Sample records for quantitative transmission disequilibrium

  1. Linkage disequilibrium fine mapping of quantitative trait loci: A simulation study

    PubMed Central

    Abdallah, Jihad M; Goffinet, Bruno; Cierco-Ayrolles, Christine; Pérez-Enciso, Miguel

    2003-01-01

    Recently, the use of linkage disequilibrium (LD) to locate genes which affect quantitative traits (QTL) has received an increasing interest, but the plausibility of fine mapping using linkage disequilibrium techniques for QTL has not been well studied. The main objectives of this work were to (1) measure the extent and pattern of LD between a putative QTL and nearby markers in finite populations and (2) investigate the usefulness of LD in fine mapping QTL in simulated populations using a dense map of multiallelic or biallelic marker loci. The test of association between a marker and QTL and the power of the test were calculated based on single-marker regression analysis. The results show the presence of substantial linkage disequilibrium with closely linked marker loci after 100 to 200 generations of random mating. Although the power to test the association with a frequent QTL of large effect was satisfactory, the power was low for the QTL with a small effect and/or low frequency. More powerful, multi-locus methods may be required to map low frequent QTL with small genetic effects, as well as combining both linkage and linkage disequilibrium information. The results also showed that multiallelic markers are more useful than biallelic markers to detect linkage disequilibrium and association at an equal distance. PMID:12939203

  2. Adaptive transmission disequilibrium test for family trio design.

    PubMed

    Yuan, Min; Tian, Xin; Zheng, Gang; Yang, Yaning

    2009-01-01

    The transmission disequilibrium test (TDT) is a standard method to detect association using family trio design. It is optimal for an additive genetic model. Other TDT-type tests optimal for recessive and dominant models have also been developed. Association tests using family data, including the TDT-type statistics, have been unified to a class of more comprehensive and flexable family-based association tests (FBAT). TDT-type tests have high efficiency when the genetic model is known or correctly specified, but may lose power if the model is mis-specified. Hence tests that are robust to genetic model mis-specification yet efficient are preferred. Constrained likelihood ratio test (CLRT) and MAX-type test have been shown to be efficiency robust. In this paper we propose a new efficiency robust procedure, referred to as adaptive TDT (aTDT). It uses the Hardy-Weinberg disequilibrium coefficient to identify the potential genetic model underlying the data and then applies the TDT-type test (or FBAT for general applications) corresponding to the selected model. Simulation demonstrates that aTDT is efficiency robust to model mis-specifications and generally outperforms the MAX test and CLRT in terms of power. We also show that aTDT has power close to, but much more robust, than the optimal TDT-type test based on a single genetic model. Applications to real and simulated data from Genetic Analysis Workshop (GAW) illustrate the use of our adaptive TDT.

  3. Transmission disequilibrium testing of arginine vasopressin receptor 1A (AVPR1A) polymorphisms in autism.

    PubMed

    Kim, S-J; Young, L J; Gonen, D; Veenstra-VanderWeele, J; Courchesne, R; Courchesne, E; Lord, C; Leventhal, B L; Cook, E H; Insel, T R

    2002-01-01

    Impairment in social reciprocity is a central component of autism. In preclinical studies, arginine vasopressin (AVP) has been shown to increase a range of social behaviors, including affiliation and attachment, via the V(1a) receptor (AVPR1A) in the brain. Both the behavioral effects of AVP and the neural distribution of the V1a receptor vary greatly across mammalian species. This difference in regional receptor expression as well as differences in social behavior may result from a highly variable repetitive sequence in the 5' flanking region of the V1a gene (AVPR1A). Given this comparative evidence for a role in inter-species variation in social behavior, we explored whether within our own species, variation in the human AVPR1A may contribute to individual variations in social behavior, with autism representing an extreme form of social impairment. We genotyped two microsatellite polymorphisms from the 5' flanking region of AVPR1A for 115 autism trios and found nominally significant transmission disequilibrium between autism and one of the microsatellite markers by Multiallelic Transmission/Disequilibrium test (MTDT) that was not significant after Bonferroni correction. We also screened approximately 2 kb of the 5' flanking region and the coding region and identified 10 single nucleotide polymorphisms.

  4. Linkage disequilibrium interval mapping of quantitative trait loci.

    PubMed

    Boitard, Simon; Abdallah, Jihad; de Rochambeau, Hubert; Cierco-Ayrolles, Christine; Mangin, Brigitte

    2006-03-16

    For many years gene mapping studies have been performed through linkage analyses based on pedigree data. Recently, linkage disequilibrium methods based on unrelated individuals have been advocated as powerful tools to refine estimates of gene location. Many strategies have been proposed to deal with simply inherited disease traits. However, locating quantitative trait loci is statistically more challenging and considerable research is needed to provide robust and computationally efficient methods. Under a three-locus Wright-Fisher model, we derived approximate expressions for the expected haplotype frequencies in a population. We considered haplotypes comprising one trait locus and two flanking markers. Using these theoretical expressions, we built a likelihood-maximization method, called HAPim, for estimating the location of a quantitative trait locus. For each postulated position, the method only requires information from the two flanking markers. Over a wide range of simulation scenarios it was found to be more accurate than a two-marker composite likelihood method. It also performed as well as identity by descent methods, whilst being valuable in a wider range of populations. Our method makes efficient use of marker information, and can be valuable for fine mapping purposes. Its performance is increased if multiallelic markers are available. Several improvements can be developed to account for more complex evolution scenarios or provide robust confidence intervals for the location estimates.

  5. [Transmission disequilibrium test for nonsyndromic cleft lip and palate and segment homeobox gene-1 gene].

    PubMed

    Wu, Ping-An; Li, Yun-Liang; Wu, Han-Jiang; Wang, Kai; Fan, Guo-Zheng

    2007-09-01

    To investigate the relationship between muscle segment homeobox gene-1 (MSX1) and the genetic susceptibility of nonsyndromic cleft lip and palate (NSCLP) in Hunan Hans. One microsatellite DNA marker CA repeat in MSX1 intron region was used as genetic marker. The genotypes of 387 members in 129 NSCLP nuclear family trios were analyzed by polymerase chain reaction (PCR) and denaturing polyacrylamide gel electrophoresis. Then transmission disequilibrium test (TDT) and Logistic regression analysis were used to conduct association analysis. TDT analysis confirmed that CA4 allele in CL/P and CPO groups preferentially transmitted to the affected offspring (P = 0.018, P = 0.041). Logistic regression analysis indicated that the recessive model of inheritance was supported, and CA4 itself or CA4 acting as a marker for a disease allele or haplotype was inherited in a recessive fashion (P = 0.009). MSX1 gene is associated with NSCLP, and MSX1 gene may be directly involved either in the etiology of NSCLP or in linkage disequilibrium with disease-predisposing sites.

  6. Dosage Transmission Disequilibrium Test (dTDT) for Linkage and Association Detection

    PubMed Central

    Zhang, Zhehao; Wang, Jen-Chyong; Howells, William; Lin, Peng; Agrawal, Arpana; Edenberg, Howard J.; Tischfield, Jay A.; Schuckit, Marc A.; Bierut, Laura J.; Goate, Alison; Rice, John P.

    2013-01-01

    Both linkage and association studies have been successfully applied to identify disease susceptibility genes with genetic markers such as microsatellites and Single Nucleotide Polymorphisms (SNPs). As one of the traditional family-based studies, the Transmission/Disequilibrium Test (TDT) measures the over-transmission of an allele in a trio from its heterozygous parents to the affected offspring and can be potentially useful to identify genetic determinants for complex disorders. However, there is reduced information when complete trio information is unavailable. In this study, we developed a novel approach to “infer” the transmission of SNPs by combining both the linkage and association data, which uses microsatellite markers from families informative for linkage together with SNP markers from the offspring who are genotyped for both linkage and a Genome-Wide Association Study (GWAS). We generalized the traditional TDT to process these inferred dosage probabilities, which we name as the dosage-TDT (dTDT). For evaluation purpose, we developed a simulation procedure to assess its operating characteristics. We applied the dTDT to the simulated data and documented the power of the dTDT under a number of different realistic scenarios. Finally, we applied our methods to a family study of alcohol dependence (COGA) and performed individual genotyping on complete families for the top signals. One SNP (rs4903712 on chromosome 14) remained significant after correcting for multiple testing Methods developed in this study can be adapted to other platforms and will have widespread applicability in genomic research when case-control GWAS data are collected in families with existing linkage data. PMID:23691058

  7. Exploiting excess sharing: a more powerful test of linkage for affected sib pairs than the transmission/disequilibrium test.

    PubMed Central

    Wicks, J

    2000-01-01

    The transmission/disequilibrium test (TDT) is a popular, simple, and powerful test of linkage, which can be used to analyze data consisting of transmissions to the affected members of families with any kind pedigree structure, including affected sib pairs (ASPs). Although it is based on the preferential transmission of a particular marker allele across families, it is not a valid test of association for ASPs. Martin et al. devised a similar statistic for ASPs, Tsp, which is also based on preferential transmission of a marker allele but which is a valid test of both linkage and association for ASPs. It is, however, less powerful than the TDT as a test of linkage for ASPs. What I show is that the differences between the TDT and Tsp are due to the fact that, although both statistics are based on preferential transmission of a marker allele, the TDT also exploits excess sharing in identity-by-descent transmissions to ASPs. Furthermore, I show that both of these statistics are members of a family of "TDT-like" statistics for ASPs. The statistics in this family are based on preferential transmission but also, to varying extents, exploit excess sharing. From this family of statistics, we see that, although the TDT exploits excess sharing to some extent, it is possible to do so to a greater extent-and thus produce a more powerful test of linkage, for ASPs, than is provided by the TDT. Power simulations conducted under a number of disease models are used to verify that the most powerful member of this family of TDT-like statistics is more powerful than the TDT for ASPs. PMID:10788332

  8. Exploiting excess sharing: a more powerful test of linkage for affected sib pairs than the transmission/disequilibrium test.

    PubMed

    Wicks, J

    2000-06-01

    The transmission/disequilibrium test (TDT) is a popular, simple, and powerful test of linkage, which can be used to analyze data consisting of transmissions to the affected members of families with any kind pedigree structure, including affected sib pairs (ASPs). Although it is based on the preferential transmission of a particular marker allele across families, it is not a valid test of association for ASPs. Martin et al. devised a similar statistic for ASPs, Tsp, which is also based on preferential transmission of a marker allele but which is a valid test of both linkage and association for ASPs. It is, however, less powerful than the TDT as a test of linkage for ASPs. What I show is that the differences between the TDT and Tsp are due to the fact that, although both statistics are based on preferential transmission of a marker allele, the TDT also exploits excess sharing in identity-by-descent transmissions to ASPs. Furthermore, I show that both of these statistics are members of a family of "TDT-like" statistics for ASPs. The statistics in this family are based on preferential transmission but also, to varying extents, exploit excess sharing. From this family of statistics, we see that, although the TDT exploits excess sharing to some extent, it is possible to do so to a greater extent-and thus produce a more powerful test of linkage, for ASPs, than is provided by the TDT. Power simulations conducted under a number of disease models are used to verify that the most powerful member of this family of TDT-like statistics is more powerful than the TDT for ASPs.

  9. The Power to Detect Linkage Disequilibrium with Quantitative Traits in Selected Samples

    PubMed Central

    Abecasis, Gonçalo R.; Cookson, William O. C.; Cardon, Lon R.

    2001-01-01

    Results from power studies for linkage detection have led to many ongoing and planned collections of phenotypically extreme nuclear families. Given the great expense of collecting these families and the imminent availability of a dense diallelic marker map, the families are likely to be used in allelic-association as well as linkage studies. However, optimal selection strategies for linkage may not be equally powerful for association. We examine the power to detect linkage disequilibrium for quantitative traits after phenotypic selection. The results encompass six selection strategies that are in widespread use, including single selection (two designs), affected sib pairs, concordant and discordant pairs, and the extreme-concordant and -discordant design. Selection of sibships on the basis of one extreme proband with high or low trait scores provides as much power as discordant sib pairs but requires the screening and phenotyping of substantially fewer initial families from which to select. Analysis of the role of allele frequencies within each selection design indicates that common trait alleles generally offer the most power, but similarities between the marker- and trait-allele frequencies are much more important than the trait-locus frequency alone. Some of the most widespread selection designs, such as single selection, yield power gains only when both the marker and quantitative trait loci (QTL) are relatively rare in the population. In contrast, discordant pairs and the extreme-proband design provide power for the broadest range of QTL–marker-allele frequency differences. Overall, proband selection from either tail provides the best balance of power, robustness, and simplicity of ascertainment for family-based association analysis. PMID:11349228

  10. Quantitative transmission Raman spectroscopy of pharmaceutical tablets and capsules.

    PubMed

    Johansson, Jonas; Sparén, Anders; Svensson, Olof; Folestad, Staffan; Claybourn, Mike

    2007-11-01

    Quantitative analysis of pharmaceutical formulations using the new approach of transmission Raman spectroscopy has been investigated. For comparison, measurements were also made in conventional backscatter mode. The experimental setup consisted of a Raman probe-based spectrometer with 785 nm excitation for measurements in backscatter mode. In transmission mode the same system was used to detect the Raman scattered light, while an external diode laser of the same type was used as excitation source. Quantitative partial least squares models were developed for both measurement modes. The results for tablets show that the prediction error for an independent test set was lower for the transmission measurements with a relative root mean square error of about 2.2% as compared with 2.9% for the backscatter mode. Furthermore, the models were simpler in the transmission case, for which only a single partial least squares (PLS) component was required to explain the variation. The main reason for the improvement using the transmission mode is a more representative sampling of the tablets compared with the backscatter mode. Capsules containing mixtures of pharmaceutical powders were also assessed by transmission only. The quantitative results for the capsules' contents were good, with a prediction error of 3.6% w/w for an independent test set. The advantage of transmission Raman over backscatter Raman spectroscopy has been demonstrated for quantitative analysis of pharmaceutical formulations, and the prospects for reliable, lean calibrations for pharmaceutical analysis is discussed.

  11. Significant Admixture Linkage Disequilibrium across 30 cM around the FY Locus in African Americans

    PubMed Central

    Lautenberger, James A.; Stephens, J. Claiborne; O'Brien, Stephen J.; Smith, Michael W.

    2000-01-01

    Scientists, to understand the importance of allelic polymorphisms on phenotypes that are quantitative and environmentally interacting, are now turning to population-association screens, especially in instances in which pedigree analysis is difficult. Because association screens require linkage disequilibrium between markers and disease loci, maximizing the degree of linkage disequilibrium increases the chances of discovering functional gene-marker associations. One theoretically valid approach—mapping by admixture linkage disequilibrium (MALD), using recently admixed African Americans—is empirically evaluated here by measurement of marker associations with 15 short tandem repeats (STRs) and an insertion/deletion polymorphism of the AT3 locus in a 70-cM segment at 1q22-23, around the FY (Duffy) locus. The FY polymorphism (−46T→C) disrupts the GATA promoter motif, specifically blocking FY erythroid expression and has a nearly fixed allele-frequency difference between European Americans and native Africans that is likely a consequence of a selective advantage of FY−/− in malaria infections. Analysis of linkage disequilibrium around the FY gene has indicated that there is strong and consistent linkage disequilibrium between FY and three flanking loci (D1S303, SPTA1, and D1S484) spanning 8 cM. We observed significant linkage-disequilibrium signals over a 30-cM region from −4.4 to 16.3 cM (from D1S2777 to D1S196) for STRs and at 26.4 cM (AT3), which provided quantitative estimates of centimorgan limits, by MALD assessment in African American population-association analyses, of 5–10 cM. PMID:10712211

  12. Marker selection for the transmission/disequilibrium test, in recently admixed populations.

    PubMed Central

    Kaplan, N L; Martin, E R; Morris, R W; Weir, B S

    1998-01-01

    Recent admixture between genetically differentiated populations can result in high levels of association between alleles at loci that are <=10 cM apart. The transmission/disequilibrium test (TDT) proposed by Spielman et al. (1993) can be a powerful test of linkage between disease and marker loci in the presence of association and therefore could be a useful test of linkage in admixed populations. The degree of association between alleles at two loci depends on the differences in allele frequencies, at the two loci, in the founding populations; therefore, the choice of marker is important. For a multiallelic marker, one strategy that may improve the power of the TDT is to group marker alleles within a locus, on the basis of information about the founding populations and the admixed population, thereby collapsing the marker into one with fewer alleles. We have examined the consequences of collapsing a microsatellite into a two-allele marker, when two founding populations are assumed for the admixed population, and have found that if there is random mating in the admixed population, then typically there is a collapsing for which the power of the TDT is greater than that for the original microsatellite marker. A method is presented for finding the optimal collapsing that has minimal dependence on the disease and that uses estimates either of marker allele frequencies in the two founding populations or of marker allele frequencies in the current, admixed population and in one of the founding populations. Furthermore, this optimal collapsing is not always the collapsing with the largest difference in allele frequencies in the founding populations. To demonstrate this strategy, we considered a recent data set, published previously, that provides frequency estimates for 30 microsatellites in 13 populations. PMID:9497257

  13. Does probabilistic modelling of linkage disequilibrium evolution improve the accuracy of QTL location in animal pedigree?

    PubMed

    Cierco-Ayrolles, Christine; Dejean, Sébastien; Legarra, Andrés; Gilbert, Hélène; Druet, Tom; Ytournel, Florence; Estivals, Delphine; Oumouhou, Naïma; Mangin, Brigitte

    2010-10-22

    Since 2001, the use of more and more dense maps has made researchers aware that combining linkage and linkage disequilibrium enhances the feasibility of fine-mapping genes of interest. So, various method types have been derived to include concepts of population genetics in the analyses. One major drawback of many of these methods is their computational cost, which is very significant when many markers are considered. Recent advances in technology, such as SNP genotyping, have made it possible to deal with huge amount of data. Thus the challenge that remains is to find accurate and efficient methods that are not too time consuming. The study reported here specifically focuses on the half-sib family animal design. Our objective was to determine whether modelling of linkage disequilibrium evolution improved the mapping accuracy of a quantitative trait locus of agricultural interest in these populations. We compared two methods of fine-mapping. The first one was an association analysis. In this method, we did not model linkage disequilibrium evolution. Therefore, the modelling of the evolution of linkage disequilibrium was a deterministic process; it was complete at time 0 and remained complete during the following generations. In the second method, the modelling of the evolution of population allele frequencies was derived from a Wright-Fisher model. We simulated a wide range of scenarios adapted to animal populations and compared these two methods for each scenario. Our results indicated that the improvement produced by probabilistic modelling of linkage disequilibrium evolution was not significant. Both methods led to similar results concerning the location accuracy of quantitative trait loci which appeared to be mainly improved by using four flanking markers instead of two. Therefore, in animal half-sib designs, modelling linkage disequilibrium evolution using a Wright-Fisher model does not significantly improve the accuracy of the QTL location when compared to a

  14. Uranium disequilibrium in groundwater: An isotope dilution approach in hydrologic investigations

    USGS Publications Warehouse

    Osmond, J.K.; Rydell, H.S.; Kaufman, M.I.

    1968-01-01

    The distribution and environmental disequilibrium patterns of naturally occurring uranium isotopes (U234 and U238) in waters of the Floridan aquifer suggest that variations in the ratios of isotopic activity and concentrations can be used quantitatively to evaluate mixing proportions of waters from differing sources. Uranium is probably unique in its potential for this approach, which seems to have general usefulness in hydrologic investigations.

  15. Imaging Performance of Quantitative Transmission Ultrasound

    PubMed Central

    Lenox, Mark W.; Wiskin, James; Lewis, Matthew A.; Darrouzet, Stephen; Borup, David; Hsieh, Scott

    2015-01-01

    Quantitative Transmission Ultrasound (QTUS) is a tomographic transmission ultrasound modality that is capable of generating 3D speed-of-sound maps of objects in the field of view. It performs this measurement by propagating a plane wave through the medium from a transmitter on one side of a water tank to a high resolution receiver on the opposite side. This information is then used via inverse scattering to compute a speed map. In addition, the presence of reflection transducers allows the creation of a high resolution, spatially compounded reflection map that is natively coregistered to the speed map. A prototype QTUS system was evaluated for measurement and geometric accuracy as well as for the ability to correctly determine speed of sound. PMID:26604918

  16. Investigation of previously implicated genetic variants in chronic tic disorders: a transmission disequilibrium test approach.

    PubMed

    Abdulkadir, Mohamed; Londono, Douglas; Gordon, Derek; Fernandez, Thomas V; Brown, Lawrence W; Cheon, Keun-Ah; Coffey, Barbara J; Elzerman, Lonneke; Fremer, Carolin; Fründt, Odette; Garcia-Delgar, Blanca; Gilbert, Donald L; Grice, Dorothy E; Hedderly, Tammy; Heyman, Isobel; Hong, Hyun Ju; Huyser, Chaim; Ibanez-Gomez, Laura; Jakubovski, Ewgeni; Kim, Young Key; Kim, Young Shin; Koh, Yun-Joo; Kook, Sodahm; Kuperman, Samuel; Leventhal, Bennett; Ludolph, Andrea G; Madruga-Garrido, Marcos; Maras, Athanasios; Mir, Pablo; Morer, Astrid; Müller-Vahl, Kirsten; Münchau, Alexander; Murphy, Tara L; Plessen, Kerstin J; Roessner, Veit; Shin, Eun-Young; Song, Dong-Ho; Song, Jungeun; Tübing, Jennifer; van den Ban, Els; Visscher, Frank; Wanderer, Sina; Woods, Martin; Zinner, Samuel H; King, Robert A; Tischfield, Jay A; Heiman, Gary A; Hoekstra, Pieter J; Dietrich, Andrea

    2018-04-01

    Genetic studies in Tourette syndrome (TS) are characterized by scattered and poorly replicated findings. We aimed to replicate findings from candidate gene and genome-wide association studies (GWAS). Our cohort included 465 probands with chronic tic disorder (93% TS) and both parents from 412 families (some probands were siblings). We assessed 75 single nucleotide polymorphisms (SNPs) in 465 parent-child trios; 117 additional SNPs in 211 trios; and 4 additional SNPs in 254 trios. We performed SNP and gene-based transmission disequilibrium tests and compared nominally significant SNP results with those from a large independent case-control cohort. After quality control 71 SNPs were available in 371 trios; 112 SNPs in 179 trios; and 3 SNPs in 192 trios. 17 were candidate SNPs implicated in TS and 2 were implicated in obsessive-compulsive disorder (OCD) or autism spectrum disorder (ASD); 142 were tagging SNPs from eight monoamine neurotransmitter-related genes (including dopamine and serotonin); 10 were top SNPs from TS GWAS; and 13 top SNPs from attention-deficit/hyperactivity disorder, OCD, or ASD GWAS. None of the SNPs or genes reached significance after adjustment for multiple testing. We observed nominal significance for the candidate SNPs rs3744161 (TBCD) and rs4565946 (TPH2) and for five tagging SNPs; none of these showed significance in the independent cohort. Also, SLC1A1 in our gene-based analysis and two TS GWAS SNPs showed nominal significance, rs11603305 (intergenic) and rs621942 (PICALM). We found no convincing support for previously implicated genetic polymorphisms. Targeted re-sequencing should fully appreciate the relevance of candidate genes.

  17. Disequilibrium in planetary atmospheres and the search for habitability

    NASA Astrophysics Data System (ADS)

    Simoncini, E.

    It has long been observed that Earth's atmosphere is uniquely far from its thermochemical equilibrium state in terms of its chemical composition. Studying this state of disequilibrium is important for its potential role in the detection of life on other suitable planets \\citep{Lovelock_1965,Kleidon_2010,Simoncini_2015}. We developed a methodology to calculate the extent of atmospheric chemical disequilibrium\\citep{Simoncini_2015,Kondepudi_1996}. This tool allows us to understand, on a thermodynamic basis, how life affected - and still affects - geochemical processes on Earth, and if other planetary atmospheres are habitable or have a disequilibrium similar to the Earth's one. A new computational framework called KROME has been applied to atmospheric models in order to give a correct computation of reactions´ kinetics \\citep{Grassi_2015}. In this work we present a first computation of the extent of disequilibrium for the present Earth atmosphere, considering the specific contribution of the different atmospheric processes, such as thermochemical reactions, eddy diffusion, photochemistry, deposition, and the effect of the biosphere. We then assess the effect of life on atmospheric disequilibrium of the Earth and provide a useful discussion about how the study of atmospheric disequilibrium can help in finding habitable (exo)planets. We finally compare the chemical disequilibrium of Earth and Mars atmospheres, for present and early conditions.

  18. Equilibrium and disequilibrium chemistry of adiabatic, solar-composition planetary atmospheres

    NASA Technical Reports Server (NTRS)

    Lewis, J. S.

    1976-01-01

    The impact of atmospheric and cloud-structure models on the nonequilibrium chemical behavior of the atmospheres of the Jovian planets is discussed. Quantitative constraints on photochemical, lightning, and charged-particle production of organic matter and chromophores are emphasized whenever available. These considerations imply that inorganic chromophore production is far more important than that of organic chromophores, and that lightning is probably a negligibly significant process relative to photochemistry on Jupiter. Production of complex molecules by gas-phase disequilibrium processes on Saturn, Uranus, and Neptune is severely limited by condensation of even simple intermediates.

  19. On Detecting Biospheres from Chemical Thermodynamic Disequilibrium in Planetary Atmospheres.

    PubMed

    Krissansen-Totton, Joshua; Bergsman, David S; Catling, David C

    2016-01-01

    Atmospheric chemical disequilibrium has been proposed as a method for detecting extraterrestrial biospheres from exoplanet observations. Chemical disequilibrium is potentially a generalized biosignature since it makes no assumptions about particular biogenic gases or metabolisms. Here, we present the first rigorous calculations of the thermodynamic chemical disequilibrium in Solar System atmospheres, in which we quantify the available Gibbs energy: the Gibbs free energy of an observed atmosphere minus that of atmospheric gases reacted to equilibrium. The purely gas phase disequilibrium in Earth's atmosphere is mostly attributable to O2 and CH4. The available Gibbs energy is not unusual compared to other Solar System atmospheres and smaller than that of Mars. However, Earth's fluid envelope contains an ocean, allowing gases to react with water and requiring a multiphase calculation with aqueous species. The disequilibrium in Earth's atmosphere-ocean system (in joules per mole of atmosphere) ranges from ∼20 to 2 × 10(6) times larger than the disequilibria of other atmospheres in the Solar System, where Mars is second to Earth. Only on Earth is the chemical disequilibrium energy comparable to the thermal energy per mole of atmosphere (excluding comparison to Titan with lakes, where quantification is precluded because the mean lake composition is unknown). Earth's disequilibrium is biogenic, mainly caused by the coexistence of N2, O2, and liquid water instead of more stable nitrate. In comparison, the O2-CH4 disequilibrium is minor, although kinetics requires a large CH4 flux into the atmosphere. We identify abiotic processes that cause disequilibrium in the other atmospheres. Our metric requires minimal assumptions and could potentially be calculated from observations of exoplanet atmospheres. However, further work is needed to establish whether thermodynamic disequilibrium is a practical exoplanet biosignature, requiring an assessment of false positives, noisy

  20. Nonlinear Analysis of Time Series in Genome-Wide Linkage Disequilibrium Data

    NASA Astrophysics Data System (ADS)

    Hernández-Lemus, Enrique; Estrada-Gil, Jesús K.; Silva-Zolezzi, Irma; Fernández-López, J. Carlos; Hidalgo-Miranda, Alfredo; Jiménez-Sánchez, Gerardo

    2008-02-01

    The statistical study of large scale genomic data has turned out to be a very important tool in population genetics. Quantitative methods are essential to understand and implement association studies in the biomedical and health sciences. Nevertheless, the characterization of recently admixed populations has been an elusive problem due to the presence of a number of complex phenomena. For example, linkage disequilibrium structures are thought to be more complex than their non-recently admixed population counterparts, presenting the so-called ancestry blocks, admixed regions that are not yet smoothed by the effect of genetic recombination. In order to distinguish characteristic features for various populations we have implemented several methods, some of them borrowed or adapted from the analysis of nonlinear time series in statistical physics and quantitative physiology. We calculate the main fractal dimensions (Kolmogorov's capacity, information dimension and correlation dimension, usually named, D0, D1 and D2). We also have made detrended fluctuation analysis and information based similarity index calculations for the probability distribution of correlations of linkage disequilibrium coefficient of six recently admixed (mestizo) populations within the Mexican Genome Diversity Project [1] and for the non-recently admixed populations in the International HapMap Project [2]. Nonlinear correlations showed up as a consequence of internal structure within the haplotype distributions. The analysis of these correlations as well as the scope and limitations of these procedures within the biomedical sciences are discussed.

  1. Potential linkage disequilibrium between schizophrenia and locus D22S278 on the long arm of chromosome 22

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

    Moises, H.W.; Yang, L.; Havsteen, B.

    Locus D22S278 at 22q12 has been implicated in schizophrenia by sib-pair analysis. In order to replicate these results, we performed the transmission test for linkage disequilibrium (TDT) in 113 unrelated schizophrenic patients and their 226 parents. Evidence for potential linkage disequilibrium was obtained between schizophrenia and allele 243 of the marker AFM 182xd12 at the locus D22S278 (P = 0.02). The results of our study suggest a detectable oligogenic gene in a multigene system for schizophrenia closely linked to D22S278 on the long arm of chromosome 22. If confirmed by others, this finding could lead to the identification of amore » schizophrenia susceptibility gene. 12 refs., 1 tab.« less

  2. Single-Cell Based Quantitative Assay of Chromosome Transmission Fidelity

    PubMed Central

    Zhu, Jin; Heinecke, Dominic; Mulla, Wahid A.; Bradford, William D.; Rubinstein, Boris; Box, Andrew; Haug, Jeffrey S.; Li, Rong

    2015-01-01

    Errors in mitosis are a primary cause of chromosome instability (CIN), generating aneuploid progeny cells. Whereas a variety of factors can influence CIN, under most conditions mitotic errors are rare events that have been difficult to measure accurately. Here we report a green fluorescent protein−based quantitative chromosome transmission fidelity (qCTF) assay in budding yeast that allows sensitive and quantitative detection of CIN and can be easily adapted to high-throughput analysis. Using the qCTF assay, we performed genome-wide quantitative profiling of genes that affect CIN in a dosage-dependent manner and identified genes that elevate CIN when either increased (icCIN) or decreased in copy number (dcCIN). Unexpectedly, qCTF screening also revealed genes whose change in copy number quantitatively suppress CIN, suggesting that the basal error rate of the wild-type genome is not minimized, but rather, may have evolved toward an optimal level that balances both stability and low-level karyotype variation for evolutionary adaptation. PMID:25823586

  3. Role for syn-eruptive plagioclase disequilibrium crystallisation in basaltic magma ascent dynamics

    NASA Astrophysics Data System (ADS)

    La Spina, Giuseppe; Burton, Mike; de'Michieli Vitturi, Mattia; Arzilli, Fabio

    2017-04-01

    Magma ascent dynamics in volcanic conduits play a key role in determining the eruptive style of a volcano. The lack of direct observations inside the conduit means that numerical conduit models, constrained with observational data, provide invaluable tools for quantitative insights into complex magma ascent dynamics. The highly nonlinear, interdependent processes involved in magma ascent dynamics require several simplifications when modelling their ascent. For example, timescales of magma ascent in conduit models are typically assumed to be much longer than crystallisation and gas exsolution for basaltic eruptions. However, it is now recognized that basaltic magmas may rise fast enough for disequilibrium processes to play a key role on the ascent dynamics. The quantification of the characteristic times for crystallisation and exsolution processes are fundamental to our understanding of such disequilibria and ascent dynamics. Using observations from Mount Etna's 2001 eruption and a magma ascent model we are able to constrain timescales for crystallisation and exsolution processes. Our results show that plagioclase reaches equilibrium in 1-2 h, whereas ascent times were 1 h. Furthermore, we have related the amount of plagioclase in erupted products with the ascent dynamics of basaltic eruptions. We find that relatively high plagioclase content requires crystallisation in a shallow reservoir, whilst a low plagioclase content reflects a disequilibrium crystallisation occurring during a fast ascent from depth to the surface. Using these new constraints on disequilibrium plagioclase crystallisation we also reproduce observed crystal abundances for different basaltic eruptions: Etna 2002/2003, Stromboli 2007 (effusive eruption) and 1930 (paroxysm) and different Pu'u' O'o eruptions at Kilauea (episodes 49-53). Therefore, our results show that disequilibrium processes play a key role on the ascent dynamics of basaltic magmas and cannot be neglected when describing basaltic

  4. Single-Cell Based Quantitative Assay of Chromosome Transmission Fidelity.

    PubMed

    Zhu, Jin; Heinecke, Dominic; Mulla, Wahid A; Bradford, William D; Rubinstein, Boris; Box, Andrew; Haug, Jeffrey S; Li, Rong

    2015-03-30

    Errors in mitosis are a primary cause of chromosome instability (CIN), generating aneuploid progeny cells. Whereas a variety of factors can influence CIN, under most conditions mitotic errors are rare events that have been difficult to measure accurately. Here we report a green fluorescent protein-based quantitative chromosome transmission fidelity (qCTF) assay in budding yeast that allows sensitive and quantitative detection of CIN and can be easily adapted to high-throughput analysis. Using the qCTF assay, we performed genome-wide quantitative profiling of genes that affect CIN in a dosage-dependent manner and identified genes that elevate CIN when either increased (icCIN) or decreased in copy number (dcCIN). Unexpectedly, qCTF screening also revealed genes whose change in copy number quantitatively suppress CIN, suggesting that the basal error rate of the wild-type genome is not minimized, but rather, may have evolved toward an optimal level that balances both stability and low-level karyotype variation for evolutionary adaptation. Copyright © 2015 Zhu et al.

  5. MIDAS: software for analysis and visualisation of interallelic disequilibrium between multiallelic markers

    PubMed Central

    Gaunt, Tom R; Rodriguez, Santiago; Zapata, Carlos; Day, Ian NM

    2006-01-01

    Background Various software tools are available for the display of pairwise linkage disequilibrium across multiple single nucleotide polymorphisms. The HapMap project also presents these graphics within their website. However, these approaches are limited in their use of data from multiallelic markers and provide limited information in a graphical form. Results We have developed a software package (MIDAS – Multiallelic Interallelic Disequilibrium Analysis Software) for the estimation and graphical display of interallelic linkage disequilibrium. Linkage disequilibrium is analysed for each allelic combination (of one allele from each of two loci), between all pairwise combinations of any type of multiallelic loci in a contig (or any set) of many loci (including single nucleotide polymorphisms, microsatellites, minisatellites and haplotypes). Data are presented graphically in a novel and informative way, and can also be exported in tabular form for other analyses. This approach facilitates visualisation of patterns of linkage disequilibrium across genomic regions, analysis of the relationships between different alleles of multiallelic markers and inferences about patterns of evolution and selection. Conclusion MIDAS is a linkage disequilibrium analysis program with a comprehensive graphical user interface providing novel views of patterns of linkage disequilibrium between all types of multiallelic and biallelic markers. Availability Available from and PMID:16643648

  6. Disequilibrium biosignatures over Earth history and implications for detecting exoplanet life.

    PubMed

    Krissansen-Totton, Joshua; Olson, Stephanie; Catling, David C

    2018-01-01

    Chemical disequilibrium in planetary atmospheres has been proposed as a generalized method for detecting life on exoplanets through remote spectroscopy. Among solar system planets with substantial atmospheres, the modern Earth has the largest thermodynamic chemical disequilibrium due to the presence of life. However, how this disequilibrium changed over time and, in particular, the biogenic disequilibria maintained in the anoxic Archean or less oxic Proterozoic eons are unknown. We calculate the atmosphere-ocean disequilibrium in the Precambrian using conservative proxy- and model-based estimates of early atmospheric and oceanic compositions. We omit crustal solids because subsurface composition is not detectable on exoplanets, unlike above-surface volatiles. We find that (i) disequilibrium increased through time in step with the rise of oxygen; (ii) both the Proterozoic and Phanerozoic may have had remotely detectable biogenic disequilibria due to the coexistence of O 2 , N 2 , and liquid water; and (iii) the Archean had a biogenic disequilibrium caused by the coexistence of N 2 , CH 4 , CO 2 , and liquid water, which, for an exoplanet twin, may be remotely detectable. On the basis of this disequilibrium, we argue that the simultaneous detection of abundant CH 4 and CO 2 in a habitable exoplanet's atmosphere is a potential biosignature. Specifically, we show that methane mixing ratios greater than 10 -3 are potentially biogenic, whereas those exceeding 10 -2 are likely biogenic due to the difficulty in maintaining large abiotic methane fluxes to support high methane levels in anoxic atmospheres. Biogenicity would be strengthened by the absence of abundant CO, which should not coexist in a biological scenario.

  7. An Association Between Functional Polymorphisms of the Interleukin 1 Gene Complex and Schizophrenia Using Transmission Disequilibrium Test.

    PubMed

    Kapelski, Pawel; Skibinska, Maria; Maciukiewicz, Malgorzata; Pawlak, Joanna; Dmitrzak-Weglarz, Monika; Szczepankiewicz, Aleksandra; Zaremba, Dorota; Twarowska-Hauser, Joanna

    2016-12-01

    IL1 gene complex has been implicated in the etiology of schizophrenia. To assess whether IL1 gene complex is associated with susceptibility to schizophrenia in Polish population we conducted family-based study. Functional polymorphisms from IL1A (rs1800587, rs17561, rs11677416), IL1B (rs1143634, rs1143643, rs16944, rs4848306, rs1143623, rs1143633, rs1143627) and IL1RN (rs419598, rs315952, rs9005, rs4251961) genes were genotyped in 143 trio with schizophrenia. Statistical analysis was performed using transmission disequilibrium test. We have found a trend toward an association of rs1143627, rs16944, rs1143623 in IL1B gene with the risk of schizophrenia. Our results show a protective effect of allele T of rs4251961 in IL1RN against schizophrenia. We also performed haplotype analysis of IL1 gene complex and found a trend toward an association with schizophrenia of GAGG haplotype (rs1143627, rs16944, rs1143623, rs4848306) in IL1B gene, haplotypes: TG (rs315952, rs9005) and TT (rs4251961, rs419598) in IL1RN. Haplotype CT (rs4251961, rs419598) in IL1RN was found to be associated with schizophrenia. After correction for multiple testing associations did not reach significance level. Our results might support theory that polymorphisms of interleukin 1 complex genes (rs1143627, rs16944, rs1143623, rs4848306 in IL1B gene and rs4251961, rs419598, rs315952, rs9005 in IL1RN gene) are involved in the pathogenesis of schizophrenia, however, none of the results reach significance level after correction for multiple testing.

  8. Disequilibrium condensation environments in space - A frontier in thermodynamics

    NASA Technical Reports Server (NTRS)

    De, B. R.

    1979-01-01

    The thermal-disequilibrium aspect of the problem of dust-particle formation from a gas phase in an open space environment is discussed in an effort to draw attention to the space condensation environment as an interesting arena for application and extension of the ideas and formalisms of nonequilibrium thermodynamics. It is shown that quasi-steady states with a disequilibrium between the gas-phase kinetic temperature and the condensed-phase internal temperature appear to be the norm of condensation environments in space. Consideration of the case of condensation onto a bulk condensed phase indicates that these quasi-steady states may constitute Prigogine dissipative structures. It is suggested that a proper study of the process of condensation in a space environment should include any effects arising from thermal disequilibrium.

  9. Disequilibrium biosignatures over Earth history and implications for detecting exoplanet life

    PubMed Central

    Krissansen-Totton, Joshua; Olson, Stephanie; Catling, David C.

    2018-01-01

    Chemical disequilibrium in planetary atmospheres has been proposed as a generalized method for detecting life on exoplanets through remote spectroscopy. Among solar system planets with substantial atmospheres, the modern Earth has the largest thermodynamic chemical disequilibrium due to the presence of life. However, how this disequilibrium changed over time and, in particular, the biogenic disequilibria maintained in the anoxic Archean or less oxic Proterozoic eons are unknown. We calculate the atmosphere-ocean disequilibrium in the Precambrian using conservative proxy- and model-based estimates of early atmospheric and oceanic compositions. We omit crustal solids because subsurface composition is not detectable on exoplanets, unlike above-surface volatiles. We find that (i) disequilibrium increased through time in step with the rise of oxygen; (ii) both the Proterozoic and Phanerozoic may have had remotely detectable biogenic disequilibria due to the coexistence of O2, N2, and liquid water; and (iii) the Archean had a biogenic disequilibrium caused by the coexistence of N2, CH4, CO2, and liquid water, which, for an exoplanet twin, may be remotely detectable. On the basis of this disequilibrium, we argue that the simultaneous detection of abundant CH4 and CO2 in a habitable exoplanet’s atmosphere is a potential biosignature. Specifically, we show that methane mixing ratios greater than 10−3 are potentially biogenic, whereas those exceeding 10−2 are likely biogenic due to the difficulty in maintaining large abiotic methane fluxes to support high methane levels in anoxic atmospheres. Biogenicity would be strengthened by the absence of abundant CO, which should not coexist in a biological scenario. PMID:29387792

  10. Disequilibrium, complexity, the Schottky effect, and q-entropies, in paramagnetism

    NASA Astrophysics Data System (ADS)

    Pennini, F.; Plastino, A.

    2017-12-01

    We investigate connections between statistical quantifiers and paramagnetism. More concretely, we apply the notions of (i) disequilibrium and (ii) statistical complexity, to a paramagnetic system of non-coupled dipoles. Interesting insights are thereby obtained. In particular, we encounter a kind of criticality, not associated to the temperature but to the disequilibrium.

  11. THE ROLE OF TEMPERATURE DISEQUILIBRIUM IN MONITORING LOW VOLATILITY CONTAMINANT MIGRATION

    EPA Science Inventory

    Temperature disequilibrium is a common phenomenon within and among envirornnental media at local regional continental and global scales. The significance of temperature disequilibrium on low vapor pressure environmental contaminant migration has only rarely been addressed in the ...

  12. Evidence, from family studies, for linkage disequilibrium between TGFA and a gene for nonsyndromic cleft lip with or without cleft palate

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

    Feng, Hongshu; Lee, A.; Gasser, D.L.

    1994-11-01

    The inheritance of alleles of the transforming growth factor alpha (TGFA) locus has been studied in families affected with cleft lip with or without cleft palate (CL/P), by using the transmission/disequilibrium test described by Spielman and colleagues. Only heterozygous parents with an affected child can be included in this test, but within such families a significantly greater frequency of C2 alleles were transmitted to affected children than would be expected by chance. There was no evidence that the total number of C2 alleles transmitted to affected and unaffected children differed significantly from random segregation. These data provide evidence from withinmore » families that a gene for susceptibility to CL/P is in significant linkage disequilibrium with the C2 allele of the TGFA locus. 30 refs., 1 fig., 2 tabs.« less

  13. Maximum likelihood estimation of linkage disequilibrium in half-sib families.

    PubMed

    Gomez-Raya, L

    2012-05-01

    Maximum likelihood methods for the estimation of linkage disequilibrium between biallelic DNA-markers in half-sib families (half-sib method) are developed for single and multifamily situations. Monte Carlo computer simulations were carried out for a variety of scenarios regarding sire genotypes, linkage disequilibrium, recombination fraction, family size, and number of families. A double heterozygote sire was simulated with recombination fraction of 0.00, linkage disequilibrium among dams of δ=0.10, and alleles at both markers segregating at intermediate frequencies for a family size of 500. The average estimates of δ were 0.17, 0.25, and 0.10 for Excoffier and Slatkin (1995), maternal informative haplotypes, and the half-sib method, respectively. A multifamily EM algorithm was tested at intermediate frequencies by computer simulation. The range of the absolute difference between estimated and simulated δ was between 0.000 and 0.008. A cattle half-sib family was genotyped with the Illumina 50K BeadChip. There were 314,730 SNP pairs for which the sire was a homo-heterozygote with average estimates of r2 of 0.115, 0.067, and 0.111 for half-sib, Excoffier and Slatkin (1995), and maternal informative haplotypes methods, respectively. There were 208,872 SNP pairs for which the sire was double heterozygote with average estimates of r2 across the genome of 0.100, 0.267, and 0.925 for half-sib, Excoffier and Slatkin (1995), and maternal informative haplotypes methods, respectively. Genome analyses for all possible sire genotypes with 829,042 tests showed that ignoring half-sib family structure leads to upward biased estimates of linkage disequilibrium. Published inferences on population structure and evolution of cattle should be revisited after accommodating existing half-sib family structure in the estimation of linkage disequilibrium.

  14. Maximum Likelihood Estimation of Linkage Disequilibrium in Half-Sib Families

    PubMed Central

    Gomez-Raya, L.

    2012-01-01

    Maximum likelihood methods for the estimation of linkage disequilibrium between biallelic DNA-markers in half-sib families (half-sib method) are developed for single and multifamily situations. Monte Carlo computer simulations were carried out for a variety of scenarios regarding sire genotypes, linkage disequilibrium, recombination fraction, family size, and number of families. A double heterozygote sire was simulated with recombination fraction of 0.00, linkage disequilibrium among dams of δ = 0.10, and alleles at both markers segregating at intermediate frequencies for a family size of 500. The average estimates of δ were 0.17, 0.25, and 0.10 for Excoffier and Slatkin (1995), maternal informative haplotypes, and the half-sib method, respectively. A multifamily EM algorithm was tested at intermediate frequencies by computer simulation. The range of the absolute difference between estimated and simulated δ was between 0.000 and 0.008. A cattle half-sib family was genotyped with the Illumina 50K BeadChip. There were 314,730 SNP pairs for which the sire was a homo-heterozygote with average estimates of r2 of 0.115, 0.067, and 0.111 for half-sib, Excoffier and Slatkin (1995), and maternal informative haplotypes methods, respectively. There were 208,872 SNP pairs for which the sire was double heterozygote with average estimates of r2 across the genome of 0.100, 0.267, and 0.925 for half-sib, Excoffier and Slatkin (1995), and maternal informative haplotypes methods, respectively. Genome analyses for all possible sire genotypes with 829,042 tests showed that ignoring half-sib family structure leads to upward biased estimates of linkage disequilibrium. Published inferences on population structure and evolution of cattle should be revisited after accommodating existing half-sib family structure in the estimation of linkage disequilibrium. PMID:22377635

  15. Convective dynamics and chemical disequilibrium in the atmospheres of substellar objects

    NASA Astrophysics Data System (ADS)

    Bordwell, Baylee; Brown, Benjamin P.; Oishi, Jeffrey S.

    2017-11-01

    The thousands of substellar objects now known provide a unique opportunity to test our understanding of atmospheric dynamics across a range of environments. The chemical timescales of certain species transition from being much shorter than the dynamical timescales to being much longer than them at a point in the atmosphere known as the quench point. This transition leads to a state of dynamical disequilibrium, the effects of which can be used to probe the atmospheric dynamics of these objects. Unfortunately, due to computational constraints, models that inform the interpretation of these observations are run at dynamical parameters which are far from realistic values. In this study, we explore the behavior of a disequilibrium chemical process with increasingly realistic planetary conditions, to quantify the effects of the approximations used in current models. We simulate convection in 2-D, plane-parallel, polytropically-stratified atmospheres, into which we add reactive passive tracers that explore disequilibrium behavior. We find that as we increase the Rayleigh number, and thus achieve more realistic planetary conditions, the behavior of these tracers does not conform to the classical predictions of disequilibrium chemistry.

  16. Matrix Effects in Quantitative Assessment of Pharmaceutical Tablets Using Transmission Raman and Near-Infrared (NIR) Spectroscopy.

    PubMed

    Sparén, Anders; Hartman, Madeleine; Fransson, Magnus; Johansson, Jonas; Svensson, Olof

    2015-05-01

    Raman spectroscopy can be an alternative to near-infrared spectroscopy (NIR) for nondestructive quantitative analysis of solid pharmaceutical formulations. Compared with NIR spectra, Raman spectra have much better selectivity, but subsampling was always an issue for quantitative assessment. Raman spectroscopy in transmission mode has reduced this issue, since a large volume of the sample is measured in transmission mode. The sample matrix, such as particle size of the drug substance in a tablet, may affect the Raman signal. In this work, matrix effects in transmission NIR and Raman spectroscopy were systematically investigated for a solid pharmaceutical formulation. Tablets were manufactured according to an experimental design, varying the factors particle size of the drug substance (DS), particle size of the filler, compression force, and content of drug substance. All factors were varied at two levels plus a center point, except the drug substance content, which was varied at five levels. Six tablets from each experimental point were measured with transmission NIR and Raman spectroscopy, and their concentration of DS was determined for a third of those tablets. Principal component analysis of NIR and Raman spectra showed that the drug substance content and particle size, the particle size of the filler, and the compression force affected both NIR and Raman spectra. For quantitative assessment, orthogonal partial least squares regression was applied. All factors varied in the experimental design influenced the prediction of the DS content to some extent, both for NIR and Raman spectroscopy, the particle size of the filler having the largest effect. When all matrix variations were included in the multivariate calibrations, however, good predictions of all types of tablets were obtained, both for NIR and Raman spectroscopy. The prediction error using transmission Raman spectroscopy was about 30% lower than that obtained with transmission NIR spectroscopy.

  17. The score statistic of the LD-lod analysis: detecting linkage adaptive to linkage disequilibrium.

    PubMed

    Huang, J; Jiang, Y

    2001-01-01

    We study the properties of a modified lod score method for testing linkage that incorporates linkage disequilibrium (LD-lod). By examination of its score statistic, we show that the LD-lod score method adaptively combines two sources of information: (a) the IBD sharing score which is informative for linkage regardless of the existence of LD and (b) the contrast between allele-specific IBD sharing scores which is informative for linkage only in the presence of LD. We also consider the connection between the LD-lod score method and the transmission-disequilibrium test (TDT) for triad data and the mean test for affected sib pair (ASP) data. We show that, for triad data, the recessive LD-lod test is asymptotically equivalent to the TDT; and for ASP data, it is an adaptive combination of the TDT and the ASP mean test. We demonstrate that the LD-lod score method has relatively good statistical efficiency in comparison with the ASP mean test and the TDT for a broad range of LD and the genetic models considered in this report. Therefore, the LD-lod score method is an interesting approach for detecting linkage when the extent of LD is unknown, such as in a genome-wide screen with a dense set of genetic markers. Copyright 2001 S. Karger AG, Basel

  18. Measuring changes in transmission of neglected tropical diseases, malaria, and enteric pathogens from quantitative antibody levels.

    PubMed

    Arnold, Benjamin F; van der Laan, Mark J; Hubbard, Alan E; Steel, Cathy; Kubofcik, Joseph; Hamlin, Katy L; Moss, Delynn M; Nutman, Thomas B; Priest, Jeffrey W; Lammie, Patrick J

    2017-05-01

    Serological antibody levels are a sensitive marker of pathogen exposure, and advances in multiplex assays have created enormous potential for large-scale, integrated infectious disease surveillance. Most methods to analyze antibody measurements reduce quantitative antibody levels to seropositive and seronegative groups, but this can be difficult for many pathogens and may provide lower resolution information than quantitative levels. Analysis methods have predominantly maintained a single disease focus, yet integrated surveillance platforms would benefit from methodologies that work across diverse pathogens included in multiplex assays. We developed an approach to measure changes in transmission from quantitative antibody levels that can be applied to diverse pathogens of global importance. We compared age-dependent immunoglobulin G curves in repeated cross-sectional surveys between populations with differences in transmission for multiple pathogens, including: lymphatic filariasis (Wuchereria bancrofti) measured before and after mass drug administration on Mauke, Cook Islands, malaria (Plasmodium falciparum) before and after a combined insecticide and mass drug administration intervention in the Garki project, Nigeria, and enteric protozoans (Cryptosporidium parvum, Giardia intestinalis, Entamoeba histolytica), bacteria (enterotoxigenic Escherichia coli, Salmonella spp.), and viruses (norovirus groups I and II) in children living in Haiti and the USA. Age-dependent antibody curves fit with ensemble machine learning followed a characteristic shape across pathogens that aligned with predictions from basic mechanisms of humoral immunity. Differences in pathogen transmission led to shifts in fitted antibody curves that were remarkably consistent across pathogens, assays, and populations. Mean antibody levels correlated strongly with traditional measures of transmission intensity, such as the entomological inoculation rate for P. falciparum (Spearman's rho = 0.75). In

  19. A Quantitative Transmission Line Experiment

    ERIC Educational Resources Information Center

    Johnston, D. C.; Silbernagel, B. G.

    1969-01-01

    Describes modifications of a commercially available strip-type transmission line, which makes possible reproducible measurements of standing waves on the line. Experimental data yield values for the characteristic impedance, phase velocity and line wavelength of radiation in the transmission line, and the dielectric constant of material in the…

  20. Identification of a psoriasis susceptibility candidate gene by linkage disequilibrium mapping with a localized single nucleotide polymorphism map.

    PubMed

    Hewett, Duncan; Samuelsson, Lena; Polding, Joanne; Enlund, Fredrik; Smart, Devi; Cantone, Kathryn; See, Chee Gee; Chadha, Sapna; Inerot, Annica; Enerback, Charlotta; Montgomery, Doug; Christodolou, Chris; Robinson, Phil; Matthews, Paul; Plumpton, Mary; Wahlstrom, Jan; Swanbeck, Gunnar; Martinsson, Tommy; Roses, Allen; Riley, John; Purvis, Ian

    2002-03-01

    Psoriasis is a chronic inflammatory disease of the skin with both genetic and environmental risk factors. Here we describe the creation of a single-nucleotide polymorphism (SNP) map spanning 900-1200 kb of chromosome 3q21, which had been previously recognized as containing a psoriasis susceptibility locus, PSORS5. We genotyped 644 individuals, from 195 Swedish psoriatic families, for 19 polymorphisms. Linkage disequilibrium (LD) between marker and disease was assessed using the transmission/disequilibrium test (TDT). In the TDT analysis, alleles of three of these SNPs showed significant association with disease (P<0.05). A 160-kb interval encompassing these three SNPs was sequenced, and a coding sequence consisting of 13 exons was identified. The predicted protein shares 30-40% homology with the family of cation/chloride cotransporters. A five-marker haplotype spanning the 3' half of this gene is associated with psoriasis to a P value of 3.8<10(-5). We have called this gene SLC12A8, coding for a member of the solute carrier family 12 proteins. It belongs to a class of genes that were previously unrecognized as playing a role in psoriasis pathogenesis.

  1. Measuring changes in transmission of neglected tropical diseases, malaria, and enteric pathogens from quantitative antibody levels

    PubMed Central

    van der Laan, Mark J.; Hubbard, Alan E.; Steel, Cathy; Kubofcik, Joseph; Hamlin, Katy L.; Moss, Delynn M.; Nutman, Thomas B.; Priest, Jeffrey W.; Lammie, Patrick J.

    2017-01-01

    Background Serological antibody levels are a sensitive marker of pathogen exposure, and advances in multiplex assays have created enormous potential for large-scale, integrated infectious disease surveillance. Most methods to analyze antibody measurements reduce quantitative antibody levels to seropositive and seronegative groups, but this can be difficult for many pathogens and may provide lower resolution information than quantitative levels. Analysis methods have predominantly maintained a single disease focus, yet integrated surveillance platforms would benefit from methodologies that work across diverse pathogens included in multiplex assays. Methods/Principal findings We developed an approach to measure changes in transmission from quantitative antibody levels that can be applied to diverse pathogens of global importance. We compared age-dependent immunoglobulin G curves in repeated cross-sectional surveys between populations with differences in transmission for multiple pathogens, including: lymphatic filariasis (Wuchereria bancrofti) measured before and after mass drug administration on Mauke, Cook Islands, malaria (Plasmodium falciparum) before and after a combined insecticide and mass drug administration intervention in the Garki project, Nigeria, and enteric protozoans (Cryptosporidium parvum, Giardia intestinalis, Entamoeba histolytica), bacteria (enterotoxigenic Escherichia coli, Salmonella spp.), and viruses (norovirus groups I and II) in children living in Haiti and the USA. Age-dependent antibody curves fit with ensemble machine learning followed a characteristic shape across pathogens that aligned with predictions from basic mechanisms of humoral immunity. Differences in pathogen transmission led to shifts in fitted antibody curves that were remarkably consistent across pathogens, assays, and populations. Mean antibody levels correlated strongly with traditional measures of transmission intensity, such as the entomological inoculation rate for P

  2. Chemical evolution of the Earth: Equilibrium or disequilibrium process?

    NASA Technical Reports Server (NTRS)

    Sato, M.

    1985-01-01

    To explain the apparent chemical incompatibility of the Earth's core and mantle or the disequilibrium process, various core forming mechanisms have been proposed, i.e., rapid disequilibrium sinking of molten iron, an oxidized core or protocore materials, and meteorite contamination of the upper mantle after separation from the core. Adopting concepts used in steady state thermodynamics, a method is devised for evaluating how elements should distribute stable in the Earth's interior for the present gradients of temperature, pressure, and gravitational acceleration. Thermochemical modeling gives useful insights into the nature of chemical evolution of the Earth without overly speculative assumptions. Further work must be done to reconcile siderophile elements, rare gases, and possible light elements in the outer core.

  3. A systematic retrieval analysis of secondary eclipse spectra. III. Diagnosing chemical disequilibrium in planetary atmospheres

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

    Line, Michael R.; Yung, Yuk L., E-mail: mrl@gps.caltech.edu

    2013-12-10

    Chemical disequilibrium has recently become a relevant topic in the study of the atmospheres of transiting extrasolar planets, brown dwarfs, and directly imaged exoplanets. We present a new way of assessing whether or not a Jovian-like atmosphere is in chemical disequilibrium from observations of detectable or inferred gases such as H{sub 2}O, CH{sub 4}, CO, and H{sub 2}. Our hypothesis, based on previous kinetic modeling studies, is that cooler atmospheres will show stronger signs of disequilibrium than hotter atmospheres. We verify this with chemistry-transport models and show that planets with temperatures less than ∼1200 K are likely to show themore » strongest signs of disequilibrium due to the vertical quenching of CO, and that our new approach is able to capture this process. We also find that in certain instances a planetary composition may appear in equilibrium when it actually is not due to the degeneracy in the shape of the vertical mixing ratio profiles. We determine the state of disequilibrium in eight exoplanets using the results from secondary eclipse temperature and abundance retrievals. We find that all of the planets in our sample are consistent with thermochemical equilibrium to within 3σ. Future observations are needed to further constrain the abundances in order to definitively identify disequilibrium in exoplanet atmospheres.« less

  4. General framework for comparative quantitative studies on transmission of tick-borne diseases using Lyme borreliosis in Europe as an example.

    PubMed

    Randolph, S E; Craine, N G

    1995-11-01

    Models of tick-borne diseases must take account of the particular biological features of ticks that contrast with those of insect vectors. A general framework is proposed that identifies the parameters of the transmission dynamics of tick-borne diseases to allow a quantitative assessment of the relative contributions of different host species and alternative transmission routes to the basic reproductive number, Ro, of such diseases. Taking the particular case of the transmission of the Lyme borreliosis spirochaete, Borrelia burgdorferi, by Ixodes ticks in Europe, and using the best, albeit still inadequate, estimates of the parameter values and a set of empirical data from Thetford Forest, England, we show that squirrels and the transovarial transmission route make quantitatively very significant contributions to Ro. This approach highlights the urgent need for more robust estimates of certain crucial parameter values, particularly the coefficients of transmission between ticks and vertebrates, before we can progress to full models that incorporate seasonality and heterogeneity among host populations for the natural dynamics of transmission of borreliosis and other tick-borne diseases.

  5. Role of syn-eruptive plagioclase disequilibrium crystallization in basaltic magma ascent dynamics.

    PubMed

    La Spina, G; Burton, M; De' Michieli Vitturi, M; Arzilli, F

    2016-12-12

    Timescales of magma ascent in conduit models are typically assumed to be much longer than crystallization and gas exsolution for basaltic eruptions. However, it is now recognized that basaltic magmas may rise fast enough for disequilibrium processes to play a key role on the ascent dynamics. The quantification of the characteristic times for crystallization and exsolution processes are fundamental to our understanding of such disequilibria and ascent dynamics. Here we use observations from Mount Etna's 2001 eruption and a magma ascent model to constrain timescales for crystallization and exsolution processes. Our results show that plagioclase reaches equilibrium in 1-2 h, whereas ascent times were <1 h. Using these new constraints on disequilibrium plagioclase crystallization we also reproduce observed crystal abundances for different basaltic eruptions. The strong relation between magma ascent rate and disequilibrium crystallization and exsolution plays a key role in controlling eruption dynamics in basaltic volcanism.

  6. Role of syn-eruptive plagioclase disequilibrium crystallization in basaltic magma ascent dynamics

    PubMed Central

    La Spina, G.; Burton, M.; de' Michieli Vitturi, M.; Arzilli, F.

    2016-01-01

    Timescales of magma ascent in conduit models are typically assumed to be much longer than crystallization and gas exsolution for basaltic eruptions. However, it is now recognized that basaltic magmas may rise fast enough for disequilibrium processes to play a key role on the ascent dynamics. The quantification of the characteristic times for crystallization and exsolution processes are fundamental to our understanding of such disequilibria and ascent dynamics. Here we use observations from Mount Etna's 2001 eruption and a magma ascent model to constrain timescales for crystallization and exsolution processes. Our results show that plagioclase reaches equilibrium in 1–2 h, whereas ascent times were <1 h. Using these new constraints on disequilibrium plagioclase crystallization we also reproduce observed crystal abundances for different basaltic eruptions. The strong relation between magma ascent rate and disequilibrium crystallization and exsolution plays a key role in controlling eruption dynamics in basaltic volcanism. PMID:27941750

  7. Effect of Linkage Disequilibrium on the Identification of Functional Variants

    PubMed Central

    Thomas, Alun; Abel, Haley J; Di, Yanming; Faye, Laura L; Jin, Jing; Liu, Jin; Wu, Zheyan; Paterson, Andrew D

    2011-01-01

    We summarize the contributions of Group 9 of Genetic Analysis Workshop 17. This group addressed the problems of linkage disequilibrium and other longer range forms of allelic association when evaluating the effects of genotypes on phenotypes. Issues raised by long-range associations, whether a result of selection, stratification, possible technical errors, or chance, were less expected but proved to be important. Most contributors focused on regression methods of various types to illustrate problematic issues or to develop adaptations for dealing with high-density genotype assays. Study design was also considered, as was graphical modeling. Although no method emerged as uniformly successful, most succeeded in reducing false-positive results either by considering clusters of loci within genes or by applying smoothing metrics that required results from adjacent loci to be similar. Two unexpected results that questioned our assumptions of what is required to model linkage disequilibrium were observed. The first was that correlations between loci separated by large genetic distances can greatly inflate single-locus test statistics, and, whether the result of selection, stratification, possible technical errors, or chance, these correlations seem overabundant. The second unexpected result was that applying principal components analysis to genome-wide genotype data can apparently control not only for population structure but also for linkage disequilibrium. PMID:22128051

  8. Magnesium isotopic evidence for chemical disequilibrium among cumulus minerals in layered mafic intrusion

    NASA Astrophysics Data System (ADS)

    Chen, Lie-Meng; Teng, Fang-Zhen; Song, Xie-Yan; Hu, Rui-Zhong; Yu, Song-Yue; Zhu, Dan; Kang, Jian

    2018-04-01

    Magnesium isotopic compositions of olivine, clinopyroxene, and ilmenite from the Baima intrusion, SW China, for the first time, are investigated to constrain the magnitude and mechanisms of Mg isotope fractionation among cumulus minerals in layered mafic intrusions and to evaluate their geological implications. Olivine and clinopyroxene have limited Mg isotope variations, with δ26Mg ranging from -0.33 to +0.05‰ and from -0.29 to -0.13‰, respectively, similar to those of mantle xenolithic peridotites. By contrast, ilmenites display extremely large Mg isotopic variation, with δ26Mg ranging from -0.50 to +1.90‰. The large inter-mineral fractionations of Mg isotopes between ilmenite and silicates may reflect both equilibrium and kinetic processes. A few ilmenites have lighter Mg isotopic compositions than coexisting silicates and contain high MgO contents without compositional zoning, indicating equilibrium fractionation. The implication is that the light Mg isotopic compositions of lunar high-Ti basalts may result from an isotopically light source enriched in cumulate ilmenites. On the other hand, most ilmenites have heavy Mg isotopic compositions, coupled with high MgO concentration and chemical zoning, which can be quantitatively modeled by kinetic Mg isotope fractionations induced by subsolidus Mg-Fe exchange between ilmenite and ferromagnesian silicates during the cooling of the Baima intrusion. The extensive occurrence of kinetic Mg isotope fractionation in ilmenites implies the possibility of widespread compositional disequilibrium among igneous minerals in magma chambers. Consequently, disequilibrium effects need to be considered in studies of basaltic magma evolution, magma chamber processes, and magmatic Fe-Ti oxide ore genesis.

  9. Measuring quantitative autism traits in families: informant effect or intergenerational transmission?

    PubMed

    De la Marche, Wouter; Noens, Ilse; Kuppens, Sofie; Spilt, Jantine L; Boets, Bart; Steyaert, Jean

    2015-04-01

    Autism spectrum disorders (ASD) have a high degree of heritability, but there is still much debate about specific causal genes and pathways. To gain insight into patterns of transmission, research has focused on the relatedness of quantitative autism traits (QAT) between family members, mostly using questionnaires. Yet, different kinds of bias may influence research results. In this paper, we focus on possible informant effects and, taking these into account, on possible intergenerational transmission of QAT. This study used multiple informant data retrieved via the Social Responsiveness Scale from 170 families with at least one member with ASD. Using intraclass correlations (ICCs) and mixed model analyses, we investigated inter-informant agreement and differences between parent and teacher reports on children and between self- and other-reports on adults. Using structural equation modelling (SEM), we investigated the relatedness of QAT between family members in ASD families. Parent-teacher agreement about social responsiveness was poor, especially for children with ASD, though agreement between parents was moderate to strong for affected and unaffected children. Agreement between self- and other-report in adult men was good, but only moderate in women. Agreement did not differ between adults with and without ASD. While accounting for informant effects, our SEM results corroborated the assortative mating theory and the intergenerational transmission of QAT from both fathers and mothers to their offspring.

  10. Quantitative study of mammalian cells by scanning transmission soft X-ray microscopy

    NASA Astrophysics Data System (ADS)

    Shinohara, K.; Ohigashi, T.; Toné, S.; Kado, M.; Ito, A.

    2017-06-01

    Molecular distribution in mammalian cells was studied by soft X-ray scanning transmission microscopy with respect to the quantitative aspect of analysis. NEXAFS profiles at the C, N and O K-absorption edges were combined and used for the analysis. For the estimation of quantity for nucleic acids and proteins, NEXAFS profiles of DNA and bovine serum albumin (BSA) at the N K-absorption edge were applied assuming that those were their representatives. The method has a potential to explore the other molecular components than nucleic acids and proteins.

  11. Mapping genes underlying ethnic differences in disease risk by linkage disequilibrium in recently admixed populations.

    PubMed Central

    McKeigue, P M

    1997-01-01

    Where recent admixture has occurred between two populations that have different disease rates for genetic reasons, family-based association studies can be used to map the genes underlying these differences, if the ancestry of the alleles at each locus examined can be assigned to one of the two founding populations. This article explores the statistical power and design requirements of this approach. Markers suitable for assigning the ancestry of genomic regions could be defined by grouping alleles at closely spaced microsatellite loci into haplotypes, or generated by representational difference analysis. For a given relative risk between populations, the sample size required to detect a disease locus that accounts for this relative risk by linkage-disequilibrium mapping in an admixed population is not critically dependent on assumptions about genotype penetrances or allele frequencies. Using the transmission-disequilibrium test to search the genome for a locus that accounts for a relative risk of between 2 and 3 in a high-risk population, compared with a low-risk population, generally requires between 150 and 800 case-parent pairs of mixed descent. The optimal strategy is to conduct an initial study using markers spaced at < or = 10 cM with cases from the second and third generations of mixed descent, and then to map the disease loci more accurately in a subsequent study of a population with a longer history of admixture. This approach has greater statistical power than allele-sharing designs and has obvious applications to the genetics of hypertension, non-insulin-dependent diabetes, and obesity. PMID:8981962

  12. Estimating glacier response times and disequilibrium in a changing climate

    NASA Astrophysics Data System (ADS)

    Christian, J. E.; Koutnik, M.; Roe, G.

    2017-12-01

    Glaciers respond to climate variations according to a characteristic timescale that, for most mountain glaciers, is on the order of 10—100 years. An important consequence of this multi-decadal memory is that a glacier's transient response to a climate trend exhibits a persistent lag behind the equilibrium response. In the context of anthropogenic warming, this means that most glaciers are currently well out of equilibrium, and that a substantial amount of retreat is committed even without further warming. The degree of disequilibrium depends fundamentally on the glacier response timescale, making it an important parameter to constrain. A common and robust metric for the response timescale is τ=H/bt, where H and bt are characteristic values for ice thickness and the terminus mass-balance rate, respectively. However, sparse observations, climate variability, and glacier disequilibrium make it difficult to define these characteristic values. We compare several sources of uncertainty that will affect estimates of the response timescale and thus the degree of disequilibrium. Ice thickness is poorly constrained for many glaciers, which bears directly on estimates of the response timescale. However, errors may also arise from estimating thickness and mass-balance rates in a variable climate. We assess how noisy mass balance and observed terminus fluctuations introduce sampling errors into estimates of the glacier's response timescale and the expected equilibrium response to a climate change. Additionally, the instantaneous value of τ evolves during sustained warming as the glacier thins and retreats. Perhaps counterintuitively, τ can increase if retreat into higher elevations exceeds thinning. This has implications for estimating the timescale based on currently observed geometry and mass balance. We use shallow-ice and 3-stage linear models to explore these effects with synthetic glacier geometries and climate forcings. In this way, we can diagnose the geometric and

  13. Linkage Disequilibrium in a Finite Population That Is Partially Selfing

    PubMed Central

    Golding, G. B.; Strobeck, C.

    1980-01-01

    The linkage disequilibrium expected in a finite, partially selfing population is analyzed, assuming the infinite allele model. Formulas for the expected sum of squares of the linkage disequilibria and the squared standard linkage disequilibrium are derived from the equilibrium values of sixteen inbreeding coefficients required to describe the behavior of the system. These formulas are identical to those obtained with random mating if the effective population size Ne = (1-½S)N and the effective recombination value re = (1-S)r/(1-½S), where S is the proportion of selfing, are substituted for the population size and the recombination value. Therefore, the effect of partial selfing at equilibrium is to reduce the population size by a factor 1-½S and the recombination value by a factor (1-S)/(1-½S). PMID:17249017

  14. Patterns of linkage disequilibrium at PARK16 may explain variances in genetic association studies.

    PubMed

    Li, Huihua; Teo, Yik-Ying; Tan, Eng-King

    2015-09-01

    Reproducing genomewide association studies findings in different populations is challenging, because the reproducibility fundamentally relies on the similar patterns of linkage disequilibrium between the unknown causal variants and the genotyped single-nucleotide polymorphisms (SNPs). The PARK16 locus was reported to alter the risk of Parkinson's disease (PD) in genomewide association studies in Japanese and Caucasians. We evaluated the regional linkage disequilibrium pattern at PARK16 locus in Caucasians, Japanese, and Chinese from HapMap and Chinese, Malays, and Indians from the Singapore Genome Variation Project, using the traditional heatmaps and targeted analysis of PARK16 gene via Monte Carlo simulation through varLD scores of these ethnic groups. One hundred SNPs in Caucasians, 95 SNPs in Chinese, 78 SNPs in Japanese from HapMap, 86 SNPs in Chinese, 99 SNPs in Indians, and 97 SNPs in Malays from the Singapore Genome Variation Project were included. Our targeted analysis showed that the linkage disequilibrium pattern of SNPs close to rs947211 was similar in Caucasians and Asians, including Chinese, Japanese, and Malay (all P > 0.0001), whereas different linkage disequilibrium patterns around rs823128, rs823156, and rs708730 were found between Caucasians and these Asian groups (all P < 0.0001). Our study suggests a higher chance to detect the association between rs947211 and PD in Chinese, Malay, and other Caucasian groups because of the similar linkage disequilibrium pattern around rs947211. The associations between rs823128/rs823156/rs708730 and PD are more likely to be replicated in Chinese and Malay populations. © 2015 International Parkinson and Movement Disorder Society.

  15. Quantitative Microbial Risk Assessment and Infectious Disease Transmission Modeling of Waterborne Enteric Pathogens.

    PubMed

    Brouwer, Andrew F; Masters, Nina B; Eisenberg, Joseph N S

    2018-04-20

    Waterborne enteric pathogens remain a global health threat. Increasingly, quantitative microbial risk assessment (QMRA) and infectious disease transmission modeling (IDTM) are used to assess waterborne pathogen risks and evaluate mitigation. These modeling efforts, however, have largely been conducted independently for different purposes and in different settings. In this review, we examine the settings where each modeling strategy is employed. QMRA research has focused on food contamination and recreational water in high-income countries (HICs) and drinking water and wastewater in low- and middle-income countries (LMICs). IDTM research has focused on large outbreaks (predominately LMICs) and vaccine-preventable diseases (LMICs and HICs). Human ecology determines the niches that pathogens exploit, leading researchers to focus on different risk assessment research strategies in different settings. To enhance risk modeling, QMRA and IDTM approaches should be integrated to include dynamics of pathogens in the environment and pathogen transmission through populations.

  16. Linkage Disequilibrium Under Recurrent Bottlenecks

    PubMed Central

    Schaper, E.; Eriksson, A.; Rafajlovic, M.; Sagitov, S.; Mehlig, B.

    2012-01-01

    To model deviations from selectively neutral genetic variation caused by different forms of selection, it is necessary to first understand patterns of neutral variation. Best understood is neutral genetic variation at a single locus. But, as is well known, additional insights can be gained by investigating multiple loci. The resulting patterns reflect the degree of association (linkage) between loci and provide information about the underlying multilocus gene genealogies. The statistical properties of two-locus gene genealogies have been intensively studied for populations of constant size, as well as for simple demographic histories such as exponential population growth and single bottlenecks. By contrast, the combined effect of recombination and sustained demographic fluctuations is poorly understood. Addressing this issue, we study a two-locus Wright–Fisher model of a population subject to recurrent bottlenecks. We derive coalescent approximations for the covariance of the times to the most recent common ancestor at two loci in samples of two chromosomes. This covariance reflects the degree of association and thus linkage disequilibrium between these loci. We find, first, that an effective population-size approximation describes the numerically observed association between two loci provided that recombination occurs either much faster or much more slowly than the population-size fluctuations. Second, when recombination occurs frequently between but rarely within bottlenecks, we observe that the association of gene histories becomes independent of physical distance over a certain range of distances. Third, we show that in this case, a commonly used measure of linkage disequilibrium, σd2 (closely related to r^2), fails to capture the long-range association between two loci. The reason is that constituent terms, each reflecting the long-range association, cancel. Fourth, we analyze a limiting case in which the long-range association can be described in terms of

  17. Plasmodium knowlesi transmission: integrating quantitative approaches from epidemiology and ecology to understand malaria as a zoonosis.

    PubMed

    Brock, P M; Fornace, K M; Parmiter, M; Cox, J; Drakeley, C J; Ferguson, H M; Kao, R R

    2016-04-01

    The public health threat posed by zoonotic Plasmodium knowlesi appears to be growing: it is increasingly reported across South East Asia, and is the leading cause of malaria in Malaysian Borneo. Plasmodium knowlesi threatens progress towards malaria elimination as aspects of its transmission, such as spillover from wildlife reservoirs and reliance on outdoor-biting vectors, may limit the effectiveness of conventional methods of malaria control. The development of new quantitative approaches that address the ecological complexity of P. knowlesi, particularly through a focus on its primary reservoir hosts, will be required to control it. Here, we review what is known about P. knowlesi transmission, identify key knowledge gaps in the context of current approaches to transmission modelling, and discuss the integration of these approaches with clinical parasitology and geostatistical analysis. We highlight the need to incorporate the influences of fine-scale spatial variation, rapid changes to the landscape, and reservoir population and transmission dynamics. The proposed integrated approach would address the unique challenges posed by malaria as a zoonosis, aid the identification of transmission hotspots, provide insight into the mechanistic links between incidence and land use change and support the design of appropriate interventions.

  18. Effects of instrument imperfections on quantitative scanning transmission electron microscopy.

    PubMed

    Krause, Florian F; Schowalter, Marco; Grieb, Tim; Müller-Caspary, Knut; Mehrtens, Thorsten; Rosenauer, Andreas

    2016-02-01

    Several instrumental imperfections of transmission electron microscopes are characterized and their effects on the results of quantitative scanning electron microscopy (STEM) are investigated and quantified using simulations. Methods to either avoid influences of these imperfections during acquisition or to include them in reference calculations are proposed. Particularly, distortions inflicted on the diffraction pattern by an image-aberration corrector can cause severe errors of more than 20% if not accounted for. A procedure for their measurement is proposed here. Furthermore, afterglow phenomena and nonlinear behavior of the detector itself can lead to incorrect normalization of measured intensities. Single electrons accidentally impinging on the detector are another source of error but can also be exploited for threshold-less calibration of STEM images to absolute dose, incident beam current determination and measurement of the detector sensitivity. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Weak-beam scanning transmission electron microscopy for quantitative dislocation density measurement in steels.

    PubMed

    Yoshida, Kenta; Shimodaira, Masaki; Toyama, Takeshi; Shimizu, Yasuo; Inoue, Koji; Yoshiie, Toshimasa; Milan, Konstantinovic J; Gerard, Robert; Nagai, Yasuyoshi

    2017-04-01

    To evaluate dislocations induced by neutron irradiation, we developed a weak-beam scanning transmission electron microscopy (WB-STEM) system by installing a novel beam selector, an annular detector, a high-speed CCD camera and an imaging filter in the camera chamber of a spherical aberration-corrected transmission electron microscope. The capabilities of the WB-STEM with respect to wide-view imaging, real-time diffraction monitoring and multi-contrast imaging are demonstrated using typical reactor pressure vessel steel that had been used in an European nuclear reactor for 30 years as a surveillance test piece with a fluence of 1.09 × 1020 neutrons cm-2. The quantitatively measured size distribution (average loop size = 3.6 ± 2.1 nm), number density of the dislocation loops (3.6 × 1022 m-3) and dislocation density (7.8 × 1013 m m-3) were carefully compared with the values obtained via conventional weak-beam transmission electron microscopy studies. In addition, cluster analysis using atom probe tomography (APT) further demonstrated the potential of the WB-STEM for correlative electron tomography/APT experiments. © The Author 2017. Published by Oxford University Press on behalf of The Japanese Society of Microscopy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. Accurate virus quantitation using a Scanning Transmission Electron Microscopy (STEM) detector in a scanning electron microscope.

    PubMed

    Blancett, Candace D; Fetterer, David P; Koistinen, Keith A; Morazzani, Elaine M; Monninger, Mitchell K; Piper, Ashley E; Kuehl, Kathleen A; Kearney, Brian J; Norris, Sarah L; Rossi, Cynthia A; Glass, Pamela J; Sun, Mei G

    2017-10-01

    A method for accurate quantitation of virus particles has long been sought, but a perfect method still eludes the scientific community. Electron Microscopy (EM) quantitation is a valuable technique because it provides direct morphology information and counts of all viral particles, whether or not they are infectious. In the past, EM negative stain quantitation methods have been cited as inaccurate, non-reproducible, and with detection limits that were too high to be useful. To improve accuracy and reproducibility, we have developed a method termed Scanning Transmission Electron Microscopy - Virus Quantitation (STEM-VQ), which simplifies sample preparation and uses a high throughput STEM detector in a Scanning Electron Microscope (SEM) coupled with commercially available software. In this paper, we demonstrate STEM-VQ with an alphavirus stock preparation to present the method's accuracy and reproducibility, including a comparison of STEM-VQ to viral plaque assay and the ViroCyt Virus Counter. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  1. Linkage disequilibrium and association mapping.

    PubMed

    Weir, B S

    2008-01-01

    Linkage disequilibrium refers to the association between alleles at different loci. The standard definition applies to two alleles in the same gamete, and it can be regarded as the covariance of indicator variables for the states of those two alleles. The corresponding correlation coefficient rho is the parameter that arises naturally in discussions of tests of association between markers and genetic diseases. A general treatment of association tests makes use of the additive and nonadditive components of variance for the disease gene. In almost all expressions that describe the behavior of association tests, additive variance components are modified by the squared correlation coefficient rho2 and the nonadditive variance components by rho4, suggesting that nonadditive components have less influence than additive components on association tests.

  2. Local thermodynamic equilibrium for globally disequilibrium open systems under stress

    NASA Astrophysics Data System (ADS)

    Podladchikov, Yury

    2016-04-01

    Predictive modeling of far and near equilibrium processes is essential for understanding of patterns formation and for quantifying of natural processes that are never in global equilibrium. Methods of both equilibrium and non-equilibrium thermodynamics are needed and have to be combined. For example, predicting temperature evolution due to heat conduction requires simultaneous use of equilibrium relationship between internal energy and temperature via heat capacity (the caloric equation of state) and disequilibrium relationship between heat flux and temperature gradient. Similarly, modeling of rocks deforming under stress, reactions in system open for the porous fluid flow, or kinetic overstepping of the equilibrium reaction boundary necessarily needs both equilibrium and disequilibrium material properties measured under fundamentally different laboratory conditions. Classical irreversible thermodynamics (CIT) is the well-developed discipline providing the working recipes for the combined application of mutually exclusive experimental data such as density and chemical potential at rest under constant pressure and temperature and viscosity of the flow under stress. Several examples will be presented.

  3. Objective breast tissue image classification using Quantitative Transmission ultrasound tomography

    NASA Astrophysics Data System (ADS)

    Malik, Bilal; Klock, John; Wiskin, James; Lenox, Mark

    2016-12-01

    Quantitative Transmission Ultrasound (QT) is a powerful and emerging imaging paradigm which has the potential to perform true three-dimensional image reconstruction of biological tissue. Breast imaging is an important application of QT and allows non-invasive, non-ionizing imaging of whole breasts in vivo. Here, we report the first demonstration of breast tissue image classification in QT imaging. We systematically assess the ability of the QT images’ features to differentiate between normal breast tissue types. The three QT features were used in Support Vector Machines (SVM) classifiers, and classification of breast tissue as either skin, fat, glands, ducts or connective tissue was demonstrated with an overall accuracy of greater than 90%. Finally, the classifier was validated on whole breast image volumes to provide a color-coded breast tissue volume. This study serves as a first step towards a computer-aided detection/diagnosis platform for QT.

  4. Refining the Use of Linkage Disequilibrium as a Robust Signature of Selective Sweeps

    PubMed Central

    Jacobs, Guy S.; Sluckin, Timothy J.; Kivisild, Toomas

    2016-01-01

    During a selective sweep, characteristic patterns of linkage disequilibrium can arise in the genomic region surrounding a selected locus. These have been used to infer past selective sweeps. However, the recombination rate is known to vary substantially along the genome for many species. We here investigate the effectiveness of current (Kelly’s ZnS and ωmax) and novel statistics at inferring hard selective sweeps based on linkage disequilibrium distortions under different conditions, including a human-realistic demographic model and recombination rate variation. When the recombination rate is constant, Kelly’s ZnS offers high power, but is outperformed by a novel statistic that we test, which we call Zα. We also find this statistic to be effective at detecting sweeps from standing variation. When recombination rate fluctuations are included, there is a considerable reduction in power for all linkage disequilibrium-based statistics. However, this can largely be reversed by appropriately controlling for expected linkage disequilibrium using a genetic map. To further test these different methods, we perform selection scans on well-characterized HapMap data, finding that all three statistics—ωmax, Kelly’s ZnS, and Zα—are able to replicate signals at regions previously identified as selection candidates based on population differentiation or the site frequency spectrum. While ωmax replicates most candidates when recombination map data are not available, the ZnS and Zα statistics are more successful when recombination rate variation is controlled for. Given both this and their higher power in simulations of selective sweeps, these statistics are preferred when information on local recombination rate variation is available. PMID:27516617

  5. Population structure and its effect on haplotype diversity and linkage disequilibrium surrounding the xa5 locus of rice (Oryza sativa L.).

    PubMed Central

    Garris, Amanda J; McCouch, Susan R; Kresovich, Stephen

    2003-01-01

    To assess the usefulness of linkage disequilibrium mapping in an autogamous, domesticated species, we have characterized linkage disequilibrium in the candidate region for xa5, a recessive gene conferring race-specific resistance to bacterial blight in rice. This trait and locus have good mapping information, a tractable phenotype, and available sequence data, but no cloned gene. We sampled 13 short segments from the 70-kb candidate region in 114 accessions of Oryza sativa. Five additional segments were sequenced from the adjacent 45-kb region in resistant accessions to estimate the distance at which linkage disequilibrium decays. The data show significant linkage disequilibrium between sites 100 kb apart. The presence of the xa5 resistant reaction in two ecotypes and in accessions with different haplotypes in the candidate region may indicate multiple origins or genetic heterogeneity for resistance. In addition, genetic differentiation between ecotypes emphasizes the need for controlling for population structure in the design of linkage disequilibrium studies in rice. PMID:14573486

  6. Linking environmental filtering and disequilibrium to biogeography with a community climate framework.

    PubMed

    Blonder, Benjamin; Nogués-Bravo, David; Borregaard, Michael K; Donoghue, John C; Jørgensen, Peter M; Kraft, Nathan J B; Lessard, Jean-Philippe; Morueta-Holme, Naia; Sandel, Brody; Svenning, Jens-Christian; Violle, Cyrille; Rahbek, Carsten; Enquist, Brian J

    2015-04-01

    We present a framework to measure the strength of environmental filtering and disequilibrium of the species composition of a local community across time, relative to past, current, and future climates. We demonstrate the framework by measuring the impact of climate change on New World forests, integrating data for climate niches of more than 14000 species, community composition of 471 New World forest plots, and observed climate across the most recent glacial-interglacial interval. We show that a majority of communities have species compositions that are strongly filtered and are more in equilibrium with current climate than random samples from the regional pool. Variation in the level of current community disequilibrium can be predicted from Last Glacial Maximum climate and will increase with near-future climate change.

  7. Statistical manifestation of quantum correlations via disequilibrium

    NASA Astrophysics Data System (ADS)

    Pennini, F.; Plastino, A.

    2017-12-01

    The statistical notion of disequilibrium (D) was introduced by López-Ruiz, Mancini, and Calbet (LMC) (1995) [1] more than 20 years ago. D measures the amount of ;correlational structure; of a system. We wish to use D to analyze one of the simplest types of quantum correlations, those present in gaseous systems due to symmetry considerations. To this end we extend the LMC formalism to the grand canonical environment and show that D displays distinctive behaviors for simple gases, that allow for interesting insights into their structural properties.

  8. Accurate Virus Quantitation Using a Scanning Transmission Electron Microscopy (STEM) Detector in a Scanning Electron Microscope

    DTIC Science & Technology

    2017-06-29

    Accurate Virus Quantitation Using a Scanning Transmission Electron Microscopy (STEM) Detector in a Scanning Electron Microscope Candace D Blancett1...L Norris2, Cynthia A Rossi4 , Pamela J Glass3, Mei G Sun1,* 1 Pathology Division, United States Army Medical Research Institute of Infectious...Diseases (USAMRIID), 1425 Porter Street, Fort Detrick, Maryland, 21702 2Biostatistics Division, United States Army Medical Research Institute of

  9. The transmission/disequilibrium test and parental-genotype reconstruction: the reconstruction-combined transmission/ disequilibrium test.

    PubMed Central

    Knapp, M

    1999-01-01

    Spielman and Ewens recently proposed a method for testing a marker for linkage with a disease, which combines data from families with and without information on parental genotypes. For some families without parental-genotype information, it may be possible to reconstruct missing parental genotypes from the genotypes of their offspring. The treatment of such a reconstructed family as if parental genotypes have been typed, however, can introduce bias. In the present study, a new method is presented that employs parental-genotype reconstruction and corrects for the biases resulting from reconstruction. The results of an application of this method to a real data set and of a simulation study suggest that this approach may increase the power to detect linkage. PMID:10053021

  10. Refining the Use of Linkage Disequilibrium as a Robust Signature of Selective Sweeps.

    PubMed

    Jacobs, Guy S; Sluckin, Tim J; Kivisild, Toomas

    2016-08-01

    During a selective sweep, characteristic patterns of linkage disequilibrium can arise in the genomic region surrounding a selected locus. These have been used to infer past selective sweeps. However, the recombination rate is known to vary substantially along the genome for many species. We here investigate the effectiveness of current (Kelly's [Formula: see text] and [Formula: see text]) and novel statistics at inferring hard selective sweeps based on linkage disequilibrium distortions under different conditions, including a human-realistic demographic model and recombination rate variation. When the recombination rate is constant, Kelly's [Formula: see text] offers high power, but is outperformed by a novel statistic that we test, which we call [Formula: see text] We also find this statistic to be effective at detecting sweeps from standing variation. When recombination rate fluctuations are included, there is a considerable reduction in power for all linkage disequilibrium-based statistics. However, this can largely be reversed by appropriately controlling for expected linkage disequilibrium using a genetic map. To further test these different methods, we perform selection scans on well-characterized HapMap data, finding that all three statistics-[Formula: see text] Kelly's [Formula: see text] and [Formula: see text]-are able to replicate signals at regions previously identified as selection candidates based on population differentiation or the site frequency spectrum. While [Formula: see text] replicates most candidates when recombination map data are not available, the [Formula: see text] and [Formula: see text] statistics are more successful when recombination rate variation is controlled for. Given both this and their higher power in simulations of selective sweeps, these statistics are preferred when information on local recombination rate variation is available. Copyright © 2016 by the Genetics Society of America.

  11. Germany's Persistent Balance-of-Payments Disequilibrium Revisited. German Studies Notes.

    ERIC Educational Resources Information Center

    Kindleberger, Charles P.

    This essay compares Germany's persistent financial disequilibrium with the balance of payments situation in the United States. Delivered at a Symposium on German Economic Growth and Stability, the author concentrates on Germany's balance of payments surplus and presents U.S. figures mainly as a point of comparison. The material on Germany has been…

  12. Nucleon-Alpha Particle Disequilibrium and Short-Lived r-Process Radioactivities

    NASA Technical Reports Server (NTRS)

    Meyer, B. S.; Clayton, D. D.; Chellapilla, S.; The, L.-S.

    2002-01-01

    r-Process yields can be extremely sensitive to expansion parameters when a persistent disequilibrium between free nucleons and alpha particles is present. This may provide a natural scenario for understanding the variation of heavy and light r-process isotopes in different r-process events. Additional information is contained in the original extended abstract.

  13. Mapping by admixture linkage disequilibrium in human populations: Limits and guidelines

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

    Stephens, J.C.; Briscoe, D.; O`Brien, S.J.

    1994-10-01

    Certain human hereditary conditions, notably those with low penetrance and those which require an environmental event such as infectious disease exposure, are difficult to localize in pedigree analysis, because of uncertainty in the phenotype of an affected patient`s relatives. An approach to locating these genes in human cohort studies would be to use association analysis, which depends on linkage disequilibrium of flanking polymorphic DNA markers. In theory, a high degree of linkage disequilibrium between genes separated by 10-20 cM will be generated and persist in populations that have a history of recent (3-20 generations ago) admixture between genetically differentiated racialmore » groups, such as has occurred in African Americans and Hispanic populations. We have conducted analytic and computer simulations to quantify the effect of genetic, genomic, and population parameters that affect the amount and ascertainment of linkage disequilibrium in populations with a history of genetic admixture. Our goal is to thoroughly explore the ranges of all relevant parameters or factors (e.g., sample size and degree of genetic differentiation between populations) that may be involved in gene localization studies, in hopes of prescribing guidelines for an efficient mapping strategy. The results provide reasonable limits on sample size (200-300 patients), marker number (200-300 in 20-cM intervals), and allele differentiation (loci with allele frequency difference of {ge}.3 between admixed parent populations) to produce an efficient approach (>95% ascertainment) for locating genes not easily tracked in human pedigrees. 321 refs., 8 figs., 7 tabs.« less

  14. [Analysis of HLA haplotype frequency and linkage disequilibrium in patients with acute lymphoblastic leukemia from Northern Chinese Han].

    PubMed

    Gao, Su-qing; Cheng, Liang-hong; Lu, Liang; Jing, Shi-zheng; Cheng, Xi; Zhang, Yin-ze; Zou, Hong-yan; Deng, Zhi-hui

    2009-02-01

    To analyze the difference between the frequencies of HLA-A-B, B-DRB1 and A-B-DRB1 haplotype, as well as their linkage disequilibrium pattern in patients with acute lymphoblastic leukemia(ALL) and healthy controls from Northern Chinese Han. The frequencies of HLA-A-B, B-DRB1, A-B-DR haplotypes and linkage disequilibrium were estimated by Expectation Maximization method based on the genotypes of 643 patients with ALL and 2 0359 unrelated healthy donors, and the statistical significance between the two groups were estimated by chi-square test. Linkage disequilibrium was analyzed with population genetic methods. The most common HLA-A-B, B-DRB1, and A-B-DR haplotypes were A30-B13, A2-B46, A33-B58, B13-DR7, B46-DR9, B52-DR15, B58-DR17, A30-B13-DR7, A33-B58-DR17 and A1-B37-DR10 in both groups. The frequencies of A30-B13, A2-B46, A33-B44, B13-DR7, A30-B13-DR7 and A2-B46-DR9 haplotypes and linkage disequilibrium value were significantly decreased (P<0.05) in the patient group than that in the control group. On the other hand, the frequencies of A2-B52, A31-B61, A24- B8, B60-DR9, B27-DR4, B52-DR14, B44-DR17, B27-DR12 and A11-B27-DR12 haplotypes and linkage disequilibrium value were significantly increased (P<0.05) in the patient group than that in the control group. There are some common and positive linkage disequilibrium haplotypes in both the ALL patients and the healthy donors in Northern Chinese Han. Interestingly, some haplotypes and their linkage disequilibrium patterns had significantly different distributions between the two groups. The study provided basic data for the relationship of ALL and HLA haplotype and for finding the HLA-A, B, DR matching donors.

  15. Transmission versus reflectance spectroscopy for quantitation

    NASA Astrophysics Data System (ADS)

    Gardner, Craig M.

    2018-01-01

    The objective of this work was to compare the accuracy of analyte concentration estimation when using transmission versus diffuse reflectance spectroscopy of a scattering medium. Monte Carlo ray tracing of light through the medium was used in conjunction with pure component absorption spectra and Beer-Lambert absorption along each ray's pathlength to generate matched sets of pseudoabsorbance spectra, containing water and six analytes present in skin. PLS regression models revealed an improvement in accuracy when using transmission compared to reflectance for a range of medium thicknesses and instrument noise levels. An analytical expression revealed the source of the accuracy degradation with reflectance was due both to the reduced collection efficiency for a fixed instrument etendue and to the broad pathlength distribution that detected light travels in the medium before exiting from the incident side.

  16. Quantitative 3D high resolution transmission ultrasound tomography: creating clinically relevant images (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Wiskin, James; Klock, John; Iuanow, Elaine; Borup, Dave T.; Terry, Robin; Malik, Bilal H.; Lenox, Mark

    2017-03-01

    There has been a great deal of research into ultrasound tomography for breast imaging over the past 35 years. Few successful attempts have been made to reconstruct high-resolution images using transmission ultrasound. To this end, advances have been made in 2D and 3D algorithms that utilize either time of arrival or full wave data to reconstruct images with high spatial and contrast resolution suitable for clinical interpretation. The highest resolution and quantitative accuracy result from inverse scattering applied to full wave data in 3D. However, this has been prohibitively computationally expensive, meaning that full inverse scattering ultrasound tomography has not been considered clinically viable. Here we show the results of applying a nonlinear inverse scattering algorithm to 3D data in a clinically useful time frame. This method yields Quantitative Transmission (QT) ultrasound images with high spatial and contrast resolution. We reconstruct sound speeds for various 2D and 3D phantoms and verify these values with independent measurements. The data are fully 3D as is the reconstruction algorithm, with no 2D approximations. We show that 2D reconstruction algorithms can introduce artifacts into the QT breast image which are avoided by using a full 3D algorithm and data. We show high resolution gross and microscopic anatomic correlations comparing cadaveric breast QT images with MRI to establish imaging capability and accuracy. Finally, we show reconstructions of data from volunteers, as well as an objective visual grading analysis to confirm clinical imaging capability and accuracy.

  17. Significant linkage disequilibrium between the Huntington disease gene and the loci D4S10 and D4S95 in the Dutch population

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

    Skraastad, M.I.; Van de Vosse, E.; Belfroid, R.

    1992-10-01

    Significant linkage disequilibrium has been found between the Huntington disease (HD) gene and DNA markers located around D4S95 and D4S98. The linkage-disequilibrium studies favor the proximal location of the HD gene, in contrast to the conflicting results of recombination analyses. The authors have analyzed 45 Dutch HD families with 19 DNA markers and have calculated the strength of linkage disequilibrium. Highly significant linkage disequilibrium has been detected with D4S95, consistent with the studies in other populations. In contrast with most other studies, however, the area of linkage disequilibrium extends from D4S10 proximally to D4S95, covering 1,100 kb. These results confirmmore » that the HD gene most likely maps near D4S95. 28 refs., 1 fig., 2 tabs.« less

  18. Transmission versus reflectance spectroscopy for quantitation.

    PubMed

    Gardner, Craig M

    2018-01-01

    The objective of this work was to compare the accuracy of analyte concentration estimation when using transmission versus diffuse reflectance spectroscopy of a scattering medium. Monte Carlo ray tracing of light through the medium was used in conjunction with pure component absorption spectra and Beer-Lambert absorption along each ray's pathlength to generate matched sets of pseudoabsorbance spectra, containing water and six analytes present in skin. PLS regression models revealed an improvement in accuracy when using transmission compared to reflectance for a range of medium thicknesses and instrument noise levels. An analytical expression revealed the source of the accuracy degradation with reflectance was due both to the reduced collection efficiency for a fixed instrument etendue and to the broad pathlength distribution that detected light travels in the medium before exiting from the incident side. (2018) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).

  19. Inferring outcrossing in the homothallic fungus Sclerotinia sclerotiorum using linkage disequilibrium decay

    USDA-ARS?s Scientific Manuscript database

    The occurrence and frequency of outcrossing in homothallic fungal species in nature is an unresolved question. Here we report detection of frequent outcrossing in the homothallic fungus Sclerotinia sclerotiorum. In using multilocus linkage disequilibrium (LD) to infer recombination among microsatell...

  20. Disequilibrium dynamics in a Keynesian model with time delays

    NASA Astrophysics Data System (ADS)

    Gori, Luca; Guerrini, Luca; Sodini, Mauro

    2018-05-01

    The aim of this research is to analyse a Keynesian goods market closed economy by considering a continuous-time setup with fixed delays. The work compares dynamic results based on linear and nonlinear adjustment mechanisms through which the aggregate supply (production) reacts to a disequilibrium in the goods market and consumption depends on income at a preceding date. Both analytical and geometrical (stability switching curves) techniques are used to characterise the stability properties of the stationary equilibrium.

  1. Using SNP markers to dissect linkage disequilibrium at a major quantitative trait locus for resistance to the potato cyst nematode Globodera pallida on potato chromosome V.

    PubMed

    Achenbach, Ute; Paulo, Joao; Ilarionova, Evgenyia; Lübeck, Jens; Strahwald, Josef; Tacke, Eckhard; Hofferbert, Hans-Reinhard; Gebhardt, Christiane

    2009-02-01

    The damage caused by the parasitic root cyst nematode Globodera pallida is a major yield-limiting factor in potato cultivation . Breeding for resistance is facilitated by the PCR-based marker 'HC', which is diagnostic for an allele conferring high resistance against G. pallida pathotype Pa2/3 that has been introgressed from the wild potato species Solanum vernei into the Solanum tuberosum tetraploid breeding pool. The major quantitative trait locus (QTL) controlling this nematode resistance maps on potato chromosome V in a hot spot for resistance to various pathogens including nematodes and the oomycete Phytophthora infestans. An unstructured sample of 79 tetraploid, highly heterozygous varieties and breeding clones was selected based on presence (41 genotypes) or absence (38 genotypes) of the HC marker. Testing the clones for resistance to G. pallida confirmed the diagnostic power of the HC marker. The 79 individuals were genotyped for 100 single nucleotide polymorphisms (SNPs) at 10 loci distributed over 38 cM on chromosome V. Forty-five SNPs at six loci spanning 2 cM in the interval between markers GP21-GP179 were associated with resistance to G. pallida. Based on linkage disequilibrium (LD) between SNP markers, six LD groups comprising between 2 and 18 SNPs were identified. The LD groups indicated the existence of multiple alleles at a single resistance locus or at several, physically linked resistance loci. LD group C comprising 18 SNPs corresponded to the 'HC' marker. LD group E included 16 SNPs and showed an association peak, which positioned one nematode resistance locus physically close to the R1 gene family.

  2. Dose limited reliability of quantitative annular dark field scanning transmission electron microscopy for nano-particle atom-counting.

    PubMed

    De Backer, A; Martinez, G T; MacArthur, K E; Jones, L; Béché, A; Nellist, P D; Van Aert, S

    2015-04-01

    Quantitative annular dark field scanning transmission electron microscopy (ADF STEM) has become a powerful technique to characterise nano-particles on an atomic scale. Because of their limited size and beam sensitivity, the atomic structure of such particles may become extremely challenging to determine. Therefore keeping the incoming electron dose to a minimum is important. However, this may reduce the reliability of quantitative ADF STEM which will here be demonstrated for nano-particle atom-counting. Based on experimental ADF STEM images of a real industrial catalyst, we discuss the limits for counting the number of atoms in a projected atomic column with single atom sensitivity. We diagnose these limits by combining a thorough statistical method and detailed image simulations. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Thickness dependence of scattering cross-sections in quantitative scanning transmission electron microscopy.

    PubMed

    Martinez, G T; van den Bos, K H W; Alania, M; Nellist, P D; Van Aert, S

    2018-04-01

    In quantitative scanning transmission electron microscopy (STEM), scattering cross-sections have been shown to be very sensitive to the number of atoms in a column and its composition. They correspond to the integrated intensity over the atomic column and they outperform other measures. As compared to atomic column peak intensities, which saturate at a given thickness, scattering cross-sections increase monotonically. A study of the electron wave propagation is presented to explain the sensitivity of the scattering cross-sections. Based on the multislice algorithm, we analyse the wave propagation inside the crystal and its link to the scattered signal for the different probe positions contained in the scattering cross-section for detector collection in the low-, middle- and high-angle regimes. The influence to the signal from scattering of neighbouring columns is also discussed. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Effects of Demographic History on the Detection of Recombination Hotspots from Linkage Disequilibrium

    PubMed Central

    Dapper, Amy L; Payseur, Bret A

    2018-01-01

    Abstract In some species, meiotic recombination is concentrated in small genomic regions. These “recombination hotspots” leave signatures in fine-scale patterns of linkage disequilibrium, raising the prospect that the genomic landscape of hotspots can be characterized from sequence variation. This approach has led to the inference that hotspots evolve rapidly in some species, but are conserved in others. Historic demographic events, such as population bottlenecks, are known to affect patterns of linkage disequilibrium across the genome, violating population genetic assumptions of this approach. Although such events are prevalent, demographic history is generally ignored when making inferences about the evolution of recombination hotspots. To determine the effect of demography on the detection of recombination hotspots, we use the coalescent to simulate haplotypes with a known recombination landscape. We measure the ability of popular linkage disequilibrium-based programs to detect hotspots across a range of demographic histories, including population bottlenecks, hidden population structure, population expansions, and population contractions. We find that demographic events have the potential to greatly reduce the power and increase the false positive rate of hotspot discovery. Neither the power nor the false positive rate of hotspot detection can be predicted without also knowing the demographic history of the sample. Our results suggest that ignoring demographic history likely overestimates the power to detect hotspots and therefore underestimates the degree of hotspot sharing between species. We suggest strategies for incorporating demographic history into population genetic inferences about recombination hotspots. PMID:29045724

  5. Direct observation of Sr vacancies in SrTiO 3 by quantitative scanning transmission electron microscopy

    DOE PAGES

    Kim, Honggyu; Zhang, Jack Y.; Raghavan, Santosh; ...

    2016-12-22

    Unveiling the identity, spatial configuration, and microscopic structure of point defects is one of the key challenges in materials science. Here, we demonstrate that quantitative scanning transmission electron microscopy (STEM) can be used to directly observe Sr vacancies in SrTiO 3 and to determine the atom column relaxations around them. By combining recent advances in quantitative STEM, including variableangle, high-angle annular dark-field imaging and rigid registration methods, with frozen phonon multislice image simulations, we identify which Sr columns contain vacancies and quantify the number of vacancies in them. Here, picometer precision measurements of the surrounding atom column positions show thatmore » the nearest-neighbor Ti atoms are displaced away from the Sr vacancies. The results open up a new methodology for studying the microscopic mechanisms by which point defects control materials properties.« less

  6. Direct observation of Sr vacancies in SrTiO 3 by quantitative scanning transmission electron microscopy

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

    Kim, Honggyu; Zhang, Jack Y.; Raghavan, Santosh

    Unveiling the identity, spatial configuration, and microscopic structure of point defects is one of the key challenges in materials science. Here, we demonstrate that quantitative scanning transmission electron microscopy (STEM) can be used to directly observe Sr vacancies in SrTiO 3 and to determine the atom column relaxations around them. By combining recent advances in quantitative STEM, including variableangle, high-angle annular dark-field imaging and rigid registration methods, with frozen phonon multislice image simulations, we identify which Sr columns contain vacancies and quantify the number of vacancies in them. Here, picometer precision measurements of the surrounding atom column positions show thatmore » the nearest-neighbor Ti atoms are displaced away from the Sr vacancies. The results open up a new methodology for studying the microscopic mechanisms by which point defects control materials properties.« less

  7. Novel measures of linkage disequilibrium that correct the bias due to population structure and relatedness.

    PubMed

    Mangin, B; Siberchicot, A; Nicolas, S; Doligez, A; This, P; Cierco-Ayrolles, C

    2012-03-01

    Among the several linkage disequilibrium measures known to capture different features of the non-independence between alleles at different loci, the most commonly used for diallelic loci is the r(2) measure. In the present study, we tackled the problem of the bias of r(2) estimate, which results from the sample structure and/or the relatedness between genotyped individuals. We derived two novel linkage disequilibrium measures for diallelic loci that are both extensions of the usual r(2) measure. The first one, r(S)(2), uses the population structure matrix, which consists of information about the origins of each individual and the admixture proportions of each individual genome. The second one, r(V)(2), includes the kinship matrix into the calculation. These two corrections can be applied together in order to correct for both biases and are defined either on phased or unphased genotypes.We proved that these novel measures are linked to the power of association tests under the mixed linear model including structure and kinship corrections. We validated them on simulated data and applied them to real data sets collected on Vitis vinifera plants. Our results clearly showed the usefulness of the two corrected r(2) measures, which actually captured 'true' linkage disequilibrium unlike the usual r(2) measure.

  8. Quantitative assessment of the probability of bluetongue virus transmission by bovine semen and effectiveness of preventive measures.

    PubMed

    Napp, S; Allepuz, A; García-Bocanegra, I; Alba, A; Vilar, M J; Casal, J

    2011-03-15

    Given that bluetongue (BT) may potentially be transmitted by semen, that the disease has significantly expanded in recent years, and that millions of doses of cattle semen are annually traded throughout the world, the transmission of bluetongue virus (BTV) by semen could have severe consequences in the cattle industry. The hypothesis that infected bulls could excrete BTV in their semen led to restrictions on international trade of ruminant semen and the establishment of measures to prevent BTV transmission by semen. However, neither the risk of BTV transmission by semen nor the effectiveness of these measures was estimated quantitatively. The objective of the study was to assess, in case of introduction of BTV into a bovine semen collection centre (SCC), both the risk of BTV transmission by bovine semen and the risk reduction achieved by some of the preventive measures, by means of a stochastic risk assessment model. The model was applied to different scenarios, depending on for example the type of diagnostic test and the interval between the controls (testing) of donor bulls, or the rate of BTV spread within the SCC. Enzyme-linked immunosorbant assay (ELISA) controls of donor bulls every 60 days seemed to be an ineffective method for reducing the risk of BTV transmission in contrast to polymerase chain reaction (PCR) tests every 28 days. An increase in the rate of spread within the SCC resulted in a reduced risk of BTV transmission by semen. The storage of semen for 30 days prior to dispatch seemed to be an efficient way of reducing the risk of transmission by semen. The sensitivity analysis identified the probability of BTV shedding in semen as a crucial parameter in the probability of BTV transmission by semen. However, there is a great degree of uncertainty associated with this parameter, with significant differences depending on the BTV serotype. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Effects of Demographic History on the Detection of Recombination Hotspots from Linkage Disequilibrium.

    PubMed

    Dapper, Amy L; Payseur, Bret A

    2018-02-01

    In some species, meiotic recombination is concentrated in small genomic regions. These "recombination hotspots" leave signatures in fine-scale patterns of linkage disequilibrium, raising the prospect that the genomic landscape of hotspots can be characterized from sequence variation. This approach has led to the inference that hotspots evolve rapidly in some species, but are conserved in others. Historic demographic events, such as population bottlenecks, are known to affect patterns of linkage disequilibrium across the genome, violating population genetic assumptions of this approach. Although such events are prevalent, demographic history is generally ignored when making inferences about the evolution of recombination hotspots. To determine the effect of demography on the detection of recombination hotspots, we use the coalescent to simulate haplotypes with a known recombination landscape. We measure the ability of popular linkage disequilibrium-based programs to detect hotspots across a range of demographic histories, including population bottlenecks, hidden population structure, population expansions, and population contractions. We find that demographic events have the potential to greatly reduce the power and increase the false positive rate of hotspot discovery. Neither the power nor the false positive rate of hotspot detection can be predicted without also knowing the demographic history of the sample. Our results suggest that ignoring demographic history likely overestimates the power to detect hotspots and therefore underestimates the degree of hotspot sharing between species. We suggest strategies for incorporating demographic history into population genetic inferences about recombination hotspots. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  10. Quantitative transmission characteristics of different H5 low pathogenic avian influenza viruses in Muscovy ducks.

    PubMed

    Niqueux, Éric; Picault, Jean-Paul; Amelot, Michel; Allée, Chantal; Lamandé, Josiane; Guillemoto, Carole; Pierre, Isabelle; Massin, Pascale; Blot, Guillaume; Briand, François-Xavier; Rose, Nicolas; Jestin, Véronique

    2014-01-10

    EU annual serosurveillance programs show that domestic duck flocks have the highest seroprevalence of H5 antibodies, demonstrating the circulation of notifiable avian influenza virus (AIV) according to OIE, likely low pathogenic (LP). Therefore, transmission characteristics of LPAIV within these flocks can help to understand virus circulation and possible risk of propagation. This study aimed at estimating transmission parameters of four H5 LPAIV (three field strains from French poultry and decoy ducks, and one clonal reverse-genetics strain derived from one of the former), using a SIR model to analyze data from experimental infections in SPF Muscovy ducks. The design was set up to accommodate rearing on wood shavings with a low density of 1.6 ducks/m(2): 10 inoculated ducks were housed together with 15 contact-exposed ducks. Infection was monitored by RNA detection on oropharyngeal and cloacal swabs using real-time RT-PCR with a cutoff corresponding to 2-7 EID50. Depending on the strain, the basic reproduction number (R0) varied from 5.5 to 42.7, confirming LPAIV could easily be transmitted to susceptible Muscovy ducks. The lowest R0 estimate was obtained for a H5N3 field strain, due to lower values of transmission rate and duration of infectious period, whereas reverse-genetics derived H5N1 strain had the highest R0. Frequency and intensity of clinical signs were also variable between strains, but apparently not associated with longer infectious periods. Further comparisons of quantitative transmission parameters may help to identify relevant viral genetic markers for early detection of potentially more virulent strains during surveillance of LPAIV. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. A model that helps explain Sr-isotope disequilibrium between feldspar phenocrysts and melt in large-volume silicic magma systems

    USGS Publications Warehouse

    Duffield, W.A.; Ruiz, J.

    1998-01-01

    Feldspar phenocrysts of silicic volcanic rocks are commonly in Sr-isotopic disequilibrium with groundmass. In some cases the feldspar is more radiogenic, and in others it is less radiogenic. Several explanations have been published previously, but none of these is able to accommodate both senses of disequilibrium. We present a model by which either more- or less-radiogenic feldspar (or even both within a single eruptive unit) can originate. The model requires a magma body open to interaction with biotite- and feldspar-bearing wall rock. Magma is incrementally contaminated as wall rock melts incongruently. Biotite preferentially melts first, followed by feldspar. Such melting behavior, which is supported by both field and experimental studies, first contaminates magma with a relatively radiogenic addition, followed by a less-radiogenic addition. Feldspar phenocrysts lag behind melt (groundmass of volcanic rock) in incorporating the influx of contaminant, thus resulting in Sr-isotopic disequilibrium between the crystals and melt. The sense of disequilibrium recorded in a volcanic rock depends on when eruption quenches the contamination process. This model is testable by isotopic fingerprinting of individual feldspar crystals. For a given set of geologic boundary conditions, specific core-to-rim Sr-isotopic profiles are expectable. Moreover, phenocrysts that nucleate at different times during the contamination process should record different and predictable parts of the history. Initial results of Sr-isotopic fingerprinting of sanidine phenocrysts from the Taylor Creek Rhyolite are consistent with the model. More tests of the model are desirable.Feldspar phenocrysts of silicic volcanic rocks are commonly in Sr-isotopic disequilibrium with groundmass. In some cases the feldspar is more radiogenic, and in others it is less radiogenic. Several explanations have been published previously, but none of these is able to accommodate both senses of disequilibrium. We present a

  12. Ecological disequilibrium drives insect pest and pathogen accumulation in non-native trees

    PubMed Central

    Burgess, Treena I.; Le Roux, Johannes J.; Richardson, David M.; Slippers, Bernard; Wingfield, Michael J.

    2017-01-01

    Abstract Non-native trees have become dominant components of many landscapes, including urban ecosystems, commercial forestry plantations, fruit orchards and as invasives in natural ecosystems. Often, these trees have been separated from their natural enemies (i.e. insects and pathogens) leading to ecological disequilibrium, that is, the immediate breakdown of historically co-evolved interactions once introduced into novel environments. Long-established, non-native tree plantations provide useful experiments to explore the dimensions of such ecological disequilibria. We quantify the status quo of non-native insect pests and pathogens catching up with their tree hosts (planted Acacia, Eucalyptus and Pinus species) in South Africa, and examine which native South African enemy species utilize these trees as hosts. Interestingly, pines, with no confamilial relatives in South Africa and the longest residence time (almost two centuries), have acquired only one highly polyphagous native pathogen. This is in contrast to acacias and eucalypts, both with many native and confamilial relatives in South Africa that have acquired more native pathogens. These patterns support the known role of phylogenetic relatedness of non-native and native floras in influencing the likelihood of pathogen shifts between them. This relationship, however, does not seem to hold for native insects. Native insects appear far more likely to expand their feeding habits onto non-native tree hosts than are native pathogens, although they are generally less damaging. The ecological disequilibrium conditions of non-native trees are deeply rooted in the eco-evolutionary experience of the host plant, co-evolved natural enemies and native organisms from the introduced range. We should expect considerable spatial and temporal variation in ecological disequilibrium conditions among non-native taxa, which can be significantly influenced by biosecurity and management practices. PMID:28013250

  13. Testing for linkage disequilibrium in the New Zealand radiata pine breeding population

    Treesearch

    S. Kumar; Craig Echt; P.L. Wilcox; T.E. Richardson

    2004-01-01

    Linkage analysis is commonly uscd to find marker-trait associations within the full-sib families of forest tree and other species. Study of marker-trait associations at the population level is termed linkage-disequilibrium (LD) mapping. A female-tester design comprising 200 full-sib families generated by crossing 40 pollen parents with five female parents was used to...

  14. Unconsciously Indigenous Leadership: The Role of Cognitive Disequilibrium in Preparing Democratic Educational Leaders

    ERIC Educational Resources Information Center

    Farmer, Tod Allen

    2008-01-01

    This paper focuses on the role of cognitive disequilibrium in preparing democratic educational leaders. Followers emerge into leaders with what are many times unconsciously socialized norms and values indigenous to their local culture. One of the roles of a democratic leadership preparation program is to challenge these unconsciously accepted…

  15. Extended Intermarker Linkage Disequilibrium in the Afrikaners

    PubMed Central

    Hall, Diana; Wijsman, Ellen M.; Roos, J. Louw; Gogos, Joseph A.; Karayiorgou, Maria

    2002-01-01

    In this study we conducted an investigation of the background level of linkage disequilibrium (LD) in the Afrikaner population to evaluate the appropriateness of this genetic isolate for mapping complex traits. We analyzed intermarker LD in 62 nuclear families using microsatellite markers covering extended chromosomal regions. The markers were selected to allow the first direct comparison of long-range LD in the Afrikaners to LD in other demographic groups. Using several statistical measures, we find significant evidence for LD in the Afrikaners extending remarkably over a 6-cM range. In contrast, LD decays significantly beyond 3-cM distances in the other founder and outbred populations examined. This study strongly supports the appropriateness of the Afrikaner population for genome-wide scans that exploit LD to map common, multigenic disorders. PMID:12045148

  16. Extended intermarker linkage disequilibrium in the Afrikaners.

    PubMed

    Hall, Diana; Wijsman, Ellen M; Roos, J Louw; Gogos, Joseph A; Karayiorgou, Maria

    2002-06-01

    In this study we conducted an investigation of the background level of linkage disequilibrium (LD) in the Afrikaner population to evaluate the appropriateness of this genetic isolate for mapping complex traits. We analyzed intermarker LD in 62 nuclear families using microsatellite markers covering extended chromosomal regions. The markers were selected to allow the first direct comparison of long-range LD in the Afrikaners to LD in other demographic groups. Using several statistical measures, we find significant evidence for LD in the Afrikaners extending remarkably over a 6-cM range. In contrast, LD decays significantly beyond 3-cM distances in the other founder and outbred populations examined. This study strongly supports the appropriateness of the Afrikaner population for genome-wide scans that exploit LD to map common, multigenic disorders.

  17. Quantitative Tracking of Salmonella Enteritidis Transmission Routes Using Barcode-Tagged Isogenic Strains in Chickens: Proof-of-Concept Study

    PubMed Central

    Yang, Yichao; Ricke, Steven C.; Tellez, Guillermo; Kwon, Young Min

    2017-01-01

    Salmonella is an important foodborne bacterial pathogen, however, a fundamental understanding on Salmonella transmission routes within a poultry flock remains unclear. In this study, a series of barcode-tagged strains were constructed by inserting six random nucleotides into a functionally neutral region on the chromosome of S. Enteritidis as a tool for quantitative tracking of Salmonella transmission in chickens. Six distinct barcode-tagged strains were used for infection or contamination at either low dose (103 CFUs; three strains) or high dose (105 CFUs; three strains) in three independent experiments (Experiment 1 oral gavage; Experiment 2 contaminated feed; Experiment 3 contaminated water). For all chick experiments, cecal and foot-wash samples were collected from a subset of the chickens at days 7 or/and 14, from which genomic DNA was extracted and used to amplify the barcode regions. After the resulting PCR amplicons were pooled and analyzed by MiSeq sequencing, a total of approximately 1.5 million reads containing the barcode sequences were analyzed to determine the relative frequency of every barcode-tagged strain in each sample. In Experiment 1, the high dose of oral infection was correlated with greater dominance of the strains in the ceca of the respective seeder chickens and also in the contact chickens yet at lesser degrees. When chicks were exposed to contaminated feed (Experiment 2) or water (Experiment 3), there were no clear patterns of the barcode-tagged strains in relation to the dosage, except that the strains introduced at low dose required a longer time to colonize the ceca with contaminated feed. Most foot-wash samples contained only one to three strains for the majority of the samples, suggesting potential existence of an unknown mechanism(s) for strain exclusion. These results demonstrated the proof of concept of using barcode tagged to investigate transmission dynamics of Salmonella in chickens in a quantitative manner. PMID:28261587

  18. Identification of positive selection signatures in pigs by comparing linkage disequilibrium variances.

    PubMed

    Li, X; Yang, S; Dong, K; Tang, Z; Li, K; Fan, B; Wang, Z; Liu, B

    2017-10-01

    Selection affects the patterns of linkage disequilibrium (LD) around the site of a beneficial allele with an increase in LD among the hitchhiking alleles. Comparing the differences in regional LD between pig populations could help to identify putative genomic regions with potential adaptations for economic traits. In this study, using Illumina Porcine SNP60K BeadChip genotyping data from 207 Chinese indigenous, 117 South American village and 408 Large White pigs, we estimated the variation of genome-wide LD between populations using the varld program. The top 0.1% standardized VarLD scores were used as a criterion for all comparisons, and compared with LD blocks, a total of four selection signatures on Sus scrofa chromosome (SSC) 7, 9, 13 and 14 were identified in all populations. These signatures overlapped with quantitative trait loci for linoleic acid content, age at puberty, number of muscle fibers per unit area, hip structure and body weight traits in pigs. Among them, one of the signatures (56.5-56.6 Mb on SSC7) in Large White pigs harbored the ADAMTSL3 gene, which is known to affect body length. The findings of this study seem to point toward recent selection in different pig populations. Further investigations are encouraged to confirm the selection signatures detected by varld in the present study. © 2017 Stichting International Foundation for Animal Genetics.

  19. Insights into solar nebula formation of pyrrhotite from nanoscale disequilibrium phases produced by H2S sulfidation of Fe metal

    DOE PAGES

    Gainsforth, Z; Lauretta, DS; Tamura, N; ...

    2017-09-01

    © 2017 by Walter de Gruyter Berlin/Boston. Lauretta (2005) produced sulfide in the laboratory by exposing canonical nebular metal analogs to H 2 S gas under temperatures and pressures relevant to the formation of the Solar System. The resulting reactions produced a suite of sulfides and nanophase materials not visible at the microprobe scale, but which we have now analyzed by TEM for comparison with interplanetary dust samples and comet Wild 2 samples returned by the Stardust mission. We find the unexpected result that disequilibrium formation favors pyrrhotite over troilite and also produces minority schreibersite, daubréelite, barringerite, taenite, oldhamite, andmore » perryite at the metal-sulfide interface. TEM identification of nanophases and analysis of pyrrhotite superlattice reflections illuminate the formation pathway of disequilibrium sulfide. We discuss the conditions under which such disequilibrium can occur, and implications for formation of sulfide found in extraterrestrial materials.« less

  20. Revealing misassembled segments in the bovine reference genome by high resolution linkage disequilibrium scan

    USDA-ARS?s Scientific Manuscript database

    Misassembly signatures, created by shuffling the order of sequences while assembling a genome, can be easily seen by analyzing the unexpected behaviour of the linkage disequilibrium (LD) decay. A heuristic process was proposed to identify those misassembly signatures and presented the ones found in ...

  1. Map-based molecular diversity, linkage disequilibrium and association mapping of fruit traits in melon

    USDA-ARS?s Scientific Manuscript database

    The wide phenotypic diversity, in melon fruits, is the result of consumer preferences combined with genotype fitness to the different agro-climatic zones. There is no sufficient information with respect to the extent of genetic divergence, population structure and linkage disequilibrium (LD) in mel...

  2. Demographic Disequilibrium in Early Twentieth Century Thailand: Falling Mortality, Rising Fertility, or Both?

    PubMed

    Carmichael, Gordon A

    2008-07-17

    Estimates of Thai crude birth and death rates date from 1920 when the former was around 20 per thousand higher than the latter, implying natural increase of 2 percent per annum. Such disequilibrium cannot have been the norm over the long term historical past, when population growth must have been comparatively slow. This paper explores the bases for likely past relative equilibrium between Siamese birth and death rates, then seeks to explain the disequilibrium apparent by 1920. Classic demographic transition theory postulates initially high birth and death rates, this equilibrium eventually being broken by falling mortality. In Thailand, however, there is likely to have been both significant mortality decline and appreciable fertility increase after 1850, as the virtual elimination of indigenous warfare, rapid growth of the export rice economy and the demise of slavery and corvée labour created a new domestic environment. Characterized by more dispersed, often frontier, settlement, this environment was unprecedentedly sedate and settled, afforded ordinary households a previously unknown level of control over their resources of labour, and generated optimism about prospects for the next generation.

  3. Demographic Disequilibrium in Early Twentieth Century Thailand: Falling Mortality, Rising Fertility, or Both?

    PubMed Central

    Carmichael, Gordon A.

    2011-01-01

    Estimates of Thai crude birth and death rates date from 1920 when the former was around 20 per thousand higher than the latter, implying natural increase of 2 percent per annum. Such disequilibrium cannot have been the norm over the long term historical past, when population growth must have been comparatively slow. This paper explores the bases for likely past relative equilibrium between Siamese birth and death rates, then seeks to explain the disequilibrium apparent by 1920. Classic demographic transition theory postulates initially high birth and death rates, this equilibrium eventually being broken by falling mortality. In Thailand, however, there is likely to have been both significant mortality decline and appreciable fertility increase after 1850, as the virtual elimination of indigenous warfare, rapid growth of the export rice economy and the demise of slavery and corvée labour created a new domestic environment. Characterized by more dispersed, often frontier, settlement, this environment was unprecedentedly sedate and settled, afforded ordinary households a previously unknown level of control over their resources of labour, and generated optimism about prospects for the next generation. PMID:21966299

  4. Investigating fold structures of 2D materials by quantitative transmission electron microscopy.

    PubMed

    Wang, Zhiwei; Zhang, Zengming; Liu, Wei; Wang, Zhong Lin

    2017-04-01

    We report an approach developed for deriving 3D structural information of 2D membrane folds based on the recently-established quantitative transmission electron microscopy (TEM) in combination with density functional theory (DFT) calculations. Systematic multislice simulations reveal that the membrane folding leads to sufficiently strong electron scattering which enables a precise determination of bending radius. The image contrast depends also on the folding angles of 2D materials due to the variation of projection potentials, which however exerts much smaller effect compared with the bending radii. DFT calculations show that folded edges are typically characteristic of (fractional) nanotubes with the same curvature retained after energy optimization. Owing to the exclusion of Stobbs factor issue, numerical simulations were directly used in comparison with the experimental measurements on an absolute contrast scale, which results in a successful determination of bending radius of folded monolayer MoS 2 films. The method should be applicable to characterizing all 2D membranes with 3D folding features. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Neuroendocrine–immune disequilibrium and endometriosis: an interdisciplinary approach

    PubMed Central

    Tariverdian, Nadja; Theoharides, Theoharis C.; Siedentopf, Friederike; Gutiérrez, Gabriela; Jeschke, Udo; Rabinovich, Gabriel A.; Blois, Sandra M.

    2007-01-01

    Endometriosis, a chronic disease characterized by endometrial tissue located outside the uterine cavity, affects one fourth of young women and is associated with chronic pelvic pain and infertility. However, an in-depth understanding of the pathophysiology and effective treatment strategies of endometriosis is still largely elusive. Inadequate immune and neuroendocrine responses are significantly involved in the pathophysiology of endometriosis, and key findings are summarized in the present review. We discuss here the role of different immune mechanisms particularly adhesion molecules, protein–glycan interactions, and pro-angiogenic mediators in the development and progression of the disease. Finally, we introduce the concept of endometrial dissemination as result of a neuroendocrine-immune disequilibrium in response to high levels of perceived stress caused by cardinal clinical symptoms of endometriosis. PMID:17621704

  6. A quantitative risk assessment of multiple factors influencing HIV/AIDS transmission through unprotected sex among HIV-seropositive men.

    PubMed

    Gerbi, Gemechu B; Habtemariam, Tsegaye; Tameru, Berhanu; Nganwa, David; Robnett, Vinaida

    2012-01-01

    The objective of this study is to conduct a quantitative risk assessment of multiple factors influencing HIV/AIDS transmission through unprotected sexual practices among HIV-seropositive men. A knowledgebase was developed by reviewing different published sources. The data were collected from different sources including Centers for Disease Control and Prevention, selected journals, and reports. The risk pathway scenario tree was developed based on a comprehensive review of published literature. The variables are organized into nine major parameter categories. Monte Carlo simulations for the quantitative risk assessment of HIV/AIDS transmission was executed with the software @Risk 4.0 (Palisade Corporation). Results show that the value for the likelihood of unprotected sex due to having less knowledge about HIV/AIDS and negative attitude toward condom use and safer sex ranged from 1.24 × 10(-5) to 8.47 × 10(-4) with the mean and standard deviation of 1.83 × 10(-4) and 8.63 × 10(-5), respectively. The likelihood of unprotected sex due to having greater anger-hostility, anxiety, less satisfied with aspects of life, and greater depressive symptoms ranged from 2.76 × 10(-9) to 5.34 × 10(-7) with the mean and standard deviation of 5.23 × 10(-8) and 3.58 × 10(-8), respectively. The findings suggest that HIV/AIDS research and intervention programs must be focused on behavior, and the broader setting within which individual risky behaviors occur.

  7. Population-Specific Patterns of Linkage Disequilibrium and SNP Variation in Spring and Winter Polyploid Wheat

    USDA-ARS?s Scientific Manuscript database

    Single nucleotide polymorphisms (SNPs) are ideally suited for the construction of high-resolution genetic maps, studying population evolutionary history and performing genome-wide association mapping experiments. Here we used a genome-wide set of 1536 SNPs to study linkage disequilibrium (LD) and po...

  8. A first insight into population structure and linkage disequilibrium in the US peanut minicore collection

    USDA-ARS?s Scientific Manuscript database

    Knowledge of genetic diversity, population structure, and degree of linkage disequilibrium (LD) in target association mapping populations is of great importance and is a prerequisite for LD-based mapping. In the present study, 96 genotypes comprising 92 accessions of the US peanut minicore collectio...

  9. Cytonuclear disequilibrium and genetic drift in a natural population of ponderosa pine.

    PubMed Central

    Latta, R G; Linhart, Y B; Mitton, J B

    2001-01-01

    We measured the cytonuclear disequilibrium between 11 nuclear allozyme loci and both mitochondrial and chloroplast DNA haplotypes in a natural population of ponderosa pine (Pinus ponderosa, Laws). Three allozyme loci showed significant associations with mtDNA variation, while two other loci showed significant association with cpDNA. However, the absolute number of individuals involved in any of the associations was small, such that in none of the nuclear-organellar combinations was the difference between observed and expected numbers >11 individuals. Patterns of association were not consistent across loci or organellar genomes, suggesting that they are not the result of mating patterns, which would act uniformly on all loci. This pattern of disequilibria is consistent with the action of genetic drift and with existing knowledge of the structure of this population and thus does not imply the action of other evolutionary processes. The overall magnitude (normalized disequilibrium) of associations was greater for maternally inherited mtDNA than for paternally inherited cpDNA, though this difference was neither large nor significant. Such significant disequilibria involving the paternally inherited organelle indicate that not only are there a limited number of seed parents, but the effective number of pollen parents is also limited. PMID:11404345

  10. Experimental investigation of alternative transmission functions: Quantitative evidence for the importance of nonlinear transmission dynamics in host-parasite systems.

    PubMed

    Orlofske, Sarah A; Flaxman, Samuel M; Joseph, Maxwell B; Fenton, Andy; Melbourne, Brett A; Johnson, Pieter T J

    2018-05-01

    Understanding pathogen transmission is crucial for predicting and managing disease. Nonetheless, experimental comparisons of alternative functional forms of transmission remain rare, and those experiments that are conducted are often not designed to test the full range of possible forms. To differentiate among 10 candidate transmission functions, we used a novel experimental design in which we independently varied four factors-duration of exposure, numbers of parasites, numbers of hosts and parasite density-in laboratory infection experiments. We used interactions between amphibian hosts and trematode parasites as a model system and all candidate models incorporated parasite depletion. An additional manipulation involving anaesthesia addressed the effects of host behaviour on transmission form. Across all experiments, nonlinear transmission forms involving either a power law or a negative binomial function were the best-fitting models and consistently outperformed the linear density-dependent and density-independent functions. By testing previously published data for two other host-macroparasite systems, we also found support for the same nonlinear transmission forms. Although manipulations of parasite density are common in transmission studies, the comprehensive set of variables tested in our experiments revealed that variation in density alone was least likely to differentiate among competing transmission functions. Across host-pathogen systems, nonlinear functions may often more accurately represent transmission dynamics and thus provide more realistic predictions for infection. © 2017 The Authors. Journal of Animal Ecology published by John Wiley & Sons Ltd on behalf of British Ecological Society.

  11. Th-230 - U-238 series disequilibrium of the Olkaria rhyolites Gregory Rift Valley, Kenya: Residence times

    NASA Technical Reports Server (NTRS)

    Black, S.; Macdonald, R.; Kelly, M.

    1993-01-01

    U-series disequilibrium analyses have been conducted on samples from Olkaria rhyolite centers with ages being available for all but one center using both internal and whole rock isochrons. 67 percent of the rhyolites analyzed show U-Th disequilibrium, ranging from 27 percent excess thorium to 36 percent excess uranium. Internal and whole rock isochrons give crystallization/formation ages between 65 ka and 9 ka, in every case these are substantially older than the eruptive dates. The residence times of the rhyolites (U-Th age minus the eruption date) have decreased almost linearly with time, from 45 ka to 7 Ka suggesting a possible increase of activity within the system related to increased basaltic input. The long residence times are mirrored by large Rn-222 fluxes from the centers which cannot be explained by larger U contents.

  12. Genetic Diversity, Population Structure, and Linkage Disequilibrium in Bread Wheat (Triticum aestivum L.).

    PubMed

    Tascioglu, Tulin; Metin, Ozge Karakas; Aydin, Yildiz; Sakiroglu, Muhammet; Akan, Kadir; Uncuoglu, Ahu Altinkut

    2016-08-01

    Bread wheat (Triticum aestivum L.) gene pool was analyzed with 117 microsatellite markers scattered throughout A, B, and D genomes. Ninety microsatellite markers were giving 1620 polymorphic alleles in 55 different bread wheat genotypes. These genotypes were found to be divided into three subgroups based on Bayesian model and Principal component analysis. The highest polymorphism information content value for the markers resides on A genome was estimated for wmc262 marker located on 4A chromosome with the polymorphism information content value of 0.960. The highest polymorphism information content value (0.954) among the markers known to be located on B genome was realized for wmc44 marker located on 1B chromosome. The highest polymorphism information content value for the markers specific to D genome was found in gwm174 marker located on 5D chromosome with the polymorphism information content value of 0.948. The presence of linkage disequilibrium between 81 pairwise SSR markers reside on the same chromosome was tested and very limited linkage disequilibrium was observed. The results confirmed that the most distant genotype pairs were as follows Ceyhan-99-Behoth 6, Gerek 79-Douma 40989, and Karahan-99-Douma 48114.

  13. Quantitative Description of Crystal Nucleation and Growth from in Situ Liquid Scanning Transmission Electron Microscopy.

    PubMed

    Ievlev, Anton V; Jesse, Stephen; Cochell, Thomas J; Unocic, Raymond R; Protopopescu, Vladimir A; Kalinin, Sergei V

    2015-12-22

    Recent advances in liquid cell (scanning) transmission electron microscopy (S)TEM has enabled in situ nanoscale investigations of controlled nanocrystal growth mechanisms. Here, we experimentally and quantitatively investigated the nucleation and growth mechanisms of Pt nanostructures from an aqueous solution of K2PtCl6. Averaged statistical, network, and local approaches have been used for the data analysis and the description of both collective particles dynamics and local growth features. In particular, interaction between neighboring particles has been revealed and attributed to reduction of the platinum concentration in the vicinity of the particle boundary. The local approach for solving the inverse problem showed that particles dynamics can be simulated by a stationary diffusional model. The obtained results are important for understanding nanocrystal formation and growth processes and for optimization of synthesis conditions.

  14. Searching for disease-susceptibility loci by testing for Hardy-Weinberg disequilibrium in a gene bank of affected individuals.

    PubMed

    Lee, Wen-Chung

    2003-09-01

    The future of genetic studies of complex human diseases will rely more and more on the epidemiologic association paradigm. The author proposes to scan the genome for disease-susceptibility gene(s) by testing for deviation from Hardy-Weinberg equilibrium in a gene bank of affected individuals. A power formula is presented, which is very accurate as revealed by Monte Carlo simulations. If the disease-susceptibility gene is recessive with an allele frequency of < or = 0.5 or dominant with an allele frequency of > or = 0.5, the number of subjects needed by the present method is smaller than that needed by using a case-parents design (using either the transmission/disequilibrium test or the 2-df likelihood ratio test). However, the method cannot detect genes with a multiplicative mode of inheritance, and the validity of the method relies on the assumption that the source population from which the cases arise is in Hardy-Weinberg equilibrium. Thus, it is prone to produce false positive and false negative results. Nevertheless, the method enables rapid gene hunting in an existing gene bank of affected individuals with no extra effort beyond simple calculations.

  15. Genomic polymorphism, recombination, and linkage disequilibrium in human major histocompatibility complex-encoded antigen-processing genes.

    PubMed Central

    van Endert, P M; Lopez, M T; Patel, S D; Monaco, J J; McDevitt, H O

    1992-01-01

    Recently, two subunits of a large cytosolic protease and two putative peptide transporter proteins were found to be encoded by genes within the class II region of the major histocompatibility complex (MHC). These genes have been suggested to be involved in the processing of antigenic proteins for presentation by MHC class I molecules. Because of the high degree of polymorphism in MHC genes, and previous evidence for both functional and polypeptide sequence polymorphism in the proteins encoded by the antigen-processing genes, we tested DNA from 27 consanguineous human cell lines for genomic polymorphism by restriction fragment length polymorphism (RFLP) analysis. These studies demonstrate a strong linkage disequilibrium between TAP1 and LMP2 RFLPs. Moreover, RFLPs, as well as a polymorphic stop codon in the telomeric TAP2 gene, appear to be in linkage disequilibrium with HLA-DR alleles and RFLPs in the HLA-DO gene. A high rate of recombination, however, seems to occur in the center of the complex, between the TAP1 and TAP2 genes. Images PMID:1360671

  16. Uneven recombination and linkage disequilibrium across a reference SNP map for common bean (Phaseolus vulgaris L.)

    USDA-ARS?s Scientific Manuscript database

    Linkage disequilibrium (LD) and recombination (R) analyses are the basis for plant breeding. LD and R vary by breeding system, by generation of inbreeding or outcrossing and by region of the chromosome. Common bean (Phaseolus vulgaris L.) is a favored food legume with a small sequenced genome and n=...

  17. Linkage disequilibrium at the SCA2 locus

    PubMed Central

    Didierjean, O.; Cancel, G.; Stevanin, G.; Durr, A.; Burk, K.; Benomar, A.; Lezin, A.; Belal, S.; Abada-Bendid, M.; Klockgether, T.; Brice, A.

    1999-01-01

    Spinocerebellar ataxia type 2 (SCA2) is caused by the expansion of an unstable CAG repeat encoding a polyglutamine tract. Repeats with 32 to 200 CAGs are associated with the disease, whereas normal chromosomes contain 13 to 33 repeats. We tested 220 families of different geographical origins for the SCA2 mutation. Thirty three were positive (15%). Twenty three families with at least two affected subjects were tested for linkage disequilibium (LD) between the SCA2 mutation and three microsatellite markers, two of which (D12S1332-D12S1333) closely flanked the mutation; the other (D12S1672) was intragenic. Many different haplotypes were observed, indicating the occurrence of several ancestral mutations. However, the same haplotype, not observed in controls, was detected in the German, the Serbian, and some of the French families, suggesting a founder effect or recurrent mutations on an at risk haplotype.


Keywords: linkage disequilibrium; SCA2; trinucleotide repeat expansion; founder effect PMID:10353790

  18. The effect of missing data on linkage disequilibrium mapping and haplotype association analysis in the GAW14 simulated datasets

    PubMed Central

    McCaskie, Pamela A; Carter, Kim W; McCaskie, Simon R; Palmer, Lyle J

    2005-01-01

    We used our newly developed linkage disequilibrium (LD) plotting software, JLIN, to plot linkage disequilibrium between pairs of single-nucleotide polymorphisms (SNPs) for three chromosomes of the Genetic Analysis Workshop 14 Aipotu simulated population to assess the effect of missing data on LD calculations. Our haplotype analysis program, SIMHAP, was used to assess the effect of missing data on haplotype-phenotype association. Genotype data was removed at random, at levels of 1%, 5%, and 10%, and the LD calculations and haplotype association results for these levels of missingness were compared to those for the complete dataset. It was concluded that ignoring individuals with missing data substantially affects the number of regions of LD detected which, in turn, could affect tagging SNPs chosen to generate haplotypes. PMID:16451612

  19. Linkage Disequilibrium and Inversion-Typing of the Drosophila melanogaster Genome Reference Panel

    PubMed Central

    Houle, David; Márquez, Eladio J.

    2015-01-01

    We calculated the linkage disequilibrium between all pairs of variants in the Drosophila Genome Reference Panel with minor allele count ≥5. We used r2 ≥ 0.5 as the cutoff for a highly correlated SNP. We make available the list of all highly correlated SNPs for use in association studies. Seventy-six percent of variant SNPs are highly correlated with at least one other SNP, and the mean number of highly correlated SNPs per variant over the whole genome is 83.9. Disequilibrium between distant SNPs is also common when minor allele frequency (MAF) is low: 37% of SNPs with MAF < 0.1 are highly correlated with SNPs more than 100 kb distant. Although SNPs within regions with polymorphic inversions are highly correlated with somewhat larger numbers of SNPs, and these correlated SNPs are on average farther away, the probability that a SNP in such regions is highly correlated with at least one other SNP is very similar to SNPs outside inversions. Previous karyotyping of the DGRP lines has been inconsistent, and we used LD and genotype to investigate these discrepancies. When previous studies agreed on inversion karyotype, our analysis was almost perfectly concordant with those assignments. In discordant cases, and for inversion heterozygotes, our results suggest errors in two previous analyses or discordance between genotype and karyotype. Heterozygosities of chromosome arms are, in many cases, surprisingly highly correlated, suggesting strong epsistatic selection during the inbreeding and maintenance of the DGRP lines. PMID:26068573

  20. Evaluating the Evidence for Transmission Distortion in Human Pedigrees

    PubMed Central

    Meyer, Wynn K.; Arbeithuber, Barbara; Ober, Carole; Ebner, Thomas; Tiemann-Boege, Irene; Hudson, Richard R.; Przeworski, Molly

    2012-01-01

    Children of a heterozygous parent are expected to carry either allele with equal probability. Exceptions can occur, however, due to meiotic drive, competition among gametes, or viability selection, which we collectively term “transmission distortion” (TD). Although there are several well-characterized examples of these phenomena, their existence in humans remains unknown. We therefore performed a genome-wide scan for TD by applying the transmission disequilibrium test (TDT) genome-wide to three large sets of human pedigrees of European descent: the Framingham Heart Study (FHS), a founder population of European origin (HUTT), and a subset of the Autism Genetic Resource Exchange (AGRE). Genotyping error is an important confounder in this type of analysis. In FHS and HUTT, despite extensive quality control, we did not find sufficient evidence to exclude genotyping error in the strongest signals. In AGRE, however, many signals extended across multiple SNPs, a pattern highly unlikely to arise from genotyping error. We identified several candidate regions in this data set, notably a locus in 10q26.13 displaying a genome-wide significant TDT in combined female and male transmissions and a signature of recent positive selection, as well as a paternal TD signal in 6p21.1, the same region in which a significant TD signal was previously observed in 30 European males. Neither region replicated in FHS, however, and the paternal signal was not visible in sperm competition assays or as allelic imbalance in sperm. In maternal transmissions, we detected no strong signals near centromeres or telomeres, the regions predicted to be most susceptible to female-specific meiotic drive, but we found a significant enrichment of top signals among genes involved in cell junctions. These results illustrate both the potential benefits and the challenges of using the TDT to study transmission distortion and provide candidates for investigation in future studies. PMID:22377632

  1. Using Algorithms in Solving Synapse Transmission Problems.

    ERIC Educational Resources Information Center

    Stencel, John E.

    1992-01-01

    Explains how a simple three-step algorithm can aid college students in solving synapse transmission problems. Reports that all of the students did not completely understand the algorithm. However, many learn a simple working model of synaptic transmission and understand why an impulse will pass across a synapse quantitatively. Students also see…

  2. Anonymous marker loci within 400 kb of HLA-A generate haplotypes in linkage disequilibrium with the hemochromatosis gene (HFE)

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

    Yaouanq, J.; Perichon, M.; Treut, A.L.

    1994-02-01

    The hemochromatosis gene (HFE) maps to 6p21.3 and is less than 1 cM from the HLA class I gene; however, the precise physical location of the gene has remained elusive and controversial. The unambiguous identification of a crossover event within hemochromatosis families is very difficult; it is particularly hampered by the variability of the phenotypic expression as well as by the sex- and age-related penetrance of the disease. For these considerations, traditional linkage analysis could prove of limited value in further refining the extrapolated physical position of HFE. The authors therefore embarked upon a linkage-disequilibrium analysis of HFE and normalmore » chromosomes for the Brittany population. In this report, 66 hemochromatosis families yielding 151 hemochromatosis chromosomes and 182 normal chromosomes were RFLP-typed with a battery of probes, including two newly derived polymorphic markers from the 6.7 and HLA-F loci located 150 and 250 kb telomeric to HLA-A, respectively. The results suggest a strong peak of existing linkage disequilibrium focused within the i82-to-6.7 interval (approximately 250 kb). The zone of linkage disequilibrium is flanked by the i97 locus, positioned 30 kb proximal to i82, and the HLA-F gene, found 250 kb distal to HLA-A, markers of which display no significant association with HFE. These data support the possibility that HFE resides within the 400-kb expanse of DNA between i97 and HLA-F. Alternatively, the very tight association of HLA-A3 and allele 1 of the 6.7 locus, both of which are comprised by the major ancestral or founder HFE haplotype in Brittany, supports the possibility that the disease gene may reside immediately telomeric to the 6.7 locus within the linkage-disequilibrium zone. Additionally, hemochromatosis haplotypes possessing HLA-A11 and the low-frequency HLA-F polymorphism (allele 2) are supportive of a separate founder chromosome containing a second, independently arising mutant allele. 69 refs., 1 fig., 5

  3. Increasingly inbred and fragmented populations of Plasmodium vivax associated with the eastward decline in malaria transmission across the Southwest Pacific

    PubMed Central

    Waltmann, Andreea; Koepfli, Cristian; Tessier, Natacha; Karl, Stephan; Fola, Abebe; Darcy, Andrew W.; Wini, Lyndes; Harrison, G. L. Abby; Barnadas, Céline; Jennison, Charlie; Karunajeewa, Harin; Boyd, Sarah; Whittaker, Maxine; Kazura, James; Bahlo, Melanie; Mueller, Ivo

    2018-01-01

    The human malaria parasite Plasmodium vivax is more resistant to malaria control strategies than Plasmodium falciparum, and maintains high genetic diversity even when transmission is low. To investigate whether declining P. vivax transmission leads to increasing population structure that would facilitate elimination, we genotyped samples from across the Southwest Pacific region, which experiences an eastward decline in malaria transmission, as well as samples from two time points at one site (Tetere, Solomon Islands) during intensified malaria control. Analysis of 887 P. vivax microsatellite haplotypes from hyperendemic Papua New Guinea (PNG, n = 443), meso-hyperendemic Solomon Islands (n = 420), and hypoendemic Vanuatu (n = 24) revealed increasing population structure and multilocus linkage disequilibrium yet a modest decline in diversity as transmission decreases over space and time. In Solomon Islands, which has had sustained control efforts for 20 years, and Vanuatu, which has experienced sustained low transmission for many years, significant population structure was observed at different spatial scales. We conclude that control efforts will eventually impact P. vivax population structure and with sustained pressure, populations may eventually fragment into a limited number of clustered foci that could be targeted for elimination. PMID:29373596

  4. Increasingly inbred and fragmented populations of Plasmodium vivax associated with the eastward decline in malaria transmission across the Southwest Pacific.

    PubMed

    Waltmann, Andreea; Koepfli, Cristian; Tessier, Natacha; Karl, Stephan; Fola, Abebe; Darcy, Andrew W; Wini, Lyndes; Harrison, G L Abby; Barnadas, Céline; Jennison, Charlie; Karunajeewa, Harin; Boyd, Sarah; Whittaker, Maxine; Kazura, James; Bahlo, Melanie; Mueller, Ivo; Barry, Alyssa E

    2018-01-01

    The human malaria parasite Plasmodium vivax is more resistant to malaria control strategies than Plasmodium falciparum, and maintains high genetic diversity even when transmission is low. To investigate whether declining P. vivax transmission leads to increasing population structure that would facilitate elimination, we genotyped samples from across the Southwest Pacific region, which experiences an eastward decline in malaria transmission, as well as samples from two time points at one site (Tetere, Solomon Islands) during intensified malaria control. Analysis of 887 P. vivax microsatellite haplotypes from hyperendemic Papua New Guinea (PNG, n = 443), meso-hyperendemic Solomon Islands (n = 420), and hypoendemic Vanuatu (n = 24) revealed increasing population structure and multilocus linkage disequilibrium yet a modest decline in diversity as transmission decreases over space and time. In Solomon Islands, which has had sustained control efforts for 20 years, and Vanuatu, which has experienced sustained low transmission for many years, significant population structure was observed at different spatial scales. We conclude that control efforts will eventually impact P. vivax population structure and with sustained pressure, populations may eventually fragment into a limited number of clustered foci that could be targeted for elimination.

  5. MICA diversity and linkage disequilibrium with HLA-B alleles in renal-transplant candidates in southern Brazil.

    PubMed

    Yamakawa, Roger Haruki; Saito, Patrícia Keiko; Gelmini, Geórgia Fernanda; da Silva, José Samuel; Bicalho, Maria da Graça; Borelli, Sueli Donizete

    2017-01-01

    The major histocompatibility complex (MHC) class I chain-related gene A (MICA) is located centromerically to the human leukocyte antigen (HLA)-B. The short distance between these loci in the MHC indicates the presence of linkage disequilibrium (LD). Similarly to the HLA, the MICA is highly polymorphic, and this polymorphism has not been well documented in different populations. In this study, we estimated the allelic frequencies of MICA and the linkage disequilibrium with HLA-B alleles in 346 renal-transplant candidates in southern Brazil. MICA and HLA were typed using the polymerase chain reaction-sequence-specific primer method (PCR-SSO), combined with the Luminex technology. A total of 19 MICA allele groups were identified. The most frequent allele groups were MICA*008 (21.6%), MICA*002 (17.0%) and MICA*004 (14.8%). The most common haplotypes were MICA*009-B*51 (7.8%), MICA*004-B*44 (6.06%) and MICA*002-B*35 (5.63%). As expected from the proximity of the MICA and HLA-B loci, most haplotypes showed strong LD. Renal patients and healthy subjects in the same region of Brazil showed statistically significant differences in their MICA polymorphisms. The MICA*027 allele group was more frequent in renal patients (Pc = 0.018, OR: 3.421, 95% CI: 1.516-7.722), while the MICA*019 allele group was more frequent in healthy subjects (Pc = 0.001, OR: 0.027, 95% CI: 0.002-0.469). This study provided information on the distribution of MICA polymorphisms and linkage disequilibrium with HLA-B alleles in Brazilian renal-transplant candidates. This information should help to determine the mechanisms of susceptibility to different diseases in patients with chronic kidney disease, and to elucidate the mechanisms involved in allograft rejection associated with MICA polymorphisms in a Brazilian population.

  6. Dynamics of a durable commodity market involving trade at disequilibrium

    NASA Astrophysics Data System (ADS)

    Panchuk, A.; Puu, T.

    2018-05-01

    The present work considers a simple model of a durable commodity market involving two agents who trade stocks of two different types. Stock commodities, in contrast to flow commodities, remain on the market from period to period and, consequently, there is neither unique demand function nor unique supply function exists. We also set up exact conditions for trade at disequilibrium, the issue being usually neglected, though a fact of reality. The induced iterative system has infinite number of fixed points and path dependent dynamics. We show that a typical orbit is either attracted to one of the fixed points or eventually sticks at a no-trade point. For the latter the stock distribution always remains the same while the price displays periodic or chaotic oscillations.

  7. Disequilibrium δ18O values in microbial carbonates as a tracer of metabolic production of dissolved inorganic carbon

    NASA Astrophysics Data System (ADS)

    Thaler, Caroline; Millo, Christian; Ader, Magali; Chaduteau, Carine; Guyot, François; Ménez, Bénédicte

    2017-02-01

    Carbon and oxygen stable isotope compositions of carbonates are widely used to retrieve paleoenvironmental information. However, bias may exist in such reconstructions as carbonate precipitation is often associated with biological activity. Several skeleton-forming eukaryotes have been shown to precipitate carbonates with significant offsets from isotopic equilibrium with water. Although poorly understood, the origin of these biologically-induced isotopic shifts in biogenic carbonates, commonly referred to as "vital effects", could be related to metabolic effects that may not be restricted to mineralizing eukaryotes. The aim of our study was to determine whether microbially-mediated carbonate precipitation can also produce offsets from equilibrium for oxygen isotopes. We present here δ18O values of calcium carbonates formed by the activity of Sporosarcina pasteurii, a carbonatogenic bacterium whose ureolytic activity produces ammonia (thus increasing pH) and dissolved inorganic carbon (DIC) that precipitates as solid carbonates in the presence of Ca2+. We show that the 1000 lnαCaCO3-H2O values for these bacterially-precipitated carbonates are up to 24.7‰ smaller than those expected for precipitation at isotopic equilibrium. A similar experiment run in the presence of carbonic anhydrase (an enzyme able to accelerate oxygen isotope equilibration between DIC and water) resulted in δ18O values of microbial carbonates in line with values expected at isotopic equilibrium with water. These results demonstrate for the first time that bacteria can induce calcium carbonate precipitation in strong oxygen isotope disequilibrium with water, similarly to what is observed for eukaryotes. This disequilibrium effect can be unambiguously ascribed to oxygen isotope disequilibrium between DIC and water inherited from the oxygen isotope composition of the ureolytically produced CO2, probably combined with a kinetic isotope effect during CO2 hydration/hydroxylation. The fact that

  8. A study of disequilibrium between 220Rn and 216Po for 220Rn measurements using a flow-through Lucas scintillation cell.

    PubMed

    Sathyabama, N; Datta, D; Gaware, J J; Mayya, Y S; Tripathi, R M

    2014-01-01

    Lucas-type scintillation cells (LSCs) are commonly used for rapid measurements of (220)Rn concentrations in flow-through mode in field and for calibration experiments in laboratories. However, in those measurements, equilibrium between (220)Rn and (216)Po is generally assumed and two alpha particles are considered to be emitted per (220)Rn decay due to very short half-life of (216)Po. In this paper, a small, yet significant disequilibrium existing between (220)Rn and (216)Po has been examined and shown that less than two alpha particles are actually emitted per (220)Rn decay in the cell when flow is maintained. A theoretical formula has been derived for the first time for a correction factor (CF) to be applied to this measured concentration to account for the disequilibrium. The existence of this disequilibrium has been verified experimentally and is found to increase with the increase in the ratio of flow rate to cell volume. The reason for the disequilibrium is attributed to the flushing out of (216)Po formed in the cell before its decay due to the flow. Uncertainties in measured concentrations have been estimated and the estimated CF values have been found to be significant for the flow rates considered above 5 dm(3) min(-1) for a cell of volume 0.125 dm(3). The calculated values of the CF are about 1.055 to 1.178 in the flow rate range of 4 to 15 dm(3) min(-1) for the cell of volume 0.125 dm(3), while the corresponding experimental values are 1.023 to 1.264. This is a systematic error introduced in (220)Rn measurements using a flow-through LSC, which can be removed either by correct formulation or by proper design of a measurement set-up.

  9. Excess Maternal Transmission of Markers in TCOF1 Among Cleft Palate Case-Parent Trios From Three Populations

    PubMed Central

    Sull, Jae Woong; Liang, Kung-Yee; Hetmanski, Jacqueline B.; Fallin, M. Daniele; Ingersoll, Roxanne G.; Park, Ji Wan; Wu-Chou, Yah-Huei; Chen, Philip K.; Chong, Samuel S.; Cheah, Felicia; Yeow, Vincent; Park, Beyoung Yun; Jee, Sun Ha; Jabs, Ethylin W.; Redett, Richard; Scott, Alan F.; Beaty, Terri H.

    2009-01-01

    Isolated cleft palate is among the most common human birth defects. The TCOF1 gene has been suggested as a candidate gene for cleft palate based on animal models. This study tests for association between markers in TCOF1 and isolated, nonsyndromic cleft palate using a case-parent trio design considering parent-of-origin effects. Case-parent trios from three populations (comprising a total of 81 case-parent trios) were genotyped for single nucleotide polymorphisms (SNPs) in the TCOF1 gene. We used the transmission disequilibrium test and the transmission asymmetry test on individual SNPs. When all trios were combined, the odds ratio for transmission of the minor allele, OR(transmission), was significant for SNP rs15251 (OR = 2.88, P = 0.007), as well as rs2255796 and rs2569062 (OR = 2.08, P = 0.03; OR = 2.43, P = 0.041; respectively) when parent of origin was not considered. The transmission asymmetry test also revealed one SNP (rs15251) showing excess maternal transmission significant at the P = 0.005 level (OR = 6.50). Parent-of-origin effects were assessed using the parent-of-origin likelihood ratio test on both SNPs and haplotypes. While the parent-of-origin likelihood ratio test was only marginally significant for this SNP (P = 0.136), analysis of haplotypes of rs2255796 and rs15251 suggested excess maternal transmission. Therefore, these data suggest TCOF1 may influence risk of cleft palate through a parent-of-origin effect. PMID:18688869

  10. Linkage Disequilibrium and Inversion-Typing of the Drosophila melanogaster Genome Reference Panel.

    PubMed

    Houle, David; Márquez, Eladio J

    2015-06-10

    We calculated the linkage disequilibrium between all pairs of variants in the Drosophila Genome Reference Panel with minor allele count ≥5. We used r(2) ≥ 0.5 as the cutoff for a highly correlated SNP. We make available the list of all highly correlated SNPs for use in association studies. Seventy-six percent of variant SNPs are highly correlated with at least one other SNP, and the mean number of highly correlated SNPs per variant over the whole genome is 83.9. Disequilibrium between distant SNPs is also common when minor allele frequency (MAF) is low: 37% of SNPs with MAF < 0.1 are highly correlated with SNPs more than 100 kb distant. Although SNPs within regions with polymorphic inversions are highly correlated with somewhat larger numbers of SNPs, and these correlated SNPs are on average farther away, the probability that a SNP in such regions is highly correlated with at least one other SNP is very similar to SNPs outside inversions. Previous karyotyping of the DGRP lines has been inconsistent, and we used LD and genotype to investigate these discrepancies. When previous studies agreed on inversion karyotype, our analysis was almost perfectly concordant with those assignments. In discordant cases, and for inversion heterozygotes, our results suggest errors in two previous analyses or discordance between genotype and karyotype. Heterozygosities of chromosome arms are, in many cases, surprisingly highly correlated, suggesting strong epsistatic selection during the inbreeding and maintenance of the DGRP lines. Copyright © 2015 Houle and Márquez.

  11. Genetic diversity, linkage disequilibrium, population structure and construction of a core collection of Prunus avium L. landraces and bred cultivars.

    PubMed

    Campoy, José Antonio; Lerigoleur-Balsemin, Emilie; Christmann, Hélène; Beauvieux, Rémi; Girollet, Nabil; Quero-García, José; Dirlewanger, Elisabeth; Barreneche, Teresa

    2016-02-24

    Depiction of the genetic diversity, linkage disequilibrium (LD) and population structure is essential for the efficient organization and exploitation of genetic resources. The objectives of this study were to (i) to evaluate the genetic diversity and to detect the patterns of LD, (ii) to estimate the levels of population structure and (iii) to identify a 'core collection' suitable for association genetic studies in sweet cherry. A total of 210 genotypes including modern cultivars and landraces from 16 countries were genotyped using the RosBREED cherry 6 K SNP array v1. Two groups, mainly bred cultivars and landraces, respectively, were first detected using STRUCTURE software and confirmed by Principal Coordinate Analysis (PCoA). Further analyses identified nine subgroups using STRUCTURE and Discriminant Analysis of Principal Components (DAPC). Several sub-groups correspond to different eco-geographic regions of landraces distribution. Linkage disequilibrium was evaluated showing lower values than in peach, the reference Prunus species. A 'core collection' containing 156 accessions was selected using the maximum length sub tree method. The present study constitutes the first population genetics analysis in cultivated sweet cherry using a medium-density SNP (single nucleotide polymorphism) marker array. We provided estimations of linkage disequilibrium, genetic structure and the definition of a first INRA's Sweet Cherry core collection useful for breeding programs, germplasm management and association genetics studies.

  12. [Transmission dynamic model for echinococcosis granulosus: establishment and application].

    PubMed

    Yang, Shi-Jie; Wu, Wei-Ping

    2009-06-01

    A dynamic model of disease can be used to quantitatively describe the pattern and characteristics of disease transmission, predict the disease status and evaluate the efficacy of control strategy. This review summarizes the basic transmission dynamic models of echinococcosis granulosus and their application.

  13. Significant evidence for linkage disequilibrium over a 5-cM region among Afrikaners.

    PubMed

    Gordon, D; Simonic, I; Ott, J

    2000-05-15

    We explore the extent of deviations from Hardy-Weinberg equilibrium (HWE) at a marker locus and linkage disequilibrium (LD) between pairs of marker loci in the Afrikaner population of South Africa. DNA samples were used for genotyping of 23 loci on six chromosomes. The samples were collected from 91 healthy unrelated Afrikaner adults. Exact tests were used to determine evidence for deviations from HWE at a single marker locus or LD between pairs of marker loci. At the 0.05 level of significance, evidence was found for deviation from HWE at only one of the 23 loci. At the same level of significance, LD was found among 8 of the 34 intrachromosomal pairs of loci. On chromosome 21, there was evidence for LD (P = 0.02) between a pair of loci with a genetic distance of 5.51 cM. On chromosome 2, there was evidence for LD between a pair of loci with a genetic distance of 5.28 cM (P = 0.002) and a pair of loci with a genetic distance of 3.68 cM (P = 0.0004). Detailed analysis of LD for one locus pair indicated that only a few of all alleles participated in the LD and that strong LD was most often positive. Our findings indicate that Afrikaans-speaking Afrikaners represent one of those special populations deemed particularly suitable for disequilibrium mapping. Copyright 2000 Academic Press.

  14. Assessing signatures of selection through variation in linkage disequilibrium between taurine and indicine cattle

    PubMed Central

    2014-01-01

    Background Signatures of selection are regions in the genome that have been preferentially increased in frequency and fixed in a population because of their functional importance in specific processes. These regions can be detected because of their lower genetic variability and specific regional linkage disequilibrium (LD) patterns. Methods By comparing the differences in regional LD variation between dairy and beef cattle types, and between indicine and taurine subspecies, we aim at finding signatures of selection for production and adaptation in cattle breeds. The VarLD method was applied to compare the LD variation in the autosomal genome between breeds, including Angus and Brown Swiss, representing taurine breeds, and Nelore and Gir, representing indicine breeds. Genomic regions containing the top 0.01 and 0.1 percentile of signals were characterized using the UMD3.1 Bos taurus genome assembly to identify genes in those regions and compared with previously reported selection signatures and regions with copy number variation. Results For all comparisons, the top 0.01 and 0.1 percentile included 26 and 165 signals and 17 and 125 genes, respectively, including TECRL, BT.23182 or FPPS, CAST, MYOM1, UVRAG and DNAJA1. Conclusions The VarLD method is a powerful tool to identify differences in linkage disequilibrium between cattle populations and putative signatures of selection with potential adaptive and productive importance. PMID:24592996

  15. Convective Dynamics and Disequilibrium Chemistry in the Atmospheres of Giant Planets and Brown Dwarfs

    NASA Astrophysics Data System (ADS)

    Bordwell, Baylee; Brown, Benjamin P.; Oishi, Jeffrey S.

    2018-02-01

    Disequilibrium chemical processes significantly affect the spectra of substellar objects. To study these effects, dynamical disequilibrium has been parameterized using the quench and eddy diffusion approximations, but little work has been done to explore how these approximations perform under realistic planetary conditions in different dynamical regimes. As a first step toward addressing this problem, we study the localized, small-scale convective dynamics of planetary atmospheres by direct numerical simulation of fully compressible hydrodynamics with reactive tracers using the Dedalus code. Using polytropically stratified, plane-parallel atmospheres in 2D and 3D, we explore the quenching behavior of different abstract chemical species as a function of the dynamical conditions of the atmosphere as parameterized by the Rayleigh number. We find that in both 2D and 3D, chemical species quench deeper than would be predicted based on simple mixing-length arguments. Instead, it is necessary to employ length scales based on the chemical equilibrium profile of the reacting species in order to predict quench points and perform chemical kinetics modeling in 1D. Based on the results of our simulations, we provide a new length scale, derived from the chemical scale height, that can be used to perform these calculations. This length scale is simple to calculate from known chemical data and makes reasonable predictions for our dynamical simulations.

  16. Expert review on poliovirus immunity and transmission.

    PubMed

    Duintjer Tebbens, Radboud J; Pallansch, Mark A; Chumakov, Konstantin M; Halsey, Neal A; Hovi, Tapani; Minor, Philip D; Modlin, John F; Patriarca, Peter A; Sutter, Roland W; Wright, Peter F; Wassilak, Steven G F; Cochi, Stephen L; Kim, Jong-Hoon; Thompson, Kimberly M

    2013-04-01

    Successfully managing risks to achieve wild polioviruses (WPVs) eradication and address the complexities of oral poliovirus vaccine (OPV) cessation to stop all cases of paralytic poliomyelitis depends strongly on our collective understanding of poliovirus immunity and transmission. With increased shifting from OPV to inactivated poliovirus vaccine (IPV), numerous risk management choices motivate the need to understand the tradeoffs and uncertainties and to develop models to help inform decisions. The U.S. Centers for Disease Control and Prevention hosted a meeting of international experts in April 2010 to review the available literature relevant to poliovirus immunity and transmission. This expert review evaluates 66 OPV challenge studies and other evidence to support the development of quantitative models of poliovirus transmission and potential outbreaks. This review focuses on characterization of immunity as a function of exposure history in terms of susceptibility to excretion, duration of excretion, and concentration of excreted virus. We also discuss the evidence of waning of host immunity to poliovirus transmission, the relationship between the concentration of poliovirus excreted and infectiousness, the importance of different transmission routes, and the differences in transmissibility between OPV and WPV. We discuss the limitations of the available evidence for use in polio risk models, and conclude that despite the relatively large number of studies on immunity, very limited data exist to directly support quantification of model inputs related to transmission. Given the limitations in the evidence, we identify the need for expert input to derive quantitative model inputs from the existing data. © 2012 Society for Risk Analysis.

  17. Excess maternal transmission of markers in TCOF1 among cleft palate case-parent trios from three populations.

    PubMed

    Sull, Jae Woong; Liang, Kung-Yee; Hetmanski, Jacqueline B; Fallin, M Daniele; Ingersoll, Roxanne G; Park, Ji Wan; Wu-Chou, Yah-Huei; Chen, Philip K; Chong, Samuel S; Cheah, Felicia; Yeow, Vincent; Park, Beyoung Yun; Jee, Sun Ha; Jabs, Ethylin W; Redett, Richard; Scott, Alan F; Beaty, Terri H

    2008-09-15

    Isolated cleft palate is among the most common human birth defects. The TCOF1 gene has been suggested as a candidate gene for cleft palate based on animal models. This study tests for association between markers in TCOF1 and isolated, nonsyndromic cleft palate using a case-parent trio design considering parent-of-origin effects. Case-parent trios from three populations (comprising a total of 81 case-parent trios) were genotyped for single nucleotide polymorphisms (SNPs) in the TCOF1 gene. We used the transmission disequilibrium test and the transmission asymmetry test on individual SNPs. When all trios were combined, the odds ratio for transmission of the minor allele, OR(transmission), was significant for SNP rs15251 (OR = 2.88, P = 0.007), as well as rs2255796 and rs2569062 (OR = 2.08, P = 0.03; OR = 2.43, P = 0.041; respectively) when parent of origin was not considered. The transmission asymmetry test also revealed one SNP (rs15251) showing excess maternal transmission significant at the P = 0.005 level (OR = 6.50). Parent-of-origin effects were assessed using the parent-of-origin likelihood ratio test on both SNPs and haplotypes. While the parent-of-origin likelihood ratio test was only marginally significant for this SNP (P = 0.136), analysis of haplotypes of rs2255796 and rs15251 suggested excess maternal transmission. Therefore, these data suggest TCOF1 may influence risk of cleft palate through a parent-of-origin effect. Copyright 2008 Wiley-Liss, Inc.

  18. Quantitative Cryo-Scanning Transmission Electron Microscopy of Biological Materials.

    PubMed

    Elbaum, Michael

    2018-05-11

    Electron tomography provides a detailed view into the 3D structure of biological cells and tissues. Physical fixation by vitrification of the aqueous medium provides the most faithful preservation of biological specimens in the native, fully hydrated state. Cryo-microscopy is challenging, however, because of the sensitivity to electron irradiation and due to the weak electron scattering of organic material. Tomography is even more challenging because of the dependence on multiple exposures of the same area. Tomographic imaging is typically performed in wide-field transmission electron microscopy (TEM) mode with phase contrast generated by defocus. Scanning transmission electron microscopy (STEM) is an alternative mode based on detection of scattering from a focused probe beam, without imaging optics following the specimen. While careful configuration of the illumination and detectors is required to generate useful contrast, STEM circumvents the major restrictions of phase contrast TEM to very thin specimens and provides a signal that is more simply interpreted in terms of local composition and density. STEM has gained popularity in recent years for materials science. The extension of STEM to cryomicroscopy and tomography of cells and macromolecules is summarized herein. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Ultrafast Screening and Quantitation of Pesticides in Food and Environmental Matrices by Solid-Phase Microextraction-Transmission Mode (SPME-TM) and Direct Analysis in Real Time (DART).

    PubMed

    Gómez-Ríos, Germán Augusto; Gionfriddo, Emanuela; Poole, Justen; Pawliszyn, Janusz

    2017-07-05

    The direct interface of microextraction technologies to mass spectrometry (MS) has unquestionably revolutionized the speed and efficacy at which complex matrices are analyzed. Solid Phase Micro Extraction-Transmission Mode (SPME-TM) is a technology conceived as an effective synergy between sample preparation and ambient ionization. Succinctly, the device consists of a mesh coated with polymeric particles that extracts analytes of interest present in a given sample matrix. This coated mesh acts as a transmission-mode substrate for Direct Analysis in Real Time (DART), allowing for rapid and efficient thermal desorption/ionization of analytes previously concentrated on the coating, and dramatically lowering the limits of detection attained by sole DART analysis. In this study, we present SPME-TM as a novel tool for the ultrafast enrichment of pesticides present in food and environmental matrices and their quantitative determination by MS via DART ionization. Limits of quantitation in the subnanogram per milliliter range can be attained, while total analysis time does not exceed 2 min per sample. In addition to target information obtained via tandem MS, retrospective studies of the same sample via high-resolution mass spectrometry (HRMS) were accomplished by thermally desorbing a different segment of the microextraction device.

  20. The Effect of Educational Disequilibrium in Field Work on Graduate Social Work Students' Self-Concept and Mental Health

    ERIC Educational Resources Information Center

    Ying, Yu-Wen

    2011-01-01

    The author used a mixed methods design to assess field work-related educational disequilibrium and its effect on the self-concept and mental health of MSW students. Twenty-eight advanced, fourth-semester MSW students were compared with 37 entering, first-semester MSW students in practice-related sense of accomplishment. Compared with first-year…

  1. Short Communication Mendelian inheritance, linkage, and genotypic disequilibrium in microsatellite loci of Hymenaea stigonocarpa Mart. ex Hayne (Fabaceae-Caesalpinioideae).

    PubMed

    Moraes, M A; Kubota, T Y K; Silva, E C B; Silva, A M; Cambuim, J; Moraes, M L T; Furlani Junior, E; Sebbenn, A M

    2016-07-29

    Hymenaea stigonocarpa is a deciduous and monoecious Neotropical tree species pollinated by bats. Due to overexploitation and habitat destruction, the population size has drastically diminished in nature. No previous study has investigated Mendelian inheritance, linkage, and genotypic disequilibrium in the available microsatellite markers in this species. So, our aim was to estimate these parameters using six microsatellite loci in a sample of 470 adults and 219 juveniles from two populations of H. stigonocarpa. In addition, 30 seeds per tree from 35 seed-trees were collected. Each seed was kept record of the seed-trees and fruit origin. Based on the six microsatellite loci, we found that only 10.6% of the cases showed significant deviations from Mendelian segregation and 15.3% showed linkage. We detected no evidence of genotypic disequilibrium between the loci in the adult trees or juveniles. Thus, our results suggest that these loci can be used with great accuracy in future genetic analyses of H. stigonocarpa populations.

  2. Atmospheric transmission calculations for optical frequencies

    NASA Technical Reports Server (NTRS)

    Shaik, Kamran

    1989-01-01

    A quantitative study of the transmission loss through the entire atmosphere for optical frequencies likely to be used for an earth-space communication link using existing data bases on scattering and absorption characteristics of the atmospheric constituents is presented.

  3. Detecting Recombination Hotspots from Patterns of Linkage Disequilibrium.

    PubMed

    Wall, Jeffrey D; Stevison, Laurie S

    2016-08-09

    With recent advances in DNA sequencing technologies, it has become increasingly easy to use whole-genome sequencing of unrelated individuals to assay patterns of linkage disequilibrium (LD) across the genome. One type of analysis that is commonly performed is to estimate local recombination rates and identify recombination hotspots from patterns of LD. One method for detecting recombination hotspots, LDhot, has been used in a handful of species to further our understanding of the basic biology of recombination. For the most part, the effectiveness of this method (e.g., power and false positive rate) is unknown. In this study, we run extensive simulations to compare the effectiveness of three different implementations of LDhot. We find large differences in the power and false positive rates of these different approaches, as well as a strong sensitivity to the window size used (with smaller window sizes leading to more accurate estimation of hotspot locations). We also compared our LDhot simulation results with comparable simulation results obtained from a Bayesian maximum-likelihood approach for identifying hotspots. Surprisingly, we found that the latter computationally intensive approach had substantially lower power over the parameter values considered in our simulations. Copyright © 2016 Wall and Stevison.

  4. 210Pb in the western Indian Ocean: distribution, disequilibrium, and partitioning between dissolved and particulate phases

    NASA Astrophysics Data System (ADS)

    Chung, Y.

    1987-09-01

    Dissolved 210Pb profiles are presented for 13 GEOSECS stations in the western Indian Ocean. In surface water away from high southern latitudes, 210Pb is in excess over 226Ra due to the atmospheric fallout from decay of 222Rn. Except in the Circumpolar region, the dissolved 210Pb profiles display a gentle mid-depth maximum similar to the corresponding 226Ra profiles. The 210Pb/ 226Ra activity ratio ranges from 1.6 in the surface water east of Madagascar to 0.4 or less in the bottom water of all the basins. The lowest ratio observed was 0.1 in the Gulf of Aden very close to the continental land mass. A ratio of 0.6 divides the western Indian Ocean horizontally into two portions, with the contour at shallower depth in the north than in the south. The deep water disequilibrium is thus more extensive north of Madagascar than south of it. It appears that locality and bottom topography play a strong role in controlling the distributions of 210Pb and 226Ra as well as their extent of disequilibrium in the water column. The mean residence time for Pb with respect to particulate and boundary scavenging in the deep water ranges from about 15 to 75 years.

  5. Population genetics of Cryptosporidium meleagridis in humans and birds: evidence for cross-species transmission.

    PubMed

    Wang, Yuanfei; Yang, Wenli; Cama, Vitaliano; Wang, Lin; Cabrera, Lilia; Ortega, Ynes; Bern, Caryn; Feng, Yaoyu; Gilman, Robert; Xiao, Lihua

    2014-07-01

    Population genetic studies have been used to understand the transmission of pathogens in humans and animals, especially the role of zoonotic infections and evolution and dispersal of virulent subtypes. In this study, we analysed the genetic diversity and population structure of Cryptosporidium meleagridis, the only known Cryptosporidium species that infects both avian and mammalian hosts and is responsible for approximately 10% of human cryptosporidiosis in some areas. A total of 62 C. meleagridis specimens from children, AIDS patients, and birds in Lima, Peru were characterised by sequence analysis of the ssrRNA gene and five minisatellite, microsatellite and polymorphic markers in chromosome 6, including the 60 kDa glycoprotein (gp60), 47 kDa glycoprotein (CP47), a serine repeat antigen (MSC6-5), retinitis pigmentosa GTPase regulator (RPGR) and thrombospondin protein 8 (TSP8). The multilocus sequence analysis identified concurrent infections with Cryptosporidium hominis in four AIDS patients and three children. Unique subtypes of C. meleagridis ranged from eight at the gp60 locus (gene diversity -Hd=0.651), three at the RPGR (Hd=0.556), three at the MSC6-5 locus (Hd=0.242), two at TSP8 (Hd=0.198), to one at CP47 (monomorphic), much lower than that of C. hominis in the same area. Intragenic linkage disequilibrium was strong and complete at all gene loci. Intergenic linkage disequilibrium was highly significant (P<0.001) for all pairs of polymorphic loci. Two major groups of subtypes were seen, with most subtypes belonging to group 1. Within group 1, there was no clear population segregation, and two of the 14 multilocus subtypes of C. meleagridis were found in both AIDS patients and birds. We believe that these results provide the first evidence of a clonal population structure of C. meleagridis and the likely occurrence of cross-species transmission of C. meleagridis between birds and humans. Published by Elsevier Ltd.

  6. A linkage disequilibrium perspective on the genetic mosaic of speciation in two hybridizing Mediterranean white oaks

    PubMed Central

    Goicoechea, P G; Herrán, A; Durand, J; Bodénès, C; Plomion, C; Kremer, A

    2015-01-01

    We analyzed the genetic mosaic of speciation in two hybridizing Mediterranean white oaks from the Iberian Peninsula (Quercus faginea Lamb. and Quercus pyrenaica Willd.). The two species show ecological divergence in flowering phenology, leaf morphology and composition, and in their basic or acidic soil preferences. Ninety expressed sequence tag-simple sequence repeats (EST-SSRs) and eight nuclear SSRs were genotyped in 96 trees from each species. Genotyping was designed in two steps. First, we used 69 markers evenly distributed over the 12 linkage groups (LGs) of the oak linkage map to confirm the species genetic identity of the sampled genotypes, and searched for differentiation outliers. Then, we genotyped 29 additional markers from the chromosome bins containing the outliers and repeated the multilocus scans. We found one or two additional outliers within four saturated bins, thus confirming that outliers are organized into clusters. Linkage disequilibrium (LD) was extensive; even for loosely linked and for independent markers. Consequently, score tests for association between two-marker haplotypes and the ‘species trait' showed a broad genomic divergence, although substantial variation across the genome and within LGs was also observed. We discuss the influence of several confounding effects on neutrality tests and review the evolutionary processes leading to extensive LD. Finally, we examine how LD analyses within regions that contain outlier clusters and quantitative trait loci can help to identify regions of divergence and/or genomic hitchhiking in the light of predictions from ecological speciation theory. PMID:25515016

  7. Assessing microsatellite linkage disequilibrium in wild, cultivated, and mapping populations of Theobroma cacao L and its impact on association mapping

    USDA-ARS?s Scientific Manuscript database

    Linkage disequilibrium (LD) is the nonrandom association of alleles and loci within sets of genetic data and when measured over the genomes of a species can provide important indications for how future association analyses should proceed. This information can be advantageous especially for slow-gro...

  8. Sample selection and spatial models of housing price indexes, and, A disequilibrium analysis of the U.S. gasoline market using panel data

    NASA Astrophysics Data System (ADS)

    Hu, Haixin

    This dissertation consists of two parts. The first part studies the sample selection and spatial models of housing price index using transaction data on detached single-family houses of two California metropolitan areas from 1990 through 2008. House prices are often spatially correlated due to shared amenities, or when the properties are viewed as close substitutes in a housing submarket. There have been many studies that address spatial correlation in the context of housing markets. However, none has used spatial models to construct housing price indexes at zip code level for the entire time period analyzed in this dissertation to the best of my knowledge. In this paper, I study a first-order autoregressive spatial model with four different weighing matrix schemes. Four sets of housing price indexes are constructed accordingly. Gatzlaff and Haurin (1997, 1998) study the sample selection problem in housing index by using Heckman's two-step method. This method, however, is generally inefficient and can cause multicollinearity problem. Also, it requires data on unsold houses in order to carry out the first-step probit regression. Maximum likelihood (ML) method can be used to estimate a truncated incidental model which allows one to correct for sample selection based on transaction data only. However, convergence problem is very prevalent in practice. In this paper I adopt Lewbel's (2007) sample selection correction method which does not require one to model or estimate the selection model, except for some very general assumptions. I then extend this method to correct for spatial correlation. In the second part, I analyze the U.S. gasoline market with a disequilibrium model that allows lagged-latent variables, endogenous prices, and panel data with fixed effects. Most existing studies (see the survey of Espey, 1998, Energy Economics) of the gasoline market assume equilibrium. In practice, however, prices do not always adjust fast enough to clear the market

  9. Transmission disequilibrium of small CNVs in simplex autism.

    PubMed

    Krumm, Niklas; O'Roak, Brian J; Karakoc, Emre; Mohajeri, Kiana; Nelson, Ben; Vives, Laura; Jacquemont, Sebastien; Munson, Jeff; Bernier, Raphe; Eichler, Evan E

    2013-10-03

    We searched for disruptive, genic rare copy-number variants (CNVs) among 411 families affected by sporadic autism spectrum disorder (ASD) from the Simons Simplex Collection by using available exome sequence data and CoNIFER (Copy Number Inference from Exome Reads). Compared to high-density SNP microarrays, our approach yielded ∼2× more smaller genic rare CNVs. We found that affected probands inherited more CNVs than did their siblings (453 versus 394, p = 0.004; odds ratio [OR] = 1.19) and that the probands' CNVs affected more genes (921 versus 726, p = 0.02; OR = 1.30). These smaller CNVs (median size 18 kb) were transmitted preferentially from the mother (136 maternal versus 100 paternal, p = 0.02), although this bias occurred irrespective of affected status. The excess burden of inherited CNVs among probands was driven primarily by sibling pairs with discordant social-behavior phenotypes (p < 0.0002, measured by Social Responsiveness Scale [SRS] score), which contrasts with families where the phenotypes were more closely matched or less extreme (p > 0.5). Finally, we found enrichment of brain-expressed genes unique to probands, especially in the SRS-discordant group (p = 0.0035). In a combined model, our inherited CNVs, de novo CNVs, and de novo single-nucleotide variants all independently contributed to the risk of autism (p < 0.05). Taken together, these results suggest that small transmitted rare CNVs play a role in the etiology of simplex autism. Importantly, the small size of these variants aids in the identification of specific genes as additional risk factors associated with ASD. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  10. Single nucleotide polymorphisms generated by genotyping by sequencing to characterize genome-wide diversity, linkage disequilibrium, and selective sweeps in cultivated watermelon

    USDA-ARS?s Scientific Manuscript database

    Large datasets containing single nucleotide polymorphisms (SNPs) are used to analyze genome-wide diversity in a robust collection of cultivars from representative accessions, across the world. The extent of linkage disequilibrium (LD) within a population determines the number of markers required fo...

  11. Equilibrium and Disequilibrium of River Basins: Effects on Stream Captures in Serra do Mar and Serra da Mantiqueira, Brazil

    NASA Astrophysics Data System (ADS)

    DA Silva, L. M.

    2015-12-01

    Landscapes are mainly driven by river processes that control the dynamic reorganization of networks. Discovering and identifying whether river basins are in geometric equilibrium or disequilibrium requires an analysis of water divides, channels that shift laterally or expand upstream and river captures. Issues specifically discussed include the variation of drainage area change and erosion rates of the basins. In southeastern Brazil there are two main escarpments with extensive geomorphic surfaces: Serra do Mar and Serra da Mantiqueira Mountains. These landscapes are constituted of Neoproterozoic and early Paleozoic rocks, presenting steep escarpments with low-elevation coastal plains and higher elevation interior plateaus. To identify whether river basins and river profiles are in equilibrium or disequilibrium in Serra do Mar and Serra da Mantiqueira Mountains, we used the proxy (χ), evaluating the effect of drainage area change and erosion rates. We selected basins that drain both sides of these two main escarpments (oceanic and continental sides) and have denudation rates derived from pre-existing cosmogenic isotopes data (Rio de Janeiro, Paraná and Minas Gerais). Despite being an ancient and tectonically stable landscape, part of the coastal plain of Serra do Mar Mountain in Rio de Janeiro and Paraná is in geometric disequilibrium, with water divides moving in the direction of higher χ values. To achieve equilibrium, some basins located in the continental side are retracting and disappearing, losing area to the coastal basins. On the contrary, there are some adjacent sub-basins that are close to equilibrium, without strong contrasts in χ values. The same pattern was observed in Serra da Mantiqueira (Minas Gerais state), with stream captures and river network reorganization in its main rivers. The initial results suggest a strong contrast between erosion rates in the continental and the oceanic portions of the escarpments.

  12. Contrasting Transmission Dynamics of Co-endemic Plasmodium vivax and P. falciparum: Implications for Malaria Control and Elimination

    PubMed Central

    Noviyanti, Rintis; Coutrier, Farah; Utami, Retno A. S.; Trimarsanto, Hidayat; Tirta, Yusrifar K.; Trianty, Leily; Kusuma, Andreas; Sutanto, Inge; Kosasih, Ayleen; Kusriastuti, Rita; Hawley, William A.; Laihad, Ferdinand; Lobo, Neil; Marfurt, Jutta; Clark, Taane G.; Price, Ric N.; Auburn, Sarah

    2015-01-01

    Background Outside of Africa, P. falciparum and P. vivax usually coexist. In such co-endemic regions, successful malaria control programs have a greater impact on reducing falciparum malaria, resulting in P. vivax becoming the predominant species of infection. Adding to the challenges of elimination, the dormant liver stage complicates efforts to monitor the impact of ongoing interventions against P. vivax. We investigated molecular approaches to inform the respective transmission dynamics of P. falciparum and P. vivax and how these could help to prioritize public health interventions. Methodology/ Principal Findings Genotype data generated at 8 and 9 microsatellite loci were analysed in 168 P. falciparum and 166 P. vivax isolates, respectively, from four co-endemic sites in Indonesia (Bangka, Kalimantan, Sumba and West Timor). Measures of diversity, linkage disequilibrium (LD) and population structure were used to gauge the transmission dynamics of each species in each setting. Marked differences were observed in the diversity and population structure of P. vivax versus P. falciparum. In Bangka, Kalimantan and Timor, P. falciparum diversity was low, and LD patterns were consistent with unstable, epidemic transmission, amenable to targeted intervention. In contrast, P. vivax diversity was higher and transmission appeared more stable. Population differentiation was lower in P. vivax versus P. falciparum, suggesting that the hypnozoite reservoir might play an important role in sustaining local transmission and facilitating the spread of P. vivax infections in different endemic settings. P. vivax polyclonality varied with local endemicity, demonstrating potential utility in informing on transmission intensity in this species. Conclusions/ Significance Molecular approaches can provide important information on malaria transmission that is not readily available from traditional epidemiological measures. Elucidation of the transmission dynamics circulating in a given

  13. Contrasting Transmission Dynamics of Co-endemic Plasmodium vivax and P. falciparum: Implications for Malaria Control and Elimination.

    PubMed

    Noviyanti, Rintis; Coutrier, Farah; Utami, Retno A S; Trimarsanto, Hidayat; Tirta, Yusrifar K; Trianty, Leily; Kusuma, Andreas; Sutanto, Inge; Kosasih, Ayleen; Kusriastuti, Rita; Hawley, William A; Laihad, Ferdinand; Lobo, Neil; Marfurt, Jutta; Clark, Taane G; Price, Ric N; Auburn, Sarah

    2015-05-01

    Outside of Africa, P. falciparum and P. vivax usually coexist. In such co-endemic regions, successful malaria control programs have a greater impact on reducing falciparum malaria, resulting in P. vivax becoming the predominant species of infection. Adding to the challenges of elimination, the dormant liver stage complicates efforts to monitor the impact of ongoing interventions against P. vivax. We investigated molecular approaches to inform the respective transmission dynamics of P. falciparum and P. vivax and how these could help to prioritize public health interventions. Genotype data generated at 8 and 9 microsatellite loci were analysed in 168 P. falciparum and 166 P. vivax isolates, respectively, from four co-endemic sites in Indonesia (Bangka, Kalimantan, Sumba and West Timor). Measures of diversity, linkage disequilibrium (LD) and population structure were used to gauge the transmission dynamics of each species in each setting. Marked differences were observed in the diversity and population structure of P. vivax versus P. falciparum. In Bangka, Kalimantan and Timor, P. falciparum diversity was low, and LD patterns were consistent with unstable, epidemic transmission, amenable to targeted intervention. In contrast, P. vivax diversity was higher and transmission appeared more stable. Population differentiation was lower in P. vivax versus P. falciparum, suggesting that the hypnozoite reservoir might play an important role in sustaining local transmission and facilitating the spread of P. vivax infections in different endemic settings. P. vivax polyclonality varied with local endemicity, demonstrating potential utility in informing on transmission intensity in this species. Molecular approaches can provide important information on malaria transmission that is not readily available from traditional epidemiological measures. Elucidation of the transmission dynamics circulating in a given setting will have a major role in prioritising malaria control strategies

  14. Quantitative ptychographic reconstruction by applying a probe constraint

    NASA Astrophysics Data System (ADS)

    Reinhardt, J.; Schroer, C. G.

    2018-04-01

    The coherent scanning technique X-ray ptychography has become a routine tool for high-resolution imaging and nanoanalysis in various fields of research such as chemistry, biology or materials science. Often the ptychographic reconstruction results are analysed in order to yield absolute quantitative values for the object transmission and illuminating probe function. In this work, we address a common ambiguity encountered in scaling the object transmission and probe intensity via the application of an additional constraint to the reconstruction algorithm. A ptychographic measurement of a model sample containing nanoparticles is used as a test data set against which to benchmark in the reconstruction results depending on the type of constraint used. Achieving quantitative absolute values for the reconstructed object transmission is essential for advanced investigation of samples that are changing over time, e.g., during in-situ experiments or in general when different data sets are compared.

  15. Linkage disequilibrium in HLA cannot be explained by selective recombination.

    PubMed

    Termijtelen, A; D'Amaro, J; van Rood, J J; Schreuder, G M

    1995-11-01

    Some combinations of HLA-A, -B and -DR antigens occur more frequently than would be expected from their gene frequencies in the population. This phenomenon, referred to as Linkage Disequilibrium (LD) has been the origin of many speculations. One hypothesis to explain LD is that some haplotypes are protected from recombination. A second hypothesis is that these HLA antigens preferentially recombine after cross-over to create an LD haplotype. We tested these 2 hypotheses: from a pool of over 10,000 families typed in our department, we analyzed 126 families in which HLA-A:B or B:DR recombinant offspring was documented. To overcome a possible bias in our material, we used the non-recombined haplotypes from the same 126 families as a control group. Our results show that the number of cross-overs through LD haplotypes is not significantly lower then would be expected if recombination occurred randomly. Also the number of LD haplotypes created upon recombination was not significantly increased.

  16. Delayed, disequilibrium degassing in rhyolite magma: Decompression experiments and implications for explosive volcanism

    USGS Publications Warehouse

    Mangan, M.; Sisson, T.

    2000-01-01

    Recent numerical models and analog shock tube experiments show that disequilibrium degassing during magma ascent may lead to violent vesiculation very near the surface. In this study a series of decompression experiments using crystal-free, rhyolite melt were conducted to examine the development of large supersaturations due to delayed, homogenous (spontaneous) bubble nucleation. Melts were saturated at 900??C and 200 MPa with either 5.2 wt% dissolved H2O, or with 4.2 wt% H2O and 640 ppm CO2, and isothermally decompressed at linear rates of either 0.003, 0.025, or 8.5 MPa/s to final pressures between 25 and 175 MPa. Additional isobaric saturation experiments (900??C, 200-25 MPa) using pure H2O or mixed H2O-CO2 fluids establish reference equilibrium solubility curves/values. Homogenous nucleation is triggered in both H2O-only and H2O-CO2 experiments once the supersaturation pressure (??Pss) reaches ?? 120-150 MPa and the melt contains ?? two times its equilibrium water contents. Bubble number density and nucleation rate depend on the supersaturation pressure, with values on the order of 102/cm3 and < 1/cm3/s for ??Pss~120 MPa; 106/cm3 and 103-105/cm3/s for ??Pss??~130-150 MPa; and 107/cm3 and 106/cm3/s for ??Pss??160-175 MPa. Nucleation rates are consistent with classical nucleation theory, and infer an activation energy for nucleation of 1.5 x 10-18 J/nucleus, a critical bubble radius of 2 x 10-9 m, and an effective surface tension for rhyolite at 5.2 wt% H2O and 900??C of 0.10-0.11 N/m. The long nucleation delay limits the time available for subsequent diffusion such that disequilibrium dissolved H2O and CO2 contents persist to the end of our runs. The disequilibrium degassing paths inferred from our experiments contrast markedly with the equilibrium or quasi-equilibrium paths found in other studies where bubble nucleation occurs heterogenously on crystals or other discontinuities in the melt at low ??Pss. Homogenous and heterogenous nucleation rates are

  17. Mercury flux from salt marsh sediments: Insights from a comparison between 224Ra/228Th disequilibrium and core incubation methods

    NASA Astrophysics Data System (ADS)

    Shi, Xiangming; Mason, Robert P.; Charette, Matthew A.; Mazrui, Nashaat M.; Cai, Pinghe

    2018-02-01

    In aquatic environments, sediments are the main location of mercury methylation. Thus, accurate quantification of methylmercury (MeHg) fluxes at the sediment-water interface is vital to understanding the biogeochemical cycling of mercury, especially the toxic MeHg species, and their bioaccumulation. Traditional approaches, such as core incubations, are difficult to maintain at in-situ conditions during assays, leading to over/underestimation of benthic fluxes. Alternatively, the 224Ra/228Th disequilibrium method for tracing the transfer of dissolved substances across the sediment-water interface, has proven to be a reliable approach for quantifying benthic fluxes. In this study, the 224Ra/228Th disequilibrium and core incubation methods were compared to examine the benthic fluxes of both 224Ra and MeHg in salt marsh sediments of Barn Island, Connecticut, USA from May to August, 2016. The two methods were comparable for 224Ra but contradictory for MeHg. The radiotracer approach indicated that sediments were always the dominant source of both total mercury (THg) and MeHg. The core incubation method for MeHg produced similar results in May and August, but an opposite pattern in June and July, which suggested sediments were a sink of MeHg, contrary to the evidence of significant MeHg gradients between overlying water and porewater at the sediment-water interface. The potential reasons for such differences are discussed. Overall, we conclude that the 224Ra/228Th disequilibrium approach is preferred for estimating the benthic flux of MeHg and that sediment is indeed an important MeHg source in this marshland, and likely in other shallow coastal waters.

  18. Novel linkage disequilibrium clustering algorithm identifies new lupus genes on meta-analysis of GWAS datasets.

    PubMed

    Saeed, Mohammad

    2017-05-01

    Systemic lupus erythematosus (SLE) is a complex disorder. Genetic association studies of complex disorders suffer from the following three major issues: phenotypic heterogeneity, false positive (type I error), and false negative (type II error) results. Hence, genes with low to moderate effects are missed in standard analyses, especially after statistical corrections. OASIS is a novel linkage disequilibrium clustering algorithm that can potentially address false positives and negatives in genome-wide association studies (GWAS) of complex disorders such as SLE. OASIS was applied to two SLE dbGAP GWAS datasets (6077 subjects; ∼0.75 million single-nucleotide polymorphisms). OASIS identified three known SLE genes viz. IFIH1, TNIP1, and CD44, not previously reported using these GWAS datasets. In addition, 22 novel loci for SLE were identified and the 5 SLE genes previously reported using these datasets were verified. OASIS methodology was validated using single-variant replication and gene-based analysis with GATES. This led to the verification of 60% of OASIS loci. New SLE genes that OASIS identified and were further verified include TNFAIP6, DNAJB3, TTF1, GRIN2B, MON2, LATS2, SNX6, RBFOX1, NCOA3, and CHAF1B. This study presents the OASIS algorithm, software, and the meta-analyses of two publicly available SLE GWAS datasets along with the novel SLE genes. Hence, OASIS is a novel linkage disequilibrium clustering method that can be universally applied to existing GWAS datasets for the identification of new genes.

  19. Linkage disequilibrium, SNP frequency change due to selection, and association mapping in popcorn chromosome regions containing QTLs for quality traits

    PubMed Central

    Paes, Geísa Pinheiro; Viana, José Marcelo Soriano; Silva, Fabyano Fonseca e; Mundim, Gabriel Borges

    2016-01-01

    Abstract The objectives of this study were to assess linkage disequilibrium (LD) and selection-induced changes in single nucleotide polymorphism (SNP) frequency, and to perform association mapping in popcorn chromosome regions containing quantitative trait loci (QTLs) for quality traits. Seven tropical and two temperate popcorn populations were genotyped for 96 SNPs chosen in chromosome regions containing QTLs for quality traits. The populations were phenotyped for expansion volume, 100-kernel weight, kernel sphericity, and kernel density. The LD statistics were the difference between the observed and expected haplotype frequencies (D), the proportion of D relative to the expected maximum value in the population, and the square of the correlation between the values of alleles at two loci. Association mapping was based on least squares and Bayesian approaches. In the tropical populations, D-values greater than 0.10 were observed for SNPs separated by 100-150 Mb, while most of the D-values in the temperate populations were less than 0.05. Selection for expansion volume indirectly led to increase in LD values, population differentiation, and significant changes in SNP frequency. Some associations were observed for expansion volume and the other quality traits. The candidate genes are involved with starch, storage protein, lipid, and cell wall polysaccharides synthesis. PMID:27007903

  20. Linkage disequilibrium, SNP frequency change due to selection, and association mapping in popcorn chromosome regions containing QTLs for quality traits.

    PubMed

    Paes, Geísa Pinheiro; Viana, José Marcelo Soriano; Silva, Fabyano Fonseca E; Mundim, Gabriel Borges

    2016-03-01

    The objectives of this study were to assess linkage disequilibrium (LD) and selection-induced changes in single nucleotide polymorphism (SNP) frequency, and to perform association mapping in popcorn chromosome regions containing quantitative trait loci (QTLs) for quality traits. Seven tropical and two temperate popcorn populations were genotyped for 96 SNPs chosen in chromosome regions containing QTLs for quality traits. The populations were phenotyped for expansion volume, 100-kernel weight, kernel sphericity, and kernel density. The LD statistics were the difference between the observed and expected haplotype frequencies (D), the proportion of D relative to the expected maximum value in the population, and the square of the correlation between the values of alleles at two loci. Association mapping was based on least squares and Bayesian approaches. In the tropical populations, D-values greater than 0.10 were observed for SNPs separated by 100-150 Mb, while most of the D-values in the temperate populations were less than 0.05. Selection for expansion volume indirectly led to increase in LD values, population differentiation, and significant changes in SNP frequency. Some associations were observed for expansion volume and the other quality traits. The candidate genes are involved with starch, storage protein, lipid, and cell wall polysaccharides synthesis.

  1. Cognitive Disequilibrium and Service-Learning in Physical Education Teacher Education: Perceptions of Pre-Service Teachers in a Study Abroad Experience

    ERIC Educational Resources Information Center

    Ward, Stephen; Pellet, Heidi Henschel; Perez, Mark I.

    2017-01-01

    Purpose: The purpose of this study was to explore preservice teachers' experiences of cognitive disequilibrium (CD) theory during a service-learning project in a study abroad experience. Method: A case study with 8 participants was used. Data sources consisted of: Formal interviews, videos of planning, videos of teaching, videos of reflection…

  2. Genetic variation, population structure and linkage disequilibrium in Switchgrass with ISSR, SCoT and EST-SSR markers.

    PubMed

    Zhang, Yu; Yan, Haidong; Jiang, Xiaomei; Wang, Xiaoli; Huang, Linkai; Xu, Bin; Zhang, Xinquan; Zhang, Lexin

    2016-01-01

    To evaluate genetic variation, population structure, and the extent of linkage disequilibrium (LD), 134 switchgrass ( Panicum virgatum L.) samples were analyzed with 51 markers, including 16 ISSRs, 20 SCoTs, and 15 EST-SSRs. In this study, a high level of genetic variation was observed in the switchgrass samples and they had an average Nei's gene diversity index (H) of 0.311. A total of 793 bands were obtained, of which 708 (89.28 %) were polymorphic. Using a parameter marker index (MI), the efficiency of the three types of markers (ISSR, SCoT, and EST-SSR) in the study were compared and we found that SCoT had a higher marker efficiency than the other two markers. The 134 switchgrass samples could be divided into two sub-populations based on STRUCTURE, UPGMA clustering, and principal coordinate analyses (PCA), and upland and lowland ecotypes could be separated by UPGMA clustering and PCA analyses. Linkage disequilibrium analysis revealed an average r 2 of 0.035 across all 51 markers, indicating a trend of higher LD in sub-population 2 than that in sub-population 1 ( P  < 0.01). The population structure revealed in this study will guide the design of future association studies using these switchgrass samples.

  3. A reliability design method for a lithium-ion battery pack considering the thermal disequilibrium in electric vehicles

    NASA Astrophysics Data System (ADS)

    Xia, Quan; Wang, Zili; Ren, Yi; Sun, Bo; Yang, Dezhen; Feng, Qiang

    2018-05-01

    With the rapid development of lithium-ion battery technology in the electric vehicle (EV) industry, the lifetime of the battery cell increases substantially; however, the reliability of the battery pack is still inadequate. Because of the complexity of the battery pack, a reliability design method for a lithium-ion battery pack considering the thermal disequilibrium is proposed in this paper based on cell redundancy. Based on this method, a three-dimensional electric-thermal-flow-coupled model, a stochastic degradation model of cells under field dynamic conditions and a multi-state system reliability model of a battery pack are established. The relationships between the multi-physics coupling model, the degradation model and the system reliability model are first constructed to analyze the reliability of the battery pack and followed by analysis examples with different redundancy strategies. By comparing the reliability of battery packs of different redundant cell numbers and configurations, several conclusions for the redundancy strategy are obtained. More notably, the reliability does not monotonically increase with the number of redundant cells for the thermal disequilibrium effects. In this work, the reliability of a 6 × 5 parallel-series configuration is the optimal system structure. In addition, the effect of the cell arrangement and cooling conditions are investigated.

  4. Divergence between human populations estimated from linkage disequilibrium.

    PubMed

    Sved, John A; McRae, Allan F; Visscher, Peter M

    2008-12-01

    Observed linkage disequilibrium (LD) between genetic markers in different populations descended independently from a common ancestral population can be used to estimate their absolute time of divergence, because the correlation of LD between populations will be reduced each generation by an amount that, approximately, depends only on the recombination rate between markers. Although drift leads to divergence in allele frequencies, it has less effect on divergence in LD values. We derived the relationship between LD and time of divergence and verified it with coalescent simulations. We then used HapMap Phase II data to estimate time of divergence between human populations. Summed over large numbers of pairs of loci, we find a positive correlation of LD between African and non-African populations at levels of up to approximately 0.3 cM. We estimate that the observed correlation of LD is consistent with an effective separation time of approximately 1,000 generations or approximately 25,000 years before present. The most likely explanation for such relatively low separation times is the existence of substantial levels of migration between populations after the initial separation. Theory and results from coalescent simulations confirm that low levels of migration can lead to a downward bias in the estimate of separation time.

  5. Disequilibrium growth of olivine in mafic magmas revealed by phosphorus zoning patterns of olivine from mafic-ultramafic intrusions

    NASA Astrophysics Data System (ADS)

    Xing, Chang-Ming; Wang, Christina Yan; Tan, Wei

    2017-12-01

    Olivine from mafic-ultramafic intrusions rarely displays growth zoning in major and some minor elements, such as Fe, Mg and Ni, due to fast diffusion of these elements at high temperatures. These elements in olivine are thus not useful in deciphering magma chamber processes, such as magma convection, multiple injection and mixing. High-resolution X-ray elemental intensity mapping reveals distinct P zoning patterns of olivine from two mafic-ultramafic intrusions in SW China. Polyhedral olivine grains from lherzolite and dunite of the Abulangdang intrusion show P-rich dendrites similar to those observed in volcanic rocks. Rounded olivine grains from net-textured Fe-Ti oxide ores of the Baima layered intrusion have irregular P-rich patches/bands crosscut and interlocked by P-poor olivine domains. P-rich patches/bands contain 250 to 612 ppm P, much higher than P-poor olivine domains with 123 to 230 ppm P. In electron backscattered diffraction (EBSD) maps, P-rich patches/bands within a single olivine grain have the same crystallographic orientation, indicating that they were remnants of the same crystal. Thus, both P-rich patches/bands and P-poor olivine domains in the same grain show a disequilibrium texture and clearly record two-stage growth. The P-rich patches/bands are likely the remnants of a polyhedral olivine crystal that formed in the first stage, whereas the P-poor olivine domains containing rounded Ti-rich magnetite and Fe-rich melt inclusions may have formed from an Fe-rich ambient melt in the second stage. The complex P zoning of olivine can be attributed to the dissolution of early polyhedral olivine and re-precipitation from the Fe-rich ambient melt. The early polyhedral olivine was in chemical disequilibrium with the ambient melt that may have been developed by silicate liquid immiscibility in a crystal mush. Our study implies that olivine crystals in igneous cumulates with an equilibrium appearance may have experienced disequilibrium growth processes

  6. Small-scale disequilibrium in a magmatic inclusion and its more silicic host

    NASA Technical Reports Server (NTRS)

    Davidson, Jon P.; Holden, Peter; Halliday, Alex N.; De Silva, Shanaka L.

    1990-01-01

    An investigation of small-scale isotopic, compositional, and mineralogical variation across the interface of a basaltic-andesite inclusion and its dacitic host from Cerro-Chascon, a Holocene dome in northern Chile, is discussed. Serial sectioning across the interface of the inclusion and its host dacite, complemented by microdrill sampling and detailed microprobe work, has enabled an examination of the scale of mixing and chemical disequilibrium. The composition of the inclusion is found to be relatively homogeneous; the dacite host is heterogeneous on a small scale; the isotopic composition in the marginal zone shows the highest Sr-87/Sr-86 and lowest Nd-143/Nd-144; the large plagioclase crystals in the inclusions and host are xenocrystic. These differences are reconciled with a model of magma evolution in a crustal magma chamber.

  7. Genomewide Linkage Disequilibrium Mapping of Severe Bipolar Disorder in a Population Isolate

    PubMed Central

    Ophoff, Roel A.; Escamilla, Michael A.; Service, Susan K.; Spesny, Mitzi; Meshi, Dar B.; Poon, Wingman; Molina, Julio; Fournier, Eduardo; Gallegos, Alvaro; Mathews, Carol; Neylan, Thomas; Batki, Steven L.; Roche, Erin; Ramirez, Margarita; Silva, Sandra; De Mille, Melissa C.; Dong, Penny; Leon, Pedro E.; Reus, Victor I.; Sandkuijl, Lodewijk A.; Freimer, Nelson B.

    2002-01-01

    Genomewide association studies may offer the best promise for genetic mapping of complex traits. Such studies in outbred populations require very densely spaced single-nucleotide polymorphisms. In recently founded population isolates, however, extensive linkage disequilibrium (LD) may make these studies feasible with currently available sets of short tandem repeat markers, spaced at intervals as large as a few centimorgans. We report the results of a genomewide association study of severe bipolar disorder (BP-I), using patients from the isolated population of the central valley of Costa Rica. We observed LD with BP-I on several chromosomes; the most striking results were in proximal 8p, a region that has previously shown linkage to schizophrenia. This region could be important for severe psychiatric disorders, rather than for a specific phenotype. PMID:12119601

  8. The Second Economy in Disequilibrium and Shortage Models of Centrally Planned Economies

    DTIC Science & Technology

    1988-07-01

    CPEs 70 IV. The Second Economy in Disequilibrium Models 76 A. General Equilibrium Models with a Second Economy 78 B. The Portes Macroeconomic ...44,~g3 C AC4 v- 44,A0-.’ 3-3. 3 ~ .1 a a 0, a~ 0.a c 63 9 o -o.a- *~~~t a A . 2. 0 V 0 m -6 o 0 *Z 1 0 6Q 446O l ~ 4 ~ ~ ~ 1 0 v 90 3 ~ . 0 6 C a A OA ...A - - A C A A A C - - C * - A AY 0 - - A C A - A A - - ’A - ’A 4 A C A 6- C A ’A A - - .C A - - - - oA A A A 6-C - .C ’AA - A A A CI 4 = A

  9. Linkage disequilibrium matches forensic genetic records to disjoint genomic marker sets.

    PubMed

    Edge, Michael D; Algee-Hewitt, Bridget F B; Pemberton, Trevor J; Li, Jun Z; Rosenberg, Noah A

    2017-05-30

    Combining genotypes across datasets is central in facilitating advances in genetics. Data aggregation efforts often face the challenge of record matching-the identification of dataset entries that represent the same individual. We show that records can be matched across genotype datasets that have no shared markers based on linkage disequilibrium between loci appearing in different datasets. Using two datasets for the same 872 people-one with 642,563 genome-wide SNPs and the other with 13 short tandem repeats (STRs) used in forensic applications-we find that 90-98% of forensic STR records can be connected to corresponding SNP records and vice versa. Accuracy increases to 99-100% when ∼30 STRs are used. Our method expands the potential of data aggregation, but it also suggests privacy risks intrinsic in maintenance of databases containing even small numbers of markers-including databases of forensic significance.

  10. Constraints on the origin of Os-isotope disequilibrium in included and interstitial sulfides in mantle peridotites: Implications for the interpretation of Os-isotope signatures in MORB and Abyssal Peridotites

    NASA Astrophysics Data System (ADS)

    Lassiter, J. C.

    2016-12-01

    The use of isotope variations in basalts to probe the composition and evolution of the mantle is predicated on the assumption of local (i.e., grain-scale) isotopic equilibrium during mantle melting (Hofmann & Hart, 1978). However, several studies report Os-isotope disequilibrium in distinct populations of sulfides in some peridotites. In principle, grain-scale isotopic heterogeneity could reflect variable radiogenic ingrowth in ancient sulfides with variable Re/Os, or partial re-equilibration of low-Re/Os sulfides with high-Re/Os silicate phases along grain boundaries during mantle melting (e.g., Alard et al., 2005). Both cases require that sulfides fail to maintain isotopic equilibrium with neighboring phases over geologically long ( Ga) time scales. The preservation of Os-isotope disequilibrium in peridotites has been ascribed to the armoring effect of low-[Os] silicates, which limit diffusive exchange between isolated Os-rich phases. This raises the prospect that peridotite-derived melts may not inherit the Os-isotope composition of their source. The timescale required for diffusive equilibration between separate sulfide grains or between Os-rich sulfides and Os-poor silicates is a function of average sulfide size and spacing, Os diffusivity in armoring silicate minerals, and Os partitioning between silicate and sulfide phases. For typical sulfide abundances and sizes in mantle peridotites, neighboring sulfides are expected to re-equilibrate in less than a few 10s of m.y. at adiabatic mantle temperatures, even for very high (>106) sulfide/silicate KD values. Maintenance of disequilibrium requires very large sulfides (>100 um) separated by several mm and diffusion rates (D < 10-20 m2/s) slower than for most other elements in olivine. Equilibration timescales between sulfides and surrounding silicates are similar, so that large-scale isotopic disequilibrium between sulfides and silicates is also unlikely within the convecting mantle. Instead, observed grain

  11. HLA-DR4 as a risk allele for autism acting in mothers of probands possibly during pregnancy.

    PubMed

    Johnson, William G; Buyske, Steven; Mars, Audrey E; Sreenath, Madhura; Stenroos, Edward S; Williams, Tanishia A; Stein, Rosanne; Lambert, George H

    2009-06-01

    To test whether HLA-DR4 acts in the mother, possibly during pregnancy, to contribute to the phenotype of autistic disorder in her fetus. Transmission disequilibrium testing in case mothers and maternal grandparents. Previous studies have consistently shown increased frequency of HLA-DR4 in probands with autism and their mothers, but not their fathers. However, this has been documented only in case-control studies and not by a more direct study design to determine whether HLA-DR4 acts in mothers during pregnancy to contribute to autism in their affected offspring. We genotyped for HLA-DR alleles in members of 31 families with parents and maternal grandparents. Probands with autism were tested using the Autism Diagnostic Observation Schedule-Western Psychological Services and Autism Diagnostic Interview, Revised. There was 80% power to detect an odds ratio of 3.6. Participants were all families from New Jersey and were similar in number to earlier studies of autism and HLA-DR4. Analysis was by standard transmission disequilibrium testing. As a secondary test we examined the possibility of maternal imprinting. Significant transmission disequilibrium for HLA-DR4 was seen (odds ratio, 4.67; 95% confidence interval, 1.34-16.24; P = .008) for transmissions from maternal grandparents to mothers of probands, supporting a role for HLA-DR4 as an autism risk factor acting in mothers during pregnancy. Transmission disequilibrium was not seen for HLA-DR4 transmissions from parents to probands or from mothers to probands. The HLA-DR4 gene may act in mothers of children with autism during pregnancy to contribute to autism in their offspring. Further studies are required to confirm these findings.

  12. FORWARD AND INVERSE MODELING OF THE EMISSION AND TRANSMISSION SPECTRUM OF GJ 436B: INVESTIGATING METAL ENRICHMENT, TIDAL HEATING, AND CLOUDS

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

    Morley, Caroline V.; Knutson, Heather; Line, Michael

    The Neptune-mass GJ 436b is one of the most studied transiting exoplanets with repeated measurements of its thermal emission and transmission spectra. We build on previous studies to answer outstanding questions about this planet, including its potentially high metallicity and tidal heating of its interior. We present new observations of GJ 436b’s thermal emission at 3.6 and 4.5 μ m, which reduce uncertainties in estimates of GJ 436b’s flux at those wavelengths and demonstrate consistency between Spitzer observations spanning more than 7 yr. We analyze the Spitzer thermal emission photometry and Hubble WFC3 transmission spectrum. We use a dual-pronged modelingmore » approach of both self-consistent and retrieval models. We vary the metallicity, intrinsic luminosity from tidal heating, disequilibrium chemistry, and heat redistribution. We also study clouds and photochemical hazes, but do not find strong evidence for either. The self-consistent and retrieval models combine to suggest that GJ 436b has a high atmospheric metallicity, with best fits at or above several hundred times solar metallicity, tidal heating warming its interior with best-fit intrinsic effective temperatures around 300–350 K, and disequilibrium chemistry. High metal enrichments (>600× solar) occur from the accretion of rocky, rather than icy, material. Assuming the interior temperature T {sub int} ∼ 300–350 K, we find a dissipation factor Q ′ ∼ 2 × 10{sup 5}–10{sup 6}, larger than Neptune’s Q ′, implying a long tidal circularization timescale for the orbit. We suggest that Neptune-mass planets may be more diverse than imagined, with metal enhancements spanning several orders of magnitude, to perhaps over 1000× solar metallicity. High-fidelity observations with instruments like the James Webb Space Telescope will be critical for characterizing this diversity.« less

  13. Forward and Inverse Modeling of the Emission and Transmission Spectrum of GJ 436b: Investigating Metal Enrichment, Tidal Heating, and Clouds

    NASA Astrophysics Data System (ADS)

    Morley, Caroline V.; Knutson, Heather; Line, Michael; Fortney, Jonathan J.; Thorngren, Daniel; Marley, Mark S.; Teal, Dillon; Lupu, Roxana

    2017-02-01

    The Neptune-mass GJ 436b is one of the most studied transiting exoplanets with repeated measurements of its thermal emission and transmission spectra. We build on previous studies to answer outstanding questions about this planet, including its potentially high metallicity and tidal heating of its interior. We present new observations of GJ 436b’s thermal emission at 3.6 and 4.5 μm, which reduce uncertainties in estimates of GJ 436b’s flux at those wavelengths and demonstrate consistency between Spitzer observations spanning more than 7 yr. We analyze the Spitzer thermal emission photometry and Hubble WFC3 transmission spectrum. We use a dual-pronged modeling approach of both self-consistent and retrieval models. We vary the metallicity, intrinsic luminosity from tidal heating, disequilibrium chemistry, and heat redistribution. We also study clouds and photochemical hazes, but do not find strong evidence for either. The self-consistent and retrieval models combine to suggest that GJ 436b has a high atmospheric metallicity, with best fits at or above several hundred times solar metallicity, tidal heating warming its interior with best-fit intrinsic effective temperatures around 300-350 K, and disequilibrium chemistry. High metal enrichments (>600× solar) occur from the accretion of rocky, rather than icy, material. Assuming the interior temperature Tint ˜ 300-350 K, we find a dissipation factor Q‧ ˜ 2 × 105-106, larger than Neptune’s Q‧, implying a long tidal circularization timescale for the orbit. We suggest that Neptune-mass planets may be more diverse than imagined, with metal enhancements spanning several orders of magnitude, to perhaps over 1000× solar metallicity. High-fidelity observations with instruments like the James Webb Space Telescope will be critical for characterizing this diversity.

  14. Intrahaplotypic Variants Differentiate Complex Linkage Disequilibrium within Human MHC Haplotypes

    PubMed Central

    Lam, Tze Hau; Tay, Matthew Zirui; Wang, Bei; Xiao, Ziwei; Ren, Ee Chee

    2015-01-01

    Distinct regions of long-range genetic fixation in the human MHC region, known as conserved extended haplotypes (CEHs), possess unique genomic characteristics and are strongly associated with numerous diseases. While CEHs appear to be homogeneous by SNP analysis, the nature of fine variations within their genomic structure is unknown. Using multiple, MHC-homozygous cell lines, we demonstrate extensive sequence conservation in two common Asian MHC haplotypes: A33-B58-DR3 and A2-B46-DR9. However, characterization of phase-resolved MHC haplotypes revealed unique intra-CEH patterns of variation and uncovered 127 single nucleotide variants (SNVs) which are missing from public databases. We further show that the strong linkage disequilibrium structure within the human MHC that typically confounds precise identification of genetic features can be resolved using intra-CEH variants, as evidenced by rs3129063 and rs448489, which affect expression of ZFP57, a gene important in methylation and epigenetic regulation. This study demonstrates an improved strategy that can be used towards genetic dissection of diseases. PMID:26593880

  15. Plasmodium vivax population structure and transmission dynamics in Sabah Malaysia.

    PubMed

    Abdullah, Noor Rain; Barber, Bridget E; William, Timothy; Norahmad, Nor Azrina; Satsu, Umi Rubiah; Muniandy, Prem Kumar; Ismail, Zakiah; Grigg, Matthew J; Jelip, Jenarun; Piera, Kim; von Seidlein, Lorenz; Yeo, Tsin W; Anstey, Nicholas M; Price, Ric N; Auburn, Sarah

    2013-01-01

    Despite significant progress in the control of malaria in Malaysia, the complex transmission dynamics of P. vivax continue to challenge national efforts to achieve elimination. To assess the impact of ongoing interventions on P. vivax transmission dynamics in Sabah, we genotyped 9 short tandem repeat markers in a total of 97 isolates (8 recurrences) from across Sabah, with a focus on two districts, Kota Marudu (KM, n = 24) and Kota Kinabalu (KK, n = 21), over a 2 year period. STRUCTURE analysis on the Sabah-wide dataset demonstrated multiple sub-populations. Significant differentiation (F ST  = 0.243) was observed between KM and KK, located just 130 Km apart. Consistent with low endemic transmission, infection complexity was modest in both KM (mean MOI  = 1.38) and KK (mean MOI  = 1.19). However, population diversity remained moderate (H E  = 0.583 in KM and H E  = 0.667 in KK). Temporal trends revealed clonal expansions reflecting epidemic transmission dynamics. The haplotypes of these isolates declined in frequency over time, but persisted at low frequency throughout the study duration. A diverse array of low frequency isolates were detected in both KM and KK, some likely reflecting remnants of previous expansions. In accordance with clonal expansions, high levels of Linkage Disequilibrium (I A (S) >0.5 [P<0.0001] in KK and KM) declined sharply when identical haplotypes were represented once (I A (S)  = 0.07 [P = 0.0076] in KM, and I A (S) = -0.003 [P = 0.606] in KK). All 8 recurrences, likely to be relapses, were homologous to the prior infection. These recurrences may promote the persistence of parasite lineages, sustaining local diversity. In summary, Sabah's shrinking P. vivax population appears to have rendered this low endemic setting vulnerable to epidemic expansions. Migration may play an important role in the introduction of new parasite strains leading to epidemic expansions, with important implications for

  16. Plasmodium vivax Population Structure and Transmission Dynamics in Sabah Malaysia

    PubMed Central

    Abdullah, Noor Rain; Barber, Bridget E.; William, Timothy; Norahmad, Nor Azrina; Satsu, Umi Rubiah; Muniandy, Prem Kumar; Ismail, Zakiah; Grigg, Matthew J.; Jelip, Jenarun; Piera, Kim; von Seidlein, Lorenz; Yeo, Tsin W.; Anstey, Nicholas M.; Price, Ric N.; Auburn, Sarah

    2013-01-01

    Despite significant progress in the control of malaria in Malaysia, the complex transmission dynamics of P. vivax continue to challenge national efforts to achieve elimination. To assess the impact of ongoing interventions on P. vivax transmission dynamics in Sabah, we genotyped 9 short tandem repeat markers in a total of 97 isolates (8 recurrences) from across Sabah, with a focus on two districts, Kota Marudu (KM, n = 24) and Kota Kinabalu (KK, n = 21), over a 2 year period. STRUCTURE analysis on the Sabah-wide dataset demonstrated multiple sub-populations. Significant differentiation (F ST  = 0.243) was observed between KM and KK, located just 130 Km apart. Consistent with low endemic transmission, infection complexity was modest in both KM (mean MOI  = 1.38) and KK (mean MOI  = 1.19). However, population diversity remained moderate (H E  = 0.583 in KM and H E  = 0.667 in KK). Temporal trends revealed clonal expansions reflecting epidemic transmission dynamics. The haplotypes of these isolates declined in frequency over time, but persisted at low frequency throughout the study duration. A diverse array of low frequency isolates were detected in both KM and KK, some likely reflecting remnants of previous expansions. In accordance with clonal expansions, high levels of Linkage Disequilibrium (I A S >0.5 [P<0.0001] in KK and KM) declined sharply when identical haplotypes were represented once (I A S  = 0.07 [P = 0.0076] in KM, and I A S = -0.003 [P = 0.606] in KK). All 8 recurrences, likely to be relapses, were homologous to the prior infection. These recurrences may promote the persistence of parasite lineages, sustaining local diversity. In summary, Sabah's shrinking P. vivax population appears to have rendered this low endemic setting vulnerable to epidemic expansions. Migration may play an important role in the introduction of new parasite strains leading to epidemic expansions, with important implications for malaria

  17. Disequilibrium in the uranium and actinium series in oil scale samples.

    PubMed

    Landsberger, S; Tamalis, D; Leblanc, C; Yoho, M D

    2017-01-01

    We have investigated the disequilibrium of the uranium and actinium series and have found both 226 Ra (90,200 ± 4300 Bq/kg) and 228 Ra have activity concentrations orders of magnitude higher that 238 U (1.83 ± 0.36 Bq/kg) and 232 Th (7.0 ± 0.4) which are at the head of the decay series. As well the activity concentration of 210 Pb (24,400 ± 1200 Bg/kg) was about 3.6 times less than 226 Ra. Once an efficiency curve was constructed summing corrections for specific isotopes in the decay change also needed to be taken in consideration. Furthermore, self-attenuation of the photons especially the 46.5 keV belonging to 210 Pb was calculated to be 78% since the scale had elevated elemental concentrations of high-Z elements such as barium and strontium. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Quantitative genetic bases of anthocyanin variation in grape (Vitis vinifera L. ssp. sativa) berry: a quantitative trait locus to quantitative trait nucleotide integrated study.

    PubMed

    Fournier-Level, Alexandre; Le Cunff, Loïc; Gomez, Camila; Doligez, Agnès; Ageorges, Agnès; Roux, Catherine; Bertrand, Yves; Souquet, Jean-Marc; Cheynier, Véronique; This, Patrice

    2009-11-01

    The combination of QTL mapping studies of synthetic lines and association mapping studies of natural diversity represents an opportunity to throw light on the genetically based variation of quantitative traits. With the positional information provided through quantitative trait locus (QTL) mapping, which often leads to wide intervals encompassing numerous genes, it is now feasible to directly target candidate genes that are likely to be responsible for the observed variation in completely sequenced genomes and to test their effects through association genetics. This approach was performed in grape, a newly sequenced genome, to decipher the genetic architecture of anthocyanin content. Grapes may be either white or colored, ranging from the lightest pink to the darkest purple tones according to the amount of anthocyanin accumulated in the berry skin, which is a crucial trait for both wine quality and human nutrition. Although the determinism of the white phenotype has been fully identified, the genetic bases of the quantitative variation of anthocyanin content in berry skin remain unclear. A single QTL responsible for up to 62% of the variation in the anthocyanin content was mapped on a Syrah x Grenache F(1) pseudo-testcross. Among the 68 unigenes identified in the grape genome within the QTL interval, a cluster of four Myb-type genes was selected on the basis of physiological evidence (VvMybA1, VvMybA2, VvMybA3, and VvMybA4). From a core collection of natural resources (141 individuals), 32 polymorphisms revealed significant association, and extended linkage disequilibrium was observed. Using a multivariate regression method, we demonstrated that five polymorphisms in VvMybA genes except VvMybA4 (one retrotransposon, three single nucleotide polymorphisms and one 2-bp insertion/deletion) accounted for 84% of the observed variation. All these polymorphisms led to either structural changes in the MYB proteins or differences in the VvMybAs promoters. We concluded that

  19. Emerging Infectious Diseases and Blood Safety: Modeling the Transfusion-Transmission Risk.

    PubMed

    Kiely, Philip; Gambhir, Manoj; Cheng, Allen C; McQuilten, Zoe K; Seed, Clive R; Wood, Erica M

    2017-07-01

    While the transfusion-transmission (TT) risk associated with the major transfusion-relevant viruses such as HIV is now very low, during the last 20 years there has been a growing awareness of the threat to blood safety from emerging infectious diseases, a number of which are known to be, or are potentially, transfusion transmissible. Two published models for estimating the transfusion-transmission risk from EIDs, referred to as the Biggerstaff-Petersen model and the European Upfront Risk Assessment Tool (EUFRAT), respectively, have been applied to several EIDs in outbreak situations. We describe and compare the methodological principles of both models, highlighting their similarities and differences. We also discuss the appropriateness of comparing results from the two models. Quantitating the TT risk of EIDs can inform decisions about risk mitigation strategies and their cost-effectiveness. Finally, we present a qualitative risk assessment for Zika virus (ZIKV), an EID agent that has caused several outbreaks since 2007. In the latest and largest ever outbreak, several probable cases of transfusion-transmission ZIKV have been reported, indicating that it is transfusion-transmissible and therefore a risk to blood safety. We discuss why quantitative modeling the TT risk of ZIKV is currently problematic. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  20. Extreme isotopologue disequilibrium in molecular SIMS species during SHRIMP geochronology

    NASA Astrophysics Data System (ADS)

    Magee, Charles W., Jr.; Danišík, Martin; Mernagh, Terry

    2017-12-01

    The current limitation in the accuracy and precision of inter-element analysis in secondary ion mass spectrometry (SIMS) is the ability to find measurable quantities that allow relative differences in ionization and transmission efficiency of secondary ions to be normalized. In uranium-thorium-lead geochronology, the ability to make these corrections, or "calibrate" the data, results in an accuracy limit of approximately 1 %. This study looks at the ionization of uranium and thorium oxide species, which are traditionally used in U-Pb calibration, to explore the conditions under which isotopologues, or molecular species whose composition differs only in the isotopic composition of one or more atoms in the molecule, remain in or deviate from equilibrium. Isotopologue deficits of up to 0.2 (200 ‰) below ideal mixing are observed in UO2+ species during SIMS gechronological analyses using the SHRIMP IIe SIMS instrument. These are identified by bombarding natural U-bearing minerals with an 18O2- primary beam. The large anomalies are associated with repeat analyses down a single SIMS sputtering crater (Compston et al., 1984), analysis of high-uranium, radiation-damaged zircon, and analysis of baddeleyite. Analysis of zircon under routine conditions yield UO2+ isotopologue anomalies generally within a few percent of equilibrium. The conditions under which the isotopologue anomalies are observed are also conditions in which the UOx-based corrections, or calibration, for relative U vs. Pb ionization efficiencies fail. The existence of these isotopologue anomalies suggest that failure of the various UOx species to equilibrate with each other is the reason that none of them will successfully correct the U  / Pb ratio. No simple isotopologue-based correction is apparent. However, isotopologue disequilibrium appears to be a more sensitive tool for detecting high-U calibration breakdowns than Raman spectroscopy, which showed sharper peaks for ˜ 37 Ma high

  1. Quantitative Differences in Salivary Pathogen Load during Tick Transmission Underlie Strain-Specific Variation in Transmission Efficiency of Anaplasma marginale

    USDA-ARS?s Scientific Manuscript database

    The relative fitness of arthropod-borne pathogens within the vector can be a major determinant of pathogen prevalence within the mammalian host population. Strains of the tick-borne rickettsia Anaplasma marginale differ markedly in transmission efficiency with consequent impact on pathogen strain st...

  2. No association detected between a D{sub 3} receptor gene-expressed variant and schizophrenia

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

    Rothschild, L.G.; Badner, J.; Cravchik, A.

    1996-04-09

    A missense polymorphism (glycine to serine) in the first exon of the dopamine D{sub 3} (DRD3) gene was examined in a sib-pairs schizophrenia collection by the transmission test for linkage disequilibrium (TDT). No association due to linkage disequilibrium was detected using TDT. Additionally, no evidence for excess homozygosity was found. 26 refs., 3 tabs.

  3. Linkage disequilibrium between STRPs and SNPs across the human genome.

    PubMed

    Payseur, Bret A; Place, Michael; Weber, James L

    2008-05-01

    Patterns of linkage disequilibrium (LD) reveal the action of evolutionary processes and provide crucial information for association mapping of disease genes. Although recent studies have described the landscape of LD among single nucleotide polymorphisms (SNPs) from across the human genome, associations involving other classes of molecular variation remain poorly understood. In addition to recombination and population history, mutation rate and process are expected to shape LD. To test this idea, we measured associations between short-tandem-repeat polymorphisms (STRPs), which can mutate rapidly and recurrently, and SNPs in 721 regions across the human genome. We directly compared STRP-SNP LD with SNP-SNP LD from the same genomic regions in the human HapMap populations. The intensity of STRP-SNP LD, measured by the average of D', was reduced, consistent with the action of recurrent mutation. Nevertheless, a higher fraction of STRP-SNP pairs than SNP-SNP pairs showed significant LD, on both short (up to 50 kb) and long (cM) scales. These results reveal the substantial effects of mutational processes on LD at STRPs and provide important measures of the potential of STRPs for association mapping of disease genes.

  4. Linkage disequilibrium levels in Bos indicus and Bos taurus cattle using medium and high density SNP chip data and different minor allele frequency distributions

    USDA-ARS?s Scientific Manuscript database

    Linkage disequilibrium (LD), the observed correlation between alleles at different loci in the genome, is a determinant parameter in many applications of molecular genetics. With the wider use of genomic technologies in animal breeding and animal genetics, it is worthwhile revising and improving the...

  5. Evidence for disequilibrium of ortho and para hydrogen on Jupiter from Voyager IRIS measurements

    NASA Technical Reports Server (NTRS)

    Conrath, B. J.; Gierasch, P. J.

    1983-01-01

    Preliminary results of an analysis of the ortho state/para state ratio (parallel/antiparallel) for molecular H2 in the Jovian atmosphere using Voyager IR spectrometer (IRIS) data are reported. The study was undertaken to expand the understanding of the thermodynamics of a predominantly H2 atmosphere, which takes about 100 million sec to reach equilibrium. IRIS data provided 4.3/cm resolution in the 300-700/cm spectral range dominated by H2 lines. Approximately 600 spectra were examined to detect any disequilibrium between the hydrogen species. The results indicate that the ortho-para ratio is not in an equilibrium state in the upper Jovian troposphere. A thorough mapping of the para-state molecules in the upper atmosphere could therefore aid in mapping the atmospheric flowfield.

  6. Trace element zoning as a record of chemical disequilibrium during garnet growth

    NASA Astrophysics Data System (ADS)

    Chernoff, Carlotta B.; Carlson, William D.

    1999-06-01

    Trace element concentrations in pelitic garnets from the Picuris Range of New Mexico display precipitous changes coincident with abrupt variations in Ca concentration. These patterns probably arise from the transitory participation of different trace element enriched phases in the garnet forming reaction. Changes in the reactant and product assemblages occur at different times during the reaction history for crystals of different size, so they cannot be the result of any event affecting the entire rock, such as a change in pressure, temperature, or fluid composition. Instead, they reflect kinetic factors that cause Ca, Y, Yb, P, Ti, Sc, Zr, Hf, Sr, Na, and Li to fail to achieve chemical equilibrium during garnet growth. Caution is needed to avoid misinterpreting excursions in the concentration of these elements as event markers recording simultaneous rockwide changes in intensive parameters, when in fact they may record transient disequilibrium states that are local in scope, and not contemporaneous.

  7. Inferring Admixture Histories of Human Populations Using Linkage Disequilibrium

    PubMed Central

    Loh, Po-Ru; Lipson, Mark; Patterson, Nick; Moorjani, Priya; Pickrell, Joseph K.; Reich, David; Berger, Bonnie

    2013-01-01

    Long-range migrations and the resulting admixtures between populations have been important forces shaping human genetic diversity. Most existing methods for detecting and reconstructing historical admixture events are based on allele frequency divergences or patterns of ancestry segments in chromosomes of admixed individuals. An emerging new approach harnesses the exponential decay of admixture-induced linkage disequilibrium (LD) as a function of genetic distance. Here, we comprehensively develop LD-based inference into a versatile tool for investigating admixture. We present a new weighted LD statistic that can be used to infer mixture proportions as well as dates with fewer constraints on reference populations than previous methods. We define an LD-based three-population test for admixture and identify scenarios in which it can detect admixture events that previous formal tests cannot. We further show that we can uncover phylogenetic relationships among populations by comparing weighted LD curves obtained using a suite of references. Finally, we describe several improvements to the computation and fitting of weighted LD curves that greatly increase the robustness and speed of the calculations. We implement all of these advances in a software package, ALDER, which we validate in simulations and apply to test for admixture among all populations from the Human Genome Diversity Project (HGDP), highlighting insights into the admixture history of Central African Pygmies, Sardinians, and Japanese. PMID:23410830

  8. Genetics coupled to quantitative intact proteomics links heritable aphid and endosymbiont protein expression to circulative polerovirus transmission.

    PubMed

    Cilia, M; Tamborindeguy, C; Fish, T; Howe, K; Thannhauser, T W; Gray, S

    2011-03-01

    Yellow dwarf viruses in the family Luteoviridae, which are the causal agents of yellow dwarf disease in cereal crops, are each transmitted most efficiently by different species of aphids in a circulative manner that requires the virus to interact with a multitude of aphid proteins. Aphid proteins differentially expressed in F2 Schizaphis graminum genotypes segregating for the ability to transmit Cereal yellow dwarf virus-RPV (CYDV-RPV) were identified using two-dimensional difference gel electrophoresis (DIGE) coupled to either matrix-assisted laser desorption ionization-tandem mass spectrometry or online nanoscale liquid chromatography coupled to electrospray tandem mass spectrometry. A total of 50 protein spots, containing aphid proteins and proteins from the aphid's obligate and maternally inherited bacterial endosymbiont, Buchnera, were identified as differentially expressed between transmission-competent and refractive aphids. Surprisingly, in virus transmission-competent F2 genotypes, the isoelectric points of the Buchnera proteins did not match those in the maternal Buchnera proteome as expected, but instead they aligned with the Buchnera proteome of the transmission-competent paternal parent. Among the aphid proteins identified, many were involved in energy metabolism, membrane trafficking, lipid signaling, and the cytoskeleton. At least eight aphid proteins were expressed as heritable, isoelectric point isoform pairs, one derived from each parental lineage. In the F2 genotypes, the expression of aphid protein isoforms derived from the competent parental lineage aligned with the virus transmission phenotype with high precision. Thus, these isoforms are candidate biomarkers for CYDV-RPV transmission in S. graminum. Our combined genetic and DIGE approach also made it possible to predict where several of the proteins may be expressed in refractive aphids with different barriers to transmission. Twelve proteins were predicted to act in the hindgut of the aphid

  9. Cloud Properties Derived from Surface-Based Near-Infrared Spectral Transmission

    NASA Technical Reports Server (NTRS)

    Pilewskie, Peter; Twomey, S.; Gore, Warren J. Y. (Technical Monitor)

    1996-01-01

    Surface based near-infrared cloud spectral transmission measurements from a recent precipitation/cloud physics field study are used to determine cloud physical properties and relate them to other remote sensing and in situ measurements. Asymptotic formulae provide an effective means of closely approximating the qualitative and quantitative behavior of transmission computed by more laborious detailed methods. Relationships derived from asymptotic formulae are applied to measured transmission spectra to test objectively the internal consistency of data sets acquired during the field program and they confirmed the quality of the measurements. These relationships appear to be very useful in themselves, not merely as a quality control measure, but also a potentially valuable remote-sensing technique in its own right. Additional benefits from this analysis have been the separation of condensed water (cloud) transmission and water vapor transmission and the development of a method to derive cloud liquid water content.

  10. U isotopes distribution in the Lower Rhone River and its implication on radionuclides disequilibrium within the decay series.

    PubMed

    Zebracki, Mathilde; Cagnat, Xavier; Gairoard, Stéphanie; Cariou, Nicolas; Eyrolle-Boyer, Frédérique; Boulet, Béatrice; Antonelli, Christelle

    2017-11-01

    The large rivers are main pathways for the delivery of suspended sediments into coastal environments, affecting the biogeochemical fluxes and the ecosystem functioning. The radionuclides from 238 U and 232 Th-series can be used to understand the dynamic processes affecting both catchment soil erosion and sediment delivery to oceans. Based on annual water discharge the Rhone River represents the largest river of the Mediterranean Sea. The Rhone valley also represents the largest concentration in nuclear power plants in Europe. A radioactive disequilibrium between particulate 226 Ra (p) and 238 U (p) was observed in the suspended sediment discharged by the Lower Rhone River (Eyrolle et al. 2012), and a fraction of particulate 234 Th was shown to derive from dissolved 238 U (d) (Zebracki et al. 2013). This extensive study has investigated the dissolved U isotopes distribution in the Lower Rhone River and its implication on particulate radionuclides disequilibrium within the decay series. The suspended sediment and filtered river waters were collected at low and high water discharges. During the 4-months of the study, two flood events generated by the Rhone southern tributaries were monitored. In river waters, the total U (d) concentration and U isotopes distribution were obtained through Q-ICP-MS measurements. The Lower Rhone River has displayed non-conservative U-behavior, and the variations in U (d) concentration between southern tributaries were related to the differences in bedrock lithology. The artificially occurring 236 U was detected in the Rhone River at low water discharges, and was attributed to the liquid releases from nuclear industries located along the river. The ( 235 U/ 238 U) (d) activity ratio (=AR) in river waters was representative of the 235 U natural abundance on Earth. The ( 226 Ra/ 238 U) (p) AR in suspended sediment has indicated a radioactive disequilibrium (average 1.3 ± 0.1). The excess of 234 Th in suspended sediment =( 234 Th xs

  11. The linkage disequilibrium pattern of the angiotensin converting enzyme gene in Arabic and Asian population groups.

    PubMed

    Kharrat, Najla; Abdelmouleh, Wafa; Abdelhedi, Rania; Alfadhli, Suad; Rebai, Ahmed

    2012-01-01

    DNA variations within the Angiotensin-Converting Enzyme (ACE) gene have been shown to be involved in the aetiology of several common diseases and the therapeutic response. This study reports a comparison of haplotype analysis of five SNPs in the ACE gene region using a sample of 100 healthy subjects derived from five different populations (Tunisian, Iranian, Kuwaiti, Bahraini and Indian). Strong linkage disequilibrium was found among all SNPs studied for all populations. Two SNPs (rs1800764 and rs4340) were identified as key SNPs for all populations. These SNPs will be valuable for future effective association studies of the ACE gene polymorphisms in Arab and Asian populations.

  12. A short purification process for quantitative isolation of PrPSc from naturally occurring and experimental transmissible spongiform encephalopathies

    PubMed Central

    Polymenidou, Magdalini; Verghese-Nikolakaki, Susan; Groschup, Martin; Chaplin, Melanie J; Stack, Mick J; Plaitakis, Andreas; Sklaviadis, Theodoros

    2002-01-01

    Background Transmissible spongiform encephalopathies (TSEs) are neurodegenerative diseases affecting both humans and animals. They are associated with post-translational conversion of the normal cellular prion protein (PrPC) into a heat- and protease-resistant abnormal isoform (PrPSc). Detection of PrPSc in individuals is widely utilized for the diagnosis of prion diseases. Methods TSE brain tissue samples have been processed in order to quantitatively isolate PrPSc. The protocol includes an initial homogenization, digestion with proteinase K and salt precipitation. Results Here we show that over 97 percent of the PrPSc present can be precipitated from infected brain material using this simple salting-out procedure for proteins. No chemically harsh conditions are used during the process in order to conserve the native quality of the isolated protein. Conclusion The resulting PrPSc-enriched preparation should provide a suitable substrate for analyzing the structure of the prion agent and for scavenging for other molecules with which it may associate. In comparison with most methods that exist today, the one described in this study is rapid, cost-effective and does not demand expensive laboratory equipment. PMID:12370086

  13. Measuring and partitioning the high-order linkage disequilibrium by multiple order Markov chains.

    PubMed

    Kim, Yunjung; Feng, Sheng; Zeng, Zhao-Bang

    2008-05-01

    A map of the background levels of disequilibrium between nearby markers can be useful for association mapping studies. In order to assess the background levels of linkage disequilibrium (LD), multilocus LD measures are more advantageous than pairwise LD measures because the combined analysis of pairwise LD measures is not adequate to detect simultaneous allele associations among multiple markers. Various multilocus LD measures based on haplotypes have been proposed. However, most of these measures provide a single index of association among multiple markers and does not reveal the complex patterns and different levels of LD structure. In this paper, we employ non-homogeneous, multiple order Markov Chain models as a statistical framework to measure and partition the LD among multiple markers into components due to different orders of marker associations. Using a sliding window of multiple markers on phased haplotype data, we compute corresponding likelihoods for different Markov Chain (MC) orders in each window. The log-likelihood difference between the lowest MC order model (MC0) and the highest MC order model in each window is used as a measure of the total LD or the overall deviation from the gametic equilibrium for the window. Then, we partition the total LD into lower order disequilibria and estimate the effects from two-, three-, and higher order disequilibria. The relationship between different orders of LD and the log-likelihood difference involving two different orders of MC models are explored. By applying our method to the phased haplotype data in the ENCODE regions of the HapMap project, we are able to identify high/low multilocus LD regions. Our results reveal that the most LD in the HapMap data is attributed to the LD between adjacent pairs of markers across the whole region. LD between adjacent pairs of markers appears to be more significant in high multilocus LD regions than in low multilocus LD regions. We also find that as the multilocus total LD

  14. Transmission and storage of medical images with patient information.

    PubMed

    Acharya U, Rajendra; Subbanna Bhat, P; Kumar, Sathish; Min, Lim Choo

    2003-07-01

    Digital watermarking is a technique of hiding specific identification data for copyright authentication. This technique is adapted here for interleaving patient information with medical images, to reduce storage and transmission overheads. The text data is encrypted before interleaving with images to ensure greater security. The graphical signals are interleaved with the image. Two types of error control-coding techniques are proposed to enhance reliability of transmission and storage of medical images interleaved with patient information. Transmission and storage scenarios are simulated with and without error control coding and a qualitative as well as quantitative interpretation of the reliability enhancement resulting from the use of various commonly used error control codes such as repetitive, and (7,4) Hamming code is provided.

  15. Bovine meat versus pork in Toxoplasma gondii transmission in Italy: A quantitative risk assessment model.

    PubMed

    Belluco, Simone; Patuzzi, Ilaria; Ricci, Antonia

    2018-03-23

    Toxoplasma gondii is a widespread zoonotic parasite with a high seroprevalence in the human population and the ability to infect almost all warm blooded animals. Humans can acquire toxoplasmosis from different transmission routes and food plays a critical role. Within the food category, meat is of utmost importance, as it may contain bradyzoites inside tissue cysts, which can potentially cause infection after ingestion if parasites are not inactivated through freezing or cooking before consumption. In Italy, the most commonly consumed meat-producing animal species are bovines and pigs. However, T. gondii prevalence and consumption habits for meat of these animal species are very different. There is debate within the scientific community concerning which of these animal species is the main source of meat-derived human toxoplasmosis. The aim of this work was to build a quantitative risk assessment model to estimate the yearly probability of acquiring toxoplasmosis infection due to consumption of bovine meat and pork (excluding cured products) in Italy, taking into account the different eating habits. The model was fitted with data obtained from the literature regarding: bradyzoite concentrations, portion size, dose-response relation, prevalence of T. gondii in bovines and swine, meat consumption and meat preparation habits. Alternative handling scenarios were considered. The model estimated the risk per year of acquiring T. gondii infection in Italy from bovine and swine meat to be 0.034% and 0.019%, respectively. Results suggest that, due to existing eating habits, bovine meat can be a not negligible source of toxoplasmosis in Italy. Copyright © 2017. Published by Elsevier B.V.

  16. Mapping the Rust Resistant Loci MXC3 and MER in P. trichocarpa and Assessing the Intermarker Linkage Disequilibrium in MXC3 Region

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

    Yin, Tongming; Difazio, Stephen P.; Gunter, Lee E

    In an attempt to elucidate the molecular mechanisms of Melampsora rust resistance in Populus trichocarpa, we have mapped two resistance loci, MXC3 and MER, and intensively characterized the flanking genomic sequence for the MXC3 locus and the level of linkage disequilibrium (LD) in natural populations. We used an interspecific backcross pedigree and a genetic map that was highly saturated with AFLP and SSR markers, and assembled shotgun-sequence data in the region containing markers linked to MXC3. The two loci were mapped to different linkage groups. Linkage disequilibrium for MXC3 was confined to two closely linked regions spanning 34 and 16more » kb, respectively. The MXC3 region also contained six disease-resistance candidate genes. The MER and MXC3 loci are clearly distinct, and may have different mechanisms of resistance, as different classes of putative resistance genes were present near each locus. The suppressed recombination previously observed in the MXC3 region was possibly caused by extensive hemizygous rearrangements confined to the original parent tree. The relatively low observed LD may facilitate association studies using candidate genes for rust resistance, but will probably inhibit marker-aided selection.« less

  17. Atmospheric Dynamics and Disequilibrium CO/CH4 Chemistry in the Atmosphere of the Transiting Planet HD 209458b

    NASA Astrophysics Data System (ADS)

    Cooper, C. S.; Showman, A. P.

    2005-08-01

    Chemical equilibrium considerations predict that carbon will be present in the atmosphere of HD 209458b as either CO or CH4. Assuming a solar abundance distribution of elements, the concentrations of these species are controlled by temperature and pressure only. In cooler regions, however, vigorous mass transport can occur on time scales shorter than the time scale for interconversion between CO and CH4. This results in excess [CO]/[CH4] relative to the concentrations attained in chemical equilibrium. In this work, we adapt the model of HD 209458b's meteorology used in Cooper & Showman (2005) to treat the disequilibrium chemistry of carbon. Cooper & Showman (2005) show that high-speed winds ( ˜ 4 km s-1) and large temperature contrasts ( ˜ 500 K) are plausible near the photosphere. We model CO and CH4 as passive tracers; i.e., they follow but do not disturb the fluid dynamics of the system. Our simulations will yield maps of the distribution of CO and CH4 to help guide efforts to detect the presence of carbon on this planet. Though CO was not detected on HD 209458b (Deming et al. 2005) by transmission spectroscopy, its presence in the atmosphere cannot be ruled out. For example, CO could be present over much of the dayside hemisphere but depleted near the limbs. The distribution of CO in the atmosphere is diagnostic of temperature at the pressure levels probed by various CO absorption features (Bézard & Lellouch 2002). A positive CO detection would also rule out the hypothesis that the ratio C/O > 1 on this extrasolar planet (e.g., Fortney et al. 2005). This research is supported by NSF grant AST-0307664 and NASA GSRP NGT5-50462.

  18. A Simple Configuration for Quantitative Phase Contrast Microscopy of Transmissible Samples

    NASA Astrophysics Data System (ADS)

    Sengupta, Chandan; Dasgupta, Koustav; Bhattacharya, K.

    Phase microscopy attempts to visualize and quantify the phase distribution of samples which are otherwise invisible under microscope without the use of stains. The two principal approaches to phase microscopy are essentially those of Fourier plane modulation and interferometric techniques. Although the former, first proposed by Zernike, had been the harbinger of phase microscopy, it was the latter that allowed for quantitative evaluation of phase samples. However interferometric techniques are fraught with associated problems such as complicated setup involving mirrors and beam-splitters, the need for a matched objective in the reference arm and also the need for vibration isolation. The present work proposes a single element cube beam-splitter (CBS) interferometer combined with a microscope objective (MO) for interference microscopy. Because of the monolithic nature of the interferometer, the system is almost insensitive to vibrations and relatively simple to align. It will be shown that phase shifting properties may also be introduced by suitable and proper use of polarizing devices. Initial results showing the quantitative three dimensional phase profiles of simulated and actual biological specimens are presented.

  19. Nucleotide diversity and linkage disequilibrium in wild avocado (Persea americana Mill.).

    PubMed

    Chen, Haofeng; Morrell, Peter L; de la Cruz, Marlene; Clegg, Michael T

    2008-01-01

    Resequencing studies provide the ultimate resolution of genetic diversity because they identify all mutations in a gene that are present within the sampled individuals. We report a resequencing study of Persea americana, a subtropical tree species native to Meso- and Central America and the progenitor of cultivated avocado. The sample includes 21 wild accessions from Mexico, Costa Rica, Ecuador, and the Dominican Republic. Estimated levels of nucleotide polymorphism and linkage disequilibrium (LD) are obtained from fully resolved haplotype data from 4 nuclear loci that span 5960 nucleotide sites. Results show that, although avocado is a subtropical tree crop and a predominantly outcrossing plant, the overall level of genetic variation is not exceptionally high (nucleotide diversity at silent sites, pi(sil) = 0.0102) compared with available estimates from temperate plant species. Intralocus LD decays rapidly to half the initial value within about 1 kb. Estimates of recombination rate (based on the sequence data) show that the rate is not exceptionally high when compared with annual plants such as wild barley or maize. Interlocus LD is significant owing to substantial population structure induced by mixing of the 3 botanical races of avocado.

  20. Linkage disequilibrium network analysis (LDna) gives a global view of chromosomal inversions, local adaptation and geographic structure.

    PubMed

    Kemppainen, Petri; Knight, Christopher G; Sarma, Devojit K; Hlaing, Thaung; Prakash, Anil; Maung Maung, Yan Naung; Somboon, Pradya; Mahanta, Jagadish; Walton, Catherine

    2015-09-01

    Recent advances in sequencing allow population-genomic data to be generated for virtually any species. However, approaches to analyse such data lag behind the ability to generate it, particularly in nonmodel species. Linkage disequilibrium (LD, the nonrandom association of alleles from different loci) is a highly sensitive indicator of many evolutionary phenomena including chromosomal inversions, local adaptation and geographical structure. Here, we present linkage disequilibrium network analysis (LDna), which accesses information on LD shared between multiple loci genomewide. In LD networks, vertices represent loci, and connections between vertices represent the LD between them. We analysed such networks in two test cases: a new restriction-site-associated DNA sequence (RAD-seq) data set for Anopheles baimaii, a Southeast Asian malaria vector; and a well-characterized single nucleotide polymorphism (SNP) data set from 21 three-spined stickleback individuals. In each case, we readily identified five distinct LD network clusters (single-outlier clusters, SOCs), each comprising many loci connected by high LD. In A. baimaii, further population-genetic analyses supported the inference that each SOC corresponds to a large inversion, consistent with previous cytological studies. For sticklebacks, we inferred that each SOC was associated with a distinct evolutionary phenomenon: two chromosomal inversions, local adaptation, population-demographic history and geographic structure. LDna is thus a useful exploratory tool, able to give a global overview of LD associated with diverse evolutionary phenomena and identify loci potentially involved. LDna does not require a linkage map or reference genome, so it is applicable to any population-genomic data set, making it especially valuable for nonmodel species. © 2015 The Authors. Molecular Ecology Resources Published by John Wiley & Sons Ltd.

  1. Detecting introgressive hybridization between free-ranging domestic dogs and wild wolves (Canis lupus) by admixture linkage disequilibrium analysis.

    PubMed

    Verardi, A; Lucchini, V; Randi, E

    2006-09-01

    Occasional crossbreeding between free-ranging domestic dogs and wild wolves (Canis lupus) has been detected in some European countries by mitochondrial DNA sequencing and genotyping unlinked microsatellite loci. Maternal and unlinked genomic markers, however, might underestimate the extent of introgressive hybridization, and their impacts on the preservation of wild wolf gene pools. In this study, we genotyped 220 presumed Italian wolves, 85 dogs and 7 known hybrids at 16 microsatellites belonging to four different linkage groups (plus four unlinked microsatellites). Population clustering and individual assignments were performed using a Bayesian procedure implemented in structure 2.1, which models the gametic disequilibrium arising between linked loci during admixtures, aiming to trace hybridization events further back in time and infer the population of origin of chromosomal blocks. Results indicate that (i) linkage disequilibrium was higher in wolves than in dogs; (ii) 11 out of 220 wolves (5.0%) were likely admixed, a proportion that is significantly higher than one admixed genotype in 107 wolves found previously in a study using unlinked markers; (iii) posterior maximum-likelihood estimates of the recombination parameter r revealed that introgression in Italian wolves is not recent, but could have continued for the last 70 (+/- 20) generations, corresponding to approximately 140-210 years. Bayesian clustering showed that, despite some admixture, wolf and dog gene pools remain sharply distinct (the average proportions of membership to wolf and dog clusters were Q(w) = 0.95 and Q(d) = 0.98, respectively), suggesting that hybridization was not frequent, and that introgression in nature is counteracted by behavioural or selective constraints.

  2. Genome scan for linkage to asthma using a linkage disequilibrium-lod score test.

    PubMed

    Jiang, Y; Slager, S L; Huang, J

    2001-01-01

    We report a genome-wide linkage study of asthma on the German and Collaborative Study on the Genetics of Asthma (CSGA) data. Using a combined linkage and linkage disequilibrium test and the nonparametric linkage score, we identified 13 markers from the German data, 1 marker from the African American (CSGA) data, and 7 markers from the Caucasian (CSGA) data in which the p-values ranged between 0.0001 and 0.0100. From our analysis and taking into account previous published linkage studies of asthma, we suggest that three regions in chromosome 5 (around D5S418, D5S644, and D5S422), one region in chromosome 6 (around three neighboring markers D6S1281, D6S291, and D6S1019), one region in chromosome 11 (around D11S2362), and two regions in chromosome 12 (around D12S351 and D12S324) especially merit further investigation.

  3. Climate change and dengue: a critical and systematic review of quantitative modelling approaches

    PubMed Central

    2014-01-01

    Background Many studies have found associations between climatic conditions and dengue transmission. However, there is a debate about the future impacts of climate change on dengue transmission. This paper reviewed epidemiological evidence on the relationship between climate and dengue with a focus on quantitative methods for assessing the potential impacts of climate change on global dengue transmission. Methods A literature search was conducted in October 2012, using the electronic databases PubMed, Scopus, ScienceDirect, ProQuest, and Web of Science. The search focused on peer-reviewed journal articles published in English from January 1991 through October 2012. Results Sixteen studies met the inclusion criteria and most studies showed that the transmission of dengue is highly sensitive to climatic conditions, especially temperature, rainfall and relative humidity. Studies on the potential impacts of climate change on dengue indicate increased climatic suitability for transmission and an expansion of the geographic regions at risk during this century. A variety of quantitative modelling approaches were used in the studies. Several key methodological issues and current knowledge gaps were identified through this review. Conclusions It is important to assemble spatio-temporal patterns of dengue transmission compatible with long-term data on climate and other socio-ecological changes and this would advance projections of dengue risks associated with climate change. PMID:24669859

  4. Generalized disequilibrium test for association in qualitative traits incorporating imprinting effects based on extended pedigrees.

    PubMed

    Li, Jian-Long; Wang, Peng; Fung, Wing Kam; Zhou, Ji-Yuan

    2017-10-16

    For dichotomous traits, the generalized disequilibrium test with the moment estimate of the variance (GDT-ME) is a powerful family-based association method. Genomic imprinting is an important epigenetic phenomenon and currently, there has been increasing interest of incorporating imprinting to improve the test power of association analysis. However, GDT-ME does not take imprinting effects into account, and it has not been investigated whether it can be used for association analysis when the effects indeed exist. In this article, based on a novel decomposition of the genotype score according to the paternal or maternal source of the allele, we propose the generalized disequilibrium test with imprinting (GDTI) for complete pedigrees without any missing genotypes. Then, we extend GDTI and GDT-ME to accommodate incomplete pedigrees with some pedigrees having missing genotypes, by using a Monte Carlo (MC) sampling and estimation scheme to infer missing genotypes given available genotypes in each pedigree, denoted by MCGDTI and MCGDT-ME, respectively. The proposed GDTI and MCGDTI methods evaluate the differences of the paternal as well as maternal allele scores for all discordant relative pairs in a pedigree, including beyond first-degree relative pairs. Advantages of the proposed GDTI and MCGDTI test statistics over existing methods are demonstrated by simulation studies under various simulation settings and by application to the rheumatoid arthritis dataset. Simulation results show that the proposed tests control the size well under the null hypothesis of no association, and outperform the existing methods under various imprinting effect models. The existing GDT-ME and the proposed MCGDT-ME can be used to test for association even when imprinting effects exist. For the application to the rheumatoid arthritis data, compared to the existing methods, MCGDTI identifies more loci statistically significantly associated with the disease. Under complete and incomplete

  5. Genetics coupled to quantitative intact proteomics links heritable aphid and endosymbiont protein isoform expression to polerovirus transmission

    USDA-ARS?s Scientific Manuscript database

    Yellow dwarf viruses in the family Luteoviridae, such as Cereal yellow dwarf virus-RPV (CYDV-RPV), are vectored by aphids and cause the most economically important virus disease of cereal crops worldwide. The identification of aphid proteins mediating virus transmission will better define transmiss...

  6. Quantitative analysis of transmittance and photoluminescence using a low cost apparatus

    NASA Astrophysics Data System (ADS)

    Onorato, P.; Malgieri, M.; De Ambrosis, A.

    2016-01-01

    We show how a low cost spectrometer, based on the use of inexpensive diffraction transmission gratings coupled with a commercial digital photo camera or a cellphone, can be assembled and employed to obtain quantitative spectra of different sources. In particular, we discuss its use in studying the spectra of fluorescent colored ink, used in highlighting pens, for which the transmission band and the emission peaks are measured and related to the ink color.

  7. Estimating malaria transmission from humans to mosquitoes in a noisy landscape.

    PubMed

    Reiner, Robert C; Guerra, Carlos; Donnelly, Martin J; Bousema, Teun; Drakeley, Chris; Smith, David L

    2015-10-06

    A basic quantitative understanding of malaria transmission requires measuring the probability a mosquito becomes infected after feeding on a human. Parasite prevalence in mosquitoes is highly age-dependent, and the unknown age-structure of fluctuating mosquito populations impedes estimation. Here, we simulate mosquito infection dynamics, where mosquito recruitment is modelled seasonally with fractional Brownian noise, and we develop methods for estimating mosquito infection rates. We find that noise introduces bias, but the magnitude of the bias depends on the 'colour' of the noise. Some of these problems can be overcome by increasing the sampling frequency, but estimates of transmission rates (and estimated reductions in transmission) are most accurate and precise if they combine parity, oocyst rates and sporozoite rates. These studies provide a basis for evaluating the adequacy of various entomological sampling procedures for measuring malaria parasite transmission from humans to mosquitoes and for evaluating the direct transmission-blocking effects of a vaccine. © 2015 The Authors.

  8. Estimating malaria transmission from humans to mosquitoes in a noisy landscape

    PubMed Central

    Reiner, Robert C.; Guerra, Carlos; Donnelly, Martin J.; Bousema, Teun; Drakeley, Chris; Smith, David L.

    2015-01-01

    A basic quantitative understanding of malaria transmission requires measuring the probability a mosquito becomes infected after feeding on a human. Parasite prevalence in mosquitoes is highly age-dependent, and the unknown age-structure of fluctuating mosquito populations impedes estimation. Here, we simulate mosquito infection dynamics, where mosquito recruitment is modelled seasonally with fractional Brownian noise, and we develop methods for estimating mosquito infection rates. We find that noise introduces bias, but the magnitude of the bias depends on the ‘colour' of the noise. Some of these problems can be overcome by increasing the sampling frequency, but estimates of transmission rates (and estimated reductions in transmission) are most accurate and precise if they combine parity, oocyst rates and sporozoite rates. These studies provide a basis for evaluating the adequacy of various entomological sampling procedures for measuring malaria parasite transmission from humans to mosquitoes and for evaluating the direct transmission-blocking effects of a vaccine. PMID:26400195

  9. Localization of an ataxia-telangiectasia gene by linkage disequilibrium in the Costa Rican population

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

    Uhrhammer, N.A.; Lange, E.; Gatti, R.A.

    1994-09-01

    Linkage disequilibrium (LD) was studied in 27 Costa Rican families with ataxia-telangiectasia. Previous studies indicate that the ATA and ATC gene(s) are on chromosome 11q22.3, between D11S1819 and D11S927. We studied the ordered loci D11-S1816, S1817, S1343, S1819, S384, S535, S1295, S1818, S927, S1300 and S1004 by PCR and Southern blotting. We noted moderate LD at the more distant markers S1816, S1300, and S1004. LD was higher at markers closer to A-T, and also where A-T was associated with rarer alleles. This broad region of disequilibrium did not by itself contribute to further localization of the A-T gene(s). We analyzedmore » 54 affected chromosomal haplotypes. The most common haplotype occurred 34 times, including some that had recombined outside the known A-T region. Other haplotypes occurred seven times, five times, two occurred twice, and the four remaining were unique. The most common haplotype had `broken` at S927 in five different patients, placing A-T proximal to this marker. We looked for recombination events in 15 of the families to further localize A-T. We observed one family with a recombination event placing A-T distal to S1819. A second family appears to either not link to 11q22.3 or to have a double-crossover between the markers S384 and S927; two affected sibs share haplotypes for the entire region studied, and a normal sib shared the same two haplotypes. Since all or part of this A-T haplotype occurs in 32 other, unrelated, Costa Rican patients, we anticipate a double-crossover in the 1600 kb between the informative flanking markers. All other families show segregation patterns consistent with placing A-T at 11q22.3. These results demonstrate that the major A-T gene in the Costa Rican population is located between S1819 and S927 at 11q22.3.« less

  10. Force transmissibility versus displacement transmissibility

    NASA Astrophysics Data System (ADS)

    Lage, Y. E.; Neves, M. M.; Maia, N. M. M.; Tcherniak, D.

    2014-10-01

    It is well-known that when a single-degree-of-freedom (sdof) system is excited by a continuous motion of the foundation, the force transmissibility, relating the force transmitted to the foundation to the applied force, equals the displacement transmissibility. Recent developments in the generalization of the transmissibility to multiple-degree-of-freedom (mdof) systems have shown that similar simple and direct relations between both types of transmissibility do not appear naturally from the definitions, as happens in the sdof case. In this paper, the authors present their studies on the conditions under which it is possible to establish a relation between force transmissibility and displacement transmissibility for mdof systems. As far as the authors are aware, such a relation is not currently found in the literature, which is justified by being based on recent developments in the transmissibility concept for mdof systems. Indeed, it does not appear naturally, but the authors observed that the needed link is present when the displacement transmissibility is obtained between the same coordinates where the applied and reaction forces are considered in the force transmissibility case; this implies that the boundary conditions are not exactly the same and instead follow some rules. This work presents a formal derivation of the explicit relation between the force and displacement transmissibilities for mdof systems, and discusses its potential and limitations. The authors show that it is possible to obtain the displacement transmissibility from measured forces, and the force transmissibility from measured displacements, opening new perspectives, for example, in the identification of applied or transmitted forces. With this novel relation, it becomes possible, for example, to estimate the force transmissibility matrix with the structure off its supports, in free boundary conditions, and without measuring the forces. As far as force identification is concerned, this

  11. Characteristics of the transmission of autoregressive sub-patterns in financial time series

    NASA Astrophysics Data System (ADS)

    Gao, Xiangyun; An, Haizhong; Fang, Wei; Huang, Xuan; Li, Huajiao; Zhong, Weiqiong

    2014-09-01

    There are many types of autoregressive patterns in financial time series, and they form a transmission process. Here, we define autoregressive patterns quantitatively through an econometrical regression model. We present a computational algorithm that sets the autoregressive patterns as nodes and transmissions between patterns as edges, and then converts the transmission process of autoregressive patterns in a time series into a network. We utilised daily Shanghai (securities) composite index time series to study the transmission characteristics of autoregressive patterns. We found statistically significant evidence that the financial market is not random and that there are similar characteristics between parts and whole time series. A few types of autoregressive sub-patterns and transmission patterns drive the oscillations of the financial market. A clustering effect on fluctuations appears in the transmission process, and certain non-major autoregressive sub-patterns have high media capabilities in the financial time series. Different stock indexes exhibit similar characteristics in the transmission of fluctuation information. This work not only proposes a distinctive perspective for analysing financial time series but also provides important information for investors.

  12. Characteristics of the transmission of autoregressive sub-patterns in financial time series

    PubMed Central

    Gao, Xiangyun; An, Haizhong; Fang, Wei; Huang, Xuan; Li, Huajiao; Zhong, Weiqiong

    2014-01-01

    There are many types of autoregressive patterns in financial time series, and they form a transmission process. Here, we define autoregressive patterns quantitatively through an econometrical regression model. We present a computational algorithm that sets the autoregressive patterns as nodes and transmissions between patterns as edges, and then converts the transmission process of autoregressive patterns in a time series into a network. We utilised daily Shanghai (securities) composite index time series to study the transmission characteristics of autoregressive patterns. We found statistically significant evidence that the financial market is not random and that there are similar characteristics between parts and whole time series. A few types of autoregressive sub-patterns and transmission patterns drive the oscillations of the financial market. A clustering effect on fluctuations appears in the transmission process, and certain non-major autoregressive sub-patterns have high media capabilities in the financial time series. Different stock indexes exhibit similar characteristics in the transmission of fluctuation information. This work not only proposes a distinctive perspective for analysing financial time series but also provides important information for investors. PMID:25189200

  13. Genetic Structure, Linkage Disequilibrium and Signature of Selection in Sorghum: Lessons from Physically Anchored DArT Markers

    PubMed Central

    Bouchet, Sophie; Pot, David; Deu, Monique; Rami, Jean-François; Billot, Claire; Perrier, Xavier; Rivallan, Ronan; Gardes, Laëtitia; Xia, Ling; Wenzl, Peter; Kilian, Andrzej; Glaszmann, Jean-Christophe

    2012-01-01

    Population structure, extent of linkage disequilibrium (LD) as well as signatures of selection were investigated in sorghum using a core sample representative of worldwide diversity. A total of 177 accessions were genotyped with 1122 informative physically anchored DArT markers. The properties of DArTs to describe sorghum genetic structure were compared to those of SSRs and of previously published RFLP markers. Model-based (STRUCTURE software) and Neighbor-Joining diversity analyses led to the identification of 6 groups and confirmed previous evolutionary hypotheses. Results were globally consistent between the different marker systems. However, DArTs appeared more robust in terms of data resolution and bayesian group assignment. Whole genome linkage disequilibrium as measured by mean r2 decreased from 0.18 (between 0 to 10 kb) to 0.03 (between 100 kb to 1 Mb), stabilizing at 0.03 after 1 Mb. Effects on LD estimations of sample size and genetic structure were tested using i. random sampling, ii. the Maximum Length SubTree algorithm (MLST), and iii. structure groups. Optimizing population composition by the MLST reduced the biases in small samples and seemed to be an efficient way of selecting samples to make the best use of LD as a genome mapping approach in structured populations. These results also suggested that more than 100,000 markers may be required to perform genome-wide association studies in collections covering worldwide sorghum diversity. Analysis of DArT markers differentiation between the identified genetic groups pointed out outlier loci potentially linked to genes controlling traits of interest, including disease resistance genes for which evidence of selection had already been reported. In addition, evidence of selection near a homologous locus of FAR1 concurred with sorghum phenotypic diversity for sensitivity to photoperiod. PMID:22428056

  14. Genetic structure, linkage disequilibrium and signature of selection in Sorghum: lessons from physically anchored DArT markers.

    PubMed

    Bouchet, Sophie; Pot, David; Deu, Monique; Rami, Jean-François; Billot, Claire; Perrier, Xavier; Rivallan, Ronan; Gardes, Laëtitia; Xia, Ling; Wenzl, Peter; Kilian, Andrzej; Glaszmann, Jean-Christophe

    2012-01-01

    Population structure, extent of linkage disequilibrium (LD) as well as signatures of selection were investigated in sorghum using a core sample representative of worldwide diversity. A total of 177 accessions were genotyped with 1122 informative physically anchored DArT markers. The properties of DArTs to describe sorghum genetic structure were compared to those of SSRs and of previously published RFLP markers. Model-based (STRUCTURE software) and Neighbor-Joining diversity analyses led to the identification of 6 groups and confirmed previous evolutionary hypotheses. Results were globally consistent between the different marker systems. However, DArTs appeared more robust in terms of data resolution and bayesian group assignment. Whole genome linkage disequilibrium as measured by mean r(2) decreased from 0.18 (between 0 to 10 kb) to 0.03 (between 100 kb to 1 Mb), stabilizing at 0.03 after 1 Mb. Effects on LD estimations of sample size and genetic structure were tested using i. random sampling, ii. the Maximum Length SubTree algorithm (MLST), and iii. structure groups. Optimizing population composition by the MLST reduced the biases in small samples and seemed to be an efficient way of selecting samples to make the best use of LD as a genome mapping approach in structured populations. These results also suggested that more than 100,000 markers may be required to perform genome-wide association studies in collections covering worldwide sorghum diversity. Analysis of DArT markers differentiation between the identified genetic groups pointed out outlier loci potentially linked to genes controlling traits of interest, including disease resistance genes for which evidence of selection had already been reported. In addition, evidence of selection near a homologous locus of FAR1 concurred with sorghum phenotypic diversity for sensitivity to photoperiod.

  15. Potential effect of climate change on malaria transmission in Africa.

    PubMed

    Tanser, Frank C; Sharp, Brian; le Sueur, David

    2003-11-29

    Climate change is likely to affect transmission of vector-borne diseases such as malaria. We quantitatively estimated current malaria exposure and assessed the potential effect of projected climate scenarios on malaria transmission. We produced a spatiotemporally validated (against 3791 parasite surveys) model of Plasmodium falciparum malaria transmission in Africa. Using different climate scenarios from the Hadley Centre global climate model (HAD CM3) climate experiments, we projected the potential effect of climate change on transmission patterns. Our model showed sensitivity and specificity of 63% and 96%, respectively (within 1 month temporal accuracy), when compared with the parasite surveys. We estimate that on average there are 3.1 billion person-months of exposure (445 million people exposed) in Africa per year. The projected scenarios would estimate a 5-7% potential increase (mainly altitudinal) in malaria distribution with surprisingly little increase in the latitudinal extents of the disease by 2100. Of the overall potential increase (although transmission will decrease in some countries) of 16-28% in person-months of exposure (assuming a constant population), a large proportion will be seen in areas of existing transmission. The effect of projected climate change indicates that a prolonged transmission season is as important as geographical expansion in correct assessment of the effect of changes in transmission patterns. Our model constitutes a valid baseline against which climate scenarios can be assessed and interventions planned.

  16. Temperature and precipitation records from stalagmites grown under disequilibrium conditions: A model approach.

    NASA Astrophysics Data System (ADS)

    Mühlinghaus, C.; Scholz, D.; Mangini, A.

    2009-04-01

    To reconstruct past variations in Earth's climate, a variety of climate archives are studied. During the last decades stalagmites came into focus due to their long, continuous growth and absolute dating techniques. In this study a numerical model was developed, which calculates variations in temperature and precipitation during the growth period of stalagmites grown under isotopic disequilibrium conditions using the isotope profiles both along the growth axis and individual growth layers as well as the growth depth relation. The model is based on the inversion and combination of existing models (Dreybrodt 1999, Kaufmann et al. 2004, Mühlinghaus et al. 2007, Scholz et al. 2008, Mühlinghaus et al. 2008b) and incorporates important parameters describing the cave and the overlying soil. Beside the dependence on temperature and water supply it depends on the isotopic composition of the drip water, the pCO2 pressure of the soil and the cave atmosphere as well as on the mixing coefficient, which describes mixing between the impinging drop and the existing solution layer. To determine the characteristics of temperature and precipitation, in a first step all other parameters are assumed to remain constant over the whole growth period to simplify calculations. This allows to run the model with only two input variables: the isotopic composition ^13C of the drip water and a temperature information at any point of time during the growth period of the stalagmite (e.g. the recent cave temperature). All other parameters are determined by the model. The CSM (Combined Stalagmite Model, Mühlinghaus et al. 2008a) was applied to three stalagmites from the Marcelo Arévalo cave in Southern Patagonia, Chile (Schimpf 2005, Kilian et al. 2006, Schimpf et al. in prep). These stalagmites grew in a small cave next to each other during the last 4500 years. However, their isotopic profiles along the growth axis show different kinetic influences. Despite these conditions, the temperature

  17. A TEM study of disequilibrium plagioclase breakdown at high pressure: the role of infiltrating fluid

    NASA Astrophysics Data System (ADS)

    Wayte, Gavin J.; Worden, Richard H.; Rubie, David C.; Droop, Giles T. R.

    1989-04-01

    High-pressure metamorphism (˜600° C, ˜20 kbar) of the Allalin Gabbro (Western Alps) resulted in the breakdown of plagioclase (˜An63) to fine-grained zoisite, jadeite, kyanite and quartz. In rare cases this reaction failed to reach completion. The resulting textures of partial reaction have been studied by transmission and analytical electron microscopy. In localised regions of a plagioclase crystal where the extent of reaction is <10%, only zoisite developed and the orientation relationship 1 410_2004_Article_BF00372216_TeX2GIFE1.gif left( {100} right)_{{text{Zo}}} //left( {101} right)_{{text{P1}}} and 1 410_2004_Article_BF00372216_TeX2GIFE2.gif left( {012} right)_{{text{Zo}}} //left( {010} right)_{{text{P1}}} is frequently present. In regions where 10 50% of plagioclase has transformed, the reaction plagioclase+H2O→zoisite+kyanite+quartz +(NaSiCa-1Al-1)pl has occurred. The systematic orientation relationship between plagioclase and zoisite is absent at ≥50% transformation. Complete breakdown of plagioclase occurred in localized micron-scale domains by the reaction plagioclase+H2O→zoisite+jadeite+kyanite+quartz and the reaction products are variably orientated with respect to each other. Incomplete reaction, together with the concentration of reaction products around cracks in original plagioclase grains, suggests that extent of reaction was controlled primarily by the availability of H2O. The textural observations are interpreted in terms of two possible disequilibrium reaction models. (1) Plagioclase persists metastably with its original igneous composition to a pressure > 17 kbar at 600° C. Reaction to the equilibrium assemblage then develops adjacent to cracks in response to the presence of aqueous fluid. At intracrystalline sites, only partial reaction occurs because Jadeite, and sometimes kyanite and quartz, fail to nucleate for kinetic reasons. (2) Localized regions of a plagioclase crystal partially equilibrate at several stages during the

  18. Quantitative and histological assessment of maternal-fetal transmission of Trypanosoma cruzi in guinea pigs: An experimental model of congenital Chagas disease

    PubMed Central

    Torres-Vargas, Jatziri; Jiménez-Coello, Matilde; Guzmán-Marín, Eugenia; Acosta-Viana, Karla Y.; Yadon, Zaida E.; Gutiérrez-Blanco, Eduardo; Guillermo-Cordero, José Leonardo

    2018-01-01

    Objective We evaluated the effect of Trypanosoma cruzi infection on fertility, gestation outcome, and maternal-fetal transmission in guinea pigs (Cavia porcellus). Methods Animals were infected with T. cruzi H4 strain (TcI lineage) before gestation (IBG) or during gestation (IDG). Tissue and sera samples of dams and fetuses were obtained near parturition. Results All IBG and IDG dams were seropositive by two tests, and exhibited blood parasite load of 1.62±2.2 and 50.1±62 parasites/μl, respectively, by quantitative PCR. Histological evaluation showed muscle fiber degeneration and cellular necrosis in all infected dams. Parasite nests were not detected in infected dams by histology. However, qPCR analysis detected parasites-eq/g heart tissue of 153±104.7 and 169.3±129.4 in IBG and IDG dams, respectively. All fetuses of infected dams were positive for anti-parasite IgG antibodies and tissue parasites by qPCR, but presented a low level of tissue inflammatory infiltrate. Fetuses of IDG (vs. IBG) dams exhibited higher degree of muscle fiber degeneration and cellular necrosis in the heart and skeletal tissues. The placental tissue exhibited no inflammatory lesions and amastigote nests, yet parasites-eq/g of 381.2±34.3 and 79.2±84.9 were detected in IDG and IBG placentas, respectively. Fetal development was compromised, and evidenced by a decline in weight, crow-rump length, and abdominal width in both groups. Conclusions T. cruzi TcI has a high capacity of congenital transmission even when it was inoculated at a very low dose before or during gestation. Tissue lesions, parasite load, and fetal under development provide evidence for high virulence of the parasite during pregnancy. Despite finding of high parasite burden by qPCR, placentas were protected from cellular damage. Our studies offer an experimental model to study the efficacy of vaccines and drugs against congenital transmission of T. cruzi. These results also call for T. cruzi screening in pregnant women

  19. Dynamics of Mechanical Signal Transmission through Prestressed Stress Fibers

    PubMed Central

    Hwang, Yongyun; Barakat, Abdul I.

    2012-01-01

    Transmission of mechanical stimuli through the actin cytoskeleton has been proposed as a mechanism for rapid long-distance mechanotransduction in cells; however, a quantitative understanding of the dynamics of this transmission and the physical factors governing it remains lacking. Two key features of the actin cytoskeleton are its viscoelastic nature and the presence of prestress due to actomyosin motor activity. We develop a model of mechanical signal transmission through prestressed viscoelastic actin stress fibers that directly connect the cell surface to the nucleus. The analysis considers both temporally stationary and oscillatory mechanical signals and accounts for cytosolic drag on the stress fibers. To elucidate the physical parameters that govern mechanical signal transmission, we initially focus on the highly simplified case of a single stress fiber. The results demonstrate that the dynamics of mechanical signal transmission depend on whether the applied force leads to transverse or axial motion of the stress fiber. For transverse motion, mechanical signal transmission is dominated by prestress while fiber elasticity has a negligible effect. Conversely, signal transmission for axial motion is mediated uniquely by elasticity due to the absence of a prestress restoring force. Mechanical signal transmission is significantly delayed by stress fiber material viscosity, while cytosolic damping becomes important only for longer stress fibers. Only transverse motion yields the rapid and long-distance mechanical signal transmission dynamics observed experimentally. For simple networks of stress fibers, mechanical signals are transmitted rapidly to the nucleus when the fibers are oriented largely orthogonal to the applied force, whereas the presence of fibers parallel to the applied force slows down mechanical signal transmission significantly. The present results suggest that cytoskeletal prestress mediates rapid mechanical signal transmission and allows

  20. A-TEEMTM, a new molecular fingerprinting technique: simultaneous absorbance-transmission and fluorescence excitation-emission matrix method

    NASA Astrophysics Data System (ADS)

    Quatela, Alessia; Gilmore, Adam M.; Steege Gall, Karen E.; Sandros, Marinella; Csatorday, Karoly; Siemiarczuk, Alex; (Ben Yang, Boqian; Camenen, Loïc

    2018-04-01

    We investigate the new simultaneous absorbance-transmission and fluorescence excitation-emission matrix method for rapid and effective characterization of the varying components from a mixture. The absorbance-transmission and fluorescence excitation-emission matrix method uniquely facilitates correction of fluorescence inner-filter effects to yield quantitative fluorescence spectral information that is largely independent of component concentration. This is significant because it allows one to effectively monitor quantitative component changes using multivariate methods and to generate and evaluate spectral libraries. We present the use of this novel instrument in different fields: i.e. tracking changes in complex mixtures including natural water, wine as well as monitoring stability and aggregation of hormones for biotherapeutics.

  1. Extended Linkage Disequilibrium Surrounding the Hemoglobin E Variant Due to Malarial Selection

    PubMed Central

    Ohashi, Jun ; Naka, Izumi ; Patarapotikul, Jintana ; Hananantachai, Hathairad ; Brittenham, Gary ; Looareesuwan, Sornchai ; Clark, Andrew G. ; Tokunaga, Katsushi 

    2004-01-01

    The hemoglobin E variant (HbE; β26Glu→Lys) is concentrated in parts of Southeast Asia where malaria is endemic, and HbE carrier status has been shown to confer some protection against Plasmodium falciparum malaria. To examine the effect of natural selection on the pattern of linkage disequilibrium (LD) and to infer the evolutionary history of the HbE variant, we analyzed biallelic markers surrounding the HbE variant in a Thai population. Pairwise LD analysis of HbE and 43 surrounding biallelic markers revealed LD of HbE extending beyond 100 kb, whereas no LD was observed between non-HbE variants and the same markers. The inferred haplotype network suggests a single origin of the HbE variant in the Thai population. Forward-in-time computer simulations under a variety of selection models indicate that the HbE variant arose 1,240–4,440 years ago. These results support the conjecture that the HbE mutation occurred recently, and the allele frequency has increased rapidly. Our study provides another clear demonstration that a high-resolution LD map across the human genome can detect recent variants that have been subjected to positive selection. PMID:15114532

  2. Extended linkage disequilibrium surrounding the hemoglobin E variant due to malarial selection.

    PubMed

    Ohashi, Jun; Naka, Izumi; Patarapotikul, Jintana; Hananantachai, Hathairad; Brittenham, Gary; Looareesuwan, Sornchai; Clark, Andrew G; Tokunaga, Katsushi

    2004-06-01

    The hemoglobin E variant (HbE; ( beta )26Glu-->Lys) is concentrated in parts of Southeast Asia where malaria is endemic, and HbE carrier status has been shown to confer some protection against Plasmodium falciparum malaria. To examine the effect of natural selection on the pattern of linkage disequilibrium (LD) and to infer the evolutionary history of the HbE variant, we analyzed biallelic markers surrounding the HbE variant in a Thai population. Pairwise LD analysis of HbE and 43 surrounding biallelic markers revealed LD of HbE extending beyond 100 kb, whereas no LD was observed between non-HbE variants and the same markers. The inferred haplotype network suggests a single origin of the HbE variant in the Thai population. Forward-in-time computer simulations under a variety of selection models indicate that the HbE variant arose 1,240-4,440 years ago. These results support the conjecture that the HbE mutation occurred recently, and the allele frequency has increased rapidly. Our study provides another clear demonstration that a high-resolution LD map across the human genome can detect recent variants that have been subjected to positive selection.

  3. Energy & Climate: Getting Quantitative

    NASA Astrophysics Data System (ADS)

    Wolfson, Richard

    2011-11-01

    A noted environmentalist claims that buying an SUV instead of a regular car is energetically equivalent to leaving your refrigerator door open for seven years. A fossil-fuel apologist argues that solar energy is a pie-in-the-sky dream promulgated by na"ive environmentalists, because there's nowhere near enough solar energy to meet humankind's energy demand. A group advocating shutdown of the Vermont Yankee nuclear plant claims that 70% of its electrical energy is lost in transmission lines. Around the world, thousands agitate for climate action, under the numerical banner ``350.'' Neither the environmentalist, the fossil-fuel apologist, the antinuclear activists, nor most of those marching under the ``350'' banner can back up their assertions with quantitative arguments. Yet questions about energy and its environmental impacts almost always require quantitative answers. Physics can help! This poster gives some cogent examples, based on the newly published 2^nd edition of the author's textbook Energy, Environment, and Climate.

  4. The changing distribution of a major surgical procedure across hospitals: were supply shifts and disequilibrium important?

    PubMed

    Friedman, B; Elixhauser, A

    1995-01-01

    This paper describes and analyzes the changing distribution across hospitals in the U.S. of total hip replacement surgery (THR) for the period 1980-1987. THR is one of the most costly single procedures contributing to health care expenses. Also, the use of THR exhibits a particularly high degree of geographic variation. Recent research pointed to shifts in demand as one plausible economic explanation for increasing use of THR. This paper questions whether shifts in supply may have been large enough to explain changes in patient mix and the relationship of patient mix to the number of procedures performed at a particular hospital. In addition, the relationship between total use of THR and the local availability of orthopaedic surgeons as well as the average allowable Medicare fee for standardized physician services is analyzed. These relationships might yield evidence to support a scenario of induced demand beyond the optimum for patients' welfare, or evidence of supply increase within a disequilibrium scenario. This study, using data for all THR patients in a large sample of hospitals, tends to reject the formulation of a market with independent supply and demand shifts where the supply shifts were the dominant forces. Hospitals with a larger number of THRs performed did not see a higher percentage of older, sicker, and lower income patients. It was more likely that demand shifts generated increases in capacity for surgical services. Moreover, there was little evidence for a persistent disequilibrium and only weak evidence for inducement. Also, we found little evidence that hospitals responded to financial incentives inherent in the Medicare payment system after 1983 to select among THR candidates in favour of those with below average expected cost. We did observe increased concentration over time of THR procedures in facilities with high volume--suggesting plausible demand shifts towards hospitals with a priori quality and cost advantages or who obtained those

  5. Chromosome-wide linkage disequilibrium as a consequence of meiotic drive

    PubMed Central

    Dyer, Kelly A.; Charlesworth, Brian; Jaenike, John

    2007-01-01

    Adaptation by natural selection proceeds most efficiently when alleles compete solely on the basis of their effects on the survival and reproduction of their carriers. A major condition for this is equal Mendelian segregation, but meiotic drive can short-circuit this process. The evolution of drive often involves multiple, interacting genetic components, together with enhancers and suppressors of drive. Chromosomal inversions that suppress crossing over are also frequently associated with drive systems. This study investigates the effects of these processes on patterns of molecular evolution in the fly Drosophila recens, which is polymorphic for a driving X chromosome (XD). Whereas standard wild-type chromosomes exhibit high levels of polymorphism at multiple loci, all of the XD chromosomes effectively carry a single multilocus haplotype that spans at least 130 cM. The XD is associated with a complex set of inversions that completely suppresses recombination between the standard wild-type chromosome and XD in heterozygous females, which maintain nonrandom associations among loci that presumably interact epistatically for the expression of drive. The long-term costs of foregoing recombination may be substantial; in combination with its low equilibrium frequency, this makes the XD chromosome susceptible to the accumulation of deleterious mutations. Consistent with this, XD chromosomes are apparently fixed for a recessive mutation that causes female sterility. Thus, the XD in D. recens appears to be in chromosome-wide linkage disequilibrium and in the early stages of mutational degradation. PMID:17242362

  6. Accounting for linkage disequilibrium in association analysis of diverse populations.

    PubMed

    Charles, Bashira A; Shriner, Daniel; Rotimi, Charles N

    2014-04-01

    The National Human Genome Research Institute's catalog of published genome-wide association studies (GWAS) lists over 10,000 genetic variants collectively associated with over 800 human diseases or traits. Most of these GWAS have been conducted in European-ancestry populations. Findings gleaned from these studies have led to identification of disease-associated loci and biologic pathways involved in disease etiology. In multiple instances, these genomic findings have led to the development of novel medical therapies or evidence for prescribing a given drug as the appropriate treatment for a given individual beyond phenotypic appearances or socially defined constructs of race or ethnicity. Such findings have implications for populations throughout the globe and GWAS are increasingly being conducted in more diverse populations. A major challenge for investigators seeking to follow up genomic findings between diverse populations is discordant patterns of linkage disequilibrium (LD). We provide an overview of common measures of LD and opportunities for their use in novel methods designed to address challenges associated with following up GWAS conducted in European-ancestry populations in African-ancestry populations or, more generally, between populations with discordant LD patterns. We detail the strengths and weaknesses associated with different approaches. We also describe application of these strategies in follow-up studies of populations with concordant LD patterns (replication) or discordant LD patterns (transferability) as well as fine-mapping studies. We review application of these methods to a variety of traits and diseases. © 2014 WILEY PERIODICALS, INC.

  7. Creation of a bovine herpes virus 1 (BoHV-1) quantitative particle standard by transmission electron microscopy and comparison with established standards for use in real-time PCR.

    PubMed

    Hoferer, Marc; Braun, Anne; Sting, Reinhard

    2017-07-01

    Standards are pivotal for pathogen quantification by real-time PCR (qPCR); however, the creation of a complete and universally applicable virus particle standard is challenging. In the present study a procedure based on purification of bovine herpes virus type 1 (BoHV-1) and subsequent quantification by transmission electron microscopy (TEM) is described. Accompanying quantitative quality controls of the TEM preparation procedure using qPCR yielded recovery rates of more than 95% of the BoHV-1 virus particles on the grid used for virus counting, which was attributed to pre-treatment of the grid with 5% bovine albumin. To compare the value of the new virus particle standard for use in qPCR, virus counter based quantification and established pure DNA standards represented by a plasmid and an oligonucleotide were included. It could be shown that the numbers of virus particles, plasmid and oligonucleotide equivalents were within one log10 range determined on the basis of standard curves indicating that different approaches provide comparable quantitative values. However, only virus particles represent a complete, universally applicable quantitative virus standard that meets the high requirements of an RNA and DNA virus gold standard. In contrast, standards based on pure DNA have to be considered as sub-standard due to limited applications. Copyright © 2017 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

  8. USE OF GENOTOXIC ACTIVITY PROFILES IN ASSESSMENT OF CARCINOGENESIS AND TRANSMISSIBLE GENETIC EFFECTS

    EPA Science Inventory

    A methodology has been developed to display and evaluate multiple test quantitative information on genetic toxicants for purposes of assessing carcinogenesis and transmissible genetic effects. ose Information is collected from the open literature: either the lowest effective dose...

  9. Estimating effective population size from linkage disequilibrium between unlinked loci: theory and application to fruit fly outbreak populations.

    PubMed

    Sved, John A; Cameron, Emilie C; Gilchrist, A Stuart

    2013-01-01

    There is a substantial literature on the use of linkage disequilibrium (LD) to estimate effective population size using unlinked loci. The Ne estimates are extremely sensitive to the sampling process, and there is currently no theory to cope with the possible biases. We derive formulae for the analysis of idealised populations mating at random with multi-allelic (microsatellite) loci. The 'Burrows composite index' is introduced in a novel way with a 'composite haplotype table'. We show that in a sample of diploid size S, the mean value of x2 or r2 from the composite haplotype table is biased by a factor of 1-1/(2S-1)2, rather than the usual factor 1+1/(2S-1) for a conventional haplotype table. But analysis of population data using these formulae leads to Ne estimates that are unrealistically low. We provide theory and simulation to show that this bias towards low Ne estimates is due to null alleles, and introduce a randomised permutation correction to compensate for the bias. We also consider the effect of introducing a within-locus disequilibrium factor to r2, and find that this factor leads to a bias in the Ne estimate. However this bias can be overcome using the same randomised permutation correction, to yield an altered r2 with lower variance than the original r2, and one that is also insensitive to null alleles. The resulting formulae are used to provide Ne estimates on 40 samples of the Queensland fruit fly, Bactrocera tryoni, from populations with widely divergent Ne expectations. Linkage relationships are known for most of the microsatellite loci in this species. We find that there is little difference in the estimated Ne values from using known unlinked loci as compared to using all loci, which is important for conservation studies where linkage relationships are unknown.

  10. Nucleotide Sequence Diversity and Linkage Disequilibrium of Four Nuclear Loci in Foxtail Millet (Setaria italica).

    PubMed

    He, Shui-Lian; Yang, Yang; Morrell, Peter L; Yi, Ting-Shuang

    2015-01-01

    Foxtail millet (Setaria italica (L.) Beauv) is one of the earliest domesticated grains, which has been cultivated in northern China by 8,700 years before present (YBP) and across Eurasia by 4,000 YBP. Owing to a small genome and diploid nature, foxtail millet is a tractable model crop for studying functional genomics of millets and bioenergy grasses. In this study, we examined nucleotide sequence diversity, geographic structure, and levels of linkage disequilibrium at four nuclear loci (ADH1, G3PDH, IGS1 and TPI1) in representative samples of 311 landrace accessions across its cultivated range. Higher levels of nucleotide sequence and haplotype diversity were observed in samples from China relative to other sampled regions. Genetic assignment analysis classified the accessions into seven clusters based on nucleotide sequence polymorphisms. Intralocus LD decayed rapidly to half the initial value within ~1.2 kb or less.

  11. speed-ne: Software to simulate and estimate genetic effective population size (Ne ) from linkage disequilibrium observed in single samples.

    PubMed

    Hamilton, Matthew B; Tartakovsky, Maria; Battocletti, Amy

    2018-05-01

    The genetic effective population size, N e , can be estimated from the average gametic disequilibrium (r2^) between pairs of loci, but such estimates require evaluation of assumptions and currently have few methods to estimate confidence intervals. speed-ne is a suite of matlab computer code functions to estimate Ne^ from r2^ with a graphical user interface and a rich set of outputs that aid in understanding data patterns and comparing multiple estimators. speed-ne includes functions to either generate or input simulated genotype data to facilitate comparative studies of Ne^ estimators under various population genetic scenarios. speed-ne was validated with data simulated under both time-forward and time-backward coalescent models of genetic drift. Three classes of estimators were compared with simulated data to examine several general questions: what are the impacts of microsatellite null alleles on Ne^, how should missing data be treated, and does disequilibrium contributed by reduced recombination among some loci in a sample impact Ne^. Estimators differed greatly in precision in the scenarios examined, and a widely employed Ne^ estimator exhibited the largest variances among replicate data sets. speed-ne implements several jackknife approaches to estimate confidence intervals, and simulated data showed that jackknifing over loci and jackknifing over individuals provided ~95% confidence interval coverage for some estimators and should be useful for empirical studies. speed-ne provides an open-source extensible tool for estimation of Ne^ from empirical genotype data and to conduct simulations of both microsatellite and single nucleotide polymorphism (SNP) data types to develop expectations and to compare Ne^ estimators. © 2018 John Wiley & Sons Ltd.

  12. Quantifying human-environment interactions using videography in the context of infectious disease transmission.

    PubMed

    Julian, Timothy R; Bustos, Carla; Kwong, Laura H; Badilla, Alejandro D; Lee, Julia; Bischel, Heather N; Canales, Robert A

    2018-05-08

    Quantitative data on human-environment interactions are needed to fully understand infectious disease transmission processes and conduct accurate risk assessments. Interaction events occur during an individual's movement through, and contact with, the environment, and can be quantified using diverse methodologies. Methods that utilize videography, coupled with specialized software, can provide a permanent record of events, collect detailed interactions in high resolution, be reviewed for accuracy, capture events difficult to observe in real-time, and gather multiple concurrent phenomena. In the accompanying video, the use of specialized software to capture humanenvironment interactions for human exposure and disease transmission is highlighted. Use of videography, combined with specialized software, allows for the collection of accurate quantitative representations of human-environment interactions in high resolution. Two specialized programs include the Virtual Timing Device for the Personal Computer, which collects sequential microlevel activity time series of contact events and interactions, and LiveTrak, which is optimized to facilitate annotation of events in real-time. Opportunities to annotate behaviors at high resolution using these tools are promising, permitting detailed records that can be summarized to gain information on infectious disease transmission and incorporated into more complex models of human exposure and risk.

  13. A Quantitative Approach to Scar Analysis

    PubMed Central

    Khorasani, Hooman; Zheng, Zhong; Nguyen, Calvin; Zara, Janette; Zhang, Xinli; Wang, Joyce; Ting, Kang; Soo, Chia

    2011-01-01

    Analysis of collagen architecture is essential to wound healing research. However, to date no consistent methodologies exist for quantitatively assessing dermal collagen architecture in scars. In this study, we developed a standardized approach for quantitative analysis of scar collagen morphology by confocal microscopy using fractal dimension and lacunarity analysis. Full-thickness wounds were created on adult mice, closed by primary intention, and harvested at 14 days after wounding for morphometrics and standard Fourier transform-based scar analysis as well as fractal dimension and lacunarity analysis. In addition, transmission electron microscopy was used to evaluate collagen ultrastructure. We demonstrated that fractal dimension and lacunarity analysis were superior to Fourier transform analysis in discriminating scar versus unwounded tissue in a wild-type mouse model. To fully test the robustness of this scar analysis approach, a fibromodulin-null mouse model that heals with increased scar was also used. Fractal dimension and lacunarity analysis effectively discriminated unwounded fibromodulin-null versus wild-type skin as well as healing fibromodulin-null versus wild-type wounds, whereas Fourier transform analysis failed to do so. Furthermore, fractal dimension and lacunarity data also correlated well with transmission electron microscopy collagen ultrastructure analysis, adding to their validity. These results demonstrate that fractal dimension and lacunarity are more sensitive than Fourier transform analysis for quantification of scar morphology. PMID:21281794

  14. Entomologic considerations in the study of onchocerciasis transmission.

    PubMed

    Vargas, L; Díaz-Nájera, A

    1980-01-01

    The entomological resources utilized for a better understanding of Onchocerca volvulus transmission are discussed in this paper. Vector density, anthropohilia, gonotrophic cycyle, parous condition longevity and probability of survival in days after the infectious meal are assessed here in order to integrate an overall picture. The concept of vectorial capacity is developed stressing the quantitative aspects. Parasitism of the black-flies by filariae that are doubtfully identified as O. volvulus is also mentioned here.

  15. Resolved 12CH2D2 and 13CH3D in CH4 as Sensitive Indicators of Disequilibrium and Equilibrium during Microbial Methane Cycling

    NASA Astrophysics Data System (ADS)

    Ash, J. L.; Egger, M.; Slomp, C. P.; Kohl, I. E.; Treude, T.; Rumble, D.; Young, E. D.

    2016-12-01

    The ability to measure the relative concentrations of at least two doubly-substituted rare isotopologues of gases with biogeochemical relevance provides new constraints on sources and sinks of these gases. In particular, as shown recently for O2, the use of two independent, rare isotopologues allows for detection of thermodynamic intra-species equilibrium and disequilibrium. Here, we report the first measurements of fully resolved 13CH3D and 12CH2D2 from natural samples of microbial methane gas. A suite of sedimentary methane samples from the Bornholm Basin in the Baltic Sea was collected during IODP Exp. 347. Sample depths range from 2-20 meters below seafloor (mbsf). Methane concentrations decrease with depth, and mcrA (a marker for methanogenesis and methanotropy) is present throughout. See Figure. Both Δ13CH3D and Δ12CH2D2 increase with depth as methane concentrations decrease with the shallowest samples exhibiting disequilibrium by up to 2‰ in Δ13CH3D and 13‰ in Δ12CH2D2 while the deepest samples approach isotopic thermodynamic equilibrium (marked by grey bars in Figure). The Fe-mediated anaerobic oxidation of methane (Fe-AOM) has been inferred in these sediments by geochemical modeling . Slow methane cycling by methanogensis and methanotrophy is likely responsible for the approach to isotopic bond order equilibrium in CH4 with depth, consistent with Fe-AOM. While axenic culturing experiments generate methane with large deficits in 12CH2D2 (reported at this meeting), these data from the Baltic Sea demonstrate that isotopic equilibrium can be achieved during microbial recycling of methane. In the absence of Δ12CH2D2, the Δ13CH3D values alone could be misinterpreted as representing gradients in temperature due perhaps to exothermic organic matter degradation. The combination of both mass-18 rare isotopologues of methane provides the means to distinguish equilibrium from disequilibrium and probe microbial methane cycling even where Δ13CH3D suggests

  16. Correlative Instrumental Neutron Activation Analysis, Light Microscopy, Transmission Electron Microscopy, and X-ray Microanalysis for Qualitative and Quantitative Detection of Colloidal Gold Spheres in Biological Specimens

    NASA Astrophysics Data System (ADS)

    Hillyer, Julián F.; Albrecht, Ralph M.

    1998-10-01

    : Colloidal gold, conjugated to ligands or antibodies, is routinely used as a label for the detection of cell structures by light (LM) and electron microscopy (EM). To date, several methods to count the number of colloidal gold labels have been employed with limited success. Instrumental neutron activation analysis (INAA), a physical method for the analysis of the elemental composition of materials, can be used to provide a quantitative index of gold accumulation in bulk specimens. Given that gold is not naturally found in biological specimens in any substantial amount and that colloidal gold and ligand conjugates can be prepared to yield uniform bead sizes, the amount of label can be calculated in bulk biological samples by INAA. Here we describe the use of INAA, LM, transmission EM, and X-ray microanalysis (EDX) in a model to determine both distribution (localization) and amount of colloidal gold at the organ, tissue, cellular, and ultrastructural levels in whole animal systems following administration. In addition, the sensitivity for gold in biological specimens by INAA is compared with that of inductively coupled plasma mass spectrometry (ICP-MS). The correlative use of INAA, LM, TEM, and EDX can be useful, for example, in the quantitative and qualitative tracking of various labeled molecular species following administration in vivo.

  17. Passive Fourier-transform infrared spectroscopy of chemical plumes: an algorithm for quantitative interpretation and real-time background removal

    NASA Astrophysics Data System (ADS)

    Polak, Mark L.; Hall, Jeffrey L.; Herr, Kenneth C.

    1995-08-01

    We present a ratioing algorithm for quantitative analysis of the passive Fourier-transform infrared spectrum of a chemical plume. We show that the transmission of a near-field plume is given by tau plume = (Lobsd - Lbb-plume)/(Lbkgd - Lbb-plume), where tau plume is the frequency-dependent transmission of the plume, L obsd is the spectral radiance of the scene that contains the plume, Lbkgd is the spectral radiance of the same scene without the plume, and Lbb-plume is the spectral radiance of a blackbody at the plume temperature. The algorithm simultaneously achieves background removal, elimination of the spectrometer internal signature, and quantification of the plume spectral transmission. It has applications to both real-time processing for plume visualization and quantitative measurements of plume column densities. The plume temperature (Lbb-plume ), which is not always precisely known, can have a profound effect on the quantitative interpretation of the algorithm and is discussed in detail. Finally, we provide an illustrative example of the use of the algorithm on a trichloroethylene and acetone plume.

  18. Wealth Transmission and Inequality Among Hunter-Gatherers

    PubMed Central

    Hill, Kim; Marlowe, Frank; Nolin, David; Wiessner, Polly; Gurven, Michael; Bowles, Samuel; Mulder, Monique Borgerhoff; Hertz, Tom; Bell, Adrian

    2010-01-01

    We report quantitative estimates of intergenerational transmission and population-wide inequality for wealth measures in a set of hunter-gatherer populations. Wealth is defined broadly as factors that contribute to individual or household well-being, ranging from embodied forms such as weight and hunting success to material forms such household goods, as well as relational wealth in exchange partners. Intergenerational wealth transmission is low to moderate in these populations, but is still expected to have measurable influence on an individual’s life chances. Wealth inequality (measured with Gini coefficients) is moderate for most wealth types, matching what qualitative ethnographic research has generally indicated (if not the stereotype of hunter-gatherers as extreme egalitarians). We discuss some plausible mechanisms for these patterns, and suggest ways in which future research could resolve questions about the role of wealth in hunter-gatherer social and economic life. PMID:21151711

  19. Genome-wide distribution of genetic diversity and linkage disequilibrium in a mass-selected population of maritime pine

    PubMed Central

    2014-01-01

    Background The accessibility of high-throughput genotyping technologies has contributed greatly to the development of genomic resources in non-model organisms. High-density genotyping arrays have only recently been developed for some economically important species such as conifers. The potential for using genomic technologies in association mapping and breeding depends largely on the genome wide patterns of diversity and linkage disequilibrium in current breeding populations. This study aims to deepen our knowledge regarding these issues in maritime pine, the first species used for reforestation in south western Europe. Results Using a new map merging algorithm, we first established a 1,712 cM composite linkage map (comprising 1,838 SNP markers in 12 linkage groups) by bringing together three already available genetic maps. Using rigorous statistical testing based on kernel density estimation and resampling we identified cold and hot spots of recombination. In parallel, 186 unrelated trees of a mass-selected population were genotyped using a 12k-SNP array. A total of 2,600 informative SNPs allowed to describe historical recombination, genetic diversity and genetic structure of this recently domesticated breeding pool that forms the basis of much of the current and future breeding of this species. We observe very low levels of population genetic structure and find no evidence that artificial selection has caused a reduction in genetic diversity. By combining these two pieces of information, we provided the map position of 1,671 SNPs corresponding to 1,192 different loci. This made it possible to analyze the spatial pattern of genetic diversity (H e ) and long distance linkage disequilibrium (LD) along the chromosomes. We found no particular pattern in the empirical variogram of H e across the 12 linkage groups and, as expected for an outcrossing species with large effective population size, we observed an almost complete lack of long distance LD. Conclusions These

  20. A feature selection approach towards progressive vector transmission over the Internet

    NASA Astrophysics Data System (ADS)

    Miao, Ru; Song, Jia; Feng, Min

    2017-09-01

    WebGIS has been applied for visualizing and sharing geospatial information popularly over the Internet. In order to improve the efficiency of the client applications, the web-based progressive vector transmission approach is proposed. Important features should be selected and transferred firstly, and the methods for measuring the importance of features should be further considered in the progressive transmission. However, studies on progressive transmission for large-volume vector data have mostly focused on map generalization in the field of cartography, but rarely discussed on the selection of geographic features quantitatively. This paper applies information theory for measuring the feature importance of vector maps. A measurement model for the amount of information of vector features is defined based upon the amount of information for dealing with feature selection issues. The measurement model involves geometry factor, spatial distribution factor and thematic attribute factor. Moreover, a real-time transport protocol (RTP)-based progressive transmission method is then presented to improve the transmission of vector data. To clearly demonstrate the essential methodology and key techniques, a prototype for web-based progressive vector transmission is presented, and an experiment of progressive selection and transmission for vector features is conducted. The experimental results indicate that our approach clearly improves the performance and end-user experience of delivering and manipulating large vector data over the Internet.

  1. Linkage disequilibrium compared between five populations of domestic sheep.

    PubMed

    Meadows, Jennifer R S; Chan, Eva K F; Kijas, James W

    2008-09-30

    The success of genome-wide scans depends on the strength and magnitude of linkage disequilibrium (LD) present within the populations under investigation. High density SNP arrays are currently in development for the sheep genome, however little is known about the behaviour of LD in this livestock species. This study examined the behaviour of LD within five sheep populations using two LD metrics, D' and x2'. Four economically important Australian sheep flocks, three pure breeds (White Faced Suffolk, Poll Dorset, Merino) and a crossbred population (Merino x Border Leicester), along with an inbred Australian Merino museum flock were analysed. Short range LD (0 - 5 cM) was observed in all five populations, however the persistence with increasing distance and magnitude of LD varied considerably between populations. Average LD (x2') for markers spaced up to 20 cM exceeded the non-syntenic average within the White Faced Suffolk, Poll Dorset and Macarthur Merino. LD decayed faster within the Merino and Merino x Border Leicester, with LD below or consistent with observed background levels. Using marker-marker LD as a guide to the behaviour of marker-QTL LD, estimates of minimum marker spacing were made. For a 95% probability of detecting QTL, a microsatellite marker would be required every 0.1 - 2.5 centimorgans, depending on the population used. Sheep populations were selected which were inbred (Macarthur Merino), highly heterogeneous (Merino) or intermediate between these two extremes. This facilitated analysis and comparison of LD (x2') between populations. The strength and magnitude of LD was found to differ markedly between breeds and aligned closely with both observed levels of genetic diversity and expectations based on breed history. This confirmed that breed specific information is likely to be important for genome wide selection and during the design of successful genome scans where tens of thousands of markers will be required.

  2. Detection of linkage disequilibrium between the myotonic dystrophy locus and a new polymorphic DNA marker.

    PubMed Central

    Harley, H G; Brook, J D; Floyd, J; Rundle, S A; Crow, S; Walsh, K V; Thibault, M C; Harper, P S; Shaw, D J

    1991-01-01

    We have examined the linkage of two new polymorphic DNA markers (D19S62 and D19S63) and a previously unreported polymorphism with an existing DNA marker (ERCC1) to the myotonic dystrophy (DM) locus. In addition, we have used pulsed-field gel electrophoresis to obtain a fine-structure map of this region. The detection of linkage disequilibrium between DM and one of these markers (D19S63) is the first demonstration of this phenomenon in a heterogeneous DM population. The results suggest that at least 58% of DM patients in the British population, as well as those in a French-Canadian subpopulation, are descended from the same ancestral DM mutation. We discuss the implications of this finding in terms of strategies for cloning the DM gene, for a possible role in modification of risk for prenatal and presymptomatic testing, and we speculate on the origin and number of existing mutations which may result in a DM phenotype. PMID:2063878

  3. Heat transfer to two-phase air/water mixtures flowing in small tubes with inlet disequilibrium

    NASA Technical Reports Server (NTRS)

    Janssen, J. M.; Florschuetz, L. W.; Fiszdon, J. P.

    1986-01-01

    The cooling of gas turbine components was the subject of considerable research. The problem is difficult because the available coolant, compressor bleed air, is itself quite hot and has relatively poor thermophysical properties for a coolant. Injecting liquid water to evaporatively cool the air prior to its contact with the hot components was proposed and studied, particularly as a method of cooling for contingency power applications. Injection of a small quantity of cold liquid water into a relatively hot coolant air stream such that evaporation of the liquid is still in process when the coolant contacts the hot component was studied. No approach was found whereby heat transfer characteristics could be confidently predicted for such a case based solely on prior studies. It was not clear whether disequilibrium between phases at the inlet to the hot component section would improve cooling relative to that obtained where equilibrium was established prior to contact with the hot surface.

  4. Optical Ptychographic Microscope for Quantitative Bio-Mechanical Imaging

    NASA Astrophysics Data System (ADS)

    Anthony, Nicholas; Cadenazzi, Guido; Nugent, Keith; Abbey, Brian

    The role that mechanical forces play in biological processes such as cell movement and death is becoming of significant interest to further develop our understanding of the inner workings of cells. The most common method used to obtain stress information is photoelasticity which maps a samples birefringence, or its direction dependent refractive indices, using polarized light. However this method only provides qualitative data and for stress information to be useful quantitative data is required. Ptychography is a method for quantitatively determining the phase of a samples complex transmission function. The technique relies upon the collection of multiple overlapping coherent diffraction patterns from laterally displaced points on the sample. The overlap of measurement points provides complementary information that significantly aids in the reconstruction of the complex wavefield exiting the sample and allows for quantitative imaging of weakly interacting specimens. Here we describe recent advances at La Trobe University Melbourne on achieving quantitative birefringence mapping using polarized light ptychography with applications in cell mechanics. Australian Synchrotron, ARC Centre of Excellence for Advanced Molecular Imaging.

  5. Mineral disequilibrium in lavas explained by convective self-mixing in open magma chambers.

    PubMed

    Couch, S; Sparks, R S; Carroll, M R

    2001-06-28

    Characteristic features of many porphyritic andesite and dacite lavas are that they are rich in crystals and display a range of disequilibrium features, including reversely zoned crystals, resorption surfaces, wide ranges of mineral compositions and minerals which are not in equilibrium with the surrounding rock matrix. These features are often interpreted as evidence of the mixing of magmas of contrasting composition, temperature and origin. Here, however, we propose that such features can also be caused by convection within a magma body with a single composition, that is heated from below and cooled from above. We describe petrological observations of andesite lava erupted at the Soufrière Hills volcano, Montserrat, which indicate a heating event and the intermingling of crystals that have very different thermal histories. We present experimental data on a representative groundmass composition of this lava, which indicate that it is difficult to explain the calcic compositions of plagioclase overgrowth rims and microphenocrysts unless parts of the magma were at temperatures much higher than the inferred average temperature. The concept of convective self-mixing allows us to explain the occurrence of compositions of minerals that apparently cannot coexist under equilibrium conditions.

  6. Serotonin transporter gene polymorphisms and hyperserotonemia in autistic disorder.

    PubMed

    Betancur, C; Corbex, M; Spielewoy, C; Philippe, A; Laplanche, J L; Launay, J M; Gillberg, C; Mouren-Siméoni, M C; Hamon, M; Giros, B; Nosten-Bertrand, M; Leboyer, M

    2002-01-01

    Previous studies have provided conflicting evidence regarding the association of the serotonin transporter (5-HTT) gene with autism. Two polymorphisms have been identified in the human 5-HTT gene, a VNTR in intron 2 and a functional deletion/insertion in the promoter region (5-HTTLPR) with short and long variants. Positive associations of the 5-HTTLPR polymorphism with autism have been reported by two family-based studies, but one found preferential transmission of the short allele and the other of the long allele. Two subsequent studies failed to find evidence of transmission disequilibrium at the 5-HTTLPR locus. These conflicting results could be due to heterogeneity of clinical samples with regard to serotonin (5-HT) blood levels, which have been found to be elevated in some autistic subjects. Thus, we examined the association of the 5-HTTLPR and VNTR polymorphisms of the 5-HTT gene with autism, and we investigated the relationship between 5-HTT variants and whole-blood 5-HT. The transmission/disequilibrium test (TDT) revealed no linkage disequilibrium at either loci in a sample of 96 families comprising 43 trios and 53 sib pairs. Furthermore, no significant relationship between 5-HT blood levels and 5-HTT gene polymorphisms was found. Our results suggest that the 5-HTT gene is unlikely to play a major role as a susceptibility factor in autism.

  7. Estimation of linkage disequilibrium and interspecific gene flow in Ficedula flycatchers by a newly developed 50k single-nucleotide polymorphism array

    PubMed Central

    Kawakami, Takeshi; Backström, Niclas; Burri, Reto; Husby, Arild; Olason, Pall; Rice, Amber M; Ålund, Murielle; Qvarnström, Anna; Ellegren, Hans

    2014-01-01

    With the access to draft genome sequence assemblies and whole-genome resequencing data from population samples, molecular ecology studies will be able to take truly genome-wide approaches. This now applies to an avian model system in ecological and evolutionary research: Old World flycatchers of the genus Ficedula, for which we recently obtained a 1.1 Gb collared flycatcher genome assembly and identified 13 million single-nucleotide polymorphism (SNP)s in population resequencing of this species and its sister species, pied flycatcher. Here, we developed a custom 50K Illumina iSelect flycatcher SNP array with markers covering 30 autosomes and the Z chromosome. Using a number of selection criteria for inclusion in the array, both genotyping success rate and polymorphism information content (mean marker heterozygosity = 0.41) were high. We used the array to assess linkage disequilibrium (LD) and hybridization in flycatchers. Linkage disequilibrium declined quickly to the background level at an average distance of 17 kb, but the extent of LD varied markedly within the genome and was more than 10-fold higher in ‘genomic islands’ of differentiation than in the rest of the genome. Genetic ancestry analysis identified 33 F1 hybrids but no later-generation hybrids from sympatric populations of collared flycatchers and pied flycatchers, contradicting earlier reports of backcrosses identified from much fewer number of markers. With an estimated divergence time as recently as <1 Ma, this suggests strong selection against F1 hybrids and unusually rapid evolution of reproductive incompatibility in an avian system. PMID:24784959

  8. INS VNTR is not associated with childhood obesity in 1,023 families: a family-based study.

    PubMed

    Bouatia-Naji, Nabila; De Graeve, Franck; Brönner, Günter; Lecoeur, Cécile; Vatin, Vincent; Durand, Emmanuelle; Lichtner, Peter; Nguyen, Thuy T; Heude, Barbara; Weill, Jacques; Lévy-Marchal, Claire; Hebebrand, Johannes; Froguel, Philippe; Meyre, David

    2008-06-01

    Previous studies have described genetic associations of the insulin gene variable number tandem repeat (INS VNTR) variant with childhood obesity and associated phenotypes. We aimed to assess the contribution of INS VNTR genotypes to childhood obesity and variance of insulin resistance, insulin secretion, and birth weight using family-based design. Participants were either French or German whites. We used transmission disequilibrium tests (TDTs) for assessing binary traits and quantitative pedigree disequilibrium tests for assessing continuous traits. In contrast to previous findings, we did not observe any familial association with childhood obesity (T = 50%, P = 0.77) in the 1,023 families tested. In French obese children, INS VNTR did not associate with fasting insulin levels (P = 0.23) and class I allele showed only borderline association with increased insulin secretion index at 30 min (P = 0.03). INS VNTR did not associate with birth weight in obese children (P = 0.98) and TDT analyses in 350 French families with history of low birth weight (LBW) showed no association with this condition (P = 0.92). In summary, our study, the largest performed so far, does not support the previously reported associations between INS VNTR and childhood obesity, insulin resistance, or birth weight, and does not suggest any major role for this variant in modulating these traits.

  9. Statistical correction of the Winner’s Curse explains replication variability in quantitative trait genome-wide association studies

    PubMed Central

    Pe’er, Itsik

    2017-01-01

    Genome-wide association studies (GWAS) have identified hundreds of SNPs responsible for variation in human quantitative traits. However, genome-wide-significant associations often fail to replicate across independent cohorts, in apparent inconsistency with their apparent strong effects in discovery cohorts. This limited success of replication raises pervasive questions about the utility of the GWAS field. We identify all 332 studies of quantitative traits from the NHGRI-EBI GWAS Database with attempted replication. We find that the majority of studies provide insufficient data to evaluate replication rates. The remaining papers replicate significantly worse than expected (p < 10−14), even when adjusting for regression-to-the-mean of effect size between discovery- and replication-cohorts termed the Winner’s Curse (p < 10−16). We show this is due in part to misreporting replication cohort-size as a maximum number, rather than per-locus one. In 39 studies accurately reporting per-locus cohort-size for attempted replication of 707 loci in samples with similar ancestry, replication rate matched expectation (predicted 458, observed 457, p = 0.94). In contrast, ancestry differences between replication and discovery (13 studies, 385 loci) cause the most highly-powered decile of loci to replicate worse than expected, due to difference in linkage disequilibrium. PMID:28715421

  10. Improved cancer risk stratification and diagnosis via quantitative phase microscopy (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Liu, Yang; Uttam, Shikhar; Pham, Hoa V.; Hartman, Douglas J.

    2017-02-01

    Pathology remains the gold standard for cancer diagnosis and in some cases prognosis, in which trained pathologists examine abnormality in tissue architecture and cell morphology characteristic of cancer cells with a bright-field microscope. The limited resolution of conventional microscope can result in intra-observer variation, missed early-stage cancers, and indeterminate cases that often result in unnecessary invasive procedures in the absence of cancer. Assessment of nanoscale structural characteristics via quantitative phase represents a promising strategy for identifying pre-cancerous or cancerous cells, due to its nanoscale sensitivity to optical path length, simple sample preparation (i.e., label-free) and low cost. I will present the development of quantitative phase microscopy system in transmission and reflection configuration to detect the structural changes in nuclear architecture, not be easily identifiable by conventional pathology. Specifically, we will present the use of transmission-mode quantitative phase imaging to improve diagnostic accuracy of urine cytology and the nuclear dry mass is progressively correlate with negative, atypical, suspicious and positive cytological diagnosis. In a second application, we will present the use of reflection-mode quantitative phase microscopy for depth-resolved nanoscale nuclear architecture mapping (nanoNAM) of clinically prepared formalin-fixed, paraffin-embedded tissue sections. We demonstrated that the quantitative phase microscopy system detects a gradual increase in the density alteration of nuclear architecture during malignant transformation in animal models of colon carcinogenesis and in human patients with ulcerative colitis, even in tissue that appears histologically normal according to pathologists. We evaluated the ability of nanoNAM to predict "future" cancer progression in patients with ulcerative colitis.

  11. Use of linkage disequilibrium approaches to map genes for bipolar disorder in the Costa Rican population

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

    Escamilla, M.A.; Reus, V.I.; Smith, L.B.

    1996-05-31

    Linkage disequilibrium (LD) analysis provides a powerful means for screening the genome to map the location of disease genes, such as those for bipolar disorder (BP). As described in this paper, the population of the Central Valley of Costa Rica, which is descended from a small number of founders, should be suitable for LD mapping; this assertion is supported by reconstruction of extended haplotypes shared by distantly related individuals in this population suffering low-frequency hearing loss (LFHL1), which has previously been mapped by linkage analysis. A sampling strategy is described for applying LD methods to map genes for BP, andmore » clinical and demographic characteristics of an initially collected sample are discussed. This sample will provide a complement to a previously collected set of Costa Rican BP families which is under investigation using standard linkage analysis. 42 refs., 4 figs., 2 tabs.« less

  12. Temporal dynamics of linkage disequilibrium in two populations of bighorn sheep

    PubMed Central

    Miller, Joshua M; Poissant, Jocelyn; Malenfant, René M; Hogg, John T; Coltman, David W

    2015-01-01

    Linkage disequilibrium (LD) is the nonrandom association of alleles at two markers. Patterns of LD have biological implications as well as practical ones when designing association studies or conservation programs aimed at identifying the genetic basis of fitness differences within and among populations. However, the temporal dynamics of LD in wild populations has received little empirical attention. In this study, we examined the overall extent of LD, the effect of sample size on the accuracy and precision of LD estimates, and the temporal dynamics of LD in two populations of bighorn sheep (Ovis canadensis) with different demographic histories. Using over 200 microsatellite loci, we assessed two metrics of multi-allelic LD, D′, and χ′2. We found that both populations exhibited high levels of LD, although the extent was much shorter in a native population than one that was founded via translocation, experienced a prolonged bottleneck post founding, followed by recent admixture. In addition, we observed significant variation in LD in relation to the sample size used, with small sample sizes leading to depressed estimates of the extent of LD but inflated estimates of background levels of LD. In contrast, there was not much variation in LD among yearly cross-sections within either population once sample size was accounted for. Lack of pronounced interannual variability suggests that researchers may not have to worry about interannual variation when estimating LD in a population and can instead focus on obtaining the largest sample size possible. PMID:26380673

  13. Patterns of linkage disequilibrium and haplotype distribution in disease candidate genes.

    PubMed

    Long, Ji-Rong; Zhao, Lan-Juan; Liu, Peng-Yuan; Lu, Yan; Dvornyk, Volodymyr; Shen, Hui; Liu, Yong-Jun; Zhang, Yuan-Yuan; Xiong, Dong-Hai; Xiao, Peng; Deng, Hong-Wen

    2004-05-24

    The adequacy of association studies for complex diseases depends critically on the existence of linkage disequilibrium (LD) between functional alleles and surrounding SNP markers. We examined the patterns of LD and haplotype distribution in eight candidate genes for osteoporosis and/or obesity using 31 SNPs in 1,873 subjects. These eight genes are apolipoprotein E (APOE), type I collagen alpha1 (COL1A1), estrogen receptor-alpha (ER-alpha), leptin receptor (LEPR), parathyroid hormone (PTH)/PTH-related peptide receptor type 1 (PTHR1), transforming growth factor-beta1 (TGF-beta1), uncoupling protein 3 (UCP3), and vitamin D (1,25-dihydroxyvitamin D3) receptor (VDR). Yin yang haplotypes, two high-frequency haplotypes composed of completely mismatching SNP alleles, were examined. To quantify LD patterns, two common measures of LD, D' and r2, were calculated for the SNPs within the genes. The haplotype distribution varied in the different genes. Yin yang haplotypes were observed only in PTHR1 and UCP3. D' ranged from 0.020 to 1.000 with the average of 0.475, whereas the average r2 was 0.158 (ranging from 0.000 to 0.883). A decay of LD was observed as the intermarker distance increased, however, there was a great difference in LD characteristics of different genes or even in different regions within gene. The differences in haplotype distributions and LD patterns among the genes underscore the importance of characterizing genomic regions of interest prior to association studies.

  14. Patterns of linkage disequilibrium in mitochondrial DNA of 16 ruminant populations.

    PubMed

    Slate, J; Phua, S H

    2003-03-01

    Mitochondrial DNA (mtDNA) is a widely employed molecular tool in phylogeography, in the inference of human evolutionary history, in dating the domestication of livestock and in forensic science. In humans and other vertebrates the popularity of mtDNA can be partially attributed to an assumption of strict maternal inheritance, such that there is no recombination between mitochondrial lineages. The recent demonstration that linkage disequilibrium (LD) declines as a function of distance between polymorphic sites in hominid mitochondrial genomes has been interpreted as evidence of recombination between mtDNA haplotypes, and hence nonclonal inheritance. However, critics of mtDNA recombination have suggested that this association is an artefact of an inappropriate measure of LD or of sequencing error, and subsequent studies of other populations have failed to replicate the initial finding. Here we report the analysis of 16 ruminant populations and present evidence that LD significantly declines with distance in five of them. A meta-analysis of the data indicates a nonsignificant trend of LD declining with distance. Most of the earlier criticisms of patterns between LD and distance in hominid mtDNA are not applicable to this data set. Our results suggest that either ruminant mtDNA is not strictly clonal or that compensatory selection has influenced patterns of variation at closely linked sites within the mitochondrial control region. The potential impact of these processes should be considered when using mtDNA as a tool in vertebrate population genetic, phylogenetic and forensic studies.

  15. Quantitative characterization of nanoscale polycrystalline magnets with electron magnetic circular dichroism.

    PubMed

    Muto, Shunsuke; Rusz, Ján; Tatsumi, Kazuyoshi; Adam, Roman; Arai, Shigeo; Kocevski, Vancho; Oppeneer, Peter M; Bürgler, Daniel E; Schneider, Claus M

    2014-01-01

    Electron magnetic circular dichroism (EMCD) allows the quantitative, element-selective determination of spin and orbital magnetic moments, similar to its well-established X-ray counterpart, X-ray magnetic circular dichroism (XMCD). As an advantage over XMCD, EMCD measurements are made using transmission electron microscopes, which are routinely operated at sub-nanometre resolution, thereby potentially allowing nanometre magnetic characterization. However, because of the low intensity of the EMCD signal, it has not yet been possible to obtain quantitative information from EMCD signals at the nanoscale. Here we demonstrate a new approach to EMCD measurements that considerably enhances the outreach of the technique. The statistical analysis introduced here yields robust quantitative EMCD signals. Moreover, we demonstrate that quantitative magnetic information can be routinely obtained using electron beams of only a few nanometres in diameter without imposing any restriction regarding the crystalline order of the specimen.

  16. Transmission and scattering of acoustic energy in turbulent flows

    NASA Astrophysics Data System (ADS)

    Gaitonde, Datta; Unnikrishnan, S.

    2017-11-01

    Sound scattering and transmission in turbulent jets are explored through a control volume analysis of a Large-Eddy Simulation. The fluctuating momentum flux across any control surface is first split into its rotational turbulent ((ρu)'H) and the irrotational-isentropic acoustic ((ρu)'A) components using momentum potential theory (MPT). The former has low spatio-temporal coherence, while the latter exhibits a persistent wavepacket form. The energy variable, specifically, total fluctuating enthalpy, is also split into its turbulent and acoustic modes, HH' and HA' respectively. Scattering of acoustic energy is then (ρu)'HHA' , and transmission is (ρu)'AHA' . This facilitates a quantitative comparison of scattering versus transmission in the presence of acoustic energy sources, also obtained from MPT, in any turbulent scenario. The wavepacket converts stochastic sound sources into coherent sound radiation. Turbulent eddies are not only sources of sound, but also play a strong role in scattering, particularly near the lipline. The net acoustic flux from the jet is the transport of HA' by the wavepacket, whose axisymmetric and higher azimuthal modes contribute to downstream and sideline radiation respectively.

  17. 47 CFR 25.212 - Narrowband analog transmissions, digital transmissions, and video transmissions in the GSO Fixed...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... transmissions, and video transmissions in the GSO Fixed-Satellite Service. 25.212 Section 25.212... Technical Standards § 25.212 Narrowband analog transmissions, digital transmissions, and video transmissions... narrowband and/or wideband digital services, including digital video services, if the maximum input spectral...

  18. 47 CFR 25.212 - Narrowband analog transmissions, digital transmissions, and video transmissions in the GSO Fixed...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... transmissions, and video transmissions in the GSO Fixed-Satellite Service. 25.212 Section 25.212... Technical Standards § 25.212 Narrowband analog transmissions, digital transmissions, and video transmissions... narrowband and/or wideband digital services, including digital video services, if the maximum input spectral...

  19. 47 CFR 25.212 - Narrowband analog transmissions, digital transmissions, and video transmissions in the GSO Fixed...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... transmissions, and video transmissions in the GSO Fixed-Satellite Service. 25.212 Section 25.212... Technical Standards § 25.212 Narrowband analog transmissions, digital transmissions, and video transmissions... narrowband and/or wideband digital services, including digital video services, if the maximum input spectral...

  20. Natural Allelic Diversity, Genetic Structure and Linkage Disequilibrium Pattern in Wild Chickpea

    PubMed Central

    Kujur, Alice; Das, Shouvik; Badoni, Saurabh; Kumar, Vinod; Singh, Mohar; Bansal, Kailash C.; Tyagi, Akhilesh K.; Parida, Swarup K.

    2014-01-01

    Characterization of natural allelic diversity and understanding the genetic structure and linkage disequilibrium (LD) pattern in wild germplasm accessions by large-scale genotyping of informative microsatellite and single nucleotide polymorphism (SNP) markers is requisite to facilitate chickpea genetic improvement. Large-scale validation and high-throughput genotyping of genome-wide physically mapped 478 genic and genomic microsatellite markers and 380 transcription factor gene-derived SNP markers using gel-based assay, fluorescent dye-labelled automated fragment analyser and matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass array have been performed. Outcome revealed their high genotyping success rate (97.5%) and existence of a high level of natural allelic diversity among 94 wild and cultivated Cicer accessions. High intra- and inter-specific polymorphic potential and wider molecular diversity (11–94%) along with a broader genetic base (13–78%) specifically in the functional genic regions of wild accessions was assayed by mapped markers. It suggested their utility in monitoring introgression and transferring target trait-specific genomic (gene) regions from wild to cultivated gene pool for the genetic enhancement. Distinct species/gene pool-wise differentiation, admixed domestication pattern, and differential genome-wide recombination and LD estimates/decay observed in a six structured population of wild and cultivated accessions using mapped markers further signifies their usefulness in chickpea genetics, genomics and breeding. PMID:25222488

  1. Construction of the model for the Genetic Analysis Workshop 14 simulated data: genotype-phenotype relationships, gene interaction, linkage, association, disequilibrium, and ascertainment effects for a complex phenotype.

    PubMed

    Greenberg, David A; Zhang, Junying; Shmulewitz, Dvora; Strug, Lisa J; Zimmerman, Regina; Singh, Veena; Marathe, Sudhir

    2005-12-30

    The Genetic Analysis Workshop 14 simulated dataset was designed 1) To test the ability to find genes related to a complex disease (such as alcoholism). Such a disease may be given a variety of definitions by different investigators, have associated endophenotypes that are common in the general population, and is likely to be not one disease but a heterogeneous collection of clinically similar, but genetically distinct, entities. 2) To observe the effect on genetic analysis and gene discovery of a complex set of gene x gene interactions. 3) To allow comparison of microsatellite vs. large-scale single-nucleotide polymorphism (SNP) data. 4) To allow testing of association to identify the disease gene and the effect of moderate marker x marker linkage disequilibrium. 5) To observe the effect of different ascertainment/disease definition schemes on the analysis. Data was distributed in two forms. Data distributed to participants contained about 1,000 SNPs and 400 microsatellite markers. Internet-obtainable data consisted of a finer 10,000 SNP map, which also contained data on controls. While disease characteristics and parameters were constant, four "studies" used varying ascertainment schemes based on differing beliefs about disease characteristics. One of the studies contained multiplex two- and three-generation pedigrees with at least four affected members. The simulated disease was a psychiatric condition with many associated behaviors (endophenotypes), almost all of which were genetic in origin. The underlying disease model contained four major genes and two modifier genes. The four major genes interacted with each other to produce three different phenotypes, which were themselves heterogeneous. The population parameters were calibrated so that the major genes could be discovered by linkage analysis in most datasets. The association evidence was more difficult to calibrate but was designed to find statistically significant association in 50% of datasets. We also

  2. Scanning transmission ion microscopy mass measurements for quantitative trace element analysis within biological samples and validation using atomic force microscopy thickness measurements

    NASA Astrophysics Data System (ADS)

    Devès, Guillaume; Cohen-Bouhacina, Touria; Ortega, Richard

    2004-10-01

    We used the nuclear microprobe techniques, micro-PIXE (particle-induced X-ray emission), micro-RBS (Rutherford backscattering spectrometry) and scanning transmission ion microscopy (STIM) in order to perform the characterization of trace element content and spatial distribution within biological samples (dehydrated cultured cells, tissues). The normalization of PIXE results was usually expressed in terms of sample dry mass as determined by micro-RBS recorded simultaneously to micro-PIXE. However, the main limit of RBS mass measurement is the sample mass loss occurring during irradiation and which could be up to 30% of the initial sample mass. We present here a new methodology for PIXE normalization and quantitative analysis of trace element within biological samples based on dry mass measurement performed by mean of STIM. The validation of STIM cell mass measurements was obtained in comparison with AFM sample thickness measurements. Results indicated the reliability of STIM mass measurement performed on biological samples and suggested that STIM should be performed for PIXE normalization. Further information deriving from direct confrontation of AFM and STIM analysis could as well be obtained, like in situ measurements of cell specific gravity within cells compartment (nucleolus and cytoplasm).

  3. Precise Estimation of Allele Frequencies of Single-Nucleotide Polymorphisms by a Quantitative SSCP Analysis of Pooled DNA

    PubMed Central

    Sasaki, Tomonari; Tahira, Tomoko; Suzuki, Akari; Higasa, Koichiro; Kukita, Yoji; Baba, Shingo; Hayashi, Kenshi

    2001-01-01

    We show that single-nucleotide polymorphisms (SNPs) of moderate to high heterozygosity (minor allele frequencies >10%) can be efficiently detected, and their allele frequencies accurately estimated, by pooling the DNA samples and applying a capillary-based SSCP analysis. In this method, alleles are separated into peaks, and their frequencies can be reliably and accurately quantified from their peak heights (SD <1.8%). We found that as many as 40% of publicly available SNPs that were analyzed by this method have widely differing allele frequency distributions among groups of different ethnicity (parents of Centre d'Etude Polymorphisme Humaine families vs. Japanese individuals). These results demonstrate the effectiveness of the present pooling method in the reevaluation of candidate SNPs that have been collected by examination of limited numbers of individuals. The method should also serve as a robust quantitative technique for studies in which a precise estimate of SNP allele frequencies is essential—for example, in linkage disequilibrium analysis. PMID:11083945

  4. Rényi entropy measure of noise-aided information transmission in a binary channel.

    PubMed

    Chapeau-Blondeau, François; Rousseau, David; Delahaies, Agnès

    2010-05-01

    This paper analyzes a binary channel by means of information measures based on the Rényi entropy. The analysis extends, and contains as a special case, the classic reference model of binary information transmission based on the Shannon entropy measure. The extended model is used to investigate further possibilities and properties of stochastic resonance or noise-aided information transmission. The results demonstrate that stochastic resonance occurs in the information channel and is registered by the Rényi entropy measures at any finite order, including the Shannon order. Furthermore, in definite conditions, when seeking the Rényi information measures that best exploit stochastic resonance, then nontrivial orders differing from the Shannon case usually emerge. In this way, through binary information transmission, stochastic resonance identifies optimal Rényi measures of information differing from the classic Shannon measure. A confrontation of the quantitative information measures with visual perception is also proposed in an experiment of noise-aided binary image transmission.

  5. Small passenger car transmission test-Chevrolet 200 transmission

    NASA Technical Reports Server (NTRS)

    Bujold, M. P.

    1980-01-01

    The small passenger car transmission was tested to supply electric vehicle manufacturers with technical information regarding the performance of commerically available transmissions which would enable them to design a more energy efficient vehicle. With this information the manufacturers could estimate vehicle driving range as well as speed and torque requirements for specific road load performance characteristics. A 1979 Chevrolet Model 200 automatic transmission was tested per a passenger car automatic transmission test code (SAE J651b) which required drive performance, coast performance, and no load test conditions. The transmission attained maximum efficiencies in the mid-eighty percent range for both drive performance tests and coast performance tests. Torque, speed and efficiency curves map the complete performance characteristics for Chevrolet Model 200 transmission.

  6. LD2SNPing: linkage disequilibrium plotter and RFLP enzyme mining for tag SNPs

    PubMed Central

    Chang, Hsueh-Wei; Chuang, Li-Yeh; Chang, Yan-Jhu; Cheng, Yu-Huei; Hung, Yu-Chen; Chen, Hsiang-Chi; Yang, Cheng-Hong

    2009-01-01

    Background Linkage disequilibrium (LD) mapping is commonly used to evaluate markers for genome-wide association studies. Most types of LD software focus strictly on LD analysis and visualization, but lack supporting services for genotyping. Results We developed a freeware called LD2SNPing, which provides a complete package of mining tools for genotyping and LD analysis environments. The software provides SNP ID- and gene-centric online retrievals for SNP information and tag SNP selection from dbSNP/NCBI and HapMap, respectively. Restriction fragment length polymorphism (RFLP) enzyme information for SNP genotype is available to all SNP IDs and tag SNPs. Single and multiple SNP inputs are possible in order to perform LD analysis by online retrieval from HapMap and NCBI. An LD statistics section provides D, D', r2, δQ, ρ, and the P values of the Hardy-Weinberg Equilibrium for each SNP marker, and Chi-square and likelihood-ratio tests for the pair-wise association of two SNPs in LD calculation. Finally, 2D and 3D plots, as well as plain-text output of the results, can be selected. Conclusion LD2SNPing thus provides a novel visualization environment for multiple SNP input, which facilitates SNP association studies. The software, user manual, and tutorial are freely available at . PMID:19500380

  7. Normal modes of a superconducting transmission-line resonator with embedded lumped element circuit components

    NASA Astrophysics Data System (ADS)

    Mortensen, Henrik Lund; Mølmer, Klaus; Andersen, Christian Kraglund

    2016-11-01

    We present a method to identify the coupled, normal modes of a superconducting transmission line with an embedded lumped element circuit. We evaluate the effective transmission-line nonlinearities in the case of Kerr-like Josephson interactions in the circuit and in the case where the embedded circuit constitutes a qubit degree of freedom, which is Rabi coupled to the field in the transmission line. Our theory quantitatively accounts for the very high and positive Kerr nonlinearities observed in a recent experiment [M. Rehák, P. Neilinger, M. Grajcar, G. Oelsner, U. Hübner, E. Il'ichev, and H.-G. Meyer, Appl. Phys. Lett. 104, 162604 (2014), 10.1063/1.4873719], and we can evaluate the accomplishments of modified versions of the experimental circuit.

  8. Summary of studies on the blue-green autofluorescence and light transmission of the ocular lens

    NASA Astrophysics Data System (ADS)

    Van Best, Jaap A.; Kuppens, Esmeralda V.

    1996-07-01

    This paper reviews previous work done to demonstrate the clinical relevance of the measurement of blue-green autofluorescence and light transmission of the ocular lens. These can be determined quantitatively with fluorophotometry in a few seconds. Autofluorescence and transmission values are determined in healthy volunteers, in patients with insulin-dependent diabetes mellitus, and in patients with untreated glaucoma or untreated ocular hypertension. The lens autofluorescence of healthy volunteers increased linearly and transmission decreased exponentially with age. Each year of diabetes induced an increase of autofluorescence equal to one extra year of age. Untreated glaucoma or ocular hypertension had no significant effect on lens autofluorescence and transmission. Increased autofluorescence and decreased transmission values in comparison with values of a healthy population are proved to be indicative for an increased risk of developing cataract and the clinical usefulness of these measures is demonstrated. Diabetes is a risk factor for developing cataracts while untreated glaucoma or ocular hypertension is not.

  9. BK virus has tropism for human salivary gland cells in vitro: Implications for transmission

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

    Jeffers, Liesl K.; Madden, Vicki; Webster-Cyriaque, Jennifer, E-mail: jennifer@med.unc.ed

    Background: In this study, it was determined that BKV is shed in saliva and an in vitro model system was developed whereby BKV can productively infect both submandibular (HSG) and parotid (HSY) salivary gland cell lines. Results: BKV was detected in oral fluids using quantitative real-time PCR (QRTPCR). BKV infection was determined using quantitative RT-PCR, immunofluorescence and immunoblotting assays. The infectivity of BKV was inhibited by pre-incubation of the virus with gangliosides that saturated the major capsid protein, VP1, halting receptor mediated BKV entry into salivary gland cells. Examination of infected cultures by transmission electron microscopy revealed 45-50 nm BKmore » virions clearly visible within the cells. Subsequent to infection, encapsidated BK virus was detected in the supernatant. Conclusion: We thus demonstrated that BKV was detected in oral fluids and that BK infection and replication occur in vitro in salivary gland cells. These data collectively suggest the potential for BKV oral route of transmission and oral pathogenesis.« less

  10. Linkage disequilibrium and signatures of positive selection around LINE-1 retrotransposons in the human genome.

    PubMed

    Kuhn, Alexandre; Ong, Yao Min; Cheng, Ching-Yu; Wong, Tien Yin; Quake, Stephen R; Burkholder, William F

    2014-06-03

    Insertions of the human-specific subfamily of LINE-1 (L1) retrotransposon are highly polymorphic across individuals and can critically influence the human transcriptome. We hypothesized that L1 insertions could represent genetic variants determining important human phenotypic traits, and performed an integrated analysis of L1 elements and single nucleotide polymorphisms (SNPs) in several human populations. We found that a large fraction of L1s were in high linkage disequilibrium with their surrounding genomic regions and that they were well tagged by SNPs. However, L1 variants were only partially captured by SNPs on standard SNP arrays, so that their potential phenotypic impact would be frequently missed by SNP array-based genome-wide association studies. We next identified potential phenotypic effects of L1s by looking for signatures of natural selection linked to L1 insertions; significant extended haplotype homozygosity was detected around several L1 insertions. This finding suggests that some of these L1 insertions may have been the target of recent positive selection.

  11. Patterns of Genetic Structure and Linkage Disequilibrium in a Large Collection of Pea Germplasm

    PubMed Central

    Siol, Mathieu; Jacquin, Françoise; Chabert-Martinello, Marianne; Smýkal, Petr; Le Paslier, Marie-Christine; Aubert, Grégoire; Burstin, Judith

    2017-01-01

    Pea (Pisum sativum, L.) is a major pulse crop used both for animal and human alimentation. Owing to its association with nitrogen-fixing bacteria, it is also a valuable component for low-input cropping systems. To evaluate the genetic diversity and the scale of linkage disequilibrium (LD) decay in pea, we genotyped a collection of 917 accessions, gathering elite cultivars, landraces, and wild relatives using an array of ∼13,000 single nucleotide polymorphisms (SNP). Genetic diversity is broadly distributed across three groups corresponding to wild/landraces peas, winter types, and spring types. At a finer subdivision level, genetic groups relate to local breeding programs and type usage. LD decreases steeply as genetic distance increases. When considering subsets of the data, LD values can be higher, even if the steep decay remains. We looked for genomic regions exhibiting high level of differentiation between wild/landraces, winter, and spring pea, respectively. Two regions on linkage groups 5 and 6 containing 33 SNPs exhibit stronger differentiation between winter and spring peas than would be expected under neutrality. Interestingly, QTL for resistance to cold acclimation and frost resistance have been identified previously in the same regions. PMID:28611254

  12. Population genomic structure and linkage disequilibrium analysis of South African goat breeds using genome-wide SNP data.

    PubMed

    Mdladla, K; Dzomba, E F; Huson, H J; Muchadeyi, F C

    2016-08-01

    The sustainability of goat farming in marginal areas of southern Africa depends on local breeds that are adapted to specific agro-ecological conditions. Unimproved non-descript goats are the main genetic resources used for the development of commercial meat-type breeds of South Africa. Little is known about genetic diversity and the genetics of adaptation of these indigenous goat populations. This study investigated the genetic diversity, population structure and breed relations, linkage disequilibrium, effective population size and persistence of gametic phase in goat populations of South Africa. Three locally developed meat-type breeds of the Boer (n = 33), Savanna (n = 31), Kalahari Red (n = 40), a feral breed of Tankwa (n = 25) and unimproved non-descript village ecotypes (n = 110) from four goat-producing provinces of the Eastern Cape, KwaZulu-Natal, Limpopo and North West were assessed using the Illumina Goat 50K SNP Bead Chip assay. The proportion of SNPs with minor allele frequencies >0.05 ranged from 84.22% in the Tankwa to 97.58% in the Xhosa ecotype, with a mean of 0.32 ± 0.13 across populations. Principal components analysis, admixture and pairwise FST identified Tankwa as a genetically distinct population and supported clustering of the populations according to their historical origins. Genome-wide FST identified 101 markers potentially under positive selection in the Tankwa. Average linkage disequilibrium was highest in the Tankwa (r(2)  = 0.25 ± 0.26) and lowest in the village ecotypes (r(2) range = 0.09 ± 0.12 to 0.11 ± 0.14). We observed an effective population size of <150 for all populations 13 generations ago. The estimated correlations for all breed pairs were lower than 0.80 at marker distances >100 kb with the exception of those in Savanna and Tswana populations. This study highlights the high level of genetic diversity in South African indigenous goats as well as the utility of the genome-wide SNP marker panels in

  13. 'Signs of disequilibrium chemistry in extrasolar hot-Jupiter type planets?'

    NASA Astrophysics Data System (ADS)

    Rocha, Graca; Swain, Mark; Line, Michael; West, Robert

    2018-01-01

    In the recent years Infrared spectroscopy of hot exoplanets has been revealing their atmospheric composition. For example the spectra of the planet HD189733b exhibits signatures of CH4, CO2, CO and H2O molecules (Swain et al 2008, 2009, etc.). The original 2008 detection of CH4 was a surprise because it is not thermochemically favored at the relatively high temperature (~1300 K) of the atmosphere of HD 189733b. More recent analysis of HD 189733b measurements (Swain, Line, Deroo 2014) implied a CH4 enhancement of ~1000x greater than has been assumed. Significantly more data has recently become available from WFC3 observations (Mccullah et al. 2014, Crozet at al. 2015) of this planet. In the meantime theoretical models by Moses et al. 2011 showed that large enhancement of quenched methane is possible due to transport if vertical eddy diffusion is significant.In this talk we will present results from a new study of CH4 enhancement in the atmosphere of HD189733b. We analysise the transit spectra of this planet obtained with the Hubble Space Telescope, combining the shorter wavelength 1.1-1.6 μm data from WFC3 measurements with the 1.5-2.4 μm data from NICMOS measurements. We also introduce a new methodology, implemented within a Bayesian framework, where hypothesis testing is conducted via evidence based model selection. Our analysis indicates, for the first time, that the observed excess of Methane in HD189733b’s atmosphere requires disequilibrium chemistry. However the Evidence has a modest discriminatory power amongst a subset of models. Furthermore our constraints confirm Swain et al. 2014 results with an excess of Methane with a mixing ratio of 10 2.26 ppm with EvidencelogZ=-58.602 +/- 0.109.

  14. Serotonin transporter gene polymorphisms and hyperserotonemia in autistic disorder

    PubMed Central

    Betancur, Catalina; Corbex, Marylis; Spielewoy, Cécile; Philippe, Anne; Laplanche, Jean-Louis; Launay, Jean-Marie; Gillberg, Christopher; Mouren-Simeoni, Marie-Christine; Hamon, Michel; Giros, Bruno; Nosten-Bertrand, Marika; Leboyer, Marion

    2002-01-01

    Previous studies have provided conflicting evidence regarding the association of the serotonin transporter (5-HTT) gene with autism. Two polymorphisms have been identified in the human 5-HTT gene, a VNTR in intron 21 and a functional deletion/insertion in the promoter region (5-HTTLPR) with short and long variants.2 Positive associations of the 5-HTTLPR polymorphism with autism have been reported by two family-based studies, but one found preferential transmission of the short allele3 and the other of the long allele.4 Two subsequent studies failed to find evidence of transmission disequilibrium at the 5-HTTLPR locus.5,6 These conflicting results could be due to heterogeneity of clinical samples with regard to serotonin (5-HT) blood levels, which have been found to be elevated in some autistic subjects.7–9 Thus, we examined the association of the 5-HTTLPR and VNTR polymorphisms of the 5-HTT gene with autism, and we investigated the relationship between 5-HTT variants and whole-blood 5-HT. The transmission/disequilibrium test (TDT) revealed no linkage disequilibrium at either loci in a sample of 96 families comprising 43 trios and 53 sib pairs. Furthermore, no significant relationship between 5-HT blood levels and 5-HTT gene polymorphisms was found. Our results suggest that the 5-HTT gene is unlikely to play a major role as a susceptibility factor in autism. PMID:11803447

  15. A Family-Based Association Study of CYP11A1 and CYP11B1 Gene Polymorphisms With Autism in Chinese Trios.

    PubMed

    Deng, Hong-Zhu; You, Cong; Xing, Yu; Chen, Kai-Yun; Zou, Xiao-Bing

    2016-05-01

    Autism spectrum disorder is a group of neurodevelopmental disorders with the higher prevalence in males. Our previous studies have indicated lower progesterone levels in the children with autism spectrum disorder, suggesting involvement of the cytochrome P-450scc gene (CYP11A1) and cytochrome P-45011beta gene (CYP11B1) as candidate genes in autism spectrum disorder. The aim of this study was to investigate the family-based genetic association between single-nucleotide polymorphisms, rs2279357 in the CYP11A1 gene and rs4534 and rs4541 in the CYP11B1 gene and autism spectrum disorder in Chinese children, which were selected according to the location in the coding region and 5' and 3' regions and minor allele frequencies of greater than 0.05 in the Chinese populations. The transmission disequilibrium test and case-control association analyses were performed in 100 Chinese Han autism spectrum disorder family trios. The genotype and allele frequency of the 3 single-nucleotide polymorphisms had no statistical difference between the children with autism spectrum disorder and their parents (P> .05). Transmission disequilibrium test analysis showed transmission disequilibrium of CYP11A1 gene rs2279357 single-nucleotide polymorphisms (χ(2)= 5.038,P< .001). Our findings provide further support for the hypothesis that a susceptibility gene for autism spectrum disorder exists within or near the CYP11A1 gene in the Han Chinese population. © The Author(s) 2015.

  16. Support of positive association in family-based genetic analysis between COL27A1 and Tourette syndrome.

    PubMed

    Liu, Shiguo; Yu, Xiaoxia; Xu, Quanchen; Cui, Jiajia; Yi, Mingji; Zhang, Xinhua; Ge, Yinlin; Ma, Xu

    2015-08-03

    Recently, a genome-wide association study has indicated associations between single nucleotide polymorphisms in the Collagen Type XXVII Alpha 1 gene (COL27A1) and Tourette syndrome in several ethnic populations. To clarify the global relevance of the previously identified SNPs in the development of Tourette syndrome, the associations between polymorphisms in COL27A1 and Tourette syndrome were assessed in Chinese trios. PCR-directed sequencing was used to evaluate the genetic contributions of three SNPs in COL27A1(rs4979356, rs4979357 and rs7868992) using haplotype relative risk (HRR) and transmission disequilibrium tests (TDT) with a total of 260 Tourette syndrome trios. The family-based association was significant between Tourette syndrome and rs4979356 (TDT: χ2 = 4.804, P = 0.033; HRR = 1.75, P = 0.002; HHRR = 1.32, P = 0.027), and transmission disequilibrium was suspected for rs4979357 (TDT: χ2 = 3.969, P = 0.053; HRR = 1.84, P = 0.001; HHRR = 1.29, P = 0.044). No statistically significant allele transfer was found for rs7868992 (TDT: χ2 = 2.177, P = 0.158). Although the TDT results did not remain significant after applying the conservative Bonferroni correction (p = 0.005), the significant positive HRR analysis confirmed the possibility of showing transmission disequilibrium, which provides evidence for an involvement of COL27A1in the development of TS. However, these results need to be verified with larger datasets from different populations.

  17. Quantifying the transmission potential of pandemic influenza

    NASA Astrophysics Data System (ADS)

    Chowell, Gerardo; Nishiura, Hiroshi

    2008-03-01

    This article reviews quantitative methods to estimate the basic reproduction number of pandemic influenza, a key threshold quantity to help determine the intensity of interventions required to control the disease. Although it is difficult to assess the transmission potential of a probable future pandemic, historical epidemiologic data is readily available from previous pandemics, and as a reference quantity for future pandemic planning, mathematical and statistical analyses of historical data are crucial. In particular, because many historical records tend to document only the temporal distribution of cases or deaths (i.e. epidemic curve), our review focuses on methods to maximize the utility of time-evolution data and to clarify the detailed mechanisms of the spread of influenza. First, we highlight structured epidemic models and their parameter estimation method which can quantify the detailed disease dynamics including those we cannot observe directly. Duration-structured epidemic systems are subsequently presented, offering firm understanding of the definition of the basic and effective reproduction numbers. When the initial growth phase of an epidemic is investigated, the distribution of the generation time is key statistical information to appropriately estimate the transmission potential using the intrinsic growth rate. Applications of stochastic processes are also highlighted to estimate the transmission potential using similar data. Critically important characteristics of influenza data are subsequently summarized, followed by our conclusions to suggest potential future methodological improvements.

  18. A Consensus Genetic Map for Pinus taeda and Pinus elliottii and Extent of Linkage Disequilibrium in Two Genotype-Phenotype Discovery Populations of Pinus taeda

    PubMed Central

    Westbrook, Jared W.; Chhatre, Vikram E.; Wu, Le-Shin; Chamala, Srikar; Neves, Leandro Gomide; Muñoz, Patricio; Martínez-García, Pedro J.; Neale, David B.; Kirst, Matias; Mockaitis, Keithanne; Nelson, C. Dana; Peter, Gary F.; Echt, Craig S.

    2015-01-01

    A consensus genetic map for Pinus taeda (loblolly pine) and Pinus elliottii (slash pine) was constructed by merging three previously published P. taeda maps with a map from a pseudo-backcross between P. elliottii and P. taeda. The consensus map positioned 3856 markers via genotyping of 1251 individuals from four pedigrees. It is the densest linkage map for a conifer to date. Average marker spacing was 0.6 cM and total map length was 2305 cM. Functional predictions of mapped genes were improved by aligning expressed sequence tags used for marker discovery to full-length P. taeda transcripts. Alignments to the P. taeda genome mapped 3305 scaffold sequences onto 12 linkage groups. The consensus genetic map was used to compare the genome-wide linkage disequilibrium in a population of distantly related P. taeda individuals (ADEPT2) used for association genetic studies and a multiple-family pedigree used for genomic selection (CCLONES). The prevalence and extent of LD was greater in CCLONES as compared to ADEPT2; however, extended LD with LGs or between LGs was rare in both populations. The average squared correlations, r2, between SNP alleles less than 1 cM apart were less than 0.05 in both populations and r2 did not decay substantially with genetic distance. The consensus map and analysis of linkage disequilibrium establish a foundation for comparative association mapping and genomic selection in P. taeda and P. elliottii. PMID:26068575

  19. Variation in Tomato spotted wilt virus titer in Frankliniella occidentalis and its association with frequency of transmission.

    PubMed

    Rotenberg, Dorith; Krishna Kumar, Nallur K; Ullman, Diane E; Montero-Astúa, Mauricio; Willis, David K; German, Thomas L; Whitfield, Anna E

    2009-04-01

    Tomato spotted wilt virus (TSWV) is transmitted in a persistent propagative manner by Frankliniella occidentalis, the western flower thrips. While it is well established that vector competence depends on TSWV acquisition by young larvae and virus replication within the insect, the biological factors associated with frequency of transmission have not been well characterized. We hypothesized that the number of transmission events by a single adult thrips is determined, in part, by the amount of virus harbored (titer) by the insect. Transmission time-course experiments were conducted using a leaf disk assay to determine the efficiency and frequency of TSWV transmission following 2-day inoculation access periods (IAPs). Virus titer in individual adult thrips was determined by real-time quantitative reverse transcriptase-PCR (qRT-PCR) at the end of the experiments. On average, 59% of adults transmitted the virus during the first IAP (2 to 3 days post adult-eclosion). Male thrips were more efficient at transmitting TSWV multiple times compared with female thrips of the same cohort. However, females harbored two to three times more copies of TSWV-N RNA per insect, indicating that factors other than absolute virus titer in the insect contribute to a successful transmission event. Examination of virus titer in individual insects at the end of the third IAP (7 days post adult-eclosion) revealed significant and consistent positive associations between frequency of transmission and virus titer. Our data support the hypothesis that a viruliferous thrips is more likely to transmit multiple times if it harbors a high titer of virus. This quantitative relationship provides new insights into the biological parameters that may influence the spread of TSWV by thrips.

  20. Small passenger car transmission test: Mercury Lynx ATX transmission

    NASA Technical Reports Server (NTRS)

    Bujold, M. P.

    1981-01-01

    The testing of a Mercury Lynx automatic transmission is reported. The transmission was tested in accordance with a passenger car automatic transmission test code (SAE J65lb) which required drive performance, coast performance, and no load test conditions. Under these conditions, the transmission attained maximum efficiencies in the mid-ninety percent range both for drive performance test and coast performance tests. The torque, speed, and efficiency curves are presented, which provide the complete performance characteristics for the Mercury Lynx automatic transmission.

  1. Transmission eigenvalues

    NASA Astrophysics Data System (ADS)

    Cakoni, Fioralba; Haddar, Houssem

    2013-10-01

    In inverse scattering theory, transmission eigenvalues can be seen as the extension of the notion of resonant frequencies for impenetrable objects to the case of penetrable dielectrics. The transmission eigenvalue problem is a relatively late arrival to the spectral theory of partial differential equations. Its first appearance was in 1986 in a paper by Kirsch who was investigating the denseness of far-field patterns for scattering solutions of the Helmholtz equation or, in more modern terminology, the injectivity of the far-field operator [1]. The paper of Kirsch was soon followed by a more systematic study by Colton and Monk in the context of developing the dual space method for solving the inverse scattering problem for acoustic waves in an inhomogeneous medium [2]. In this paper they showed that for a spherically stratified media transmission eigenvalues existed and formed a discrete set. Numerical examples were also given showing that in principle transmission eigenvalues could be determined from the far-field data. This first period of interest in transmission eigenvalues was concluded with papers by Colton et al in 1989 [3] and Rynne and Sleeman in 1991 [4] showing that for an inhomogeneous medium (not necessarily spherically stratified) transmission eigenvalues, if they existed, formed a discrete set. For the next seventeen years transmission eigenvalues were ignored. This was mainly due to the fact that, with the introduction of various sampling methods to determine the shape of an inhomogeneous medium from far-field data, transmission eigenvalues were something to be avoided and hence the fact that transmission eigenvalues formed at most a discrete set was deemed to be sufficient. In addition, questions related to the existence of transmission eigenvalues or the structure of associated eigenvectors were recognized as being particularly difficult due to the nonlinearity of the eigenvalue problem and the special structure of the associated transmission

  2. Genetic Structure, Linkage Disequilibrium and Association Mapping of Verticillium Wilt Resistance in Elite Cotton (Gossypium hirsutum L.) Germplasm Population

    PubMed Central

    Zhao, Yunlei; Wang, Hongmei; Chen, Wei; Li, Yunhai

    2014-01-01

    Understanding the population structure and linkage disequilibrium in an association panel can effectively avoid spurious associations and improve the accuracy in association mapping. In this study, one hundred and fifty eight elite cotton (Gossypium hirsutum L.) germplasm from all over the world, which were genotyped with 212 whole genome-wide marker loci and phenotyped with an disease nursery and greenhouse screening method, were assayed for population structure, linkage disequilibrium, and association mapping of Verticillium wilt resistance. A total of 480 alleles ranging from 2 to 4 per locus were identified from all collections. Model-based analysis identified two groups (G1 and G2) and seven subgroups (G1a–c, G2a–d), and differentiation analysis showed that subgroup having a single origin or pedigree was apt to differentiate with those having a mixed origin. Only 8.12% linked marker pairs showed significant LD (P<0.001) in this association panel. The LD level for linked markers is significantly higher than that for unlinked markers, suggesting that physical linkage strongly influences LD in this panel, and LD level was elevated when the panel was classified into groups and subgroups. The LD decay analysis for several chromosomes showed that different chromosomes showed a notable change in LD decay distances for the same gene pool. Based on the disease nursery and greenhouse environment, 42 marker loci associated with Verticillium wilt resistance were identified through association mapping, which widely were distributed among 15 chromosomes. Among which 10 marker loci were found to be consistent with previously identified QTLs and 32 were new unreported marker loci, and QTL clusters for Verticillium wilt resistanc on Chr.16 were also proved in our study, which was consistent with the strong linkage in this chromosome. Our results would contribute to association mapping and supply the marker candidates for marker-assisted selection of Verticillium wilt

  3. SU-E-T-554: Comparison of Electron Disequilibrium Factor in External Photon Beams for Different Models of Linear Accelerators

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

    LIU, B; Zhu, T

    Purpose: The dose in the buildup region of a photon beam is usually determined by the transport of the primary secondary electrons and the contaminating electrons from accelerator head. This can be quantified by the electron disequilibrium factor, E, defined as the ratio between total dose and equilibrium dose (proportional to total kerma), E = 1 in regions beyond buildup region. Ecan be different among accelerators of different models and/or manufactures of the same machine. This study compares E in photon beams from different machine models/ Methods: Photon beam data such as fractional depth dose curve (FDD) and phantom scattermore » factors as a function of field size and phantom depth were measured for different Linac machines. E was extrapolated from these fractional depth dose data while taking into account inverse-square law. The ranges of secondary electron were chosen as 3 and 6 cm for 6 and 15 MV photon beams, respectively. The field sizes range from 2x2 to 40x40 cm{sup 2}. Results: The comparison indicates the standard deviations of electron contamination among different machines are about 2.4 - 3.3% at 5 mm depth for 6 MV and 1.2 - 3.9% at 1 cm depth for 15 MV for the same field size. The corresponding maximum deviations are 3.0 - 4.6% and 2 - 4% for 6 and 15 MV, respectively. Both standard and maximum deviations are independent of field sizes in the buildup region for 6 MV photons, and slightly decreasing with increasing field size at depths up to 1 cm for 15 MV photons. Conclusion: The deviations of electron disequilibrium factor for all studied Linacs are less than 3% beyond the depth of 0.5 cm for the photon beams for the full range of field sizes (2-40 cm) so long as they are from the same manufacturer.« less

  4. Small passenger car transmission test; Chevrolet LUV transmission

    NASA Technical Reports Server (NTRS)

    Bujold, M. P.

    1980-01-01

    A 1978 Chevrolet LUV manual transmission tested per the applicable portions of a passenger car automatic transmission test code (SAE J65lb) which required drive performance, coast performance, and no load test conditions. Under these test conditions, the transmission attained maximum efficiencies in the upper ninety percent range for both drive performance tests and coast performance tests. The major results of this test (torque, speed, and efficiency curves) are presented. Graphs map the complete performance characteristics for the Chevrolet LUV transmission.

  5. A linkage and family-based association analysis of a potential neurocognitive endophenotype of bipolar disorder.

    PubMed

    Savitz, Jonathan; van der Merwe, Lize; Solms, Mark; Ramesar, Rajkumar

    2007-01-01

    The identification of the genetic variants underpinning bipolar disorder (BPD) has been impeded by a complex pattern of inheritance characterized by genetic and phenotypic heterogeneity, genetic epistasis, and gene-environment interactions. In this paper two strategies were used to ameliorate these confounding factors. A unique South African sample including 190 individuals of the relatively, reproductively isolated Afrikaner population was assessed with a battery of neuropsychological tests in an attempt to identify a BPD-associated quantitative trait or endophenotype. BPD individuals performed significantly worse than their unaffected relatives on visual and verbal memory tasks, a finding congruent with the literature. Afocused linkage and family-based association study was carried out using this memory-related endophenotype. In the largest 77-strong Afrikaner pedigree significant evidence for linkage was detected on chromosome 22q11, a region previously implicated in BPD. The quantitative transmission disequilibrium tests-based association analysis suggested that functional variants of the DRD4 and MAO-A genes modulate memory-related cognition. We speculate that polymorphisms at these loci may predispose to a subtype of BPD characterized by memory-related deficits.

  6. Exploring the interactome: microfluidic isolation of proteins and interacting partners for quantitative analysis by electron microscopy.

    PubMed

    Giss, Dominic; Kemmerling, Simon; Dandey, Venkata; Stahlberg, Henning; Braun, Thomas

    2014-05-20

    Multimolecular protein complexes are important for many cellular processes. However, the stochastic nature of the cellular interactome makes the experimental detection of complex protein assemblies difficult and quantitative analysis at the single molecule level essential. Here, we present a fast and simple microfluidic method for (i) the quantitative isolation of endogenous levels of untagged protein complexes from minute volumes of cell lysates under close to physiological conditions and (ii) the labeling of specific components constituting these complexes. The method presented uses specific antibodies that are conjugated via a photocleavable linker to magnetic beads that are trapped in microcapillaries to immobilize the target proteins. Proteins are released by photocleavage, eluted, and subsequently analyzed by quantitative transmission electron microscopy at the single molecule level. Additionally, before photocleavage, immunogold can be employed to label proteins that interact with the primary target protein. Thus, the presented method provides a new way to study the interactome and, in combination with single molecule transmission electron microscopy, to structurally characterize the large, dynamic, heterogeneous multimolecular protein complexes formed.

  7. Zika virus transmission to mouse ear by mosquito bite: a laboratory model that replicates the natural transmission process.

    PubMed

    Secundino, Nagila Francinete Costa; Chaves, Barbara Aparecida; Orfano, Alessandra Silva; Silveira, Karine Renata Dias; Rodrigues, Nilton Barnabe; Campolina, Thais Bonifácio; Nacif-Pimenta, Rafael; Villegas, Luiz Eduardo Martinez; Silva, Breno Melo; Lacerda, Marcus Vinícius Guimarães; Norris, Douglas Eric; Pimenta, Paulo Filemon Paolucci

    2017-07-20

    Zika disease has transformed into a serious global health problem due to the rapid spread of the arbovirus and alarming severity including congenital complications, microcephaly and Guillain-Barré syndrome. Zika virus (ZIKV) is primarily transmitted to humans through the bite of an infective mosquito, with Aedes aegypti being the main vector. We successfully developed a ZIKV experimental transmission model by single infectious Ae. aegypti bite to a laboratory mouse using circulating Brazilian strains of both arbovirus and vector. Mosquitoes were orally infected and single Ae. aegypti were allowed to feed on mouse ears 14 days post-infection. Additionally, salivary gland (SG) homogenates from infected mosquitoes were intrathoracically inoculated into naïve Ae. aegypti. Mosquito and mouse tissue samples were cultured in C6/36 cells and processed by quantitative real-time PCR. A total of 26 Ae. aegypti were allowed to feed individually on mouse ears. Of these, 17 mosquitoes fed, all to full engorgement. The transmission rate of ZIKV by bite from these engorged mosquitoes to mouse ears was 100%. The amount of virus inoculated into the ears by bites ranged from 2 × 10 2 -2.1 × 10 10 ZIKV cDNA copies and was positively correlated with ZIKV cDNA quantified from SGs dissected from mosquitoes post-feeding. Replicating ZIKV was confirmed in macerated SGs (2.45 × 10 7 cDNA copies), mouse ear tissue (1.15 × 10 3 cDNA copies, and mosquitoes 14 days post-intrathoracic inoculation (1.49 × 10 7 cDNA copies) by cytopathic effect in C6/36 cell culture and qPCR. Our model illustrates successful transmission of ZIKV by an infectious mosquito bite to a live vertebrate host. This approach offers a comprehensive tool for evaluating the development of infection in and transmission from mosquitoes, and the vertebrate-ZIKV interaction and progression of infection following a natural transmission process.

  8. Quantitative contrast-enhanced ultrasound imaging: a review of sources of variability

    PubMed Central

    Tang, M.-X.; Mulvana, H.; Gauthier, T.; Lim, A. K. P.; Cosgrove, D. O.; Eckersley, R. J.; Stride, E.

    2011-01-01

    Ultrasound provides a valuable tool for medical diagnosis offering real-time imaging with excellent spatial resolution and low cost. The advent of microbubble contrast agents has provided the additional ability to obtain essential quantitative information relating to tissue vascularity, tissue perfusion and even endothelial wall function. This technique has shown great promise for diagnosis and monitoring in a wide range of clinical conditions such as cardiovascular diseases and cancer, with considerable potential benefits in terms of patient care. A key challenge of this technique, however, is the existence of significant variations in the imaging results, and the lack of understanding regarding their origin. The aim of this paper is to review the potential sources of variability in the quantification of tissue perfusion based on microbubble contrast-enhanced ultrasound images. These are divided into the following three categories: (i) factors relating to the scanner setting, which include transmission power, transmission focal depth, dynamic range, signal gain and transmission frequency, (ii) factors relating to the patient, which include body physical differences, physiological interaction of body with bubbles, propagation and attenuation through tissue, and tissue motion, and (iii) factors relating to the microbubbles, which include the type of bubbles and their stability, preparation and injection and dosage. It has been shown that the factors in all the three categories can significantly affect the imaging results and contribute to the variations observed. How these factors influence quantitative imaging is explained and possible methods for reducing such variations are discussed. PMID:22866229

  9. HIV Transmission

    PubMed Central

    Shaw, George M.; Hunter, Eric

    2012-01-01

    HIV-1 is transmitted by sexual contact across mucosal surfaces, by maternal-infant exposure, and by percutaneous inoculation. For reasons that are still incompletely understood, CCR5-tropic viruses (R5 viruses) are preferentially transmitted by all routes. Transmission is followed by an orderly appearance of viral and host markers of infection in the blood plasma. In the acute phase of infection, HIV-1 replicates exponentially and diversifies randomly, allowing for an unambiguous molecular identification of transmitted/founder virus genomes and a precise characterization of the population bottleneck to virus transmission. Sexual transmission of HIV-1 most often results in productive clinical infection arising from a single virus, highlighting the extreme bottleneck and inherent inefficiency in virus transmission. It remains to be determined if HIV-1 transmission is largely a stochastic process whereby any reasonably fit R5 virus can be transmitted or if there are features of transmitted/founder viruses that facilitate their transmission in a biologically meaningful way. Human tissue explant models of HIV-1 infection and animal models of SIV/SHIV/HIV-1 transmission, coupled with new challenge virus strains that more closely reflect transmitted/founder viruses, have the potential to elucidate fundamental mechanisms in HIV-1 transmission relevant to vaccine design and other prevention strategies. PMID:23043157

  10. Using quantitative disease dynamics as a tool for guiding response to avian influenza in poultry in the United States of America☆

    PubMed Central

    Pepin, K.M.; Spackman, E.; Brown, J.D.; Pabilonia, K.L.; Garber, L.P.; Weaver, J.T.; Kennedy, D.A.; Patyk, K.A.; Huyvaert, K.P.; Miller, R.S.; Franklin, A.B.; Pedersen, K.; Bogich, T.L.; Rohani, P.; Shriner, S.A.; Webb, C.T.; Riley, S.

    2014-01-01

    Wild birds are the primary source of genetic diversity for influenza A viruses that eventually emerge in poultry and humans. Much progress has been made in the descriptive ecology of avian influenza viruses (AIVs), but contributions are less evident from quantitative studies (e.g., those including disease dynamic models). Transmission between host species, individuals and flocks has not been measured with sufficient accuracy to allow robust quantitative evaluation of alternate control protocols. We focused on the United States of America (USA) as a case study for determining the state of our quantitative knowledge of potential AIV emergence processes from wild hosts to poultry. We identified priorities for quantitative research that would build on existing tools for responding to AIV in poultry and concluded that the following knowledge gaps can be addressed with current empirical data: (1) quantification of the spatio-temporal relationships between AIV prevalence in wild hosts and poultry populations, (2) understanding how the structure of different poultry sectors impacts within-flock transmission, (3) determining mechanisms and rates of between-farm spread, and (4) validating current policy-decision tools with data. The modeling studies we recommend will improve our mechanistic understanding of potential AIV transmission patterns in USA poultry, leading to improved measures of accuracy and reduced uncertainty when evaluating alternative control strategies. PMID:24462191

  11. Using quantitative disease dynamics as a tool for guiding response to avian influenza in poultry in the United States of America.

    PubMed

    Pepin, K M; Spackman, E; Brown, J D; Pabilonia, K L; Garber, L P; Weaver, J T; Kennedy, D A; Patyk, K A; Huyvaert, K P; Miller, R S; Franklin, A B; Pedersen, K; Bogich, T L; Rohani, P; Shriner, S A; Webb, C T; Riley, S

    2014-03-01

    Wild birds are the primary source of genetic diversity for influenza A viruses that eventually emerge in poultry and humans. Much progress has been made in the descriptive ecology of avian influenza viruses (AIVs), but contributions are less evident from quantitative studies (e.g., those including disease dynamic models). Transmission between host species, individuals and flocks has not been measured with sufficient accuracy to allow robust quantitative evaluation of alternate control protocols. We focused on the United States of America (USA) as a case study for determining the state of our quantitative knowledge of potential AIV emergence processes from wild hosts to poultry. We identified priorities for quantitative research that would build on existing tools for responding to AIV in poultry and concluded that the following knowledge gaps can be addressed with current empirical data: (1) quantification of the spatio-temporal relationships between AIV prevalence in wild hosts and poultry populations, (2) understanding how the structure of different poultry sectors impacts within-flock transmission, (3) determining mechanisms and rates of between-farm spread, and (4) validating current policy-decision tools with data. The modeling studies we recommend will improve our mechanistic understanding of potential AIV transmission patterns in USA poultry, leading to improved measures of accuracy and reduced uncertainty when evaluating alternative control strategies. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

  12. Estimation of linkage disequilibrium and analysis of genetic diversity in Korean chicken lines.

    PubMed

    Seo, Dongwon; Lee, Doo Ho; Choi, Nuri; Sudrajad, Pita; Lee, Seung-Hwan; Lee, Jun-Heon

    2018-01-01

    The development of genetic markers for animal breeding is an effective strategy to reduce the time and cost required to improve economically important traits. To implement genomic selection in the multibreed chicken population of Korea, an understanding of the linkage disequilibrium (LD) status of the target population is essential. In this study, we performed population genetic analyses to investigate LD decay, the effective population size, and breed diversity using 600K high-density single nucleotide polymorphism genotypes of 189 native chickens in 14 lines (including Korean native chicken, imported and adapted purebred and commercial chickens). The results indicated that commercial native chickens have less calculated LD (average, r2 = 0.13-0.26) and purebred native chickens have more calculated LD (average, r2 = 0.24-0.37) across the entire genome. The effective population sizes of the examined lines showed patterns opposite to those of population LD. The phylogeny and admixture analyses showed that commercial and purebred chickens were well distinguished, except for Rhode Island Red (RIR) purebred lines of NC (NIAS_RIR_C) and ND (NIAS_RIR_D). These lines are difficult to distinguish clearly because they originated from the same respective breeds. The results of this study may provide important information for the development of genetic markers that can be used in breeding to improve the economic traits of native chickens.

  13. Estimation of linkage disequilibrium and analysis of genetic diversity in Korean chicken lines

    PubMed Central

    Seo, Dongwon; Lee, Doo Ho; Choi, Nuri; Sudrajad, Pita; Lee, Seung-Hwan

    2018-01-01

    The development of genetic markers for animal breeding is an effective strategy to reduce the time and cost required to improve economically important traits. To implement genomic selection in the multibreed chicken population of Korea, an understanding of the linkage disequilibrium (LD) status of the target population is essential. In this study, we performed population genetic analyses to investigate LD decay, the effective population size, and breed diversity using 600K high-density single nucleotide polymorphism genotypes of 189 native chickens in 14 lines (including Korean native chicken, imported and adapted purebred and commercial chickens). The results indicated that commercial native chickens have less calculated LD (average, r2 = 0.13–0.26) and purebred native chickens have more calculated LD (average, r2 = 0.24–0.37) across the entire genome. The effective population sizes of the examined lines showed patterns opposite to those of population LD. The phylogeny and admixture analyses showed that commercial and purebred chickens were well distinguished, except for Rhode Island Red (RIR) purebred lines of NC (NIAS_RIR_C) and ND (NIAS_RIR_D). These lines are difficult to distinguish clearly because they originated from the same respective breeds. The results of this study may provide important information for the development of genetic markers that can be used in breeding to improve the economic traits of native chickens. PMID:29425208

  14. Recent advances in the application of transmission Raman spectroscopy to pharmaceutical analysis.

    PubMed

    Buckley, Kevin; Matousek, Pavel

    2011-06-25

    This article reviews recent advances in transmission Raman spectroscopy and its applications, from the perspective of pharmaceutical analysis. The emerging concepts enable rapid non-invasive volumetric analysis of pharmaceutical formulations and could lead to many important applications in pharmaceutical settings, including quantitative bulk analysis of intact pharmaceutical tablets and capsules in quality and process control. Crown Copyright © 2010. Published by Elsevier B.V. All rights reserved.

  15. Genome-wide patterns of recombination, linkage disequilibrium and nucleotide diversity from pooled resequencing and single nucleotide polymorphism genotyping unlock the evolutionary history of Eucalyptus grandis.

    PubMed

    Silva-Junior, Orzenil B; Grattapaglia, Dario

    2015-11-01

    We used high-density single nucleotide polymorphism (SNP) data and whole-genome pooled resequencing to examine the landscape of population recombination (ρ) and nucleotide diversity (ϴw ), assess the extent of linkage disequilibrium (r(2) ) and build the highest density linkage maps for Eucalyptus. At the genome-wide level, linkage disequilibrium (LD) decayed within c. 4-6 kb, slower than previously reported from candidate gene studies, but showing considerable variation from absence to complete LD up to 50 kb. A sharp decrease in the estimate of ρ was seen when going from short to genome-wide inter-SNP distances, highlighting the dependence of this parameter on the scale of observation adopted. Recombination was correlated with nucleotide diversity, gene density and distance from the centromere, with hotspots of recombination enriched for genes involved in chemical reactions and pathways of the normal metabolic processes. The high nucleotide diversity (ϴw = 0.022) of E. grandis revealed that mutation is more important than recombination in shaping its genomic diversity (ρ/ϴw = 0.645). Chromosome-wide ancestral recombination graphs allowed us to date the split of E. grandis (1.7-4.8 million yr ago) and identify a scenario for the recent demographic history of the species. Our results have considerable practical importance to Genome Wide Association Studies (GWAS), while indicating bright prospects for genomic prediction of complex phenotypes in eucalypt breeding. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

  16. Comparison of cluster-based and source-attribution methods for estimating transmission risk using large HIV sequence databases.

    PubMed

    Le Vu, Stéphane; Ratmann, Oliver; Delpech, Valerie; Brown, Alison E; Gill, O Noel; Tostevin, Anna; Fraser, Christophe; Volz, Erik M

    2018-06-01

    Phylogenetic clustering of HIV sequences from a random sample of patients can reveal epidemiological transmission patterns, but interpretation is hampered by limited theoretical support and statistical properties of clustering analysis remain poorly understood. Alternatively, source attribution methods allow fitting of HIV transmission models and thereby quantify aspects of disease transmission. A simulation study was conducted to assess error rates of clustering methods for detecting transmission risk factors. We modeled HIV epidemics among men having sex with men and generated phylogenies comparable to those that can be obtained from HIV surveillance data in the UK. Clustering and source attribution approaches were applied to evaluate their ability to identify patient attributes as transmission risk factors. We find that commonly used methods show a misleading association between cluster size or odds of clustering and covariates that are correlated with time since infection, regardless of their influence on transmission. Clustering methods usually have higher error rates and lower sensitivity than source attribution method for identifying transmission risk factors. But neither methods provide robust estimates of transmission risk ratios. Source attribution method can alleviate drawbacks from phylogenetic clustering but formal population genetic modeling may be required to estimate quantitative transmission risk factors. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  17. Small passenger car transmission test: Dodge Omni A-404 transmission

    NASA Technical Reports Server (NTRS)

    Bujold, M. P.

    1980-01-01

    The small passenger car transmission test was initiated to supply electric vehicle manufacturers with technical information regarding the performance of commercially available transmissions. This transmission was tested in accordance with a passenger car automatic transmission test code (SAE J65lb) which required drive performance, coast performance, and no load test conditions. Under these test conditions, the transmission attained maximum efficiencies in the mid eighty percent range for both drive performance test and coast performance tests.

  18. Quantitative risk assessment of WSSV transmission through partial harvesting and transport practices for shrimp aquaculture in Mexico.

    PubMed

    Sanchez-Zazueta, Edgar; Martínez-Cordero, Francisco Javier; Chávez-Sánchez, María Cristina; Montoya-Rodríguez, Leobardo

    2017-10-01

    This quantitative risk assessment provided an analytical framework to estimate white spot syndrome virus (WSSV) transmission risks in the following different scenarios: (1) partial harvest from rearing ponds and (2) post-harvest transportation, assuming that the introduction of contaminated water with viral particles into shrimp culture ponds is the main source of viral transmission risk. Probabilities of infecting shrimp with waterborne WSSV were obtained by approaching the functional form that best fits (likelihood ratio test) published data on the dose-response relationship for WSSV orally inoculated through water into shrimp. Expert opinion defined the ranges for the following uncertain factors: (1) the concentrations of WSSV in the water spilled from the vehicles transporting the infected shrimp, (2) the total volume of these spills, and (3) the dilution into culture ponds. Multiple scenarios were analysed, starting with a viral load (VL) of 1×10 2 mL -1 in the contaminated water spilled that reached the culture pond, whose probability of infection of an individual shrimp (P i ) was negligible (1.7×10 -7 ). Increasing the VL to 1×10 4.5 mL -1 and 1×10 7 mL -1 yielded results into very low (P i =5.3×10 -5 ) and high risk (P i =1.6×10 -2 ) categories, respectively. Furthermore, different pond stocking density (SD) scenarios (20 and 30 post-larvae [PL]/m 2 ) were evaluated, and the probability of infection of at least one out of the total number of shrimp exposed (P N ) was derived; for the scenarios with a low VL (1×10 2 mL -1 ), the P N remained at a negligible risk level (P N , 2.4×10 -7 to 1.8×10 -6 ). For most of the scenarios with the moderate VL (1×10 4.5 mL -1 ), the P N scaled up to a low risk category (P N , 1.1×10 -4 to 5.6×10 -4 ), whereas for the scenarios with a high VL (1×10 7 mL -1 ), the risk levels were high (P N , 2.3×10 -2 to 3.5×10 -2 ) or very high (P N , 1.1×10 -1 to 1.6×10 -1 ) depending on the volume of contaminated water

  19. Information extraction and transmission techniques for spaceborne synthetic aperture radar images

    NASA Technical Reports Server (NTRS)

    Frost, V. S.; Yurovsky, L.; Watson, E.; Townsend, K.; Gardner, S.; Boberg, D.; Watson, J.; Minden, G. J.; Shanmugan, K. S.

    1984-01-01

    Information extraction and transmission techniques for synthetic aperture radar (SAR) imagery were investigated. Four interrelated problems were addressed. An optimal tonal SAR image classification algorithm was developed and evaluated. A data compression technique was developed for SAR imagery which is simple and provides a 5:1 compression with acceptable image quality. An optimal textural edge detector was developed. Several SAR image enhancement algorithms have been proposed. The effectiveness of each algorithm was compared quantitatively.

  20. Heritability and Familiality of Temperament and Character Dimensions in Korean Families with Schizophrenic Linkage Disequilibrium.

    PubMed

    Lee, Byung Dae; Park, Je Min; Lee, Young Min; Moon, Eunsoo; Jeong, Hee Jeong; Chung, Young In; Yi, Young Mi

    2016-05-31

    Categorical syndromes such as schizophrenia may represent complexes of many continuous psychological structural phenotypes along several dimensions of personality development/degeneration. The present study investigated the heritability and familiality of personality dimensions in Korean families with schizophrenic linkage disequilibrium (LD). We recruited 179 probands (with schizophrenia) as well as, whenever possible, their parents and siblings. We used the Temperament and Character Inventory (TCI) to measure personality and symptomatic dimensions. The heritability of personality dimensions in a total of 472 family members was estimated using Sequential Oligogenic Linkage Analysis Routines (SOLAR). To measure familiality, we compared the personality dimensions of family members with those of 336 healthy unrelated controls using analysis of variance (ANOVA) analysis. Three of the seven TCI variables were significantly heritable and were included in subsequent analyses. The three groups (control, unaffected first-degree relative, case) were found to significantly differ from one another, with the expected order of average group scores, for all heritable dimensions. Despite several study limitations with respect to family recruitment and phenotyping, our results show that aberrations in several personality dimensions related to genetic-environment coactions or interactions may underlie the complexity of the schizophrenic syndrome.

  1. On the transmission of terahertz radiation through silicon-based structures

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

    Persano, Anna, E-mail: anna.persano@le.imm.cnr.it; Francioso, Luca; Cola, Adriano

    2014-07-28

    We report on the transmission of a terahertz (THz) radiation through prototype structures based on a p-type silicon substrate. In particular, the bare substrate and progressively more complicated multilayer structures were investigated, allowing to address the effect on the transmission of different factors, such as the orientation of interdigitated contacts with respect to the polarized beam, the temperature, and the current flowing through a conductive SnO{sub 2} nanorods layer. A suitable experimental set-up was developed for the direct spectral measurement of transmission in the range of 0.75–1.1 THz at room and low temperatures. A simple Drude-Lorentz model was formulated, findingmore » a quantitative agreement with the experimental transmission spectrum of the bare substrate at room temperature. For the multilayer structures, the spectra variations observed with temperature are well accounted by the corresponding change of the mobility of holes in the silicon p-type substrate. The influence of the contact orientation is consistent with that of a polarizing metallic grating. Finally, Joule heating effects are observed in the spectra performed as a function of the current flowing through the SnO{sub 2} nanorods layer. The experimental results shown here, together with their theoretical interpretation, provide insights for the development of devices fabricated on conductive substrates aimed to absorb/modulate radiation in the THz range.« less

  2. How do tympanic-membrane perforations affect human middle-ear sound transmission?

    PubMed

    Voss, S E; Rosowski, J J; Merchant, S N; Peake, W T

    2001-01-01

    Although tympanic-membrane (TM) perforations are common sequelae of middle-ear disease, the hearing losses they cause have not been accurately determined, largely because additional pathological conditions occur in these ears. Our measurements of acoustic transmission before and after making controlled perforations in cadaver ears show that perforations cause frequency-dependent loss that: (1) is largest at low frequencies; (2) increases as perforation size increases; and (3) does not depend on perforation location. The dominant loss mechanism is the reduction in sound-pressure difference across the TM. Measurements of middle-ear air-space sound pressures show that transmission via direct acoustic stimulation of the oval and round windows is generally negligible. A quantitative model predicts the influence of middle-ear air-space volume on loss; with larger volumes, loss is smaller.

  3. Nitrogen Isotopic Disequilibrium in the Cape York III A Iron

    NASA Astrophysics Data System (ADS)

    Zipfel, J.; Kim, Y.; Marti, K.

    1995-09-01

    disequilibrium as observed in Cape York include (a) survival of primary isotopic heterogeneities; (b) N loss during secondary processes, e.g., metamorphic heating and shock deformation: (a) Graphite grains within metal of the Acapulco meteorite were identified as carrier of isotopically distinct N and C components and were interpreted as surviving (possibly presolar) grains unaffected by the igneous alteration of the bulk meteorite (5). Obviously such grains exchanged N isotopically with metal and chromite, but not with sulfides and silicates, as these do not carry the light N of metal and chromite (6). The mechanism of this exchange is, however, unclear. No graphite has been observed so far in Cape York. Yet, isotopic heterogeneities in the precursor material of Cape York can not be excluded. During melting of the parent asteroid one would expect homogenization of the nitrogen isotopes. Since chromite and metal crystallize at high temperatures, a probable exchange of N between the S-rich melt and a distinct N reservoir at lower temperature might explain the disequilibrium. (b) Troilite nodules in Cape York indicate a small degree of shock deformation (2,3,5). One might argue that some N was lost and the residue fractionated during this event. However, 107Ag/109Ag ratios from metal and troilite correlate with Pd/Ag ratios, which is not the case in severely shocked magmatic irons (7). In addition, similar isotopic N fractionations are found in the "magmatic" Acapulco meteorite, which shows no indication of shock deformation. Therefore, secondary loss of N preferentially from troilite can be excluded. References: [1] Haak H. and Scott E. (1993) GCA, 57, 3457-3472. [2] Buchwald V. (1975) Handbook of Iron Meteorites, Vols. 1_3, Univ. of California and Arizona State Univ., Berkeley. [3] Kracher A et al. (1977) Geochem. J., 11, 207-217. [4] Murty S. and Marti K. (1994) GCA, 58, 1841-1848. [5] El Goresy A. et al. (1995) Nature, 373, 496-499. [6] Kim Y. et al. (1992) LPS XXIII, 691

  4. The improbable transmission of Trypanosoma cruzi to human: the missing link in the dynamics and control of Chagas disease.

    PubMed

    Nouvellet, Pierre; Dumonteil, Eric; Gourbière, Sébastien

    2013-11-01

    Chagas disease has a major impact on human health in Latin America and is becoming of global concern due to international migrations. Trypanosoma cruzi, the etiological agent of the disease, is one of the rare human parasites transmitted by the feces of its vector, as it is unable to reach the salivary gland of the insect. This stercorarian transmission is notoriously poorly understood, despite its crucial role in the ecology and evolution of the pathogen and the disease. The objective of this study was to quantify the probability of T. cruzi vectorial transmission to humans, and to use such an estimate to predict human prevalence from entomological data. We developed several models of T. cruzi transmission to estimate the probability of transmission from vector to host. Using datasets from the literature, we estimated the probability of transmission per contact with an infected triatomine to be 5.8 × 10(-4) (95%CI: [2.6 ; 11.0] × 10(-4)). This estimate was consistent across triatomine species, robust to variations in other parameters, and corresponded to 900-4,000 contacts per case. Our models subsequently allowed predicting human prevalence from vector abundance and infection rate in 7/10 independent datasets covering various triatomine species and epidemiological situations. This low probability of T. cruzi transmission reflected well the complex and unlikely mechanism of transmission via insect feces, and allowed predicting human prevalence from basic entomological data. Although a proof of principle study would now be valuable to validate our models' predictive ability in an even broader range of entomological and ecological settings, our quantitative estimate could allow switching the evaluation of disease risk and vector control program from purely entomological indexes to parasitological measures, as commonly done for other major vector borne diseases. This might lead to different quantitative perspectives as these indexes are well known not to be

  5. Knowledge transmission model with differing initial transmission and retransmission process

    NASA Astrophysics Data System (ADS)

    Wang, Haiying; Wang, Jun; Small, Michael

    2018-10-01

    Knowledge transmission is a cyclic dynamic diffusion process. The rate of acceptance of knowledge differs upon whether or not the recipient has previously held the knowledge. In this paper, the knowledge transmission process is divided into an initial and a retransmission procedure, each with its own transmission and self-learning parameters. Based on epidemic spreading model, we propose a naive-evangelical-agnostic (VEA) knowledge transmission model and derive mean-field equations to describe the dynamics of knowledge transmission in homogeneous networks. Theoretical analysis identifies a criterion for the persistence of knowledge, i.e., the reproduction number R0 depends on the minor effective parameters between the initial and retransmission process. Moreover, the final size of evangelical individuals is only related to retransmission process parameters. Numerical simulations validate the theoretical analysis. Furthermore, the simulations indicate that increasing the initial transmission parameters, including first transmission and self-learning rates of naive individuals, can accelerate the velocity of knowledge transmission efficiently but have no effect on the final size of evangelical individuals. In contrast, the retransmission parameters, including retransmission and self-learning rates of agnostic individuals, have a significant effect on the rate of knowledge transmission, i.e., the larger parameters the greater final density of evangelical individuals.

  6. The Isotopologue Record of Repeat Vital Effect Offenders: Tracking (Dis)equilibrium Effects in Sea Urchins and Nannofossil Using Clumped Isotopes

    NASA Astrophysics Data System (ADS)

    John, C. M.; Davies, A.; Drury, A. J.

    2016-12-01

    Vital effects vary between species and affect various isotopic systems in unequal proportion. The magnitude of the response of different isotopic systems might thus be key in understanding biologically-mediated disequilibrium, especially in groups that show a tendency to be "repeat offenders" with regards to vital effects. Here we present carbon, oxygen, and clumped isotope data from echinoderm calcite and nannofossil ooze, both of which exhibit strong vital effects in bulk isotopes. Our study is the first to investigate the clumped isotope (dis)equilibrium of echinoids. Results from two echinoids, three marine gastropods and a bivalve mollusk from modern beach deposits of Bali, Indonesia, highlight a significant offset in clumped isotopes of a regular echinoid test from expected values, interpreted as evidence of a similar "vital effect" as observed in surface corals. This is in contrast to the test of an irregular "sand dollar" echinoid, with clumped isotope values within error of expected sea surface temperature. Furthermore, data on the inter-skeletal variability in the clumped isotopic composition of two regular echinoid species shows that the spines of the echinoids are in equilibrium with seawater with respect to clumped isotopes, but the test is not. For the nannofossil material, no clumped isotope vital effects are observed, consistent with previously published studies but at odds with strong vital effects in carbon and oxygen isotopes, often correlated with cell-size. In addition, we reveal that the <63 micron fraction of deep-sea ooze could constitute useful material for clumped isotope studies. An intriguing result of our study is that vital effects are mostly absent in clumped isotopes, even in phylums known for important isotopic effects. It remains to be explained why some parts of the echinoids show clear vital effects, notably enrichment in clumped isotopes of urchin tests. Mechanisms that could explain this include pH effects during calcification

  7. Sulfur isotopic disequilibrium and fluid-rock interaction during metamorphism of sulfidic black shales from the Waterville-Augusta area, Maine, USA

    USGS Publications Warehouse

    Oliver, N.H.S.; Hoering, T.C.; Johnson, T.W.; Rumble, D.; Shanks, Wayne C.

    1992-01-01

    Sulfur isotope ratios of pyrite (py) and pyrrhotite (po) from regionally metamorphosed graphitic sulfidic schists and related rocks from south-central Maine, USA, were analysed using SO2 and SF6 techniques. There is a broad range in ??34S values for both pyrite and pyrrhotite at most outcrops, up to 8%. and overall the values are isotopically light, averaging ~ -27??? for the entire data set, suggesting that the rocks have not been grossly isotopically disturbed by regional metamorphism from their inferred organic-rich sedimentary origins. At all temperatures from chlorite to sillimanite grades, sulfide analysed from veins and blebs within the schists show predominantly disequilibrium fractionations ranging from ??34Spy-po -3.0 to +3.5???, as do matrix sulfides from rocks that attained temperatures 500??C do matrix pyrite-pyrrhotite pairs with polygonal or aligned granoblastic microstructures approach isotopic equilibrium at millimeter to centimeter scales, suggesting that the process that favoured equilibration was recrystallization accompanying metamorphism and deformation. This disequilibrium may be a function of preferential interaction of one of the phases with an infiltrating fluid, but the lack of any systematic trends in the data, particularly with both negative and positive ??34Spy-po at some outcrops, does not permit ready identification of fluid sources, fluxes, or compositions. By combining published fluid fluxes for the area and a knowledge of the mass of sulfur contained in the rocks and the inferred infiltrating fluid, it appears that sulfur should have been homogenized over at least 10's to 1000's of meters, if equilibrium had been attained between rock sulfides and an infiltrating fluid of constant composition. That this did not occur was probably due to lack of equilibration between sulfides and the fluid but may also have arisen because of channelling of fluid flow along rather than across layers, or a lack of fluid infiltration through this unit

  8. Two quantitative trait loci affect ACE activities in Mexican-Americans.

    PubMed

    Kammerer, Candace M; Gouin, Nicolas; Samollow, Paul B; VandeBerg, Jane F; Hixson, James E; Cole, Shelley A; MacCluer, Jean W; Atwood, Larry D

    2004-02-01

    Angiotensin-converting enzyme (ACE) activity is highly heritable and has been associated with cardiovascular disease. We are studying the effects of genes and environmental factors on hypertension and related phenotypes, such as ACE activity, in Mexican-American families. In the current study, we performed multipoint linkage analysis to search for quantitative trait loci (QTLs) that affect ACE activities on data from 793 individuals from 29 pedigrees from the San Antonio Family Heart Study. As expected, we obtained strong evidence (maximum log of the odds [LOD]=4.57, genomic P=0.003) that a QTL for ACE activity is located on chromosome 17 near the ACE structural locus. We subsequently performed linkage analyses conditional on the effect of this QTL and obtained strong evidence (LOD=3.34) for a second QTL on chromosome 4 near D4S1548. We next incorporated the ACEIns/Del genotypes in our analyses and removed the evidence for the chromosome 17 QTL (maximum LOD=0.60); however, we retained our evidence for the QTL on chromosome 4q. We conclude that the QTL on chromosome 17 is tightly linked to ACE and is in strong disequilibrium with the insertion/deletion polymorphism, which is consistent with other reports. We also have evidence that an additional QTL affects ACE activity. Identification of this additional QTL might lead to alternate means of prophylaxis.

  9. Small passenger car transmission test; Ford C4 transmission

    NASA Technical Reports Server (NTRS)

    Bujold, M. P.

    1980-01-01

    A 1979 Ford C4 automatic transmission was tested per a passenger car automatic transmission test code (SAE J651b) which required drive performance, coast performance, and no load test conditions. Under these test conditions, the transmission attained maximum efficiencies in the mid-eighty percent range for both drive performance tests and coast performance tests. The major results of this test (torque, speed, and efficiency curves) are presented. Graphs map the complete performance characteristics for the Ford C4 transmission.

  10. Quantifying Transmission.

    PubMed

    Woolhouse, Mark

    2017-07-01

    Transmissibility is the defining characteristic of infectious diseases. Quantifying transmission matters for understanding infectious disease epidemiology and designing evidence-based disease control programs. Tracing individual transmission events can be achieved by epidemiological investigation coupled with pathogen typing or genome sequencing. Individual infectiousness can be estimated by measuring pathogen loads, but few studies have directly estimated the ability of infected hosts to transmit to uninfected hosts. Individuals' opportunities to transmit infection are dependent on behavioral and other risk factors relevant given the transmission route of the pathogen concerned. Transmission at the population level can be quantified through knowledge of risk factors in the population or phylogeographic analysis of pathogen sequence data. Mathematical model-based approaches require estimation of the per capita transmission rate and basic reproduction number, obtained by fitting models to case data and/or analysis of pathogen sequence data. Heterogeneities in infectiousness, contact behavior, and susceptibility can have substantial effects on the epidemiology of an infectious disease, so estimates of only mean values may be insufficient. For some pathogens, super-shedders (infected individuals who are highly infectious) and super-spreaders (individuals with more opportunities to transmit infection) may be important. Future work on quantifying transmission should involve integrated analyses of multiple data sources.

  11. Cost-effectiveness of quantitative hepatitis B virus surface antigen testing in pregnancy in predicting vertical transmission risk.

    PubMed

    Samadi Kochaksaraei, Golasa; Congly, Stephen E; Matwiy, Trudy; Castillo, Eliana; Martin, Steven R; Charlton, Carmen L; Coffin, Carla S

    2016-11-01

    Vertical transmission of hepatitis B virus (HBV) can occur despite immunoprophylaxis in mothers with high HBV DNA levels (>5-7 log 10 IU/ml). Quantitative hepatitis B surface antigen (qHBsAg) testing could be used as a surrogate marker to identify high viral load carriers, but there is limited data in pregnancy. We conducted a prospective observational study to determine the cost-effectiveness and utility of qHBsAg as a valid surrogate marker of HBV DNA. Pregnant patients with chronic hepatitis B were recruited from a tertiary referral centre. HBV DNA levels and qHBsAg were assessed in the second to third trimester. Statistical analysis was performed by Spearman's rank correlation and student's t-test. The cost-effectiveness of qHBsAg as compared to HBV DNA testing was calculated. Ninety nine women with 103 pregnancies, median age 32 years, 65% Asian, 23% African and 12% other [Hispanic, Caucasian] were enrolled. Overall, 23% (23/99) were HBV e Ag (HBeAg)-positive. A significant correlation between qHBsAg and HBV DNA levels was noted in HBeAg-positive patients (r = 0.79, P < 0.05) but not in HBeAg-negative patients (r = 0.17, P = 0.06). In receiver operating characteristic analysis, the optimal qHBsAg cut-off values for predicting maternal viraemia associated with immunoprophylaxis failure (i.e., HBV DNA ≥7 log 10 IU/ml) was 4.3 log 10 IU/ml (accuracy 98.7%, sensitivity 94.7%, specificity 94.4%) (95% CI, 97-100%, P < 0.05). Use of HBV DNA as compared to qHBsAg costs approximately $20 000 more per infection prevented. In resource poor regions, qHBsAg could be used as a more cost-effective marker for high maternal viraemia, and indicate when anti-HBV nucleos/tide analogue therapy should be used to prevent HBV immunoprophylaxis failure. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Quantitating and Dating Recent Gene Flow between European and East Asian Populations

    PubMed Central

    Qin, Pengfei; Zhou, Ying; Lou, Haiyi; Lu, Dongsheng; Yang, Xiong; Wang, Yuchen; Jin, Li; Chung, Yeun-Jun; Xu, Shuhua

    2015-01-01

    Historical records indicate that extensive cultural, commercial and technological interaction occurred between European and Asian populations. What have been the biological consequences of these contacts in terms of gene flow? We systematically estimated gene flow between Eurasian groups using genome-wide polymorphisms from 34 populations representing Europeans, East Asians, and Central/South Asians. We identified recent gene flow between Europeans and Asians in most populations we studied, including East Asians and Northwestern Europeans, which are normally considered to be non-admixed populations. In addition we quantitatively estimated the extent of this gene flow using two statistical approaches, and dated admixture events based on admixture linkage disequilibrium. Our results indicate that most genetic admixtures occurred between 2,400 and 310 years ago and show the admixture proportions to be highly correlated with geographic locations, with the highest admixture proportions observed in Central Asia and the lowest in East Asia and Northwestern Europe. Interestingly, we observed a North-to-South decline of European gene flow in East Asians, suggesting a northern path of European gene flow diffusing into East Asian populations. Our findings contribute to an improved understanding of the history of human migration and the evolutionary mechanisms that have shaped the genetic structure of populations in Eurasia. PMID:25833680

  13. Quantitatively in Situ Imaging Silver Nanowire Hollowing Kinetics

    DOE PAGES

    Yu, Le; Yan, Zhongying; Cai, Zhonghou; ...

    2016-09-28

    We report the in-situ investigation of the morphological evolution of silver nanowires to hollow silver oxide nanotubes using transmission x-ray microscopy (TXM). Complex silver diffusion kinetics and hollowing process via the Kirkendall effect have been captured in real time. Further quantitative x-ray absorption analysis reveals the difference between the longitudinal and radial diffusions. In conclusion, the diffusion coefficient of silver in its oxide nanoshell is, for the first time, calculated to be 1.2 × 10 -13 cm 2/s from the geometrical parameters extracted from the TXM images.

  14. Direct quantitation of thoracic gallium-67 uptake in sarcoidosis

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

    Bourguet, P.; Delaval, P.; Herry, J.Y.

    1986-10-01

    A method of direct quantitation of /sup 67/Ga uptake in the lung is described. The attenuation coefficient requires calculation and is obtained simply for each patient by transmission using a planar radionuclide source. The validity of the method was tested with a phantom (error less than 10%). Forty-three patients with pulmonary and/or mediastinal sarcoidosis were classified. The different groups of patients as defined clinically and radiographically (controls, nonactive, and active sarcoidosis) were well-differentiated (p less than 0.001).

  15. Frameshifted prion proteins as pathological agents: quantitative considerations.

    PubMed

    Wills, Peter R

    2013-05-21

    A quantitatively consistent explanation for the titres of infectivity found in a variety of prion-containing preparations is provided on the basis that the ætiological agents of transmissible spongiform encephalopathy comprise a very small population fraction of prion protein (PrP) variants, which contain frameshifted elements in their N-terminal octapeptide-repeat regions. A mechanism for the replication of frameshifted prions is described and calculations are performed to obtain estimates of the concentration of these PrP variants in normal and infected brain, as well as their enrichment in products of protein misfolding cyclic amplification. These calculations resolve the lack of proper quantitative correlation between measures of infectivity and the presence of conformationally-altered, protease-resistant variants of PrP. Experiments, which could confirm or eventually exclude the role of frameshifted variants in the ætiology of prion disease, are suggested. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. The spatial coherence function in scanning transmission electron microscopy and spectroscopy.

    PubMed

    Nguyen, D T; Findlay, S D; Etheridge, J

    2014-11-01

    We investigate the implications of the form of the spatial coherence function, also referred to as the effective source distribution, for quantitative analysis in scanning transmission electron microscopy, and in particular for interpreting the spatial origin of imaging and spectroscopy signals. These questions are explored using three different source distribution models applied to a GaAs crystal case study. The shape of the effective source distribution was found to have a strong influence not only on the scanning transmission electron microscopy (STEM) image contrast, but also on the distribution of the scattered electron wavefield and hence on the spatial origin of the detected electron intensities. The implications this has for measuring structure, composition and bonding at atomic resolution via annular dark field, X-ray and electron energy loss STEM imaging are discussed. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Fluvial drainage networks: the fractal approach as an improvement of quantitative geomorphic analyses

    NASA Astrophysics Data System (ADS)

    Melelli, Laura; Liucci, Luisa; Vergari, Francesca; Ciccacci, Sirio; Del Monte, Maurizio

    2014-05-01

    , suggesting a greater disequilibrium in the last ones. The quantitative analysis points out the segments of the basin boundaries where the fault activity is more efficient and the resulting geomorphological implications.

  18. Functional linear models for association analysis of quantitative traits.

    PubMed

    Fan, Ruzong; Wang, Yifan; Mills, James L; Wilson, Alexander F; Bailey-Wilson, Joan E; Xiong, Momiao

    2013-11-01

    Functional linear models are developed in this paper for testing associations between quantitative traits and genetic variants, which can be rare variants or common variants or the combination of the two. By treating multiple genetic variants of an individual in a human population as a realization of a stochastic process, the genome of an individual in a chromosome region is a continuum of sequence data rather than discrete observations. The genome of an individual is viewed as a stochastic function that contains both linkage and linkage disequilibrium (LD) information of the genetic markers. By using techniques of functional data analysis, both fixed and mixed effect functional linear models are built to test the association between quantitative traits and genetic variants adjusting for covariates. After extensive simulation analysis, it is shown that the F-distributed tests of the proposed fixed effect functional linear models have higher power than that of sequence kernel association test (SKAT) and its optimal unified test (SKAT-O) for three scenarios in most cases: (1) the causal variants are all rare, (2) the causal variants are both rare and common, and (3) the causal variants are common. The superior performance of the fixed effect functional linear models is most likely due to its optimal utilization of both genetic linkage and LD information of multiple genetic variants in a genome and similarity among different individuals, while SKAT and SKAT-O only model the similarities and pairwise LD but do not model linkage and higher order LD information sufficiently. In addition, the proposed fixed effect models generate accurate type I error rates in simulation studies. We also show that the functional kernel score tests of the proposed mixed effect functional linear models are preferable in candidate gene analysis and small sample problems. The methods are applied to analyze three biochemical traits in data from the Trinity Students Study. © 2013 WILEY

  19. Optimization-Based Approach for Joint X-Ray Fluorescence and Transmission Tomographic Inversion

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

    Di, Zichao; Leyffer, Sven; Wild, Stefan M.

    2016-01-01

    Fluorescence tomographic reconstruction, based on the detection of photons coming from fluorescent emission, can be used for revealing the internal elemental composition of a sample. On the other hand, conventional X-ray transmission tomography can be used for reconstructing the spatial distribution of the absorption coefficient inside a sample. In this work, we integrate both X-ray fluorescence and X-ray transmission data modalities and formulate a nonlinear optimization-based approach for reconstruction of the elemental composition of a given object. This model provides a simultaneous reconstruction of both the quantitative spatial distribution of all elements and the absorption effect in the sample. Mathematicallymore » speaking, we show that compared with the single-modality inversion (i.e., the X-ray transmission or fluorescence alone), the joint inversion provides a better-posed problem, which implies a better recovery. Therefore, the challenges in X-ray fluorescence tomography arising mainly from the effects of self-absorption in the sample are partially mitigated. The use of this technique is demonstrated on the reconstruction of several synthetic samples.« less

  20. Germline transmission in transgenic Huntington's disease monkeys.

    PubMed

    Moran, Sean; Chi, Tim; Prucha, Melinda S; Ahn, Kwang Sung; Connor-Stroud, Fawn; Jean, Sherrie; Gould, Kenneth; Chan, Anthony W S

    2015-07-15

    Transgenic nonhuman primate models are an increasingly popular model for neurologic and neurodegenerative disease because their brain functions and neural anatomies closely resemble those of humans. Transgenic Huntington's disease monkeys (HD monkeys) developed clinical features similar to those seen in HD patients, making the monkeys suitable for a preclinical study of HD. However, until HD monkey colonies can be readily expanded, their use in preclinical studies will be limited. In the present study, we confirmed germline transmission of the mutant huntingtin (mHTT) transgene in both embryonic stem cells generated from three male HD monkey founders (F0) and in second-generation offspring (F1) produced via artificial insemination by using intrauterine insemination technique. A total of five offspring were produced from 15 females that were inseminated by intrauterine insemination using semen collected from the three HD founders (5 of 15, 33%). Thus far, sperm collected from the HD founder (rHD8) has led to two F1 transgenic HD monkeys with germline transmission rate at 100% (2 of 2). mHTT expression was confirmed by quantitative real-time polymerase chain reaction using skin fibroblasts from the F1 HD monkeys and induced pluripotent stem cells established from one of the F1 HD monkeys (rHD8-2). Here, we report the stable germline transmission and expression of the mHTT transgene in HD monkeys, which suggest possible expansion of HD monkey colonies for preclinical and biomedical research studies. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Impact of population structure, effective bottleneck time, and allele frequency on linkage disequilibrium maps

    PubMed Central

    Zhang, Weihua; Collins, Andrew; Gibson, Jane; Tapper, William J.; Hunt, Sarah; Deloukas, Panos; Bentley, David R.; Morton, Newton E.

    2004-01-01

    Genetic maps in linkage disequilibrium (LD) units play the same role for association mapping as maps in centimorgans provide at much lower resolution for linkage mapping. Association mapping of genes determining disease susceptibility and other phenotypes is based on the theory of LD, here applied to relations with three phenomena. To test the theory, markers at high density along a 10-Mb continuous segment of chromosome 20q were studied in African-American, Asian, and Caucasian samples. Population structure, whether created by pooling samples from divergent populations or by the mating pattern in a mixed population, is accurately bioassayed from genotype frequencies. The effective bottleneck time for Eurasians is substantially less than for migration out of Africa, reflecting later bottlenecks. The classical dependence of allele frequency on mutation age does not hold for the generally shorter time span of inbreeding and LD. Limitation of the classical theory to mutation age justifies the assumption of constant time in a LD map, except for alleles that were rare at the effective bottleneck time or have arisen since. This assumption is derived from the Malecot model and verified in all samples. Tested measures of relative efficiency, support intervals, and localization error determine the operating characteristics of LD maps that are applicable to every sexually reproducing species, with implications for association mapping, high-resolution linkage maps, evolutionary inference, and identification of recombinogenic sequences. PMID:15604137

  2. Linkage disequilibrium and population structure in wild and domesticated populations of Phaseolus vulgaris L.

    PubMed Central

    Rossi, Monica; Bitocchi, Elena; Bellucci, Elisa; Nanni, Laura; Rau, Domenico; Attene, Giovanna; Papa, Roberto

    2009-01-01

    Together with the knowledge of the population structure, a critical aspect for the planning of association and/or population genomics studies is the level of linkage disequilibrium (LD) that characterizes the species and the population used for such an analysis. We have analyzed the population structure and LD in wild and domesticated populations of Phaseolus vulgaris L. using amplified fragment length polymorphism markers, most of which were genetically mapped in two recombinant inbred populations. Our results reflect the previous knowledge of the occurrence of two major wild gene pools of P. vulgaris, from which two independent domestication events originated, one in the Andes and one in Mesoamerica. The high level of LD in the whole sample was mostly due to the gene pool structure, with a much higher LD in domesticated compared to wild populations. In relation to association studies, our results also suggest that whole-genome-scan approaches are feasible in the common bean. Interestingly, an excess of inter-chromosomal LD was found in the domesticated populations, which suggests an important role for epistatic selection during domestication. Moreover, our results indicate the occurrence of a strong bottleneck in the Andean wild population before domestication, suggesting a Mesoamerican origin of P. vulgaris. Finally, our data support the occurrence of a single domestication event in Mesoamerica, and the same scenario in the Andes. PMID:25567895

  3. Impact of population structure, effective bottleneck time, and allele frequency on linkage disequilibrium maps.

    PubMed

    Zhang, Weihua; Collins, Andrew; Gibson, Jane; Tapper, William J; Hunt, Sarah; Deloukas, Panos; Bentley, David R; Morton, Newton E

    2004-12-28

    Genetic maps in linkage disequilibrium (LD) units play the same role for association mapping as maps in centimorgans provide at much lower resolution for linkage mapping. Association mapping of genes determining disease susceptibility and other phenotypes is based on the theory of LD, here applied to relations with three phenomena. To test the theory, markers at high density along a 10-Mb continuous segment of chromosome 20q were studied in African-American, Asian, and Caucasian samples. Population structure, whether created by pooling samples from divergent populations or by the mating pattern in a mixed population, is accurately bioassayed from genotype frequencies. The effective bottleneck time for Eurasians is substantially less than for migration out of Africa, reflecting later bottlenecks. The classical dependence of allele frequency on mutation age does not hold for the generally shorter time span of inbreeding and LD. Limitation of the classical theory to mutation age justifies the assumption of constant time in a LD map, except for alleles that were rare at the effective bottleneck time or have arisen since. This assumption is derived from the Malecot model and verified in all samples. Tested measures of relative efficiency, support intervals, and localization error determine the operating characteristics of LD maps that are applicable to every sexually reproducing species, with implications for association mapping, high-resolution linkage maps, evolutionary inference, and identification of recombinogenic sequences.

  4. Bordetella pertussis transmission

    PubMed Central

    Trainor, Elizabeth A.; Nicholson, Tracy L.; Merkel, Tod J.

    2015-01-01

    Bordetella pertussis and B. bronchiseptica are Gram-negative bacterial respiratory pathogens. Bordetella pertussis is the causative agent of whooping cough and is considered a human-adapted variant of B. bronchiseptica. Bordetella pertussis and B. bronchiseptica share mechanisms of pathogenesis and are genetically closely related. However, despite the close genetic relatedness, these Bordetella species differ in several classic fundamental aspects of bacterial pathogens such as host range, pathologies and persistence. The development of the baboon model for the study of B. pertussis transmission, along with the development of the swine and mouse model for the study of B. bronchiseptica, has enabled the investigation of different aspects of transmission including the route, attack rate, role of bacterial and host factors, and the impact of vaccination on transmission. This review will focus on B. pertussis transmission and how animal models of B. pertussis transmission and transmission models using the closely related B. bronchiseptica have increased our understanding of B. pertussis transmission. PMID:26374235

  5. An investigation of the use of transmission ultrasound to measure acoustic attenuation changes in thermal therapy.

    PubMed

    Parmar, Neeta; Kolios, Michael C

    2006-07-01

    The potential of using a commercial ultrasound transmission imaging system to quantitatively monitor tissue attenuation changes after thermal therapy was investigated. The ultrasound transmission imaging system used, the AcoustoCam (Imperium Inc., MD) allows ultrasonic images to be captured using principles similar to that of a CCD-type camera that collects light. Ultrasound energy is focused onto a piezoelectric array by an acoustic lens system, creating a gray scale acoustic image. In this work, the pixel values from the acoustic images were assigned acoustic attenuation values by imaging polyacrylamide phantoms of varying known attenuation. After the calibration procedure, data from heated polyacrylamide/bovine serum albumin (BSA) based tissue-mimicking (TM) phantoms and porcine livers were acquired. Samples were heated in water at temperatures of 35, 45, 55, 65, and 75 degrees C for 1 h. Regions of interest were chosen in the images and acoustic attenuation values before and after heating were compared. An increase in ultrasound attenuation was found in phantoms containing BSA and in porcine liver. In the presence of BSA, attenuation in the TM phantom increased by a factor of 1.5, while without BSA no significant changes were observed. The attenuation of the porcine liver increased by up to a factor of 2.4, consistent with previously reported studies. The study demonstrates the feasibility of using a quantitative ultrasound transmission imaging system for monitoring thermal therapy.

  6. NASA transmission research and its probable effects on helicopter transmission design

    NASA Technical Reports Server (NTRS)

    Zaretsky, E. V.; Coy, J. J.; Townsend, D. P.

    1983-01-01

    Transmissions studied for application to helicopters in addition to the more conventional geared transmissions include hybrid (traction/gear), bearingless planetary, and split torque transmissions. Research is being performed to establish the validity of analysis and computer codes developed to predict the performance, efficiency, life, and reliability of these transmissions. Results of this research should provide the transmission designer with analytical tools to design for minimum weight and noise with maximum life and efficiency. In addition, the advantages and limitations of drive systems as well as the more conventional systems will be defined.

  7. NASA transmission research and its probable effects on helicopter transmission design

    NASA Technical Reports Server (NTRS)

    Zaretsky, E. V.; Coy, J. J.; Townsend, D. P.

    1984-01-01

    Transmissions studied for application to helicopters in addition to the more conventional geared transmissions include hybrid (traction/gear), bearingless planetary, and split torque transmissions. Research is being performed to establish the validity of analysis and computer codes developed to predict the performance, efficiency, life, and reliability of these transmissions. Results of this research should provide the transmission designer with analytical tools to design for minimum weight and noise with maximum life and efficiency. In addition, the advantages and limitations of drive systems as well as the more conventional systems will be defined.

  8. Planning Electric Transmission Lines: A Review of Recent Regional Transmission Plans

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

    Eto, Joseph H.

    The first Quadrennial Energy Review (QER) recommends that the U.S. Department of Energy (DOE) conduct a national review of transmission plans and assess the barriers and incentives to their implementation. DOE tasked Lawrence Berkeley National Laboratory (LBNL) to prepare two reports to support the agency’s response to this recommendation. This report reviews regional transmission plans and regional transmission planning processes that have been directed by Federal Energy Regulatory Commission (FERC) Order Nos. 890 and 1000. We focus on the most recent regional transmission plans (those issued in 2015 and through approximately mid-year 2016) and current regional transmission planning processes. Amore » companion report focuses on non-plan-related factors that affect transmission projects.« less

  9. Evaluation of Pleistocene groundwater flow through fractured tuffs using a U-series disequilibrium approach, Pahute Mesa, Nevada, USA

    USGS Publications Warehouse

    Paces, James B.; Nichols, Paul J.; Neymark, Leonid A.; Rajaram, Harihar

    2013-01-01

    Groundwater flow through fractured felsic tuffs and lavas at the Nevada National Security Site represents the most likely mechanism for transport of radionuclides away from underground nuclear tests at Pahute Mesa. To help evaluate fracture flow and matrix–water exchange, we have determined U-series isotopic compositions on more than 40 drill core samples from 5 boreholes that represent discrete fracture surfaces, breccia zones, and interiors of unfractured core. The U-series approach relies on the disruption of radioactive secular equilibrium between isotopes in the uranium-series decay chain due to preferential mobilization of 234U relative to 238U, and U relative to Th. Samples from discrete fractures were obtained by milling fracture surfaces containing thin secondary mineral coatings of clays, silica, Fe–Mn oxyhydroxides, and zeolite. Intact core interiors and breccia fragments were sampled in bulk. In addition, profiles of rock matrix extending 15 to 44 mm away from several fractures that show evidence of recent flow were analyzed to investigate the extent of fracture/matrix water exchange. Samples of rock matrix have 234U/238U and 230Th/238U activity ratios (AR) closest to radioactive secular equilibrium indicating only small amounts of groundwater penetrated unfractured matrix. Greater U mobility was observed in welded-tuff matrix with elevated porosity and in zeolitized bedded tuff. Samples of brecciated core were also in secular equilibrium implying a lack of long-range hydraulic connectivity in these cases. Samples of discrete fracture surfaces typically, but not always, were in radioactive disequilibrium. Many fractures had isotopic compositions plotting near the 230Th-234U 1:1 line indicating a steady-state balance between U input and removal along with radioactive decay. Numerical simulations of U-series isotope evolution indicate that 0.5 to 1 million years are required to reach steady-state compositions. Once attained, disequilibrium 234U/238U

  10. Mapping influenza transmission in the ferret model to transmission in humans

    PubMed Central

    Buhnerkempe, Michael G; Gostic, Katelyn; Park, Miran; Ahsan, Prianna; Belser, Jessica A; Lloyd-Smith, James O

    2015-01-01

    The controversy surrounding 'gain-of-function' experiments on high-consequence avian influenza viruses has highlighted the role of ferret transmission experiments in studying the transmission potential of novel influenza strains. However, the mapping between influenza transmission in ferrets and in humans is unsubstantiated. We address this gap by compiling and analyzing 240 estimates of influenza transmission in ferrets and humans. We demonstrate that estimates of ferret secondary attack rate (SAR) explain 66% of the variation in human SAR estimates at the subtype level. Further analysis shows that ferret transmission experiments have potential to identify influenza viruses of concern for epidemic spread in humans, though small sample sizes and biological uncertainties prevent definitive classification of human transmissibility. Thus, ferret transmission experiments provide valid predictions of pandemic potential of novel influenza strains, though results should continue to be corroborated by targeted virological and epidemiological research. DOI: http://dx.doi.org/10.7554/eLife.07969.001 PMID:26329460

  11. Genetic diversity and population structure of Plasmodium falciparum in Thailand, a low transmission country.

    PubMed

    Pumpaibool, Tepanata; Arnathau, Céline; Durand, Patrick; Kanchanakhan, Naowarat; Siripoon, Napaporn; Suegorn, Aree; Sitthi-Amorn, Chitr; Renaud, François; Harnyuttanakorn, Pongchai

    2009-07-14

    structure of P. falciparum populations in Thailand with those in the French Guyana, Congo and Cameroon revealed a significant genetic differentiation between all of them, except the two African countries, whilst the genetic variability of P. falciparum amongst countries showed overlapping distributions. Plasmodium falciparum shows genetically structured populations across local areas of Thailand. Although Thailand is considered to be a low transmission area, a relatively high level of genetic diversity and no linkage disequilibrium was found in five of the studied areas, the exception being the Yala province (Southern peninsular Thailand), where a clonal population structure was revealed and in Kanchanaburi province (Western Thailand). This finding is particularly relevant in the context of malaria control, because it could help in understanding the special dynamics of parasite populations in areas with different histories of, and exposure to, drug regimens.

  12. Linkage disequilibrium between polymorphisms of ABCB1 and ABCC2 to predict the treatment outcome of Malaysians with complex partial seizures on treatment with carbamazepine mono-therapy at the Kuala Lumpur Hospital.

    PubMed

    Subenthiran, Soobitha; Abdullah, Noor Rain; Joseph, Joyce Pauline; Muniandy, Prem Kumar; Mok, Boon Teck; Kee, Chee Cheong; Ismail, Zakiah; Mohamed, Zahurin

    2013-01-01

    Carbamazepine (CBZ) is used as the first line of treatment of Complex Partial Seizures (CPS) in the Epilepsy Clinic, Neurology Department of Kuala Lumpur Hospital (KLH). More than 30% of the patients remain drug resistant to CBZ mono-therapy. CBZ is transported by the P-glycoprotein (P-gp). The P-gp encoded by the ABCB1 and ABCC2 genes are expressed in drug resistant patients with epilepsy. A few studies have shown significant association between CBZ resistant epilepsy and Linkage Disequilibrium (LD) with adjacent polymorphisms of these genes. Our study is aimed at determining the correlation between patients' response to CBZ mono-therapy to Single Nucleotide Polymorphisms G2677T and C3435T of the ABCB1 gene as well as G1249A and -24C>T of the ABCC2 gene. 314 patients with CPS were recruited from the Neurology Department of the KLH based on stringent inclusion and exclusion criteria, of whom 152 were responders and the other 162 were non-responders. DNA was extracted from their blood samples and Taqman technology for allelic discrimination was performed. Results were described as genotype frequencies. The SHEsis analysis platform was used to calculate linkage disequilibrium index and infer haplotype frequencies. Haploview was used to do permutation test to obtain a corrected p-value. Resistance to treatment with CBZ mono-therapy was significantly associated with the 2677TT and the 3435TT genotypes while it was not significantly associated with the G1249A and -24C>T polymorphisms. The GCGC haplotype combination of the 2677G>T, 3435C>T, 1249G>A and -24C>T respectively was found to be extremely significant (p = 1.10e-20) with good drug response to CBZ mono-therapy. Linkage disequilibrium between the 2677G>T, 3435C>T, 1249G>A and -24C>T SNPs may be used as a reliable screening marker to determine the treatment outcome of CBZ mono-therapy with CPS irrespective of race or gender.

  13. Bordetella pertussis transmission.

    PubMed

    Trainor, Elizabeth A; Nicholson, Tracy L; Merkel, Tod J

    2015-11-01

    Bordetella pertussis and B. bronchiseptica are Gram-negative bacterial respiratory pathogens. Bordetella pertussis is the causative agent of whooping cough and is considered a human-adapted variant of B. bronchiseptica. Bordetella pertussis and B. bronchiseptica share mechanisms of pathogenesis and are genetically closely related. However, despite the close genetic relatedness, these Bordetella species differ in several classic fundamental aspects of bacterial pathogens such as host range, pathologies and persistence. The development of the baboon model for the study of B. pertussis transmission, along with the development of the swine and mouse model for the study of B. bronchiseptica, has enabled the investigation of different aspects of transmission including the route, attack rate, role of bacterial and host factors, and the impact of vaccination on transmission. This review will focus on B. pertussis transmission and how animal models of B. pertussis transmission and transmission models using the closely related B. bronchiseptica have increased our understanding of B. pertussis transmission. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. Measuring nanometre-scale electric fields in scanning transmission electron microscopy using segmented detectors.

    PubMed

    Brown, H G; Shibata, N; Sasaki, H; Petersen, T C; Paganin, D M; Morgan, M J; Findlay, S D

    2017-11-01

    Electric field mapping using segmented detectors in the scanning transmission electron microscope has recently been achieved at the nanometre scale. However, converting these results to quantitative field measurements involves assumptions whose validity is unclear for thick specimens. We consider three approaches to quantitative reconstruction of the projected electric potential using segmented detectors: a segmented detector approximation to differential phase contrast and two variants on ptychographical reconstruction. Limitations to these approaches are also studied, particularly errors arising from detector segment size, inelastic scattering, and non-periodic boundary conditions. A simple calibration experiment is described which corrects the differential phase contrast reconstruction to give reliable quantitative results despite the finite detector segment size and the effects of plasmon scattering in thick specimens. A plasmon scattering correction to the segmented detector ptychography approaches is also given. Avoiding the imposition of periodic boundary conditions on the reconstructed projected electric potential leads to more realistic reconstructions. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. The Improbable Transmission of Trypanosoma cruzi to Human: The Missing Link in the Dynamics and Control of Chagas Disease

    PubMed Central

    Nouvellet, Pierre; Dumonteil, Eric; Gourbière, Sébastien

    2013-01-01

    Chagas disease has a major impact on human health in Latin America and is becoming of global concern due to international migrations. Trypanosoma cruzi, the etiological agent of the disease, is one of the rare human parasites transmitted by the feces of its vector, as it is unable to reach the salivary gland of the insect. This stercorarian transmission is notoriously poorly understood, despite its crucial role in the ecology and evolution of the pathogen and the disease. The objective of this study was to quantify the probability of T. cruzi vectorial transmission to humans, and to use such an estimate to predict human prevalence from entomological data. We developed several models of T. cruzi transmission to estimate the probability of transmission from vector to host. Using datasets from the literature, we estimated the probability of transmission per contact with an infected triatomine to be 5.8×10−4 (95%CI: [2.6 ; 11.0]×10−4). This estimate was consistent across triatomine species, robust to variations in other parameters, and corresponded to 900–4,000 contacts per case. Our models subsequently allowed predicting human prevalence from vector abundance and infection rate in 7/10 independent datasets covering various triatomine species and epidemiological situations. This low probability of T. cruzi transmission reflected well the complex and unlikely mechanism of transmission via insect feces, and allowed predicting human prevalence from basic entomological data. Although a proof of principle study would now be valuable to validate our models' predictive ability in an even broader range of entomological and ecological settings, our quantitative estimate could allow switching the evaluation of disease risk and vector control program from purely entomological indexes to parasitological measures, as commonly done for other major vector borne diseases. This might lead to different quantitative perspectives as these indexes are well known not to be

  16. Quantifying the impact of community quarantine on SARS transmission in Ontario: estimation of secondary case count difference and number needed to quarantine.

    PubMed

    Bondy, Susan J; Russell, Margaret L; Laflèche, Julie Ml; Rea, Elizabeth

    2009-12-24

    Community quarantine is controversial, and the decision to use and prepare for it should be informed by specific quantitative evidence of benefit. Case-study reports on 2002-2004 SARS outbreaks have discussed the role of quarantine in the community in transmission. However, this literature has not yielded quantitative estimates of the reduction in secondary cases attributable to quarantine as would be seen in other areas of health policy and cost-effectiveness analysis. Using data from the 2003 Ontario, Canada, SARS outbreak, two novel expressions for the impact of quarantine are presented. Secondary Case Count Difference (SCCD) reflects reduction in the average number of transmissions arising from a SARS case in quarantine, relative to not in quarantine, at onset of symptoms. SCCD was estimated using Poisson and negative binomial regression models (with identity link function) comparing the number of secondary cases to each index case for quarantine relative to non-quarantined index cases. The inverse of this statistic is proposed as the number needed to quarantine (NNQ) to prevent one additional secondary transmission. Our estimated SCCD was 0.133 fewer secondary cases per quarantined versus non-quarantined index case; and a NNQ of 7.5 exposed individuals to be placed in community quarantine to prevent one additional case of transmission in the community. This analysis suggests quarantine can be an effective preventive measure, although these estimates lack statistical precision. Relative to other health policy areas, literature on quarantine tends to lack in quantitative expressions of effectiveness, or agreement on how best to report differences in outcomes attributable to control measure. We hope to further this discussion through presentation of means to calculate and express the impact of population control measures. The study of quarantine effectiveness presents several methodological and statistical challenges. Further research and discussion are needed to

  17. Quantifying the impact of community quarantine on SARS transmission in Ontario: estimation of secondary case count difference and number needed to quarantine

    PubMed Central

    2009-01-01

    Background Community quarantine is controversial, and the decision to use and prepare for it should be informed by specific quantitative evidence of benefit. Case-study reports on 2002-2004 SARS outbreaks have discussed the role of quarantine in the community in transmission. However, this literature has not yielded quantitative estimates of the reduction in secondary cases attributable to quarantine as would be seen in other areas of health policy and cost-effectiveness analysis. Methods Using data from the 2003 Ontario, Canada, SARS outbreak, two novel expressions for the impact of quarantine are presented. Secondary Case Count Difference (SCCD) reflects reduction in the average number of transmissions arising from a SARS case in quarantine, relative to not in quarantine, at onset of symptoms. SCCD was estimated using Poisson and negative binomial regression models (with identity link function) comparing the number of secondary cases to each index case for quarantine relative to non-quarantined index cases. The inverse of this statistic is proposed as the number needed to quarantine (NNQ) to prevent one additional secondary transmission. Results Our estimated SCCD was 0.133 fewer secondary cases per quarantined versus non-quarantined index case; and a NNQ of 7.5 exposed individuals to be placed in community quarantine to prevent one additional case of transmission in the community. This analysis suggests quarantine can be an effective preventive measure, although these estimates lack statistical precision. Conclusions Relative to other health policy areas, literature on quarantine tends to lack in quantitative expressions of effectiveness, or agreement on how best to report differences in outcomes attributable to control measure. We hope to further this discussion through presentation of means to calculate and express the impact of population control measures. The study of quarantine effectiveness presents several methodological and statistical challenges

  18. Towards quantitative PET/MRI: a review of MR-based attenuation correction techniques.

    PubMed

    Hofmann, Matthias; Pichler, Bernd; Schölkopf, Bernhard; Beyer, Thomas

    2009-03-01

    Positron emission tomography (PET) is a fully quantitative technology for imaging metabolic pathways and dynamic processes in vivo. Attenuation correction of raw PET data is a prerequisite for quantification and is typically based on separate transmission measurements. In PET/CT attenuation correction, however, is performed routinely based on the available CT transmission data. Recently, combined PET/magnetic resonance (MR) has been proposed as a viable alternative to PET/CT. Current concepts of PET/MRI do not include CT-like transmission sources and, therefore, alternative methods of PET attenuation correction must be found. This article reviews existing approaches to MR-based attenuation correction (MR-AC). Most groups have proposed MR-AC algorithms for brain PET studies and more recently also for torso PET/MR imaging. Most MR-AC strategies require the use of complementary MR and transmission images, or morphology templates generated from transmission images. We review and discuss these algorithms and point out challenges for using MR-AC in clinical routine. MR-AC is work-in-progress with potentially promising results from a template-based approach applicable to both brain and torso imaging. While efforts are ongoing in making clinically viable MR-AC fully automatic, further studies are required to realize the potential benefits of MR-based motion compensation and partial volume correction of the PET data.

  19. HAADF-STEM atom counting in atom probe tomography specimens: Towards quantitative correlative microscopy.

    PubMed

    Lefebvre, W; Hernandez-Maldonado, D; Moyon, F; Cuvilly, F; Vaudolon, C; Shinde, D; Vurpillot, F

    2015-12-01

    The geometry of atom probe tomography tips strongly differs from standard scanning transmission electron microscopy foils. Whereas the later are rather flat and thin (<20 nm), tips display a curved surface and a significantly larger thickness. As far as a correlative approach aims at analysing the same specimen by both techniques, it is mandatory to explore the limits and advantages imposed by the particular geometry of atom probe tomography specimens. Based on simulations (electron probe propagation and image simulations), the possibility to apply quantitative high angle annular dark field scanning transmission electron microscopy to of atom probe tomography specimens has been tested. The influence of electron probe convergence and the benefice of deconvolution of electron probe point spread function electron have been established. Atom counting in atom probe tomography specimens is for the first time reported in this present work. It is demonstrated that, based on single projections of high angle annular dark field imaging, significant quantitative information can be used as additional input for refining the data obtained by correlative analysis of the specimen in APT, therefore opening new perspectives in the field of atomic scale tomography. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Automated manual transmission controller

    DOEpatents

    Lawrie, Robert E.; Reed, Jr., Richard G.; Bernier, David R.

    1999-12-28

    A powertrain system for a hybrid vehicle. The hybrid vehicle includes a heat engine, such as a diesel engine, and an electric machine, which operates as both an electric motor and an alternator, to power the vehicle. The hybrid vehicle also includes a manual-style transmission configured to operate as an automatic transmission from the perspective of the driver. The engine and the electric machine drive an input shaft which in turn drives an output shaft of the transmission. In addition to driving the transmission, the electric machine regulates the speed of the input shaft in order to synchronize the input shaft during either an upshift or downshift of the transmission by either decreasing or increasing the speed of the input shaft. When decreasing the speed of the input shaft, the electric motor functions as an alternator to produce electrical energy which may be stored by a storage device. Operation of the transmission is controlled by a transmission controller which receives input signals and generates output signals to control shift and clutch motors to effect smooth launch, upshift shifts, and downshifts of the transmission, so that the transmission functions substantially as an automatic transmission from the perspective of the driver, while internally substantially functioning as a manual transmission.

  1. Comparison of Cliff-Lorimer-Based Methods of Scanning Transmission Electron Microscopy (STEM) Quantitative X-Ray Microanalysis for Application to Silicon Oxycarbides Thin Films.

    PubMed

    Parisini, Andrea; Frabboni, Stefano; Gazzadi, Gian Carlo; Rosa, Rodolfo; Armigliato, Aldo

    2018-06-01

    In this work, we compare the results of different Cliff-Lorimer (Cliff & Lorimer 1975) based methods in the case of a quantitative energy dispersive spectrometry investigation of light elements in ternary C-O-Si thin films. To determine the Cliff-Lorimer (C-L) k-factors, we fabricated, by focused ion beam, a standard consisting of a wedge lamella with a truncated tip, composed of two parallel SiO2 and 4H-SiC stripes. In 4H-SiC, it was not possible to obtain reliable k-factors from standard extrapolation methods owing to the strong CK-photon absorption. To overcome this problem, an extrapolation method exploiting the shape of the truncated tip of the lamella is proposed herein. The k-factors thus determined, were then used in an application of the C-L quantification procedure to a defect found at the SiO2/4H-SiC interface in the channel region of a metal-oxide field-effect-transistor device. As in this procedure, the sample thickness is required, a method to determine this quantity from the averaged and normalized scanning transmission electron microscopy intensity is also detailed. Monte Carlo simulations were used to investigate the discrepancy between experimental and theoretical k-factors and to bridge the gap between the k-factor and the Watanabe and Williams ζ-factor methods (Watanabe & Williams, 2006).

  2. Support of positive association in family-based genetic analysis between COL27A1 and Tourette syndrome

    PubMed Central

    Liu, Shiguo; Yu, Xiaoxia; Xu, Quanchen; Cui, Jiajia; Yi, Mingji; Zhang, Xinhua; Ge, Yinlin; Ma, Xu

    2015-01-01

    Recently, a genome-wide association study has indicated associations between single nucleotide polymorphisms in the Collagen Type XXVII Alpha 1 gene (COL27A1) and Tourette syndrome in several ethnic populations. To clarify the global relevance of the previously identified SNPs in the development of Tourette syndrome, the associations between polymorphisms in COL27A1and Tourette syndrome were assessed in Chinese trios. PCR-directed sequencing was used to evaluate the genetic contributions of three SNPs in COL27A1(rs4979356, rs4979357 and rs7868992) using haplotype relative risk (HRR) and transmission disequilibrium tests (TDT) with a total of 260 Tourette syndrome trios. The family-based association was significant between Tourette syndrome and rs4979356 (TDT: χ2 = 4.804, P = 0.033; HRR = 1.75, P = 0.002; HHRR = 1.32, P = 0.027), and transmission disequilibrium was suspected for rs4979357 (TDT: χ2 = 3.969, P = 0.053; HRR = 1.84, P = 0.001; HHRR = 1.29, P = 0.044). No statistically significant allele transfer was found for rs7868992 (TDT: χ2 = 2.177, P = 0.158). Although the TDT results did not remain significant after applying the conservative Bonferroni correction (p = 0.005), the significant positive HRR analysis confirmed the possibility of showing transmission disequilibrium, which provides evidence for an involvement of COL27A1in the development of TS. However, these results need to be verified with larger datasets from different populations. PMID:26235311

  3. Role of mechanical ventilation in the airborne transmission of infectious agents in buildings.

    PubMed

    Luongo, J C; Fennelly, K P; Keen, J A; Zhai, Z J; Jones, B W; Miller, S L

    2016-10-01

    Infectious disease outbreaks and epidemics such as those due to SARS, influenza, measles, tuberculosis, and Middle East respiratory syndrome coronavirus have raised concern about the airborne transmission of pathogens in indoor environments. Significant gaps in knowledge still exist regarding the role of mechanical ventilation in airborne pathogen transmission. This review, prepared by a multidisciplinary group of researchers, focuses on summarizing the strengths and limitations of epidemiologic studies that specifically addressed the association of at least one heating, ventilating and/or air-conditioning (HVAC) system-related parameter with airborne disease transmission in buildings. The purpose of this literature review was to assess the quality and quantity of available data and to identify research needs. This review suggests that there is a need for well-designed observational and intervention studies in buildings with better HVAC system characterization and measurements of both airborne exposures and disease outcomes. Studies should also be designed so that they may be used in future quantitative meta-analyses. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. 3D imaging of a rice pollen grain using transmission X-ray microscopy.

    PubMed

    Wang, Shengxiang; Wang, Dajiang; Wu, Qiao; Gao, Kun; Wang, Zhili; Wu, Ziyu

    2015-07-01

    For the first time, the three-dimensional (3D) ultrastructure of an intact rice pollen cell has been obtained using a full-field transmission hard X-ray microscope operated in Zernike phase contrast mode. After reconstruction and segmentation from a series of projection images, complete 3D structural information of a 35 µm rice pollen grain is presented at a resolution of ∼100 nm. The reconstruction allows a clear differentiation of various subcellular structures within the rice pollen grain, including aperture, lipid body, mitochondrion, nucleus and vacuole. Furthermore, quantitative information was obtained about the distribution of cytoplasmic organelles and the volume percentage of each kind of organelle. These results demonstrate that transmission X-ray microscopy can be quite powerful for non-destructive investigation of 3D structures of whole eukaryotic cells.

  5. Cell-to-cell Transmission of Polyglutamine Aggregates in C. elegans

    PubMed Central

    Kim, Dong-Kyu; Cho, Kyu-Won; Ahn, Woo Jung; Perez-Acuña, Dayana; Jeong, Hyunsu; Lee, He-Jin

    2017-01-01

    Huntington disease (HD) is an inherited neurodegenerative disorder characterized by motor and cognitive dysfunction caused by expansion of polyglutamine (polyQ) repeat in exon 1 of huntingtin (HTT). In patients, the number of glutamine residues in polyQ tracts are over 35, and it is correlated with age of onset, severity, and disease progression. Expansion of polyQ increases the propensity for HTT protein aggregation, process known to be implicated in neurodegeneration. These pathological aggregates can be transmitted from neuron to another neuron, and this process may explain the pathological spreading of polyQ aggregates. Here, we developed an in vivo model for studying transmission of polyQ aggregates in a highly quantitative manner in real time. HTT exon 1 with expanded polyQ was fused with either N-terminal or C-terminal fragments of Venus fluorescence protein and expressed in pharyngeal muscles and associated neurons, respectively, of C. elegans. Transmission of polyQ proteins was detected using bimolecular fluorescence complementation (BiFC). Mutant polyQ (Q97) was transmitted much more efficiently than wild type polyQ (Q25) and forms numerous inclusion bodies as well. The transmission of Q97 was gradually increased with aging of animal. The animals with polyQ transmission exhibited degenerative phenotypes, such as nerve degeneration, impaired pharyngeal pumping behavior, and reduced life span. The C. elegans model presented here would be a useful in vivo model system for the study of polyQ aggregate propagation and might be applied to the screening of genetic and chemical modifiers of the propagation. PMID:29302199

  6. Understanding the effects of different HIV transmission models in individual-based microsimulation of HIV epidemic dynamics in people who inject drugs

    PubMed Central

    MONTEIRO, J.F.G.; ESCUDERO, D.J.; WEINREB, C.; FLANIGAN, T.; GALEA, S.; FRIEDMAN, S.R.; MARSHALL, B.D.L.

    2017-01-01

    SUMMARY We investigated how different models of HIV transmission, and assumptions regarding the distribution of unprotected sex and syringe-sharing events (‘risk acts’), affect quantitative understanding of HIV transmission process in people who inject drugs (PWID). The individual-based model simulated HIV transmission in a dynamic sexual and injecting network representing New York City. We constructed four HIV transmission models: model 1, constant probabilities; model 2, random number of sexual and parenteral acts; model 3, viral load individual assigned; and model 4, two groups of partnerships (low and high risk). Overall, models with less heterogeneity were more sensitive to changes in numbers risk acts, producing HIV incidence up to four times higher than that empirically observed. Although all models overestimated HIV incidence, micro-simulations with greater heterogeneity in the HIV transmission modelling process produced more robust results and better reproduced empirical epidemic dynamics. PMID:26753627

  7. Observations of 231Pa/ 235U disequilibrium in volcanic rocks

    NASA Astrophysics Data System (ADS)

    Pickett, David A.; Murrell, Michael T.

    1997-04-01

    We present here the first survey of ( 231Pa/ 235U) ratios in volcanic rocks; such measurements are made possible by new mass spectrometric techniques. The data place new constraints on the timing and extent of magma source and evolutionary processes, particularly due to the sensitivity of the 231Pa- 235U pair and its intermediate time scale ( 231Pat 1/2 = 33 ky). ( 231Pa/ 235U) is found to vary widely, from 0.2 in carbonatites to 1.1-2.9 in basalts and 0.9-2.2 in arcs. Substantial Pa enrichment is nearly ubiquitous, suggestive of the relative incompatibility of Pa, qualitatively consistent with available partitioning data. The level of 231Pa- 235U disequilibrium typically far exceeds that of 230Th- 238U and is comparable to 226Ra- 230Th. The high ( 231Pa/ 235U) ratios in MORB and other basalts reflect a large degree of discrimination between two incompatible elements, posing challenges for modelling of melt generation and migration. Fundamental differences in ( 231Pa/ 235U) among different basaltic environments are likely related to contrasts in melting zone conditions (e.g., melting rate). Strong ( 231Pa/ 235U) disequilibria in continental basalts, for which ( 230Th/ 238U) disequilibria are small or absent, demonstrate that Pa-U fractionation is possible in both garnet and spinel mantle stability fields. In arcs, correlation of ( 231Pa/ 235U) and ( 230Th/ 238U) is consistent with U enrichment via slab-derived fluids, a process which is additional to the still dominant Pa enrichment. An important new constraint is provided by the observation that the near-equilibrium ( 230Th/ 238U) common to arcs and continental basalts is not typically accompanied by near-equilibrium ( 231Pa/ 235U), arguing against the influence of long magma history, crustal material, or equilibrium mantle sources in affecting decay-series ratios. Small sample sets from two silicic centers illustrate: (1) recent, rapid U enrichment in the magma chamber (El Chichón); and (2) the failure of

  8. Measuring U-series Disequilibrium in Weathering Rinds to Study the Influence of Environmental Factors to Weathering Rates in Tropical Basse-Terre Island (French Guadeloupe)

    NASA Astrophysics Data System (ADS)

    Guo, J.; Ma, L.; Sak, P. B.; Gaillardet, J.; Chabaux, F. J.; Brantley, S. L.

    2015-12-01

    Chemical weathering is a critical process to global CO2 consumption, river/ocean chemistry, and nutrient import to biosphere. Weathering rinds experience minimal physical erosion and provide a well-constrained system to study the chemical weathering process. Here, we applied U-series disequilibrium dating method to study weathering advance rates on the wet side of Basse-Terre Island, French Guadeloupe, aiming to understand the role of the precipitation in controlling weathering rates and elucidate the behavior and immobilization mechanisms of U-series isotopes during rind formation. Six weathering clasts from 5 watersheds with mean annual precipitation varying from 2000 to 3000 mm/yr were measured for U-series isotope ratios and major element compositions on linear core-to-rind transects. One sample experienced complete core-to-rind transformation, while the rest clasts contain both rinds and unweathered cores. Our results show that the unweathered cores are under U-series secular equilibrium, while all the rind materials show significant U-series disequilibrium. For most rinds, linear core-to-rind increases of (230Th/232Th) activity ratios suggest a simple continuous U addition history. However, (234U/238U) and (238U/232Th) trends in several clasts show evidences of remobilization of Uranium besides the U addition, complicating the use of U-series dating method. The similarity between U/Th ratios and major elements trends like Fe, Al, P in some transects and the ongoing leaching experiments suggest that redox and organic colloids could control the mobilization of U-series isotopes in the rinds. Rind formation ages and weathering advance rate (0.07-0.29mm/kyr) were calculated for those rinds with a simple U-addition history. Our preliminary results show that local precipitation gradient significantly influenced the weathering advance rate, revealing the potential of estimating weathering advance rates at a large spatial scale using the U-series dating method.

  9. Simulation study on transient electric shock characteristics of human body under high voltage ac transmission lines

    NASA Astrophysics Data System (ADS)

    Huang, Tao; Zou, Yanhui; Lv, Jianhong; Yang, Jinchun; Tao, Li; Zhou, Jianfei

    2017-09-01

    Human body under high-voltage AC transmission lines will produce a certain induced voltage due to the electrostatic induction. When the human body contacts with some grounded objects, the charges transfer from the body to the ground and produce contact current which may cause transient electric shock. Using CDEGS and ATP/EMTP, the paper proposes a method for quantitatively calculating the transient electric shock characteristics. It calculates the human body voltage, discharge current and discharge energy under certain 500kV compact-type transmission lines and predicts the corresponding human feelings. The results show that the average root value of discharge current is less than 10mA when the human body is under the 500kV compact-type transmission lines and the human body is overall safe if the transmission lines satisfy the relevant design specifications. It concludes that the electric field strength above the ground should be limited to 4kV/m through the residential area for the purpose of reducing the electromagnetic impact.

  10. Linkage disequilibrium between polymorphisms at the 5{prime} untranslated region and intron 5 (Dde I) of the antithrombin III (ATIII) gene in the Chinese

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

    Tay, J.S.H.; Liu, Y.; Low, P.S.

    A length polymorphism at the 5{prime} untranslated region of exon 1 and an RFLP (Dde I) in intron 5 (nt 160) of the ATIII gene were amplified by polymerase chain reaction with primers of published sequences. DNA fragments were size-fractionated by agarose gel electrophoresis (3% NuSieve and 1% Seakem GTG) and photographed over a UV transilluminator. A strong linkage disequilibrium was observed between these two polymorphisms of the ATIII gene in the Chinese ({chi}{sup 2} = 63.7; {triangle} 0.42, P < 0.001). The estimated frequencies of the three haplotypes were found to be 0.37 for SD+, 0.40 for LD+ andmore » 0.23 for LD-.« less

  11. Two-Oxide Disequilibrium: A New Geospeedometer Based on Diffusion in Ilmenite

    NASA Astrophysics Data System (ADS)

    Williams, K. B.; Krawczynski, M. J.; Van Orman, J. A.

    2016-12-01

    Diffusion-annealing experiments were conducted in a 0.5" piston cylinder apparatus to investigate diffusivity of Fe2+, Mg2+, and Mn2+ in ilmenite solid solutions between 800ºC and 1000ºC. Polycrystalline ilmenite (FeTiO3) was juxtaposed against either an oriented geikielite (MgTiO3) single crystal or polycrystalline Mn-bearing (5 mol% Mn) ilmenite, in a "diffusion-couple" geometry. Geikielite single crystals were synthesized at Los Alamos National Laboratory, cut into 1 mm edge-length cubes, and polished either perpendicular or parallel to the c-axis. Polycrystalline ilmenite starting materials were synthesized by mixing high purity reagent-grade oxides (FeO, MnO, and TiO2) and sintering in a piston cylinder apparatus, then cut into wafers and polished. Experimental run products were analyzed by electron microprobe at Washington University in St. Louis. Microprobe analyses were obtained perpendicularly across the diffusion interface for each experiment. Experimental diffusion profiles create smooth curves that, when fit with an error function, define Fe-Mg and Fe-Mn interdiffusion coefficients in ilmenite. The diffusion coefficients do not appear compositionally dependent, but do show significant anisotropy. Preliminary results suggest diffusion activation energies are lower in ilmenite than in titanomagnetite [1]. Ilmenite-titanomagnetite equilibria define pre-eruptive temperatures and oxygen fugacities. However, oxides often exist out of equilibrium [2]. We use the cation diffusion data for ilmenite and existing data on titanomagnetite to establish two-oxide disequilibrium as a geospeedometer. Our data constrain oxide-oxide re-equilibration timescales at Mt. Unzen to months, consistent with estimates from zoned, single crystals of magnetite [3,4]. Future experiments will examine the effect of oxygen fugacity on diffusivity in ilmenite solid solutions. References:[1] Van Orman & Crispin (2010) RiMG 72, 757-825.[2] Bacon & Hirschmann (1988) Am. Min. 73, 57

  12. Experimental pig-to-pig transmission dynamics for African swine fever virus, Georgia 2007/1 strain.

    PubMed

    Guinat, C; Gubbins, S; Vergne, T; Gonzales, J L; Dixon, L; Pfeiffer, D U

    2016-01-01

    African swine fever virus (ASFV) continues to cause outbreaks in domestic pigs and wild boar in Eastern European countries. To gain insights into its transmission dynamics, we estimated the pig-to-pig basic reproduction number (R 0) for the Georgia 2007/1 ASFV strain using a stochastic susceptible-exposed-infectious-recovered (SEIR) model with parameters estimated from transmission experiments. Models showed that R 0 is 2·8 [95% confidence interval (CI) 1·3-4·8] within a pen and 1·4 (95% CI 0·6-2·4) between pens. The results furthermore suggest that ASFV genome detection in oronasal samples is an effective diagnostic tool for early detection of infection. This study provides quantitative information on transmission parameters for ASFV in domestic pigs, which are required to more effectively assess the potential impact of strategies for the control of between-farm epidemic spread in European countries.

  13. Essays on electricity transmission investment and financial transmission rights

    NASA Astrophysics Data System (ADS)

    Shang, Wenzhuo

    The U.S. electric power industry has been going through fundamental restructuring and realignment since the 1990's. Many issues and problems have emerged during the transition, and both economists and engineers have been looking for the solutions fervently. In this dissertation, which consists primarily of three essays, we apply economics theory and techniques to the power industry and address two related issues, transmission investment and financial transmission rights (FTRs). The first essay takes the decentralized perspective and investigates the efficiency attribute of market-based transmission investment under perfect competition. We clarify, for the first time, the nature of the externality created by loop flows that causes transmission investment to be inefficient. Our findings have important implications for better understanding of transmission market design and creating incentives for efficient transmission investment. In the second essay, we define several rules for allocating transmission investment cost within the framework of cooperative game theory. These rules provide fair, stable or efficient cost allocations in theory and are good benchmarks against which the allocation mechanism in practice can be compared and improved upon. In the last essay, we make exploratory efforts in analyzing and assessing empirically the performance of the Midwest independent system operator (MISO) FTR auction market. We reveal some stylized facts about this young market and find that it is not efficient under the risk-neutrality assumption. We also point out and correct the drawbacks in previous related work and suggest about more complete empirical work in future. In all, this dissertation makes both theoretic and empirical analysis of the two hot issues related to the power industry and comes up with findings that have important implications for the development of this industry.

  14. A public choice framework for controlling transmissible and evolving diseases

    PubMed Central

    Althouse, Benjamin M.; Bergstrom, Theodore C.; Bergstrom, Carl T.

    2009-01-01

    Control measures used to limit the spread of infectious disease often generate externalities. Vaccination for transmissible diseases can reduce the incidence of disease even among the unvaccinated, whereas antimicrobial chemotherapy can lead to the evolution of antimicrobial resistance and thereby limit its own effectiveness over time. We integrate the economic theory of public choice with mathematical models of infectious disease to provide a quantitative framework for making allocation decisions in the presence of these externalities. To illustrate, we present a series of examples: vaccination for tetanus, vaccination for measles, antibiotic treatment of otitis media, and antiviral treatment of pandemic influenza. PMID:20018681

  15. Precise determination of the refractive index of suspended particles: light transmission as a function of refractive index mismatch

    NASA Astrophysics Data System (ADS)

    McClymer, J. P.

    2016-08-01

    Many fluids appear white because refractive index differences lead to multiple scattering. In this paper, we use safe, low-cost commercial index matching fluids to quantitatively study light transmission as a function of index mismatch, reduce multiple scattering to allow single scattering probes, and to precisely determine the index of refraction of suspended material. The transmission profile is compared with Rayleigh-Gans and Mie theory predictions. The procedure is accessible as a student laboratory project, while providing advantages over other standard methods of measuring the refractive index of an unknown nanoparticle, making it valuable to researchers.

  16. AUTOMOTIVE DIESEL MAINTENANCE 2. UNIT XXII, MICHIGAN/CLARK TRANSMISSION--CONVERTER/TRANSMISSION.

    ERIC Educational Resources Information Center

    Minnesota State Dept. of Education, St. Paul. Div. of Vocational and Technical Education.

    THIS MODULE OF A 25-MODULE COURSE IS DESIGNED TO DEVELOP A DETAILED UNDERSTANDING OF A SPECIFIC POWER CONVERTER AND TRANSMISSION USED ON DIESEL POWERED EQUIPMENT. TOPICS ARE A CLOSER LOOK AT THE CONVERTER, CONVERTER ASSEMBLY AND INSTALLATION, TRANSMISSION FUNCTION, AND TRANSMISSION SHIFTING. THE MODULE CONSISTS OF A SELF-INSTRUCTIONAL PROGRAMED…

  17. Plant-mediated interspecific horizontal transmission of an intracellular symbiont in insects

    PubMed Central

    Gonella, Elena; Pajoro, Massimo; Marzorati, Massimo; Crotti, Elena; Mandrioli, Mauro; Pontini, Marianna; Bulgari, Daniela; Negri, Ilaria; Sacchi, Luciano; Chouaia, Bessem; Daffonchio, Daniele; Alma, Alberto

    2015-01-01

    Intracellular reproductive manipulators, such as Candidatus Cardinium and Wolbachia are vertically transmitted to progeny but rarely show co-speciation with the host. In sap-feeding insects, plant tissues have been proposed as alternative horizontal routes of interspecific transmission, but experimental evidence is limited. Here we report results from experiments that show that Cardinium is horizontally transmitted between different phloem sap-feeding insect species through plants. Quantitative PCR and in situ hybridization experiments indicated that the leafhopper Scaphoideus titanus releases Cardinium from its salivary glands during feeding on both artificial media and grapevine leaves. Successional time-course feeding experiments with S. titanus initially fed sugar solutions or small areas of grapevine leaves followed by feeding by the phytoplasma vector Macrosteles quadripunctulatus or the grapevine feeder Empoasca vitis revealed that the symbionts were transmitted to both species. Explaining interspecific horizontal transmission through plants improves our understanding of how symbionts spread, their lifestyle and the symbiont-host intermixed evolutionary pattern. PMID:26563507

  18. Plant-mediated interspecific horizontal transmission of an intracellular symbiont in insects.

    PubMed

    Gonella, Elena; Pajoro, Massimo; Marzorati, Massimo; Crotti, Elena; Mandrioli, Mauro; Pontini, Marianna; Bulgari, Daniela; Negri, Ilaria; Sacchi, Luciano; Chouaia, Bessem; Daffonchio, Daniele; Alma, Alberto

    2015-11-13

    Intracellular reproductive manipulators, such as Candidatus Cardinium and Wolbachia are vertically transmitted to progeny but rarely show co-speciation with the host. In sap-feeding insects, plant tissues have been proposed as alternative horizontal routes of interspecific transmission, but experimental evidence is limited. Here we report results from experiments that show that Cardinium is horizontally transmitted between different phloem sap-feeding insect species through plants. Quantitative PCR and in situ hybridization experiments indicated that the leafhopper Scaphoideus titanus releases Cardinium from its salivary glands during feeding on both artificial media and grapevine leaves. Successional time-course feeding experiments with S. titanus initially fed sugar solutions or small areas of grapevine leaves followed by feeding by the phytoplasma vector Macrosteles quadripunctulatus or the grapevine feeder Empoasca vitis revealed that the symbionts were transmitted to both species. Explaining interspecific horizontal transmission through plants improves our understanding of how symbionts spread, their lifestyle and the symbiont-host intermixed evolutionary pattern.

  19. Epidemiological role of birds in the transmission and maintenance of zoonoses.

    PubMed

    Contreras, A; Gómez-Martín, A; Paterna, A; Tatay-Dualde, J; Prats-Van Der Ham, M; Corrales, J C; De La Fe, C; Sánchez, A

    2016-12-01

    The risk of zoonoses spreading from birds to humans is lower, quantitatively speaking, than the risk of transmission between other host groups, because the two taxonomic groups share fewer pathogens. Nevertheless, birds have a number of epidemiological characteristics that make them extremely important hosts in the transmission and maintenance of zoonoses, including their susceptibility to pathogens that are extremely hazardous to humans (such as highly pathogenic avian influenza virus, West Nile virus and Chlamydia psittaci) and their ability to travel long distances, especially in the case of migratory birds. The fact that the human diet includes poultry products (meat, eggs and their by-products) also means that most human cases of foodborne zoonoses are infections of avian origin. Lastly, close contact between humans and pet birds or urban birds leads to interactions of public health concern. This article sets out to describe the main factors that determine the role of birds in the epidemiology of zoonotic infections. © OIE (World Organisation for Animal Health), 2016.

  20. Refined mapping of a gene responsible for Fukuyama-type congenital muscular dystrophy: Evidence for strong linkage disequilibrium

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

    Toda, Tatsushi; Ikegawa, Shiro; Okui, Keiko

    1994-11-01

    Fukuyama-type congenital muscular dystrophy (FCMD), the second most common form of childhood muscular dystrophy in Japan, is an autosomal recessive severe muscular dystrophy associated with an anomaly of the brain. After our initial mapping of the FCMD locus to chromosome 9q31-33, we further defined the locus within a region of {approximately}5 cM between loci D9S127 and CA246, by homozygosity mapping in patients born to consanguineous marriages and by recombination analyses in other families. We also found evidence for strong linkage disequilibrium between FCMD and a polymorphic microsatellite marker, mfd220, which showed no recombination and a lod score of (Z) 17.49.more » A {open_quotes}111-bp{close_quotes} allele for the mfd220 was observed in 22 (34%) of 64 FCMD chromosomes, but it was present in only 1 of 120 normal chromosomes. This allelic association with FCMD was highly significant ({chi}{sup 2} = 50.7; P < .0001). Hence, we suspect that the FCMD gene could lie within a few hundred kilobases of the mfd220 locus. 32 refs., 2 figs., 2 tabs.« less

  1. The combined use of heat-pulse flowmeter logging and packer testing for transmissive fracture recognition

    NASA Astrophysics Data System (ADS)

    Lo, Hung-Chieh; Chen, Po-Jui; Chou, Po-Yi; Hsu, Shih-Meng

    2014-06-01

    This paper presents an improved borehole prospecting methodology based on a combination of techniques in the hydrogeological characterization of fractured rock aquifers. The approach is demonstrated by on-site tests carried out in the Hoshe Experimental Forest site and the Tailuge National Park, Taiwan. Borehole televiewer logs are used to obtain fracture location and distribution along boreholes. The heat-pulse flow meter log is used to measure vertical velocity flow profiles which can be analyzed to estimate fracture transmissivity and to indicate hydraulic connectivity between fractures. Double-packer hydraulic tests are performed to determine the rock mass transmissivity. The computer program FLASH is used to analyze the data from the flowmeter logs. The FLASH program is confirmed as a useful tool which quantitatively predicts the fracture transmissivity in comparison to the hydraulic properties obtained from packer tests. The location of conductive fractures and their transmissivity is identified, after which the preferential flow paths through the fracture network are precisely delineated from a cross-borehole test. The results provide robust confirmation of the use of combined flowmeter and packer methods in the characterization of fractured-rock aquifers, particularly in reference to the investigation of groundwater resource and contaminant transport dynamics.

  2. AQUIFER TRANSMISSIVITY

    EPA Science Inventory

    Evaluation of groundwater resources requires the knowledge of the capacity of aquifers to store and transmit ground water. This requires estimates of key hydraulic parameters, such as the transmissivity, among others. The transmissivity T (m2/sec) is a hydrauli...

  3. Inference of R 0 and Transmission Heterogeneity from the Size Distribution of Stuttering Chains

    PubMed Central

    Blumberg, Seth; Lloyd-Smith, James O.

    2013-01-01

    For many infectious disease processes such as emerging zoonoses and vaccine-preventable diseases, and infections occur as self-limited stuttering transmission chains. A mechanistic understanding of transmission is essential for characterizing the risk of emerging diseases and monitoring spatio-temporal dynamics. Thus methods for inferring and the degree of heterogeneity in transmission from stuttering chain data have important applications in disease surveillance and management. Previous researchers have used chain size distributions to infer , but estimation of the degree of individual-level variation in infectiousness (as quantified by the dispersion parameter, ) has typically required contact tracing data. Utilizing branching process theory along with a negative binomial offspring distribution, we demonstrate how maximum likelihood estimation can be applied to chain size data to infer both and the dispersion parameter that characterizes heterogeneity. While the maximum likelihood value for is a simple function of the average chain size, the associated confidence intervals are dependent on the inferred degree of transmission heterogeneity. As demonstrated for monkeypox data from the Democratic Republic of Congo, this impacts when a statistically significant change in is detectable. In addition, by allowing for superspreading events, inference of shifts the threshold above which a transmission chain should be considered anomalously large for a given value of (thus reducing the probability of false alarms about pathogen adaptation). Our analysis of monkeypox also clarifies the various ways that imperfect observation can impact inference of transmission parameters, and highlights the need to quantitatively evaluate whether observation is likely to significantly bias results. PMID:23658504

  4. Quantitative analysis of lentiviral transgene expression in mice over seven generations.

    PubMed

    Wang, Yong; Song, Yong-tao; Liu, Qin; Liu, Cang'e; Wang, Lu-lu; Liu, Yu; Zhou, Xiao-yang; Wu, Jun; Wei, Hong

    2010-10-01

    Lentiviral transgenesis is now recognized as an extremely efficient and cost-effective method to produce transgenic animals. Transgenes delivered by lentiviral vectors exhibited inheritable expression in many species including those which are refractory to genetic modification such as non-human primates. However, epigenetic modification was frequently observed in lentiviral integrants, and transgene expression found to be inversely correlated with methylation density. Recent data showed that about one-third lentiviral integrants exhibited hypermethylation and low expression, but did not demonstrate whether those integrants with high expression could remain constant expression and hypomethylated during long term germline transmission. In this study, using lentiviral eGFP transgenic mice as the experimental animals, lentiviral eGFP expression levels and its integrant numbers in genome were quantitatively analyzed by fluorescent quantitative polymerase-chain reaction (FQ-PCR), using the house-keeping gene ribosomal protein S18 (Rps18) and the single copy gene fatty acid binding protein of the intestine (Fabpi) as the internal controls respectively. The methylation densities of the integrants were quantitatively analyzed by bisulfite sequencing. We found that the lentiviral integrants with high expression exhibited a relative constant expression level per integrant over at least seven generations. Besides, the individuals containing these integrants exhibited eGFP expression levels which were positively and almost linearly correlated with the integrant numbers in their genomes, suggesting that no remarkable position effect on transgene expression of the integrants analyzed was observed. In addition, over seven generations the methylation density of these integrants did not increase, but rather decreased remarkably, indicating that these high expressing integrants were not subjected to de novo methylation during at least seven generations of germline transmission. Taken

  5. Multi-frequency Axial Transmission Bone Ultrasonometer

    PubMed Central

    Tatarinov, Alexey; Egorov, Vladimir; Sarvazyan, Noune; Sarvazyan, Armen

    2014-01-01

    The last decade has seen a surge in the development of axial transmission QUS (Quantitative UltraSound) technologies for the assessment of long bones using various modes of acoustic waves. The condition of cortical bones and the development of osteoporosis are determined by numerous mechanical, micro-structural, and geometrical or macro-structural bone properties like hardness, porosity and cortical thickness. Such complex manifestations of osteoporosis require the evaluation of multiple parameters with different sensitivities to the various properties of bone that are affected by the disease. This objective may be achieved by using a multi-frequency ultrasonic examination The ratio of the acoustic wavelength to the cortical thickness can be changed by varying the frequency of the ultrasonic pulse propagating through the long bone that results in the change in composition of the induced wave comprised of a set of numerous modes of guided, longitudinal, and surface acoustic waves. The multi-frequency axial transmission QUS method developed at Artann Laboratories (Trenton, NJ) is implemented in the Bone Ultrasonic Scanner (BUSS). In the current version of the BUSS, a train of ultrasonic pulses with 60, 100, 400, 800, and 1200 kHz frequencies is used. The developed technology was tested on a variety of bone phantoms simulating normal, osteopenic, and osteoporotic bones. The results of this study confirm the feasibility of the multi-frequency approach for the assessment of the processes leading to osteoporosis. PMID:24206675

  6. Relationship Between Health Literacy, Knowledge of Health Status, and Beliefs about HIV/AIDS Transmission among Ryan White Clients in Miami

    ERIC Educational Resources Information Center

    Mooss, Angela; Brock-Getz, Petra; Ladner, Robert; Fiano, Theresa

    2013-01-01

    Objective: The aim of this study was to examine the relationships between health literacy, knowledge of health status, and human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) transmission beliefs among recipients of Ryan White care. Design: Quota and convenience sampled, quantitative analysis captured with closed and…

  7. Finite-difference interblock transmissivity for unconfined aquifers and for aquifers having smoothly varying transmissivity

    USGS Publications Warehouse

    Goode, D.J.; Appel, C.A.

    1992-01-01

    More accurate alternatives to the widely used harmonic mean interblock transmissivity are proposed for block-centered finite-difference models of ground-water flow in unconfined aquifers and in aquifers having smoothly varying transmissivity. The harmonic mean is the exact interblock transmissivity for steady-state one-dimensional flow with no recharge if the transmissivity is assumed to be spatially uniform over each finite-difference block, changing abruptly at the block interface. However, the harmonic mean may be inferior to other means if transmissivity varies in a continuous or smooth manner between nodes. Alternative interblock transmissivity functions are analytically derived for the case of steady-state one-dimensional flow with no recharge. The second author has previously derived the exact interblock transmissivity, the logarithmic mean, for one-dimensional flow when transmissivity is a linear function of distance in the direction of flow. We show that the logarithmic mean transmissivity is also exact for uniform flow parallel to the direction of changing transmissivity in a two- or three-dimensional model, regardless of grid orientation relative to the flow vector. For the case of horizontal flow in a homogeneous unconfined or water-table aquifer with a horizontal bottom and with areally distributed recharge, the exact interblock transmissivity is the unweighted arithmetic mean of transmissivity at the nodes. This mean also exhibits no grid-orientation effect for unidirectional flow in a two-dimensional model. For horizontal flow in an unconfined aquifer with no recharge where hydraulic conductivity is a linear function of distance in the direction of flow the exact interblock transmissivity is the product of the arithmetic mean saturated thickness and the logarithmic mean hydraulic conductivity. For several hypothetical two- and three-dimensional cases with smoothly varying transmissivity or hydraulic conductivity, the harmonic mean is shown to yield

  8. Pellicle transmission uniformity requirements

    NASA Astrophysics Data System (ADS)

    Brown, Thomas L.; Ito, Kunihiro

    1998-12-01

    Controlling critical dimensions of devices is a constant battle for the photolithography engineer. Current DUV lithographic process exposure latitude is typically 12 to 15% of the total dose. A third of this exposure latitude budget may be used up by a variable related to masking that has not previously received much attention. The emphasis on pellicle transmission has been focused on increasing the average transmission. Much less, attention has been paid to transmission uniformity. This paper explores the total demand on the photospeed latitude budget, the causes of pellicle transmission nonuniformity and examines reasonable expectations for pellicle performance. Modeling is used to examine how the two primary errors in pellicle manufacturing contribute to nonuniformity in transmission. World-class pellicle transmission uniformity standards are discussed and a comparison made between specifications of other components in the photolithographic process. Specifications for other materials or parameters are used as benchmarks to develop a proposed industry standard for pellicle transmission uniformity.

  9. Measuring demand for flat water recreation using a two-stage/disequilibrium travel cost model with adjustment for overdispersion and self-selection

    NASA Astrophysics Data System (ADS)

    McKean, John R.; Johnson, Donn; Taylor, R. Garth

    2003-04-01

    An alternate travel cost model is applied to an on-site sample to estimate the value of flat water recreation on the impounded lower Snake River. Four contiguous reservoirs would be eliminated if the dams are breached to protect endangered Pacific salmon and steelhead trout. The empirical method applies truncated negative binomial regression with adjustment for endogenous stratification. The two-stage decision model assumes that recreationists allocate their time among work and leisure prior to deciding among consumer goods. The allocation of time and money among goods in the second stage is conditional on the predetermined work time and income. The second stage is a disequilibrium labor market which also applies if employers set work hours or if recreationists are not in the labor force. When work time is either predetermined, fixed by contract, or nonexistent, recreationists must consider separate prices and budgets for time and money.

  10. Comparison of semi-quantitative and quantitative dynamic contrast-enhanced MRI evaluations of vertebral marrow perfusion in a rat osteoporosis model.

    PubMed

    Zhu, Jingqi; Xiong, Zuogang; Zhang, Jiulong; Qiu, Yuyou; Hua, Ting; Tang, Guangyu

    2017-11-14

    This study aims to investigate the technical feasibility of semi-quantitative and quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in the assessment of longitudinal changes of marrow perfusion in a rat osteoporosis model, using bone mineral density (BMD) measured by micro-computed tomography (micro-CT) and histopathology as the gold standards. Fifty rats were randomly assigned to the control group (n=25) and ovariectomy (OVX) group whose bilateral ovaries were excised (n=25). Semi-quantitative and quantitative DCE-MRI, micro-CT, and histopathological examinations were performed on lumbar vertebrae at baseline and 3, 6, 9, and 12 weeks after operation. The differences between the two groups in terms of semi-quantitative DCE-MRI parameter (maximum enhancement, E max ), quantitative DCE-MRI parameters (volume transfer constant, K trans ; interstitial volume, V e ; and efflux rate constant, K ep ), micro-CT parameter (BMD), and histopathological parameter (microvessel density, MVD) were compared at each of the time points using an independent-sample t test. The differences in these parameters between baseline and other time points in each group were assessed via Bonferroni's multiple comparison test. A Pearson correlation analysis was applied to assess the relationships between DCE-MRI, micro-CT, and histopathological parameters. In the OVX group, the E max values decreased significantly compared with those of the control group at weeks 6 and 9 (p=0.003 and 0.004, respectively). The K trans values decreased significantly compared with those of the control group from week 3 (p<0.05). However, the V e values decreased significantly only at week 9 (p=0.032), and no difference in the K ep was found between two groups. The BMD values of the OVX group decreased significantly compared with those of the control group from week 3 (p<0.05). Transmission electron microscopy showed tighter gaps between vascular endothelial cells with swollen mitochondria

  11. Downhole transmission system

    DOEpatents

    Hall, David R [Provo, UT; Fox, Joe [Spanish Fork, UT

    2008-01-15

    A transmission system in a downhole component comprises a data transmission element in both ends of the downhole component. Each data transmission element houses an electrically conducting coil in a MCEI circular trough. An electrical conductor connects both the transmission elements. The electrical conductor comprises at least three electrically conductive elements insulated from each other. In the preferred embodiment the electrical conductor comprises an electrically conducting outer shield, an electrically conducting inner shield and an electrical conducting core. In some embodiments of the present invention, the electrical conductor comprises an electrically insulating jacket. In other embodiments, the electrical conductor comprises a pair of twisted wires. In some embodiments, the electrical conductor comprises semi-conductive material.

  12. Printed circuit dispersive transmission line

    DOEpatents

    Ikezi, H.; Lin-Liu, Y.R.; DeGrassie, J.S.

    1991-08-27

    A printed circuit dispersive transmission line structure is disclosed comprising an insulator, a ground plane formed on one surface of the insulator, a first transmission line formed on a second surface of the insulator, and a second transmission line also formed on the second surface of the insulator and of longer length than the first transmission line and periodically intersecting the first transmission line. In a preferred embodiment, the transmission line structure exhibits highly dispersive characteristics by designing the length of one of the transmission line between two adjacent periodic intersections to be longer than the other. 5 figures.

  13. Printed circuit dispersive transmission line

    DOEpatents

    Ikezi, Hiroyuki; Lin-Liu, Yuh-Ren; DeGrassie, John S.

    1991-01-01

    A printed circuit dispersive transmission line structure is disclosed comprising an insulator, a ground plane formed on one surface of the insulator, a first transmission line formed on a second surface of the insulator, and a second transmission line also formed on the second surface of the insulator and of longer length than the first transmission line and periodically intersecting the first transmission line. In a preferred embodiment, the transmission line structure exhibits highly dispersive characteristics by designing the length of one of the transmission line between two adjacent periodic intersections to be longer than the other.

  14. Genetic Diversity of Plasmodium falciparum in Haiti: Insights from Microsatellite Markers

    PubMed Central

    Carter, Tamar E.; Malloy, Halley; Existe, Alexandre; Memnon, Gladys; St. Victor, Yves; Okech, Bernard A.; Mulligan, Connie J.

    2015-01-01

    Hispaniola, comprising Haiti and the Dominican Republic, has been identified as a candidate for malaria elimination. However, incomplete surveillance data in Haiti hamper efforts to assess the impact of ongoing malaria control interventions. Characteristics of the genetic diversity of Plasmodium falciparum populations can be used to assess parasite transmission, which is information vital to evaluating malaria elimination efforts. Here we characterize the genetic diversity of P. falciparum samples collected from patients at seven sites in Haiti using 12 microsatellite markers previously employed in population genetic analyses of global P. falciparum populations. We measured multiplicity of infections, level of genetic diversity, degree of population geographic substructure, and linkage disequilibrium (defined as non-random association of alleles from different loci). For low transmission populations like Haiti, we expect to see few multiple infections, low levels of genetic diversity, high degree of population structure, and high linkage disequilibrium. In Haiti, we found low levels of multiple infections (12.9%), moderate to high levels of genetic diversity (mean number of alleles per locus = 4.9, heterozygosity = 0.61), low levels of population structure (highest pairwise Fst = 0.09 and no clustering in principal components analysis), and moderate linkage disequilibrium (ISA = 0.05, P<0.0001). In addition, population bottleneck analysis revealed no evidence for a reduction in the P. falciparum population size in Haiti. We conclude that the high level of genetic diversity and lack of evidence for a population bottleneck may suggest that Haiti’s P. falciparum population has been stable and discuss the implications of our results for understanding the impact of malaria control interventions. We also discuss the relevance of parasite population history and other host and vector factors when assessing transmission intensity from genetic diversity data. PMID:26462203

  15. Th-230 - U-238 series disequilibrium of the Olkaria basalts Gregory Rift Valley, Kenya

    NASA Technical Reports Server (NTRS)

    Black, S.; Macdonald, R.; Kelly, M.

    1993-01-01

    U-Th disequilibrium analyses of the Naivasha basalts show a very small (U-238/Th-230) ratios which are lower than any previously analyzed basalts. The broadly positive internal isochron trend from one sample indicates that the basalts may have source heterogeneities, this is supported by earlier work. The Naivasha complex comprises a bimodal suite of basalts and rhyolites. The basalts are divided into two stratigraphic groups each of a transitional nature. The early basalt series (EBS) which were erupted prior to the Group 1 comendites and, the late basalt series (LBS) which erupted temporally between the Broad Acres and the Ololbutot centers. The basalts represent a very small percentage of the overall eruptive volume of material at Naivasha (less than 2 percent). The analyzed samples come from four stratigraphic units in close proximity around Ndabibi, Hell's Gate and Akira areas. The earliest units occur as vesicular flows from the Ndabibi plain. These basalts are olivine-plagioclase phyric with the associated hawaiites being sparsely plagioclase phyric. An absolute age of 0.5Ma was estimated for these basalts. The next youngest basalts flows occur as younger tuft cones in the Ndabibi area and are mainly olivine-plagioclase-clinopyroxcene phyric with one purely plagioclase phyric sample. The final phase of activity at Ndabibi resulted in much younger tuft cones consisting of air fall ashes and lapilli tufts. Many of these contain resorbed plagioclase phenocrysts with sample number 120c also being clinopyroxene phyric. The isotopic evidence for the basalt formation is summarized.

  16. A tool for selecting SNPs for association studies based on observed linkage disequilibrium patterns.

    PubMed

    De La Vega, Francisco M; Isaac, Hadar I; Scafe, Charles R

    2006-01-01

    The design of genetic association studies using single-nucleotide polymorphisms (SNPs) requires the selection of subsets of the variants providing high statistical power at a reasonable cost. SNPs must be selected to maximize the probability that a causative mutation is in linkage disequilibrium (LD) with at least one marker genotyped in the study. The HapMap project performed a genome-wide survey of genetic variation with about a million SNPs typed in four populations, providing a rich resource to inform the design of association studies. A number of strategies have been proposed for the selection of SNPs based on observed LD, including construction of metric LD maps and the selection of haplotype tagging SNPs. Power calculations are important at the study design stage to ensure successful results. Integrating these methods and annotations can be challenging: the algorithms required to implement these methods are complex to deploy, and all the necessary data and annotations are deposited in disparate databases. Here, we present the SNPbrowser Software, a freely available tool to assist in the LD-based selection of markers for association studies. This stand-alone application provides fast query capabilities and swift visualization of SNPs, gene annotations, power, haplotype blocks, and LD map coordinates. Wizards implement several common SNP selection workflows including the selection of optimal subsets of SNPs (e.g. tagging SNPs). Selected SNPs are screened for their conversion potential to either TaqMan SNP Genotyping Assays or the SNPlex Genotyping System, two commercially available genotyping platforms, expediting the set-up of genetic studies with an increased probability of success.

  17. Drivers of Tuberculosis Transmission.

    PubMed

    Mathema, Barun; Andrews, Jason R; Cohen, Ted; Borgdorff, Martien W; Behr, Marcel; Glynn, Judith R; Rustomjee, Roxana; Silk, Benjamin J; Wood, Robin

    2017-11-03

    Measuring tuberculosis transmission is exceedingly difficult, given the remarkable variability in the timing of clinical disease after Mycobacterium tuberculosis infection; incident disease can result from either a recent (ie, weeks to months) or a remote (ie, several years to decades) infection event. Although we cannot identify with certainty the timing and location of tuberculosis transmission for individuals, approaches for estimating the individual probability of recent transmission and for estimating the fraction of tuberculosis cases due to recent transmission in populations have been developed. Data used to estimate the probable burden of recent transmission include tuberculosis case notifications in young children and trends in tuberculin skin test and interferon γ-release assays. More recently, M. tuberculosis whole-genome sequencing has been used to estimate population levels of recent transmission, identify the distribution of specific strains within communities, and decipher chains of transmission among culture-positive tuberculosis cases. The factors that drive the transmission of tuberculosis in communities depend on the burden of prevalent tuberculosis; the ways in which individuals live, work, and interact (eg, congregate settings); and the capacity of healthcare and public health systems to identify and effectively treat individuals with infectious forms of tuberculosis. Here we provide an overview of these factors, describe tools for measurement of ongoing transmission, and highlight knowledge gaps that must be addressed. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

  18. Increased level of linkage disequilibrium in rural compared with urban communities: a factor to consider in association-study design.

    PubMed

    Vitart, Veronique; Carothers, Andrew D; Hayward, Caroline; Teague, Peter; Hastie, Nicholas D; Campbell, Harry; Wright, Alan F

    2005-05-01

    Few studies have investigated genetic differentiation within nonisolate European populations, despite the initiation of large national sample collections such as U.K. Biobank. Here, we used short tandem repeat markers to explore fine-scale genetic structure and to examine the extent of linkage disequilibrium (LD) within national subpopulations. We studied 955 unrelated individuals of local ancestry from nine Scottish rural regions and the urban center of Edinburgh, as well as 96 unrelated individuals from the general U.K. population. Despite little overall differentiation on the basis of allele frequencies, there were clear differences among subpopulations in the extent of pairwise LD, measured between a subset of X-linked markers, that reflected presumed differences in the depths of the underlying genealogies within these subpopulations. Therefore, there are strategic advantages in studying rural subpopulations, in terms of increased power and reduced cost, that are lost by sampling across regions or within urban populations. Similar rural-urban contrasts are likely to exist in many other populations with stable rural subpopulations, which could influence the design of genetic association studies and national biobank data collections.

  19. Detection of Campylobacter jejuni in Lizard Faeces from Central Australia Using Quantitative PCR

    PubMed Central

    Whiley, Harriet; McLean, Ryan; Ross, Kirstin

    2016-01-01

    Worldwide, Campylobacter is a significant cause of gastrointestinal illness. It is predominately considered a foodborne pathogen, with human exposure via non-food transmission routes generally overlooked. Current literature has been exploring environmental reservoirs of campylobacteriosis including potential wildlife reservoirs. Given the close proximity between lizards and human habitats in Central Australia, this study examined the presence of Campylobacter jejuni from lizard faeces collected from this region. Of the 51 samples collected, 17 (33%) (this included 14/46 (30%) wild and 3/5 (60%) captive lizard samples) were positive for C. jejuni using quantitative PCR (qPCR). This was the first study to investigate the presence of C. jejuni in Australian lizards. This has public health implications regarding the risk of campylobacteriosis from handling of pet reptiles and through cross-contamination or contact with wild lizard faeces. Additionally this has implication for horizontal transmission via lizards of C. jejuni to food production farms. Further research is needed on this environmental reservoir and potential transmission routes to reduce the risk to public health. PMID:28025556

  20. Automated manual transmission clutch controller

    DOEpatents

    Lawrie, Robert E.; Reed, Jr., Richard G.; Rausen, David J.

    1999-11-30

    A powertrain system for a hybrid vehicle. The hybrid vehicle includes a heat engine, such as a diesel engine, and an electric machine, which operates as both an electric motor and an alternator, to power the vehicle. The hybrid vehicle also includes a manual-style transmission configured to operate as an automatic transmission from the perspective of the driver. The engine and the electric machine drive an input shaft which in turn drives an output shaft of the transmission. In addition to driving the transmission, the electric machine regulates the speed of the input shaft in order to synchronize the input shaft during either an upshift or downshift of the transmission by either decreasing or increasing the speed of the input shaft. When decreasing the speed of the input shaft, the electric motor functions as an alternator to produce electrical energy which may be stored by a storage device. Operation of the transmission is controlled by a transmission controller which receives input signals and generates output signals to control shift and clutch motors to effect smooth launch, upshift shifts, and downshifts of the transmission, so that the transmission functions substantially as an automatic transmission from the perspective of the driver, while internally substantially functioning as a manual transmission.

  1. Family-based transmission analysis of HLA genetic markers in Sardinian children with autistic spectrum disorders.

    PubMed

    Guerini, Franca R; Bolognesi, Elisabetta; Manca, Salvatorica; Sotgiu, Stefano; Zanzottera, Milena; Agliardi, Cristina; Usai, Sonia; Clerici, Mario

    2009-03-01

    Analyses of a 6-Mb region spanning the human leukocyte antigen (HLA) region from the HLA-DR to the HFE gene were performed in 37 families of Sardinian ancestry, all of whom had at least one autistic child, to identify genetic markers associated with autism spectrum disorders (ASD) development. In particular, four microsatellites (MIB, D6S265, MOGc, and D6S2239) and three single-nucleotide polymorphisms (SNPs; two in positions -308 and -238 in the promoter of the TNF-alpha and SNP rs2857766 [V142L] in exon 3 of the MOG gene) were analyzed. An intrafamilial case-control method (affected family-based controls) and transmission disequilibrium test analysis were used to evaluate the association of microsatellite and SNP markers with ASD-affected children. Results indicated positive associations with ASD for D6S265*220 (p < 0.01) and MOGc*131 (p < 0.05) and negative associations for MOGc*117 and MIB*346 alleles (p < 0.01) in ASD children. Polymorphism haplotype analysis indicated that D6S265 allele *220 and MOGc allele *131 were significantly more likely to be transmitted together, as a whole haplotype, to ASD children (p < 0.05). Conversely, the D6S265*224-MOGc*117-rs2857766(G) haplotype was significantly less frequently transmitted to ASD children (p < 0.01). The results present novel gene markers, reinforcing the hypothesis that genetic factors play a pivotal role in the pathogenesis of ASD.

  2. Preferential transmission of genetic risk variants of candidate loci at 6p21 from asymptomatic grandparents to mothers of children with neonatal lupus.

    PubMed

    Saxena, Amit; McDonnell, Erin; Ramos, Paula S; Sajuthi, Satria; Marion, Miranda C; Langefeld, Carl D; Buyon, Jill P; Clancy, Robert M

    2012-03-01

    Neonatal lupus (NL) occurs in fetuses exposed to maternal anti-SSA/Ro and/or anti-SSB/La antibodies, although the mothers themselves may not manifest any clinical disease. A focus on transmission of risk factors for NL from maternal grandparents to mothers of children with NL may yield dividends toward understanding the aggregation of autoantibodies and genetic factors in affected families. This study was perforned to determine the role of maternal grandparents in the development of the autoimmune phenotype of mothers of children with NL. Fifty-one mothers of children with cardiac and/or cutaneous NL, 48 maternal grandmothers, and 35 maternal grandfathers in the Research Registry for Neonatal Lupus were interrogated for clinical symptoms by questionnaire and underwent laboratory assessments, including determination of anti-SSA/Ro and anti-SSB/La antibody status (by enzyme-linked immunosorbent assay) and genotype at rs1800629 (TNFα) and rs7775397 (C6orf10) (allelic discrimination). The transmission disequilibrium test (TDT) was computed to test for nonrandom transmission from maternal grandparents to mothers of children with NL. The common phenotypic feature in mothers of children with NL was the autoantibody and not the clinical profile; 7 had lupus, 14 had Sjögren's syndrome, 7 had both, and 23 were asymptomatic. Mothers of children with NL were significantly enriched for the risk alleles at both TNFα and C6orf10. The grandparents of children with NL carried minimal burden for autoimmune disease or abnormal antibody production and were not enriched in the genetic risk factors. However, the TDT analysis showed significant excess transmission of the risk alleles at both TNFα (odds ratio [OR] 6.67, P = 3.93 × 10(-4) ) and C6orf10 (OR 35.0, P = 3.74 × 10(-5) ) to mothers of children with NL. Mothers of children with NL are enriched for the TNFα and C6orf10 risk alleles, which are preferentially inherited from the asymptomatic maternal grandparents. These

  3. Technique to quantitatively measure magnetic properties of thin structures at <10 NM spatial resolution

    DOEpatents

    Bajt, Sasa

    2003-07-08

    A highly sensitive and high resolution magnetic microscope images magnetic properties quantitatively. Imaging is done with a modified transmission electron microscope that allows imaging of the sample in a zero magnetic field. Two images from closely spaced planes, one in focus and one slightly out of focus, are sufficient to calculate the absolute values of the phase change imparted to the electrons, and hence obtain the magnetization vector field distribution.

  4. Transmission Planning Analysis Tool

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

    2015-06-23

    Developed to solve specific problem: Assist transmission planning for regional transfers in interconnected power systems. This work was originated in a study for the U.S. Department of State, to recommend transmission reinforcements for the Central American regional system that interconnects 6 countries. Transmission planning analysis is currently performed by engineers with domainspecific and systemspecific knowledge without a unique methodology. The software codes of this disclosure assists engineers by defining systematic analysis procedures to help identify weak points and make decisions on transmission planning of regional interconnected power systems. Transmission Planning Analysis Tool groups PSS/E results of multiple AC contingency analysismore » and voltage stability analysis and QV analysis of many scenarios of study and arrange them in a systematic way to aid power system planning engineers or transmission operators in effective decision]making process or in the off]line study environment.« less

  5. Accuracy of Genomic Prediction in Switchgrass (Panicum virgatum L.) Improved by Accounting for Linkage Disequilibrium

    PubMed Central

    Ramstein, Guillaume P.; Evans, Joseph; Kaeppler, Shawn M.; Mitchell, Robert B.; Vogel, Kenneth P.; Buell, C. Robin; Casler, Michael D.

    2016-01-01

    Switchgrass is a relatively high-yielding and environmentally sustainable biomass crop, but further genetic gains in biomass yield must be achieved to make it an economically viable bioenergy feedstock. Genomic selection (GS) is an attractive technology to generate rapid genetic gains in switchgrass, and meet the goals of a substantial displacement of petroleum use with biofuels in the near future. In this study, we empirically assessed prediction procedures for genomic selection in two different populations, consisting of 137 and 110 half-sib families of switchgrass, tested in two locations in the United States for three agronomic traits: dry matter yield, plant height, and heading date. Marker data were produced for the families’ parents by exome capture sequencing, generating up to 141,030 polymorphic markers with available genomic-location and annotation information. We evaluated prediction procedures that varied not only by learning schemes and prediction models, but also by the way the data were preprocessed to account for redundancy in marker information. More complex genomic prediction procedures were generally not significantly more accurate than the simplest procedure, likely due to limited population sizes. Nevertheless, a highly significant gain in prediction accuracy was achieved by transforming the marker data through a marker correlation matrix. Our results suggest that marker-data transformations and, more generally, the account of linkage disequilibrium among markers, offer valuable opportunities for improving prediction procedures in GS. Some of the achieved prediction accuracies should motivate implementation of GS in switchgrass breeding programs. PMID:26869619

  6. Quantitative Scanning Transmission Electron Microscopy of Electronic and Nanostructured Materials

    NASA Astrophysics Data System (ADS)

    Yankovich, Andrew B.

    Electronic and nanostructured materials have been investigated using advanced scanning transmission electron microscopy (STEM) techniques. The first topic is the microstructure of Ga and Sb-doped ZnO. Ga-doped ZnO is a candidate transparent conducting oxide material. The microstructure of GZO thin films grown by MBE under different growth conditions and different substrates were examined using various electron microscopy (EM) techniques. The microstructure, prevalent defects, and polarity in these films strongly depend on the growth conditions and substrate. Sb-doped ZnO nanowires have been shown to be the first route to stable p-type ZnO. Using Z-contrast STEM, I have showed that an unusual microstructure of Sb-decorated head-to-head inversion domain boundaries and internal voids contain all the Sb in the nanowires and cause the p-type conduction. InGaN thin films and InGaN / GaN quantum wells (QW) for light emitting diodes are the second topic. Low-dose Z-contrast STEM, PACBED, and EDS on InGaN QW LED structures grown by MOCVD show no evidence for nanoscale composition variations, contradicting previous reports. In addition, a new extended defect in GaN and InGaN was discovered. The defect consists of a faceted pyramid-shaped void that produces a threading dislocation along the [0001] growth direction, and is likely caused by carbon contamination during growth. Non-rigid registration (NRR) and high-precision STEM of nanoparticles is the final topic. NRR is a new image processing technique that corrects distortions arising from the serial nature of STEM acquisition that previously limited the precision of locating atomic columns and counting the number of atoms in images. NRR was used to demonstrate sub-picometer precision in STEM images of single crystal Si and GaN, the best achieved in EM. NRR was used to measure the atomic surface structure of Pt nanoacatalysts and Au nanoparticles, which revealed new bond length variation phenomenon of surface atoms. In

  7. Nanoscale deformation analysis with high-resolution transmission electron microscopy and digital image correlation

    DOE PAGES

    Wang, Xueju; Pan, Zhipeng; Fan, Feifei; ...

    2015-09-10

    We present an application of the digital image correlation (DIC) method to high-resolution transmission electron microscopy (HRTEM) images for nanoscale deformation analysis. The combination of DIC and HRTEM offers both the ultrahigh spatial resolution and high displacement detection sensitivity that are not possible with other microscope-based DIC techniques. We demonstrate the accuracy and utility of the HRTEM-DIC technique through displacement and strain analysis on amorphous silicon. Two types of error sources resulting from the transmission electron microscopy (TEM) image noise and electromagnetic-lens distortions are quantitatively investigated via rigid-body translation experiments. The local and global DIC approaches are applied for themore » analysis of diffusion- and reaction-induced deformation fields in electrochemically lithiated amorphous silicon. As a result, the DIC technique coupled with HRTEM provides a new avenue for the deformation analysis of materials at the nanometer length scales.« less

  8. Linkage disequilibrium with HLA-DRB1-DQB1 haplotypes explains the association of TNF-308G>A variant with type 1 diabetes in a Brazilian cohort.

    PubMed

    Patente, Thiago A; Monteiro, Maria B; Vieira, Suzana M; Rossi da Silva, Maria E; Nery, Márcia; Queiroz, Márcia; Azevedo, Mirela J; Canani, Luis H; Parisi, Maria C; Pavin, Elizabeth J; Mainardi, Débora; Javor, Juraj; Velho, Gilberto; Coimbra, Cássio N; Corrêa-Giannella, Maria Lúcia

    2015-08-15

    A functional variant in the promoter region of the gene encoding tumor necrosis factor (TNF; rs1800629, -308G>A) showed to confer susceptibility to T1D. However, TNF rs1800629 was found, in several populations, to be in linkage disequilibrium with HLA susceptibility haplotypes to T1D. We evaluated the association of TNF rs1800629 with T1D in a cohort of Brazilian subjects, and assessed the impact of HLA susceptibility haplotypes in this association. 659 subjects with T1D and 539 control subjects were genotyped for TNF-308G>A variant. HLA-DRB1 and HLA-DQB1 genes were genotyped in a subset of 313 subjects with T1D and 139 control subjects. Associations with T1D were observed for the A-allele of rs1800629 (OR 1.69, 95% CI 1.33-2.15, p<0.0001, in a codominant model) and for 3 HLA haplotypes: DRB1*03:01-DQB1*02:01 (OR 5.37, 95% CI 3.23-8.59, p<0.0001), DRB1*04:01-DQB1*03:02 (OR 2.95, 95% CI 1.21-7.21, p=0.01) and DRB1*04:02-DQB1*03:02 (OR 2.14, 95% CI 1.02-4.50, p=0.04). Linkage disequilibrium was observed between TNF rs1800629 and HLA-DRB1 and HLA-DQB1 alleles. In a stepwise regression analysis HLA haplotypes, but not TNF rs1800629, remained independently associated with T1D. Our results do not support an independent effect of allelic variations of TNF in the genetic susceptibility to T1D. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Calculating the potential for within-flight transmission of influenza A (H1N1)

    PubMed Central

    2009-01-01

    Background Clearly air travel, by transporting infectious individuals from one geographic location to another, significantly affects the rate of spread of influenza A (H1N1). However, the possibility of within-flight transmission of H1N1 has not been evaluated; although it is known that smallpox, measles, tuberculosis, SARS and seasonal influenza can be transmitted during commercial flights. Here we present the first quantitative risk assessment to assess the potential for within-flight transmission of H1N1. Methods We model airborne transmission of infectious viral particles of H1N1 within a Boeing 747 using methodology from the field of quantitative microbial risk assessment. Results The risk of catching H1N1 will essentially be confined to passengers travelling in the same cabin as the source case. Not surprisingly, we find that the longer the flight the greater the number of infections that can be expected. We calculate that H1N1, even during long flights, poses a low to moderate within-flight transmission risk if the source case travels First Class. Specifically, 0-1 infections could occur during a 5 hour flight, 1-3 during an 11 hour flight and 2-5 during a 17 hour flight. However, within-flight transmission could be significant, particularly during long flights, if the source case travels in Economy Class. Specifically, two to five infections could occur during a 5 hour flight, 5-10 during an 11 hour flight and 7-17 during a 17 hour flight. If the aircraft is only partially loaded, under certain conditions more infections could occur in First Class than in Economy Class. During a 17 hour flight, a greater number of infections would occur in First Class than in Economy if the First Class Cabin is fully occupied, but Economy class is less than 30% full. Conclusions Our results provide insights into the potential utility of air travel restrictions on controlling influenza pandemics in the winter of 2009/2010. They show travel by one infectious individual

  10. Calculating the potential for within-flight transmission of influenza A (H1N1).

    PubMed

    Wagner, Bradley G; Coburn, Brian J; Blower, Sally

    2009-12-24

    Clearly air travel, by transporting infectious individuals from one geographic location to another, significantly affects the rate of spread of influenza A (H1N1). However, the possibility of within-flight transmission of H1N1 has not been evaluated; although it is known that smallpox, measles, tuberculosis, SARS and seasonal influenza can be transmitted during commercial flights. Here we present the first quantitative risk assessment to assess the potential for within-flight transmission of H1N1. We model airborne transmission of infectious viral particles of H1N1 within a Boeing 747 using methodology from the field of quantitative microbial risk assessment. The risk of catching H1N1 will essentially be confined to passengers travelling in the same cabin as the source case. Not surprisingly, we find that the longer the flight the greater the number of infections that can be expected. We calculate that H1N1, even during long flights, poses a low to moderate within-flight transmission risk if the source case travels First Class. Specifically, 0-1 infections could occur during a 5 hour flight, 1-3 during an 11 hour flight and 2-5 during a 17 hour flight. However, within-flight transmission could be significant, particularly during long flights, if the source case travels in Economy Class. Specifically, two to five infections could occur during a 5 hour flight, 5-10 during an 11 hour flight and 7-17 during a 17 hour flight. If the aircraft is only partially loaded, under certain conditions more infections could occur in First Class than in Economy Class. During a 17 hour flight, a greater number of infections would occur in First Class than in Economy if the First Class Cabin is fully occupied, but Economy class is less than 30% full. Our results provide insights into the potential utility of air travel restrictions on controlling influenza pandemics in the winter of 2009/2010. They show travel by one infectious individual, rather than causing a single outbreak of H1N

  11. Chromosome-wide linkage disequilibrium caused by an inversion polymorphism in the white-throated sparrow (Zonotrichia albicollis).

    PubMed

    Huynh, L Y; Maney, D L; Thomas, J W

    2011-04-01

    Chromosomal inversions have been of long-standing interest to geneticists because they are capable of suppressing recombination and facilitating the formation of adaptive gene complexes. An exceptional inversion polymorphism (ZAL2(m)) in the white-throated sparrow (Zonotrichia albicollis) is linked to variation in plumage, social behavior and mate choice, and is maintained in the population by negative assortative mating. The ZAL2(m) polymorphism is a complex inversion spanning > 100 Mb and has been proposed to be a strong suppressor of recombination, as well as a potential model for studying neo-sex chromosome evolution. To quantify and evaluate these features of the ZAL2(m) polymorphism, we generated sequence from 8 ZAL2(m) and 16 ZAL2 chromosomes at 58 loci inside and 4 loci outside the inversion. Inside the inversion we found that recombination was completely suppressed between ZAL2 and ZAL2(m), resulting in uniformly high levels of genetic differentiation (F(ST)=0.94), the formation of two distinct haplotype groups representing the alternate chromosome arrangements and extensive linkage disequilibrium spanning ~104 Mb within the inversion, whereas gene flow was not suppressed outside the inversion. Finally, although ZAL2(m) homozygotes are exceedingly rare in the population, occurring at a frequency of < 1%, we detected evidence of historical recombination between ZAL2(m) chromosomes inside the inversion, refuting its potential status as a non-recombining autosome.

  12. Turnstiles and bifurcators: the disequilibrium converting engines that put metabolism on the road.

    PubMed

    Branscomb, Elbert; Russell, Michael J

    2013-02-01

    The Submarine Hydrothermal Alkaline Spring Theory for the emergence of life holds that it is the ordered delivery of hydrogen and methane in alkaline hydrothermal solutions at a spontaneously precipitated inorganic osmotic and catalytic membrane to the carbon dioxide and other electron acceptors in the earliest acidulous cool ocean that, through these gradients, drove life into being. That such interactions between hydrothermal fuels and potential oxidants have so far not been accomplished in the lab is because some steps along the necessary metabolic pathways are endergonic and must therefore be driven by being coupled to thermodynamically larger exergonic processes. But coupling of this kind is far from automatic and it is not enough to merely sum the ΔGs of two supposedly coupled reactions and show their combined thermodynamic viability. An exergonic reaction will not drive an endergonic one unless 'forced' to do so by being tied to it mechanistically via an organized "engine" of "Free Energy Conversion" (FEC). Here we discuss the thermodynamics of FEC and advance proposals regarding the nature and roles of the FEC devices that could, in principle, have arisen spontaneously in the alkaline hydrothermal context and have forced the onset of a protometabolism. The key challenge is to divine what these initial engines of life were in physicochemical terms and as part of that, what structures provided the first "turnstile-like" mechanisms needed to couple the partner processes in free energy conversion; in particular to couple the dissipation of geochemically given gradients to, say, the reduction of CO(2) to formate and the generation of a pyrophosphate disequilibrium. This article is part of a Special Issue entitled: The evolutionary aspects of bioenergetic systems. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. A network control theory approach to modeling and optimal control of zoonoses: case study of brucellosis transmission in sub-Saharan Africa.

    PubMed

    Roy, Sandip; McElwain, Terry F; Wan, Yan

    2011-10-01

    Developing control policies for zoonotic diseases is challenging, both because of the complex spread dynamics exhibited by these diseases, and because of the need for implementing complex multi-species surveillance and control efforts using limited resources. Mathematical models, and in particular network models, of disease spread are promising as tools for control-policy design, because they can provide comprehensive quantitative representations of disease transmission. A layered dynamical network model for the transmission and control of zoonotic diseases is introduced as a tool for analyzing disease spread and designing cost-effective surveillance and control. The model development is achieved using brucellosis transmission among wildlife, cattle herds, and human sub-populations in an agricultural system as a case study. Precisely, a model that tracks infection counts in interacting animal herds of multiple species (e.g., cattle herds and groups of wildlife for brucellosis) and in human subpopulations is introduced. The model is then abstracted to a form that permits comprehensive targeted design of multiple control capabilities as well as model identification from data. Next, techniques are developed for such quantitative design of control policies (that are directed to both the animal and human populations), and for model identification from snapshot and time-course data, by drawing on recent results in the network control community. The modeling approach is shown to provide quantitative insight into comprehensive control policies for zoonotic diseases, and in turn to permit policy design for mitigation of these diseases. For the brucellosis-transmission example in particular, numerous insights are obtained regarding the optimal distribution of resources among available control capabilities (e.g., vaccination, surveillance and culling, pasteurization of milk) and points in the spread network (e.g., transhumance vs. sedentary herds). In addition, a preliminary

  14. A Network Control Theory Approach to Modeling and Optimal Control of Zoonoses: Case Study of Brucellosis Transmission in Sub-Saharan Africa

    PubMed Central

    Roy, Sandip; McElwain, Terry F.; Wan, Yan

    2011-01-01

    Background Developing control policies for zoonotic diseases is challenging, both because of the complex spread dynamics exhibited by these diseases, and because of the need for implementing complex multi-species surveillance and control efforts using limited resources. Mathematical models, and in particular network models, of disease spread are promising as tools for control-policy design, because they can provide comprehensive quantitative representations of disease transmission. Methodology/Principal Findings A layered dynamical network model for the transmission and control of zoonotic diseases is introduced as a tool for analyzing disease spread and designing cost-effective surveillance and control. The model development is achieved using brucellosis transmission among wildlife, cattle herds, and human sub-populations in an agricultural system as a case study. Precisely, a model that tracks infection counts in interacting animal herds of multiple species (e.g., cattle herds and groups of wildlife for brucellosis) and in human subpopulations is introduced. The model is then abstracted to a form that permits comprehensive targeted design of multiple control capabilities as well as model identification from data. Next, techniques are developed for such quantitative design of control policies (that are directed to both the animal and human populations), and for model identification from snapshot and time-course data, by drawing on recent results in the network control community. Conclusions/Significance The modeling approach is shown to provide quantitative insight into comprehensive control policies for zoonotic diseases, and in turn to permit policy design for mitigation of these diseases. For the brucellosis-transmission example in particular, numerous insights are obtained regarding the optimal distribution of resources among available control capabilities (e.g., vaccination, surveillance and culling, pasteurization of milk) and points in the spread network (e

  15. Bayes Factor based on the Trend Test Incorporating Hardy-Weinberg Disequilibrium: More Powerful to Detect Genetic Association

    PubMed Central

    Xu, Jinfeng; Yuan, Ao; Zheng, Gang

    2012-01-01

    Summary In the analysis of case-control genetic association, the trend test and Pearson’s test are the two most commonly used tests. In genome-wide association studies (GWAS), Bayes factor is a useful tool to support significant p-values, and a better measure than p-value when results are compared across studies with different sample sizes. When reporting the p-value of the trend test, we propose a Bayes factor directly based on the trend test. To improve the power to detect association under recessive or dominant genetic models, we propose a Bayes factor based on the trend test and incorporating Hardy-Weinberg disequilibrium in cases. When the true model is unknown, or both the trend test and Pearson’s test or other robust tests are applied in genome-wide scans, we propose a joint Bayes factor, combining the previous two Bayes factors. All three Bayes factors studied in this paper have closed forms and are easy to compute without integrations, so they can be reported along with p-values, especially in GWAS. We discuss how to use each of them and how to specify priors. Simulation studies and applications to three GWAS are provided to illustrate their usefulness to detect non-additive gene susceptibility in practice. PMID:22607017

  16. Multilocus Patterns of Nucleotide Diversity, Linkage Disequilibrium and Demographic History of Norway Spruce [Picea abies (L.) Karst

    PubMed Central

    Heuertz, Myriam; De Paoli, Emanuele; Källman, Thomas; Larsson, Hanna; Jurman, Irena; Morgante, Michele; Lascoux, Martin; Gyllenstrand, Niclas

    2006-01-01

    DNA polymorphism at 22 loci was studied in an average of 47 Norway spruce [Picea abies (L.) Karst.] haplotypes sampled in seven populations representative of the natural range. The overall nucleotide variation was limited, being lower than that observed in most plant species so far studied. Linkage disequilibrium was also restricted and did not extend beyond a few hundred base pairs. All populations, with the exception of the Romanian population, could be divided into two main domains, a Baltico–Nordic and an Alpine one. Mean Tajima's D and Fay and Wu's H across loci were both negative, indicating the presence of an excess of both rare and high-frequency-derived variants compared to the expected frequency spectrum in a standard neutral model. Multilocus neutrality tests based on D and H led to the rejection of the standard neutral model and exponential growth in the whole population as well as in the two main domains. On the other hand, in all three cases the data are compatible with a severe bottleneck occurring some hundreds of thousands of years ago. Hence, demographic departures from equilibrium expectations and population structure will have to be accounted for when detecting selection at candidate genes and in association mapping studies, respectively. PMID:17057229

  17. Disequilibrium dihedral angles in layered intrusions: the microstructural record of fractionation

    NASA Astrophysics Data System (ADS)

    Holness, Marian; Namur, Olivier; Cawthorn, Grant

    2013-04-01

    The dihedral angle formed at junctions between two plagioclase grains and a grain of augite is only rarely in textural equilibrium in gabbros from km-scale crustal layered intrusions. The median of a population of these disequilibrium angles, Θcpp, varies systematically within individual layered intrusions, remaining constant over large stretches of stratigraphy with significant increases or decreases associated with the addition or reduction respectively of the number of phases on the liquidus of the bulk magma. The step-wise changes in Θcpp are present in Upper Zone of the Bushveld Complex, the Megacyclic Unit I of the Sept Iles Intrusion, and the Layered Series of the Skaergaard Intrusion. The plagioclase-bearing cumulates of Rum have a bimodal distribution of Θcpp, dependent on whether the cumulus assemblage includes clinopyroxene. The presence of the step-wise changes is independent of the order of arrival of cumulus phases and of the composition of either the cumulus phases or the interstitial liquid inferred to be present in the crystal mush. Step-wise changes in the rate of change in enthalpy with temperature (ΔH) of the cooling and crystallizing magma correspond to the observed variation of Θcpp, with increases of both ΔH and Θcpp associated with the addition of another liquidus phase, and decreases of both associated with the removal of a liquidus phase. The replacement of one phase by another (e.g. olivine ⇔ orthpyroxene) has little effect on ΔH and no discernible effect on Θcpp. An increase of ΔH is manifest by an increase in the fraction of the total enthalpy budget that is the latent heat of crystallization (the fractional latent heat). It also results in an increase in the amount crystallized in each incremental temperature drop (the crystal productivity). An increased fractional latent heat and crystal productivity result in an increased rate of plagioclase growth compared to that of augite during the final stages of solidification

  18. Analysis of vaginal microbicide film hydration kinetics by quantitative imaging refractometry.

    PubMed

    Rinehart, Matthew; Grab, Sheila; Rohan, Lisa; Katz, David; Wax, Adam

    2014-01-01

    We have developed a quantitative imaging refractometry technique, based on holographic phase microscopy, as a tool for investigating microscopic structural changes in water-soluble polymeric materials. Here we apply the approach to analyze the structural degradation of vaginal topical microbicide films due to water uptake. We implemented transmission imaging of 1-mm diameter film samples loaded into a flow chamber with a 1.5×2 mm field of view. After water was flooded into the chamber, interference images were captured and analyzed to obtain high resolution maps of the local refractive index and subsequently the volume fraction and mass density of film material at each spatial location. Here, we compare the hydration dynamics of a panel of films with varying thicknesses and polymer compositions, demonstrating that quantitative imaging refractometry can be an effective tool for evaluating and characterizing the performance of candidate microbicide film designs for anti-HIV drug delivery.

  19. Transmission rights and market power

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

    Bushnell, J.

    1999-10-01

    Most of the concerns about physical transmission rights relate to the ability to implicitly or explicitly remove that transmission capacity from the market-place. Under a very strict form of physical right, owners could simply choose not to sell it if they don't want to use it. Modifications that require the release of spare capacity back into an open market could potentially alleviate this problem but there is concern that such releases would not occur far enough in advance to be of much use to schedulers. Similarly, the transmission capacity that is made available for use by non-rights holders can alsomore » be manipulated by the owners of transmission rights. The alternative form, financial transmission rights, provide to their owners congestion payments, but physical control of transmission paths. In electricity markets such as California's, even financial transmission rights could potentially be utilized to effectively withhold transmission capacity from the marketplace. However, methods for withholding transmission capacity are somewhat more convoluted, and probably more difficult, for owners of financial rights than for owners of physical rights. In this article, the author discusses some of the potential concerns over transmission rights and their use for the exercise of various forms of market power.« less

  20. Transmission of two Australian strains of murine cytomegalovirus (MCMV) in enclosure populations of house mice (Mus domesticus).

    PubMed

    Farroway, L N; Gorman, S; Lawson, M A; Harvey, N L; Jones, D A; Shellam, G R; Singleton, G R

    2005-08-01

    To control plagues of free-living mice (Mus domesticus) in Australia, a recombinant murine cytomegalovirus (MCMV) expressing fertility proteins is being developed as an immunocontraceptive agent. Real-time quantitative PCR was used to monitor the transmission of two genetically variable field strains of MCMV through mouse populations after 25% of founding mice were infected with the N1 strain, followed by the G4 strain 6 weeks later. Pathogen-free wild-derived mice were released into outdoor enclosures located in northwestern Victoria (Australia). Of those mice not originally inoculated with virus, N1 DNA was detected in more than 80% of founder mice and a third of their offspring and similarly, G4 DNA was detected in 13% of founder mice and in 3% of their offspring. Thus, prior immunity to N1 did not prevent transmission of G4. This result is promising for successful transmission of an immunocontraceptive vaccine through Australian mouse populations where MCMV infection is endemic.

  1. Linkage Disequilibrium Mapping in Domestic Dog Breeds Narrows the Progressive Rod-Cone Degeneration (prcd) Interval and Identifies Ancestral Disease Transmitting Chromosome

    PubMed Central

    Goldstein, Orly; Zangerl, Barbara; Pearce-Kelling, Sue; Sidjanin, Duska J.; Kijas, James W.; Felix, Jeanette; Acland, Gregory M; Aguirre, Gustavo D.

    2014-01-01

    Canine progressive rod-cone degeneration (prcd) is a retinal disease previously mapped to a broad, gene-rich centromeric region of canine chromosome 9. As allelic disorders are present in multiple breeds, we used linkage disequilibrium (LD) to narrow the ∼6.4 Mb interval candidate region. Multiple dog breeds, each representing genetically isolated populations, were typed for SNPs and other polymorphisms identified from BACs. The candidate region was initially localized to a 1.5 Mb zero recombination interval between growth factor receptor-bound protein 2 (GRB2) and SEC14-like 1 (SEC14L). A fine-scale haplotype of the region was developed which reduced the LD interval to 106 Kb, and identified a conserved haplotype of 98 polymorphisms present in all prcd-affected chromosomes from 14 different dog breeds. The findings strongly suggest that a common ancestor transmitted the prcd disease allele to many of the modern dog breeds, and demonstrate the power of LD approach in the canine model. PMID:16859891

  2. Transmission Kikuchi diffraction and transmission electron forescatter imaging of electropolished and FIB manufactured TEM specimens

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

    Zieliński, W., E-mail: wiziel@inmat.pw.edu.pl; Płociński, T.; Kurzydłowski, K.J.

    2015-06-15

    We present a study of the efficiency of the utility of scanning electron microscope (SEM)-based transmission methods for characterizing grain structure in thinned bulk metals. Foils of type 316 stainless steel were prepared by two methods commonly used for transmission electron microscopy — double-jet electropolishing and focused ion beam milling. A customized holder allowed positioning of the foils in a configuration appropriate for both transmission electron forward scatter diffraction, and for transmission imaging by the use of a forescatter detector with two diodes. We found that both crystallographic orientation maps and dark-field transmitted images could be obtained for specimens preparedmore » by either method. However, for both methods, preparation-induced artifacts may affect the quality or accuracy of transmission SEM data, especially those acquired by the use of transmission Kikuchi diffraction. Generally, the quality of orientation data was better for specimens prepared by electropolishing, due to the absence of ion-induced damage. - Highlights: • The transmission imaging and diffraction techniques are emerging in scanning electron microscopy (SEM) as promising new field of materials characterization. • The manuscript titled: “Transmission Kikuchi Diffraction and Transmission Electron Forescatter Imaging of Electropolished and FIB Manufactured TEM Specimens” documents how different specimen thinning procedures can effect efficiency of transmission Kikuchi diffraction and transmission electron forescatter imaging. • The abilities to make precision crystallographic orientation maps and dark-field images in transmission was studied on electropolished versus focus ion beam manufactured TEM specimens. • Depending on the need, electropolished and focused ion beam technique may produce suitable specimens for transmission imaging and diffraction in SEM.« less

  3. A linked donor-recipient study to evaluate parvovirus B19 transmission by blood component transfusion.

    PubMed

    Kleinman, Steven H; Glynn, Simone A; Lee, Tzong-Hae; Tobler, Leslie H; Schlumpf, Karen S; Todd, Deborah S; Qiao, Hannah; Yu, Mei-Ying W; Busch, Michael P

    2009-10-22

    Parvovirus B19V infection can be a serious infection for hematology patients with underlying hemolysis or compromised erythropoiesis syndromes. Although case reports of B19V transmission by blood component transfusion (as contrasted to manufactured plasma derivatives) are rare, no studies have systematically determined a rate of transmission to recipients transfused with B19V DNA-positive components. We used a linked donor and recipient repository and a sensitive, quantitative B19V DNA polymerase chain reaction (PCR) assay to assess such transmission in B19V-susceptible (ie, anti-B19V immunoglobulin G [IgG] negative) recipients. We assessed 112 B19V DNA-positive components from 105 donors (of 12 529 tested donations) transfused into a population of surgical patients with a pretransfusion B19V IgG seroprevalence of 78%. We found no transmission to 24 susceptible recipients from transfusion of components with B19V DNA at concentrations less than 10(6) IU/mL (upper 95% confidence interval, 11.7%). We found an anamnestic IgG response in one pretransfusion seropositive recipient transfused with a component containing greater than 10(10) IU/mL B19V DNA. These findings show either that transmission from components with less than 10(6) IU/mL does not occur, or, if it does, it is an uncommon event. These data do not support the need to routinely screen blood donations with a sensitive B19V DNA nucleic acid assay.

  4. 75 FR 62023 - Transmission Planning and Cost Allocation by Transmission Owning and Operating Public Utilities

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-07

    ...] Transmission Planning and Cost Allocation by Transmission Owning and Operating Public Utilities September 29... (75 FR 37884) proposing to amend the transmission planning and cost allocation requirements... transmission needs driven by public policy requirements established by state or federal laws or regulations...

  5. Quantitative proton imaging from multiple physics processes: a proof of concept

    NASA Astrophysics Data System (ADS)

    Bopp, C.; Rescigno, R.; Rousseau, M.; Brasse, D.

    2015-07-01

    Proton imaging is developed in order to improve the accuracy of charged particle therapy treatment planning. It makes it possible to directly map the relative stopping powers of the materials using the information on the energy loss of the protons. In order to reach a satisfactory spatial resolution in the reconstructed images, the position and direction of each particle is recorded upstream and downstream from the patient. As a consequence of individual proton detection, information on the transmission rate and scattering of the protons is available. Image reconstruction processes are proposed to make use of this information. A proton tomographic acquisition of an anthropomorphic head phantom was simulated. The transmission rate of the particles was used to reconstruct a map of the macroscopic cross section for nuclear interactions of the materials. A two-step iterative reconstruction process was implemented to reconstruct a map of the inverse scattering length of the materials using the scattering of the protons. Results indicate that, while the reconstruction processes should be optimized, it is possible to extract quantitative information from the transmission rate and scattering of the protons. This suggests that proton imaging could provide additional knowledge on the materials that may be of use to further improve treatment planning.

  6. Quantitative proton imaging from multiple physics processes: a proof of concept.

    PubMed

    Bopp, C; Rescigno, R; Rousseau, M; Brasse, D

    2015-07-07

    Proton imaging is developed in order to improve the accuracy of charged particle therapy treatment planning. It makes it possible to directly map the relative stopping powers of the materials using the information on the energy loss of the protons. In order to reach a satisfactory spatial resolution in the reconstructed images, the position and direction of each particle is recorded upstream and downstream from the patient. As a consequence of individual proton detection, information on the transmission rate and scattering of the protons is available. Image reconstruction processes are proposed to make use of this information. A proton tomographic acquisition of an anthropomorphic head phantom was simulated. The transmission rate of the particles was used to reconstruct a map of the macroscopic cross section for nuclear interactions of the materials. A two-step iterative reconstruction process was implemented to reconstruct a map of the inverse scattering length of the materials using the scattering of the protons. Results indicate that, while the reconstruction processes should be optimized, it is possible to extract quantitative information from the transmission rate and scattering of the protons. This suggests that proton imaging could provide additional knowledge on the materials that may be of use to further improve treatment planning.

  7. Investigation of Ion Transmission Effects on Intact Protein Quantification in a Triple Quadrupole Mass Spectrometer

    NASA Astrophysics Data System (ADS)

    Wang, Evelyn H.; Appulage, Dananjaya Kalu; McAllister, Erin A.; Schug, Kevin A.

    2017-09-01

    Recently, direct intact protein quantitation using triple quadrupole mass spectrometry (QqQ-MS) and multiple reaction monitoring (MRM) was demonstrated (J. Am. Soc. Mass Spectrom. 27, 886-896 (2016)). Even though QqQ-MS is known to provide extraordinary detection sensitivity for quantitative analysis, we found that intact proteins exhibited a less than 5% ion transmission from the first quadrupole to the third quadrupole mass analyzer in the presence of zero collision energy (ZCE). With the goal to enhance intact protein quantitation sensitivity, ion scattering effects, proton transfer effects, and mass filter resolution widths were examined for their contributions to the lost signal. Protein standards myoglobin and ubiquitin along with small molecules reserpine and vancomycin were analyzed together with various collision induced dissociation (CID) gases (N2, He, and Ar) at different gas pressures. Mass resolution settings played a significant role in reducing ion transmission signal. By narrowing the mass resolution window by 0.35 m/z on each side, roughly 75%-90% of the ion signal was lost. The multiply charged proteins experienced additional proton transfer effects, corresponding to 10-fold signal reduction. A study of increased sensitivity of the method was also conducted with various MRM summation techniques. Although the degree of enhancement was analyte-dependent, an up to 17-fold increase in sensitivity was observed for ubiquitin using a summation of multiple MRM transitions. Biological matrix, human urine, and equine plasma were spiked with proteins to demonstrate the specificity of the method. This study provides additional insight into optimizing the use and sensitivity of QqQ-MS for intact protein quantification. [Figure not available: see fulltext.

  8. 75 FR 37883 - Transmission Planning and Cost Allocation by Transmission Owning and Operating Public Utilities

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-30

    ... Planning and Cost Allocation by Transmission Owning and Operating Public Utilities; Proposed Rule #0;#0...] Transmission Planning and Cost Allocation by Transmission Owning and Operating Public Utilities Issued June 17... Transmission Services by Public Utilities; Recovery of Stranded Costs by Public Utilities and Transmitting...

  9. Classic flea-borne transmission does not drive plague epizootics in prairie dogs.

    PubMed

    Webb, Colleen T; Brooks, Christopher P; Gage, Kenneth L; Antolin, Michael F

    2006-04-18

    We lack a clear understanding of the enzootic maintenance of the bacterium (Yersinia pestis) that causes plague and the sporadic epizootics that occur in its natural rodent hosts. A key to elucidating these epidemiological dynamics is determining the dominant transmission routes of plague. Plague can be acquired from the bites of infectious fleas (which is generally considered to occur via a blocked flea vector), inhalation of infectious respiratory droplets, or contact with a short-term infectious reservoir. We present results from a plague modeling approach that includes transmission from all three sources of infection simultaneously and uses sensitivity analysis to determine their relative importance. Our model is completely parameterized by using data from the literature and our own field studies of plague in the black-tailed prairie dog (Cynomys ludovicianus). Results of the model are qualitatively and quantitatively consistent with independent data from our field sites. Although infectious fleas might be an important source of infection and transmission via blocked fleas is a dominant paradigm in the literature, our model clearly predicts that this form of transmission cannot drive epizootics in prairie dogs. Rather, a short-term reservoir is required for epizootic dynamics. Several short-term reservoirs have the potential to affect the prairie dog system. Our model predictions of the residence time of the short-term reservoir suggest that other small mammals, infectious prairie dog carcasses, fleas that transmit plague without blockage of the digestive tract, or some combination of these three are the most likely of the candidate infectious reservoirs.

  10. Quantitative energy-filtered TEM imaging of interfaces

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

    Bentley, J.; Kenik, E.A.; Siangchaew, K.

    Quantitative elemental mapping by inner shell core-loss energy-filtered transmission electron microscopy (TEM) with a Gatan Imaging Filter (GIF) interfaced to a Philips CM30 TEM operated with a LaB{sub 6} filament at 300 kV has been applied to interfaces in a range of materials. In sensitized type 304L stainless steel aged 15 h at 600{degrees}C, grain-boundary Cr depletion occurs between Cr-rich intergranular M{sub 23}C{sub 6} particles. Images of net Cr L{sub 23} intensity show segregation profiles that agree quantitatively with focused-probe spectrum-line measurements recorded with a Gatan PEELS on a Philips EM400T/FEG (0.8 nA in 2-nm-diam probe) of the same regions.more » Rare-earth oxide additives that are used for the liquid-phase sintering of Si{sub 3}N{sub 4} generate second phases of complex composition at grain boundaries and edges. These grain boundary phases often control corrosion, crack growth and creep damage behavior. High resolution imaging has been widely and with focused probes can be compromised by beam damage, but elemental mapping by EFTEM appears not to cause appreciable beam damage.« less

  11. Genome-wide linkage disequilibrium and past effective population size in three Korean cattle breeds.

    PubMed

    Sudrajad, P; Seo, D W; Choi, T J; Park, B H; Roh, S H; Jung, W Y; Lee, S S; Lee, J H; Kim, S; Lee, S H

    2017-02-01

    The routine collection and use of genomic data are useful for effectively managing breeding programs for endangered populations. Linkage disequilibrium (LD) using high-density DNA markers has been widely used to determine population structures and predict the genomic regions that are associated with economic traits in beef cattle. The extent of LD also provides information about historical events, including past effective population size (N e ), and it allows inferences on the genetic diversity of breeds. The objective of this study was to estimate the LD and N e in three Korean cattle breeds that are genetically similar but have different coat colors (Brown, Brindle and Jeju Black Hanwoo). Brindle and Jeju Black are endangered breeds with small populations, whereas Brown Hanwoo is the main breeding population in Korea. DNA samples from these cattle breeds were genotyped using the Illumina BovineSNP50 Bead Chip. We examined 13 cattle breeds, including European taurines, African taurines and indicines, and hybrids to compare their LD values. Brown Hanwoo consistently had the lowest mean LD compared to Jeju Black, Brindle and the other 13 cattle breeds (0.13, 0.19, 0.21 and 0.15-0.22 respectively). The high LD values of Brindle and Jeju Black contributed to small N e values (53 and 60 respectively), which were distinct from that of Brown Hanwoo (531) for 11 generations ago. The differences in LD and N e for each breed reflect the breeding strategy applied. The N e for these endangered cattle breeds remain low; thus, effort is needed to bring them back to a sustainable tract. © 2016 Stichting International Foundation for Animal Genetics.

  12. Visualizing gold nanoparticle uptake in live cells with liquid scanning transmission electron microscopy.

    PubMed

    Peckys, Diana B; de Jonge, Niels

    2011-04-13

    The intracellular uptake of 30 nm diameter gold nanoparticles (Au-NPs) was studied at the nanoscale in pristine eukaryotic cells. Live COS-7 cells were maintained in a microfluidic chamber and imaged using scanning transmission electron microscopy. A quantitative image analysis showed that Au-NPs bound to the membranes of vesicles, possibly lysosomes, and occupied 67% of the available surface area. The vesicles accumulated to form a micrometer-sized cluster after 24 h of incubation. Two clusters were analyzed and found to consist of 117 ± 9 and 164 ± 4 NP-filled vesicles.

  13. Squirrelpox virus: assessing prevalence, transmission and environmental degradation.

    PubMed

    Collins, Lisa M; Warnock, Neil D; Tosh, David G; McInnes, Colin; Everest, David; Montgomery, W Ian; Scantlebury, Mike; Marks, Nikki; Dick, Jaimie T A; Reid, Neil

    2014-01-01

    Red squirrels (Sciurus vulgaris) declined in Great Britain and Ireland during the last century, due to habitat loss and the introduction of grey squirrels (Sciurus carolinensis), which competitively exclude the red squirrel and act as a reservoir for squirrelpox virus (SQPV). The disease is generally fatal to red squirrels and their ecological replacement by grey squirrels is up to 25 times faster where the virus is present. We aimed to determine: (1) the seropositivity and prevalence of SQPV DNA in the invasive and native species at a regional scale; (2) possible SQPV transmission routes; and, (3) virus degradation rates under differing environmental conditions. Grey (n = 208) and red (n = 40) squirrel blood and tissues were sampled. Enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qPCR) techniques established seropositivity and viral DNA presence, respectively. Overall 8% of squirrels sampled (both species combined) had evidence of SQPV DNA in their tissues and 22% were in possession of antibodies. SQPV prevalence in sampled red squirrels was 2.5%. Viral loads were typically low in grey squirrels by comparison to red squirrels. There was a trend for a greater number of positive samples in spring and summer than in winter. Possible transmission routes were identified through the presence of viral DNA in faeces (red squirrels only), urine and ectoparasites (both species). Virus degradation analyses suggested that, after 30 days of exposure to six combinations of environments, there were more intact virus particles in scabs kept in warm (25 °C) and dry conditions than in cooler (5 and 15 °C) or wet conditions. We conclude that SQPV is present at low prevalence in invasive grey squirrel populations with a lower prevalence in native red squirrels. Virus transmission could occur through urine especially during warm dry summer conditions but, more notably, via ectoparasites, which are shared by both species.

  14. Evolution and Use of Dynamic Transmission Models for Measles and Rubella Risk and Policy Analysis.

    PubMed

    Thompson, Kimberly M

    2016-07-01

    The devastation caused by periodic measles outbreaks motivated efforts over more than a century to mathematically model measles disease and transmission. Following the identification of rubella, which similarly presents with fever and rash and causes congenital rubella syndrome (CRS) in infants born to women first infected with rubella early in pregnancy, modelers also began to characterize rubella disease and transmission. Despite the relatively large literature, no comprehensive review to date provides an overview of dynamic transmission models for measles and rubella developed to support risk and policy analysis. This systematic review of the literature identifies quantitative measles and/or rubella dynamic transmission models and characterizes key insights relevant for prospective modeling efforts. Overall, measles and rubella represent some of the relatively simplest viruses to model due to their ability to impact only humans and the apparent life-long immunity that follows survival of infection and/or protection by vaccination, although complexities arise due to maternal antibodies and heterogeneity in mixing and some models considered potential waning immunity and reinfection. This review finds significant underreporting of measles and rubella infections and widespread recognition of the importance of achieving and maintaining high population immunity to stop and prevent measles and rubella transmission. The significantly lower transmissibility of rubella compared to measles implies that all countries could eliminate rubella and CRS by using combination of measles- and rubella-containing vaccines (MRCVs) as they strive to meet regional measles elimination goals, which leads to the recommendation of changing the formulation of national measles-containing vaccines from measles only to MRCV as the standard of care. © 2016 Society for Risk Analysis.

  15. Infrared-optical transmission and reflection measurements on loose powders

    NASA Astrophysics Data System (ADS)

    Kuhn, J.; Korder, S.; Arduini-Schuster, M. C.; Caps, R.; Fricke, J.

    1993-09-01

    A method is described to determine quantitatively the infrared-optical properties of loose powder beds via directional-hemispherical transmission and reflection measurements. Instead of the integration of the powders into a potassium bromide (KBr) or a paraffin oil matrix, which would drastically alter the scattering behavior, the powders are placed onto supporting layers of polyethylene (PE) and KBr. A commercial spectrometer is supplemented by an external optics, which enables measurements on horizontally arranged samples. For data evaluation we use a solution of the equation of radiative transfer in the 3-flux approximation under boundary conditions adapted to the PE or KBr/powder system. A comparison with Kubelka-Munk's theory and Schuster's 2-flux approximation is performed, which shows that 3-flux approximation yields results closest to the exact solution. Equations are developed, which correct transmission and reflection of the samples for the influence of the supporting layer and calculate the specific extinction and the albedo of the powder and thus enables us to separate scattering and absorption part of the extinction spectrum. Measurements on TiO2 powder are presented, which show the influence of preparation techniques and data evaluation with different methods to obtain the albedo. The specific extinction of various TiO2 powders is presented.

  16. Automated magnification calibration in transmission electron microscopy using Fourier analysis of replica images.

    PubMed

    van der Laak, Jeroen A W M; Dijkman, Henry B P M; Pahlplatz, Martin M M

    2006-03-01

    The magnification factor in transmission electron microscopy is not very precise, hampering for instance quantitative analysis of specimens. Calibration of the magnification is usually performed interactively using replica specimens, containing line or grating patterns with known spacing. In the present study, a procedure is described for automated magnification calibration using digital images of a line replica. This procedure is based on analysis of the power spectrum of Fourier transformed replica images, and is compared to interactive measurement in the same images. Images were used with magnification ranging from 1,000 x to 200,000 x. The automated procedure deviated on average 0.10% from interactive measurements. Especially for catalase replicas, the coefficient of variation of automated measurement was considerably smaller (average 0.28%) compared to that of interactive measurement (average 3.5%). In conclusion, calibration of the magnification in digital images from transmission electron microscopy may be performed automatically, using the procedure presented here, with high precision and accuracy.

  17. Value transmissions between parents and children: gender and developmental phase as transmission belts.

    PubMed

    Roest, Annette M C; Dubas, Judith Semon; Gerris, Jan R M

    2010-02-01

    This study applied the gender role model of socialization theory, the developmental aging theory, and the topic salience perspective to the investigation of parent-child value transmissions. Specifically, we examined whether the bi-directionality and selectivity of value transmissions differed as a function of parents' and children's gender and children's developmental phase (adolescence versus emerging adulthood). Transmissions between parents and children from 402 Dutch families on the topics of work as duty and hedonism were studied across a 5-year period using structural equation modeling. As expected, we did not find convincing support for the general models of gender socialization and developmental aging. Instead, parent-child value transmissions appeared to be qualified by value salience. Particularly, high salience of work as duty for fathers was related with great paternal involvement in transmissions on this value orientation and high salience of hedonism for sons and adolescents was linked to transmissions from these groups to parents. Copyright (c) 2009 The Association for Professionals in Services for Adolescents. Published by Elsevier Ltd. Published by Elsevier Ltd. All rights reserved.

  18. Analysis of Vaginal Microbicide Film Hydration Kinetics by Quantitative Imaging Refractometry

    PubMed Central

    Rinehart, Matthew; Grab, Sheila; Rohan, Lisa; Katz, David; Wax, Adam

    2014-01-01

    We have developed a quantitative imaging refractometry technique, based on holographic phase microscopy, as a tool for investigating microscopic structural changes in water-soluble polymeric materials. Here we apply the approach to analyze the structural degradation of vaginal topical microbicide films due to water uptake. We implemented transmission imaging of 1-mm diameter film samples loaded into a flow chamber with a 1.5×2 mm field of view. After water was flooded into the chamber, interference images were captured and analyzed to obtain high resolution maps of the local refractive index and subsequently the volume fraction and mass density of film material at each spatial location. Here, we compare the hydration dynamics of a panel of films with varying thicknesses and polymer compositions, demonstrating that quantitative imaging refractometry can be an effective tool for evaluating and characterizing the performance of candidate microbicide film designs for anti-HIV drug delivery. PMID:24736376

  19. Whole genome sequences are required to fully resolve the linkage disequilibrium structure of human populations.

    PubMed

    Pengelly, Reuben J; Tapper, William; Gibson, Jane; Knut, Marcin; Tearle, Rick; Collins, Andrew; Ennis, Sarah

    2015-09-03

    An understanding of linkage disequilibrium (LD) structures in the human genome underpins much of medical genetics and provides a basis for disease gene mapping and investigating biological mechanisms such as recombination and selection. Whole genome sequencing (WGS) provides the opportunity to determine LD structures at maximal resolution. We compare LD maps constructed from WGS data with LD maps produced from the array-based HapMap dataset, for representative European and African populations. WGS provides up to 5.7-fold greater SNP density than array-based data and achieves much greater resolution of LD structure, allowing for identification of up to 2.8-fold more regions of intense recombination. The absence of ascertainment bias in variant genotyping improves the population representativeness of the WGS maps, and highlights the extent of uncaptured variation using array genotyping methodologies. The complete capture of LD patterns using WGS allows for higher genome-wide association study (GWAS) power compared to array-based GWAS, with WGS also allowing for the analysis of rare variation. The impact of marker ascertainment issues in arrays has been greatest for Sub-Saharan African populations where larger sample sizes and substantially higher marker densities are required to fully resolve the LD structure. WGS provides the best possible resource for LD mapping due to the maximal marker density and lack of ascertainment bias. WGS LD maps provide a rich resource for medical and population genetics studies. The increasing availability of WGS data for large populations will allow for improved research utilising LD, such as GWAS and recombination biology studies.

  20. Accuracy of genomic prediction in switchgrass ( Panicum virgatum L.) improved by accounting for linkage disequilibrium

    DOE PAGES

    Ramstein, Guillaume P.; Evans, Joseph; Kaeppler, Shawn M.; ...

    2016-02-11

    Switchgrass is a relatively high-yielding and environmentally sustainable biomass crop, but further genetic gains in biomass yield must be achieved to make it an economically viable bioenergy feedstock. Genomic selection (GS) is an attractive technology to generate rapid genetic gains in switchgrass, and meet the goals of a substantial displacement of petroleum use with biofuels in the near future. In this study, we empirically assessed prediction procedures for genomic selection in two different populations, consisting of 137 and 110 half-sib families of switchgrass, tested in two locations in the United States for three agronomic traits: dry matter yield, plant height,more » and heading date. Marker data were produced for the families’ parents by exome capture sequencing, generating up to 141,030 polymorphic markers with available genomic-location and annotation information. We evaluated prediction procedures that varied not only by learning schemes and prediction models, but also by the way the data were preprocessed to account for redundancy in marker information. More complex genomic prediction procedures were generally not significantly more accurate than the simplest procedure, likely due to limited population sizes. Nevertheless, a highly significant gain in prediction accuracy was achieved by transforming the marker data through a marker correlation matrix. Our results suggest that marker-data transformations and, more generally, the account of linkage disequilibrium among markers, offer valuable opportunities for improving prediction procedures in GS. Furthermore, some of the achieved prediction accuracies should motivate implementation of GS in switchgrass breeding programs.« less

  1. Accuracy of genomic prediction in switchgrass ( Panicum virgatum L.) improved by accounting for linkage disequilibrium

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

    Ramstein, Guillaume P.; Evans, Joseph; Kaeppler, Shawn M.

    Switchgrass is a relatively high-yielding and environmentally sustainable biomass crop, but further genetic gains in biomass yield must be achieved to make it an economically viable bioenergy feedstock. Genomic selection (GS) is an attractive technology to generate rapid genetic gains in switchgrass, and meet the goals of a substantial displacement of petroleum use with biofuels in the near future. In this study, we empirically assessed prediction procedures for genomic selection in two different populations, consisting of 137 and 110 half-sib families of switchgrass, tested in two locations in the United States for three agronomic traits: dry matter yield, plant height,more » and heading date. Marker data were produced for the families’ parents by exome capture sequencing, generating up to 141,030 polymorphic markers with available genomic-location and annotation information. We evaluated prediction procedures that varied not only by learning schemes and prediction models, but also by the way the data were preprocessed to account for redundancy in marker information. More complex genomic prediction procedures were generally not significantly more accurate than the simplest procedure, likely due to limited population sizes. Nevertheless, a highly significant gain in prediction accuracy was achieved by transforming the marker data through a marker correlation matrix. Our results suggest that marker-data transformations and, more generally, the account of linkage disequilibrium among markers, offer valuable opportunities for improving prediction procedures in GS. Furthermore, some of the achieved prediction accuracies should motivate implementation of GS in switchgrass breeding programs.« less

  2. A numerical study on the correlation between fracture transmissivity, hydraulic aperture and transport aperture

    NASA Astrophysics Data System (ADS)

    Sawada, A.; Takebe, A.; Sakamoto, K.

    2006-12-01

    Quantitative evaluation of the groundwater velocity in the fractures is a key part of contaminants transport assessment especially in the radioactive waste disposal programs. In a hydrogeological model such as the discrete fracture network model, the transport aperture of water conducting fracture is one of the important parameters for evaluating groundwater velocity. Tracer tests that measure velocity (or transport aperture) are few compared with flow tests that measure transmissivity (or hydraulic aperture). Thus it is useful to estimate transport properties from flow properties. It is commonly assumed that flow and transport aperture are the same, and that aperture is related to the cube root of transmissivity by the parallel-plate analog. Actual field experiments, however, show transport and hydraulic apertures are not always the same, and that transport aperture relates to an empirical constant times the square root of transmissivity. Compared with these field results, the cubic law underestimates transport aperture and overestimates velocity. A possible source of this discrepancy is in-plane heterogeneity of aperture and transmissivity. To study this behavior, numerical simulations using MAFIC were conducted for a single fracture model with a heterogeneous aperture distribution. The simulations varied three parameters - the mean geometrical aperture, JRC (Joint Roughness Coefficient), and the contact area ratio (fracture contact area divided by total fracture area). For each model we determined the equivalent transmissivity and cubic-law aperture under steady flow conditions. Then we simulated mass transport using particle tracking through the same fracture. The transport aperture was estimated from the particle peak arrival time at the downstream boundary. The results show that the mean geometrical aperture is the most sensitive parameter among the three variable parameters in this study. It is also found that the contact area ratio affects transmissivity

  3. A two-locus model of spatially varying stabilizing or directional selection on a quantitative trait

    PubMed Central

    Geroldinger, Ludwig; Bürger, Reinhard

    2014-01-01

    The consequences of spatially varying, stabilizing or directional selection on a quantitative trait in a subdivided population are studied. A deterministic two-locus two-deme model is employed to explore the effects of migration, the degree of divergent selection, and the genetic architecture, i.e., the recombination rate and ratio of locus effects, on the maintenance of genetic variation. The possible equilibrium configurations are determined as functions of the migration rate. They depend crucially on the strength of divergent selection and the genetic architecture. The maximum migration rates are investigated below which a stable fully polymorphic equilibrium or a stable single-locus polymorphism can exist. Under stabilizing selection, but with different optima in the demes, strong recombination may facilitate the maintenance of polymorphism. However usually, and in particular with directional selection in opposite direction, the critical migration rates are maximized by a concentrated genetic architecture, i.e., by a major locus and a tightly linked minor one. Thus, complementing previous work on the evolution of genetic architectures in subdivided populations subject to diversifying selection, it is shown that concentrated architectures may aid the maintenance of polymorphism. Conditions are obtained when this is the case. Finally, the dependence of the phenotypic variance, linkage disequilibrium, and various measures of local adaptation and differentiation on the parameters is elaborated. PMID:24726489

  4. A two-locus model of spatially varying stabilizing or directional selection on a quantitative trait.

    PubMed

    Geroldinger, Ludwig; Bürger, Reinhard

    2014-06-01

    The consequences of spatially varying, stabilizing or directional selection on a quantitative trait in a subdivided population are studied. A deterministic two-locus two-deme model is employed to explore the effects of migration, the degree of divergent selection, and the genetic architecture, i.e., the recombination rate and ratio of locus effects, on the maintenance of genetic variation. The possible equilibrium configurations are determined as functions of the migration rate. They depend crucially on the strength of divergent selection and the genetic architecture. The maximum migration rates are investigated below which a stable fully polymorphic equilibrium or a stable single-locus polymorphism can exist. Under stabilizing selection, but with different optima in the demes, strong recombination may facilitate the maintenance of polymorphism. However usually, and in particular with directional selection in opposite direction, the critical migration rates are maximized by a concentrated genetic architecture, i.e., by a major locus and a tightly linked minor one. Thus, complementing previous work on the evolution of genetic architectures in subdivided populations subject to diversifying selection, it is shown that concentrated architectures may aid the maintenance of polymorphism. Conditions are obtained when this is the case. Finally, the dependence of the phenotypic variance, linkage disequilibrium, and various measures of local adaptation and differentiation on the parameters is elaborated. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Linkage disequilibrium analysis in young populations: Pseudo-vitamin D-deficiency rickets and the founder effect in French Canadians

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

    Labuda, M.; Glorieux, F.H.; Labuda, D.

    1996-09-01

    Pseudo-vitamin D-deficiency rickets (PDDR) was mapped close to D12S90 and between proximal D12S312 and distal (D12S305, D12S104) microsatellites that were subsequently found on a single YAC clone. Analysis of a complex haplotype in linkage disequilibrium (LD) with the disease discriminated among distinct founder effects in French Canadian populations in Acadia and in Charlevoix-Saguenay-Lac-Saint-Jean (Ch-SLSJ), as well as an earlier one in precolonial Europe. A simple demographic model suggested the historical age of the founder effect in Ch-SLSJ to be {approximately}12 generations. The corresponding LD data are consistent with this figure when they are analyzed within the framework of Luria-Delbruck model,more » which takes into account the population growth. Population sampling due to a limited number of first settlers and the rapid demographic expansion appear to have played a major role in the founding of PDDR in Ch-SLSJ and, presumably, other genetic disorders endemic to French Canada. Similarly, the founder effect in Ashkenazim, coinciding with their early settlement in medieval Poland and subsequent expansion eastward, could explain the origin of frequent genetic diseases in this population. 48 refs., 5 figs., 2 tabs.« less

  6. Multilocus Patterns of Nucleotide Diversity, Population Structure and Linkage Disequilibrium in Boechera stricta, a Wild Relative of Arabidopsis

    PubMed Central

    Song, Bao-Hua; Windsor, Aaron J.; Schmid, Karl J.; Ramos-Onsins, Sebastian; Schranz, M. Eric; Heidel, Andrew J.; Mitchell-Olds, Thomas

    2009-01-01

    Information about polymorphism, population structure, and linkage disequilibrium (LD) is crucial for association studies of complex trait variation. However, most genomewide studies have focused on model systems, with very few analyses of undisturbed natural populations. Here, we sequenced 86 mapped nuclear loci for a sample of 46 genotypes of Boechera stricta and two individuals of B. holboellii, both wild relatives of Arabidopsis. Isolation by distance was significant across the species range of B. stricta, and three geographic groups were identified by structure analysis, principal coordinates analysis, and distance-based phylogeny analyses. The allele frequency spectrum indicated a genomewide deviation from an equilibrium neutral model, with silent nucleotide diversity averaging 0.004. LD decayed rapidly, declining to background levels in ∼10 kb or less. For tightly linked SNPs separated by <1 kb, LD was dependent on the reference population. LD was lower in the specieswide sample than within populations, suggesting that low levels of LD found in inbreeding species such as B. stricta, Arabidopsis thaliana, and barley may result from broad geographic sampling that spans heterogeneous genetic groups. Finally, analyses also showed that inbreeding B. stricta and A. thaliana have ∼45% higher recombination per kilobase than outcrossing A. lyrata. PMID:19104077

  7. The Genetic Diversity and Structure of Linkage Disequilibrium of the MTHFR Gene in Populations of Northern Eurasia.

    PubMed

    Trifonova, E A; Eremina, E R; Urnov, F D; Stepanov, V A

    2012-01-01

    The structure of the haplotypes and linkage disequilibrium (LD) of the methylenetetrahydrofolate reductase gene (MTHFR) in 9 population groups from Northern Eurasia and populations of the international HapMap project was investigated in the present study. The data suggest that the architecture of LD in the human genome is largely determined by the evolutionary history of populations; however, the results of phylogenetic and haplotype analyses seems to suggest that in fact there may be a common "old" mechanism for the formation of certain patterns of LD. Variability in the structure of LD and the level of diversity of MTHFRhaplotypes cause a certain set of tagSNPs with an established prognostic significance for each population. In our opinion, the results obtained in the present study are of considerable interest for understanding multiple genetic phenomena: namely, the association of interpopulation differences in the patterns of LD with structures possessing a genetic susceptibility to complex diseases, and the functional significance of the pleiotropicMTHFR gene effect. Summarizing the results of this study, a conclusion can be made that the genetic variability analysis with emphasis on the structure of LD in human populations is a powerful tool that can make a significant contribution to such areas of biomedical science as human evolutionary biology, functional genomics, genetics of complex diseases, and pharmacogenomics.

  8. 234Th: 238U disequilibrium as an indicator of sediment resuspension in Thermaikos Gulf, northwestern Aegean Sea

    NASA Astrophysics Data System (ADS)

    Muir, G. K. P.; Pates, J. M.; Karageorgis, A. P.; Kaberi, H.

    2005-12-01

    234Th: 238U disequilibria have been used extensively as tracers of particle dynamics in marine environments. 234Th ( t1/2=24.1 days) can be used as "proxy" for particle reactive pollutants, due to their similar rapid rate of scavenging onto particles and subsequent removal from the water column, to the sediments. Radioactive disequilibrium can be exploited to determine the rates and time-scales of processes occurring over days to months; in this instance the residence times of dissolved and particulate species with the benthic nepheloid layer (BNL). Three sampling cruises were undertaken in Thermaikos Gulf (NW Aegean Sea) during contrasting periods, to examine the impact of natural and anthropogenic activity on sediment resuspension. September and October 2001 represented background and trawling periods, respectively; January 2002 represented a mixed period, of trawling and storms. Dissolved 234Th is scavenged actively at the BNL, in the presence of suspended particulate material (SPM), with a mean residence time of 16 days. There is a weak inverse correlation between dissolved 234Th residence time and SPM concentration in the BNL, with the shortest residence times occurring during October 2001. No relationship was observed between particulate 234Th activities and SPM concentrations, indicating that particles are rapidly removed from the system, either by sinking or advection. The mean particulate 234Th residence time is 5 days.

  9. Automated manual transmission shift sequence controller

    DOEpatents

    Lawrie, Robert E.; Reed, Richard G.; Rausen, David J.

    2000-02-01

    A powertrain system for a hybrid vehicle. The hybrid vehicle includes a heat engine, such as a diesel engine, and an electric machine, which operates as both, an electric motor and an alternator, to power the vehicle. The hybrid vehicle also includes a manual-style transmission configured to operate as an automatic transmission from the perspective of the driver. The engine and the electric machine drive an input shaft which in turn drives an output shaft of the transmission. In addition to driving the transmission, the electric machine regulates the speed of the input shaft in order to synchronize the input shaft during either an upshift or downshift of the transmission by either decreasing or increasing the speed of the input shaft. When decreasing the speed of the input shaft, the electric motor functions as an alternator to produce electrical energy which may be stored by a storage device. Operation of the transmission is controlled by a transmission controller which receives input signals and generates output signals to control shift and clutch motors to effect smooth launch, upshift shifts, and downshifts of the transmission, so that the transmission functions substantially as an automatic transmission from the perspective of the driver, while internally substantially functioning as a manual transmission.

  10. Automated manual transmission mode selection controller

    DOEpatents

    Lawrie, Robert E.

    1999-11-09

    A powertrain system for a hybrid vehicle. The hybrid vehicle includes a heat engine, such as a diesel engine, and an electric machine, which operates as both an electric motor and an alternator, to power the vehicle. The hybrid vehicle also includes a manual-style transmission configured to operate as an automatic transmission from the perspective of the driver. The engine and the electric machine drive an input shaft which in turn drives an output shaft of the transmission. In addition to driving the transmission, the electric machine regulates the speed of the input shaft in order to synchronize the input shaft during either an upshift or downshift of the transmission by either decreasing or increasing the speed of the input shaft. When decreasing the speed of the input shaft, the electric motor functions as an alternator to produce electrical energy which may be stored by a storage device. Operation of the transmission is controlled by a transmission controller which receives input signals and generates output signals to control shift and clutch motors to effect smooth launch, upshift shifts, and downshifts of the transmission, so that the transmission functions substantially as an automatic transmission from the perspective of the driver, while internally substantially functioning as a manual transmission.

  11. Energy transmission using recyclable quantum entanglement

    PubMed Central

    Ye, Ming-Yong; Lin, Xiu-Min

    2016-01-01

    It is known that faster-than-light (FTL) transmission of energy could be achieved if the transmission were considered in the framework of non-relativistic classical mechanics. Here we show that FTL transmission of energy could also be achieved if the transmission were considered in the framework of non-relativistic quantum mechanics. In our transmission protocol a two-spin Heisenberg model is considered and the energy is transmitted by two successive local unitary operations on the initially entangled spins. Our protocol does not mean that FTL transmission can be achieved in reality when the theory of relativity is considered, but it shows that quantum entanglement can be used in a recyclable way in energy transmission. PMID:27465431

  12. Transmission of Chronic Wasting Disease in Wisconsin White-Tailed Deer: Implications for Disease Spread and Management

    PubMed Central

    Jennelle, Christopher S.; Henaux, Viviane; Wasserberg, Gideon; Thiagarajan, Bala; Rolley, Robert E.; Samuel, Michael D.

    2014-01-01

    Few studies have evaluated the rate of infection or mode of transmission for wildlife diseases, and the implications of alternative management strategies. We used hunter harvest data from 2002 to 2013 to investigate chronic wasting disease (CWD) infection rate and transmission modes, and address how alternative management approaches affect disease dynamics in a Wisconsin white-tailed deer population. Uncertainty regarding demographic impacts of CWD on cervid populations, human and domestic animal health concerns, and potential economic consequences underscore the need for strategies to control CWD distribution and prevalence. Using maximum-likelihood methods to evaluate alternative multi-state deterministic models of CWD transmission, harvest data strongly supports a frequency-dependent transmission structure with sex-specific infection rates that are two times higher in males than females. As transmissible spongiform encephalopathies are an important and difficult-to-study class of diseases with major economic and ecological implications, our work supports the hypothesis of frequency-dependent transmission in wild deer at a broad spatial scale and indicates that effective harvest management can be implemented to control CWD prevalence. Specifically, we show that harvest focused on the greater-affected sex (males) can result in stable population dynamics and control of CWD within the next 50 years, given the constraints of the model. We also provide a quantitative estimate of geographic disease spread in southern Wisconsin, validating qualitative assessments that CWD spreads relatively slowly. Given increased discovery and distribution of CWD throughout North America, insights from our study are valuable to management agencies and to the general public concerned about the impacts of CWD on white-tailed deer populations. PMID:24658535

  13. Transmission of chronic wasting disease in Wisconsin white-tailed deer: Implications for disease spread and management

    USGS Publications Warehouse

    Jennelle, Christopher S.; Henaux, Viviane; Wasserberg, Gideon; Thiagarajan, Bala; Rolley, Robert E.; Samuel, Michael D.

    2014-01-01

    Few studies have evaluated the rate of infection or mode of transmission for wildlife diseases, and the implications of alternative management strategies. We used hunter harvest data from 2002 to 2013 to investigate chronic wasting disease (CWD) infection rate and transmission modes, and address how alternative management approaches affect disease dynamics in a Wisconsin white-tailed deer population. Uncertainty regarding demographic impacts of CWD on cervid populations, human and domestic animal health concerns, and potential economic consequences underscore the need for strategies to control CWD distribution and prevalence. Using maximum-likelihood methods to evaluate alternative multi-state deterministic models of CWD transmission, harvest data strongly supports a frequency-dependent transmission structure with sex-specific infection rates that are two times higher in males than females. As transmissible spongiform encephalopathies are an important and difficult-to-study class of diseases with major economic and ecological implications, our work supports the hypothesis of frequency-dependent transmission in wild deer at a broad spatial scale and indicates that effective harvest management can be implemented to control CWD prevalence. Specifically, we show that harvest focused on the greater-affected sex (males) can result in stable population dynamics and control of CWD within the next 50 years, given the constraints of the model. We also provide a quantitative estimate of geographic disease spread in southern Wisconsin, validating qualitative assessments that CWD spreads relatively slowly. Given increased discovery and distribution of CWD throughout North America, insights from our study are valuable to management agencies and to the general public concerned about the impacts of CWD on white-tailed deer populations.

  14. The extent of linkage disequilibrium in beef cattle breeds using high-density SNP genotypes.

    PubMed

    Porto-Neto, Laercio R; Kijas, James W; Reverter, Antonio

    2014-03-24

    The extent of linkage disequilibrium (LD) between molecular markers impacts genome-wide association studies and implementation of genomic selection. The availability of high-density single nucleotide polymorphism (SNP) genotyping platforms makes it possible to investigate LD at an unprecedented resolution. In this work, we characterised LD decay in breeds of beef cattle of taurine, indicine and composite origins and explored its variation across autosomes and the X chromosome. In each breed, LD decayed rapidly and r2 was less than 0.2 for marker pairs separated by 50 kb. The LD decay curves clustered into three groups of similar LD decay that distinguished the three main cattle types. At short distances between markers (<10 kb), taurine breeds showed higher LD (r2=0.45) than their indicine (r2=0.25) and composite (r2=0.32) counterparts. This higher LD in taurine breeds was attributed to a smaller effective population size and a stronger bottleneck during breed formation. Using all SNPs on only the X chromosome, the three cattle types could still be distinguished. However for taurine breeds, the LD decay on the X chromosome was much faster and the background level much lower than for indicine breeds and composite populations. When using only SNPs that were polymorphic in all breeds, the analysis of the X chromosome mimicked that of the autosomes. The pattern of LD mirrored some aspects of the history of breed populations and showed a sharp decay with increasing physical distance between markers. We conclude that the availability of the HD chip can be used to detect association signals that remained hidden when using lower density genotyping platforms, since LD dropped below 0.2 at distances of 50 kb.

  15. Extent of Linkage Disequilibrium in the Domestic Cat, Felis silvestris catus, and Its Breeds

    PubMed Central

    Alhaddad, Hasan; Khan, Razib; Grahn, Robert A.; Gandolfi, Barbara; Mullikin, James C.; Cole, Shelley A.; Gruffydd-Jones, Timothy J.; Häggström, Jens; Lohi, Hannes; Longeri, Maria; Lyons, Leslie A.

    2013-01-01

    Domestic cats have a unique breeding history and can be used as models for human hereditary and infectious diseases. In the current era of genome-wide association studies, insights regarding linkage disequilibrium (LD) are essential for efficient association studies. The objective of this study is to investigate the extent of LD in the domestic cat, Felis silvestris catus, particularly within its breeds. A custom illumina GoldenGate Assay consisting of 1536 single nucleotide polymorphisms (SNPs) equally divided over ten 1 Mb chromosomal regions was developed, and genotyped across 18 globally recognized cat breeds and two distinct random bred populations. The pair-wise LD descriptive measure (r 2) was calculated between the SNPs in each region and within each population independently. LD decay was estimated by determining the non-linear least-squares of all pair-wise estimates as a function of distance using established models. The point of 50% decay of r2 was used to compare the extent of LD between breeds. The longest extent of LD was observed in the Burmese breed, where the distance at which r2 ≈ 0.25 was ∼380 kb, comparable to several horse and dog breeds. The shortest extent of LD was found in the Siberian breed, with an r2 ≈ 0.25 at approximately 17 kb, comparable to random bred cats and human populations. A comprehensive haplotype analysis was also conducted. The haplotype structure of each region within each breed mirrored the LD estimates. The LD of cat breeds largely reflects the breeds’ population history and breeding strategies. Understanding LD in diverse populations will contribute to an efficient use of the newly developed SNP array for the cat in the design of genome-wide association studies, as well as to the interpretation of results for the fine mapping of disease and phenotypic traits. PMID:23308248

  16. Carbon and oxygen isotopic disequilibrium during calcification of Globigerina bulloides in the Southern ocean

    NASA Astrophysics Data System (ADS)

    K, P.; Ghosh, P.; N, A.

    2015-12-01

    Oxygen and carbon isotopes in planktonic foraminifera Globigerina bulloides recovered from the water column of 0-1000 m depth across the meridional transect i.e. 10°N to 53°S of Indian ocean were compared with the available data from the core-top samples across the same transect. We also recorded in situ temperatures of the water column based on probe (CTD) profiles. The δ18O and δ13C values measured in the core top samples matches with the tow results. The equilibrium δ18O of calcite calculated from known temperature and δ18O of water column allowed us to compare the observed δ18O of formaminieral shell with the expected equilibrium values. Our comparison of carbonate composition in the samples between 10°N till 40°S showed excellent match with the expected equilibrium δ18O values established from the water collected at depth range of ~75-200m, however beyond 40°S the disequilibrium was pronounced with heavier δ18O (enriched by ~1.5‰) recorded in the carbonate as compared with the expected equilibrium δ18O values established from water. This observation was further verified with δ13C measurement of shell carbonates comparing with the equilibrium δ13C of calcite calculated with known temperature and δ13C of dissolved inorganic carbon in the water column. The δ13C of the shell carbonate was found heavier as compared to the expected equilibrium δ13C. Both δ18O and δ13C showed simultaneous enrichment signature in the region beyond 40°S suggesting role of processes such as leaching along with dissolution of shell carbonate in a relatively acidic condition.

  17. Extent of linkage disequilibrium in the domestic cat, Felis silvestris catus, and its breeds.

    PubMed

    Alhaddad, Hasan; Khan, Razib; Grahn, Robert A; Gandolfi, Barbara; Mullikin, James C; Cole, Shelley A; Gruffydd-Jones, Timothy J; Häggström, Jens; Lohi, Hannes; Longeri, Maria; Lyons, Leslie A

    2013-01-01

    Domestic cats have a unique breeding history and can be used as models for human hereditary and infectious diseases. In the current era of genome-wide association studies, insights regarding linkage disequilibrium (LD) are essential for efficient association studies. The objective of this study is to investigate the extent of LD in the domestic cat, Felis silvestris catus, particularly within its breeds. A custom illumina GoldenGate Assay consisting of 1536 single nucleotide polymorphisms (SNPs) equally divided over ten 1 Mb chromosomal regions was developed, and genotyped across 18 globally recognized cat breeds and two distinct random bred populations. The pair-wise LD descriptive measure (r(2)) was calculated between the SNPs in each region and within each population independently. LD decay was estimated by determining the non-linear least-squares of all pair-wise estimates as a function of distance using established models. The point of 50% decay of r(2) was used to compare the extent of LD between breeds. The longest extent of LD was observed in the Burmese breed, where the distance at which r(2) ≈ 0.25 was ∼380 kb, comparable to several horse and dog breeds. The shortest extent of LD was found in the Siberian breed, with an r(2) ≈ 0.25 at approximately 17 kb, comparable to random bred cats and human populations. A comprehensive haplotype analysis was also conducted. The haplotype structure of each region within each breed mirrored the LD estimates. The LD of cat breeds largely reflects the breeds' population history and breeding strategies. Understanding LD in diverse populations will contribute to an efficient use of the newly developed SNP array for the cat in the design of genome-wide association studies, as well as to the interpretation of results for the fine mapping of disease and phenotypic traits.

  18. Quantitative genetics

    USDA-ARS?s Scientific Manuscript database

    The majority of economically important traits targeted for cotton improvement are quantitatively inherited. In this chapter, the current state of cotton quantitative genetics is described and separated into four components. These components include: 1) traditional quantitative inheritance analysis, ...

  19. Transmission dynamics: critical questions and challenges

    PubMed Central

    2017-01-01

    This article overviews the dynamics of disease transmission in one-host–one-parasite systems. Transmission is the result of interacting host and pathogen processes, encapsulated with the environment in a ‘transmission triangle’. Multiple transmission modes and their epidemiological consequences are often not understood because the direct measurement of transmission is difficult. However, its different components can be analysed using nonlinear transmission functions, contact matrices and networks. A particular challenge is to develop such functions for spatially extended systems. This is illustrated for vector transmission where a ‘perception kernel’ approach is developed that incorporates vector behaviour in response to host spacing. A major challenge is understanding the relative merits of the large number of approaches to quantifying transmission. The evolution of transmission mode itself has been a rather neglected topic, but is important in the context of understanding disease emergence and genetic variation in pathogens. Disease impacts many biological processes such as community stability, the evolution of sex and speciation, yet the importance of different transmission modes in these processes is not understood. Broader approaches and ideas to disease transmission are important in the public health realm for combating newly emerging infections. This article is part of the themed issue ‘Opening the black box: re-examining the ecology and evolution of parasite transmission’. PMID:28289255

  20. Household transmission of influenza virus

    PubMed Central

    Tsang, Tim K.; Lau, Lincoln L. H.; Cauchemez, Simon; Cowling, Benjamin J.

    2015-01-01

    Human influenza viruses cause regular epidemics and occasional pandemics with a substantial public health burden. Household transmission studies have provided valuable information on the dynamics of influenza transmission. We reviewed published studies and found that once one household member is infected with influenza, the risk of infection in a household contact can be up to 38%, and the delay between onset in index and secondary cases is around 3 days. Younger age was associated with higher susceptibility. In the future, household transmission studies will provide information on transmission dynamics including the correlation of virus shedding and symptoms with transmission, and the correlation of new measures of immunity with protection against infection. PMID:26612500

  1. Rotavirus vaccine strain transmission by vaccinated infants in the foster home.

    PubMed

    Miura, Hiroki; Kawamura, Yoshiki; Sugata, Ken; Koshiyama, Nozomi; Yoshikawa, Akiko; Komoto, Satoshi; Taniguchi, Koki; Ihira, Masaru; Yoshikawa, Tetsushi

    2017-01-01

    Previous studies have demonstrated the transmission of rotavirus vaccine strains from vaccinated children to nonvaccinated siblings. We sought to fully elucidate the safety of rotavirus (RV) vaccination in closed contact circumstance, such as the foster home for future assessment of the vaccine safety in an neonatal intensive care unit. Stool samples were collected from 4 RV vaccinated (160 samples) and 23 unvaccinated (766 samples) infants. RV viral RNA loads were measured using real-time reverse transcription polymerase chain reaction (RT-PCR). RV vaccine strain RNA was persistently detected in stool samples collected from the four vaccine recipients and one unvaccinated infant, but not in the stool samples collected from the 22 other unvaccinated infants. The unvaccinated infant who tested positive for the RV vaccine strain was vaccinated prior to enrollment in this study. The quantitative real-time RT-PCR data revealed a peak viral RNA load 1 week after vaccination followed by a gradual decrease. The current study suggests that RV vaccination may be safe in a close contact environment because there was limited transmission from RV vaccinated to unvaccinated infants. J. Med. Virol. 89:79-84, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  2. Series Transmission Line Transformer

    DOEpatents

    Buckles, Robert A.; Booth, Rex; Yen, Boris T.

    2004-06-29

    A series transmission line transformer is set forth which includes two or more of impedance matched sets of at least two transmissions lines such as shielded cables, connected in parallel at one end ans series at the other in a cascading fashion. The cables are wound about a magnetic core. The series transmission line transformer (STLT) which can provide for higher impedance ratios and bandwidths, which is scalable, and which is of simpler design and construction.

  3. The linkage disequilibrium maps of three human chromosomes across four populations reflect their demographic history and a common underlying recombination pattern

    PubMed Central

    De La Vega, Francisco M.; Isaac, Hadar; Collins, Andrew; Scafe, Charles R.; Halldórsson, Bjarni V.; Su, Xiaoping; Lippert, Ross A.; Wang, Yu; Laig-Webster, Marion; Koehler, Ryan T.; Ziegle, Janet S.; Wogan, Lewis T.; Stevens, Junko F.; Leinen, Kyle M.; Olson, Sheri J.; Guegler, Karl J.; You, Xiaoqing; Xu, Lily H.; Hemken, Heinz G.; Kalush, Francis; Itakura, Mitsuo; Zheng, Yi; de Thé, Guy; O'Brien, Stephen J.; Clark, Andrew G.; Istrail, Sorin; Hunkapiller, Michael W.; Spier, Eugene G.; Gilbert, Dennis A.

    2005-01-01

    The extent and patterns of linkage disequilibrium (LD) determine the feasibility of association studies to map genes that underlie complex traits. Here we present a comparison of the patterns of LD across four major human populations (African-American, Caucasian, Chinese, and Japanese) with a high-resolution single-nucleotide polymorphism (SNP) map covering almost the entire length of chromosomes 6, 21, and 22. We constructed metric LD maps formulated such that the units measure the extent of useful LD for association mapping. LD reaches almost twice as far in chromosome 6 as in chromosomes 21 or 22, in agreement with their differences in recombination rates. By all measures used, out-of-Africa populations showed over a third more LD than African-Americans, highlighting the role of the population's demography in shaping the patterns of LD. Despite those differences, the long-range contour of the LD maps is remarkably similar across the four populations, presumably reflecting common localization of recombination hot spots. Our results have practical implications for the rational design and selection of SNPs for disease association studies. PMID:15781572

  4. WE-AB-207A-10: Transmission Characteristics of a Two Dimensional Antiscatter Grid Prototype for CBCT

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

    Altunbas, C; Kavanagh, B; Miften, M

    2016-06-15

    Purpose: Scattered radiation remains to be a major contributor to image quality degradation in CBCT. To address the scatter problem, a focused, 2D antiscatter grid (2DASG) prototype was designed, and fabricated using additive manufacturing processes. Its scatter and primary transmission properties were characterized using a linac mounted CBCT system. Methods: The prototype 2DASG was composed of rectangular grid holes separated by tungsten septa, and has a grid pitch of 2.91 mm, grid ratio of 8, and a septal thickness of 0.1 mm. Each grid hole was aligned or focused towards the x-ray source in half-fan (i.e. offset detector) geometry ofmore » the Varian TrueBeam CBCT system. Scatter and primary transmission experiments were performed by using acrylic blocks and the beam-stop method. Transmission properties of a radiographic ASG (1DASG) (grid ratio of 10) was also performed by using the identical setup. Results: At 30 cm phantom thickness, scatter to primary ratio (SPR) was 4.51 without any ASG device. SPR was reduced to 1.28 with 1DASG, and it was further reduced to 0.28 with 2DASG. Scatter transmission fraction (Ts) of 1DASG was 21%, and Ts was reduced to 5.8% with 2DASG. The average primary transmission fraction (Tp) of 1DASG was 70.6%, whereas Tp increased to 85.1% with 2DASG. Variation of Tp across 40 cm length (the long axis of flat panel detector) was 2.6%. Conclusion: When compared to conventional ASGs, the focused 2DASG can vastly improve scatter suppression and primary transmission performance. Due to precise alignment of 2DASG’s grid holes with respect to beam divergence, high degree of primary transmission through the 2DASG was maintained across the full length of the prototype. We strongly believe that robust scatter rejection and primary transmission characteristics of our 2DASG can translate into both improved quantitative accuracy and soft tissue resolution in linac mounted CBCT systems.« less

  5. Semi-quantitative estimation of cellular SiO2 nanoparticles using flow cytometry combined with X-ray fluorescence measurements.

    PubMed

    Choi, Seo Yeon; Yang, Nuri; Jeon, Soo Kyung; Yoon, Tae Hyun

    2014-09-01

    In this study, we have demonstrated feasibility of a semi-quantitative approach for the estimation of cellular SiO2 nanoparticles (NPs), which is based on the flow cytometry measurements of their normalized side scattering intensity. In order to improve our understanding on the quantitative aspects of cell-nanoparticle interactions, flow cytometry, transmission electron microscopy, and X-ray fluorescence experiments were carefully performed for the HeLa cells exposed to SiO2 NPs with different core diameters, hydrodynamic sizes, and surface charges. Based on the observed relationships among the experimental data, a semi-quantitative cellular SiO2 NPs estimation method from their normalized side scattering and core diameters was proposed, which can be applied for the determination of cellular SiO2 NPs within their size-dependent linear ranges. © 2014 International Society for Advancement of Cytometry.

  6. Qualitative and quantitative processing of side-scan sonar data

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

    Dwan, F.S.; Anderson, A.L.; Hilde, T.W.C.

    1990-06-01

    Modern side-scan sonar systems allow vast areas of seafloor to be rapidly imaged and quantitatively mapped in detail. The application of remote sensing image processing techniques can be used to correct for various distortions inherent in raw sonography. Corrections are possible for water column, slant-range, aspect ratio, speckle and striping noise, multiple returns, power drop-off, and for georeferencing. The final products reveal seafloor features and patterns that are geometrically correct, georeferenced, and have improved signal/noise ratio. These products can be merged with other georeferenced data bases for further database management and information extraction. In order to compare data collected bymore » different systems from a common area and to ground truth measurements and geoacoustic models, quantitative correction must be made for calibrated sonar system and bathymetry effects. Such data inversion must account for system source level, beam pattern, time-varying gain, processing gain, transmission loss, absorption, insonified area, and grazing angle effects. Seafloor classification can then be performed on the calculated back-scattering strength using Lambert's Law and regression analysis. Examples are given using both approaches: image analysis and inversion of data based on the sonar equation.« less

  7. Genome wide linkage disequilibrium and genetic structure in Sicilian dairy sheep breeds.

    PubMed

    Mastrangelo, Salvatore; Di Gerlando, Rosalia; Tolone, Marco; Tortorici, Lina; Sardina, Maria Teresa; Portolano, Baldassare

    2014-10-10

    The recent availability of sheep genome-wide SNP panels allows providing background information concerning genome structure in domestic animals. The aim of this work was to investigate the patterns of linkage disequilibrium (LD), the genetic diversity and population structure in Valle del Belice, Comisana, and Pinzirita dairy sheep breeds using the Illumina Ovine SNP50K Genotyping array. Average r (2) between adjacent SNPs across all chromosomes was 0.155 ± 0.204 for Valle del Belice, 0.156 ± 0.208 for Comisana, and 0.128 ± 0.188 for Pinzirita breeds, and some variations in LD value across chromosomes were observed, in particular for Valle del Belice and Comisana breeds. Average values of r (2) estimated for all pairwise combinations of SNPs pooled over all autosomes were 0.058 ± 0.023 for Valle del Belice, 0.056 ± 0.021 for Comisana, and 0.037 ± 0.017 for Pinzirita breeds. The LD declined as a function of distance and average r (2) was lower than the values observed in other sheep breeds. Consistency of results among the several used approaches (Principal component analysis, Bayesian clustering, F ST, Neighbor networks) showed that while Valle del Belice and Pinzirita breeds formed a unique cluster, Comisana breed showed the presence of substructure. In Valle del Belice breed, the high level of genetic differentiation within breed, the heterogeneous cluster in Admixture analysis, but at the same time the highest inbreeding coefficient, suggested that the breed had a wide genetic base with inbred individuals belonging to the same flock. The Sicilian breeds were characterized by low genetic differentiation and high level of admixture. Pinzirita breed displayed the highest genetic diversity (He, Ne) whereas the lowest value was found in Valle del Belice breed. This study has reported for the first time estimates of LD and genetic diversity from a genome-wide perspective in Sicilian dairy sheep breeds. Our results indicate that breeds formed non

  8. Nucleotide variability and linkage disequilibrium patterns in the porcine MUC4 gene

    PubMed Central

    2012-01-01

    Background MUC4 is a type of membrane anchored glycoprotein and serves as the major constituent of mucus that covers epithelial surfaces of many tissues such as trachea, colon and cervix. MUC4 plays important roles in the lubrication and protection of the surface epithelium, cell proliferation and differentiation, immune response, cell adhesion and cancer development. To gain insights into the evolution of the porcine MUC4 gene, we surveyed the nucleotide variability and linkage disequilibrium (LD) within this gene in Chinese indigenous breeds and Western commercial breeds. Results A total of 53 SNPs covering the MUC4 gene were genotyped on 5 wild boars and 307 domestic pigs representing 11 Chinese breeds and 3 Western breeds. The nucleotide variability, haplotype phylogeny and LD extent of MUC4 were analyzed in these breeds. Both Chinese and Western breeds had considerable nucleotide diversity at the MUC4 locus. Western pig breeds like Duroc and Large White have comparable nucleotide diversity as many of Chinese breeds, thus artificial selection for lean pork production have not reduced the genetic variability of MUC4 in Western commercial breeds. Haplotype phylogeny analyses indicated that MUC4 had evolved divergently in Chinese and Western pigs. The dendrogram of genetic differentiation between breeds generally reflected demographic history and geographical distribution of these breeds. LD patterns were unexpectedly similar between Chinese and Western breeds, in which LD usually extended less than 20 kb. This is different from the presumed high LD extent (more than 100 kb) in Western commercial breeds. The significant positive Tajima’D, and Fu and Li’s D statistics in a few Chinese and Western breeds implied that MUC4 might undergo balancing selection in domestic breeds. Nevertheless, we cautioned that the significant statistics could be upward biased by SNP ascertainment process. Conclusions Chinese and Western breeds have similar nucleotide diversity

  9. Nucleotide variability and linkage disequilibrium patterns in the porcine MUC4 gene.

    PubMed

    Yang, Ming; Yang, Bin; Yan, Xueming; Ouyang, Jing; Zeng, Weihong; Ai, Huashui; Ren, Jun; Huang, Lusheng

    2012-07-13

    MUC4 is a type of membrane anchored glycoprotein and serves as the major constituent of mucus that covers epithelial surfaces of many tissues such as trachea, colon and cervix. MUC4 plays important roles in the lubrication and protection of the surface epithelium, cell proliferation and differentiation, immune response, cell adhesion and cancer development. To gain insights into the evolution of the porcine MUC4 gene, we surveyed the nucleotide variability and linkage disequilibrium (LD) within this gene in Chinese indigenous breeds and Western commercial breeds. A total of 53 SNPs covering the MUC4 gene were genotyped on 5 wild boars and 307 domestic pigs representing 11 Chinese breeds and 3 Western breeds. The nucleotide variability, haplotype phylogeny and LD extent of MUC4 were analyzed in these breeds. Both Chinese and Western breeds had considerable nucleotide diversity at the MUC4 locus. Western pig breeds like Duroc and Large White have comparable nucleotide diversity as many of Chinese breeds, thus artificial selection for lean pork production have not reduced the genetic variability of MUC4 in Western commercial breeds. Haplotype phylogeny analyses indicated that MUC4 had evolved divergently in Chinese and Western pigs. The dendrogram of genetic differentiation between breeds generally reflected demographic history and geographical distribution of these breeds. LD patterns were unexpectedly similar between Chinese and Western breeds, in which LD usually extended less than 20 kb. This is different from the presumed high LD extent (more than 100 kb) in Western commercial breeds. The significant positive Tajima'D, and Fu and Li's D statistics in a few Chinese and Western breeds implied that MUC4 might undergo balancing selection in domestic breeds. Nevertheless, we cautioned that the significant statistics could be upward biased by SNP ascertainment process. Chinese and Western breeds have similar nucleotide diversity but evolve divergently in the MUC4

  10. Rapakivi texture formation via disequilibrium melting in a contact partial melt zone, Antarctica

    NASA Astrophysics Data System (ADS)

    Currier, R. M.

    2017-12-01

    In the McMurdo Dry Valleys of Antarctica, a Jurassic aged dolerite sill induced partial melting of granite in the shallow crust. The melt zone can be traced in full, from high degrees of melting (>60%) along the dolerite contact, to no apparent signs of melting, 10s of meters above the contact. Within this melt zone, the well-known rapakivi texture is found, arrested in various stages of development. High above the contact, and at low degrees of melting, K-feldspar crystals are slightly rounded and unmantled. In the lower half of the melt zone, mantles of cellular textured plagioclase appear on K-feldspar, and thicken towards the contact heat source. At the highest degrees of melting, cellular-textured plagioclase completely replaces restitic K-feldspar. Because of the complete exposure and intact context, the leading models of rapakivi texture formation can be tested against this system. The previously proposed mechanisms of subisothermal decompression, magma-mixing, and hydrothermal exsolution all fail to adequately describe rapakivi generation in this melt zone. Preferred here is a closed system model that invokes the production of a heterogeneous, disequilibrium melt through rapid heating, followed by calcium and sodium rich melt reacting in a peritectic fashion with restitic K-feldspar crystals. This peritectic reaction results in the production of plagioclase of andesine-oligoclase composition—which is consistent with not just mantles in the melt zone, but globally as well. The thickness of the mantle is diffusion limited, and thus a measure of the diffusive length scale of sodium and calcium over the time scale of melting. Thermal modeling provides a time scale of melting that is consistent with the thickness of observed mantles. Lastly, the distribution of mantled feldspars is highly ordered in this melt zone, but if it were mobilized and homogenized—mixing together cellular plagioclase, mantled feldspars, and unmantled feldspars—the result would be

  11. Clines in quantitative traits: The role of migration patterns and selection scenarios

    PubMed Central

    Geroldinger, Ludwig; Bürger, Reinhard

    2015-01-01

    The existence, uniqueness, and shape of clines in a quantitative trait under selection toward a spatially varying optimum is studied. The focus is on deterministic diploid two-locus n-deme models subject to various migration patterns and selection scenarios. Migration patterns may exhibit isolation by distance, as in the stepping-stone model, or random dispersal, as in the island model. The phenotypic optimum may change abruptly in a single environmental step, more gradually, or not at all. Symmetry assumptions are imposed on phenotypic optima and migration rates. We study clines in the mean, variance, and linkage disequilibrium (LD). Clines result from polymorphic equilibria. The possible equilibrium configurations are determined as functions of the migration rate. Whereas for weak migration, many polymorphic equilibria may be simultaneously stable, their number decreases with increasing migration rate. Also for intermediate migration rates polymorphic equilibria are in general not unique, however, for loci of equal effects the corresponding clines in the mean, variance, and LD are unique. For sufficiently strong migration, no polymorphism is maintained. Both migration pattern and selection scenario exert strong influence on the existence and shape of clines. The results for discrete demes are compared with those from models in which space varies continuously and dispersal is modeled by diffusion. Comparisons with previous studies, which investigated clines under neutrality or under linkage equilibrium, are performed. If there is no long-distance migration, the environment does not change abruptly, and linkage is not very tight, populations are almost everywhere close to linkage equilibrium. PMID:25446959

  12. 77 FR 32183 - Transmission Planning and Cost Allocation by Transmission Owning and Operating Public Utilities

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-31

    ... it would not wait for systemic problems to undermine transmission planning before action is taken... that the development of transmission facilities can involve long lead times and complex problems... rather than allowing the problems in transmission planning and cost allocation to continue or to increase...

  13. Understanding Ebola Virus Transmission

    PubMed Central

    Judson, Seth; Prescott, Joseph; Munster, Vincent

    2015-01-01

    An unprecedented number of Ebola virus infections among healthcare workers and patients have raised questions about our understanding of Ebola virus transmission. Here, we explore different routes of Ebola virus transmission between people, summarizing the known epidemiological and experimental data. From this data, we expose important gaps in Ebola virus research pertinent to outbreak situations. We further propose experiments and methods of data collection that will enable scientists to fill these voids in our knowledge about the transmission of Ebola virus. PMID:25654239

  14. HVDC power transmission technology assessment

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

    Hauth, R.L.; Tatro, P.J.; Railing, B.D.

    1997-04-01

    The purpose of this study was to develop an assessment of the national utility system`s needs for electric transmission during the period 1995-2020 that could be met by future reduced-cost HVDC systems. The assessment was to include an economic evaluation of HVDC as a means for meeting those needs as well as a comparison with competing technologies such as ac transmission with and without Flexible AC Transmission System (FACTS) controllers. The role of force commutated dc converters was to be assumed where appropriate. The assessment begins by identifying the general needs for transmission in the U.S. in the context ofmore » a future deregulated power industry. The possible roles for direct current transmission are then postulated in terms of representative scenarios. A few of the scenarios are illustrated with the help of actual U.S. system examples. non-traditional applications as well as traditional applications such as long lines and asynchronous interconnections are discussed. The classical ``break-even distance`` concept for comparing HVDC and ac lines is used to assess the selected scenarios. The impact of reduced-cost converters is reflected in terms of the break-even distance. This report presents a comprehensive review of the functional benefits of HVDC transmission and updated cost data for both ac and dc system components. It also provides some provocative thoughts on how direct current transmission might be applied to better utilize and expand our nation`s increasingly stressed transmission assets.« less

  15. Elucidation of hepatitis C virus transmission and early diversification by single genome sequencing.

    PubMed

    Li, Hui; Stoddard, Mark B; Wang, Shuyi; Blair, Lily M; Giorgi, Elena E; Parrish, Erica H; Learn, Gerald H; Hraber, Peter; Goepfert, Paul A; Saag, Michael S; Denny, Thomas N; Haynes, Barton F; Hahn, Beatrice H; Ribeiro, Ruy M; Perelson, Alan S; Korber, Bette T; Bhattacharya, Tanmoy; Shaw, George M

    2012-01-01

    A precise molecular identification of transmitted hepatitis C virus (HCV) genomes could illuminate key aspects of transmission biology, immunopathogenesis and natural history. We used single genome sequencing of 2,922 half or quarter genomes from plasma viral RNA to identify transmitted/founder (T/F) viruses in 17 subjects with acute community-acquired HCV infection. Sequences from 13 of 17 acute subjects, but none of 14 chronic controls, exhibited one or more discrete low diversity viral lineages. Sequences within each lineage generally revealed a star-like phylogeny of mutations that coalesced to unambiguous T/F viral genomes. Numbers of transmitted viruses leading to productive clinical infection were estimated to range from 1 to 37 or more (median = 4). Four acutely infected subjects showed a distinctly different pattern of virus diversity that deviated from a star-like phylogeny. In these cases, empirical analysis and mathematical modeling suggested high multiplicity virus transmission from individuals who themselves were acutely infected or had experienced a virus population bottleneck due to antiviral drug therapy. These results provide new quantitative and qualitative insights into HCV transmission, revealing for the first time virus-host interactions that successful vaccines or treatment interventions will need to overcome. Our findings further suggest a novel experimental strategy for identifying full-length T/F genomes for proteome-wide analyses of HCV biology and adaptation to antiviral drug or immune pressures.

  16. Elucidation of Hepatitis C Virus Transmission and Early Diversification by Single Genome Sequencing

    PubMed Central

    Li, Hui; Stoddard, Mark B.; Wang, Shuyi; Blair, Lily M.; Giorgi, Elena E.; Parrish, Erica H.; Learn, Gerald H.; Hraber, Peter; Goepfert, Paul A.; Saag, Michael S.; Denny, Thomas N.; Haynes, Barton F.; Hahn, Beatrice H.; Ribeiro, Ruy M.; Perelson, Alan S.; Korber, Bette T.; Bhattacharya, Tanmoy; Shaw, George M.

    2012-01-01

    A precise molecular identification of transmitted hepatitis C virus (HCV) genomes could illuminate key aspects of transmission biology, immunopathogenesis and natural history. We used single genome sequencing of 2,922 half or quarter genomes from plasma viral RNA to identify transmitted/founder (T/F) viruses in 17 subjects with acute community-acquired HCV infection. Sequences from 13 of 17 acute subjects, but none of 14 chronic controls, exhibited one or more discrete low diversity viral lineages. Sequences within each lineage generally revealed a star-like phylogeny of mutations that coalesced to unambiguous T/F viral genomes. Numbers of transmitted viruses leading to productive clinical infection were estimated to range from 1 to 37 or more (median = 4). Four acutely infected subjects showed a distinctly different pattern of virus diversity that deviated from a star-like phylogeny. In these cases, empirical analysis and mathematical modeling suggested high multiplicity virus transmission from individuals who themselves were acutely infected or had experienced a virus population bottleneck due to antiviral drug therapy. These results provide new quantitative and qualitative insights into HCV transmission, revealing for the first time virus-host interactions that successful vaccines or treatment interventions will need to overcome. Our findings further suggest a novel experimental strategy for identifying full-length T/F genomes for proteome-wide analyses of HCV biology and adaptation to antiviral drug or immune pressures. PMID:22927816

  17. The evolution of plant virus transmission pathways.

    PubMed

    Hamelin, Frédéric M; Allen, Linda J S; Prendeville, Holly R; Hajimorad, M Reza; Jeger, Michael J

    2016-05-07

    The evolution of plant virus transmission pathways is studied through transmission via seed, pollen, or a vector. We address the questions: under what circumstances does vector transmission make pollen transmission redundant? Can evolution lead to the coexistence of multiple virus transmission pathways? We restrict the analysis to an annual plant population in which reproduction through seed is obligatory. A semi-discrete model with pollen, seed, and vector transmission is formulated to investigate these questions. We assume vector and pollen transmission rates are frequency-dependent and density-dependent, respectively. An ecological stability analysis is performed for the semi-discrete model and used to inform an evolutionary study of trade-offs between pollen and seed versus vector transmission. Evolutionary dynamics critically depend on the shape of the trade-off functions. Assuming a trade-off between pollen and vector transmission, evolution either leads to an evolutionarily stable mix of pollen and vector transmission (concave trade-off) or there is evolutionary bi-stability (convex trade-off); the presence of pollen transmission may prevent evolution of vector transmission. Considering a trade-off between seed and vector transmission, evolutionary branching and the subsequent coexistence of pollen-borne and vector-borne strains is possible. This study contributes to the theory behind the diversity of plant-virus transmission patterns observed in nature. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. "Narrowing the transmission gap: A synthesis of three decades of research on intergenerational transmission of attachment": Correction.

    PubMed

    2018-04-01

    Reports an error in "Narrowing the transmission gap: A synthesis of three decades of research on intergenerational transmission of attachment" by Marije L. Verhage, Carlo Schuengel, Sheri Madigan, R. M. Pasco Fearon, Mirjam Oosterman, Rosalinda Cassibba, Marian J. Bakermans-Kranenburg and Marinus H. van IJzendoorn ( Psychological Bulletin , 2016[Apr], Vol 142[4], 337-366). In the article, there are errors in Table 7. The percentages of the attachment classifications do not add up to 100%. The corrected version of Table 7 is provided in the erratum. (The following abstract of the original article appeared in record 2015-55801-001.) Twenty years ago, meta-analytic results (k = 19) confirmed the association between caregiver attachment representations and child-caregiver attachment (Van IJzendoorn, 1995). A test of caregiver sensitivity as the mechanism behind this intergenerational transmission showed an intriguing "transmission gap." Since then, the intergenerational transmission of attachment and the transmission gap have been studied extensively, and now extend to diverse populations from all over the globe. Two decades later, the current review revisited the effect sizes of intergenerational transmission, the heterogeneity of the transmission effects, and the size of the transmission gap. Analyses were carried out with a total of 95 samples (total N = 4,819). All analyses confirmed intergenerational transmission of attachment, with larger effect sizes for secure-autonomous transmission (r = .31) than for unresolved transmission (r = .21), albeit with significantly smaller effect sizes than 2 decades earlier (r = .47 and r = .31, respectively). Effect sizes were moderated by risk status of the sample, biological relatedness of child-caregiver dyads, and age of the children. Multivariate moderator analyses showed that unpublished and more recent studies had smaller effect sizes than published and older studies. Path analyses showed that the transmission could not

  19. Quantitative evaluation of infection control models in the prevention of nosocomial transmission of SARS virus to healthcare workers: implication to nosocomial viral infection control for healthcare workers.

    PubMed

    Yen, Muh-Yong; Lu, Yun-Ching; Huang, Pi-Hsiang; Chen, Chen-Ming; Chen, Yee-Chun; Lin, Yusen E

    2010-07-01

    Healthcare workers (HCWs) are at high risk of acquiring emerging infections while caring for patients, as has been shown in the recent SARS and swine flu epidemics. Using SARS as an example, we determined the effectiveness of infection control measures (ICMs) by logistic regression and structural equation modelling (SEM), a quantitative methodology that can test a hypothetical model and validates causal relationships among ICMs. Logistic regression showed that installing hand wash stations in the emergency room (p = 0.012, odds ratio = 1.07) was the only ICM significantly associated with the protection of HCWs from acquiring the SARS virus. The structural equation modelling results showed that the most important contributing factor (highest proportion of effectiveness) was installation of a fever screening station outside the emergency department (51%). Other measures included traffic control in the emergency department (19%), availability of an outbreak standard operation protocol (12%), mandatory temperature screening (9%), establishing a hand washing setup at each hospital checkpoint (3%), adding simplified isolation rooms (3%), and a standardized patient transfer protocol (3%). Installation of fever screening stations outside of the hospital and implementing traffic control in the emergency department contributed to 70% of the effectiveness in the prevention of SARS transmission. Our approach can be applied to the evaluation of control measures for other epidemic infectious diseases, including swine flu and avian flu.

  20. Natural and experimental hepatitis E virus genotype 3-infection in European wild boar is transmissible to domestic pigs.

    PubMed

    Schlosser, Josephine; Eiden, Martin; Vina-Rodriguez, Ariel; Fast, Christine; Dremsek, Paul; Lange, Elke; Ulrich, Rainer G; Groschup, Martin H

    2014-11-26

    Hepatitis E virus (HEV) is the causative agent of acute hepatitis E in humans in developing countries, but sporadic and autochthonous cases do also occur in industrialised countries. In Europe, food-borne zoonotic transmission of genotype 3 (gt3) has been associated with domestic pig and wild boar. However, little is known about the course of HEV infection in European wild boar and their role in HEV transmission to domestic pigs. To investigate the transmissibility and pathogenesis of wild boar-derived HEVgt3, we inoculated four wild boar and four miniature pigs intravenously. Using quantitative real-time RT-PCR viral RNA was detected in serum, faeces and in liver, spleen and lymph nodes. The antibody response evolved after fourteen days post inoculation. Histopathological findings included mild to moderate lymphoplasmacytic hepatitis which was more prominent in wild boar than in miniature pigs. By immunohistochemical methods, viral antigens were detected mainly in Kupffer cells and liver sinusoidal endothelial cells, partially associated with hepatic lesions, but also in spleen and lymph nodes. While clinical symptoms were subtle and gross pathology was inconspicuous, increased liver enzyme levels in serum indicated hepatocellular injury. As the faecal-oral route is supposed to be the most likely transmission route, we included four contact animals to prove horizontal transmission. Interestingly, HEVgt3-infection was also detected in wild boar and miniature pigs kept in contact to intravenously inoculated wild boar. Given the high virus loads and long duration of viral shedding, wild boar has to be considered as an important HEV reservoir and transmission host in Europe.

  1. Space Weather, Geomagnetic Disturbances and Impact on the High-Voltage Transmission Systems

    NASA Technical Reports Server (NTRS)

    Pullkkinen, A.

    2011-01-01

    Geomagnetically induced currents (GIC) affecting the performance of high-voltage power transmission systems are one of the most significant hazards space weather poses on the operability of critical US infrastructure. The severity of the threat was emphasized, for example, in two recent reports: the National Research Council (NRC) report "Severe Space Weather Events--Understanding Societal and Economic Impacts: A Workshop Report" and the North American Electric Reliability Corporation (NERC) report "HighImpact, Low-Frequency Event Risk to the North American Bulk Power System." The NRC and NERC reports demonstrated the important national security dimension of space weather and GIC and called for comprehensive actions to forecast and mitigate the hazard. In this paper we will give a brief overview of space weather storms and accompanying geomagnetic storm events that lead to GIC. We will also review the fundamental principles of how GIC can impact the power transmission systems. Space weather has been a subject of great scientific advances that have changed the wonder of the past to a quantitative field of physics with true predictive power of today. NASA's Solar Shield system aimed at forecasting of GIC in the North American high-voltage power transmission system can be considered as one of the ultimate fruits of those advances. We will review the fundamental principles of the Solar Shield system and provide our view of the way forward in the science of GIC.

  2. Quantitative analysis of the effects of vertical magnetic fields on microsegregation in Te-doped LEC GaAs

    NASA Technical Reports Server (NTRS)

    Carlson, D. J.; Witt, A. F.

    1992-01-01

    Using near-IR transmission microscopy with computational absorption analysis, the effects of axial magnetic fields on micro- and macrosegregation during LP-LEC growth of GaAs were quantitatively investigated with a spatial resolution approaching 2 microns. Segregation inhomogeneities exceeding one order of magnitude are found to be related to fluid dynamics of the melt. The applicability of the BPS theory as well as the nonapplicability of the Cochran analysis are established.

  3. Continuously Variable Transmission

    NASA Technical Reports Server (NTRS)

    Grana, D. C.

    1985-01-01

    Chain slides along two cones, in novel transmission concept. Transmission includes chain drive between two splined shafts. Chain sprockets follow surfaces of two cones. As one chain sprocket moves toward smaller diameter other chain sprocket moves toward larger diameter, thereby changing "gear" ratio. Movement initiated by tension applied to chain by planetary gear mechanism. Device positive, simple, and efficient over wide range of speed ratios.

  4. The quantitative analysis of silicon carbide surface smoothing by Ar and Xe cluster ions

    NASA Astrophysics Data System (ADS)

    Ieshkin, A. E.; Kireev, D. S.; Ermakov, Yu. A.; Trifonov, A. S.; Presnov, D. E.; Garshev, A. V.; Anufriev, Yu. V.; Prokhorova, I. G.; Krupenin, V. A.; Chernysh, V. S.

    2018-04-01

    The gas cluster ion beam technique was used for the silicon carbide crystal surface smoothing. The effect of processing by two inert cluster ions, argon and xenon, was quantitatively compared. While argon is a standard element for GCIB, results for xenon clusters were not reported yet. Scanning probe microscopy and high resolution transmission electron microscopy techniques were used for the analysis of the surface roughness and surface crystal layer quality. The gas cluster ion beam processing results in surface relief smoothing down to average roughness about 1 nm for both elements. It was shown that xenon as the working gas is more effective: sputtering rate for xenon clusters is 2.5 times higher than for argon at the same beam energy. High resolution transmission electron microscopy analysis of the surface defect layer gives values of 7 ± 2 nm and 8 ± 2 nm for treatment with argon and xenon clusters.

  5. Down hole transmission system

    DOEpatents

    Hall, David R [Provo, UT; Hall, Jr., H. Tracy

    2007-07-24

    A transmission system in a downhole component comprises a data transmission element in both ends of the downhole component. Each data transmission element houses an electrically conducting coil in a MCEI circular trough. The electrically conducting coil comprises at least two generally fractional loops. In the preferred embodiment, the transmission elements are connected by an electrical conductor. Preferably, the electrical conductor is a coaxial cable. Preferably, the MCEI trough comprises ferrite. In the preferred embodiment, the fractional loops are connected by a connecting cable. In one aspect of the present invention, the connecting cable is a pair of twisted wires. In one embodiment the connecting cable is a shielded pair of twisted wires. In another aspect of the present invention, the connecting cable is a coaxial cable. The connecting cable may be disposed outside of the MCEI circular trough.

  6. A quantitative study of nanoparticle skin penetration with interactive segmentation.

    PubMed

    Lee, Onseok; Lee, See Hyun; Jeong, Sang Hoon; Kim, Jaeyoung; Ryu, Hwa Jung; Oh, Chilhwan; Son, Sang Wook

    2016-10-01

    In the last decade, the application of nanotechnology techniques has expanded within diverse areas such as pharmacology, medicine, and optical science. Despite such wide-ranging possibilities for implementation into practice, the mechanisms behind nanoparticle skin absorption remain unknown. Moreover, the main mode of investigation has been qualitative analysis. Using interactive segmentation, this study suggests a method of objectively and quantitatively analyzing the mechanisms underlying the skin absorption of nanoparticles. Silica nanoparticles (SNPs) were assessed using transmission electron microscopy and applied to the human skin equivalent model. Captured fluorescence images of this model were used to evaluate degrees of skin penetration. These images underwent interactive segmentation and image processing in addition to statistical quantitative analyses of calculated image parameters including the mean, integrated density, skewness, kurtosis, and area fraction. In images from both groups, the distribution area and intensity of fluorescent silica gradually increased in proportion to time. Since statistical significance was achieved after 2 days in the negative charge group and after 4 days in the positive charge group, there is a periodic difference. Furthermore, the quantity of silica per unit area showed a dramatic change after 6 days in the negative charge group. Although this quantitative result is identical to results obtained by qualitative assessment, it is meaningful in that it was proven by statistical analysis with quantitation by using image processing. The present study suggests that the surface charge of SNPs could play an important role in the percutaneous absorption of NPs. These findings can help achieve a better understanding of the percutaneous transport of NPs. In addition, these results provide important guidance for the design of NPs for biomedical applications.

  7. The transmission process: A combinatorial stochastic process for the evolution of transmission trees over networks.

    PubMed

    Sainudiin, Raazesh; Welch, David

    2016-12-07

    We derive a combinatorial stochastic process for the evolution of the transmission tree over the infected vertices of a host contact network in a susceptible-infected (SI) model of an epidemic. Models of transmission trees are crucial to understanding the evolution of pathogen populations. We provide an explicit description of the transmission process on the product state space of (rooted planar ranked labelled) binary transmission trees and labelled host contact networks with SI-tags as a discrete-state continuous-time Markov chain. We give the exact probability of any transmission tree when the host contact network is a complete, star or path network - three illustrative examples. We then develop a biparametric Beta-splitting model that directly generates transmission trees with exact probabilities as a function of the model parameters, but without explicitly modelling the underlying contact network, and show that for specific values of the parameters we can recover the exact probabilities for our three example networks through the Markov chain construction that explicitly models the underlying contact network. We use the maximum likelihood estimator (MLE) to consistently infer the two parameters driving the transmission process based on observations of the transmission trees and use the exact MLE to characterize equivalence classes over the space of contact networks with a single initial infection. An exploratory simulation study of the MLEs from transmission trees sampled from three other deterministic and four random families of classical contact networks is conducted to shed light on the relation between the MLEs of these families with some implications for statistical inference along with pointers to further extensions of our models. The insights developed here are also applicable to the simplest models of "meme" evolution in online social media networks through transmission events that can be distilled from observable actions such as "likes", "mentions

  8. Knowledge of pregnant women on transmission of HIV infection through breast feeding.

    PubMed

    Kasinga, F; Mogotlane, S M; van Rensburg, G H

    2008-09-01

    Although breast-feeding is nature's way of providing nutrition to the baby, in HIV positive mothers this has been identified as one of the means through which HIV infection is transmitted from the mother to the child. In Africa where children under the age of 5 are killed by preventable diseases like diarrhoea, the issue of HIV transmission through breast feeding poses an added huge problem. Research has, however shown that exclusive infant feeding, be it breast or formula, reduces the risk substantially. It is imperative that mothers be informed about safer methods of infant feeding so that HIV infection is kept to a minimum. The objective of the study was to explore and describe the knowledge that pregnant women had about mother to child transmission of HIV infection through breast-feeding. A non-experimental quantitative exploratory and descriptive research design was used to explore the knowledge women had on mother to child transmission of HIV infection through breast-feeding. From the data collected, it showed that although women were aware of the susceptibility of children to HIV infection if fed on breast and formula feeds simultaneously by HIV positive mothers, exclusive feeding was a problem as people associated the practise with a positive HIV status. Women who had not disclosed their HIV status and were HIV positive, found it difficult to comply with the requirement to exclusively feed their infants. These either continued with complementary feeds or did not collect the free formula milk supply preferring instead to buy the formula feeds privately. In this study it was recommended that information on transmission of HIV infection from mother to child through breast -feeding including the benefits of exclusive infant feeding, be it breast or formula, for the first three to six months be provided to the community so that relatives can support the mother on infant feeding method of choice.

  9. Quantitative Transmission Electron Microscopy of Nanoparticles and Thin-Film Formation in Electroless Metallization of Polymeric Surfaces

    NASA Astrophysics Data System (ADS)

    Dutta, Aniruddha; Heinrich, Helge; Kuebler, Stephen; Grabill, Chris; Bhattacharya, Aniket

    2011-03-01

    Gold nanoparticles(Au-NPs) act as nucleation sites for electroless deposition of silver on functionalized SU8 polymeric surfaces. Here we report the nanoscale morphology of Au and Ag nanoparticles as studied by Transmission Electron Microscopy (TEM). Scanning TEM with a high-angle annular dark-field detector is used to obtain atomic number contrast. From the intensity-calibrated plan-view scanning TEM images we determine the mean thickness and the volume distribution of the Au-NPs on the surface of the functionalized polymer. We also report the height and the radius distribution of the gold nanoparticles obtained from STEM images taking into consideration the experimental errors. The cross sectional TEM images yield the density and the average distance of the Au and Ag nanoparticles on the surface of the polymer. Supported by grant NSF, Chemistry Division.

  10. Validation of the FEA of a deep drawing process with additional force transmission

    NASA Astrophysics Data System (ADS)

    Behrens, B.-A.; Bouguecha, A.; Bonk, C.; Grbic, N.; Vucetic, M.

    2017-10-01

    In order to meet requirements by automotive industry like decreasing the CO2 emissions, which reflects in reducing vehicles mass in the car body, the chassis and the powertrain, the continuous innovation and further development of existing production processes are required. In sheet metal forming processes the process limits and components characteristics are defined through the process specific loads. While exceeding the load limits, a failure in the material occurs, which can be avoided by additional force transmission activated in the deep drawing process before the process limit is achieved. This contribution deals with experimental investigations of a forming process with additional force transmission regarding the extension of the process limits. Based on FEA a tool system is designed and developed by IFUM. For this purpose, the steel material HCT600 is analyzed numerically. Within the experimental investigations, the deep drawing processes, with and without the additional force transmission are carried out. Here, a comparison of the produced rectangle cups is done. Subsequently, the identical deep drawing processes are investigated numerically. Thereby, the values of the punch reaction force and displacement are estimated and compared with experimental results. Thus, the validation of material model is successfully carried out on process scale. For further quantitative verification of the FEA results the experimental determined geometry of the rectangular cup is measured optically with ATOS system of the company GOM mbH and digitally compared with external software Geomagic®QualifyTM. The goal of this paper is the verification of the transferability of the FEA model for a conventional deep drawing process to a deep drawing process with additional force transmission with a counter punch.

  11. The evolution of plant virus transmission pathways

    Treesearch

    Frédéric M. Hamelin; Linda J.S. Allen; Holly R. Prendeville; M. Reza Hajimorad; Michael J. Jeger

    2016-01-01

    The evolution of plant virus transmission pathways is studied through transmission via seed, pollen, oravector. We address the questions: under what circumstances does vector transmission make pollen transmission redundant? Can evolution lead to the coexistence of multiple virus transmission pathways? We restrict the analysis to an annual plant population in which...

  12. Household transmission of SARS, 2003

    PubMed Central

    Wilson-Clark, Samantha D.; Deeks, Shelley L.; Gournis, Effie; Hay, Karen; Bondy, Susan; Kennedy, Erin; Johnson, Ian; Rea, Elizabeth; Kuschak, Theodore; Green, Diane; Abbas, Zahid; Guarda, Brenda

    2006-01-01

    Background In the 2003 outbreak in Toronto (in Ontario, Canada) of severe acute respiratory syndrome (SARS), about 20% of cases resulted from household transmission. The purpose of our study was to determine characteristics associated with the transmission of SARS within households. Methods A retrospective cohort of SARS-affected households was studied to determine risk factors for household transmission. Questionnaires addressed characteristics of the index case, the household and behaviours among household members. Potential risk factors for secondary transmission of infection were assessed in regression models appropriate to the outcome (secondary cases) and nonindependence of household members. Results The 74 households that participated included 18 secondary cases and 158 uninfected household members in addition to the 74 index cases. The household secondary attack rate was 10.2% (95% confidence interval [CI] 6.7%–23.5%). There was a linear association between the time the index patient spent at home after symptom onset and the secondary attack rate. Infected health care workers who were index cases had lower rates of household transmission. Interpretation SARS transmission in households is complex and increases with the length of time an ill person spends at home. Risk of transmission was lower when the index case was a health care worker. Rapid case identification is the public health measure most useful in minimizing exposure in the home. PMID:17098951

  13. Vibration transmission through rolling element bearings in geared rotor system, part 1. Ph.D. Thesis Final Report

    NASA Technical Reports Server (NTRS)

    Singh, Rajendra; Lim, Teik Chin

    1989-01-01

    A mathematical model is proposed to examine the vibration transmission through rolling element bearings in geared rotor systems. Current bearing models, based on either ideal boundary conditions for the shaft or purely translational stiffness element description, cannot explain how the vibratory motion may be transmitted from the rotating shaft to the casing. This study clarifies this issue qualitatively and quantitatively by developing a comprehensive bearing stiffness matrix of dimension 6 model for the precision rolling element bearings from basic principles. The proposed bearing formulation is extended to analyze the overall geared rotor system dynamics including casing and mounts. The bearing stiffness matrix is included in discrete system models using lumped parameter and/or dynamic finite element techniques. Eigensolution and forced harmonic response due to rotating mass unbalance or kinematic transmission error excitation for a number of examples are computed.

  14. Quantitative Phase Fraction Detection in Organic Photovoltaic Materials through EELS Imaging

    DOE PAGES

    Dyck, Ondrej; Hu, Sheng; Das, Sanjib; ...

    2015-11-24

    Organic photovoltaic materials have recently seen intense interest from the research community. Improvements in device performance are occurring at an impressive rate; however, visualization of the active layer phase separation still remains a challenge. Our paper outlines the application of two electron energy-loss spectroscopic (EELS) imaging techniques that can complement and enhance current phase detection techniques. Specifically, the bulk plasmon peak position, often used to produce contrast between phases in energy filtered transmission electron microscopy (EFTEM), is quantitatively mapped across a sample cross section. One complementary spectrum image capturing the carbon and sulfur core loss edges is compared with themore » plasmon peak map and found to agree quite well, indicating that carbon and sulfur density differences between the two phases also allows phase discrimination. Additionally, an analytical technique for determining absolute atomic areal density is used to produce an absolute carbon and sulfur areal density map. We also show how these maps may be re-interpreted as a phase ratio map, giving quantitative information about the purity of the phases within the junction.« less

  15. Squirrelpox Virus: Assessing Prevalence, Transmission and Environmental Degradation

    PubMed Central

    Tosh, David G.; McInnes, Colin; Everest, David; Montgomery, W. Ian; Scantlebury, Mike; Marks, Nikki; Dick, Jaimie T. A.

    2014-01-01

    Red squirrels (Sciurus vulgaris) declined in Great Britain and Ireland during the last century, due to habitat loss and the introduction of grey squirrels (Sciurus carolinensis), which competitively exclude the red squirrel and act as a reservoir for squirrelpox virus (SQPV). The disease is generally fatal to red squirrels and their ecological replacement by grey squirrels is up to 25 times faster where the virus is present. We aimed to determine: (1) the seropositivity and prevalence of SQPV DNA in the invasive and native species at a regional scale; (2) possible SQPV transmission routes; and, (3) virus degradation rates under differing environmental conditions. Grey (n = 208) and red (n = 40) squirrel blood and tissues were sampled. Enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qPCR) techniques established seropositivity and viral DNA presence, respectively. Overall 8% of squirrels sampled (both species combined) had evidence of SQPV DNA in their tissues and 22% were in possession of antibodies. SQPV prevalence in sampled red squirrels was 2.5%. Viral loads were typically low in grey squirrels by comparison to red squirrels. There was a trend for a greater number of positive samples in spring and summer than in winter. Possible transmission routes were identified through the presence of viral DNA in faeces (red squirrels only), urine and ectoparasites (both species). Virus degradation analyses suggested that, after 30 days of exposure to six combinations of environments, there were more intact virus particles in scabs kept in warm (25°C) and dry conditions than in cooler (5 and 15°C) or wet conditions. We conclude that SQPV is present at low prevalence in invasive grey squirrel populations with a lower prevalence in native red squirrels. Virus transmission could occur through urine especially during warm dry summer conditions but, more notably, via ectoparasites, which are shared by both species. PMID

  16. Automated Transmission Loss Measurement in the Structural Acoustic Loads and Transmission Facility at NASA Langley Research Center

    NASA Technical Reports Server (NTRS)

    Klos, J.; Brown, S. A.

    2002-01-01

    A technique to measure the radiated acoustic intensity and transmission loss of panels is documented in this paper. This facility has been upgraded to include a test fixture that scans the acoustic intensity radiated from a panel on the anechoic receiving room side of the transmission loss window. The acoustic intensity incident on the panel from the reverberant side of the transmission loss window is estimated from measurements made using six stationary microphones in the reverberant source room. From the measured incident and radiated intensity, the sound power transmission loss is calculated. The setup of the facility and data acquisition system are documented. A transmission loss estimate of a typical panel is shown. The measurement-to-measurement and setup-to-setup repeatability of the transmission loss estimate are assessed. Conclusions are drawn about the ability to measure changes in transmission loss due to changes in panel construction.

  17. An Insight on Right of Way and its Cost for Power Transmission Cable and Conventional Overhead Transmission Lines

    NASA Astrophysics Data System (ADS)

    Khandelwal, P.; Pachori, A.; Khandelwal, T.

    2013-12-01

    This paper provides the complete information related to Right of Way (RoW) for the construction of new power transmission line (TL) in terms of present cost for overhead transmission line and underground XLPE transmission cable. The former part of the paper describes the general procedure and rules for acquisition of land for RoW by transmission asset owner (TAO) while in the later part the cost associated to acquire RoW and its impact on the cost of adjacent land have been detailed. It also discusses the actual dismantling cost including the cost of waste metal what TAO get after completion of lifecycle of TL due to increase in metal prices. In this paper cost of RoW after completion of lifecycle of TL is also highlighted. This paper compares the cost of RoW for overhead transmission line and underground XLPE transmission cable for construction of new TL. Also for old transmission infrastructure cost of RoW for change from overhead transmission line to underground XLPE transmission cable is detailed by application of replacement model.

  18. Transmission line design for the lunar environment

    NASA Technical Reports Server (NTRS)

    Gaustad, Krista L.; Gordon, Lloyd B.

    1990-01-01

    How the mass, operating temperature, and efficiency of a transmission line operating on the moon are affected by its operating parameters, the lunar environment, and the choice of materials is examined. The key transmission line parameters which have an effect on mass, operating temperature, and efficiency are voltage, power loss, and waveform. The choice of waveform for transmission will be influenced by the waveform of the source and load, and therefore an analysis of both DC and AC transmission is necessary for a complete understanding of lunar power transmission. The data presented are for the DC case only; however, the discussion of the environmental effects and of material selection is pertinent to both AC and DC transmission. The operating voltage is shown to be a key parameter in transmission line design. The role efficiency plays in transmission line design is also examined. The analyses include above- and below-the-surface operation for both a vacuum-insulated, two-wire, transmission line, and a solid-dielectric-insulated, coaxial, transmission line.

  19. Qualitative and quantitative interpretation of SEM image using digital image processing.

    PubMed

    Saladra, Dawid; Kopernik, Magdalena

    2016-10-01

    The aim of the this study is improvement of qualitative and quantitative analysis of scanning electron microscope micrographs by development of computer program, which enables automatic crack analysis of scanning electron microscopy (SEM) micrographs. Micromechanical tests of pneumatic ventricular assist devices result in a large number of micrographs. Therefore, the analysis must be automatic. Tests for athrombogenic titanium nitride/gold coatings deposited on polymeric substrates (Bionate II) are performed. These tests include microshear, microtension and fatigue analysis. Anisotropic surface defects observed in the SEM micrographs require support for qualitative and quantitative interpretation. Improvement of qualitative analysis of scanning electron microscope images was achieved by a set of computational tools that includes binarization, simplified expanding, expanding, simple image statistic thresholding, the filters Laplacian 1, and Laplacian 2, Otsu and reverse binarization. Several modifications of the known image processing techniques and combinations of the selected image processing techniques were applied. The introduced quantitative analysis of digital scanning electron microscope images enables computation of stereological parameters such as area, crack angle, crack length, and total crack length per unit area. This study also compares the functionality of the developed computer program of digital image processing with existing applications. The described pre- and postprocessing may be helpful in scanning electron microscopy and transmission electron microscopy surface investigations. © 2016 The Authors Journal of Microscopy © 2016 Royal Microscopical Society.

  20. High cycle fatigue in the transmission electron microscope

    DOE PAGES

    Bufford, Daniel C.; Stauffer, Douglas; Mook, William M.; ...

    2016-06-28

    One of the most common causes of structural failure in metals is fatigue induced by cyclic loading. Historically, microstructure-level analysis of fatigue cracks has primarily been performed post mortem. However, such investigations do not directly reveal the internal structural processes at work near micro- and nanoscale fatigue cracks and thus do not provide direct evidence of active microstructural mechanisms. In this paper, the tension–tension fatigue behavior of nanocrystalline Cu was monitored in real time at the nanoscale by utilizing a new capability for quantitative cyclic mechanical loading performed in situ in a transmission electron microscope (TEM). Controllable loads were appliedmore » at frequencies from one to several hundred hertz, enabling accumulations of 10 6 cycles within 1 h. The nanometer-scale spatial resolution of the TEM allows quantitative fatigue crack growth studies at very slow crack growth rates, measured here at ~10 –12 m·cycle –1. This represents an incipient threshold regime that is well below the tensile yield stress and near the minimum conditions for fatigue crack growth. Evidence of localized deformation and grain growth within 150 nm of the crack tip was observed by both standard imaging and precession electron diffraction orientation mapping. Finally, these observations begin to reveal with unprecedented detail the local microstructural processes that govern damage accumulation, crack nucleation, and crack propagation during fatigue loading in nanocrystalline Cu.« less

  1. High cycle fatigue in the transmission electron microscope

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

    Bufford, Daniel C.; Stauffer, Douglas; Mook, William M.

    One of the most common causes of structural failure in metals is fatigue induced by cyclic loading. Historically, microstructure-level analysis of fatigue cracks has primarily been performed post mortem. However, such investigations do not directly reveal the internal structural processes at work near micro- and nanoscale fatigue cracks and thus do not provide direct evidence of active microstructural mechanisms. In this paper, the tension–tension fatigue behavior of nanocrystalline Cu was monitored in real time at the nanoscale by utilizing a new capability for quantitative cyclic mechanical loading performed in situ in a transmission electron microscope (TEM). Controllable loads were appliedmore » at frequencies from one to several hundred hertz, enabling accumulations of 10 6 cycles within 1 h. The nanometer-scale spatial resolution of the TEM allows quantitative fatigue crack growth studies at very slow crack growth rates, measured here at ~10 –12 m·cycle –1. This represents an incipient threshold regime that is well below the tensile yield stress and near the minimum conditions for fatigue crack growth. Evidence of localized deformation and grain growth within 150 nm of the crack tip was observed by both standard imaging and precession electron diffraction orientation mapping. Finally, these observations begin to reveal with unprecedented detail the local microstructural processes that govern damage accumulation, crack nucleation, and crack propagation during fatigue loading in nanocrystalline Cu.« less

  2. Quantifying the effects of temperature on mosquito and parasite traits that determine the transmission potential of human malaria.

    PubMed

    Shapiro, Lillian L M; Whitehead, Shelley A; Thomas, Matthew B

    2017-10-01

    Malaria transmission is known to be strongly impacted by temperature. The current understanding of how temperature affects mosquito and parasite life history traits derives from a limited number of empirical studies. These studies, some dating back to the early part of last century, are often poorly controlled, have limited replication, explore a narrow range of temperatures, and use a mixture of parasite and mosquito species. Here, we use a single pairing of the Asian mosquito vector, An. stephensi and the human malaria parasite, P. falciparum to conduct a comprehensive evaluation of the thermal performance curves of a range of mosquito and parasite traits relevant to transmission. We show that biting rate, adult mortality rate, parasite development rate, and vector competence are temperature sensitive. Importantly, we find qualitative and quantitative differences to the assumed temperature-dependent relationships. To explore the overall implications of temperature for transmission, we first use a standard model of relative vectorial capacity. This approach suggests a temperature optimum for transmission of 29°C, with minimum and maximum temperatures of 12°C and 38°C, respectively. However, the robustness of the vectorial capacity approach is challenged by the fact that the empirical data violate several of the model's simplifying assumptions. Accordingly, we present an alternative model of relative force of infection that better captures the observed biology of the vector-parasite interaction. This model suggests a temperature optimum for transmission of 26°C, with a minimum and maximum of 17°C and 35°C, respectively. The differences between the models lead to potentially divergent predictions for the potential impacts of current and future climate change on malaria transmission. The study provides a framework for more detailed, system-specific studies that are essential to develop an improved understanding on the effects of temperature on malaria

  3. Assortative sexual mixing patterns in male-female and male-male partnerships in Melbourne, Australia: implications for HIV and sexually transmissible infection transmission.

    PubMed

    Chow, Eric P F; Read, Tim R H; Law, Matthew G; Chen, Marcus Y; Bradshaw, Catriona S; Fairley, Christopher K

    2016-10-01

    Assortative mixing patterns have become a new and important focus in HIV/sexually transmissible infection (STI) research in recent years. There are very limited data on sexual mixing patterns, particularly in an Australian population. Male-female and male-male partnerships attending the Melbourne Sexual Health Centre (MSHC) between 2011 and 2014 were included. Correlation of age between two individuals within a partnership was examined by using Spearman's rank correlation. The Newman's assortativity coefficient was used as an aggregate quantitative measurement of sexual mixing for number of partners and condom use. 1165 male-female and 610 male-male partnerships were included in the analysis. There was a strong positive correlation of age in both male-female (rho=0.709; P<0.001) and male-male partnerships (rho=0.553; P<0.001). The assortative mixing pattern for number of partners was similar in male-female (r=0.255; 95% CI: 0.221-0.289) and male-male partnerships (r=0.264; 95% CI: 0.218-0.309). There was a stronger assortative mixing pattern for condom use in male-male (r=0.517, 95% CI: 0.465-0.569) compared with male-female (r=0.382; 95% CI: 0.353-0.412) partnerships. Male-female and male-male partnerships have a high assortativity mixing pattern for age, number of partners and condom use. The sexual mixing pattern is not purely assortative, and hence it may lead to increased HIV and STI transmission in certain risk groups.

  4. 49 CFR 191.13 - Distribution systems reporting transmission pipelines; transmission or gathering systems...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Distribution systems reporting transmission pipelines; transmission or gathering systems reporting distribution pipelines. 191.13 Section 191.13 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF...

  5. Serotonin transporter gene promoter polymorphism and autism: a family-based genetic association study in Japanese population.

    PubMed

    Koishi, Shinko; Yamamoto, Kenji; Matsumoto, Hideo; Koishi, Seiji; Enseki, Youichi; Oya, Akitoshi; Asakura, Arata; Aoki, Yutaka; Atsumi, Mariko; Iga, Tomiei; Inomata, Jyoji; Inoko, Hidetoshi; Sasaki, Tsukasa; Nanba, Eiji; Kato, Nobumasa; Ishii, Tetsuo; Yamazaki, Kosuke

    2006-05-01

    Autism is now widely accepted as a biological disorder which, by and large, starts before birth. It has been shown that serotonin (5-HT) is associated with several psychological processes and hyperserotoninemia is observed in some autistic patients. The results of previous reports about family-based association studies between the serotonin transporter (5-HTT) gene promoter polymorphism and autism are controversial. In this study, an analysis using the transmission/disequilibrium test (TDT) between the 5-HTT gene promoter polymorphism and autism in 104 trios, all ethnically Japanese, showed no significant linkage disequilibrium (P=0.17). Recently, it has been reported that some haplotypes at the serotonin transporter locus may be associated with the pathogenesis of autism. Therefore, further investigations by haplotype analyses are necessary to confirm the implications of genetic variants of the serotonin transporter in the etiology of autism.

  6. Atomic bonding effects in annular dark field scanning transmission electron microscopy. II. Experiments

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

    Odlyzko, Michael L.; Held, Jacob T.; Mkhoyan, K. Andre, E-mail: mkhoyan@umn.edu

    2016-07-15

    Quantitatively calibrated annular dark field scanning transmission electron microscopy (ADF-STEM) imaging experiments were compared to frozen phonon multislice simulations adapted to include chemical bonding effects. Having carefully matched simulation parameters to experimental conditions, a depth-dependent bonding effect was observed for high-angle ADF-STEM imaging of aluminum nitride. This result is explained by computational predictions, systematically examined in the preceding portion of this study, showing the propagation of the converged STEM beam to be highly sensitive to net interatomic charge transfer. Thus, although uncertainties in experimental conditions and simulation accuracy remain, the computationally predicted experimental bonding effect withstands the experimental testing reportedmore » here.« less

  7. Quantifying Transmission Investment in Malaria Parasites

    PubMed Central

    Greischar, Megan A.; Mideo, Nicole; Read, Andrew F.; Bjørnstad, Ottar N.

    2016-01-01

    Many microparasites infect new hosts with specialized life stages, requiring a subset of the parasite population to forgo proliferation and develop into transmission forms. Transmission stage production influences infectivity, host exploitation, and the impact of medical interventions like drug treatment. Predicting how parasites will respond to public health efforts on both epidemiological and evolutionary timescales requires understanding transmission strategies. These strategies can rarely be observed directly and must typically be inferred from infection dynamics. Using malaria as a case study, we test previously described methods for inferring transmission stage investment against simulated data generated with a model of within-host infection dynamics, where the true transmission investment is known. We show that existing methods are inadequate and potentially very misleading. The key difficulty lies in separating transmission stages produced by different generations of parasites. We develop a new approach that performs much better on simulated data. Applying this approach to real data from mice infected with a single Plasmodium chabaudi strain, we estimate that transmission investment varies from zero to 20%, with evidence for variable investment over time in some hosts, but not others. These patterns suggest that, even in experimental infections where host genetics and other environmental factors are controlled, parasites may exhibit remarkably different patterns of transmission investment. PMID:26890485

  8. Extent of Linkage Disequilibrium and Effective Population Size in Four South African Sanga Cattle Breeds.

    PubMed

    Makina, Sithembile O; Taylor, Jeremy F; van Marle-Köster, Este; Muchadeyi, Farai C; Makgahlela, Mahlako L; MacNeil, Michael D; Maiwashe, Azwihangwisi

    2015-01-01

    Knowledge on the extent of linkage disequilibrium (LD) in livestock populations is essential to determine the minimum distance between markers required for effective coverage when conducting genome-wide association studies (GWAS). This study evaluated the extent of LD, persistence of allelic phase and effective population size (Ne) for four Sanga cattle breeds in South Africa including the Afrikaner (n = 44), Nguni (n = 54), Drakensberger (n = 47), and Bonsmara breeds (n = 46), using Angus (n = 31) and Holstein (n = 29) as reference populations. We found that moderate LD extends up to inter-marker distances of 40-60 kb in Angus (0.21) and Holstein (0.21) and up to 100 kb in Afrikaner (0.20). This suggests that genomic selection and association studies performed within these breeds using an average inter-marker r (2)≥ 0.20 would require about 30,000-50,000 SNPs. However, r (2)≥ 0.20 extended only up to 10-20 kb in the Nguni and Drakensberger and 20-40 kb in the Bonsmara indicating that 75,000 to 150,000 SNPs would be necessary for GWAS in these breeds. Correlation between alleles at contiguous loci indicated that phase was not strongly preserved between breeds. This suggests the need for breed-specific reference populations in which a much greater density of markers should be scored to identify breed specific haplotypes which may then be imputed into multi-breed commercial populations. Analysis of effective population size based on the extent of LD, revealed Ne = 95 (Nguni), Ne = 87 (Drakensberger), Ne = 77 (Bonsmara), and Ne = 41 (Afrikaner). Results of this study form the basis for implementation of genomic selection programs in the Sanga breeds of South Africa.

  9. Extent of Linkage Disequilibrium and Effective Population Size in Four South African Sanga Cattle Breeds

    PubMed Central

    Makina, Sithembile O.; Taylor, Jeremy F.; van Marle-Köster, Este; Muchadeyi, Farai C.; Makgahlela, Mahlako L.; MacNeil, Michael D.; Maiwashe, Azwihangwisi

    2015-01-01

    Knowledge on the extent of linkage disequilibrium (LD) in livestock populations is essential to determine the minimum distance between markers required for effective coverage when conducting genome-wide association studies (GWAS). This study evaluated the extent of LD, persistence of allelic phase and effective population size (Ne) for four Sanga cattle breeds in South Africa including the Afrikaner (n = 44), Nguni (n = 54), Drakensberger (n = 47), and Bonsmara breeds (n = 46), using Angus (n = 31) and Holstein (n = 29) as reference populations. We found that moderate LD extends up to inter-marker distances of 40–60 kb in Angus (0.21) and Holstein (0.21) and up to 100 kb in Afrikaner (0.20). This suggests that genomic selection and association studies performed within these breeds using an average inter-marker r2≥ 0.20 would require about 30,000–50,000 SNPs. However, r2≥ 0.20 extended only up to 10–20 kb in the Nguni and Drakensberger and 20–40 kb in the Bonsmara indicating that 75,000 to 150,000 SNPs would be necessary for GWAS in these breeds. Correlation between alleles at contiguous loci indicated that phase was not strongly preserved between breeds. This suggests the need for breed-specific reference populations in which a much greater density of markers should be scored to identify breed specific haplotypes which may then be imputed into multi-breed commercial populations. Analysis of effective population size based on the extent of LD, revealed Ne = 95 (Nguni), Ne = 87 (Drakensberger), Ne = 77 (Bonsmara), and Ne = 41 (Afrikaner). Results of this study form the basis for implementation of genomic selection programs in the Sanga breeds of South Africa. PMID:26648975

  10. Transmission Line Security Monitor

    ScienceCinema

    None

    2017-12-09

    The Transmission Line Security Monitor is a multi-sensor monitor that mounts directly on high-voltage transmission lines to detect, characterize and communicate terrorist activity, human tampering and threatening conditions around support towers. For more information about INL's critical infrastructure protection research, visit http://www.facebook.com/idahonationallaboratory.

  11. Quantitative comparison of bright field and annular bright field imaging modes for characterization of oxygen octahedral tilts

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

    Kim, Young-Min; Pennycook, Stephen J.; Borisevich, Albina Y.

    Octahedral tilt behavior is increasingly recognized as an important contributing factor to the physical behavior of perovskite oxide materials and especially their interfaces, necessitating the development of high-resolution methods of tilt mapping. There are currently two major approaches for quantitative imaging of tilts in scanning transmission electron microscopy (STEM), bright field (BF) and annular bright field (ABF). In this study, we show that BF STEM can be reliably used for measurements of oxygen octahedral tilts. While optimal conditions for BF imaging are more restricted with respect to sample thickness and defocus, we find that BF imaging with an aberration-corrected microscopemore » with the accelerating voltage of 300 kV gives us the most accurate quantitative measurement of the oxygen column positions. Using the tilted perovskite structure of BiFeO 3 (BFO) as our test sample, we simulate BF and ABF images in a wide range of conditions, identifying the optimal imaging conditions for each mode. Finally, we show that unlike ABF imaging, BF imaging remains directly quantitatively interpretable for a wide range of the specimen mistilt, suggesting that it should be preferable to the ABF STEM imaging for quantitative structure determination.« less

  12. Quantitative comparison of bright field and annular bright field imaging modes for characterization of oxygen octahedral tilts

    DOE PAGES

    Kim, Young-Min; Pennycook, Stephen J.; Borisevich, Albina Y.

    2017-04-29

    Octahedral tilt behavior is increasingly recognized as an important contributing factor to the physical behavior of perovskite oxide materials and especially their interfaces, necessitating the development of high-resolution methods of tilt mapping. There are currently two major approaches for quantitative imaging of tilts in scanning transmission electron microscopy (STEM), bright field (BF) and annular bright field (ABF). In this study, we show that BF STEM can be reliably used for measurements of oxygen octahedral tilts. While optimal conditions for BF imaging are more restricted with respect to sample thickness and defocus, we find that BF imaging with an aberration-corrected microscopemore » with the accelerating voltage of 300 kV gives us the most accurate quantitative measurement of the oxygen column positions. Using the tilted perovskite structure of BiFeO 3 (BFO) as our test sample, we simulate BF and ABF images in a wide range of conditions, identifying the optimal imaging conditions for each mode. Finally, we show that unlike ABF imaging, BF imaging remains directly quantitatively interpretable for a wide range of the specimen mistilt, suggesting that it should be preferable to the ABF STEM imaging for quantitative structure determination.« less

  13. An Annotated Bibliography of High-Voltage Direct-Current Transmission and Flexible AC Transmission (FACTS) Devices, 1991-1993.

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

    Litzenberger, Wayne; Lava, Val

    1994-08-01

    References are contained for HVDC systems, converter stations and components, overhead transmission lines, cable transmission, system design and operations, simulation of high voltage direct current systems, high-voltage direct current installations, and flexible AC transmission system (FACTS).

  14. Transmission ultrasonography. [time delay spectrometry for soft tissue transmission imaging

    NASA Technical Reports Server (NTRS)

    Heyser, R. C.; Le Croissette, D. H.

    1973-01-01

    Review of the results of the application of an advanced signal-processing technique, called time delay spectrometry, in obtaining soft tissue transmission images by transmission ultrasonography, both in vivo and in vitro. The presented results include amplitude ultrasound pictures and phase ultrasound pictures obtained by this technique. While amplitude ultrasonographs of tissue are closely analogous to X-ray pictures in that differential absorption is imaged, phase ultrasonographs represent an entirely new source of information based on differential time of propagation. Thus, a new source of information is made available for detailed analysis.

  15. Effectiveness of cough etiquette maneuvers in disrupting the chain of transmission of infectious respiratory diseases

    PubMed Central

    2013-01-01

    Background The effectiveness of recommended measures, such as “cover your mouth when coughing”, in disrupting the chain of transmission of infectious respiratory diseases (IRD) has been questioned. The objective of the current study was to determine the effectiveness of simple primary respiratory hygiene/cough etiquette maneuvers in blocking droplets expelled as aerosol during coughing. Method In this study, 31 healthy non-smokers performed cough etiquette maneuvers in an effort to cover their voluntarily elicited best effort coughs in an open bench format. A laser diffraction system was used to obtain accurate, non-invasive, quantitative, real time measurements of the size and number of droplets emitted during the assessed cough etiquette maneuvers. Results Recommended cough etiquette maneuvers did not block the release and dispersion of a variety of different diameter droplets to the surrounding environment. Droplets smaller than one-micron size dominate the total number of droplets leaked when practicing assessed maneuvers. Conclusions All the assessed cough etiquette maneuvers, performed as recommended, do not block droplets expelled as aerosol when coughing. This aerosol can penetrate profound levels of the respiratory system. Practicing these assessed primary respiratory hygiene/cough etiquette maneuvers would still permit direct, indirect, and/or airborne transmission and spread of IRD, such as influenza and Tuberculosis. All the assessed cough etiquette maneuvers, as recommended, do not fully interrupt the chain of transmission of IRD. This knowledge urges us all to critically review recommended CE and to search for new evidence-based procedures that effectively disrupt the transmission of respiratory pathogens. Interrupting the chain of transmission of IRD will optimize the protection of first responders, paramedics, nurses, and doctors working in triage sites, emergency rooms, intensive care units, and the general public against cough

  16. Risk Analysis using Corrosion Rate Parameter on Gas Transmission Pipeline

    NASA Astrophysics Data System (ADS)

    Sasikirono, B.; Kim, S. J.; Haryadi, G. D.; Huda, A.

    2017-05-01

    In the oil and gas industry, the pipeline is a major component in the transmission and distribution process of oil and gas. Oil and gas distribution process sometimes performed past the pipeline across the various types of environmental conditions. Therefore, in the transmission and distribution process of oil and gas, a pipeline should operate safely so that it does not harm the surrounding environment. Corrosion is still a major cause of failure in some components of the equipment in a production facility. In pipeline systems, corrosion can cause failures in the wall and damage to the pipeline. Therefore it takes care and periodic inspections or checks on the pipeline system. Every production facility in an industry has a level of risk for damage which is a result of the opportunities and consequences of damage caused. The purpose of this research is to analyze the level of risk of 20-inch Natural Gas Transmission Pipeline using Risk-based inspection semi-quantitative based on API 581 associated with the likelihood of failure and the consequences of the failure of a component of the equipment. Then the result is used to determine the next inspection plans. Nine pipeline components were observed, such as a straight pipes inlet, connection tee, and straight pipes outlet. The risk assessment level of the nine pipeline’s components is presented in a risk matrix. The risk level of components is examined at medium risk levels. The failure mechanism that is used in this research is the mechanism of thinning. Based on the results of corrosion rate calculation, remaining pipeline components age can be obtained, so the remaining lifetime of pipeline components are known. The calculation of remaining lifetime obtained and the results vary for each component. Next step is planning the inspection of pipeline components by NDT external methods.

  17. Environmental and Behavioural Determinants of Leptospirosis Transmission: A Systematic Review.

    PubMed

    Mwachui, Mwanajaa Abdalla; Crump, Lisa; Hartskeerl, Rudy; Zinsstag, Jakob; Hattendorf, Jan

    2015-01-01

    Leptospirosis is one of the most widespread zoonotic diseases, which is of global medical and veterinary importance, and also a re-emerging infectious disease. The main tracks of transmission are known; however, the relative importance of each of the components and the respective environmental risk factors are unclear. We aimed to assess and specify quantitative evidence of environmental risks of leptospirosis transmission. A database of pre-selected studies, with publication dates from 1970 until 2008, was provided by an expert group. The database has been updated until 2015 using a text mining algorithm. Study selection was based on stringent quality criteria. A descriptive data analysis was performed to calculate the medians of the log transformed odds ratios. From a selection of 2723 unique publications containing information on leptospirosis, 428 papers dealing with risk factors were identified. Of these, 53 fulfilled the quality criteria, allowing us to identify trends in different geo-climatic regions. Water associated exposures were, with few exceptions, associated with an increased leptospirosis risk. In resource poor countries, floods and rainfall were of particular importance, whereas recreational water activities were more relevant in developed countries. Rodents were associated with increased leptospirosis risk, but the variation among studies was high, which might be partly explained by differences in exposure definition. Livestock contact was commonly associated with increased risk; however, several studies found no association. The median odds ratios associated with dog and cat contacts were close to unity. Sanitation and behavioural risk factors were almost always strongly associated with leptospirosis, although their impact was rarely investigated in Europe or North America. This review confirms the complex environmental transmission pathways of leptospirosis, as previously established. Although, floods appeared to be among the most important

  18. Combined scanning transmission X-ray and electron microscopy for the characterization of bacterial endospores.

    PubMed

    Jamroskovic, Jan; Shao, Paul P; Suvorova, Elena; Barak, Imrich; Bernier-Latmani, Rizlan

    2014-09-01

    Endospores (also referred to as bacterial spores) are bacterial structures formed by several bacterial species of the phylum Firmicutes. Spores form as a response to environmental stress. These structures exhibit remarkable resistance to harsh environmental conditions such as exposure to heat, desiccation, and chemical oxidants. The spores include several layers of protein and peptidoglycan that surround a core harboring DNA as well as high concentrations of calcium and dipicolinic acid (DPA). A combination of scanning transmission X-ray microscopy, scanning transmission electron microscopy, and energy dispersive spectroscopy was used for the direct quantitative characterization of bacterial spores. The concentration and localization of DPA, Ca(2+) , and other elements were determined and compared for the core and cortex of spores from two distinct genera: Bacillus subtilis and Desulfotomaculum reducens. This micro-spectroscopic approach is uniquely suited for the direct study of individual bacterial spores, while classical molecular and biochemical methods access only bulk characteristics. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  19. Value Transmissions between Parents and Children: Gender and Developmental Phase as Transmission Belts

    ERIC Educational Resources Information Center

    Roest, Annette M. C.; Dubas, Judith Semon; Gerris, Jan R. M.

    2010-01-01

    This study applied the gender role model of socialization theory, the developmental aging theory, and the topic salience perspective to the investigation of parent-child value transmissions. Specifically, we examined whether the bi-directionality and selectivity of value transmissions differed as a function of parents' and children's gender and…

  20. Advances in the detection of as in environmental samples using low energy X-ray fluorescence in a scanning transmission X-ray microscope: arsenic immobilization by an Fe(II)-oxidizing freshwater bacteria.

    PubMed

    Hitchcock, A P; Obst, M; Wang, J; Lu, Y S; Tyliszczak, T

    2012-03-06

    Speciation and quantitative mapping of elements, organic and inorganic compounds, and mineral phases in environmental samples at high spatial resolution is needed in many areas of geobiochemistry and environmental science. Scanning transmission X-ray microscopes (STXMs) provide a focused beam which can interrogate samples at a fine spatial scale. Quantitative chemical information can be extracted using the transmitted and energy-resolved X-ray fluorescence channels simultaneously. Here we compare the relative merits of transmission and low-energy X-ray fluorescence detection of X-ray absorption for speciation and quantitative analysis of the spatial distribution of arsenic(V) within cell-mineral aggregates formed by Acidovorax sp. strain BoFeN1, an anaerobic nitrate-reducing Fe(II)-oxidizing β-proteobacteria isolated from the sediments of Lake Constance. This species is noted to be highly tolerant to high levels of As(V). Related, As-tolerant Acidovorax-strains have been found in As-contaminated groundwater wells in Bangladesh and Cambodia wherein they might influence the mobility of As by providing sorption sites which might have different properties as compared to chemically formed Fe-minerals. In addition to demonstrating the lower detection limits that are achieved with X-ray fluorescence relative to transmission detection in STXM, this study helps to gain insights into the mechanisms of As immobilization by biogenic Fe-mineral formation and to further the understanding of As-resistance of anaerobic Fe(II)-oxidizing bacteria.