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Sample records for extreme phenotype sampling

  1. Detecting the Common and Individual Effects of Rare Variants on Quantitative Traits by Using Extreme Phenotype Sampling

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    Ya-Jing Zhou

    2016-01-01

    Full Text Available Next-generation sequencing technology has made it possible to detect rare genetic variants associated with complex human traits. In recent literature, various methods specifically designed for rare variants are proposed. These tests can be broadly classified into burden and nonburden tests. In this paper, we take advantage of the burden and nonburden tests, and consider the common effect and the individual deviations from the common effect. To achieve robustness, we use two methods of combining p-values, Fisher’s method and the minimum-p method. In rare variant association studies, to improve the power of the tests, we explore the advantage of the extreme phenotype sampling. At first, we dichotomize the continuous phenotypes before analysis, and the two extremes are treated as two different groups representing a dichotomous phenotype. We next compare the powers of several methods based on extreme phenotype sampling and random sampling. Extensive simulation studies show that our proposed methods by using extreme phenotype sampling are the most powerful or very close to the most powerful one in various settings of true models when the same sample size is used.

  2. Assessing gene-environment interaction effects of FTO, MC4R and lifestyle factors on obesity using an extreme phenotype sampling design: Results from the HUNT study.

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    Bjørnland, Thea; Langaas, Mette; Grill, Valdemar; Mostad, Ingrid Løvold

    2017-01-01

    Our aim was to assess the influence of age, gender and lifestyle factors on the effect of the obesity-promoting alleles of FTO and MCR4. The HUNT study comprises health information on the population of Nord-Trøndelag county, Norway. Extreme phenotype participants (gender-wise lower and upper quartiles of waist-hip-ratio and BMI ≥ 35 kg/m2) in the third survey, HUNT3 (2006-08), were genotyped for the single-nucleotide polymorphisms rs9939609 (FTO) and rs17782313 (MC4R); 25686 participants were successfully genotyped. Extreme sampling was chosen to increase power to detect genetic and gene-environment effects on waist-hip-ratio and BMI. Statistical inference was based on linear regression models and a missing-covariate likelihood approach for the extreme phenotype sampling design. Environmental factors were physical activity, diet (artificially sweetened beverages) and smoking. Longitudinal analysis was performed using material from HUNT2 (1995-97). Cross-sectional and longitudinal genetic effects indicated stronger genetic associations with obesity in young than in old, as well as differences between women and men. We observed larger genetic effects among physically inactive compared to active individuals. This interaction was age-dependent and seen mainly in 20-40 year olds. We observed a greater FTO effect among men with a regular intake of artificially sweetened beverages, compared to non-drinkers. Interaction analysis of smoking was mainly inconclusive. In a large all-adult and area-based population survey the effects of obesity-promoting minor-alleles of FTO and MCR4, and interactions with life style factors are age- and gender-related. These findings appear relevant when designing individualized treatment for and prophylaxis against obesity.

  3. Sample Handling in Extreme Environments

    Science.gov (United States)

    Avellar, Louisa; Badescu, Mircea; Sherrit, Stewart; Bar-Cohen, Yoseph

    2013-01-01

    Harsh environments, such as that on Venus, preclude the use of existing equipment for functions that involve interaction with the environment. The operating limitations of current high temperature electronics are well below the actual temperature and pressure found on Venus (460 deg C and 92 atm), so proposed lander configurations typically include a pressure vessel where the science instruments are kept at Earth-like temperature and pressure (25 deg C and 1 atm). The purpose of this project was to develop and demonstrate a method for sample transfer from an external drill to internal science instruments for a lander on Venus. The initial concepts were string and pneumatically driven systems; and the latter system was selected for its ability to deliver samples at very high speed. The pneumatic system was conceived to be driven by the pressure difference between the Venusian atmosphere and the inside of the lander. The pneumatic transfer of a small capsule was demonstrated, and velocity data was collected from the lab experiment. The sample transfer system was modeled using CAD software and prototyped using 3D printing. General structural and thermal analyses were performed to approximate the proposed system's mass and effects on the temperature and pressure inside of the lander. Additionally, a sampler breadboard for use on Titan was tested and functionality problems were resolved.

  4. Sample Handling in Extreme Environments

    Science.gov (United States)

    Avellar, Louisa; Badescu, Mircea; Sherrit, Stewart; Bar-Cohen, Yoseph

    2013-01-01

    Harsh environments, such as that on Venus, preclude the use of existing equipment for functions that involve interaction with the environment. The operating limitations of current high temperature electronics are well below the actual temperature and pressure found on Venus (460 deg C and 92 atm), so proposed lander configurations typically include a pressure vessel where the science instruments are kept at Earth-like temperature and pressure (25 deg C and 1 atm). The purpose of this project was to develop and demonstrate a method for sample transfer from an external drill to internal science instruments for a lander on Venus. The initial concepts were string and pneumatically driven systems; and the latter system was selected for its ability to deliver samples at very high speed. The pneumatic system was conceived to be driven by the pressure difference between the Venusian atmosphere and the inside of the lander. The pneumatic transfer of a small capsule was demonstrated, and velocity data was collected from the lab experiment. The sample transfer system was modeled using CAD software and prototyped using 3D printing. General structural and thermal analyses were performed to approximate the proposed system's mass and effects on the temperature and pressure inside of the lander. Additionally, a sampler breadboard for use on Titan was tested and functionality problems were resolved.

  5. Sample size calculation in metabolic phenotyping studies.

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    Billoir, Elise; Navratil, Vincent; Blaise, Benjamin J

    2015-09-01

    The number of samples needed to identify significant effects is a key question in biomedical studies, with consequences on experimental designs, costs and potential discoveries. In metabolic phenotyping studies, sample size determination remains a complex step. This is due particularly to the multiple hypothesis-testing framework and the top-down hypothesis-free approach, with no a priori known metabolic target. Until now, there was no standard procedure available to address this purpose. In this review, we discuss sample size estimation procedures for metabolic phenotyping studies. We release an automated implementation of the Data-driven Sample size Determination (DSD) algorithm for MATLAB and GNU Octave. Original research concerning DSD was published elsewhere. DSD allows the determination of an optimized sample size in metabolic phenotyping studies. The procedure uses analytical data only from a small pilot cohort to generate an expanded data set. The statistical recoupling of variables procedure is used to identify metabolic variables, and their intensity distributions are estimated by Kernel smoothing or log-normal density fitting. Statistically significant metabolic variations are evaluated using the Benjamini-Yekutieli correction and processed for data sets of various sizes. Optimal sample size determination is achieved in a context of biomarker discovery (at least one statistically significant variation) or metabolic exploration (a maximum of statistically significant variations). DSD toolbox is encoded in MATLAB R2008A (Mathworks, Natick, MA) for Kernel and log-normal estimates, and in GNU Octave for log-normal estimates (Kernel density estimates are not robust enough in GNU octave). It is available at http://www.prabi.fr/redmine/projects/dsd/repository, with a tutorial at http://www.prabi.fr/redmine/projects/dsd/wiki. © The Author 2015. Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  6. Infill sampling criteria to locate extremes

    CSIR Research Space (South Africa)

    Watson, AG

    1995-07-01

    Full Text Available concise statement of the single-sample, Gaussian-based, objective function: E\\[Z~,,+,,IS\\] = ~z~,>ts + W(~Cx))'Oz,,,,+s 596 Watson and Barnes where W( ) is the peculiar function W(~(x)) = ~(~(x)) + ~(x) 9 ,I,(~(x)) ~b...) and (3), not the "quick-and- Figure 1. Contours of exhaustive dataset: 625 observations on 25 x 25 grid. Sampling to Locate Extremes 601 Figure 2, Contours of log-transformed exhaustive data set: 625 observations on 25 x...

  7. Extreme spermatogenesis failure: andrological phenotype and intracytoplasmic sperm injection outcomes.

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    Plouvier, P; Barbotin, A-L; Boitrelle, F; Dewailly, D; Mitchell, V; Rigot, J-M; Lefebvre-Khalil, V; Robin, G

    2017-03-01

    Patients with very low sperm count through direct sperm examination can exhibit extreme oligozoospermia or cryptozoospermia (after centrifugation). The management of these patients is a real challenge for both clinicians and biologists. In this retrospective and comparative cohort study, we compared the andrological phenotype of patients with extreme alterations of spermatogenesis and assessed whether the origin of spermatozoa (testicular or ejaculate) had any influence on intracytoplasmic sperm injection (ICSI) outcomes. A total of 161 ICSI cycles were performed using ejaculated spermatozoa from 75 patients with extreme oligozoospermia (EOS) or cryptozoospermia (CS) and 150 ICSI cycles using extracted testicular spermatozoa from 74 patients with non-obstructive azoospermia (NOA). Physical, hormonal, ultrasound assessments, and ICSI outcomes were performed in each group. Cryptorchidism was significantly more frequent in the NOA group (60.8% vs. 22.6%, p = 0.001). FSH levels were significantly higher [18.9 IU/L (5.9-27.0) vs. 15.3 IU/L (9.0-46.5), p = 0.001] and the majority of inhibin B levels measured were found mostly undetectable in the NOA group as compared to EOS/CS group (31.1% vs. 10.7%, p = 0.0004). Moreover, we found no significant differences in the respect to the fertilization rates (48.9% and 43.3%, p = 0.43), implantation rates (17.4% and 15.9%, p = 0.77), and percentage of top quality embryo (22.4% and 20.4%, p = 0.73) between the two groups. The clinical pregnancy rates per embryo transferred were comparable in both groups (28.3% and 27.4%, p = 0.89). In this study, we showed for the first time a different andrological phenotype between EOS/CS and NOA groups. Indeed, cryptorchidism was significantly more frequent with more severe endocrine parameters found in the NOA group. These results reflect a more profound alteration in spermatogenesis in NOA patients. However, there was no difference in ICSI outcomes between NOA and EOS

  8. Sleep phenotyping in a mouse model of extreme trait anxiety.

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    Vladimira Jakubcakova

    Full Text Available BACKGROUND: There is accumulating evidence that anxiety impairs sleep. However, due to high sleep variability in anxiety disorders, it has been difficult to state particular changes in sleep parameters caused by anxiety. Sleep profiling in an animal model with extremely high vs. low levels of trait anxiety might serve to further define sleep patterns associated with this psychopathology. METHODOLOGY/PRINCIPAL FINDINGS: Sleep-wake behavior in mouse lines with high (HAB, low (LAB and normal (NAB anxiety-related behaviors was monitored for 24 h during baseline and recovery after 6 h sleep deprivation (SD. The amounts of each vigilance state, sleep architecture, and EEG spectral variations were compared between the mouse lines. In comparison to NAB mice, HAB mice slept more and exhibited consistently increased delta power during non-rapid eye movement (NREM sleep. Their sleep patterns were characterized by heavy fragmentation, reduced maintenance of wakefulness, and frequent intrusions of rapid eye movement (REM sleep. In contrast, LAB mice showed a robust sleep-wake rhythm with remarkably prolonged sleep latency and a long, persistent period of wakefulness. In addition, the accumulation of delta power after SD was impaired in the LAB line, as compared to HAB mice. CONCLUSIONS/SIGNIFICANCE: Sleep-wake patterns were significantly different between HAB and LAB mice, indicating that the genetic predisposition to extremes in trait anxiety leaves a biological scar on sleep quality. The enhanced sleep demand observed in HAB mice, with a strong drive toward REM sleep, may resemble a unique phenotype reflecting not only elevated anxiety but also a depression-like attribute.

  9. Novel SCN9A mutations underlying extreme pain phenotypes: unexpected electrophysiological and clinical phenotype correlations.

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    Emery, Edward C; Habib, Abdella M; Cox, James J; Nicholas, Adeline K; Gribble, Fiona M; Woods, C Geoffrey; Reimann, Frank

    2015-05-20

    The importance of NaV1.7 (encoded by SCN9A) in the regulation of pain sensing is exemplified by the heterogeneity of clinical phenotypes associated with its mutation. Gain-of-function mutations are typically pain-causing and have been associated with inherited erythromelalgia (IEM) and paroxysmal extreme pain disorder (PEPD). IEM is usually caused by enhanced NaV1.7 channel activation, whereas mutations that alter steady-state fast inactivation often lead to PEPD. In contrast, nonfunctional mutations in SCN9A are known to underlie congenital insensitivity to pain (CIP). Although well documented, the correlation between SCN9A genotypes and clinical phenotypes is still unclear. Here we report three families with novel SCN9A mutations. In a multiaffected dominant family with IEM, we found the heterozygous change L245 V. Electrophysiological characterization showed that this mutation did not affect channel activation but instead resulted in incomplete fast inactivation and a small hyperpolarizing shift in steady-state slow inactivation, characteristics more commonly associated with PEPD. In two compound heterozygous CIP patients, we found mutations that still retained functionality of the channels, with two C-terminal mutations (W1775R and L1831X) exhibiting a depolarizing shift in channel activation. Two mutations (A1236E and L1831X) resulted in a hyperpolarizing shift in steady-state fast inactivation. To our knowledge, these are the first descriptions of mutations with some retained channel function causing CIP. This study emphasizes the complex genotype-phenotype correlations that exist for SCN9A and highlights the C-terminal cytoplasmic region of NaV1.7 as a critical region for channel function, potentially facilitating analgesic drug development studies.

  10. Sample Return Systems for Extreme Environments Project

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    National Aeronautics and Space Administration — Since the Apollo era, sample return missions have been primarily limited to asteroid sampling. More comprehensive sampling could yield critical information on the...

  11. Extreme Environment Sampling System Deployment Mechanism Project

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    National Aeronautics and Space Administration — Future Venus or Comet mission architectures may feature robotic sampling systems comprised of a Sampling Tool and Deployment Mechanism. Since 2005, Honeybee has been...

  12. Sample Return Systems for Extreme Environments Project

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    National Aeronautics and Space Administration — In Phase I we were able to demonstrate that sample return missions utilizing high velocity penetrators (0.1- 1 km/s) could provide substantial new capabilities for...

  13. Alternative Sampling Strategies for Cytochrome P450 Phenotyping.

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    De Kesel, Pieter M M; Lambert, Willy E; Stove, Christophe P

    2016-02-01

    Interindividual variability in the expression and function of drug metabolizing cytochrome P (CYP) 450 enzymes, determined by a combination of genetic, non-genetic and environmental parameters, is a major source of variable drug response. Phenotyping by administration of a selective enzyme substrate, followed by the determination of a specific phenotyping metric, is an appropriate approach to assess the in vivo activity of CYP450 enzymes as it takes into account all influencing factors. A phenotyping protocol should be as simple and convenient as possible. Typically, phenotyping metrics are determined in traditional matrices, such as blood, plasma or urine. Several sampling strategies have been proposed as an alternative for these traditional sampling techniques. In this review, we provide a comprehensive overview of available methods using dried blood spots (DBS), hair, oral fluid, exhaled breath and sweat for in vivo CYP450 phenotyping. We discuss the relation between phenotyping metrics measured in these samples and those in conventional matrices, along with the advantages and limitations of the alternative sampling techniques. Reliable phenotyping procedures for several clinically relevant CYP450 enzymes, including CYP1A2, CYP2C19 and CYP2D6, are currently available for oral fluid, breath or DBS, while additional studies are needed for other CYP450 isoforms, such as CYP3A4. The role of hair analysis for this purpose remains to be established. Being non- or minimally invasive, these sampling strategies provide convenient and patient-friendly alternatives for classical phenotyping procedures, which may contribute to the implementation of CYP450 phenotyping in clinical practice.

  14. Phenotypic extremes in liveborn monozygotic twins with mosaic Edwards syndrome.

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    Bussmann, Neidin; Cunningham, Katie; Green, Andrew; Ryan, C Anthony

    2015-11-11

    Mosaic trisomy 18 (Edwards syndrome) in monozygotic diamniotic liveborn twins is rare. We describe such a case involving preterm male infants. Although both infants had a low percentage of trisomy 18 cells in peripheral blood leucocytes, their varied phenotypic presentation of mosaic trisomy 18 resulted in one twin surviving, with the other twin's demise at 1 month of age. Despite the presence of trisomy 18 in peripheral leucocytes, further analysis of a buccal smear and skin biopsy of the surviving twin did not show evidence of trisomy 18. Establishing such diagnoses in a timely manner is imperative for the child, parents and clinicians. The clinical course of these twins reflects the unpredictable prognosis associated with the diagnosis of mosaic trisomy 18, and emphasises the challenges that can be encountered when counselling parents.

  15. Extreme phenotypic plasticity in metabolic physiology of Antarctic Demosponges

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    Simon Anthony Morley

    2016-01-01

    Full Text Available Seasonal measurements of the metabolic physiology of four Antarctic demosponges and their associated assemblages, maintained in a flow through aquarium facility, demonstrated one of the largest differences in seasonal strategies between species and their associated sponge communities. The sponge oxygen consumption measured here exhibited both the lowest and highest seasonal changes for any Antarctic species; metabolic rates varied from a 25% decrease to a 5.8 fold increase from winter to summer, a range which was greater than all 17 Antarctic marine species (encompassing 8 phyla previously investigated and amongst the highest recorded for any marine environment. The differences in nitrogen excretion, metabolic substrate utilisation and tissue composition between species were, overall, greater than seasonal changes. The largest seasonal difference in tissue composition was an increase in CHN (Carbon, Hydrogen and Nitrogen content in Homaxinella balfourensis, a pioneer species in ice-scour regions, which changed growth form to a twig-like morph in winter. The considerable flexibility in seasonal and metabolic physiology across the Demospongiae likely enables these species to respond to rapid environmental change such as ice-scour, reductions in sea ice cover and ice-shelf collapse in the Polar Regions, shifting the paradigm that polar sponges always live life in the slow lane. Great phenotypic plasticity in physiology has been linked to differences in symbiotic community composition, and this is likely to be a key factor in the global success of sponges in all marine environments and their dominant role in many climax communities.

  16. Power Analysis and Sample Size Determination in Metabolic Phenotyping.

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    Blaise, Benjamin J; Correia, Gonçalo; Tin, Adrienne; Young, J Hunter; Vergnaud, Anne-Claire; Lewis, Matthew; Pearce, Jake T M; Elliott, Paul; Nicholson, Jeremy K; Holmes, Elaine; Ebbels, Timothy M D

    2016-05-17

    Estimation of statistical power and sample size is a key aspect of experimental design. However, in metabolic phenotyping, there is currently no accepted approach for these tasks, in large part due to the unknown nature of the expected effect. In such hypothesis free science, neither the number or class of important analytes nor the effect size are known a priori. We introduce a new approach, based on multivariate simulation, which deals effectively with the highly correlated structure and high-dimensionality of metabolic phenotyping data. First, a large data set is simulated based on the characteristics of a pilot study investigating a given biomedical issue. An effect of a given size, corresponding either to a discrete (classification) or continuous (regression) outcome is then added. Different sample sizes are modeled by randomly selecting data sets of various sizes from the simulated data. We investigate different methods for effect detection, including univariate and multivariate techniques. Our framework allows us to investigate the complex relationship between sample size, power, and effect size for real multivariate data sets. For instance, we demonstrate for an example pilot data set that certain features achieve a power of 0.8 for a sample size of 20 samples or that a cross-validated predictivity QY(2) of 0.8 is reached with an effect size of 0.2 and 200 samples. We exemplify the approach for both nuclear magnetic resonance and liquid chromatography-mass spectrometry data from humans and the model organism C. elegans.

  17. The Estimation of Probability of Extreme Events for Small Samples

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    Pisarenko, V. F.; Rodkin, M. V.

    2017-02-01

    The most general approach to the study of rare extreme events is based on the extreme value theory. The fundamental General Extreme Value Distribution lies in the basis of this theory serving as the limit distribution for normalized maxima. It depends on three parameters. Usually the method of maximum likelihood (ML) is used for the estimation that possesses well-known optimal asymptotic properties. However, this method works efficiently only when sample size is large enough ( 200-500), whereas in many applications the sample size does not exceed 50-100. For such sizes, the advantage of the ML method in efficiency is not guaranteed. We have found that for this situation the method of statistical moments (SM) works more efficiently over other methods. The details of the estimation for small samples are studied. The SM is applied to the study of extreme earthquakes in three large virtual seismic zones, representing the regime of seismicity in subduction zones, intracontinental regime of seismicity, and the regime in mid-ocean ridge zones. The 68%-confidence domains for pairs of parameter (ξ, σ) and (σ, μ) are derived.

  18. Extremely Isolated Galaxies I. Sample and Simulation Analysis

    CERN Document Server

    Spector, O

    2016-01-01

    We have selected a sample of extremely isolated galaxies (EIGs) from the local Universe ($\\mbox{z} < 0.024$), using a simple isolation criterion: having no known neighbours closer than $300\\,{\\rm km\\,s}^{-1}$ ($3\\,h^{-1}\\,\\mbox{Mpc}$) in the three-dimensional redshift space $(\\alpha,\\delta,\\mbox{z})$. The sample is unique both in its level of isolation and in the fact that it utilizes HI redshifts from the Arecibo Legacy Fast ALFA survey (ALFALFA). We analysed the EIG sample using cosmological simulations and found that it contains extremely isolated galaxies with normal mass haloes which have evolved gradually with little or no "major events" (major mergers, or major mass-loss events) in the last $3\\,\\mbox{Gyr}$. The fraction of EIGs which deviate from this definition (false positives) is 5%-10%. For the general population of dark matter haloes it was further found that the mass accretion (relative to the current halo mass) is affected by the halo environment mainly through strong interactions with its ne...

  19. An importance sampling algorithm for estimating extremes of perpetuity sequences

    DEFF Research Database (Denmark)

    Collamore, Jeffrey F.

    2012-01-01

    In a wide class of problems in insurance and financial mathematics, it is of interest to study the extremal events of a perpetuity sequence. This paper addresses the problem of numerically evaluating these rare event probabilities. Specifically, an importance sampling algorithm is described which...... is efficient in the sense that it exhibits bounded relative error, and which is optimal in an appropriate asymptotic sense. The main idea of the algorithm is to use a ``dual" change of measure, which is employed to an associated Markov chain over a randomly-stopped time interval. The algorithm also makes use...

  20. Whole exome sequencing of extreme age-related macular degeneration phenotypes

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    Sardell, Rebecca J.; Bailey, Jessica N Cooke; Courtenay, Monique D.; Whitehead, Patrice; Laux, Reneé A.; Adams, Larry D.; Fortun, Jorge A.; Brantley, Milam A.; Kovach, Jaclyn L.; Schwartz, Stephen G.; Agarwal, Anita; Scott, William K.; Haines, Jonathan L.

    2016-01-01

    Purpose Demographic, environmental, and genetic risk factors for age-related macular degeneration (AMD) have been identified; however, a substantial portion of the variance in AMD disease risk and heritability remains unexplained. To identify AMD risk variants and generate hypotheses for future studies, we performed whole exome sequencing for 75 individuals whose phenotype was not well predicted by their genotype at known risk loci. We hypothesized that these phenotypically extreme individuals were more likely to carry rare risk or protective variants with large effect sizes. Methods A genetic risk score was calculated in a case–control set of 864 individuals (467 AMD cases, 397 controls) based on 19 common (≥1% minor allele frequency, MAF) single nucleotide variants previously associated with the risk of advanced AMD in a large meta-analysis of advanced cases and controls. We then selected for sequencing 39 cases with bilateral choroidal neovascularization with the lowest genetic risk scores to detect risk variants and 36 unaffected controls with the highest genetic risk score to detect protective variants. After minimizing the influence of 19 common genetic risk loci on case-control status, we targeted single variants of large effect and the aggregate effect of weaker variants within genes and pathways. Single variant tests were conducted on all variants, while gene-based and pathway analyses were conducted on three subsets of data: 1) rare (≤1% MAF in the European population) stop, splice, or damaging missense variants, 2) all rare variants, and 3) all variants. All analyses controlled for the effects of age and sex. Results No variant, gene, or pathway outside regions known to be associated with risk for advanced AMD reached genome-wide significance. However, we identified several variants with substantial differences in allele frequency between cases and controls with strong additive effects on affection status after controlling for age and sex

  1. Liver transcriptome profile in pigs with extreme phenotypes of intramuscular fatty acid composition

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    Ramayo-Caldas Yuliaxis

    2012-10-01

    Full Text Available Abstract Background New advances in high-throughput technologies have allowed for the massive analysis of genomic data, providing new opportunities for the characterization of the transcriptome architectures. Recent studies in pigs have employed RNA-Seq to explore the transcriptome of different tissues in a reduced number of animals. The main goal of this study was the identification of differentially-expressed genes in the liver of Iberian x Landrace crossbred pigs showing extreme phenotypes for intramuscular fatty acid composition using RNA-Seq. Results The liver transcriptomes of two female groups (H and L with phenotypically extreme intramuscular fatty acid composition were sequenced using RNA-Seq. A total of 146 and 180 unannotated protein-coding genes were identified in intergenic regions for the L and H groups, respectively. In addition, a range of 5.8 to 7.3% of repetitive elements was found, with SINEs being the most abundant elements. The expression in liver of 186 (L and 270 (H lncRNAs was also detected. The higher reproducibility of the RNA-Seq data was validated by RT-qPCR and porcine expression microarrays, therefore showing a strong correlation between RT-qPCR and RNA-Seq data (ranking from 0.79 to 0.96, as well as between microarrays and RNA-Seq (r=0.72. A differential expression analysis between H and L animals identified 55 genes differentially-expressed between groups. Pathways analysis revealed that these genes belong to biological functions, canonical pathways and three gene networks related to lipid and fatty acid metabolism. In concordance with the phenotypic classification, the pathways analysis inferred that linolenic and arachidonic acids metabolism was altered between extreme individuals. In addition, a connection was observed among the top three networks, hence suggesting that these genes are interconnected and play an important role in lipid and fatty acid metabolism. Conclusions In the present study RNA-Seq was used

  2. Antarctic climate change: extreme events disrupt plastic phenotypic response in Adelie penguins.

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    Amélie Lescroël

    Full Text Available In the context of predicted alteration of sea ice cover and increased frequency of extreme events, it is especially timely to investigate plasticity within Antarctic species responding to a key environmental aspect of their ecology: sea ice variability. Using 13 years of longitudinal data, we investigated the effect of sea ice concentration (SIC on the foraging efficiency of Adélie penguins (Pygoscelis adeliae breeding in the Ross Sea. A 'natural experiment' brought by the exceptional presence of giant icebergs during 5 consecutive years provided unprecedented habitat variation for testing the effects of extreme events on the relationship between SIC and foraging efficiency in this sea-ice dependent species. Significant levels of phenotypic plasticity were evident in response to changes in SIC in normal environmental conditions. Maximum foraging efficiency occurred at relatively low SIC, peaking at 6.1% and decreasing with higher SIC. The 'natural experiment' uncoupled efficiency levels from SIC variations. Our study suggests that lower summer SIC than currently observed would benefit the foraging performance of Adélie penguins in their southernmost breeding area. Importantly, it also provides evidence that extreme climatic events can disrupt response plasticity in a wild seabird population. This questions the predictive power of relationships built on past observations, when not only the average climatic conditions are changing but the frequency of extreme climatic anomalies is also on the rise.

  3. Antarctic climate change: extreme events disrupt plastic phenotypic response in Adélie penguins.

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    Lescroël, Amélie; Ballard, Grant; Grémillet, David; Authier, Matthieu; Ainley, David G

    2014-01-01

    In the context of predicted alteration of sea ice cover and increased frequency of extreme events, it is especially timely to investigate plasticity within Antarctic species responding to a key environmental aspect of their ecology: sea ice variability. Using 13 years of longitudinal data, we investigated the effect of sea ice concentration (SIC) on the foraging efficiency of Adélie penguins (Pygoscelis adeliae) breeding in the Ross Sea. A 'natural experiment' brought by the exceptional presence of giant icebergs during 5 consecutive years provided unprecedented habitat variation for testing the effects of extreme events on the relationship between SIC and foraging efficiency in this sea-ice dependent species. Significant levels of phenotypic plasticity were evident in response to changes in SIC in normal environmental conditions. Maximum foraging efficiency occurred at relatively low SIC, peaking at 6.1% and decreasing with higher SIC. The 'natural experiment' uncoupled efficiency levels from SIC variations. Our study suggests that lower summer SIC than currently observed would benefit the foraging performance of Adélie penguins in their southernmost breeding area. Importantly, it also provides evidence that extreme climatic events can disrupt response plasticity in a wild seabird population. This questions the predictive power of relationships built on past observations, when not only the average climatic conditions are changing but the frequency of extreme climatic anomalies is also on the rise.

  4. Whole-genome resequencing of extreme phenotypes in collared flycatchers highlights the difficulty of detecting quantitative trait loci in natural populations.

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    Kardos, Marty; Husby, Arild; McFarlane, S Eryn; Qvarnström, Anna; Ellegren, Hans

    2016-05-01

    Dissecting the genetic basis of phenotypic variation in natural populations is a long-standing goal in evolutionary biology. One open question is whether quantitative traits are determined only by large numbers of genes with small effects, or whether variation also exists in large-effect loci. We conducted genomewide association analyses of forehead patch size (a sexually selected trait) on 81 whole-genome-resequenced male collared flycatchers with extreme phenotypes, and on 415 males sampled independent of patch size and genotyped with a 50K SNP chip. No SNPs were genomewide statistically significantly associated with patch size. Simulation-based power analyses suggest that the power to detect large-effect loci responsible for 10% of phenotypic variance was 0.8 for resequencing of extreme phenotypes (N = 243), but power remained 0.8 when analysing 415 randomly sampled phenotypes. However, power of the 50K SNP chip to detect large-effect loci was nearly 0.8 in simulations with a small effective population size of 1500. These results suggest that reliably detecting large-effect trait loci in large natural populations will often require thousands of individuals and near complete sampling of the genome. Encouragingly, far fewer individuals and loci will often be sufficient to reliably detect large-effect loci in small populations with widespread strong linkage disequilibrium.

  5. Fast temperature spectrometer for samples under extreme conditions.

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    Zhang, Dongzhou; Jackson, Jennifer M; Zhao, Jiyong; Sturhahn, Wolfgang; Alp, E Ercan; Toellner, Thomas S; Hu, Michael Y

    2015-01-01

    We have developed a multi-wavelength Fast Temperature Readout (FasTeR) spectrometer to capture a sample's transient temperature fluctuations, and reduce uncertainties in melting temperature determination. Without sacrificing accuracy, FasTeR features a fast readout rate (about 100 Hz), high sensitivity, large dynamic range, and a well-constrained focus. Complimenting a charge-coupled device spectrometer, FasTeR consists of an array of photomultiplier tubes and optical dichroic filters. The temperatures determined by FasTeR outside of the vicinity of melting are, generally, in good agreement with results from the charge-coupled device spectrometer. Near melting, FasTeR is capable of capturing transient temperature fluctuations, at least on the order of 300 K/s. A software tool, SIMFaster, is described and has been developed to simulate FasTeR and assess design configurations. FasTeR is especially suitable for temperature determinations that utilize ultra-fast techniques under extreme conditions. Working in parallel with the laser-heated diamond-anvil cell, synchrotron Mössbauer spectroscopy, and X-ray diffraction, we have applied the FasTeR spectrometer to measure the melting temperature of (57)Fe0.9Ni0.1 at high pressure.

  6. Extreme phenotypic variation in Cetraria aculeata (lichenized Ascomycota): adaptation or incidental modification?

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    Pérez-Ortega, Sergio; Fernández-Mendoza, Fernando; Raggio, José; Vivas, Mercedes; Ascaso, Carmen; Sancho, Leopoldo G.; Printzen, Christian; de los Ríos, Asunción

    2012-01-01

    Background and Aims Phenotypic variability is a successful strategy in lichens for colonizing different habitats. Vagrancy has been reported as a specific adaptation for lichens living in steppe habitats around the world. Among the facultatively vagrant species, the cosmopolitan Cetraria aculeata apparently forms extremely modified vagrant thalli in steppe habitats of Central Spain. The aim of this study was to investigate whether these changes are phenotypic plasticity (a single genotype producing different phenotypes), by characterizing the anatomical and ultrastructural changes observed in vagrant morphs, and measuring differences in ecophysiological performance. Methods Specimens of vagrant and attached populations of C. aculeata were collected on the steppes of Central Spain. The fungal internal transcribed spacer (ITS), glyceraldehyde-3-phosphate dehydrogenase (GPD) and the large sub-unit of the mitochondrial ribosomal DNA (mtLSUm), and the algal ITS and actin were studied within a population genetics framework. Semi-thin and ultrathin sections were analysed by means of optical, scanning electron and transmission electron microscopy. Gas exchange and chlorophyll fluorescence were used to compare the physiological performance of both morphs. Key Results and Conclusions Vagrant and attached morphs share multilocus haplotypes which may indicate that they belong to the same species in spite of their completely different anatomy. However, differentiation tests suggested that vagrant specimens do not represent a random sub-set of the surrounding population. The morphological differences were related to anatomical and ultrastructural differences. Large intercalary growth rates of thalli after the loss of the basal–apical thallus polarity may be the cause of the increased growth shown by vagrant specimens. The anatomical and morphological changes lead to greater duration of ecophysiological activity in vagrant specimens. Although the anatomical and physiological

  7. Transcriptional control of anthocyanin biosynthetic genes in extreme phenotypes for berry pigmentation of naturally occurring grapevines

    Directory of Open Access Journals (Sweden)

    Castellarin Simone D

    2007-08-01

    Full Text Available Abstract Background Fruit coloration of red-skinned grapevines is mainly due to anthocyanin pigments. We analysed a panel of nine cultivars that included extreme phenotypes for berry colour, ranging from green (absence of anthocyanins to red, purple, violet and blue. Expression of six genes of the anthocyanin pathway coding for flavanone-hydroxylase (F3H, flavonoid 3'-hydroxylase (F3'H, flavonoid 3',5'-hydroxylase (F3'5'H, UDP-glucose:flavonoid-3-O-glucosyltransferase (UFGT, glutathione-S-transferase (GST, O-methyltransferase (OMT and four transcription factors (MybA, MybB, MybC, MybD was analysed by quantitative RT-PCR at four developmental stages from before the onset of ripening until full maturity and compared to anthocyanin metabolites. Results Total anthocyanin content at full maturity correlated well with the cumulative expression of F3H, UFGT and GST throughout ripening. Transcripts of the last two genes were absent in the green-skinned cultivar 'Sauvignonasse', also known as 'Tocai friulano', and were at least 10-fold less abundant in pale red cultivars, such as 'Pinot gris' and 'Gewürztraminer', compared to fully coloured cultivars. Predominance of tri-hydroxylated anthocyanins (delphinidin, petunidin and malvidin in cultivars bearing dark berries with violet and blue hue was associated with higher ratios of F3'5'H/F3'H transcription, compared to red-skinned cultivars. Higher levels of OMT transcripts were observed in berries of cultivars that accumulated methoxylated forms of anthocyanins more abundantly than non-methoxylated forms. Conclusion Colour variation of the grape berry conforms to a peculiar pattern of genotype-specific expression of the whole set of anthocyanin genes in a direct transcript-metabolite-phenotype relationship. Cumulative mRNA levels of the structural genes and their relative abundance throughout ripening explained per se the final phenotype for anthocyanin content, anthocyanin composition, colour intensity

  8. Combined use of phenotypic and genotypic information in sampling animalsfor genotyping in detection of quantitative trait loci

    DEFF Research Database (Denmark)

    Ansari-Mahyari, S; Berg, P

    2008-01-01

    Conventional selective genotyping which is using the extreme phenotypes (EP) was compared with alternative criteria to find the most informative animals for genotyping with respects to mapping quantitative trait loci (QTL). Alternative sampling strategies were based on minimizing the sampling error...... of the estimated QTL effect (MinERR) and maximizing likelihood ratio test (MaxLRT) using both phenotypic and genotypic information. In comparison, animals were randomly genotyped either within or across families. One hundred data sets were simulated each with 30 half-sib families and 120 daughters per family....... The strategies were compared in these datasets with respect to estimated effect and position of a QTL within a previously defined genomic region at genotyping 10, 20 or 30% of the animals. Combined linkage disequilibrium linkage analysis (LDLA) was applied in a variance component approach. Power to detect QTL...

  9. On bootstrap sample size in extreme value theory

    NARCIS (Netherlands)

    J.L. Geluk (Jaap); L.F.M. de Haan (Laurens)

    2002-01-01

    textabstractIt has been known for a long time that for bootstrapping the probability distribution of the maximum of a sample consistently, the bootstrap sample size needs to be of smaller order than the original sample size. See Jun Shao and Dongsheng Tu (1995), Ex. 3.9,p. 123. We show that the same

  10. Population-based resequencing of APOA1 in 10,330 individuals: spectrum of genetic variation, phenotype, and comparison with extreme phenotype approach.

    Science.gov (United States)

    Haase, Christiane L; Frikke-Schmidt, Ruth; Nordestgaard, Børge G; Tybjærg-Hansen, Anne

    2012-01-01

    Rare genetic variants, identified by in-detail resequencing of loci, may contribute to complex traits. We used the apolipoprotein A-I gene (APOA1), a major high-density lipoprotein (HDL) gene, and population-based resequencing to determine the spectrum of genetic variants, the phenotypic characteristics of these variants, and how these results compared with results based on resequencing only the extremes of the apolipoprotein A-I (apoA-I) distribution. First, we resequenced APOA1 in 10,330 population-based participants in the Copenhagen City Heart Study. The spectrum and distribution of genetic variants was determined as a function of the number of individuals resequenced. Second, apoA-I and HDL cholesterol phenotypes were determined for nonsynonymous (NS) and synonymous (S) variants and were validated in the Copenhagen General Population Study (n = 45,239). Third, observed phenotypes were compared with those predicted using an extreme phenotype approach based on the apoA-I distribution. Our results are as follows: First, population-based resequencing of APOA1 identified 40 variants of which only 7 (18%) had minor allele frequencies >1%, and most were exceedingly rare. Second, 0.27% of individuals in the general population were heterozygous for NS variants which were associated with substantial reductions in apoA-I (up to 39 mg/dL) and/or HDL cholesterol (up to 0.9 mmol/L) and, surprisingly, 0.41% were heterozygous for variants predisposing to amyloidosis. NS variants associated with a hazard ratio of 1.72 (1.09-2.70) for myocardial infarction (MI), largely driven by A164S, a variant not associated with apoA-I or HDL cholesterol levels. Third, using the extreme apoA-I phenotype approach, NS variants correctly predicted the apoA-I phenotype observed in the population-based resequencing. However, using the extreme approach, between 79% (screening 0-1(st) percentile) and 21% (screening 0-20(th) percentile) of all variants were not identified; among these were variants

  11. Extreme Samples on the Eysenck Personality Questionnaire Psychoticism Scale.

    Science.gov (United States)

    Loo, Robert; Shiomi, Kunio

    1983-01-01

    Examined the P scale of the Eysenck Personality Questionnaire in three samples of normal Canadian and Japanese students who obtained either very high or very low means on the P scale. Psychometric problems were identified in the sample with a low P mean. Recommended that the scale be renamed. (JAC)

  12. Differences in muscle transcriptome among pigs phenotypically extreme for fatty acid composition.

    Directory of Open Access Journals (Sweden)

    Anna Puig-Oliveras

    Full Text Available BACKGROUND: Besides having an impact on human health, the porcine muscle fatty acid profile determines meat quality and taste. The RNA-Seq technologies allowed us to explore the pig muscle transcriptome with an unprecedented detail. The aim of this study was to identify differentially-expressed genes between two groups of 6 sows belonging to an Iberian × Landrace backcross with extreme phenotypes according to FA profile. RESULTS: We sequenced the muscle transcriptome acquiring 787.5 M of 75 bp paired-end reads. About 85.1% of reads were mapped to the reference genome. Of the total reads, 79.1% were located in exons, 6.0% in introns and 14.9% in intergenic regions, indicating expressed regions not annotated in the reference genome. We identified a 34.5% of the intergenic regions as interspersed repetitive regions. We predicted a total of 2,372 putative proteins. Pathway analysis with 131 differentially-expressed genes revealed that the most statistically-significant metabolic pathways were related with lipid metabolism. Moreover, 18 of the differentially-expressed genes were located in genomic regions associated with IMF composition in an independent GWAS study in the same genetic background. Thus, our results indicate that the lipid metabolism of FAs is differently modulated when the FA composition in muscle differs. For instance, a high content of PUFA may reduce FA and glucose uptake resulting in an inhibition of the lipogenesis. These results are consistent with previous studies of our group analysing the liver and the adipose tissue transcriptomes providing a view of each of the main organs involved in lipid metabolism. CONCLUSIONS: The results obtained in the muscle transcriptome analysis increase the knowledge of the gene regulation of IMF deposition, FA profile and meat quality, in terms of taste and nutritional value. Besides, our results may be important in terms of human health.

  13. Differences in Muscle Transcriptome among Pigs Phenotypically Extreme for Fatty Acid Composition

    Science.gov (United States)

    Puig-Oliveras, Anna; Ramayo-Caldas, Yuliaxis; Corominas, Jordi; Estellé, Jordi; Pérez-Montarelo, Dafne; Hudson, Nicholas J.; Casellas, Joaquim; Folch, Josep M.; Ballester, Maria

    2014-01-01

    Background Besides having an impact on human health, the porcine muscle fatty acid profile determines meat quality and taste. The RNA-Seq technologies allowed us to explore the pig muscle transcriptome with an unprecedented detail. The aim of this study was to identify differentially-expressed genes between two groups of 6 sows belonging to an Iberian × Landrace backcross with extreme phenotypes according to FA profile. Results We sequenced the muscle transcriptome acquiring 787.5 M of 75 bp paired-end reads. About 85.1% of reads were mapped to the reference genome. Of the total reads, 79.1% were located in exons, 6.0% in introns and 14.9% in intergenic regions, indicating expressed regions not annotated in the reference genome. We identified a 34.5% of the intergenic regions as interspersed repetitive regions. We predicted a total of 2,372 putative proteins. Pathway analysis with 131 differentially-expressed genes revealed that the most statistically-significant metabolic pathways were related with lipid metabolism. Moreover, 18 of the differentially-expressed genes were located in genomic regions associated with IMF composition in an independent GWAS study in the same genetic background. Thus, our results indicate that the lipid metabolism of FAs is differently modulated when the FA composition in muscle differs. For instance, a high content of PUFA may reduce FA and glucose uptake resulting in an inhibition of the lipogenesis. These results are consistent with previous studies of our group analysing the liver and the adipose tissue transcriptomes providing a view of each of the main organs involved in lipid metabolism. Conclusions The results obtained in the muscle transcriptome analysis increase the knowledge of the gene regulation of IMF deposition, FA profile and meat quality, in terms of taste and nutritional value. Besides, our results may be important in terms of human health. PMID:24926690

  14. Extreme eigenvalues of sample covariance and correlation matrices

    DEFF Research Database (Denmark)

    Heiny, Johannes

    This thesis is concerned with asymptotic properties of the eigenvalues of high-dimensional sample covariance and correlation matrices under an infinite fourth moment of the entries. In the first part, we study the joint distributional convergence of the largest eigenvalues of the sample covariance...... of the problem at hand. We develop a theory for the point process of the normalized eigenvalues of the sample covariance matrix in the case where rows and columns of the data are linearly dependent. Based on the weak convergence of this point process we derive the limit laws of various functionals...... of the eigenvalues. In the second part, we show that the largest and smallest eigenvalues of a highdimensional sample correlation matrix possess almost sure non-random limits if the truncated variance of the entry distribution is “almost slowly varying”, a condition we describe via moment properties of self...

  15. Purifying Nucleic Acids from Samples of Extremely Low Biomass

    Science.gov (United States)

    La Duc, Myron; Osman, Shariff; Venkateswaran, Kasthuri

    2008-01-01

    A new method is able to circumvent the bias to which one commercial DNA extraction method falls prey with regard to the lysing of certain types of microbial cells, resulting in a truncated spectrum of microbial diversity. By prefacing the protocol with glass-bead-beating agitation (mechanically lysing a much more encompassing array of cell types and spores), the resulting microbial diversity detection is greatly enhanced. In preliminary studies, a commercially available automated DNA extraction method is effective at delivering total DNA yield, but only the non-hardy members of the bacterial bisque were represented in clone libraries, suggesting that this method was ineffective at lysing the hardier cell types. To circumvent such a bias in cells, yet another extraction method was devised. In this technique, samples are first subjected to a stringent bead-beating step, and then are processed via standard protocols. Prior to being loaded into extraction vials, samples are placed in micro-centrifuge bead tubes containing 50 micro-L of commercially produced lysis solution. After inverting several times, tubes are agitated at maximum speed for two minutes. Following agitation, tubes are centrifuged at 10,000 x g for one minute. At this time, the aqueous volumes are removed from the bead tubes and are loaded into extraction vials to be further processed via extraction regime. The new method couples two independent methodologies in such as way as to yield the highest concentration of PCR-amplifiable DNA with consistent and reproducible results and with the most accurate and encompassing report of species richness.

  16. A tongue for all seasons: extreme phenotypic flexibility in salamandrid newts.

    Science.gov (United States)

    Heiss, Egon; Handschuh, Stephan; Aerts, Peter; Van Wassenbergh, Sam

    2017-04-21

    Many organisms faced with seasonally fluctuating abiotic and biotic conditions respond by altering their phenotype to account for the demands of environmental changes. Here we discovered that newts, which switch seasonally between an aquatic and terrestrial lifestyle, grow a complex adhesive system on their tongue pad consisting of slender lingual papillae and mucus-producing cells to increase the efficiency of prey capture as they move from water onto land. The adhesive system is reduced again as newts switch back to their aquatic stage, where they use suction to capture prey. As suction performance is also enhanced seasonally by reshaping of the mouth due to the growth of labial lobes, our results show that newts are exceptional in exhibiting phenotypic flexibility in two alternating components (i.e. tongue pad and labial lobes) within a single functional system, and suggest that this form of phenotypic flexibility demands complex genetic regulation.

  17. Prognosis of complicated clinical course of varicose veins of lower extremities on the basis of analysis of phenotypic characteristics of connective tissue dysplasia

    OpenAIRE

    Tsarev О.А.; Anisimov A.Yu.; Zakharov N.N.

    2015-01-01

    Aim: to identify the phenotypic characteristics of indeterminate connective tissue dysplasia, which help to predict the progression of varicose veins of lower extremities and disease recurrence after surgery. Material and Methods. The long-term results of surgical treatment of 60 patients with varicose veins of lower extremities in a 5-year period after phlebectomy were analyzed. The phenotypic characteristics of indeterminate connective tissue dysplasia were researched. 24 patients had recur...

  18. The Structure of The Extended Psychosis Phenotype in Early Adolescence-A Cross-sample Replication

    NARCIS (Netherlands)

    Wigman, Johanna T. W.; Vollebergh, Wilma A. M.; Raaijmakers, Quinten A. W.; Iedema, Jurjen; van Dorsselaer, Saskia; Ormel, Johan; Verhulst, Frank C.; van Os, Jim

    2011-01-01

    The extended psychosis phenotype, or the expression of nonclinical positive psychotic experiences, is already prevalent in adolescence and has a dose-response risk relationship with later psychotic disorder. In 2 large adolescent general population samples (n = 5422 and n = 2230), prevalence and str

  19. The Structure of The Extended Psychosis Phenotype in Early Adolescence-A Cross-sample Replication

    NARCIS (Netherlands)

    Wigman, Johanna T. W.; Vollebergh, Wilma A. M.; Raaijmakers, Quinten A. W.; Iedema, Jurjen; van Dorsselaer, Saskia; Ormel, Johan; Verhulst, Frank C.; van Os, Jim

    The extended psychosis phenotype, or the expression of nonclinical positive psychotic experiences, is already prevalent in adolescence and has a dose-response risk relationship with later psychotic disorder. In 2 large adolescent general population samples (n = 5422 and n = 2230), prevalence and

  20. SAIL--a software system for sample and phenotype availability across biobanks and cohorts.

    Science.gov (United States)

    Gostev, Mikhail; Fernandez-Banet, Julio; Rung, Johan; Dietrich, Joern; Prokopenko, Inga; Ripatti, Samuli; McCarthy, Mark I; Brazma, Alvis; Krestyaninova, Maria

    2011-02-15

    The Sample avAILability system-SAIL-is a web based application for searching, browsing and annotating biological sample collections or biobank entries. By providing individual-level information on the availability of specific data types (phenotypes, genetic or genomic data) and samples within a collection, rather than the actual measurement data, resource integration can be facilitated. A flexible data structure enables the collection owners to provide descriptive information on their samples using existing or custom vocabularies. Users can query for the available samples by various parameters combining them via logical expressions. The system can be scaled to hold data from millions of samples with thousands of variables. SAIL is available under Aferro-GPL open source license: https://github.com/sail.

  1. SAIL—a software system for sample and phenotype availability across biobanks and cohorts

    Science.gov (United States)

    Gostev, Mikhail; Fernandez-Banet, Julio; Rung, Johan; Dietrich, Joern; Prokopenko, Inga; Ripatti, Samuli; McCarthy, Mark I.; Brazma, Alvis; Krestyaninova, Maria

    2011-01-01

    Summary: The Sample avAILability system—SAIL—is a web based application for searching, browsing and annotating biological sample collections or biobank entries. By providing individual-level information on the availability of specific data types (phenotypes, genetic or genomic data) and samples within a collection, rather than the actual measurement data, resource integration can be facilitated. A flexible data structure enables the collection owners to provide descriptive information on their samples using existing or custom vocabularies. Users can query for the available samples by various parameters combining them via logical expressions. The system can be scaled to hold data from millions of samples with thousands of variables. Availability: SAIL is available under Aferro-GPL open source license: https://github.com/sail. Contact: gostev@ebi.ac.uk, support@simbioms.org Supplementary information: Supplementary data are available at Bioinformatics online and from http://www.simbioms.org. PMID:21169373

  2. Limit theory for the sample autocorrelations and extremes of a GARCH (1,1) process

    NARCIS (Netherlands)

    Mikosch, T; Starica, C

    2000-01-01

    The asymptotic theory for the sample autocorrelations and extremes of a GARCH(I, 1) process is provided. Special attention is given to the case when the sum of the ARCH and GARCH parameters is close to 1, that is, when one is close to an infinite Variance marginal distribution. This situation has be

  3. Genetic and pharmacogenomic data on smoking: the bigger sample size, the less reliable phenotype? A critical review.

    Science.gov (United States)

    Lazary, Judit; Dome, Peter; Faludi, Gabor

    2011-03-01

    Increasing amount of genetic data on nicotine dependence (ND) is available in the literature, sometimes extremely large population size is reported but the study design is not always consequent. Phenotypic measures can vary from a simple 6-item self-rating scale to breath CO or serum cotinine level test but in genetic investigations this is not sophisticated; moreover the population stratification is also usually ignored. In contrast, possibly because of the strict traditions of pharmacological investigations, pharmacogenomic studies on smoking cessation therapy use more reliable phenotypic measures with high quality design consequently involving fewer participants. In spite of the heavy epidemiological data on smoking in Hungary, genetic background of heavy smoking is still not studied in this population. In this review we sum up the most important, replicated results but we also provide some critical remarks about the methodological shortcomings of these studies. Keeping in mind the value of large scale population ND association studies we would also like to emphasize that the clinical implementation of studies with larger samples but with weaker methodology and statistical analyses is limited. Similar to many other psychiatric disorders, ND is a multifactorial condition, therefore the measure of genetic effects requires a more complex study design.

  4. The Structure of The Extended Psychosis Phenotype in Early Adolescence—A Cross-sample Replication

    Science.gov (United States)

    Wigman, Johanna T. W.; Vollebergh, Wilma A. M.; Raaijmakers, Quinten A. W.; Iedema, Jurjen; van Dorsselaer, Saskia; Ormel, Johan; Verhulst, Frank C.; van Os, Jim

    2011-01-01

    The extended psychosis phenotype, or the expression of nonclinical positive psychotic experiences, is already prevalent in adolescence and has a dose-response risk relationship with later psychotic disorder. In 2 large adolescent general population samples (n = 5422 and n = 2230), prevalence and structure of the extended psychosis phenotype was investigated. Positive psychotic experiences, broadly defined, were reported by the majority of adolescents. Exploratory analysis with Structural Equation Modelling (Exploratory Factor Analysis followed by Confirmatory Factor Analysis [CFA]) in sample 1 suggested that psychotic experiences were best represented by 5 underlying dimensions; CFA in sample 2 provided a replication of this model. Dimensions were labeled Hallucinations, Delusions, Paranoia, Grandiosity, and Paranormal beliefs. Prevalences differed strongly, Hallucinations having the lowest and Paranoia having the highest rates. Girls reported more experiences on all dimensions, except Grandiosity, and from age 12 to 16 years rates increased. Hallucinations, Delusions, and Paranoia, but not Grandiosity and Paranormal beliefs, were associated with distress and general measures of psychopathology. Thus, only some of the dimensions of the extended psychosis phenotype in young people may represent a continuum with more severe psychopathology and predict later psychiatric disorder. PMID:20044595

  5. Prognosis of complicated clinical course of varicose veins of lower extremities on the basis of analysis of phenotypic characteristics of connective tissue dysplasia

    Directory of Open Access Journals (Sweden)

    Tsarev О.А.

    2015-12-01

    Full Text Available Aim: to identify the phenotypic characteristics of indeterminate connective tissue dysplasia, which help to predict the progression of varicose veins of lower extremities and disease recurrence after surgery. Material and Methods. The long-term results of surgical treatment of 60 patients with varicose veins of lower extremities in a 5-year period after phlebectomy were analyzed. The phenotypic characteristics of indeterminate connective tissue dysplasia were researched. 24 patients had recurrence of varicose veins of lower extremities associated with disease progression; 36 patients did not have recurrence of varicose veins of lower extremities. Results. All the patients demonstrated the signs of indeterminate connective tissue dysplasia, whereas their frequency was different. There were specified nine phenotypic characteristics of indeterminate connective tissue dysplasia, which were significantly more frequent for patients with recurrence of varicose vein disease of lower extremities: 1 postural abnormality, 2 flat foot, 3 skin pallor, 4 hyperextension of skin, 5 positive "wrist test", 6 positive "pollex test", 7 diastasis recti abdominis, 8 myopia, 9 hematomas which form quickly. Conclusion. The determined sum of phenotypic characters of indeterminate connective tissue dysplasia allows to predict progression of varicose vein disease of lower extremities, and offers new opportunities for improving the results of surgical treatment via developing special therapeutic measures aimed at improving lifestyle and dysplasia treatment.

  6. Small-sample likelihood inference in extreme-value regression models

    CERN Document Server

    Ferrari, Silvia L P

    2012-01-01

    We deal with a general class of extreme-value regression models introduced by Barreto- Souza and Vasconcellos (2011). Our goal is to derive an adjusted likelihood ratio statistic that is approximately distributed as \\c{hi}2 with a high degree of accuracy. Although the adjusted statistic requires more computational effort than its unadjusted counterpart, it is shown that the adjustment term has a simple compact form that can be easily implemented in standard statistical software. Further, we compare the finite sample performance of the three classical tests (likelihood ratio, Wald, and score), the gradient test that has been recently proposed by Terrell (2002), and the adjusted likelihood ratio test obtained in this paper. Our simulations favor the latter. Applications of our results are presented. Key words: Extreme-value regression; Gradient test; Gumbel distribution; Likelihood ratio test; Nonlinear models; Score test; Small-sample adjustments; Wald test.

  7. Gastric extremely well differentiated adenocarcinoma of gastric phenotype: as a gastric counterpart of adenoma malignum of the uterine cervix

    Directory of Open Access Journals (Sweden)

    Ae Lee Won

    2005-05-01

    Full Text Available Abstract Background Most of gastric adenocarcinoma can be simply diagnosed by microscopic examination of biopsy specimen. Rarely the structural and cellular atypia of tumor cells is too insignificant to discriminate from benign foveolar epithelium. Case presentation A 67-year-old male presented with a gastric mass incidentally found on the abdominal computed tomography (CT for routine medical examination. Gastric endoscopic examination revealed a huge fungating mass at the cardia and mucosal biopsy was performed. Microscopically the biopsy specimen showed proliferation of bland looking foveolar epithelia in the inflammatory background and diagnosed as foveolar epithelial hyperplasia. Because the clinical and endoscopic features of this patient were strongly suggestive of malignancy, the patient underwent radical total gastrectomy. The resected stomach revealed a huge fungating tumor at the cardia. The cut surface of the tumor was whitish gelatinous. Microscopically the tumor was sharply demarcated from surrounding mucosa and composed of very well formed glandular structures without significant cellular atypia, which invaded into the whole layer of the gastric wall. Tumor glands were occasionally complicated or dilated, and glandular lumina were filled with abundant mucin. Immunohistochemically the tumor cells revealed no overexpression of p53 protein but high Ki-67 labeling index. The tumor cells and intraluminal mucin were diffusely expressed MUC1 and MUC5AC and only focally expressed MUC2. On abdominal CT taken after 12 months demonstrated peritoneal carcinomatosis and multiple metastatic foci in the lung. Conclusion The clinicopathologic profiles of gastric extremely well differentiated adenocarcinoma of gastric phenotype include cardiac location, fungating gross type, very similar histology to foveolar epithelial hyperplasia, foveolar mucin phenotype, lack of p53 overexpressoin and high proliferative index.

  8. Multivariate genetic analysis of atopy phenotypes in a selected sample of twins

    DEFF Research Database (Denmark)

    Thomsen, SF; Ulrik, Charlotte Suppli; Kyvik, KO

    2006-01-01

    , airway hyper-responsiveness (AHR), and positive skin prick test (posSPT) in a sample of adult twins. METHODS: Within a sampling frame of 21,162 twin subjects, 20-49 years of age, from the Danish Twin Registry, a total of 575 subjects (256 intact pairs and 63 single twins), who either themselves and....../or their co-twins reported a history of asthma at a nationwide questionnaire survey, were clinically examined. Symptoms of wheeze and rhinitis were obtained by interview; airway responsiveness and skin test reactivity were measured using standard techniques. Correlations in liability between the different...... traits were estimated and latent factor models of genetic and environmental effects were fitted to the observed data using maximum likelihood methods. RESULTS: The various phenotypic correlations between wheeze, rhinitis, AHR and posSPT were all significant and ranged between 0.50 and 0.86. Traits...

  9. Manipulation of Samples at Extreme Temperatures for Fast in-situ Synchrotron Measurements

    Energy Technology Data Exchange (ETDEWEB)

    Weber, Richard [Materials Development, Inc., Arlington Heights, IL (United States)

    2016-04-22

    An aerodynamic sample levitation system with laser beam heating was integrated with the APS beamlines 6 ID-D, 11 ID-C and 20 BM-B. The new capability enables in-situ measurements of structure and XANES at extreme temperatures (300-3500 °C) and in conditions that completely avoid contact with container surfaces. In addition to maintaining a high degree of sample purity, the use of aerodynamic levitation enables deep supercooling and greatly enhanced glass formation from a wide variety of melts and liquids. Development and integration of controlled extreme sample environments and new measurement techniques is an important aspect of beamline operations and user support. Processing and solidifying liquids is a critical value-adding step in manufacturing semiconductors, optical materials, metals and in the operation of many energy conversion devices. Understanding structural evolution is of fundamental importance in condensed materials, geology, and biology. The new capability provides unique possibilities for materials research and helps to develop and maintain a competitive materials manufacturing and energy utilization industry. Test samples were used to demonstrate key features of the capability including experiments on hot crystalline materials, liquids at temperatures from about 500 to 3500 °C. The use of controlled atmospheres using redox gas mixtures enabled in-situ changes in the oxidation states of cations in melts. Significant innovations in this work were: (i) Use of redox gas mixtures to adjust the oxidation state of cations in-situ (ii) Operation with a fully enclosed system suitable for work with nuclear fuel materials (iii) Making high quality high energy in-situ x-ray diffraction measurements (iv) Making high quality in-situ XANES measurements (v) Publishing high impact results (vi) Developing independent funding for the research on nuclear materials This SBIR project work led to a commercial instrument product for the niche market of processing and

  10. [Phenotypic characterization and distribution of Yersinia in human and environmental samples].

    Science.gov (United States)

    Javier Castillo, F; Larraz, V; Asunción Lafarga, M; Navarro, M; Gómez-Lus, R

    1994-01-01

    The distribution of species and phenotypes of Yersinia isolated from environmental samples over an eight year period are compared to that of stool cultures obtained from patients of the same geographical location (Zaragoza, Spain). The number of samples and the percentage contamination were as follows: wastewater 362, 67.4%, freshwater 523, 13.4%, raw food 607, 24.5% and cooked food 1134, 7.9%. Yersinia enterocolitica was isolated significantly more frequently than other species in wastewater, while Yersinia intermedia was the most significant species found in freshwater. Significant differences between the percentage isolates of identified species in raw and cooked foods were not found. Fifteen different serogroups were identified from faeces, thirteen of which were also isolated from environmental samples. Three serogroups of Y. enterocolitica associated with human disease were isolated from the patients faeces as follows: O:3, 145 cases; O:8, 3 cases and O:5,27, 1 case. A low proportion were isolated from food: O:3, 3 strains; O:8, 2 strains and O:5,27, 5 strains. Only one isolate from serogroup O:3 was obtained from freshwater.

  11. Power and sample size calculations in the presence of phenotype errors for case/control genetic association studies

    Directory of Open Access Journals (Sweden)

    Finch Stephen J

    2005-04-01

    Full Text Available Abstract Background Phenotype error causes reduction in power to detect genetic association. We present a quantification of phenotype error, also known as diagnostic error, on power and sample size calculations for case-control genetic association studies between a marker locus and a disease phenotype. We consider the classic Pearson chi-square test for independence as our test of genetic association. To determine asymptotic power analytically, we compute the distribution's non-centrality parameter, which is a function of the case and control sample sizes, genotype frequencies, disease prevalence, and phenotype misclassification probabilities. We derive the non-centrality parameter in the presence of phenotype errors and equivalent formulas for misclassification cost (the percentage increase in minimum sample size needed to maintain constant asymptotic power at a fixed significance level for each percentage increase in a given misclassification parameter. We use a linear Taylor Series approximation for the cost of phenotype misclassification to determine lower bounds for the relative costs of misclassifying a true affected (respectively, unaffected as a control (respectively, case. Power is verified by computer simulation. Results Our major findings are that: (i the median absolute difference between analytic power with our method and simulation power was 0.001 and the absolute difference was no larger than 0.011; (ii as the disease prevalence approaches 0, the cost of misclassifying a unaffected as a case becomes infinitely large while the cost of misclassifying an affected as a control approaches 0. Conclusion Our work enables researchers to specifically quantify power loss and minimum sample size requirements in the presence of phenotype errors, thereby allowing for more realistic study design. For most diseases of current interest, verifying that cases are correctly classified is of paramount importance.

  12. The jigsaw puzzle of sequence phenotype inference: Piecing together Shannon entropy, importance sampling, and Empirical Bayes.

    Science.gov (United States)

    Shreif, Zeina; Striegel, Deborah A; Periwal, Vipul

    2015-09-07

    A nucleotide sequence 35 base pairs long can take 1,180,591,620,717,411,303,424 possible values. An example of systems biology datasets, protein binding microarrays, contain activity data from about 40,000 such sequences. The discrepancy between the number of possible configurations and the available activities is enormous. Thus, albeit that systems biology datasets are large in absolute terms, they oftentimes require methods developed for rare events due to the combinatorial increase in the number of possible configurations of biological systems. A plethora of techniques for handling large datasets, such as Empirical Bayes, or rare events, such as importance sampling, have been developed in the literature, but these cannot always be simultaneously utilized. Here we introduce a principled approach to Empirical Bayes based on importance sampling, information theory, and theoretical physics in the general context of sequence phenotype model induction. We present the analytical calculations that underlie our approach. We demonstrate the computational efficiency of the approach on concrete examples, and demonstrate its efficacy by applying the theory to publicly available protein binding microarray transcription factor datasets and to data on synthetic cAMP-regulated enhancer sequences. As further demonstrations, we find transcription factor binding motifs, predict the activity of new sequences and extract the locations of transcription factor binding sites. In summary, we present a novel method that is efficient (requiring minimal computational time and reasonable amounts of memory), has high predictive power that is comparable with that of models with hundreds of parameters, and has a limited number of optimized parameters, proportional to the sequence length.

  13. A Comparison of Three Self-Report Measures of the Broader Autism Phenotype in a Non-Clinical Sample

    Science.gov (United States)

    Ingersoll, Brooke; Hopwood, Christopher J.; Wainer, Allison; Donnellan, M. Brent

    2011-01-01

    Three self-report measures of the broader autism phenotype (BAP) were evaluated in terms of their internal consistency, distribution of scores, factor structure, and criterion-related validity in a non-clinical sample. All measures showed a continuous distribution. The SRS-A and BAPQ showed expected sex differences and were superior to the AQ in…

  14. Impact of REV-ERB alpha gene polymorphisms on obesity phenotypes in adult and adolescent samples.

    Science.gov (United States)

    Goumidi, L; Grechez, A; Dumont, J; Cottel, D; Kafatos, A; Moreno, L A; Molnar, D; Moschonis, G; Gottrand, F; Huybrechts, I; Dallongeville, J; Amouyel, P; Delaunay, F; Meirhaeghe, A

    2013-05-01

    REV-ERBα has been shown to regulate adipogenesis and lipid metabolism as well as to link the circadian timing system to whole body metabolic homeostasis. We thus tested whether polymorphisms in REV-ERBα could be associated with metabolic phenotypes in human population samples. We analyzed the associations between 5 REV-ERBα polymorphisms and anthropometric (body weight, body mass index (BMI), waist and hip circumferences), biochemical (plasma lipid, glucose and insulin levels) and clinical (systolic and diastolic blood pressure) variables in three population-based studies (MONICA Lille n=1155 adults, MONA LISA Lille n=1170 adults and HELENA n=1155 adolescents). We assessed in vitro, the potential influence of one REV-ERBα polymorphism in transient transfection assays using two different cell lines. We observed significant and consistent associations between the T minor allele of the REV-ERBα rs2071427 polymorphism (located in intron 1) and higher BMI (mean allele effect=+0.33 kg m(-2)) in the MONICA Lille (P=0.02), MONA LISA (P=0.02) and HELENA (P=0.03) studies. The odds ratios for obesity associated with this allele were 1.67 (1.00-2.79) (P=0.05) in MONICA Lille, 1.29 (1.01-1.65) (P=0.04) in MONA LISA Lille and the odds ratio for overweight was 1.48 (1.08-2.03) (P=0.01) in HELENA. In transfection experiments in human hepatocyte-derived cell lines, the REV-ERBα intron 1 directed the transcription of a luciferase reporter gene independently of the rs2071427 polymorphism. Our results suggest that the REV-ERBα rs2071427 polymorphism modulates body fat mass in both adult and young people.

  15. The cross-sectional GRAS sample: A comprehensive phenotypical data collection of schizophrenic patients

    Directory of Open Access Journals (Sweden)

    Oestereich Cornelia

    2010-11-01

    Full Text Available Abstract Background Schizophrenia is the collective term for an exclusively clinically diagnosed, heterogeneous group of mental disorders with still obscure biological roots. Based on the assumption that valuable information about relevant genetic and environmental disease mechanisms can be obtained by association studies on patient cohorts of ≥ 1000 patients, if performed on detailed clinical datasets and quantifiable biological readouts, we generated a new schizophrenia data base, the GRAS (Göttingen Research Association for Schizophrenia data collection. GRAS is the necessary ground to study genetic causes of the schizophrenic phenotype in a 'phenotype-based genetic association study' (PGAS. This approach is different from and complementary to the genome-wide association studies (GWAS on schizophrenia. Methods For this purpose, 1085 patients were recruited between 2005 and 2010 by an invariable team of traveling investigators in a cross-sectional field study that comprised 23 German psychiatric hospitals. Additionally, chart records and discharge letters of all patients were collected. Results The corresponding dataset extracted and presented in form of an overview here, comprises biographic information, disease history, medication including side effects, and results of comprehensive cross-sectional psychopathological, neuropsychological, and neurological examinations. With >3000 data points per schizophrenic subject, this data base of living patients, who are also accessible for follow-up studies, provides a wide-ranging and standardized phenotype characterization of as yet unprecedented detail. Conclusions The GRAS data base will serve as prerequisite for PGAS, a novel approach to better understanding 'the schizophrenias' through exploring the contribution of genetic variation to the schizophrenic phenotypes.

  16. Eating Problems at Age 6 Years in a Whole Population Sample of Extremely Preterm Children

    Science.gov (United States)

    Samara, Muthanna; Johnson, Samantha; Lamberts, Koen; Marlow, Neil; Wolke, Dieter

    2010-01-01

    Aim: The aim of this study was to investigate the prevalence of eating problems and their association with neurological and behavioural disabilities and growth among children born extremely preterm (EPC) at age 6 years. Method: A standard questionnaire about eating was completed by parents of 223 children (125 males [56.1%], 98 females [43.9%])…

  17. Mirror extreme BMI phenotypes associated with gene dosage at the chromosome 16p11.2 locus.

    Science.gov (United States)

    Jacquemont, Sébastien; Reymond, Alexandre; Zufferey, Flore; Harewood, Louise; Walters, Robin G; Kutalik, Zoltán; Martinet, Danielle; Shen, Yiping; Valsesia, Armand; Beckmann, Noam D; Thorleifsson, Gudmar; Belfiore, Marco; Bouquillon, Sonia; Campion, Dominique; de Leeuw, Nicole; de Vries, Bert B A; Esko, Tõnu; Fernandez, Bridget A; Fernández-Aranda, Fernando; Fernández-Real, José Manuel; Gratacòs, Mònica; Guilmatre, Audrey; Hoyer, Juliane; Jarvelin, Marjo-Riitta; Kooy, R Frank; Kurg, Ants; Le Caignec, Cédric; Männik, Katrin; Platt, Orah S; Sanlaville, Damien; Van Haelst, Mieke M; Villatoro Gomez, Sergi; Walha, Faida; Wu, Bai-Lin; Yu, Yongguo; Aboura, Azzedine; Addor, Marie-Claude; Alembik, Yves; Antonarakis, Stylianos E; Arveiler, Benoît; Barth, Magalie; Bednarek, Nathalie; Béna, Frédérique; Bergmann, Sven; Beri, Mylène; Bernardini, Laura; Blaumeiser, Bettina; Bonneau, Dominique; Bottani, Armand; Boute, Odile; Brunner, Han G; Cailley, Dorothée; Callier, Patrick; Chiesa, Jean; Chrast, Jacqueline; Coin, Lachlan; Coutton, Charles; Cuisset, Jean-Marie; Cuvellier, Jean-Christophe; David, Albert; de Freminville, Bénédicte; Delobel, Bruno; Delrue, Marie-Ange; Demeer, Bénédicte; Descamps, Dominique; Didelot, Gérard; Dieterich, Klaus; Disciglio, Vittoria; Doco-Fenzy, Martine; Drunat, Séverine; Duban-Bedu, Bénédicte; Dubourg, Christèle; El-Sayed Moustafa, Julia S; Elliott, Paul; Faas, Brigitte H W; Faivre, Laurence; Faudet, Anne; Fellmann, Florence; Ferrarini, Alessandra; Fisher, Richard; Flori, Elisabeth; Forer, Lukas; Gaillard, Dominique; Gerard, Marion; Gieger, Christian; Gimelli, Stefania; Gimelli, Giorgio; Grabe, Hans J; Guichet, Agnès; Guillin, Olivier; Hartikainen, Anna-Liisa; Heron, Délphine; Hippolyte, Loyse; Holder, Muriel; Homuth, Georg; Isidor, Bertrand; Jaillard, Sylvie; Jaros, Zdenek; Jiménez-Murcia, Susana; Helas, Géraldine Joly; Jonveaux, Philippe; Kaksonen, Satu; Keren, Boris; Kloss-Brandstätter, Anita; Knoers, Nine V A M; Koolen, David A; Kroisel, Peter M; Kronenberg, Florian; Labalme, Audrey; Landais, Emilie; Lapi, Elisabetta; Layet, Valérie; Legallic, Solenn; Leheup, Bruno; Leube, Barbara; Lewis, Suzanne; Lucas, Josette; MacDermot, Kay D; Magnusson, Pall; Marshall, Christian; Mathieu-Dramard, Michèle; McCarthy, Mark I; Meitinger, Thomas; Mencarelli, Maria Antonietta; Merla, Giuseppe; Moerman, Alexandre; Mooser, Vincent; Morice-Picard, Fanny; Mucciolo, Mafalda; Nauck, Matthias; Ndiaye, Ndeye Coumba; Nordgren, Ann; Pasquier, Laurent; Petit, Florence; Pfundt, Rolph; Plessis, Ghislaine; Rajcan-Separovic, Evica; Ramelli, Gian Paolo; Rauch, Anita; Ravazzolo, Roberto; Reis, Andre; Renieri, Alessandra; Richart, Cristobal; Ried, Janina S; Rieubland, Claudine; Roberts, Wendy; Roetzer, Katharina M; Rooryck, Caroline; Rossi, Massimiliano; Saemundsen, Evald; Satre, Véronique; Schurmann, Claudia; Sigurdsson, Engilbert; Stavropoulos, Dimitri J; Stefansson, Hreinn; Tengström, Carola; Thorsteinsdóttir, Unnur; Tinahones, Francisco J; Touraine, Renaud; Vallée, Louis; van Binsbergen, Ellen; Van der Aa, Nathalie; Vincent-Delorme, Catherine; Visvikis-Siest, Sophie; Vollenweider, Peter; Völzke, Henry; Vulto-van Silfhout, Anneke T; Waeber, Gérard; Wallgren-Pettersson, Carina; Witwicki, Robert M; Zwolinksi, Simon; Andrieux, Joris; Estivill, Xavier; Gusella, James F; Gustafsson, Omar; Metspalu, Andres; Scherer, Stephen W; Stefansson, Kari; Blakemore, Alexandra I F; Beckmann, Jacques S; Froguel, Philippe

    2011-08-31

    Both obesity and being underweight have been associated with increased mortality. Underweight, defined as a body mass index (BMI) ≤ 18.5 kg per m(2) in adults and ≤ -2 standard deviations from the mean in children, is the main sign of a series of heterogeneous clinical conditions including failure to thrive, feeding and eating disorder and/or anorexia nervosa. In contrast to obesity, few genetic variants underlying these clinical conditions have been reported. We previously showed that hemizygosity of a ∼600-kilobase (kb) region on the short arm of chromosome 16 causes a highly penetrant form of obesity that is often associated with hyperphagia and intellectual disabilities. Here we show that the corresponding reciprocal duplication is associated with being underweight. We identified 138 duplication carriers (including 132 novel cases and 108 unrelated carriers) from individuals clinically referred for developmental or intellectual disabilities (DD/ID) or psychiatric disorders, or recruited from population-based cohorts. These carriers show significantly reduced postnatal weight and BMI. Half of the boys younger than five years are underweight with a probable diagnosis of failure to thrive, whereas adult duplication carriers have an 8.3-fold increased risk of being clinically underweight. We observe a trend towards increased severity in males, as well as a depletion of male carriers among non-medically ascertained cases. These features are associated with an unusually high frequency of selective and restrictive eating behaviours and a significant reduction in head circumference. Each of the observed phenotypes is the converse of one reported in carriers of deletions at this locus. The phenotypes correlate with changes in transcript levels for genes mapping within the duplication but not in flanking regions. The reciprocal impact of these 16p11.2 copy-number variants indicates that severe obesity and being underweight could have mirror aetiologies

  18. The occurrence and experience of impulsivity and extreme positive mood in a non-clinical sample

    OpenAIRE

    Rawlings, Jodie

    2012-01-01

    The literature has struggled to reach an acceptable definition for the construct of impulsivity. Different models have variously suggested that the crux of the impulsivity construct lies in lack of planning, difficulties in concentration, failure of inhibition or attraction to sensation or immediate reward. More recently, research has suggested that impulsivity is increased in conditions of extreme affect, either positive or negative. The development of a novel measure of affective impulsivit...

  19. Sample environment for in situ synchrotron corrosion studies of materials in extreme environments

    Science.gov (United States)

    Elbakhshwan, Mohamed S.; Gill, Simerjeet K.; Motta, Arthur T.; Weidner, Randy; Anderson, Thomas; Ecker, Lynne E.

    2016-10-01

    A new in situ sample environment has been designed and developed to study the interfacial interactions of nuclear cladding alloys with high temperature steam. The sample environment is particularly optimized for synchrotron X-ray diffraction studies for in situ structural analysis. The sample environment is highly corrosion resistant and can be readily adapted for steam environments. The in situ sample environment design complies with G2 ASTM standards for studying corrosion in zirconium and its alloys and offers remote temperature and pressure monitoring during the in situ data collection. The use of the in situ sample environment is exemplified by monitoring the oxidation of metallic zirconium during exposure to steam at 350 °C. The in situ sample environment provides a powerful tool for fundamental understanding of corrosion mechanisms by elucidating the substoichiometric oxide phases formed during the early stages of corrosion, which can provide a better understanding of the oxidation process.

  20. SCN9A mutations in paroxysmal extreme pain disorder: allelic variants underlie distinct channel defects and phenotypes.

    Science.gov (United States)

    Fertleman, Caroline R; Baker, Mark D; Parker, Keith A; Moffatt, Sarah; Elmslie, Frances V; Abrahamsen, Bjarke; Ostman, Johan; Klugbauer, Norbert; Wood, John N; Gardiner, R Mark; Rees, Michele

    2006-12-07

    Paroxysmal extreme pain disorder (PEPD), previously known as familial rectal pain (FRP, or OMIM 167400), is an inherited condition characterized by paroxysms of rectal, ocular, or submandibular pain with flushing. A genome-wide linkage search followed by mutational analysis of the candidate gene SCN9A, which encodes hNa(v)1.7, identified eight missense mutations in 11 families and 2 sporadic cases. Functional analysis in vitro of three of these mutant Na(v)1.7 channels revealed a reduction in fast inactivation, leading to persistent sodium current. Other mutations in SCN9A associated with more negative activation thresholds are known to cause primary erythermalgia (PE). Carbamazepine, a drug that is effective in PEPD, but not PE, showed selective block of persistent current associated with PEPD mutants, but did not affect the negative activation threshold of a PE mutant. PEPD and PE are allelic variants with distinct underlying biophysical mechanisms and represent a separate class of peripheral neuronal sodium channelopathy.

  1. Multivariate genetic analysis of atopy phenotypes in a selected sample of twins

    DEFF Research Database (Denmark)

    Thomsen, SF; Ulrik, Charlotte Suppli; Kyvik, KO

    2006-01-01

    BACKGROUND: Atopic traits often co-occur and this can potentially be caused by common aetiological relationships between traits, i.e. a common genetic or a common environmental background. OBJECTIVE: To estimate to what extent the same genetic and environmental factors influence wheeze, rhinitis...... traits were estimated and latent factor models of genetic and environmental effects were fitted to the observed data using maximum likelihood methods. RESULTS: The various phenotypic correlations between wheeze, rhinitis, AHR and posSPT were all significant and ranged between 0.50 and 0.86. Traits...... that showed highest genetic correlations were wheeze-rhinitis (rho(A)=0.95), wheeze-AHR (rho(A)=0.85) and rhinitis-posSPT (rho(A)=0.92), whereas lower genetic correlations were observed for rhinitis-AHR (rho(A)=0.43) and AHR-posSPT (rho(A)=0.59). Traits with a high degree of environmental sharing were...

  2. A novel nuclear-encoded mitochondrial poly(A polymerase PAPD1 is a potential candidate gene for the extreme obesity related phenotypes in mammals

    Directory of Open Access Journals (Sweden)

    Qianjun Xiao, Xiao-Lin Wu, Jennifer J. Michal, Jerry J. Reeves, Jan R. Busboom, Gary H. Thorgaard, Zhihua Jiang

    2006-01-01

    Full Text Available People with obesity, especially extreme obesity, are at risk for many health problems. However, the responsible genes remain unknown in >95% of severe obesity cases. Our previous genome-wide scan of Wagyu x Limousin F2 cattle crosses with extreme phenotypes revealed a molecular marker significantly associated with intramuscular fat deposition. Characterization of this marker showed that it is orthologous to the human gene KIAA1462 located on HSA10p11.23, where a major quantitative trait locus for morbid obesity has been reported. The newly identified mitochondrial poly(A polymerase associated domain containing 1 (PAPD1 gene, which is located near this marker, is particularly interesting because the polymerase is required for the polyadenylation and stabilization of mammalian mitochondrial mRNAs. In the present study, both cDNA and genomic DNA sequences were annotated for the bovine PAPD1 gene and ten genetic markers were detected in the promoter and exon 1 region. Among seven markers assayed on ~ 250 Wagyu x Limousin F2 animals, two single nucleotide polymorphisms (SNPs in the promoter region were significantly associated with intramuscular fat (P<0.05. However, there was a significant interaction (P<0.05 between a third SNP, which causes an amino acid change in coding exon 1, and each of these two promoter SNPs on intramuscular fat deposition. In particular, the differences between double heterozygous animals at two polymorphic sites and the slim genotype animals exceeded 2.3 standard deviations for the trait in both cases. Our study provides evidence for a new mechanism – the involvement of compound heterosis in extreme obesity, which warrants further examination.

  3. Identification and mapping stripe rust resistance gene YrLM168a using extreme individuals and recessive phenotype class in a complicate genetic background.

    Science.gov (United States)

    Feng, Junyan; Chen, Guoyue; Wei, Yuming; Liu, Yaxi; Jiang, Qiantao; Li, Wei; Pu, Zhien; Lan, Xiujin; Dai, Shoufen; Zhang, Min; Zheng, Youliang

    2015-12-01

    The identification and characterization of resistance genes effective against stripe rust of wheat is beneficial for modern wheat breeding programs. Molecular markers to such genes facilitate their deployment. The variety Milan has resistance that is effective against the predominant stripe rust races in the Sichuan region. Two resistant and two susceptible F8 lines from a cross between Milan and the susceptible variety Chuannong 16 were used to investigate inheritance of the Milan resistance. Three F2 populations were developed from crosses between the resistant lines and their susceptible sibling lines (LM168a × LM168c, LM168c × LM168a, LM168b × LM168d) and used for genetic analysis and molecular mapping of the genes for resistance. The stripe rust resistance in LM168a and LM168b was conferred by a single dominant gene, temporarily designated as YrLM168a. Forty-five extreme susceptible plants from the F2 families of LM168d × LM168b were genotyped with 836 simple sequence repeat (SSR) markers to map YrLM168a. YrLM168a was mapped in chromosome 6BL. The nearest flanking markers Xwmc756 and Xbarc146 were 4.6 and 4.6 cM away from the gene at both sides, respectively. The amplification results of twenty extreme resistant (IT 0) and susceptible (IT 4) F2 plants of LM168c × LM168a and LM168a × LM168c with marker Xwmc756 further validated the mapping results. The study suggested that extreme individuals and recessive phenotype class can be successfully used for mapping genes, which should be efficient and reliable. In addition, the flanking markers near YrLM168a should be helpful in marker-assisted breeding.

  4. Mirror extreme BMI phenotypes associated with gene dosage at the chromosome 16p11.2 locus

    Science.gov (United States)

    Jacquemont, Sébastien; Reymond, Alexandre; Zufferey, Flore; Harewood, Louise; Walters, Robin G.; Kutalik, Zoltán; Martinet, Danielle; Shen, Yiping; Valsesia, Armand; Beckmann, Noam D.; Thorleifsson, Gudmar; Belfiore, Marco; Bouquillon, Sonia; Campion, Dominique; De Leeuw, Nicole; De Vries, Bert B. A.; Esko, Tõnu; Fernandez, Bridget A.; Fernández-Aranda, Fernando; Fernández-Real, José Manuel; Gratacòs, Mònica; Guilmatre, Audrey; Hoyer, Juliane; Jarvelin, Marjo-Riitta; Kooy, Frank R.; Kurg, Ants; Le Caignec, Cédric; Männik, Katrin; Platt, Orah S.; Sanlaville, Damien; Van Haelst, Mieke M.; Villatoro Gomez, Sergi; Walha, Faida; Wu, Bai-Lin; Yu, Yongguo; Aboura, Azzedine; Addor, Marie-Claude; Alembik, Yves; Antonarakis, Stylianos E.; Arveiler, Benoît; Barth, Magalie; Bednarek, Nathalie; Béna, Frédérique; Bergmann, Sven; Beri, Mylène; Bernardini, Laura; Blaumeiser, Bettina; Bonneau, Dominique; Bottani, Armand; Boute, Odile; Brunner, Han G.; Cailley, Dorothée; Callier, Patrick; Chiesa, Jean; Chrast, Jacqueline; Coin, Lachlan; Coutton, Charles; Cuisset, Jean-Marie; Cuvellier, Jean-Christophe; David, Albert; De Freminville, Bénédicte; Delobel, Bruno; Delrue, Marie-Ange; Demeer, Bénédicte; Descamps, Dominique; Didelot, Gérard; Dieterich, Klaus; Disciglio, Vittoria; Doco-Fenzy, Martine; Drunat, Séverine; Duban-Bedu, Bénédicte; Dubourg, Christèle; El-Sayed Moustafa, Julia S.; Elliott, Paul; Faas, Brigitte H. W.; Faivre, Laurence; Faudet, Anne; Fellmann, Florence; Ferrarini, Alessandra; Fisher, Richard; Flori, Elisabeth; Forer, Lukas; Gaillard, Dominique; Gerard, Marion; Gieger, Christian; Gimelli, Stefania; Gimelli, Giorgio; Grabe, Hans J.; Guichet, Agnès; Guillin, Olivier; Hartikainen, Anna-Liisa; Heron, Délphine; Hippolyte, Loyse; Holder, Muriel; Homuth, Georg; Isidor, Bertrand; Jaillard, Sylvie; Jaros, Zdenek; Jiménez-Murcia, Susana; Joly Helas, Géraldine; Jonveaux, Philippe; Kaksonen, Satu; Keren, Boris; Kloss-Brandstätter, Anita; Knoers, Nine V. A. M.; Koolen, David A.; Kroisel, Peter M.; Kronenberg, Florian; Labalme, Audrey; Landais, Emilie; Lapi, Elisabetta; Layet, Valérie; Legallic, Solenn; Leheup, Bruno; Leube, Barbara; Lewis, Suzanne; Lucas, Josette; Macdermot, Kay D.; Magnusson, Pall; Marshall, Christian R.; Mathieu-Dramard, Michèle; Mccarthy, Mark I.; Meitinger, Thomas; Antonietta Mencarelli, Maria; Merla, Giuseppe; Moerman, Alexandre; Mooser, Vincent; Morice-Picard, Fanny; Mucciolo, Mafalda; Nauck, Matthias; Coumba Ndiaye, Ndeye; Nordgren, Ann; Pasquier, Laurent; Petit, Florence; Pfundt, Rolph; Plessis, Ghislaine; Rajcan-Separovic, Evica; Paolo Ramelli, Gian; Rauch, Anita; Ravazzolo, Roberto; Reis, Andre; Renieri, Alessandra; Richart, Cristobal; Ried, Janina S.; Rieubland, Claudine; Roberts, Wendy; Roetzer, Katharina M.; Rooryck, Caroline; Rossi, Massimiliano; Saemundsen, Evald; Satre, Véronique; Schurmann, Claudia; Sigurdsson, Engilbert; Stavropoulos, Dimitri J.; Stefansson, Hreinn; Tengström, Carola; Thorsteinsdóttir, Unnur; Tinahones, Francisco J.; Touraine, Renaud; Vallée, Louis; Van Binsbergen, Ellen; Van Der Aa, Nathalie; Vincent-Delorme, Catherine; Visvikis-Siest, Sophie; Vollenweider, Peter; Völzke, Henry; Vulto-Van Silfhout, Anneke T.; Waeber, Gérard; Wallgren-Pettersson, Carina; Witwicki, Robert M.; Zwolinksi, Simon; Andrieux, Joris; Estivill, Xavier; Gusella, James F.; Gustafsson, Omar; Metspalu, Andres; Scherer, Stephen W.; Stefansson, Kari; Blakemore, Alexandra I. F.; Beckmann, Jacques S.; Froguel, Philippe

    2011-01-01

    Both underweight and obesity have been associated with increased mortality1,2. Underweight, defined as body mass index (BMI) ≤ 18,5 kg/m2 in adults 3 and ≤ −2 standard deviations (SD) in children4,5, is the main sign of a series of heterogeneous clinical conditions such as failure to thrive (FTT) 6–8, feeding and eating disorder and/or anorexia nervosa9,10. In contrast to obesity, few genetic variants underlying these clinical conditions have been reported 11, 12. We previously demonstrated that hemizygosity of a ~600 kb region on the short arm of chromosome 16 (chr16:29.5–30.1Mb), causes a highly-penetrant form of obesity often associated with hyperphagia and intellectual disabilities13. Here we show that the corresponding reciprocal duplication is associated with underweight. We identified 138 (132 novel cases) duplication carriers (108 unrelated carriers) from over 95,000 individuals clinically-referred for developmental or intellectual disabilities (DD/ID), psychiatric disorders or recruited from population-based cohorts. These carriers show significantly reduced postnatal weight (mean Z-score −0.6; p=4.4×10−4) and BMI (mean Z-score −0.5; p=2.0×10−3). In particular, half of the boys younger than 5 years are underweight with a probable diagnosis of FTT, while adult duplication carriers have an 8.7-fold (p=5.9×10−11; CI_95=[4.5–16.6]) increased risk of being clinically underweight. We observe a significant trend towards increased severity in males, as well as a depletion of male carriers among non-medically ascertained cases. These features are associated with an unusually high frequency of selective and restrictive feeding behaviours and a significant reduction in head circumference (mean Z-score −0.9; p=7.8×10−6). Each of the observed phenotypes is the converse of one reported in carriers of deletions at this locus, correlating with changes in transcript levels for genes mapping within the duplication but not within flanking

  5. Measurement of extremely (2) H-enriched water samples by laser spectrometry: application to batch electrolytic concentration of environmental tritium samples.

    Science.gov (United States)

    Wassenaar, L I; Kumar, B; Douence, C; Belachew, D L; Aggarwal, P K

    2016-02-15

    Natural water samples artificially or experimentally enriched in deuterium ((2) H) at concentrations up to 10,000 ppm are required for various medical, environmental and hydrological tracer applications, but are difficult to measure using conventional stable isotope ratio mass spectrometry. Here we demonstrate that off-axis integrated cavity output (OA-ICOS) laser spectrometry, along with (2) H-enriched laboratory calibration standards and appropriate analysis templates, allows for low-cost, fast, and accurate determinations of water samples having δ(2) HVSMOW-SLAP values up to at least 57,000 ‰ (~9000 ppm) at a processing rate of 60 samples per day. As one practical application, extremely (2) H-enriched samples were measured by laser spectrometry and compared to the traditional (3) H Spike-Proxy method in order to determine tritium enrichment factors in the batch electrolysis of environmental waters. Highly (2) H-enriched samples were taken from different sets of electrolytically concentrated standards and low-level (tritium samples, and all cases returned accurate and precise initial low-level (3) H results. The ability to quickly and accurately measure extremely (2) H-enriched waters by laser spectrometry will facilitate the use of deuterium as a tracer in numerous environmental and other applications. For low-level tritium operations, this new analytical ability facilitated a 10-20 % increase in sample productivity through the elimination of spike standards and gravimetrics, and provides immediate feedback on electrolytic enrichment cell performance. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  6. Perspectives of extreme sample environment in neutron scattering and consequences for instrumentation

    Indian Academy of Sciences (India)

    Michael Steiner

    2008-11-01

    Because neutrons can penetrate bulky pieces of matter, increasingly complex sample environment is requested by the users of neutron beams. This corresponds to the ever-growing complexity of the scientific problems addressed by neutron scatterers. Until now such requirements could be satisfied by sample environment, which could be added to the instruments without major modifications. Now it becomes evident, that for certain applications further progress is possible only by bringing the neutrons to the sample environment instead of bringing the sample environment to the neutrons. As one of the first examples of this concept we will discuss the high field magnet (HFM), which Hahn-Meitner-Institute Berlin (HMI) and the National High Magnetic Field Laboratory Tallahassy (NHFML) are constructing jointly for BENSC at HMI. At BENSC the HMI has built in the meantime a dedicated instrument based on the TOF principle to be equipped with the HFM to enable experiments at fields up to 25 T.

  7. [A limited sampling strategy of phenotyping probe midazolam to predict inhibited activities of hepatic CYP3A in rats].

    Science.gov (United States)

    Zhu, Xue-hui; Jiao, Jian-jie; Zhang, Cai-li; Lou, Jian-shi; Liu, Chang-xiao

    2008-09-01

    The present study was to evaluate feasibility of a limited sampling strategy (LSS) in the prediction of inhibited hepatic CYP3A activity with systemic clearance of midazolam (MDZ), a hepatic CYP3A activity phenotyping probe. Rats were pretreated with a serial doses of ketoconazole, a selective inhibitor on CYP3A. Blood samples were collected and detected for MDZ at specified time points after intravenous injection of MDZ. Stepwise regression analysis and a Jack-knife validation procedures were performed in one group of rats as training set to establish the most informative LSS model for accurately estimating the clearance of MDZ. Another group of rats with same treatment was used as validation set to estimate the individual clearance based on predictive equations derived from the training set. Bland-Altman plots showed a good agreement between the systemic clearance calculated from DAS (CLobs) and corresponding parameter that was derived from three LSS models (CLest). LSS models derived from two or three sampling time points, including 60, 90 min, 30, 60, 90 min and 30, 60, 120 min, exhibited a good accuracy and acceptable error for estimating the CLobs of MDZ to evaluate hepatic CYP3A activity, especially the 60, 90 min LSS model is most accurate and convenient. The results supported that limited plasma sampling to predict the systemic clearance of MDZ is easier than the usual method for estimating CYP3A phenotyping when the hepatic activity of CYP3A is reduced in the rat. The present study provided theoretical basis and laboratory evidence for LSS to clinically evaluate metabolizing function of liver and

  8. State-of-art methodology of marine natural products chemistry: structure determination with extremely small sample amounts.

    Science.gov (United States)

    Murata, M; Oishi, T; Yoshida, M

    2006-01-01

    Structure elucidation studies on natural products are reviewed emphasizing extremely small sample amounts. Previous studies on insect pheromones, periplanones, and bean-originating kairomones, glycinoeclepins, are described briefly. Recent examples are selected from marine natural products such as ciguatoxin, dolastatin-3, and aurisides. A more detailed description is given of a sperm-activating and attracting factor (SAAF), which may be the smallest sample amount used in the structure elucidation of novel non-peptidic natural products. SAAF was isolated from the eggs of the ascidian, Ciona intestinalis, and its structure was deduced with only approximately 4 microg (6 nmol) of sample. Based upon the proposed structure, two epimers were synthesized from chenodeoxycholic acid in 17 steps, leading to the identification of SAAF as a novel sterol sulfate.

  9. Extreme 13C depletion of CCl2F2 in firn air samples from NEEM, Greenland

    NARCIS (Netherlands)

    Zuiderweg, A.T.; Holzinger, R.; Röckmann, T.

    2012-01-01

    A series of 12 high volume air samples collected from the S2 firn core during the North Greenland Eemian Ice Drilling (NEEM) 2009 campaign have been measured for mixing ratio and stable carbon isotope composition of the chlorofluorocarbon CFC- 12 (CCl2F2). While the mixing ratio measurements compare

  10. Extension of GWAS results for lipid-related phenotypes to extreme obesity using electronic health record (EHR data and the Metabochip.

    Directory of Open Access Journals (Sweden)

    Ankita eParihar

    2014-08-01

    Full Text Available A variety of health-related data are commonly deposited into electronic health records (EHRs, including laboratory, diagnostic, and medication information. The digital nature of EHR data facilitates efficient extraction of these data for research studies, including genome-wide association studies (GWAS. Previous GWAS have identified numerous SNPs associated with variation in total cholesterol (TC, low-density lipoprotein cholesterol (LDL-C, high-density lipoprotein cholesterol (HDL-C, and triglycerides (TG. These findings have led to the development of specialized genotyping platforms that can be used for fine-mapping and replication in other populations. We have combined the efficiency of EHR data and the economic advantages of the Illumina Metabochip, a custom designed SNP chip targeted to traits related to coronary artery disease, myocardial infarction, and type 2 diabetes, to conduct a GWAS for lipid traits in a population with extreme obesity. Our genome wide analysis identified association of SNPs residing at previously lipid associated loci with all lipid phenotypes, as well as 14 of 24 previously identified lipid-associated SNPs, although for a number of known lipid SNPs and body weight SNPs no association was found. Association analysis using several approaches to adjust for use of lipid lowering medications resulted in fewer and less strongly associated SNPs. The availability of phenotype data from the EHR and the economic efficiency of the specialized Metabochip can be exploited to conduct multi-faceted analyses for GWAS.

  11. A cross-sectional, randomized cluster sample survey of household vulnerability to extreme heat among slum dwellers in ahmedabad, india.

    Science.gov (United States)

    Tran, Kathy V; Azhar, Gulrez S; Nair, Rajesh; Knowlton, Kim; Jaiswal, Anjali; Sheffield, Perry; Mavalankar, Dileep; Hess, Jeremy

    2013-06-18

    Extreme heat is a significant public health concern in India; extreme heat hazards are projected to increase in frequency and severity with climate change. Few of the factors driving population heat vulnerability are documented, though poverty is a presumed risk factor. To facilitate public health preparedness, an assessment of factors affecting vulnerability among slum dwellers was conducted in summer 2011 in Ahmedabad, Gujarat, India. Indicators of heat exposure, susceptibility to heat illness, and adaptive capacity, all of which feed into heat vulnerability, was assessed through a cross-sectional household survey using randomized multistage cluster sampling. Associations between heat-related morbidity and vulnerability factors were identified using multivariate logistic regression with generalized estimating equations to account for clustering effects. Age, preexisting medical conditions, work location, and access to health information and resources were associated with self-reported heat illness. Several of these variables were unique to this study. As sociodemographics, occupational heat exposure, and access to resources were shown to increase vulnerability, future interventions (e.g., health education) might target specific populations among Ahmedabad urban slum dwellers to reduce vulnerability to extreme heat. Surveillance and evaluations of future interventions may also be worthwhile.

  12. Effects of sample size on estimation of rainfall extremes at high temperatures

    Directory of Open Access Journals (Sweden)

    B. Boessenkool

    2017-09-01

    Full Text Available High precipitation quantiles tend to rise with temperature, following the so-called Clausius–Clapeyron (CC scaling. It is often reported that the CC-scaling relation breaks down and even reverts for very high temperatures. In our study, we investigate this reversal using observational climate data from 142 stations across Germany. One of the suggested meteorological explanations for the breakdown is limited moisture supply. Here we argue that, instead, it could simply originate from undersampling. As rainfall frequency generally decreases with higher temperatures, rainfall intensities as dictated by CC scaling are less likely to be recorded than for moderate temperatures. Empirical quantiles are conventionally estimated from order statistics via various forms of plotting position formulas. They have in common that their largest representable return period is given by the sample size. In small samples, high quantiles are underestimated accordingly. The small-sample effect is weaker, or disappears completely, when using parametric quantile estimates from a generalized Pareto distribution (GPD fitted with L moments. For those, we obtain quantiles of rainfall intensities that continue to rise with temperature.

  13. The association between candidate migraine susceptibility loci and severe migraine phenotype in a clinical sample

    DEFF Research Database (Denmark)

    Esserlind, Ann-Louise; Christensen, Anne Francke; Steinberg, Stacy

    2016-01-01

    INTRODUCTION: The objective of the study was to follow up and to test whether 12 previously identified migraine-associated single nucleotide polymorphisms were associated as risk factors and/or modifying factors for severe migraine traits in a Danish clinic-based population. METHODS: Semi...... polymorphisms showed nominal association with many lifetime attacks and prolonged migraine attacks. CONCLUSION: Our study supports previously reported findings on the association of several single nucleotide polymorphisms with migraine. It also suggests that the migraine susceptibility loci may be risk factors......-structured migraine interviews, blood sampling and genotyping were performed on 1806 unrelated migraineurs recruited from the Danish Headache Center. Genotyping was also performed on a control group of 6415 people with no history of migraine. Association analyses were carried out using logistic regression and odds...

  14. Mapping quantitative trait loci from a single-tail sample of the phenotype distribution including survival data.

    Science.gov (United States)

    Sillanpää, Mikko J; Hoti, Fabian

    2007-12-01

    A new effective Bayesian quantitative trait locus (QTL) mapping approach for the analysis of single-tail selected samples of the phenotype distribution is presented. The approach extends the affected-only tests to single-tail sampling with quantitative traits such as the log-normal survival time or censored/selected traits. A great benefit of the approach is that it enables the utilization of multiple-QTL models, is easy to incorporate into different data designs (experimental and outbred populations), and can potentially be extended to epistatic models. In inbred lines, the method exploits the fact that the parental mating type and the linkage phases (haplotypes) are known by definition. In outbred populations, two-generation data are needed, for example, selected offspring and one of the parents (the sires) in breeding material. The idea is to statistically (computationally) generate a fully complementary, maximally dissimilar, observation for each offspring in the sample. Bayesian data augmentation is then used to sample the space of possible trait values for the pseudoobservations. The benefits of the approach are illustrated using simulated data sets and a real data set on the survival of F(2) mice following infection with Listeria monocytogenes.

  15. Genome-wide linkage analysis of longitudinal phenotypes using sigma(2)(A) random effects (SSARs) fitted by Gibbs sampling

    NARCIS (Netherlands)

    Palmer, LJ; Scurrah, KJ; Tobin, M; Patel, [No Value; Celedon, JC; Burton, PR; Weiss, ST

    2003-01-01

    The study of change in intermediate phenotypes over time is important in genetics. In this paper we explore a new approach to phenotype definition in the genetic analysis of longitudinal phenotypes. We utilized data from the longitudinal Framingham Heart Study Family Cohort to investigate the famili

  16. Preliminary Blood Pressure Screening in a Representative Sample of Extremely Obese Kuwaiti Adolescents

    Directory of Open Access Journals (Sweden)

    Rima Abdul Razzak

    2013-01-01

    Full Text Available A relationship between blood pressure (BP and obesity has been found in young adults, but no data are available for adolescents in Kuwait. 257 adolescent (11–19 years participants were categorized into two groups according to their BMI; 48 nonobese (21 males: 43.7% and 27 females: 56.3% with mean age of years and 209 obese (128 males: 61.25% and 81 females: 38.75% with mean age of years. The mean BMI was  kg/m2 for the nonobese group and  kg/m3 for the obese group. Most BP measures based on a single screening were significantly higher in the obese group. The prevalence of elevated BP was significantly higher in the obese subjects (nonobese: 13%; obese: 63%; . In the obese group, there was a significant positive correlation between total sample BMI and all BP measures except the pulse pressure. There was a similar rate of elevated blood pressure between males and females (64% versus 60%; . For both isolated systolic elevated BP and isolated diastolic elevated BP, the prevalences were comparable between the males (systolic: 42%; diastolic: 5% and females (systolic: 34%; diastolic: 14%. Only systolic BP was positively correlated with BMI in obese adolescent males (Spearman ; , with a significant correlation between BMI with diastolic (Spearman ; and mean BP (Spearman ; in females.

  17. Two-dimensional resonant magnetic soft X-ray scattering set-up for extreme sample environment.

    Science.gov (United States)

    Stanescu, Stefan; Mocuta, Cristian; Merlet, Frederic; Barbier, Antoine

    2013-01-01

    The newly built MagSAXS (magnetic small-angle X-ray scattering) set-up dedicated to the direct two-dimensional measurement of magnetic scattering using polarized synchrotron radiation in extreme sample environments is presented. Pure optical transport of the image is used to record the magnetic scattering with a two-dimensional CCD visible-light camera. The set-up is able to probe magnetic correlation lengths from the micrometer down to the nanometer scale. A detailed layout is presented along with preliminary results obtained at several beamlines at Synchrotron SOLEIL. The presented examples underline the wide range of possible applications spanning from correlation lengths determination to Fourier transform holography.

  18. Determination of extremely low (236)U/(238)U isotope ratios in environmental samples by sector-field inductively coupled plasma mass spectrometry using high-efficiency sample introduction.

    Science.gov (United States)

    Boulyga, Sergei F; Heumann, Klaus G

    2006-01-01

    A method by inductively coupled plasma mass spectrometry (ICP-MS) was developed which allows the measurement of (236)U at concentration ranges down to 3 x 10(-14)g g(-1) and extremely low (236)U/(238)U isotope ratios in soil samples of 10(-7). By using the high-efficiency solution introduction system APEX in connection with a sector-field ICP-MS a sensitivity of more than 5,000 counts fg(-1) uranium was achieved. The use of an aerosol desolvating unit reduced the formation rate of uranium hydride ions UH(+)/U(+) down to a level of 10(-6). An abundance sensitivity of 3 x 10(-7) was observed for (236)U/(238)U isotope ratio measurements at mass resolution 4000. The detection limit for (236)U and the lowest detectable (236)U/(238)U isotope ratio were improved by more than two orders of magnitude compared with corresponding values by alpha spectrometry. Determination of uranium in soil samples collected in the vicinity of Chernobyl nuclear power plant (NPP) resulted in that the (236)U/(238)U isotope ratio is a much more sensitive and accurate marker for environmental contamination by spent uranium in comparison to the (235)U/(238)U isotope ratio. The ICP-MS technique allowed for the first time detection of irradiated uranium in soil samples even at distances more than 200 km to the north of Chernobyl NPP (Mogilev region). The concentration of (236)U in the upper 0-10 cm soil layers varied from 2 x 10(-9)g g(-1) within radioactive spots close to the Chernobyl NPP to 3 x 10(-13)g g(-1) on a sampling site located by >200 km from Chernobyl.

  19. Methodological Considerations in Estimation of Phenotype Heritability Using Genome-Wide SNP Data, Illustrated by an Analysis of the Heritability of Height in a Large Sample of African Ancestry Adults

    Science.gov (United States)

    Chen, Fang; He, Jing; Zhang, Jianqi; Chen, Gary K.; Thomas, Venetta; Ambrosone, Christine B.; Bandera, Elisa V.; Berndt, Sonja I.; Bernstein, Leslie; Blot, William J.; Cai, Qiuyin; Carpten, John; Casey, Graham; Chanock, Stephen J.; Cheng, Iona; Chu, Lisa; Deming, Sandra L.; Driver, W. Ryan; Goodman, Phyllis; Hayes, Richard B.; Hennis, Anselm J. M.; Hsing, Ann W.; Hu, Jennifer J.; Ingles, Sue A.; John, Esther M.; Kittles, Rick A.; Kolb, Suzanne; Leske, M. Cristina; Monroe, Kristine R.; Murphy, Adam; Nemesure, Barbara; Neslund-Dudas, Christine; Nyante, Sarah; Ostrander, Elaine A; Press, Michael F.; Rodriguez-Gil, Jorge L.; Rybicki, Ben A.; Schumacher, Fredrick; Stanford, Janet L.; Signorello, Lisa B.; Strom, Sara S.; Stevens, Victoria; Van Den Berg, David; Wang, Zhaoming; Witte, John S.; Wu, Suh-Yuh; Yamamura, Yuko; Zheng, Wei; Ziegler, Regina G.; Stram, Alexander H.; Kolonel, Laurence N.; Marchand, Loïc Le; Henderson, Brian E.; Haiman, Christopher A.; Stram, Daniel O.

    2015-01-01

    Height has an extremely polygenic pattern of inheritance. Genome-wide association studies (GWAS) have revealed hundreds of common variants that are associated with human height at genome-wide levels of significance. However, only a small fraction of phenotypic variation can be explained by the aggregate of these common variants. In a large study of African-American men and women (n = 14,419), we genotyped and analyzed 966,578 autosomal SNPs across the entire genome using a linear mixed model variance components approach implemented in the program GCTA (Yang et al Nat Genet 2010), and estimated an additive heritability of 44.7% (se: 3.7%) for this phenotype in a sample of evidently unrelated individuals. While this estimated value is similar to that given by Yang et al in their analyses, we remain concerned about two related issues: (1) whether in the complete absence of hidden relatedness, variance components methods have adequate power to estimate heritability when a very large number of SNPs are used in the analysis; and (2) whether estimation of heritability may be biased, in real studies, by low levels of residual hidden relatedness. We addressed the first question in a semi-analytic fashion by directly simulating the distribution of the score statistic for a test of zero heritability with and without low levels of relatedness. The second question was addressed by a very careful comparison of the behavior of estimated heritability for both observed (self-reported) height and simulated phenotypes compared to imputation R2 as a function of the number of SNPs used in the analysis. These simulations help to address the important question about whether today's GWAS SNPs will remain useful for imputing causal variants that are discovered using very large sample sizes in future studies of height, or whether the causal variants themselves will need to be genotyped de novo in order to build a prediction model that ultimately captures a large fraction of the variability

  20. Methodological Considerations in Estimation of Phenotype Heritability Using Genome-Wide SNP Data, Illustrated by an Analysis of the Heritability of Height in a Large Sample of African Ancestry Adults.

    Directory of Open Access Journals (Sweden)

    Fang Chen

    Full Text Available Height has an extremely polygenic pattern of inheritance. Genome-wide association studies (GWAS have revealed hundreds of common variants that are associated with human height at genome-wide levels of significance. However, only a small fraction of phenotypic variation can be explained by the aggregate of these common variants. In a large study of African-American men and women (n = 14,419, we genotyped and analyzed 966,578 autosomal SNPs across the entire genome using a linear mixed model variance components approach implemented in the program GCTA (Yang et al Nat Genet 2010, and estimated an additive heritability of 44.7% (se: 3.7% for this phenotype in a sample of evidently unrelated individuals. While this estimated value is similar to that given by Yang et al in their analyses, we remain concerned about two related issues: (1 whether in the complete absence of hidden relatedness, variance components methods have adequate power to estimate heritability when a very large number of SNPs are used in the analysis; and (2 whether estimation of heritability may be biased, in real studies, by low levels of residual hidden relatedness. We addressed the first question in a semi-analytic fashion by directly simulating the distribution of the score statistic for a test of zero heritability with and without low levels of relatedness. The second question was addressed by a very careful comparison of the behavior of estimated heritability for both observed (self-reported height and simulated phenotypes compared to imputation R2 as a function of the number of SNPs used in the analysis. These simulations help to address the important question about whether today's GWAS SNPs will remain useful for imputing causal variants that are discovered using very large sample sizes in future studies of height, or whether the causal variants themselves will need to be genotyped de novo in order to build a prediction model that ultimately captures a large fraction of the

  1. Phenotypic and genotypic characterization of sorbitol-negative of slow-fermenting (suspected O157) Escherichia coli isolated from milk samples in Lombardy region

    NARCIS (Netherlands)

    Picozzi, C.; Foschino, R.; Heuvelink, A.E.; Beumer, R.R.

    2005-01-01

    Aims: To investigate phenotypic and genotypic aspects of sorbitol-negative or slow-fermenting Escherichia coli, suspected to belong to O157 serogroup, isolated in Italy. Methods and Results: Milk samples originating from goats and cows were screened for the presence of E. coli O157 with cultural met

  2. Extreme differentiation in single samples from the olivine-rich zone of the Palisades Sill, NY and NJ

    Science.gov (United States)

    Chau, K. X.; Sen, G.; Naslund, H. R.

    2007-12-01

    The Palisades Sill, NY and NJ, has long been the focus of much attention due to its potential contributions to the understanding of igneous differentiation. Many early authors, including N.L. Bowen, thought of the intrusion as an ideal example of crystal settling because of an olivine-rich zone that occurs close to the base of the sill. Later investigations demonstrated that at least three geochemically distinct batches of magma were emplaced at different levels within this body, one of which produced the olivine-rich zone. Here we report the results of our detailed electron probe study of 27 olivine grains, 134 plagioclase grains, and 181 pyroxene grains from four samples of the olivine-rich zone. In one of the rocks plagioclase ranges from An84 (large grain; core) to An0.5 (interstitial plagioclase), whereas olivine ranges from Fo81 - Fo69. These ranges are comparable to our other samples. The plagioclase range is far greater than what is shown by the Skaergaard (An25 - An69) and Bushveld (An30 - An80) intrusions. Though the sill has long been known to be vertically differentiated, such extreme differentiation in individual thumb-sized samples was not expected. The implication is that interstitial melt pockets were so well enclosed (i.e., zero permeability) by the surrounding crystals that they were sealed off from further communication with larger volumes of melt that may have existed at a higher levels in the sill at that time. That is, compaction and associated filter pressing was not efficient in removing the interstitial melt. It is unlikely that such a situation could occur if the olivine-rich zone formed early from a large body of magma because the load pressure of the overlying crystals and melt would be too great to avoid compaction. A better explanation is that the olivine-rich zone was emplaced as a separate magma batch (as suggested by several previous workers based on bulk rock geochemistry) in a mostly solidified magma-crystal mush. In this setting

  3. NLTE strontium abundance in a sample of extremely metal poor stars and the Sr/Ba ratio in the early Galaxy

    CERN Document Server

    Andrievsky, S M; Korotin, S A; Francois, P; Spite, M; Bonifacio, P; Cayrel, R; Hill, V

    2011-01-01

    Heavy element abundances in extremely metal-poor stars provide strong constraints on the processes of forming these elements in the first stars. We attempt to determine precise abundances of strontium in a homogeneous sample of extremely metal-poor stars. The abundances of strontium in 54 very or extremely metal-poor stars, was redetermined by abandoning the local thermodynamic equilibrium (LTE) hypothesis, and fitting non-LTE (NLTE) profiles to the observed spectral lines. The corrected Sr abundances and previously obtained NLTE Ba abundances are compared to the predictions of several hypothetical formation processes for the lighter neutron-capture elements. Our NLTE abundances confirm the previously determined huge scatter of the strontium abundance in low metallicity stars. This scatter is also found (and is even larger) at very low metallicities (i. e. early in the chemical evolution). The Sr abundance in the extremely metal-poor (EMP) stars is compatible with the main r-process involved in other processe...

  4. Evaluation of Mutual Drug-Drug Interaction within Geneva Cocktail for Cytochrome P450 Phenotyping using Innovative Dried Blood Sampling Method.

    Science.gov (United States)

    Bosilkovska, Marija; Samer, Caroline; Déglon, Julien; Thomas, Aurélien; Walder, Bernhard; Desmeules, Jules; Daali, Youssef

    2016-09-01

    Cytochrome P450 (CYP) activity can be assessed using a 'cocktail' phenotyping approach. Recently, we have developed a cocktail (Geneva cocktail) which combines the use of low-dose probes with a low-invasiveness dried blood spots (DBS) sampling technique and a single analytical method for the phenotyping of six major CYP isoforms. We have previously demonstrated that modulation of CYP activity after pre-treatment with CYP inhibitors/inducer could be reliably predicted using Geneva cocktail. To further validate this cocktail, in this study, we have verified whether probe drugs contained in the latter cause mutual drug-drug interactions. In a randomized, four-way, Latin-square crossover study, 30 healthy volunteers received low-dose caffeine, flurbiprofen, omeprazole, dextromethorphan and midazolam (a previously validated combination with no mutual drug-drug interactions); fexofenadine alone; bupropion alone; or all seven drugs simultaneously (Geneva cocktail). Pharmacokinetic profiles of the probe drugs and their metabolites were determined in DBS samples using both conventional micropipette sampling and new microfluidic device allowing for self-sampling. The 90% confidence intervals for the geometric mean ratios of AUC metabolite/AUC probe for CYP probes administered alone or within Geneva cocktail fell within the 0.8-1.25 bioequivalence range indicating the absence of pharmacokinetic interaction. The same result was observed for the chosen phenotyping indices, that is metabolic ratios at 2 hr (CYP1A2, CYP3A) or 3 hr (CYP2B6, CYP2C9, CYP2C19, CYP2D6) post-cocktail administration. DBS sampling could successfully be performed using a new microfluidic device. In conclusion, Geneva cocktail combined with an innovative DBS sampling device can be used routinely as a test for simultaneous CYP phenotyping. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  5. Phenotypic Data Collection and Sample Preparation for Genomics of Wood Formation and Cellulosic Biomass Traits in Sunflower: Ames, IA location.

    Energy Technology Data Exchange (ETDEWEB)

    Marek, Laura F.

    2011-06-17

    Three fields were planted in Ames in 2010, two association mapping fields, N3 and A, and a recombinant inbred line field, N13. Phenotype data and images were transferred to UGA to support genetic and genomic analyses of woody biomass-related traits.

  6. Thermal discomfort with cold extremities in relation to age, gender, and body mass index in a random sample of a Swiss urban population

    Directory of Open Access Journals (Sweden)

    Orgül Selim

    2010-06-01

    Full Text Available Abstract Background The aim of this epidemiological study was to investigate the relationship of thermal discomfort with cold extremities (TDCE to age, gender, and body mass index (BMI in a Swiss urban population. Methods In a random population sample of Basel city, 2,800 subjects aged 20-40 years were asked to complete a questionnaire evaluating the extent of cold extremities. Values of cold extremities were based on questionnaire-derived scores. The correlation of age, gender, and BMI to TDCE was analyzed using multiple regression analysis. Results A total of 1,001 women (72.3% response rate and 809 men (60% response rate returned a completed questionnaire. Statistical analyses revealed the following findings: Younger subjects suffered more intensely from cold extremities than the elderly, and women suffered more than men (particularly younger women. Slimmer subjects suffered significantly more often from cold extremities than subjects with higher BMIs. Conclusions Thermal discomfort with cold extremities (a relevant symptom of primary vascular dysregulation occurs at highest intensity in younger, slimmer women and at lowest intensity in elderly, stouter men.

  7. Detection of KPC Carbapenemase in Pseudomonas aeruginosa Isolated From Clinical Samples Using Modified Hodge Test and Boronic Acid Phenotypic Methods and Their Comparison With the Polymerase Chain Reaction

    Science.gov (United States)

    Falahat, Saeed; Shojapour, Mana; Sadeghi, Abdorrahim

    2016-01-01

    Background Bacterial resistance to antibiotics has become a major source of concern for public health. Pseudomonas aeruginosa strains are important opportunistic pathogens. These bacteria have a high resistance to a wide range of existing antimicrobials and antibiotics. Objectives The present study was performed to evaluate the frequency of KPC in P. aeruginosa isolated from clinical samples of educational hospitals of Arak University of Medical Sciences, using the mentioned phenotypic and genotypic methods. Materials and Methods One hundred and eight non-duplicate clinical isolates of P. aeruginosa were collected from hospitals of Arak University of Medical Sciences, Arak, Iran. Antibacterial susceptibility was determined by the disk diffusion method. KPC production was confirmed by the Modified Hodge Test (MHT), which is a phenotypic test, and combined-disk test with boronic acid and the Polymerase Chain Reaction (PCR). Results In the present study, 13 isolates (12%) of P. aeruginosa were positive for KPC, using PCR. Comparison of the two phenotypic methods used in this study showed that boronic acid is more sensitive than MHT in identification of KPC-producing strains (84.6% vs. 77%). Conclusions Utilization of reliable methods for identifying carbapenemase-producing strains and determining their antibiotic resistance pattern could have a very important role in treatment of infections caused by these strains. A substantial amount of P. aeruginosa isolated from clinical samples of hospitals in Arak (Iran) produce KPC carbapenemase. Due to their low specificity, MHT and boronic acid phenotypic methods could not completely identify KPC-producing P. aeruginosa. However, the sensitivity of boronic acid phenotypic method in detection of KPC was higher than MHT.

  8. Personality disorders as maladaptive, extreme variants of normal personality: borderline personality disorder and neuroticism in a substance using sample.

    Science.gov (United States)

    Samuel, Douglas B; Carroll, Kathleen M; Rounsaville, Bruce J; Ball, Samuel A

    2013-10-01

    Although the current diagnostic manual conceptualizes personality disorders (PDs) as categorical entities, an alternative perspective is that PDs represent maladaptive extreme versions of the same traits that describe normal personality. Existing evidence indicates that normal personality traits, such as those assessed by the five-factor model (FFM), share a common structure and obtain reasonably predictable correlations with the PDs. However, very little research has investigated whether PDs are more extreme than normal personality traits. Utilizing item-response theory analyses, the authors of the current study extend previous research to demonstrate that the diagnostic criterion for borderline personality disorder and FFM neuroticism could be fit along a single latent dimension. Furthermore, the authors' findings indicate that the borderline criteria assessed the shared latent trait at a level that was more extreme (d = 1.11) than FFM neuroticism. This finding provides further evidence for dimensional understanding of personality pathology and suggests that a trait model in DSM-5 should span normal and abnormal personality functioning, but focus on the extremes of these common traits.

  9. Selection, phenotyping and identification of acid and hydrogen peroxide producing bacteria from vaginal samples of Canadian and East African women.

    Directory of Open Access Journals (Sweden)

    John J Schellenberg

    Full Text Available The common but poorly understood condition known as bacterial vaginosis (BV increases vulnerability to HIV infection and is associated with the absence of H(2O(2-producing Lactobacillus. Vaginal lactic acid bacteria (LAB produce anti-HIV factors such as organic acids and hydrogen peroxide (H(2O(2, and may bind and inactivate HIV particles during scavenging of mannose. These factors define potential criteria for initial selection of candidate probiotics to block heterosexual transmission of HIV. Therefore, the primary goal of this study was to characterize acid production on mannose and H(2O(2 production in vaginal isolates from Canadian adolescents (192 isolates, 16 individuals and commercial sex workers in Nairobi, Kenya (576 isolates, 96 individuals. Selection of isolates from H(2O(2-detecting media suggested an idiosyncratic individual-level profile and extensive phenotypic diversity, including the identification of a subset of "double-strong" acid- and H(2O(2-producers with phenotypes similar to well-characterized probiotic strains. Molecular fingerprinting of all isolates by capillary electrophoresis of 16S-23S rRNA interspacer amplicons was coupled with chaperonin-60 universal target (cpn60 UT sequencing in a subset, tentatively identifying 96% of isolates although only 19% were sequenced. Most isolates belonged to Lactobacillus, Streptococcus, Bifidobacterium or Gardnerella, with a total of 37 species in 15 genera, as well as 5 potentially novel organisms, identified in this study. This sensitivity was likely enhanced by phenotype-based selection on two chromogenic media formulations. Identification of double-strong isolates may provide a rational basis for selection and further characterization of vaginal probiotics, with potential application as part of HIV prevention initiatives in western Canada and East Africa.

  10. Several Inequalities for Moments of Extreme Values of Samples%关于样本极值的矩的几个不等式

    Institute of Scientific and Technical Information of China (English)

    康殿统

    2006-01-01

    Several inequalities for moments of extreme values of samples extracted from two starshaped ordered populations are extended by replacing the star-shaped order with the NBUE (new better that used in expectation) order.%把在星形序下成立的关于样本极值的几个矩的不等式推广到了在NBUE序下也成立.

  11. Phenotypic, molecular characterization, antimicrobial susceptibility and draft genome sequence of Corynebacterium argentoratense strains isolated from clinical samples

    Directory of Open Access Journals (Sweden)

    I. Fernández-Natal

    2016-03-01

    Full Text Available During a 12-year period we isolated five Corynebacterium argentoratense strains identified by phenotypic methods, including the use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF and 16S rRNA gene sequencing. In addition, antimicrobial susceptibility was determined, and genome sequencing for the detection of antibiotic resistance genes was performed. The organisms were isolated from blood and throat cultures and could be identified by all methods used. All strains were resistant to cotrimoxazole, and resistance to β-lactams was partly present. Two strains were resistant to erythromycin and clindamycin. The draft genome sequences of theses isolates revealed the presence of the erm(X resistance gene that is embedded in the genetic structure of the transposable element Tn5423. Although rarely reported as a human pathogen, C. argentoratense can be involved in bacteraemia and probably in other infections. Our results also show that horizontal transfer of genes responsible for antibiotic resistance is occurring in this species.

  12. Searching in the Dark: Phenotyping Diabetic Retinopathy in a De-Identified Electronic Medical Record Sample of African Americans.

    Science.gov (United States)

    Restrepo, Nicole A; Farber-Eger, Eric; Crawford, Dana C

    2016-01-01

    A hurdle to EMR-based studies is the characterization and extraction of complex phenotypes not readily defined by single diagnostic/procedural codes. Here we developed an algorithm utilizing data mining techniques to identify a diabetic retinopathy (DR) cohort of type-2 diabetic African Americans from the Vanderbilt University de-identified EMR system. The algorithm incorporates a combination of diagnostic codes, current procedural terminology billing codes, medications, and text matching to identify DR when gold-standard digital photography results were unavailable. DR cases were identified with a positive predictive value of 75.3% and an accuracy of 84.8%. Controls were classified with a negative predictive value of 1.0% as could be assessed. Limited studies of DR have been performed in African Americans who are at an elevated risk of DR. Identification of EMR-based African American cohorts may help stimulate new biomedical studies that could elucidate differences in risk for the development of DR and other complex diseases.

  13. Cocktail approach for in vivo phenotyping of 5 major CYP450 isoenzymes: development of an effective sampling, extraction, and analytical procedure and pilot study with comparative genotyping.

    Science.gov (United States)

    Wohlfarth, Ariane; Naue, Jana; Lutz-Bonengel, Sabine; Dresen, Sebastian; Auwärter, Volker

    2012-08-01

    In this study, the authors developed a phenotyping method for CYP1A2, 2C9, 2C19, 2D6, and 3A4 using a cocktail of 100 mg caffeine, 125 mg tolbutamide, 20 mg omeprazole, 30 mg dextromethorphan, and 2 mg midazolam. A simple sampling scheme was established collecting 3 blood samples at 0, 4, and 24 hours followed by solid-phase extraction and liquid chromatography/tandem mass spectrometry analysis. After addition of 8 deuterated internal standards and extraction, the analytes were separated using gradient elution with ammonium acetate and methanol. Data acquisition was performed on a triple quadrupole linear ion trap mass spectrometer in multiple-reaction monitoring mode with positive electrospray ionization. The assay was validated according to international guidelines: limits of quantification (LOQs) were between 0.25 and 1.0 ng/mL for all analytes, except for paraxanthine and caffeine (20 ng/mL). Extraction efficiencies ranged between 77% and 103% and matrix effects between 23% and 95%; precision and accuracy data fulfilled accepted criteria. Calibration curves from LOQ to 1000 ng/mL were established for undiluted and 1:10 diluted plasma (r > 0.998). The method was tested in a pilot study with 14 volunteers. Additional genotyping of the probands generally demonstrated good accordance with the measured phenotyping indices but also disclosed certain contradictory results.

  14. Instrument developments for chemical and physical characterization, mapping and sampling of extreme environments (Antarctic sub ice environment)

    Science.gov (United States)

    Vogel, S. W.; Powell, R. D.; Griffith, I.; Lawson, T.; Schiraga, S.; Ludlam, G.; Oen, J.

    2009-12-01

    A number of instrumentation is currently under development designed to enable the study of subglacial environments in Antarctica through narrow kilometer long boreholes. Instrumentation includes: - slim line Sub-Ice ROV (SIR), - Geochemical Instrumentation Package for Sub Ice Environments (GIPSIE) to study geochemical fluxes in water and across the sediment water interface (CO2, CH4, dO, NH4, NO3, Si, PO4, pH, redox, T, H2, HS, O2, N2O, CTD, particle size, turbidity, color camera, current meter and automated water sampler) with real-time telemetry for targeted sampling, - long term energy-balance mooring system, - active source slide hammer sediment corer, and - integration of a current sensor into the ITP profiler. The instrumentation design is modular and suitable for remote operated as well as autonomous long-term deployment. Of interest to the broader science community is the development of the GIPSIE and efforts to document the effect of sample recovery from depth on the sample chemistry. The GIPSIE is a geochemical instrumentation package with life stream telemetry, allowing for user controlled targeted sampling of water column and the water sediment interphase for chemical and biological work based on actual measurements and not a preprogrammed automated system. The porewater profiler (pH, redox, T, H2, HS, O2, N2O) can penetrate the upper 50 cm of sediment and penetration is documented with real time video. Associated with GIPSIE is an on-site lab set-up, utilizing a set of identical sensors. Comparison between the insitu measurements and measurements taken onsite directly after samples are recovered from depth permits assessing the effect of sample recovery on water and sediment core chemistry. Sample recovery related changes are mainly caused by changes in the pressure temperature field and exposure of samples to atmospheric conditions. Exposure of anaerobic samples to oxygen is here a specific concern. Recovery from depth effects in generally p

  15. Complete genome sequence, metabolic model construction and phenotypic characterization of Geobacillus LC300, an extremely thermophilic, fast growing, xylose-utilizing bacterium.

    Science.gov (United States)

    Cordova, Lauren T; Long, Christopher P; Venkataramanan, Keerthi P; Antoniewicz, Maciek R

    2015-11-01

    We have isolated a new extremely thermophilic fast-growing Geobacillus strain that can efficiently utilize xylose, glucose, mannose and galactose for cell growth. When grown aerobically at 72 °C, Geobacillus LC300 has a growth rate of 2.15 h(-1) on glucose and 1.52 h(-1) on xylose (doubling time less than 30 min). The corresponding specific glucose and xylose utilization rates are 5.55 g/g/h and 5.24 g/g/h, respectively. As such, Geobacillus LC300 grows 3-times faster than E. coli on glucose and xylose, and has a specific xylose utilization rate that is 3-times higher than the best metabolically engineered organism to date. To gain more insight into the metabolism of Geobacillus LC300 its genome was sequenced using PacBio's RS II single-molecule real-time (SMRT) sequencing platform and annotated using the RAST server. Based on the genome annotation and the measured biomass composition a core metabolic network model was constructed. To further demonstrate the biotechnological potential of this organism, Geobacillus LC300 was grown to high cell-densities in a fed-batch culture, where cells maintained a high xylose utilization rate under low dissolved oxygen concentrations. All of these characteristics make Geobacillus LC300 an attractive host for future metabolic engineering and biotechnology applications.

  16. Protein expression and genetic structure of the coral Porites lobata in an environmentally extreme Samoan back reef: Does host genotype limit phenotypic plasticity?

    Science.gov (United States)

    Barshis, D.J.; Stillman, J.H.; Gates, R.D.; Toonen, R.J.; Smith, L.W.; Birkeland, C.

    2010-01-01

    The degree to which coral reef ecosystems will be impacted by global climate change depends on regional and local differences in corals' susceptibility and resilience to environmental stressors. Here, we present data from a reciprocal transplant experiment using the common reef building coral Porites lobata between a highly fluctuating back reef environment that reaches stressful daily extremes, and a more stable, neighbouring forereef. Protein biomarker analyses assessing physiological contributions to stress resistance showed evidence for both fixed and environmental influence on biomarker response. Fixed influences were strongest for ubiquitin-conjugated proteins with consistently higher levels found in back reef source colonies both pre and post-transplant when compared with their forereef conspecifics. Additionally, genetic comparisons of back reef and forereef populations revealed significant population structure of both the nuclear ribosomal and mitochondrial genomes of the coral host (FST = 0.146 P < 0.0001, FST = 0.335 P < 0.0001 for rDNA and mtDNA, respectively), whereas algal endosymbiont populations were genetically indistinguishable between the two sites. We propose that the genotype of the coral host may drive limitations to the physiological responses of these corals when faced with new environmental conditions. This result is important in understanding genotypic and environmental interactions in the coral algal symbiosis and how corals may respond to future environmental changes. ?? 2010 Blackwell Publishing Ltd.

  17. Extreme emission-line galaxies out to z$\\sim$1 in zCOSMOS-20k. I. Sample and characterization of global properties

    CERN Document Server

    Amorín, Ricardo; Contini, T; Vílchez, J M; Bolzonella, M; Tasca, L A M; Lamareille, F; Zamorani, G; Maier, C; Carollo, C M; Kneib, J -P; Fèvre, O Le; Lilly, S; Mainieri, V; Renzini, A; Scodeggio, M; Bardelli, S; Bongiorno, A; Caputi, K; Cucciati, O; de la Torre, S; de Ravel, L; Franzetti, P; Garilli, B; Iovino, A; Kampczyk, P; Knobel, C; Kovač, K; Borgne, J -F Le; Mignoli, V Le Brun M; Pellò, R; Peng, Y; Presotto, V; Ricciardelli, E; Silverman, J D; Tanaka, M; Tresse, L; Vergani, D; Zucca, E

    2014-01-01

    We present a large sample of 183 extreme emission-line galaxies (EELGs) at redshift 0.11 < z < 0.93 selected from the 20k zCOSMOS Bright Survey by their unusually large [OIII]5007 equivalent widths. Based on emission-line diagnostics, 165 purely star-forming EELGs and 18 narrow-line AGN candidates are identified. Using multiwavelength COSMOS photometry, HST-ACS I-band imaging and optical zCOSMOS spectroscopy we characterize their main physical properties. EELGs are small (R_50 ~ 1.3 kpc), low-mass (M*/Msol~10^7-10^10) galaxies forming stars at unusually high rates (SFR~0.1-35 Msol/yr), being among the highest specific SFRs galaxies in zCOSMOS. Consistently, the EELGs are luminous and extremely compact at rest-frame UV wavelengths and include strong Ly$\\alpha$ emitters, as revealed by GALEX spectroscopy. Using both direct and strong-line methods, we show that zCOSMOS EELGs are low-metallicity systems (12+log(O/H)=8.16 in the median) including several extremely metal-deficient galaxies (<10% solar). Fi...

  18. How extreme are extremes?

    Science.gov (United States)

    Cucchi, Marco; Petitta, Marcello; Calmanti, Sandro

    2016-04-01

    High temperatures have an impact on the energy balance of any living organism and on the operational capabilities of critical infrastructures. Heat-wave indicators have been mainly developed with the aim of capturing the potential impacts on specific sectors (agriculture, health, wildfires, transport, power generation and distribution). However, the ability to capture the occurrence of extreme temperature events is an essential property of a multi-hazard extreme climate indicator. Aim of this study is to develop a standardized heat-wave indicator, that can be combined with other indices in order to describe multiple hazards in a single indicator. The proposed approach can be used in order to have a quantified indicator of the strenght of a certain extreme. As a matter of fact, extremes are usually distributed in exponential or exponential-exponential functions and it is difficult to quickly asses how strong was an extreme events considering only its magnitude. The proposed approach simplify the quantitative and qualitative communication of extreme magnitude

  19. The Genome of the Self-Fertilizing Mangrove Rivulus Fish, Kryptolebias marmoratus: A Model for Studying Phenotypic Plasticity and Adaptations to Extreme Environments.

    Science.gov (United States)

    Kelley, Joanna L; Yee, Muh-Ching; Brown, Anthony P; Richardson, Rhea R; Tatarenkov, Andrey; Lee, Clarence C; Harkins, Timothy T; Bustamante, Carlos D; Earley, Ryan L

    2016-08-16

    The mangrove rivulus (Kryptolebias marmoratus) is one of two preferentially self-fertilizing hermaphroditic vertebrates. This mode of reproduction makes mangrove rivulus an important model for evolutionary and biomedical studies because long periods of self-fertilization result in naturally homozygous genotypes that can produce isogenic lineages without significant limitations associated with inbreeding depression. Over 400 isogenic lineages currently held in laboratories across the globe show considerable among-lineage variation in physiology, behavior, and life history traits that is maintained under common garden conditions. Temperature mediates the development of primary males and also sex change between hermaphrodites and secondary males, which makes the system ideal for the study of sex determination and sexual plasticity. Mangrove rivulus also exhibit remarkable adaptations to living in extreme environments, and the system has great promise to shed light on the evolution of terrestrial locomotion, aerial respiration, and broad tolerances to hypoxia, salinity, temperature, and environmental pollutants. Genome assembly of the mangrove rivulus allows the study of genes and gene families associated with the traits described above. Here we present a de novo assembled reference genome for the mangrove rivulus, with an approximately 900 Mb genome, including 27,328 annotated, predicted, protein-coding genes. Moreover, we are able to place more than 50% of the assembled genome onto a recently published linkage map. The genome provides an important addition to the linkage map and transcriptomic tools recently developed for this species that together provide critical resources for epigenetic, transcriptomic, and proteomic analyses. Moreover, the genome will serve as the foundation for addressing key questions in behavior, physiology, toxicology, and evolutionary biology.

  20. The Genome of the Self-Fertilizing Mangrove Rivulus Fish, Kryptolebias marmoratus: A Model for Studying Phenotypic Plasticity and Adaptations to Extreme Environments

    Science.gov (United States)

    Kelley, Joanna L.; Yee, Muh-Ching; Brown, Anthony P.; Richardson, Rhea R.; Tatarenkov, Andrey; Lee, Clarence C.; Harkins, Timothy T.; Bustamante, Carlos D.; Earley, Ryan L.

    2016-01-01

    The mangrove rivulus (Kryptolebias marmoratus) is one of two preferentially self-fertilizing hermaphroditic vertebrates. This mode of reproduction makes mangrove rivulus an important model for evolutionary and biomedical studies because long periods of self-fertilization result in naturally homozygous genotypes that can produce isogenic lineages without significant limitations associated with inbreeding depression. Over 400 isogenic lineages currently held in laboratories across the globe show considerable among-lineage variation in physiology, behavior, and life history traits that is maintained under common garden conditions. Temperature mediates the development of primary males and also sex change between hermaphrodites and secondary males, which makes the system ideal for the study of sex determination and sexual plasticity. Mangrove rivulus also exhibit remarkable adaptations to living in extreme environments, and the system has great promise to shed light on the evolution of terrestrial locomotion, aerial respiration, and broad tolerances to hypoxia, salinity, temperature, and environmental pollutants. Genome assembly of the mangrove rivulus allows the study of genes and gene families associated with the traits described above. Here we present a de novo assembled reference genome for the mangrove rivulus, with an approximately 900 Mb genome, including 27,328 annotated, predicted, protein-coding genes. Moreover, we are able to place more than 50% of the assembled genome onto a recently published linkage map. The genome provides an important addition to the linkage map and transcriptomic tools recently developed for this species that together provide critical resources for epigenetic, transcriptomic, and proteomic analyses. Moreover, the genome will serve as the foundation for addressing key questions in behavior, physiology, toxicology, and evolutionary biology. PMID:27324916

  1. THE ROLE OF IRON IN Deinococcus radiodurans ENGINEERED FOR GROWTH ON TOLUENE AND THE ROLE OF MANGANESE IN THE EXTREME RADIATION RESISTANCE PHENOTYPE

    Energy Technology Data Exchange (ETDEWEB)

    Hassan Brim; Elena K. Gaidamakova; Vera Y. Matrosova; Min Zhai; Amudhan Venkateswaran; Marina Omelchenko; Kira S. Makarova; Lawrence P. Wackett; James K. Fredrickson; Michael J. Daly

    2004-03-17

    Toluene and other fuel hydrocarbons are commonly found in association with radionuclides at numerous Department of Energy (DOE) sites, frequently occurring together with Cr(VI) and other heavy metals. In this study, the extremely radiation resistant bacterium Deinococcus radiodurans was engineered for complete toluene mineralization by cloned expression of tod and xyl genes of Pseudomonas putida. The recombinant Tod/Xyl strain showed significant incorporation of carbon from the toluene aromatic ring into cellular macromolecules and carbon dioxide, in the absence or presence of chronic radiation. We have shown that intracellular iron concentrations in wild-type D. radiodurans in minimal medium are exceptionally low and not sufficient to support growth on toluene using Fe-dependent oxygenases cloned from P. putida. Introducing the fur mutation into D. radiodurans increased intracellular Fe levels, and imparted on the engineered strain the ability to grow on meta-toluate as the sole carbon and energy source. The organism's native Cr(VI) reduction capabilities were facilitated by toluene when present as the sole carbon and energy source in natural sediment analogues of DOE contaminated environments. The engineered bacteria were able to oxidize toluene under both minimal and complex nutrient conditions, which is important since both conditions have environmental equivalents in the context of bioremediation processes. As such, the Tod/Xyl strain is providing a model for understanding the role of Fe and reduction of metals coupled to organic contaminant oxidation in aerobic radionuclide contaminated sediments. We have shown that D. radiodurans contains high intracellular manganese levels, and that Mn restriction sensitizes cells to irradiation. We propose that the unusually high Mn/Fe ratio of D. radiodurans facilitates survival by quenching oxidative stress during recovery.

  2. THE ROLE OF IRON IN Deinococcus radiodurans ENGINEERED FOR GROWTH ON TOLUENE AND THE ROLE OF MANGANESE IN THE EXTREME RADIATION RESISTANCE PHENOTYPE

    Energy Technology Data Exchange (ETDEWEB)

    Hassan Brim; Elena K. Gaidamakova; Vera Y. Matrosova; Min Zhai; Amudhan Venkateswaran; Marina Omelchenko; Kira S. Makarova; Lawrence P. Wackett; James K. Fredrickson; Michael J. Daly

    2004-03-17

    Toluene and other fuel hydrocarbons are commonly found in association with radionuclides at numerous Department of Energy (DOE) sites, frequently occurring together with Cr(VI) and other heavy metals. In this study, the extremely radiation resistant bacterium Deinococcus radiodurans was engineered for complete toluene mineralization by cloned expression of tod and xyl genes of Pseudomonas putida. The recombinant Tod/Xyl strain showed significant incorporation of carbon from the toluene aromatic ring into cellular macromolecules and carbon dioxide, in the absence or presence of chronic radiation. We have shown that intracellular iron concentrations in wild-type D. radiodurans in minimal medium are exceptionally low and not sufficient to support growth on toluene using Fe-dependent oxygenases cloned from P. putida. Introducing the fur mutation into D. radiodurans increased intracellular Fe levels, and imparted on the engineered strain the ability to grow on meta-toluate as the sole carbon and energy source. The organism's native Cr(VI) reduction capabilities were facilitated by toluene when present as the sole carbon and energy source in natural sediment analogues of DOE contaminated environments. The engineered bacteria were able to oxidize toluene under both minimal and complex nutrient conditions, which is important since both conditions have environmental equivalents in the context of bioremediation processes. As such, the Tod/Xyl strain is providing a model for understanding the role of Fe and reduction of metals coupled to organic contaminant oxidation in aerobic radionuclide contaminated sediments. We have shown that D. radiodurans contains high intracellular manganese levels, and that Mn restriction sensitizes cells to irradiation. We propose that the unusually high Mn/Fe ratio of D. radiodurans facilitates survival by quenching oxidative stress during recovery.

  3. Extreme robustness of scaling in sample space reducing processes explains Zipf's law in diffusion on directed networks

    CERN Document Server

    Corominas-Murtra, Bernat; Thurner, Stefan

    2016-01-01

    Sample Space Reducing processes (SSRP) offer an alternative new mechanism to understand the emergence of scaling in countless phenomena. We demonstrate that the scaling exponents associated to the dynamics of SSRPs converge to Zipf's law for a large class of systems. We show that Zipf's law emerges as a generic feature of diffusion on directed networks, regardless of its details, and that the exponent of the visiting time distribution is related to the amount of cycles in the network. These results are relevant for a series of applications in traffic, transport, and supply chain management.

  4. Extreme robustness of scaling in sample space reducing processes explains Zipf’s law in diffusion on directed networks

    Science.gov (United States)

    Corominas-Murtra, Bernat; Hanel, Rudolf; Thurner, Stefan

    2016-09-01

    It has been shown recently that a specific class of path-dependent stochastic processes, which reduce their sample space as they unfold, lead to exact scaling laws in frequency and rank distributions. Such sample space reducing processes offer an alternative new mechanism to understand the emergence of scaling in countless processes. The corresponding power law exponents were shown to be related to noise levels in the process. Here we show that the emergence of scaling is not limited to the simplest SSRPs, but holds for a huge domain of stochastic processes that are characterised by non-uniform prior distributions. We demonstrate mathematically that in the absence of noise the scaling exponents converge to -1 (Zipf’s law) for almost all prior distributions. As a consequence it becomes possible to fully understand targeted diffusion on weighted directed networks and its associated scaling laws in node visit distributions. The presence of cycles can be properly interpreted as playing the same role as noise in SSRPs and, accordingly, determine the scaling exponents. The result that Zipf’s law emerges as a generic feature of diffusion on networks, regardless of its details, and that the exponent of visiting times is related to the amount of cycles in a network could be relevant for a series of applications in traffic-, transport- and supply chain management.

  5. Sampling

    CERN Document Server

    Thompson, Steven K

    2012-01-01

    Praise for the Second Edition "This book has never had a competitor. It is the only book that takes a broad approach to sampling . . . any good personal statistics library should include a copy of this book." —Technometrics "Well-written . . . an excellent book on an important subject. Highly recommended." —Choice "An ideal reference for scientific researchers and other professionals who use sampling." —Zentralblatt Math Features new developments in the field combined with all aspects of obtaining, interpreting, and using sample data Sampling provides an up-to-date treat

  6. Distinct variants of extreme psychopathic individuals in society at large: evidence from a population-based sample.

    Science.gov (United States)

    Drislane, Laura E; Patrick, Christopher J; Sourander, Andre; Sillanmäki, Lauri; Aggen, Steven H; Elonheimo, Henrik; Parkkola, Kai; Multimäki, Petteri; Kendler, Kenneth S

    2014-04-01

    This study used model-based cluster analysis to identify subtypes of men who scored high in overall psychopathy (i.e., ≥ 95th percentile on the Triarchic Psychopathy Measure; n = 193) from a larger sample evaluated for service in the Finnish military (N = 4043). Cluster variates consisted of scores on distinct facets of psychopathy together with a measure of negative affectivity. The best-fitting model specified 2 clusters, representing "primary" (n = 110) and "secondary" psychopathy (n = 83) groups. Compared to a low-psychopathy comparison group (n = 1878), both psychopathy subgroups showed markedly elevated levels of externalizing symptoms and criminal behavior. Secondary psychopathic participants also reported high levels of internalizing problems including anxiousness, depression, and somatization, and scored higher on the disinhibition facet of psychopathy relative to the primary group. By contrast, primary psychopathic individuals reported fewer internalizing problems than either the secondary psychopathy or comparison groups and scored higher on the boldness facet of psychopathy. Primary psychopathic participants also had higher rates of violent crimes than the secondary psychopaths. Implications for conceptualizing and studying psychopathy in nonforensic populations are discussed.

  7. Antibiotic Resistance and the Frequency of Extended-Spectrum B-Lactamase in Acinetobacter baumannii Isolated from Clinical Samples through Phenotypic Methods

    Directory of Open Access Journals (Sweden)

    Somayeh Vafaei

    2013-07-01

    Full Text Available AbstractBackground and objectives: Nowadays Acinetobacter baumannii is as one of the problematic opportunistic pathogens, especially in intensive care because of the incidence of drug-resistant strains in the world. The purpose of current study was to define the antibiotic susceptibility patterns and detect the prevalence of producing strains of extended-spectrum β-lactamase (ESBL in A. baumannii isolates which had been isolated from clinical samples with combined disk test.Materials and methods: This study was conducted in 3 major hospitals in Tehran on 500 clinical samples during 6 months. After identification of isolates in species level using cultural and biochemical methods, in order to determine sensitivity of 100 isolates of A. baumannii to 11 antibiotics, the susceptibility tests were carried out according to CLSI guidelines using disk diffusion method. Also MIC (Minimum inhibitory concentrations was determined for cefepime and ceftazidime, and finally to identify of producing strains of ESBL was applied phenotypic method of combined disk. Results: In this survey, 100 A. baumannii strains, 30 A. lwoffii strains and other Acinetobacter species were isolated from patients. The majority of isolates were from blood specimens. Isolates of A.baumannii revealed the highest resistance to cefepime, ceftriaxone, amikacin, imipenem, piperacillin - tazobactam, meropenem, gentamicin, tobramycina and tetracycline, respectively. Ampicillin - sulbactam and polymyxin B considered as effective drugs in this study. Multi-drug resistance in these strains was 70%. The Total isolates studied the Minimum inhibitory concentrations of ceftazidime in 84% samples was MIC ≥ 128 μg/ml and Minimum inhibitory concentrations of cefepime in 91% samples was MIC≥ 128 μg/ml. According to the results of combined disk test, 20% of total samples were demonstrated to be ESBL positive.Conclusion: Regarding to produce of ESBL in this bacterium and possibility of

  8. Characterization of multi-drug resistant ESBL producing nonfermenter bacteria isolated from patients blood samples using phenotypic methods in Shiraz (Iran

    Directory of Open Access Journals (Sweden)

    Maneli Amin Shahidi

    2015-10-01

    Full Text Available Background and Aim: The emergence of  nonfermenter bacteria that are resistant to multidrug resistant ESBL  are  nowadays a principal problem  for hospitalized patients. The present study aimed at surveying the emergence of nonfermenter bacteria resistant to multi-drug ESBL producing isolated from patients blood samples using BACTEC 9240 automatic system in Shiraz. Materials and Methods: In this cross-sectional study, 4825 blood specimens were collected from hospitalized patients in Shiraz (Iran, and positive samples were detected by means of  BACTEC 9240 automatic system. The isolates  containing nonfermenter bacteria were identified based on biochemical tests embedded in the API-20E system. Antibiotic sensitivity  test was performed  and identification of  ESBL producing strains were done  using phenotypic detection of extended spectrum beta-lactamase producing isolates(DDST according to CLSI(2013 guidelines.   Results: Out of 4825 blood samples, 1145 (24% specimen were gram-positive using BACTEC system. Among all isolated microorganisms, 206 isolates were non-fermenting gram- negative bacteria. The most common non-fermenter isolates were Pseudomonas spp. (48%, Acinetobacter spp. (41.7% ,and Stenotrophomonas spp. (8.2%. Seventy of them (81.4% were  Acinetobacter spp. which were ESBL positive. Among &beta-lactam antibiotics, Pseudomonas spp. showed  the best sensitivity to piperacillin-tazobactam (46.5%.  Conclusion: It was found that  &beta-lactam antibiotics are not effective against more than 40% of Pseudomonas spp. infections and 78% Acinetobacter infections. Emergence of multi-drug resistant strains that are resistant to most antibiotic classes is a major public health problem in Iran. To resolve this problem using of practical guidelines is critical.

  9. Limited sampling strategy of partial area-under-the-concentration-time-curves to estimate midazolam systemic clearance for cytochrome P450 3A phenotyping

    Science.gov (United States)

    Masters, Joanna C.; Harano, Denise M.; Greenberg, Howard E.; Tsunoda, Shirley M.; Jang, In-Jin; Ma, Joseph D.

    2014-01-01

    Objective Intravenous (IV) midazolam is the preferred cytochrome P450 (CYP) 3A probe for phenotyping, with systemic clearance (CL) estimating hepatic CYP3A activity. A limited sampling strategy was conducted to determine if partial area-under-the-concentration-time-curves (AUCs) could reliably estimate midazolam systemic CL during conditions of CYP3A baseline activity, inhibition and induction/activation. Methods Midazolam plasma concentrations during CYP3A baseline (n=93), inhibition (n=40), and induction/activation (n=33) were obtained from seven studies in healthy adults. Non-compartmental analysis determined observed CL (CLobs) and partial AUCs. Linear regression equations were derived from partial AUCs to estimate CL (CLpred) during CYP3A baseline, inhibition and induction/activation. Pre-established criterion for linear regression analysis was r2 ≥0.9. CLpred was compared to CLobs, and relative bias and precision were assessed using percent mean prediction error (%MPE) and percent mean absolute error (%MAE). Results During CYP3A baseline and inhibition, all evaluated partial AUCs failed to meet criterion of r2 ≥0.9 and/or %MAE midazolam partial AUC0–1, AUC0–2, and AUC0–4 reliably estimated systemic CL, and consequently hepatic CYP3A activity in healthy adults. PMID:25004135

  10. Clinical and cytogenetic features of a Brazilian sample of patients with phenotype of oculo-auriculo-vertebral spectrum: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Alessandra Pawelec da Silva

    Full Text Available CONTEXT AND OBJECTIVE: Oculo-auriculo-vertebral spectrum (OAVS is considered to be a defect of embryogenesis involving structures originating from the first branchial arches. Our objective was to describe the clinical and cytogenetic findings from a sample of patients with the phenotype of OAVS.DESIGN AND SETTING: Cross-sectional study in a referral hospital in southern Brazil.METHODS: The sample consisted of 23 patients who presented clinical findings in at least two of these four areas: orocraniofacial, ocular, auricular and vertebral. The patients underwent a clinical protocol and cytogenetic evaluation through high-resolution karyotyping, fluorescence in situ hybridization for 5p and 22q11 microdeletions and investigation of chromosomal instability for Fanconi anemia.RESULTS: Cytogenetic abnormalities were observed in three cases (13% and consisted of: 47,XX,+mar; mos 47,XX,+mar/46,XX; and 46,XX,t(6;10(q13; q24. We observed cases of OAVS with histories of gestational exposition to fluoxetine, retinoic acid and crack. One of our patients was a discordant monozygotic twin who had shown asymmetrical growth restriction during pregnancy. Our patients with OAVS were characterized by a broad clinical spectrum and some presented atypical findings such as lower-limb reduction defect and a tumor in the right arm, suggestive of hemangioma/lymphangioma.CONCLUSIONS: We found a wide range of clinical characteristics among the patients with OAVS. Different chromosomal abnormalities and gestational expositions were also observed. Thus, our findings highlight the heterogeneity of the etiology of OAVS and the importance of these factors in the clinical and cytogenetic evaluation of these patients.

  11. The frequency of Listeria monocytogenes strains recovered from clinical and non-clinical samples using phenotypic methods and confirmed by PCR

    Directory of Open Access Journals (Sweden)

    abazar pournajaf

    2013-09-01

    Full Text Available Background: Listeria monocytogenes is a facultative intracellular pathogen that causes listeriosis which has extensive clinical manifestations. Infections with L. monocytogenes are a serious threat to immunocompromised persons. The aim of this study was to determine the frequency of L. monocytogenes strains recovered from clinical and non-clinical samples using phenotypic methods and confirmed by PCR. Materials and Methods: In this study, 617 specimens were analyzed. All specimens were cultured in the specific PALCAM agar. Colonies were initially identified by routine biochemical tests. Finally, PCR assays using primers specific for inlA gene were performed. Results: In all, 46 (8.2% L. monocytogenes isolates were recovered from 617 specimens. Fourteen (8.2% strains, including 4 (7.5%, 2 (5.7%, 5 (14.2% and 3 (8.5% isolates were obtained from placental tissue, urine, vaginal and rectal swabs, respectively. In addition, 9 (7.4% strains of L. monocytogenes which were isolated from 107 different dairy products originated from cheese 5 (7.1%, cream 2 (10% and kashk 2 (11.7%, respectively. Among 11 (5.2% strains isolated from 210 different meat products, 5 (5.5%, 4 (7.2% and 2 (3% strains belonged to sausage, meat and poultry extracts, respectively. Finally, 12 (9.2% Listeria strains were recovered from 130 animal specimens that included 6 (10%, 4 (8% and 2 (10% strains from goat, sheep and cattle, respectively. Furthermore, all Listeria isolates (100% were found to be carriers of  inlA gene in PCR assay. Conclusion: The present study showed that the clinical and non-clinical specimens were contaminated with L. monocytogenes. So, it seems necessary to use a simple and standard technique such as PCR for rapid detection of this organism from various sources.

  12. Determination of extremely low {sup 236}U/{sup 238}U isotope ratios in environmental samples by sector-field inductively coupled plasma mass spectrometry using high-efficiency sample introduction

    Energy Technology Data Exchange (ETDEWEB)

    Boulyga, Sergei F. [Institute of Inorganic Chemistry and Analytical Chemistry, Johannes Gutenberg-University Mainz, Duesbergweg 10-14, 55099 Mainz (Germany)]. E-mail: sergei.boulyga@univie.ac.at; Heumann, Klaus G. [Institute of Inorganic Chemistry and Analytical Chemistry, Johannes Gutenberg-University Mainz, Duesbergweg 10-14, 55099 Mainz (Germany)

    2006-07-01

    A method by inductively coupled plasma mass spectrometry (Icp-Ms) was developed which allows the measurement of {sup 236}U at concentration ranges down to 3 x 10{sup -14} g g{sup -1} and extremely low {sup 236}U/{sup 238}U isotope ratios in soil samples of 10{sup -7}. By using the high-efficiency solution introduction system APEX in connection with a sector-field ICP-MS a sensitivity of more than 5000 counts fg{sup -1} uranium was achieved. The use of an aerosol desolvating unit reduced the formation rate of uranium hydride ions UH{sup +}/U{sup +} down to a level of 10{sup -6}. An abundance sensitivity of 3 x 10{sup -7} was observed for {sup 236}U/{sup 238}U isotope ratio measurements at mass resolution 4000. The detection limit for {sup 236}U and the lowest detectable {sup 236}U/{sup 238}U isotope ratio were improved by more than two orders of magnitude compared with corresponding values by alpha spectrometry. Determination of uranium in soil samples collected in the vicinity of Chernobyl nuclear power plant (NPP) resulted in that the {sup 236}U/{sup 238}U isotope ratio is a much more sensitive and accurate marker for environmental contamination by spent uranium in comparison to the {sup 235}U/{sup 238}U isotope ratio. The ICP-MS technique allowed for the first time detection of irradiated uranium in soil samples even at distances more than 200 km to the north of Chernobyl NPP (Mogilev region). The concentration of {sup 236}U in the upper 0-10 cm soil layers varied from 2 x 10{sup -9} g g{sup -1} within radioactive spots close to the Chernobyl NPP to 3 x 10{sup -13} g g{sup -1} on a sampling site located by >200 km from Chernobyl.

  13. Detection of vancomycin resistance in enterococcus species isolated from clinical samples and feces of colonized patients by phenotypic and genotypic methods

    Directory of Open Access Journals (Sweden)

    Priyanka Paul Biswas

    2016-01-01

    Full Text Available Background: The aim of this study was to find out the clinical correlation between the presence of vancomycin-resistant genes (van A and van B and their expression as detected by phenotypic tests in colonized patients and in clinical isolates. Materials and Methods: Enterococci were isolated from various clinical samples and also from fecal specimens of colonized patients at the time of admission, after 48 h and after 5 days of admission. Identification to species level was done using standard methods. Vancomycin susceptibility in Enterococci was detected by disc diffusion test. Minimum inhibitory concentration was determined by agar dilution method. Multiplex polymerase chain reaction (PCR was used to detect the presence of van genes. Results: Out of all the clinical and fecal samples processed, 12.0% isolates were either vancomycin resistant or vancomycin intermediate. Further, these isolates carried van A or van B genes as confirmed by PCR methods. Expression of van A gene was found to be more in Enterococcus faecalis (28.3% as compared to Enterococcus faecium (25.0% in both clinical and fecal isolates. 16.6% strains of E. faecium and 15.0% strains each of E. faecalis and Enterococcus gallinarum were found to carry van B genes. The overall prevalence of vancomycin resistant Enterococci (VRE in colonized patients was about 9.6%. Prior administration of antibiotics had significant effect (P = 0.001 on VRE carriage. Urinary tract infection was the most common infection caused by vancomycin susceptible Enterococci (VSE, 105/214 (49.0% and VRE, 13/36 (36.1%. There was no significant difference (P = 0.112 in the distribution of VRE and VSE in different infection types. Both clinical and fecal VRE showed maximum resistance to penicillin, ampicillin, and piperacillin. Resistance to linezolid was 2.8% in clinically isolated VRE. Conclusion: VRE in our study were found to be resistant to a number of commonly used antibiotics. The frequency of isolation

  14. Phenotypic characterization and 16S rDNA identification of culturable non-obligate halophilic bacterial communities from a hypersaline lake, La Sal del Rey, in extreme South Texas (USA)

    Science.gov (United States)

    2012-01-01

    phenotypic diversity with regards to the types and number of positive tests from the strip. Isolates taken from water samples at the highest salinity (420 ppt) tended to be less diverse and have only a limited number of positive tests. Sequencing of 16S DNA displayed the presence of members of bacterial genera Bacillus, Halomonas, Pseudomonas, Exiguobacterium and others. The genus Bacillus was most commonly identified. None of the isolates were members of the Archaea probably due to dilution of salts in the samples. Conclusions The La Sal del Rey ecosystem supports a robust and diverse bacterial community despite the high salinity of the lake and soil. However, salinity does appear to a limiting factor with regards to the density and diversity of the bacterial communities that inhabit the lake and surrounding area. PMID:22480362

  15. Impact of Glycoprotein IIb/IIIa Inhibitors Use on Outcomes After Lower Extremity Endovascular Interventions From Nationwide Inpatient Sample (2006-2011).

    Science.gov (United States)

    Echeverria, Angela; Krajcer, Zvonimir

    2016-10-01

    Anticoagulant and antiplatelet medications are necessary in peripheral endovascular intervention, but a standardized approach has not yet been established. Glycoprotein IIb/IIIa inhibitor use in endovascular lower extremity interventions decreased overall amputation rates. Glycoprotein IIb/IIIa inhibitor use in endovascular lower extremity interventions increased postprocedural bleeding and complications requiring intervention.

  16. Extreme Heat

    Science.gov (United States)

    ... Landslides & Debris Flow Nuclear Blast Nuclear Power Plants Power Outages Pandemic Radiological Dispersion Device Severe Weather Snowstorms & Extreme ... Landslides & Debris Flow Nuclear Blast Nuclear Power Plants Power Outages Pandemic Radiological Dispersion Device Severe Weather Snowstorms & Extreme ...

  17. Phenotype definition in epilepsy.

    Science.gov (United States)

    Winawer, Melodie R

    2006-05-01

    Phenotype definition consists of the use of epidemiologic, biological, molecular, or computational methods to systematically select features of a disorder that might result from distinct genetic influences. By carefully defining the target phenotype, or dividing the sample by phenotypic characteristics, we can hope to narrow the range of genes that influence risk for the trait in the study population, thereby increasing the likelihood of finding them. In this article, fundamental issues that arise in phenotyping in epilepsy and other disorders are reviewed, and factors complicating genotype-phenotype correlation are discussed. Methods of data collection, analysis, and interpretation are addressed, focusing on epidemiologic studies. With this foundation in place, the epilepsy subtypes and clinical features that appear to have a genetic basis are described, and the epidemiologic studies that have provided evidence for the heritability of these phenotypic characteristics, supporting their use in future genetic investigations, are reviewed. Finally, several molecular approaches to phenotype definition are discussed, in which the molecular defect, rather than the clinical phenotype, is used as a starting point.

  18. Mandelbrot's Extremism

    NARCIS (Netherlands)

    Beirlant, J.; Schoutens, W.; Segers, J.J.J.

    2004-01-01

    In the sixties Mandelbrot already showed that extreme price swings are more likely than some of us think or incorporate in our models.A modern toolbox for analyzing such rare events can be found in the field of extreme value theory.At the core of extreme value theory lies the modelling of maxima

  19. Sex differences in utilization and outcomes of catheter-directed thrombolysis in patients with proximal lower extremity deep venous thrombosis - Insights from the Nationwide Inpatient Sample.

    Science.gov (United States)

    Lakhter, Vladimir; Zack, Chad J; Brailovsky, Yevgeniy; Chatterjee, Saurav; Aggarwal, Vikas; Rao, Koneti A; Crabbe, Deborah; Zhao, Huaqing; Choi, Eric; Kolluri, Raghu; Bashir, Riyaz

    2017-04-01

    Catheter-directed thrombolysis (CDT) is being increasingly used for the treatment of proximal lower extremity (LE) deep venous thrombosis (DVT). However, sex differences in utilization and safety outcomes of CDT in these patients are unknown. The Nationwide Inpatient Sample (NIS) database was used to identify all patients with a principal discharge diagnosis of proximal LE or caval DVT who underwent CDT between January 2005 and December 2011 in the United States. We evaluated the comparative safety outcomes of CDT among a propensity-matched group of 1731 men versus 1731 women. Among 108,243 patients with proximal LE or caval DVT, 4826 patients (4.5%) underwent CDT. Overall, women underwent CDT less often compared to men (4.1% vs 4.9%, p<0.01, respectively). The rates of CDT increased between 2005 and 2011 for both women (2.1% to 5.9%, p<0.01) and men (2.5% to 7.5%, p<0.01). There was no significant difference in in-hospital mortality (1.2% vs 1.3%, p=0.76). Women were noted to have higher rates of blood transfusions (11.7% vs 8.8%, p<0.01), but lower rates of intracranial hemorrhage (0.5% vs 1.2%, p=0.03) and gastrointestinal bleeding (0.9% vs 2.2%, p<0.01) compared with men. Women were more likely to undergo inferior vena cava filter placement (37.0% vs 32.1%, p<0.01). In this large nationwide cohort, women with proximal DVT were less likely to receive CDT compared to men. Although mortality rates were similar, women were noted to have higher blood transfusion rates while men had more episodes of intracranial and gastrointestinal bleeding.

  20. Association and ancestry analysis of sequence variants in ADH and ALDH using alcohol-related phenotypes in a Native American community sample.

    Science.gov (United States)

    Peng, Qian; Gizer, Ian R; Libiger, Ondrej; Bizon, Chris; Wilhelmsen, Kirk C; Schork, Nicholas J; Ehlers, Cindy L

    2014-12-01

    Higher rates of alcohol use and other drug-dependence have been observed in some Native American (NA) populations relative to other ethnic groups in the US. Previous studies have shown that alcohol dehydrogenase (ADH) genes and aldehyde dehydrogenase (ALDH) genes may affect the risk of development of alcohol dependence, and that polymorphisms within these genes may differentially affect risk for the disorder depending on the ethnic group evaluated. We evaluated variations in the ADH and ALDH genes in a large study investigating risk factors for substance use in a NA population. We assessed ancestry admixture and tested for associations between alcohol-related phenotypes in the genomic regions around the ADH1-7 and ALDH2 and ALDH1A1 genes. Seventy-two ADH variants showed significant evidence of association with a severity level of alcohol drinking-related dependence symptoms phenotype. These significant variants spanned across the entire 7 ADH gene cluster regions. Two significant associations, one in ADH and one in ALDH2, were observed with alcohol dependence diagnosis. Seventeen variants showed significant association with the largest number of alcohol drinks ingested during any 24-hour period. Variants in or near ADH7 were significantly negatively associated with alcohol-related phenotypes, suggesting a potential protective effect of this gene. In addition, our results suggested that a higher degree of NA ancestry is associated with higher frequencies of potential risk variants and lower frequencies of potential protective variants for alcohol dependence phenotypes. © 2014 Wiley Periodicals, Inc.

  1. Phenotypic plasticity and modularity allow for the production of novel mosaic phenotypes in ants

    OpenAIRE

    Londe, Sylvain; Monnin, Thibaud; Cornette, Raphaël; Debat, Vincent; Brian L Fisher; Molet, Mathieu

    2015-01-01

    International audience; Background: The origin of discrete novelties remains unclear. Some authors suggest that qualitative phenotypic changes may result from the reorganization of preexisting phenotypic traits during development (i.e., developmental recombination) following genetic or environmental changes. Because ants combine high modularity with extreme phenotypic plasticity (queen and worker castes), their diversified castes could have evolved by developmental recombination. We performed...

  2. Characterization of Fusarium graminearum isolates recovered from wheat samples from Argentina by Fourier transform infrared spectroscopy: Phenotypic diversity and detection of specific markers of aggressiveness.

    Science.gov (United States)

    Fígoli, Cecilia B; Rojo, Rodrigo; Gasoni, Laura A; Kikot, Gisele; Leguizamón, Mariana; Gamba, Raúl R; Bosch, Alejandra; Alconada, Teresa M

    2017-03-06

    Fusarium graminearum is the primary causal agent of Fusarium head blight of wheat in Argentina. This disease affects crop yields and grain quality also reducing the wheat end-use, and causing mycotoxin contamination. The aim of this work was to analyze the phenotypic characteristics associated with phenotypic diversity and aggressiveness of 34 F. graminearum sensu stricto isolates recovered from Argentinean fields in the 2008 growing season using the Fourier Transform Infrared (FTIR) dried film technology. We applied this technique also to search for spectral specific markers associated with aggressiveness. The combination of FTIR technology with hierarchical cluster analysis allowed us to determine that this population constitutes a highly diverse and heterogeneous group of fungi with significant phenotypic variance. Still, when the spectral features of a set of these isolates were compared against their aggressiveness, as measured by disease severity, thousand grains weight, and relative yield reduction, we found that the more aggressive isolates were richer in lipid content. Therefore, we could define several spectroscopic markers (>CH stretching modes in the 3000-2800 window, >CO and CO vibrational modes of esters at 1765-1707cm(-1) and 1474-900cm(-1), respectively), mostly assigned to lipid content that could be associated with F. graminearum aggressiveness. All together, by the application of FTIR techniques and simple multivariate analyses, it was possible to gain significant insights into the phenotypic characterization of F. graminearum local isolates, and to establish the existence of a direct relationship between lipid content and fungal aggressiveness. Considering that lipids have a major role as mediators in the interaction between plants and fungi our results could represent an attractive outcome in the study of Fusarium pathogenesis. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Molecular mechanisms of phenotypic plasticity in social insects

    Science.gov (United States)

    Polyphenism in insects, whereby a single genome expresses different phenotypes in response to environmental cues, is a fascinating biological phenomenon. Social insects are especially intriguing examples of phenotypic plasticity because division of labor results in the development of extreme morphol...

  4. Extreme cosmos

    CERN Document Server

    Gaensler, Bryan

    2011-01-01

    The universe is all about extremes. Space has a temperature 270°C below freezing. Stars die in catastrophic supernova explosions a billion times brighter than the Sun. A black hole can generate 10 million trillion volts of electricity. And hypergiants are stars 2 billion kilometres across, larger than the orbit of Jupiter. Extreme Cosmos provides a stunning new view of the way the Universe works, seen through the lens of extremes: the fastest, hottest, heaviest, brightest, oldest, densest and even the loudest. This is an astronomy book that not only offers amazing facts and figures but also re

  5. Mouse phenotyping.

    Science.gov (United States)

    Fuchs, Helmut; Gailus-Durner, Valérie; Adler, Thure; Aguilar-Pimentel, Juan Antonio; Becker, Lore; Calzada-Wack, Julia; Da Silva-Buttkus, Patricia; Neff, Frauke; Götz, Alexander; Hans, Wolfgang; Hölter, Sabine M; Horsch, Marion; Kastenmüller, Gabi; Kemter, Elisabeth; Lengger, Christoph; Maier, Holger; Matloka, Mikolaj; Möller, Gabriele; Naton, Beatrix; Prehn, Cornelia; Puk, Oliver; Rácz, Ildikó; Rathkolb, Birgit; Römisch-Margl, Werner; Rozman, Jan; Wang-Sattler, Rui; Schrewe, Anja; Stöger, Claudia; Tost, Monica; Adamski, Jerzy; Aigner, Bernhard; Beckers, Johannes; Behrendt, Heidrun; Busch, Dirk H; Esposito, Irene; Graw, Jochen; Illig, Thomas; Ivandic, Boris; Klingenspor, Martin; Klopstock, Thomas; Kremmer, Elisabeth; Mempel, Martin; Neschen, Susanne; Ollert, Markus; Schulz, Holger; Suhre, Karsten; Wolf, Eckhard; Wurst, Wolfgang; Zimmer, Andreas; Hrabě de Angelis, Martin

    2011-02-01

    Model organisms like the mouse are important tools to learn more about gene function in man. Within the last 20 years many mutant mouse lines have been generated by different methods such as ENU mutagenesis, constitutive and conditional knock-out approaches, knock-down, introduction of human genes, and knock-in techniques, thus creating models which mimic human conditions. Due to pleiotropic effects, one gene may have different functions in different organ systems or time points during development. Therefore mutant mouse lines have to be phenotyped comprehensively in a highly standardized manner to enable the detection of phenotypes which might otherwise remain hidden. The German Mouse Clinic (GMC) has been established at the Helmholtz Zentrum München as a phenotyping platform with open access to the scientific community (www.mousclinic.de; [1]). The GMC is a member of the EUMODIC consortium which created the European standard workflow EMPReSSslim for the systemic phenotyping of mouse models (http://www.eumodic.org/[2]). Copyright © 2010 Elsevier Inc. All rights reserved.

  6. Extreme emission-line galaxies out to z similar to 1 in zCOSMOS I. Sample and characterization of global properties

    NARCIS (Netherlands)

    Amorin, R.; Perez-Montero, F.; Contini, T.; Vilchez, J. M.; Bolzonella, M.; Tasca, L. A. M.; Lamareille, F.; Zamorani, G.; Maier, C.; Carollo, C. M.; Kneib, J. -P.; Le Fevre, O.; Lilly, S.; Mainieri, V.; Renzinis, A.; Scodeggio, M.; Bardelli, S.; Bongiorno, A.; Caputi, K.; Cucciati, O.; de la Torre, S.; de Ravel, L.; Franzetti, P.; Garilli, B.; Iovino, A.; Kampczyk, P.; Knobel, C.; Kovac, K.; Le Borgne, J. -F.; Le Brun, V.; Mignoli, M.; Pello, R.; Peng, Y.; Presotto, V.; Ricciardelli, E.; Silverman, J. D.; Tanaka, M.; Tresse, L.; Vergani, D.; Zucca, E.

    2015-01-01

    Context. The study of large and representative samples of low-metallicity star-forming galaxies at different cosmic epochs is of great interest to the detailed understanding of the assembly history and evolution of low-mass galaxies. Aims. We present a thorough characterization of a large sample of

  7. Detection of the Klebsiella pneumoniae carbapenemase (KPC) in K. pneumoniae Isolated from the Clinical Samples by the Phenotypic and Genotypic Methods

    Science.gov (United States)

    Bina, Masoume; Pournajaf, Abazar; Mirkalantari, Shiva; Talebi, Malihe; Irajian, Gholamreza

    2015-01-01

    Background and Objective: The production of carbapenemases especially Klebsiella pneumoniae carbapenemase (KPC) is the most important mechanism of enzymatic resistance in isolated Enterobacteriaceae such as K. pneumoniae . The purpose of this study was detected of the carbapenemase producer K. pneumoniae strains with phenotypic and genotypic methods. Method: Out of 800 strains, 270 K. pneumoniae strains (33.7%), were obtained. Antibiotic susceptibility test was performed by disk diffusion method in accordance with CLSI guidelines. Carbapenem resistant strains were identified by the Modified Hodge Test based on CLSI instruction and PCR for surveying the presence of bla -KPC gene. Results: A total 270 K. pneumoniae strains were collected. Antibiotic susceptibility test results showed the highest and lowest resistance was related to piperacillin (60.6%) and carbapenems (14.6%) respectively. 80.5% (33 of 41) isolates were positive by MHT, but all of them (100%) were negative for amplification of the bla -KPC gene in the PCR method. Conclusion: The MHT was an appropriate method for approving carbapenemase production. Moreover, a laboratory could accept the carbapenemase production with PCR method for the bla-KPC gene, which has the additional profit of validating which KPC is present. PMID:26351485

  8. The relationship between purely stochastic sampling error and the number of technical replicates used to estimate concentration at an extreme dilution.

    Science.gov (United States)

    Irwin, Peter L; Nguyen, Ly-Huong T; Chen, Chin-Yi

    2010-09-01

    For any analytical system the population mean (μ) number of entities (e.g., cells or molecules) per tested volume, surface area, or mass also defines the population standard deviation (σ = square root(μ)). For a preponderance of analytical methods, σ is very small relative to μ due to their large limit of detection (>10(2) per volume). However, in theory at least, DNA-based detection methods (real-time, quantitative or qPCR) can detect ≈ 1 DNA molecule per tested volume (i.e., μ ≈ 1) whereupon errors of random sampling can cause sample means (mean) to substantially deviate from μ if the number of samplings (n), or "technical replicates", per observation is too small. In this work the behaviors of two measures of sampling error (each replicated fivefold) are examined under the influence of n. For all data (μ = 1.25, 2.5, 5, 7.5, 10, and 20) a large sample of individual analytical counts (x) were created and randomly assigned into N integral-valued sub-samples each containing between 2 and 50 repeats (n) whereupon N × n = 322 to 361. From these data the average μ-normalized deviation of σ from each sub-sample's standard deviation estimate (s(j), j = 1 to N; N = 7 [n = 50] to 180 [n = 2]) was calculated (Δ). Alternatively, the average μ-normalized deviation of μ from each sub-sample's mean estimate (mean(j)) was also evaluated (Δ'). It was found that both of these empirical measures of sampling error were proportional to ⁻²√n . μ. Derivative (∂/∂n · Δ or Δ') analyses of our results indicate that a large number of samplings (n ≈ 33 +/- 3.1) are requisite to achieve a nominal sampling error for samples with a μ ≈ 1. This result argues that pathogen detection is most economically performed, even using highly sensitive techniques such as qPCR, when some form of organism cultural enrichment is utilized and which results in a binomial response. Thus, using a specific gene PCR-based (+ or -) most probable number (MPN

  9. Phenotypic stability via ammi model with bootstrap re-sampling Estabilidade fenotípica através da reamostragem “bootstrap” no modelo AMMI

    Directory of Open Access Journals (Sweden)

    Osmir José Lavoranti

    2010-06-01

    Full Text Available Reliable evaluation of the stability of genotypes and environment is of prime concern to plant breeders, but the lack of a comprehensive analysis of the structure of the GE interaction has been a stumbling block to the recommendation of varieties. The Additive Main Effects and Multiplicative Interaction (AMMI Model currently offers the good approach to interpretation and  understanding of the GE interaction but lacks a way of assessing the stability of its estimates. The present contribution proposes the use of bootstrap resampling
    in the AMMI Model, and applies it to obtain both a graphical and a numerical analysis of the phenotypic
    stability of 20 Eucalyptus grandis progenies from Australia that were planted in seven environments in the Southern and Southeastern regions of Brazil. The results showed distinct behaviors of genotypes and
    environments and the genotype x environment interaction was significant (p value < 0.01. The bootstrap coefficient of stability based on the squared Mahalanobis distance of the scores showed that genotypes and environments can be differentiated in terms of their stabilities. Graphical analysis of the AMMI biplot provided a better understanding of the interpretation of phenotypic stability. The proposed AMMI bootstrap eliminated the uncertainties regarding the identification of low scores in traditional analyses.As posições críticas dos estatísticos, que atuam em programas de melhoramento genético, referem-se à falta de uma análise criteriosa da estrutura da interação do genótipo com o ambiente (GE como um dos principais problemas para a recomendação de cultivares. A metodologia AMMI (additive main effects and multiplicative interaction analysis propõe ser mais eficiente que as análises usuais na interpretação e compreensão da interação GE, entretanto, à dificuldade de se interpretar a interação quando há baixa explicação do primeiro componente principal; à dificuldade de

  10. Association studies of novel obesity-related gene variants with quantitative metabolic phenotypes in a population-based sample of 6,039 Danish individuals

    DEFF Research Database (Denmark)

    Burgdorf, K S; Gjesing, A P; Grarup, N

    2012-01-01

    in an epidemiological setting. METHODS: By applying an additive genetic model, 14 WHR-associated gene variants and 18 BMI-associated variants were investigated for their relationships with glucose-related metabolic traits in treatment-naive individuals from the population-based Inter99 study sample (n¿=¿6,039). RESULTS...

  11. Phenotypic plasticity and modularity allow for the production of novel mosaic phenotypes in ants.

    Science.gov (United States)

    Londe, Sylvain; Monnin, Thibaud; Cornette, Raphaël; Debat, Vincent; Fisher, Brian L; Molet, Mathieu

    2015-01-01

    The origin of discrete novelties remains unclear. Some authors suggest that qualitative phenotypic changes may result from the reorganization of preexisting phenotypic traits during development (i.e., developmental recombination) following genetic or environmental changes. Because ants combine high modularity with extreme phenotypic plasticity (queen and worker castes), their diversified castes could have evolved by developmental recombination. We performed a quantitative morphometric study to investigate the developmental origins of novel phenotypes in the ant Mystrium rogeri, which occasionally produces anomalous 'intercastes.' Our analysis compared the variation of six morphological modules with body size using a large sample of intercastes. We confirmed that intercastes are conspicuous mosaics that recombine queen and worker modules. In addition, we found that many other individuals traditionally classified as workers or queens also exhibit some level of mosaicism. The six modules had distinct profiles of variation suggesting that each module responds differentially to factors that control body size and polyphenism. Mosaicism appears to result from each module responding differently yet in an ordered and predictable manner to intermediate levels of inducing factors that control polyphenism. The order of module response determines which mosaic combinations are produced. Because the frequency of mosaics and their canalization around a particular phenotype may evolve by selection on standing genetic variation that affects the plastic response (i.e., genetic accommodation), developmental recombination is likely to play an important role in the evolution of novel castes in ants. Indeed, we found that most mosaics have queen-like head and gaster but a worker-like thorax congruent with the morphology of ergatoid queens and soldiers, respectively. Ergatoid queens of M. oberthueri, a sister species of M. rogeri, could have evolved from intercastes produced ancestrally

  12. Extreme-temperature lab on a chip for optogalvanic spectroscopy of ultra small samples - key components and a first integration attempt

    Science.gov (United States)

    Berglund, Martin; Khaji, Zahra; Klintberg, Lena; Persson, Anders; Sturesson, Peter; Söderberg Breivik, Johan; Thornell, Greger

    2016-10-01

    This is a short summary of the authors’ recent R&D on valves, combustors, plasma sources, and pressure and temperature sensors, realized in high-temperature co-fired ceramics, and an account for the first attempt to monolithically integrate them to form a lab on a chip for sample administration, preparation and analysis, as a stage in optogalvanic spectroscopy.

  13. Sap-flow measurement and scale transferring from sample trees to entire forest stand of Populus euphratica in desert riparian forest in extreme arid region

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Understanding how the transpiration of this vegetation type responds to environmental stress is important for determining the wa-ter-balance dynamics of the riparian ecosystem threatened by groundwater depletion. Transpiration and sap flow were measured using the heat-pulse technique. The results were then projected up to the stand level to investigate the stand’s water-use in relation to climate forcing in the desert riparian forest in an extreme arid region. This study took place from April through October 2003 and from May through October 2004. The experimental site was selected in the Populus euphratica Forest Reserve (101o10’ E, 41o59’ N) in Ejina county, in the lower Heihe River basin, China. The sapwood area was used as a scalar to extrapolate the stand-water consumption from the whole trees’ water consumption measured by the heat-pulse velocity recorder (HPVR). Scale transferring from a series of individual trees to a stand was done according to the existing natural variations between trees under given environmental conditions. The application of the biometric parameters available from individual tree and stand levels was proved suitable for this purpose. A significant correlation between the sapwood area and tree diameter at breast height (DBH) was found. The prediction model is well fitted by the power model. On the basis of the prediction model, the sapwood area can be cal-culated by DBH. The sap-flow density can then be used to extrapolate the stand-water use by means of a series of mathematical models.

  14. Associations of four circulating chemokines with multiple atherosclerosis phenotypes in a large population-based sample: results from the dallas heart study.

    Science.gov (United States)

    Castillo, Leticia; Rohatgi, Anand; Ayers, Colby R; Owens, Andrew W; Das, Sandeep R; Khera, Amit; McGuire, Darren K; de Lemos, James A

    2010-05-01

    Specific chemokines contribute to vascular inflammation and may be useful biomarkers to detect atherosclerosis. The chemokines CXCL1 and CCL11 have previously been studied in animal or human models of atherosclerosis, while CXCL2 and CCL23 have not. Among 2,454 subjects enrolled in the Dallas Heart Study, a multi-ethnic population-based sample, we measured plasma CCL11, CCL23, CXCL1, and CXCL2, and associated levels with coronary artery calcium (CAC) by computed tomography, and aortic wall thickness, plaque burden, and compliance by magnetic resonance imaging. Elevated chemokine levels were defined as greater than or equal to the median for CCL11 and CCL23 and greater than or equal to the upper detection limit for CXCL1 and CXCL2. Elevated CCL23 (P < 0.01) and CXCL1 (P = 0.01), but not CCL11 and CXCL2, associated with CAC in univariable analyses. After adjustment for traditional risk factors, elevated CCL23 remained associated with CAC (OR 1.3, 95% CI 1.0-1.7; P = 0.02), while the association with CXCL1 was modestly attenuated (OR 1.4, 95% CI 1.0-2.1; P = 0.06). CCL23 also associated with aortic wall thickness, plaque, and compliance in univariable analyses (P < 0.05 for each), but these associations were attenuated after multivariable adjustment. The novel chemotactic protein, CCL23, which has not been previously studied in atherosclerosis, is independently associated with coronary atherosclerosis, suggesting that this chemokine merits further study in animal and human models.

  15. Stabilization of a high-order harmonic generation seeded extreme ultraviolet free electron laser by time-synchronization control with electro-optic sampling

    Institute of Scientific and Technical Information of China (English)

    H.Tomizawa; T.Sato; K.Ogawa; K.Togawa; T.Tanaka; T.Hara; M.Yabashi; H.Tanaka; T.Ishikawa; T.Togashi; S.Matsubara; Y.Okayasu; T.Watanabe; E.J.Takahashi; K.Midorikawa; M.Aoyama; K.Yamakawa; S.Owada; A.Iwasaki; K.Yamanouchi

    2015-01-01

    A fully coherent free electron laser(FEL) seeded with a higher-order harmonic(HH) pulse from high-order harmonic generation(HHG) is successfully operated for a sufficiently prolonged time in pilot user experiments by using a timing drift feedback. For HHG-seeded FELs, the seeding laser pulses have to be synchronized with electron bunches. Despite seeded FELs being non-chaotic light sources in principle, external laser-seeded FELs are often unstable in practice because of a timing jitter and a drift between the seeding laser pulses and the accelerated electron bunches. Accordingly,we constructed a relative arrival-timing monitor based on non-invasive electro-optic sampling(EOS). The EOS monitor made uninterrupted shot-to-shot monitoring possible even during the seeded FEL operation. The EOS system was then used for arrival-timing feedback with an adjustability of 100 fs for continual operation of the HHG-seeded FEL. Using the EOS-based beam drift controlling system, the HHG-seeded FEL was operated over half a day with an effective hit rate of 20%–30%. The output pulse energy was 20 μJ at the 61.2 nm wavelength. Towards seeded FELs in the water window region, we investigated our upgrade plan to seed high-power FELs with HH photon energy of 30–100 e V and lase at shorter wavelengths of up to 2 nm through high-gain harmonic generation(HGHG) at the energy-upgraded SPring-8Compact SASE Source(SCSS) accelerator. We studied a benefit as well as the feasibility of the next HHG-seeded FEL machine with single-stage HGHG with tunability of a lasing wavelength.

  16. Mitochondriogenesis genes and extreme longevity.

    Science.gov (United States)

    Santiago, Catalina; Garatachea, Nuria; Yvert, Thomas; Rodríguez-Romo, Gabriel; Santos-Lozano, Alejandro; Fiuza-Luces, Carmen; Lucia, Alejandro

    2013-02-01

    Genes of the proliferator-activated receptor delta (PPARD)-peroxisome proliferator-activated receptor γ coactivator 1α (PPARGC1A, also termed PGC1-α)-nuclear respiratory factor (NRF)-mitochondrial transcription Factor A (TFAM) mitochondriogenesis pathway can influence health/disease phenotypes, yet their association with extreme longevity is not known. We studied the association of five common polymorphisms in genes of this pathway (rs2267668, rs8192678, rs6949152, rs12594956, rs1937) and extreme longevity using a case (107 centenarians)-control (284 young adults) design. We found no between-group differences in allele/genotype frequencies, except for CC genotype in rs1937 (p=0.003), with no representation in controls (0%), versus 2.8% in centenarians (2 men, 1 woman). In summary, the studied genetic variants of the PPARD-PPARGC1A-NRF-TFAM pathway were not associated with extreme longevity, yet a marginal association could exist for rs1937.

  17. Intronic mutation in the growth hormone (GH) receptor gene from a girl with Laron syndrome and extremely high serum GH binding protein: extended phenotypic study in a very large pedigree.

    Science.gov (United States)

    Silbergeld, A; Dastot, F; Klinger, B; Kanety, H; Eshet, R; Amselem, S; Laron, Z

    1997-01-01

    Laron syndrome (LS) is a hereditary form of GH resistance due to molecular defects in the GH receptor (GHR). Most of the identified mutations are located in the extracellular domain of the receptor, resulting in a lack of serum GHBP in the majority of LS patients. We present an LS patient with supranormal levels of serum GHBP, in addition to 35 of her relatives. The proband is a 3.5 year-old Druse girl with severe short stature (height SDS -5.1), high GH (250 micrograms/l), low IGF-I (2.7 nmol/l) and IGFBP-3 (410 micrograms/l), both unresponsive to exogenous GH. The binding capacity of the serum GHBP was 22 nM (adult reference serum, 0.7 nM), with an affinity constant Ka = 1.9 x 10(9) M-1 comparable to that of normal sera (Ka = 1.7-2.1 x 10(9) M-1). The apparent MW of the GHBP was approximately 60-80 kDa, similar to that of control sera. In the proband's sister, parents, grandparents and uncles, extremely high GHBP values were observed (43.0 +/- 4.8 RSB, n = 10) compared with normal adults (0.81 +/- 0.06 RSB) (p T substitution at nucleotide 785-1 preceding exon 8, a sequence that encodes the transmembrane domain. This mutation, which destroys the invariant dinucleotide of the splice acceptor site, is expected to alter GHR mRNA splicing and to be responsible for skipping exon 8. The resulting truncated protein that retains GH binding activity is probably no longer anchored in the cell membrane, affecting signal transmission in the homozygous patient and causing high GHBP levels in the heterozygous relatives.

  18. Phenotypic mismatches reveal escape from arms-race coevolution.

    Science.gov (United States)

    Hanifin, Charles T; Brodie, Edmund D; Brodie, Edmund D

    2008-03-11

    Because coevolution takes place across a broad scale of time and space, it is virtually impossible to understand its dynamics and trajectories by studying a single pair of interacting populations at one time. Comparing populations across a range of an interaction, especially for long-lived species, can provide insight into these features of coevolution by sampling across a diverse set of conditions and histories. We used measures of prey traits (tetrodotoxin toxicity in newts) and predator traits (tetrodotoxin resistance of snakes) to assess the degree of phenotypic mismatch across the range of their coevolutionary interaction. Geographic patterns of phenotypic exaggeration were similar in prey and predators, with most phenotypically elevated localities occurring along the central Oregon coast and central California. Contrary to expectations, however, these areas of elevated traits did not coincide with the most intense coevolutionary selection. Measures of functional trait mismatch revealed that over one-third of sampled localities were so mismatched that reciprocal selection could not occur given current trait distributions. Estimates of current locality-specific interaction selection gradients confirmed this interpretation. In every case of mismatch, predators were "ahead" of prey in the arms race; the converse escape of prey was never observed. The emergent pattern suggests a dynamic in which interacting species experience reciprocal selection that drives arms-race escalation of both prey and predator phenotypes at a subset of localities across the interaction. This coadaptation proceeds until the evolution of extreme phenotypes by predators, through genes of large effect, allows snakes to, at least temporarily, escape the arms race.

  19. Phenotypic mismatches reveal escape from arms-race coevolution.

    Directory of Open Access Journals (Sweden)

    Charles T Hanifin

    2008-03-01

    Full Text Available Because coevolution takes place across a broad scale of time and space, it is virtually impossible to understand its dynamics and trajectories by studying a single pair of interacting populations at one time. Comparing populations across a range of an interaction, especially for long-lived species, can provide insight into these features of coevolution by sampling across a diverse set of conditions and histories. We used measures of prey traits (tetrodotoxin toxicity in newts and predator traits (tetrodotoxin resistance of snakes to assess the degree of phenotypic mismatch across the range of their coevolutionary interaction. Geographic patterns of phenotypic exaggeration were similar in prey and predators, with most phenotypically elevated localities occurring along the central Oregon coast and central California. Contrary to expectations, however, these areas of elevated traits did not coincide with the most intense coevolutionary selection. Measures of functional trait mismatch revealed that over one-third of sampled localities were so mismatched that reciprocal selection could not occur given current trait distributions. Estimates of current locality-specific interaction selection gradients confirmed this interpretation. In every case of mismatch, predators were "ahead" of prey in the arms race; the converse escape of prey was never observed. The emergent pattern suggests a dynamic in which interacting species experience reciprocal selection that drives arms-race escalation of both prey and predator phenotypes at a subset of localities across the interaction. This coadaptation proceeds until the evolution of extreme phenotypes by predators, through genes of large effect, allows snakes to, at least temporarily, escape the arms race.

  20. Multivariate Analysis of Genotype-Phenotype Association.

    Science.gov (United States)

    Mitteroecker, Philipp; Cheverud, James M; Pavlicev, Mihaela

    2016-04-01

    With the advent of modern imaging and measurement technology, complex phenotypes are increasingly represented by large numbers of measurements, which may not bear biological meaning one by one. For such multivariate phenotypes, studying the pairwise associations between all measurements and all alleles is highly inefficient and prevents insight into the genetic pattern underlying the observed phenotypes. We present a new method for identifying patterns of allelic variation (genetic latent variables) that are maximally associated-in terms of effect size-with patterns of phenotypic variation (phenotypic latent variables). This multivariate genotype-phenotype mapping (MGP) separates phenotypic features under strong genetic control from less genetically determined features and thus permits an analysis of the multivariate structure of genotype-phenotype association, including its dimensionality and the clustering of genetic and phenotypic variables within this association. Different variants of MGP maximize different measures of genotype-phenotype association: genetic effect, genetic variance, or heritability. In an application to a mouse sample, scored for 353 SNPs and 11 phenotypic traits, the first dimension of genetic and phenotypic latent variables accounted for >70% of genetic variation present in all 11 measurements; 43% of variation in this phenotypic pattern was explained by the corresponding genetic latent variable. The first three dimensions together sufficed to account for almost 90% of genetic variation in the measurements and for all the interpretable genotype-phenotype association. Each dimension can be tested as a whole against the hypothesis of no association, thereby reducing the number of statistical tests from 7766 to 3-the maximal number of meaningful independent tests. Important alleles can be selected based on their effect size (additive or nonadditive effect on the phenotypic latent variable). This low dimensionality of the genotype-phenotype map

  1. Multivariate Analysis of Genotype–Phenotype Association

    Science.gov (United States)

    Mitteroecker, Philipp; Cheverud, James M.; Pavlicev, Mihaela

    2016-01-01

    With the advent of modern imaging and measurement technology, complex phenotypes are increasingly represented by large numbers of measurements, which may not bear biological meaning one by one. For such multivariate phenotypes, studying the pairwise associations between all measurements and all alleles is highly inefficient and prevents insight into the genetic pattern underlying the observed phenotypes. We present a new method for identifying patterns of allelic variation (genetic latent variables) that are maximally associated—in terms of effect size—with patterns of phenotypic variation (phenotypic latent variables). This multivariate genotype–phenotype mapping (MGP) separates phenotypic features under strong genetic control from less genetically determined features and thus permits an analysis of the multivariate structure of genotype–phenotype association, including its dimensionality and the clustering of genetic and phenotypic variables within this association. Different variants of MGP maximize different measures of genotype–phenotype association: genetic effect, genetic variance, or heritability. In an application to a mouse sample, scored for 353 SNPs and 11 phenotypic traits, the first dimension of genetic and phenotypic latent variables accounted for >70% of genetic variation present in all 11 measurements; 43% of variation in this phenotypic pattern was explained by the corresponding genetic latent variable. The first three dimensions together sufficed to account for almost 90% of genetic variation in the measurements and for all the interpretable genotype–phenotype association. Each dimension can be tested as a whole against the hypothesis of no association, thereby reducing the number of statistical tests from 7766 to 3—the maximal number of meaningful independent tests. Important alleles can be selected based on their effect size (additive or nonadditive effect on the phenotypic latent variable). This low dimensionality of the

  2. Versatile lipid profiling by liquid chromatography-high resolution mass spectrometry using all ion fragmentation and polarity switching. Preliminary application for serum samples phenotyping related to canine mammary cancer.

    Science.gov (United States)

    Gallart-Ayala, H; Courant, F; Severe, S; Antignac, J-P; Morio, F; Abadie, J; Le Bizec, B

    2013-09-24

    Lipids represent an extended class of substances characterized by such high variety and complexity that makes their unified analyses by liquid chromatography coupled to either high resolution or tandem mass spectrometry (LC-HRMS or LC-MS/MS) a real challenge. In the present study, a new versatile methodology associating ultra high performance liquid chromatography coupled to high resolution tandem mass spectrometry (UHPLC-HRMS/MS) have been developed for a comprehensive analysis of lipids. The use of polarity switching and "all ion fragmentation" (AIF) have been two action levels particularly exploited to finally permit the detection and identification of a multi-class and multi-analyte extended range of lipids in a single run. For identification purposes, both higher energy collision dissociation (HCD) and in-source CID (collision induced dissociation) fragmentation were evaluated in order to obtain information about the precursor and product ions in the same spectra. This approach provides both class-specific and lipid-specific fragments, enhancing lipid identification. Finally, the developed method was applied for differential phenotyping of serum samples collected from pet dogs developing spontaneous malignant mammary tumors and health controls. A biological signature associated with the presence of cancer was then successfully revealed from this lipidome analysis, which required to be further investigated and confirmed at larger scale.

  3. Versatile lipid profiling by liquid chromatography–high resolution mass spectrometry using all ion fragmentation and polarity switching. Preliminary application for serum samples phenotyping related to canine mammary cancer

    Energy Technology Data Exchange (ETDEWEB)

    Gallart-Ayala, H., E-mail: laberca@oniris-nantes.fr [LUNAM, Ecole Nationale Vétérinaire, Agroalimentaire et de l’Alimentation Nantes Atlantique (Oniris), USC 1329 INRA Laboratoire d’Etude des résidus et Contaminants dans les Aliments (LABERCA), Site de la Chantrerie – CS50707, 44307 Nantes cedex 3 (France); Courant, F.; Severe, S.; Antignac, J.-P. [LUNAM, Ecole Nationale Vétérinaire, Agroalimentaire et de l’Alimentation Nantes Atlantique (Oniris), USC 1329 INRA Laboratoire d’Etude des résidus et Contaminants dans les Aliments (LABERCA), Site de la Chantrerie – CS50707, 44307 Nantes cedex 3 (France); Morio, F.; Abadie, J. [LUNAM, Ecole Nationale Vétérinaire, Agroalimentaire et de l’Alimentation Nantes Atlantique (Oniris), Cancers Animaux, Modèles pour la Recherche en Oncologie Comparée (AMaROC), Site de la Chantrerie–CS50707, 44307 Nantes cedex 3 (France); Le Bizec, B. [LUNAM, Ecole Nationale Vétérinaire, Agroalimentaire et de l’Alimentation Nantes Atlantique (Oniris), USC 1329 INRA Laboratoire d’Etude des résidus et Contaminants dans les Aliments (LABERCA), Site de la Chantrerie – CS50707, 44307 Nantes cedex 3 (France)

    2013-09-24

    Graphical abstract: -- Highlights: •Lipidomics, high resolution mass spectrometry, polarity switching, serum, canine mammary cancer. -- Abstract: Lipids represent an extended class of substances characterized by such high variety and complexity that makes their unified analyses by liquid chromatography coupled to either high resolution or tandem mass spectrometry (LC–HRMS or LC–MS/MS) a real challenge. In the present study, a new versatile methodology associating ultra high performance liquid chromatography coupled to high resolution tandem mass spectrometry (UHPLC–HRMS/MS) have been developed for a comprehensive analysis of lipids. The use of polarity switching and “all ion fragmentation” (AIF) have been two action levels particularly exploited to finally permit the detection and identification of a multi-class and multi-analyte extended range of lipids in a single run. For identification purposes, both higher energy collision dissociation (HCD) and in-source CID (collision induced dissociation) fragmentation were evaluated in order to obtain information about the precursor and product ions in the same spectra. This approach provides both class-specific and lipid-specific fragments, enhancing lipid identification. Finally, the developed method was applied for differential phenotyping of serum samples collected from pet dogs developing spontaneous malignant mammary tumors and health controls. A biological signature associated with the presence of cancer was then successfully revealed from this lipidome analysis, which required to be further investigated and confirmed at larger scale.

  4. Effects of low birth weight, maternal smoking in pregnancy and social class on the phenotypic manifestation of Attention Deficit Hyperactivity Disorder and associated antisocial behaviour: investigation in a clinical sample

    Directory of Open Access Journals (Sweden)

    van den Bree Marianne BM

    2007-06-01

    Full Text Available Abstract Background Attention Deficit Hyperactivity Disorder (ADHD is a genetically influenced condition although indicators of environmental risk including maternal smoking during pregnancy, low birth weight and low social class have also been found to be associated with the disorder. ADHD is a phenotypically heterogeneous disorder in terms of the predominant symptom types (inattention, hyperactive-impulsivity, their severity and comorbidity, notably Conduct Disorder. It is possible that these different clinical manifestations of the disorder may arise because of the differing effects of the environmental indicators of environmental risk. We set out to test this hypothesis. Methods In a sample of 356 children diagnosed with ADHD, we sought to investigate possible effects of three indicators of environmental risk – maternal smoking during pregnancy, birth weight and social class – on comorbid Conduct Disorder, conduct disorder symptoms and inattentive and hyperactive-impulsive symptom severity. Results Multiple regression analysis revealed that, after controlling for significant covariates, greater hyperactive-impulsive symptom severity was significantly associated with maternal smoking during pregnancy (r2 = 0.02, Beta = 0.11, t = 1.96, p = 0.05 and social class (r2 = 0.02, Beta = 0.12, t = 2.19, p = 0.03 whilst none of the environmental risk indicators significantly predicted number of inattentive symptoms. Conduct Disorder symptoms were positively predicted by maternal smoking in pregnancy (r2 = 0.04, Beta = 0.18, t = 3.34, p = 0.001 whilst both maternal smoking during pregnancy and social class significantly predicted a diagnosis of Conduct Disorder (OR = 3.14, 95% CI: 1.54, 6.41, Wald = 9.95, p = 0.002 and (OR = 1.95 95% CI: 1.18, 3.23 Wald = 6.78, p = 0.009 respectively. Conclusion These findings suggest that indicators of environmental risk, in this instance maternal smoking in pregnancy and environmental adversity indexed by lower

  5. Extremely Preterm Birth

    Science.gov (United States)

    ... Events Advocacy For Patients About ACOG Extremely Preterm Birth Home For Patients Search FAQs Extremely Preterm Birth ... Spanish FAQ173, June 2016 PDF Format Extremely Preterm Birth Pregnancy When is a baby considered “preterm” or “ ...

  6. Phenotypic commonalities in familial and sporadic Parkinson disease.

    Science.gov (United States)

    Baba, Yasuhiko; Markopoulou, Katerina; Putzke, John D; Whaley, Nathaniel R; Farrer, Matthew J; Wszolek, Zbigniew K; Uitti, Ryan J

    2006-04-01

    Parkinson disease (PD) is a clinically well-documented neurodegenerative disorder. However, the mechanism or mechanisms of its phenotypic expressions are still unknown. To compare phenotypes by examining demographic and clinical features of patients with familial PD and sporadic PD and with or without a family history of PD. Historical review of patients with sporadic PD in clinic-based samples and individual patients diagnosed with PD from families whose linkage to mutations or loci has been identified. Movement disorder clinic in a referral center. A total of 1277 patients with sporadic PD and 40 patients with familial PD. Clinical features, including distribution by sex, initial motor symptom, location of initial motor symptom, and frequency of asymmetric motor symptoms. Despite different etiologic backgrounds, both familial and sporadic PD exhibited several interesting commonalities, including a higher incidence in men, tremor as the initial motor symptom (predominantly involving the upper extremities), and asymmetric parkinsonism during disease course. The increased incidence of parkinsonism in men with familial PD suggests that the sex disparity is more likely the result of a protective effect against development of PD in women than of an increased risk in men that is associated with environmental factors. Phenotypic similarity among familial and sporadic PD indicates that a similar topographic distribution of the nigrostriatal lesion exists in patients with either form of PD regardless of apparent genetic influence.

  7. Measuring extremal dependencies in web graphs

    NARCIS (Netherlands)

    Volkovich, Y.; Litvak, Nelli; Zwart, B.

    We analyze dependencies in power law graph data (Web sample, Wikipedia sample and a preferential attachment graph) using statistical inference for multivariate regular variation. The well developed theory of regular variation is widely applied in extreme value theory, telecommunications and

  8. Microglia phenotype diversity

    NARCIS (Netherlands)

    Olah, M.; Biber, K.; Vinet, J.; Boddeke, H. W. G. M.

    2011-01-01

    Microglia, the tissue macrophages of the brain, have under healthy conditions a resting phenotype that is characterized by a ramified morphology. With their fine processes microglia are continuously scanning their environment. Upon any homeostatic disturbance microglia rapidly change their phenotype

  9. Microglia phenotype diversity

    NARCIS (Netherlands)

    Olah, M.; Biber, K.; Vinet, J.; Boddeke, H. W. G. M.

    2011-01-01

    Microglia, the tissue macrophages of the brain, have under healthy conditions a resting phenotype that is characterized by a ramified morphology. With their fine processes microglia are continuously scanning their environment. Upon any homeostatic disturbance microglia rapidly change their phenotype

  10. Microglia phenotype diversity

    NARCIS (Netherlands)

    Olah, M.; Biber, K.; Vinet, J.; Boddeke, H. W. G. M.

    Microglia, the tissue macrophages of the brain, have under healthy conditions a resting phenotype that is characterized by a ramified morphology. With their fine processes microglia are continuously scanning their environment. Upon any homeostatic disturbance microglia rapidly change their phenotype

  11. Extreme phenotypes in hypercholesterolemia : From genotype to therapy

    NARCIS (Netherlands)

    Sjouke, B.

    2017-01-01

    Familial hypercholesterolemia (FH) is an inherited disorder of cholesterol metabolism, resulting in increased LDL-cholesterol levels and, as a consequence, an increased risk for coronary heart disease. Recently, many causal FH mutations in different genes have been identified and advances in genetic

  12. Statistical Model of Extreme Shear

    DEFF Research Database (Denmark)

    Larsen, Gunner Chr.; Hansen, Kurt Schaldemose

    2004-01-01

    In order to continue cost-optimisation of modern large wind turbines, it is important to continously increase the knowledge on wind field parameters relevant to design loads. This paper presents a general statistical model that offers site-specific prediction of the probability density function...... by a model that, on a statistically consistent basis, describe the most likely spatial shape of an extreme wind shear event. Predictions from the model have been compared with results from an extreme value data analysis, based on a large number of high-sampled full-scale time series measurements...... are consistent, given the inevitabel uncertainties associated with model as well as with the extreme value data analysis. Keywords: Statistical model, extreme wind conditions, statistical analysis, turbulence, wind loading, statistical analysis, turbulence, wind loading, wind shear, wind turbines....

  13. Multidimensional extremal dependence coefficients

    OpenAIRE

    2017-01-01

    Extreme values modeling has attracting the attention of researchers in diverse areas such as the environment, engineering, or finance. Multivariate extreme value distributions are particularly suitable to model the tails of multidimensional phenomena. The analysis of the dependence among multivariate maxima is useful to evaluate risk. Here we present new multivariate extreme value models, as well as, coefficients to assess multivariate extremal dependence.

  14. The European Extreme Right and Religious Extremism

    Directory of Open Access Journals (Sweden)

    Jean-Yves Camus

    2007-12-01

    Full Text Available The ideology of the Extreme Right in Western Europe is rooted in Catholic fundamentalism and Counter-Revolutionary ideas. However, the Extreme Right, like all other political families, has had to adjust to an increasingly secular society. The old link between religion and the Extreme Right has thus been broken and in fact already was when Fascism overtook Europe: Fascism was secular, sometimes even anti-religious, in its essence. Although Catholic fundamentalists still retain strong positions within the apparatus of several Extreme Right parties (Front National, the vote for the Extreme Right is generally weak among regular churchgoers and strong among non-believers. In several countries, the vote for the Extreme Right is stronger among Protestant voters than among Catholics, since while Catholics may support Christian-Democratic parties, there are very few political parties linked to Protestant churches. Presently, it also seems that Paganism is becoming the dominant religious creed within the Extreme Right. In a multicultural Europe, non-Christian forms of religious fundamentalism such as Islamism also exist with ideological similarities to the Extreme Right, but this is not sufficient to categorize Islamism as a form of Fascism. Some Islamist groups seek alliances with the Extreme Right on the basis of their common dislike for Israel and the West, globalization and individual freedom of thought.

  15. Extreme conditions (p, T, H)

    Energy Technology Data Exchange (ETDEWEB)

    Mesot, J. [Lab. for Neutron Scattering ETH Zurich, Zurich (Switzerland) and Paul Scherrer Institute, Villigen (Switzerland)

    1996-11-01

    The aim of this paper is to summarize the sample environment which will be accessible at the SINQ. In order to illustrate the type of experiments which will be feasible under extreme conditions of temperature, magnetic field and pressure at the SINQ a few selected examples are also given. (author) 7 figs., 14 refs.

  16. Characterizing Extreme Ionospheric Storms

    Science.gov (United States)

    Sparks, L.; Komjathy, A.; Altshuler, E.

    2011-12-01

    Ionospheric storms consist of disturbances of the upper atmosphere that generate regions of enhanced electron density typically lasting several hours. Depending upon the storm magnitude, gradients in electron density can sometimes become large and highly localized. The existence of such localized, dense irregularities is a major source of positioning error for users of the Global Positioning System (GPS). Consequently, satellite-based augmentation systems have been implemented to improve the accuracy and to ensure the integrity of user position estimates derived from GPS measurements. Large-scale irregularities generally do not pose a serious threat to estimate integrity as they can be readily detected by such systems. Of greater concern, however, are highly localized irregularities that interfere with the propagation of a signal detected by a user measurement but are poorly sampled by the receivers in the system network. The most challenging conditions have been found to arise following disturbances of large magnitude that occur only rarely over the course of a solar cycle. These extremely disturbed conditions exhibit behavior distinct from moderately disturbed conditions and, hence, have been designated "extreme storms". In this paper we examine and compare the behavior of the extreme ionospheric storms of solar cycle 23 (or, more precisely, extreme storms occurring between January 1, 2000, and December 31, 2008), as represented in maps of vertical total electron content. To identify these storms, we present a robust means of quantifying the regional magnitude of an ionospheric storm. Ionospheric storms are observed frequently to occur in conjunction with magnetic storms, i.e., periods of geophysical activity as measured by magnetometers. While various geomagnetic indices, such as the disturbance storm time (Dst) and the planetary Kp index, have long been used to rank the magnitudes of distinct magnetic storms, no comparable, generally recognized index exists for

  17. Single cell dynamic phenotyping

    OpenAIRE

    Katherin Patsch; Chi-Li Chiu; Mark Engeln; Agus, David B.; Parag Mallick; Shannon M. Mumenthaler; Daniel Ruderman

    2016-01-01

    Live cell imaging has improved our ability to measure phenotypic heterogeneity. However, bottlenecks in imaging and image processing often make it difficult to differentiate interesting biological behavior from technical artifact. Thus there is a need for new methods that improve data quality without sacrificing throughput. Here we present a 3-step workflow to improve dynamic phenotype measurements of heterogeneous cell populations. We provide guidelines for image acquisition, phenotype track...

  18. Statistical Model of Extreme Shear

    DEFF Research Database (Denmark)

    Hansen, Kurt Schaldemose; Larsen, Gunner Chr.

    2005-01-01

    In order to continue cost-optimisation of modern large wind turbines, it is important to continuously increase the knowledge of wind field parameters relevant to design loads. This paper presents a general statistical model that offers site-specific prediction of the probability density function...... by a model that, on a statistically consistent basis, describes the most likely spatial shape of an extreme wind shear event. Predictions from the model have been compared with results from an extreme value data analysis, based on a large number of full-scale measurements recorded with a high sampling rate...

  19. Extreme Ionizing-Radiation-Resistant Bacterium

    Science.gov (United States)

    Vaishampayan, Parag A.; Venkateswaran, Kasthuri J.; Schwendner, Petra

    2013-01-01

    There is a growing concern that desiccation and extreme radiation-resistant, non-spore-forming microorganisms associated with spacecraft surfaces can withstand space environmental conditions and subsequent proliferation on another solar body. Such forward contamination would jeopardize future life detection or sample return technologies. The prime focus of NASA s planetary protection efforts is the development of strategies for inactivating resistance-bearing micro-organisms. Eradi cation techniques can be designed to target resistance-conferring microbial populations by first identifying and understanding their physiologic and biochemical capabilities that confers its elevated tolerance (as is being studied in Deinococcus phoenicis, as a result of this description). Furthermore, hospitals, food, and government agencies frequently use biological indicators to ensure the efficacy of a wide range of radiation-based sterilization processes. Due to their resistance to a variety of perturbations, the nonspore forming D. phoenicis may be a more appropriate biological indicator than those currently in use. The high flux of cosmic rays during space travel and onto the unshielded surface of Mars poses a significant hazard to the survival of microbial life. Thus, radiation-resistant microorganisms are of particular concern that can survive extreme radiation, desiccation, and low temperatures experienced during space travel. Spore-forming bacteria, a common inhabitant of spacecraft assembly facilities, are known to tolerate these extreme conditions. Since the Viking era, spores have been utilized to assess the degree and level of microbiological contamination on spacecraft and their associated spacecraft assembly facilities. Members of the non-sporeforming bacterial community such as Deinococcus radiodurans can survive acute exposures to ionizing radiation (5 kGy), ultraviolet light (1 kJ/m2), and desiccation (years). These resistive phenotypes of Deinococcus enhance the

  20. Legacy to the extreme

    NARCIS (Netherlands)

    A. van Deursen (Arie); T. Kuipers (Tobias); L.M.F. Moonen (Leon)

    2000-01-01

    textabstractWe explore the differences between developing a system using extreme programming techniques, and maintaining a legacy system. We investigate whether applying extreme programming techniques to legacy maintenance is useful and feasible.

  1. Legacy to the extreme

    NARCIS (Netherlands)

    Deursen, A. van; Kuipers, T.; Moonen, L.M.F.

    2000-01-01

    We explore the differences between developing a system using extreme programming techniques, and maintaining a legacy system. We investigate whether applying extreme programming techniques to legacy maintenance is useful and feasible.

  2. Extreme environment electronics

    CERN Document Server

    Cressler, John D

    2012-01-01

    Unfriendly to conventional electronic devices, circuits, and systems, extreme environments represent a serious challenge to designers and mission architects. The first truly comprehensive guide to this specialized field, Extreme Environment Electronics explains the essential aspects of designing and using devices, circuits, and electronic systems intended to operate in extreme environments, including across wide temperature ranges and in radiation-intense scenarios such as space. The Definitive Guide to Extreme Environment Electronics Featuring contributions by some of the world's foremost exp

  3. Deficiently Extremal Gorenstein Algebras

    Indian Academy of Sciences (India)

    Pavinder Singh

    2011-08-01

    The aim of this article is to study the homological properties of deficiently extremal Gorenstein algebras. We prove that if / is an odd deficiently extremal Gorenstein algebra with pure minimal free resolution, then the codimension of / must be odd. As an application, the structure of pure minimal free resolution of a nearly extremal Gorenstein algebra is obtained.

  4. Extreme value distributions

    CERN Document Server

    Ahsanullah, Mohammad

    2016-01-01

    The aim of the book is to give a through account of the basic theory of extreme value distributions. The book cover a wide range of materials available to date. The central ideas and results of extreme value distributions are presented. The book rwill be useful o applied statisticians as well statisticians interrested to work in the area of extreme value distributions.vmonograph presents the central ideas and results of extreme value distributions.The monograph gives self-contained of theory and applications of extreme value distributions.

  5. Phenotyping of robustness and milk quality

    OpenAIRE

    Berry, D. P.; McParland, S.; Bastin, Catherine; Wall, E.; Gengler, Nicolas; Soyeurt, Hélène

    2013-01-01

    A phenotype describes the outcome of the interacting development between the genotype of an individual and its specific environment throughout life. Animal breeding currently exploits large data sets of phenotypic and pedigree information to estimate the genetic merit of animals. Here we describe rapid, low-cost phenomic tools for dairy cattle. We give particular emphasis to infrared spectroscopy of milk because the necessary spectral data are already routinely available on milk samples from ...

  6. Extreme Velocity Wind Sensor

    Science.gov (United States)

    Perotti, Jose; Voska, Ned (Technical Monitor)

    2002-01-01

    This presentation provides an overview of the development of new hurricane wind sensor (Extreme Velocity Wind Sensor) for the Kennedy Space Center (KSC) which is designed to withstand winds of up to three hundred miles an hour. The proposed Extreme Velocity Wind Sensor contains no moveable components that would be exposed to extreme wind conditions. Topics covered include: need for new hurricane wind sensor, conceptual design, software applications, computational fluid dynamic simulations of design concept, preliminary performance tests, and project status.

  7. Phenotypic covariance at species’ borders

    Science.gov (United States)

    2013-01-01

    Background Understanding the evolution of species limits is important in ecology, evolution, and conservation biology. Despite its likely importance in the evolution of these limits, little is known about phenotypic covariance in geographically marginal populations, and the degree to which it constrains, or facilitates, responses to selection. We investigated phenotypic covariance in morphological traits at species’ borders by comparing phenotypic covariance matrices (P), including the degree of shared structure, the distribution of strengths of pair-wise correlations between traits, the degree of morphological integration of traits, and the ranks of matricies, between central and marginal populations of three species-pairs of coral reef fishes. Results Greater structural differences in P were observed between populations close to range margins and conspecific populations toward range centres, than between pairs of conspecific populations that were both more centrally located within their ranges. Approximately 80% of all pair-wise trait correlations within populations were greater in the north, but these differences were unrelated to the position of the sampled population with respect to the geographic range of the species. Conclusions Neither the degree of morphological integration, nor ranks of P, indicated greater evolutionary constraint at range edges. Characteristics of P observed here provide no support for constraint contributing to the formation of these species’ borders, but may instead reflect structural change in P caused by selection or drift, and their potential to evolve in the future. PMID:23714580

  8. How extreme is extreme hourly precipitation?

    Science.gov (United States)

    Papalexiou, Simon Michael; Dialynas, Yannis G.; Pappas, Christoforos

    2016-04-01

    The importance of accurate representation of precipitation at fine time scales (e.g., hourly), directly associated with flash flood events, is crucial in hydrological design and prediction. The upper part of a probability distribution, known as the distribution tail, determines the behavior of extreme events. In general, and loosely speaking, tails can be categorized in two families: the subexponential and the hyperexponential family, with the first generating more intense and more frequent extremes compared to the latter. In past studies, the focus has been mainly on daily precipitation, with the Gamma distribution being the most popular model. Here, we investigate the behaviour of tails of hourly precipitation by comparing the upper part of empirical distributions of thousands of records with three general types of tails corresponding to the Pareto, Lognormal, and Weibull distributions. Specifically, we use thousands of hourly rainfall records from all over the USA. The analysis indicates that heavier-tailed distributions describe better the observed hourly rainfall extremes in comparison to lighter tails. Traditional representations of the marginal distribution of hourly rainfall may significantly deviate from observed behaviours of extremes, with direct implications on hydroclimatic variables modelling and engineering design.

  9. Phenotypic MicroRNA Microarrays

    OpenAIRE

    2013-01-01

    Microarray technology has become a very popular approach in cases where multiple experiments need to be conducted repeatedly or done with a variety of samples. In our lab, we are applying our high density spots microarray approach to microscopy visualization of the effects of transiently introduced siRNA or cDNA on cellular morphology or phenotype. In this publication, we are discussing the possibility of using this micro-scale high throughput process to study the role of microRNAs in the bio...

  10. Wine Expertise Predicts Taste Phenotype.

    Science.gov (United States)

    Hayes, John E; Pickering, Gary J

    2012-03-01

    Taste phenotypes have long been studied in relation to alcohol intake, dependence, and family history, with contradictory findings. However, on balance - with appropriate caveats about populations tested, outcomes measured and psychophysical methods used - an association between variation in taste responsiveness and some alcohol behaviors is supported. Recent work suggests super-tasting (operationalized via propylthiouracil (PROP) bitterness) not only associates with heightened response but also with more acute discrimination between stimuli. Here, we explore relationships between food and beverage adventurousness and taste phenotype. A convenience sample of wine drinkers (n=330) were recruited in Ontario and phenotyped for PROP bitterness via filter paper disk. They also filled out a short questionnaire regarding willingness to try new foods, alcoholic beverages and wines as well as level of wine involvement, which was used to classify them as a wine expert (n=110) or wine consumer (n=220). In univariate logisitic models, food adventurousness predicted trying new wines and beverages but not expertise. Likewise, wine expertise predicted willingness to try new wines and beverages but not foods. In separate multivariate logistic models, willingness to try new wines and beverages was predicted by expertise and food adventurousness but not PROP. However, mean PROP bitterness was higher among wine experts than wine consumers, and the conditional distribution functions differed between experts and consumers. In contrast, PROP means and distributions did not differ with food adventurousness. These data suggest individuals may self-select for specific professions based on sensory ability (i.e., an active gene-environment correlation) but phenotype does not explain willingness to try new stimuli.

  11. Statistical models for trisomic phenotypes

    Energy Technology Data Exchange (ETDEWEB)

    Lamb, N.E.; Sherman, S.L.; Feingold, E. [Emory Univ., Atlanta, GA (United States)

    1996-01-01

    Certain genetic disorders are rare in the general population but more common in individuals with specific trisomies, which suggests that the genes involved in the etiology of these disorders may be located on the trisomic chromosome. As with all aneuploid syndromes, however, a considerable degree of variation exists within each phenotype so that any given trait is present only among a subset of the trisomic population. We have previously presented a simple gene-dosage model to explain this phenotypic variation and developed a strategy to map genes for such traits. The mapping strategy does not depend on the simple model but works in theory under any model that predicts that affected individuals have an increased likelihood of disomic homozygosity at the trait locus. This paper explores the robustness of our mapping method by investigating what kinds of models give an expected increase in disomic homozygosity. We describe a number of basic statistical models for trisomic phenotypes. Some of these are logical extensions of standard models for disomic phenotypes, and some are more specific to trisomy. Where possible, we discuss genetic mechanisms applicable to each model. We investigate which models and which parameter values give an expected increase in disomic homozygosity in individuals with the trait. Finally, we determine the sample sizes required to identify the increased disomic homozygosity under each model. Most of the models we explore yield detectable increases in disomic homozygosity for some reasonable range of parameter values, usually corresponding to smaller trait frequencies. It therefore appears that our mapping method should be effective for a wide variety of moderately infrequent traits, even though the exact mode of inheritance is unlikely to be known. 21 refs., 8 figs., 1 tab.

  12. Detectors in Extreme Conditions

    Energy Technology Data Exchange (ETDEWEB)

    Blaj, G. [SLAC National Accelerator Lab., Menlo Park, CA (United States); Carini, G. [SLAC National Accelerator Lab., Menlo Park, CA (United States); Carron, S. [SLAC National Accelerator Lab., Menlo Park, CA (United States); Haller, G. [SLAC National Accelerator Lab., Menlo Park, CA (United States); Hart, P. [SLAC National Accelerator Lab., Menlo Park, CA (United States); Hasi, J. [SLAC National Accelerator Lab., Menlo Park, CA (United States); Herrmann, S. [SLAC National Accelerator Lab., Menlo Park, CA (United States); Kenney, C. [SLAC National Accelerator Lab., Menlo Park, CA (United States); Segal, J. [SLAC National Accelerator Lab., Menlo Park, CA (United States); Tomada, A. [SLAC National Accelerator Lab., Menlo Park, CA (United States)

    2015-08-06

    Free Electron Lasers opened a new window on imaging the motion of atoms and molecules. At SLAC, FEL experiments are performed at LCLS using 120Hz pulses with 1012 - 1013 photons in 10 femtoseconds (billions of times brighter than the most powerful synchrotrons). This extreme detection environment raises unique challenges, from obvious to surprising. Radiation damage is a constant threat due to accidental exposure to insufficiently attenuated beam, focused beam and formation of ice crystals reflecting the beam onto the detector. Often high power optical lasers are also used (e.g., 25TW), increasing the risk of damage or impeding data acquisition through electromagnetic pulses (EMP). The sample can contaminate the detector surface or even produce shrapnel damage. Some experiments require ultra high vacuum (UHV) with strict design, surface contamination and cooling requirements - also for detectors. The setup is often changed between or during experiments with short turnaround times, risking mechanical and ESD damage, requiring work planning, training of operators and sometimes continuous participation of the LCLS Detector Group in the experiments. The detectors used most often at LCLS are CSPAD cameras for hard x-rays and pnCCDs for soft x-rays.

  13. Alteration of a human intestinal microbiota under extreme life environment in the Antarctica.

    Science.gov (United States)

    Jin, Jong-Sik; Touyama, Mutsumi; Yamada, Shin; Yamazaki, Takashi; Benno, Yoshimi

    2014-01-01

    The human intestinal microbiota (HIM) settles from birth and continues to change phenotype by some factors (e.g. host's diet) throughout life. However, the effect of extreme life environment on human HIM composition is not well known. To understand HIM fluctuation under extreme life environment in humans, fecal samples were collected from six Japanese men on a long Antarctic expedition. They explored Antarctica for 3 months and collected their fecal samples at once-monthly intervals. Using terminal restriction fragment length polymorphism (T-RFLP) and real time polymerase chain reaction (PCR) analysis, the composition of HIM in six subjects was investigated. Three subjects presented restoration of HIM after the expedition compared versus before and during the expedition. Two thirds samples collected during the expedition belonged to the same cluster in dendrogram. However, all through the expedition, T-RFLP patterns showed interindividual variability. Especially, Bifidobacterium spp. showed a tendency to decrease during and restore after the expedition. A reduction of Bifidobacterium spp. was observed in five subjects the first 1 month of the expedition. Bacteroides thetaiotaomicron, which is thought to proliferate during emotional stress, significantly decreased in one subject, indicating that other factors in addition to emotional stress may affect the composition of HIM in this study. These findings could be helpful to understand the effect of extreme life environment on HIM.

  14. Classifying Returns as Extreme

    DEFF Research Database (Denmark)

    Christiansen, Charlotte

    2014-01-01

    I consider extreme returns for the stock and bond markets of 14 EU countries using two classification schemes: One, the univariate classification scheme from the previous literature that classifies extreme returns for each market separately, and two, a novel multivariate classification scheme tha...

  15. The Burmese python genome reveals the molecular basis for extreme adaptation in snakes.

    Science.gov (United States)

    Castoe, Todd A; de Koning, A P Jason; Hall, Kathryn T; Card, Daren C; Schield, Drew R; Fujita, Matthew K; Ruggiero, Robert P; Degner, Jack F; Daza, Juan M; Gu, Wanjun; Reyes-Velasco, Jacobo; Shaney, Kyle J; Castoe, Jill M; Fox, Samuel E; Poole, Alex W; Polanco, Daniel; Dobry, Jason; Vandewege, Michael W; Li, Qing; Schott, Ryan K; Kapusta, Aurélie; Minx, Patrick; Feschotte, Cédric; Uetz, Peter; Ray, David A; Hoffmann, Federico G; Bogden, Robert; Smith, Eric N; Chang, Belinda S W; Vonk, Freek J; Casewell, Nicholas R; Henkel, Christiaan V; Richardson, Michael K; Mackessy, Stephen P; Bronikowski, Anne M; Bronikowsi, Anne M; Yandell, Mark; Warren, Wesley C; Secor, Stephen M; Pollock, David D

    2013-12-17

    Snakes possess many extreme morphological and physiological adaptations. Identification of the molecular basis of these traits can provide novel understanding for vertebrate biology and medicine. Here, we study snake biology using the genome sequence of the Burmese python (Python molurus bivittatus), a model of extreme physiological and metabolic adaptation. We compare the python and king cobra genomes along with genomic samples from other snakes and perform transcriptome analysis to gain insights into the extreme phenotypes of the python. We discovered rapid and massive transcriptional responses in multiple organ systems that occur on feeding and coordinate major changes in organ size and function. Intriguingly, the homologs of these genes in humans are associated with metabolism, development, and pathology. We also found that many snake metabolic genes have undergone positive selection, which together with the rapid evolution of mitochondrial proteins, provides evidence for extensive adaptive redesign of snake metabolic pathways. Additional evidence for molecular adaptation and gene family expansions and contractions is associated with major physiological and phenotypic adaptations in snakes; genes involved are related to cell cycle, development, lungs, eyes, heart, intestine, and skeletal structure, including GRB2-associated binding protein 1, SSH, WNT16, and bone morphogenetic protein 7. Finally, changes in repetitive DNA content, guanine-cytosine isochore structure, and nucleotide substitution rates indicate major shifts in the structure and evolution of snake genomes compared with other amniotes. Phenotypic and physiological novelty in snakes seems to be driven by system-wide coordination of protein adaptation, gene expression, and changes in the structure of the genome.

  16. The Burmese python genome reveals the molecular basis for extreme adaptation in snakes

    Science.gov (United States)

    Castoe, Todd A.; de Koning, A. P. Jason; Hall, Kathryn T.; Card, Daren C.; Schield, Drew R.; Fujita, Matthew K.; Ruggiero, Robert P.; Degner, Jack F.; Daza, Juan M.; Gu, Wanjun; Reyes-Velasco, Jacobo; Shaney, Kyle J.; Castoe, Jill M.; Fox, Samuel E.; Poole, Alex W.; Polanco, Daniel; Dobry, Jason; Vandewege, Michael W.; Li, Qing; Schott, Ryan K.; Kapusta, Aurélie; Minx, Patrick; Feschotte, Cédric; Uetz, Peter; Ray, David A.; Hoffmann, Federico G.; Bogden, Robert; Smith, Eric N.; Chang, Belinda S. W.; Vonk, Freek J.; Casewell, Nicholas R.; Henkel, Christiaan V.; Richardson, Michael K.; Mackessy, Stephen P.; Bronikowski, Anne M.; Yandell, Mark; Warren, Wesley C.; Secor, Stephen M.; Pollock, David D.

    2013-01-01

    Snakes possess many extreme morphological and physiological adaptations. Identification of the molecular basis of these traits can provide novel understanding for vertebrate biology and medicine. Here, we study snake biology using the genome sequence of the Burmese python (Python molurus bivittatus), a model of extreme physiological and metabolic adaptation. We compare the python and king cobra genomes along with genomic samples from other snakes and perform transcriptome analysis to gain insights into the extreme phenotypes of the python. We discovered rapid and massive transcriptional responses in multiple organ systems that occur on feeding and coordinate major changes in organ size and function. Intriguingly, the homologs of these genes in humans are associated with metabolism, development, and pathology. We also found that many snake metabolic genes have undergone positive selection, which together with the rapid evolution of mitochondrial proteins, provides evidence for extensive adaptive redesign of snake metabolic pathways. Additional evidence for molecular adaptation and gene family expansions and contractions is associated with major physiological and phenotypic adaptations in snakes; genes involved are related to cell cycle, development, lungs, eyes, heart, intestine, and skeletal structure, including GRB2-associated binding protein 1, SSH, WNT16, and bone morphogenetic protein 7. Finally, changes in repetitive DNA content, guanine-cytosine isochore structure, and nucleotide substitution rates indicate major shifts in the structure and evolution of snake genomes compared with other amniotes. Phenotypic and physiological novelty in snakes seems to be driven by system-wide coordination of protein adaptation, gene expression, and changes in the structure of the genome. PMID:24297902

  17. Phenotypic plasticity in development and evolution: facts and concepts

    Science.gov (United States)

    Fusco, Giuseppe; Minelli, Alessandro

    2010-01-01

    This theme issue pursues an exploration of the potential of taking into account the environmental sensitivity of development to explaining the evolution of metazoan life cycles, with special focus on complex life cycles and the role of developmental plasticity. The evolution of switches between alternative phenotypes as a response to different environmental cues and the evolution of the control of the temporal expression of alternative phenotypes within an organism's life cycle are here treated together as different dimensions of the complex relationships between genotype and phenotype, fostering the emergence of a more general and comprehensive picture of phenotypic evolution through a quite diverse sample of case studies. This introductory article reviews fundamental facts and concepts about phenotypic plasticity, adopting the most authoritative terminology in use in the current literature. The main topics are types and components of phenotypic variation, the evolution of organismal traits through plasticity, the origin and evolution of phenotypic plasticity and its adaptive value. PMID:20083631

  18. Biolog phenotype microarrays.

    Science.gov (United States)

    Shea, April; Wolcott, Mark; Daefler, Simon; Rozak, David A

    2012-01-01

    Phenotype microarrays nicely complement traditional genomic, transcriptomic, and proteomic analysis by offering opportunities for researchers to ground microbial systems analysis and modeling in a broad yet quantitative assessment of the organism's physiological response to different metabolites and environments. Biolog phenotype assays achieve this by coupling tetrazolium dyes with minimally defined nutrients to measure the impact of hundreds of carbon, nitrogen, phosphorous, and sulfur sources on redox reactions that result from compound-induced effects on the electron transport chain. Over the years, we have used Biolog's reproducible and highly sensitive assays to distinguish closely related bacterial isolates, to understand their metabolic differences, and to model their metabolic behavior using flux balance analysis. This chapter describes Biolog phenotype microarray system components, reagents, and methods, particularly as they apply to bacterial identification, characterization, and metabolic analysis.

  19. [Crossing borders. The motivation of extreme sportsmen].

    Science.gov (United States)

    Opaschowski, H W

    2005-08-01

    In his article "Crossing borders -- the motivation of extreme sportsmen" the author gets systematically to the bottom of the question of why extreme sportsmen voluntarily take risks and endanger themselves. Within the scope of a representative sampling 217 extreme sportsmen -- from the fields of mountain biking, trekking and free climbing, canoyning, river rafting and deep sea diving, paragliding, parachuting, bungee jumping and survival training -- give information about their personal motives. What fascinates them? The attraction of risk? The search for sensation? Or the drop out of everyday life? And what comes afterwards? Does in the end the whole life become an extreme sport? Fact is: they live extremely, because they want to move beyond well-trodden paths. To escape the boredom of everyday life they are searching for the kick, the thrill, the no-limit experience. It's about calculated risk between altitude flight and deep sea adventure.

  20. KSHV Induction of Angiogenic and Lymphangiogenic Phenotypes

    Directory of Open Access Journals (Sweden)

    Terri A. DiMiao

    2012-03-01

    Full Text Available Kaposi’s Sarcoma is a highly vascularized tumor supporting large amounts of neo-angiogenesis. The major cell type in KS tumors is the spindle cell, a cell that expresses markers of lymphatic endothelium. KSHV, the etiologic agent of KS, is found in the spindle cells of all KS tumors. Considering the extreme extent of angiogenesis in KS tumors at all stages it has been proposed that KSHV directly induces angiogenesis in a paracrine fashion. In accordance with this theory, KSHV infection of endothelial cells in culture induces a number of host pathways involved in activation of angiogenesis and a number of KSHV genes themselves can induce pathways involved in angiogenesis. Because spindle cells are phenotypically endothelial in nature, activation through the induction of angiogenic and/or lymphangiogenic phenotypes by the virus may also be directly involved in spindle cell growth and tumor induction. Accordingly, KSHV infection of endothelial cells induces cell autonomous angiogenic phenotypes to activate host cells. KSHV infection can also reprogram blood endothelial cells to lymphatic endothelium. However, KSHV induces some blood endothelial specific genes upon infection of lymphatic endothelial cells creating a phenotypic intermediate between blood and lymphatic endothelium. Induction of pathways involved in angiogenesis and lymphangiogenesis are likely to be critical for tumor cell growth and spread. Thus, induction of both cell autonomous and non-autonomous changes in angiogenic and lymphangiogenic pathways by KSHV likely plays a key role in the formation of KS tumors.

  1. Moving in extreme environments

    DEFF Research Database (Denmark)

    Lucas, Samuel J E; Helge, Jørn W; Schütz, Uwe H W;

    2016-01-01

    This review addresses human capacity for movement in the context of extreme loading and with it the combined effects of metabolic, biomechanical and gravitational stress on the human body. This topic encompasses extreme duration, as occurs in ultra-endurance competitions (e.g. adventure racing...... and transcontinental races) and expeditions (e.g. polar crossings), to the more gravitationally limited load carriage (e.g. in the military context). Juxtaposed to these circumstances is the extreme metabolic and mechanical unloading associated with space travel, prolonged bedrest and sedentary lifestyle, which may...

  2. Extremal surface barriers

    Energy Technology Data Exchange (ETDEWEB)

    Engelhardt, Netta; Wall, Aron C. [Department of Physics, University of California,Santa Barbara, CA 93106 (United States)

    2014-03-13

    We present a generic condition for Lorentzian manifolds to have a barrier that limits the reach of boundary-anchored extremal surfaces of arbitrary dimension. We show that any surface with nonpositive extrinsic curvature is a barrier, in the sense that extremal surfaces cannot be continuously deformed past it. Furthermore, the outermost barrier surface has nonnegative extrinsic curvature. Under certain conditions, we show that the existence of trapped surfaces implies a barrier, and conversely. In the context of AdS/CFT, these barriers imply that it is impossible to reconstruct the entire bulk using extremal surfaces. We comment on the implications for the firewall controversy.

  3. Measuring extremal dependencies in web graphs

    NARCIS (Netherlands)

    Volkovich, Y.; Litvak, Nelli; Zwart, B.

    2008-01-01

    We analyze dependencies in power law graph data (Web sample, Wikipedia sample and a preferential attachment graph) using statistical inference for multivariate regular variation. The well developed theory of regular variation is widely applied in extreme value theory, telecommunications and mathemat

  4. Renal phenotypic investigations of megalin-deficient patients

    DEFF Research Database (Denmark)

    Storm, Tina; Tranebjærg, Lisbeth; Frykholm, Carina

    2013-01-01

    causes the extremely rare Donnai-Barrow/Facio-Oculo-Acustico-Renal (DB/FOAR) syndrome characterized by a characteristic and multifaceted phenotype including low-molecular-weight proteinuria. In this study, we examined the role of megalin for tubular protein reabsorption in humans through analysis...

  5. Analysis of extreme events

    CSIR Research Space (South Africa)

    Khuluse, S

    2009-04-01

    Full Text Available ) determination of the distribution of the damage and (iii) preparation of products that enable prediction of future risk events. The methodology provided by extreme value theory can also be a powerful tool in risk analysis...

  6. Extreme environments and exobiology.

    Science.gov (United States)

    Friedmann, E I

    1993-01-01

    Ecological research on extreme environments can be applied to exobiological problems such as the question of life on Mars. If life forms (fossil or extant) are found on Mars, their study will help to solve fundamental questions about the nature of life on Earth. Extreme environments that are beyond the range of adaptability of their inhabitants are defined as "absolute extreme". Such environments can serve as terrestrial models for the last stages of life in the history of Mars, when the surface cooled down and atmosphere and water disappeared. The cryptoendolithic microbial community in porous rocks of the Ross Desert in Antarctica and the microbial mats at the bottom of frozen Antarctic lakes are such examples. The microbial communities of Siberian permafrost show that, in frozen but stable communities, long-term survival is possible. In the context of terraforming Mars, selected microorganisms isolated from absolute extreme environments are considered for use in creation of a biological carbon cycle.

  7. Venous Ultrasound (Extremities)

    Science.gov (United States)

    ... News Physician Resources Professions Site Index A-Z Ultrasound - Venous (Extremities) Venous ultrasound uses sound waves to ... limitations of Venous Ultrasound Imaging? What is Venous Ultrasound Imaging? Ultrasound is safe and painless, and produces ...

  8. Statistics of extremes

    CERN Document Server

    Gumbel, E J

    2012-01-01

    This classic text covers order statistics and their exceedances; exact distribution of extremes; the 1st asymptotic distribution; uses of the 1st, 2nd, and 3rd asymptotes; more. 1958 edition. Includes 44 tables and 97 graphs.

  9. The DFNA10 phenotype.

    NARCIS (Netherlands)

    Leenheer, E. de; Huygen, P.L.M.; Wayne, S.; Smith, R.J.H.; Cremers, C.W.R.J.

    2001-01-01

    We present a detailed analysis of the DFNA10 phenotype based on data from 25 hearing-impaired persons coming from a large American pedigree segregating for deafness at the DFNA10 locus (chromosome 6q22.3-23.2). Cross-sectional analysis of air conduction threshold-on-age data from all available last-

  10. Mixed phenotype acute leukemia

    Institute of Scientific and Technical Information of China (English)

    Ye Zixing; Wang Shujie

    2014-01-01

    Objective To highlight the current understanding of mixed phenotype acute leukemia (MPAL).Data sources We collected the relevant articles in PubMed (from 1985 to present),using the terms "mixed phenotype acute leukemia","hybrid acute leukemia","biphenotypic acute leukemia",and "mixed lineage leukemia".We also collected the relevant studies in WanFang Data base (from 2000 to present),using the terms "mixed phenotype acute leukemia" and "hybrid acute leukemia".Study selection We included all relevant studies concerning mixed phenotype acute leukemia in English and Chinese version,with no limitation of research design.The duplicated articles are excluded.Results MPAL is a rare subgroup of acute leukemia which expresses the myeloid and lymphoid markers simultaneously.The clinical manifestations of MPAL are similar to other acute leukemias.The World Health Organization classification and the European Group for Immunological classification of Leukaemias 1998 cdteria are most widely used.MPAL does not have a standard therapy regimen.Its treatment depends mostly on the patient's unique immunophenotypic and cytogenetic features,and also the experience of individual physician.The lack of effective treatment contributes to an undesirable prognosis.Conclusion Our understanding about MPAL is still limited.The diagnostic criteria have not been unified.The treatment of MPAL remains to be investigated.The prognostic factor is largely unclear yet.A better diagnostic cdteria and targeted therapeutics will improve the therapy effect and a subsequently better prognosis.

  11. COPD: Definition and Phenotypes

    DEFF Research Database (Denmark)

    Vestbo, J.

    2014-01-01

    particles or gases. Exacerbations and comorbidities contribute to the overall severity in individual patients. The evolution of this definition and the diagnostic criteria currently in use are discussed. COPD is increasingly divided in subgroups or phenotypes based on specific features and association...

  12. Binding of nontarget microorganisms from food washes to anti-Salmonella and anti-E. coli O157 immunomagnetic beads: minimizing the errors of random sampling in extreme dilute systems.

    Science.gov (United States)

    Irwin, Peter; Nguyen, Thi Ly-Huong; Chen, Chin-Yi

    2008-05-01

    For most applications, 3-5 observations, or samplings (n), are utilized to estimate total aerobic plate count in an average population (μ) that is greater than about 50 cells, or colony forming units (CFU), per sampled volume. We have chosen to utilize a 6 × 6 drop plate method for bacterial colony selection because it offers the means to rapidly perform all requisite dilutions in a 96-well format and plate these dilutions on solid media using minimal materials. Besides traditional quantitative purposes, we also need to select colonies which are well-separated from each other for the purpose of bacterial identification. To achieve this goal using the drop plate format requires the utilization of very dilute solutions (μ food samples along with most probable number (MPN) analyses and it was found that the two enumeration methods did not differ significantly.

  13. Phenotyping large tomato plants in the greenhouse usig a 3D light-field camera

    NARCIS (Netherlands)

    Polder, G.; Hofstee, J.W.

    2014-01-01

    Plant phenotyping is an emerging science that links genomics with functional plant characteristics. The recent availability of extremely fast high-throughput genotyping technologies has invoked high-throughput phenotyping to become a major bottleneck in the plant breeding programs. As a consequence

  14. Phenotyping large tomato plants in the greenhouse usig a 3D light-field camera

    NARCIS (Netherlands)

    Polder, G.; Hofstee, J.W.

    2014-01-01

    Plant phenotyping is an emerging science that links genomics with functional plant characteristics. The recent availability of extremely fast high-throughput genotyping technologies has invoked high-throughput phenotyping to become a major bottleneck in the plant breeding programs. As a consequence

  15. Population genomics of divergence among extreme and intermediate color forms in a polymorphic insect.

    Science.gov (United States)

    Lozier, Jeffrey D; Jackson, Jason M; Dillon, Michael E; Strange, James P

    2016-02-01

    Geographic variation in insect coloration is among the most intriguing examples of rapid phenotypic evolution and provides opportunities to study mechanisms of phenotypic change and diversification in closely related lineages. The bumble bee Bombus bifarius comprises two geographically disparate color groups characterized by red-banded and black-banded abdominal pigmentation, but with a range of spatially and phenotypically intermediate populations across western North America. Microsatellite analyses have revealed that B. bifarius in the USA are structured into two major groups concordant with geography and color pattern, but also suggest ongoing gene flow among regional populations. In this study, we better resolve the relationships among major color groups to better understand evolutionary mechanisms promoting and maintaining such polymorphism. We analyze >90,000 and >25,000 single-nucleotide polymorphisms derived from transcriptome (RNAseq) and double digest restriction site associated DNA sequencing (ddRAD), respectively, in representative samples from spatial and color pattern extremes in B. bifarius as well as phenotypic and geographic intermediates. Both ddRAD and RNAseq data illustrate substantial genome-wide differentiation of the red-banded (eastern) color form from both black-banded (western) and intermediate (central) phenotypes and negligible differentiation among the latter populations, with no obvious admixture among bees from the two major lineages. Results thus indicate much stronger background differentiation among B. bifarius lineages than expected, highlighting potential challenges for revealing loci underlying color polymorphism from population genetic data alone. These findings will have significance for resolving taxonomic confusion in this species and in future efforts to investigate color-pattern evolution in B. bifarius and other polymorphic bumble bee species.

  16. Extreme Programming: Maestro Style

    Science.gov (United States)

    Norris, Jeffrey; Fox, Jason; Rabe, Kenneth; Shu, I-Hsiang; Powell, Mark

    2009-01-01

    "Extreme Programming: Maestro Style" is the name of a computer programming methodology that has evolved as a custom version of a methodology, called extreme programming that has been practiced in the software industry since the late 1990s. The name of this version reflects its origin in the work of the Maestro team at NASA's Jet Propulsion Laboratory that develops software for Mars exploration missions. Extreme programming is oriented toward agile development of software resting on values of simplicity, communication, testing, and aggressiveness. Extreme programming involves use of methods of rapidly building and disseminating institutional knowledge among members of a computer-programming team to give all the members a shared view that matches the view of the customers for whom the software system is to be developed. Extreme programming includes frequent planning by programmers in collaboration with customers, continually examining and rewriting code in striving for the simplest workable software designs, a system metaphor (basically, an abstraction of the system that provides easy-to-remember software-naming conventions and insight into the architecture of the system), programmers working in pairs, adherence to a set of coding standards, collaboration of customers and programmers, frequent verbal communication, frequent releases of software in small increments of development, repeated testing of the developmental software by both programmers and customers, and continuous interaction between the team and the customers. The environment in which the Maestro team works requires the team to quickly adapt to changing needs of its customers. In addition, the team cannot afford to accept unnecessary development risk. Extreme programming enables the Maestro team to remain agile and provide high-quality software and service to its customers. However, several factors in the Maestro environment have made it necessary to modify some of the conventional extreme

  17. A new method to infer causal phenotype networks using QTL and phenotypic information.

    Directory of Open Access Journals (Sweden)

    Huange Wang

    Full Text Available In the context of genetics and breeding research on multiple phenotypic traits, reconstructing the directional or causal structure between phenotypic traits is a prerequisite for quantifying the effects of genetic interventions on the traits. Current approaches mainly exploit the genetic effects at quantitative trait loci (QTLs to learn about causal relationships among phenotypic traits. A requirement for using these approaches is that at least one unique QTL has been identified for each trait studied. However, in practice, especially for molecular phenotypes such as metabolites, this prerequisite is often not met due to limited sample sizes, high noise levels and small QTL effects. Here, we present a novel heuristic search algorithm called the QTL+phenotype supervised orientation (QPSO algorithm to infer causal directions for edges in undirected phenotype networks. The two main advantages of this algorithm are: first, it does not require QTLs for each and every trait; second, it takes into account associated phenotypic interactions in addition to detected QTLs when orienting undirected edges between traits. We evaluate and compare the performance of QPSO with another state-of-the-art approach, the QTL-directed dependency graph (QDG algorithm. Simulation results show that our method has broader applicability and leads to more accurate overall orientations. We also illustrate our method with a real-life example involving 24 metabolites and a few major QTLs measured on an association panel of 93 tomato cultivars. Matlab source code implementing the proposed algorithm is freely available upon request.

  18. Histologic and Phenotypic Factors and MC1R Status Associated with BRAF(V600E), BRAF(V600K), and NRAS Mutations in a Community-Based Sample of 414 Cutaneous Melanomas.

    Science.gov (United States)

    Hacker, Elke; Olsen, Catherine M; Kvaskoff, Marina; Pandeya, Nirmala; Yeo, Abrey; Green, Adèle C; Williamson, Richard M; Triscott, Joe; Wood, Dominic; Mortimore, Rohan; Hayward, Nicholas K; Whiteman, David C

    2016-04-01

    Cutaneous melanomas arise through causal pathways involving interplay between exposure to UV radiation and host factors, resulting in characteristic patterns of driver mutations in BRAF, NRAS, and other genes. To gain clearer insights into the factors contributing to somatic mutation genotypes in melanoma, we collected clinical and epidemiologic data, performed skin examinations, and collected saliva and tumor samples from a community-based series of 414 patients aged 18 to 79, newly diagnosed with cutaneous melanoma. We assessed constitutional DNA for nine common polymorphisms in melanocortin-1 receptor gene (MC1R). Tumor DNA was assessed for somatic mutations in 25 different genes. We observed mutually exclusive mutations in BRAF(V600E) (26%), BRAF(V600K) (8%), BRAF(other) (5%), and NRAS (9%). Compared to patients with BRAF wild-type melanomas, those with BRAF(V600E) mutants were significantly younger, had more nevi but fewer actinic keratoses, were more likely to report a family history of melanoma, and had tumors that were more likely to harbor neval remnants. BRAF(V600K) mutations were also associated with high nevus counts. Both BRAF(V600K) and NRAS mutants were associated with older age but not with high sun exposure. We also found no association between MC1R status and any somatic mutations in this community sample of cutaneous melanomas, contrary to earlier reports.

  19. Neurocognitive Phenotypes in Severe Childhood Psychiatric Disorders.

    Science.gov (United States)

    Kavanaugh, Brian C; Dupont-Frechette, Jennifer A; Tellock, Perrin P; Maher, Isolde D; Haisley, Lauren D; Holler, Karen A

    2016-10-01

    This study investigated the presence of potential neurocognitive phenotypes within a severe childhood psychiatric sample. A medical chart review was conducted for 106 children who received a neuropsychological evaluation during children's psychiatric inpatient program hospitalization. A hierarchical cluster analysis was conducted to identify distinct clinical clusters based on neurocognitive measures. Cluster analysis identified four distinct clusters, subsequently labeled neurocognitive phenotypes: "intact cognition" (27%), "global dysfunction" (20%), "organization/planning" (21%), and "inhibition-memory" (32%). Significant differences were identified in history of legal involvement and antipsychotic medications at hospital admission. Differences between none-minimal and moderate-high neurocognitive dysfunction were identified in age, amount of diagnoses and antipsychotic medications at admission, and hospital length of stay. Current findings provide preliminary evidence of underlying neurocognitive phenotypes within severe childhood psychiatric disorders. Findings highlight the importance of neuropsychological evaluation in the treatment of childhood psychiatric disorders.

  20. Statistics of Extremes

    KAUST Repository

    Davison, Anthony C.

    2015-04-10

    Statistics of extremes concerns inference for rare events. Often the events have never yet been observed, and their probabilities must therefore be estimated by extrapolation of tail models fitted to available data. Because data concerning the event of interest may be very limited, efficient methods of inference play an important role. This article reviews this domain, emphasizing current research topics. We first sketch the classical theory of extremes for maxima and threshold exceedances of stationary series. We then review multivariate theory, distinguishing asymptotic independence and dependence models, followed by a description of models for spatial and spatiotemporal extreme events. Finally, we discuss inference and describe two applications. Animations illustrate some of the main ideas. © 2015 by Annual Reviews. All rights reserved.

  1. Extremely deformable structures

    CERN Document Server

    2015-01-01

    Recently, a new research stimulus has derived from the observation that soft structures, such as biological systems, but also rubber and gel, may work in a post critical regime, where elastic elements are subject to extreme deformations, though still exhibiting excellent mechanical performances. This is the realm of ‘extreme mechanics’, to which this book is addressed. The possibility of exploiting highly deformable structures opens new and unexpected technological possibilities. In particular, the challenge is the design of deformable and bi-stable mechanisms which can reach superior mechanical performances and can have a strong impact on several high-tech applications, including stretchable electronics, nanotube serpentines, deployable structures for aerospace engineering, cable deployment in the ocean, but also sensors and flexible actuators and vibration absorbers. Readers are introduced to a variety of interrelated topics involving the mechanics of extremely deformable structures, with emphasis on ...

  2. Precursors of extreme increments

    CERN Document Server

    Hallerberg, S; Holstein, D; Kantz, H; Hallerberg, Sarah; Altmann, Eduardo G.; Holstein, Detlef; Kantz, Holger

    2006-01-01

    We investigate precursors and predictability of extreme events in time series, which consist in large increments within successive time steps. In order to understand the predictability of this class of extreme events, we study analytically the prediction of extreme increments in AR(1)-processes. The resulting strategies are then applied to predict sudden increases in wind speed recordings. In both cases we evaluate the success of predictions via creating receiver operator characteristics (ROC-plots). Surprisingly, we obtain better ROC-plots for completely uncorrelated Gaussian random numbers than for AR(1)-correlated data. Furthermore, we observe an increase of predictability with increasing event size. Both effects can be understood by using the likelihood ratio as a summary index for smooth ROC-curves.

  3. Weather and Climate Extremes.

    Science.gov (United States)

    1997-09-01

    Antarctica’s highest (New Zealand Antarctic Society, 1974). This extreme exceeded the record of 58°F (14.4°C) that occurred on 20 October 1956 at Esperanza ... Esperanza (also known as Bahia Esperanza , Hope Bay) was in operation from 1945 through the early 1960s. Meteorological/Climatological Factors: This extreme...cm) Location: Grand Ilet, La R’eunion Island [21°00’S, 55°30’E] Date: 26 January 1980 WORLD’S GREATEST 24-HOUR RAINFALL 72 in (182.5 cm

  4. Adventure and Extreme Sports.

    Science.gov (United States)

    Gomez, Andrew Thomas; Rao, Ashwin

    2016-03-01

    Adventure and extreme sports often involve unpredictable and inhospitable environments, high velocities, and stunts. These activities vary widely and include sports like BASE jumping, snowboarding, kayaking, and surfing. Increasing interest and participation in adventure and extreme sports warrants understanding by clinicians to facilitate prevention, identification, and treatment of injuries unique to each sport. This article covers alpine skiing and snowboarding, skateboarding, surfing, bungee jumping, BASE jumping, and whitewater sports with emphasis on epidemiology, demographics, general injury mechanisms, specific injuries, chronic injuries, fatality data, and prevention. Overall, most injuries are related to overuse, trauma, and environmental or microbial exposure.

  5. Extremal graph theory

    CERN Document Server

    Bollobas, Bela

    2004-01-01

    The ever-expanding field of extremal graph theory encompasses a diverse array of problem-solving methods, including applications to economics, computer science, and optimization theory. This volume, based on a series of lectures delivered to graduate students at the University of Cambridge, presents a concise yet comprehensive treatment of extremal graph theory.Unlike most graph theory treatises, this text features complete proofs for almost all of its results. Further insights into theory are provided by the numerous exercises of varying degrees of difficulty that accompany each chapter. A

  6. Association of alkaline phosphatase phenotypes with arthritides

    Directory of Open Access Journals (Sweden)

    Padmini A

    2004-01-01

    Full Text Available Arthritides, a symmetrical polyarticular disease of the bone are a heterogenous group of disorders in which hereditary and environmental factors in combination with an altered immune response appear to play a causative and pathogenic role in its occurrence. Alkaline phosphatase (ALP is an enzyme found in all tissues, with particularly high concentrations of ALP observed in the liver, bile ducts, placenta, and bone.Alkaline phosphatase is an orthophosphoric monoester phosphohydrolase catalyzing the hydrolysis of organic esters at alkaline pH, indicating that alkaline phosphatase is involved in fundamental biological processes.1 The present study envisages on identifying the specific electromorphic association of alkaline phosphatase with arthritides. Phenotyping of serum samples was carried out by PAGE (Polyacrylamide gel electrophoresis following Davies (19642 protocol on 41 juvenile arthritis, 150 rheumatoid arthritis and 100 osteo arthritis apart from, 25 normal children and 100 adult healthy subjects. Phenotyping of alkaline phosphatase revealed an increase in preponderance of p+ and p++ phenotypes in juvenile, rheumatoid and osteo arthritic patients. However a significant association of these phenotypes was observed only with rheumatoid arthritis condition (c2:17.46. Similarly, a significant increase of p+ phenotypes in female rheumatoid arthritis patients was observed (c2:14.973, suggesting that the decrease in p° (tissue non specific synthesis/secretion of alkaline phosphatase could be associated with decreased mineralization and ossification process in arthritis condition.

  7. Extreme values, regular variation and point processes

    CERN Document Server

    Resnick, Sidney I

    1987-01-01

    Extremes Values, Regular Variation and Point Processes is a readable and efficient account of the fundamental mathematical and stochastic process techniques needed to study the behavior of extreme values of phenomena based on independent and identically distributed random variables and vectors It presents a coherent treatment of the distributional and sample path fundamental properties of extremes and records It emphasizes the core primacy of three topics necessary for understanding extremes the analytical theory of regularly varying functions; the probabilistic theory of point processes and random measures; and the link to asymptotic distribution approximations provided by the theory of weak convergence of probability measures in metric spaces The book is self-contained and requires an introductory measure-theoretic course in probability as a prerequisite Almost all sections have an extensive list of exercises which extend developments in the text, offer alternate approaches, test mastery and provide for enj...

  8. Why do people buy dogs with potential welfare problems related to extreme conformation and inherited disease?

    DEFF Research Database (Denmark)

    Sandøe, Peter; Kondrup, Sara Vincentzen; Bennett, P.C.

    2017-01-01

    number of dog breeds suffer from welfare problems due to extreme phenotypes and high levels of inherited diseases but the popularity of such breeds is not declining. Using a survey of owners of two popular breeds with extreme physical features (French Bulldog and Chihuahua), one with a high load...

  9. Phenotypic heterogeneity of monogenic frontotemporal dementia

    Directory of Open Access Journals (Sweden)

    Alberto eBenussi

    2015-09-01

    Full Text Available Frontotemporal dementia (FTD is a genetically and pathologically heterogeneous disorder characterized by personality changes, language impairment and deficits of executive functions associated with frontal and temporal lobe degeneration. Different phenotypes have been defined on the basis of presenting clinical symptoms, i.e. the behavioral variant of FTD (bvFTD, the agrammatic variant of Primary Progressive Aphasia (avPPA and the semantic variant of PPA (svPPA. Some patients have an associated movement disorder, either parkinsonism, as in Progressive Supranuclear Palsy (PSP and Corticobasal Syndrome (CBS, or motor neuron disease (FTD-MND. A family history of dementia is found in 40% of cases of FTD and about 10% have a clear autosomal dominant inheritance. Genetic studies have identified several genes associated to monogenic FTD: microtubule-associated protein tau (MAPT, progranulin (GRN, TAR DNA-binding protein 43 (TARBDP, valosin-containing protein (VCP, charged multivesicular body protein 2B (CHMP2B, fused in sarcoma (FUS and the hexanucleotide repeat expansion in intron 1 of the chromosome 9 open reading frame 72 (C9orf72. Patients often present with an extensive phenotypic variability, even among different members of the same kindred carrying an identical disease mutation. The objective of the present work is to review and evaluate available literature data in order to highlight recent advances in clinical, biological and neuroimaging features of monogenic frontotemporal lobar degeneration and try to identify different mechanisms underlying the extreme phenotypic heterogeneity that characterizes this disease.

  10. Extremity perfusion for sarcoma

    NARCIS (Netherlands)

    Hoekstra, Harald Joan

    2008-01-01

    For more than 50 years, the technique of extremity perfusion has been explored in the limb salvage treatment of local, recurrent, and multifocal sarcomas. The "discovery" of tumor necrosis factor-or. in combination with melphalan was a real breakthrough in the treatment of primarily irresectable ext

  11. Hydrological extremes and security

    Science.gov (United States)

    Kundzewicz, Z. W.; Matczak, P.

    2015-04-01

    Economic losses caused by hydrological extremes - floods and droughts - have been on the rise. Hydrological extremes jeopardize human security and impact on societal livelihood and welfare. Security can be generally understood as freedom from threat and the ability of societies to maintain their independent identity and their functional integrity against forces of change. Several dimensions of security are reviewed in the context of hydrological extremes. The traditional interpretation of security, focused on the state military capabilities, has been replaced by a wider understanding, including economic, societal and environmental aspects that get increasing attention. Floods and droughts pose a burden and serious challenges to the state that is responsible for sustaining economic development, and societal and environmental security. The latter can be regarded as the maintenance of ecosystem services, on which a society depends. An important part of it is water security, which can be defined as the availability of an adequate quantity and quality of water for health, livelihoods, ecosystems and production, coupled with an acceptable level of water-related risks to people, environments and economies. Security concerns arise because, over large areas, hydrological extremes - floods and droughts - are becoming more frequent and more severe. In terms of dealing with water-related risks, climate change can increase uncertainties, which makes the state's task to deliver security more difficult and more expensive. However, changes in population size and development, and level of protection, drive exposure to hydrological hazards.

  12. Acute lower extremity ischaemia

    African Journals Online (AJOL)

    tend to impact at arterial bifurcations, the commonest site being the ... Other ominous signs of advanced ischaemia include bluish ... Recommended standards for lower extremity ischaemia*. Doppler signals ... of the embolectomy procedure. An ... in a cath-lab or angio-suite under local ... We serially measure the aPTT and.

  13. Extremity perfusion for sarcoma

    NARCIS (Netherlands)

    Hoekstra, Harald Joan

    2008-01-01

    For more than 50 years, the technique of extremity perfusion has been explored in the limb salvage treatment of local, recurrent, and multifocal sarcomas. The "discovery" of tumor necrosis factor-or. in combination with melphalan was a real breakthrough in the treatment of primarily irresectable

  14. Statistics of Local Extremes

    DEFF Research Database (Denmark)

    Larsen, Gunner Chr.; Bierbooms, W.; Hansen, Kurt Schaldemose

    2003-01-01

    . A theoretical expression for the probability density function associated with local extremes of a stochasticprocess is presented. The expression is basically based on the lower four statistical moments and a bandwidth parameter. The theoretical expression is subsequently verified by comparison with simulated...

  15. de Sitter Extremal Surfaces

    CERN Document Server

    Narayan, K

    2015-01-01

    We study extremal surfaces in de Sitter space in the Poincare slicing in the upper patch, anchored on spatial subregions at the future boundary ${\\cal I}^+$, restricted to constant boundary Euclidean time slices (focussing on strip subregions). We find real extremal surfaces of minimal area as the boundaries of past lightcone wedges of the subregions in question: these are null surfaces with vanishing area. We find also complex extremal surfaces as complex extrema of the area functional, and the area is not always real-valued. In $dS_4$ the area is real and has some structural resemblance with entanglement entropy in a dual $CFT_3$. There are parallels with analytic continuation from the Ryu-Takayanagi expressions for holographic entanglement entropy in $AdS$. We also discuss extremal surfaces in the $dS$ black brane and the de Sitter "bluewall" studied previously. The $dS_4$ black brane complex surfaces exhibit a real finite cutoff-independent extensive piece. In the bluewall geometry, there are real surface...

  16. Moving in extreme environments

    DEFF Research Database (Denmark)

    Lucas, Samuel J E; Helge, Jørn W; Schütz, Uwe H W

    2016-01-01

    and transcontinental races) and expeditions (e.g. polar crossings), to the more gravitationally limited load carriage (e.g. in the military context). Juxtaposed to these circumstances is the extreme metabolic and mechanical unloading associated with space travel, prolonged bedrest and sedentary lifestyle, which may...

  17. Extremal Coupled Map Lattices

    CERN Document Server

    Abramson, G; Abramson, Guillermo; Vega, Jose Luis

    1999-01-01

    We propose a model for co-evolving ecosystems that takes into account two levels of description of an organism, for instance genotype and phenotype. Performance at the macroscopic level forces mutations at the microscopic level. These, in turn, affect the dynamics of the macroscopic variables. In some regions of parameter space, the system self-organises into a state with localised activity and power law distributions.

  18. Phenotypic and genotypic evaluation of beta-lactamases (ESBL and KPC) among enterobacteria isolated from community-acquired monomicrobial urinary tract infections.

    Science.gov (United States)

    Dias, Vanessa Cordeiro; da Silva, Vânia Lúcia; Barros, Renata; Bastos, André Netto; de Andrade Bastos, Lucas Quinnet; de Andrade Bastos, Victor Quinnet; Diniz, Cláudio Galuppo

    2014-12-01

    Beta-lactamases enzymes such as extended-spectrum beta-lactamases (ESBL) and carbapenemase type beta-lactamases (KPC) confer resistance to beta-lactam drugs among Gram-negative rods, mainly Enterobacteriaceae, as those frequently related to urinary tract infections (UTI). The aim of this study was to evaluate ESBL and KPC among enterobacteria isolated from monomicrobial UTI and to establish correlations between the presence of genetic markers and the phenotypic resistance to beta-lactam antibiotics. Out of 12 304 urine samples collected during 2009, 93 enterobacteria showing an ESBL phenotype were recovered. Imipenem was used for KPC screening and modified disk approximation assay was used for detection of ESBL phenotype. Polymerase chain reaction was used for screening of bla(SHV), bla(TEM), bla(CTX-M), and bla(KPC). Considering the isolated bacteria showing ESBL phenotype 56% of the isolates were positive for two genes. The bla(TEM) was the most frequent (87·1%). Neither KPC phenotype nor bla(KPC)-harboring bacteria were observed. Monitoring the antimicrobial resistance is extremely important to sustain empirical therapy of community-acquired urinary tract infections (Co-UTI).

  19. Behavioral and life history responses to extreme climatic conditions: Studies on a migratory songbird

    OpenAIRE

    2011-01-01

    Behavioral responses to environmental change are the mechanisms that allow for rapid phenotypic change preventing temporary or permanent damage and hence preventing reductions in fitness. Extreme climatic events are by definition rare, although they are predicted to increase in amplitude and frequency in the coming years. However, our current knowledge about behavioral responses to such extreme events is scarce. Here I analyze two examples of the effects of extreme weather events on behavior ...

  20. Klinefelter syndrome (KS): genetics, clinical phenotype and hypogonadism.

    Science.gov (United States)

    Bonomi, M; Rochira, V; Pasquali, D; Balercia, G; Jannini, E A; Ferlin, A

    2017-02-01

    Klinefelter Syndrome (KS) is characterized by an extreme heterogeneity in its clinical and genetic presentation. The relationship between clinical phenotype and genetic background has been partially disclosed; nevertheless, physicians are aware that several aspects concerning this issue are far to be fully understood. By improving our knowledge on the role of some genetic aspects as well as on the KS, patients' interindividual differences in terms of health status will result in a better management of this chromosomal disease. The aim of this review is to provide an update on both genetic and clinical phenotype and their interrelationships.

  1. Non-extremal branes

    Directory of Open Access Journals (Sweden)

    Pablo Bueno

    2015-04-01

    Full Text Available We prove that for arbitrary black brane solutions of generic Supergravities there is an adapted system of variables in which the equations of motion are exactly invariant under electric–magnetic duality, i.e. the interchange of a given extended object by its electromagnetic dual. We obtain thus a procedure to automatically construct the electromagnetic dual of a given brane without needing to solve any further equation. We apply this procedure to construct the non-extremal (p,q-string of Type-IIB String Theory (new in the literature, explicitly showing how the dual (p,q-five-brane automatically arises in this construction. In addition, we prove that the system of variables used is suitable for a generic characterization of every double-extremal Supergravity brane solution, which we perform in full generality.

  2. Tibetans at extreme altitude.

    Science.gov (United States)

    Wu, Tianyi; Li, Shupin; Ward, Michal P

    2005-01-01

    Between 1960 and 2003, 13 Chinese expeditions successfully reached the summit of Chomolungma (Mt Everest or Sagarmatha). Forty-five of the 80 summiteers were Tibetan highlanders. During these and other high-altitude expeditions in Tibet, a series of medical and physiological investigations were carried out on the Tibetan mountaineers. The results suggest that these individuals are better adapted to high altitude and that, at altitude, they have a greater physical capacity than Han (ethnic Chinese) lowland newcomers. They have higher maximal oxygen uptake, greater ventilation, more brisk hypoxic ventilatory responses, larger lung volumes, greater diffusing capacities, and a better quality of sleep. Tibetans also have a lower incidence of acute mountain sickness and less body weight loss. These differences appear to represent genetic adaptations and are obviously significant for humans at extreme altitude. This paper reviews what is known about the physiologic responses of Tibetans at extreme altitudes.

  3. Extremal periodic wave profiles

    Directory of Open Access Journals (Sweden)

    E. van Groesen

    2007-01-01

    Full Text Available As a contribution to deterministic investigations into extreme fluid surface waves, in this paper wave profiles of prescribed period that have maximal crest height will be investigated. As constraints the values of the momentum and energy integrals are used in a simplified description with the KdV model. The result is that at the boundary of the feasible region in the momentum-energy plane, the only possible profiles are the well known cnoidal wave profiles. Inside the feasible region the extremal profiles of maximal crest height are "cornered" cnoidal profiles: cnoidal profiles of larger period, cut-off and periodically continued with the prescribed period so that at the maximal crest height a corner results.

  4. Extreme Photonics & Applications

    CERN Document Server

    Hall, Trevor J; Paredes, Sofia A

    2010-01-01

    "Extreme Photonics & Applications" arises from the 2008 NATO Advanced Study Institute in Laser Control & Monitoring in New Materials, Biomedicine, Environment, Security and Defense. Leading experts in the manipulation of light offered by recent advances in laser physics and nanoscience were invited to give lectures in their fields of expertise and participate in discussions on current research, applications and new directions. The sum of their contributions to this book is a primer for the state of scientific knowledge and the issues within the subject of photonics taken to the extreme frontiers: molding light at the ultra-finest scales, which represents the beginning of the end to limitations in optical science for the benefit of 21st Century technological societies. Laser light is an exquisite tool for physical and chemical research. Physicists have recently developed pulsed lasers with such short durations that one laser shot takes the time of one molecular vibration or one electron rotation in an ...

  5. Extremal Hairy Black Holes

    CERN Document Server

    Gonzalez, P A; Saavedra, Joel; Vasquez, Yerko

    2014-01-01

    We consider a gravitating system consisting of a scalar field minimally coupled to gravity with a self-interacting potential and an U(1) electromagnetic field. Solving the coupled Einstein-Maxwell-scalar system we find exact hairy charged black hole solutions with the scalar field regular everywhere. We go to the zero temperature limit and we study the effect of the scalar field on the near horizon geometry of an extremal black hole. We find that except a critical value of the charge of the black hole there is also a critical value of the charge of the scalar field beyond of which the extremal black hole is destabilized. We study the thermodynamics of these solutions and we find that if the space is flat then at low temperature the Reissner-Nordstr\\"om black hole is thermodynamically preferred, while if the space is AdS the hairy charged black hole is thermodynamically preferred at low temperature.

  6. Religious Extremism in Pakistan

    Science.gov (United States)

    2014-12-01

    Face (July 2008): 32. 21 Ahmed Rashid , Pakistan on the Brink: The Future of America, Pakistan, and Afghanistan (New York: Viking, 2012). 22 Brian J...promoting extremism. Commentators such as Jessica Stern, Alan Richards, Hussain Haqqani, Ahmed Rashid , and Ali Riaz are a few of the scholars who...www.jstor.org/stable/3183558; See also Ahmed Rashid , Descent Into Chaos: The United States and the Failure of Nation Building in Pakistan, Afghanistan, and

  7. USACE Extreme Sea levels

    Science.gov (United States)

    2014-03-14

    report summarising the results of the research, together with a set of recommendations arising from the research. This report describes progress to...Southampton University at HR Wallingford and subsequent teleconference with Heidi Moritz and Kate White. The notes summarising the findings of the...suggestion was made that we may want to begin talking about extreme water levels separate from storms. Ivan mentioned an analysis of storminess which

  8. Extreme geomagnetically induced currents

    Science.gov (United States)

    Kataoka, Ryuho; Ngwira, Chigomezyo

    2016-12-01

    We propose an emergency alert framework for geomagnetically induced currents (GICs), based on the empirically extreme values and theoretical upper limits of the solar wind parameters and of d B/d t, the time derivative of magnetic field variations at ground. We expect this framework to be useful for preparing against extreme events. Our analysis is based on a review of various papers, including those presented during Extreme Space Weather Workshops held in Japan in 2011, 2012, 2013, and 2014. Large-amplitude d B/d t values are the major cause of hazards associated with three different types of GICs: (1) slow d B/d t with ring current evolution (RC-type), (2) fast d B/d t associated with auroral electrojet activity (AE-type), and (3) transient d B/d t of sudden commencements (SC-type). We set "caution," "warning," and "emergency" alert levels during the main phase of superstorms with the peak Dst index of less than -300 nT (once per 10 years), -600 nT (once per 60 years), or -900 nT (once per 100 years), respectively. The extreme d B/d t values of the AE-type GICs are 2000, 4000, and 6000 nT/min at caution, warning, and emergency levels, respectively. For the SC-type GICs, a "transient alert" is also proposed for d B/d t values of 40 nT/s at low latitudes and 110 nT/s at high latitudes, especially when the solar energetic particle flux is unusually high.

  9. Extremes in nature

    CERN Document Server

    Salvadori, Gianfausto; Kottegoda, Nathabandu T

    2007-01-01

    This book is about the theoretical and practical aspects of the statistics of Extreme Events in Nature. Most importantly, this is the first text in which Copulas are introduced and used in Geophysics. Several topics are fully original, and show how standard models and calculations can be improved by exploiting the opportunities offered by Copulas. In addition, new quantities useful for design and risk assessment are introduced.

  10. An ontology for microbial phenotypes.

    Science.gov (United States)

    Chibucos, Marcus C; Zweifel, Adrienne E; Herrera, Jonathan C; Meza, William; Eslamfam, Shabnam; Uetz, Peter; Siegele, Deborah A; Hu, James C; Giglio, Michelle G

    2014-11-30

    Phenotypic data are routinely used to elucidate gene function in organisms amenable to genetic manipulation. However, previous to this work, there was no generalizable system in place for the structured storage and retrieval of phenotypic information for bacteria. The Ontology of Microbial Phenotypes (OMP) has been created to standardize the capture of such phenotypic information from microbes. OMP has been built on the foundations of the Basic Formal Ontology and the Phenotype and Trait Ontology. Terms have logical definitions that can facilitate computational searching of phenotypes and their associated genes. OMP can be accessed via a wiki page as well as downloaded from SourceForge. Initial annotations with OMP are being made for Escherichia coli using a wiki-based annotation capture system. New OMP terms are being concurrently developed as annotation proceeds. We anticipate that diverse groups studying microbial genetics and associated phenotypes will employ OMP for standardizing microbial phenotype annotation, much as the Gene Ontology has standardized gene product annotation. The resulting OMP resource and associated annotations will facilitate prediction of phenotypes for unknown genes and result in new experimental characterization of phenotypes and functions.

  11. Predicting phenotypic diversity and the underlying quantitative molecular transitions.

    Directory of Open Access Journals (Sweden)

    Claudiu A Giurumescu

    2009-04-01

    Full Text Available During development, signaling networks control the formation of multicellular patterns. To what extent quantitative fluctuations in these complex networks may affect multicellular phenotype remains unclear. Here, we describe a computational approach to predict and analyze the phenotypic diversity that is accessible to a developmental signaling network. Applying this framework to vulval development in C. elegans, we demonstrate that quantitative changes in the regulatory network can render approximately 500 multicellular phenotypes. This phenotypic capacity is an order-of-magnitude below the theoretical upper limit for this system but yet is large enough to demonstrate that the system is not restricted to a select few outcomes. Using metrics to gauge the robustness of these phenotypes to parameter perturbations, we identify a select subset of novel phenotypes that are the most promising for experimental validation. In addition, our model calculations provide a layout of these phenotypes in network parameter space. Analyzing this landscape of multicellular phenotypes yielded two significant insights. First, we show that experimentally well-established mutant phenotypes may be rendered using non-canonical network perturbations. Second, we show that the predicted multicellular patterns include not only those observed in C. elegans, but also those occurring exclusively in other species of the Caenorhabditis genus. This result demonstrates that quantitative diversification of a common regulatory network is indeed demonstrably sufficient to generate the phenotypic differences observed across three major species within the Caenorhabditis genus. Using our computational framework, we systematically identify the quantitative changes that may have occurred in the regulatory network during the evolution of these species. Our model predictions show that significant phenotypic diversity may be sampled through quantitative variations in the regulatory network

  12. Eukaryotic diversity at pH extremes

    Directory of Open Access Journals (Sweden)

    Linda A. Amaral-Zettler

    2013-01-01

    Full Text Available Extremely acidic (pH<3 and extremely alkaline (pH>9 environments support a diversity of single-cell and to a lesser extent, multicellular eukaryotic life. This study compared alpha and beta diversity in eukaryotic communities from 7 diverse aquatic environments with pH values ranging from 2 to 11 using massively-parallel pyrotag sequencing targeting the V9 hypervariable region of the 18S ribosomal RNA (rRNA gene. A total of 946 Operational Taxonomic Units (OTUs were recovered at a 6% cut-off level (94% similarity across the sampled environments. Hierarchical clustering of the samples segregated the communities into acidic and alkaline groups. Similarity Percentage Analysis (SIMPER followed by Indicator OTU Analysis (IOA and Non-metric Multidimensional Scaling (NMDS were used to determine which characteristic groups of eukaryotic taxa typify acidic or alkaline extremes and the extent to which pH explains eukaryotic community structure in these environments. Spain’s Rio Tinto yielded the fewest observed OTUs while Nebraska Sandhills alkaline lakes yielded the most. Distinct OTUs, including metazoan OTUs, numerically dominated pH extreme sites. Indicator OTUs included the diatom Pinnularia and unidentified opisthokonts (Fungi and Filasterea in the extremely acidic environments, and the ciliate Frontonia across the extremely alkaline sites. Inferred from NMDS, pH explained only a modest fraction of the variation across the datasets, indicating that other factors influence the underlying community structure in these environments. The findings from this study suggest that the ability for eukaryotes to adapt to pH extremes over a broad range of values may be rare, but further study of taxa that can broadly adapt across diverse acidic and alkaline environments respectively present good models for understanding adaptation and should be targeted for future investigations.

  13. Application of Phenotype Microarray technology to soil microbiology

    Science.gov (United States)

    Mocali, Stefano

    2016-04-01

    It is well established that soil microorganisms are extremely diverse and only a small fraction has been successfully cultured in the laboratory. Furthermore, addressing the functionality of genomes is one of the most important and challenging tasks of today's biology. In particular the ability to link genotypes to corresponding phenotypes is of interest in the reconstruction and biotechnological manipulation of metabolic pathways. High-throughput culture in micro wells provides a method for rapid screening of a wide variety of growth conditions and commercially available plates contain a large number of substrates, nutrient sources, and inhibitors, which can provide an assessment of the phenotype of an organism. Thus, over the last years, Phenotype Microarray (PM) technology has been used to address many specific issues related to the metabolic functionality of microorganisms. However, computational tools that could directly link PM data with the gene(s) of interest followed by the extraction of information on gene-phenotype correlation are still missing. Here potential applications of phenotype arrays to soil microorganisms, use of the plates in stress response studies and for assessment of phenotype of environmental communities are described. Considerations and challenges in data interpretation and visualization, including data normalization, statistics, and curve fitting are also discussed. In particular, here we present DuctApe, a suite that allows the analysis of both genomic sequences and PM data, to find metabolic differences among PM experiments and to correlate them with KEGG pathways and gene presence/absence patterns.

  14. Accurate Breakpoint Mapping in Apparently Balanced Translocation Families with Discordant Phenotypes Using Whole Genome Mate-Pair Sequencing

    DEFF Research Database (Denmark)

    Aristidou, Constantia; Koufaris, Costas; Theodosiou, Athina

    2017-01-01

    Familial apparently balanced translocations (ABTs) segregating with discordant phenotypes are extremely challenging for interpretation and counseling due to the scarcity of publications and lack of routine techniques for quick investigation. Recently, next generation sequencing has emerged...

  15. Global nutrient profiling by Phenotype MicroArrays: a tool complementing genomic and proteomic studies in conidial fungi

    National Research Council Canada - National Science Library

    Atanasova, Lea; Druzhinina, Irina S

    2010-01-01

    .... They are also important pathogens of animals including humans and agricultural crops. These various applications and extremely versatile natural phenotypes have led to the constantly growing list of complete genomes which are now available...

  16. High-throughput mouse phenotyping.

    Science.gov (United States)

    Gates, Hilary; Mallon, Ann-Marie; Brown, Steve D M

    2011-04-01

    Comprehensive phenotyping will be required to reveal the pleiotropic functions of a gene and to uncover the wider role of genetic loci within diverse biological systems. The challenge will be to devise phenotyping approaches to characterise the thousands of mutants that are being generated as part of international efforts to acquire a mutant for every gene in the mouse genome. In order to acquire robust datasets of broad based phenotypes from mouse mutants it is necessary to design and implement pipelines that incorporate standardised phenotyping platforms that are validated across diverse mouse genetics centres or mouse clinics. We describe here the rationale and methodology behind one phenotyping pipeline, EMPReSSslim, that was designed as part of the work of the EUMORPHIA and EUMODIC consortia, and which exemplifies some of the challenges facing large-scale phenotyping. EMPReSSslim captures a broad range of data on diverse biological systems, from biochemical to physiological amongst others. Data capture and dissemination is pivotal to the operation of large-scale phenotyping pipelines, including the definition of parameters integral to each phenotyping test and the associated ontological descriptions. EMPReSSslim data is displayed within the EuroPhenome database, where a variety of tools are available to allow the user to search for interesting biological or clinical phenotypes. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. Extreme Programming Pocket Guide

    CERN Document Server

    Chromatic

    2003-01-01

    Extreme Programming (XP) is a radical new approach to software development that has been accepted quickly because its core practices--the need for constant testing, programming in pairs, inviting customer input, and the communal ownership of code--resonate with developers everywhere. Although many developers feel that XP is rooted in commonsense, its vastly different approach can bring challenges, frustrations, and constant demands on your patience. Unless you've got unlimited time (and who does these days?), you can't always stop to thumb through hundreds of pages to find the piece of info

  18. Mycetoma of lower extremity

    Directory of Open Access Journals (Sweden)

    Sahariah S

    1978-01-01

    Full Text Available Ten cases of mycetoma of the lower extremity were seen and treated at the Postgraduate Institute of Medical Education & Research, Chandigarh, India, during the years 1973 to 1975. Six were treated by conservative method e.g. antibiotics, sulfonamides and immobilization of the part while remaining four were submitted t o surgery. Four out o f six from the first group had recurrence and has been put on second line of therapy. Recurrence occurred in only one case from the second group and he required an above knee amputation while the remaining three are free of disease and are well rehabilitated.

  19. Metagenomics of extreme environments.

    Science.gov (United States)

    Cowan, D A; Ramond, J-B; Makhalanyane, T P; De Maayer, P

    2015-06-01

    Whether they are exposed to extremes of heat or cold, or buried deep beneath the Earth's surface, microorganisms have an uncanny ability to survive under these conditions. This ability to survive has fascinated scientists for nearly a century, but the recent development of metagenomics and 'omics' tools has allowed us to make huge leaps in understanding the remarkable complexity and versatility of extremophile communities. Here, in the context of the recently developed metagenomic tools, we discuss recent research on the community composition, adaptive strategies and biological functions of extremophiles.

  20. Winter Storms and Extreme Cold

    Science.gov (United States)

    ... Landslides & Debris Flow Nuclear Blast Nuclear Power Plants Power Outages Pandemic Radiological Dispersion Device Severe Weather Snowstorms & Extreme ... Landslides & Debris Flow Nuclear Blast Nuclear Power Plants Power Outages Pandemic Radiological Dispersion Device Severe Weather Snowstorms & Extreme ...

  1. Phenotype-genotype correlation in β-thalassemia

    OpenAIRE

    Galanello, R; Perseu, L.; S. Satta; F.R. Demartis; Campus, S.

    2011-01-01

    The clinical manifestations of β-thalassemia are extremely heterogeneous, ranging from severe transfusion-dependent anemia, to the mild non transfusion dependent thalassemia intermedia and to the asymptomatic carrier state. The remarkable phenotypic variability is primary due to variations in the different globin genes (primary gene modifiers). The main pathophysiological determinant of the severity of β-thalassemia syndromes is the extent of a/non-a globin chain imbalance. Therefor...

  2. Factors and processes modulating phenotypes in neuronopathic lysosomal storage diseases

    OpenAIRE

    Jakóbkiewicz-Banecka, Joanna; Gabig-Cimińska, Magdalena; Banecka-Majkutewicz, Zyta; Banecki, Bogdan; Węgrzyn, Alicja; Węgrzyn, Grzegorz

    2013-01-01

    Lysosomal storage diseases are inherited metabolic disorders caused by genetic defects causing deficiency of various lysosomal proteins, and resultant accumulation of non-degraded compounds. They are multisystemic diseases, and in most of them (>70 %) severe brain dysfunctions are evident. However, expression of various phenotypes in particular diseases is extremely variable, from non-neuronopathic to severely neurodegenerative in the deficiency of the same enzyme. Although all lysosomal stor...

  3. The Genetic Basis of Mendelian Phenotypes: Discoveries, Challenges, and Opportunities.

    Science.gov (United States)

    Chong, Jessica X; Buckingham, Kati J; Jhangiani, Shalini N; Boehm, Corinne; Sobreira, Nara; Smith, Joshua D; Harrell, Tanya M; McMillin, Margaret J; Wiszniewski, Wojciech; Gambin, Tomasz; Coban Akdemir, Zeynep H; Doheny, Kimberly; Scott, Alan F; Avramopoulos, Dimitri; Chakravarti, Aravinda; Hoover-Fong, Julie; Mathews, Debra; Witmer, P Dane; Ling, Hua; Hetrick, Kurt; Watkins, Lee; Patterson, Karynne E; Reinier, Frederic; Blue, Elizabeth; Muzny, Donna; Kircher, Martin; Bilguvar, Kaya; López-Giráldez, Francesc; Sutton, V Reid; Tabor, Holly K; Leal, Suzanne M; Gunel, Murat; Mane, Shrikant; Gibbs, Richard A; Boerwinkle, Eric; Hamosh, Ada; Shendure, Jay; Lupski, James R; Lifton, Richard P; Valle, David; Nickerson, Deborah A; Bamshad, Michael J

    2015-08-06

    Discovering the genetic basis of a Mendelian phenotype establishes a causal link between genotype and phenotype, making possible carrier and population screening and direct diagnosis. Such discoveries also contribute to our knowledge of gene function, gene regulation, development, and biological mechanisms that can be used for developing new therapeutics. As of February 2015, 2,937 genes underlying 4,163 Mendelian phenotypes have been discovered, but the genes underlying ∼50% (i.e., 3,152) of all known Mendelian phenotypes are still unknown, and many more Mendelian conditions have yet to be recognized. This is a formidable gap in biomedical knowledge. Accordingly, in December 2011, the NIH established the Centers for Mendelian Genomics (CMGs) to provide the collaborative framework and infrastructure necessary for undertaking large-scale whole-exome sequencing and discovery of the genetic variants responsible for Mendelian phenotypes. In partnership with 529 investigators from 261 institutions in 36 countries, the CMGs assessed 18,863 samples from 8,838 families representing 579 known and 470 novel Mendelian phenotypes as of January 2015. This collaborative effort has identified 956 genes, including 375 not previously associated with human health, that underlie a Mendelian phenotype. These results provide insight into study design and analytical strategies, identify novel mechanisms of disease, and reveal the extensive clinical variability of Mendelian phenotypes. Discovering the gene underlying every Mendelian phenotype will require tackling challenges such as worldwide ascertainment and phenotypic characterization of families affected by Mendelian conditions, improvement in sequencing and analytical techniques, and pervasive sharing of phenotypic and genomic data among researchers, clinicians, and families. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  4. An importance sampling algorithm for estimating extremes of perpetuity sequences

    DEFF Research Database (Denmark)

    Collamore, Jeffrey F.

    2012-01-01

    is efficient in the sense that it exhibits bounded relative error, and which is optimal in an appropriate asymptotic sense. The main idea of the algorithm is to use a ``dual" change of measure, which is employed to an associated Markov chain over a randomly-stopped time interval. The algorithm also makes use...

  5. Update on the phenotypic spectrum of Lesch-Nyhan disease and its attenuated variants.

    Science.gov (United States)

    Torres, Rosa J; Puig, Juan G; Jinnah, H A

    2012-04-01

    Congenital deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT) results in a spectrum of clinical phenotypes. All of these phenotypes are associated with marked overproduction of uric acid and related problems such as hyperuricemia, urate nephrolithiasis, tophi, and gout. The mildest phenotypes include only problems related to overproduction of uric acid. The most severe phenotype is known as Lesch-Nyhan disease, in which the phenotype also includes severe motor handicap, intellectual disability, and self-injurious behavior. In between these two extremes is a continuous spectrum of phenotypes with varying degrees of motor and cognitive handicap but no self-injurious behavior. The pathogenesis of overproduction of uric acid in HPRT deficiency is well-understood, and treatments are available to control it. The pathogenesis of the neurobehavioral problems is less well-understood, and effective treatments for them are lacking.

  6. Environmental variation, hybridization, and phenotypic diversification in Cuatro Ciénegas pupfishes.

    Science.gov (United States)

    Tobler, M; Carson, E W

    2010-07-01

    Hybridization can generate novel phenotypes, and in combination with divergent selection along environmental gradients, can play a driving role in phenotypic diversification. This study examined the influence of introgressive hybridization and environmental variation on the phenotypic diversity of two pupfish species (Cyprinodon atrorus and Cyprinodon bifasciatus) endemic to the Cuatro Ciénegas basin, Mexico. These species occupy opposite environmental extremes and are comprised of multiple, intraspecifically isolated populations. However, interspecific hybridization occurs to various degrees within connecting, intermediate environments. Using geometric morphometric analysis, extensive variation of body shape was observed between and within species, and phenotypic variation was strongly correlated with environmental conditions. Furthermore, some introgressed populations exhibited unique phenotypes not found in either of the parents, and overall morphospace occupation was significantly higher in introgressed populations when compared to the parentals. Overall, we find environmental variation and transgressive segregation both appear to have been important in shaping phenotypic variation in this system.

  7. COMPUTER APPROACHES TO WHEAT HIGH-THROUGHPUT PHENOTYPING

    Directory of Open Access Journals (Sweden)

    Afonnikov D.

    2012-08-01

    Full Text Available The growing need for rapid and accurate approaches for large-scale assessment of phenotypic characters in plants becomes more and more obvious in the studies looking into relationships between genotype and phenotype. This need is due to the advent of high throughput methods for analysis of genomes. Nowadays, any genetic experiment involves data on thousands and dozens of thousands of plants. Traditional ways of assessing most phenotypic characteristics (those with reliance on the eye, the touch, the ruler are little effective on samples of such sizes. Modern approaches seek to take advantage of automated phenotyping, which warrants a much more rapid data acquisition, higher accuracy of the assessment of phenotypic features, measurement of new parameters of these features and exclusion of human subjectivity from the process. Additionally, automation allows measurement data to be rapidly loaded into computer databases, which reduces data processing time.In this work, we present the WheatPGE information system designed to solve the problem of integration of genotypic and phenotypic data and parameters of the environment, as well as to analyze the relationships between the genotype and phenotype in wheat. The system is used to consolidate miscellaneous data on a plant for storing and processing various morphological traits and genotypes of wheat plants as well as data on various environmental factors. The system is available at www.wheatdb.org. Its potential in genetic experiments has been demonstrated in high-throughput phenotyping of wheat leaf pubescence.

  8. Eukaryotic diversity at pH extremes.

    Science.gov (United States)

    Amaral-Zettler, Linda A

    2012-01-01

    Extremely acidic (pH 9) environments support a diversity of single-cell and to a lesser extent, multicellular eukaryotic life. This study compared alpha and beta diversity in eukaryotic communities from seven diverse aquatic environments with pH values ranging from 2 to 11 using massively-parallel pyrotag sequencing targeting the V9 hypervariable region of the 18S ribosomal RNA (rRNA) gene. A total of 946 operational taxonomic units (OTUs) were recovered at a 6% cut-off level (94% similarity) across the sampled environments. Hierarchical clustering of the samples segregated the communities into acidic and alkaline groups. Similarity percentage (SIMPER) analysis followed by indicator OTU analysis (IOA) and non-metric multidimensional scaling (NMDS) were used to determine which characteristic groups of eukaryotic taxa typify acidic or alkaline extremes and the extent to which pH explains eukaryotic community structure in these environments. Spain's Rio Tinto yielded the fewest observed OTUs while Nebraska Sandhills alkaline lakes yielded the most. Distinct OTUs, including metazoan OTUs, numerically dominated pH extreme sites. Indicator OTUs included the diatom Pinnularia and unidentified opisthokonts (Fungi and Filasterea) in the extremely acidic environments, and the ciliate Frontonia across the extremely alkaline sites. Inferred from NMDS, pH explained only a modest fraction of the variation across the datasets, indicating that other factors influence the underlying community structure in these environments. The findings from this study suggest that the ability for eukaryotes to adapt to pH extremes over a broad range of values may be rare, but further study of taxa that can broadly adapt across diverse acidic and alkaline environments, respectively present good models for understanding adaptation and should be targeted for future investigations.

  9. The Broad Autism Phenotype Questionnaire

    Science.gov (United States)

    Hurley, Robert S. E.; Losh, Molly; Parlier, Morgan; Reznick, J. Steven; Piven, Joseph

    2007-01-01

    The broad autism phenotype (BAP) is a set of personality and language characteristics that reflect the phenotypic expression of the genetic liability to autism, in non-autistic relatives of autistic individuals. These characteristics are milder but qualitatively similar to the defining features of autism. A new instrument designed to measure the…

  10. Plant Phenotype Characterization System

    Energy Technology Data Exchange (ETDEWEB)

    Daniel W McDonald; Ronald B Michaels

    2005-09-09

    This report is the final scientific report for the DOE Inventions and Innovations Project: Plant Phenotype Characterization System, DE-FG36-04GO14334. The period of performance was September 30, 2004 through July 15, 2005. The project objective is to demonstrate the viability of a new scientific instrument concept for the study of plant root systems. The root systems of plants are thought to be important in plant yield and thus important to DOE goals in renewable energy sources. The scientific study and understanding of plant root systems is hampered by the difficulty in observing root activity and the inadequacy of existing root study instrumentation options. We have demonstrated a high throughput, non-invasive, high resolution technique for visualizing plant root systems in-situ. Our approach is based upon low-energy x-ray radiography and the use of containers and substrates (artificial soil) which are virtually transparent to x-rays. The system allows us to germinate and grow plant specimens in our containers and substrates and to generate x-ray images of the developing root system over time. The same plant can be imaged at different times in its development. The system can be used for root studies in plant physiology, plant morphology, plant breeding, plant functional genomics and plant genotype screening.

  11. Caracterização fenotípica da resistência a antimicrobianos e detecção do gene mecA em Staphylococcus spp. coagulase-negativos isolados de amostras animais e humanas Phenotypic characterization of antimicrobial resistance and detection of the mecA gene in coagulase-negative Staphylococcus spp. isolates from animal and human samples

    Directory of Open Access Journals (Sweden)

    Lidiane de Castro Soares

    2008-08-01

    Full Text Available Os estafilococos coagulase-negativos (ECN fazem parte da microbiota normal da pele e, apesar de terem sido considerados saprófitas por muito tempo, o seu significado clínico como agente etiológico tem aumentado com o passar dos anos. Neste estudo, foram obtidos 72 isolados de ECN a partir de amostras do conduto auditivo de cães, de mastite bovina e de infecções humanas. Staphylococcus xylosus foi o microrganismo mais isolado, nas amostras animais, e S. cohnii subsp. cohnii em humanos. Os isolados foram avaliados de modo a traçar o perfil fenotípico de sua resistência aos antimicrobianos mais indicados no tratamento de infecções estafilocócicas. Foi detectado um elevado nível de resistência à penicilina e ampicilina. A gentamicina, a vancomicina e a associação ampicilina+sulbactam foram eficientes frente aos isolados testados. A resistência à oxacilina foi avaliada por meio dos testes de difusão em disco modificada, ágar screen, microdiluição em caldo e diluição em ágar para constatar, se à semelhança do que ocorre com os estafilococos coagulase-positivo, esta pode ser mediada pelo gene mecA e apresentada de forma heterogênea. A presença do gene mecA foi determinada pelo método da Reação em Cadeia de Polimerase (PCR, sendo 5,6% dos isolados mecA positivos.Coagulase-negative staphylococci (SCN make part of the normal microbiota skin and although they have been considered saprophytics for years, nowadays their clinical significance as an etiologic agent has increased. In this study, 72 SCN isolates obtained from external ear canals of dogs, bovine mastitis and human nosocomial infections were evaluated. Staphylococcus xylosus was the most prevalent microorganism in animal samples and S. cohnii subsp. cohnii in human samples. SCN isolates were evaluated in order to establish a phenotypical resistance pattern towards the most indicated antibiotics for staphyloccocal infections. A high level of resistance to penicillin

  12. Sex hormone binding globulin phenotypes

    DEFF Research Database (Denmark)

    Cornelisse, M M; Bennett, Patrick; Christiansen, M

    1994-01-01

    Human sex hormone binding globulin (SHBG) is encoded by a normal and a variant allele. The resulting SHBG phenotypes (the homozygous normal SHBG, the heterozygous SHBG and the homozygous variant SHBG phenotype) can be distinguished by their electrophoretic patterns. We developed a novel detection....... This method of detection was used to determine the distribution of SHBG phenotypes in healthy controls of both sexes and in five different pathological conditions characterized by changes in the SHBG level or endocrine disturbances (malignant and benign ovarian neoplasms, hirsutism, liver cirrhosis...... on the experimental values. Differences in SHBG phenotypes do not appear to have any clinical significance and no sex difference was found in the SHBG phenotype distribution....

  13. Global phenotypic characterization of bacteria.

    Science.gov (United States)

    Bochner, Barry R

    2009-01-01

    The measure of the quality of a systems biology model is how well it can reproduce and predict the behaviors of a biological system such as a microbial cell. In recent years, these models have been built up in layers, and each layer has been growing in sophistication and accuracy in parallel with a global data set to challenge and validate the models in predicting the content or activities of genes (genomics), proteins (proteomics), metabolites (metabolomics), and ultimately cell phenotypes (phenomics). This review focuses on the latter, the phenotypes of microbial cells. The development of Phenotype MicroArrays, which attempt to give a global view of cellular phenotypes, is described. In addition to their use in fleshing out and validating systems biology models, there are many other uses of this global phenotyping technology in basic and applied microbiology research, which are also described.

  14. Global phenotypic characterization of bacteria

    Science.gov (United States)

    Bochner, Barry R

    2009-01-01

    The measure of the quality of a systems biology model is how well it can reproduce and predict the behaviors of a biological system such as a microbial cell. In recent years, these models have been built up in layers, and each layer has been growing in sophistication and accuracy in parallel with a global data set to challenge and validate the models in predicting the content or activities of genes (genomics), proteins (proteomics), metabolites (metabolomics), and ultimately cell phenotypes (phenomics). This review focuses on the latter, the phenotypes of microbial cells. The development of Phenotype MicroArrays, which attempt to give a global view of cellular phenotypes, is described. In addition to their use in fleshing out and validating systems biology models, there are many other uses of this global phenotyping technology in basic and applied microbiology research, which are also described. PMID:19054113

  15. Precipitation extremes under climate change

    CERN Document Server

    O'Gorman, Paul A

    2015-01-01

    The response of precipitation extremes to climate change is considered using results from theory, modeling, and observations, with a focus on the physical factors that control the response. Observations and simulations with climate models show that precipitation extremes intensify in response to a warming climate. However, the sensitivity of precipitation extremes to warming remains uncertain when convection is important, and it may be higher in the tropics than the extratropics. Several physical contributions govern the response of precipitation extremes. The thermodynamic contribution is robust and well understood, but theoretical understanding of the microphysical and dynamical contributions is still being developed. Orographic precipitation extremes and snowfall extremes respond differently from other precipitation extremes and require particular attention. Outstanding research challenges include the influence of mesoscale convective organization, the dependence on the duration considered, and the need to...

  16. Extremely red quasars in BOSS

    Science.gov (United States)

    Hamann, Fred; Zakamska, Nadia L.; Ross, Nicholas; Paris, Isabelle; Alexandroff, Rachael M.; Villforth, Carolin; Richards, Gordon T.; Herbst, Hanna; Brandt, W. Niel; Cook, Ben; Denney, Kelly D.; Greene, Jenny E.; Schneider, Donald P.; Strauss, Michael A.

    2017-01-01

    Red quasars are candidate young objects in an early transition stage of massive galaxy evolution. Our team recently discovered a population of extremely red quasars (ERQs) in the Baryon Oscillation Spectroscopic Survey (BOSS) that has a suite of peculiar emission-line properties including large rest equivalent widths (REWs), unusual `wingless' line profiles, large N V/Lyα, N V/C IV, Si IV/C IV and other flux ratios, and very broad and blueshifted [O III] λ5007. Here we present a new catalogue of C IV and N V emission-line data for 216 188 BOSS quasars to characterize the ERQ line properties further. We show that they depend sharply on UV-to-mid-IR colour, secondarily on REW(C IV), and not at all on luminosity or the Baldwin Effect. We identify a `core' sample of 97 ERQs with nearly uniform peculiar properties selected via i-W3 ≥ 4.6 (AB) and REW(C IV) ≥ 100 Å at redshifts 2.0-3.4. A broader search finds 235 more red quasars with similar unusual characteristics. The core ERQs have median luminosity ˜ 47.1, sky density 0.010 deg-2, surprisingly flat/blue UV spectra given their red UV-to-mid-IR colours, and common outflow signatures including BALs or BAL-like features and large C IV emission-line blueshifts. Their SEDs and line properties are inconsistent with normal quasars behind a dust reddening screen. We argue that the core ERQs are a unique obscured quasar population with extreme physical conditions related to powerful outflows across the line-forming regions. Patchy obscuration by small dusty clouds could produce the observed UV extinctions without substantial UV reddening.

  17. "Triangular" extremal dilatonic dyons

    CERN Document Server

    Gal'tsov, Dmitri; Orlov, Dmitri

    2014-01-01

    Explicit dyonic dilaton black holes of the four-dimensional Einstein-Maxwell-dilaton theory are known only for two particular values of the dilaton coupling constant $a =1,\\sqrt{3}$, while for other $a$ numerical evidence was presented earlier about existence of extremal dyons in theories with the discrete sequence of dilaton couplings $a=\\sqrt{n(n+1)/2}$ with integer $n$. Apart from the lower members $n=1,\\,2$, this family of theories does not have motivation from supersymmetry or higher dimensions, and so far the above quantization rule has not been derived analytically. We fill this gap showing that this rule follows from analyticity of the dilaton at the $AdS_2\\times S^2$ event horizon with $n$ being the leading dilaton power in the series expansion. We also present generalization for asymptotically anti-de Sitter dyonic black holes with spherical, plane and hyperbolic topology of the horizon.

  18. Extreme skin depth waveguides

    CERN Document Server

    Jahani, Saman

    2014-01-01

    Recently, we introduced a paradigm shift in light confinement strategy and introduced a class of extreme skin depth (e-skid) photonic structures (S. Jahani and Z. Jacob, "Transparent sub-diffraction optics: nanoscale light confinement without metal," Optica 1, 96-100 (2014)). Here, we analytically establish that figures of merit related to light confinement in dielectric waveguides are fundamentally tied to the skin depth of waves in the cladding. We contrast the propagation characteristics of the fundamental mode of e-skid waveguides and conventional waveguides to show that the decay constant in the cladding is dramatically larger in e-skid waveguides, which is the origin of sub-diffraction confinement. Finally, we propose an approach to verify the reduced skin depth in experiment using the decrease in the Goos-H\\"anchen phase shift.

  19. Pulsars and Extreme Physics

    Science.gov (United States)

    Bell-Burnell, Jocelyn

    2004-10-01

    Pulsars were discovered 35 years ago. What do we know about them now, and what have they taught us about the extremes of physics? With an average density comparable to that of the nucleus, magnetic fields around 108 T and speeds close to c these objects have stretched our understanding of the behaviour of matter. They serve as extrememly accurate clocks with which to carry out precision experiments in relativity. Created in cataclysmic explosions, pulsars are a (stellar) form of life after death. After half a billion revolutions most pulsars finally die, but amazingly some are born again to yet another, even weirder, afterlife. Pulsar research continues lively, delivering exciting, startling and almost unbelievable results!

  20. Fine mapping quantitative trait loci under selective phenotyping strategies based on linkage and linkage disequilibrium criteria

    DEFF Research Database (Denmark)

    Ansari-Mahyari, S; Berg, P; Lund, M S

    2009-01-01

    In fine mapping of a large-scale experimental population where collection of phenotypes are very expensive, difficult to record or time-demanding, selective phenotyping could be used to phenotype the most informative individuals. Linkage analyses based sampling criteria (LAC) and linkage...... disequilibrium-based sampling criteria (LDC) for selecting individuals to phenotype are compared to random phenotyping in a quantitative trait loci (QTL) verification experiment using stochastic simulation. Several strategies based on LAC and LDC for selecting the most informative 30%, 40% or 50% of individuals...... for phenotyping to extract maximum power and precision in a QTL fine mapping experiment were developed and assessed. Linkage analyses for the mapping was performed for individuals sampled on LAC within families and combined linkage disequilibrium and linkage analyses was performed for individuals sampled across...

  1. From metabolome to phenotype

    DEFF Research Database (Denmark)

    Khakimov, Bekzod; Rasmussen, Morten Arendt; Kannangara, Rubini Maya

    2017-01-01

    for ideal vegetable protein production and for augmented β-glucan production. Seeds from three barley lines (Bomi, lys3.a and lys5.f) were sampled eight times during grain filling and analysed for metabolites using gas chromatography-mass spectrometry (GC-MS). The lys3.a mutation disrupts a regulator gene...

  2. Alterations in Skin Temperature and Sleep in the Fear of Harm Phenotype of Pediatric Bipolar Disorder

    Directory of Open Access Journals (Sweden)

    Patricia J. Murphy

    2014-08-01

    Full Text Available In children diagnosed with pediatric bipolar disorder (PBD, disturbances in the quality of sleep and wakefulness are prominent. A novel phenotype of PBD called Fear of Harm (FOH associated with separation anxiety and aggressive obsessions is associated with sleep onset insomnia, parasomnias (nightmares, night-terrors, enuresis, REM sleep-related problems, and morning sleep inertia. Children with FOH often experience thermal discomfort (e.g., feeling hot, excessive sweating in neutral ambient temperature conditions, as well as no discomfort during exposure to the extreme cold, and alternate noticeably between being excessively hot in the evening and cold in the morning. We hypothesized that these sleep- and temperature-related symptoms were overt symptoms of an impaired ability to dissipate heat, particularly in the evening hours near the time of sleep onset. We measured sleep/wake variables using actigraphy, and nocturnal skin temperature variables using thermal patches and a wireless device, and compared these data between children with PBD/FOH and a control sample of healthy children. The results are suggestive of a thermoregulatory dysfunction that is associated with sleep onset difficulties. Further, they are consistent with our hypothesis that alterations in neural circuitry common to thermoregulation and emotion regulation underlie affective and behavioral symptoms of the FOH phenotype.

  3. Phenotypic plasticity, costs of phenotypes, and costs of plasticity

    DEFF Research Database (Denmark)

    Callahan, Hilary S; Maughan, Heather; Steiner, Uli

    2008-01-01

    Why are some traits constitutive and others inducible? The term costs often appears in work addressing this issue but may be ambiguously defined. This review distinguishes two conceptually distinct types of costs: phenotypic costs and plasticity costs. Phenotypic costs are assessed from patterns...... of covariation, typically between a focal trait and a separate trait relevant to fitness. Plasticity costs, separable from phenotypic costs, are gauged by comparing the fitness of genotypes with equivalent phenotypes within two environments but differing in plasticity and fitness. Subtleties associated with both...... types of costs are illustrated by a body of work addressing predator-induced plasticity. Such subtleties, and potential interplay between the two types of costs, have also been addressed, often in studies involving genetic model organisms. In some instances, investigators have pinpointed the mechanistic...

  4. ADAPTIVE CHEMOREFLECTORY MECHANISMS RESPONDING TO EXTREME FACTORS

    Directory of Open Access Journals (Sweden)

    S. G. Krivoschekov

    2014-01-01

    Full Text Available An analysis of adaptive chemoreflectory mechanisms responding of extreme factors opens prospects for understanding of a role of a phenotype in this process, and also for search of new methods of the forecast and diagnostics. We analysed individual-typological variability of hypoxic tolerance and muscular working capacity at healthy people with various kinds of habitual sports activity. It is established, that formatting of new neuro-visceral interactions which occurs under the influence of individual training process, is reflected in reactivity of cardiovascular and respiratory systems in response to hypoxia. Adaptive strategy produces changes in systemic response to hypoxia which correlates with aerobic work capacity and EEG activity of a brain at sportsmen of different specializations. Individually-typological characteristics of sportsmen (typology of nervous system also mediate EEG response to hypoxia, but they can be modified by the influence of phenotypic adaptive mechanisms (aerobic, anaerobic or mixed type of individual training process. The obtained results testify, that sports loadings forms specific adjustment of mechanisms of chemoreflectory regulation of cardiovascular and respiratory systems.

  5. Detection and attribution of extreme weather disasters

    Science.gov (United States)

    Huggel, Christian; Stone, Dáithí; Hansen, Gerrit

    2014-05-01

    Single disasters related to extreme weather events have caused loss and damage on the order of up to tens of billions US dollars over the past years. Recent disasters fueled the debate about whether and to what extent these events are related to climate change. In international climate negotiations disaster loss and damage is now high on the agenda, and related policy mechanisms have been discussed or are being implemented. In view of funding allocation and effective risk reduction strategies detection and attribution to climate change of extreme weather events and disasters is a key issue. Different avenues have so far been taken to address detection and attribution in this context. Physical climate sciences have developed approaches, among others, where variables that are reasonably sampled over climatically relevant time periods and related to the meteorological characteristics of the extreme event are examined. Trends in these variables (e.g. air or sea surface temperatures) are compared between observations and climate simulations with and without anthropogenic forcing. Generally, progress has been made in recent years in attribution of changes in the chance of some single extreme weather events to anthropogenic climate change but there remain important challenges. A different line of research is primarily concerned with losses related to the extreme weather events over time, using disaster databases. A growing consensus is that the increase in asset values and in exposure are main drivers of the strong increase of economic losses over the past several decades, and only a limited number of studies have found trends consistent with expectations from climate change. Here we propose a better integration of existing lines of research in detection and attribution of extreme weather events and disasters by applying a risk framework. Risk is thereby defined as a function of the probability of occurrence of an extreme weather event, and the associated consequences

  6. Women in extreme poverty.

    Science.gov (United States)

    1994-01-01

    Population is estimated to increase from 5.5 billion in 1990 to 10 billion by 2050; the poverty level is expected to increase from 1 billion to 2-3 billion people. Women in development has been promoted throughout the UN and development system, but women in poverty who perform work in the informal sector are still uncounted, and solutions are elusive. The issue of extreme poverty can not be approached as just another natural disaster with immediate emergency relief. Many people live in precarious economic circumstances throughout their lives. Recent research reveals a greater understanding of the underlying causes and the need for inclusion of poor women in sustainable development. Sanitation, water, housing, health facilities need to be improved. Women must have access to education, opportunities for trading, and loans on reasonable terms. UNESCO makes available a book on survival strategies for poor women in the informal sector. The profile shows common problems of illiteracy, broken marriages, and full time involvement in provision of subsistence level existence. Existence is a fragile balance. Jeanne Vickers' "Women and the World" offers simple, low cost interventions for aiding extremely poor women. The 1992 Commission on the Status of Women was held in Vienna. Excerpts from several speeches are provided. The emphasis is on some global responses and an analysis of solutions. The recommendation is for attention to the gender dimension of poverty. Women's dual role contributes to greater disadvantages. Women are affected differently by macroeconomic factors, and that there is intergenerational transfer of poverty. Social services should be viewed as investments and directed to easing the burdens on time and energy. Public programs must be equipped to deal with poverty and to bring about social and economic change. Programs must be aware of the different distribution of resources within households. Women must be recognized as principal economic providers within

  7. Extreme winds in Denmark

    Energy Technology Data Exchange (ETDEWEB)

    Kristensen, L.; Rathmann, O.; Hansen, S.O.

    1999-02-01

    Wind-speed data from four sites in Denmark have been analyzed in order to obtain estimates of the basic wind velocity which is defined as the 50-year wind speed under standard conditions, i.e. ten-minute averages at the height 10 m over a uniform terrain with the roughness length 0.05 m. The sites are, from west, Skjern (15 years), Kegnaes (7 years), Sprogoe (20 years), and Tystofte (15 years). The data are ten minute averages of wind speed, wind direction, temperature and pressure. The last two quantities are used to determine the air density {rho}. The data are cleaned for terrain effects by means of a slightly modified WASP technique where the sector speed-up factors and roughness lengths are linearly smoothed with a direction resolution of one degree. Assuming geotropic balance, all the wind-velocity data are transformed to friction velocity u{sub *} and direction at standard conditions by means of the geotropic drag law for neutral stratification. The basic wind velocity in 30 deg. sectors are obtained through ranking of the largest values of the friction velocity pressure 1/2{rho}u{sub *}{sup 2} taken both one every two months and once every year. The main conclusion is that the basic wind velocity is significantly larger at Skjern, close to the west coast of Jutland, than at any of the other sites. Irrespective of direction, the present standard estimates of 50-year wind are 25 {+-} 1 m/s at Skern and 22 {+-} 1 m/s at the other three sites. These results are in agreement with those obtained by Jensen and Franck (1970) and Abild (1994) and supports the conclusion that the wind climate at the west coast of Jutland is more extreme than in any other part of the country. Simple procedures to translate in a particular direction sector the standard basic wind velocity to conditions with a different roughness length and height are presented. It is shown that a simple scheme makes it possible to calculate the total 50-year extreme load on a general structure without

  8. Stacked Extreme Learning Machines.

    Science.gov (United States)

    Zhou, Hongming; Huang, Guang-Bin; Lin, Zhiping; Wang, Han; Soh, Yeng Chai

    2015-09-01

    Extreme learning machine (ELM) has recently attracted many researchers' interest due to its very fast learning speed, good generalization ability, and ease of implementation. It provides a unified solution that can be used directly to solve regression, binary, and multiclass classification problems. In this paper, we propose a stacked ELMs (S-ELMs) that is specially designed for solving large and complex data problems. The S-ELMs divides a single large ELM network into multiple stacked small ELMs which are serially connected. The S-ELMs can approximate a very large ELM network with small memory requirement. To further improve the testing accuracy on big data problems, the ELM autoencoder can be implemented during each iteration of the S-ELMs algorithm. The simulation results show that the S-ELMs even with random hidden nodes can achieve similar testing accuracy to support vector machine (SVM) while having low memory requirements. With the help of ELM autoencoder, the S-ELMs can achieve much better testing accuracy than SVM and slightly better accuracy than deep belief network (DBN) with much faster training speed.

  9. Solar extreme events

    CERN Document Server

    Hudson, Hugh S

    2015-01-01

    Solar flares and CMEs have a broad range of magnitudes. This review discusses the possibility of "extreme events," defined as those with magnitudes greater than have been seen in the existing historical record. For most quantitative measures, this direct information does not extend more than a century and a half into the recent past. The magnitude distributions (occurrence frequencies) of solar events (flares/CMEs) typically decrease with the parameter measured or inferred (peak flux, mass, energy etc. Flare radiation fluxes tend to follow a power law slightly flatter than $S^{-2}$, where S represents a peak flux; solar particle events (SPEs) follow a still flatter power law up to a limiting magnitude, and then appear to roll over to a steeper distribution, which may take an exponential form or follow a broken power law. This inference comes from the terrestrial $^{14}$C record and from the depth dependence of various radioisotope proxies in the lunar regolith and in meteorites. Recently major new observation...

  10. Finding our way through phenotypes.

    Directory of Open Access Journals (Sweden)

    Andrew R Deans

    2015-01-01

    Full Text Available Despite a large and multifaceted effort to understand the vast landscape of phenotypic data, their current form inhibits productive data analysis. The lack of a community-wide, consensus-based, human- and machine-interpretable language for describing phenotypes and their genomic and environmental contexts is perhaps the most pressing scientific bottleneck to integration across many key fields in biology, including genomics, systems biology, development, medicine, evolution, ecology, and systematics. Here we survey the current phenomics landscape, including data resources and handling, and the progress that has been made to accurately capture relevant data descriptions for phenotypes. We present an example of the kind of integration across domains that computable phenotypes would enable, and we call upon the broader biology community, publishers, and relevant funding agencies to support efforts to surmount today's data barriers and facilitate analytical reproducibility.

  11. Finding our way through phenotypes.

    Science.gov (United States)

    Deans, Andrew R; Lewis, Suzanna E; Huala, Eva; Anzaldo, Salvatore S; Ashburner, Michael; Balhoff, James P; Blackburn, David C; Blake, Judith A; Burleigh, J Gordon; Chanet, Bruno; Cooper, Laurel D; Courtot, Mélanie; Csösz, Sándor; Cui, Hong; Dahdul, Wasila; Das, Sandip; Dececchi, T Alexander; Dettai, Agnes; Diogo, Rui; Druzinsky, Robert E; Dumontier, Michel; Franz, Nico M; Friedrich, Frank; Gkoutos, George V; Haendel, Melissa; Harmon, Luke J; Hayamizu, Terry F; He, Yongqun; Hines, Heather M; Ibrahim, Nizar; Jackson, Laura M; Jaiswal, Pankaj; James-Zorn, Christina; Köhler, Sebastian; Lecointre, Guillaume; Lapp, Hilmar; Lawrence, Carolyn J; Le Novère, Nicolas; Lundberg, John G; Macklin, James; Mast, Austin R; Midford, Peter E; Mikó, István; Mungall, Christopher J; Oellrich, Anika; Osumi-Sutherland, David; Parkinson, Helen; Ramírez, Martín J; Richter, Stefan; Robinson, Peter N; Ruttenberg, Alan; Schulz, Katja S; Segerdell, Erik; Seltmann, Katja C; Sharkey, Michael J; Smith, Aaron D; Smith, Barry; Specht, Chelsea D; Squires, R Burke; Thacker, Robert W; Thessen, Anne; Fernandez-Triana, Jose; Vihinen, Mauno; Vize, Peter D; Vogt, Lars; Wall, Christine E; Walls, Ramona L; Westerfeld, Monte; Wharton, Robert A; Wirkner, Christian S; Woolley, James B; Yoder, Matthew J; Zorn, Aaron M; Mabee, Paula

    2015-01-01

    Despite a large and multifaceted effort to understand the vast landscape of phenotypic data, their current form inhibits productive data analysis. The lack of a community-wide, consensus-based, human- and machine-interpretable language for describing phenotypes and their genomic and environmental contexts is perhaps the most pressing scientific bottleneck to integration across many key fields in biology, including genomics, systems biology, development, medicine, evolution, ecology, and systematics. Here we survey the current phenomics landscape, including data resources and handling, and the progress that has been made to accurately capture relevant data descriptions for phenotypes. We present an example of the kind of integration across domains that computable phenotypes would enable, and we call upon the broader biology community, publishers, and relevant funding agencies to support efforts to surmount today's data barriers and facilitate analytical reproducibility.

  12. Epigenetics in heart failure phenotypes

    Directory of Open Access Journals (Sweden)

    Alexander Berezin

    2016-12-01

    Full Text Available Chronic heart failure (HF is a leading clinical and public problem posing a higher risk of morbidity and mortality in different populations. HF appears to be in both phenotypic forms: HF with reduced left ventricular ejection fraction (HFrEF and HF with preserved left ventricular ejection fraction (HFpEF. Although both HF phenotypes can be distinguished through clinical features, co-morbidity status, prediction score, and treatment, the clinical outcomes in patients with HFrEF and HFpEF are similar. In this context, investigation of various molecular and cellular mechanisms leading to the development and progression of both HF phenotypes is very important. There is emerging evidence that epigenetic regulation may have a clue in the pathogenesis of HF. This review represents current available evidence regarding the implication of epigenetic modifications in the development of different HF phenotypes and perspectives of epigenetic-based therapies of HF.

  13. The human adult cardiomyocyte phenotype

    NARCIS (Netherlands)

    Bird, SD; Doevendans, PA; van Rooijen, MA; de la Riviere, AB; Hassink, RJ; Passier, R; Mummery, CL

    2003-01-01

    Aim: Determination of the phenotype of adult human atrial and ventricular myocytes based on gene expression and morphology. Methods: Atrial and ventricular cardiomyocytes were obtained from patients undergoing cardiac surgery using a modified isolation procedure. Myocytes were isolated and cultured

  14. EHR Big Data Deep Phenotyping

    National Research Council Canada - National Science Library

    L. J. Frey; L. Lenert; G. Lopez-Campos S. M. Meystre; G. K. Savova; K. C. Kipper-Schuler; J. F. Hurdle J. Zvárová; T. Dostálová; P. Hanzlíc∨ek; Z. Teuberová; M. Nagy; M. Pieš; M. Seydlová; Eliášová; H. Šimková Petra Knaup; Oliver Bott; Christian Kohl; Christian Lovis; Sebastian Garde

    2014-01-01

    Objectives: Given the quickening speed of discovery of variant disease drivers from combined patient genotype and phenotype data, the objective is to provide methodology using big data technology to support...

  15. Testing the island effect on phenotypic diversification: insights from the Hemidactylus geckos of the Socotra Archipelago.

    Science.gov (United States)

    Garcia-Porta, Joan; Šmíd, Jiří; Sol, Daniel; Fasola, Mauro; Carranza, Salvador

    2016-04-13

    Island colonization is often assumed to trigger extreme levels of phenotypic diversification. Yet, empirical evidence suggests that it does not always so. In this study we test this hypothesis using a completely sampled mainland-island system, the arid clade of Hemidactylus, a group of geckos mainly distributed across Africa, Arabia and the Socotra Archipelago. To such purpose, we generated a new molecular phylogeny of the group on which we mapped body size and head proportions. We then explored whether island and continental taxa shared the same morphospace and differed in their disparities and tempos of evolution. Insular species produced the most extreme sizes of the radiation, involving accelerated rates of evolution and higher disparities compared with most (but not all) of the continental groups. In contrast, head proportions exhibited constant evolutionary rates across the radiation and similar disparities in islands compared with the continent. These results, although generally consistent with the notion that islands promote high morphological disparity, reveal at the same time a complex scenario in which different traits may experience different evolutionary patterns in the same mainland-island system and continental groups do not always present low levels of morphological diversification compared to insular groups.

  16. Extremal almost-Kahler metrics

    CERN Document Server

    Lejmi, Mehdi

    2009-01-01

    We generalize the notion of the Futaki invariant and extremal vector field to the general almost-Kahler case and we prove the periodicity of the extremal vector field when the symplectic form represents an integral cohomology class modulo torsion. We give also an explicit formula of the hermitian scalar curvature which allows us to obtain examples of non-integrable extremal almost-Kahler metrics saturating LeBrun's estimates.

  17. Upper extremity amputations and prosthetics.

    Science.gov (United States)

    Ovadia, Steven A; Askari, Morad

    2015-02-01

    Upper extremity amputations are most frequently indicated by severe traumatic injuries. The location of the injury will determine the level of amputation. Preservation of extremity length is often a goal. The amputation site will have important implications on the functional status of the patient and options for prosthetic reconstruction. Advances in amputation techniques and prosthetic reconstructions promote improved quality of life. In this article, the authors review the principles of upper extremity amputation, including techniques, amputation sites, and prosthetic reconstructions.

  18. Genome-wide population-based association study of extremely overweight young adults--the GOYA study.

    Directory of Open Access Journals (Sweden)

    Lavinia Paternoster

    Full Text Available Thirty-two common variants associated with body mass index (BMI have been identified in genome-wide association studies, explaining ∼1.45% of BMI variation in general population cohorts. We performed a genome-wide association study in a sample of young adults enriched for extremely overweight individuals. We aimed to identify new loci associated with BMI and to ascertain whether using an extreme sampling design would identify the variants known to be associated with BMI in general populations.From two large Danish cohorts we selected all extremely overweight young men and women (n = 2,633, and equal numbers of population-based controls (n = 2,740, drawn randomly from the same populations as the extremes, representing ∼212,000 individuals. We followed up novel (at the time of the study association signals (p<0.001 from the discovery cohort in a genome-wide study of 5,846 Europeans, before attempting to replicate the most strongly associated 28 SNPs in an independent sample of Danish individuals (n = 20,917 and a population-based cohort of 15-year-old British adolescents (n = 2,418. Our discovery analysis identified SNPs at three loci known to be associated with BMI with genome-wide confidence (P<5×10(-8; FTO, MC4R and FAIM2. We also found strong evidence of association at the known TMEM18, GNPDA2, SEC16B, TFAP2B, SH2B1 and KCTD15 loci (p<0.001, and nominal association (p<0.05 at a further 8 loci known to be associated with BMI. However, meta-analyses of our discovery and replication cohorts identified no novel associations.Our results indicate that the detectable genetic variation associated with extreme overweight is very similar to that previously found for general BMI. This suggests that population-based study designs with enriched sampling of individuals with the extreme phenotype may be an efficient method for identifying common variants that influence quantitative traits and a valid alternative to genotyping all

  19. Likelihood estimators for multivariate extremes

    KAUST Repository

    Huser, Raphaël

    2015-11-17

    The main approach to inference for multivariate extremes consists in approximating the joint upper tail of the observations by a parametric family arising in the limit for extreme events. The latter may be expressed in terms of componentwise maxima, high threshold exceedances or point processes, yielding different but related asymptotic characterizations and estimators. The present paper clarifies the connections between the main likelihood estimators, and assesses their practical performance. We investigate their ability to estimate the extremal dependence structure and to predict future extremes, using exact calculations and simulation, in the case of the logistic model.

  20. Extreme UV QSOs

    CERN Document Server

    Bianchi, Luciana; Efremova, Boryana; Herald, James E; Bressan, Alessandro; Martin, Cristopher

    2009-01-01

    We present a sample of spectroscopically confirmed QSOs with FUV-NUV color (as measured by GALEX photometry) bluer than canonical QSO templates and than the majority of known QSOs. We analyze their FUV to NIR colors, luminosities and optical spectra. The sample includes a group of 150 objects at low redshift (z $<$ 0.5), and a group of 21 objects with redshift 1.7$<$z$<$2.6. For the low redshift objects, the "blue" FUV-NUV color may be caused by enhanced Ly$\\alpha$ emission, since Ly$\\alpha$ transits the GALEX FUV band from z=0.1 to z=0.47. Synthetic QSO templates constructed with Ly$\\alpha$ up to 3 times stronger than in standard templates match the observed UV colors of our low redshift sample. The H$\\alpha$ emission increases, and the optical spectra become bluer, with increasing absolute UV luminosity. The UV-blue QSOs at redshift about 2, where the GALEX bands sample restframe about 450-590A (FUV) and about 590-940A(NUV), are fainter than the average of UV-normal QSOs at similar redshift in NUV,...

  1. Concordance between two phenotypic assays and ultradeep pyrosequencing for determining HIV-1 tropism.

    Science.gov (United States)

    Saliou, Adrien; Delobel, Pierre; Dubois, Martine; Nicot, Florence; Raymond, Stéphanie; Calvez, Vincent; Masquelier, Bernard; Izopet, Jacques

    2011-06-01

    There have been few studies on the concordance between phenotypic assays for predicting human immunodeficiency virus type 1 (HIV-1) coreceptor usage. The sensitivity of ultradeep pyrosequencing combined with genotyping tools is similar to that of phenotypic assays for detecting minor CXCR4-using variants. We evaluated the agreement between two phenotypic assays, the Toulouse tropism test (TTT) and the Trofile assay, and ultradeep pyrosequencing for determining the tropism of HIV-1 quasispecies. The concordance between the TTT and Trofile assays was assessed for 181 samples successfully phenotyped by both assays. The TTT was 86% concordant with the standard Trofile assay and 91.7% with its enhanced-sensitivity version. The concordance between phenotypic characterization of HIV-1 tropism and ultradeep pyrosequencing genotypic prediction was further studied in selected samples. The HIV-1 tropism inferred from ultradeep pyrosequencing of 11 samples phenotyped as X4 and dualtropic and 12 phenotyped as R5-tropic agreed closely with the results of phenotyping. However, ultradeep pyrosequencing detected minor CXCR4-using variants in 3 of 12 samples phenotyped as R5-tropic. Ultradeep pyrosequencing also detected minor CXCR4-using variants that had been missed by direct sequencing in 6 of 9 samples phenotyped as X4-tropic but genotyped as R5-tropic by direct sequencing. Ultradeep pyrosequencing was 87% concordant with the Trofile and TTT phenotypic assays and was in the same range of sensitivity (0.4%) than these two phenotypic assays (0.3 to 0.5%) for detecting minor CXCR4-using variants. Ultradeep pyrosequencing provides a new way to improve the performance of genotypic prediction of HIV-1 tropism to match that of the phenotypic assays.

  2. The digital revolution in phenotyping

    Science.gov (United States)

    Oellrich, Anika; Collier, Nigel; Groza, Tudor; Rebholz-Schuhmann, Dietrich; Shah, Nigam; Bodenreider, Olivier; Boland, Mary Regina; Georgiev, Ivo; Liu, Hongfang; Livingston, Kevin; Luna, Augustin; Mallon, Ann-Marie; Manda, Prashanti; Robinson, Peter N.; Rustici, Gabriella; Simon, Michelle; Wang, Liqin; Winnenburg, Rainer; Dumontier, Michel

    2016-01-01

    Phenotypes have gained increased notoriety in the clinical and biological domain owing to their application in numerous areas such as the discovery of disease genes and drug targets, phylogenetics and pharmacogenomics. Phenotypes, defined as observable characteristics of organisms, can be seen as one of the bridges that lead to a translation of experimental findings into clinical applications and thereby support ‘bench to bedside’ efforts. However, to build this translational bridge, a common and universal understanding of phenotypes is required that goes beyond domain-specific definitions. To achieve this ambitious goal, a digital revolution is ongoing that enables the encoding of data in computer-readable formats and the data storage in specialized repositories, ready for integration, enabling translational research. While phenome research is an ongoing endeavor, the true potential hidden in the currently available data still needs to be unlocked, offering exciting opportunities for the forthcoming years. Here, we provide insights into the state-of-the-art in digital phenotyping, by means of representing, acquiring and analyzing phenotype data. In addition, we provide visions of this field for future research work that could enable better applications of phenotype data. PMID:26420780

  3. An association analysis between psychophysical characteristics and genome-wide gene expression changes in human adaptation to the extreme climate at the Antarctic Dome Argus.

    Science.gov (United States)

    Xu, C; Ju, X; Song, D; Huang, F; Tang, D; Zou, Z; Zhang, C; Joshi, T; Jia, L; Xu, W; Xu, K-F; Wang, Q; Xiong, Y; Guo, Z; Chen, X; Huang, F; Xu, J; Zhong, Y; Zhu, Y; Peng, Y; Wang, L; Zhang, X; Jiang, R; Li, D; Jiang, T; Xu, D; Jiang, C

    2015-04-01

    Genome-wide gene expression measurements have enabled comprehensive studies that integrate the changes of gene expression and phenotypic information to uncover their novel associations. Here we reported the association analysis between psychophysical phenotypes and genome-wide gene expression changes in human adaptation to one of the most extreme climates on Earth, the Antarctic Dome Argus. Dome A is the highest ice feature in Antarctica, and may be the coldest, driest and windiest location on earth. It is considered unapproachable due to its hostile environment. In 2007, a Chinese team of 17 male explorers made the expedition to Dome A for scientific investigation. Overall, 133 psychophysical phenotypes were recorded, and genome-wide gene expression profiles from the blood samples of the explorers were measured before their departure and upon their arrival at Dome A. We found that mood disturbances, including tension (anxiety), depression, anger and fatigue, had a strong, positive, linear relationship with the level of a male sex hormone, testosterone, using the Pearson correlation coefficient (PCC) analysis. We also demonstrated that significantly lowest-level Gene Ontology groups in changes of gene expression in blood cells with erythrocyte removal were consistent with the adaptation of the psychophysical characteristics. Interestingly, we discovered a list of genes that were strongly related to significant phenotypes using phenotype and gene expression PCC analysis. Importantly, among the 70 genes that were identified, most were significantly related to mood disturbances, where 42 genes have been reported in the literature mining, suggesting that the other 28 genes were likely novel genes involved in the mood disturbance mechanism. Taken together, our association analysis provides a reliable method to uncover novel genes and mechanisms related to phenotypes, although further studies are needed.

  4. Extremely Red Quasars in BOSS

    CERN Document Server

    Hamann, Fred; Ross, Nicholas; Paris, Isabelle; Alexandroff, Rachael M; Villforth, Carolin; Richards, Gordon T; Herbst, Hanna; Brandt, W Niel; Cook, Ben; Denney, Kelly D; Greene, Jenny E; Schneider, Donald P; Strauss, Michael A

    2016-01-01

    Red quasars are candidate young objects in an early transition stage of massive galaxy evolution. Our team recently discovered a population of extremely red quasars (ERQs) in the Baryon Oscillation Spectroscopic Survey (BOSS) that has a suite of peculiar emission-line properties including large rest equivalent widths (REWs), unusual "wingless" line profiles, large NV/Lya, NV/CIV, SiIV/CIV and other flux ratios, and very broad and blueshifted [OIII] 5007. Here we present a new catalog of CIV and NV emission-line data for 216,188 BOSS quasars to characterize the ERQ line properties further. We show that they depend sharply on UV-to-mid-IR color, secondarily on REW(CIV), and not at all on luminosity or the Baldwin Effect. We identify a "core" sample of 97 ERQs with nearly uniform peculiar properties selected via i-W3 > 4.6 (AB) and REW(CIV) > 100 A at redshifts 2.0-3.4. A broader search finds 235 more red quasars with similar unusual characteristics. The core ERQs have median luminosity log L (ergs/s) ~ 47.1, sk...

  5. An Automated Field Phenotyping Pipeline for Application in Grapevine Research

    Directory of Open Access Journals (Sweden)

    Anna Kicherer

    2015-02-01

    Full Text Available Due to its perennial nature and size, the acquisition of phenotypic data in grapevine research is almost exclusively restricted to the field and done by visual estimation. This kind of evaluation procedure is limited by time, cost and the subjectivity of records. As a consequence, objectivity, automation and more precision of phenotypic data evaluation are needed to increase the number of samples, manage grapevine repositories, enable genetic research of new phenotypic traits and, therefore, increase the efficiency in plant research. In the present study, an automated field phenotyping pipeline was setup and applied in a plot of genetic resources. The application of the PHENObot allows image acquisition from at least 250 individual grapevines per hour directly in the field without user interaction. Data management is handled by a database (IMAGEdata. The automatic image analysis tool BIVcolor (Berries in Vineyards-color permitted the collection of precise phenotypic data of two important fruit traits, berry size and color, within a large set of plants. The application of the PHENObot represents an automated tool for high-throughput sampling of image data in the field. The automated analysis of these images facilitates the generation of objective and precise phenotypic data on a larger scale.

  6. Phenotypic and genetic diversity in Sinorhizobium meliloti and S. medicae from drought and salt affected regions of Morocco

    Directory of Open Access Journals (Sweden)

    Udupa Sripada M

    2010-01-01

    Full Text Available Abstract Background Sinorhizobium meliloti and S. medicae are symbiotic nitrogen fixing bacteria in root nodules of forage legume alfalfa (Medicago sativa L.. In Morocco, alfalfa is usually grown in marginal soils of arid and semi-arid regions frequently affected by drought, extremes of temperature and soil pH, soil salinity and heavy metals, which affect biological nitrogen fixing ability of rhizobia and productivity of the host. This study examines phenotypic diversity for tolerance to the above stresses and genotypic diversity at Repetitive Extragenic Pallindromic DNA regions of Sinorhizobium nodulating alfalfa, sampled from marginal soils of arid and semi-arid regions of Morocco. Results RsaI digestion of PCR amplified 16S rDNA of the 157 sampled isolates, assigned 136 isolates as S. meliloti and the rest as S. medicae. Further phenotyping of these alfalfa rhizobia for tolerance to the environmental stresses revealed a large degree of variation: 55.41%, 82.16%, 57.96% and 3.18% of the total isolates were tolerant to NaCl (>513 mM, water stress (-1.5 MPa, high temperature (40°C and low pH (3.5, respectively. Sixty-seven isolates of S. meliloti and thirteen isolates of S. medicae that were tolerant to salinity were also tolerant to water stress. Most of the isolates of the two species showed tolerance to heavy metals (Cd, Mn and Zn and antibiotics (chloramphenicol, spectinomycin, streptomycin and tetracycline. The phenotypic clusters observed by the cluster analysis clearly showed adaptations of the S. meliloti and S. medicae strains to the multiple stresses. Genotyping with rep-PCR revealed higher genetic diversity within these phenotypic clusters and classified all the 157 isolates into 148 genotypes. No relationship between genotypic profiles and the phenotypes was observed. The Analysis of Molecular Variance revealed that largest proportion of significant (P Conclusion High degree of phenotypic and genotypic diversity is present in S

  7. Analysis of Carotenoid Production by Halorubrum sp. TBZ126; an Extremely Halophilic Archeon from Urmia Lake

    Science.gov (United States)

    Naziri, Davood; Hamidi, Masoud; Hassanzadeh, Salar; Tarhriz, Vahideh; Maleki Zanjani, Bahram; Nazemyieh, Hossein; Hejazi, Mohammd Amin; Hejazi, Mohammad Saeid

    2014-01-01

    Purpose: Carotenoids are of great interest in many scientific disciplines because of their wide distribution, diverse functions and interesting properties. The present report describes a new natural source for carotenoid production. Methods: Halorubrum sp., TBZ126, an extremely halophilic archaeon, was isolated from Urmia Lack following culture of water sample on marine agar medium and incubation at 30 °C. Then single colonies were cultivated in broth media. After that the cells were collected and carotenoids were extracted with acetone-methanol (7:3 v/v). The identification of carotenoids was performed by UV-VIS spectroscopy and confirmed by thin layer chromatography (TLC) in the presence of antimony pentachloride (SbCl5). The production profile was analyzed using liquid-chromatography mass spectroscopy (LC-MS) techniques. Phenotypic characteristics of the isolate were carried out and the 16S rRNA gene was amplified using polymerase chain reaction (PCR). Results: LC-MS analytical results revealed that produced carotenoids are bacterioruberin, lycopene and β-carotene. Bacterioruberin was found to be the predominant produced carotenoid. 16S rRNA analysis showed that TBZ126 has 100% similarity with Halorubrum chaoviator Halo-G*T (AM048786). Conclusion: Halorubrum sp. TBZ126, isolated from Urmia Lake has high capacity in the production of carotenoids. This extremely halophilic archaeon could be considered as a prokaryotic candidate for carotenoid production source for future studies. PMID:24409411

  8. Analysis of Carotenoid Production by Halorubrum sp. TBZ126; an Extremely Halophilic Archeon from Urmia Lake

    Directory of Open Access Journals (Sweden)

    Davood Naziri

    2014-03-01

    Full Text Available Purpose: Carotenoids are of great interest in many scientific disciplines because of their wide distribution, diverse functions and interesting properties. The present report describes a new natural source for carotenoid production. Methods: Halorubrum sp., TBZ126, an extremely halophilic archaeon, was isolated from Urmia Lack following culture of water sample on marine agar medium and incubation at 30 °C. Then single colonies were cultivated in broth media. After that the cells were collected and carotenoids were extracted with acetone-methanol (7:3 v/v. The identification of carotenoids was performed by UV-VIS spectroscopy and confirmed by thin layer chromatography (TLC in the presence of antimony pentachloride (SbCl5. The production profile was analyzed using liquid-chromatography mass spectroscopy (LC-MS techniques. Phenotypic characteristics of the isolate were carried out and the 16S rRNA gene was amplified using polymerase chain reaction (PCR. Results: LC-MS analytical results revealed that produced carotenoids are bacterioruberin, lycopene and β-carotene. Bacterioruberin was found to be the predominant produced carotenoid. 16S rRNA analysis showed that TBZ126 has 100% similarity with Halorubrum chaoviator Halo-G*T (AM048786. Conclusion: Halorubrum sp. TBZ126, isolated from Urmia Lake has high capacity in the production of carotenoids. This extremely halophilic archaeon could be considered as a prokaryotic candidate for carotenoid production source for future studies.

  9. 基于样本熵和极端学习机的超短期风电功率组合预测模型%Combined Model for Ultra Short-term Wind Power Prediction Based on Sample Entropy and Extreme Learning Machine

    Institute of Scientific and Technical Information of China (English)

    张学清; 梁军; 张熙; 张峰; 张利; 徐兵

    2013-01-01

    该文提出一种经验模态分解(empirical mode 该文提出一种经验模态分解(empirical mode decomposition,EMD)-样本熵(sample entropy,SE)和极端学习机(extreme learning machine,ELM)相结合的风电功率超短期预测方法。该方法首先利用 EMD-SE 将风电功率时间序列分解为一系列复杂度差异明显的风电子序列;其次利用最小二乘支持向量机(least squares support vector machine, LSSVM)、极端学习机和经原始岭回归(primal ridge regression,PRR)改进的极端学习机(PRR-ELM)对各子序列建立组合预测模型,并采用交叉验证法和重构相空间法确定各模型的参数和输入向量维数,以提高各组合模型的预测精度;最后以某一风电场实际采集的数据为算例,结果表明基于EMD-SE理论的ELM和PRR-ELM组合预测模型在预测精度和训练速度上都明显优于 EMD-SE 理论和 LSSVM 的组合模型,且其预测结果更接近于真实值,为实现风电功率在线的较高精度超短期预测提供了可能。%An ultra short-term wind power combined prediction approach based on empirical mode decomposition (EMD)-sample entropy (SE) and extreme learning machine (ELM) was proposed. Firstly, the wind power time series was decomposed into a series of wind power subsequences with obvious differences in complex degree by using EMD-SE. Secondly, the prediction models of each subsequence were constructed with least squares support vector machine (LSSVM), extreme learning machine (ELM) and ELM improved by primal ridge regression (PRR-ELM), of which the parameters and the input vector dimensions were determined by cross validation and chaotic phase space theory to improve the forecasting accuracy of each prediction model. Finally, taking the actual collecting data of certain a wind farm for an example, the simulation results illustrate that ELM and PRR-ELM prediction model based on EMD-SE are much better than the combined LSSVM model

  10. Attitude extremity, consensus and diagnosticity

    NARCIS (Netherlands)

    van der Pligt, J.; Ester, P.; van der Linden, J.

    1983-01-01

    Studied the effects of attitude extremity on perceived consensus and willingness to ascribe trait terms to others with either pro- or antinuclear attitudes. 611 Ss rated their attitudes toward nuclear energy on a 5-point scale. Results show that attitude extremity affected consensus estimates. Trait

  11. Gender, Education, Extremism and Security

    Science.gov (United States)

    Davies, Lynn

    2008-01-01

    This paper examines the complex relationships between gender, education, extremism and security. After defining extremism and fundamentalism, it looks first at the relationship of gender to violence generally, before looking specifically at how this plays out in more extremist violence and terrorism. Religious fundamentalism is also shown to have…

  12. Grassland responses to precipitation extremes

    Science.gov (United States)

    Grassland ecosystems are naturally subjected to periods of prolonged drought and sequences of wet years. Climate change is expected to enhance the magnitude and frequency of extreme events at the intraannual and multiyear scales. Are grassland responses to extreme precipitation simply a response to ...

  13. Baldwin effect under multipeaked fitness landscapes: Phenotypic fluctuation accelerates evolutionary rate

    Science.gov (United States)

    Saito, Nen; Ishihara, Shuji; Kaneko, Kunihiko

    2013-05-01

    Phenotypic fluctuations and plasticity can generally affect the course of evolution, a process known as the Baldwin effect. Several studies have recast this effect and claimed that phenotypic plasticity accelerates evolutionary rate (the Baldwin expediting effect); however, the validity of this claim is still controversial. In this study, we investigate the evolutionary population dynamics of a quantitative genetic model under a multipeaked fitness landscape, in order to evaluate the validity of the effect. We provide analytical expressions for the evolutionary rate and average population fitness. Our results indicate that under a multipeaked fitness landscape, phenotypic fluctuation always accelerates evolutionary rate, but it decreases the average fitness. As an extreme case of the trade-off between the rate of evolution and average fitness, phenotypic fluctuation is shown to accelerate the error catastrophe, in which a population fails to sustain a high-fitness peak. In the context of our findings, we discuss the role of phenotypic plasticity in adaptive evolution.

  14. Modeling extreme risks in ecology.

    Science.gov (United States)

    Burgman, Mark; Franklin, James; Hayes, Keith R; Hosack, Geoffrey R; Peters, Gareth W; Sisson, Scott A

    2012-11-01

    Extreme risks in ecology are typified by circumstances in which data are sporadic or unavailable, understanding is poor, and decisions are urgently needed. Expert judgments are pervasive and disagreements among experts are commonplace. We outline approaches to evaluating extreme risks in ecology that rely on stochastic simulation, with a particular focus on methods to evaluate the likelihood of extinction and quasi-extinction of threatened species, and the likelihood of establishment and spread of invasive pests. We evaluate the importance of assumptions in these assessments and the potential of some new approaches to account for these uncertainties, including hierarchical estimation procedures and generalized extreme value distributions. We conclude by examining the treatment of consequences in extreme risk analysis in ecology and how expert judgment may better be harnessed to evaluate extreme risks.

  15. Genetic and Environmental Regulation on Longitudinal Change of Metabolic Phenotypes in Danish and Chinese Adult Twins

    DEFF Research Database (Denmark)

    Li, Shuxia; Kyvik, Kirsten Ohm; Pang, Zengchang

    2016-01-01

    OBJECTIVE: The rate of change in metabolic phenotypes can be highly indicative of metabolic disorders and disorder-related modifications. We analyzed data from longitudinal twin studies on multiple metabolic phenotypes in Danish and Chinese twins representing two populations of distinct ethnic...... environmental contribution to blood pressure but no genetic contribution to longitudinal change in body mass traits. CONCLUSION: Our results emphasize the major contribution of unique environment to the observed intra-individual variation in all metabolic phenotypes in both samples, and meanwhile reveal...... differential patterns of genetic and common environmental regulation on changes over time in metabolic phenotypes across the two samples....

  16. Phenotypic screens targeting neurodegenerative diseases.

    Science.gov (United States)

    Zhang, Minhua; Luo, Guangrui; Zhou, Yanjiao; Wang, Shaohui; Zhong, Zhong

    2014-01-01

    Neurodegenerative diseases affect millions of people worldwide, and the incidences increase as the population ages. Disease-modifying therapy that prevents or slows disease progression is still lacking, making neurodegenerative diseases an area of high unmet medical need. Target-based drug discovery for disease-modifying agents has been ongoing for many years, without much success due to incomplete understanding of the molecular mechanisms underlying neurodegeneration. Phenotypic screening, starting with a disease-relevant phenotype to screen for compounds that change the outcome of biological pathways rather than activities at certain specific targets, offers an alternative approach to find small molecules or targets that modulate the key characteristics of neurodegeneration. Phenotypic screens that focus on amelioration of disease-specific toxins, protection of neurons from degeneration, or promotion of neuroregeneration could be potential fertile grounds for discovering therapeutic agents for neurodegenerative diseases. In this review, we will summarize the progress of compound screening using these phenotypic-based strategies for this area, with a highlight on unique considerations for disease models, assays, and screening methodologies. We will further provide our perspectives on how best to use phenotypic screening to develop drug leads for neurodegenerative diseases.

  17. Chromosomal phenotypes and submicroscopic abnormalities

    Directory of Open Access Journals (Sweden)

    Devriendt Koen

    2004-01-01

    Full Text Available Abstract The finding, during the last decade, that several common, clinically delineated syndromes are caused by submicroscopic deletions or, more rarely, by duplications, has provided a powerful tool in the annotation of the human genome. Since most microdeletion/microduplication syndromes are defined by a common deleted/duplicated region, abnormal dosage of genes located within these regions can explain the phenotypic similarities among individuals with a specific syndrome. As such, they provide a unique resource towards the genetic dissection of complex phenotypes such as congenital heart defects, mental and growth retardation and abnormal behaviour. In addition, the study of phenotypic differences in individuals with the same microdeletion syndrome may also become a treasury for the identification of modifying factors for complex phenotypes. The molecular analysis of these chromosomal anomalies has led to a growing understanding of their mechanisms of origin. Novel tools to uncover additional submicroscopic chromosomal anomalies at a higher resolution and higher speed, as well as the novel tools at hand for deciphering the modifying factors and epistatic interactors, are 'on the doorstep' and will, besides their obvious diagnostic role, play a pivotal role in the genetic dissection of complex phenotypes.

  18. Clustering high-dimensional mixed data to uncover sub-phenotypes: joint analysis of phenotypic and genotypic data.

    Science.gov (United States)

    McParland, D; Phillips, C M; Brennan, L; Roche, H M; Gormley, I C

    2017-06-30

    The LIPGENE-SU.VI.MAX study, like many others, recorded high-dimensional continuous phenotypic data and categorical genotypic data. LIPGENE-SU.VI.MAX focuses on the need to account for both phenotypic and genetic factors when studying the metabolic syndrome (MetS), a complex disorder that can lead to higher risk of type 2 diabetes and cardiovascular disease. Interest lies in clustering the LIPGENE-SU.VI.MAX participants into homogeneous groups or sub-phenotypes, by jointly considering their phenotypic and genotypic data, and in determining which variables are discriminatory. A novel latent variable model that elegantly accommodates high dimensional, mixed data is developed to cluster LIPGENE-SU.VI.MAX participants using a Bayesian finite mixture model. A computationally efficient variable selection algorithm is incorporated, estimation is via a Gibbs sampling algorithm and an approximate BIC-MCMC criterion is developed to select the optimal model. Two clusters or sub-phenotypes ('healthy' and 'at risk') are uncovered. A small subset of variables is deemed discriminatory, which notably includes phenotypic and genotypic variables, highlighting the need to jointly consider both factors. Further, 7 years after the LIPGENE-SU.VI.MAX data were collected, participants underwent further analysis to diagnose presence or absence of the MetS. The two uncovered sub-phenotypes strongly correspond to the 7-year follow-up disease classification, highlighting the role of phenotypic and genotypic factors in the MetS and emphasising the potential utility of the clustering approach in early screening. Additionally, the ability of the proposed approach to define the uncertainty in sub-phenotype membership at the participant level is synonymous with the concepts of precision medicine and nutrition. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  19. Microhabitats reduce animal's exposure to climate extremes.

    Science.gov (United States)

    Scheffers, Brett R; Edwards, David P; Diesmos, Arvin; Williams, Stephen E; Evans, Theodore A

    2014-02-01

    Extreme weather events, such as unusually hot or dry conditions, can cause death by exceeding physiological limits, and so cause loss of population. Survival will depend on whether or not susceptible organisms can find refuges that buffer extreme conditions. Microhabitats offer different microclimates to those found within the wider ecosystem, but do these microhabitats effectively buffer extreme climate events relative to the physiological requirements of the animals that frequent them? We collected temperature data from four common microhabitats (soil, tree holes, epiphytes, and vegetation) located from the ground to canopy in primary rainforests in the Philippines. Ambient temperatures were monitored from outside of each microhabitat and from the upper forest canopy, which represent our macrohabitat controls. We measured the critical thermal maxima (CTmax ) of frog and lizard species, which are thermally sensitive and inhabit our microhabitats. Microhabitats reduced mean temperature by 1-2 °C and reduced the duration of extreme temperature exposure by 14-31 times. Microhabitat temperatures were below the CTmax of inhabitant frogs and lizards, whereas macrohabitats consistently contained lethal temperatures. Microhabitat temperatures increased by 0.11-0.66 °C for every 1 °C increase in macrohabitat temperature, and this nonuniformity in temperature change influenced our forecasts of vulnerability for animal communities under climate change. Assuming uniform increases of 6 °C, microhabitats decreased the vulnerability of communities by up to 32-fold, whereas under nonuniform increases of 0.66 to 3.96 °C, microhabitats decreased the vulnerability of communities by up to 108-fold. Microhabitats have extraordinary potential to buffer climate and likely reduce mortality during extreme climate events. These results suggest that predicted changes in distribution due to mortality and habitat shifts that are derived from macroclimatic samples and that assume

  20. High levels of interspecific gene flow in an endemic cichlid fish adaptive radiation from an extreme lake environment.

    Science.gov (United States)

    Ford, Antonia G P; Dasmahapatra, Kanchon K; Rüber, Lukas; Gharbi, Karim; Cezard, Timothee; Day, Julia J

    2015-07-01

    Studying recent adaptive radiations in isolated insular systems avoids complicating causal events and thus may offer clearer insight into mechanisms generating biological diversity. Here, we investigate evolutionary relationships and genomic differentiation within the recent radiation of Alcolapia cichlid fish that exhibit extensive phenotypic diversification, and which are confined to the extreme soda lakes Magadi and Natron in East Africa. We generated an extensive RAD data set of 96 individuals from multiple sampling sites and found evidence for genetic admixture between species within Lake Natron, with the highest levels of admixture between sympatric populations of the most recently diverged species. Despite considerable environmental separation, populations within Lake Natron do not exhibit isolation by distance, indicating panmixia within the lake, although individuals within lineages clustered by population in phylogenomic analysis. Our results indicate exceptionally low genetic differentiation across the radiation despite considerable phenotypic trophic variation, supporting previous findings from smaller data sets; however, with the increased power of densely sampled SNPs, we identify genomic peaks of differentiation (FST outliers) between Alcolapia species. While evidence of ongoing gene flow and interspecies hybridization in certain populations suggests that Alcolapia species are incompletely reproductively isolated, the identification of outlier SNPs under diversifying selection indicates the radiation is undergoing adaptive divergence.

  1. Spatial dependence of extreme rainfall

    Science.gov (United States)

    Radi, Noor Fadhilah Ahmad; Zakaria, Roslinazairimah; Satari, Siti Zanariah; Azman, Muhammad Az-zuhri

    2017-05-01

    This study aims to model the spatial extreme daily rainfall process using the max-stable model. The max-stable model is used to capture the dependence structure of spatial properties of extreme rainfall. Three models from max-stable are considered namely Smith, Schlather and Brown-Resnick models. The methods are applied on 12 selected rainfall stations in Kelantan, Malaysia. Most of the extreme rainfall data occur during wet season from October to December of 1971 to 2012. This period is chosen to assure the available data is enough to satisfy the assumption of stationarity. The dependence parameters including the range and smoothness, are estimated using composite likelihood approach. Then, the bootstrap approach is applied to generate synthetic extreme rainfall data for all models using the estimated dependence parameters. The goodness of fit between the observed extreme rainfall and the synthetic data is assessed using the composite likelihood information criterion (CLIC). Results show that Schlather model is the best followed by Brown-Resnick and Smith models based on the smallest CLIC's value. Thus, the max-stable model is suitable to be used to model extreme rainfall in Kelantan. The study on spatial dependence in extreme rainfall modelling is important to reduce the uncertainties of the point estimates for the tail index. If the spatial dependency is estimated individually, the uncertainties will be large. Furthermore, in the case of joint return level is of interest, taking into accounts the spatial dependence properties will improve the estimation process.

  2. Extreme Thrombocytosis and Cardiovascular Surgery

    Science.gov (United States)

    Natelson, Ethan A.

    2012-01-01

    Extreme thrombocytosis is a major risk factor for excessive bleeding and for thrombosis, either of which can complicate cardiovascular surgical and interventional procedures. Extreme thrombocytosis can also cause an unusual syndrome, erythromelalgia, that results in a type of chronic microvascular occlusive arterial disease. We present the differential diagnosis of conditions that may lead to extreme thrombocytosis, 3 cases (each of which illustrates a different potential complication), and a review of the pertinent medical literature. Correcting excessive thrombocytosis is typically not difficult, whether electively or acutely, and effective therapy usually controls thrombosis and excessive hemorrhage postprocedurally. PMID:23304015

  3. Sampling algorithms

    CERN Document Server

    Tillé, Yves

    2006-01-01

    Important progresses in the methods of sampling have been achieved. This book draws up an inventory of methods that can be useful for selecting samples. Forty-six sampling methods are described in the framework of general theory. This book is suitable for experienced statisticians who are familiar with the theory of survey sampling.

  4. Balanced sampling

    NARCIS (Netherlands)

    Brus, D.J.

    2015-01-01

    In balanced sampling a linear relation between the soil property of interest and one or more covariates with known means is exploited in selecting the sampling locations. Recent developments make this sampling design attractive for statistical soil surveys. This paper introduces balanced sampling

  5. Sample Design.

    Science.gov (United States)

    Ross, Kenneth N.

    1987-01-01

    This article considers various kinds of probability and non-probability samples in both experimental and survey studies. Throughout, how a sample is chosen is stressed. Size alone is not the determining consideration in sample selection. Good samples do not occur by accident; they are the result of a careful design. (Author/JAZ)

  6. Balanced sampling

    NARCIS (Netherlands)

    Brus, D.J.

    2015-01-01

    In balanced sampling a linear relation between the soil property of interest and one or more covariates with known means is exploited in selecting the sampling locations. Recent developments make this sampling design attractive for statistical soil surveys. This paper introduces balanced sampling

  7. Slice Sampling

    CERN Document Server

    Neal, R M

    2000-01-01

    Markov chain sampling methods that automatically adapt to characteristics of the distribution being sampled can be constructed by exploiting the principle that one can sample from a distribution by sampling uniformly from the region under the plot of its density function. A Markov chain that converges to this uniform distribution can be constructed by alternating uniform sampling in the vertical direction with uniform sampling from the horizontal `slice' defined by the current vertical position, or more generally, with some update that leaves the uniform distribution over this slice invariant. Variations on such `slice sampling' methods are easily implemented for univariate distributions, and can be used to sample from a multivariate distribution by updating each variable in turn. This approach is often easier to implement than Gibbs sampling, and more efficient than simple Metropolis updates, due to the ability of slice sampling to adaptively choose the magnitude of changes made. It is therefore attractive f...

  8. Mesenchymal stem cell subpopulations: phenotype, property and therapeutic potential.

    Science.gov (United States)

    Mo, Miaohua; Wang, Shan; Zhou, Ying; Li, Hong; Wu, Yaojiong

    2016-09-01

    Mesenchymal stem cells (MSC) are capable of differentiating into cells of multiple cell lineages and have potent paracrine effects. Due to their easy preparation and low immunogenicity, MSC have emerged as an extremely promising therapeutic agent in regenerative medicine for diverse diseases. However, MSC are heterogeneous with respect to phenotype and function in current isolation and cultivation regimes, which often lead to incomparable experimental results. In addition, there may be specific stem cell subpopulations with definite differentiation capacity toward certain lineages in addition to stem cells with multi-differentiation potential. Recent studies have identified several subsets of MSC which exhibit distinct features and biological activities, and enhanced therapeutic potentials for certain diseases. In this review, we give an overview of these subsets for their phenotypic, biological and functional properties.

  9. Distribution profile of paraoxonase phenotypes among the Gujaratis

    Directory of Open Access Journals (Sweden)

    Patel A

    2007-01-01

    Full Text Available Background: Paraoxonase (PON1 can hydrolyze organophosphate pesticides (OP and has a key role in the susceptibility of human in OP toxicity. The human-enzyme shows polymorphism and variations in the distribution profile of its phenotypes among different ethnic groups have been observed. Aims: To see the distribution pattern of total PON1 activity in 45 healthy attendants of poisoning cases; 121 healthy unrelated farm-labours and 59 normal subjects of trauma. Materials and Methods: The PON1 activities from serum/plasma samples of these healthy normal individuals were estimated with/without addition of 1M NaCl in order to determine salt-stimulated and basal activity. The PON 1 phenotypes were determined on the basis of percent activation of enzyme activity. Results: Tri-modal distribution of basal PON1 activity was observed among all these individuals. 52.0% of the individuals belonged to Phenotype A, 46.6% to phenotype AB while 1.4% to Phenotype B with gene frequency of allele-A and allele-B being 0.753 and 0.247 respectively in excellent agreement with Hardy-Weinberg equilibrium. Conclusion: Maximum number of individuals belonged to phenotype-A (low PON1 activity showing potential vulnerability towards Op-poisoning.

  10. Small colony variant of methicillin-resistant Staphylococcus pseudintermedius ST71 presenting as a sticky phenotype.

    Science.gov (United States)

    Savini, Vincenzo; Carretto, Edoardo; Polilli, Ennio; Marrollo, Roberta; Santarone, Stella; Fazii, Paolo; D'Antonio, Domenico; Rossano, Alexandra; Perreten, Vincent

    2014-04-01

    We first observed the phenomenon of small colony variants (SCVs) in a Staphylococcus pseudintermedius sequence type 71 (ST71) strain, isolated from a non-pet owner. Although we found that small-sized colonies share main features with Staphylococcus aureus SCVs, they nevertheless show a novel, particular, and sticky phenotype, whose expression was extremely stable, even after subcultivation.

  11. Extreme hypertriglyceridemia managed with insulin.

    Science.gov (United States)

    Thuzar, Moe; Shenoy, Vasant V; Malabu, Usman H; Schrale, Ryan; Sangla, Kunwarjit S

    2014-01-01

    Extreme hypertriglyceridemia can lead to acute pancreatitis and rapid lowering of serum triglycerides (TG) is necessary for preventing such life-threatening complications. However, there is no established consensus on the acute management of extreme hypertriglyceridemia. We retrospectively reviewed 10 cases of extreme hypertriglyceridemia with mean serum TG on presentation of 101.5 ± 23.4 mmol/L (8982 ± 2070 mg/dL) managed with insulin. Serum TG decreased by 87 ± 4% in 24 hours in those patients managed with intravenous insulin and fasting and 40 ± 8.4% in those managed with intravenous insulin alone (P = .0003). The clinical course was uncomplicated in all except 1 patient who subsequently developed a pancreatic pseudocyst. Thus, combination of intravenous insulin with fasting appears to be an effective, simple, and safe treatment strategy in immediate management of extreme hypertriglyceridemia. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

  12. Moment methods in extremal geometry

    NARCIS (Netherlands)

    De Laat, D.

    2016-01-01

    In this thesis we develop techniques for solving problems in extremal geometry. We give an infinite dimensional generalization of moment techniques from polynomial optimization. We use this to construct semidefinite programming hierarchies for approximating optimal packing densities and ground state

  13. Moment methods in extremal geometry

    NARCIS (Netherlands)

    De Laat, D.

    2016-01-01

    In this thesis we develop techniques for solving problems in extremal geometry. We give an infinite dimensional generalization of moment techniques from polynomial optimization. We use this to construct semidefinite programming hierarchies for approximating optimal packing densities and ground state

  14. Surrogate-assisted feature extraction for high-throughput phenotyping.

    Science.gov (United States)

    Yu, Sheng; Chakrabortty, Abhishek; Liao, Katherine P; Cai, Tianrun; Ananthakrishnan, Ashwin N; Gainer, Vivian S; Churchill, Susanne E; Szolovits, Peter; Murphy, Shawn N; Kohane, Isaac S; Cai, Tianxi

    2017-04-01

    Phenotyping algorithms are capable of accurately identifying patients with specific phenotypes from within electronic medical records systems. However, developing phenotyping algorithms in a scalable way remains a challenge due to the extensive human resources required. This paper introduces a high-throughput unsupervised feature selection method, which improves the robustness and scalability of electronic medical record phenotyping without compromising its accuracy. The proposed Surrogate-Assisted Feature Extraction (SAFE) method selects candidate features from a pool of comprehensive medical concepts found in publicly available knowledge sources. The target phenotype's International Classification of Diseases, Ninth Revision and natural language processing counts, acting as noisy surrogates to the gold-standard labels, are used to create silver-standard labels. Candidate features highly predictive of the silver-standard labels are selected as the final features. Algorithms were trained to identify patients with coronary artery disease, rheumatoid arthritis, Crohn's disease, and ulcerative colitis using various numbers of labels to compare the performance of features selected by SAFE, a previously published automated feature extraction for phenotyping procedure, and domain experts. The out-of-sample area under the receiver operating characteristic curve and F -score from SAFE algorithms were remarkably higher than those from the other two, especially at small label sizes. SAFE advances high-throughput phenotyping methods by automatically selecting a succinct set of informative features for algorithm training, which in turn reduces overfitting and the needed number of gold-standard labels. SAFE also potentially identifies important features missed by automated feature extraction for phenotyping or experts.

  15. Deformations of extremal toric manifolds

    CERN Document Server

    Rollin, Yann

    2012-01-01

    Let $X$ be a compact toric extremal K\\"ahler manifold. Using the work of Sz\\'ekelyhidi, we provide a simple criterion on the fan describing $X$ to ensure the existence of complex deformations of $X$ that carry extremal metrics. As an example, we find new CSC metrics on 4-points blow-ups of $\\C\\P^1\\times\\C\\P^1$.

  16. Large Extremity Peripheral Nerve Repair

    Science.gov (United States)

    2015-10-01

    IL, Kochevar IE, Redmond RW. Large extremity peripheral nerve repair. Military Health System Research Symposium (MHSRS) Fort Lauderdale, FL. August...some notable discoveries that may impact military health care in the near future. There is a clear need in military medicine to improve outcomes in...membranes or “caul” intact was considered extremely lucky. Children were gifted with life-long happiness , the ability to see spirits, and protection

  17. Observed Statistics of Extreme Waves

    Science.gov (United States)

    2006-12-01

    9 Figure 5. An energy stealing wave as a solution to the NLS equation . (From: Dysthe and...shown that nonlinear interaction between four colliding waves can produce extreme wave behavior. He utilized the NLS equation in his numerical ...2000) demonstrated the formation of extreme waves using the Korteweg de Vries ( KdV ) equation , which is valid in shallow water. It was shown in the

  18. Weather Extremes Around the World

    Science.gov (United States)

    1974-04-01

    or ever has occurred. According to M. A. Arkin, "... record extremes must be taken with a grain of salt .... Ř He explains that news of an extreme...the edge of the Danakil Depression, a salt desert. By averaging the annual mean daily maximum temperature of 106°F36 atid the annual mean daily...increased by orographic lifting.1" Asa result of these monsoon disturbances, which are still not fully understood, the eastern Himalayan 105 106

  19. Leaf segmentation in plant phenotyping

    NARCIS (Netherlands)

    Scharr, Hanno; Minervini, Massimo; French, Andrew P.; Klukas, Christian; Kramer, David M.; Liu, Xiaoming; Luengo, Imanol; Pape, Jean Michel; Polder, Gerrit; Vukadinovic, Danijela; Yin, Xi; Tsaftaris, Sotirios A.

    2016-01-01

    Image-based plant phenotyping is a growing application area of computer vision in agriculture. A key task is the segmentation of all individual leaves in images. Here we focus on the most common rosette model plants, Arabidopsis and young tobacco. Although leaves do share appearance and shape cha

  20. Forensic DNA phenotyping : Regulatory issues

    NARCIS (Netherlands)

    Koops, E.J.; Schellekens, M.H.M.

    2008-01-01

    Forensic DNA phenotyping is an interesting new investigation method: crime-scene DNA is analyzed to compose a description of the unknown suspect, including external and behavioral features, geographic origin and perhaps surname. This method is allowed in some countries but prohibited in a few

  1. Forensic DNA phenotyping : Regulatory issues

    NARCIS (Netherlands)

    Koops, E.J.; Schellekens, M.H.M.

    2008-01-01

    Forensic DNA phenotyping is an interesting new investigation method: crime-scene DNA is analyzed to compose a description of the unknown suspect, including external and behavioral features, geographic origin and perhaps surname. This method is allowed in some countries but prohibited in a few others

  2. Phenotypic characterization of oral mucosa: what is normal?

    Science.gov (United States)

    Valach, Jaroslav; Foltán, René; Vlk, Marek; Szabo, Pavol; Smetana, Karel

    2017-01-31

    Knowledge of the phenotypic pattern of oral squamous epithelium is important in the histopathologic evaluation of lesions including cancer. The literature on normal epithelium is controversial as the phenotype has not been evaluated in samples from completely healthy tissue donors without a history of tobacco and alcohol exposure. In this study, we evaluated normal upper lip fornix and gingival mucosa from carefully selected young healthy donors without a history of smoking and alcohol exposure, and keratin types 8, 10, 14, and 17, filaggrin, and Ki67 were investigated in these donors. The results were compared with profile of epithelium from leukoplakia. The results demonstrated that the phenotypic patterns of gingiva and upper lip fornix mucosa were different. Surprisingly, a high proportion of gingival samples exhibited keratin 8 and a suprabasal signal for keratin 14. These patterns were compared with that of human oral leukoplakia, and some phenotypic similarities were noted. These results demonstrated oral epithelium phenotypic plasticity based on functional requirements of the microenvironment, which can be used in diagnosis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Irrigation mitigates against heat extremes

    Science.gov (United States)

    Thiery, Wim; Fischer, Erich; Visser, Auke; Hirsch, Annette L.; Davin, Edouard L.; Lawrence, Dave; Hauser, Mathias; Seneviratne, Sonia I.

    2017-04-01

    Irrigation is an essential practice for sustaining global food production and many regional economies. Emerging scientific evidence indicates that irrigation substantially affects mean climate conditions in different regions of the world. Yet how this practice influences climate extremes is currently unknown. Here we use gridded observations and ensemble simulations with the Community Earth System Model to assess the impacts of irrigation on climate extremes. While the influence of irrigation on annual mean temperatures is limited, we find a large impact on temperature extremes, with a particularly strong cooling during the hottest day of the year (-0.78 K averaged over irrigated land). The strong influence on hot extremes stems from the timing of irrigation and its influence on land-atmosphere coupling strength. Together these effects result in asymmetric temperature responses, with a more pronounced cooling during hot and/or dry periods. The influence of irrigation is even more pronounced when considering subgrid-scale model output, suggesting that local effects of land management are far more important than previously thought. Finally we find that present-day irrigation is partly masking GHG-induced warming of extreme temperatures, with particularly strong effects in South Asia. Our results overall underline that irrigation substantially reduces our exposure to hot temperature extremes and highlight the need to account for irrigation in future climate projections.

  4. Behavioral and life history responses to extreme climatic conditions: Studies on a migratory songbird

    Institute of Scientific and Technical Information of China (English)

    A. P. Mφller

    2011-01-01

    Behavioral responses to environmental change are the mechanisms that allow for rapid phenotypic change preventing temporary or permanent damage and hence preventing reductions in fitness. Extreme climatic events are by definition rare, although they are predicted to increase in amplitude and frequency in the coming years. However, our current knowledge about behavioral responses to such extreme events is scarce. Here I analyze two examples of the effects of extreme weather events on behavior and life history: (1) A comparison of behavior and life history during extremely warm and extremely cold years relative to normal years; and (2) a comparison of behavior before and after the extremely early snowfall in fall 1974 when numerous birds died in the Alps during September-October. Behavioral and life history responses of barn swallows Hirundo rustica to extremely cold and extremely warm years were positively correlated, with particularly large effect sizes in cold years. Extreme mortality in barn swallows during fall migration 1974 in the Alps eliminated more than 40% of the breeding population across large areas in Central and Northern Europe, and this affected first arrival date, changes in timing and extent of reproduction and changes in degree of breeding sociality supposedly as a consequence of correlated responses to selection. Finally, I provide directions for research that will allow us to better understand behavior and life history changes in response to extreme climate change [Current Zoology 57 (3): 351-362,2011].

  5. Behavioral and life history responses to extreme climatic conditions: Studies on a migratory songbird

    Directory of Open Access Journals (Sweden)

    A. P. Møller

    2011-06-01

    Full Text Available Behavioral responses to environmental change are the mechanisms that allow for rapid phenotypic change preventing temporary or permanent damage and hence preventing reductions in fitness. Extreme climatic events are by definition rare, although they are predicted to increase in amplitude and frequency in the coming years. However, our current knowledge about behavioral responses to such extreme events is scarce. Here I analyze two examples of the effects of extreme weather events on behavior and life history: (1 A comparison of behavior and life history during extremely warm and extremely cold years relative to normal years; and (2 a comparison of behavior before and after the extremely early snowfall in fall 1974 when numerous birds died in the Alps during September-October. Behavioral and life history responses of barn swallows Hirundo rustica to extremely cold and extremely warm years were positively correlated, with particularly large effect sizes in cold years. Extreme mortality in barn swallows during fall migration 1974 in the Alps eliminated more than 40% of the breeding population across large areas in Central and Northern Europe, and this affected first arrival date, changes in timing and extent of reproduction and changes in degree of breeding sociality supposedly as a consequence of correlated responses to selection. Finally, I provide directions for research that will allow us to better understand behavior and life history changes in response to extreme climate change [Current Zoology 57 (3: 351–362, 2011].

  6. Uremic parkinsonism with atypical phenotypes and radiologic features.

    Science.gov (United States)

    Yoon, Jee-Eun; Kim, Ji Sun; Park, Jeong-Ho; Lee, Kyung-Bok; Roh, Hakjae; Park, Sung Tae; Cho, Jin Whan; Ahn, Moo-young

    2016-04-01

    Uremic encephalopathy with bilateral basal ganglia lesions has been reported as an acute neurometabolic disease which shows reversible clinical course and brain imaging features. The exact nature and pathophysiology have not been well established. We encountered two patients who showed a relapsing and aggravating course and an atypical phenotype including parkinsonism with paroxysmal dystonic head tremor and acute onset monoparesis of the lower extremity. They also showed unusual radiological findings which revealed combined lesions in the basal ganglia and cortex, persistent hemorrhagic transformation, and focal ischemic lesion in the internal capsule. Herein, we present the unusual phenomenology with atypical radiologic findings and suggest the possible multifactorial pathogenesis of uremic encephalopathy.

  7. Strong and parallel salinity-induced phenotypic plasticity in one generation of threespine stickleback.

    Science.gov (United States)

    Mazzarella, A B; Voje, K L; Hansson, T H; Taugbøl, A; Fischer, B

    2015-03-01

    Phenotypic plasticity is a major factor contributing to variation of organisms in nature, yet its evolutionary significance is insufficiently understood. One example system where plasticity might have played an important role in an adaptive radiation is the threespine stickleback (Gasterosteus aculeatus), a fish that has diversified after invading freshwater lakes repeatedly from the marine habitat. The parallel phenotypic changes that occurred in this radiation were extremely rapid. This study evaluates phenotypic plasticity in stickleback body shape in response to salinity in fish stemming from a wild freshwater population. Using a split-clutch design, we detected surprisingly large phenotypically plastic changes in body shape after one generation. Fish raised in salt water developed shallower bodies and longer jaws, and these changes were consistent and parallel across families. Although this work highlights the effect of phenotypic plasticity, we also find indications that constraints may play a role in biasing the direction of possible phenotypic change. The slopes of the allometric relationship of individual linear traits did not change across treatments, indicating that plastic change does not affect the covariation of traits with overall size. We conclude that stickleback have a large capacity for plastic phenotypic change in response to salinity and that plasticity and evolutionary constraints have likely contributed to the phenotypic diversification of these fish.

  8. Capillary sample

    Science.gov (United States)

    ... several times a day using capillary blood sampling. Disadvantages to capillary blood sampling include: Only a limited ... do not constitute endorsements of those other sites. Copyright 1997-2017, A.D.A.M., Inc. Duplication ...

  9. Conditional simulation of extremal Gaussian processes

    CERN Document Server

    Dombry, Clément

    2012-01-01

    Recently the regular conditional distributions of max-infinitely divisible processes were derived by \\citet{Dombry2011} and although these conditional distributions have complicated closed forms, \\citet{Dombry2011b} introduce an algorithm to get conditional realizations of Brown-Resnick processes. In this paper we derive the regular conditional distributions of the max-stable process introduced by \\citet{Schlather2002} and adapt the framework of \\citet{Dombry2011b} to this specific process. We test the methods on simulated data and give an application to extreme temperatures in Switzerland. Results show that the proposed sampling scheme provide accurate conditional simulations and can handle real-sized problems.

  10. Properties of Extreme Poin Rainfall II

    DEFF Research Database (Denmark)

    Mikkelsen, Peter Steen; Harremoës, Poul; Rosbjerg, Dan

    1995-01-01

    As an alternative to the traditional non-parametric method the partial duration series approach with exponentially distributed exceedances is used to model extreme values of depth and maximum 10 min intensity per rainfall event, measured at gauges placed at different locations in Denmark....... A statistically significant regional variation is documented and shown to be of importance to engineering application. The apparent variability is divided into sampling uncertainty and uncertainty caused by true regional variability. Further, a method for assessing the total inherent design uncertainty, taking...

  11. Deinococcus geothermalis: the pool of extreme radiation resistance genes shrinks.

    Directory of Open Access Journals (Sweden)

    Kira S Makarova

    Full Text Available Bacteria of the genus Deinococcus are extremely resistant to ionizing radiation (IR, ultraviolet light (UV and desiccation. The mesophile Deinococcus radiodurans was the first member of this group whose genome was completely sequenced. Analysis of the genome sequence of D. radiodurans, however, failed to identify unique DNA repair systems. To further delineate the genes underlying the resistance phenotypes, we report the whole-genome sequence of a second Deinococcus species, the thermophile Deinococcus geothermalis, which at its optimal growth temperature is as resistant to IR, UV and desiccation as D. radiodurans, and a comparative analysis of the two Deinococcus genomes. Many D. radiodurans genes previously implicated in resistance, but for which no sensitive phenotype was observed upon disruption, are absent in D. geothermalis. In contrast, most D. radiodurans genes whose mutants displayed a radiation-sensitive phenotype in D. radiodurans are conserved in D. geothermalis. Supporting the existence of a Deinococcus radiation response regulon, a common palindromic DNA motif was identified in a conserved set of genes associated with resistance, and a dedicated transcriptional regulator was predicted. We present the case that these two species evolved essentially the same diverse set of gene families, and that the extreme stress-resistance phenotypes of the Deinococcus lineage emerged progressively by amassing cell-cleaning systems from different sources, but not by acquisition of novel DNA repair systems. Our reconstruction of the genomic evolution of the Deinococcus-Thermus phylum indicates that the corresponding set of enzymes proliferated mainly in the common ancestor of Deinococcus. Results of the comparative analysis weaken the arguments for a role of higher-order chromosome alignment structures in resistance; more clearly define and substantially revise downward the number of uncharacterized genes that might participate in DNA repair and

  12. Deinococcus geothermalis: The Pool of Extreme Radiation Resistance Genes Shrinks

    Energy Technology Data Exchange (ETDEWEB)

    Makarova, Kira S. [National Center for Biotechnology Information; Omelchenko, Marina [National Center for Biotechnology Information; Gaidamakova, Elena [Uniformed Services University of the Health Sciences (USUHS); Matrosova, Vera [Uniformed Services University of the Health Sciences (USUHS); Vasilenko, Alexander [Uniformed Services University of the Health Sciences (USUHS); Zhai, Min [Uniformed Services University of the Health Sciences (USUHS); Lapidus, Alla L. [U.S. Department of Energy, Joint Genome Institute; Copeland, A [U.S. Department of Energy, Joint Genome Institute; Kim, Edwin [U.S. Department of Energy, Joint Genome Institute; Land, Miriam L [ORNL; Mavromatis, K [U.S. Department of Energy, Joint Genome Institute; Pitluck, Samual [U.S. Department of Energy, Joint Genome Institute; Richardson, P M [U.S. Department of Energy, Joint Genome Institute; Detter, J. Chris [U.S. Department of Energy, Joint Genome Institute; Brettin, Tom [Los Alamos National Laboratory (LANL); Saunders, Elizabeth H [Los Alamos National Laboratory (LANL); Lai, Barry [Argonne National Laboratory (ANL); Ravel, Bruce [Argonne National Laboratory (ANL); Kemner, Kenneth M [Argonne National Laboratory (ANL); Wolf, Yuri [National Center for Biotechnology Information; Sorokin, Alexei [Genetique Microbienne; Gerasimova, Anna [Research Institute of Genetics and Selection of Industrial Microorganisms, Mosco; Gelfand, Mikhail [Moscow State University; Fredrickson, James K [Pacific Northwest National Laboratory (PNNL); Koonin, Eugene [National Center for Biotechnology Information; Daly, Michael [Uniformed Services University of the Health Sciences (USUHS)

    2007-01-01

    Bacteria of the genus Deinococcus are extremely resistant to ionizing radiation (IR), ultraviolet light (UV) and desiccation. The mesophile Deinococcus radiodurans was the first member of this group whose genome was completely sequenced. Analysis of the genome sequence of D. radiodurans, however, failed to identify unique DNA repair systems. To further delineate the genes underlying the resistance phenotypes, we report the whole-genome sequence of a second Deinococcus species, the thermophile Deinococcus geothermalis, which at its optimal growth temperature is as resistant to IR, UV and desiccation as D. radiodurans, and a comparative analysis of the two Deinococcus genomes. Many D. radiodurans genes previously implicated in resistance, but for which no sensitive phenotype was observed upon disruption, are absent in D. geothermalis. In contrast, most D. radiodurans genes whose mutants displayed a radiation-sensitive phenotype in D. radiodurans are conserved in D. geothermalis. Supporting the existence of a Deinococcus radiation response regulon, a common palindromic DNA motif was identified in a conserved set of genes associated with resistance, and a dedicated transcriptional regulator was predicted. We present the case that these two species evolved essentially the same diverse set of gene families, and that the extreme stress-resistance phenotypes of the Deinococcus lineage emerged progressively by amassing cell-cleaning systems from different sources, but not by acquisition of novel DNA repair systems. Our reconstruction of the genomic evolution of the Deinococcus-Thermus phylum indicates that the corresponding set of enzymes proliferated mainly in the common ancestor of Deinococcus. Results of the comparative analysis weaken the arguments for a role of higher-order chromosome alignment structures in resistance; more clearly define and substantially revise downward the number of uncharacterized genes that might participate in DNA repair and contribute to

  13. Deinococcus geothermalis: The Pool of Extreme Radiation Resistance Genes Shrinks

    Energy Technology Data Exchange (ETDEWEB)

    Makarova, Kira S.; Omelchenko, Marina V.; Gaidamakova, Elena K.; Matrosova, Vera Y.; Vasilenko, Alexander; Zhai, Min; Lapidus, Alla; Copeland, Alex; Kim, Edwin; Land, Miriam; Mavrommatis, Konstantinos; Pitluck, Samuel; Richardson, Paul M.; Detter, Chris; Brettin, Thomas; Saunders, Elizabeth; Lai, Barry; Ravel, Bruce; Kemner, Kenneth M.; Wolf, Yuri I.; Sorokin, Alexander; Gerasimova, Anna V.; Gelfand, Mikhail S.; Fredrickson, James K.; Koonin, Eugene V.; Daly, Michael J.

    2007-07-24

    Bacteria of the genus Deinococcus are extremely resistant to ionizing radiation (IR), ultraviolet light (UV) and desiccation. The mesophile Deinococcus radiodurans was the first member of this group whose genome was completely sequenced. Analysis of the genome sequence of D. radiodurans, however, failed to identify unique DNA repair systems. To further delineate the genes underlying the resistance phenotypes, we report the whole-genome sequence of a second Deinococcus species, the thermophile Deinococcus geothermalis, which at itsoptimal growth temperature is as resistant to IR, UV and desiccation as D. radiodurans, and a comparative analysis of the two Deinococcus genomes. Many D. radiodurans genes previously implicated in resistance, but for which no sensitive phenotype was observed upon disruption, are absent in D. geothermalis. In contrast, most D. radiodurans genes whose mutants displayed a radiation-sensitive phenotype in D. radiodurans are conserved in D. geothermalis. Supporting the existence of a Deinococcus radiation response regulon, a common palindromic DNA motif was identified in a conserved set of genes associated with resistance, and a dedicated transcriptional regulator was predicted. We present the case that these two species evolved essentially the same diverse set of gene families, and that the extreme stress-resistance phenotypes of the Deinococcus lineage emerged progressively by amassing cell-cleaning systems from different sources, but not by acquisition of novel DNA repair systems. Our reconstruction of the genomic evolution of the Deinococcus-Thermus phylum indicates that the corresponding set of enzymes proliferated mainly in the common ancestor of Deinococcus. Results of the comparative analysis weaken the arguments for a role of higher-order chromosome alignment structures in resistance; more clearly define and substantially revise downward the number of uncharacterized genes that might participate in DNA repair and contribute to

  14. Microbiome Heterogeneity Characterizing Intestinal Tissue and Inflammatory Bowel Disease Phenotype.

    Science.gov (United States)

    Tyler, Andrea D; Kirsch, Richard; Milgrom, Raquel; Stempak, Joanne M; Kabakchiev, Boyko; Silverberg, Mark S

    2016-04-01

    Inflammatory bowel disease has been associated with differential abundance of numerous organisms when compared to healthy controls (HCs); however, few studies have investigated variability in the microbiome across intestinal locations and how this variability might be related to disease location and phenotype. In this study, we have analyzed the microbiome of a large cohort of individuals recruited at Mount Sinai Hospital in Toronto, Canada. Biopsies were taken from subjects with Crohn's disease, ulcerative colitis, and HC, and also individuals having undergone ileal pouch-anal anastomosis for treatment of ulcerative colitis or familial adenomatous polyposis. Microbial 16S rRNA was sequenced using the Illumina MiSeq platform. We observed a great deal of variability in the microbiome characterizing different sampling locations. Samples from pouch and afferent limb were comparable in microbial composition. When comparing sigmoid and terminal ileum samples, more differences were observed. The greatest number of differentially abundant microbes was observed when comparing either pouch or afferent limb samples to sigmoid or terminal ileum. Despite these differences, we were able to observe modest microbial variability between inflammatory bowel disease phenotypes and HCs, even when controlling for sampling location and additional experimental factors. Most detected associations were observed between HCs and Crohn's disease, with decreases in specific genera in the families Ruminococcaceae and Lachnospiraceae characterizing tissue samples from individuals with Crohn's disease. This study highlights important considerations when analyzing the composition of the microbiome and also provides useful insight into differences in the microbiome characterizing these seemingly related phenotypes.

  15. Assessing Climate Variability using Extreme Rainfall and ...

    African Journals Online (AJOL)

    user1

    As noted by the Bureau of Meteorology, Canada, to examine whether such ... their local climate, a threshold considered extreme in one part of Australia could be ... (extreme frequency); the average intensity of rainfall from extreme events.

  16. Are hourly precipitation extremes increasing faster than daily precipitation extremes?

    Science.gov (United States)

    Barbero, Renaud; Fowler, Hayley; Blenkinsop, Stephen; Lenderink, Geert

    2016-04-01

    Extreme precipitation events appear to be increasing with climate change in many regions of the world, including the United States. These extreme events have large societal impacts, as seen during the recent Texas-Oklahoma flooding in May 2015 which caused several billion in damages and left 47 deaths in its path. Better understanding of past changes in the characteristics of extreme rainfall events is thus critical for reliable projections of future changes. Although it has been documented in several studies that daily precipitation extremes are increasing across parts of the contiguous United States, very few studies have looked at hourly extremes. However, this is of primary importance as recent studies on the temperature scaling of extreme precipitation have shown that increases above the Clausius-Clapeyron (~ 7% °C-1) are possible for hourly precipitation. In this study, we used hourly precipitation data (HPD) from the National Climatic Data Center and extracted more than 1,000 stations across the US with more than 40 years of data spanning the period 1950-2010. As hourly measurements are often associated with a range of issues, the data underwent multiple quality control processes to exclude erroneous data. While no significant changes were found in annual maximum precipitation using both hourly and daily resolution datasets, significant increasing trends in terms of frequency of episodes exceeding present-day 95th percentiles of wet hourly/daily precipitation were observed across a significant portion of the US. The fraction of stations with significant increasing trends falls outside the confidence interval range during all seasons but the summer. While less than 12% of stations exhibit significant trends at the daily scale in the wintertime, more than 45% of stations, mostly clustered in central and Northern United States, show significant increasing trends at the hourly scale. This suggests that short-duration storms have increased faster than daily

  17. Rising Precipitation Extremes across Nepal

    Directory of Open Access Journals (Sweden)

    Ramchandra Karki

    2017-01-01

    Full Text Available As a mountainous country, Nepal is most susceptible to precipitation extremes and related hazards, including severe floods, landslides and droughts that cause huge losses of life and property, impact the Himalayan environment, and hinder the socioeconomic development of the country. Given that the countrywide assessment of such extremes is still lacking, we present a comprehensive picture of prevailing precipitation extremes observed across Nepal. First, we present the spatial distribution of daily extreme precipitation indices as defined by the Expert Team on Climate Change Detection, Monitoring and Indices (ETCCDMI from 210 stations over the period of 1981–2010. Then, we analyze the temporal changes in the computed extremes from 76 stations, featuring long-term continuous records for the period of 1970–2012, by applying a non-parametric Mann−Kendall test to identify the existence of a trend and Sen’s slope method to calculate the true magnitude of this trend. Further, the local trends in precipitation extremes have been tested for their field significance over the distinct physio-geographical regions of Nepal, such as the lowlands, middle mountains and hills and high mountains in the west (WL, WM and WH, respectively, and likewise, in central (CL, CM and CH and eastern (EL, EM and EH Nepal. Our results suggest that the spatial patterns of high-intensity precipitation extremes are quite different to that of annual or monsoonal precipitation. Lowlands (Terai and Siwaliks that feature relatively low precipitation and less wet days (rainy days are exposed to high-intensity precipitation extremes. Our trend analysis suggests that the pre-monsoonal precipitation is significantly increasing over the lowlands and CH, while monsoonal precipitation is increasing in WM and CH and decreasing in CM, CL and EL. On the other hand, post-monsoonal precipitation is significantly decreasing across all of Nepal while winter precipitation is decreasing

  18. Book review: Extreme ocean waves

    Science.gov (United States)

    Geist, Eric L.

    2017-01-01

    Extreme Ocean Waves”, edited by E. Pelinovsky and C. Kharif, second edition, Springer International Publishing, 2016; ISBN: 978-3-319-21574-7, ISBN (eBook): 978-3-319-21575-4The second edition of “Extreme Ocean Waves” published by Springer is an update of a collection of 12 papers edited by Efim Pelinovsky and Christian Kharif following the April 2007 meeting of the General Assembly of the European Geosciences Union. In this edition, three new papers have been added and three more have been substantially revised. Color figures are now included, which greatly aids in reading several of the papers, and is especially helpful in visualizing graphs as in the paper on symbolic computation of nonlinear wave resonance (Tobisch et al.). A note on terminology: extreme waves in this volume broadly encompass different types of waves, including deep-water and shallow-water rogue waves (which are alternatively termed freak waves), and internal waves. One new paper on tsunamis (Viroulet et al.) is now included in the second edition of this volume. Throughout the book, the reader will find a combination of laboratory, theoretical, and statistical/empirical treatment necessary for the complete examination of this subject. In the Introduction, the editors underscore the importance of studying extreme waves, documenting a dramatic instance of damaging extreme waves that recently occurred in 2014.

  19. Extreme lattices: symmetries and decorrelation

    Science.gov (United States)

    Andreanov, A.; Scardicchio, A.; Torquato, S.

    2016-11-01

    We study statistical and structural properties of extreme lattices, which are the local minima in the density landscape of lattice sphere packings in d-dimensional Euclidean space {{{R}}d} . Specifically, we ascertain statistics of the densities and kissing numbers as well as the numbers of distinct symmetries of the packings for dimensions 8 through 13 using the stochastic Voronoi algorithm. The extreme lattices in a fixed dimension of space d (d≥slant 8 ) are dominated by typical lattices that have similar packing properties, such as packing densities and kissing numbers, while the best and the worst packers are in the long tails of the distribution of the extreme lattices. We also study the validity of the recently proposed decorrelation principle, which has important implications for sphere packings in general. The degree to which extreme-lattice packings decorrelate as well as how decorrelation is related to the packing density and symmetry of the lattices as the space dimension increases is also investigated. We find that the extreme lattices decorrelate with increasing dimension, while the least symmetric lattices decorrelate faster.

  20. Crenarchaeal biofilm formation under extreme conditions.

    Directory of Open Access Journals (Sweden)

    Andrea Koerdt

    Full Text Available BACKGROUND: Biofilm formation has been studied in much detail for a variety of bacterial species, as it plays a major role in the pathogenicity of bacteria. However, only limited information is available for the development of archaeal communities that are frequently found in many natural environments. METHODOLOGY: We have analyzed biofilm formation in three closely related hyperthermophilic crenarchaeotes: Sulfolobus acidocaldarius, S. solfataricus and S. tokodaii. We established a microtitre plate assay adapted to high temperatures to determine how pH and temperature influence biofilm formation in these organisms. Biofilm analysis by confocal laser scanning microscopy demonstrated that the three strains form very different communities ranging from simple carpet-like structures in S. solfataricus to high density tower-like structures in S. acidocaldarius in static systems. Lectin staining indicated that all three strains produced extracellular polysaccharides containing glucose, galactose, mannose and N-acetylglucosamine once biofilm formation was initiated. While flagella mutants had no phenotype in two days old static biofilms of S. solfataricus, a UV-induced pili deletion mutant showed decreased attachment of cells. CONCLUSION: The study gives first insights into formation and development of crenarchaeal biofilms in extreme environments.

  1. Independent test assessment using the extreme value distribution theory.

    Science.gov (United States)

    Almeida, Marcio; Blondell, Lucy; Peralta, Juan M; Kent, Jack W; Jun, Goo; Teslovich, Tanya M; Fuchsberger, Christian; Wood, Andrew R; Manning, Alisa K; Frayling, Timothy M; Cingolani, Pablo E; Sladek, Robert; Dyer, Thomas D; Abecasis, Goncalo; Duggirala, Ravindranath; Blangero, John

    2016-01-01

    The new generation of whole genome sequencing platforms offers great possibilities and challenges for dissecting the genetic basis of complex traits. With a very high number of sequence variants, a naïve multiple hypothesis threshold correction hinders the identification of reliable associations by the overreduction of statistical power. In this report, we examine 2 alternative approaches to improve the statistical power of a whole genome association study to detect reliable genetic associations. The approaches were tested using the Genetic Analysis Workshop 19 (GAW19) whole genome sequencing data. The first tested method estimates the real number of effective independent tests actually being performed in whole genome association project by the use of an extreme value distribution and a set of phenotype simulations. Given the familiar nature of the GAW19 data and the finite number of pedigree founders in the sample, the number of correlations between genotypes is greater than in a set of unrelated samples. Using our procedure, we estimate that the effective number represents only 15 % of the total number of independent tests performed. However, even using this corrected significance threshold, no genome-wide significant association could be detected for systolic and diastolic blood pressure traits. The second approach implements a biological relevance-driven hypothesis tested by exploiting prior computational predictions on the effect of nonsynonymous genetic variants detected in a whole genome sequencing association study. This guided testing approach was able to identify 2 promising single-nucleotide polymorphisms (SNPs), 1 for each trait, targeting biologically relevant genes that could help shed light on the genesis of the human hypertension. The first gene, PFH14, associated with systolic blood pressure, interacts directly with genes involved in calcium-channel formation and the second gene, MAP4, encodes a microtubule-associated protein and had already been

  2. EPE The Extreme Physics Explorer

    Science.gov (United States)

    Garcia, Michael; Elvis, Martin; Bookbinder, Jay; Brenneman, Laura; Bulbul, Esra; Nulsen, Paul; Patnaude, Dan; Smith, Randall; Bandler, Simon; Okajima, Takashi; Ptak, Andy; Figueroa-Feliciano, Enectali; Chakrabarty, Deepto; Danner, Rolf; Daily, Dean; Fraser, George; Willingale, Richard; Miller, Jon; Turner, T. J.; Risalti, Guido; Galeazzi, Massimiliano

    2012-01-01

    The Extreme Physics Explorer (EPE) is a mission concept that will address fundamental and timely questions in astrophysics which are primary science objectives of IXO. The reach of EPE to the areas outlined in NASA RFI NNH11ZDA018L is shown as a table. The dark green indicates areas in which EPE can do the basic IXO science, and the light green areas where EPE can contribute but will not reach the full IXO capability. To address these science questions, EPE will trace orbits close to the event horizon of black holes, measure black hole spin in active galactic nuclei (AGN), use spectroscopy to characterize outflows and the environment of AGN, map bulk motions and turbulence in galaxy clusters, and observe the process of cosmic feedback where black holes inject energy on galactic and intergalactic scales. EPE gives up the high resolution imaging of IXO in return for lightweight, high TRL foil mirrors which will provide >20 times the effective area of ASTRO-H and similar spatial resolution, with a beam sufficient to study point sources and nearby galaxies and clusters. Advances in micro-calorimeters allow improved performance at high rates with twice the energy resolution of ASTRO-H. A lower TRL option would provide 200 times the area of ASTRO-H using a micro-channel plate optic (MCPO) and a deployable optical bench. Both options are in the middle range of RFI missions at between $600M and $1000M. The EPE foil optic has direct heritage to ASTRO-H, allowing robust cost estimates. The spacecraft is entirely off the shelf and introduces no difficult requirements. The mission could be started and launched in this decade to an L2 orbit, with a three-year lifetime and consumables for 5 years. While ASTRO-H will give us the first taste of high-resolution, non-dispersive X-ray spectroscopy, it will be limited to small numbers of objects in many categories. EPE will give us the first statistically significant samples in each of these categories.

  3. Phenotypic deconstruction of gene circuitry.

    Science.gov (United States)

    Lomnitz, Jason G; Savageau, Michael A

    2013-06-01

    It remains a challenge to obtain a global perspective on the behavioral repertoire of complex nonlinear gene circuits. In this paper, we describe a method for deconstructing complex systems into nonlinear sub-systems, based on mathematically defined phenotypes, which are then represented within a system design space that allows the repertoire of qualitatively distinct phenotypes of the complex system to be identified, enumerated, and analyzed. This method efficiently characterizes large regions of system design space and quickly generates alternative hypotheses for experimental testing. We describe the motivation and strategy in general terms, illustrate its use with a detailed example involving a two-gene circuit with a rich repertoire of dynamic behavior, and discuss experimental means of navigating the system design space.

  4. Phenotypic spectrum of GABRA1

    DEFF Research Database (Denmark)

    Johannesen, Katrine; Marini, Carla; Pfeffer, Siona

    2016-01-01

    myoclonic epilepsy (2), photosensitive idiopathic generalized epilepsy (1), and generalized epilepsy with febrile seizures plus (1) to severe epileptic encephalopathies (11). In the epileptic encephalopathy group, the patients had seizures beginning between the first day of life and 15 months, with a mean...... of 7 months. Predominant seizure types in all patients were tonic-clonic in 9 participants (56%) and myoclonic seizures in 5 (31%). EEG showed a generalized photoparoxysmal response in 6 patients (37%). Four selected mutations studied functionally revealed a loss of function, without a clear genotype......-phenotype correlation. CONCLUSIONS: GABRA1 mutations make a significant contribution to the genetic etiology of both benign and severe epilepsy syndromes. Myoclonic and tonic-clonic seizures with pathologic response to photic stimulation are common and shared features in both mild and severe phenotypes....

  5. Deciphering the Galaxy Guppy phenotype

    Directory of Open Access Journals (Sweden)

    Philip Shaddock

    2011-01-01

    Full Text Available Animal breeding hobbyists have been useful to science because they identify and isolate colorcoat mutations that geneticists can in turn use in their studies of the development and differentiation ofcolor cells. This paper discusses a very interesting color mutant, the Japanese Galaxy, tracing its creationfrom back to a self-educated genetics hobbyist, Hoskiki Tsutsui. The paper discusses a constituent genepreviously studied by Dr. Violet Phang, the snakeskin gene (the linked body and fin genes Ssb and Sst.And it discusses a gene previously unknown to science, the Schimmelpfennig Platinum gene (Sc.Through crossing experiments, the author determines that the combination of these two genes producesan intermediate phenotype, the Medusa. Incorporating the Grass (Gr, another gene unknown to sciencegene into the Medusa through a crossover produces the Galaxy phenotype. Microscope studies of thesnakeskin pattern in Galaxies and snakeskins reveals some parallels with similar studies made of theZebrafish Danio.

  6. Automated phenotyping of permanent crops

    Science.gov (United States)

    McPeek, K. Thomas; Steddom, Karl; Zamudio, Joseph; Pant, Paras; Mullenbach, Tyler

    2017-05-01

    AGERpoint is defining a new technology space for the growers' industry by introducing novel applications for sensor technology and data analysis to growers of permanent crops. Serving data to a state-of-the-art analytics engine from a cutting edge sensor platform, a new paradigm in precision agriculture is being developed that allows growers to understand the unique needs of each tree, bush or vine in their operation. Autonomous aerial and terrestrial vehicles equipped with multiple varieties of remote sensing technologies give AGERpoint the ability to measure key morphological and spectral features of permanent crops. This work demonstrates how such phenotypic measurements combined with machine learning algorithms can be used to determine the variety of crops (e.g., almond and pecan trees). This phenotypic and varietal information represents the first step in enabling growers with the ability to tailor their management practices to individual plants and maximize their economic productivity.

  7. Phenotyping jasmonate regulation of senescence.

    Science.gov (United States)

    Seltmann, Martin A; Berger, Susanne

    2013-01-01

    Osmotic stress induces several senescence-like processes in leaves, such as specific changes in gene expression and yellowing. These processes are dependent on the accumulation of jasmonates and on intact jasmonate signaling. This chapter describes the treatment of Arabidopsis thaliana leaves with sorbitol as an osmotic stress agent and the determination of the elicited phenotypes encompassing chlorophyll loss, degradation of plastidial membrane lipids, and induction of genes regulated by senescence and jasmonate.

  8. Functional metagenomics of extreme environments.

    Science.gov (United States)

    Mirete, Salvador; Morgante, Verónica; González-Pastor, José Eduardo

    2016-04-01

    The bioprospecting of enzymes that operate under extreme conditions is of particular interest for many biotechnological and industrial processes. Nevertheless, there is a considerable limitation to retrieve novel enzymes as only a small fraction of microorganisms derived from extreme environments can be cultured under standard laboratory conditions. Functional metagenomics has the advantage of not requiring the cultivation of microorganisms or previous sequence information to known genes, thus representing a valuable approach for mining enzymes with new features. In this review, we summarize studies showing how functional metagenomics was employed to retrieve genes encoding for proteins involved not only in molecular adaptation and resistance to extreme environmental conditions but also in other enzymatic activities of biotechnological interest.

  9. Genotypic diversity and phenotypic traits of Streptococcus mutans isolates and their relation to severity of early childhood caries.

    Science.gov (United States)

    Valdez, Remberto Marcelo Argandoña; Duque, Cristiane; Caiaffa, Karina Sampaio; Dos Santos, Vanessa Rodrigues; Loesch, Maria Luiza de Aguiar; Colombo, Natalia Helena; Arthur, Rodrigo Alex; Negrini, Thais de Cássia; Boriollo, Marcelo Fabiano Gomes; Delbem, Alberto Carlos Botazzo

    2017-07-14

    Early childhood caries (ECC) is an aggressive condition that can affect teeth of young children. This study aimed to evaluate genotypic diversity and phenotypic traits of S. mutans isolated from dental biofilms of children with different caries status in comparison with caries free (CF) children. Streptococcus mutans strains were isolated from supragingival biofilm samples of CF, ECC and severe-ECC (S-ECC) children and genotyped by arbitrary-primer polymerase chain reaction - AP-PCR. S. mutans genotypes were tested for their ability to reduce the suspension pH through glycolysis, to tolerate extreme acid challenge and by their ability to form biofilm. Response variables were analyzed by ANOVA/Tukey or Kruskal-Wallis/Mann-Whitney tests at a 5% of significance. There was an increase in the prevalence of Streptococcus mutans in biofilms with the severity of dental caries. No differences in genotypic diversity and in acidogenicity of genotypes were found among CF, ECC and S-ECC children. S mutans strains with genotypes more characteristic for ECC and S-ECC children formed more biofilms than those identified in CF children. The strains isolated from S-ECC children were highly acid tolerant. Although S. mutans genotypic diversity was similar among the groups of children, phenotypic traits of S. mutans, especially the acid tolerance response, could explain the severity of early childhood caries.

  10. Genetic background of phenotypic variation

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    A noteworthy feature of the living world is its bewildering variability. A key issue in several biological disciplines is the achievement of an understanding of the hereditary basis of this variability. Two opposing, but not necessarily irreconcilable conceptions attempt to explain the underlying mechanism. The gene function paradigm postulates that phenotypic variance is generated by the polymorphism in the coding sequences of genes. However, comparisons of a great number of homologous gene and protein sequences have revealed that they predominantly remained functionally conserved even across distantly related phylogenic taxa. Alternatively, the gene regulation paradigm assumes that differences in the cis-regulatory region of genes do account for phenotype variation within species. An extension of this latter concept is that phenotypic variability is generated by the polyrnorphism in the overall gene expression profiles of gene networks.In other words, the activity of a particular gene is a system property determined both by the cis-regulatory sequences of the given genes and by the other genes of a gene network, whose expressions vary among individuals, too. Novel proponents of gene function paradigm claim that functional genetic variance within the coding sequences of regulatory genes is critical for the generation of morphological polymorphism. Note, however, that these developmental genes play direct regulatory roles in the control of gene expression.

  11. Adaptive evolution of molecular phenotypes

    Science.gov (United States)

    Held, Torsten; Nourmohammad, Armita; Lässig, Michael

    2014-09-01

    Molecular phenotypes link genomic information with organismic functions, fitness, and evolution. Quantitative traits are complex phenotypes that depend on multiple genomic loci. In this paper, we study the adaptive evolution of a quantitative trait under time-dependent selection, which arises from environmental changes or through fitness interactions with other co-evolving phenotypes. We analyze a model of trait evolution under mutations and genetic drift in a single-peak fitness seascape. The fitness peak performs a constrained random walk in the trait amplitude, which determines the time-dependent trait optimum in a given population. We derive analytical expressions for the distribution of the time-dependent trait divergence between populations and of the trait diversity within populations. Based on this solution, we develop a method to infer adaptive evolution of quantitative traits. Specifically, we show that the ratio of the average trait divergence and the diversity is a universal function of evolutionary time, which predicts the stabilizing strength and the driving rate of the fitness seascape. From an information-theoretic point of view, this function measures the macro-evolutionary entropy in a population ensemble, which determines the predictability of the evolutionary process. Our solution also quantifies two key characteristics of adapting populations: the cumulative fitness flux, which measures the total amount of adaptation, and the adaptive load, which is the fitness cost due to a population's lag behind the fitness peak.

  12. Differences in muscle transcriptome among pigs phenotypically extreme for fatty acid composition

    NARCIS (Netherlands)

    Puig-Oliveras, A.; Ramayo-Caldas, Y.; Corominas, J.; Estelle, J.; Perez-Montarelo, D.; Hudson, N.J.; Casellas, J.; Folch Maria Ballester, J.M.

    2014-01-01

    BACKGROUND: Besides having an impact on human health, the porcine muscle fatty acid profile determines meat quality and taste. The RNA-Seq technologies allowed us to explore the pig muscle transcriptome with an unprecedented detail. The aim of this study was to identify differentially-expressed gene

  13. Language sampling

    DEFF Research Database (Denmark)

    Rijkhoff, Jan; Bakker, Dik

    1998-01-01

    This article has two aims: [1] to present a revised version of the sampling method that was originally proposed in 1993 by Rijkhoff, Bakker, Hengeveld and Kahrel, and [2] to discuss a number of other approaches to language sampling in the light of our own method. We will also demonstrate how our ...... sampling method is used with different genetic classifications (Voegelin & Voegelin 1977, Ruhlen 1987, Grimes ed. 1997) and argue that —on the whole— our sampling technique compares favourably with other methods, especially in the case of exploratory research.......This article has two aims: [1] to present a revised version of the sampling method that was originally proposed in 1993 by Rijkhoff, Bakker, Hengeveld and Kahrel, and [2] to discuss a number of other approaches to language sampling in the light of our own method. We will also demonstrate how our...

  14. Dissecting complex phenotypes using the genomics of twins

    DEFF Research Database (Denmark)

    Tan, Qihua; Ohm Kyvik, Kirsten; Kruse, Torben A

    2010-01-01

    Genetics in the post-genomic period is shifting from structural to functional genetics or genomics. Meanwhile, the use of twins is largely expanding from traditional heritability estimation for disease phenotypes to the study of both diseases and various molecular phenotypes, such as the regulatory...... phenotypes in functional genomics concerning gene expression and regulation, by engaging both classical twin design and marker-based gene mapping techniques in genetic epidemiology. New research designs have been proposed for making novel uses of twins in studying the molecular basis in the epigenetics...... of human diseases. Besides, twins not only serve as ideal samples for disease gene mapping using conventional genetic markers but also represent an excellent model for associating DNA copy number variations, a structural genetic marker, with human diseases. It is believed that, with the rapid development...

  15. Phenotypic plasticity with instantaneous but delayed switches

    NARCIS (Netherlands)

    Utz, Margarete; Jeschke, Jonathan M.; Loeschcke, Volker; Gabriel, Wilfried

    2014-01-01

    Phenotypic plasticity is a widespread phenomenon, allowing organisms to better adapt to changing environments. Most empirical and theoretical studies are restricted to irreversible plasticity where the expression of a specific phenotype is mostly determined during development. However, reversible pl

  16. Heatshield for Extreme Entry Environment Technology (HEEET)

    Science.gov (United States)

    Venkatapathy, E.; Ellerby, D.; Stackpoole, M..; Peterson, K.; Gage, P.; Beerman, A.; Blosser, M.; Chinnapongse, R.; Dillman, R.; Feldman, J.; Gasch, M.; Munk, M.; Prabhu, D.; Poteet, C.

    2013-01-01

    Heat-shield for Extreme Entry Technology (HEEET) project is based on the 3-D Woven TPS, an emerging innovative and game changing technology funded by SMD and STMD to fill the ablative TPS gap that exists currently for reaching the depths of Saturn and Venus. Woven TPS technology will address the challenges currently faced by the Venus, Saturn, and higher speed sample return mission Science community due to lack of availability of the only TPS, namely Carbon Phenolic and enable the Science community to move forward with proposals in this decade with Woven TPS. This presentation describes the approach in maturing the technology in the next three years enabling NF-4 mission proposers to address the challenges of Venus, Saturn or higher speed sample return missions.

  17. Language sampling

    DEFF Research Database (Denmark)

    Rijkhoff, Jan; Bakker, Dik

    1998-01-01

    This article has two aims: [1] to present a revised version of the sampling method that was originally proposed in 1993 by Rijkhoff, Bakker, Hengeveld and Kahrel, and [2] to discuss a number of other approaches to language sampling in the light of our own method. We will also demonstrate how our...... sampling method is used with different genetic classifications (Voegelin & Voegelin 1977, Ruhlen 1987, Grimes ed. 1997) and argue that —on the whole— our sampling technique compares favourably with other methods, especially in the case of exploratory research....

  18. Extreme climatic events in relation to global change and their impact on life histories

    Institute of Scientific and Technical Information of China (English)

    Juan MORENO; Anders Pape Mφller

    2011-01-01

    Extreme weather conditions occur at an increasing rate as evidenced by higher frequency of hurricanes and more extreme precipitation and temperature anomalies. Such extreme environmental conditions will have important implications for all living organisms through greater frequency of reproductive failure and reduced adult survival. We review examples of reproductive failure and reduced survival related to extreme weather conditions. Phenotypic plasticity may not be sufficient to allow adaptation to extreme weather for many animals. Theory predicts reduced reproductive effort as a response to increased stochasticity. We predict that patterns of natural selection will change towards truncation selection as environmental conditions become more extreme. Such changes in patterns of selection may facilitate adaptation to extreme events. However, effects of selection on reproductive effort are difficult to detect. We present a number of predictions for the effects of extreme weather conditions in need of empirical tests. Finally, we suggest a number of empirical reviews that could improve our ability to judge the effects of extreme environmental conditions on life history.

  19. Extreme climatic events in relation to global change and their impact on life histories

    Directory of Open Access Journals (Sweden)

    Juan MORENO, Anders Pape Møller

    2011-06-01

    Full Text Available Extreme weather conditions occur at an increasing rate as evidenced by higher frequency of hurricanes and more extreme precipitation and temperature anomalies. Such extreme environmental conditions will have important implications for all living organisms through greater frequency of reproductive failure and reduced adult survival. We review examples of reproductive failure and reduced survival related to extreme weather conditions. Phenotypic plasticity may not be sufficient to allow adaptation to extreme weather for many animals. Theory predicts reduced reproductive effort as a response to increased stochasticity. We predict that patterns of natural selection will change towards truncation selection as environmental conditions become more extreme. Such changes in patterns of selection may facilitate adaptation to extreme events. However, effects of selection on reproductive effort are difficult to detect. We present a number of predictions for the effects of extreme weather conditions in need of empirical tests. Finally, we suggest a number of empirical reviews that could improve our ability to judge the effects of extreme environmental conditions on life history [Current Zoology 57 (3: 375–389, 2011].

  20. Extreme Conditions Modeling Workshop Report

    Energy Technology Data Exchange (ETDEWEB)

    Coe, R. G.; Neary, V. S.; Lawson, M. J.; Yu, Y.; Weber, J.

    2014-07-01

    Sandia National Laboratories (SNL) and the National Renewable Energy Laboratory (NREL) hosted the Wave Energy Converter (WEC) Extreme Conditions Modeling (ECM) Workshop in Albuquerque, NM on May 13th-14th, 2014. The objective of the workshop was to review the current state of knowledge on how to model WECs in extreme conditions (e.g. hurricanes and other large storms) and to suggest how U.S. Department of Energy (DOE) and national laboratory resources could be used to improve ECM methods for the benefit of the wave energy industry.

  1. Automation Rover for Extreme Environments

    Science.gov (United States)

    Sauder, Jonathan; Hilgemann, Evan; Johnson, Michael; Parness, Aaron; Hall, Jeffrey; Kawata, Jessie; Stack, Kathryn

    2017-01-01

    Almost 2,300 years ago the ancient Greeks built the Antikythera automaton. This purely mechanical computer accurately predicted past and future astronomical events long before electronics existed1. Automata have been credibly used for hundreds of years as computers, art pieces, and clocks. However, in the past several decades automata have become less popular as the capabilities of electronics increased, leaving them an unexplored solution for robotic spacecraft. The Automaton Rover for Extreme Environments (AREE) proposes an exciting paradigm shift from electronics to a fully mechanical system, enabling longitudinal exploration of the most extreme environments within the solar system.

  2. Extreme Weather and Natural Disasters

    CERN Document Server

    Healey, Justin

    2012-01-01

    Australia is a vast land in which weather varies significantly in different parts of the continent. Recent extreme weather events in Australia, such as the Queensland floods and Victorian bushfires, are brutal reminders of nature's devastating power. Is global warming increasing the rate of natural disasters? What part do La Niña and El Niño play in the extreme weather cycle? Cyclones, floods, severe storms, bushfires, landslides, earthquakes, tsunamis - what are the natural and man-made causes of these phenomena, how predictable are they, and how prepared are we for the impacts of natural dis

  3. Uncommon upper extremity compression neuropathies.

    Science.gov (United States)

    Knutsen, Elisa J; Calfee, Ryan P

    2013-08-01

    Hand surgeons routinely treat carpal and cubital tunnel syndromes, which are the most common upper extremity nerve compression syndromes. However, more infrequent nerve compression syndromes of the upper extremity may be encountered. Because they are unusual, the diagnosis of these nerve compression syndromes is often missed or delayed. This article reviews the causes, proposed treatments, and surgical outcomes for syndromes involving compression of the posterior interosseous nerve, the superficial branch of the radial nerve, the ulnar nerve at the wrist, and the median nerve proximal to the wrist. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Sampling Development

    Science.gov (United States)

    Adolph, Karen E.; Robinson, Scott R.

    2011-01-01

    Research in developmental psychology requires sampling at different time points. Accurate depictions of developmental change provide a foundation for further empirical studies and theories about developmental mechanisms. However, overreliance on widely spaced sampling intervals in cross-sectional and longitudinal designs threatens the validity of…

  5. World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonisation Project: I. Surgical phenotype data collection in endometriosis research

    DEFF Research Database (Denmark)

    Becker, Christian M.; Laufer, Marc R.; Stratton, Pamela;

    2014-01-01

    ObjectiveTo standardize the recording of surgical phenotypic information on endometriosis and related sample collections obtained at laparoscopy, allowing large-scale collaborative research into the condition.......ObjectiveTo standardize the recording of surgical phenotypic information on endometriosis and related sample collections obtained at laparoscopy, allowing large-scale collaborative research into the condition....

  6. Extreme cervical elongation after sacrohysteropexy

    NARCIS (Netherlands)

    Vierhout, M.E.; Futterer, J.J.

    2013-01-01

    We present a case of extreme cervical elongation with a cervix of 12 cm after an unusual operation in which the uterine corpus was directly fixed to the promontory, and which became symptomatic after 8 years. The possible pathophysiology of cervical elongation is discussed. Diagnosing a case of seve

  7. Applied extreme-value statistics

    Energy Technology Data Exchange (ETDEWEB)

    Kinnison, R.R.

    1983-05-01

    The statistical theory of extreme values is a well established part of theoretical statistics. Unfortunately, it is seldom part of applied statistics and is infrequently a part of statistical curricula except in advanced studies programs. This has resulted in the impression that it is difficult to understand and not of practical value. In recent environmental and pollution literature, several short articles have appeared with the purpose of documenting all that is necessary for the practical application of extreme value theory to field problems (for example, Roberts, 1979). These articles are so concise that only a statistician can recognise all the subtleties and assumptions necessary for the correct use of the material presented. The intent of this text is to expand upon several recent articles, and to provide the necessary statistical background so that the non-statistician scientist can recognize and extreme value problem when it occurs in his work, be confident in handling simple extreme value problems himself, and know when the problem is statistically beyond his capabilities and requires consultation.

  8. Astrobiology: Life in Extreme Environments

    Science.gov (United States)

    Kaur, Preeti

    2011-01-01

    Astrobiology is the study of the origin, evolution and distribution of life in the universe. It seeks to answer two important scientific questions: how did we get here and are we alone in the universe? Scientists begin by studying life on Earth and its limits. The discovery of extremophiles on Earth capable of surviving extremes encourages the…

  9. Extreme Energy Events Monitoring report

    CERN Document Server

    Baimukhamedova, Nigina

    2015-01-01

    Following paper reflects the progress I made on Summer Student Program within Extreme Energy Events Monitor project I was working on. During 8 week period I managed to build a simple detector system that is capable of triggering events similar to explosions (sudden change in sound levels) and measuring approximate location of the event. Source codes are available upon request and settings described further.

  10. Generic Hurricane Extreme Seas State

    DEFF Research Database (Denmark)

    Wehmeyer, Christof; Skourup, Jesper; Frigaard, Peter

    2012-01-01

    the US east coast and the Gulf of Mexico (1851 - 2009) and Japanese east coast (1951 -2009) form the basis for Weibull extreme value analyses to determine return period respective maximum wind speeds. Unidirectional generic sea state spectra are obtained by application of the empirical models...

  11. Astrobiology: Life in Extreme Environments

    Science.gov (United States)

    Kaur, Preeti

    2011-01-01

    Astrobiology is the study of the origin, evolution and distribution of life in the universe. It seeks to answer two important scientific questions: how did we get here and are we alone in the universe? Scientists begin by studying life on Earth and its limits. The discovery of extremophiles on Earth capable of surviving extremes encourages the…

  12. The impact of beneficial plant-associated microbes on plant phenotypic plasticity.

    Science.gov (United States)

    Goh, Chooi-Hua; Veliz Vallejos, Debora F; Nicotra, Adrienne B; Mathesius, Ulrike

    2013-07-01

    Plants show phenotypic plasticity in response to changing or extreme abiotic environments; but over millions of years they also have co-evolved to respond to the presence of soil microbes. Studies on phenotypic plasticity in plants have focused mainly on the effects of the changing environments on plants' growth and survival. Evidence is now accumulating that the presence of microbes can alter plant phenotypic plasticity in a broad range of traits in response to a changing environment. In this review, we discuss the effects of microbes on plant phenotypic plasticity in response to changing environmental conditions, and how this may affect plant fitness. By using a range of specific plant-microbe interactions as examples, we demonstrate that one way that microbes can alleviate the effect of environmental stress on plants and thus increase plant fitness is to remove the stress, e.g., nutrient limitation, directly. Furthermore, microbes indirectly affect plant phenotypic plasticity and fitness through modulation of plant development and defense responses. In doing so, microbes affect fitness by both increasing or decreasing the degree of phenotypic plasticity, depending on the phenotype and the environmental stress studied, with no clear difference between the effect of prokaryotic and eukaryotic microbes in general. Additionally, plants have the ability to modulate microbial behaviors, suggesting that they manipulate bacteria, enhancing interactions that help them cope with stressful environments. Future challenges remain in the identification of the many microbial signals that modulate phenotypic plasticity, the characterization of plant genes, e.g. receptors, that mediate the microbial effects on plasticity, and the elucidation of the molecular mechanisms that link phenotypic plasticity with fitness. The characterization of plant and microbial mutants defective in signal synthesis or perception, together with carefully designed glasshouse or field experiments that

  13. COMP and Col9A3 mutations and their relationship to the pseudoachondroplasia phenotype.

    Science.gov (United States)

    Jung, Woon-Won; Balce, Gracia Cielo; Cho, Jae-Woo; Jung, Sung-Chul; Hong, Suk-Joo; Song, Hae-Ryong

    2010-12-01

    While pseudoachondroplasia (PSACH) is almost exclusively caused by cartilage oligomeric matrix protein (COMP) mutations, many patients identified with the PSACH phenotype do not have this mutation, suggesting gene and locus heterogeneity. In order to further characterize this entity, we studied 32 clinically and radiographically diagnosed PSACH patients, among 19 families. COMP and collagen (Col) IX (A1, A2 and A3) mutations, were determined. Patients who tested negative for pathological gene mutations but who were identified with the PSACH phenotype, were included. The phenotypes were characterized according to height deviation (cm) from normal, lower extremity mechanical axis deviation (MAD), cervical and thoracolumbar spine involvement, pelvic index, as well as hip, knee, ankle and hand involvement. We report an 81% mutation detection rate for PSACH, of which COMP+Col9A3 mutations were more prevalent (61%) than COMP mutations alone (30%). Of our PSACH patients, 19% tested negative for both COMP and Col9A3 mutations, and they presented with the greatest mean height deviations, but the least mean MADs. While all the PSACH mutations consistently produced the severe phenotype, the V426A mutation in Col9A3 produced the most severe. Mother-daughter and father-son phenotypic similarities were noted in the COMP+Col9A3 families. Col9A3 and gender play confounding roles in the phenotypic severity of PSACH. The presence of the PSACH phenotype in patients who tested negative for known mutations further confirms the genetic heterogeneity of this condition.

  14. High-throughput Phenotyping and Genomic Selection: The Frontiers of Crop Breeding Converge

    Institute of Scientific and Technical Information of China (English)

    Llorenc Cabrera-Bosquet; José Crossa; Jarislav von Zitzewitz; Maria Dolors Serret; José Luis Araus

    2012-01-01

    Genomic selection (GS) and high-throughput phenotyping have recently been captivating the interest of the crop breeding community from both the public and private sectors world-wide.Both approaches promise to revolutionize the prediction of complex traits,including growth,yield and adaptation to stress.Whereas high-throughput phenotyping may help to improve understanding of crop physiology,most powerful techniques for high-throughput field phenotyping are empirical rather than analytical and comparable to genomic selection.Despite the fact that the two methodological approaches represent the extremes of what is understood as the breeding process (phenotype versus genome),they both consider the targeted traits (e.g.grain yield,growth,phenology,plant adaptation to stress) as a black box instead of dissecting them as a set of secondary traits (i.e.physiological) putatively related to the target trait.Both GS and high-throughput phenotyping have in common their empirical approach enabling breeders to use genome profile or phenotype without understanding the underlying biology.This short review discusses the main aspects of both approaches and focuses on the case of genomic selection of maize flowering traits and near-infrared spectroscopy (NIRS) and plant spectral reflectance as high-throughput field phenotyping methods for complex traits such as crop growth and yield.

  15. Are extreme events (statistically) special? (Invited)

    Science.gov (United States)

    Main, I. G.; Naylor, M.; Greenhough, J.; Touati, S.; Bell, A. F.; McCloskey, J.

    2009-12-01

    We address the generic problem of testing for scale-invariance in extreme events, i.e. are the biggest events in a population simply a scaled model of those of smaller size, or are they in some way different? Are large earthquakes for example ‘characteristic’, do they ‘know’ how big they will be before the event nucleates, or is the size of the event determined only in the avalanche-like process of rupture? In either case what are the implications for estimates of time-dependent seismic hazard? One way of testing for departures from scale invariance is to examine the frequency-size statistics, commonly used as a bench mark in a number of applications in Earth and Environmental sciences. Using frequency data however introduces a number of problems in data analysis. The inevitably small number of data points for extreme events and more generally the non-Gaussian statistical properties strongly affect the validity of prior assumptions about the nature of uncertainties in the data. The simple use of traditional least squares (still common in the literature) introduces an inherent bias to the best fit result. We show first that the sampled frequency in finite real and synthetic data sets (the latter based on the Epidemic-Type Aftershock Sequence model) converge to a central limit only very slowly due to temporal correlations in the data. A specific correction for temporal correlations enables an estimate of convergence properties to be mapped non-linearly on to a Gaussian one. Uncertainties closely follow a Poisson distribution of errors across the whole range of seismic moment for typical catalogue sizes. In this sense the confidence limits are scale-invariant. A systematic sample bias effect due to counting whole numbers in a finite catalogue makes a ‘characteristic’-looking type extreme event distribution a likely outcome of an underlying scale-invariant probability distribution. This highlights the tendency of ‘eyeball’ fits to unconsciously (but

  16. NIH Mouse Metabolic Phenotyping Centers: the power of centralized phenotyping

    Science.gov (United States)

    Kent Lloyd, K. C.; Cline, Gary W.; Wasserman, David H.

    2013-01-01

    The Mouse Metabolic Phenotyping Centers (MMPCs) were founded in 2001 by the National Institutes of Health (NIH) to advance biomedical research by providing the scientific community with standardized, high-quality phenotyping services for mouse models of diabetes, obesity, and their complications. The intent is to allow researchers to take optimum advantage of the many new mouse models produced in labs and in high-throughput public efforts. The six MMPCs are located at universities around the country and perform complex metabolic tests in intact mice and hormone and analyte assays in tissues on a fee-for-service basis. Testing is subsidized by the NIH in order to reduce the barriers for mouse researchers. Although data derived from these tests belong to the researcher submitting mice or tissues, these data are archived after publication in a public database run by the MMPC Coordinating and Bioinformatics Unit. It is hoped that data from experiments performed in many mouse models of metabolic diseases, using standard protocols, will be useful in understanding the nature of these complex disorders. The current areas of expertise include energy balance and body composition, insulin action and secretion, whole-body and tissue carbohydrate and lipid metabolism, cardiovascular and renal function, and metabolic pathway kinetics. In addition to providing services, the MMPC staff provides expertise and advice to researchers, and works to develop and refine test protocols to best meet the community’s needs in light of current scientific developments. Test technology is disseminated by publications and through annual courses. PMID:22940748

  17. Knowledge-based analysis of phenotypes

    KAUST Repository

    Hoendorf, Robert

    2016-01-27

    Phenotypes are the observable characteristics of an organism, and they are widely recorded in biology and medicine. To facilitate data integration, ontologies that formally describe phenotypes are being developed in several domains. I will describe a formal framework to describe phenotypes. A formalized theory of phenotypes is not only useful for domain analysis, but can also be applied to assist in the diagnosis of rare genetic diseases, and I will show how our results on the ontology of phenotypes is now applied in biomedical research.

  18. Extremal non-BPS black holes and entropy extremization

    CERN Document Server

    Lópes-Cardoso, G; Lust, D; Perz, J; Cardoso, Gabriel Lopes; Grass, Viviane; Lust, Dieter; Perz, Jan

    2006-01-01

    At the horizon, a static extremal black hole solution in N=2 supergravity in four dimensions is determined by a set of so-called attractor equations which, in the absence of higher-curvature interactions, can be derived as extremization conditions for the black hole potential or, equivalently, for the entropy function. We contrast both methods by explicitly solving the attractor equations for a one-modulus prepotential associated with the conifold. We find that near the conifold point, the non-supersymmetric solution has a substantially different behavior than the supersymmetric solution. We analyze the stability of the solutions and the extrema of the resulting entropy as a function of the modulus. For the non-BPS solution the region of attractivity and the maximum of the entropy do not coincide with the conifold point.

  19. Satisfaction with upper extremity surgery in individuals with tetraplegia

    DEFF Research Database (Denmark)

    Gregersen, Hanne; Lybæk, Mille; Lauge Johannesen, Inger

    2015-01-01

    OBJECTIVE: To supplement the scant information available regarding the satisfaction of patients with tetraplegia following upper extremity reconstructive surgery for such individuals with spinal cord injury (SCI). STUDY DESIGN: Retrospective study with questionnaire follow-up. SETTING: The Danish...... questions (P satisfaction with upper extremity surgery is high. It can have a positive impact on life in general, ability to perform ADL, as well as supplying an increased level of independence....... to strongly disagree regarding satisfaction. Forty patients completed the questionnaire. RESULTS: Median time from first surgery was 13 years (2-36). Sixty-five percent of the sample had a C5-C6 SCI, with 64% experiencing complete injury. Initially, 76% of the sample expressed general satisfaction with life......OBJECTIVE: To supplement the scant information available regarding the satisfaction of patients with tetraplegia following upper extremity reconstructive surgery for such individuals with spinal cord injury (SCI). STUDY DESIGN: Retrospective study with questionnaire follow-up. SETTING: The Danish...

  20. Phenotype of normal hairline maturation.

    Science.gov (United States)

    Rassman, William R; Pak, Jae P; Kim, Jino

    2013-08-01

    Hairlines change shape with age, starting at birth. A good head of hair is frequently present some time after ages 3 to 5 years. The look of childhood has its corresponding hairline, and, as the child grows and develops into adulthood, facial morphology migrate changes from a childlike look to a more mature look. This article discusses the dynamics of hairline evolution and the phenotypic variations of the front and side hairlines in men and women. A modeling system is introduced that provides a common language to define the various anatomic points of the full range of hairlines.

  1. Analysis of Pena Shokeir phenotype.

    Science.gov (United States)

    Hall, J G

    1986-09-01

    At this point in time, we recognize that "Pena Shokeir" is not a diagnosis or a specific syndrome but rather a description of a phenotype produced by fetal akinesia or decreased in utero movement. In its "full blown" form, it is characterized by polyhydramnios, intrauterine growth retardation, pulmonary hypoplasia, craniofacial and limb anomalies, congenital contractures, short umbilical cord, and lethality. From the cases thus far reported, we would anticipate that the phenotype is present in a very heterogeneous group of disorders--heterogeneous both with regard to the specific anomalies present and with regard to the causes (which must include many environmental agents and multiple genetic forms). One challenge for the future is to better describe and delineate specific entities. In the meantime, we would do well to use the terms "Pena Shokeir phenotype" or "fetal akinesia/hypokinesia sequence," which do not imply a single entity. There are many practical aspects of recognizing this phenotype. The presence of any one of the cardinal signs of the fetal akinesia/hypokinesia sequence should alert the physician to look for the other associated anomalies, since specific treatment may be indicated, and catch-up or compensatory growth may occur, if given a chance. The ability to provide prenatal diagnosis and perhaps prenatal treatment in the future may allow us to alter dramatically the natural history of some cases. In others, we need to establish when treatment is possible and when it gives no benefit. Perhaps the most important insight gained from the study of the fetal akinesia sequence is the reaffirmation of the concept that function is an integral part of normal development. Specific structures do not develop in isolation but are part of a carefully timed and integrated system. The "use" of a structure in utero is necessary for its continuing and normal development. The old adage "use it or lose it" seems to apply just as appropriately to prenatal normal

  2. The Human Phenotype Ontology in 2017

    Science.gov (United States)

    Köhler, Sebastian; Vasilevsky, Nicole A.; Engelstad, Mark; Foster, Erin; McMurry, Julie; Aymé, Ségolène; Baynam, Gareth; Bello, Susan M.; Boerkoel, Cornelius F.; Boycott, Kym M.; Brudno, Michael; Buske, Orion J.; Chinnery, Patrick F.; Cipriani, Valentina; Connell, Laureen E.; Dawkins, Hugh J.S.; DeMare, Laura E.; Devereau, Andrew D.; de Vries, Bert B.A.; Firth, Helen V.; Freson, Kathleen; Greene, Daniel; Hamosh, Ada; Helbig, Ingo; Hum, Courtney; Jähn, Johanna A.; James, Roger; Krause, Roland; F. Laulederkind, Stanley J.; Lochmüller, Hanns; Lyon, Gholson J.; Ogishima, Soichi; Olry, Annie; Ouwehand, Willem H.; Pontikos, Nikolas; Rath, Ana; Schaefer, Franz; Scott, Richard H.; Segal, Michael; Sergouniotis, Panagiotis I.; Sever, Richard; Smith, Cynthia L.; Straub, Volker; Thompson, Rachel; Turner, Catherine; Turro, Ernest; Veltman, Marijcke W.M.; Vulliamy, Tom; Yu, Jing; von Ziegenweidt, Julie; Zankl, Andreas; Züchner, Stephan; Zemojtel, Tomasz; Jacobsen, Julius O.B.; Groza, Tudor; Smedley, Damian; Mungall, Christopher J.; Haendel, Melissa; Robinson, Peter N.

    2017-01-01

    Deep phenotyping has been defined as the precise and comprehensive analysis of phenotypic abnormalities in which the individual components of the phenotype are observed and described. The three components of the Human Phenotype Ontology (HPO; www.human-phenotype-ontology.org) project are the phenotype vocabulary, disease-phenotype annotations and the algorithms that operate on these. These components are being used for computational deep phenotyping and precision medicine as well as integration of clinical data into translational research. The HPO is being increasingly adopted as a standard for phenotypic abnormalities by diverse groups such as international rare disease organizations, registries, clinical labs, biomedical resources, and clinical software tools and will thereby contribute toward nascent efforts at global data exchange for identifying disease etiologies. This update article reviews the progress of the HPO project since the debut Nucleic Acids Research database article in 2014, including specific areas of expansion such as common (complex) disease, new algorithms for phenotype driven genomic discovery and diagnostics, integration of cross-species mapping efforts with the Mammalian Phenotype Ontology, an improved quality control pipeline, and the addition of patient-friendly terminology. PMID:27899602

  3. Evidence of concurrent local adaptation and high phenotypic plasticity in a polar microeukaryote.

    Science.gov (United States)

    Rengefors, Karin; Logares, Ramiro; Laybourn-Parry, Johanna; Gast, Rebecca J

    2015-05-01

    Here we investigated whether there is evidence of local adaptation in strains of an ancestrally marine dinoflagellate to the lacustrine environment they now inhabit (optimal genotypes) and/or if they have evolved phenotypic plasticity (a range of phenotypes). Eleven strains of Polarella glacialis were isolated and cultured from three different environments: the polar seas, a hyposaline and a hypersaline Antarctic lake. Local adaptation was tested by comparing growth rates of lacustrine and marine strains at their own and reciprocal site conditions. To determine phenotypic plasticity, we measured the reaction norm for salinity. We found evidence of both, limited local adaptation and higher phenotypic plasticity in lacustrine strains when compared with marine ancestors. At extreme high salinities, local lake strains outperformed other strains, and at extreme low salinities, strains from the hyposaline lake outperformed all other strains. The data suggest that lake populations may have evolved higher phenotypic plasticity in the lake habitats compared with the sea, presumably due to the high temporal variability in salinity in the lacustrine systems. Moreover, the interval of salinity tolerance differed between strains from the hyposaline and hypersaline lakes, indicating local adaptation promoted by different salinity.

  4. Social networking among upper extremity patients.

    Science.gov (United States)

    Rozental, Tamara D; George, Tina M; Chacko, Aron T

    2010-05-01

    Despite their rising popularity, the health care profession has been slow to embrace social networking sites. These are Web-based initiatives, designed to bring people with common interests or activities under a common umbrella. The purpose of this study is to evaluate social networking patterns among upper extremity patients. A total of 742 anonymous questionnaires were distributed among upper extremity outpatients, with a 62% response rate (462 were completed). Demographic characteristics (gender, age, level of education, employment, type of health insurance, and income stratification) were defined, and data on computer ownership and frequency of social networking use were collected. Social network users and nonusers were compared according to their demographic and socioeconomic characteristics. Our patient cohort consisted of 450 patients. Of those 450 patients, 418 had a high school education or higher, and 293 reported a college or graduate degree. The majority of patients (282) were employed at the time of the survey, and income was evenly distributed among U.S. Census Bureau quintiles. A total of 349 patients reported computer ownership, and 170 reported using social networking sites. When compared to nonusers, social networking users were younger (pnetworking use. Most users (n = 114) regularly visit a single site. Facebook was the most popular site visited (n=142), followed by MySpace (n=28) and Twitter (n=16). Of the 450 upper extremity patients in our sample, 170 use social networking sites. Younger age, higher level of education, and computer ownership were associated with social networking use. Physicians should consider expanding their use of social networking sites to reach their online patient populations. Copyright 2010 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

  5. Phenotypic plasticity in bacterial plasmids.

    Science.gov (United States)

    Turner, Paul E

    2004-01-01

    Plasmid pB15 was previously shown to evolve increased horizontal (infectious) transfer at the expense of reduced vertical (intergenerational) transfer and vice versa, a key trade-off assumed in theories of parasite virulence. Whereas the models predict that susceptible host abundance should determine which mode of transfer is selectively favored, host density failed to mediate the trade-off in pB15. One possibility is that the plasmid's transfer deviates from the assumption that horizontal spread (conjugation) occurs in direct proportion to cell density. I tested this hypothesis using Escherichia coli/pB15 associations in laboratory serial culture. Contrary to most models of plasmid transfer kinetics, my data show that pB15 invades static (nonshaking) bacterial cultures only at intermediate densities. The results can be explained by phenotypic plasticity in traits governing plasmid transfer. As cells become more numerous, the plasmid's conjugative transfer unexpectedly declines, while the trade-off between transmission routes causes vertical transfer to increase. Thus, at intermediate densities the plasmid's horizontal transfer can offset selection against plasmid-bearing cells, but at high densities pB15 conjugates so poorly that it cannot invade. I discuss adaptive vs. nonadaptive causes for the phenotypic plasticity, as well as potential mechanisms that may lead to complex transfer dynamics of plasmids in liquid environments. PMID:15166133

  6. Modelling neuroinflammatory phenotypes in vivo

    Directory of Open Access Journals (Sweden)

    Wyss-Coray Tony

    2004-07-01

    Full Text Available Abstract Inflammation of the central nervous system is an important but poorly understood part of neurological disease. After acute brain injury or infection there is a complex inflammatory response that involves activation of microglia and astrocytes and increased production of cytokines, chemokines, acute phase proteins, and complement factors. Antibodies and T lymphocytes may be involved in the response as well. In neurodegenerative disease, where injury is more subtle but consistent, the inflammatory response is continuous. The purpose of this prolonged response is unclear, but it is likely that some of its components are beneficial and others are harmful. Animal models of neurological disease can be used to dissect the specific role of individual mediators of the inflammatory response and assess their potential benefit. To illustrate this approach, we discuss how mutant mice expressing different levels of the cytokine transforming growth factor β-1 (TGF-β1, a major modulator of inflammation, produce important neuroinflammatory phenotypes. We then demonstrate how crosses of TGF-β1 mutant mice with mouse models of Alzheimer's disease (AD produced important new information on the role of inflammation in AD and on the expression of different neuropathological phenotypes that characterize this disease.

  7. Phenotypic variability in Patau syndrome.

    Science.gov (United States)

    Caba, Lavinia; Rusu, Cristina; Butnariu, Lacramioara; Panzaru, Monica; Braha, Elena; Volosciuc, M; Popescu, Roxana; Gramescu, Mihaela; Bujoran, C; Martiniuc, Violeta; Covic, M; Gorduza, E V

    2013-01-01

    Patau syndrome has an incidence of 1/10.000-20.000, the clinical diagnosis being suggested by the triad cleft lip and palate, microphthalmia/anophthalmia and postaxial polydactyly. Most frequent cytogenetic abnormality is free and homogeneous trisomy 13 (80.0%), rarely being detected trisomy mosaics or Robertsonian translocations. The objective of the study was to identify phenotypic features of trisomy 13. The retrospective study was conducted on a trial group of 14 cases diagnosed cytogenetically with trisomy 13 between January 2000 and December 2012 at lasi Medical Genetics Centre. Of the 14 cases, 3 were evaluated pathologically (two aborted foetuses and one stillborn), 8 cases were detected in the neonatal period, and 3 in infancy. Clinical diagnosis was supported by the identification of a model of abnormal development, mainly characterized by: maxillary cleft (lip and palate--5 cases; lip--1 case), ocular abnormalities (microphthalmia/anophthalmia--7 cases; cyclopia--1 case), postaxial polydactyly (7 cases), scalp defects (6 cases), congenital heart anomalies (10 cases, 6 patients with atrial septal defect), complete holoprosencephaly (4 cases), ear abnormalities (11 cases), broad nasal root (10 cases). An important issue in confirming the phenotypic variability of Patau syndrome is that the classic clinical triad was identified only in one case. Patau syndrome is a disease with variable expression and is characterized by a pattern of abnormal prenatal development characterized by facial dysmorphia, polydactyly and severe birth defects (heart, brain) that generate an increased in utero and perinatal mortality.

  8. Classifying Returns as Extreme: European Stock and Bond Markets

    DEFF Research Database (Denmark)

    Christiansen, Charlotte

    whereby a shorter sample period is needed. For the bond markets the simultaneous extreme return variable (used for analyzing integration and contagion of financial markets) is not statistically different for the two schemes. For the stock markets there are differences, but they are disappearing...

  9. Planck early results. XIV. ERCSC validation and extreme radio sources

    DEFF Research Database (Denmark)

    Lavonen, N.; León-Tavares, J.; Savolainen, P.;

    2011-01-01

    by Planck. The ERCSC source positions and flux density scales are found to be consistent with the ground-based observations. We present and discuss the spectral energy distributions of a sample of "extreme" radio sources, to illustrate the richness of the ERCSC for the study of extragalactic radio sources...

  10. AN ELIMINATION ALGORITHM OF EXTREME VALUES FOR INTEGRATED TRISPECTRUM

    Institute of Scientific and Technical Information of China (English)

    Liang Zongchuang; Liu Xingzhao; Liu Yongtan

    2002-01-01

    In this paper, an algorithm for eliminating extreme values and reducing the estimation variance of an integrated trispectrum under low signal-to-noise ratio and short data sample conditions is presented. An analysis of the results of simulations using this algorithm and comparison with the conventional power spectrum and integrated trispectrum methods are presented.

  11. New Clues on the Nature of Extremely Red Galaxies

    CERN Document Server

    Cimatti, A; Alighieri, S S; Pozzetti, L; Mannucci, F; Renzini, A; Oliva, E; Zamorani, G; Andreani, P; Röttgering, H J A

    1999-01-01

    We present near-infrared VLT-UT1+ISAAC spectroscopy of a sample of 9 extremely red galaxies (ERGs) with R-K>5 and K0.8. We discuss the general implications of our findings in relation with the problem of the formation of early type galaxies.

  12. On causality of extreme events

    CERN Document Server

    Zanin, Massimiliano

    2016-01-01

    Multiple metrics have been developed to detect causality relations between data describing the elements constituting complex systems, all of them considering their evolution through time. Here we propose a metric able to detect causality within static data sets, by analysing how extreme events in one element correspond to the appearance of extreme events in a second one. The metric is able to detect both linear and non-linear causalities; to analyse both cross-sectional and longitudinal data sets; and to discriminate between real causalities and correlations caused by confounding factors. We validate the metric through synthetic data, dynamical and chaotic systems, and data representing the human brain activity in a cognitive task.

  13. Extreme Conditions Modeling Workshop Report

    Energy Technology Data Exchange (ETDEWEB)

    Coe, Ryan Geoffrey [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States); Neary, Vincent Sinclair [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States); Lawon, Michael J. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Yu, Yi-Hsiang [National Renewable Energy Lab. (NREL), Golden, CO (United States); Weber, Jochem [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2014-07-01

    Sandia National Laboratories (SNL) and the National Renewable Energy Laboratory (NREL) hosted the Wave Energy Converter (WEC) Extreme Conditions Modeling (ECM) Workshop in Albuquerque, New Mexico on May 13–14, 2014. The objective of the workshop was to review the current state of knowledge on how to numerically and experimentally model WECs in extreme conditions (e.g. large ocean storms) and to suggest how national laboratory resources could be used to improve ECM methods for the benefit of the wave energy industry. More than 30 U.S. and European WEC experts from industry, academia, and national research institutes attended the workshop, which consisted of presentations from W EC developers, invited keynote presentations from subject matter experts, breakout sessions, and a final plenary session .

  14. Cacti with Extremal PI Index

    Directory of Open Access Journals (Sweden)

    Chunxiang Wang

    2016-12-01

    Full Text Available The vertex PI index PI(G=∑ xy∈E(G [n xy (x‎+‎n xy (y] PI(G=∑xy∈E(G[nxy(x‎+‎nxy(y] is a distance-based molecular structure descriptor‎, ‎where n xy (x nxy(x denotes the number of vertices which are closer to the vertex x x than to the vertex y y and which has been the considerable research in computational chemistry dating back to Harold Wiener in 1947‎. ‎A connected graph is a cactus if any two of its cycles have at most one common vertex‎. ‎In this paper‎, ‎we completely determine the extremal graphs with the greatest and smallest vertex PI indices mong all cacti with a fixed number of vertices‎. ‎As a consequence‎, ‎we obtain the sharp bounds with corresponding extremal cacti and extend a known result‎.

  15. On causality of extreme events

    Directory of Open Access Journals (Sweden)

    Massimiliano Zanin

    2016-06-01

    Full Text Available Multiple metrics have been developed to detect causality relations between data describing the elements constituting complex systems, all of them considering their evolution through time. Here we propose a metric able to detect causality within static data sets, by analysing how extreme events in one element correspond to the appearance of extreme events in a second one. The metric is able to detect non-linear causalities; to analyse both cross-sectional and longitudinal data sets; and to discriminate between real causalities and correlations caused by confounding factors. We validate the metric through synthetic data, dynamical and chaotic systems, and data representing the human brain activity in a cognitive task. We further show how the proposed metric is able to outperform classical causality metrics, provided non-linear relationships are present and large enough data sets are available.

  16. On causality of extreme events

    Science.gov (United States)

    2016-01-01

    Multiple metrics have been developed to detect causality relations between data describing the elements constituting complex systems, all of them considering their evolution through time. Here we propose a metric able to detect causality within static data sets, by analysing how extreme events in one element correspond to the appearance of extreme events in a second one. The metric is able to detect non-linear causalities; to analyse both cross-sectional and longitudinal data sets; and to discriminate between real causalities and correlations caused by confounding factors. We validate the metric through synthetic data, dynamical and chaotic systems, and data representing the human brain activity in a cognitive task. We further show how the proposed metric is able to outperform classical causality metrics, provided non-linear relationships are present and large enough data sets are available. PMID:27330866

  17. Upper Extremity Injuries in Gymnasts.

    Science.gov (United States)

    Wolf, Megan R; Avery, Daniel; Wolf, Jennifer Moriatis

    2017-02-01

    Gymnastics is a unique sport, which loads the wrist and arms as weight-bearing extremities. Because of the load demands on the wrist in particular, stress fractures, physeal injury, and overuse syndromes may be observed. This spectrum of injury has been termed "gymnast's wrist," and incorporates such disorders as wrist capsulitis, ligamentous tears, triangular fibrocartilage complex tears, chondromalacia of the carpus, stress fractures, distal radius physeal arrest, and grip lock injury.

  18. Racial Extremism in the Army

    Science.gov (United States)

    1998-04-01

    example, one soldier has a picture of Martin Luther King ;. another has a picture of Ronald Reagan). What is legal, appropriate action? (1) The particular...degree requirements for the 46h Judge Advocate Officer Graduate Course. 2 Virginia A. White, Killings Tied to Racism , FAYETTEVILLE OBSERVER-TIMES...causes to lure new members to their organizations. Lieutenant Colonel Edwin W. Anderson, Jr ., Right Wing Extremism in America and its Implications for

  19. Typologies of Extreme Longevity Myths

    OpenAIRE

    2010-01-01

    Purpose. Political, national, religious, and other motivations have led the media and even scientists to errantly accept extreme longevity claims prima facie. We describe various causes of false claims of extraordinary longevity. Design and Methods. American Social Security Death Index files for the period 1980–2009 were queried for individuals with birth and death dates yielding ages 110+ years of age. Frequency was compared to a list of age-validated supercentenarians maintained by the Ge...

  20. Promoting Exit from Violent Extremism

    DEFF Research Database (Denmark)

    Dalgaard-Nielsen, Anja

    2013-01-01

    A number of Western countries are currently adding exit programs targeting militant Islamists to their counterterrorism efforts. Drawing on research into voluntary exit from violent extremism, this article identifies themes and issues that seem to cause doubt, leading to exit. It then provides...... the influence attempt as subtle as possible, use narratives and self-affirmatory strategies to reduce resistance to persuasion, and consider the possibility to promote attitudinal change via behavioral change as an alternative to seek to influence beliefs directly....

  1. FastID: Extremely Fast Forensic DNA Comparisons

    Science.gov (United States)

    2017-05-19

    FastID: Extremely Fast Forensic DNA Comparisons Darrell O. Ricke, PhD Bioengineering Systems & Technologies Massachusetts Institute of...Technology Lincoln Laboratory Lexington, MA USA Darrell.Ricke@ll.mit.edu Abstract—Rapid analysis of DNA forensic samples can have a critical impact on...time sensitive investigations. Analysis of forensic DNA samples by massively parallel sequencing is creating the next gold standard for DNA

  2. Moderate and extreme maternal obesity.

    LENUS (Irish Health Repository)

    Abdelmaboud, M O

    2012-05-01

    The aim of this study was to investigate the prevalence of moderate and extreme obesity among an Irish obstetric population over a 10-year period, and to evaluate the obstetric features of such pregnancies. Of 31,869 women delivered during the years 2000-2009, there were 306 women in the study group, including 173 in the moderate or Class 2 obese category (BMI 35-39.9) and 133 in the extreme or Class 3 obese category (BMI > or = 40).The prevalence of obese women with BMI > or = 35 was 9.6 per 1000 (0.96%), with an upward trend observed from 2.1 per 1000 in the year 2000, to 11.8 per 1000 in the year 2009 (P = 0.001). There was an increase in emergency caesarean section (EMCS) risk for primigravida versus multigravid women, within both obese categories (P < 0.001). However, there was no significant difference in EMCS rates observed between Class 2 and Class 3 obese women, when matched for parity. The prevalence of moderate and extreme obesity reported in this population is high, and appears to be increasing. The increased rates of abdominal delivery, and the levels of associated morbidity observed, have serious implications for such women embarking on pregnancy.

  3. Technology improves upper extremity rehabilitation.

    Science.gov (United States)

    Kowalczewski, Jan; Prochazka, Arthur

    2011-01-01

    Stroke survivors with hemiparesis and spinal cord injury (SCI) survivors with tetraplegia find it difficult or impossible to perform many activities of daily life. There is growing evidence that intensive exercise therapy, especially when supplemented with functional electrical stimulation (FES), can improve upper extremity function, but delivering the treatment can be costly, particularly after recipients leave rehabilitation facilities. Recently, there has been a growing level of interest among researchers and healthcare policymakers to deliver upper extremity treatments to people in their homes using in-home teletherapy (IHT). The few studies that have been carried out so far have encountered a variety of logistical and technical problems, not least the difficulty of conducting properly controlled and blinded protocols that satisfy the requirements of high-level evidence-based research. In most cases, the equipment and communications technology were not designed for individuals with upper extremity disability. It is clear that exercise therapy combined with interventions such as FES, supervised over the Internet, will soon be adopted worldwide in one form or another. Therefore it is timely that researchers, clinicians, and healthcare planners interested in assessing IHT be aware of the pros and cons of the new technology and the factors involved in designing appropriate studies of it. It is crucial to understand the technical barriers, the role of telesupervisors, the motor improvements that participants can reasonably expect and the process of optimizing IHT-exercise therapy protocols to maximize the benefits of the emerging technology.

  4. Typologies of Extreme Longevity Myths

    Directory of Open Access Journals (Sweden)

    Robert D. Young

    2010-01-01

    Full Text Available Purpose. Political, national, religious, and other motivations have led the media and even scientists to errantly accept extreme longevity claims prima facie. We describe various causes of false claims of extraordinary longevity. Design and Methods. American Social Security Death Index files for the period 1980–2009 were queried for individuals with birth and death dates yielding ages 110+ years of age. Frequency was compared to a list of age-validated supercentenarians maintained by the Gerontology Research Group who died during the same time period. Age claims of 110+ years and the age validation experiences of the authors facilitated a list of typologies of false age claims. Results. Invalid age claim rates increase with age from 65% at age 110-111 to 98% by age 115 to 100% for 120+ years. Eleven typologies of false claims were: Religious Authority Myth, Village Elder Myth, Fountain of Youth Myth (substance, Shangri-La Myth (geographic, Nationalist Pride, Spiritual Practice, Familial Longevity, Individual and/or Family Notoriety, Military Service, Administrative Entry Error, and Pension-Social Entitlement Fraud. Conclusions. Understanding various causes of false extreme age claims is important for placing current, past, and future extreme longevity claims in context and for providing a necessary level of skepticism.

  5. Ameloblastoma Phenotypes Reflected in Distinct Transcriptome Profiles

    Science.gov (United States)

    Hu, Shijia; Parker, Joel; Divaris, Kimon; Padilla, Ricardo; Murrah, Valerie; Wright, John Timothy

    2016-01-01

    Ameloblastoma is a locally invasive benign neoplasm derived from odontogenic epithelium and presents with diverse phenotypes yet to be characterized molecularly. High recurrence rates of 50–80% with conservative treatment in some sub-types warrants radical surgical resections resulting in high morbidity. The objective of the study was to characterize the transcriptome of ameloblastoma and identify relevant genes and molecular pathways using normal odontogenic tissue (human “dentome”) for comparison. Laser capture microdissection was used to obtain neoplastic epithelial tissue from 17 tumors which were examined using the Agilent 44 k whole genome microarray. Ameloblastoma separated into 2 distinct molecular clusters that were associated with pre-secretory ameloblast and odontoblast. Within the pre-secretory cluster, 9/10 of samples were of the follicular type while 6/7 of the samples in the odontoblast cluster were of the plexiform type (p ameloblastoma sub-types and have implications for the use of tailored treatment. PMID:27491308

  6. Transcriptome and network changes in climbers at extreme altitudes.

    Directory of Open Access Journals (Sweden)

    Fang Chen

    Full Text Available Extreme altitude can induce a range of cellular and systemic responses. Although it is known that hypoxia underlies the major changes and that the physiological responses include hemodynamic changes and erythropoiesis, the molecular mechanisms and signaling pathways mediating such changes are largely unknown. To obtain a more complete picture of the transcriptional regulatory landscape and networks involved in extreme altitude response, we followed four climbers on an expedition up Mount Xixiabangma (8,012 m, and collected blood samples at four stages during the climb for mRNA and miRNA expression assays. By analyzing dynamic changes of gene networks in response to extreme altitudes, we uncovered a highly modular network with 7 modules of various functions that changed in response to extreme altitudes. The erythrocyte differentiation module is the most prominently up-regulated, reflecting increased erythrocyte differentiation from hematopoietic stem cells, probably at the expense of differentiation into other cell lineages. These changes are accompanied by coordinated down-regulation of general translation. Network topology and flow analyses also uncovered regulators known to modulate hypoxia responses and erythrocyte development, as well as unknown regulators, such as the OCT4 gene, an important regulator in stem cells and assumed to only function in stem cells. We predicted computationally and validated experimentally that increased OCT4 expression at extreme altitude can directly elevate the expression of hemoglobin genes. Our approach established a new framework for analyzing the transcriptional regulatory network from a very limited number of samples.

  7. Phenotypic plasticity: molecular mechanisms and adaptive significance.

    Science.gov (United States)

    Kelly, Scott A; Panhuis, Tami M; Stoehr, Andrew M

    2012-04-01

    Phenotypic plasticity can be broadly defined as the ability of one genotype to produce more than one phenotype when exposed to different environments, as the modification of developmental events by the environment, or as the ability of an individual organism to alter its phenotype in response to changes in environmental conditions. Not surprisingly, the study of phenotypic plasticity is innately interdisciplinary and encompasses aspects of behavior, development, ecology, evolution, genetics, genomics, and multiple physiological systems at various levels of biological organization. From an ecological and evolutionary perspective, phenotypic plasticity may be a powerful means of adaptation and dramatic examples of phenotypic plasticity include predator avoidance, insect wing polymorphisms, the timing of metamorphosis in amphibians, osmoregulation in fishes, and alternative reproductive tactics in male vertebrates. From a human health perspective, documented examples of plasticity most commonly include the results of exercise, training, and/or dieting on human morphology and physiology. Regardless of the discipline, phenotypic plasticity has increasingly become the target of a plethora of investigations with the methodological approaches utilized ranging from the molecular to whole organsimal. In this article, we provide a brief historical outlook on phenotypic plasticity; examine its potential adaptive significance; emphasize recent molecular approaches that provide novel insight into underlying mechanisms, and highlight examples in fishes and insects. Finally, we highlight examples of phenotypic plasticity from a human health perspective and underscore the use of mouse models as a powerful tool in understanding the genetic architecture of phenotypic plasticity.

  8. High Pressure Atmospheric Sampling Inlet System for Venus or the Gas Giants Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Thorleaf Research, Inc. proposes to develop a miniaturized high pressure atmospheric sampling inlet system for sample acquisition in extreme planetary environments,...

  9. Outcomes for extremely premature infants.

    Science.gov (United States)

    Glass, Hannah C; Costarino, Andrew T; Stayer, Stephen A; Brett, Claire M; Cladis, Franklyn; Davis, Peter J

    2015-06-01

    Premature birth is a significant cause of infant and child morbidity and mortality. In the United States, the premature birth rate, which had steadily increased during the 1990s and early 2000s, has decreased annually for 7 years and is now approximately 11.39%. Human viability, defined as gestational age at which the chance of survival is 50%, is currently approximately 23 to 24 weeks in developed countries. Infant girls, on average, have better outcomes than infant boys. A relatively uncomplicated course in the intensive care nursery for an extremely premature infant results in a discharge date close to the prenatal estimated date of confinement. Despite technological advances and efforts of child health experts during the last generation, the extremely premature infant (less than 28 weeks gestation) and extremely low birth weight infant (death and disability with 30% to 50% mortality and, in survivors, at least 20% to 50% risk of morbidity. The introduction of continuous positive airway pressure, mechanical ventilation, and exogenous surfactant increased survival and spurred the development of neonatal intensive care in the 1970s through the early 1990s. Routine administration of antenatal steroids during premature labor improved neonatal mortality and morbidity in the late 1990s. The recognition that chronic postnatal administration of steroids to infants should be avoided may have improved outcomes in the early 2000s. Evidence from recent trials attempting to define the appropriate target for oxygen saturation in preterm infants suggests arterial oxygen saturation between 91% and 95% (compared with 85%-89%) avoids excess mortality; however, final analyses of data from these trials have not been published, so definitive recommendations are still pending. The development of neonatal neurocritical intensive care units may improve neurocognitive outcomes in this high-risk group. Long-term follow-up to detect and address developmental, learning, behavioral, and

  10. Predicting Predictable about Natural Catastrophic Extremes

    Science.gov (United States)

    Kossobokov, Vladimir

    2015-04-01

    By definition, an extreme event is rare one in a series of kindred phenomena. Usually (e.g. in Geophysics), it implies investigating a small sample of case-histories with a help of delicate statistical methods and data of different quality, collected in various conditions. Many extreme events are clustered (far from independent) and follow fractal or some other "strange" distribution (far from uniform). Evidently, such an "unusual" situation complicates search and definition of reliable precursory behaviors to be used for forecast/prediction purposes. Making forecast/prediction claims reliable and quantitatively probabilistic in the frames of the most popular objectivists' viewpoint on probability requires a long series of "yes/no" forecast/prediction outcomes, which cannot be obtained without an extended rigorous test of the candidate method. The set of errors ("success/failure" scores and space-time measure of alarms) and other information obtained in such a control test supplies us with data necessary to judge the candidate's potential as a forecast/prediction tool and, eventually, to find its improvements. This is to be done first in comparison against random guessing, which results confidence (measured in terms of statistical significance). Note that an application of the forecast/prediction tools could be very different in cases of different natural hazards, costs and benefits that determine risks, and, therefore, requires determination of different optimal strategies minimizing reliable estimates of realistic levels of accepted losses. In their turn case specific costs and benefits may suggest a modification of the forecast/prediction tools for a more adequate "optimal" application. Fortunately, the situation is not hopeless due to the state-of-the-art understanding of the complexity and non-linear dynamics of the Earth as a Physical System and pattern recognition approaches applied to available geophysical evidences, specifically, when intending to predict

  11. Genetic and environmental dissections of sub-phenotypes of metabolic syndrome in the chinese population: a twin-based heritability study

    DEFF Research Database (Denmark)

    Duan, Haiping; Pang, Zengchang; Zhang, Dongfeng

    2011-01-01

    Objective: We perform a comprehensive heritability study on multiple phenotypes related to metabolic syndrome using Chinese twins to assess the genetic and environmental effects in determining the variation and covariation of the phenotypes in the Chinese population. Methods: The studied sample...... of the phenotypes. Conclusions: Our results showed significant genetic contributions to the sub-phenotypes of metabolic syndrome. Although pleiotropic genetic control may exist for some physiologically similar phenotypes, our results do not support a common genetic mechanism among the phenotypes covered in our...

  12. Work sampling

    OpenAIRE

    Salas Bacalla, julio; FII-UNMSM

    2014-01-01

    Work sampling is a method of indirect measurement, which means instantaneous observations, to determine the amount of uptime or downtime in a production process El muestreo de trabajo es un método de medición indirecto, que mediante observaciones instantaneas, permite determinar la cantidad de tiempo en actividad o inactividad en un proceso productivo

  13. Testing for tail behavior using extreme spacings

    CERN Document Server

    Rojo, J

    2010-01-01

    Methodologies to test hypotheses about the tail-heaviness of an underlying distribution are introduced based on results of Rojo (1996) using the limiting behavior of the extreme spacings. The tests are consistent and have point-wise robust levels in the sense of Lehmann (2005) and Lehmann and Loh (1990). Simulation results based on these new methodologies indicate that the tests exhibit good control of the probability of Type I error and have good power properties for finite sample sizes. The tests are compared with a test proposed by Bryson (1974) and it is seen that, although Bryson's test is competitive with the tests proposed here, Bryson's test does not have point-wise robust levels. The operating characteristics of the tests are also explored when the data is blocked. It turns out that the power increases substantially by blocking. The methodology is illustrated by analyzing various data sets.

  14. Phenotypic checkpoints regulate neuronal development.

    Science.gov (United States)

    Ben-Ari, Yehezkel; Spitzer, Nicholas C

    2010-11-01

    Nervous system development proceeds by sequential gene expression mediated by cascades of transcription factors in parallel with sequences of patterned network activity driven by receptors and ion channels. These sequences are cell type- and developmental stage-dependent and modulated by paracrine actions of substances released by neurons and glia. How and to what extent these sequences interact to enable neuronal network development is not understood. Recent evidence demonstrates that CNS development requires intermediate stages of differentiation providing functional feedback that influences gene expression. We suggest that embryonic neuronal functions constitute a series of phenotypic checkpoint signatures; neurons failing to express these functions are delayed or developmentally arrested. Such checkpoints are likely to be a general feature of neuronal development and constitute presymptomatic signatures of neurological disorders when they go awry.

  15. Phenotypic Plasticity and Species Coexistence.

    Science.gov (United States)

    Turcotte, Martin M; Levine, Jonathan M

    2016-10-01

    Ecologists are increasingly interested in predicting how intraspecific variation and changing trait values impact species interactions and community composition. For many traits, much of this variation is caused by phenotypic plasticity, and thus the impact of plasticity on species coexistence deserves robust quantification. Partly due to a lack of sound theoretical expectations, empirical studies make contradictory claims regarding plasticity effects on coexistence. Our critical review of this literature, framed in modern coexistence theory, reveals that plasticity affects species interactions in ways that could impact stabilizing niche differences and competitive asymmetries. However, almost no study integrates these measures to quantify the net effect of plasticity on species coexistence. To address this challenge, we outline novel empirical approaches grounded in modern theory.

  16. Estrogen, inflammation, and platelet phenotype.

    Science.gov (United States)

    Miller, Virginia M; Jayachandran, Muthuvel; Hashimoto, Kazumori; Heit, John A; Owen, Whyte G

    2008-01-01

    Although exogenous estrogenic therapies increase the risk of thrombosis, the effects of estrogen on formed elements of blood are uncertain. This article examines the genomic and nongenomic actions of estrogen on platelet phenotype that may contribute to increased thrombotic risk. To determine aggregation, secretion, protein expression, and thrombin generation, platelets were collected from experimental animals of varying hormonal status and from women enrolled in the Kronos Early Estrogen Prevention Study. Estrogen receptor beta predominates in circulating platelets. Estrogenic treatment in ovariectomized animals decreased platelet aggregation and adenosine triphosphate (ATP) secretion. However, acute exposure to 17beta-estradiol did not reverse decreases in platelet ATP secretion invoked by lipopolysaccharide. Thrombin generation was positively correlated to the number of circulating microvesicles expressing phosphatidylserine. Assessing the effect of estrogen treatments on blood platelets may lead to new ways of identifying women at risk for adverse thrombotic events with such therapies.

  17. Evolution of phenotypic plasticity in colonizing species.

    Science.gov (United States)

    Lande, Russell

    2015-05-01

    I elaborate an hypothesis to explain inconsistent empirical findings comparing phenotypic plasticity in colonizing populations or species with plasticity from their native or ancestral range. Quantitative genetic theory on the evolution of plasticity reveals that colonization of a novel environment can cause a transient increase in plasticity: a rapid initial increase in plasticity accelerates evolution of a new optimal phenotype, followed by slow genetic assimilation of the new phenotype and reduction of plasticity. An association of colonization with increased plasticity depends on the difference in the optimal phenotype between ancestral and colonized environments, the difference in mean, variance and predictability of the environment, the cost of plasticity, and the time elapsed since colonization. The relative importance of these parameters depends on whether a phenotypic character develops by one-shot plasticity to a constant adult phenotype or by labile plasticity involving continuous and reversible development throughout adult life. © 2014 John Wiley & Sons Ltd.

  18. FYPO: the fission yeast phenotype ontology.

    Science.gov (United States)

    Harris, Midori A; Lock, Antonia; Bähler, Jürg; Oliver, Stephen G; Wood, Valerie

    2013-07-01

    To provide consistent computable descriptions of phenotype data, PomBase is developing a formal ontology of phenotypes observed in fission yeast. The fission yeast phenotype ontology (FYPO) is a modular ontology that uses several existing ontologies from the open biological and biomedical ontologies (OBO) collection as building blocks, including the phenotypic quality ontology PATO, the Gene Ontology and Chemical Entities of Biological Interest. Modular ontology development facilitates partially automated effective organization of detailed phenotype descriptions with complex relationships to each other and to underlying biological phenomena. As a result, FYPO supports sophisticated querying, computational analysis and comparison between different experiments and even between species. FYPO releases are available from the Subversion repository at the PomBase SourceForge project page (https://sourceforge.net/p/pombase/code/HEAD/tree/phenotype_ontology/). The current version of FYPO is also available on the OBO Foundry Web site (http://obofoundry.org/).

  19. Metabolomic phenotyping of a cloned pig model

    DEFF Research Database (Denmark)

    Clausen, Morten Rahr; Christensen, Kirstine Lykke; Hedemann, Mette Skou

    2011-01-01

    and possibly also phenotypes and this offer an extra level of experimental control which could possibly make them a desirable tool for intervention studies. Therefore, in the present study, we address how phenotype and phenotypic variation is affected by cloning, through comparison of cloned pigs and normal...... outbred pigs. Results The metabolic phenotype of cloned pigs (n = 5) was for the first time elucidated by nuclear magnetic resonance (NMR)-based metabolomic analysis of multiple bio-fluids including plasma, bile and urine. The metabolic phenotype of the cloned pigs was compared with normal outbred pigs (n...... = 6) by multivariate data analysis, which revealed differences in the metabolic phenotypes. Plasma lactate was higher for cloned vs control pigs, while multiple metabolites were altered in the bile. However a lower inter-individual variability for cloned pigs compared with control pigs could...

  20. The Extreme Ultraviolet Variability of Quasars

    CERN Document Server

    Punsly, Brian; Zhang, Shaohua; Muzahid, Sowgat; O'Dea, Christopher P

    2016-01-01

    We study the extreme ultraviolet (EUV) variability (rest frame wavelengths 500 - 920 $\\AA$) of high luminosity quasars using HST (low to intermediate redshift sample) and SDSS (high redshift sample) archives. The combined HST and SDSS data indicates a much more pronounced variability when the sampling time between observations in the quasar rest frame is $> 2\\times 10^{7}$ sec compared to $2\\times 10^{7}$ sec in the quasar rest frame, $55\\%$ of the quasars (21/38) show evidence of EUV variability. The propensity for variability does not show any statistically significant change between $2.5\\times 10^{7}$ sec and $3.16\\times 10^{7}$ sec (1 yr). The temporal behavior is one of a threshold time interval for significant variability as opposed to a gradual increase on these time scales. A threshold time scale can indicate a characteristic spatial dimension of the EUV region. We explore this concept in the context of the slim disk models of accretion. We find that for rapidly spinning black holes, the radial infall...

  1. A Search for Extremely Young Stellar Objects

    Institute of Scientific and Technical Information of China (English)

    吴月芳; 王均智; 吴京文

    2003-01-01

    We have observed 22 sources in 13CO and C18O J = 1 - 0 lines with a 13.7-m telescope at Qinghai station of PMO, NAOC. The samples were chosen with new criteria so that the sources are much redder and fainter than those chosen before. All the 22 sources were detected with the pair lines of 13CO and C18O and are suitable for analysing star formation except one multiple emission source IRAS 20300+3909. Physical parameters were derived from the local thermodynamic equilibrium assumption. The excitation temperature and column density of C18O are 13K and 1.5 × 1015 cm-2, respectively, on the average. 11 sources in the samples have line widths larger than 3 km/s. The IRAS colour indices are larger than those of class-O objects. The intermediate and farinfrared energy distributions show that the emission peaks of the samples fall in far infrared or longer wavelengths except IRAS 20149+3955, indicating that they may be very young stellar objects. Analyses of line widths and bolometric luminosity show that seven of those sources may be extremely young high or intermediate mass stellar objects.

  2. Joubert syndrome: A model for untangling recessive disorders with extreme genetic heterogeneity

    Science.gov (United States)

    R, Bachmann-Gagescu; JC, Dempsey; IG, Phelps; BJ, O’Roak; DM, Knutzen; TC, Rue; GE, Ishak; CR, Isabella; N, Gorden; J, Adkins; EA, Boyle; N, de Lacy; D, O’Day; A, Alswaid; AR, Devi; L, Lingappa; C, Lourenço; L, Martorell; À, Garcia-Cazorla; H, Ozyürek; G, Haliloğlu; B, Tuysuz; M, Topçu; P, Chance; MA, Parisi; I, Glass; J, Shendure; D, Doherty

    2016-01-01

    Background Joubert syndrome (JS) is a recessive neurodevelopmental disorder characterized by hypotonia, ataxia, cognitive impairment, abnormal eye movements, respiratory control disturbances, and a distinctive mid-hindbrain malformation. JS demonstrates substantial phenotypic variability and genetic heterogeneity. This study provides a comprehensive view of the current genetic basis, phenotypic range and gene-phenotype associations in JS. Methods We sequenced 27 JS-associated genes in 440 affected individuals (375 families) from a cohort of 532 individuals (440 families) with JS, using molecular inversion probe-based targeted capture and next generation sequencing. Variant pathogenicity was defined using the Combined Annotation Dependent Depletion (CADD) algorithm with an optimized score cut-off. Results We identified presumed causal variants in 62% of pedigrees, including the first B9D2 mutations associated with JS. 253 different mutations in 23 genes highlight the extreme genetic heterogeneity of JS. Phenotypic analysis revealed that only 34% of individuals have a “pure JS” phenotype. Retinal disease is present in 30% of individuals, renal disease in 25%, coloboma in 17%, polydactyly in 15%, liver fibrosis in 14% and encephalocele in 8%. Loss of CEP290 function is associated with retinal dystrophy, while loss of TMEM67 function is associated with liver fibrosis and coloboma, but we observe no clear-cut distinction between JS-subtypes. Conclusion This work illustrates how combining advanced sequencing techniques with phenotypic data addresses extreme genetic heterogeneity to provide diagnostic and carrier testing, guide medical monitoring for progressive complications, facilitate interpretation of genome-wide sequencing results in individuals with a variety of phenotypes, and enable gene-specific treatments in the future. PMID:26092869

  3. Resolution of Disease Phenotypes Resulting from Multilocus Genomic Variation.

    Science.gov (United States)

    Posey, Jennifer E; Harel, Tamar; Liu, Pengfei; Rosenfeld, Jill A; James, Regis A; Coban Akdemir, Zeynep H; Walkiewicz, Magdalena; Bi, Weimin; Xiao, Rui; Ding, Yan; Xia, Fan; Beaudet, Arthur L; Muzny, Donna M; Gibbs, Richard A; Boerwinkle, Eric; Eng, Christine M; Sutton, V Reid; Shaw, Chad A; Plon, Sharon E; Yang, Yaping; Lupski, James R

    2017-01-05

    Whole-exome sequencing can provide insight into the relationship between observed clinical phenotypes and underlying genotypes. We conducted a retrospective analysis of data from a series of 7374 consecutive unrelated patients who had been referred to a clinical diagnostic laboratory for whole-exome sequencing; our goal was to determine the frequency and clinical characteristics of patients for whom more than one molecular diagnosis was reported. The phenotypic similarity between molecularly diagnosed pairs of diseases was calculated with the use of terms from the Human Phenotype Ontology. A molecular diagnosis was rendered for 2076 of 7374 patients (28.2%); among these patients, 101 (4.9%) had diagnoses that involved two or more disease loci. We also analyzed parental samples, when available, and found that de novo variants accounted for 67.8% (61 of 90) of pathogenic variants in autosomal dominant disease genes and 51.7% (15 of 29) of pathogenic variants in X-linked disease genes; both variants were de novo in 44.7% (17 of 38) of patients with two monoallelic variants. Causal copy-number variants were found in 12 patients (11.9%) with multiple diagnoses. Phenotypic similarity scores were significantly lower among patients in whom the phenotype resulted from two distinct mendelian disorders that affected different organ systems (50 patients) than among patients with disorders that had overlapping phenotypic features (30 patients) (median score, 0.21 vs. 0.36; P=1.77×10(-7)). In our study, we found multiple molecular diagnoses in 4.9% of cases in which whole-exome sequencing was informative. Our results show that structured clinical ontologies can be used to determine the degree of overlap between two mendelian diseases in the same patient; the diseases can be distinct or overlapping. Distinct disease phenotypes affect different organ systems, whereas overlapping disease phenotypes are more likely to be caused by two genes encoding proteins that interact within

  4. Phenotypic plasticity and diversity in insects

    OpenAIRE

    Moczek, Armin P.

    2010-01-01

    Phenotypic plasticity in general and polyphenic development in particular are thought to play important roles in organismal diversification and evolutionary innovation. Focusing on the evolutionary developmental biology of insects, and specifically that of horned beetles, I explore the avenues by which phenotypic plasticity and polyphenic development have mediated the origins of novelty and diversity. Specifically, I argue that phenotypic plasticity generates novel targets for evolutionary pr...

  5. Marital assortment and phenotypic convergence: longitudinal evidence.

    Science.gov (United States)

    Caspi, A; Herbener, E S

    1993-01-01

    This study provides a direct test of whether the observed similarity of spouses is due to initial assortment rather than to convergence of phenotypes. With data from three well-known longitudinal studies, phenotypic convergence is examined using both variable- and person-centered analyses. The longitudinal evidence does not support the hypothesis that couples increasingly resemble each other with time. Spouse correlations most likely reflect initial assortment at marriage and not the convergence of phenotypes.

  6. Geographic atrophy phenotype identification by cluster analysis.

    Science.gov (United States)

    Monés, Jordi; Biarnés, Marc

    2017-07-20

    To identify ocular phenotypes in patients with geographic atrophy secondary to age-related macular degeneration (GA) using a data-driven cluster analysis. This was a retrospective analysis of data from a prospective, natural history study of patients with GA who were followed for ≥6 months. Cluster analysis was used to identify subgroups within the population based on the presence of several phenotypic features: soft drusen, reticular pseudodrusen (RPD), primary foveal atrophy, increased fundus autofluorescence (FAF), greyish FAF appearance and subfoveal choroidal thickness (SFCT). A comparison of features between the subgroups was conducted, and a qualitative description of the new phenotypes was proposed. The atrophy growth rate between phenotypes was then compared. Data were analysed from 77 eyes of 77 patients with GA. Cluster analysis identified three groups: phenotype 1 was characterised by high soft drusen load, foveal atrophy and slow growth; phenotype 3 showed high RPD load, extrafoveal and greyish FAF appearance and thin SFCT; the characteristics of phenotype 2 were midway between phenotypes 1 and 3. Phenotypes differed in all measured features (p≤0.013), with decreases in the presence of soft drusen, foveal atrophy and SFCT seen from phenotypes 1 to 3 and corresponding increases in high RPD load, high FAF and greyish FAF appearance. Atrophy growth rate differed between phenotypes 1, 2 and 3 (0.63, 1.91 and 1.73 mm(2)/year, respectively, p=0.0005). Cluster analysis identified three distinct phenotypes in GA. One of them showed a particularly slow growth pattern. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  7. Sampling Strategy

    Science.gov (United States)

    2008-01-01

    Three locations to the right of the test dig area are identified for the first samples to be delivered to the Thermal and Evolved Gas Analyzer (TEGA), the Wet Chemistry Lab (WCL), and the Optical Microscope (OM) on NASA's Phoenix Mars Lander. These sampling areas are informally labeled 'Baby Bear', 'Mama Bear', and 'Papa Bear' respectively. This image was taken on the seventh day of the Mars mission, or Sol 7 (June 1, 2008) by the Surface Stereo Imager aboard NASA's Phoenix Mars Lander. The Phoenix Mission is led by the University of Arizona, Tucson, on behalf of NASA. Project management of the mission is by NASA's Jet Propulsion Laboratory, Pasadena, Calif. Spacecraft development is by Lockheed Martin Space Systems, Denver.

  8. Phenotypic and genotypic characterization of Rhodococcus equi isolated from sputum

    Directory of Open Access Journals (Sweden)

    Paulo da Silva

    Full Text Available INTRODUCTION: Rhodococcus equi is an opportunistic pathogen, causing rhodococcosis, a condition that can be confused with tuberculosis. Often, without identifying M. tuberculosis, physicians initiate empiric treatment for tuberculosis. R. equi and M. tuberculosis have different susceptibility to drugs. Identification of R. equi is based on a variety of phenotypic, chromatographic, and genotypic characteristics. OBJECTIVE: This study aimed to characterize bacterial isolates from sputum samples suggestive of R. equi. METHODS: The phenotypic identification included biochemical assays; thin-layer chromatography (TLC and polymerase chain reaction (PCR were used for genotypic identification. RESULTS: Among 78 Gram-positive and partially acid-fast bacilli isolated from the sputum of tuberculosis-suspected patients, 51 were phenotypically and genotypically characterized as R. equi based on literature data. Mycolic acid analysis showed that all suspected R. equi had compounds with a retention factor (Rf between 0.4-0.5. Genotypic characterization indicated the presence of the choE gene 959 bp fragments in 51 isolates CAMP test positive. Twenty-two CAMP test negative isolates were negative for the choE gene. Five isolates presumptively identified as R. equi, CAMP test positive, were choE gene negative, and probably belonged to other bacterial species. CONCLUSIONS: The phenotypic and molecular techniques used constitute a good methodological tool to identify R. equi.

  9. Phenotypic and genotypic characterization of Rhodococcus equi isolated from sputum.

    Science.gov (United States)

    Silva, Paulo da; Santos, Adolfo Carlos Barreto; Sato, Daisy Nakamura; Silva, Jaqueline Otero; Medeiros, Marta Inês Cazentini; Carneiro, Ana Maria Machado; Leite, Sergio Roberto de Andrade; Leite, Clarice Queico Fujimura

    2012-01-01

    Rhodococcus equi is an opportunistic pathogen, causing rhodococcosis, a condition that can be confused with tuberculosis. Often, without identifying M. tuberculosis, physicians initiate empiric treatment for tuberculosis. R. equi and M. tuberculosis have different susceptibility to drugs. Identification of R. equi is based on a variety of phenotypic, chromatographic, and genotypic characteristics. This study aimed to characterize bacterial isolates from sputum samples suggestive of R. equi. The phenotypic identification included biochemical assays; thin-layer chromatography (TLC) and polymerase chain reaction (PCR) were used for genotypic identification. Among 78 Gram-positive and partially acid-fast bacilli isolated from the sputum of tuberculosis-suspected patients, 51 were phenotypically and genotypically characterized as R. equi based on literature data. Mycolic acid analysis showed that all suspected R. equi had compounds with a retention factor (R(f)) between 0.4-0.5. Genotypic characterization indicated the presence of the choE gene 959bp fragments in 51 isolates CAMP test positive. Twenty-two CAMP test negative isolates were negative for the choE gene. Five isolates presumptively identified as R. equi, CAMP test positive, were choE gene negative, and probably belonged to other bacterial species. The phenotypic and molecular techniques used constitute a good methodological tool to identify R. equi. Copyright © 2012 Elsevier Editora Ltda. All rights reserved.

  10. Immunogenetic phenotypes in inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Marla C Dubinsky; Kent Taylor; Stephan R Targan; Jerome I Rotter

    2006-01-01

    The currently accepted etiopathogenic hypothesis suggests that the chronic intestinal inflammation and related systemic manifestations characteristic of inflammatory bowel disease (IBD) are due to an overly aggressive or pathologic immune response to resident luminal bacterial constituents. Predisposing factors are genetic dysregulation of mucosal immune responses and/or barrier function, with onset triggered by environmental stimuli. These factors and their interactions may also be important determinants of disease phenotype and disease progression. The emergence of immunogenetic phenotypes lends support to the proposed hypothesis that susceptibility genes regulate distinct immune processes, driven by luminal antigens, expressed as specific immune phenotypes which in turn influence clinical phenotypes in IBD patient

  11. Phenotypic plasticity's impacts on diversification and speciation.

    Science.gov (United States)

    Pfennig, David W; Wund, Matthew A; Snell-Rood, Emilie C; Cruickshank, Tami; Schlichting, Carl D; Moczek, Armin P

    2010-08-01

    Phenotypic plasticity (the ability of a single genotype to produce multiple phenotypes in response to variation in the environment) is commonplace. Yet its evolutionary significance remains controversial, especially in regard to whether and how it impacts diversification and speciation. Here, we review recent theory on how plasticity promotes: (i) the origin of novel phenotypes, (ii) divergence among populations and species, (iii) the formation of new species and (iv) adaptive radiation. We also discuss the latest empirical support for each of these evolutionary pathways to diversification and identify potentially profitable areas for future research. Generally, phenotypic plasticity can play a largely underappreciated role in driving diversification and speciation.

  12. The phenotypic variance gradient - a novel concept.

    Science.gov (United States)

    Pertoldi, Cino; Bundgaard, Jørgen; Loeschcke, Volker; Barker, James Stuart Flinton

    2014-11-01

    Evolutionary ecologists commonly use reaction norms, which show the range of phenotypes produced by a set of genotypes exposed to different environments, to quantify the degree of phenotypic variance and the magnitude of plasticity of morphometric and life-history traits. Significant differences among the values of the slopes of the reaction norms are interpreted as significant differences in phenotypic plasticity, whereas significant differences among phenotypic variances (variance or coefficient of variation) are interpreted as differences in the degree of developmental instability or canalization. We highlight some potential problems with this approach to quantifying phenotypic variance and suggest a novel and more informative way to plot reaction norms: namely "a plot of log (variance) on the y-axis versus log (mean) on the x-axis, with a reference line added". This approach gives an immediate impression of how the degree of phenotypic variance varies across an environmental gradient, taking into account the consequences of the scaling effect of the variance with the mean. The evolutionary implications of the variation in the degree of phenotypic variance, which we call a "phenotypic variance gradient", are discussed together with its potential interactions with variation in the degree of phenotypic plasticity and canalization.

  13. Phenotypic screening: the future of antibody discovery.

    Science.gov (United States)

    Gonzalez-Munoz, Andrea L; Minter, Ralph R; Rust, Steven J

    2016-01-01

    Most antibody therapeutics have been isolated from high throughput target-based screening. However, as the number of validated targets diminishes and the target space becomes increasingly competitive, alternative strategies, such as phenotypic screening, are gaining momentum. Here, we review successful phenotypic screens, including those used to isolate antibodies against cancer and infectious agents. We also consider exciting advances in the expression and phenotypic screening of antibody repertoires in single cell autocrine systems. As technologies continue to develop, we believe that antibody phenotypic screening will increase further in popularity and has the potential to provide the next generation of therapeutic antibodies.

  14. Differentiation and Distribution of Marrow Stem Cells in Flex-Flow Environments Demonstrate Support of the Valvular Phenotype.

    Directory of Open Access Journals (Sweden)

    Sasmita Rath

    Full Text Available For treatment of critical heart valve diseases, prosthetic valves perform fairly well in most adults; however, for pediatric patients, there is the added requirement that the replacement valve grows with the child, thus extremely limiting current treatment options. Tissue engineered heart valves (TEHV, such as those derived from autologous bone marrow stem cells (BMSCs, have the potential to recapitulate native valve architecture and accommodate somatic growth. However, a fundamental pre-cursor in promoting directed integration with native tissues rather than random, uncontrolled growth requires an understanding of BMSC mechanobiological responses to valve-relevant mechanical environments. Here, we report on the responses of human BMSC-seeded polymer constructs to the valve-relevant stress states of: (i steady flow alone, (ii cyclic flexure alone, and (iii the combination of cyclic flexure and steady flow (flex-flow. BMSCs were seeded onto a PGA: PLLA polymer scaffold and cultured in static culture for 8 days. Subsequently, the aforementioned mechanical conditions, (groups consisting of steady flow alone-850ml/min, cyclic flexure alone-1 Hz, and flex-flow-850ml/min and 1 Hz were applied for an additional two weeks. We found samples from the flex-flow group exhibited a valve-like distribution of cells that expressed endothelial (preference to the surfaces and myofibroblast (preference to the intermediate region phenotypes. We interpret that this was likely due to the presence of both appreciable fluid-induced shear stress magnitudes and oscillatory shear stresses, which were concomitantly imparted onto the samples. These results indicate that flex-flow mechanical environments support directed in vitro differentiation of BMSCs uniquely towards a heart valve phenotype, as evident by cellular distribution and expression of specific gene markers. A priori guidance of BMSC-derived, engineered tissue growth under flex-flow conditions may serve to

  15. Identification of genomic regions associated with phenotypic variation between dog breeds using selection mapping

    DEFF Research Database (Denmark)

    Vaysse, Amaury; Ratnakumar, Abhirami; Derrien, Thomas;

    2011-01-01

    across the genome in dog breeds are the result of both selection and genetic drift, but extended blocks of homozygosity on a megabase scale appear to be best explained by selection. Further elucidation of the variants under selection will help to uncover the genetic basis of complex traits and disease....... breeds using a newly developed high-density genotyping array consisting of >170,000 evenly spaced SNPs. We first identify 44 genomic regions exhibiting extreme differentiation across multiple breeds. Genetic variation in these regions correlates with variation in several phenotypic traits that vary...... to provide a list of variants that may directly affect these traits. This study provides a catalogue of genomic regions showing extreme reduction in genetic variation or population differentiation in dogs, including many linked to phenotypic variation. The many blocks of reduced haplotype diversity observed...

  16. Outcomes for Extremely Premature Infants

    Science.gov (United States)

    Glass, Hannah C.; Costarino, Andrew T.; Stayer, Stephen A.; Brett, Claire; Cladis, Franklyn; Davis, Peter J.

    2015-01-01

    Premature birth is a significant cause of infant and child morbidity and mortality. In the United States, the premature birth rate, which had steadily increased during the 1990s and early 2000s, has decreased annually for four years and is now approximately 11.5%. Human viability, defined as gestational age at which the chance of survival is 50%, is currently approximately 23–24 weeks in developed countries. Infant girls, on average, have better outcomes than infant boys. A relatively uncomplicated course in the intensive care nursery for an extremely premature infant results in a discharge date close to the prenatal EDC. Despite technological advances and efforts of child health experts during the last generation, the extremely premature infant (less than 28 weeks gestation) and extremely low birth weight infant (ELBW) (premature labor improved neonatal mortality and morbidity in the late 1990s. The recognition that chronic postnatal administration of steroids to infants should be avoided may have improved outcomes in the early 2000s. Evidence from recent trials attempting to define the appropriate target for oxygen saturation in preterm infants suggests arterial oxygen saturation between 91–95% (compared to 85–89%) avoids excess mortality. However, final analyses of data from these trials have not been published, so definitive recommendations are still pending The development of neonatal neurocognitive care visits may improve neurocognitive outcomes in this high-risk group. Long-term follow up to detect and address developmental, learning, behavioral, and social problems is critical for children born at these early gestational ages. The striking similarities in response to extreme prematurity in the lung and brain imply that agents and techniques that benefit one organ are likely to also benefit the other. Finally, since therapy and supportive care continue to change, the outcomes of ELBW infants are ever evolving. Efforts to minimize injury, preserve

  17. Gravity and Extreme Magnetism SMEX

    Science.gov (United States)

    2012-01-01

    The Gravity and Extreme Magnetism SMEX mission will be the first mission to catalogue the X-ray polarisation of many astrophysical objects including black-holes and pulsars. This first of its kind mission is enabled by the novel use of a time projection chamber as an X-ray polarimeter. The detector has been developed over the last 5 years, with the current effort charged toward a demonstration of it's technical readiness to be at level 6 prior to the preliminary design review. This talk will describe the design GEMS polarimeter and the results to date from the engineering test unit.

  18. Communication path for extreme environments

    Science.gov (United States)

    Jorgensen, Charles C. (Inventor); Betts, Bradley J. (Inventor)

    2010-01-01

    Methods and systems for using one or more radio frequency identification devices (RFIDs), or other suitable signal transmitters and/or receivers, to provide a sensor information communication path, to provide location and/or spatial orientation information for an emergency service worker (ESW), to provide an ESW escape route, to indicate a direction from an ESW to an ES appliance, to provide updated information on a region or structure that presents an extreme environment (fire, hazardous fluid leak, underwater, nuclear, etc.) in which an ESW works, and to provide accumulated thermal load or thermal breakdown information on one or more locations in the region.

  19. Ionization Chamber Measures Extreme Ultraviolet

    Science.gov (United States)

    Carlson, Robert W.

    1987-01-01

    Ionization chamber operates in nearly total photon absorption as stable, self-calibrating detector of ionizing extreme ultraviolet radiation. Working gas of instrument is neon; photoionization properties well known and readily applicable to absolute measurements. Designed for measurements of solar ultraviolet flux aboard sounding rocket, instrument used on Earth to measure ultraviolet radiation in vacuum systems. Ionization chamber collects positive neon ions and electrons produced by irradiation of neon gas by ultraviolet photons. Approximately one ion produced by each photon; consequently, photoionization current nearly proportional to photon flux.

  20. Extreme Geomagnetic Storms - 1868 - 2010

    Science.gov (United States)

    Vennerstrom, S.; Lefevre, L.; Dumbović, M.; Crosby, N.; Malandraki, O.; Patsou, I.; Clette, F.; Veronig, A.; Vršnak, B.; Leer, K.; Moretto, T.

    2016-05-01

    We present the first large statistical study of extreme geomagnetic storms based on historical data from the time period 1868 - 2010. This article is the first of two companion papers. Here we describe how the storms were selected and focus on their near-Earth characteristics. The second article presents our investigation of the corresponding solar events and their characteristics. The storms were selected based on their intensity in the aa index, which constitutes the longest existing continuous series of geomagnetic activity. They are analyzed statistically in the context of more well-known geomagnetic indices, such as the Kp and Dcx/Dst index. This reveals that neither Kp nor Dcx/Dst provide a comprehensive geomagnetic measure of the extreme storms. We rank the storms by including long series of single magnetic observatory data. The top storms on the rank list are the New York Railroad storm occurring in May 1921 and the Quebec storm from March 1989. We identify key characteristics of the storms by combining several different available data sources, lists of storm sudden commencements (SSCs) signifying occurrence of interplanetary shocks, solar wind in-situ measurements, neutron monitor data, and associated identifications of Forbush decreases as well as satellite measurements of energetic proton fluxes in the near-Earth space environment. From this we find, among other results, that the extreme storms are very strongly correlated with the occurrence of interplanetary shocks (91 - 100 %), Forbush decreases (100 %), and energetic solar proton events (70 %). A quantitative comparison of these associations relative to less intense storms is also presented. Most notably, we find that most often the extreme storms are characterized by a complexity that is associated with multiple, often interacting, solar wind disturbances and that they frequently occur when the geomagnetic activity is already elevated. We also investigate the semiannual variation in storm occurrence

  1. Advances in upper extremity prosthetics.

    Science.gov (United States)

    Zlotolow, Dan A; Kozin, Scott H

    2012-11-01

    Until recently, upper extremity prostheses had changed little since World War II. In 2006, the Defense Advanced Research Projects Agency responded to an increasing number of military amputees with the Revolutionizing Prosthetics program. The program has yielded several breakthroughs both in the engineering of new prosthetic arms and in the control of those arms. Direct brain-wave control of a limb with 22° of freedom may be within reach. In the meantime, advances such as individually powered digits have opened the door to multifunctional full and partial hand prostheses. Restoring sensation to the prosthetic limb remains a major challenge to full integration of the limb into a patient's self-image.

  2. A rare case of haemolytic disease of newborn with Bombay phenotype mother

    Directory of Open Access Journals (Sweden)

    Shamee Shastry

    2013-01-01

    Full Text Available We are reporting a rare case of severe hemolytic disease of newborn (HDN with Bombay phenotype mother. A retrospective study of a case with severe haemolytic disease of newborn with Bombay phenotype mother was done. Blood grouping, antibody screening, and lectin study was done on the blood sample of the baby and mother to confirm the diagnosis. Hematological and biochemical parameters were obtained from the hospital laboratory information system for the analysis. Blood group of the baby was A positive, direct antiglobulin test was negative. Blood group of the mother was confirmed to be Bombay phenotype, Hematological parameters showed all the signs of ongoing hemolysis and the bilirubin level was in the zone of exchange transfusion. Due to the unavailability of this rare phenotype blood unit, baby was managed conservatively. Anticipating the fetal anemia and HDN with mothers having Bombay phenotype and prior notification to the transfusion services will be of great help in optimizing the neonatal care and outcome.

  3. A rare case of haemolytic disease of newborn with Bombay phenotype mother.

    Science.gov (United States)

    Shastry, Shamee; Lewis, Leslie E; Bhat, Sudha S

    2013-07-01

    We are reporting a rare case of severe hemolytic disease of newborn (HDN) with Bombay phenotype mother. A retrospective study of a case with severe haemolytic disease of newborn with Bombay phenotype mother was done. Blood grouping, antibody screening, and lectin study was done on the blood sample of the baby and mother to confirm the diagnosis. Hematological and biochemical parameters were obtained from the hospital laboratory information system for the analysis. Blood group of the baby was A positive, direct antiglobulin test was negative. Blood group of the mother was confirmed to be Bombay phenotype, Hematological parameters showed all the signs of ongoing hemolysis and the bilirubin level was in the zone of exchange transfusion. Due to the unavailability of this rare phenotype blood unit, baby was managed conservatively. Anticipating the fetal anemia and HDN with mothers having Bombay phenotype and prior notification to the transfusion services will be of great help in optimizing the neonatal care and outcome.

  4. CYP1A2 phenotyping in dried blood spots and microvolumes of whole blood and plasma.

    Science.gov (United States)

    De Kesel, Pieter M M; Lambert, Willy E; Stove, Christophe P

    2014-01-01

    Phenotyping, using caffeine as probe substrate, is a proper method to assess CYP1A2 activity. We evaluated the utility of dried blood spots (DBS) for CYP1A2 phenotyping. LC-MS/MS methods were developed and validated for quantitation of caffeine and its metabolite paraxanthine in DBS, whole blood and plasma. All parameters met the pre-established criteria. While recovery, matrix effects and precision were unaffected by hematocrit (Hct), there was a Hct effect on accuracy, although for the evaluated Hct interval (0.36-0.50) it remained within acceptable limits. The phenotyping methods were successfully applied in healthy volunteers. Excellent method performance and highly comparable phenotyping indices in DBS, whole blood and plasma, combined with the benefits of DBS sampling, illustrate the suitability of DBS-based CYP1A2 phenotyping.

  5. Prevention of Lower Extremity Injuries in Basketball

    OpenAIRE

    2015-01-01

    Context: Lower extremity injuries are common in basketball, yet it is unclear how prophylactic interventions affect lower extremity injury incidence rates. Objective: To analyze the effectiveness of current lower extremity injury prevention programs in basketball athletes, focusing on injury rates of (1) general lower extremity injuries, (2) ankle sprains, and (3) anterior cruciate ligament (ACL) tears. Data Sources: PubMed, MEDLINE, CINAHL, SPORTDiscus, and the Cochrane Register of Controlle...

  6. Sex differences in genetic architecture of complex phenotypes?

    Directory of Open Access Journals (Sweden)

    Jacqueline M Vink

    Full Text Available We examined sex differences in familial resemblance for a broad range of behavioral, psychiatric and health related phenotypes (122 complex traits in children and adults. There is a renewed interest in the importance of genotype by sex interaction in, for example, genome-wide association (GWA studies of complex phenotypes. If different genes play a role across sex, GWA studies should consider the effect of genetic variants separately in men and women, which affects statistical power. Twin and family studies offer an opportunity to compare resemblance between opposite-sex family members to the resemblance between same-sex relatives, thereby presenting a test of quantitative and qualitative sex differences in the genetic architecture of complex traits. We analyzed data on lifestyle, personality, psychiatric disorder, health, growth, development and metabolic traits in dizygotic (DZ same-sex and opposite-sex twins, as these siblings are perfectly matched for age and prenatal exposures. Sample size varied from slightly over 300 subjects for measures of brain function such as EEG power to over 30,000 subjects for childhood psychopathology and birth weight. For most phenotypes, sample sizes were large, with an average sample size of 9027 individuals. By testing whether the resemblance in DZ opposite-sex pairs is the same as in DZ same-sex pairs, we obtain evidence for genetic qualitative sex-differences in the genetic architecture of complex traits for 4% of phenotypes. We conclude that for most traits that were examined, the current evidence is that same the genes are operating in men and women.

  7. A Bayesian approach to analyzing phenotype microarray data enables estimation of microbial growth parameters

    OpenAIRE

    Gerstgrasser, Matthias; Nicholls, Sarah; Stout, Michael; Smart, Katherine; Powell, Chris; Kypraios, Theodore; Stekel, Dov J.

    2016-01-01

    Biolog phenotype microarrays enable simultaneous, high throughput analysis of cell cultures in different environments. The output is high-density time-course data showing redox curves (approximating growth) for each experimental condition. The software provided with the Omnilog incubator/reader summarizes each time-course as a single datum, so most of the information is not used. However, the time courses can be extremely varied and often contain detailed qualitative (shape of curve) and quan...

  8. Dynamics of extremal black holes

    CERN Document Server

    Giddings, Steven B

    1992-01-01

    Particle scattering and radiation by a magnetically charged, dilatonic black hole is investigated near the extremal limit at which the mass is a constant times the charge. Near this limit a neighborhood of the horizon of the black hole is closely approximated by a trivial product of a two-dimensional black hole with a sphere. This is shown to imply that the scattering of long-wavelength particles can be described by a (previously analyzed) two-dimensional effective field theory, and is related to the formation/evaporation of two-dimensional black holes. The scattering proceeds via particle capture followed by Hawking re-emission, and naively appears to violate unitarity. However this conclusion can be altered when the effects of backreaction are included. Particle-hole scattering is discussed in the light of a recent analysis of the two-dimensional backreaction problem. It is argued that the quantum mechanical possibility of scattering off of extremal black holes implies the potential existence of additional ...

  9. EXTREMAL CONTROL FOR PHOTOVOLTAIC PANELS

    Directory of Open Access Journals (Sweden)

    Genevieve DAPHIN TANGUY

    2016-11-01

    Full Text Available In this paper a methodology for extremal control of photovoltaic panels has been designed through the use of an embedded polynomial controller using robust approaches and algorithms. Also, a framework for testing solar trackers in a hard ware in the loop (HIL configuration has been established. Efficient gradient based optimization methods were put in place in order to determine the parameters of the employed photovoltaic panel, as well as for computing the Maximum Power Point (MPP. Further a numerical RST controller has been computed in order to allow the panel to follow the movement of the sun to obtain a maximum energetic efficiency. A robustness analysis and correction procedure has been done on the RST polynomial algorithm. The hardware in the loop configuration allows for the development of a test and development platform which can be used for bringing improvements to the current design and also test different control approaches. For this, a microcontroller based solution was chosen. The achieved performances of the closed loop photovoltaic panel (PP system are validated in simulation using the MATLAB / SIMULINK environment and the WinPim & WinReg dedicated software. As it will be seen further in this paper, the extremal control of this design resides in a sequential set of computations used for obtaining the new Maximum Power Point at each change in the system.

  10. Modelling of extreme gusts for design calculations (NewGust)

    Energy Technology Data Exchange (ETDEWEB)

    Bierbooms, W.; Po-Wen Cheng [Delft Univ. of Technology, Inst. for Wind Energy, Delft (Netherlands); Larsen, G. [Risoe National Lab., Roskilde (Denmark); Juul Pedersen, B. [Vestas Wind Systems A/S, Lem (Denmark); Hansen, K. [Tecnical Univ. of Denmark (Denmark)

    1999-03-01

    The main objective of the NewGust project is to come to a realistic and verified description of extreme gusts based on the stochastic properties of wind. In this paper the first results of the project are presented. Theoretical considerations indicate that the shape of extreme gusts is very sharp. Based on simulated wind time series, mean gust shapes (for several amplitudes and mean wind speeds) are determined and compared with the theoretical curves. The resemblance turned out to be very good. Furthermore, the influence of the sampling rate and the dynamics of a cup anemometer on the empirical mean gust shape are examined. The promising results are confirmed by a (preliminary) verification based on measured wind time series, available from the database on wind characteristics. The mean shape of gusts, of certain amplitude, together with their probability of occurrence can be used to obtain the distribution of the extreme response of wind turbines to gust loading. (au)

  11. Juvenile rheumatoid arthritis. Aquatic exercise and lower-extremity function.

    Science.gov (United States)

    Bacon, M C; Nicholson, C; Binder, H; White, P H

    1991-06-01

    This pilot study investigates the effects of aquatic therapeutic exercise on lower-extremity range of motion, gait, balance, and functional mobility in children with juvenile arthritis. Eleven patients, aged 4-13, with lower-extremity joint involvement, diagnosed as functional class I-III, completed a 6-week program of aquatic exercise aimed at increasing lower-extremity range of motion and strength. Despite the small sample size and short duration of the study program, significant improvement was noted in external and internal hip rotation, bilaterally (p Aquatic exercises performed in a group setting can serve as an enjoyable and beneficial part of therapy for children with arthritis. Further investigation is recommended to determine fully the effects of aquatic therapeutic exercise on mobility and fitness in children with juvenile arthritis.

  12. The Integrated periodogram of a dependent extremal event sequence

    DEFF Research Database (Denmark)

    Mikosch, Thomas Valentin; Zhao, Yuwei

    2015-01-01

    We investigate the asymptotic properties of the integrated periodogram calculated from a sequence of indicator functions of dependent extremal events. An event in Euclidean space is extreme if it occurs far away from the origin. We use a regular variation condition on the underlying stationary.......i.d. case a Brownian bridge appears. In the general case, we propose a stationary bootstrap procedure for approximating the distribution of the limiting process. The developed theory can be used to construct classical goodness-of-fit tests such as the Grenander–Rosenblatt and Cramér–von Mises tests which...... are based only on the extremes in the sample. We apply the test statistics to simulated and real-life data....

  13. Detailed Analysis of Solar Data Related to Historical Extreme Geomagnetic Storms: 1868 – 2010

    DEFF Research Database (Denmark)

    Lefèvre, Laure; Vennerstrøm, Susanne; Dumbović, Mateja

    2016-01-01

    An analysis of historical Sun–Earth connection events in the context of the most extreme space weather events of the last ∼ 150 years is presented. To identify the key factors leading to these extreme events, a sample of the most important geomagnetic storms was selected based mainly on the well-...

  14. Unmanned Aerial Vehicle Remote Sensing for Field-Based Crop Phenotyping: Current Status and Perspectives

    Directory of Open Access Journals (Sweden)

    Guijun Yang

    2017-06-01

    Full Text Available Phenotyping plays an important role in crop science research; the accurate and rapid acquisition of phenotypic information of plants or cells in different environments is helpful for exploring the inheritance and expression patterns of the genome to determine the association of genomic and phenotypic information to increase the crop yield. Traditional methods for acquiring crop traits, such as plant height, leaf color, leaf area index (LAI, chlorophyll content, biomass and yield, rely on manual sampling, which is time-consuming and laborious. Unmanned aerial vehicle remote sensing platforms (UAV-RSPs equipped with different sensors have recently become an important approach for fast and non-destructive high throughput phenotyping and have the advantage of flexible and convenient operation, on-demand access to data and high spatial resolution. UAV-RSPs are a powerful tool for studying phenomics and genomics. As the methods and applications for field phenotyping using UAVs to users who willing to derive phenotypic parameters from large fields and tests with the minimum effort on field work and getting highly reliable results are necessary, the current status and perspectives on the topic of UAV-RSPs for field-based phenotyping were reviewed based on the literature survey of crop phenotyping using UAV-RSPs in the Web of Science™ Core Collection database and cases study by NERCITA. The reference for the selection of UAV platforms and remote sensing sensors, the commonly adopted methods and typical applications for analyzing phenotypic traits by UAV-RSPs, and the challenge for crop phenotyping by UAV-RSPs were considered. The review can provide theoretical and technical support to promote the applications of UAV-RSPs for crop phenotyping.

  15. Unmanned Aerial Vehicle Remote Sensing for Field-Based Crop Phenotyping: Current Status and Perspectives.

    Science.gov (United States)

    Yang, Guijun; Liu, Jiangang; Zhao, Chunjiang; Li, Zhenhong; Huang, Yanbo; Yu, Haiyang; Xu, Bo; Yang, Xiaodong; Zhu, Dongmei; Zhang, Xiaoyan; Zhang, Ruyang; Feng, Haikuan; Zhao, Xiaoqing; Li, Zhenhai; Li, Heli; Yang, Hao

    2017-01-01

    Phenotyping plays an important role in crop science research; the accurate and rapid acquisition of phenotypic information of plants or cells in different environments is helpful for exploring the inheritance and expression patterns of the genome to determine the association of genomic and phenotypic information to increase the crop yield. Traditional methods for acquiring crop traits, such as plant height, leaf color, leaf area index (LAI), chlorophyll content, biomass and yield, rely on manual sampling, which is time-consuming and laborious. Unmanned aerial vehicle remote sensing platforms (UAV-RSPs) equipped with different sensors have recently become an important approach for fast and non-destructive high throughput phenotyping and have the advantage of flexible and convenient operation, on-demand access to data and high spatial resolution. UAV-RSPs are a powerful tool for studying phenomics and genomics. As the methods and applications for field phenotyping using UAVs to users who willing to derive phenotypic parameters from large fields and tests with the minimum effort on field work and getting highly reliable results are necessary, the current status and perspectives on the topic of UAV-RSPs for field-based phenotyping were reviewed based on the literature survey of crop phenotyping using UAV-RSPs in the Web of Science™ Core Collection database and cases study by NERCITA. The reference for the selection of UAV platforms and remote sensing sensors, the commonly adopted methods and typical applications for analyzing phenotypic traits by UAV-RSPs, and the challenge for crop phenotyping by UAV-RSPs were considered. The review can provide theoretical and technical support to promote the applications of UAV-RSPs for crop phenotyping.

  16. Unmanned Aerial Vehicle Remote Sensing for Field-Based Crop Phenotyping: Current Status and Perspectives

    Science.gov (United States)

    Yang, Guijun; Liu, Jiangang; Zhao, Chunjiang; Li, Zhenhong; Huang, Yanbo; Yu, Haiyang; Xu, Bo; Yang, Xiaodong; Zhu, Dongmei; Zhang, Xiaoyan; Zhang, Ruyang; Feng, Haikuan; Zhao, Xiaoqing; Li, Zhenhai; Li, Heli; Yang, Hao

    2017-01-01

    Phenotyping plays an important role in crop science research; the accurate and rapid acquisition of phenotypic information of plants or cells in different environments is helpful for exploring the inheritance and expression patterns of the genome to determine the association of genomic and phenotypic information to increase the crop yield. Traditional methods for acquiring crop traits, such as plant height, leaf color, leaf area index (LAI), chlorophyll content, biomass and yield, rely on manual sampling, which is time-consuming and laborious. Unmanned aerial vehicle remote sensing platforms (UAV-RSPs) equipped with different sensors have recently become an important approach for fast and non-destructive high throughput phenotyping and have the advantage of flexible and convenient operation, on-demand access to data and high spatial resolution. UAV-RSPs are a powerful tool for studying phenomics and genomics. As the methods and applications for field phenotyping using UAVs to users who willing to derive phenotypic parameters from large fields and tests with the minimum effort on field work and getting highly reliable results are necessary, the current status and perspectives on the topic of UAV-RSPs for field-based phenotyping were reviewed based on the literature survey of crop phenotyping using UAV-RSPs in the Web of Science™ Core Collection database and cases study by NERCITA. The reference for the selection of UAV platforms and remote sensing sensors, the commonly adopted methods and typical applications for analyzing phenotypic traits by UAV-RSPs, and the challenge for crop phenotyping by UAV-RSPs were considered. The review can provide theoretical and technical support to promote the applications of UAV-RSPs for crop phenotyping. PMID:28713402

  17. Phenotypic plasticity of southern ocean diatoms: key to success in the sea ice habitat?

    Directory of Open Access Journals (Sweden)

    Olivia Sackett

    Full Text Available Diatoms are the primary source of nutrition and energy for the Southern Ocean ecosystem. Microalgae, including diatoms, synthesise biological macromolecules such as lipids, proteins and carbohydrates for growth, reproduction and acclimation to prevailing environmental conditions. Here we show that three key species of Southern Ocean diatom (Fragilariopsis cylindrus, Chaetoceros simplex and Pseudo-nitzschia subcurvata exhibited phenotypic plasticity in response to salinity and temperature regimes experienced during the seasonal formation and decay of sea ice. The degree of phenotypic plasticity, in terms of changes in macromolecular composition, was highly species-specific and consistent with each species' known distribution and abundance throughout sea ice, meltwater and pelagic habitats, suggesting that phenotypic plasticity may have been selected for by the extreme variability of the polar marine environment. We argue that changes in diatom macromolecular composition and shifts in species dominance in response to a changing climate have the potential to alter nutrient and energy fluxes throughout the Southern Ocean ecosystem.

  18. [Amyloidosis of familial Mediterranean fever (FMF)--insights to FMF phenotype II].

    Science.gov (United States)

    Livneh, Avi

    2006-10-01

    Amyloidosis is the most grievous manifestation of Familial Mediterranean Fever (FMF), occurring in a high proportion of untreated patients. Continuously elevated serum amyloid A (SAA) levels during remissions, rather than a pulsatile rise during FMF attacks, underlies the development of amyloidosis. FMF phenotype II is one extreme of AA amyloidosis, evolving despite a complete absence of FMF attacks. FMF phenotype II is diagnosed in patients with AA amyloidosis in the context of a family history of FMF. In these patients and in patients with AA amyloidosis without family history of FMF and with unknown precipitating disease, MEFV gene analysis is mandatory. Moreover, since FMF phenotype II is an actual hazard, a cost-benefit analysis suggests that MEFV mutation determination in all first-degree family members of FMF patients is warranted, as it will significantly reduce future patient treatment costs.

  19. Genetic Similarities between Compulsive Overeating and Addiction Phenotypes: A Case for "Food Addiction"?

    Science.gov (United States)

    Carlier, Nina; Marshe, Victoria S; Cmorejova, Jana; Davis, Caroline; Müller, Daniel J

    2015-12-01

    There exists a continuous spectrum of overeating, where at the extremes there are casual overindulgences and at the other a 'pathological' drive to consume palatable foods. It has been proposed that pathological eating behaviors may be the result of addictive appetitive behavior and loss of ability to regulate the consumption of highly processed foods containing refined carbohydrates, fats, salt, and caffeine. In this review, we highlight the genetic similarities underlying substance addiction phenotypes and overeating compulsions seen in individuals with binge eating disorder. We relate these similarities to findings from neuroimaging studies on reward processing and clinical diagnostic criteria based on addiction phenotypes. The abundance of similarities between compulsive overeating and substance addictions puts forth a case for a 'food addiction' phenotype as a valid, diagnosable disorder.

  20. Personal gravimetric dust sampling and risk assessment.

    CSIR Research Space (South Africa)

    Unsted, AD

    1996-03-01

    Full Text Available . At all the sampling sites extremely large variation in dust concentrations were measured on a day to day and shift basis. Correlation of dust concentrations between personal and stationary samples was very poor as was the correlation between quartz...

  1. Genetic and Environmental Regulation on Longitudinal Change of Metabolic Phenotypes in Danish and Chinese Adult Twins.

    Science.gov (United States)

    Li, Shuxia; Kyvik, Kirsten Ohm; Pang, Zengchang; Zhang, Dongfeng; Duan, Haiping; Tan, Qihua; Hjelmborg, Jacob; Kruse, Torben; Dalgård, Christine

    2016-01-01

    The rate of change in metabolic phenotypes can be highly indicative of metabolic disorders and disorder-related modifications. We analyzed data from longitudinal twin studies on multiple metabolic phenotypes in Danish and Chinese twins representing two populations of distinct ethnic, cultural, social-economic backgrounds and geographical environments. The study covered a relatively large sample of 502 pairs of Danish adult twins followed up for a long period of 12 years with a mean age at intake of 38 years (range: 18-65) and a total of 181 Chinese adult twin pairs traced for about 7 years with a mean baseline age of 39.5 years (range: 23-64). The classical twin models were fitted to the longitudinal change in each phenotypephenotype) to estimate the genetic and environmental contributions to the variation in Δphenotype. Moderate to high contributions by the unique environment were estimated for all phenotypes in both Danish (from 0.51 for low density lipoprotein cholesterol up to 0.72 for triglycerides) and Chinese (from 0.41 for triglycerides up to 0.73 for diastolic blood pressure) twins; low to moderate genetic components were estimated for long-term change in most of the phenotypes in Danish twins except for triglycerides and hip circumference. Compared with Danish twins, the Chinese twins tended to have higher genetic control over the longitudinal changes in lipids (except high density lipoprotein cholesterol) and glucose, higher unique environmental contribution to blood pressure but no genetic contribution to longitudinal change in body mass traits. Our results emphasize the major contribution of unique environment to the observed intra-individual variation in all metabolic phenotypes in both samples, and meanwhile reveal differential patterns of genetic and common environmental regulation on changes over time in metabolic phenotypes across the two samples.

  2. The Edgeworth expansion for distributions of extreme values

    Institute of Scientific and Technical Information of China (English)

    CHENG; Shihong(

    2001-01-01

    [1] Gnedenko, B. V., Sur la distribution limite du terme maximum d'une serie aleatoire, Annals of Math., 1943, 44: 423.[2] de Haan, L., On regular variation and its application to the weak convergence of sample extreme, Math. Centre Tract 32, Amsterdam: Math. Centrum, 1970.[3] Hall, P., On the rate of convergence of normal extremes, J. Appl. Probab., 1979, 16: 433.[4] Hall, W. J., Wellner, J. A., The rate of convergence in law of the maximum of an exponential samples, Statist. Neerlandica, 1979, 33: 151.[5] Davis, R., The rate of convergence in distribution of the maxima, Statist. Neerlandica, 1982, 36: 31.[6] Smith, R., Uniform rates of convergence in extreme value theory, Adv. in Appl. Probab., 1982, 14: 543.[7] Resnick, S. I., Uniform rates of convergence to extreme value distribution, Probability and Statistis: Essays in Honor of Franklin Graybill, Amsterdam: North-Holland, 1986.[8] Resnick, S. I., Extreme Values, Regular variation, and Point Processes, New York: Springer, 1987.[9] de Haan, L., Resnick, S. I., Second order regular variation and rates of convergence in extreme value theory, Annals of Probab., 1996, 24: 97.[10] Geluk, J. L., de Haan, L., Regular variation, extensions and Tauberian theorems, CWI Tract 40, Amsterdam: Center for Mathematics and Computer Science, 1987.[11] de Haan, L., Stadtmuller, U., Generalized regular variation of second order, J. Austral. Math. Soc. Ser. A, 1998, 61: 381.[12] Omey, E., Willekens, E., Π-variation with remainder, J. London Math. Soc., 1988, 37: 105.[13] Vervaat, W., Functional central limit theorems for processes with positive drift and their inverses, Z. Wahrsch. Verw. Gebiete, 1972, 23: 249.

  3. The Human Phenotype Ontology project: linking molecular biology and disease through phenotype data

    NARCIS (Netherlands)

    Kohler, S.; Doelken, S.C.; Mungall, C.J.; Bauer, S.; Firth, H.V.; Bailleul-Forestier, I.; Black, G.C.M.; Brown, D.L.; Brudno, M.; Campbell, J.; FitzPatrick, D.R.; Eppig, J.T.; Jackson, A.P.; Freson, K.; Girdea, M.; Helbig, I.; Hurst, J.A.; Jahn, J.; Jackson, L.G.; Kelly, A.M.; Ledbetter, D.H.; Mansour, S.; Martin, C.L.; Moss, C.; Mumford, A.; Ouwehand, W.H.; Park, S.M.; Riggs, E.R.; Scott, R.H.; Sisodiya, S.; Vooren, S. van der; Wapner, R.J.; Wilkie, A.O.; Wright, C.F.; Silfhout, A.T. van; Leeuw, N. de; Vries, B. de; Washingthon, N.L.; Smith, C.L.; Westerfield, M.; Schofield, P.; Ruef, B.J.; Gkoutos, G.V.; Haendel, M.; Smedley, D.; Lewis, S.E.; Robinson, P.N.

    2014-01-01

    The Human Phenotype Ontology (HPO) project, available at http://www.human-phenotype-ontology.org, provides a structured, comprehensive and well-defined set of 10,088 classes (terms) describing human phenotypic abnormalities and 13,326 subclass relations between the HPO classes. In addition we have d

  4. Metabolomics as a tool for target identification in strain improvement: the influence of phenotype definition.

    Science.gov (United States)

    Braaksma, Machtelt; Bijlsma, Sabina; Coulier, Leon; Punt, Peter J; van der Werf, Mariët J

    2011-01-01

    For the optimization of microbial production processes, the choice of the quantitative phenotype to be optimized is crucial. For instance, for the optimization of product formation, either product concentration or productivity can be pursued, potentially resulting in different targets for strain improvement. The choice of a quantitative phenotype is highly relevant for classical improvement approaches, and even more so for modern systems biology approaches. In this study, the information content of a metabolomics dataset was determined with respect to different quantitative phenotypes related to the formation of specific products. To this end, the production of two industrially relevant products by Aspergillus niger was evaluated: (i) the enzyme glucoamylase, and (ii) the more complex product group of secreted proteases, consisting of multiple enzymes. For both products, six quantitative phenotypes associated with activity and productivity were defined, also taking into account different time points of sampling during the fermentation. Both linear and nonlinear relationships between the metabolome data and the different quantitative phenotypes were considered. The multivariate data analysis tool partial least-squares (PLS) was used to evaluate the information content of the datasets for all the different quantitative phenotypes defined. Depending on the product studied, different quantitative phenotypes were found to have the highest information content in specific metabolomics datasets. A detailed analysis of the metabolites that showed strong correlation with these quantitative phenotypes revealed that various sugar derivatives correlated with glucoamylase activity. For the reduction of protease activity, mainly as-yet-unidentified compounds correlated.

  5. The need for agriculture phenotyping: "moving from genotype to phenotype".

    Science.gov (United States)

    Boggess, Mark V; Lippolis, John D; Hurkman, William J; Fagerquist, Clifton K; Briggs, Steve P; Gomes, Aldrin V; Righetti, Pier Giorgio; Bala, Kumar

    2013-11-20

    Increase in the world population has called for the increased demand for agricultural productivity. Traditional methods to augment crop and animal production are facing exacerbating pressures in keeping up with population growth. This challenge has in turn led to the transformational change in the use of biotechnology tools to meet increased productivity for both plant and animal systems. Although many challenges exist, the use of proteomic techniques to understand agricultural problems is steadily increasing. This review discusses the impact of genomics, proteomics, metabolomics and phenotypes on plant, animal and bacterial systems to achieve global food security and safety and we highlight examples of intra and extra mural research work that is currently being done to increase agricultural productivity. This review focuses on the global demand for increased agricultural productivity arising from population growth and how we can address this challenge using biotechnology. With a population well above seven billion humans, in a very unbalanced nutritional state (20% overweight, 20% risking starvation) drastic measures have to be taken at the political, infrastructure and scientific levels. While we cannot influence politics, it is our duty as scientists to see what can be done to feed humanity. Hence we highlight the transformational change in the use of biotechnology tools over traditional methods to increase agricultural productivity (plant and animal). Specifically, this review deals at length on how a three-pronged attack, namely combined genomics, proteomics and metabolomics, can help to ensure global food security and safety. This article is part of a Special Issue entitled: Translational Plant Proteomics. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. The Cognitive Phenotype of Spina Bifida Meningomyelocele

    Science.gov (United States)

    Dennis, Maureen; Barnes, Marcia A.

    2010-01-01

    A cognitive phenotype is a product of both assets and deficits that specifies what individuals with spina bifida meningomyelocele (SBM) can and cannot do and why they can or cannot do it. In this article, we review the cognitive phenotype of SBM and describe the processing assets and deficits that cut within and across content domains, sensory…

  7. Emerging semantics to link phenotype and environment

    Directory of Open Access Journals (Sweden)

    Anne E. Thessen

    2015-12-01

    Full Text Available Understanding the interplay between environmental conditions and phenotypes is a fundamental goal of biology. Unfortunately, data that include observations on phenotype and environment are highly heterogeneous and thus difficult to find and integrate. One approach that is likely to improve the status quo involves the use of ontologies to standardize and link data about phenotypes and environments. Specifying and linking data through ontologies will allow researchers to increase the scope and flexibility of large-scale analyses aided by modern computing methods. Investments in this area would advance diverse fields such as ecology, phylogenetics, and conservation biology. While several biological ontologies are well-developed, using them to link phenotypes and environments is rare because of gaps in ontological coverage and limits to interoperability among ontologies and disciplines. In this manuscript, we present (1 use cases from diverse disciplines to illustrate questions that could be answered more efficiently using a robust linkage between phenotypes and environments, (2 two proof-of-concept analyses that show the value of linking phenotypes to environments in fishes and amphibians, and (3 two proposed example data models for linking phenotypes and environments using the extensible observation ontology (OBOE and the Biological Collections Ontology (BCO; these provide a starting point for the development of a data model linking phenotypes and environments.

  8. The Cognitive Phenotype of Spina Bifida Meningomyelocele

    Science.gov (United States)

    Dennis, Maureen; Barnes, Marcia A.

    2010-01-01

    A cognitive phenotype is a product of both assets and deficits that specifies what individuals with spina bifida meningomyelocele (SBM) can and cannot do and why they can or cannot do it. In this article, we review the cognitive phenotype of SBM and describe the processing assets and deficits that cut within and across content domains, sensory…

  9. Effects of polyandry on male phenotypic diversity.

    Science.gov (United States)

    Barbosa, M; Dornelas, M; Magurran, A E

    2010-11-01

    Polyandry has the potential to affect the distribution of phenotypes and to shape the direction of sexual selection. Here, we explore this potential using Trinidadian guppies as a model system and ask whether polyandry leads to directional and/or diversifying selection of male phenotypic traits. In this study, we compare the phenotypic diversity of offspring from multiply and singly sired broods. To quantify phenotypic diversity, we first combine phenotypic traits using multivariate methods, and then take the dispersion of individuals in multivariate space as our measure of diversity. We show that, when each trait is examined separately, polyandry generates offspring with a higher proportion of bright coloration, indicating directional selection. However, our multivariate approach reveals that this directionality is accompanied by an increase in phenotypic diversity. These results suggest that polyandry (i) selects for the production of sons with the preferred brighter colour phenotypes whereas (ii) enhancing the diversity of male sexual traits. Promoting phenotypic diversity may be advantageous in coping with environmental and reproductive variability by increasing long-term fitness. © 2010 The Authors. Journal Compilation © 2010 European Society For Evolutionary Biology.

  10. Disc degeneration-related clinical phenotypes.

    Science.gov (United States)

    Battié, Michele C; Lazáry, Aron; Fairbank, Jeremy; Eisenstein, Stephen; Heywood, Chris; Brayda-Bruno, Marco; Varga, Péter Pál; McCall, Iain

    2014-06-01

    The phenotype, or observable trait of interest, is at the core of studies identifying associated genetic variants and their functional pathways, as well as diagnostics. Yet, despite remarkable technological developments in genotyping and progress in genetic research, relatively little attention has been paid to the equally important issue of phenotype. This is especially true for disc degeneration-related disorders, and the concept of degenerative disc disease, in particular, where there is little consensus or uniformity of definition. Greater attention and rigour are clearly needed in the development of disc degeneration-related clinical phenotypes if we are to see more rapid advancements in knowledge of this area. When selecting phenotypes, a basic decision is whether to focus directly on the complex clinical phenotype (e.g. the clinical syndrome of spinal stenosis), which is ultimately of interest, or an intermediate phenotype (e.g. dural sac cross-sectional area). While both have advantages, it cannot be assumed that associated gene variants will be similarly relevant to both. Among other considerations are factors influencing phenotype identification, comorbidities that are often present, and measurement issues. Genodisc, the European research consortium project on disc-related clinical pathologies has adopted a strategy that will allow for the careful characterisation and examination of both the complex clinical phenotypes of interest and their components.

  11. Regulatory mechanisms link phenotypic plasticity to evolvability

    NARCIS (Netherlands)

    van Gestel, Jordi; Weissing, Franz J

    2016-01-01

    Organisms have a remarkable capacity to respond to environmental change. They can either respond directly, by means of phenotypic plasticity, or they can slowly adapt through evolution. Yet, how phenotypic plasticity links to evolutionary adaptability is largely unknown. Current studies of plasticit

  12. The Neuroanatomy of the Autistic Phenotype

    Science.gov (United States)

    Fahim, Cherine; Meguid, Nagwa A.; Nashaat, Neveen H.; Yoon, Uicheul; Mancini-Marie, Adham; Evans, Alan C.

    2012-01-01

    The autism phenotype is associated with an excess of brain volume due in part to decreased pruning during development. Here we aimed at assessing brain volume early in development to further elucidate previous findings in autism and determine whether this pattern is restricted to idiopathic autism or shared within the autistic phenotype (fragile X…

  13. Adjusting phenotypes by noise control.

    Directory of Open Access Journals (Sweden)

    Kyung H Kim

    2012-01-01

    Full Text Available Genetically identical cells can show phenotypic variability. This is often caused by stochastic events that originate from randomness in biochemical processes involving in gene expression and other extrinsic cellular processes. From an engineering perspective, there have been efforts focused on theory and experiments to control noise levels by perturbing and replacing gene network components. However, systematic methods for noise control are lacking mainly due to the intractable mathematical structure of noise propagation through reaction networks. Here, we provide a numerical analysis method by quantifying the parametric sensitivity of noise characteristics at the level of the linear noise approximation. Our analysis is readily applicable to various types of noise control and to different types of system; for example, we can orthogonally control the mean and noise levels and can control system dynamics such as noisy oscillations. As an illustration we applied our method to HIV and yeast gene expression systems and metabolic networks. The oscillatory signal control was applied to p53 oscillations from DNA damage. Furthermore, we showed that the efficiency of orthogonal control can be enhanced by applying extrinsic noise and feedback. Our noise control analysis can be applied to any stochastic model belonging to continuous time Markovian systems such as biological and chemical reaction systems, and even computer and social networks. We anticipate the proposed analysis to be a useful tool for designing and controlling synthetic gene networks.

  14. Phenotypic screening for developmental neurotoxicity ...

    Science.gov (United States)

    There are large numbers of environmental chemicals with little or no available information on their toxicity, including developmental neurotoxicity. Because of the resource-intensive nature of traditional animal tests, high-throughput (HTP) methods that can rapidly evaluate chemicals for the potential to affect the developing brain are being explored. Typically, HTP screening uses biochemical and molecular assays to detect the interaction of a chemical with a known target or molecular initiating event (e.g., the mechanism of action). For developmental neurotoxicity, however, the mechanism(s) is often unknown. Thus, we have developed assays for detecting chemical effects on the key events of neurodevelopment at the cellular level (e.g., proliferation, differentiation, neurite growth, synaptogenesis, network formation). Cell-based assays provide a test system at a level of biological complexity that encompasses many potential neurotoxic mechanisms. For example, phenotypic assessment of neurite outgrowth at the cellular level can detect chemicals that target kinases, ion channels, or esterases at the molecular level. The results from cell-based assays can be placed in a conceptual framework using an Adverse Outcome Pathway (AOP) which links molecular, cellular, and organ level effects with apical measures of developmental neurotoxicity. Testing a wide range of concentrations allows for the distinction between selective effects on neurodevelopmental and non-specific

  15. Bronchiectasis: Phenotyping a Complex Disease.

    Science.gov (United States)

    Chalmers, James D

    2017-03-15

    Bronchiectasis is a long-neglected disease currently experiencing a surge in interest. It is a highly complex condition with numerous aetiologies, co-morbidities and a heterogeneous disease presentation and clinical course. The past few years have seen major advances in our understanding of the disease, primarily through large real-life cohort studies. The main outcomes of interest in bronchiectasis are symptoms, exacerbations, treatment response, disease progression and death. We are now more able to identify clearly the radiological, clinical, microbiological and inflammatory contributors to these outcomes. Over the past couple of years, multidimensional scoring systems such as the Bronchiectasis Severity Index have been introduced to predict disease severity and mortality. Although there are currently no licensed therapies for bronchiectasis, an increasing number of clinical trials are planned or ongoing. While this emerging evidence is awaited, bronchiectasis guidelines will continue to be informed largely by real-life evidence from observational studies and patient registries. Key developments in the bronchiectasis field include the establishment of international disease registries and characterisation of disease phenotypes using cluster analysis and biological data.

  16. Investigating the Association between Autistic-Like and Internalizing Traits in a Community-Based Twin Sample

    Science.gov (United States)

    Hallett, Victoria; Ronald, Angelica; Happe, Francesca

    2009-01-01

    The phenotypic and etiologic relation between internalizing and autistic-like traits is studied using a community-based twin sample. Internalizing and autistic-like traits showed moderate phenotypic overlap but have specific genetic influences.

  17. EHR-based phenotyping: Bulk learning and evaluation.

    Science.gov (United States)

    Chiu, Po-Hsiang; Hripcsak, George

    2017-06-01

    In data-driven phenotyping, a core computational task is to identify medical concepts and their variations from sources of electronic health records (EHR) to stratify phenotypic cohorts. A conventional analytic framework for phenotyping largely uses a manual knowledge engineering approach or a supervised learning approach where clinical cases are represented by variables encompassing diagnoses, medicinal treatments and laboratory tests, among others. In such a framework, tasks associated with feature engineering and data annotation remain a tedious and expensive exercise, resulting in poor scalability. In addition, certain clinical conditions, such as those that are rare and acute in nature, may never accumulate sufficient data over time, which poses a challenge to establishing accurate and informative statistical models. In this paper, we use infectious diseases as the domain of study to demonstrate a hierarchical learning method based on ensemble learning that attempts to address these issues through feature abstraction. We use a sparse annotation set to train and evaluate many phenotypes at once, which we call bulk learning. In this batch-phenotyping framework, disease cohort definitions can be learned from within the abstract feature space established by using multiple diseases as a substrate and diagnostic codes as surrogates. In particular, using surrogate labels for model training renders possible its subsequent evaluation using only a sparse annotated sample. Moreover, statistical models can be trained and evaluated, using the same sparse annotation, from within the abstract feature space of low dimensionality that encapsulates the shared clinical traits of these target diseases, collectively referred to as the bulk learning set. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Predictability of extreme values in geophysical models

    Directory of Open Access Journals (Sweden)

    A. E. Sterk

    2012-09-01

    Full Text Available Extreme value theory in deterministic systems is concerned with unlikely large (or small values of an observable evaluated along evolutions of the system. In this paper we study the finite-time predictability of extreme values, such as convection, energy, and wind speeds, in three geophysical models. We study whether finite-time Lyapunov exponents are larger or smaller for initial conditions leading to extremes. General statements on whether extreme values are better or less predictable are not possible: the predictability of extreme values depends on the observable, the attractor of the system, and the prediction lead time.

  19. Physiological phenotyping of plants for crop improvement.

    Science.gov (United States)

    Ghanem, Michel Edmond; Marrou, Hélène; Sinclair, Thomas R

    2015-03-01

    Future progress in crop breeding requires a new emphasis in plant physiological phenotyping for specific, well-defined traits. Success in physiological phenotyping to identify parents for use in breeding efforts for improved cultivars has been achieved by employing a multi-tier screening approach with different levels of sophistication and trait resolution. Subsequently, cultivar development required an integrated mix of classical breeding approaches and one or more tiers of phenotyping to identify genotypes expressing the desired trait. The role of high throughput systems can be useful; here, we emphasize that this approach is likely to offer useful results at an initial tier of phenotyping and will need to be complemented with more directed tiers of phenotyping. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. The Clustering of Extremely Red Objects

    CERN Document Server

    Palamara, David P; Jannuzi, Buell T; Dey, Arjun; Stern, Daniel; Pimbblet, Kevin A; Weiner, Benjamin J; Ashby, Matthew L N; Kochanek, C S; Gonzalez, Anthony; Brodwin, Mark; Floc'h, Emeric Le; Rieke, Marcia

    2012-01-01

    We measure the clustering of Extremely Red Objects (EROs) in ~8 deg^2 of the NOAO Deep Wide Field Survey Bo\\"otes field in order to establish robust links between ERO z~1.2 and local galaxy z5.0 (28,724 galaxies), (I-K_s)>4.0 (22,451 galaxies) and (I-[3.6])>5.0 (64,370 galaxies). Magnitude-limited samples show the correlation length (r_0) to increase for more luminous EROs, implying a correlation with stellar mass. We can separate star-forming and passive ERO populations using the (K_s-[24]) and ([3.6]-[24]) colors to K_s=18.4 and [3.6]=17.5, respectively. Star-forming and passive EROs in magnitude limited samples have different clustering properties and host dark halo masses, and cannot be simply understood as a single population. Based on the clustering, we find that bright passive EROs are the likely progenitors of >4L^* elliptical galaxies. Bright EROs with ongoing star formation were found to occupy denser environments than star-forming galaxies in the local Universe, making these the likely progenitors ...

  1. A Fast Reduced Kernel Extreme Learning Machine.

    Science.gov (United States)

    Deng, Wan-Yu; Ong, Yew-Soon; Zheng, Qing-Hua

    2016-04-01

    In this paper, we present a fast and accurate kernel-based supervised algorithm referred to as the Reduced Kernel Extreme Learning Machine (RKELM). In contrast to the work on Support Vector Machine (SVM) or Least Square SVM (LS-SVM), which identifies the support vectors or weight vectors iteratively, the proposed RKELM randomly selects a subset of the available data samples as support vectors (or mapping samples). By avoiding the iterative steps of SVM, significant cost savings in the training process can be readily attained, especially on Big datasets. RKELM is established based on the rigorous proof of universal learning involving reduced kernel-based SLFN. In particular, we prove that RKELM can approximate any nonlinear functions accurately under the condition of support vectors sufficiency. Experimental results on a wide variety of real world small instance size and large instance size applications in the context of binary classification, multi-class problem and regression are then reported to show that RKELM can perform at competitive level of generalized performance as the SVM/LS-SVM at only a fraction of the computational effort incurred.

  2. Proposal of Enhanced Extreme Programming Model

    Directory of Open Access Journals (Sweden)

    M. Rizwan Jameel Qureshi

    2015-01-01

    Full Text Available Extreme programming is one of the commonly used agile methodologies in software development. It is very responsive to changing requirements even in the late phases of the project. However, quality activities in extreme programming phases are implemented sequentially along with the activities that work on the functional requirements. This reduces the agility to deliver increments continuously and makes an inverse relationship between quality and agility. Due to this relationship, extreme programming does not consume enough time on making extensive documentation and robust design. To overcome these issues, an enhanced extreme programming model is proposed. Enhanced extreme programming introduces parallelism in the activities' execution through putting quality activities into a separate execution line. In this way, the focus on delivering increments quickly is achieved without affecting the quality of the final output. In enhanced extreme programming, the quality concept is extended to include refinement of all phases of classical extreme programming and creating architectural design based on the refined design documents.

  3. Phenotypic and behavioral variability within Angelman Syndrome group with UPD

    Directory of Open Access Journals (Sweden)

    Fridman Cintia

    2002-01-01

    Full Text Available The Angelman syndrome (AS (developmental delay, mental retardation, speech impairment, ataxia, outbursts of laughter, seizures can result either from a 15q11-q13 deletion, or from paternal uniparental disomy (UPD, imprinting, or UBE3A mutations. We describe here the phenotypic and behavioral variability detected in eight UPD patients out of a group of 58 AS patients studied. All of them presented developmental delay, mental retardation, ataxia, speech impairment, and frequent drooling. Only one had microcephaly, whereas in two of them the OFC (head circumference was above the 98th percentile. The weight of all patients was above the 50th percentile, and in three of them the height was above the 90th percentile. Three were able to say a few words and to communicate by gestures. Two patients presented hyperphagia, and three presented skin picking, common features in the Prader-Willi syndrome (PWS. Four patients (4/7 had wide-spaced teeth. Five presented seizures, and two others did not manifest frequent laughter. One patient was very different from the others, as he showed a better understanding and abilities to communicate, to play video games and to draw. We suggest here that there seems to be an extreme phenotypic and behavioral variability within the UPD group, and that both typical patients and those with mental retardation, language impairment, happy disposition, and hyperactivity should be tested for AS.

  4. Otopalatodigital spectrum disorders: refinement of the phenotypic and mutational spectrum.

    Science.gov (United States)

    Moutton, Sébastien; Fergelot, Patricia; Naudion, Sophie; Cordier, Marie-Pierre; Solé, Guilhem; Guerineau, Elodie; Hubert, Christophe; Rooryck, Caroline; Vuillaume, Marie-Laure; Houcinat, Nada; Deforges, Julie; Bouron, Julie; Devès, Sylvie; Le Merrer, Martine; David, Albert; Geneviève, David; Giuliano, Fabienne; Journel, Hubert; Megarbane, André; Faivre, Laurence; Chassaing, Nicolas; Francannet, Christine; Sarrazin, Elisabeth; Stattin, Eva-Lena; Vigneron, Jacqueline; Leclair, Danielle; Abadie, Caroline; Sarda, Pierre; Baumann, Clarisse; Delrue, Marie-Ange; Arveiler, Benoit; Lacombe, Didier; Goizet, Cyril; Coupry, Isabelle

    2016-08-01

    Otopalatodigital spectrum disorders (OPDSD) constitute a group of dominant X-linked osteochondrodysplasias including four syndromes: otopalatodigital syndromes type 1 and type 2 (OPD1 and OPD2), frontometaphyseal dysplasia, and Melnick-Needles syndrome. These syndromes variably associate specific facial and extremities features, hearing loss, cleft palate, skeletal dysplasia and several malformations, and show important clinical overlap over the different entities. FLNA gain-of-function mutations were identified in these conditions. FLNA encodes filamin A, a scaffolding actin-binding protein. Here, we report phenotypic descriptions and molecular results of FLNA analysis in a large series of 27 probands hypothesized to be affected by OPDSD. We identified 11 different missense mutations in 15 unrelated probands (n=15/27, 56%), of which seven were novel, including one of unknown significance. Segregation analyses within families made possible investigating 20 additional relatives carrying a mutation. This series allows refining the phenotypic and mutational spectrum of FLNA mutations causing OPDSD, and providing suggestions to avoid the overdiagnosis of OPD1.

  5. Interpretation of Extreme Scattering Events

    CERN Document Server

    Walker, M A

    2000-01-01

    Extreme Scattering Events are sometimes manifest in the light-curves of compact radio-quasars at frequencies of a few GHz. These events are not understood. The model which appears to offer the best explanation requires a new population of AU-sized, neutral gas clouds; these clouds would then make up a large fraction of the Galaxy's dark matter. Independent of the question of which theoretical model is correct, if we extrapolate the observed behaviour to low radio-frequencies, we expect that the sky should be criss-crossed by a network of narrow caustics, at frequencies below about 700 MHz. Consequently at these frequencies sources should typically manifest additional, faint images which are substantially delayed with respect to the primary image. Although some examples of this type of behaviour are already known, it is expected that these are just the tip of the iceberg, with strong selection biases having been imposed by the instrumentation employed to date.

  6. QCD matter in extreme environments

    CERN Document Server

    Fukushima, Kenji

    2011-01-01

    We review various theoretical approaches to the states of QCD matter out of quarks and gluons in extreme environments such as the high-temperature states at zero and finite baryon density and the dimensionally reduced state under an intense magnetic field. The topics at high temperature include the Polyakov loop and the 't Hooft loop in the perturbative regime, the Polyakov loop behaviour and the phase transition in some of non-perturbative methods; the strong-coupling expansion, the large-Nc limit and the holographic QCD models. These analyses are extended to hot and dense matter with a finite baryon chemical potential. We point out that the difficulty in the finite-density problem has similarity to that under a strong magnetic field. We make a brief summary of results related to the topological contents probed by the magnetic field and the Chiral Magnetic Effect. We also address the close connection to the (1+1) dimensional system.

  7. Extreme resilience in cochleate nanoparticles.

    Science.gov (United States)

    Bozó, Tamás; Brecska, Richárd; Gróf, Pál; Kellermayer, Miklós S Z

    2015-01-20

    Cochleates, prospective nanoscale drug delivery vehicles, are rolls of negatively charged phospholipid membrane layers. The membrane layers are held together by calcium ions; however, neither the magnitude of membrane interaction forces nor the overall mechanical properties of cochleates have been known. Here, we manipulated individual nanoparticles with atomic force microscopy to characterize their nanomechanical behavior. Their stiffness (4.2-12.5 N/m) and membrane-rupture forces (45.3-278 nN) are orders of magnitude greater than those of the tough viral nanoshells. Even though the fundamental building material of cochleates is a fluid membrane, the combination of supramolecular geometry, the cross-linking action of calcium, and the tight packing of the ions apparently lead to extreme mechanical resilience. The supramolecular design of cochleates may provide efficient protection for encapsulated materials and give clues to understanding biomolecular structures of similar design, such as the myelinated axon.

  8. Extreme ultraviolet Talbot interference lithography.

    Science.gov (United States)

    Li, Wei; Marconi, Mario C

    2015-10-05

    Periodic nanopatterns can be generated using lithography based on the Talbot effect or optical interference. However, these techniques have restrictions that limit their performance. High resolution Talbot lithography is limited by the very small depth of focus and the demanding requirements in the fabrication of the master mask. Interference lithography, with large DOF and high resolution, is limited to simple periodic patterns. This paper describes a hybrid extreme ultraviolet lithography approach that combines Talbot lithography and interference lithography to render an interference pattern with a lattice determined by a Talbot image. As a result, the method enables filling the arbitrary shaped cells produced by the Talbot image with interference patterns. Detailed modeling, system design and experimental results using a tabletop EUV laser are presented.

  9. Weather extremes could affect agriculture

    Science.gov (United States)

    Balcerak, Ernie

    2012-05-01

    As Earth's climate warms, agricultural producers will need to adapt. Changes, especially increases in extreme events, are already having an impact on food production, according to speakers at a 1 May session on agriculture and food security at the AGU Science Policy Conference. Christopher Field, director of the Department of Global Ecology at the Carnegie Institution for Science of Washington, D. C., pointed out the complex factors that come into play in understanding food security, including spatially varying controls and stresses, incomplete models, and the potential for threshold responses. Factors that are likely to cause problems include increasing population; increasing preference for meat, which needs more land and energy inputs to produce; climate change; and increasing use of agricultural lands for biomass energy.

  10. Reach Envelope of Human Extremities

    Institute of Scientific and Technical Information of China (English)

    YANG Jingzhou(杨景周); ZHANG Yunqing(张云清); CHEN Liping(陈立平); ABDEL-MALEK Karim

    2004-01-01

    Significant attention in recent years has been given to obtain a better understanding of human joint ranges, measurement, and functionality, especially in conjunction with commands issued by the central nervous system. While researchers have studied motor commands needed to drive a limb to follow a path trajectory, various computer algorithms have been reported that provide adequate analysis of limb modeling and motion. This paper uses a rigorous mathematical formulation to model human limbs, understand their reach envelope, delineate barriers therein where a trajectory becomes difficult to control, and help visualize these barriers. Workspaces of a typical forearm with 9 degrees of freedom, a typical finger modeled as a 4- degree-of-freedom system, and a lower extremity with 4 degrees of freedom are discussed. The results show that using the proposed formulation, joint limits play an important role in distinguishing the barriers.

  11. Generic Hurricane Extreme Seas State

    DEFF Research Database (Denmark)

    Wehmeyer, Christof; Skourup, Jesper; Frigaard, Peter

    2012-01-01

    Extreme sea states, which the IEC 61400-3 (2008) standard requires for the ultimate limit state (ULS) analysis of offshore wind turbines are derived to establish the design basis for the conceptual layout of deep water floating offshore wind turbine foundations in hurricane affected areas...... data is required for a type specific conceptual design. ULS conditions for different return periods are developed, which can subsequently be applied in siteindependent analysis and conceptual design. Recordings provided by National Oceanic and Atmospheric Administration (NOAA), of hurricanes along...... for hurricane generates seas by Young (1998, 2003, and 2006), requiring maximum wind speeds, forward velocity and radius to maximum wind speed. An averaged radius to maximum sustained wind speeds, according to Hsu et al. (1998) and averaged forward speed of cyclonic storms are applied in the initial state...

  12. Pneumatic tourniquets in extremity surgery.

    LENUS (Irish Health Repository)

    Wakai, A

    2012-02-03

    Pneumatic tourniquets maintain a relatively bloodless field during extremity surgery, minimize blood loss, aid identification of vital structures, and expedite the procedure. However, they may induce an ischemia-reperfusion injury with potentially harmful local and systemic consequences. Modern pneumatic tourniquets are designed with mechanisms to regulate and maintain pressure. Routine maintenance helps ensure that these systems are working properly. The complications of tourniquet use include postoperative swelling, delay of recovery of muscle power, compression neurapraxia, wound hematoma with the potential for infection, vascular injury, tissue necrosis, and compartment syndrome. Systemic complications can also occur. The incidence of complications can be minimized by use of wider tourniquets, careful preoperative patient evaluation, and adherence to accepted principles of tourniquet use.

  13. Diarrheagenic Escherichia coli Markers and Phenotypes among Fecal E. coli Isolates Collected from Nicaraguan Infants ▿

    OpenAIRE

    Reyes, Daniel; Vilchez, Samuel; Paniagua, Margarita; Colque-Navarro, Patricia; Weintraub, Andrej; Möllby, Roland; Kühn, Inger

    2010-01-01

    We analyzed the prevalence of diarrheagenic Escherichia coli (DEC) markers and common phenotypes in 2,164 E. coli isolates from 282 DEC-positive samples. Enteropathogenic E. coli (EPEC) and enteroaggregative E. coli (EAEC) were very diverse and were not correlated with diarrhea. Enterotoxigenic E. coli (ETEC) estA and enterohemorrhagic E. coli (EHEC) belonged to a few phenotypes and were significantly correlated with diarrhea.

  14. Monochorionic twins with the same blood karyotype of 46,XY/47,XYY but different phenotypes.

    Science.gov (United States)

    Wuttikonsammakit, Piyawadee; Tanawattanacharoen, Somchai; Uerpairojkit, Boonchai

    2010-02-01

    We report the case of a 13-year-old woman who was pregnant with phenotypically discordant monochorionic twins: one with cystic hygroma and hydrops, the other one normal. Fetal blood sampling was performed by intrahepatic blood collection for karyotyping of both fetuses, revealing the same genotype of 46,XY/47,XYY in 2:1 proportion. Phenotypic discordance in monozygotic twins can have various causes, such as placental vascular anatomy, differences in allocation of the number of blastomeres or genetic postzygotic events.

  15. Diarrheagenic Escherichia coli Markers and Phenotypes among Fecal E. coli Isolates Collected from Nicaraguan Infants ▿

    OpenAIRE

    2010-01-01

    We analyzed the prevalence of diarrheagenic Escherichia coli (DEC) markers and common phenotypes in 2,164 E. coli isolates from 282 DEC-positive samples. Enteropathogenic E. coli (EPEC) and enteroaggregative E. coli (EAEC) were very diverse and were not correlated with diarrhea. Enterotoxigenic E. coli (ETEC) estA and enterohemorrhagic E. coli (EHEC) belonged to a few phenotypes and were significantly correlated with diarrhea.

  16. Heritability of eleven metabolic phenotypes in Danish and Chinese twins

    DEFF Research Database (Denmark)

    Li, Shuxia; Duan, Hongmei; Pang, Zengchang

    2013-01-01

    A twin-based comparative study on the genetic influences in metabolic endophenotypes in two populations of substantial ethnic, environmental, and cultural differences was performed. Design and Methods: Data on 11 metabolic phenotypes including anthropometric measures, blood glucose, and lipids...... levels as well as blood pressure were available from 756 pairs of Danish twins (309 monozygotic and 447 dizygotic twin pairs) with a mean age of 38 years (range: 18-67) and from 325 pairs of Chinese twins (183 monozygotic and 142 dizygotic twin pairs) with a mean age of 40.5 years (range: 18-69). Twin...... similar heritability patterns in the two samples with body weight showing only a slight difference. Higher genetic influences were estimated for fasting blood glucose level in Chinese twins, whereas the Danish twins showed more genetic regulation over most lipids phenotypes. Systolic blood pressure...

  17. Screening for microbial metabolites affecting phenotype of Caenorhabditis elegans.

    Science.gov (United States)

    Yamamuro, Daisuke; Uchida, Ryuji; Takahashi, Yoko; Masuma, Rokuro; Tomoda, Hiroshi

    2011-01-01

    Microbial samples, including our library of known microbial compounds (ca. 300) and microbial culture broths (ca. 9000), were screened for small molecules affecting the phenotype of Caenorhabditis elegans. As a result, seven known compounds were found to induce phenotypic abnormality of C. elegans. Staurosporine exhibited morphological defects in the vulva and tail of C. elegans, avermectin B1a exhibited hatching inhibition of starting eggs on day 1 at 25-100 µM and growth inhibition at 0.01-12.5 µM, siccanin and antimycin A inhibited the growth of C. elegans, and fluorouracil inhibited hatching of eggs newly spawned by adult C. elegans. Toromycin induced morphological defects in the intestine. 5-(4-Methoxyphenyl)-oxazole, isolated as a fungal metabolite for the first time, inhibited the hatching of eggs newly spawned by adult C. elegans.

  18. Acquired Upper Extremity Growth Arrest.

    Science.gov (United States)

    Gauger, Erich M; Casnovsky, Lauren L; Gauger, Erica J; Bohn, Deborah C; Van Heest, Ann E

    2017-01-01

    This study reviewed the clinical history and management of acquired growth arrest in the upper extremity in pediatric patients. The records of all patients presenting from 1996 to 2012 with radiographically proven acquired growth arrest were reviewed. Records were examined to determine the etiology and site of growth arrest, management, and complications. Patients with tumors or hereditary etiology were excluded. A total of 44 patients (24 boys and 20 girls) with 51 physeal arrests who presented at a mean age of 10.6 years (range, 0.8-18.2 years) were included in the study. The distal radius was the most common site (n=24), followed by the distal humerus (n=8), metacarpal (n=6), distal ulna (n=5), proximal humerus (n=4), radial head (n=3), and olecranon (n=1). Growth arrest was secondary to trauma (n=22), infection (n=11), idiopathy (n=6), inflammation (n=2), compartment syndrome (n=2), and avascular necrosis (n=1). Twenty-six patients (59%) underwent surgical intervention to address deformity caused by the physeal arrest. Operative procedures included ipsilateral unaffected bone epiphysiodesis (n=21), shortening osteotomy (n=10), lengthening osteotomy (n=8), excision of physeal bar or bone fragment (n=2), angular correction osteotomy (n=1), and creation of single bone forearm (n=1). Four complications occurred; 3 of these required additional procedures. Acquired upper extremity growth arrest usually is caused by trauma or infection, and the most frequent site is the distal radius. Growth disturbances due to premature arrest can be treated effectively with epiphysiodesis or osteotomy. In this series, the specific site of anatomic growth arrest was the primary factor in determining treatment. [Orthopedics. 2017; 40(1):e95-e103.]. Copyright 2016, SLACK Incorporated.

  19. A Miniature Extreme Environment Powder Delivery System (M-PoDS) Project

    Data.gov (United States)

    National Aeronautics and Space Administration — This innovation is a low mass, low volume, gas based system that will acquire size selective powdered samples from the extreme ambient (such as Mars or Venus...

  20. The Extreme Conditions Beamline P02.2 and the Extreme Conditions Science Infrastructure at PETRA III

    Energy Technology Data Exchange (ETDEWEB)

    Liermann, H.-P., E-mail: hanns-peter.liermann@desy.de; Konôpková, Z. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Morgenroth, W. [University of Frankfurt, Frankfurt (Germany); Glazyrin, K.; Bednarčik, J.; McBride, E. E. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Petitgirard, S. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); University of Bayreuth, Bayreuth (Germany); Delitz, J. T.; Wendt, M.; Bican, Y.; Ehnes, A.; Schwark, I.; Rothkirch, A.; Tischer, M.; Heuer, J.; Schulte-Schrepping, H.; Kracht, T.; Franz, H. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)

    2015-06-19

    Performance description of the Extreme Conditions Beamline (ECB, P02.2) at PETRA III that is optimized for micro-diffraction at simultaneous high pressure and high and low temperatures created in different diamond anvil cells environments. Additional information of the capabilities of the Extreme Conditions Science Infrastructure for DAC work is provided. A detailed description is presented of the Extreme Conditions Beamline P02.2 for micro X-ray diffraction studies of matter at simultaneous high pressure and high/low temperatures at PETRA III, in Hamburg, Germany. This includes performance of the X-ray optics and instrumental resolution as well as an overview of the different sample environments available for high-pressure studies in the diamond anvil cell. Particularly emphasized are the high-brilliance and high-energy X-ray diffraction capabilities of the beamline in conjunction with the use of fast area detectors to conduct time-resolved compression studies in the millisecond time regime. Finally, the current capability of the Extreme Conditions Science Infrastructure to support high-pressure research at the Extreme Conditions Beamline and other PETRA III beamlines is described.