing this crucial step. Here, we developed a spontaneous metastasis model that retains the egression step of metastasis. By repeated in vivo passaging of the poorly metastatic Lewis lung carcinoma (3LL) cells, we generated a cell line (p-3LL) that readily metastasizes to lungs and liver from subcutaneous (s.c.) tumors. Interestingly, when injected intravenously, 3LL and p-3LL cells showed a similar frequency of metastasis. This suggests enhanced egression of p-3LL cells may underlie the enhanced metastatic spread from primary tumors. Microarray analysis of 3LL and p-3LL cells as well as the primary tumors derived from these cells revealed altered expression of several genes including significant upregulation of a tight junction protein, claudin-9. Increased expression of claudin-9 was confirmed in both p-3LL cells and tumors derived from these cells. Knockdown of claudin-9 expression in p-3LL cells by si-RNA significantly reduced their motility, invasiveness in vitro and metastasis in vivo. Conversely, transient overexpression of claudin-9 in 3LL cells enhanced their motility. These results suggest an essential role for claudin-9 in promoting lung cancer metastasis. PMID:26669782

  10. Next-Generation Sequencing Reveals Significant Bacterial Diversity of Botrytized Wine

    PubMed Central

    Bokulich, Nicholas A.; Joseph, C. M. Lucy; Allen, Greg; Benson, Andrew K.; Mills, David A.

    2012-01-01

    While wine fermentation has long been known to involve complex microbial communities, the composition and role of bacteria other than a select set of lactic acid bacteria (LAB) has often been assumed either negligible or detrimental. This study served as a pilot study for using barcoded amplicon next-generation sequencing to profile bacterial community structure in wines and grape musts, comparing the taxonomic depth achieved by sequencing two different domains of prokaryotic 16S rDNA (V4 and V5). This study was designed to serve two goals: 1) to empirically determine the most taxonomically informative 16S rDNA target region for barcoded amplicon sequencing of wine, comparing V4 and V5 domains of bacterial 16S rDNA to terminal restriction fragment length polymorphism (TRFLP) of LAB communities; and 2) to explore the bacterial communities of wine fermentation to better understand the biodiversity of wine at a depth previously unattainable using other techniques. Analysis of amplicons from the V4 and V5 provided similar views of the bacterial communities of botrytized wine fermentations, revealing a broad diversity of low-abundance taxa not traditionally associated with wine, as well as atypical LAB communities initially detected by TRFLP. The V4 domain was determined as the more suitable read for wine ecology studies, as it provided greater taxonomic depth for profiling LAB communities. In addition, targeted enrichment was used to isolate two species of Alphaproteobacteria from a finished fermentation. Significant differences in diversity between inoculated and uninoculated samples suggest that Saccharomyces inoculation exerts selective pressure on bacterial diversity in these fermentations, most notably suppressing abundance of acetic acid bacteria. These results determine the bacterial diversity of botrytized wines to be far higher than previously realized, providing further insight into the fermentation dynamics of these wines, and demonstrate the utility of next

  11. The Impact of DSM-IV Symptom and Clinical Significance Criteria on the Prevalence Estimates of Subthreshold and Threshold Anxiety in the Older Adult Population

    PubMed Central

    Grenier, Sébastien; Préville, Michel; Boyer, Richard; O’Connor, Kieron; Béland, Sarah-Gabrielle; Potvin, Olivier; Hudon, Carol; Brassard, Joëlle

    2013-01-01

    Objectives Subthreshold anxiety refers to a condition where individuals do not meet the full symptom criteria (i.e., the number of symptoms required for a formal diagnosis is not reached) and/or do not report significant impairment or distress in functioning (i.e., the clinical significance criterion is not met). The purpose of this study was to examine how the symptom and the clinical significance criteria may affect the prevalence estimates of anxiety problems in the older adult population and whether applying these criteria results in an identifiable older group showing more severe anxiety. Setting and Participants Data came from a large representative sample of community-dwelling older adults age 65 years and older (N = 2,784). Results Results showed that the 12-month prevalence rate of any anxiety problem varied from 5.6% when DSM-IV criteria for anxiety disorders were used to 26.2% when all subthreshold manifestations of anxiety were considered. Findings also indicated that when compared with respondents without anxiety, older adults presenting different manifestations of subthreshold or threshold anxiety appear to be more similar than different in their health and health behavior characteristics. Conclusions Subthreshold anxiety has a high prevalence and may cause significant impairment. Both symptom and clinical significance criteria do not perfectly discriminate between older adults with or without a severe anxiety problem presenting comorbid disorders and needing psychiatric help. PMID:21427640

  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. PMID:27447176

  13. Cancer-associated p53 tetramerization domain mutants: quantitative analysis reveals a low threshold for tumor suppressor inactivation

    SciTech Connect

    Kamada, R.; Anderson, C.; Nomura, T.; Sakaguchi, K.

    2011-01-07

    The tumor suppressor p53, a 393-amino acid transcription factor, induces cell cycle arrest and apoptosis in response to genotoxic stress. Its inactivation via the mutation of its gene is a key step in tumor progression, and tetramer formation is critical for p53 post-translational modification and its ability to activate or repress the transcription of target genes vital in inhibiting tumor growth. About 50% of human tumors have TP53 gene mutations; most are missense ones that presumably lower the tumor suppressor activity of p53. In this study, we explored the effects of known tumor-derived missense mutations on the stability and oligomeric structure of p53; our comprehensive, quantitative analyses encompassed the tetramerization domain peptides representing 49 such substitutions in humans. Their effects on tetrameric structure were broad, and the stability of the mutant peptides varied widely ({Delta}T{sub m} = 4.8 {approx} -46.8 C). Because formation of a tetrameric structure is critical for protein-protein interactions, DNA binding, and the post-translational modification of p53, a small destabilization of the tetrameric structure could result in dysfunction of tumor suppressor activity. We suggest that the threshold for loss of tumor suppressor activity in terms of the disruption of the tetrameric structure of p53 could be extremely low. However, other properties of the tetramerization domain, such as electrostatic surface potential and its ability to bind partner proteins, also may be important.

  14. Recent progress in revealing the biological and medical significance of the non-neuronal cholinergic system.

    PubMed

    Grando, Sergei A; Kawashima, Koichiro; Kirkpatrick, Charles J; Kummer, Wolfgang; Wessler, Ignaz

    2015-11-01

    This special issue of International Immunopharmacology is the proceedings of the Fourth International Symposium on Non-neuronal Acetylcholine that was held on August 28-30, 2014 at the Justus Liebig University of Giessen in Germany. It contains original contributions of meeting participants covering the significant progress in understanding of the biological and medical significance of the non-neuronal cholinergic system extending from exciting insights into molecular mechanisms regulating this system via miRNAs over the discovery of novel cholinergic cellular signaling circuitries to clinical implications in cancer, wound healing, immunity and inflammation, cardiovascular, respiratory and other diseases. PMID:26362206

  15. Membrane bioreactor wastewater treatment plants reveal diverse yeast and protist communities of potential significance in biofouling.

    PubMed

    Liébana, Raquel; Arregui, Lucía; Belda, Ignacio; Gamella, Luis; Santos, Antonio; Marquina, Domingo; Serrano, Susana

    2015-01-01

    The yeast community was studied in a municipal full-scale membrane bioreactor wastewater treatment plant (MBR-WWTP). The unexpectedly high diversity of yeasts indicated that the activated sludge formed a suitable environment for them to proliferate, with cellular concentrations of 2.2 ± 0.8 × 10(3) CFU ml(-1). Sixteen species of seven genera were present in the biological reactor, with Ascomycetes being the most prevalent group (93%). Most isolates were able to grow in a synthetic wastewater medium, adhere to polyethylene surfaces, and develop biofilms of variable complexity. The relationship between yeast populations and the protists in the MBR-WWTP was also studied, revealing that some protist species preyed on and ingested yeasts. These results suggest that yeast populations may play a role in the food web of a WWTP and, to some extent, contribute to membrane biofouling in MBR systems. PMID:25588128

  16. 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

  17. [Phylogenomic analysis reveals the significant expansion of gene families of Volvariella volvacea ].

    PubMed

    Gong, Ming; Tan, Qi; Chen, Mingjie; Bao, Dapeng; Wang, Hong

    2014-09-01

    [OBJECTIVE] Cryogenic autolysis of Volvariella volvacea is an unusual phenomenon of abnormal metabolism. The aim of this study was to describe this molecular feature of abnormal metabolism at the genome-level. [METHODS] We used 21 fungal species for the phylogenomic analysis and then selected 9 representative species in basidiomycetes for the comparative genomic analysis. [ RESULTS] The phylogenomic analysis shows that V. volvacea was located at the bottom of the cluster consisting of grass-degrading fungi. Phylogenetic tree shows that basidiomycetes and ascomycetes fungi have independent evolutionary trajectories. Therefore, nine representative species in basidiomycetes were chosen for the comparative genomic analysis. The result shows that compared to other grass-degrading fungi, V. volvacea has the tendency of contraction. The comparison of the number of gene families on a different scale shows that there was a significant expansion of 3 large size ( > 200) gene families (faml, fam4 and fam6) in V. volvacea with their total number significantly more than other species, representing that the molecular feature of V. volvacea is correlated with its abnormal metabolism. [ CONCLUSION] The significant expansion of 3 gene families ( > 200) in V. volvacea indicates the enhancement of their function in specific gene families, which is most likely associated with cryogenic autolysis of V. volvacea. PMID:25522588

  18. 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.

  19. 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.

  20. Association Mapping in Turkish Olive Cultivars Revealed Significant Markers Related to Some Important Agronomic Traits.

    PubMed

    Kaya, Hilal Betul; Cetin, Oznur; Kaya, Hulya Sozer; Sahin, Mustafa; Sefer, Filiz; Tanyolac, Bahattin

    2016-08-01

    Olive (Olea europaea L.) is one of the most important fruit trees especially in the Mediterranean countries due to high consumption of table olive and olive oil. In olive breeding, the phenotypic traits associated to fruit are the key factors that determine productivity. Association mapping has been used in some tree species and a lot of crop plant species, and here, we perform an initial effort to detect marker-trait associations in olive tree. In the current study, a total of 96 olive genotypes, including both oil and table olive genotypes from Turkish Olive GenBank Resources, were used to examine marker-trait associations. For olive genotyping, SNP, AFLP, and SSR marker data were selected from previously published study and association analysis was performed between these markers and 5 yield-related traits. Three different approaches were used to check for false-positive results in association tests, and association results obtained from these models were compared. Using the model utilizing both population structure and relative kinship, eleven associations were significant with FDR ≤ 0.05. The largest number of significant associations was detected for fruit weight and stone weight. Our results suggested that association mapping could be an effective approach for identifying marker-trait associations in olive genotypes, without the development of mapping populations. This study shows for the first time the use of association mapping for identifying molecular markers linked to important traits in olive tree. PMID:27209034

  1. Transcriptomic and Protein Expression Analysis Reveals Clinicopathological Significance of Bloom Syndrome Helicase (BLM) in Breast Cancer.

    PubMed

    Arora, Arvind; Abdel-Fatah, Tarek M A; Agarwal, Devika; Doherty, Rachel; Moseley, Paul M; Aleskandarany, Mohammed A; Green, Andrew R; Ball, Graham; Alshareeda, Alaa T; Rakha, Emad A; Chan, Stephen Y T; Ellis, Ian O; Madhusudan, Srinivasan

    2015-04-01

    Bloom syndrome helicase (BLM) has key roles in homologous recombination repair, telomere maintenance, and DNA replication. Germ-line mutations in the BLM gene causes Bloom syndrome, a rare disorder characterized by premature aging and predisposition to multiple cancers, including breast cancer. The clinicopathologic significance of BLM in sporadic breast cancers is unknown. We investigated BLM mRNA expression in the Molecular Taxonomy of Breast Cancer International Consortium cohort (n = 1,950) and validated in an external dataset of 2,413 tumors. BLM protein level was evaluated in the Nottingham Tenovus series comprising 1,650 breast tumors. BLM mRNA overexpression was significantly associated with high histologic grade, larger tumor size, estrogen receptor-negative (ER(-)), progesterone receptor-negative (PR(-)), and triple-negative phenotypes (ps < 0.0001). BLM mRNA overexpression was also linked to aggressive molecular phenotypes, including PAM50.Her2 (P < 0.0001), PAM50.Basal (P < 0.0001), and PAM50.LumB (P < 0.0001) and Genufu subtype (ER(+)/Her2(-)/high proliferation; P < 0.0001). PAM50.LumA tumors and Genufu subtype (ER(+)/Her2(-)/low proliferation) were more likely to express low levels of BLM mRNA (ps < 0.0001). Integrative molecular clusters (intClust) intClust.1 (P < 0.0001), intClust.5 (P < 0.0001), intClust.9 (P < 0.0001), and intClust.10 (P < 0.0001) were also more likely in tumors with high BLM mRNA expression. BLM mRNA overexpression was associated with poor breast cancer-specific survival (BCSS; ps < 0.000001). At the protein level, altered subcellular localization with high cytoplasmic BLM and low nuclear BLM was linked to aggressive phenotypes. In multivariate analysis, BLM mRNA and BLM protein levels independently influenced BCSS. This is the first and the largest study to provide evidence that BLM is a promising biomarker in breast cancer. PMID:25673821

  2. Integrated Genomic Analysis of Pancreatic Ductal Adenocarcinomas Reveals Genomic Rearrangement Events as Significant Drivers of Disease.

    PubMed

    Murphy, Stephen J; Hart, Steven N; Halling, Geoffrey C; Johnson, Sarah H; Smadbeck, James B; Drucker, Travis; Lima, Joema Felipe; Rohakhtar, Fariborz Rakhshan; Harris, Faye R; Kosari, Farhad; Subramanian, Subbaya; Petersen, Gloria M; Wiltshire, Timothy D; Kipp, Benjamin R; Truty, Mark J; McWilliams, Robert R; Couch, Fergus J; Vasmatzis, George

    2016-02-01

    Many somatic mutations have been detected in pancreatic ductal adenocarcinoma (PDAC), leading to the identification of some key drivers of disease progression, but the involvement of large genomic rearrangements has often been overlooked. In this study, we performed mate pair sequencing (MPseq) on genomic DNA from 24 PDAC tumors, including 15 laser-captured microdissected PDAC and 9 patient-derived xenografts, to identify genome-wide rearrangements. Large genomic rearrangements with intragenic breakpoints altering key regulatory genes involved in PDAC progression were detected in all tumors. SMAD4, ZNF521, and FHIT were among the most frequently hit genes. Conversely, commonly reported genes with copy number gains, including MYC and GATA6, were frequently observed in the absence of direct intragenic breakpoints, suggesting a requirement for sustaining oncogenic function during PDAC progression. Integration of data from MPseq, exome sequencing, and transcriptome analysis of primary PDAC cases identified limited overlap in genes affected by both rearrangements and point mutations. However, significant overlap was observed in major PDAC-associated signaling pathways, with all PDAC exhibiting reduced SMAD4 expression, reduced SMAD-dependent TGFβ signaling, and increased WNT and Hedgehog signaling. The frequent loss of SMAD4 and FHIT due to genomic rearrangements strongly implicates these genes as key drivers of PDAC, thus highlighting the strengths of an integrated genomic and transcriptomic approach for identifying mechanisms underlying disease initiation and progression. PMID:26676757

  3. 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

  4. 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

  5. Threshold-voltage instability in 4H-SiC MOSFETs with nitrided gate oxide revealed by non-relaxation method

    NASA Astrophysics Data System (ADS)

    Sometani, Mitsuru; Okamoto, Dai; Harada, Shinsuke; Ishimori, Hitoshi; Takasu, Shinji; Hatakeyama, Tetsuo; Takei, Manabu; Yonezawa, Yoshiyuki; Fukuda, Kenji; Okumura, Hajime

    2016-04-01

    The threshold-voltage (V th) shift of 4H-SiC MOSFETs with Ar or N2O post-oxidation annealing (POA) was measured by conventional sweep and non-relaxation methods. Although the V th shift values of both samples were almost identical when measured by the sweep method, those for the Ar POA samples were larger than those for the N2O POA samples when measured by the non-relaxation method. Thus, we can say that investigating the exact V th shifts using only the conventional sweep method is difficult. The temperature-dependent analysis of the V th shifts measured by both methods revealed that the N2O POA decreases charge trapping in the near-interface region of the SiO2.

  6. Anaerobic Threshold and Salivary α-amylase during Incremental Exercise

    PubMed Central

    Akizuki, Kazunori; Yazaki, Syouichirou; Echizenya, Yuki; Ohashi, Yukari

    2014-01-01

    [Purpose] The purpose of this study was to clarify the validity of salivary α-amylase as a method of quickly estimating anaerobic threshold and to establish the relationship between salivary α-amylase and double-product breakpoint in order to create a way to adjust exercise intensity to a safe and effective range. [Subjects and Methods] Eleven healthy young adults performed an incremental exercise test using a cycle ergometer. During the incremental exercise test, oxygen consumption, carbon dioxide production, and ventilatory equivalent were measured using a breath-by-breath gas analyzer. Systolic blood pressure and heart rate were measured to calculate the double product, from which double-product breakpoint was determined. Salivary α-amylase was measured to calculate the salivary threshold. [Results] One-way ANOVA revealed no significant differences among workloads at the anaerobic threshold, double-product breakpoint, and salivary threshold. Significant correlations were found between anaerobic threshold and salivary threshold and between anaerobic threshold and double-product breakpoint. [Conclusion] As a method for estimating anaerobic threshold, salivary threshold was as good as or better than determination of double-product breakpoint because the correlation between anaerobic threshold and salivary threshold was higher than the correlation between anaerobic threshold and double-product breakpoint. Therefore, salivary threshold is a useful index of anaerobic threshold during an incremental workload. PMID:25140097

  7. 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.

  8. 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.

  9. 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

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

    PubMed

    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

  11. 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.

  12. 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

  13. Surgically resected human tumors reveal the biological significance of the gastric cancer stem cell markers CD44 and CD26

    PubMed Central

    NISHIKAWA, SHIMPEI; KONNO, MASAMITSU; HAMABE, ATSUSHI; HASEGAWA, SHINICHIRO; KANO, YOSHIHIRO; FUKUSUMI, TAKAHITO; SATOH, TAROH; TAKIGUCHI, SHUJI; MORI, MASAKI; DOKI, YUICHIRO; ISHII, HIDESHI

    2015-01-01

    Cancer tissue is maintained by relatively small populations of cancer stem cells (CSCs), which are involved in chemotherapy resistance, recurrence and metastasis. As tumor tissues are comprised of various cells, studies of human clinical samples are important for the characterization of CSCs. In the present study, an expression profiling study was performed in which an anti-cell surface marker antibody-based array platform, a flow cytometry-based cell separation technique and a tumorigenicity analysis in immunodeficient animals were utilized. These approaches revealed that the markers cluster of differentiation (CD)44 and CD26 facilitated the fractionation of surgically resected human gastric cancer (GC) cells into the following subset populations with distinct tumorigenic potentials: Highly tumorigenic CD26+CD44+ cells (6/6 mice formed tumors), moderately tumorigenic CD26+CD44− cells (5/6 mice formed tumors), and weakly or non-tumorigenic CD26−CD44− cells (2/6 mice formed tumors). Furthermore, exposure to 5-fluorouracil significantly increased the proportion of CD26+ cells in vitro. The present study demonstrated that the combined expression of CD26 and CD44 presents a potential marker of human GC stem cells. PMID:26137071

  14. 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

  15. Molecular analysis of faecal and duodenal samples reveals significantly higher prevalence and numbers of Pseudomonas aeruginosa in irritable bowel syndrome.

    PubMed

    Kerckhoffs, Angèle P M; Ben-Amor, Kaouther; Samsom, Melvin; van der Rest, Michel E; de Vogel, Joris; Knol, Jan; Akkermans, Louis M A

    2011-02-01

    Intestinal microbiota may play a role in the pathophysiology of irritable bowel syndrome (IBS). In this case-control study, mucosa-associated small intestinal and faecal microbiota of IBS patients and healthy subjects were analysed using molecular-based methods. Duodenal mucosal brush and faecal samples were collected from 37 IBS patients and 20 healthy subjects. The bacterial 16S rRNA gene was amplified and analysed using PCR denaturing gradient gel electrophoresis (DGGE). Pooled average DGGE profiles of all IBS patients and all healthy subjects from both sampling sites were generated and fingerprints of both groups were compared. The DGGE band fragments which were confined to one group were further characterized by sequence analysis. Quantitative real-time PCR (q-PCR) was used to quantify the disease-associated microbiota. Averaged DGGE profiles of both groups were identical for 78.2 % in the small intestinal samples and for 86.25 % in the faecal samples. Cloning and sequencing of the specific bands isolated from small intestinal and faecal DGGE patterns of IBS patients showed that 45.8 % of the clones belonged to the genus Pseudomonas, of which Pseudomonas aeruginosa was the predominant species. q-PCR analysis revealed higher levels (P<0.001) of P. aeruginosa in the small intestine of IBS patients (8.3 %±0.950) than in the small intestine of healthy subjects (0.1 %±0.069). P. aeruginosa was also significantly (P<0.001) more abundant (2.34 %±0.31) in faeces of IBS patients than in faeces of healthy subjects (0.003 %±0.0027). This study shows that P. aeruginosa is detected more frequently and at higher levels in IBS patients than in healthy subjects, suggesting its potential role in the pathophysiology of IBS. PMID:20947663

  16. 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.

  17. 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

  18. 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

  19. 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

    2016-01-01

    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

  20. 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

  1. Co-evolution of cancer microenvironment reveals distinctive patterns of gastric cancer invasion: laboratory evidence and clinical significance

    PubMed Central

    2010-01-01

    Background Cancer invasion results from constant interactions between cancer cells and their microenvironment. Major components of the cancer microenvironment are stromal cells, infiltrating inflammatory cells, collagens, matrix metalloproteinases (MMP) and newly formed blood vessels. This study was to determine the roles of MMP-9, MMP-2, type IV collagen, infiltrating macrophages and tumor microvessels in gastric cancer (GC) invasion and their clinico-pathological significance. Methods Paraffin-embedded tissue sections from 37 GC patients were studied by Streptavidin-Peroxidase (SP) immunohistochemical technique to determine the levels of MMP-2, MMP-9, type IV collagen, macrophages infiltration and microvessel density (MVD). Different invasion patterns were delineated and their correlation with major clinico-pathological information was explored. Results MMP2 expression was higher in malignant gland compared to normal gland, especially nearby the basement membrane (BM). High densities of macrophages at the interface of cancer nests and stroma were found where BM integrity was destroyed. MMP2 expression was significantly increased in cases with recurrence and distant metastasis (P = 0.047 and 0.048, respectively). Infiltrating macrophages were correlated with serosa invasion (P = 0.011) and TNM stage (P = 0.001). MVD was higher in type IV collagen negative group compared to type IV collagen positive group (P = 0.026). MVD was related to infiltrating macrophages density (P = 0.040). Patients with negative MMP9 expression had better overall survival (OS) compared to those with positive MMP9 expression (Median OS 44.0 vs 13.5 mo, P = 0.036). Median OS was significantly longer in type IV collagen positive group than negative group (Median OS 25.5 vs 10.0 mo, P = 0.044). The cumulative OS rate was higher in low macrophages density group than in high macrophages density group (median OS 40.5 vs 13.0 mo, P = 0.056). Median OS was significantly longer in low MVD group than

  2. Significant Modifications of the Salivary Proteome Potentially Associated with Complications of Down Syndrome Revealed by Top-down Proteomics*

    PubMed Central

    Cabras, Tiziana; Pisano, Elisabetta; Montaldo, Caterina; Giuca, Maria Rita; Iavarone, Federica; Zampino, Giuseppe; Castagnola, Massimo; Messana, Irene

    2013-01-01

    People with Down syndrome, a frequent genetic disorder in humans, have increased risk of health problems associated with this condition. One clinical feature of Down syndrome is the increased prevalence and severity of periodontal disease in comparison with the general population. Because saliva plays an important role in maintaining oral health, in the present study the salivary proteome of Down syndrome subjects was investigated to explore modifications with respect to healthy subjects. Whole saliva of 36 Down syndrome subjects, divided in the age groups 10–17 yr and 18–50 yr, was analyzed by a top-down proteomic approach, based on the high performance liquid chromatography-electrospray ionization–MS analysis of the intact proteins and peptides, and the qualitative and quantitative profiles were compared with sex- and age-matched control groups. The results showed the following interesting features: 1) as opposed to controls, in Down syndrome subjects the concentration of the major salivary proteins of gland origin did not increase with age; as a consequence concentration of acidic proline rich proteins and S cystatins were found significantly reduced in older Down syndrome subjects with respect to matched controls; 2) levels of the antimicrobial α-defensins 1 and 2 and histatins 3 and 5 were significantly increased in whole saliva of older Down syndrome subjects with respect to controls; 3) S100A7, S100A8, and S100A12 levels were significantly increased in whole saliva of Down syndrome subjects in comparison with controls. The increased level of S100A7 and S100A12 may be of particular interest as a biomarker of early onset Alzheimer's disease, which is frequently associated with Down syndrome. PMID:23533003

  3. Networks of Food Sharing Reveal the Functional Significance of Multilevel Sociality in Two Hunter-Gatherer Groups.

    PubMed

    Dyble, Mark; Thompson, James; Smith, Daniel; Salali, Gul Deniz; Chaudhary, Nikhil; Page, Abigail E; Vinicuis, Lucio; Mace, Ruth; Migliano, Andrea Bamberg

    2016-08-01

    Like many other mammalian and primate societies [1-4], humans are said to live in multilevel social groups, with individuals situated in a series of hierarchically structured sub-groups [5, 6]. Although this multilevel social organization has been described among contemporary hunter-gatherers [5], questions remain as to the benefits that individuals derive from living in such groups. Here, we show that food sharing among two populations of contemporary hunter-gatherers-the Palanan Agta (Philippines) and Mbendjele BaYaka (Republic of Congo)-reveals similar multilevel social structures, with individuals situated in households, within sharing clusters of 3-4 households, within the wider residential camps, which vary in size. We suggest that these groupings serve to facilitate inter-sexual provisioning, kin provisioning, and risk reduction reciprocity, three levels of cooperation argued to be fundamental in human societies [7, 8]. Humans have a suite of derived life history characteristics including a long childhood and short inter-birth intervals that make offspring energetically demanding [9] and have moved to a dietary niche that often involves the exploitation of difficult to acquire foods with highly variable return rates [10-12]. This means that human foragers face both day-to-day and more long-term energetic deficits that conspire to make humans energetically interdependent. We suggest that a multilevel social organization allows individuals access to both the food sharing partners required to buffer themselves against energetic shortfalls and the cooperative partners required for skill-based tasks such as cooperative foraging. PMID:27451900

  4. 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. PMID:25393935

  5. Global Genomic Analysis of Intraductal Papillary Mucinous Neoplasms of the Pancreas Reveals Significant Molecular Differences Compared to Ductal Adenocarcinoma

    PubMed Central

    Fritz, Stefan; Fernandez-del Castillo, Carlos; Mino-Kenudson, Mari; Crippa, Stefano; Deshpande, Vikram; Lauwers, Gregory Y.; Warshaw, Andrew L.; Thayer, Sarah P.; Iafrate, A. John

    2013-01-01

    Objective To determine whether intraductal papillary mucinous neoplasms of the pancreas (IPMNs) have a different genetic background compared with ductal adenocarcinoma (PDAC). Summary Background Data The biologic and clinical behavior of IPMNs and IPMN-associated adenocarcinomas is different from PDAC in having a less aggressive tumor growth and significantly improved survival. Up to date, the molecular mechanisms underlying the clinical behavior of IPMNs are incompletely understood. Methods 128 cystic pancreatic lesions were prospectively identified during the course of 2 years. From the corresponding surgical specimens, 57 IPMNs were separated and subdivided by histologic criteria into those with low-grade dysplasia, moderate dysplasia, high-grade dysplasia, and invasive cancer. Twenty specimens were suitable for DNA isolation and subsequent performance of array CGH. Results While none of the IPMNs with low-grade dysplasia displayed detectable chromosomal aberrations, IPMNs with moderate and high-grade dysplasia showed frequent copy number alterations. Commonly lost regions were located on chromosome 5q, 6q, 10q, 11q, 13q, 18q, and 22q. The incidence of loss of chromosome 5q, 6q, and 11q was significantly higher in IPMNs with high-grade dysplasia or invasion compared with PDAC. Ten of 13 IPMNs with moderate dysplasia or malignancy had loss of part or all of chromosome 6q, with a minimal deleted region between linear positions 78.0 and 130.0. Conclusions This study is the first to use array CGH to characterize IPMNs. Recurrent cytogenetic alterations were identified and were different than those described in PDAC. Array CGH may help distinguish between these 2 entities and give insight into the differences in their biology and prognosis. PMID:19247032

  6. 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

  7. Clusterin glycopeptide variant characterization reveals significant site-specific glycan changes in the plasma of clear cell renal cell carcinoma.

    PubMed

    Gbormittah, Francisca O; Bones, Jonathan; Hincapie, Marina; Tousi, Fateme; Hancock, William S; Iliopoulos, Othon

    2015-06-01

    Cancer-related alterations in protein glycosylation may serve as diagnostic or prognostic biomarkers or may be used for monitoring disease progression. Clusterin is a medium abundance, yet heavily glycosylated, glycoprotein that is upregulated in clear cell renal cell carcinoma (ccRCC) tumors. We recently reported that the N-glycan profile of clusterin is altered in the plasma of ccRCC patients. Here, we characterized the occupancy and the degree of heterogeneity of individual N-glycosylation sites of clusterin in the plasma of patients diagnosed with localized ccRCC, before and after curative nephrectomy (n = 40). To this end, we used tandem mass spectrometry of immunoaffinity-enriched plasma samples to analyze the individual glycosylation sites in clusterin. We determined the levels of targeted clusterin glycoforms containing either a biantennary digalactosylated disialylated (A2G2S2) glycan or a core fucosylated biantennary digalactosylated disialylated (FA2G2S2) glycan at N-glycosite N374. We showed that the presence of these two clusterin glycoforms differed significantly in the plasma of patients prior to and after curative nephrectomy for localized ccRCC. Removal of ccRCC led to a significant increase in the levels of both FA2G2S2 and A2G2S2 glycans in plasma clusterin. These changes were further confirmed by lectin blotting of plasma clusterin. It is envisioned that these identified glycan alterations may provide an additional level of therapeutic or biomarker sensitivity than levels currently achievable by monitoring expression differences alone. PMID:25855029

  8. An MHC-defined primate model reveals significant rejection of bone marrow after mixed chimerism induction despite full MHC matching.

    PubMed

    Larsen, C P; Page, A; Linzie, K H; Russell, M; Deane, T; Stempora, L; Strobert, E; Penedo, M C T; Ward, T; Wiseman, R; O'Connor, D; Miller, W; Sen, S; Singh, K; Kean, L S

    2010-11-01

    In murine models, mixed hematopoietic chimerism induction leads to robust immune tolerance. However, translation to primates and to patients has been difficult. In this study, we used a novel MHC-defined rhesus macaque model to examine the impact of MHC matching on the stability of costimulation blockade-/sirolimus-mediated chimerism, and to probe possible mechanisms of bone marrow rejection after nonmyeloablative transplant. Using busulfan-based pretransplant preparation and maintenance immunosuppression with sirolimus, as well as CD28 and CD154 blockade, all recipients demonstrated donor engraftment after transplant. However, the mixed chimerism that resulted was compartmentalized, with recipients demonstrating significantly higher whole blood chimerism compared to T cell chimerism. Thus, the vast majority of T cells presenting posttransplant were recipient-rather than donor-derived. Surprisingly, even in MHC-matched transplants, rejection of donor hematopoiesis predominated after immunosuppression withdrawal. Weaning of immunosuppression was associated with a surge of antigen-experienced T cells, and transplant rejection was associated with the acquisition of donor-directed T cell alloreactivity. These results suggest that a reservoir of alloreactive cells was present despite prior costimulation blockade and sirolimus, and that the post-immunosuppression lymphocytic rebound may have lead to a phenotypic shift in these recipient T cells towards an activated, antigen-experienced phenotype, and ultimately, to transplant rejection. PMID:20849552

  9. 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.

  10. 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

  11. 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).

  12. Gamete production patterns, ploidy, and population genetics reveal evolutionary significant units in hybrid water frogs (Pelophylax esculentus).

    PubMed

    Pruvost, Nicolas B M; Hoffmann, Alexandra; Reyer, Heinz-Ulrich

    2013-09-01

    . These differences are strong evidence for a polyphyletic origin of triploids. Moreover, our findings shed light on the evolutionary potential inherent to the P. esculentus complex, where rare events due to untypical gametogenetic processes can lead to the raise, the perpetuation, and the dispersion of new evolutionary significant lineages which may also deserve special conservation measures. PMID:24101984

  13. Auricular electrical stimulation and dental pain threshold.

    PubMed Central

    Simmons, M. S.; Oleson, T. D.

    1993-01-01

    A modified double-blind evaluation of naloxone reversibility of dental analgesia produced by auricular electrical stimulation (AES) was examined in 40 subjects assigned randomly to one of four groups: AES followed by saline (AS), AES followed by naloxone (AN), placebo AES followed by saline (PS), and placebo AES followed by naloxone (PN). Dental pain threshold was tested using a hand-held dental pulp tester. A second investigator administered the true or placebo AES using an electrical stimulator. A third investigator injected intravenously saline or naloxone. The subjects and investigators 1 and 3 were blind to all treatment conditions. A repeated measures analysis of variance revealed a significant difference among the four groups. The AES groups exhibited a statistically significant 18% elevation of pain threshold, whereas the two placebo stimulation groups (PS and PN) remained essentially unchanged. The mean pain threshold increased to more than 23% for group AS, but fell to less than 12% for the subjects in group AN, who were given naloxone. These findings indicate a small but significant elevation of pain threshold by AES, an effect partially blocked by naloxone, suggesting an endogenous opioid system as one mechanism for AES analgesia. Images Figure 1 Figure 2 PMID:8185085

  14. 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.

  15. 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. PMID:25391237

  16. High-resolution magic angle spinning and 1H magnetic resonance spectroscopy reveal significantly altered neuronal metabolite profiles in CLN1 but not in CLN3.

    PubMed

    Sitter, Beathe; Autti, Taina; Tyynelä, Jaana; Sonnewald, Ursula; Bathen, Tone F; Puranen, Johanna; Santavuori, Pirkko; Haltia, Matti J; Paetau, Anders; Polvikoski, Tuomo; Gribbestad, Ingrid S; Häkkinen, Anna-Maija

    2004-09-01

    The neuronal ceroid lipofuscinoses (NCLs) are among the most severe inherited progressive neurodegenerative disorders of children. The purpose of this study was to compare the in vivo 1.5-T 1H magnetic resonance (MR) and ex vivo 14.3-T high-resolution (HR) magic angle spinning (MAS) 1H MR brain spectra of patients with infantile (CLN1) and juvenile (CLN3) types of NCL, to obtain detailed information about the alterations in the neuronal metabolite profiles in these diseases and to test the suitability of the ex vivo HR MAS (1)H MRS technique in analysis of autopsy brain tissue. Ex vivo spectra from CLN1 autopsy brain tissue (n = 9) significantly differed from those of the control (n = 9) and CLN3 (n = 5) groups, although no differences were found between the CLN3 and the control groups. Principal component analysis of ex vivo data showed that decreased levels of N-acetylaspartate (NAA), gamma-aminobutyric acid (GABA), glutamine, and glutamate as well as increased levels of inositols characterized the CLN1 spectra. Also, the intensity ratio of lipid methylene/methyl protons was decreased in spectra of CLN1 brain tissue compared with CLN3 and control brain tissue. In concordance with the ex vivo data, the in vivo spectra of late-stage patients with CLN1 (n = 3) revealed a dramatic decrease of NAA and a proportional increase of myo-inositol and lipids compared with control subjects. Again, the spectra of patients with CLN3 (n = 13) did not differ from those of controls (n = 15). In conclusion, the ex vivo and in vivo spectroscopic findings were in good agreement within all analyzed groups and revealed significant alterations in metabolite profiles in CLN1 brain tissue but not in CLN3 compared with controls. Furthermore, HR MAS 1H MR spectra facilitated refined detection of neuronal metabolites, including GABA, and composition of lipids in the autopsy brain tissue of NCL patients. PMID:15352223

  17. 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).

  18. Whole blood transcriptional profiling reveals significant down-regulation of human leukocyte antigen class I and II genes in essential thrombocythemia, polycythemia vera and myelofibrosis.

    PubMed

    Skov, Vibe; Riley, Caroline Hasselbalch; Thomassen, Mads; Larsen, Thomas Stauffer; Jensen, Morten K; Bjerrum, Ole Weis; Kruse, Torben A; Hasselbalch, Hans Carl

    2013-10-01

    Gene expression profiling studies in the Philadelphia-negative chronic myeloproliferative neoplasms have revealed significant deregulation of several immune and inflammation genes that might be of importance for clonal evolution due to defective tumor immune surveillance. Other mechanisms might be down-regulation of major histocompatibility (MHC) class I and II genes, which are used by tumor cells to escape antitumor T-cell-mediated immune responses. We have performed whole blood transcriptional profiling of genes encoding human leukocyte antigen (HLA) class I and II molecules, β2-microglobulin and members of the antigen processing machinery of HLA class I molecules (LMP2, LMP7, TAP1, TAP2 and tapasin). The findings of significant down-regulation of several of these genes may possibly be of major importance for defective tumor immune surveillance. Since up-regulation of HLA genes is recorded during treatment with epigenome modulating agents (DNA-hypomethylators and DNA-hyperacetylators [histone deacetylase inhibitors]) and interferon-α2, our findings call for prospective transcriptional studies of HLA genes during treatment with these agents. PMID:23302045

  19. 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

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

    PubMed

    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

  1. Demonstration of Trophozoites of G. Lamblia in Ileal Mucosal Biopsy Specimens May Reveal Giardiasis in Patients With Significantly Inflamed Parasite-free Duodenal Mucosa.

    PubMed

    Oberhuber, Georg; Mesteri, Ildiko; Kopf, Wolfram; Müller, Heiko

    2016-09-01

    In the majority of individuals, infestation with trophozoites of Giardia lamblia (synonymous G. duodenalis or G. intestinalis) leads to a self-limited disease. Whereas most duodenal biopsies with chronic giardiasis show little or no inflammatory reaction, some patients may develop a severe disease with significant mucosal inflammation and various degrees of villous blunting. Occasionally, the histologic changes may resemble those of celiac disease. In this paper, we describe 11 patients, 5 of them female, with chronic giardiasis and demonstrable G. lamblia in ileal biopsies. The median age was 45 years (35 to 62 y), with male patients being at least 10 years younger than female patients. All of the duodenal biopsies showed at least mild villous blunting (grading: mild, marked, or total). In the mucosa an increased number of plasma cells and lymphocytes was observed. Furthermore, varying numbers of granulocytes were found in the lamina propria and in the epithelial layer. In 1 case only, the number of intraepithelial lymphocytes was >40/100 epithelial cells thus mirroring the histologic picture of celiac disease with a flat mucosa (with negative celiac disease-specific serological findings). Interestingly enough, all mucosal biopsy specimens from the duodenum were parasite free. Therefore, giardiasis could only be revealed by the demonstration of trophozoites of G. lamblia in biopsy specimens from the terminal ileum, which had been taken simultaneously or several weeks later. In contrast to duodenal biopsies, the ileal mucosa appeared either normal or only mildly inflamed in this setting. All patients but 1 were symptomatic, with chronic diarrhea being the leading symptom. Symptoms resolved after antibiotic therapy. This study demonstrates that giardiasis may be associated with a significant duodenal pathology in biopsy specimens without discernible parasites. In the cases described here infestation with G. lamblia was only proven histologically by examination of

  2. Significant differences between Lactobacillus casei subsp. casei ATCC 393T and a commonly used plasmid-cured derivative revealed by a polyphasic study.

    PubMed

    Acedo-Félix, Evelia; Pérez-Martínez, Gaspar

    2003-01-01

    Many studies on Lactobacillus casei subsp. casei (L. casei) have been carried out using strain ATCC 393 (pLZ15-). Four strains of L. casei ATCC 393T and three of ATCC 393 (pLZ15-) were compared using phenotypic methods and many of the available genotyping techniques. These tests showed that strains of ATCC 393T obtained from independent public type-culture collections were significantly different from the plasmid-free (pLZ15-) strains of ATCC 393T. These findings were confirmed by sequencing the first 580 nt (domain I) of the 16S and 23S rDNAs of the strains. Complete sequencing of the 16S rDNA of one representative strain from each group revealed that strain ATCC 393T from culture collections was 99% similar to Lactobacillus zeae ATCC 15820T and that the strain so far considered as L. casei ATCC 393 (pLZ15-) was, in turn, 100% similar to L. casei ATCC 334 and Lactobacillus paracasei subsp. paracasei ATCC 4022. All data obtained in this work indicate that the ancestral strain of ATCC 393 (pLZ15-) might never have been the strain that is now available from culture collections. PMID:12656154

  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. PMID:25343989

  4. 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.

  5. Comparative Transcriptome Analysis Reveals Significant Differences in MicroRNA Expression and Their Target Genes between Adipose and Muscular Tissues in Cattle

    PubMed Central

    Sun, Jiajie; Zhang, Bowen; Lan, Xianyong; Zhang, Chunlei; Lei, Chuzhao; Chen, Hong

    2014-01-01

    The posttranscriptional gene regulation mediated by microRNAs (miRNAs) plays an important role in various species. However, to date limited miRNAs have been reported between fat and muscle tissues in beef cattle. In this paper, 412 known and 22 novel miRNAs in backfat as well as 334 known and 10 novel miRNAs in longissimus thoracis were identified in the Chinese Qinchuan beef cattle. Bta-miR-199a-3p, -154c, -320a and -432 were expressed at higher levels in backfat tissue, while bta-miR-1, -133a, -206, and -378 were also significantly enriched in muscle tissue. Functional analysis revealed that fat-enriched miRNAs targeted PRKAA1/2, PPARA and PPARG genes to modulate lipid and fatty acid metabolism, and muscle-enriched miRNAs targeted CSRP3 gene to present function involved in skeletal and muscular system development. The results obtained may help in the design of new selection strategies to improve beef quality. PMID:25006962

  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. PMID:23177772

  7. 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

  8. 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 Central

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

    2007-01-01

    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 × 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 ∼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 F1 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 × additive effects besides directional dominance. Positive epistatic effects reduced heterosis for growth-related traits in our materials. PMID:18039884

  9. 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.

  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. Meta-analysis reveals significant association of 3′-UTR VNTR in SLC6A3 with smoking cessation in Caucasian populations

    PubMed Central

    Ma, Yunlong; Yuan, Wenji; Cui, Wenyan; Li, Ming D.

    2015-01-01

    Many studies have examined the association between SLC6A3 3′-UTR VNTR polymorphism and smoking cessation; however, the results are inconclusive, primarily because of the small to moderate-size samples. The primary goal of this study was to determine whether this polymorphism has any effect on smoking cessation by a meta-analysis of all reported studies. We adopted a 9-repeat dominant model that considers 9-repeat and non 9-repeat as two genotypes and compared their frequencies in former vs. current smokers. Eleven studies with 5,480 participants were included. Considering the presence of study heterogeneity and differences in the availability of information from each study, three separate meta-analyses were performed with the Comprehensive Meta-Analysis statistical software (v. 2.0). The first meta-analysis provided evidence of association between the 9-repeat genotype and smoking cessation under the fixed-effects model (pooled odds ratio [OR] 1.13; 95% confidence interval [CI] 1.01, 1.27; P = 0.037) but not in the random-effects model (pooled OR 1.11; 95% CI 0.96, 1.29; P = 0.159). Given the marginal evidence of heterogeneity among studies (P = 0.10; I2 = 35.9%), which likely was caused by inclusion of an Asian-population treatment study with an opposite effect of the polymorphism on smoking cessation, we excluded these data, revealing a significant association between the 9-repeat genotype and smoking cessation under both the fixed- and random-effects models (pooled OR 1.15; 95% CI 1.02, 1.29; P = 0.02 for both models). By analyzing adjusted and unadjusted results, we performed the third meta-analysis, which showed consistently that the 9-repeat genotype was significantly associated with smoking cessation under both the fixed- and random-effects models (pooled OR 1.17; 95% CI 1.04, 1.31; P = 0.009 for both models). We conclude that the 3′-UTR VNTR polymorphism is significantly associated with smoking cessation, and smokers with one or more 9-repeat alleles

  12. 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

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

    PubMed

    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

  14. 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.

  15. 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…

  16. Whole-body vibration perception thresholds

    NASA Astrophysics Data System (ADS)

    Parsons, K. C.; Griffin, M. J.

    1988-03-01

    This paper presents the results of a series of laboratory experiments concerned with perception thresholds for whole-body vibration. The nature of absolute perception thresholds is discussed and a method of determining vibration thresholds, based upon signal detection theory, is proposed. Thresholds of subjects exposed to x-, y- and z-axis sinusoidal vibration were determined for sitting and standing subjects (from 2 to 100 Hz). Perception thresholds have also been determined for supine subjects exposed to vertical ( x-axis) sinusoidal vibration (10-63 Hz). In additional experiments the effects of complex (e.g., random) vibration and the effects of duration on the perception thresholds were investigated. The relation between perception thresholds and vibration levels, said by subjects to be unacceptable if they occurred in their own homes, was investigated as well as the effects of subjects' personality and the visual and acoustic conditions in the laboratory. For the vertical vibration of seated subjects no significant differences were found between the responses of male and female subjects. Significant differences were found between perception thresholds for sitting and standing postures. The median threshold was approximately 0·01 m/s 2 r.m.s. between 2 and 100 Hz. Perception thresholds for x-axis and y-axis vibration were not significantly different in either sitting or standing subjects but significant differences in thresholds were found between sitting and standing positions for both x-axis and y-axis vibration. Subjects tended to be more sensitive to vibration when lying than when sitting or standing. The results suggested that the perception of random vibrations can be predicted from a knowledge of the perception of its component vibrations. The number of cycles of vibration did not affect perception thresholds for vibration durations of more than about 0·25 s. Some assessments suggested that vibration at more than twice the perception threshold may not

  17. 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.

  18. 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

  19. 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 ...

  20. 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…

  1. 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…

  2. 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…

  3. Revealing the effects of nitrogen on threshold current density in GaNxAsyP1-x-y/GaP/AlzGa1-zP type I QW laser structures by hydrostatic pressure

    NASA Astrophysics Data System (ADS)

    Ünsal, Ömer L.; Gönül, Beşire

    2016-06-01

    We present a comprehensive theoretical analysis of threshold current in dilute nitride direct bandgap Ga(NAsP)/GaP/AlGaP quantum wells (QW) on silicon substrates using model calculations. The pressure dependence of band structure, radiative and non-radiative recombination rates, optical confinement factor, transparency- and threshold-carrier densities are calculated in a range of 0-1 GPa at room temperature. The effect of aluminium incorporation into cladding-layer Gallium Phosphide (GaP) with the employed five-layer slab waveguide model is considered and we have shown that incorporation of Aluminium (Al) into cladding-layer GaP increases the photon confinement in well layer. It is found that incorporation of Nitrogen (N) into GaAsP reduces the non-radiative Auger recombination rates which brings an improvement in threshold current. The comparison of our calculated results with that of the experimental data indicates that the Auger effect involving CHCC process can be considered as the dominant non-radiative loss mechanism at 300 K.

  4. Review: Genomic era analyses of RNA secondary structure and RNA-binding proteins reveal their significance to post-transcriptional regulation in plants

    PubMed Central

    Silverman, Ian M.; Li, Fan; Gregory, Brian D.

    2014-01-01

    The eukaryotic transcriptome is regulated both transcriptionally and post-transcriptionally. Transcriptional control was the major focus of early research efforts, while more recently post-transcriptional mechanisms have gained recognition for their significant regulatory importance. At the heart of post-transcriptional regulatory pathways are cis- and trans-acting features and factors including RNA secondary structure as well as RNA-binding proteins and their recognition sites on target RNAs. Recent advances in genomic methodologies have significantly improved our understanding of both RNA secondary structure and RNA-binding proteins and their regulatory effects within the eukaryotic transcriptome. In this review, we focus specifically on the collection of these regulatory moieties in plant transcriptomes. We describe the approaches for studying RNA secondary structure and RNA-protein interaction sites, with an emphasis on recent methodological advances that produce transcriptome-wide datasets. We discuss how these methods that include genome-wide RNA secondary structure determination and RNA-protein interaction site mapping are significantly improving our understanding of the functions of these two elements in post-transcriptional regulation. Finally, we delineate the need for additional genome-wide studies of RNA secondary structure and RNA-protein interactions in plants. PMID:23498863

  5. Biochemical characterization and crystal structure of a GH10 xylanase from termite gut bacteria reveal a novel structural feature and significance of its bacterial Ig-like domain.

    PubMed

    Han, Qian; Liu, Ning; Robinson, Howard; Cao, Lin; Qian, Changli; Wang, Qianfu; Xie, Lei; Ding, Haizhen; Wang, Qian; Huang, Yongping; Li, Jianyong; Zhou, Zhihua

    2013-12-01

    Bacterial Ig-like (Big) domains are commonly distributed in glycoside hydrolases (GH), but their structure and function remains undefined. Xylanase is a GH, and catalyzes the hydrolysis of the internal β-xylosidic linkages of xylan. In this study, we report the molecular cloning, biochemical and biophysical characterization, and crystal structure of a termite gut bacterial xylanase, Xyl-ORF19, which was derived from gut bacteria of a wood-feeding termite (Globitermes brachycerastes). The protein architecture of Xyl-ORF19 reveals that it has two domains, a C-terminal GH10 catalytic domain and an N-terminal Big_2 non-catalytic domain. The catalytic domain folds in an (α/β)8 barrel as most GH10 xylanases do, but it has two extra β-strands. The non-catalytic domain is structurally similar to an immunoglobulin-like domain of intimins. The recombinant enzyme without the non-catalytic domain has fairly low catalytic activity, and is different from the full-length enzyme in kinetic parameters, pH and temperature profiles, which suggests the non-catalytic domain could affect the enzyme biochemical and biophysical properties as well as the role for enzyme localization. This study provides a molecular basis for future efforts in xylanase bioengineering. PMID:23794438

  6. High-resolution melting analysis of the spa locus reveals significant diversity within sequence type 93 methicillin-resistant Staphylococcus aureus from northern Australia.

    PubMed

    Tong, S Y C; Lilliebridge, R A; Holt, D C; McDonald, M I; Currie, B J; Giffard, P M

    2009-12-01

    High-resolution melting analysis is an inherently robust, easy and inexpensive approach to the examination of genomic regions containing single-nucleotide polymorphisms and hypervariable loci. Staphylococcus aureus sequence type (ST) 93 is a singleton, Panton-Valentine leukocidin-positive clone unique to Australia. A high-resolution melting-based method for the identification of ST93 was developed, and a similar approach was used to reveal diversity within the spa locus of this lineage. Statistical and graphical methods that account for instrumental and operator-dependent variation in high-resolution melting curves were developed, to allow greater confidence and reproducibility in deciding whether another curve is truly different from the baseline curve of an amplicon with known sequence. The data support a very early acquisition, or multiple independent acquisitions, of SCCmec by ST93 methicillin-susceptible S. aureus (MSSA), and the coexistence of MSSA and methicillin-resistant S. aureus versions of the same lineage within northern Australia. PMID:19392885

  7. Gene Expression Analysis of the 26S Proteasome Subunit PSMB4 Reveals Significant Upregulation, Different Expression and Association with Proliferation in Human Pulmonary Neuroendocrine Tumours

    PubMed Central

    Mairinger, Fabian Dominik; Walter, Robert Fred Henry; Theegarten, Dirk; Hager, Thomas; Vollbrecht, Claudia; Christoph, Daniel Christian; Worm, Karl; Ting, Saskia; Werner, Robert; Stamatis, Georgios; Mairinger, Thomas; Baba, Hideo; Zarogoulidis, Konstantinos; Huang, Haidong; Li, Qiang; Tsakiridis, Kosmas; Zarogoulidis, Paul; Schmid, Kurt Werner; Wohlschlaeger, Jeremias

    2014-01-01

    Background: Proteasomal subunit PSMB4 was suggested to be a survival gene in an animal model of hepatocellular carcinoma and in glioblastoma cell lines. In pulmonary adenocarcinoma, a high expression of these genes was found to be associated with poor differentiation and survival. This study investigates the gene expression levels of 26S proteasome subunits in human pulmonary neuroendocrine tumours including typical (TC) and atypical (AC) carcinoid tumours as well as small cell (SCLC) and large cell (LCNEC) neuroendocrine carcinomas. Material and methods: Gene expression levels of proteasomal subunits (PSMA1, PSMA5, PSMB4, PSMB5 and PSMD1) were investigated in 80 neuroendocrine pulmonary tumours (each 20 TC, AC, LCNLC and SCLC) and compared to controls. mRNA levels were determined by using TaqMan assays. Immunohistochemistry on tissue microarrays (TMA) was performed to determine the expression of ki67, cleaved caspase 3 and PSMB4. Results: All proteasomal subunit gene expressions were significantly upregulated in TC, AC, SCLC and LCNEC compared to controls. PSMB4 mRNA is differently expressed between all neuroendocrine tumour subtypes demonstrating the highest expression and greatest range in LCNEC (p=0.043), and is significantly associated with proliferative activity (p=0.039). Conclusion: In line with other 26S proteasomal subunits PSMB4 is significantly increased, but differently expressed between pulmonary neuroendocrine tumours and is associated with the proliferative activity. Unlike in pulmonary adenocarcinomas, no association with biological behaviour was observed, suggesting that increased proteasomal subunit gene expression is a common and probably early event in the tumorigenesis of pulmonary neuroendocrine tumours regardless of their differentiation. PMID:25157275

  8. 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. PMID:12285009

  9. Significant Improvement of Antithrombotic Responses to Clopidogrel by Use of a Novel Conjugate as Revealed in an Arterial Model of Thrombosis.

    PubMed

    Zhang, Haoming; Lauver, D Adam; Wang, Hui; Sun, Duxin; Hollenberg, Paul F; Chen, Y Eugene; Osawa, Yoichi; Eitzman, Daniel T

    2016-10-01

    Clopidogrel is a prodrug that requires bioactivation by cytochrome P450 (P450) enzymes to a pharmacologically active metabolite for antiplatelet action. The clinical limitations of clopidogrel are in large part due to its poor pharmacokinetics resulting from inefficient bioactivation by P450s. In this study, we determined the pharmacokinetics and pharmacodynamics of a novel conjugate of clopidogrel, referred to as ClopNPT, in animal models and we evaluated its potential to overcome the limitations of clopidogrel. Results from pharmacokinetic (PK) studies showed that ClopNPT released the active metabolite with a time to maximal plasma concentration of <5 minutes in C57BL/6 mice after either oral or intravenous administration, and plasma concentrations of the active metabolite reached Cmax values of 1242 and 1100 ng/ml after a 10-mg/kg oral dose and a 5-mg/kg intravenous dose, respectively. Furthermore, ClopNPT was highly effective in preventing arterial thrombosis in rabbits and mice after vascular injuries. Formation of occlusive thrombi was prevented by ClopNPT at the 1-mg/kg dose with no significant increase in tongue bleeding time, whereas clopidogrel was ineffective at the same dose. These results suggest that ClopNPT has favorable PK/pharmacodynamic properties that can potentially overcome the attenuated PK properties of clopidogrel and thus significantly improve the efficacy of antiplatelet therapy. PMID:27511819

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

    PubMed

    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

  11. 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

  12. 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

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

    PubMed

    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

  14. 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

  15. 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.

  16. 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

  17. Screening of endocrine organ-specific humoral autoimmunity in 47,XXY Klinefelter's syndrome reveals a significant increase in diabetes-specific immunoreactivity in comparison with healthy control men.

    PubMed

    Panimolle, Francesca; Tiberti, Claudio; Granato, Simona; Semeraro, Antonella; Gianfrilli, Daniele; Anzuini, Antonella; Lenzi, Andrea; Radicioni, Antonio

    2016-04-01

    The aim of this study was to evaluate the frequency of humoral endocrine organ-specific autoimmunity in 47,XXY Klinefelter's syndrome (KS) by investigating the autoantibody profile specific to type 1 diabetes (T1DM), Addison's disease (AD), Hashimoto thyroiditis (HT), and autoimmune chronic atrophic gastritis (AG). Sixty-one adult Caucasian 47,XXY KS patients were tested for autoantibodies specific to T1DM (Insulin Abs, GAD Abs, IA-2 Abs, Znt8 Abs), HT (TPO Abs), AD (21-OH Abs), and AG (APC Abs). Thirty-five of these patients were not undergoing testosterone replacement therapy TRT (Group 1) and the remaining 26 patients started TRT before the beginning of the study (Group 2). KS autoantibody frequencies were compared to those found in 122 control men. Six of 61 KS patients (9.8 %) were positive for at least one endocrine autoantibody, compared to 6.5 % of controls. Interestingly, KS endocrine immunoreactivity was directed primarily against diabetes-specific autoantigens (8.2 %), with a significantly higher frequency than in controls (p = 0.016). Two KS patients (3.3 %) were TPO Ab positive, whereas no patients were positive for AD- and AG-related autoantigens. The autoantibody endocrine profile of untreated and treated KS patients was not significantly different. Our findings demonstrate for the first time that endocrine humoral immunoreactivity is not rare in KS patients and that it is more frequently directed against type 1 diabetes-related autoantigens, thus suggesting the importance of screening for organ-specific autoimmunity in clinical practice. Follow-up studies are needed to establish if autoantibody-positive KS patients will develop clinical T1DM. PMID:25935328

  18. 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

  19. An MHC-defined primate model reveals significant rejection of bone marrow after mixed-chimerism induction despite full MHC matching

    PubMed Central

    Larsen, Christian P.; Page, Andrew; Linzie, Kelly Hamby; Russell, Maria; Deane, Taylor; Stempora, Linda; Strobert, Elizabeth; Penedo, Maria Cecilia T.; Ward, Thea; Wiseman, Roger; O'Connor, David; Miller, Weston; Sen, Sharon; Singh, Karnail; Kean, Leslie S.

    2010-01-01

    In murine models, mixed hematopoietic chimerism-induction leads to robust immune tolerance. However, translation to primates and to patients has been difficult. In this study, we used a novel MHC-defined rhesus macaque model to examine the impact of MHC matching on the stability of costimulation blockade/sirolimus-mediated chimerism, and to probe possible mechanisms of bone marrow rejection after non-myeloablative transplant. Using busulfan-based pre-transplant preparation and maintenance immunosuppression with sirolimus, as well as CD28- and CD154-blockade, all recipients demonstrated donor engraftment after transplant. However, the mixed-chimerism that resulted was compartmentalized, with recipients demonstrating significantly higher whole blood chimerism compared to T cell chimerism Thus, the vast majority of T cells present post-transplant were recipient- rather than donor-derived. Surprisingly, even in MHC-matched transplants, rejection of donor hematopoiesis predominated after immunosuppression withdrawal. Weaning of immunosuppression was associated with a surge of antigen-experienced T cells, and transplant rejection was associated with the acquisition of donor-directed T cell alloreactivity. These results suggest that a reservoir of alloreactive cells was present despite prior costimulation blockade and sirolimus, and that the post-immunosuppression lymphocytic rebound may have lead to a phenotypic shift in these recipient T cells towards an activated, antigen experienced phenotype, and ultimately, to transplant rejection. PMID:20849552

  20. Paternity analysis reveals significant isolation and near neighbor pollen dispersal in small Cariniana legalis Mart. Kuntze populations in the Brazilian Atlantic Forest.

    PubMed

    Tambarussi, Evandro V; Boshier, David; Vencovsky, Roland; Freitas, Miguel L M; Sebbenn, Alexandre M

    2015-12-01

    Throughout the world, large trees are increasingly rare. Cariniana legalis is the tallest tree species of the Brazilian Atlantic Forest, reaching up to 60 m in height. Due to extensive deforestation of the Atlantic Forest, remnant C. legalis populations are small and spatially isolated, requiring the development of strategies for their conservation. For in situ and ex situ genetic conservation to be effective, it is important to understand the levels and patterns of spatial genetic structure (SGS), and gene flow. We investigated SGS and pollen flow in three small, physically isolated C. legalis stands using microsatellite loci. We measured, mapped, and sampled all C. legalis trees in the three stands: 65 trees from Ibicatu population, 22 trees from MGI, and 4 trees from MGII. We also collected and genotyped 600 seeds from Ibicatu, 250 seeds from MGI, and 200 seeds from MGII. Significant SGS was detected in Ibicatu up to 150 m, but substantial levels of external pollen flow were also detected in Ibicatu (8%), although not in MGI (0.4%) or MGII (0%). Selfing was highest in MGII (18%), the smallest group of trees, compared to MGI (6.4%) and Ibicatu (6%). In MGI and MGII, there was a strong pattern of mating among near-neighbors. Seed collection strategies for breeding, in situ and ex situ conservation and ecological restoration, must ensure collection from seed trees located at distances greater than 350 m and from several forest fragments. PMID:27069608

  1. Molecular Analysis of Isoniazid-Resistant Mycobacterium tuberculosis Isolates from England and Wales Reveals the Phylogenetic Significance of the ahpC −46A Polymorphism

    PubMed Central

    Baker, L. V.; Brown, T. J.; Maxwell, O.; Gibson, A. L.; Fang, Z.; Yates, M. D.; Drobniewski, F. A.

    2005-01-01

    The present study investigated the prevalence and diagnostic potential of the most commonly reported mutations associated with isoniazid resistance, katG 315Thr, katG 315Asn, inhA −15T, inhA −8A, and the oxyR-ahpC intergenic region, in a population sample of 202 isoniazid-resistant Mycobacterium tuberculosis isolates and 176 randomly selected fully sensitive isolates from England and Wales identified by using a directed oligonucleotide array and limited DNA sequencing. The strains were recovered from patients originating from 29 countries; 41 isolates were multidrug resistant. Mutations affecting katG 315, the inhA promoter, and the oxyR-ahpC intergenic region were found in 62.7, 21.9, and 30% of 169 genotypically distinct isoniazid-resistant isolates, respectively, whereas they were found in 0, 0, and 8% of susceptible strains, respectively. The frequency of mutation at each locus was unrelated to the resistance profile or previous antituberculous drug therapy. The commonest mutation in the oxyR-ahpC intergenic region, ahpC −46A, was present in 23.7% of isoniazid-resistant isolates and 7.5% of susceptible isolates. This proved to be a phylogenetic marker for a subgroup of M. tuberculosis strains originating on the Indian subcontinent, which shared IS6110-based restriction fragment length polymorphism and spoligotype features with the Delhi strain and Central Asian strain CAS1; and this marker is strongly associated with isoniazid resistance and the katG 315Thr mutation. In total, 82.8% of unrelated isoniazid-resistant isolates could be identified by analysis of just two loci: katG 315 and the inhA promoter. Analysis of the oxyR-ahpC intergenic region, although phylogenetically interesting, does not contribute significantly to further identification of isoniazid-resistant isolates. PMID:15793126

  2. Maturation processes in automatic change detection as revealed by event-related brain potentials and dipole source localization: significance for adult AD/HD.

    PubMed

    Wild-Wall, Nele; Oades, Robert D; Juran, Stephanie A

    2005-10-01

    Mismatch negativity (MMN) is an event-related potential reflecting automatic attention-related information processing marking the detection of auditory change. The bilateral scalp distribution develops by 14 years of age, and is elicited with adult latencies by 17 years. But consistent with reports of continued brain maturation after adolescence, we show here that features of the temporal and frontal lobe dipole sources also continue to develop in the third decade of life. This has consequences for studies of the developmental course of MMN anomalies, from childhood into adulthood, in attention-deficit/hyperactivity disorder. Two groups of healthy subjects with mean ages of 17 and 30 years were presented with a 3-tone auditory oddball. The duration-deviant MMN was recorded during attention to a visual discrimination (auditory-passive condition) and an active auditory discrimination. MMN amplitudes were smaller in the older subjects and the MMN lasted longer over the right hemisphere. Latencies and moments of the four dipoles in the temporal and frontal lobes did not distinguish the two subject-groups. But both temporal lobe sources were located significantly more ventrally and further left in the young adult than in the adolescent subjects. The left cingular source moved posteriorly and the right inferior frontal source moved antero-medially in the older subjects. Brain development in the third decade may cause the two frontal sources to move apart on the rostro-caudal axis but the temporal lobe sources to move left on the lateral and down on the dorsoventral axes. Thus special care is necessary in interpreting putative dysfunctional neurobiological changes in developmental attention-deficit disorders where as-yet-unspecified sub-groups may show a late developmental lag, partial lag, or no lag at all, associated with other impairments. PMID:15922470

  3. 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

  4. A combined massively parallel sequencing indicator species approach revealed significant association between sulfate-reducing bacteria and uranium-reducing microbial communities

    SciTech Connect

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

    2010-08-01

    Massively parallel sequencing has provided a more affordable and high throughput method to study microbial communities, although it has been mostly 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, USA. 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 {micro}M, and created geochemical gradients in electron donors from the inner loop injection well towards the outer loop and down-gradient 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. 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 the electron donor addition and by the groundwater flow path. A false discovery rate approach was implemented to discard false positives by chance given the large amount of data compared.

  5. 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

  6. 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

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

    SciTech Connect

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

    2010-10-01

    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 M 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.

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

    PubMed

    Klarenbeek, Alex; El Mazouari, Khalil; 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

  9. Significant association between sulfate-reducing bacteria and uranium-reducing microbial communities as revealed by a combined massively parallel sequencing-indicator species approach.

    PubMed

    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

    2010-10-01

    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

  10. Comprehensive analysis of HPV16 integration in OSCC reveals no significant impact of physical status on viral oncogene and virally disrupted human gene expression.

    PubMed

    Olthof, Nadine C; Speel, Ernst-Jan M; Kolligs, Jutta; Haesevoets, Annick; Henfling, Mieke; Ramaekers, Frans C S; Preuss, Simon F; Drebber, Uta; Wieland, Ulrike; Silling, Steffi; Lam, Wan L; Vucic, Emily A; Kremer, Bernd; Klussmann, Jens-P; Huebbers, Christian U

    2014-01-01

    Infection with high-risk human papillomavirus (HPV) type 16 is an independent risk factor for the development of oropharyngeal squamous cell carcinomas (OSCC). However, it is unclear whether viral integration is an essential hallmark in the carcinogenic process of OSCC and whether HPV integration correlates with the level of viral gene transcription and influences the expression of disrupted host genes. We analyzed 75 patients with OSCC. HPV16-positivity was proven by p16(INK4A) immunohistochemistry, PCR and FISH. Viral integration was examined using DIPS- as well as APOT-PCR. Viral E2, E6 and E7 gene expression levels were quantified by quantitative reverse transcriptase (RT-q)PCR. Expression levels of 7 human genes disrupted by the virus were extracted from mRNA expression profiling data of 32 OSCCs. Viral copy numbers were assessed by qPCR in 73 tumors. We identified 37 HPV16-human fusion products indicating viral integration in 29 (39%) OSCC. In the remaining tumors (61%) only episome-derived PCR products were detected. When comparing OSCC with or without an integration-derived fusion product, we did not find significant differences in the mean RNA expression of viral genes E2, E6 and E7 or the viral copy numbers per cell, nor did the RNA expression of the HPV-disrupted genes differ from either group of OSCC. In conclusion, our data do not support the hypothesis that integration affects the levels of viral and/or HPV-disrupted human gene transcripts. Thus constitutive, rather than a high level, of expression of oncogene transcripts appears to be required in HPV-related OSCC. PMID:24586376

  11. Phage display-mediated discovery of novel tyrosinase-targeting tetrapeptide inhibitors reveals the significance of N-terminal preference of cysteine residues and their functional sulfur atom.

    PubMed

    Lee, Yu-Ching; Hsiao, Nai-Wan; Tseng, Tien-Sheng; Chen, Wang-Chuan; Lin, Hui-Hsiung; Leu, Sy-Jye; Yang, Ei-Wen; Tsai, Keng-Chang

    2015-02-01

    Tyrosinase, a key copper-containing enzyme involved in melanin biosynthesis, is closely associated with hyperpigmentation disorders, cancer, and neurodegenerative diseases, and as such, it is an essential target in medicine and cosmetics. Known tyrosinase inhibitors possess adverse side effects, and there are no safety regulations; therefore, it is necessary to develop new inhibitors with fewer side effects and less toxicity. Peptides are exquisitely specific to their in vivo targets, with high potencies and relatively few off-target side effects. Thus, we systematically and comprehensively investigated the tyrosinase-inhibitory abilities of N- and C-terminal cysteine/tyrosine-containing tetrapeptides by constructing a phage-display random tetrapeptide library and conducting computational molecular docking studies on novel tyrosinase tetrapeptide inhibitors. We found that N-terminal cysteine-containing tetrapeptides exhibited the most potent tyrosinase-inhibitory abilities. The positional preference of cysteine residues at the N terminus in the tetrapeptides significantly contributed to their tyrosinase-inhibitory function. The sulfur atom in cysteine moieties of N- and C-terminal cysteine-containing tetrapeptides coordinated with copper ions, which then tightly blocked substrate-binding sites. N- and C-terminal tyrosine-containing tetrapeptides functioned as competitive inhibitors against mushroom tyrosinase by using the phenol ring of tyrosine to stack with the imidazole ring of His263, thus competing for the substrate-binding site. The N-terminal cysteine-containing tetrapeptide CRVI exhibited the strongest tyrosinase-inhibitory potency (with an IC50 of 2.7 ± 0.5 μM), which was superior to those of the known tyrosinase inhibitors (arbutin and kojic acid) and outperformed kojic acid-tripeptides, mimosine-FFY, and short-sequence oligopeptides at inhibiting mushroom tyrosinase. PMID:25403678

  12. 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

  13. Real-time DNA binding measurements of the ETS1 recombinant oncoproteins reveal significant kinetic differences between the p42 and p51 isoforms.

    PubMed Central

    Fisher, R. J.; Fivash, M.; Casas-Finet, J.; Erickson, J. W.; Kondoh, A.; Bladen, S. V.; Fisher, C.; Watson, D. K.; Papas, T.

    1994-01-01

    The sequence-specific DNA binding of recombinant p42 and p51 ETS1 oncoprotein was examined quantitatively to determine whether the loss of the Exon VII phosphorylation domain in p42 ETS1 or the phosphorylation of expressed Exon VII in p51 ETS1 had an effect on DNA binding activity. The kinetics of sequence-specific DNA binding was measured using real-time changes in surface plasmon resonance with BIAcore (registered trademark, Pharmacia Biosensor) technology. The real-time binding of p42 and p51 ETS1 displayed significant differences in kinetic behavior. p51 ETS1 is characterized by a fast initial binding and conversion to a stable complex, whereas p42 ETS1 exhibits a slow initial binding and conversion to a stable complex. All of the p51 ETS1 DNA binding states are characterized by rapid turnover, whereas the p42 ETS1 DNA binding states are 4-20 times more stable. A model describing these kinetic steps is presented. Stoichiometric titrations of either p42 or p51 ETS1 with specific oligonucleotides show 1:1 complex formation. The DNA sequence specificity of the p42 and p51 ETS1 as determined by mutational analysis was similar. The in vitro phosphorylation of p51 ETS1 by CAM kinase II obliterates its binding to specific DNA, suggesting that the regulation of p51 ETS1 sequence-specific DNA binding occurs through phosphorylation by a calcium-dependent second messenger. The p42 ETS1 lacks this regulatory domain (Exon VII), and binding to its specific DNA sequence is not sensitive to calcium signaling. PMID:8003962

  14. 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.

  15. A Threshold Value for the Time Delay to TB Diagnosis

    PubMed Central

    Uys, Pieter W.; Warren, Robin M.; van Helden, Paul D.

    2007-01-01

    Background In many communities where TB occurs at high incidence, the major force driving the epidemic is transmission. It is plausible that the typical long delay from the onset of infectious disease to diagnosis and commencement of treatment is almost certainly the major factor contributing to the high rate of transmission. Methodology/Principal Findings This study is confined to communities which are epidemiologically relatively isolated and which have low HIV incidence. The consequences of delays to diagnosis are analyzed and the existence of a threshold delay value is demonstrated. It is shown that unless a sufficient number of cases are detected before this threshold, the epidemic will escalate. The method used for the analysis avoids the standard computer integration of systems of differential equations since the intention is to present a line of reasoning that reveals the essential dynamics of an epidemic in an intuitively clear way that is nevertheless quantitatively realistic. Conclusions/Significance The analysis presented here shows that typical delays to diagnosis present a major obstacle to the control of a TB epidemic. Control can be achieved by optimizing the rapid identification of TB cases together with measures to increase the threshold value. A calculated and aggressive program is therefore necessary in order to bring about a reduction in the prevalence of TB in a community by decreasing the time to diagnosis in all its ramifications. Intervention strategies to increase the threshold value relative to the time to diagnosis and which thereby decrease disease incidence are discussed. PMID:17712405

  16. Hadronic resonances enhanced by thresholds

    NASA Astrophysics Data System (ADS)

    Caramés, T. F.; Valcarce, A.

    2016-07-01

    We present a neat example of a meson-baryon system where the vicinity of two different thresholds enhances the binding of a hadronic resonance, a pentaquark. As a consequence the pattern of states may change when moving among different flavor sectors, what poses a warning on naive extrapolations to heavy flavor sectors based on systematic expansions. For this purpose we simultaneously analyze the N D bar and NB two-hadron systems looking for possible bound states or resonances. When a resonance is controlled by a coupled-channel effect, going to a different flavor sector may enhance or diminish the binding. This effect may, for example, generate significant differences between the charmonium and bottomonium spectra above open-flavor thresholds or pentaquark states in the open-charm and open-bottom sectors.

  17. 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. PMID:25166161

  18. Analyzing threshold pressure limitations in microfluidic transistors for self-regulated microfluidic circuits

    PubMed Central

    Kim, Sung-Jin; Yokokawa, Ryuji; Takayama, Shuichi

    2012-01-01

    This paper reveals a critical limitation in the electro-hydraulic analogy between a microfluidic membrane-valve (μMV) and an electronic transistor. Unlike typical transistors that have similar on and off threshold voltages, in hydraulic μMVs, the threshold pressures for opening and closing are significantly different and can change, even for the same μMVs depending on overall circuit design and operation conditions. We explain, in particular, how the negative values of the closing threshold pressures significantly constrain operation of even simple hydraulic μMV circuits such as autonomously switching two-valve microfluidic oscillators. These understandings have significant implications in designing self-regulated microfluidic devices. PMID:23284181

  19. Analyzing threshold pressure limitations in microfluidic transistors for self-regulated microfluidic circuits

    NASA Astrophysics Data System (ADS)

    Kim, Sung-Jin; Yokokawa, Ryuji; Takayama, Shuichi

    2012-12-01

    This paper reveals a critical limitation in the electro-hydraulic analogy between a microfluidic membrane-valve (μMV) and an electronic transistor. Unlike typical transistors that have similar on and off threshold voltages, in hydraulic μMVs, the threshold pressures for opening and closing are significantly different and can change, even for the same μMVs depending on overall circuit design and operation conditions. We explain, in particular, how the negative values of the closing threshold pressures significantly constrain operation of even simple hydraulic μMV circuits such as autonomously switching two-valve microfluidic oscillators. These understandings have significant implications in designing self-regulated microfluidic devices.

  20. Yield threshold decision framework

    SciTech Connect

    Judd, B.R.; Younker, L.W.; Hannon, W.J.

    1989-08-17

    The USA is developing a decision analysis framework for evaluating the relative value of lower yield thresholds and related verification policies. The framework facilitates systematic analysis of the major issues in the yield threshold decision. The framework can be used to evaluate options proposed either in the inter-agency process or in the negotiations. In addition, the framework can measure the importance of uncertainties and alternative judgments, and thereby determine the advantages of additional research. Since the model is explicit and quantitative, it provides a rational, defensible approach for reaching important treaty and verification decisions. 9 figs.

  1. 78 FR 70623 - Adjustment of Nationwide Significant Risk Threshold

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-26

    ... calculated to be 17,030 (71 FR 47614, August 17, 2006). In 2007, FRA recalculated the NSRT to be 19,047 (72 FR 14850, March 29, 2007). In 2008, FRA recalculated the NSRT to be 17,610 (73 FR 30661, May 28, 2008). In 2009, FRA recalculated the NSRT to be 18,775 (74 FR 45270, September 1, 2009). In 2010,...

  2. 77 FR 546 - Adjustment of Nationwide Significant Risk Threshold

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-05

    ... Locomotive Horns at Highway-Rail Grade Crossings,'' was amended, the NSRT was 17,030 (71 FR 47614, August 17, 2006). In 2007, FRA recalculated the NSRT to be 19,047 (72 FR 14850, March 29, 2007). In 2008, FRA recalculated the NSRT to be 17,610 (73 FR 30661, May 28, 2008). In 2009, FRA recalculated the NSRT to be...

  3. 75 FR 82136 - Adjustment of Nationwide Significant Risk Threshold

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-29

    ... Locomotive Horns at Highway-Rail Grade Crossings,'' was amended, the NSRT was 17,030 (71 FR 47614, August 17, 2006). In 2007, FRA recalculated the NSRT to be 19,047 (72 FR 14850, March 29, 2007). In 2008, FRA recalculated the NSRT to be 17,610 (73 FR 30661, May 28, 2008). In 2009, FRA recalculated the NSRT to be...

  4. The effects of simulated rain on the erosion threshold and biogeochemical properties of intertidal sediments

    NASA Astrophysics Data System (ADS)

    Tolhurst, T. J.; Watts, C. W.; Vardy, S.; Saunders, J. E.; Consalvey, M. C.; Paterson, D. M.

    2008-06-01

    The effects of simulated rain on the erosion threshold and biogeochemical properties of cores of muddy intertidal sediments were measured. Rain was simulated with a trailer-mounted device that produced rain with an intensity and drop size similar to that of natural rain. Erosion thresholds were measured with a cohesive strength meter (CSM) and sediment samples for analysis of the biogeochemical properties of the sediment were collected using the cryogenic contact-core technique. Rain caused significant disruption of the sediment surface, often resulting in significantly lower erosion thresholds and increased relative erosion rates. The removal of unconsolidated surface sediments and the revealing of deeper more consolidated sediments, however, caused an increase in the measured erosion threshold and a reduction in erosion rate in some treatments. The biogeochemical properties of the sediment were significantly altered by even a short duration of rain (5 min). Bio-dependent properties such as the amount of chlorophyll a and carbohydrates were generally decreased by rain. The presence of a visible biofilm did not significantly mediate the effects of rain on erosion thresholds, in contrast to their ability to significantly reduce erosion by tidal flows.

  5. 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.

  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. Threshold improvement and acoustic gain with hearing aids.

    PubMed

    Walden, B E; Kasten, R N

    1976-01-01

    Aided speech reception thresholds were obtained from 20 hearing-impaired listeners with three hearing aids adjusted to confort settings, and with the aids adjusted to deliver 40 dB of acoustic gain. The aided speech reception threshold under each condition was substracted from the unaided speech reception threshold to yield a measure of threshold improvement. Threshold improvement and acoustic gain comparisons revealed that, at comfort setting, these two measures were quite similar. However, at the 40-dB gain setting, acoustic gain exceeded threshold improvement by an average of 5.6 dB. For the high-gain condition, it appeared that the threshold improvement obtained by subjects with relatively good unaided sensitivity was limited by the ambient noise in the test chamber. PMID:938347

  8. 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.

  9. 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.

  10. 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}}}.

  11. 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.

  12. 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

  13. Ignition threshold for impact-generated fires

    NASA Astrophysics Data System (ADS)

    Durda, Daniel D.; Kring, David A.

    2004-08-01

    Widespread fires can be generated after large impact events by atmospheric heating caused by the reaccretion of high-energy, vapor-rich plume material. We examine the threshold irradiance levels necessary for spontaneous and pilot ignition of various types of vegetation and define three specific cases for investigation: (1) 51 kW/m2 for a period of at least 2 min to spontaneously ignite wood; (2) 20 kW/m2 for a period of at least 20 min to ignite wood in the presence of an ignition source; and (3) 28 kW/m2 for a period of at least 1 min to ignite foliage, rotten wood, and forest litter. The threshold ejected plume mass for continent-wide spontaneous ignition of wood is ~2 to 6 × 1015 kg, independent of impact location but dependent on the details of the ejecta speed distribution. The threshold ejected plume mass for global spontaneous ignition of wood is in the range ~1 to 2 × 1016 kg. The threshold plume masses for continent-wide and global fires are very nearly the same for piloted ignition of wood, while the threshold plume masses for continent-wide and global ignition of leaves and forest litter are significantly lower, by a factor of ~2 to 3. Impact craters of at least 85 km diameter are needed to produce continental-scale fires, and craters of ~135 km diameter are needed for global-scale fires.

  14. 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

  15. 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.

  16. Hairpin Vortex Regeneration Threshold

    NASA Astrophysics Data System (ADS)

    Sabatino, Daniel; Maharjan, Rijan

    2015-11-01

    A free surface water channel is used to study hairpin vortex formation created by fluid injection through a narrow slot into a laminar boundary layer. Particle image velocimetry is used to calculate the circulation of the primary hairpin vortex head which is found to monotonically decrease in strength with downstream distance. When a secondary hairpin vortex is formed upstream of the primary vortex, the circulation strength of the head is comparable to the strength of the primary head at the time of regeneration. However, the legs of the primary vortex strengthen up to the moment the secondary hairpin is generated. Although the peak circulation in the legs is not directly correlated to the strength of the original elongated ring vortex, when the circulation is scaled with the injection momentum ratio it is linearly related to scaled injection time. It is proposed that the injection momentum ratio and nondimensionalized injection time based on the wall normal penetration time can be used to identify threshold conditions which produce a secondary vortex. Supported by the National Science Foundation under Grant CBET- 1040236.

  17. 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.

  18. Robust stochastic resonance for simple threshold neurons

    NASA Astrophysics Data System (ADS)

    Kosko, Bart; Mitaim, Sanya

    2004-09-01

    Simulation and theoretical results show that memoryless threshold neurons benefit from small amounts of almost all types of additive noise and so produce the stochastic-resonance or SR effect. Input-output mutual information measures the performance of such threshold systems that use subthreshold signals. The SR result holds for all possible noise probability density functions with finite variance. The only constraint is that the noise mean must fall outside a “forbidden” threshold-related interval that the user can control—a new theorem shows that this condition is also necessary. A corollary and simulations show that the SR effect occurs for right-sided beta and Weibull noise as well. These SR results further hold for the entire uncountably infinite class of alpha-stable probability density functions. Alpha-stable noise densities have infinite variance and infinite higher-order moments and often model impulsive noise environments. The stable noise densities include the special case of symmetric bell-curve densities with thick tails such as the Cauchy probability density. The SR result for alpha-stable noise densities shows that the SR effect in threshold and thresholdlike systems is robust against occasional or even frequent violent fluctuations in noise. Regression analysis reveals both an exponential relationship for the optimal noise dispersion as a function of the alpha bell-curve tail thickness and an approximate linear relationship for the SR-maximal mutual information as a function of the alpha bell-curve tail thickness.

  19. 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.

  20. 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…

  1. 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.…

  2. 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…

  3. Significant Treasures.

    ERIC Educational Resources Information Center

    Andrews, Ian A.

    1999-01-01

    Provides a crossword puzzle with an answer key corresponding to the book entitled "Significant Treasures/Tresors Parlants" that is filled with color and black-and-white prints of paintings and artifacts from 131 museums and art galleries as a sampling of the 2,200 such Canadian institutions. (CMK)

  4. Threshold selection for regional peaks-over-threshold data

    NASA Astrophysics Data System (ADS)

    Roth, Martin; Jongbloed, Geurt; Adri Buishand, T.

    2016-04-01

    A hurdle in the peaks-over-threshold approach for analyzing extreme values is the selection of the threshold. A method is developed to reduce this obstacle in the presence of multiple, similar data samples. This is for instance the case in many environmental applications. The idea is to combine threshold selection methods into a regional method. Regionalized versions of the threshold stability and the mean excess plot are presented as graphical tools for threshold selection. Moreover, quantitative approaches based on the bootstrap distribution of the spatially averaged Kolmogorov-Smirnov and Anderson-Darling test statistics are introduced. It is demonstrated that the proposed regional method leads to an increased sensitivity for too low thresholds, compared to methods that do not take into account the regional information. The approach can be used for a wide range of univariate threshold selection methods. We test the methods using simulated data and present an application to rainfall data from the Dutch water board Vallei en Veluwe.

  5. Structure-odor correlations in homologous series of alkanethiols and attempts to predict odor thresholds by 3D-QSAR studies.

    PubMed

    Polster, Johannes; Schieberle, Peter

    2015-02-11

    Homologous series of alkane-1-thiols, alkane-2-thiols, alkane-3-thiols, 2-methylalkane-1-thiols, 2-methylalkane-3-thiols, 2-methylalkane-2-thiols, and alkane-1,ω-dithiols were synthesized to study the influence of structural changes on odor qualities and odor thresholds. In particular, the odor thresholds were strongly influenced by steric effects: In all homologous series a minimum was observed for thiols with five to seven carbon atoms, whereas increasing the chain length led to an exponential increase in the odor threshold. Tertiary alkanethiols revealed clearly lower odor thresholds than found for primary or secondary thiols, whereas neither a second mercapto group in the molecule nor an additional methyl substitution lowered the threshold. To investigate the impact of the SH group, odor thresholds and odor qualities of thiols were compared to those of the corresponding alcohols and (methylthio)alkanes. Replacement of the SH group by an OH group as well as S-methylation of the thiols significantly increased the odor thresholds. By using comparative molecular field analysis, a 3D quantitative structure-activity relationship model was created, which was able to simulate the odor thresholds of alkanethiols in good agreement with the experimental results. NMR and mass spectrometric data for 46 sulfur-containing compounds are additionally supplied. PMID:25608797

  6. Photodetachment Spectroscopy of La-: Resonances and Thresholds

    NASA Astrophysics Data System (ADS)

    Walter, C. W.; Gibson, N. D.; Crocker, C.; Dungan, K. A.; Matola, B. R.

    2015-05-01

    The negative ion of lanthanum, La-, has the richest bound state spectrum ever observed for an atomic negative ion, and it has been proposed as perhaps the best candidate for laser cooling of a negative ion. In the present experiments, photodetachment thresholds and transitions between bound states of La- are investigated using tunable infrared spectroscopy. The relative signal for neutral atom production was measured with a crossed ion-beam-laser-beam apparatus over the photon energy range 290-900 meV. The spectrum reveals at least 14 sharp resonance peaks due to transitions to either bound states of the negative ion or quasibound states in the continuum. Multiple photodetachment thresholds are also observed, providing information on the binding energies for some states of La-. This material is based on work supported by the National Science Foundation under Grant No. 1068308 and 1404109.

  7. Stiffness threshold of randomly distributed carbon nanotube networks

    NASA Astrophysics Data System (ADS)

    Chen, Yuli; Pan, Fei; Guo, Zaoyang; Liu, Bin; Zhang, Jianyu

    2015-11-01

    For carbon nanotube (CNT) networks, with increasing network density, there may be sudden changes in the properties, such as the sudden change in electrical conductivity at the electrical percolation threshold. In this paper, the change in stiffness of the CNT networks is studied and especially the existence of stiffness threshold is revealed. Two critical network densities are found to divide the stiffness behavior into three stages: zero stiffness, bending dominated and stretching dominated stages. The first critical network density is a criterion to judge whether or not the network is capable of carrying load, defined as the stiffness threshold. The second critical network density is a criterion to measure whether or not most of the CNTs in network are utilized effectively to carry load, defined as bending-stretching transitional threshold. Based on the geometric probability analysis, a theoretical methodology is set up to predict the two thresholds and explain their underlying mechanisms. The stiffness threshold is revealed to be determined by the statical determinacy of CNTs in the network, and can be estimated quantitatively by the stabilization fraction of network, a newly proposed parameter in this paper. The other threshold, bending-stretching transitional threshold, which signs the conversion of dominant deformation mode, is verified to be well evaluated by the proposed defect fraction of network. According to the theoretical analysis as well as the numerical simulation, the average intersection number on each CNT is revealed as the only dominant factor for the electrical percolation and the stiffness thresholds, it is approximately 3.7 for electrical percolation threshold, and 5.2 for the stiffness threshold of 2D networks. For 3D networks, they are 1.4 and 4.4. And it also affects the bending-stretching transitional threshold, together with the CNT aspect ratio. The average intersection number divided by the fourth root of CNT aspect ratio is found to be

  8. 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.

  9. Reduced heat pain thresholds after sad-mood induction are associated with changes in thalamic activity.

    PubMed

    Wagner, Gerd; Koschke, Mandy; Leuf, Tanja; Schlösser, Ralf; Bär, Karl-Jürgen

    2009-03-01

    Negative affective states influence pain processing in healthy subjects in terms of augmented pain experience. Furthermore, our previous studies revealed that patients with major depressive disorder showed increased heat pain thresholds on the skin. Potential neurofunctional correlates of this finding were located within the fronto-thalamic network. The aim of the present study was to investigate the neurofunctional underpinnings of the influence of sad mood upon heat pain processing in healthy subjects. For this purpose, we used a combination of the Velten Mood Induction procedure and a piece of music to induce sad affect. Initially we assessed heat pain threshold after successful induction of sad mood outside the MR scanner in Experiment 1. We found a highly significant reduction in heat pain threshold on the left hand and a trend for the right. In Experiment 2, we applied thermal pain stimuli on the left hand (37, 42, and 45 degrees C) in an MRI scanner. Subjects were scanned twice, one group before and after sad-mood induction and another group before and after neutral-mood induction, respectively. Our main finding was a significant group x mood-induction interaction bilaterally in the ventrolateral nucleus of the thalamus indicating a BOLD signal increase after sad-mood induction and a BOLD signal decrease in the control group. We present evidence that induced sad affect leads to reduced heat pain thresholds in healthy subjects. This is probably due to altered lateral thalamic activity, which is potentially associated with changed attentional processes. PMID:19027763

  10. Time-course and dose-response relationships of imperatorin in the mouse maximal electroshock seizure threshold model.

    PubMed

    Luszczki, Jarogniew J; Glowniak, Kazimierz; Czuczwar, Stanislaw J

    2007-09-01

    This study was designed to evaluate the anticonvulsant effects of imperatorin (a furanocoumarin isolated from fruits of Angelica archangelica) in the mouse maximal electroshock seizure threshold model. The threshold for electroconvulsions in mice was determined at several times: 15, 30, 60 and 120 min after i.p. administration of imperatorin at increasing doses of 10, 20, 30, 40, 50 and 100 mg/kg. The evaluation of time-course relationship for imperatorin in the maximal electroshock seizure threshold test revealed that the agent produced its maximum antielectroshock action at 30 min after its i.p. administration. In this case, imperatorin at doses of 50 and 100 mg/kg significantly raised the threshold for electroconvulsions in mice by 38 and 68% (P<0.05 and P<0.001), respectively. The antiseizure effects produced by imperatorin at 15, 60 and 120 min after its systemic (i.p.) administration were less expressed than those observed for imperatorin injected 30 min before the maximal electroshock seizure threshold test. Based on this study, one can conclude that imperatorin produces the anticonvulsant effect in the maximal electroshock seizure threshold test in a dose-dependent manner. PMID:17602770

  11. Fold-change threshold screening: a robust algorithm to unmask hidden gene expression patterns in noisy aggregated transcriptome data.

    PubMed

    Hausen, Jonas; Otte, Jens C; Strähle, Uwe; Hammers-Wirtz, Monika; Hollert, Henner; Keiter, Steffen H; Ottermanns, Richard

    2015-11-01

    Transcriptomics is often used to investigate changes in an organism's genetic response to environmental contamination. Data noise can mask the effects of contaminants making it difficult to detect responding genes. Because the number of genes which are found differentially expressed in transcriptome data is often very large, algorithms are needed to reduce the number down to a few robust discriminative genes. We present an algorithm for aggregated analysis of transcriptome data which uses multiple fold-change thresholds (threshold screening) and p values from Bayesian generalized linear model in order to assess the robustness of a gene as a potential indicator for the treatments tested. The algorithm provides a robustness indicator (ROBI) as well as a significance profile, which can be used to assess the statistical significance of a given gene for different fold-change thresholds. Using ROBI, eight discriminative genes were identified from an exemplary dataset (Danio rerio FET treated with chlorpyrifos, methylmercury, and PCB) which could be potential indicators for a given substance. Significance profiles uncovered genetic effects and revealed appropriate fold-change thresholds for single genes or gene clusters. Fold-change threshold screening is a powerful tool for dimensionality reduction and feature selection in transcriptome data, as it effectively reduces the number of detected genes suitable for environmental monitoring. In addition, it is able to unmask patterns in altered genetic expression hidden by data noise and reduces the chance of type II errors, e.g., in environmental screening. PMID:26178833

  12. 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

  13. 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.

  14. Erosion thresholds and land surface morphology

    NASA Astrophysics Data System (ADS)

    Dietrich, William E.; Wilson, Cathy J.; Montgomery, David R.; McKean, James; Bauer, Romy

    1992-08-01

    We propose a graphical technique to analyze the entirety of landforms in a catchment to define quantitatively the spatial variation in the dominance of different erosion processes. High-resolution digital elevation data of a 1.2 km2 hilly area where the channel network had been mapped in the field were used in the digital terrain model, TOPOG, to test threshold theories for erosion. The land surface was divided into ˜20 m2 elements whose shapes were then classified as convergent, planar, or divergent. The entire landscape plotted on a graph of area per unit contour length against surface gradient shows each planform plotting as a separate field. A simple steady-state hydrologic model was used to predict zones of saturation and areas of high pore pressure to mimic the extreme hydrologic events responsible for erosive instability of the land surface. The field observation that saturation overland flow is rare outside convergent zones provided a significant constraint on the hydrologic parameter in the model. This model was used in threshold theories to predict areas of slope instability and areas subject to erosion by saturation overland flow, both of which can contribute to channel initiation. The proportion of convergent elements predicted to exceed the threshold varies greatly with relatively small changes in surface resistance, demonstrating a high sensitivity to land use such as cattle grazing. Overall, the landscape can be divided, using erosion threshold lines, into areas prone to channel instability due to runoff and stable areas where diffusive transport predominates.

  15. Sensory perception threshold measurement: an evaluation of semiobjective testing devices.

    PubMed

    Halar, E M; Hammond, M C; LaCava, E C; Camann, C; Ward, J

    1987-08-01

    Five semiobjective devices for testing sensory perception thresholds were concomitantly used on 36 normal subjects to determine normal threshold values, intersubject variability, and their correlation with age. The five devices include the Semmes-Weinstein monofilament (touch); three-point esthesiometer (two-point discrimination); Pfizer thermal tester (temperature); biothesiometer (vibration); and Optacon tactile tester (vibration). Each subject was tested at 12 upper extremity (UE) and ten lower extremity (LE) sites. The threshold was determined by the two-alternative forced choice method. Results showed that the mean threshold for each sensory perception modality in the UE sites was significantly lower than in the LE sites. The means of distally located sites for two-point discrimination and vibration thresholds were significantly lower than the means of the proximal sites in the UE. In the LE, touch perception threshold was significantly higher distally than proximally. Distally located nerves (median and ulnar) showed lower mean threshold values than proximally located nerves for two-point discrimination. There were also similar findings for the other sensory modalities in the UE and LE. The mean threshold of dermatomes showed significant variation across the trials for two-point discrimination and vibration sensation. Distally located dermatomes showed lower threshold values than those located proximally. The means of most sites tested for each sensory modality (except vibration tested by the Optacon) showed correlation with age. There was no difference in threshold values between men and women for any sensory modality. The mean values of standard deviation were provided for each peripheral sensory nerve and dermatome.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3619613

  16. 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.

  17. Damage thresholds for terahertz radiation

    NASA Astrophysics Data System (ADS)

    Dalzell, Danielle R.; McQuade, Jill; Vincelette, Rebecca; Ibey, Bennet; Payne, Jason; Thomas, Robert; Roach, W. P.; Roth, Caleb L.; Wilmink, Gerald J.

    2010-02-01

    Several international organizations establish minimum safety standards to ensure that workers and the general population are protected against adverse health effects associated with electromagnetic radiation. Suitable standards are typically defined using published experimental data. To date, few experimental studies have been conducted at Terahertz (THz) frequencies, and as a result, current THz standards have been defined using extrapolated estimates from neighboring spectral regions. In this study, we used computational modeling and experimental approaches to determine tissue-damage thresholds at THz frequencies. For the computational modeling efforts, we used the Arrhenius damage integral to predict damage-thresholds. We determined thresholds experimentally for both long (minutes) and short (seconds) THz exposures. For the long exposure studies, we used an in-house molecular gas THz laser (υ= 1.89 THz, 189.92 mW/cm2, 10 minutes) and excised porcine skin. For the short exposure studies, we used the Free Electron Laser (FEL) at Jefferson Laboratory (υ= 0.1-1.0 THz, 2.0-14.0 mW/cm2, 2 seconds) and wet chamois cloths. Thresholds were determined using conventional damage score determination and probit analysis techniques, and tissue temperatures were measured using infrared thermographic techniques. We found that the FEL was ideal for tissue damage studies, while our in-house THz source was not suitable to determine tissue damage thresholds. Using experimental data, the tissue damage threshold (ED50) was determined to be 7.16 W/cm2. This value was in well agreement with that predicted using our computational models. We hope that knowledge of tissue-damage thresholds at THz frequencies helps to ensure the safe use of THz radiation.

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

    PubMed

    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. PMID:27587134

  19. 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.

  20. Temporal discrimination threshold with healthy aging.

    PubMed

    Ramos, Vesper Fe Marie Llaneza; Esquenazi, Alina; Villegas, Monica Anne Faye; Wu, Tianxia; Hallett, Mark

    2016-07-01

    The temporal discrimination threshold (TDT) is the shortest interstimulus interval at which a subject can perceive successive stimuli as separate. To investigate the effects of aging on TDT, we studied tactile TDT using the method of limits with 120% of sensory threshold in each hand for each of 100 healthy volunteers, equally divided among men and women, across 10 age groups, from 18 to 79 years. Linear regression analysis showed that age was significantly related to left-hand mean, right-hand mean, and mean of 2 hands with R-square equal to 0.08, 0.164, and 0.132, respectively. Reliability analysis indicated that the 3 measures had fair-to-good reliability (intraclass correlation coefficient: 0.4-0.8). We conclude that TDT is affected by age and has fair-to-good reproducibility using our technique. PMID:27255827

  1. 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.

  2. [Skin temperature and lactate threshold during muscle work in sportsmen].

    PubMed

    Akimov, E B; Son'kin, V D

    2011-01-01

    The purpose of the investigation was to estimate change of a thermal condition of an organism during exhausting work (maximal aerobic test) on cycle ergometer on the basis of studying of dynamics of temperature of a forehead skin. Regularly training 20 men have taken part in the research--sportsmen of various specializations (skiers, rock-climbers, boxers, etc.). Temperature of forehead skin was registered by infrared thermovision chamber Nec TH 9100SL. These results compared with the data of measurements of heart rate, gas exchange, the lactate concentration in peripheral blood, and also with anthropometrical characteristics. It was shown that on dynamics of skin temperature at maximal work load it was possible to divide all subjects into 2 unequal groups: 1 (2/3 subjects, the majority of which trains endurance) - after temperature decrease take place its smooth increase up to refusal ofwork; 2 (1/3 subjects, concerning various sports specializations)--from the moment of the beginning of active evaporation of sweat the temperature decreases to the work termination. In group 1 lactate threshold (lactate concentration in blood--4 mm/l) corresponds to the beginning of rise in temperature after its decrease as a result of sweat evaporation. In group 2 lactate threshold was necessary on a phase of decrease in temperature at the moment of active evaporation of sweat. Distinctions between groups in structure of correlation relationship between the measured indicators are revealed, inversion of a sign ofcorrelation quotient in some cases were shown. Thus significant distinctions between groups in the level of the working capacity indicators were not revealed. All it testifies to existence possibility at least two various successful strategy of urgent adaptation of system of thermoregulation to intense muscular work. PMID:22117467

  3. 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

  4. Threshold and subthreshold generalized anxiety disorder among US adolescents: prevalence, sociodemographic, and clinical characteristics

    PubMed Central

    Burstein, M.; Beesdo-Baum, K.; He, J.-P.; Merikangas, K. R.

    2014-01-01

    Background Threshold and subthreshold forms of generalized anxiety disorder (GAD) are highly prevalent and impairing conditions among adults. However, there are few general population studies that have examined these conditions during the early life course. The primary objectives of this study were to: (1) examine the prevalence, and sociodemographic and clinical characteristics of threshold and subthreshold forms of GAD in a nationally representative sample of US youth; and (2) test differences in sociodemographic and clinical characteristics between threshold and subthreshold forms of the disorder. Method The National Comorbidity Survey-Adolescent Supplement is a nationally representative face-to-face survey of 10123 adolescents 13 to 18 years of age in the continental USA. Results Approximately 3% of adolescents met criteria for threshold GAD. Reducing the required duration from 6 months to 3 months resulted in a 65.7% increase in prevalence (5.0%); further relaxing the uncontrollability criterion led to an additional 20.7% increase in prevalence (6.1%). Adolescents with all forms of GAD displayed a recurrent clinical course marked by substantial impairment and co-morbidity with other psychiatric disorders. There were few significant differences in sociodemographic and clinical characteristics between threshold and subthreshold cases of GAD. Results also revealed age-related differences in the associated symptoms and clinical course of GAD. Conclusions Findings demonstrate the clinical significance of subthreshold forms of GAD among adolescent youth, highlighting the continuous nature of the GAD construct. Age-related differences in the associated symptoms and clinical course of GAD provide further support for criteria that capture variation in clinical features across development. PMID:24384401

  5. Neutrino floor at ultralow threshold

    NASA Astrophysics Data System (ADS)

    Strigari, Louis E.

    2016-05-01

    By lowering their energy threshold, direct dark matter searches can reach the neutrino floor with experimental technology that is now in development. The 7Be flux can be detected with ˜10 eV nuclear recoil energy threshold and 50 kg/yr exposure. The p e p flux can be detected with ˜3 ton/yr exposure, and the first detection of the CNO flux is possible with similar exposure. The p p flux can be detected with threshold of ˜eV and only ˜ kg /yr exposure. These can be the first pure neutral current measurements of the low-energy solar neutrino flux. Measuring this flux is important for low mass dark matter searches and for understanding the solar interior.

  6. Explosive percolation in thresholded networks

    NASA Astrophysics Data System (ADS)

    Hayasaka, Satoru

    2016-06-01

    Explosive percolation in a network is a phase transition where a large portion of nodes becomes connected with an addition of a small number of edges. Although extensively studied in random network models and reconstructed real networks, explosive percolation has not been observed in a more realistic scenario where a network is generated by thresholding a similarity matrix describing between-node associations. In this report, I examine construction schemes of such thresholded networks, and demonstrate that explosive percolation can be observed by introducing edges in a particular order.

  7. Surface characterizations of color threshold

    NASA Technical Reports Server (NTRS)

    Poirson, Allen B.; Wandell, Brian A.; Varner, Denise C.; Brainard, David H.

    1990-01-01

    The paper evaluates how well three different parametric shapes, ellipsoids, rectangles, and parallelograms, serve as models of three-dimentional detection contours. The constraints of the procedures for deriving the best-fitting shapes on inferences about the theoretical visual detection mechanisms are described. Results of two statistical tests show that only the parallelogram fits the data with more precision than the variance in repeated threshold measurements, and thus provides a slightly better fit than the other two shapes. Nevertheless it does not serve as a better guide than the ellipsoidal model for interpolating from the measurements to thresholds in novel color directions.

  8. 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

    2015-07-01

    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

  9. A critical experimental study of the classical tactile threshold theory

    PubMed Central

    2010-01-01

    Background The tactile sense is being used in a variety of applications involving tactile human-machine interfaces. In a significant number of publications the classical threshold concept plays a central role in modelling and explaining psychophysical experimental results such as in stochastic resonance (SR) phenomena. In SR, noise enhances detection of sub-threshold stimuli and the phenomenon is explained stating that the required amplitude to exceed the sensory threshold barrier can be reached by adding noise to a sub-threshold stimulus. We designed an experiment to test the validity of the classical vibrotactile threshold. Using a second choice experiment, we show that individuals can order sensorial events below the level known as the classical threshold. If the observer's sensorial system is not activated by stimuli below the threshold, then a second choice could not be above the chance level. Nevertheless, our experimental results are above that chance level contradicting the definition of the classical tactile threshold. Results We performed a three alternative forced choice detection experiment on 6 subjects asking them first and second choices. In each trial, only one of the intervals contained a stimulus and the others contained only noise. According to the classical threshold assumptions, a correct second choice response corresponds to a guess attempt with a statistical frequency of 50%. Results show an average of 67.35% (STD = 1.41%) for the second choice response that is not explained by the classical threshold definition. Additionally, for low stimulus amplitudes, second choice correct detection is above chance level for any detectability level. Conclusions Using a second choice experiment, we show that individuals can order sensorial events below the level known as a classical threshold. If the observer's sensorial system is not activated by stimuli below the threshold, then a second choice could not be above the chance level. Nevertheless, our

  10. Auricular Acupressure Can Modulate Pain Threshold.

    PubMed

    Santoro, Antonietta; Nori, Stefania Lucia; Lorusso, Letizia; Secondulfo, Carmine; Monda, Marcellino; Viggiano, Andrea

    2015-01-01

    The objective of our study was to investigate if auriculotherapy (AT) can modulate pain threshold. In our experiments, AT consisted of placing Vaccaria seeds over the "fingers point" of one ear. Two groups of healthy volunteers were enrolled for the study. Each subject was asked to perform an autoalgometric test developed by our group on three occasions: before, 1 hour after, AT and 24 hours after AT. Participants of the first group received a 2-minute long session of AT, while participants of the second group received a 2-minute long session of sham treatment, consisting of a puncture/massage above the skin of the neck. The autoalgometric test consisted of applying an increasing pressure with the finger-tips and finger-backs of four fingers by the subjects themselves (i.e., eight sites were evaluated) against a round-shaped needle for two times: until a minimum pain sensation (first time, minimal test) or a maximally tolerable pain sensation (second time, maximal test). Our results showed a significant higher pain threshold in the maximal test at 24 hours after AT compared to sham treatment. This result indicates for the first time that AT can increase pain tolerability, rather than affecting the minimal pain threshold. PMID:26236378

  11. 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.

  12. Auricular Acupressure Can Modulate Pain Threshold

    PubMed Central

    Santoro, Antonietta; Nori, Stefania Lucia; Lorusso, Letizia; Secondulfo, Carmine; Monda, Marcellino; Viggiano, Andrea

    2015-01-01

    The objective of our study was to investigate if auriculotherapy (AT) can modulate pain threshold. In our experiments, AT consisted of placing Vaccaria seeds over the “fingers point” of one ear. Two groups of healthy volunteers were enrolled for the study. Each subject was asked to perform an autoalgometric test developed by our group on three occasions: before, 1 hour after, AT and 24 hours after AT. Participants of the first group received a 2-minute long session of AT, while participants of the second group received a 2-minute long session of sham treatment, consisting of a puncture/massage above the skin of the neck. The autoalgometric test consisted of applying an increasing pressure with the finger-tips and finger-backs of four fingers by the subjects themselves (i.e., eight sites were evaluated) against a round-shaped needle for two times: until a minimum pain sensation (first time, minimal test) or a maximally tolerable pain sensation (second time, maximal test). Our results showed a significant higher pain threshold in the maximal test at 24 hours after AT compared to sham treatment. This result indicates for the first time that AT can increase pain tolerability, rather than affecting the minimal pain threshold. PMID:26236378

  13. Effects of Accelerated Aging on Fiber Damage Thresholds

    SciTech Connect

    Setchell, R.E.

    1999-02-15

    internal defects. Damage characteristics obtained from fibers subjected to each of these aging environments were compared to results from fresh fibers tested under identical conditions. A surprising result was that internal damage was not observed in any of the tested fibers. Only breakdown at the fiber entrance face and catastrophic damage at both end faces were observed. Fiber end faces were not sealed during the accelerated aging environments, and thresholds at these faces were significantly lower in the aged fibers. However, most fibers transmitted relatively high pulse energies before damaging, and a large fraction never damaged before we reached the limits of our test laser. The absence of any observable affect on internal damage thresholds is encouraging, but the current results do not rule out the possibility that some other approach to accelerated aging could reveal a growth mechanism for internal defects.

  14. Taste thresholds in patients with small-cell lung cancer.

    PubMed

    Ovesen, L; Hannibal, J; Sørensen, M

    1991-01-01

    Recognition thresholds for the four basic tastes (salt, sour, sweet and bitter) were tested by the forced-choice technique in 27 patients with small-cell lung cancer, and 22 weight-matched control patients with non-malignant diseases. No significant differences in threshold concentrations could be demonstrated. When patients who were losing weight were compared with weight-stable patients, significantly lower taste thresholds for bitter substances were found in weight losing groups in both cancer and control patients. Small-cell lung cancer patients who responded to therapy had obtained an increased threshold for bitter taste at the time of reevaluation than at the time of diagnosis, an effect that may be explained by the chemotherapeutic regimen. The results suggest that in patients with small-cell lung cancer it is not the cancer disease per se but the weight loss that often accompanies it that causes an increased taste sensitivity for bitter substances. PMID:1847701

  15. Estimating Conservation Thresholds on Rangelands

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Conservation Effects Assessment Project (CEAP) is a multi-agency effort designed to quantify the environmental and economic impacts of land conservation practices. One of USDA’s goals is to identify Conservation Thresholds, the point at which accelerated erosion occurs, and to examine the usefu...

  16. 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…

  17. New states above charm threshold

    SciTech Connect

    Eichten, Estia J.; Lane, Kenneth; Quigg, Chris; /Fermilab

    2005-11-01

    We revise and extend expectations for the properties of charmonium states that lie above charm threshold, in light of new experimental information. We refine the Cornell coupled-channel model for the coupling of c{bar c} levels to two-meson states, defining resonance masses and widths by pole positions in the complex energy plane, and suggest new targets for experiment.

  18. 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…

  19. 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

  20. Monolayer semiconductor nanocavity lasers with ultralow thresholds

    DOE PAGESBeta

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

    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

  1. 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

    2015-04-01

    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. PMID:25778703

  2. 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.

  3. Thresholds for self-motion perception in roll without and with visual fixation target - the visual-vestibular interaction effect

    PubMed Central

    Kolev, Ognyan I.

    2015-01-01

    Summary The purpose of this study was to establish the self-motion perception threshold, in roll, in the visual-vestibular interaction (VVI) state, creating an oculogyral illusion, and to compare this threshold to the self-motion perception threshold in darkness. A further aim was to investigate the dynamics of the threshold at a low frequency range (0.1–1 Hz) of sinusoidal rotation. Seven healthy subjects were tested. A motion platform was used to generate motion. Single cycles of sinusoidal acceleration at four frequencies (0.1, 0.2, 0.5 and 1 Hz) were used as motion stimuli. To avoid otolith stimulation, subjects were rotated about a vertical axis in supine position. To evoke an oculogyral illusion subjects were instructed to fixate their gaze on a cross-shaped object aligned with their head, which rotated with them. The results show a lowering of the self-motion perception threshold in the VVI state, significant for the frequencies 0.1 and 0.2 Hz (p<0.05). In all the subjects, visual fixation on the cross evoked an oculogyral illusion. The threshold in both tested conditions was frequency dependent: it decreased with increasing frequency values. However, this effect was consistently stronger in darkness across all frequencies (p<0.05). In conclusion, the application of sinusoidal rotation during roll at low frequencies in the VVI condition evokes oculogyral illusion. This interaction lowers the self-motion perception threshold compared to that measured during rotation in darkness. This testing method could be of practical benefit in clinical application for revealing brain dysfunction involving integrative mechanisms of perception. PMID:26415781

  4. The effects of goshajinkigan, a herbal medicine, on subjective symptoms and vibratory threshold in patients with diabetic neuropathy.

    PubMed

    Tawata, M; Kurihara, A; Nitta, K; Iwase, E; Gan, N; Onaya, T

    1994-12-16

    Goshajinkigan, a herbal medicine, has long been used in Japan to alleviate the subjective symptoms of diabetic neuropathy; however, its effects have not been confirmed objectively. We evaluated its effects on subjective symptoms and on vibration sensation in patients with diabetic neuropathy. The oral administration of 7.5 g/day of Goshajinkigan for 3 months (treatment period) relieved subjective symptoms of numbness in 9 of 13 patients. When the drug was discontinued for 2 months as a washout period, the subjective symptom worsened in 7 of 13 patients. Chi-square analysis revealed significant effects of Goshajiniagan on subjective symptoms (P < 0.001 for numbness and P < 0.05 for cold sensation). Vibration sensation was evaluated by measuring vibratory threshold using an SMV-5 vibrometer. There were significant changes in vibratory thresholds by paired t-test (P < 0.05) both in the upper and the lower extremities during the treatment and washout periods. Chi-square analysis also revealed a significant effect of Goshajinkigan on vibratory threshold (P < 0.01). There was no significant change in glycosylated hemoglobin as a whole during the study. These observations confirm that Goshajinkigan relieves subjective symptoms and demonstrate that it improves vibration sensation in patients with diabetic neuropathy. PMID:7705193

  5. "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…

  6. Effect of Hemoglobin Transfusion Threshold on Cerebral Hemodynamics and Oxygenation.

    PubMed

    Yamal, Jose-Miguel; Rubin, M Laura; Benoit, Julia S; Tilley, Barbara C; Gopinath, Shankar; Hannay, H Julia; Doshi, Pratik; Aisiku, Imoigele P; Robertson, Claudia S

    2015-08-15

    Cerebral dysfunction caused by traumatic brain injury may adversely affect cerebral hemodynamics and oxygenation leading to worse outcomes if oxygen capacity is decreased due to anemia. In a randomized clinical trial of 200 patients comparing transfusion thresholds <7 g/dl versus 10 g/dl, where transfusion of leukoreduced packed red blood cells was used to maintain the assigned hemoglobin threshold, no long-term neurological difference was detected. The current study examines secondary outcome measures of intracranial pressure (ICP), cerebral perfusion pressure (CPP), and brain tissue oxygenation (PbtO2) in patients enrolled in this randomized clinical trial. We observed a lower hazard for death (hazard ratio [HR]=0.12, 95% confidence interval [CI]=0.02-0.99) during the first 3 days post-injury, and a higher hazard for death after three days (HR=2.55, 95% CI=1.00-6.53) in the 10 g/dl threshold group as compared to the 7 g/dL threshold group. No significant differences were observed for ICP and CPP but MAP was slightly lower in the 7 g/dL group, although the decreased MAP did not result in increased hypotension. Overall brain tissue hypoxia events were not significantly different in the two transfusion threshold groups. When the PbtO2 catheter was placed in normal brain, however, tissue hypoxia occurred in 25% of patients in the 7 g/dL threshold group, compared to 10.2% of patients in the 10 g/dL threshold group (p=0.04). Although we observed a few differences in hemodynamic outcomes between the transfusion threshold groups, none were of major clinical significance and did not affect long-term neurological outcome and mortality. PMID:25566694

  7. 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

  8. 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.

  9. A threshold for dissipative fission

    SciTech Connect

    Thoennessen, M.; Bertsch, G.F.

    1993-09-21

    The empirical domain of validity of statistical theory is examined as applied to fission data on pre-fission data on pre-fission neutron, charged particle, and {gamma}-ray multiplicities. Systematics are found of the threshold excitation energy for the appearance of nonstatistical fission. From the data on systems with not too high fissility, the relevant phenomenological parameter is the ratio of the threshold temperature T{sub thresh} to the (temperature-dependent) fission barrier height E{sub Bar}(T). The statistical model reproduces the data for T{sub thresh}/E{sub Bar}(T) < 0.26 {plus_minus} 0.05, but underpredicts the multiplicities at higher T{sub thresh}/E{sub Bar}(T) independent of mass and fissility of the systems.

  10. Low Threshold Quantum Dot Lasers.

    PubMed

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

    2016-04-01

    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. PMID:26978011

  11. 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

  12. 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

  13. Threshold Phenomena in a Throbbing Complex Plasma

    SciTech Connect

    Mikikian, Maxime; Coueedel, Lenaiec; Cavarroc, Marjorie; Tessier, Yves; Boufendi, Laiefa

    2010-08-13

    In complex plasmas, the trapped dust particle cloud is often characterized by a central dust-free region ('void'). The void induces a spatial inhomogeneity of the dust particle distribution and is at the origin of many intricate unstable phenomena. One type of this kind of behavior is the so-called heartbeat instability consisting of successive contractions and expansions of the void. This instability is characterized by a strong nonlinear dynamics which can reveal the occurrence of incomplete sequences corresponding to failed contractions. Experimental results based on high-speed imaging are presented for the first time and underline this threshold effect in both the dust cloud motion and the evolution of the plasma light emission.

  14. Complete genome sequence and comparative analysis of grass carp reovirus strain 109 (GCReV-109) with other grass carp reovirus strains reveals no significant correlation with regional distribution.

    PubMed

    Pei, Chao; Ke, Fei; Chen, Zhong-Yuan; Zhang, Qi-Ya

    2014-09-01

    A new grass carp reovirus strain, tentatively named GCReV-109, was isolated in Hubei, China, and its complete genome sequence was determined. The genome contained 11 double-stranded RNA segments (S1-S11) covering 24,620 base pairs. All of the segments had conserved terminal nucleotides, with GUAA(U)/CU at the 5' end and UCAUC at the 3' end. Protein sequence comparison showed that GCReV-109 was most closely related to GCRV-GD108 and shared 96.6-99.5 % protein sequence identity but only shared 16.7-46.1 and 15.1-45.4 % identity with GCRV-873 and HGDRV, respectively. Phylogenetic analysis showed that grass carp reovirus strains in China can be divided into three genotypes. Further analysis revealed homology between the GCRV-109 VP56 and HGDRV VP55 proteins, as well as GCReV-109 NS38, GCRV-873 NS38, and HGDRV VP39. The results of these comparisons also indicated that the homology between viruses was not necessarily linked to their geographical distribution. Our study will help in recognizing and understanding the genome structure and genetic diversity of grass carp reovirus. PMID:24687858

  15. 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.

  16. Program For Thresholding In Digital Images

    NASA Technical Reports Server (NTRS)

    Nolf, Scott R.; Avis, Elizabeth L.; Matthews, Christine G.; Stacy, Kathryn

    1994-01-01

    THRTOOL program applies thresholding techniques to Sun rasterfiles. Provides for choice among four methods of thresholding. Written in C language and implemented on Sun series and Silicon Graphics IRIS machines.

  17. 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...

  18. Threshold Phenomena in Atomic Inner Shells

    NASA Astrophysics Data System (ADS)

    Wang, Honghong

    1995-01-01

    Two types of atomic inner-shell threshold phenomena are studied: (1) atomic inner-shell radiationless resonant Raman scattering (RRRS) as a function of excitation energy, and (2) the onset of Cu Coster-Kronig (CK) transitions due to extraatomic relaxation, as a function of cluster size. (1). The K-L_{2,3}L _{2,3} and L_{2,3 }-VV Auger spectra of P in InP were measured in the vicinity of the P K-shell ionization threshold as well as at high excess energies. The evolution of the P K-L_{2,3 }L_{2,3} ^1D Auger spectrum from the radiationless resonant Raman scattering regime into the normal Auger transition regime in InP is found to be in accordance with time-independent resonant scattering theory of inner-shell threshold phenomena. The measured RRRS intensity reveals a quasi-bound state in the bulk-sensitive P K absorption spectrum. The origins of deviations of the RRRS energy from linear dispersion are examined in terms of the finite incident-photon-energy distribution and multiple resonances. Both our measurements and semiclassical calculations show that the post-collision interaction effect is relatively small. The measured P K-L_{2,3}L_{2,3} intensities and P 1s lifetime width are found to be in good agreement with atomic calculations, revealing the predominantly atomic character of P inner-shell transitions in InP. The evolution of P L_{2,3 }-VV Auger transitions in InP is found to be sensitive to the excitation energy at the P 1s threshold; the P K-L_{2,3}L_{2,3 } Raman resonance causes changes in the L _{2,3}-VV diagram-transition line shape as well as intensity enhancement of all L _{2,3}-VV features. Applying the Cini-Sawatzky model to the line shape reveals a 0.3-eV change in the local effective Coulomb interaction U _{eff} near the resonance. The difference in the line shapes between the satellite and diagram transitions indicates a change of the local density of states in the valence band in the presence of a spectator 2p hole. The single- and double-2p

  19. 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

  20. 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

  1. Thresholds for impaired species recovery.

    PubMed

    Hutchings, Jeffrey A

    2015-06-22

    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, r(realized), 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 (N(max)), 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

  2. 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

  3. 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

  4. Mechanism of Anomalous Ellipticity Dependence of Near-threshold Harmonics in H 2 +

    NASA Astrophysics Data System (ADS)

    Nasiri Avanaki, Kobra; Telnov, Dmitry A.; Chu, Shih-I.

    2016-05-01

    We have studied the mechanism of anomalous dependence of near-threshold harmonics in H2+on ellipticity of driving field with the carrier wavelength 780 nm. The numerical procedure is based on accurate solution of the time-dependent Schrödinger equation in prolate spheroidal coordinates with the help of generalized pseudospectral method. Our analysis reveals that the origin of this phenomenon is mainly in the near-resonant excitation of πu molecular orbitals in H2+.For the lowest affected harmonic, the maximum in the ellipticity dependence of the radiation energy is exclusively due to excitation of the 1πu state; however, for higher near-threshold harmonics, higher-lying excited πu states are playing significant role as well. The closer the harmonic to the threshold, the larger number of excited states make considerable contributions. All these contributions interfere, resulting in the anomalous ellipticity dependence with a maximum at some non-zero value of the ellipticity parameter. In the vicinity of this value, the harmonics with the anomalous dependence are linearly polarized along the minor axis of the polarization ellipse of the driving field and may show strong elliptical polarization as well. This work is partially supported by DOE.

  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. PMID:27379250

  6. Anaerobic threshold: its concept and role in endurance sport.

    PubMed

    Ghosh, Asok Kumar

    2004-01-01

    aerobic to anaerobic transition intensity is one of the most significant physiological variable in endurance sports. Scientists have explained the term in various ways, like, Lactate Threshold, Ventilatory Anaerobic Threshold, Onset of Blood Lactate Accumulation, Onset of Plasma Lactate Accumulation, Heart Rate Deflection Point and Maximum Lactate Steady State. But all of these have great role both in monitoring training schedule and in determining sports performance. Individuals endowed with the possibility to obtain a high oxygen uptake need to complement with rigorous training program in order to achieve maximal performance. If they engage in endurance events, they must also develop the ability to sustain a high fractional utilization of their maximal oxygen uptake (%VO(2) max) and become physiologically efficient in performing their activity. Anaerobic threshold is highly correlated to the distance running performance as compared to maximum aerobic capacity or VO(2) max, because sustaining a high fractional utilization of the VO(2) max for a long time delays the metabolic acidosis. Training at or little above the anaerobic threshold intensity improves both the aerobic capacity and anaerobic threshold level. Anaerobic Threshold can also be determined from the speed-heart rate relationship in the field situation, without undergoing sophisticated laboratory techniques. However, controversies also exist among scientists regarding its role in high performance sports. PMID:22977357

  7. 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

  8. 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.

  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. AB161. High resolution melting analysis of buccal DNA revealed a significant association between UGT1A1 c.211G>A and neonatal hyperbilirubinemia development in Malay population

    PubMed Central

    Cheung, Tian Pei; Van Rostenberghe, Hans; Ismail, Rosliza; Nawawi, Noor Namirah; Abdullah, Nurul Amierah; Ramli, Noraida; Ibrahim, Nor Rosidah; Hj Abd Majid, Noorizan; Mohd Yusoff, Narazah; Nishio, Hisahide; Yusoff, Surini

    2015-01-01

    Background Severe neonatal hyperbilirubinemia or neonatal jaundice (NNJ) characterised by an elevated total serum bilirubin (TSB) level may result in kernicterus or even death. Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) is the key enzyme which conjugates bilirubin with glucuronic acid for the subsequent bilirubin excretion. Conversely, constitutive androstane receptor (CAR), encoded by nuclear receptor subfamily 1, group I, member 3 (NR1I3) gene, regulates bilirubin excretion by activating the components of the bilirubin clearance pathway. Thus, genetic variants in UGT1A1 and NR1I3 genes may modulate bilirubin excretion and lead to NNJ. This study aimed to determine the association between UGT1A1 and NR1I3 genetic variants and NNJ development in Malay population by genotyping the DNA isolated from buccal swabs. The accuracy and reliability of the genotyping results produced by buccal DNA was also compared with that of the whole blood DNA. Methods Buccal swabs were collected from 232 hyperbilirubinemia and 232 non-hyperbilirubinemia newborns admitted to and/or born in Hospital Universiti Sains Malaysia (HUSM). Hyperbilirubinemia subjects were those with TSB levels ≥250 µmol/L within the first week after birth while non-hyperbilirubinemia subjects were newborns without significant hyperbilirubinemia. The UGT1A1 (c.211G>A) and NR1I3 [MPJ6_1I3008 (G>A), IVS8+116T>G and 540A>G] variants were genotyped by using high resolution melting (HRM) analysis. Binary logistic regression was used to assess the association between variant genotypes and risk of NNJ. Whole blood samples were also collected from 60 subjects and genotyped to compare the HRM genotyping results with that of the buccal swabs. Results When compared with wild-type genotype, both heterozygous and homozygous variant genotypes of MPJ6_1I3008 (G>A), IVS8+116T>G and 540A>G were not significantly associated with NNJ. However, the heterozygous genotype (GA) of c.211G>A was found to increase the

  11. 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. PMID:24483506

  12. 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.

  13. 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. PMID:14766147

  14. Rainfall thresholds for the initiation of landslides in Italy

    NASA Astrophysics Data System (ADS)

    Peruccacci, S.; Brunetti, M. T.; Rossi, M.; Guzzetti, F.

    2009-04-01

    -Day-Normal (RDN). By comparing the obtained ID thresholds with other Italian ID thresholds in the literature, we establish that the new thresholds are not significantly lower than the other thresholds. We conclude proposing that the new ID thresholds be used in an Italian landslide warning system based on precipitation measurements and estimates.

  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. Relationship between Critical Flicker Fusion (CFF) Thresholds and Personality under Three Auditory Stimulus Conditions.

    ERIC Educational Resources Information Center

    Ali, M. R.; Amir, T.

    1988-01-01

    Investigated relationship between critical flicker fusion (CFF) thresholds and five personality characteristics (alienation; social nonconformity; discomfort, expression, and defensiveness) under three auditory stimulus conditions (quiet, noise, meaningful verbal stimuli). Results from 60 college students revealed that auditory stimulation and…

  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. 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. PMID:26968009

  20. 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

  1. Anger as a predictor of suicidal ideation in middle-school students in Korea: gender difference in threshold point.

    PubMed

    Lee, Jongeun; Choi, Heeseung; Kim, Mi Ja; Park, Chang Gi; Shin, Dong-soo

    2009-01-01

    Studies on gender differences in suicidal ideation and anger are limited. Furthermore, these studies focused on linear relationships, which limits the full understanding of the complex relationships and hampers identification of high-risk groups for suicidal tendencies. Hence, this study aims to assess the gender differences in: (1) the level of suicidal ideation and anger; (2) predictors for suicidal ideation; and (3) the varying association between suicidal ideation and anger. The target population for this cross-sectional, correlational study was adolescents aged 13 to 15 years living in South Korea. A total of 258 adolescents (160 boys and 98 girls) completed the Multidimensional Anger Inventory and Suicidal Ideation Questionnaire. Data were analyzed by descriptive statistics, multiple linear, and spline regression analysis. Girls reported significantly higher scores in both anger and suicidal ideation. While anger was a significant predictor for suicidal ideation only in boys, both school life satisfaction and anger were significant predictors of suicidal ideation in girls. After controlling for sociodemographic factors, the spline regression revealed a significant threshold point in the relationship between anger and suicidal ideation, particularly among girls. At the threshold anger point of 117.67, 12.5% of girls belonged to the high-risk group. The gender-specific patterns of the relationship between suicidal ideation and anger and the existence of threshold points confirmed the need for targeted suicidal preventive programs focusing on controlling anger. PMID:19764277

  2. Individual Differences Reveal Correlates of Hidden Hearing Deficits

    PubMed Central

    Masud, Salwa; Mehraei, Golbarg; Verhulst, Sarah; Shinn-Cunningham, Barbara G.

    2015-01-01

    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.” PMID:25653371

  3. 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

  4. 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. PMID:22465565

  5. Sweet Taste and Menthol Increase Cough Reflex Thresholds

    PubMed Central

    Wise, Paul M.; Breslin, Paul A.S.; Dalton, Pamela

    2015-01-01

    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. PMID:22465565

  6. 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. PMID:26243310

  7. 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.

  8. Revealing Mercury

    NASA Astrophysics Data System (ADS)

    Prockter, L. M.; Solomon, S. C.; Head, J. W.; Watters, T. R.; Murchie, S. L.; Robinson, M. S.; Chapman, C. R.; McNutt, R. L.

    2009-04-01

    -frequency distribution suggest that smooth plains on Mercury's surface range in age from the end of the period of heavy impact bombardment to as young as perhaps 1 billion years; these ongoing measurements are helping to elucidate the volcanic history of the planet. Mercury's global tectonic history is also revealed by the MESSENGER image and laser altimeter data. Significant evidence for global contraction was seen in Mariner 10 images in the form of widespread lobate scarps. The MESSENGER images show that contractional features are the dominant tectonic landform globally, and the inferred average contractional strain is at least one third greater than previously inferred from Mariner 10 observations. Only three exceptions to the dominance of contractional deformation have been found to date: extensional troughs that include prominent basin-radial systems documented in two basins, the Pantheon Fossae within the 1500-km-diameter Caloris basin and a similar set of features within a newly-imaged 700-km-diameter basin, and a circumferential trough system within the smaller, younger Raditladi basin. That these extensional tectonic features are rare on Mercury, and that they are not seen within basins elsewhere in the Solar System, pose important constraints on the thermal and mechanical evolution of Mercury's interior.

  9. 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.

  10. 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.