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Sample records for real multiplication locus

  1. Empirical Bayesian elastic net for multiple quantitative trait locus mapping

    PubMed Central

    Huang, A; Xu, S; Cai, X

    2015-01-01

    In multiple quantitative trait locus (QTL) mapping, a high-dimensional sparse regression model is usually employed to account for possible multiple linked QTLs. The QTL model may include closely linked and thus highly correlated genetic markers, especially when high-density marker maps are used in QTL mapping because of the advancement in sequencing technology. Although existing algorithms, such as Lasso, empirical Bayesian Lasso (EBlasso) and elastic net (EN) are available to infer such QTL models, more powerful methods are highly desirable to detect more QTLs in the presence of correlated QTLs. We developed a novel empirical Bayesian EN (EBEN) algorithm for multiple QTL mapping that inherits the efficiency of our previously developed EBlasso algorithm. Simulation results demonstrated that EBEN provided higher power of detection and almost the same false discovery rate compared with EN and EBlasso. Particularly, EBEN can identify correlated QTLs that the other two algorithms may fail to identify. When analyzing a real dataset, EBEN detected more effects than EN and EBlasso. EBEN provides a useful tool for inferring high-dimensional sparse model in multiple QTL mapping and other applications. An R software package ‘EBEN' implementing the EBEN algorithm is available on the Comprehensive R Archive Network (CRAN). PMID:25204301

  2. A robust multiple-locus method for quantitative trait locus analysis of non-normally distributed multiple traits.

    PubMed

    Li, Z; Möttönen, J; Sillanpää, M J

    2015-12-01

    Linear regression-based quantitative trait loci/association mapping methods such as least squares commonly assume normality of residuals. In genetics studies of plants or animals, some quantitative traits may not follow normal distribution because the data include outlying observations or data that are collected from multiple sources, and in such cases the normal regression methods may lose some statistical power to detect quantitative trait loci. In this work, we propose a robust multiple-locus regression approach for analyzing multiple quantitative traits without normality assumption. In our method, the objective function is least absolute deviation (LAD), which corresponds to the assumption of multivariate Laplace distributed residual errors. This distribution has heavier tails than the normal distribution. In addition, we adopt a group LASSO penalty to produce shrinkage estimation of the marker effects and to describe the genetic correlation among phenotypes. Our LAD-LASSO approach is less sensitive to the outliers and is more appropriate for the analysis of data with skewedly distributed phenotypes. Another application of our robust approach is on missing phenotype problem in multiple-trait analysis, where the missing phenotype items can simply be filled with some extreme values, and be treated as outliers. The efficiency of the LAD-LASSO approach is illustrated on both simulated and real data sets.

  3. Two-locus linkage analysis in multiple sclerosis (MS)

    SciTech Connect

    Tienari, P.J. Univ. of Helsinki ); Terwilliger, J.D.; Ott, J. ); Palo, J. ); Peltonen, L. )

    1994-01-15

    One of the major challenges in genetic linkage analyses is the study of complex diseases. The authors demonstrate here the use of two-locus linkage analysis in multiple sclerosis (MS), a multifactorial disease with a complex mode of inheritance. In a set of Finnish multiplex families, they have previously found evidence for linkage between MS susceptibility and two independent loci, the myelin basic protein gene (MBP) on chromosome 18 and the HLA complex on chromosome 6. This set of families provides a unique opportunity to perform linkage analysis conditional on two loci contributing to the disease. In the two-trait-locus/two-marker-locus analysis, the presence of another disease locus is parametrized and the analysis more appropriately treats information from the unaffected family member than single-disease-locus analysis. As exemplified here in MS, the two-locus analysis can be a powerful method for investigating susceptibility loci in complex traits, best suited for analysis of specific candidate genes, or for situations in which preliminary evidence for linkage already exists or is suggested. 41 refs., 6 tabs.

  4. Functional Interrogation of an Odorant Receptor Locus Reveals Multiple Axes of Transcriptional Regulation

    PubMed Central

    Fleischmann, Alexander; Abdus-Saboor, Ishmail; Sayed, Atef; Shykind, Benjamin

    2013-01-01

    The odorant receptor (OR) genes constitute the largest mammalian gene family and are expressed in a monogenic and monoallelic fashion, through an unknown mechanism that likely exploits positive and negative regulation. We devised a genetic strategy in mice to examine OR selection by determining the transcriptional activity of an exogenous promoter homologously integrated into an OR locus. Using the tetracycline-dependent transactivator responsive promoter (teto), we observed that the OR locus imposes spatial and temporal constraints on teto-driven transcription. Conditional expression experiments reveal a developmental change in the permissiveness of the locus. Further, expression of an OR transgene that suppresses endogenous ORs similarly represses the OR-integrated teto. Neurons homozygous for the teto-modified allele demonstrate predominantly monoallelic expression, despite their potential to express both copies. These data reveal multiple axes of regulation, and support a model of initiation of OR choice limited by nonpermissive chromatin and maintained by repression of nonselected alleles. PMID:23700388

  5. An autosomal locus predisposing to multiple deletions of mtDNA on chromosome 3p

    SciTech Connect

    Kaukonen, J.A.; Suomalainen, A.; Peltonen, L.; Amati, P.; Zeviani, M.

    1996-04-01

    Autosomal dominant progressive external ophthalmoplegia (adPEO) is a disorder characterized by ptosis, progressive weakness of the external eye muscles, and general muscle weakness. The patients have multiple deletions of mtDNA on Southern blots or in PCR analysis of muscle DNA and a mild deficiency of one or more respiratory-chain enzymes carrying mtDNA-encoded subunits. The pattern of inheritance indicates a nuclear gene defect predisposing to secondary mtDNA deletions. Recently, in one Finnish family, we assigned an adPEO locus to chromosome 10q23.3-24.3 but also excluded linkage to this same locus in two Italian adPEO families with a phenotype closely resembling the Finnish one. We applied a random mapping approach to informative non-10q-linked Italian families to assign the second locus for adPEO and found strong evidence for linkage on chromosome 3p14.1-21.2 in three Italian families, with a maximum two-point lod score of 4.62 at a recombination fraction of .0. However, in three additional families, linkage to the same chromosomal region was clearly absent, indicating further genetic complexity of the adPEO trait. 19 refs., 3 figs., 2 tabs.

  6. Impact of multiple insertions of two retroelements, ZAM and Idefix at an euchromatic locus.

    PubMed

    Conte, C; Calco, V; Desset, S; Leblanc, P; Dastugue, B; Vaury, C

    2000-01-01

    Transposable elements represent a large fraction of eukaryotic genomes and they are thought to play an important role in chromatin structure. ZAM and Idefix are two LTR-retrotransposons from Drosophila melanogaster very similar in structure to vertebrate retroviruses. In all the strains where their distribution has been studied, ZAM appears to be present exclusively in the intercalary heterochromatin while Idefix copies are mainly found in the centromeric heterochromatin with very few copies in euchromatin. Their distribution varies in a specific strain called RevI in which the mobilization of ZAM and Idefix is highly induced. In this strain, 15 copies of ZAM and 30 copies of Idefix are found on the chromosomal arms in addition to their usual distribution. Amongst the loci where new copies are detected, a hotspot for their insertion has been detected at the white locus where up to four elements occurred within a 3-kb fragment at the 5' end of this gene. This property of ZAM and Idefix to accumulate at a defined site provides an interesting paradigm to bring insight into the effect exerted by multiple insertions of transposable elements at an euchromatic locus.

  7. Multiple-locus variable number tandem repeats analysis for genetic fingerprinting of pathogenic bacteria.

    PubMed

    Lindstedt, Bjørn-Arne

    2005-06-01

    DNA fingerprinting has attracted considerable interest as means for identifying, tracing and preventing the dissemination of infectious agents. Various methods have been developed for typing of pathogenic bacteria, which differ in discriminative power, reproducibility and ease of interpretation. During recent years a typing method, which uses the information provided by whole genome sequencing of bacterial species, has gained increased attention. Short sequence repeat (SSR) motifs are known to undergo frequent variation in the number of repeated units through cellular mechanisms most commonly active during chromosome replication. A class of SSRs, named variable number of tandem repeats (VNTRs), has proven to be a suitable target for assessing genetic polymorphisms within bacterial species. This review attempts to give an overview of bacterial agents where VNTR-based typing, or multiple-locus variant-repeat analysis (MLVA) has been developed for typing purposes, together with addressing advantages and drawbacks associated with the use of tandem repeated DNA motifs as targets for bacterial typing and identification.

  8. Multiple alleles at a single locus control seed dormancy in Swedish Arabidopsis

    PubMed Central

    Kerdaffrec, Envel; Filiault, Danièle L; Korte, Arthur; Sasaki, Eriko; Nizhynska, Viktoria; Seren, Ümit; Nordborg, Magnus

    2016-01-01

    Seed dormancy is a complex life history trait that determines the timing of germination and is crucial for local adaptation. Genetic studies of dormancy are challenging, because the trait is highly plastic and strongly influenced by the maternal environment. Using a combination of statistical and experimental approaches, we show that multiple alleles at the previously identified dormancy locus DELAY OF GERMINATION1 jointly explain as much as 57% of the variation observed in Swedish Arabidopsis thaliana, but give rise to spurious associations that seriously mislead genome-wide association studies unless modeled correctly. Field experiments confirm that the major alleles affect germination as well as survival under natural conditions, and demonstrate that locally adaptive traits can sometimes be dissected genetically. DOI: http://dx.doi.org/10.7554/eLife.22502.001 PMID:27966430

  9. Real-time panoramic of multiple sensors

    NASA Astrophysics Data System (ADS)

    Beauvais, Jason R.

    2008-04-01

    The current state of technology limits the spectral sensitivity and field of view of any single sensor. To compensate for this limitation, singular sensors are configured in groupings of varying sensor types. In systems utilizing multiple sensors, operators can become overwhelmed with data. The effectiveness of these new multi-sensor systems requires the construction of an environment that optimizes the delivery of maximum intelligence to the operator so as to provide as much information about the environment as possible. GE Fanuc / Octec has developed such an environment; a panoramic, near-immersive visualization tool that is intuitive to use and seamlessly integrates multiple sensors into natural view with important intelligence information retained and enhanced. We will discuss methods to generate and inject metadata such as automatic detection and tracking of possible threats and the fusing of multi-spectral streams into this environment significantly raising the level of situational awareness for the operator.

  10. Mapping Multiple Sclerosis Susceptibility to the HLA-DR Locus in African Americans

    PubMed Central

    Oksenberg, Jorge R.; Barcellos, Lisa F.; Cree, Bruce A. C.; Baranzini, Sergio E.; Bugawan, Teodorica L.; Khan, Omar; Lincoln, Robin R.; Swerdlin, Amy; Mignot, Emmanuel; Lin, Ling; Goodin, Douglas; Erlich, Henry A.; Schmidt, Silke; Thomson, Glenys; Reich, David E.; Pericak-Vance, Margaret A.; Haines, Jonathan L.; Hauser, Stephen L.

    2004-01-01

    An underlying complex genetic susceptibility exists in multiple sclerosis (MS), and an association with the HLA-DRB1*1501-DQB1*0602 haplotype has been repeatedly demonstrated in high-risk (northern European) populations. It is unknown whether the effect is explained by the HLA-DRB1 or the HLA-DQB1 gene within the susceptibility haplotype, which are in strong linkage disequilibrium (LD). African populations are characterized by greater haplotypic diversity and distinct patterns of LD compared with northern Europeans. To better localize the HLA gene responsible for MS susceptibility, case-control and family-based association studies were performed for DRB1 and DQB1 loci in a large and well-characterized African American data set. A selective association with HLA-DRB1*15 was revealed, indicating a primary role for the DRB1 locus in MS independent of DQB1*0602. This finding is unlikely to be solely explained by admixture, since a substantial proportion of the susceptibility chromosomes from African American patients with MS displayed haplotypes consistent with an African origin. PMID:14669136

  11. Comparative multi-locus phylogeography confirms multiple vicariance events in co-distributed rainforest frogs

    PubMed Central

    Bell, Rayna C.; MacKenzie, Jason B.; Hickerson, Michael J.; Chavarría, Krystle L.; Cunningham, Michael; Williams, Stephen; Moritz, Craig

    2012-01-01

    Though Pleistocene refugia are frequently cited as drivers of species diversification, comparisons of molecular divergence among sister species typically indicate a continuum of divergence times from the Late Miocene, rather than a clear pulse of speciation events at the Last Glacial Maximum. Community-scale inference methods that explicitly test for multiple vicariance events, and account for differences in ancestral effective population size and gene flow, are well suited for detecting heterogeneity of species' responses to past climate fluctuations. We apply this approach to multi-locus sequence data from five co-distributed frog species endemic to the Wet Tropics rainforests of northeast Australia. Our results demonstrate at least two episodes of vicariance owing to climate-driven forest contractions: one in the Early Pleistocene and the other considerably older. Understanding how repeated cycles of rainforest contraction and expansion differentially affected lineage divergence among co-distributed species provides a framework for identifying evolutionary processes that underlie population divergence and speciation. PMID:21900325

  12. A putative vulnerability locus to multiple sclerosis maps to 5p14-p12 in a region syntenic to the murine locus Eae2.

    PubMed

    Kuokkanen, S; Sundvall, M; Terwilliger, J D; Tienari, P J; Wikström, J; Holmdahl, R; Pettersson, U; Peltonen, L

    1996-08-01

    Multiple sclerosis (MS) is a chronic inflammatory disorder characterized by multifocal damage of myelin in the central nervous system (CNS). The prevalence of this putative autoimmune disease is 0.1% in individuals of northern European origin. Family, adoption and twin studies implicate genetic factors in the aetiology. MS is widely speculated to be a multifactorial disorder with a complex mode of inheritance. Despite many studies of candidate genes, only an association with HLA-DR2-DQ6 has been generally detected, and the number of susceptibility genes remains unknown. The chronic variant of experimental allergic encephalomyelitis (EAE), a T-cell mediated autoimmune disease in rodents, represents a relevant animal model for MS given the chronic relapsing disease course and inflammatory changes of CNS observed in these demyelinating disorders. Susceptibility to EAE is also influenced by the major histocompatibility complex (MHC). Human syntenic regions to murine loci predisposing to EAE were tested as candidate regions for genetic susceptibility of MS. Three chromosomal regions (1p22-q23, 5p14-p12 and Xq13.2-q22) were screened in 21 Finnish multiplex MS families most originating from a high risk region in western Finland. Several markers yielded positive lod scores on 5p14-p12, syntenic to the murine locus Eae2. Our data provide evidence for a predisposing locus for MS on 5p14-p12.

  13. An E-M algorithm and testing strategy for multiple-locus haplotypes.

    PubMed Central

    Long, J C; Williams, R C; Urbanek, M

    1995-01-01

    This paper gives an expectation maximization (EM) algorithm to obtain allele frequencies, haplotype frequencies, and gametic disequilibrium coefficients for multiple-locus systems. It permits high polymorphism and null alleles at all loci. This approach effectively deals with the primary estimation problems associated with such systems; that is, there is not a one-to-one correspondence between phenotypic and genotypic categories, and sample sizes tend to be much smaller than the number of phenotypic categories. The EM method provides maximum-likelihood estimates and therefore allows hypothesis tests using likelihood ratio statistics that have chi 2 distributions with large sample sizes. We also suggest a data resampling approach to estimate test statistic sampling distributions. The resampling approach is more computer intensive, but it is applicable to all sample sizes. A strategy to test hypotheses about aggregate groups of gametic disequilibrium coefficients is recommended. This strategy minimizes the number of necessary hypothesis tests while at the same time describing the structure of disequilibrium. These methods are applied to three unlinked dinucleotide repeat loci in Navajo Indians and to three linked HLA loci in Gila River (Pima) Indians. The likelihood functions of both data sets are shown to be maximized by the EM estimates, and the testing strategy provides a useful description of the structure of gametic disequilibrium. Following these applications, a number of simulation experiments are performed to test how well the likelihood-ratio statistic distributions are approximated by chi 2 distributions. In most circumstances the chi 2 grossly underestimated the probability of type I errors. However, at times they also overestimated the type 1 error probability. Accordingly, we recommended hypothesis tests that use the resampling method. PMID:7887436

  14. An E-M algorithm and testing strategy for multiple-locus haplotypes

    SciTech Connect

    Long, J.C.; Williams, R.C.; Urbanek, M.

    1995-03-01

    This paper gives an expectation maximization (EM) algorithm to obtain allele frequencies, haplotype frequencies, and gametic disequilibrium coefficients for multiple-locus systems. It permits high polymorphism and null alleles at all loci. This approach effectively deals with the primary estimation problems associated with such systems; that is, there is not a one-to-one correspondence between phenotypic and genotypic categories, and sample sizes tend to be much smaller than the number of phenotypic categories. The EM method provides maximum-likelihood estimates and therefore allows hypothesis tests using likelihood ratio statistics that have X{sup 2} distributions with large sample sizes. We also suggest a data resampling approach to estimate test statistic sampling distributions. The resampling approach is more computer intensive, but it is applicable to all sample sizes. A strategy to test hypotheses about aggregate groups of gametic disequilibrium coefficients is recommended. This strategy minimizes the number of necessary hypothesis tests while at the same time describing the structure of equilibrium. These methods are applied to three unlinked dinucleotide repeat loci in Navajo Indians and to three linked HLA loci in Gila River (Pima) Indians. The likelihood functions of both data sets are shown to be maximized by the EM estimates, and the testing strategy provides a useful description of the structure of gametic disequilibrium. Following these applications, a number of simulation experiments are performed to test how well the likelihood-ratio statistic distributions are approximated by X{sup 2} distributions. In most circumstances X{sup 2} grossly underestimated the probability of type I errors. However, at times they also overestimated the type 1 error probability. Accordingly, we recommend hypothesis tests that use the resampling method. 41 refs., 3 figs., 6 tabs.

  15. Effective application of multiple locus variable number of tandem repeats analysis to tracing Staphylococcus aureus in food-processing environment.

    PubMed

    Rešková, Z; Koreňová, J; Kuchta, T

    2014-04-01

    A total of 256 isolates of Staphylococcus aureus were isolated from 98 samples (34 swabs and 64 food samples) obtained from small or medium meat- and cheese-processing plants in Slovakia. The strains were genotypically characterized by multiple locus variable number of tandem repeats analysis (MLVA), involving multiplex polymerase chain reaction (PCR) with subsequent separation of the amplified DNA fragments by an automated flow-through gel electrophoresis. With the panel of isolates, MLVA produced 31 profile types, which was a sufficient discrimination to facilitate the description of spatial and temporal aspects of contamination. Further data on MLVA discrimination were obtained by typing a subpanel of strains by multiple locus sequence typing (MLST). MLVA coupled to automated electrophoresis proved to be an effective, comparatively fast and inexpensive method for tracing S. aureus contamination of food-processing factories. Subspecies genotyping of microbial contaminants in food-processing factories may facilitate identification of spatial and temporal aspects of the contamination. This may help to properly manage the process hygiene. With S. aureus, multiple locus variable number of tandem repeats analysis (MLVA) proved to be an effective method for the purpose, being sufficiently discriminative, yet comparatively fast and inexpensive. The application of automated flow-through gel electrophoresis to separation of DNA fragments produced by multiplex PCR helped to improve the accuracy and speed of the method. © 2013 The Society for Applied Microbiology.

  16. Multiple-Locus VNTR Analysis (MLVA) for Bacterial Strain Identification - Quarterly Progress Report for the Period 4/1/00 to 6/30/00

    SciTech Connect

    Dr. Paul Keim

    2000-11-07

    Multiple locus VNTR analysis (MLVA) systems are being developed for B. anthracis, Y. pestis and F. tularensis. These are high resolution DNA fingerprinting systems that will allow for molecular epidemiology and forensic analysis of these pathogens.

  17. Multiple-Locus VNTR Analysis (MLVA) for Bacterial Strain Identification - Quarterly Progress Report for the period 7/1/00 to 10/30/00

    SciTech Connect

    Dr. Paul Keim

    2000-11-07

    Multiple locus VNTR analysis (MLVA) systems are being developed for B. anthracis, Y. pestis and F. tularensis. These are high resolution DNA fingerprinting systems that will allow for molecular epidemiology and forensic analysis of these pathogens.

  18. Evidence for Multiple Levels of Regulation of Oenococcus oeni clpP-clpL Locus Expression in Response to Stress

    PubMed Central

    Beltramo, Charlotte; Grandvalet, Cosette; Pierre, Fabrice; Guzzo, Jean

    2004-01-01

    A locus containing the clpP and clpL genes in the lactic acid bacterium Oenococcus oeni was studied. Real-time reverse transcription-PCR analysis revealed different induction factors involved in expression of these genes during stress. According to the conditions, clpP and clpL genes could be transcripted as two distinct transcripts or cotranscripted. The clpP promoter depended on the CtsR regulator, but surprisingly the clpL promoter did not. The amount of the clpL transcript depended on mRNA stability. This clp ATPase gene is at least controlled at the posttranscriptional level. PMID:15028706

  19. Evidence for multiple levels of regulation of Oenococcus oeni clpP-clpL locus expression in response to stress.

    PubMed

    Beltramo, Charlotte; Grandvalet, Cosette; Pierre, Fabrice; Guzzo, Jean

    2004-04-01

    A locus containing the clpP and clpL genes in the lactic acid bacterium Oenococcus oeni was studied. Real-time reverse transcription-PCR analysis revealed different induction factors involved in expression of these genes during stress. According to the conditions, clpP and clpL genes could be transcripted as two distinct transcripts or cotranscripted. The clpP promoter depended on the CtsR regulator, but surprisingly the clpL promoter did not. The amount of the clpL transcript depended on mRNA stability. This clp ATPase gene is at least controlled at the posttranscriptional level.

  20. Real-Time Location Tracking of Multiple Construction Laborers

    PubMed Central

    Lim, Jin-Sun; Song, Ki-Il; Lee, Hang-Lo

    2016-01-01

    A real-time location (RTL) system was developed to improve safety for multiple laborers in confined construction sites. The RTL system can monitor the location and movement of multiple laborers in real time. A portable RTL system with a low-battery mode was developed to accommodate various constraints in the construction site. A conventional RTL system that uses radio signal strength indicators (RSSIs) has high error, so an accelerometer with Bluetooth Low Energy (BLE) was added, and a calculation process is suggested. Field tests were performed for validation in underground construction and bridge overlay sites. The results show that the accelerometer and BLE can be used as effective sensors to detect the movement of laborers. When the sensor is fixed, the average error ranges 0.2–0.22 m, and when the sensor is moving, the average error ranges 0.1–0.47 m. PMID:27827973

  1. Real-Time Location Tracking of Multiple Construction Laborers.

    PubMed

    Lim, Jin-Sun; Song, Ki-Il; Lee, Hang-Lo

    2016-11-06

    A real-time location (RTL) system was developed to improve safety for multiple laborers in confined construction sites. The RTL system can monitor the location and movement of multiple laborers in real time. A portable RTL system with a low-battery mode was developed to accommodate various constraints in the construction site. A conventional RTL system that uses radio signal strength indicators (RSSIs) has high error, so an accelerometer with Bluetooth Low Energy (BLE) was added, and a calculation process is suggested. Field tests were performed for validation in underground construction and bridge overlay sites. The results show that the accelerometer and BLE can be used as effective sensors to detect the movement of laborers. When the sensor is fixed, the average error ranges 0.2-0.22 m, and when the sensor is moving, the average error ranges 0.1-0.47 m.

  2. Simultaneous real-time monitoring of multiple cortical systems

    NASA Astrophysics Data System (ADS)

    Gupta, Disha; Hill, N. Jeremy; Brunner, Peter; Gunduz, Aysegul; Ritaccio, Anthony L.; Schalk, Gerwin

    2014-10-01

    Objective. Real-time monitoring of the brain is potentially valuable for performance monitoring, communication, training or rehabilitation. In natural situations, the brain performs a complex mix of various sensory, motor or cognitive functions. Thus, real-time brain monitoring would be most valuable if (a) it could decode information from multiple brain systems simultaneously, and (b) this decoding of each brain system were robust to variations in the activity of other (unrelated) brain systems. Previous studies showed that it is possible to decode some information from different brain systems in retrospect and/or in isolation. In our study, we set out to determine whether it is possible to simultaneously decode important information about a user from different brain systems in real time, and to evaluate the impact of concurrent activity in different brain systems on decoding performance. Approach. We study these questions using electrocorticographic signals recorded in humans. We first document procedures for generating stable decoding models given little training data, and then report their use for offline and for real-time decoding from 12 subjects (six for offline parameter optimization, six for online experimentation). The subjects engage in tasks that involve movement intention, movement execution and auditory functions, separately, and then simultaneously. Main results. Our real-time results demonstrate that our system can identify intention and movement periods in single trials with an accuracy of 80.4% and 86.8%, respectively (where 50% would be expected by chance). Simultaneously, the decoding of the power envelope of an auditory stimulus resulted in an average correlation coefficient of 0.37 between the actual and decoded power envelopes. These decoders were trained separately and executed simultaneously in real time. Significance. This study yielded the first demonstration that it is possible to decode simultaneously the functional activity of multiple

  3. Empirical Bayesian LASSO-logistic regression for multiple binary trait locus mapping

    PubMed Central

    2013-01-01

    Background Complex binary traits are influenced by many factors including the main effects of many quantitative trait loci (QTLs), the epistatic effects involving more than one QTLs, environmental effects and the effects of gene-environment interactions. Although a number of QTL mapping methods for binary traits have been developed, there still lacks an efficient and powerful method that can handle both main and epistatic effects of a relatively large number of possible QTLs. Results In this paper, we use a Bayesian logistic regression model as the QTL model for binary traits that includes both main and epistatic effects. Our logistic regression model employs hierarchical priors for regression coefficients similar to the ones used in the Bayesian LASSO linear model for multiple QTL mapping for continuous traits. We develop efficient empirical Bayesian algorithms to infer the logistic regression model. Our simulation study shows that our algorithms can easily handle a QTL model with a large number of main and epistatic effects on a personal computer, and outperform five other methods examined including the LASSO, HyperLasso, BhGLM, RVM and the single-QTL mapping method based on logistic regression in terms of power of detection and false positive rate. The utility of our algorithms is also demonstrated through analysis of a real data set. A software package implementing the empirical Bayesian algorithms in this paper is freely available upon request. Conclusions The EBLASSO logistic regression method can handle a large number of effects possibly including the main and epistatic QTL effects, environmental effects and the effects of gene-environment interactions. It will be a very useful tool for multiple QTLs mapping for complex binary traits. PMID:23410082

  4. A meta-analysis identifies adolescent idiopathic scoliosis association with LBX1 locus in multiple ethnic groups.

    PubMed

    Londono, Douglas; Kou, Ikuyo; Johnson, Todd A; Sharma, Swarkar; Ogura, Yoji; Tsunoda, Tatsuhiko; Takahashi, Atsushi; Matsumoto, Morio; Herring, John A; Lam, Tsz-Ping; Wang, Xingyan; Tam, Elisa M S; Song, You-Qiang; Fan, Yan-Hui; Chan, Danny; Cheah, Kathryn S E; Qiu, Xusheng; Jiang, Hua; Huang, Dongsheng; TSRHC IS Clinical Group; International Consortium for Scoliosis Genetics; Su, Peiqiang; Sham, Pak; Cheung, Kenneth M C; Luk, Keith D K; Gordon, Derek; Qiu, Yong; Cheng, Jack; Tang, Nelson; Ikegawa, Shiro; Wise, Carol A

    2014-06-01

    Adolescent idiopathic scoliosis (AIS) is a common rotational deformity of the spine that presents in children worldwide, yet its etiology is poorly understood. Recent genome-wide association studies (GWAS) have identified a few candidate risk loci. One locus near the chromosome 10q24.31 LBX1 gene (OMIM #604255) was originally identified by a GWAS of Japanese subjects and replicated in additional Asian populations. To extend this result, and to create larger AIS cohorts for the purpose of large-scale meta-analyses in multiple ethnicities, we formed a collaborative group called the International Consortium for Scoliosis Genetics (ICSG). Here, we report the first ICSG study, a meta-analysis of the LBX1 locus in six Asian and three non-Asian cohorts. We find significant evidence for association of this locus with AIS susceptibility in all nine cohorts. Results for seven cohorts containing both genders yielded P=1.22×10-43 for rs11190870, and P=2.94×10-48 for females in all nine cohorts. Comparing the regional haplotype structures for three populations, we refined the boundaries of association to a ∼25 kb block encompassing the LBX1 gene. The LBX1 protein, a homeobox transcription factor that is orthologous to the Drosophila ladybird late gene, is involved in proper migration of muscle precursor cells, specification of cardiac neural crest cells, and neuronal determination in developing neural tubes. Our results firmly establish the LBX1 region as the first major susceptibility locus for AIS in Asian and non-Hispanic white groups, and provide a platform for larger studies in additional ancestral groups. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  5. Tag-SNP analysis of the GFI1-EVI5-RPL5-FAM69 risk locus for multiple sclerosis

    PubMed Central

    Alcina, Antonio; Fernández, Óscar; Gonzalez, Juan Ramón; Catalá-Rabasa, Antonio; Fedetz, María; Ndagire, Dorothy; Leyva, Laura; Guerrero, Miguel; Arnal, Carmen; Delgado, Concepción; Lucas, Miguel; Izquierdo, Guillermo; Matesanz, Fuencisla

    2010-01-01

    A recent genome-wide association study conducted by the International Multiple Sclerosis Genetic Consortium (IMSGC) identified, among others, a number of putative multiple sclerosis (MS) susceptibility variants at position 1p22. Twenty-one SNPs positively associated with MS were located at the GFI-EVI5-RPL5-FAM69A locus. In this study, we performed an analysis and fine mapping of this locus, genotyping eight Tag-SNPs in 732 MS patients and 974 controls from Spain. We observed an association with MS in three of eight Tag-SNPs: rs11804321 (P=0.008, OR=1.29; 95% CI=1.08–1.54), rs11808092 (P=0.048, OR=1.19; 95% CI=1.03–1.39) and rs6680578 (P=0.0082, OR=1.23; 95% CI=1.07–1.41). After correcting for multiple comparisons and using logistic regression analysis to test the addition of each SNP to the most associated SNPs, we observed that rs11804321 alone was sufficient to model the association. This Tag-SNP captures two SNPs in complete linkage disequilibrium (r2=1), both located within the 17th intron of the EVI5 gene. Our findings agree with the corresponding data of the recent IMSGC study and present new genetic evidence that points to EVI5 as a factor of susceptibility to MS. PMID:20087403

  6. The zebrafish IgH locus contains multiple transcriptional regulatory regions

    PubMed Central

    Danilova, N.; Saunders, H. L.; Ellestad, K. K.; Magor, B. G.

    2010-01-01

    Many fish have, in addition to IgM and IgD, a third isotype called IgZ or IgT. The ζ-chain locus is embedded among the Ig heavy chain V-, D- and J-elements in a manner reminiscent of the TcR δ/α locus. Isotype selection thus occurs during VDJ recombination, a process that is facilitated by intralocus transcription. Using in silico analyses and enhancer reporter vectors we identified 3 new regions within the zebrafish IgH locus through which transcription can be activated in catfish B-cell lines. Two of these, termed Eζi (Jζ to Cζ1 intronic) and Eζ3′ regions flank the ζ-chain constant domain exons. A third region, Eδ3′, resides downstream of the δ-chain exons. All regions contain predicted binding sites for transcription factors that contribute to B-cell specific transcription in fish and mammals. Each region also has proximal matrix attachment regions, which may further contribute to transcriptional activation and chromatin remodeling. We discuss possible roles for these regions during VDJ recombination. PMID:21055416

  7. Digital Real-Time Multiple Channel Multiple Mode Neutron Flux Estimation on FPGA-based Device

    NASA Astrophysics Data System (ADS)

    Thevenin, Mathieu; Barbot, Loïc; Corre, Gwénolé; Woo, Romuald; Destouches, Christophe; Normand, Stéphane

    2016-02-01

    This paper presents a complete custom full-digital instrumentation device that was designed for real-time neutron flux estimation, especially for nuclear reactor in-core measurement using subminiature Fission Chambers (FCs). Entire fully functional small-footprint design (about 1714 LUTs) is implemented on FPGA. It enables real-time acquisition and analysis of multiple channels neutron's flux both in counting mode and Campbelling mode. Experimental results obtained from this brand new device are consistent with simulation results and show good agreement within good uncertainty. This device paves the way for new applications perspectives in real-time nuclear reactor monitoring.

  8. Multiple signals at the extended 8p23 locus are associated with susceptibility to systemic lupus erythematosus.

    PubMed

    Demirci, F Yesim; Wang, Xingbin; Morris, David L; Feingold, Eleanor; Bernatsky, Sasha; Pineau, Christian; Clarke, Ann; Ramsey-Goldman, Rosalind; Manzi, Susan; Vyse, Timothy J; Kamboh, M I

    2017-06-01

    A major systemic lupus erythematosus (SLE) susceptibility locus lies within a common inversion polymorphism region (encompassing 3.8 - 4.5  Mb) located at 8p23. Initially implicated genes included FAM167A-BLK and XKR6, of which BLK received major attention due to its known role in B-cell biology. Recently, additional SLE risk carried in non-inverted background was also reported. In this case -control study, we further investigated the 'extended' 8p23 locus (~ 4  Mb) where we observed multiple SLE signals and assessed these signals for their relation to the inversion affecting this region. The study involved a North American discovery data set (~ 1200  subjects) and a replication data set (> 10 000  subjects) comprising European-descent individuals. Meta-analysis of 8p23 SNPs, with p < 0.05 in both data sets, identified 51 genome-wide significant SNPs (p < 5.0 × 10(-8)). While most of these SNPs were related to previously implicated signals (XKR6-FAM167A-BLK subregion), our results also revealed two 'new' SLE signals, including SGK223-CLDN23-MFHAS1 (6.06 × 10(-9) ≤ meta p ≤ 4.88 × 10(-8)) and CTSB (meta p = 4.87 × 10(-8)) subregions that are located > 2 Mb upstream and ~ 0.3  Mb downstream from previously reported signals. Functional assessment of relevant SNPs indicated putative cis-effects on the expression of various genes at 8p23. Additional analyses in discovery sample, where the inversion genotypes were inferred, replicated the association of non-inverted status with SLE risk and suggested that a number of SLE risk alleles are predominantly carried in non-inverted background. Our results implicate multiple (known+novel) SLE signals/genes at the extended 8p23 locus, beyond previously reported signals/genes, and suggest that this broad locus contributes to SLE risk through the effects of multiple genes/pathways. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No

  9. Genotyping of Klebsiella Pneumonia Strains Isolated from Eldly Inpatients by Multiple-locus Variable-number Tandem-repeat Analysis.

    PubMed

    Zhang, Yuan-Yuan; Xu, Ya-Ping; DU, Peng-Cheng; Qiang, Yu-Jun; Zhang, Wen; Chen, Chen; Yu, Ji-Hong; Guo, Jun

    2016-08-01

    Objective To investigate the genotype of klebsiella pneumonia strains isolated from eldly inpatients by multiple-locus variable-number tandem-repeat analysis. Methods Totally 184 klebsiella pneumonia strains,isolated from eldly inpatients,were collected,and their genome DNA were extracted. The polymorphism of 7 variable-number tandem-repeat locus in the DNA samples was analyzed by multiple primers polymerase chain reaction and capillary electrophoresis. The clustering analysis of genotyping was carried out with the BioNumerics 5.1 software. Results A total of 139 genotypes were identified in 184 klebsiella pneumonia clinical strains,showing obvious genetic polymorphisms. With clustering analysis of genotypes,all the strains were categorized into three gene clusters (genogroups 1,2,and 3). The genogroup 1 was the biggest cluster,containing 93.06% of the isolated strains. Conclusion There was a predominant cluster in the klebsiella pneumonia strains isolated from eldly inpatients in our center,and the major source of klebsiella pneumonia infection remained the nosocomial infection.

  10. Genome-Wide Association Study of Multiple Sclerosis Confirms a Novel Locus at 5p13.1

    PubMed Central

    Sanna, Serena; Gayán, Javier; Urcelay, Elena; Zara, Ilenia; Pitzalis, Maristella; Cavanillas, María L.; Arroyo, Rafael; Zoledziewska, Magdalena; Marrosu, Marisa; Fernández, Oscar; Leyva, Laura; Alcina, Antonio; Fedetz, Maria; Moreno-Rey, Concha; Velasco, Juan; Real, Luis M.; Ruiz-Peña, Juan Luis; Cucca, Francesco

    2012-01-01

    Multiple Sclerosis (MS) is the most common progressive and disabling neurological condition affecting young adults in the world today. From a genetic point of view, MS is a complex disorder resulting from the combination of genetic and non-genetic factors. We aimed to identify previously unidentified loci conducting a new GWAS of Multiple Sclerosis (MS) in a sample of 296 MS cases and 801 controls from the Spanish population. Meta-analysis of our data in combination with previous GWAS was done. A total of 17 GWAS-significant SNPs, corresponding to three different loci were identified:HLA, IL2RA, and 5p13.1. All three have been previously reported as GWAS-significant. We confirmed our observation in 5p13.1 for rs9292777 using two additional independent Spanish samples to make a total of 4912 MS cases and 7498 controls (ORpooled = 0.84; 95%CI: 0.80–0.89; p = 1.36×10-9). This SNP differs from the one reported within this locus in a recent GWAS. Although it is unclear whether both signals are tapping the same genetic association, it seems clear that this locus plays an important role in the pathogenesis of MS. PMID:22570697

  11. Genome-wide association study of multiple sclerosis confirms a novel locus at 5p13.1.

    PubMed

    Matesanz, Fuencisla; González-Pérez, Antonio; Lucas, Miguel; Sanna, Serena; Gayán, Javier; Urcelay, Elena; Zara, Ilenia; Pitzalis, Maristella; Cavanillas, María L; Arroyo, Rafael; Zoledziewska, Magdalena; Marrosu, Marisa; Fernández, Oscar; Leyva, Laura; Alcina, Antonio; Fedetz, Maria; Moreno-Rey, Concha; Velasco, Juan; Real, Luis M; Ruiz-Peña, Juan Luis; Cucca, Francesco; Ruiz, Agustín; Izquierdo, Guillermo

    2012-01-01

    Multiple Sclerosis (MS) is the most common progressive and disabling neurological condition affecting young adults in the world today. From a genetic point of view, MS is a complex disorder resulting from the combination of genetic and non-genetic factors. We aimed to identify previously unidentified loci conducting a new GWAS of Multiple Sclerosis (MS) in a sample of 296 MS cases and 801 controls from the Spanish population. Meta-analysis of our data in combination with previous GWAS was done. A total of 17 GWAS-significant SNPs, corresponding to three different loci were identified:HLA, IL2RA, and 5p13.1. All three have been previously reported as GWAS-significant. We confirmed our observation in 5p13.1 for rs9292777 using two additional independent Spanish samples to make a total of 4912 MS cases and 7498 controls (ORpooled = 0.84; 95%CI: 0.80-0.89; p = 1.36 × 10-9). This SNP differs from the one reported within this locus in a recent GWAS. Although it is unclear whether both signals are tapping the same genetic association, it seems clear that this locus plays an important role in the pathogenesis of MS.

  12. Relativistic real-space multiple scattering calculations of EELS

    NASA Astrophysics Data System (ADS)

    Jorissen, K.; Rehr, J. J.; Sorini, A.; Levine, Z. H.

    2006-03-01

    We present an extension of the real space multiple scattering code FEFF8 for ab initio, relativistic calculations of electron energy loss spectra (EELS), which is applicable both to periodic and non-periodic systems. The approach explains the observed relativistic shifts in the magic angle. In addition, the method can account for experimental parameters such as collection and convergence angles of the microscope and sample orientation. We also discuss relativistic effects on inelastic electron scattering including the density correction to the stopping power. Our results are compared with other approaches and with experiment. B. Jouffrey, P. Schattschneider and C. Hebert, Ultramicroscopy 102, 61 (2004).

  13. Genomewide scan for real-word reading subphenotypes of dyslexia: Novel chromosome 13 locus and genetic complexity

    PubMed Central

    Igo, Robert P.; Chapman, Nicola H.; Berninger, Virginia W.; Matsushita, Mark; Brkanac, Zoran; Rothstein, Joseph H.; Holzman, Ted; Nielsen, Kathleen; Raskind, Wendy H.; Wijsman, Ellen M.

    2008-01-01

    Dyslexia is a common learning disability exhibited as a delay in acquiring reading skills despite adequate intelligence and instruction. Reading single real words (real-word reading, RWR) is especially impaired in many dyslexics. We performed a genome scan, using variance-components (VC) linkage analysis and Bayesian Markov chain Monte Carlo (MCMC) joint segregation and linkage analysis, for three quantitative measures of RWR in 108 multigenerational families, with followup of the strongest signals with parametric LOD score analyses. We used single-word reading efficiency (SWE) to assess speed and accuracy of RWR, and word identification (WID) to assess accuracy alone. Adjusting SWE for WID provided a third measure of RWR efficiency. All three methods of analysis identified a strong linkage signal for SWE on chromosome 13q. Based on multipoint analysis with 13 markers we obtained a MCMC intensity ratio of 53.2 (chromosome-wide p < 0.004), a VC LOD score of 2.29, and a parametric LOD score of 2.94, based on a quantitative-trait model from MCMC segregation analysis. A weaker signal for SWE on chromosome 2q occurred in the same location as a significant linkage peak seen previously in a scan for phonological decoding. MCMC oligogenic segregation analysis identified three models of transmission for WID, which could be assigned to two distinct linkage peaks on chromosomes 12 and 15. Taken together, these results indicate a locus for efficiency and accuracy of RWR on chromosome 13, and a complex model for inheritance of RWR accuracy with loci on chromosomes 12 and 15. PMID:16331673

  14. Simultaneous Real-Time Monitoring of Multiple Cortical Systems

    PubMed Central

    Gupta, Disha; Hill, N. Jeremy; Brunner, Peter; Gunduz, Aysegul; Ritaccio, Anthony L.; Schalk, Gerwin

    2014-01-01

    Objective Real-time monitoring of the brain is potentially valuable for performance monitoring, communication, training or rehabilitation. In natural situations, the brain performs a complex mix of various sensory, motor, or cognitive functions. Thus, real-time brain monitoring would be most valuable if (a) it could decode information from multiple brain systems simultaneously, and (b) this decoding of each brain system were robust to variations in the activity of other (unrelated) brain systems. Previous studies showed that it is possible to decode some information from different brain systems in retrospect and/or in isolation. In our study, we set out to determine whether it is possible to simultaneously decode important information about a user from different brain systems in real time, and to evaluate the impact of concurrent activity in different brain systems on decoding performance. Approach We study these questions using electrocorticographic (ECoG) signals recorded in humans. We first document procedures for generating stable decoding models given little training data, and then report their use for offline and for real-time decoding from 12 subjects (6 for offline parameter optimization, 6 for online experimentation). The subjects engage in tasks that involve movement intention, movement execution and auditory functions, separately, and then simultaneously. Main results Our real-time results demonstrate that our system can identify intention and movement periods in single trials with an accuracy of 80.4% and 86.8%, respectively (where 50% would be expected by chance). Simultaneously, the decoding of the power envelope of an auditory stimulus resulted in an average correlation coefficient of 0.37 between the actual and decoded power envelope. These decoders were trained separately and executed simultaneously in real time. Significance This study yielded the first demonstration that it is possible to decode simultaneously the functional activity of multiple

  15. Multiple mobile robots real-time visual search algorithm

    NASA Astrophysics Data System (ADS)

    Yan, Caixia; Zhan, Qiang

    2010-08-01

    A multiple mobile robots visual real-time locating system is introduced, in which the global search algorithm and track search algorithm are combined together to identify the real-time position and orientation(pose) of multiple mobile robots. The switching strategy between the two algorithms is given to ensure the accuracy and improve retrieval speed. The grid search approach is used to identify target while searching globally. By checking the location in the previous frame, the maximum speed and the frame time interval, thus the track search can determine the area target robot may appear in the next frame. Then, a new search will be performed in the certain area. The global search is used if target robot is not found in the previous search otherwise track search will be used. With the experiment on the static and dynamic recognition of three robots, the search method here is proved to be high precise, fast, stable and easy to extend, all the design requirements can be well met.

  16. Real-Time Clustered Multiple Signal Classification (RTC-MUSIC).

    PubMed

    Dinh, Christoph; Esch, Lorenz; Rühle, Johannes; Bollmann, Steffen; Güllmar, Daniel; Baumgarten, Daniel; Hämäläinen, Matti S; Haueisen, Jens

    2017-09-06

    Magnetoencephalography (MEG) and electroencephalography provide a high temporal resolution, which allows estimation of the detailed time courses of neuronal activity. However, in real-time analysis of these data two major challenges must be handled: the low signal-to-noise ratio (SNR) and the limited time available for computations. In this work, we present real-time clustered multiple signal classification (RTC-MUSIC) a real-time source localization algorithm, which can handle low SNRs and can reduce the computational effort. It provides correlation information together with sparse source estimation results, which can, e.g., be used to identify evoked responses with high sensitivity. RTC-MUSIC clusters the forward solution based on an anatomical brain atlas and optimizes the scanning process inherent to MUSIC approaches. We evaluated RTC-MUSIC by analyzing MEG auditory and somatosensory data. The results demonstrate that the proposed method localizes sources reliably. For the auditory experiment the most dominant correlated source pair was located bilaterally in the superior temporal gyri. The highest activation in the somatosensory experiment was found in the contra-lateral primary somatosensory cortex.

  17. A multi-locus analysis of phylogenetic relationships within cheilostome bryozoans supports multiple origins of ascophoran frontal shields.

    PubMed

    Knight, Sarah; Gordon, Dennis P; Lavery, Shane D

    2011-11-01

    Phylogenetic relationships within the bryozoan order Cheilostomata are currently uncertain, with many morphological hypotheses proposed but scarcely tested by independent means of molecular analysis. This research uses DNA sequence data across five loci of both mitochondrial and nuclear origin from 91 species of cheilostome Bryozoa (34 species newly sequenced). This vastly improved the taxonomic coverage and number of loci used in a molecular analysis of this order and allowed a more in-depth look into the evolutionary history of Cheilostomata. Maximum likelihood and Bayesian analyses of individual loci were carried out along with a partitioned multi-locus approach, plus a range of topology tests based on morphological hypotheses. Together, these provide a comprehensive set of phylogenetic analyses of the order Cheilostomata. From these results inferences are made about the evolutionary history of this order and proposed morphological hypotheses are discussed in light of the independent evidence gained from the molecular data. Infraorder Ascophorina was demonstrated to be non-monophyletic, and there appears to be multiple origins of the ascus and associated structures involved in lophophore extension. This was further supported by the lack of monophyly within each of the four ascophoran grades (acanthostegomorph/spinocystal, hippothoomorph/gymnocystal, umbonulomorph/umbonuloid, lepraliomorph/lepralioid) defined by frontal-shield morphology. Chorizopora, currently classified in the ascophoran grade Hippothoomorpha, is phylogenetically distinct from Hippothoidae, providing strong evidence for multiple origins of the gymnocystal frontal shield type. Further evidence is produced to support the morphological hypothesis of multiple umbonuloid origins of lepralioid frontal shields, using a step-wise set of topological hypothesis tests combined with examination of multi-locus phylogenies.

  18. Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer

    PubMed Central

    Bojesen, Stig E; Pooley, Karen A; Johnatty, Sharon E; Beesley, Jonathan; Michailidou, Kyriaki; Tyrer, Jonathan P; Edwards, Stacey L; Pickett, Hilda A; Shen, Howard C; Smart, Chanel E; Hillman, Kristine M; Mai, Phuong L; Lawrenson, Kate; Stutz, Michael D; Lu, Yi; Karevan, Rod; Woods, Nicholas; Johnston, Rebecca L; French, Juliet D; Chen, Xiaoqing; Weischer, Maren; Nielsen, Sune F; Maranian, Melanie J; Ghoussaini, Maya; Ahmed, Shahana; Baynes, Caroline; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; McGuffog, Lesley; Barrowdale, Daniel; Lee, Andrew; Healey, Sue; Lush, Michael; Tessier, Daniel C; Vincent, Daniel; Bacot, Françis; Vergote, Ignace; Lambrechts, Sandrina; Despierre, Evelyn; Risch, Harvey A; González-Neira, Anna; Rossing, Mary Anne; Pita, Guillermo; Doherty, Jennifer A; Álvarez, Nuria; Larson, Melissa C; Fridley, Brooke L; Schoof, Nils; Chang-Claude, Jenny; Cicek, Mine S; Peto, Julian; Kalli, Kimberly R; Broeks, Annegien; Armasu, Sebastian M; Schmidt, Marjanka K; Braaf, Linde M; Winterhoff, Boris; Nevanlinna, Heli; Konecny, Gottfried E; Lambrechts, Diether; Rogmann, Lisa; Guénel, Pascal; Teoman, Attila; Milne, Roger L; Garcia, Joaquin J; Cox, Angela; Shridhar, Vijayalakshmi; Burwinkel, Barbara; Marme, Frederik; Hein, Rebecca; Sawyer, Elinor J; Haiman, Christopher A; Wang-Gohrke, Shan; Andrulis, Irene L; Moysich, Kirsten B; Hopper, John L; Odunsi, Kunle; Lindblom, Annika; Giles, Graham G; Brenner, Hermann; Simard, Jacques; Lurie, Galina; Fasching, Peter A; Carney, Michael E; Radice, Paolo; Wilkens, Lynne R; Swerdlow, Anthony; Goodman, Marc T; Brauch, Hiltrud; García-Closas, Montserrat; Hillemanns, Peter; Winqvist, Robert; Dürst, Matthias; Devilee, Peter; Runnebaum, Ingo; Jakubowska, Anna; Lubinski, Jan; Mannermaa, Arto; Butzow, Ralf; Bogdanova, Natalia V; Dörk, Thilo; Pelttari, Liisa M; Zheng, Wei; Leminen, Arto; Anton-Culver, Hoda; Bunker, Clareann H; Kristensen, Vessela; Ness, Roberta B; Muir, Kenneth; Edwards, Robert; Meindl, Alfons; Heitz, Florian; Matsuo, Keitaro; du Bois, Andreas; Wu, Anna H; Harter, Philipp; Teo, Soo-Hwang; Schwaab, Ira; Shu, Xiao-Ou; Blot, William; Hosono, Satoyo; Kang, Daehee; Nakanishi, Toru; Hartman, Mikael; Yatabe, Yasushi; Hamann, Ute; Karlan, Beth Y; Sangrajrang, Suleeporn; Kjaer, Susanne Krüger; Gaborieau, Valerie; Jensen, Allan; Eccles, Diana; Høgdall, Estrid; Shen, Chen-Yang; Brown, Judith; Woo, Yin Ling; Shah, Mitul; Azmi, Mat Adenan Noor; Luben, Robert; Omar, Siti Zawiah; Czene, Kamila; Vierkant, Robert A; Nordestgaard, Børge G; Flyger, Henrik; Vachon, Celine; Olson, Janet E; Wang, Xianshu; Levine, Douglas A; Rudolph, Anja; Weber, Rachel Palmieri; Flesch-Janys, Dieter; Iversen, Edwin; Nickels, Stefan; Schildkraut, Joellen M; Silva, Isabel Dos Santos; Cramer, Daniel W; Gibson, Lorna; Terry, Kathryn L; Fletcher, Olivia; Vitonis, Allison F; van der Schoot, C Ellen; Poole, Elizabeth M; Hogervorst, Frans B L; Tworoger, Shelley S; Liu, Jianjun; Bandera, Elisa V; Li, Jingmei; Olson, Sara H; Humphreys, Keith; Orlow, Irene; Blomqvist, Carl; Rodriguez-Rodriguez, Lorna; Aittomäki, Kristiina; Salvesen, Helga B; Muranen, Taru A; Wik, Elisabeth; Brouwers, Barbara; Krakstad, Camilla; Wauters, Els; Halle, Mari K; Wildiers, Hans; Kiemeney, Lambertus A; Mulot, Claire; Aben, Katja K; Laurent-Puig, Pierre; van Altena, Anne M; Truong, Thérèse; Massuger, Leon F A G; Benitez, Javier; Pejovic, Tanja; Perez, Jose Ignacio Arias; Hoatlin, Maureen; Zamora, M Pilar; Cook, Linda S; Balasubramanian, Sabapathy P; Kelemen, Linda E; Schneeweiss, Andreas; Le, Nhu D; Sohn, Christof; Brooks-Wilson, Angela; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Cybulski, Cezary; Henderson, Brian E; Menkiszak, Janusz; Schumacher, Fredrick; Wentzensen, Nicolas; Marchand, Loic Le; Yang, Hannah P; Mulligan, Anna Marie; Glendon, Gord; Engelholm, Svend Aage; Knight, Julia A; Høgdall, Claus K; Apicella, Carmel; Gore, Martin; Tsimiklis, Helen; Song, Honglin; Southey, Melissa C; Jager, Agnes; van den Ouweland, Ans M W; Brown, Robert; Martens, John W M; Flanagan, James M; Kriege, Mieke; Paul, James; Margolin, Sara; Siddiqui, Nadeem; Severi, Gianluca; Whittemore, Alice S; Baglietto, Laura; McGuire, Valerie; Stegmaier, Christa; Sieh, Weiva; Müller, Heiko; Arndt, Volker; Labrèche, France; Gao, Yu-Tang; Goldberg, Mark S; Yang, Gong; Dumont, Martine; McLaughlin, John R; Hartmann, Arndt; Ekici, Arif B; Beckmann, Matthias W; Phelan, Catherine M; Lux, Michael P; Permuth-Wey, Jenny; Peissel, Bernard; Sellers, Thomas A; Ficarazzi, Filomena; Barile, Monica; Ziogas, Argyrios; Ashworth, Alan; Gentry-Maharaj, Aleksandra; Jones, Michael; Ramus, Susan J; Orr, Nick; Menon, Usha; Pearce, Celeste L; Brüning, Thomas; Pike, Malcolm C; Ko, Yon-Dschun; Lissowska, Jolanta; Figueroa, Jonine; Kupryjanczyk, Jolanta; Chanock, Stephen J; Dansonka-Mieszkowska, Agnieszka; Jukkola-Vuorinen, Arja; Rzepecka, Iwona K; Pylkäs, Katri; Bidzinski, Mariusz; Kauppila, Saila; Hollestelle, Antoinette; Seynaeve, Caroline; Tollenaar, Rob A E M; Durda, Katarzyna; Jaworska, Katarzyna; Hartikainen, Jaana M; Kosma, Veli-Matti; Kataja, Vesa; Antonenkova, Natalia N; Long, Jirong; Shrubsole, Martha; Deming-Halverson, Sandra; Lophatananon, Artitaya; Siriwanarangsan, Pornthep; Stewart-Brown, Sarah; Ditsch, Nina; Lichtner, Peter; Schmutzler, Rita K; Ito, Hidemi; Iwata, Hiroji; Tajima, Kazuo; Tseng, Chiu-Chen; Stram, Daniel O; van den Berg, David; Yip, Cheng Har; Ikram, M Kamran; Teh, Yew-Ching; Cai, Hui; Lu, Wei; Signorello, Lisa B; Cai, Qiuyin; Noh, Dong-Young; Yoo, Keun-Young; Miao, Hui; Iau, Philip Tsau-Choong; Teo, Yik Ying; McKay, James; Shapiro, Charles; Ademuyiwa, Foluso; Fountzilas, George; Hsiung, Chia-Ni; Yu, Jyh-Cherng; Hou, Ming-Feng; Healey, Catherine S; Luccarini, Craig; Peock, Susan; Stoppa-Lyonnet, Dominique; Peterlongo, Paolo; Rebbeck, Timothy R; Piedmonte, Marion; Singer, Christian F; Friedman, Eitan; Thomassen, Mads; Offit, Kenneth; Hansen, Thomas V O; Neuhausen, Susan L; Szabo, Csilla I; Blanco, Ignacio; Garber, Judy; Narod, Steven A; Weitzel, Jeffrey N; Montagna, Marco; Olah, Edith; Godwin, Andrew K; Yannoukakos, Drakoulis; Goldgar, David E; Caldes, Trinidad; Imyanitov, Evgeny N; Tihomirova, Laima; Arun, Banu K; Campbell, Ian; Mensenkamp, Arjen R; van Asperen, Christi J; van Roozendaal, Kees E P; Meijers-Heijboer, Hanne; Collée, J Margriet; Oosterwijk, Jan C; Hooning, Maartje J; Rookus, Matti A; van der Luijt, Rob B; van Os, Theo A M; Evans, D Gareth; Frost, Debra; Fineberg, Elena; Barwell, Julian; Walker, Lisa; Kennedy, M John; Platte, Radka; Davidson, Rosemarie; Ellis, Steve D; Cole, Trevor; Paillerets, Brigitte Bressac-de; Buecher, Bruno; Damiola, Francesca; Faivre, Laurence; Frenay, Marc; Sinilnikova, Olga M; Caron, Olivier; Giraud, Sophie; Mazoyer, Sylvie; Bonadona, Valérie; Caux-Moncoutier, Virginie; Toloczko-Grabarek, Aleksandra; Gronwald, Jacek; Byrski, Tomasz; Spurdle, Amanda B; Bonanni, Bernardo; Zaffaroni, Daniela; Giannini, Giuseppe; Bernard, Loris; Dolcetti, Riccardo; Manoukian, Siranoush; Arnold, Norbert; Engel, Christoph; Deissler, Helmut; Rhiem, Kerstin; Niederacher, Dieter; Plendl, Hansjoerg; Sutter, Christian; Wappenschmidt, Barbara; Borg, Åke; Melin, Beatrice; Rantala, Johanna; Soller, Maria; Nathanson, Katherine L; Domchek, Susan M; Rodriguez, Gustavo C; Salani, Ritu; Kaulich, Daphne Gschwantler; Tea, Muy-Kheng; Paluch, Shani Shimon; Laitman, Yael; Skytte, Anne-Bine; Kruse, Torben A; Jensen, Uffe Birk; Robson, Mark; Gerdes, Anne-Marie; Ejlertsen, Bent; Foretova, Lenka; Savage, Sharon A; Lester, Jenny; Soucy, Penny; Kuchenbaecker, Karoline B; Olswold, Curtis; Cunningham, Julie M; Slager, Susan; Pankratz, Vernon S; Dicks, Ed; Lakhani, Sunil R; Couch, Fergus J; Hall, Per; Monteiro, Alvaro N A; Gayther, Simon A; Pharoah, Paul D P; Reddel, Roger R; Goode, Ellen L; Greene, Mark H; Easton, Douglas F; Berchuck, Andrew; Antoniou, Antonis C; Chenevix-Trench, Georgia; Dunning, Alison M

    2013-01-01

    TERT-locus single nucleotide polymorphisms (SNPs) and leucocyte telomere measures are reportedly associated with risks of multiple cancers. Using the iCOGs chip, we analysed ~480 TERT-locus SNPs in breast (n=103,991), ovarian (n=39,774) and BRCA1 mutation carrier (11,705) cancer cases and controls. 53,724 participants have leucocyte telomere measures. Most associations cluster into three independent peaks. Peak 1 SNP rs2736108 minor allele associates with longer telomeres (P=5.8×10−7), reduced estrogen receptor negative (ER-negative) (P=1.0×10−8) and BRCA1 mutation carrier (P=1.1×10−5) breast cancer risks, and altered promoter-assay signal. Peak 2 SNP rs7705526 minor allele associates with longer telomeres (P=2.3×10−14), increased low malignant potential ovarian cancer risk (P=1.3×10−15) and increased promoter activity. Peak 3 SNPs rs10069690 and rs2242652 minor alleles increase ER-negative (P=1.2×10−12) and BRCA1 mutation carrier (P=1.6×10−14) breast and invasive ovarian (P=1.3×10−11) cancer risks, but not via altered telomere length. The cancer-risk alleles of rs2242652 and rs10069690 respectively increase silencing and generate a truncated TERT splice-variant. PMID:23535731

  19. A novel third chromosomal locus controls susceptibility to Autographa californica multiple nucleopolyhedrovirus in the silkworm, Bombyx mori.

    PubMed

    Xu, Jian; Kusakabe, Takahiro; Yamamoto, Kimiko; Suetsugu, Yoshitaka; Mon, Hiroaki; Li, Zhiqing; Zhu, Li; Iiyama, Kazuhiro; Banno, Yutaka; Yoshimura, Kaito; Lee, Jae Man

    2014-04-01

    Baculovirus demonstrates specific infection spectrums and thus one certain host exhibits particular response to single baculovirus isolate. Autographa californica multiple nucleopolyhedrovirus (AcMNPV) is considered to be not an innate pathogen to Bombyx mori, but some silkworm strains have been identified to be permissive to AcMNPV, indicating the positive or negative involvement of certain host factors in baculovirus replications in vivo. To provide a fundamental knowledge of this process, we performed large-scale screening to investigate the responses of 448 silkworm strains against recombinant AcMNPV inoculation. By genetic analysis between permissive and resistant strains identified, we further confirmed that a potential corresponding locus on chromosome 3 regulates host responses to AcMNPV in silkworm. Additionally, we found that it is available for AcMNPV-silkworm baculovirus expression vector system to produce proteins of interest.

  20. Fine mapping reveals that promotion susceptibility locus 1 (Psl1) is a compound locus with multiple genes that modify susceptibility to skin tumor development.

    PubMed

    Angel, Joe M; Abel, Erika L; Riggs, Penny K; McClellan, S Alex; DiGiovanni, John

    2014-04-03

    Although it is well known that the majority of human cancers occur as the result of exposure to environmental carcinogens, it is clear that not all individuals exposed to a specific environmental carcinogen have the same risk of developing cancer. Considerable evidence indicates that common allelic variants of low-penetrance, tumor susceptibility genes are responsible for this interindividual variation in risk. We previously reported a skin tumor promotion susceptibility locus, Psl1, which maps to the distal portion of chromosome 9, that modified skin tumor promotion susceptibility in the mouse. Furthermore, Psl1 was shown to consist of at least two subloci (i.e., Psl1.1 and Psl1.2) and that glutathione S-transferase alpha 4 (Gsta4), which maps to Psl1.2, is a skin tumor promotion susceptibility gene. Finally, variants of human GSTA4 were found to be associated with risk of nonmelanoma skin cancer. In the current study, a combination of nested and contiguous C57BL/6 congenic mouse strains, each inheriting a different portion of the Psl1 locus from DBA/2, were tested for susceptibility to skin tumor promotion with 12-O-tetradecanoylphorbol-13-acetate. These analyses indicate that Psl1 is a compound locus with at least six genes, including Gsta4, that modify skin tumor promotion susceptibility. More than 550 protein-coding genes map within the Psl1 locus. Fine mapping of the Psl1 locus, along with two-strain haplotype analysis, gene expression analysis, and the identification of genes with amino acid variants, has produced a list of fewer than 25 candidate skin tumor promotion susceptibility genes.

  1. Production of Multiple Bacteriocins from a Single Locus by Gastrointestinal Strains of Lactobacillus salivarius▿

    PubMed Central

    O'Shea, Eileen F.; O'Connor, Paula M.; Raftis, Emma J.; O'Toole, Paul W.; Stanton, Catherine; Cotter, Paul D.; Ross, R. Paul; Hill, Colin

    2011-01-01

    Bacteriocins produced by Lactobacillus salivarius isolates derived from a gastrointestinal origin have previously demonstrated efficacy for in vivo protection against Listeria monocytogenes infection. In this study, comparative genomic analysis was employed to investigate the intraspecies diversity of seven L. salivarius isolates of human and porcine intestinal origin, based on the genome of the well-characterized bacteriocin-producing strain L. salivarius UCC118. This revealed a highly conserved megaplasmid-borne gene cluster in these strains involved in the regulation and secretion of two-component class IIb bacteriocins. However, considerable intraspecific variation was observed in the structural genes encoding the bacteriocin peptides. They ranged from close relatives of abp118, such as salivaricin P, which differs by 2 amino acids, to completely novel bacteriocins, such as salivaricin T, which is characterized in this study. Salivaricin T inhibits closely related lactobacilli and bears little homology to previously characterized salivaricins. Interestingly, the two peptides responsible for salivaricin T activity, SalTα and SalTβ, share considerable identity with the component peptides of thermophilin 13, a bacteriocin produced by Streptococcus thermophilus. Furthermore, the salivaricin locus of strain DPC6488 also encodes an additional novel one-component class IId anti-listerial bacteriocin, salivaricin L. These findings suggest a high level of redundancy in the bacteriocins that can be produced by intestinal L. salivarius isolates using the same enzymatic production and export machinery. Such diversity may contribute to their ability to dominate and compete within the complex microbiota of the mammalian gut. PMID:21984788

  2. Production of multiple bacteriocins from a single locus by gastrointestinal strains of Lactobacillus salivarius.

    PubMed

    O'Shea, Eileen F; O'Connor, Paula M; Raftis, Emma J; O'Toole, Paul W; Stanton, Catherine; Cotter, Paul D; Ross, R Paul; Hill, Colin

    2011-12-01

    Bacteriocins produced by Lactobacillus salivarius isolates derived from a gastrointestinal origin have previously demonstrated efficacy for in vivo protection against Listeria monocytogenes infection. In this study, comparative genomic analysis was employed to investigate the intraspecies diversity of seven L. salivarius isolates of human and porcine intestinal origin, based on the genome of the well-characterized bacteriocin-producing strain L. salivarius UCC118. This revealed a highly conserved megaplasmid-borne gene cluster in these strains involved in the regulation and secretion of two-component class IIb bacteriocins. However, considerable intraspecific variation was observed in the structural genes encoding the bacteriocin peptides. They ranged from close relatives of abp118, such as salivaricin P, which differs by 2 amino acids, to completely novel bacteriocins, such as salivaricin T, which is characterized in this study. Salivaricin T inhibits closely related lactobacilli and bears little homology to previously characterized salivaricins. Interestingly, the two peptides responsible for salivaricin T activity, SalTα and SalTβ, share considerable identity with the component peptides of thermophilin 13, a bacteriocin produced by Streptococcus thermophilus. Furthermore, the salivaricin locus of strain DPC6488 also encodes an additional novel one-component class IId anti-listerial bacteriocin, salivaricin L. These findings suggest a high level of redundancy in the bacteriocins that can be produced by intestinal L. salivarius isolates using the same enzymatic production and export machinery. Such diversity may contribute to their ability to dominate and compete within the complex microbiota of the mammalian gut.

  3. Multiple-Locus Departures from Panmictic Equilibrium within and between Village Gene Pools of Amerindian Tribes at Different Stages of Agglomeration

    PubMed Central

    Smouse, Peter E.; Neel, James V.; Liu, Wanda

    1983-01-01

    A comparative analysis of departures from multiple-locus Hardy-Weinberg equilibrium is presented for a set of four tribal Indian groups (the Yanomama, Makiritare, Wapishana and Ticuna) from the lowlands of South America. These tribes span a range of agglomeration and acculturation from the most traditional, swidden horticulturalists to frontier townspeople. The small-group social organization typical of traditional horticulturalists leads to substantial departures from tribal panmixia, as manifested by the distribution of multiple-locus genotypes both within and between villages. Within villages, the departures from single-locus Hardy-Weinberg equilibrium are small and nonsignificant, but the departures from gametic equilibrium (independence of loci) are substantial, even for the unlinked loci we have used to characterize these populations. The departures from single-locus homogeneity across villages are also substantial. One of the normal concomitants of increasing acculturation in this setting is an increase in agglomeration. As agglomeration increases, the departures from multiple-locus panmixia decrease, a process that can be very rapid. We discuss both the shifting balance theory of evolution and punctuated evolutionary rates in light of the small group social organization that must have obtained throughout most of human evolution. PMID:6862182

  4. Multiple myeloma: patient outcomes in real-world practice.

    PubMed

    Yong, Kwee; Delforge, Michel; Driessen, Christoph; Fink, Leah; Flinois, Alain; Gonzalez-McQuire, Sebastian; Safaei, Reza; Karlin, Lionel; Mateos, Maria-Victoria; Raab, Marc S; Schoen, Paul; Cavo, Michele

    2016-10-01

    With increasing number of therapies available for the treatment of multiple myeloma, it is timely to examine the course of patients' journeys. We investigated patient characteristics, treatment durations and outcomes, and symptom burden across the treatment pathway in Belgium, France, Germany, Italy, Spain, Switzerland and the UK. In total, 435 physicians retrospectively reviewed 4997 patient charts. Profiles of patients diagnosed with multiple myeloma during the last 12 months were similar across countries; bone pain was the most common presentation. Median duration of first-line therapy was 6 months, followed by a median treatment-free interval of 10 months; both these decreased with increasing lines of therapy, as did time to progression. Depth of response, as assessed by the treating physician, also decreased with each additional line of therapy: 74% of patients achieved at least a very good partial response at first line, compared with only 11% at fifth line. Deeper responses were associated with longer time to progression, although these were physician-judged. Toxicities and co-morbidities increased with later treatment lines, and were more likely to have led to discontinuation of treatment. These real-world data provide an insight into patient outcomes and treatment decisions being made in clinical practice. © 2016 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

  5. Month of birth, HLA-DRB1*15 locus and risk of multiple sclerosis in offspring.

    PubMed

    Guijarro-Castro, C; Sanchez-Zapardiel, E; Munoz, D; Fernandez, O; Leyva, L; Castro-Panete, M J; Picon-Munoz, C; Talise, M; Martinez-Feito, A; Paz-Artal, E

    2016-09-01

    Introduccion. El haplotipo HLA-DRB1*1501 es el marcador genetico que se ha asociado con un riesgo tres veces mayor de padecer esclerosis multiple (EM) en caucasicos occidentales. Recientemente se ha sabido que hay una asociacion entre el mes de nacimiento en abril, el genotipo HLA-DRB1 y el riesgo de EM en paises del norte de Europa y Canada. Esto apoya la teoria de que debe haber una interaccion entre un factor de riesgo estacional con un locus cercano al HLA-DRB1*15 durante la gestacion o cerca del posparto. Sujetos y metodos. Se realizo el genotipado de la presencia y subtipo de HLA-DRB1*1501 en 326 pacientes de dos centros espa˜oles y en 226 controles sin patologia neurologica. Se compararon los meses de nacimiento de la muestra de pacientes con los nacimientos mensuales locales en los mismos periodos. Resultados. Comparados los pacientes con EM que eran portadores del alelo HLA-DRB1*15 (10,3%) frente a los pacientes no portadores (3,8%), significativamente mas pacientes nacian en diciembre (p = 0,0185). Tambien se confirmaba el mismo mes de nacimiento de diciembre entre sanos portadores frente a no portadores de HLA-DRB1*15 y entre pacientes portadores de HLA-DRB1*15 frente a sanos. Conclusiones. El mes de nacimiento, el genotipo HLA-DRB1*15 y el riesgo de presentar EM estan asociados. A diferencia de los resultados obtenidos en paises del norte de Europa, donde esta asociacion se ha encontrado en el mes de abril, en Espa˜a es en diciembre. Se demuestra la interaccion de un factor de riesgo estacional en invierno en el locus HLA-DRB1*15 o cercano a este durante la gestacion o tras el nacimiento.

  6. Fine mapping of a multiple sclerosis locus to 2.5 Mb on chromosome 17q22-q24.

    PubMed

    Saarela, Janna; Schoenberg Fejzo, Marlena; Chen, Daniel; Finnilä, Saara; Parkkonen, Maikki; Kuokkanen, Satu; Sobel, Eric; Tienari, Pentti J; Sumelahti, Marja-Liisa; Wikström, Juhani; Elovaara, Irina; Koivisto, Keijo; Pirttilä, Tuula; Reunanen, Mauri; Palotie, Aarno; Peltonen, Leena

    2002-09-15

    Genome-wide linkage analyses performed in a Finnish study sample have identified four potential predisposing loci for multiple sclerosis (MS). Here we made an effort to restrict the wide linkage region on chromosome 17 with a dense set of 31 markers using multipoint linkage analyses and monitoring for shared marker alleles in MS chromosomes. We carried out the linkage analyses in 22 Finnish multiplex MS families originating from a regional subisolate that shows an exceptionally high prevalence of MS in order to minimize the genetic and environmental heterogeneity of the study sample. Thirty markers on the 23 cM initial interval gave positive pairwise LOD scores. We monitored for shared haplotypes among affected family members within a family, and identified an approximately 4 cM region flanked by the markers D17S1792 and ATA43A10 in 17 out of the 22 families (77.3%). The multipoint linkage analyses using Genehunter and SIMWALK 2.40 provided further evidence for the same 4 cM region, for example a maximal multipoint NPL score of 5.98 (P<0.0002). We observed nominal evidence for association to MS, with one marker flanking the shared region, and this association was replicated in the additional set of families. Using the combined power of linkage, association and shared haplotype analyses, we were thus able to restrict the MS locus on chromosome 17q from 23 cM to a 4 cM region covering a physical interval of approximately 2.5 Mb. Thus, this study describes the restriction of an MS locus outside the HLA region into a segment approachable by molecular tools.

  7. Multiple-Locus Variable-Number Tandem-Repeat Analysis Is a Suitable Tool for Differentiation of Mycoplasma hyopneumoniae Strains without Cultivation▿

    PubMed Central

    Vranckx, K.; Maes, D.; Calus, D.; Villarreal, I.; Pasmans, F.; Haesebrouck, F.

    2011-01-01

    An assay based on multiple-locus variable-number tandem-repeat analysis allowed differentiating and studying diversity and persistence of Mycoplasma hyopneumoniae strains in pig herds without prior cultivation. The test had a discriminatory index of >0.99 and was applied reliably to porcine bronchoalveolar lavage fluid and tracheal swabs. PMID:21389157

  8. Quality of life, treatment adherence, and locus of control: multiple family groups for chronic medical illnesses.

    PubMed

    López-Larrosa, Silvia

    2013-12-01

    The Multiple Family Groups (MFGs) approach for patients with a chronic medical illness and their families is a structured psychoeducational program that unfolds in six weekly 90-minute sessions. In the MFGs, patients and family members explore new ways to balance illness and nonillness priorities in family life (Steinglass, 1998; Steinglass, 2000 Cuadernos de Terapia Familiar, 44-45, 11; Steinglass, Ostroff, & Steinglass, 2011 Family Process, 50, 393).

  9. Real-time multi-mode neutron multiplicity counter

    DOEpatents

    Rowland, Mark S; Alvarez, Raymond A

    2013-02-26

    Embodiments are directed to a digital data acquisition method that collects data regarding nuclear fission at high rates and performs real-time preprocessing of large volumes of data into directly useable forms for use in a system that performs non-destructive assaying of nuclear material and assemblies for mass and multiplication of special nuclear material (SNM). Pulses from a multi-detector array are fed in parallel to individual inputs that are tied to individual bits in a digital word. Data is collected by loading a word at the individual bit level in parallel, to reduce the latency associated with current shift-register systems. The word is read at regular intervals, all bits simultaneously, with no manipulation. The word is passed to a number of storage locations for subsequent processing, thereby removing the front-end problem of pulse pileup. The word is used simultaneously in several internal processing schemes that assemble the data in a number of more directly useable forms. The detector includes a multi-mode counter that executes a number of different count algorithms in parallel to determine different attributes of the count data.

  10. Arabidopsis TOBAMOVIRUS MULTIPLICATION (TOM) 2 locus encodes a transmembrane protein that interacts with TOM1.

    PubMed

    Tsujimoto, Yayoi; Numaga, Takuro; Ohshima, Kiyoshi; Yano, Masa-Aki; Ohsawa, Ryuji; Goto, Derek B; Naito, Satoshi; Ishikawa, Masayuki

    2003-01-15

    The tom2-1 mutation of Arabidopsis thaliana reduces the efficiency of intracellular multiplication of tobamoviruses. The tom2-1 mutant was derived from fast-neutron-irradiated seeds, and the original mutant line also carries ttm1, a dominant modifier that increases tobamovirus multiplication efficiency in a tobamovirus-strain-specific manner in the tom2-1 genetic background. Here, we show that the tom2-1 mutation involved a deletion of approximately 20 kb in the nuclear genome. The deleted region included two genes named TOM2A and TOM2B that were both associated with the tom2-1 phenotype, whereas ttm1 corresponded to the translocation of part of the deleted region that included intact TOM2B but not TOM2A. TOM2A encodes a 280 amino acid putative four-pass transmembrane protein with a C-terminal farnesylation signal, while TOM2B encodes a 122 amino acid basic protein. The split-ubiquitin assay demonstrated an interaction of TOM2A both with itself and with TOM1, an integral membrane protein of A.thaliana presumed to be an essential constituent of tobamovirus replication complex. The data presented here suggest that TOM2A is also an integral part of the tobamovirus replication complex.

  11. Evaluating real-time immunohistochemistry on multiple tissue samples, multiple targets and multiple antibody labeling methods

    PubMed Central

    2013-01-01

    Background Immunohistochemistry (IHC) is a well-established method for the analysis of protein expression in tissue specimens and constitutes one of the most common methods performed in pathology laboratories worldwide. However, IHC is a multi-layered method based on subjective estimations and differences in staining and interpretation has been observed between facilities, suggesting that the analysis of proteins on tissue would benefit from protocol optimization and standardization. Here we describe how the emerging and operator independent tool of real-time immunohistochemistry (RT-IHC) reveals a time resolved description of antibody interacting with target protein in formalin fixed paraffin embedded tissue. The aim was to understand the technical aspects of RT-IHC, regarding generalization of the concept and to what extent it can be considered a quantitative method. Results Three different antibodies labeled with fluorescent or radioactive labels were applied on nine different tissue samples from either human or mouse, and the results for all RT-IHC analyses distinctly show that the method is generally applicable. The collected binding curves showed that the majority of the antibody-antigen interactions did not reach equilibrium within 3 hours, suggesting that standardized protocols for immunohistochemistry are sometimes inadequately optimized. The impact of tissue size and thickness as well as the position of the section on the glass petri dish was assessed in order for practical details to be further elucidated for this emerging technique. Size and location was found to affect signal magnitude to a larger extent than thickness, but the signal from all measurements were still sufficient to trace the curvature. The curvature, representing the kinetics of the interaction, was independent of thickness, size and position and may be a promising parameter for the evaluation of e.g. biopsy sections of different sizes. Conclusions It was found that RT-IHC can be used

  12. Evaluating real-time immunohistochemistry on multiple tissue samples, multiple targets and multiple antibody labeling methods.

    PubMed

    Dubois, Louise; Andersson, Karl; Asplund, Anna; Björkelund, Hanna

    2013-12-18

    Immunohistochemistry (IHC) is a well-established method for the analysis of protein expression in tissue specimens and constitutes one of the most common methods performed in pathology laboratories worldwide. However, IHC is a multi-layered method based on subjective estimations and differences in staining and interpretation has been observed between facilities, suggesting that the analysis of proteins on tissue would benefit from protocol optimization and standardization. Here we describe how the emerging and operator independent tool of real-time immunohistochemistry (RT-IHC) reveals a time resolved description of antibody interacting with target protein in formalin fixed paraffin embedded tissue. The aim was to understand the technical aspects of RT-IHC, regarding generalization of the concept and to what extent it can be considered a quantitative method. Three different antibodies labeled with fluorescent or radioactive labels were applied on nine different tissue samples from either human or mouse, and the results for all RT-IHC analyses distinctly show that the method is generally applicable. The collected binding curves showed that the majority of the antibody-antigen interactions did not reach equilibrium within 3 hours, suggesting that standardized protocols for immunohistochemistry are sometimes inadequately optimized. The impact of tissue size and thickness as well as the position of the section on the glass petri dish was assessed in order for practical details to be further elucidated for this emerging technique. Size and location was found to affect signal magnitude to a larger extent than thickness, but the signal from all measurements were still sufficient to trace the curvature. The curvature, representing the kinetics of the interaction, was independent of thickness, size and position and may be a promising parameter for the evaluation of e.g. biopsy sections of different sizes. It was found that RT-IHC can be used for the evaluation of a number

  13. Determination of Sources of Escherichia coli on Beef by Multiple-Locus Variable-Number Tandem Repeat Analysis.

    PubMed

    Yang, Xianqin; Tran, Frances; Youssef, Mohamed K; Gill, Colin O

    2015-07-01

    The possible origin of Escherichia coli found on cuts and trimmings in the breaking facility of a beef packing plant was examined using multiple-locus variable-number tandem repeat analysis. Coliforms and E. coli were enumerated in samples obtained from 160 carcasses that would enter the breaking facility when work commenced and after each of the three production breaks throughout the day, from the conveyor belt before work and after each break, and from cuts and trimmings when work commenced and after each break. Most samples yielded no E. coli, irrespective of the surface types. E. coli was recovered from 7 (<5%) carcasses, at numbers mostly ≤1.0 log CFU/160,000 cm(2). The log total numbers of E. coli recovered from the conveyor belt, cuts, and trimmings were mostly between 1 and 2 log CFU/80,000 cm(2). A total of 554 E. coli isolates were recovered. Multiple-locus variable-number tandem repeat analysis of 327 selected isolates identified 80 distinct genotypes, with 37 (46%) each containing one isolate. However, 28% of the isolates were of genotypes that were recovered from more than one sampling day. Of the 80 genotypes, 65 and 2% were found in one or all four sampling periods throughout the day. However, they represented 23 and 14% of the isolates, respectively. Of the genotypes identified for each surface type, at least one contained ≥9 isolates. No unique genotypes were associated with carcasses, but 10, 17, and 19 were uniquely associated with cuts, trimmings, and the belt, respectively. Of the isolates recovered from cuts, 49, 3, and 19% were of genotypes that were found among isolates recovered from the belt, carcasses, or both the belt and carcasses, respectively. A similar composition was found for isolates recovered from trimmings. These findings show that the E. coli found on cuts and trimmings at this beef packing plant mainly originated from the conveyor belt and that small number of E. coli strains survived the daily cleaning and sanitation

  14. Prostate cancer risk locus at 8q24 as a regulatory hub by physical interactions with multiple genomic loci across the genome.

    PubMed

    Du, Meijun; Yuan, Tiezheng; Schilter, Kala F; Dittmar, Rachel L; Mackinnon, Alexander; Huang, Xiaoyi; Tschannen, Michael; Worthey, Elizabeth; Jacob, Howard; Xia, Shu; Gao, Jianzhong; Tillmans, Lori; Lu, Yan; Liu, Pengyuan; Thibodeau, Stephen N; Wang, Liang

    2015-01-01

    Chromosome 8q24 locus contains regulatory variants that modulate genetic risk to various cancers including prostate cancer (PC). However, the biological mechanism underlying this regulation is not well understood. Here, we developed a chromosome conformation capture (3C)-based multi-target sequencing technology and systematically examined three PC risk regions at the 8q24 locus and their potential regulatory targets across human genome in six cell lines. We observed frequent physical contacts of this risk locus with multiple genomic regions, in particular, inter-chromosomal interaction with CD96 at 3q13 and intra-chromosomal interaction with MYC at 8q24. We identified at least five interaction hot spots within the predicted functional regulatory elements at the 8q24 risk locus. We also found intra-chromosomal interaction genes PVT1, FAM84B and GSDMC and inter-chromosomal interaction gene CXorf36 in most of the six cell lines. Other gene regions appeared to be cell line-specific, such as RRP12 in LNCaP, USP14 in DU-145 and SMIN3 in lymphoblastoid cell line. We further found that the 8q24 functional domains more likely interacted with genomic regions containing genes enriched in critical pathways such as Wnt signaling and promoter motifs such as E2F1 and TCF3. This result suggests that the risk locus may function as a regulatory hub by physical interactions with multiple genes important for prostate carcinogenesis. Further understanding genetic effect and biological mechanism of these chromatin interactions will shed light on the newly discovered regulatory role of the risk locus in PC etiology and progression.

  15. High Throughput Multiple Locus Variable Number of Tandem Repeat Analysis (MLVA) of Staphylococcus aureus from Human, Animal and Food Sources

    PubMed Central

    Sobral, Daniel; Schwarz, Stefan; Bergonier, Dominique; Brisabois, Anne; Feßler, Andrea T.; Gilbert, Florence B.; Kadlec, Kristina; Lebeau, Benoit; Loisy-Hamon, Fabienne; Treilles, Michaël; Pourcel, Christine; Vergnaud, Gilles

    2012-01-01

    Staphylococcus aureus is a major human pathogen, a relevant pathogen in veterinary medicine, and a major cause of food poisoning. Epidemiological investigation tools are needed to establish surveillance of S. aureus strains in humans, animals and food. In this study, we investigated 145 S. aureus isolates recovered from various animal species, disease conditions, food products and food poisoning events. Multiple Locus Variable Number of Tandem Repeat (VNTR) analysis (MLVA), known to be highly efficient for the genotyping of human S. aureus isolates, was used and shown to be equally well suited for the typing of animal S. aureus isolates. MLVA was improved by using sixteen VNTR loci amplified in two multiplex PCRs and analyzed by capillary electrophoresis ensuring a high throughput and high discriminatory power. The isolates were assigned to twelve known clonal complexes (CCs) and –a few singletons. Half of the test collection belonged to four CCs (CC9, CC97, CC133, CC398) previously described as mostly associated with animals. The remaining eight CCs (CC1, CC5, CC8, CC15, CC25, CC30, CC45, CC51), representing 46% of the animal isolates, are common in humans. Interestingly, isolates responsible for food poisoning show a CC distribution signature typical of human isolates and strikingly different from animal isolates, suggesting a predominantly human origin. PMID:22567085

  16. Multiple-Locus Variable-Number Tandem-Repeat Analysis in Genotyping Yersinia enterocolitica Strains from Human and Porcine Origins

    PubMed Central

    Laukkanen-Ninios, R.; Ortiz Martínez, P.; Siitonen, A.; Fredriksson-Ahomaa, M.; Korkeala, H.

    2013-01-01

    Sporadic and epidemiologically linked Yersinia enterocolitica strains (n = 379) isolated from fecal samples from human patients, tonsil or fecal samples from pigs collected at slaughterhouses, and pork samples collected at meat stores were genotyped using multiple-locus variable-number tandem-repeat analysis (MLVA) with six loci, i.e., V2A, V4, V5, V6, V7, and V9. In total, 312 different MLVA types were found. Similar types were detected (i) in fecal samples collected from human patients over 2 to 3 consecutive years, (ii) in samples from humans and pigs, and (iii) in samples from pigs that originated from the same farms. Among porcine strains, we found farm-specific MLVA profiles. Variations in the numbers of tandem repeats from one to four for variable-number tandem-repeat (VNTR) loci V2A, V5, V6, and V7 were observed within a farm. MLVA was applicable for serotypes O:3, O:5,27, and O:9 and appeared to be a highly discriminating tool for distinguishing sporadic and outbreak-related strains. With long-term use, interpretation of the results became more challenging due to variations in more-discriminating loci, as was observed for strains originating from pig farms. Additionally, we encountered unexpectedly short V2A VNTR fragments and sequenced them. According to the sequencing results, updated guidelines for interpreting V2A VNTR results were prepared. PMID:23637293

  17. Multiple-locus variable-number tandem-repeat analysis in genotyping Yersinia enterocolitica strains from human and porcine origins.

    PubMed

    Virtanen, S; Laukkanen-Ninios, R; Ortiz Martínez, P; Siitonen, A; Fredriksson-Ahomaa, M; Korkeala, H

    2013-07-01

    Sporadic and epidemiologically linked Yersinia enterocolitica strains (n = 379) isolated from fecal samples from human patients, tonsil or fecal samples from pigs collected at slaughterhouses, and pork samples collected at meat stores were genotyped using multiple-locus variable-number tandem-repeat analysis (MLVA) with six loci, i.e., V2A, V4, V5, V6, V7, and V9. In total, 312 different MLVA types were found. Similar types were detected (i) in fecal samples collected from human patients over 2 to 3 consecutive years, (ii) in samples from humans and pigs, and (iii) in samples from pigs that originated from the same farms. Among porcine strains, we found farm-specific MLVA profiles. Variations in the numbers of tandem repeats from one to four for variable-number tandem-repeat (VNTR) loci V2A, V5, V6, and V7 were observed within a farm. MLVA was applicable for serotypes O:3, O:5,27, and O:9 and appeared to be a highly discriminating tool for distinguishing sporadic and outbreak-related strains. With long-term use, interpretation of the results became more challenging due to variations in more-discriminating loci, as was observed for strains originating from pig farms. Additionally, we encountered unexpectedly short V2A VNTR fragments and sequenced them. According to the sequencing results, updated guidelines for interpreting V2A VNTR results were prepared.

  18. Molecular typing of Argentinian Mycobacterium avium subsp. paratuberculosis isolates by multiple-locus variable number-tandem repeat analysis.

    PubMed

    Gioffré, Andrea; Correa Muñoz, Magnolia; Alvarado Pinedo, María F; Vaca, Roberto; Morsella, Claudia; Fiorentino, María Andrea; Paolicchi, Fernando; Ruybal, Paula; Zumárraga, Martín; Travería, Gabriel E; Romano, María Isabel

    2015-06-01

    Multiple-locus variable number-tandem repeat analysis (MLVA) of Mycobacterium avium subspecies paratuberculosis (MAP) isolates may contribute to the knowledge of strain diversity in Argentina. Although the diversity of MAP has been previously investigated in Argentina using IS900-RFLP, a small number of isolates were employed, and a low discriminative power was reached. The aim of the present study was to test the genetic diversity among MAP isolates using an MLVA approach based on 8 repetitive loci. We studied 97 isolates from cattle, goat and sheep and could describe 7 different patterns: INMV1, INMV2, INMV11, INMV13, INMV16, INMV33 and one incomplete pattern. INMV1 and INMV2 were the most frequent patterns, grouping 76.3% of the isolates. We were also able to demonstrate the coexistence of genotypes in herds and co-infection at the organism level. This study shows that all the patterns described are common to those described in Europe, suggesting an epidemiological link between the continents.

  19. Molecular typing of Argentinian Mycobacterium avium subsp. paratuberculosis isolates by multiple-locus variable number-tandem repeat analysis

    PubMed Central

    Gioffré, Andrea; Correa Muñoz, Magnolia; Alvarado Pinedo, María F.; Vaca, Roberto; Morsella, Claudia; Fiorentino, María Andrea; Paolicchi, Fernando; Ruybal, Paula; Zumárraga, Martín; Travería, Gabriel E.; Romano, María Isabel

    2015-01-01

    Multiple-locus variable number-tandem repeat analysis (MLVA) of Mycobacterium avium subspecies paratuberculosis (MAP) isolates may contribute to the knowledge of strain diversity in Argentina. Although the diversity of MAP has been previously investigated in Argentina using IS900-RFLP, a small number of isolates were employed, and a low discriminative power was reached. The aim of the present study was to test the genetic diversity among MAP isolates using an MLVA approach based on 8 repetitive loci. We studied 97 isolates from cattle, goat and sheep and could describe 7 different patterns: INMV1, INMV2, INMV11, INMV13, INMV16, INMV33 and one incomplete pattern. INMV1 and INMV2 were the most frequent patterns, grouping 76.3% of the isolates. We were also able to demonstrate the coexistence of genotypes in herds and co-infection at the organism level. This study shows that all the patterns described are common to those described in Europe, suggesting an epidemiological link between the continents. PMID:26273274

  20. Polymorphic locus rs10492972 of the KIF1B gene association with multiple sclerosis in Russia: case control study.

    PubMed

    Kudryavtseva, Ekaterina A; Rozhdestvenskii, Aleksei S; Kakulya, Anastasia V; Khanokh, Elena V; Delov, Roman A; Malkova, Nadezhda A; Korobko, Denis S; Platonov, Fedor A; Aref Eva, Elena G; Zagorskaya, Natalia N; Aliferova, Valentina M; Titova, Marina A; Babenko, Sergei A; Smagina, Inna V; El Chaninova, Svetlana A; Zolovkina, Anna G; Lifshits, G I; Puzyrev, Valerii P; Filipenko, Maxim L

    2011-11-01

    Axonal degeneration is responsible for the progression of the irreversible destruction caused by multiple sclerosis (MS) resulting ultimately in permanent disability. The KIF1B protein, a member of the kinesin family, is necessary for axon growth and myelination in vertebrates. In the recent paper, Aulchenko et al. suggested that the rs10492972[C] variant of KIF1B increases susceptibility to MS, but three following replication study didn't confirm this association. We studied the association of the polymorphic locus rs10492972 present in the KIF1B gene with genetic predisposition and its occurrence in clinical presentations of MS patients resident in western Siberia and the Sakha Republic (Yakutia), Russia. rs10492972 has been genotype in 833 samples of MS patient and 689 healthy controls. Distribution of rs10492972 genotypes corresponded with a Hardy-Weinberg distribution in both the MS patient and control groups, with the frequency of the C allele being the same in both groups (33%). Frequencies of occurrence of the genotypes were not shown to be associated with different disease courses or other characteristics of the disease, such as age at onset or duration. A complete meta-analysis of all analogous studies published to date showed that the protective effect of the rs10492972[C] allele is statistically significant (OR=0.95, C.I.95% [0.90-0.99], p=0.02). Copyright © 2011. Published by Elsevier Inc.

  1. Promiscuous Rearrangements of the MYC Locus Hijack Enhancers and Super-Enhancers to Dysregulate MYC Expression in Multiple Myeloma

    PubMed Central

    Affer, Maurizio; Chesi, Marta; Chen, Wei-Dong G.; Keats, Jonathan J.; Demchenko, Yulia N.; Roschke, Anna V.; Van Wier, Scott; Fonseca, Rafael

    2014-01-01

    MYC locus rearrangements – often complex combinations of translocations, insertions, deletions, and inversions - in multiple myeloma (MM) were thought to be a late progression event, which often did not involve immunoglobulin genes. Yet germinal center activation of MYC expression has been reported to cause progression to MM in an MGUS prone mouse strain. Although previously detected in 16% of MM, we find MYC rearrangements in nearly 50% of MM, including smoldering MM, and they are heterogeneous in some cases. Rearrangements reposition MYC near a limited number of genes associated with conventional enhancers, but mostly with super-enhancers (e.g., IGH, IGL, IGK, NSMCE2, TXNDC5, FAM46C, FOXO3, IGJ, PRDM1). MYC rearrangements are associated with a significant increase of MYC expression that is monoallelic, but MM tumors lacking a rearrangement have bi-allelic MYC expression at significantly higher levels than in MGUS. We also show that germinal center activation of MYC does not cause MM in a mouse strain that rarely develops spontaneous MGUS. It appears that increased MYC expression at the MGUS/MM transition usually is bi-allelic, but sometimes can be mono-allelic if there is a MYC rearrangement. Our data suggests that MYC rearrangements, regardless of when they occur during MM pathogenesis, provide one event that contributes to tumor autonomy. PMID:24518206

  2. Characterization of Brachyspira hyodysenteriae isolates from Italy by multilocus sequence typing and multiple locus variable number tandem repeat analysis.

    PubMed

    Gasparrini, S; Alborali, G L; Pitozzi, A; Guarneri, F; Giacomini, E; Baldo, V; Scali, F; Lazzaro, M; Boniotti, M B

    2017-08-01

    To evaluate and compare the capabilities of multilocus sequence typing (MLST) and multiple locus variable number tandem repeat analysis (MLVA) techniques to characterize Brachyspira hyodysenteriae isolates and to investigate the relationship between pleuromutilin resistance and genetic variability. MLST genotyping was performed on 180 B. hyodysenteriae isolates, and the results were evaluated considering profiles from 108 other strains previously reported in the database. In total, 37 sequence types were obtained. The MLVA approach completely characterized 172 strains and grouped the isolates into 22 different profiles. The combination of MLST and MLVA showed a slight increase in the discriminatory power, identifying 33 joint profiles. An antibiotic resistance analysis showed a reduction in the susceptibility to pleuromutilins over time, and a weak association between susceptibility to valnemulin and inclusion in clonal complex 4. MLST and MLVA are reliable methods for characterizing B. hyodysenteriae strains and they have comparable discriminatory power. The genotyping of B. hyodysenteriae isolates and a database of all the genetic profiles collected during the diagnostic activities could support traditional epidemiological investigations in identifying infection sources and routes of transmission among herds, and in developing more effective control measures. © 2017 The Society for Applied Microbiology.

  3. Genetic and functional analysis of the multiple antibiotic resistance (mar) locus in Escherichia coli.

    PubMed Central

    Cohen, S P; Hächler, H; Levy, S B

    1993-01-01

    A 7.8-kbp fragment of chromosomal DNA from a region controlling multiple antibiotic resistance (Mar) in Escherichia coli has been sequenced. Within the fragment is a potential divergent promoter region including marO, which contains two pairs of direct repeats, suggesting possible operator-regulatory sites. To the left of marO (region I) are one or two transcriptional units with three putative open reading frames (ORFs) encoding 64, 157, and 70 amino acids. To the right (region II) is a transcriptional unit containing three putative ORFs (ORF125/144, ORF129, and ORF72). Of six independent Mar mutants, four had mutations within the ORF encoding the first putative protein (ORF125/144) downstream of marO, including three different single-point mutations and an IS2 insertion. One of the other mutations occurred in marO (20-bp duplication), and the other occurred in a site in marO or ORF144 (a 1-bp change). All six mutations led to increased transcription of the region II transcript. High-copy-number plasmids containing marO and the adjacent ORF125/144 region from a wild-type source but not from a Mar mutant reduced the antibiotic resistance of a Mar mutant to levels comparable to those of wild-type cells. High-copy-number plasmids containing wild-type marO alone caused an increase in resistance to tetracycline, chloramphenicol, and norfloxacin in a wild-type strain. The nature of the Mar mutations and the results of the complementation studies suggest that ORF125/144 encodes a repressor (designated MarR) which acts at marO. The second ORF (ORF129), designated marA, would encode a protein, MarA, whose sequence shows strong similarity to those of a family of positive transcriptional regulators. A Tn5 insertion in marA inactivated the multiresistance phenotype of Mar mutants. The function of ORF72, designated marB, encoding the third putative protein in the operon, and that of other ORFs detected within the 7.8-kb fragment have not yet been determined. Images PMID:8383113

  4. A Transcript Map for the 2.8-Mb Region Containing the Multiple Endocrine Neoplasia Type 1 Locus

    PubMed Central

    Guru, Siradanahalli C.; Agarwal, Sunita K.; Manickam, Pachiappan; Olufemi, Shodimu-Emmanuel; Crabtree, Judy S.; Weisemann, Jane M.; Kester, Mary Beth; Kim, Young S.; Wang, Yingping; Emmert-Buck, Michael R.; Liotta, Lance A.; Spiegel, Allen M.; Boguski, Mark S.; Roe, Bruce A.; Collins, Francis S.; Marx, Stephen J.; Burns, Lee; Chandrasekharappa, Settara C.

    1997-01-01

    Multiple endocrine neoplasia type 1 (MEN 1) is an inherited cancer syndrome in which affected individuals develop multiple parathyroid, enteropancreatic, and pituitary tumors. The locus for MEN1 is tightly linked to the marker PYGM on chromosome 11q13, and linkage analysis places the MEN1 gene within a 2-Mb interval flanked by the markers D11S1883 and D11S449. Loss of heterozygosity studies in MEN 1 and sporadic tumors suggest that the MEN1 gene encodes a tumor suppressor and have helped to narrow the location of the gene to a 600-kb interval between PYGM and D11S449. Focusing on this smaller MEN1 interval, we have identified and mapped 12 transcripts to this 600-kb region. A precise ordered map of 33 transcripts, including 12 genes known to map to this region, was generated for the 2.8-Mb D11S480–D11S913 interval. Fifteen candidate genes (of which 10 were examined exhaustively) were evaluated by Southern blot and/or dideoxy fingerprinting analysis to identify the gene harboring disease-causing mutations. [The sequence data described in this paper have been submitted to GenBank under accession nos. EST06996, U93236, AF001540–AF001547, AF001433–AF001436, AF001891–AF001893, N55476, R19205, and W37647 (see Table 1 for listing of transcripts). The BAC clone sequences have been submitted to GenBank under accession nos. AC000134, AC000159, and AC000353.] PMID:9253601

  5. A genetic locus closely linked to a protease inhibitor gene complex controls the level of multiple RNA transcripts.

    PubMed Central

    Hill, R E; Shaw, P H; Barth, R K; Hastie, N D

    1985-01-01

    The two major protease inhibitors in mouse plasma are alpha 1-protease inhibitor (alpha 1-PI), putative inhibitor of neutrophil elastase, and contrapsin, an inhibitor in vitro of trypsinlike proteases. We have shown by nucleotide sequence analysis that these two inhibitors are related (R. E. Hill, P. H. Shaw, P. A. Boyd, H. Baumann, and N. D. Hastie, Nature (London) 311:175-177, 1984). Here, we show that the contrapsin and alpha 1-PI genes are members of two different multigene families, each containing at least three genes in mice and rats. We established the chromosomal locations of these genes by analyzing the segregation of restriction fragment length polymorphisms in recombinant inbred mouse strains. These experiments show that the multiple genes in each family are clustered and that the two gene families are closely linked on chromosome 12. Thus the genes for contrapsin and alpha 1-PI are likely to have evolved by duplication of a common ancestral gene. The contrapsin multigene family codes for multiple mRNA transcripts in the liver. There is a genetic difference among inbred mouse strains in the regulation of two of these transcripts. In some inbred strains the transcripts are synthesized constitutively; in others they are induced by inflammation. We mapped in recombinant inbred strains the regulatory locus responsible for this genetic variation and found it is linked to the contrapsin multigene family, which suggests a cis-acting regulatory element. We also found that the contrapsin and the alpha 1-PI multigene families have acquired very different regulatory responses since the time of the gene duplication event. Images PMID:2427931

  6. Layered genetic control of DNA methylation and gene expression: a locus of multiple sclerosis in healthy individuals

    PubMed Central

    Shin, Jean; Bourdon, Celine; Bernard, Manon; Wilson, Michael D.; Reischl, Eva; Waldenberger, Melanie; Ruggeri, Barbara; Schumann, Gunter; Desrivieres, Sylvane; Leemans, Alexander; Abrahamowicz, Michal; Leonard, Gabriel; Richer, Louis; Bouchard, Luigi; Gaudet, Daniel; Paus, Tomas; Pausova, Zdenka

    2015-01-01

    DNA methylation may contribute to the etiology of complex genetic disorders through its impact on genome integrity and gene expression; it is modulated by DNA-sequence variants, named methylation quantitative trait loci (meQTLs). Most meQTLs influence methylation of a few CpG dinucleotides within short genomic regions (<3 kb). Here, we identified a layered genetic control of DNA methylation at numerous CpGs across a long 300 kb genomic region. This control involved a single long-range meQTL and multiple local meQTLs. The long-range meQTL explained up to 75% of variance in methylation of CpGs located over extended areas of the 300 kb region. The meQTL was identified in four samples (P = 2.8 × 10−17, 3.1 × 10−31, 4.0 × 10−71 and 5.2 × 10−199), comprising a total of 2796 individuals. The long-range meQTL was strongly associated not only with DNA methylation but also with mRNA expression of several genes within the 300 kb region (P = 7.1 × 10−18–1.0 × 10−123). The associations of the meQTL with gene expression became attenuated when adjusted for DNA methylation (causal inference test: P = 2.4 × 10−13–7.1 × 10−20), indicating coordinated regulation of DNA methylation and gene expression. Further, the long-range meQTL was found to be in linkage disequilibrium with the most replicated locus of multiple sclerosis, a disease affecting primarily the brain white matter. In middle-aged adults free of the disease, we observed that the risk allele was associated with subtle structural properties of the brain white matter found in multiple sclerosis (P = 0.02). In summary, we identified a long-range meQTL that controls methylation and expression of several genes and may be involved in increasing brain vulnerability to multiple sclerosis. PMID:26220975

  7. An Undergraduate Laboratory Experiment for Upper-Level Forensic Science, Biochemistry, or Molecular Biology Courses: Human DNA Amplification Using STR Single Locus Primers by Real-Time PCR with SYBR Green Detection

    ERIC Educational Resources Information Center

    Elkins, Kelly M.; Kadunc, Raelynn E.

    2012-01-01

    In this laboratory experiment, real-time polymerase chain reaction (real-time PCR) was conducted using published human TPOX single-locus DNA primers for validation and various student-designed short tandem repeat (STR) primers for Combined DNA Index System (CODIS) loci. SYBR Green was used to detect the amplification of the expected amplicons. The…

  8. An Undergraduate Laboratory Experiment for Upper-Level Forensic Science, Biochemistry, or Molecular Biology Courses: Human DNA Amplification Using STR Single Locus Primers by Real-Time PCR with SYBR Green Detection

    ERIC Educational Resources Information Center

    Elkins, Kelly M.; Kadunc, Raelynn E.

    2012-01-01

    In this laboratory experiment, real-time polymerase chain reaction (real-time PCR) was conducted using published human TPOX single-locus DNA primers for validation and various student-designed short tandem repeat (STR) primers for Combined DNA Index System (CODIS) loci. SYBR Green was used to detect the amplification of the expected amplicons. The…

  9. High-Resolution In Situ Genotyping of Legionella pneumophila Populations in Drinking Water by Multiple-Locus Variable-Number Tandem-Repeat Analysis Using Environmental DNA▿

    PubMed Central

    Kahlisch, Leila; Henne, Karsten; Draheim, Josefin; Brettar, Ingrid; Höfle, Manfred G.

    2010-01-01

    Central to the understanding of infections by the waterborne pathogen Legionella pneumophila is its detection at the clonal level. Currently, multiple-locus variable-number tandem-repeat (VNTR) analysis (MLVA) of L. pneumophila isolates can be used as a tool for high-resolution genotyping. Since L. pneumophila is difficult to isolate, the isolation of outbreak strains often fails due to a viable but nonculturable (VBNC) state of the respective environmental population. Therefore, we developed a cultivation-independent approach to detect single clones in drinking water. This approach is based on the extraction of DNA from drinking water followed by PCR using a set of eight VNTR primer pairs necessary for MLVA genotyping of L. pneumophila. The PCR amplicons were analyzed by single-strand conformation polymorphism (SSCP) and capillary electrophoresis to obtain the respective MLVA profiles. Parallel to the high-resolution analysis, we used the same environmental DNA to quantify the number of L. pneumophila cells in drinking water using real-time PCR with 16S rRNA gene-targeted primers. We used a set of drinking water samples from a small-scale drinking water network to test our approach. With these samples we demonstrated that the developed approach was directly applicable to DNA obtained from drinking water. We were able to detect more L. pneumophila MLVA genotypes in drinking water than we could detect by isolation. Our approach could be a valuable tool to identify outbreak strains even after the outbreak has occurred and has the potential to be applied directly to clinical material. PMID:20656879

  10. Multiple-locus variable-number tandem-repeat analysis of Brucella isolates from patients in Xinjiang China

    PubMed Central

    Zhang, Fengbo; Li, Zhiwei; La, Xiaolin; Ma, Xiumin; Zhang, Yaoxin; Ji, Ping; Jiang, Min; Hu, Jinwei; Zhang, Zhaoxia; Lu, Xiaobo; Ding, Jianbing

    2015-01-01

    Objective: This study is to characterize and identify the human Brucella strains in Xinjiang, China with multiple-locus variable-number tandem-repeat (VNTR) analysis (MLVA) scheme. Methods: Brucella strains were isolated and cultured from 62 brucellosis patients. The bacteria strains were subjected to the oxidase, catalase, rapid urease, and nitrate reduction tests, and the species identification was performed using the VITEK-2 Compact system. These Brucella strains were further identified and characterized using the 16 VNTR loci in a MLVA-16 methodology. Results: Twelve Brucella strains had been identified out of 62 patients, which were all recognized as Brucella melitensis (B. melitensis) according to the results from the VITEK-2 Compact system. Based on panel 1 (MLVA-8), these 12 Brucella isolates were clustered into three known genotypes and two new genotypes, in which 7 strains were clustered into genotype 45 (1-5-3-12-2-2-3-2), 1 strain was classified as genotype 42 (1-5-3-13-2-2-3-2), 1 stain was with genotype 62 (1-3-3-13-2-2-3-2), and the other 3 trains revealed two new genotypes, i.e., (1-5-3-12-2-3-3-2) and (1-5-3-11-2-3-3-2). Using panel 2A+2B (MLVA-16), we found that no genotypes of these strains were identical to the known genotypes, generally with differences in 2-4 loci. However, three strains shared the same genotype. Conclusion: Brucella strains in 62 brucellosis patients from Xinjiang are all identified as B. melitensis. Based on MLVA-8, two new genotypes have been discovered. These findings might contribute to the understanding of the pathogenesis and epidemiology of brucellosis in Xinjiang, China. PMID:26629067

  11. Multiple-locus variable-number tandem-repeat analysis (MLVA) genotyping of human Brucella isolates in Malaysia.

    PubMed

    Tay, Bee Yong; Ahmad, Norazah; Hashim, Rohaidah; Mohamed Zahidi, Jama'ayah; Thong, Kwai Lin; Koh, Xiu Pei; Mohd Noor, Azura

    2015-06-02

    Brucellosis is one of the most common zoonotic diseases worldwide. It can cause acute febrile illness in human and is a major health problem. Studies in human brucellosis in Malaysia is limited and so far no genotyping studies has been done on Brucella isolates. The aim of the study was to determine the genetic diversity among Brucella species isolated from human brucellosis, obtained over a 6-year period (2009-2014). In this study, the genotypic characteristics of 43 human Brucella melitensis isolates were analysed using multiple-locus variable-number tandem-repeat analysis (MLVA) which consisted of eight minisatellite loci (panel 1) and eight microsatellite loci; panels 2A (3 microsatellite loci) and panel 2B (5 microsatellite loci). Two human Brucella suis isolates were also investigated using the MLVA assay. Using panel 1 (MLVA8), two genotypes namely genotype 43 and 44 were obtained from the 43 B. melitensis isolates. Using the combination of panels 1 and 2A loci (MLVA11), two genotypes were obtained while using the complete panels 1, 2A and 2B, nine genotypes were obtained. The polymorphisms in using the complete panels (MLVA16) were observed in three loci from panel 2B, which showed a diversity index higher than 0.17. All B. melitensis isolates were closely related to the East Mediterranean group. For B. suis isolates, only genotype 6 and genotype 33 were obtained using panel 1 and MLVA11 respectively. In conclusion, the results of the present study showed a low genetic diversity among B. melitensis and B. suis isolates from human patients. Based on the MLVA16 assay, B. melitensis belonging to the East Mediterranean group is responsible for the vast majority of Brucella infections in our Malaysian patients. To our knowledge, this is the first genotyping study of human Brucella isolates in Malaysia.

  12. Multiple-locus variable-number tandem-repeat analysis of the swine dysentery pathogen, Brachyspira hyodysenteriae.

    PubMed

    Hidalgo, Alvaro; Carvajal, Ana; La, Tom; Naharro, Germán; Rubio, Pedro; Phillips, Nyree D; Hampson, David J

    2010-08-01

    The spirochete Brachyspira hyodysenteriae is the causative agent of swine dysentery, a severe colonic infection of pigs that has a considerable economic impact in many swine-producing countries. In spite of its importance, knowledge about the global epidemiology and population structure of B. hyodysenteriae is limited. Progress in this area has been hampered by the lack of a low-cost, portable, and discriminatory method for strain typing. The aim of the current study was to develop and test a multiple-locus variable-number tandem-repeat analysis (MLVA) method that could be used in basic veterinary diagnostic microbiology laboratories equipped with PCR technology or in more advanced laboratories with access to capillary electrophoresis. Based on eight loci, and when performed on isolates from different farms in different countries, as well as type and reference strains, the MLVA technique developed was highly discriminatory (Hunter and Gaston discriminatory index, 0.938 [95% confidence interval, 0.9175 to 0.9584]) while retaining a high phylogenetic value. Using the technique, the species was shown to be diverse (44 MLVA types from 172 isolates and strains), although isolates were stable in herds over time. The population structure appeared to be clonal. The finding of B. hyodysenteriae MLVA type 3 in piggeries in three European countries, as well as other, related, strains in different countries, suggests that spreading of the pathogen via carrier pigs is likely. MLVA overcame drawbacks associated with previous typing techniques for B. hyodysenteriae and was a powerful method for epidemiologic and population structure studies on this important pathogenic spirochete.

  13. Flexibility and Project Value: Interactions and Multiple Real Options

    NASA Astrophysics Data System (ADS)

    Čulík, Miroslav

    2010-06-01

    This paper is focused on a project valuation with embedded portfolio of real options including their interactions. Valuation is based on the criterion of Net Present Value on the simulation basis. Portfolio includes selected types of European-type real options: option to expand, contract, abandon and temporarily shut down and restart a project. Due to the fact, that in reality most of the managerial flexibility takes the form of portfolio of real options, selected types of options are valued not only individually, but also in combination. The paper is structured as follows: first, diffusion models for forecasting of output prices and variable costs are derived. Second, project value is estimated on the assumption, that no real options are present. Next, project value is calculated with the presence of selected European-type options; these options and their impact on project value are valued first in isolation and consequently in different combinations. Moreover, intrinsic value evolution of given real options with respect to the time of exercising is analysed. In the end, results are presented graphically; selected statistics and risk measures (Value at Risk, Expected Shortfall) of the NPV's distributions are calculated and commented.

  14. A new risk variant for multiple sclerosis at the immunoglobulin heavy chain locus associates with intrathecal IgG, IgM index and oligoclonal bands.

    PubMed

    Delgado-García, Mercedes; Matesanz, Fuencisla; Alcina, Antonio; Fedetz, María; García-Sánchez, María Isabel; Ruiz-Peña, Juan Luis; Fernández, Óscar; Pinto Medel, María Jesús; Leyva, Laura; Arnal, Carmen; Delgado, Concepción; López Guerrero, José Antonio; González-Pérez, Antonio; Sáez, María E; Villar, Luisa María; Álvarez-Cermeño, José Carlos; Picón, Carmen; Arroyo, Rafael; Varadé, Jezabel; Urcelay, Elena; Izquierdo, Guillermo; Lucas, Miguel

    2015-08-01

    Recent findings have shown a correlation between the intrathecal IgG index and variants at the immunoglobulin heavy chain (IGHC) locus in patients with multiple sclerosis (MS). The objective of this paper is to analyse the association of the locus with MS susceptibility and its relationship with intrathecal immunoglobulin (Ig) parameters. We genotyped the rs11621145 variant, located at the IGHC locus, in 2726 patients with MS and 2133 healthy controls. Associations of intrathecal IgG and IgM indexes with rs11621145 were analysed by linear regression analysis in 538 MS patients. We found that rs11621145 showed statistically significant evidence for association with susceptibility to MS (odds ratio = 0.69, p = 1.053E-09), though validation of this result in additional cohorts would be desirable. We confirmed the association between the IgG index and the rs11621145 (p = 6.85E-07, Beta = 0.207). Furthermore, rs11621145 was inversely correlated with IgM index (p = 7.24E-04, Beta = -0.277), and therefore marks a decreased likelihood of presenting IgM oligoclonal bands (odds ratio = 0.38, p = 2.35E-06). Our results suggest that the polymorphism of the IGHC locus could be altering the switching of the Ig isotype in B cells and it may be interfering with T-dependent and T-independent antibody responses. © The Author(s), 2014.

  15. Development of real-time PCR assays for specific detection of hmsH, hmsF, hmsR, and irp2 located within the 102-kb pgm locus of Yersinia pestis.

    PubMed

    Gaddy, Charla E; Cuevas, Pedro F; Hartman, Laurie J; Howe, Gerald B; Worsham, Patricia L; Minogue, Timothy D

    2014-01-01

    Virulent isolates of three pathogenic Yersinia species (Yersinia pestis, Yersinia pseudotuberculosis, and Yersinia enterocolitica) harbor a 102-kb chromosomal region which encodes elements critical for virulence. A 35-kb high pathogenicity island is contained in this region, is a known virulence determinant, contains irp1 and irp2 iron-regulating genes. An additional segment, the 68-kb high pathogenicity island, contains genetic elements responsible for conferring the Y. pestis pigmentation phenotype on Congo red agar at 28 °C. Collectively, these contiguous segments are referred to as the pigmentation (pgm) locus, the absence of which results in strain attenuation and exemption from CDC Select Agent status. In this study, we developed a set of four real-time PCR assays to detect the presence or absence of multiple virulence genes located within this region. Specifically, we designed TaqMan(®) PCR assays to individually detect three hemin storage genes (hmsH, hmsF, and hmsR) which are genetic elements that confer the pigmentation phenotype, as well as the iron-regulating status of 25 Y. pestis isolates (representing 23 different strains), thus establishing a molecular based assay capable of determining the pgm status of candidate Y. pestis isolates. Included in the validation process, was a comparison of these real-time PCR assays and newly developed conventional PCR assays targeting much larger areas of the 102-kb region (including one assay spanning hmsR and hmsF, one spanning hmsH and hsmF, one targeting hmsF, and one targeting irp2). There was high concordance between the conventional and real-time PCR assays for all Y. pestis strains tested. The results from the comparative analysis document the specificity and sensitivity of the real-time PCR assays and further solidify the ostensible benefits of real-time PCR over conventional PCR. Published by Elsevier Ltd.

  16. Real-time optical holographic tracking of multiple objects.

    PubMed

    Chao, T H; Liu, H K

    1989-01-15

    A coherent optical correlation technique for real-time simultaneous tracking of several different objects making independent movements is described, and experimental results are presented. An evaluation of this system compared with digital computing systems is made. The real-time processing capability is obtained through the use of a liquid crystal television spatial light modulator and a dichromated gelatin multifocus hololens. A coded reference beam is utilized in the separation of the output correlation plane associated with each input target so that independent tracking can be achieved.

  17. Real-time optical holographic tracking of multiple objects

    NASA Technical Reports Server (NTRS)

    Chao, Tien-Hsin; Liu, Hua-Kuang

    1989-01-01

    A coherent optical correlation technique for real-time simultaneous tracking of several different objects making independent movements is described, and experimental results are presented. An evaluation of this system compared with digital computing systems is made. The real-time processing capability is obtained through the use of a liquid crystal television spatial light modulator and a dichromated gelatin multifocus hololens. A coded reference beam is utilized in the separation of the output correlation plane associated with each input target so that independent tracking can be achieved.

  18. Children's Eyewitness Memory for Multiple Real-Life Events

    ERIC Educational Resources Information Center

    Odegard, Timothy N.; Cooper, Crystal M.; Lampinen, James M.; Reyna, Valerie F.; Brainerd, Charles J.

    2009-01-01

    The present research examined the influence of prior knowledge on children's free recall, cued recall, recognition memory, and source memory judgments for a series of similar real-life events. Forty children (5-12 years old) attended 4 thematic birthday parties and were later interviewed about the events that transpired during the parties using…

  19. Genomic matrix attachment region and chromosome conformation capture quantitative real time PCR assays identify novel putative regulatory elements at the imprinted Dlk1/Gtl2 locus.

    PubMed

    Braem, Caroline; Recolin, Bénédicte; Rancourt, Rebecca C; Angiolini, Christopher; Barthès, Pauline; Branchu, Priscillia; Court, Franck; Cathala, Guy; Ferguson-Smith, Anne C; Forné, Thierry

    2008-07-04

    We previously showed that genomic imprinting regulates matrix attachment region activities at the mouse Igf2 (insulin-like growth factor 2) locus and that these activities are functionally linked to neighboring differentially methylated regions (DMRs). Here, we investigate the similarly structured Dlk1/Gtl2 imprinted domain and show that in the mouse liver, the G/C-rich intergenic germ line-derived DMR, a sequence involved in domain-wide imprinting, is highly retained within the nuclear matrix fraction exclusively on the methylated paternal copy, reflecting its differential function on that chromosome. Therefore, not only "classical" A/T-rich matrix attachment region (MAR) sequences but also other important regulatory DNA elements (such as DMRs) can be recovered from genomic MAR assays following a high salt treatment. Interestingly, the recovery of one A/T-rich sequence (MAR4) from the "nuclear matrix" fraction is strongly correlated with gene expression. We show that this element possesses an intrinsic activity that favors transcription, and using chromosome conformation capture quantitative real time PCR assays, we demonstrate that the MAR4 interacts with the intergenic germ line-derived DMR specifically on the paternal allele but not with the Dlk1/Gtl2 promoters. Altogether, our findings shed a new light on gene regulation at this locus.

  20. Improved Real-Time Monitoring Using Multiple Expert Systems

    NASA Technical Reports Server (NTRS)

    Schwuttke, Ursula M.; Angelino, Robert; Quan, Alan G.; Veregge, John; Childs, Cynthia

    1993-01-01

    Monitor/Analyzer of Real-Time Voyager Engineering Link (MARVEL) computer program implements combination of techniques of both conventional automation and artificial intelligence to improve monitoring of complicated engineering system. Designed to support ground-based operations of Voyager spacecraft, also adapted to other systems. Enables more-accurate monitoring and analysis of telemetry, enhances productivity of monitoring personnel, reduces required number of such personnel by performing routine monitoring tasks, and helps ensure consistency in face of turnover of personnel. Programmed in C language and includes commercial expert-system software shell also written in C.

  1. The tyrosinase-positive oculocutaneous albinism gene shows locus homogeneity on chromosome 15q11-q13 and evidence of multiple mutations in southern African negroids

    SciTech Connect

    Kedda, M.A.; Stevens, G.; Manga, P.; Viljoen, C.; Jenkins, T.; Ramsay, M. Univ. of Witwatersrand, Johannesburg )

    1994-06-01

    Tyrosinase-positive oculocutaneous albinism (ty-pos OCA) is an autosomal recessive disorder of the melanin pigmentary system. South African ty-pos OCA individuals occur with two distinct phenotypes, with or without darkly pigmented patches (ephelides, or dendritic freckles) on exposed areas of the skin. These phenotypes are concordant within families, suggesting that there may be more than one mutation at the ty-pos OCA locus. Linkage studies carried out in 41 families have shown linkage between markers in the Prader-Willi/Angelman syndrome (PWS/AS) region on chromosome 15q11-q13 and ty-pos OCA. Analysis showed no obligatory crossovers between the alleles at the D15S12 locus and ty-pos OCA, suggesting that the D15S12 locus is very close to or part of the disease locus, which is postulated to be the human homologue, P, of the mouse pink-eyed dilution gene, p. Unlike caucasoid [open quotes]ty-pos OCA[close quotes] individuals, negroid ty-pos OCA individuals do not show any evidence of locus heterogeneity. Studies of allelic association between the polymorphic alleles detected at the D15S12 locus and ephelus status suggest that there was a single major mutation giving rise to ty-pos OCA without ephelides. There may, however, be two major mutations causing ty-pos OCA with ephelides, one associated with D15S12 allele 1 and the other associated with D15S12 allele 2. The two loci, GABRA5 and D15S24, flanking D15S12, are both hypervariable, and many different haplotypes were observed with the alleles at the three loci on both ty-pos OCA-associated chromosomes and [open quotes]normal[close quotes] chromosomes. No haplotype showed statistically significant association with ty-pos OCA, and thus none could be used to predict the origins of the ty-pos OCA mutations. On the basis of the D15S12 results, there is evidence for multiple ty-pos OCA mutations in southern African negroids. 31 refs., 1 fig., 3 tabs.

  2. A Domestic cat X Chromosome Linkage Map and the Sex-Linked orange Locus: Mapping of orange, Multiple Origins and Epistasis Over nonagouti

    PubMed Central

    Schmidt-Küntzel, Anne; Nelson, George; David, Victor A.; Schäffer, Alejandro A.; Eizirik, Eduardo; Roelke, Melody E.; Kehler, James S.; Hannah, Steven S.; O'Brien, Stephen J.; Menotti-Raymond, Marilyn

    2009-01-01

    A comprehensive genetic linkage map of the domestic cat X chromosome was generated with the goal of localizing the genomic position of the classic X-linked orange (O) locus. Microsatellite markers with an average spacing of 3 Mb were selected from sequence traces of the cat 1.9× whole genome sequence (WGS), including the pseudoautosomal region 1 (PAR1). Extreme variation in recombination rates (centimorgans per megabase) was observed along the X chromosome, ranging from a virtual absence of recombination events in a region estimated to be >30 Mb to recombination frequencies of 15.7 cM/Mb in a segment estimated to be <0.3 Mb. This detailed linkage map was applied to position the X-linked orange gene, placing this locus on the q arm of the X chromosome, as opposed to a previously reported location on the p arm. Fine mapping placed the locus between markers at positions 106 and 116.8 Mb in the current 1.9×-coverage sequence assembly of the cat genome. Haplotype analysis revealed potential recombination events that could reduce the size of the candidate region to 3.5 Mb and suggested multiple origins for the orange phenotype in the domestic cat. Furthermore, epistasis of orange over nonagouti was demonstrated at the genetic level. PMID:19189955

  3. The population structure of Salmonella enterica Enteritidis in Iran analyzed by multiple-locus variable-number tandem repeat analysis.

    PubMed

    Ghaderi, Rainak; Tadayon, Keyvan; Avagyan, Sargis; Khaki, Pejvak; Bidhendi, Soheila Moradi; Forbes, Ken James; Mosavari, Nader; Toroghi, Mohammad Reza; Moosakhani, Farhad; Banihashemi, Reza; Sekhavati, Mohamad; Karimnasab, Nasim

    2013-04-01

    Salmonella enterica Enteritidis is the most frequent etiological agent of salmonellosis in humans and poultry. To understand the genetic diversity of S. Enteritidis in Iran, we examined 69 chicken isolates from 18 broiler farms and six non-epidemic human isolates from six geographically distant provinces by multi-locus variable-number tandem repeat analysis (MLVA). Among SE2, SE3, SE5, SE7, SE8, SENTR4, and SENTR7, only SE5 with four and SENTR7 with two alleles, respectively, proved variable giving estimates of locus genetic diversity of 0.58 and 0. In all, six closely related MLVA profiles were identified among which three were commonly represented by human and chicken isolates. This population homogeneity contrasts with the high diversity at these loci reported elsewhere and is likely a consequence of a single clone of S. Enteritidis distributed across Iran.

  4. Association of maternal and nutrient supply line factors with DNA methylation at the imprinted IGF2/H19 locus in multiple tissues of newborn twins.

    PubMed

    Loke, Yuk Jing; Galati, John C; Morley, Ruth; Joo, Eric Ji-Hoon; Novakovic, Boris; Li, Xin; Weinrich, Blaise; Carson, Nicole; Ollikainen, Miina; Ng, Hong-Kiat; Andronikos, Roberta; Aziz, Nur Khairunnisa Abdul; Saffery, Richard; Craig, Jeffrey M

    2013-10-01

    Epigenetic events are crucial for early development, but can be influenced by environmental factors, potentially programming the genome for later adverse health outcomes. The insulin-like growth factor 2 (IGF2)/H19 locus is crucial for prenatal growth and the epigenetic state at this locus is environmentally labile. Recent studies have implicated maternal factors, including folate intake and smoking, in the regulation of DNA methylation at this locus, although data are often conflicting in the direction and magnitude of effect. Most studies have focused on single tissues and on one or two differentially-methylated regions (DMRs) regulating IGF2/H19 expression. In this study, we investigated the relationship between multiple shared and non-shared gestational/maternal factors and DNA methylation at four IGF2/H19 DMRs in five newborn cell types from 67 pairs of monozygotic and 49 pairs of dizygotic twins. Data on maternal and non-shared supply line factors were collected during the second and third trimesters of pregnancy and DNA methylation was measured via mass spectrometry using Sequenom MassArray EpiTyper analysis. Our exploratory approach showed that the site of umbilical cord insertion into the placenta in monochorionic twins has the strongest positive association with methylation in all IGF2/H19 DMRs (p<0.05). Further, evidence for tissue- and locus-specific effects were observed, emphasizing that responsiveness to environmental exposures in utero cannot be generalized across genes and tissues, potentially accounting for the lack of consistency in previous findings. Such complexity in responsiveness to environmental exposures in utero has implications for all epigenetic studies investigating the developmental origins of health and disease.

  5. Association of maternal and nutrient supply line factors with DNA methylation at the imprinted IGF2/H19 locus in multiple tissues of newborn twins

    PubMed Central

    Loke, Yuk Jing; Galati, John C; Morley, Ruth; Joo, Eric Ji-Hoon; Novakovic, Boris; Li, Xin; Weinrich, Blaise; Carson, Nicole; Ollikainen, Miina; Ng, Hong-Kiat; Andronikos, Roberta; Aziz, Nur Khairunnisa Abdul; Saffery, Richard; Craig, Jeffrey M

    2013-01-01

    Epigenetic events are crucial for early development, but can be influenced by environmental factors, potentially programming the genome for later adverse health outcomes. The insulin-like growth factor 2 (IGF2)/H19 locus is crucial for prenatal growth and the epigenetic state at this locus is environmentally labile. Recent studies have implicated maternal factors, including folate intake and smoking, in the regulation of DNA methylation at this locus, although data are often conflicting in the direction and magnitude of effect. Most studies have focused on single tissues and on one or two differentially-methylated regions (DMRs) regulating IGF2/H19 expression. In this study, we investigated the relationship between multiple shared and non-shared gestational/maternal factors and DNA methylation at four IGF2/H19 DMRs in five newborn cell types from 67 pairs of monozygotic and 49 pairs of dizygotic twins. Data on maternal and non-shared supply line factors were collected during the second and third trimesters of pregnancy and DNA methylation was measured via mass spectrometry using Sequenom MassArray EpiTyper analysis. Our exploratory approach showed that the site of umbilical cord insertion into the placenta in monochorionic twins has the strongest positive association with methylation in all IGF2/H19 DMRs (p < 0.05). Further, evidence for tissue- and locus-specific effects were observed, emphasizing that responsiveness to environmental exposures in utero cannot be generalized across genes and tissues, potentially accounting for the lack of consistency in previous findings. Such complexity in responsiveness to environmental exposures in utero has implications for all epigenetic studies investigating the developmental origins of health and disease. PMID:23917818

  6. Multiple Hepatic Regulatory Variants at the GALNT2 GWAS Locus Associated with High-Density Lipoprotein Cholesterol.

    PubMed

    Roman, Tamara S; Marvelle, Amanda F; Fogarty, Marie P; Vadlamudi, Swarooparani; Gonzalez, Arlene J; Buchkovich, Martin L; Huyghe, Jeroen R; Fuchsberger, Christian; Jackson, Anne U; Wu, Ying; Civelek, Mete; Lusis, Aldons J; Gaulton, Kyle J; Sethupathy, Praveen; Kangas, Antti J; Soininen, Pasi; Ala-Korpela, Mika; Kuusisto, Johanna; Collins, Francis S; Laakso, Markku; Boehnke, Michael; Mohlke, Karen L

    2015-12-03

    Genome-wide association studies (GWASs) have identified more than 150 loci associated with blood lipid and cholesterol levels; however, the functional and molecular mechanisms for many associations are unknown. We examined the functional regulatory effects of candidate variants at the GALNT2 locus associated with high-density lipoprotein cholesterol (HDL-C). Fine-mapping and conditional analyses in the METSIM study identified a single locus harboring 25 noncoding variants (r(2) > 0.7 with the lead GWAS variants) strongly associated with total cholesterol in medium-sized HDL (e.g., rs17315646, p = 3.5 × 10(-12)). We used luciferase reporter assays in HepG2 cells to test all 25 variants for allelic differences in regulatory enhancer activity. rs2281721 showed allelic differences in transcriptional activity (75-fold [T] versus 27-fold [C] more than the empty-vector control), as did a separate 780-bp segment containing rs4846913, rs2144300, and rs6143660 (49-fold [AT(-) haplotype] versus 16-fold [CC(+) haplotype] more). Using electrophoretic mobility shift assays, we observed differential CEBPB binding to rs4846913, and we confirmed this binding in a native chromatin context by performing chromatin-immunoprecipitation (ChIP) assays in HepG2 and Huh-7 cell lines of differing genotypes. Additionally, sequence reads in HepG2 DNase-I-hypersensitivity and CEBPB ChIP-seq signals spanning rs4846913 showed significant allelic imbalance. Allelic-expression-imbalance assays performed with RNA from primary human hepatocyte samples and expression-quantitative-trait-locus (eQTL) data in human subcutaneous adipose tissue samples confirmed that alleles associated with increased HDL-C are associated with a modest increase in GALNT2 expression. Together, these data suggest that at least rs4846913 and rs2281721 play key roles in influencing GALNT2 expression at this HDL-C locus.

  7. Evolutionary Changes in Gene Expression, Coding Sequence and Copy-Number at the Cyp6g1 Locus Contribute to Resistance to Multiple Insecticides in Drosophila

    PubMed Central

    Harrop, Thomas W. R.; Sztal, Tamar; Lumb, Christopher; Good, Robert T.; Daborn, Phillip J.; Batterham, Philip; Chung, Henry

    2014-01-01

    Widespread use of insecticides has led to insecticide resistance in many populations of insects. In some populations, resistance has evolved to multiple pesticides. In Drosophila melanogaster, resistance to multiple classes of insecticide is due to the overexpression of a single cytochrome P450 gene, Cyp6g1. Overexpression of Cyp6g1 appears to have evolved in parallel in Drosophila simulans, a sibling species of D. melanogaster, where it is also associated with insecticide resistance. However, it is not known whether the ability of the CYP6G1 enzyme to provide resistance to multiple insecticides evolved recently in D. melanogaster or if this function is present in all Drosophila species. Here we show that duplication of the Cyp6g1 gene occurred at least four times during the evolution of different Drosophila species, and the ability of CYP6G1 to confer resistance to multiple insecticides exists in D. melanogaster and D. simulans but not in Drosophila willistoni or Drosophila virilis. In D. virilis, which has multiple copies of Cyp6g1, one copy confers resistance to DDT and another to nitenpyram, suggesting that the divergence of protein sequence between copies subsequent to the duplication affected the activity of the enzyme. All orthologs tested conferred resistance to one or more insecticides, suggesting that CYP6G1 had the capacity to provide resistance to anthropogenic chemicals before they existed. Finally, we show that expression of Cyp6g1 in the Malpighian tubules, which contributes to DDT resistance in D. melanogaster, is specific to the D. melanogaster–D. simulans lineage. Our results suggest that a combination of gene duplication, regulatory changes and protein coding changes has taken place at the Cyp6g1 locus during evolution and this locus may play a role in providing resistance to different environmental toxins in different Drosophila species. PMID:24416303

  8. A novel real-time PCR assay for quantitative analysis of methylated alleles (QAMA): analysis of the retinoblastoma locus.

    PubMed

    Zeschnigk, Michael; Böhringer, Stefan; Price, Elizabeth Ann; Onadim, Zerrin; Masshöfer, Lars; Lohmann, Dietmar R

    2004-09-07

    Altered methylation patterns have been found to play a role in developmental disorders, cancer and aging. Increasingly, changes in DNA methylation are used as molecular markers of disease. Therefore, there is a need for reliable and easy to use techniques to detect and measure DNA methylation in research and routine diagnostics. We have established a novel quantitative analysis of methylated alleles (QAMA) which is essentially a major improvement over a previous method based on real-time PCR (MethyLight). This method is based on real-time PCR on bisulfite-treated DNA. A significant advantage over conventional MethyLight is gained by the use of TaqMan probes based on minor groove binder (MGB) technology. Their improved sequence specificity facilitates relative quantification of methylated and unmethylated alleles that are simultaneously amplified in single tube. This improvement allows precise measurement of the ratio of methylated versus unmethylated alleles and cuts down potential sources of inter-assay variation. Therefore, fewer control assays are required. We have used this novel technical approach to identify hypermethylation of the CpG island located in the promoter region of the retinoblastoma (RB1) gene and found that QAMA facilitates reliable and fast measurement of the relative quantity of methylated alleles and improves handling of diagnostic methylation analysis. Moreover, the simplified reaction setup and robustness inherent to the single tube assay facilitates high-throughput methylation analysis. Because the high sequence specificity inherent to the MGB technology is widely used to discriminate single nucleotide polymorphisms, QAMA potentially can be used to discriminate the methylation status of single CpG dinucleotides.

  9. Real-time optical multiple object recognition and tracking system and method

    NASA Technical Reports Server (NTRS)

    Chao, Tien-Hsin (Inventor); Liu, Hua Kuang (Inventor)

    1987-01-01

    The invention relates to an apparatus and associated methods for the optical recognition and tracking of multiple objects in real time. Multiple point spatial filters are employed that pre-define the objects to be recognized at run-time. The system takes the basic technology of a Vander Lugt filter and adds a hololens. The technique replaces time, space and cost-intensive digital techniques. In place of multiple objects, the system can also recognize multiple orientations of a single object. This later capability has potential for space applications where space and weight are at a premium.

  10. Real-time optical multiple object recognition and tracking system and method

    NASA Astrophysics Data System (ADS)

    Chao, Tien-Hsin; Liu, Hua Kuang

    1987-12-01

    The invention relates to an apparatus and associated methods for the optical recognition and tracking of multiple objects in real time. Multiple point spatial filters are employed that pre-define the objects to be recognized at run-time. The system takes the basic technology of a Vander Lugt filter and adds a hololens. The technique replaces time, space and cost-intensive digital techniques. In place of multiple objects, the system can also recognize multiple orientations of a single object. This later capability has potential for space applications where space and weight are at a premium.

  11. Identification of an imprinted master trans regulator at the KLF14 locus related to multiple metabolic phenotypes.

    PubMed

    Small, Kerrin S; Hedman, Asa K; Grundberg, Elin; Nica, Alexandra C; Thorleifsson, Gudmar; Kong, Augustine; Thorsteindottir, Unnur; Shin, So-Youn; Richards, Hannah B; Soranzo, Nicole; Ahmadi, Kourosh R; Lindgren, Cecilia M; Stefansson, Kari; Dermitzakis, Emmanouil T; Deloukas, Panos; Spector, Timothy D; McCarthy, Mark I

    2011-06-01

    Genome-wide association studies have identified many genetic variants associated with complex traits. However, at only a minority of loci have the molecular mechanisms mediating these associations been characterized. In parallel, whereas cis regulatory patterns of gene expression have been extensively explored, the identification of trans regulatory effects in humans has attracted less attention. Here we show that the type 2 diabetes and high-density lipoprotein cholesterol-associated cis-acting expression quantitative trait locus (eQTL) of the maternally expressed transcription factor KLF14 acts as a master trans regulator of adipose gene expression. Expression levels of genes regulated by this trans-eQTL are highly correlated with concurrently measured metabolic traits, and a subset of the trans-regulated genes harbor variants directly associated with metabolic phenotypes. This trans-eQTL network provides a mechanistic understanding of the effect of the KLF14 locus on metabolic disease risk and offers a potential model for other complex traits.

  12. Real-time ECG emulation: a multiple dipole model for electrocardiography simulation.

    PubMed

    Abkai, Ciamak; Hesser, Jürgen

    2009-01-01

    A new model for describing electrocardiography (ECG) is presented, which is based on multiple dipoles compared to standard single dipole approaches in vector electrocardiography. The multiple dipole parameters are derived from real data (e.g. four dipoles from 12-channel ECG) by solving the backward problem of ECG numerically. Results are transformed to a waveform description based on Gaussian mixture for every dimension of each dipole. These compact parameterized descriptors are used for a very realistic real-time simulation applying the forward solution of the proposed model.

  13. Resequencing and fine-mapping of the chromosome 12q13-14 locus associated with multiple sclerosis refines the number of implicated genes.

    PubMed

    Cortes, Adrian; Field, Judith; Glazov, Evgeny A; Hadler, Johanna; Stankovich, Jim; Brown, Matthew A

    2013-06-01

    Multiple sclerosis (MS) is a common chronic inflammatory disease of the central nervous system. Susceptibility to the disease is affected by both environmental and genetic factors. Genetic factors include haplotypes in the histocompatibility complex (MHC) and over 50 non-MHC loci reported by genome-wide association studies. Amongst these, we previously reported polymorphisms in chromosome 12q13-14 with a protective effect in individuals of European descent. This locus spans 288 kb and contains 17 genes, including several candidate genes which have potentially significant pathogenic and therapeutic implications. In this study, we aimed to fine-map this locus. We have implemented a two-phase study: a variant discovery phase where we have used next-generation sequencing and two target-enrichment strategies [long-range polymerase chain reaction (PCR) and Nimblegen's solution phase hybridization capture] in pools of 25 samples; and a genotyping phase where we genotyped 712 variants in 3577 healthy controls and 3269 MS patients. This study confirmed the association (rs2069502, P = 9.9 × 10(-11), OR = 0.787) and narrowed down the locus of association to an 86.5 kb region. Although the study was unable to pinpoint the key-associated variant, we have identified a 42 (genotyped and imputed) single-nucleotide polymorphism haplotype block likely to harbour the causal variant. No evidence of association at previously reported low-frequency variants in CYP27B1 was observed. As part of the study we compared variant discovery performance using two target-enrichment strategies. We concluded that our pools enriched with Nimblegen's solution phase hybridization capture had better sensitivity to detect true variants than the pools enriched with long-range PCR, whilst specificity was better in the long-range PCR-enriched pools compared with solution phase hybridization capture enriched pools; this result has important implications for the design of future fine-mapping studies.

  14. Multiple-locus variable-number tandem repeat analysis (MLVA) of Leptospira interrogans serovar Pomona from Argentina reveals four new genotypes.

    PubMed

    Pavan, María Elisa; Cairó, Fabián; Brihuega, Bibiana; Samartino, Luis

    2008-01-01

    Outbreaks of leptospirosis occur regularly in Argentina, but little is known about their epidemiological relationships. We have analyzed the genetic diversity of a collection of 16 strains of Leptospira interrogans serovar Pomona isolated from animals and humans in Argentina during the past 45 years. Genotyping was performed by multiple-locus variable-number tandem repeat analysis (MLVA) using the loci VNTR4, VNTR7, VNTR9, VNTR10, VNTR19, VNTR23 and VNTR31, as described by Majed et al. [Identification of variable-number tandem-repeat loci in Leptospira interrogans sensu stricto. J Clin Microbiol 2005;43:539-45]. Clustering analysis revealed four new distinct MLVA genotypes, with a dominant one. Strains with this genotype were consistently isolated since 1960 to the present, mainly from cows and pigs, but also from humans, representing 75% of the total strains studied. These strains coexisted temporally and geographically with isolates presenting the other new genotypes. VNTR4 locus, with four different alleles, presented the highest diversity between the VNTR loci analyzed. MLVA patterns obtained will be useful for future diagnostic and epidemiological tracing analysis.

  15. Multi-locus real-time PCR for quantitation of bacteria in the environment reveals Exiguobacterium to be prevalent in permafrost.

    PubMed

    Rodrigues, Debora Frigi; Tiedje, James M

    2007-02-01

    We developed a multi-locus quantitative PCR approach to minimize problems of precision, sensitivity and primer specificity for quantifying a targeted microbial group in nature. This approach also avoids a systematic error in population quantitation when 16S rRNA genes are used because of copy number heterogeneity. Specific primers were designed to assess the abundance of psychrotrophic and mesophilic Exiguobacterium spp. that excluded the thermophilic members of the genus. The chosen primers targeted genes for DNA gyrase B (gyrB), the beta subunit of the RNA polymerase gene (rpoB) and a hypothetical gene so far found only in this group. The results demonstrate that the multiple primer approach provides a more reliable estimate of population density; that the targeted Exiguobacterium group is found at a median density of 50,000 gene copies per mug of total community DNA in 27 of 29 permafrost soils but was found in only one of the four temperate and tropical soils tested.

  16. Using Multiple FPGA Architectures for Real-time Processing of Low-level Machine Vision Functions

    Treesearch

    Thomas H. Drayer; William E. King; Philip A. Araman; Joseph G. Tront; Richard W. Conners

    1995-01-01

    In this paper, we investigate the use of multiple Field Programmable Gate Array (FPGA) architectures for real-time machine vision processing. The use of FPGAs for low-level processing represents an excellent tradeoff between software and special purpose hardware implementations. A library of modules that implement common low-level machine vision operations is presented...

  17. Molecular epidemiological study of Bacillus anthracis isolated in Mongolia by multiple-locus variable-number tandem-repeat analysis for 8 loci (MLVA-8).

    PubMed

    Okutani, Akiko; Tungalag, Hurelsukh; Boldbaatar, Bazartseren; Yamada, Akio; Tserennorov, Damdindorj; Otgonchimeg, Ishtsog; Erdenebat, Adiya; Otgonbaatar, Dashdavaa; Inoue, Satoshi

    2011-01-01

    The incidence of anthrax, which is caused by Bacillus anthracis, in the human and animal population of Mongolia has increased recently, and control of this infection is a nationwide concern. In this study, 29 isolates obtained from animals and various regions in Mongolia from 2001 to 2007 were analyzed by performing multiple-locus variable-number tandem-repeat analysis for 8 loci (MLVA-8) to understand the genetic relationship between the Mongolian B. anthracis isolates. We found that all the Mongolian isolates can be classified into A3 cluster along with the Japanese and the Chinese B. anthracis isolates. Our data revealed that MLVA-8 is useful for studying the molecular epidemiology of the Mongolian B. anthracis isolates and would help characterize B. anthracis infections in Mongolia.

  18. Phylogenetic typing of Bacillus anthracis isolated in Japan by multiple locus variable-number tandem repeats and the comprehensive single nucleotide polymorphism.

    PubMed

    Okutani, Akiko; Sekizuka, Tsuyoshi; Boldbaatar, Bazartseren; Yamada, Akio; Kuroda, Makoto; Inoue, Satoshi

    2010-01-01

    Twelve strains of Bacillus anthracis isolated in Japan were subjected to multiple locus variable-number tandem repeats analysis using 25 marker loci (MLVA25). The results showed that Japanese strains could be divided into two distinct genetic clusters, A3a and A3b. By using newly devised comprehensive single nucleotide polymorphisms (SNPs) analysis, Japanese strains were also divided into two groups. The results obtained by the MLVA25 and plasmids SNP analysis well coincided, indicating that both methods were highly sensitive to discriminate B. anthracis strains. These results suggested that MLVA25 had sufficient discrimination power to identify B. anthracis at the strain level, and that MLVA25 as well as comprehensive SNPs analysis could facilitate further studies of B. anthracis strains including Japanese and other Asian strains.

  19. Multiple-locus variable number tandem repeat analysis is superior to spa typing and sufficient to characterize MRSA for surveillance purposes.

    PubMed

    Bosch, Thijs; Pluister, Gerlinde N; van Luit, Martijn; Landman, Fabian; van Santen-Verheuvel, Marga; Schot, Corrie; Witteveen, Sandra; van der Zwaluw, Kim; Heck, Max E O C; Schouls, Leo M

    2015-01-01

    Assess the best approach to type methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcal protein A (spa) typing, multiple-locus variable number tandem repeat analysis (MLVA) or both. Discriminatory power of spa typing and MLVA was determined using 20,771 MRSA isolates. There were twice as many MLVA types (MTs) as spa types present in the collection. Among the top 70% of the isolates, 37 spa types and 139 MTs were found. MLVA diversity among the top-10 spa types was high (diversity index 0.96), while spa diversity among the top-10 MTs was much lower (diversity index 0.83). The probability that two MRSA isolates with the same spa type also had the same MT was low (Wallace's coefficient 0.27). By contrast, most MRSA isolates yielding the same MT also had the same spa type (Wallace's coefficient 0.90). MLVA is superior to spa typing and will suffice to characterize MRSA isolates for surveillance.

  20. A multiple-locus variable-number tandem repeat analysis (MLVA) of Listeria monocytogenes isolated from Norwegian salmon-processing factories and from listeriosis patients.

    PubMed

    Lunestad, B T; Truong, T T T; Lindstedt, B-A

    2013-10-01

    The objective of this study was to characterize Listeria monocytogenes isolated from farmed Atlantic salmon (Salmo salar) and the processing environment in three different Norwegian factories, and compare these to clinical isolates by multiple-locus variable-number tandem repeat analysis (MLVA). The 65 L. monocytogenes isolates obtained gave 15 distinct MLVA profiles. There was great heterogeneity in the distribution of MLVA profiles in factories and within each factory. Nine of the 15 MLVA profiles found in the fish-associated isolates were found to match human profiles. The MLVA profile 07-07-09-10-06 was the most common strain in Norwegian listeriosis patients. L. monocytogenes with this profile has previously been associated with at least two known listeriosis outbreaks in Norway, neither determined to be due to fish consumption. However, since this profile was also found in fish and in the processing environment, fish should be considered as a possible food vehicle during sporadic cases and outbreaks of listeriosis.

  1. Identification of Variable-Number Tandem-Repeat (VNTR) Sequences in Acinetobacter baumannii and Interlaboratory Validation of an Optimized Multiple-Locus VNTR Analysis Typing Scheme▿†

    PubMed Central

    Pourcel, Christine; Minandri, Fabrizia; Hauck, Yolande; D'Arezzo, Silvia; Imperi, Francesco; Vergnaud, Gilles; Visca, Paolo

    2011-01-01

    Acinetobacter baumannii is an important opportunistic pathogen responsible for nosocomial outbreaks, mostly occurring in intensive care units. Due to the multiplicity of infection sources, reliable molecular fingerprinting techniques are needed to establish epidemiological correlations among A. baumannii isolates. Multiple-locus variable-number tandem-repeat analysis (MLVA) has proven to be a fast, reliable, and cost-effective typing method for several bacterial species. In this study, an MLVA assay compatible with simple PCR- and agarose gel-based electrophoresis steps as well as with high-throughput automated methods was developed for A. baumannii typing. Preliminarily, 10 potential polymorphic variable-number tandem repeats (VNTRs) were identified upon bioinformatic screening of six annotated genome sequences of A. baumannii. A collection of 7 reference strains plus 18 well-characterized isolates, including unique types and representatives of the three international A. baumannii lineages, was then evaluated in a two-center study aimed at validating the MLVA assay and comparing it with other genotyping assays, namely, macrorestriction analysis with pulsed-field gel electrophoresis (PFGE) and PCR-based sequence group (SG) profiling. The results showed that MLVA can discriminate between isolates with identical PFGE types and SG profiles. A panel of eight VNTR markers was selected, all showing the ability to be amplified and good amounts of polymorphism in the majority of strains. Independently generated MLVA profiles, composed of an ordered string of allele numbers corresponding to the number of repeats at each VNTR locus, were concordant between centers. Typeability, reproducibility, stability, discriminatory power, and epidemiological concordance were excellent. A database containing information and MLVA profiles for several A. baumannii strains is available from http://mlva.u-psud.fr/. PMID:21147956

  2. Microfluidic-chip-based multiple-locus variable-number tandem-repeat fingerprinting with new primer sets for methicillin-resistant Staphylococcus aureus.

    PubMed

    Sabat, Artur J; Chlebowicz, Monika A; Grundmann, Hajo; Arends, Jan P; Kampinga, Greetje; Meessen, Nico E L; Friedrich, Alexander W; van Dijl, Jan Maarten

    2012-07-01

    The detection of outbreaks of methicillin-resistant Staphylococcus aureus (MRSA) infections and a rapid and accurate identification of sources and routes of transmission should be conducted in hospital settings as early and swiftly as possible. In this study, we investigated the application potential of a new approach based on multiple-locus variable-number tandem-repeat fingerprinting (MLVF) and microfluidics technology for a rapid discrimination of MRSA lineages in outbreak settings. A total of 206 nonrepetitive MRSA isolates recovered from infected patients at the University Medical Center Groningen between 2000 and 2010 were tested. The results obtained by MLVF using microcapillary electrophoresis with newly designed primers were compared to those obtained by spa typing and multiple-locus variable-number tandem-repeat analysis (MLVA). The discriminatory power was 0.980 (107 patterns), 0.969 (85 allelic profiles), and 0.959 (66 types) for MLVF, MLVA, and spa typing, respectively. All methods tested showed a good concordance of results calculated by the adjusted Rand's coefficient method. Comparisons of data obtained by the three approaches allowed us to propose an 88% cutoff value for the similarity between any two MLVF patterns, which can be used in S. aureus epidemiological studies, including analyses of outbreaks and strain transmission events. Of the three tested methods, MLVF is the cheapest, fastest, and easiest to perform. MLVF applied to microfluidic polymer chips is a rapid, cheap, reproducible, and highly discriminating tool to determine the clonality of MRSA isolates and to trace the spread of MRSA strains over periods of many years. Although spa typing should be used due to its portability of data, MLVF has a high added value because it is more discriminatory.

  3. Genetic subtyping of Listeria monocytogenes via multiple-locus sequence typing using iap, sigB and actA

    PubMed Central

    YOSHIKAWA, Yuko; OCHIAI, Yoshitsugu; MOCHIZUKI, Mariko; FUJITA, Osamu; TAKANO, Takashi; HONDO, Ryo; UEDA, Fukiko

    2016-01-01

    Pulse field gel electrophoresis (PFGE) is widely used for listeriosis surveillance. Although this technique is effective for epidemiology, the data among laboratories are inconsistent. We previously reported a method for Listeria monocytogenes subtyping combined with sequence analysis of partial iap and whole genome restriction fragment length polymorphism (RFLP) using XbaI, ClaI (BanIII) and PstI. However, distinguishing subtypes was challenging, because the output comprised complicated fragment patterns. In this study, we aimed to establish a simple genotyping method that does not depend on visual observation, rather it focuses on multi-locus sequence typing (MLST) using three genes, iap, sigB and actA. Sixty-eight strains of L. monocytogenes including EGD-e as a reference strain were investigated to ensure consistency with previous data on the genetic characterization. All strains were grouped into 29 types by both analyses. Although there are some differences in classification, major clades included the same strains. Simpson’s indices of diversity (SID) by MLST and iap-RFLP-based typing were 0.967 (95% confidence interval [CI]: 0.955/0.978) and 0.967 (95% CI: 0.955/0.979), respectively. The discriminatory power of both methods can be considered almost identical. Compared with the results of 38 selected strains, the strains within the MLST clusters in this study coincided with those obtained using PFGE. Thus, the MLST strategy could help differentiate among L. monocytogenes isolates during epidemiological studies. PMID:27725353

  4. Multiple roles for UV RESISTANCE LOCUS8 in regulating gene expression and metabolite accumulation in Arabidopsis under solar ultraviolet radiation.

    PubMed

    Morales, Luis O; Brosché, Mikael; Vainonen, Julia; Jenkins, Gareth I; Wargent, Jason J; Sipari, Nina; Strid, Åke; Lindfors, Anders V; Tegelberg, Riitta; Aphalo, Pedro J

    2013-02-01

    Photomorphogenic responses triggered by low fluence rates of ultraviolet B radiation (UV-B; 280-315 nm) are mediated by the UV-B photoreceptor UV RESISTANCE LOCUS8 (UVR8). Beyond our understanding of the molecular mechanisms of UV-B perception by UVR8, there is still limited information on how the UVR8 pathway functions under natural sunlight. Here, wild-type Arabidopsis (Arabidopsis thaliana) and the uvr8-2 mutant were used in an experiment outdoors where UV-A (315-400 nm) and UV-B irradiances were attenuated using plastic films. Gene expression, PYRIDOXINE BIOSYNTHESIS1 (PDX1) accumulation, and leaf metabolite signatures were analyzed. The results show that UVR8 is required for transcript accumulation of genes involved in UV protection, oxidative stress, hormone signal transduction, and defense against herbivores under solar UV. Under natural UV-A irradiance, UVR8 is likely to interact with UV-A/blue light signaling pathways to moderate UV-B-driven transcript and PDX1 accumulation. UVR8 both positively and negatively affects UV-A-regulated gene expression and metabolite accumulation but is required for the UV-B induction of phenolics. Moreover, UVR8-dependent UV-B acclimation during the early stages of plant development may enhance normal growth under long-term exposure to solar UV.

  5. The locus for Meckel syndrome with multiple congenital anomalies maps to chromosome 17q21-q24.

    PubMed

    Paavola, P; Salonen, R; Weissenbach, J; Peltonen, L

    1995-10-01

    Autosomal recessive Meckel syndrome (OMIM 249000) (MES), first described in 1822 by Johann F. Meckel, is a major monogenic malformation syndrome with a neural tube defect leading to death of the fetus in utero or shortly after birth. The hallmarks of the syndrome are occipital meningoencephalocele, very large kidneys with multicystic dysplasia, cystic and fibrotic changes of the liver and polydactyly (Fig. 1). Other typical malformations for MES are cleft lip and palate, urinary tract anomalies, ambiguous genitals in the males and club feet. Although MES has been reported worldwide, reports on the true birth prevalence of MES in different populations are scarce. In Finland MES is effectively screened and relatively frequent with a birth prevalence of 1:9,000 and a disease gene frequency of 0.01 (ref.4) which is of the same order of magnitude as that of the most common recessive diseases belonging to the 'Finnish disease heritage', that is genetic disorders enriched or only encountered in Finland. However, in MES, comparable or even higher incidences are also reported from other populations. Here, we report the assignment of the MES locus to chromosome 17q21-q24 in the 13 cM region, and exclude some of the potential candidate genes located in this critical chromosomal region.

  6. Modeling the Philippines' real gross domestic product: A normal estimation equation for multiple linear regression

    NASA Astrophysics Data System (ADS)

    Urrutia, Jackie D.; Tampis, Razzcelle L.; Mercado, Joseph; Baygan, Aaron Vito M.; Baccay, Edcon B.

    2016-02-01

    The objective of this research is to formulate a mathematical model for the Philippines' Real Gross Domestic Product (Real GDP). The following factors are considered: Consumers' Spending (x1), Government's Spending (x2), Capital Formation (x3) and Imports (x4) as the Independent Variables that can actually influence in the Real GDP in the Philippines (y). The researchers used a Normal Estimation Equation using Matrices to create the model for Real GDP and used α = 0.01.The researchers analyzed quarterly data from 1990 to 2013. The data were acquired from the National Statistical Coordination Board (NSCB) resulting to a total of 96 observations for each variable. The data have undergone a logarithmic transformation particularly the Dependent Variable (y) to satisfy all the assumptions of the Multiple Linear Regression Analysis. The mathematical model for Real GDP was formulated using Matrices through MATLAB. Based on the results, only three of the Independent Variables are significant to the Dependent Variable namely: Consumers' Spending (x1), Capital Formation (x3) and Imports (x4), hence, can actually predict Real GDP (y). The regression analysis displays that 98.7% (coefficient of determination) of the Independent Variables can actually predict the Dependent Variable. With 97.6% of the result in Paired T-Test, the Predicted Values obtained from the model showed no significant difference from the Actual Values of Real GDP. This research will be essential in appraising the forthcoming changes to aid the Government in implementing policies for the development of the economy.

  7. Multiple Input Feature Sets from Real-Time Color and Range Data for Reliable Tracking

    SciTech Connect

    Tsap, L.V.; Goldgof, D.B.

    1999-10-19

    This paper describes a work in progress on using multiple sets of input features for robust real-time object tracking in image sequences. Traditional approaches to tracking relied mostly on segmentation of the intensity data using motion or appearance data. Recent availability of real-time range data allows us to use it as an additional unrivaled source of information. We propose a combination of intensity- and range-based input features. Range data enables localized search for' specific features which improves tracking reliability and speed. Proposed approach was successfully tested for the face and gesture tracking application.

  8. Identification of three microsatellites at the human myelin oligodendrocyte glycoprotein (MOG) locus, a gene potentially involved in multiple sclerosis

    SciTech Connect

    Borot, N.; Dolbois, L.; Coppin, H.

    1994-09-01

    The gene encoding MOG is located on the short arm of chromosome 6, less than 120 kb telomeric to HLA-F. We have cloned the MOG gene from a cosmid library. Using tandemly repeated dinucleotides, we probed the genomic region containing the human MOG gene in order to identify and localize polymorphic markers: three microsatellites were characterized in that region. Using a polymerase chain reaction-based technique, we studied length variability for these three markers among 173 healthy individuals and 167 multiple sclerosis patients. Heterozygosity varied from 50% to 60% according to the marker. Pairwise studies showed significant linkage disequilibrium between some alleles. Multiple sclerosis patients and controls were not shown to have statistically significant differences in the MOG region. Further studies on the coding regions are in progress in order to exclude any involvement of the MOG gene in multiple sclerosis.

  9. Real-time tracking of multiple objects using adaptive correlation filters with complex constraints

    NASA Astrophysics Data System (ADS)

    Diaz-Ramirez, Victor H.; Contreras, Viridiana; Kober, Vitaly; Picos, Kenia

    2013-11-01

    A real-time system for classification and tracking of multiple moving objects is proposed. The system employs a bank of composite correlation filters with complex constraints implemented in parallel on a graphics processing unit. When a scene frame is captured, the system splits the frame into several fragments on the base of a modeling kinematic prediction of target's locations. The fragments are processed with a bank of adaptive filters. The filters are synthesized with the help of an iterative algorithm, which optimizes discrimination capability for each target. Using complex constraints in the filter design, multiple objects in the input frame can be detected and classified by analyzing the intensity and phase distributions on the output complex correlation plane for each fragment. The performance of the proposed system in terms of tracking accuracy, classification efficiency and time expenses is tested and discussed with synthetic and real input-scene sequences. The results are compared with those of common techniques based on correlation filtering.

  10. Comprehensive analysis of human endogenous retrovirus group HERV-W locus transcription in multiple sclerosis brain lesions by high-throughput amplicon sequencing.

    PubMed

    Schmitt, Katja; Richter, Christin; Backes, Christina; Meese, Eckart; Ruprecht, Klemens; Mayer, Jens

    2013-12-01

    Human endogenous retroviruses (HERVs) of the HERV-W group comprise hundreds of loci in the human genome. Deregulated HERV-W expression and HERV-W locus ERVWE1-encoded Syncytin-1 protein have been implicated in the pathogenesis of multiple sclerosis (MS). However, the actual transcription of HERV-W loci in the MS context has not been comprehensively analyzed. We investigated transcription of HERV-W in MS brain lesions and white matter brain tissue from healthy controls by employing next-generation amplicon sequencing of HERV-W env-specific reverse transcriptase (RT) PCR products, thus revealing transcribed HERV-W loci and the relative transcript levels of those loci. We identified more than 100 HERV-W loci that were transcribed in the human brain, with a limited number of loci being predominantly transcribed. Importantly, relative transcript levels of HERV-W loci were very similar between MS and healthy brain tissue samples, refuting deregulated transcription of HERV-W env in MS brain lesions, including the high-level-transcribed ERVWE1 locus encoding Syncytin-1. Quantitative RT-PCR likewise did not reveal differences in MS regarding HERV-W env general transcript or ERVWE1- and ERVWE2-specific transcript levels. However, we obtained evidence for interindividual differences in HERV-W transcript levels. Reporter gene assays indicated promoter activity of many HERV-W long terminal repeats (LTRs), including structurally incomplete LTRs. Our comprehensive analysis of HERV-W transcription in the human brain thus provides important information on the biology of HERV-W in MS lesions and normal human brain, implications for study design, and mechanisms by which HERV-W may (or may not) be involved in MS.

  11. The NASA Smart Probe Project for real-time multiple microsensor tissue recognition

    NASA Technical Reports Server (NTRS)

    Andrews, Russell J.; Mah, Robert W.

    2003-01-01

    BACKGROUND: Remote surgery requires automated sensors, effectors and sensor-effector communication. The NASA Smart Probe Project has focused on the sensor aspect. METHODS: The NASA Smart Probe uses neural networks and data from multiple microsensors for a unique tissue signature in real time. Animal and human trials use several probe configurations: (1) 8-microsensor probe (2.5 mm in diameter) for rodent studies (normal and subcutaneous mammary tumor tissues), and (2) 21-gauge needle probe with 3 spectroscopic fibers and an impedance microelectrode for breast cancer diagnosis in humans. Multisensor data are collected in real time (update 100 times/s) using PCs. RESULTS: Human data (collected by NASA licensee BioLuminate) from 15 women undergoing breast biopsy distinguished normal tissue from both benign tumors and breast carcinoma. Tumor margins and necrosis are rapidly detected. CONCLUSION: Real-time tissue identification is achievable. Potential applications, including probes incorporating nanoelectrode arrays, are presented. Copyright 2003 S. Karger AG, Basel.

  12. The NASA Smart Probe Project for real-time multiple microsensor tissue recognition

    NASA Technical Reports Server (NTRS)

    Andrews, Russell J.; Mah, Robert W.

    2003-01-01

    BACKGROUND: Remote surgery requires automated sensors, effectors and sensor-effector communication. The NASA Smart Probe Project has focused on the sensor aspect. METHODS: The NASA Smart Probe uses neural networks and data from multiple microsensors for a unique tissue signature in real time. Animal and human trials use several probe configurations: (1) 8-microsensor probe (2.5 mm in diameter) for rodent studies (normal and subcutaneous mammary tumor tissues), and (2) 21-gauge needle probe with 3 spectroscopic fibers and an impedance microelectrode for breast cancer diagnosis in humans. Multisensor data are collected in real time (update 100 times/s) using PCs. RESULTS: Human data (collected by NASA licensee BioLuminate) from 15 women undergoing breast biopsy distinguished normal tissue from both benign tumors and breast carcinoma. Tumor margins and necrosis are rapidly detected. CONCLUSION: Real-time tissue identification is achievable. Potential applications, including probes incorporating nanoelectrode arrays, are presented. Copyright 2003 S. Karger AG, Basel.

  13. The NASA Smart Probe Project for real-time multiple microsensor tissue recognition.

    PubMed

    Andrews, Russell J; Mah, Robert W

    2003-01-01

    Remote surgery requires automated sensors, effectors and sensor-effector communication. The NASA Smart Probe Project has focused on the sensor aspect. The NASA Smart Probe uses neural networks and data from multiple microsensors for a unique tissue signature in real time. Animal and human trials use several probe configurations: (1) 8-microsensor probe (2.5 mm in diameter) for rodent studies (normal and subcutaneous mammary tumor tissues), and (2) 21-gauge needle probe with 3 spectroscopic fibers and an impedance microelectrode for breast cancer diagnosis in humans. Multisensor data are collected in real time (update 100 times/s) using PCs. Human data (collected by NASA licensee BioLuminate) from 15 women undergoing breast biopsy distinguished normal tissue from both benign tumors and breast carcinoma. Tumor margins and necrosis are rapidly detected. Real-time tissue identification is achievable. Potential applications, including probes incorporating nanoelectrode arrays, are presented. Copyright 2003 S. Karger AG, Basel

  14. Prevalence and molecular characterization of Escherichia coli O157:H7 by multiple locus variable number tandem repeat analysis and pulsed field gel electrophoresis in three sheep farming operations in California.

    USDA-ARS?s Scientific Manuscript database

    A yearlong study was conducted to determine the fecal prevalence of Escherichia coli O157:H7 in three sheep ranches. Strain diversity and persistence was compared using multiple locus variable number tandem repeat analysis and pulsed field gel electrophoresis. Ranch C, a feedlot, consisted of young ...

  15. Genome-wide two-locus interaction analysis identifies multiple epistatic SNP pairs that confer risk of prostate cancer: A cross-population study.

    PubMed

    Shen, Jiawei; Li, Zhiqiang; Song, Zhijian; Chen, Jianhua; Shi, Yongyong

    2017-05-01

    Prostate cancer is one of the most common carcinomas among adult males. Recently, genome-wide association studies (GWAS) have identified several susceptibility genes of prostate cancer. However, these single locus results can only explain a small proportion of the genetic etiology. In order to understand how multiple genetic variants may contribute to the penetrance of prostate cancer, we conducted a genome-wide SNP-SNP interaction study in four populations, involving 5,269 cases and 5,289 controls. We exhaustively evaluated all pairs of SNP-SNP interactions for 661,658 SNPs that were consensus in all four groups, and then performed a meta-analysis to combine the results. We found multiple variants within region 7p21.3 and 18p11.22 significantly interacted with each other and reached genome-wide significance levels. The most significant epistasis was between rs1105255 (intergenic, near RBSG3) and rs651431 (intergenic, near VAPA) (p = 1.4 × 10(-14) ). Notably, VAPA was identified to be the protein-coding transcripts as PTEN competing endogenous RNA in prostate cancer. And PTEN is a critical tumor suppressor gene frequently altered in cancers. In addition, 7p21.3 involves several pseudogenes, whose parental genes are cancer-related. Recently, growing evidence strongly suggests they are of multifaceted involvements in the pathogenesis of cancer. Multiple regulatory elements were found within 7p21.3 and 18p11.22, indicating the variants might regulate the nearby genes and confer risk of disease. Additionally, we also found several other significant epistasis, most of which were near or in cancer-related genes. Drug target enrichment analysis suggested genes in top epistasis significantly overlapped with target genes of FDA-approved drugs for treatment of prostate cancer. © 2017 UICC.

  16. Fine-scale mapping of 8q24 locus identifies multiple independent risk variants for breast cancer.

    PubMed

    Shi, Jiajun; Zhang, Yanfeng; Zheng, Wei; Michailidou, Kyriaki; Ghoussaini, Maya; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Lush, Michael; Milne, Roger L; Shu, Xiao-Ou; Beesley, Jonathan; Kar, Siddhartha; Andrulis, Irene L; Anton-Culver, Hoda; Arndt, Volker; Beckmann, Matthias W; Zhao, Zhiguo; Guo, Xingyi; Benitez, Javier; Beeghly-Fadiel, Alicia; Blot, William; Bogdanova, Natalia V; Bojesen, Stig E; Brauch, Hiltrud; Brenner, Hermann; Brinton, Louise; Broeks, Annegien; Brüning, Thomas; Burwinkel, Barbara; Cai, Hui; Canisius, Sander; Chang-Claude, Jenny; Choi, Ji-Yeob; Couch, Fergus J; Cox, Angela; Cross, Simon S; Czene, Kamila; Darabi, Hatef; Devilee, Peter; Droit, Arnaud; Dork, Thilo; Fasching, Peter A; Fletcher, Olivia; Flyger, Henrik; Fostira, Florentia; Gaborieau, Valerie; García-Closas, Montserrat; Giles, Graham G; Grip, Mervi; Guenel, Pascal; Haiman, Christopher A; Hamann, Ute; Hartman, Mikael; Miao, Hui; Hollestelle, Antoinette; Hopper, John L; Hsiung, Chia-Ni; Ito, Hidemi; Jakubowska, Anna; Johnson, Nichola; Torres, Diana; Kabisch, Maria; Kang, Daehee; Khan, Sofia; Knight, Julia A; Kosma, Veli-Matti; Lambrechts, Diether; Li, Jingmei; Lindblom, Annika; Lophatananon, Artitaya; Lubinski, Jan; Mannermaa, Arto; Manoukian, Siranoush; Le Marchand, Loic; Margolin, Sara; Marme, Frederik; Matsuo, Keitaro; McLean, Catriona; Meindl, Alfons; Muir, Kenneth; Neuhausen, Susan L; Nevanlinna, Heli; Nord, Silje; Børresen-Dale, Anne-Lise; Olson, Janet E; Orr, Nick; van den Ouweland, Ans M W; Peterlongo, Paolo; Choudary Putti, Thomas; Rudolph, Anja; Sangrajrang, Suleeporn; Sawyer, Elinor J; Schmidt, Marjanka K; Schmutzler, Rita K; Shen, Chen-Yang; Hou, Ming-Feng; Shrubsole, Matha J; Southey, Melissa C; Swerdlow, Anthony; Hwang Teo, Soo; Thienpont, Bernard; Toland, Amanda E; Tollenaar, Robert A E M; Tomlinson, Ian; Truong, Therese; Tseng, Chiu-Chen; Wen, Wanqing; Winqvist, Robert; Wu, Anna H; Har Yip, Cheng; Zamora, Pilar M; Zheng, Ying; Floris, Giuseppe; Cheng, Ching-Yu; Hooning, Maartje J; Martens, John W M; Seynaeve, Caroline; Kristensen, Vessela N; Hall, Per; Pharoah, Paul D P; Simard, Jacques; Chenevix-Trench, Georgia; Dunning, Alison M; Antoniou, Antonis C; Easton, Douglas F; Cai, Qiuyin; Long, Jirong

    2016-09-15

    Previous genome-wide association studies among women of European ancestry identified two independent breast cancer susceptibility loci represented by single nucleotide polymorphisms (SNPs) rs13281615 and rs11780156 at 8q24. A fine-mapping study across 2.06 Mb (chr8:127,561,724-129,624,067, hg19) in 55,540 breast cancer cases and 51,168 controls within the Breast Cancer Association Consortium was conducted. Three additional independent association signals in women of European ancestry, represented by rs35961416 (OR = 0.95, 95% CI = 0.93-0.97, conditional p = 5.8 × 10(-6) ), rs7815245 (OR = 0.94, 95% CI = 0.91-0.96, conditional p = 1.1 × 10(-6) ) and rs2033101 (OR = 1.05, 95% CI = 1.02-1.07, conditional p = 1.1 × 10(-4) ) were found. Integrative analysis using functional genomic data from the Roadmap Epigenomics, the Encyclopedia of DNA Elements project, the Cancer Genome Atlas and other public resources implied that SNPs rs7815245 in Signal 3, and rs1121948 in Signal 5 (in linkage disequilibrium with rs11780156, r(2)  = 0.77), were putatively functional variants for two of the five independent association signals. The results highlighted multiple 8q24 variants associated with breast cancer susceptibility in women of European ancestry.

  17. Development of a 10,000 Locus Genetic Map of the Sunflower Genome Based on Multiple Crosses

    PubMed Central

    Bowers, John E.; Bachlava, Eleni; Brunick, Robert L.; Rieseberg, Loren H.; Knapp, Steven J.; Burke, John M.

    2012-01-01

    Genetic linkage maps have the potential to facilitate the genetic dissection of complex traits and comparative analyses of genome structure, as well as molecular breeding efforts in species of agronomic importance. Until recently, the majority of such maps was based on relatively low-throughput marker technologies, which limited marker density across the genome. The availability of high-throughput genotyping technologies has, however, made possible the efficient development of high-density genetic maps. Here, we describe the analysis and integration of genotypic data from four sunflower (Helianthus annuus L.) mapping populations to produce a consensus linkage map of the sunflower genome. Although the individual maps (which contained 3500–5500 loci each) were highly colinear, we observed localized variation in recombination rates in several genomic regions. We also observed several gaps up to 26 cM in length that completely lacked mappable markers in individual crosses, presumably due to regions of identity by descent in the mapping parents. Because these regions differed by cross, the consensus map of 10,080 loci contained no such gaps, clearly illustrating the value of simultaneously analyzing multiple mapping populations. PMID:22870395

  18. Multiple-locus variable-number tandem-repeat analysis in Salmonella isolates as an effective molecular subtyping method.

    PubMed

    Hashemi, Atieh; Baghbani-Arani, Fahimeh; Ahmadiyan, Sepideh; Ghavami-Nejad, Sarvenaz

    2017-10-05

    Due to the limitations of serotyping, to differentiate closely related microbial isolates and to investigate disease outbreaks, molecular genotyping methods including multiple loci variable number of tandem repeats (VNTR) analysis (MLVA) has been developed. The usefulness of MLVA was recently demonstrated for Salmonella Infantis and Salmonella Enteritidis isolated from human sources in Iran. In the present study. The discriminatory ability of this method was investigated in 78 Iranian Salmonella enterica isolates. Salmonella strains isolated from human urine, stool, bone marrow, blood, ascites and synovial fluid sources in Iran during the years 2012 and 2015 were analyzed. Among these 78 Salmonella isolates, 70 isolates belonging to eight serotypes/serogroups, while eight were nontypeable. Six VNTR loci were amplified from all isolates. The isolates were distributed into 67 genotypes. Two out of the 6 markers (Sal20 and Sal16) were highly discriminatory for all strains (DI > 0.80) while composition of all VNTR loci produced 67 different types with 0.995 D value. The high discrimination power of MLVA in Salmonella molecular typing via combination of VNTR loci studied here, suggesting that this method is highly valuable for molecular epidemiology of Salmonella strains. Copyright © 2017. Published by Elsevier Ltd.

  19. Development of a 10,000 locus genetic map of the sunflower genome based on multiple crosses.

    PubMed

    Bowers, John E; Bachlava, Eleni; Brunick, Robert L; Rieseberg, Loren H; Knapp, Steven J; Burke, John M

    2012-07-01

    Genetic linkage maps have the potential to facilitate the genetic dissection of complex traits and comparative analyses of genome structure, as well as molecular breeding efforts in species of agronomic importance. Until recently, the majority of such maps was based on relatively low-throughput marker technologies, which limited marker density across the genome. The availability of high-throughput genotyping technologies has, however, made possible the efficient development of high-density genetic maps. Here, we describe the analysis and integration of genotypic data from four sunflower (Helianthus annuus L.) mapping populations to produce a consensus linkage map of the sunflower genome. Although the individual maps (which contained 3500-5500 loci each) were highly colinear, we observed localized variation in recombination rates in several genomic regions. We also observed several gaps up to 26 cM in length that completely lacked mappable markers in individual crosses, presumably due to regions of identity by descent in the mapping parents. Because these regions differed by cross, the consensus map of 10,080 loci contained no such gaps, clearly illustrating the value of simultaneously analyzing multiple mapping populations.

  20. Rapid identification of international multidrug-resistant Pseudomonas aeruginosa clones by multiple-locus variable number of tandem repeats analysis and investigation of their susceptibility to lytic bacteriophages.

    PubMed

    Larché, Jérôme; Pouillot, Flavie; Essoh, Christiane; Libisch, Balázs; Straut, Monica; Lee, Je Chul; Soler, Charles; Lamarca, Richard; Gleize, Elodie; Gabard, Jérôme; Vergnaud, Gilles; Pourcel, Christine

    2012-12-01

    The objective of this study was to determine the genetic diversity of multidrug-resistant (MDR) Pseudomonas aeruginosa strains isolated over a period of 12 months in two French hospitals and to test their susceptibility to bacteriophages. A total of 47 MDR isolates recovered from hospitalized patients were genotyped using multiple-locus variable number of tandem repeats analysis. The genotypes were distributed into five clones (including 19, 5, 5, 3, and 3 isolates, respectively) and 12 singletons. Comparison to 77 MDR strains from three other countries, and MLST analysis of selected isolates showed the predominance of international MDR clones. The larger clone, CC235, contained 59 isolates displaying different antibiotic resistance mechanisms, including the presence of the GES1, VIM-2, VIM-4, and IMP-1 β-lactamases. Three newly isolated P. aeruginosa bacteriophages were found to lyse 42 of the 44 analyzed strains, distributed into the different clonal complexes. This pilot study suggests that systematic genotyping of P. aeruginosa MDR strains could improve our epidemiological understanding of transmission at both the local (hospital) and the national level and that phage therapy could be an alternative or a complementary treatment to antibiotics for treating MDR-infected patients.

  1. Multiple-locus variable-nucleotide tandem repeat subtype analysis implicates European starlings as biological vectors for Escherichia coli O157:H7 in Ohio, USA.

    PubMed

    Williams, M L; Pearl, D L; Lejeune, J T

    2011-10-01

    To provide molecular epidemiological evidence of avian transmission of Escherichia coli O157:H7 between dairy farms in Ohio, this study was designed to identify genetic relatedness between isolates originating from bovine faecal samples and intestinal contents of European starlings captured on these farms. During a three-year period (2007-2009), cattle (n = 9000) and starlings (n = 430) on 150 different dairy farms in northern Ohio were sampled for the presence of E. coli O157:H7. Isolates were subjected to multiple-locus variable-nucleotide tandem repeat analysis (MLVA). Distinct allelic groups were identified on most farms; however, isolates clustering into three MLVA groups originated from both cattle and birds on different farms. Sharing of indistinguishable epidemiologically linked E. coli O157 MLVA subtypes between starlings and cattle on different farms supports the hypothesis that these birds contribute to the transmission of E. coli O157:H7 between dairy farms. A continued need exists to identify and to improve preharvest measures for controlling E. coli O157:H7. Controlling wildlife intrusion, particularly European starlings, on livestock operations, may be an important strategy for reducing dissemination of E. coli O157:H7 between farms and thereby potentially decreasing the on-farm prevalence of E. coli O157:H7 and enhancing the safety of the food supply. © 2011 The Authors. Journal of Applied Microbiology © 2011 The Society for Applied Microbiology.

  2. Hospital Drains as Reservoirs of Pseudomonas aeruginosa: Multiple-Locus Variable-Number of Tandem Repeats Analysis Genotypes Recovered from Faucets, Sink Surfaces and Patients

    PubMed Central

    Lalancette, Cindy; Charron, Dominique; Laferrière, Céline; Dolcé, Patrick; Déziel, Eric; Prévost, Michèle; Bédard, Emilie

    2017-01-01

    Identifying environmental sources of Pseudomonas aeruginosa (Pa) related to hospital-acquired infections represents a key challenge for public health. Biofilms in water systems offer protection and favorable growth conditions, and are prime reservoirs of microorganisms. A comparative genotyping survey assessing the relationship between Pa strains recovered in hospital sink biofilm and isolated in clinical specimens was conducted. Environmental strains from drain, faucet and sink-surface biofilm were recovered by a culture method after an incubation time ranging from 48 to 240 h. The genotyping of 38 environmental and 32 clinical isolates was performed using a multiple-locus variable-number of tandem repeats analysis (MLVA). More than one-third of Pa isolates were only cultivable following ≥48 h of incubation, and were predominantly from faucet and sink-surface biofilms. In total, 41/70 strains were grouped within eight genotypes (A to H). Genotype B grouped a clinical and an environmental strain isolated in the same ward, 5 months apart, suggesting this genotype could thrive in both contexts. Genotype E grouped environmental isolates that were highly prevalent throughout the hospital and that required a longer incubation time. The results from the multi-hospital follow-up study support the drain as an important reservoir of Pa dissemination to faucets, sink surfaces and patients. Optimizing the recovery of environmental strains will strengthen epidemiological investigations, facilitate pathway identification, and assist in identifying and controlling the reservoirs potentially associated to hospital-acquired infections. PMID:28792484

  3. Diversity of Mycoplasma hominis clinical isolates from Bordeaux, France, as assessed by multiple-locus variable-number tandem repeat analysis.

    PubMed

    Férandon, Cyril; Peuchant, Olivia; Renaudin, Hélène; Bébéar, Cécile

    2013-05-28

    Mycoplasma hominis is an opportunistic human mycoplasma species that can cause various urogenital infections and, less frequently, extragenital infections. The objective of this work was to study the genetic diversity of this species using a molecular typing method based on multiple-locus variable-number tandem repeat (VNTR) analysis (MLVA). The genome content of M. hominis PG21 was analysed for tandem repeats (TRs), and five of the 130 TRs identified were selected for use in an MLVA assay. The method was based on GeneScan analysis of VNTR loci using multiplex PCR with fluorescent dyes and resolution by capillary electrophoresis. This approach was used on a collection of 210 urogenital and extragenital French clinical isolates collected between 1987 and 2009. Forty MLVA types were found. The discriminatory index of our MLVA scheme was 0.924. Using this new typing tool, persistent infection was suggested for six patients and new infection for one patient. Furthermore, mother-to-child transmission was confirmed in the two cases studied. Application of MLVA to a wide range of M. hominis isolates revealed high genotypic diversity and no obvious link between the MLVA type and the isolate year of collection, the patient's age or sex, the anatomical origin of the isolates or resistance to antibiotics was found. Our MLVA scheme highlights the high genetic heterogeneity of the M. hominis species. It seems too discriminatory to be used for large epidemiological studies but has proven its usefulness for molecular studies at the individual level.

  4. Development of Multiple-Locus Variable-Number Tandem-Repeat Analysis for Molecular Subtyping of Campylobacter jejuni by Using Capillary Electrophoresis.

    PubMed

    Techaruvichit, Punnida; Takahashi, Hajime; Vesaratchavest, Mongkol; Keeratipibul, Suwimon; Kuda, Takashi; Kimura, Bon

    2015-08-15

    Campylobacter jejuni is a common cause of the frequently reported food-borne diseases in developed and developing nations. This study describes the development of multiple-locus variable-number tandem-repeat (VNTR) analysis (MLVA) using capillary electrophoresis as a novel typing method for microbial source tracking and epidemiological investigation of C. jejuni. Among 36 tandem repeat loci detected by the Tandem Repeat Finder program, 7 VNTR loci were selected and used for characterizing 60 isolates recovered from chicken meat samples from retail shops, samples from chicken meat processing factory, and stool samples. The discrimination ability of MLVA was compared with that of multilocus sequence typing (MLST). MLVA (diversity index of 0.97 with 31 MLVA types) provided slightly higher discrimination than MLST (diversity index of 0.95 with 25 MLST types). The overall concordance between MLVA and MLST was estimated at 63% by adjusted Rand coefficient. MLVA predicted MLST type better than MLST predicted MLVA type, as reflected by Wallace coefficient (Wallace coefficient for MLVA to MLST versus MLST to MLVA, 86% versus 51%). MLVA is a useful tool and can be used for effective monitoring of C. jejuni and investigation of epidemics caused by C. jejuni. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  5. The Gap in the Current Research on the Link between Health Locus of Control and Multiple Sclerosis: Lessons and Insights from a Systematic Review.

    PubMed

    Bragazzi, Nicola Luigi

    2013-01-01

    Multiple sclerosis (MS) is a chronic neurological disease whose etiology has not been fully understood yet in detail. Empirical findings show how psychosocial symptoms are very important features of the clinical presentation of MS, having a deep impact on patient's quality of life, and thus psychological coping strategies may play a central role in reducing the burden of the disease and improving patient's satisfaction of life. MS progression and relapses/exacerbations are unpredictable and may depend on factors such as stressor chronicity, frequency, severity, type, and individual patient characteristics such as depression, personality, locus of control (LOC), optimism, and perceived social support. Due to its importance for health-care delivery, rehabilitation, and nursing, here, we make a systematic review on the current state-of-the-art studies concerning the relationship between LOC and MS, according to the PRISMA guidelines, and we assess the quality and the completeness of the studies using the CONSORT instrument, underpinning their limitations, and suggesting how to fill the gap in this research field.

  6. Genetic Diversity of Neisseria meningitidis Serogroup C ST-4821 in China Based on Multiple-Locus Variable Number Tandem Repeat Analysis

    PubMed Central

    Shan, Xiaoying; Zhang, Ji; Zhou, Haijian; Zhu, Bingqing; Xu, Li; Shao, Zhujun; Jiang, Baofa

    2014-01-01

    Neisseria meningitidis sequence type (ST)-4821 was first reported in China in 2003, and a new hyper-virulent lineage has been designated as the ST-4821 complex. A large number of N. meningitidis ST-4821 strains have been identified in China since 2003; however, the microevolution characteristics of this complex are unclear. Different combinations of variable number of tandem repeats (VNTR) loci were used in multiple-locus VNTR analysis (MLVA) to analyze 118 N. meningitidis serogroup C ST-4821 strains isolated from seventeen provinces between 2003 and 2012. Additionally, MLVA with five VNTR loci was performed due to its high discriminatory power. One hundred and eighteen isolates were found to comprise 112 subtypes based on MLVA, and 16 outbreak-associated strains were clustered into one group. These data indicate a high level of diversity for N. meningitidis ST-4821 due to microevolution in the last decade. In addition, the results revealed high similarity between isolates from the same geographic origins, which is helpful when monitoring the spread of N. meningitidis serogroup C ST-4821 and will provide valuable information for the control and prevention of bacterial meningitis in China. PMID:25375168

  7. Ces locus embedded proteins control the non-ribosomal synthesis of the cereulide toxin in emetic Bacillus cereus on multiple levels

    PubMed Central

    Lücking, Genia; Frenzel, Elrike; Rütschle, Andrea; Marxen, Sandra; Stark, Timo D.; Hofmann, Thomas; Scherer, Siegfried; Ehling-Schulz, Monika

    2015-01-01

    The emetic toxin cereulide produced by Bacillus cereus is synthesized by the modular enzyme complex Ces that is encoded on a pXO1-like megaplasmid. To decipher the role of the genes adjacent to the structural genes cesA/cesB, coding for the non-ribosomal peptide synthetase (NRPS), gene inactivation- and overexpression mutants of the emetic strain F4810/72 were constructed and their impact on cereulide biosynthesis was assessed. The hydrolase CesH turned out to be a part of the complex regulatory network controlling cereulide synthesis on a transcriptional level, while the ABC transporter CesCD was found to be essential for post-translational control of cereulide synthesis. Using a gene inactivation approach, we show that the NRPS activating function of the phosphopantetheinyl transferase (PPtase) embedded in the ces locus was complemented by a chromosomally encoded Sfp-like PPtase, representing an interesting example for the functional interaction between a plasmid encoded NRPS and a chromosomally encoded activation enzyme. In summary, our results highlight the complexity of cereulide biosynthesis and reveal multiple levels of toxin formation control. ces operon internal genes were shown to play a pivotal role by acting at different levels of toxin production, thus complementing the action of the chromosomal key transcriptional regulators AbrB and CodY. PMID:26528255

  8. Predicting and Improving Recognition Memory Using Multiple Electrophysiological Signals in Real Time.

    PubMed

    Fukuda, Keisuke; Woodman, Geoffrey F

    2015-07-01

    Although people are capable of storing a virtually infinite amount of information in memory, their ability to encode new information is far from perfect. The quality of encoding varies from moment to moment and renders some memories more accessible than others. Here, we were able to forecast the likelihood that a given item will be later recognized by monitoring two dissociable fluctuations of the electroencephalogram during encoding. Next, we identified individual items that were poorly encoded, using our electrophysiological measures in real time, and we successfully improved the efficacy of learning by having participants restudy these items. Thus, our memory forecasts using multiple electrophysiological signals demonstrate the feasibility and the effectiveness of using real-time monitoring of the moment-to-moment fluctuations of the quality of memory encoding to improve learning. © The Author(s) 2015.

  9. Genetic stability of Brucella abortus isolates from an outbreak by multiple-locus variable-number tandem repeat analysis (MLVA16)

    PubMed Central

    2014-01-01

    Background Brucellosis caused by Brucella abortus is one of the most important zoonoses in the world. Multiple-locus variable-number tandem repeat analysis (MLVA16) has been shown be a useful tool to epidemiological traceback studies in B. abortus infection. Thus, the present study aimed (i) to evaluate the genetic diversity of B. abortus isolates from a brucellosis outbreak, and (ii) to investigate the in vivo stability of the MLVA16 markers. Results Three-hundred and seventy-five clinical samples, including 275 vaginal swabs and 100 milk samples, were cultured from a brucellosis outbreak in a cattle herd, which adopted RB51 vaccination and test-and-slaughter policies. Thirty-seven B. abortus isolates were obtained, eight from milk and twenty-nine from post-partum/abortion vaginal swabs, which were submitted to biotyping and genotyping by MLVA16. Twelve B. abortus isolates obtained from vaginal swabs were identified as RB51. Twenty four isolates, seven obtained from milk samples and seventeen from vaginal swabs, were identified as B. abortus biovar 3, while one isolate from vaginal swabs was identified as B. abortus biovar 1. Three distinct genotypes were observed during the brucellosis outbreak: RB observed in all isolates identified as RB51; W observed in all B. abortus biovar 3 isolates; and Z observed in the single B. abortus biovar 1 isolate. Epidemiological and molecular data show that the B. abortus biovar 1 genotype Z strain is not related to the B. abortus biovar 3 genotype W isolates, and represents a new introduction B. abortus during the outbreak. Conclusions The results of the present study on typing of multiple clinical B. abortus isolates from the same outbreak over a sixteen month period indicate the in vivo stability of MLVA16 markers, a low genetic diversity among B. abortus isolates and the usefulness of MLVA16 for epidemiological studies of bovine brucellosis. PMID:25015840

  10. Preliminary Investigation on Multiple-Locus Variable Number Tandem Repeat Analysis Profiles of Listeria Monocytogenes Isolates from Pork Meat Tested from Packaging to Fork

    PubMed Central

    Parisi, Antonio; Caruso, Marta; Pasquali, Frédérique; Manfreda, Gerardo

    2014-01-01

    Listeria monocytogenes is recognised as a public health issue and a serious challenge for the food industry. L. monocytogenes strain characterisation on the basis of serotyping and molecular typing methods is used for surveillance, epidemiological tracking and outbreak investigation purposes. Genetic variants of L. monocytogenes have diversified into four major phylogenetic lineages, with lineages 1 and 2 each containing multiple clonal groups of public health importance. Standardised tools for easy identification of clonal groups are needed to trace such groups and determine their presence in a large variety of sources. Given the current limitations of available methods for L. monocytogenes strain typing, a potentially useful approach is multiple locus variable number of tandem repeats (VNTR) analysis (MLVA). In this study, MLVA has been applied to a random group of 82 L. monocytogenes strains isolated from 8 different batches of loin chops obtained from the same facility and tested between packaging and consumption time. The strains typed were classified into 10 MLVA profiles containing a number of isolates ranging between 1 to 20. According to the identified MLVA profiles, 75.6% of the pork isolates belonged to the phylogenetic lineage 2 and serotype 1/2c, frequently associated to food isolates. However, 3 pork strains belonged to the phylogenetic lineage 1 and serotype 4b. Moreover, 17 isolates were classified in the phylogenetic lineages 2 and serotype 1/2a. Both serotypes 4b and 1/2a are frequently associated to human isolates of L. monocytogenes. These preliminary results show how the MLVA profiles can support the assessment of the risk profile of food products based on the contaminating L. monocytogenes strain types. PMID:27800312

  11. Pupil size signals mental effort deployed during multiple object tracking and predicts brain activity in the dorsal attention network and the locus coeruleus.

    PubMed

    Alnæs, Dag; Sneve, Markus Handal; Espeseth, Thomas; Endestad, Tor; van de Pavert, Steven Harry Pieter; Laeng, Bruno

    2014-04-01

    Attentional effort relates to the allocation of limited-capacity attentional resources to meet current task demands and involves the activation of top-down attentional systems in the brain. Pupillometry is a sensitive measure of this intensity aspect of top-down attentional control. Studies relate pupillary changes in response to cognitive processing to activity in the locus coeruleus (LC), which is the main hub of the brain's noradrenergic system and it is thought to modulate the operations of the brain's attentional systems. In the present study, participants performed a visual divided attention task known as multiple object tracking (MOT) while their pupil sizes were recorded by use of an infrared eye tracker and then were tested again with the same paradigm while brain activity was recorded using fMRI. We hypothesized that the individual pupil dilations, as an index of individual differences in mental effort, as originally proposed by Kahneman (1973), would be a better predictor of LC activity than the number of tracked objects during MOT. The current results support our hypothesis, since we observed pupil-related activity in the LC. Moreover, the changes in the pupil correlated with activity in the superior colliculus and the right thalamus, as well as cortical activity in the dorsal attention network, which previous studies have shown to be strongly activated during visual tracking of multiple targets. Follow-up pupillometric analyses of the MOT task in the same individuals also revealed that individual differences to cognitive load can be remarkably stable over a lag of several years. To our knowledge this is the first study using pupil dilations as an index of attentional effort in the MOT task and also relating these to functional changes in the brain that directly implicate the LC-NE system in the allocation of processing resources.

  12. Poly(dimethylsiloxane) photonic microbioreactors and multiple internal reflection systems for real time cell screening

    NASA Astrophysics Data System (ADS)

    Ortiz, Pedro; Demming, Stefanie; Fernández-Rosas, Elisabet; Ibarlucea, Bergoi; Vila-Planas, Jordi; Büttgenbach, Stephanus; Llobera, Andreu

    2011-06-01

    In this paper two different photonic lab-on-a-chip devices for real-time cell screening are presented. We discuss, in parallel, screening of cell viability and cell count using a multiple total internal reflection (MIR) system, and a microbioreactor (MBR) for continuous cell culture screening. Each device takes advantage, in different ways, of the enhanced light-analyte interaction provided by the full-field approach. Their performance and how they represent an improvement to current methods, are also discussed herein. Both devices integrate photonic components and are fabricated by soft lithography (PDMS) replica molding of SU-8 masters, thus making them low-cost and easily mass produced.

  13. Real-time multiple human perception with color-depth cameras on a mobile robot.

    PubMed

    Zhang, Hao; Reardon, Christopher; Parker, Lynne E

    2013-10-01

    The ability to perceive humans is an essential requirement for safe and efficient human-robot interaction. In real-world applications, the need for a robot to interact in real time with multiple humans in a dynamic, 3-D environment presents a significant challenge. The recent availability of commercial color-depth cameras allow for the creation of a system that makes use of the depth dimension, thus enabling a robot to observe its environment and perceive in the 3-D space. Here we present a system for 3-D multiple human perception in real time from a moving robot equipped with a color-depth camera and a consumer-grade computer. Our approach reduces computation time to achieve real-time performance through a unique combination of new ideas and established techniques. We remove the ground and ceiling planes from the 3-D point cloud input to separate candidate point clusters. We introduce the novel information concept, depth of interest, which we use to identify candidates for detection, and that avoids the computationally expensive scanning-window methods of other approaches. We utilize a cascade of detectors to distinguish humans from objects, in which we make intelligent reuse of intermediary features in successive detectors to improve computation. Because of the high computational cost of some methods, we represent our candidate tracking algorithm with a decision directed acyclic graph, which allows us to use the most computationally intense techniques only where necessary. We detail the successful implementation of our novel approach on a mobile robot and examine its performance in scenarios with real-world challenges, including occlusion, robot motion, nonupright humans, humans leaving and reentering the field of view (i.e., the reidentification challenge), human-object and human-human interaction. We conclude with the observation that the incorporation of the depth information, together with the use of modern techniques in new ways, we are able to create an

  14. Real-time spatial frequency domain imaging by single snapshot multiple frequency demodulation technique

    NASA Astrophysics Data System (ADS)

    Cao, Zili; Lin, Weihao; Chen, Xinlin; Zeng, Bixin; Xu, Min

    2017-02-01

    We have presented a novel Single Snapshot Multiple Frequency Demodulation (SSMD) method enabling single snapshot wide field imaging of optical properties of turbid media in the Spatial Frequency Domain. SSMD makes use of the orthogonality of harmonic functions and extracts the modulation transfer function (MTF) at multiple modulation frequencies and of arbitrary orientations and amplitudes simultaneously from a single structured-illuminated image at once. SSMD not only increases significantly the data acquisition speed and reduces motion artifacts but also exhibits excellent noise suppression in imaging as well. The performance of SSMD-SFDI is demonstrated with experiments on both tissue mimicking phantoms and in vivo for recovering optical properties. SSMD is ideal in the implementation of a real-time spatial frequency domain imaging platform, which will open up SFDI for vast applications in, for example, mapping the optical properties of a dynamic turbid medium or monitoring fast temporal evolutions.

  15. Upregulation of Mouse Genes in HSV-1 Latent TG after Butyrate Treatment Implicates the Multiple Roles of the LAT-ICP0 Locus

    PubMed Central

    Clement, Christian; Bhattacharjee, Partha S.; Kumar, Manish; Foster, Timothy P.; Thompson, Hilary W.

    2011-01-01

    Purpose. To determine host response by gene expression in HSV-1 latent trigeminal ganglia (TG) after sodium butyrate (NaBu) treatment. Methods. Corneas of 6-week-old female BALB/c mice were scarified and inoculated with HSV-1 17Syn+ (high phenotypic reactivator) or its mutant 17ΔPst(LAT−) (low phenotypic reactivator) at 104 plaque-forming units/eye. NaBu-induced viral reactivation was by intraperitoneal (IP) administration at postinfection (PI) day 28, followed by euthanasia after 1 hour. NaBu-treated, uninfected mice served as the control. The resultant labeled cRNA from TG isolated total RNA was hybridized to gene microarray chips containing 14,000 mouse genes. Quantitative real-time PCR was performed to confirm gene expression. Results. Differential induction of gene expression between 17Syn+ and its mutant 17ΔPst(LAT−) was designated as NaBu-induced gene expression and yielded significant upregulation of 2- to 16-fold of 0.4% (56/14,000) host genes probed, comprising mainly nucleosome assembly and binding, central nervous system structural activity, hormonal activity, and signaling activity. Approximately 0.2% (24/14,000) of the host genes, mainly of the same functional categories were downregulated 3- to 11-fold. Immune activity was minor in comparison to our reports on gene expression during latency and heat stress induction. Euchromatin analysis revealed that the LAT-ICP0 locus is amenable to the effects of NaBu. Histone activity was detected by early transcription of histone cluster 2 H2be (Hist2h2be). Conclusions. NaBu-induced reactivation of HSV-1 is twofold: drug action involving significant moderation of specific host epigenetic changes and failure to elicit or suppress immune activity at the early time point of 1 hour. PMID:20881297

  16. Distributed cerebellar plasticity implements generalized multiple-scale memory components in real-robot sensorimotor tasks

    PubMed Central

    Casellato, Claudia; Antonietti, Alberto; Garrido, Jesus A.; Ferrigno, Giancarlo; D'Angelo, Egidio; Pedrocchi, Alessandra

    2015-01-01

    The cerebellum plays a crucial role in motor learning and it acts as a predictive controller. Modeling it and embedding it into sensorimotor tasks allows us to create functional links between plasticity mechanisms, neural circuits and behavioral learning. Moreover, if applied to real-time control of a neurorobot, the cerebellar model has to deal with a real noisy and changing environment, thus showing its robustness and effectiveness in learning. A biologically inspired cerebellar model with distributed plasticity, both at cortical and nuclear sites, has been used. Two cerebellum-mediated paradigms have been designed: an associative Pavlovian task and a vestibulo-ocular reflex, with multiple sessions of acquisition and extinction and with different stimuli and perturbation patterns. The cerebellar controller succeeded to generate conditioned responses and finely tuned eye movement compensation, thus reproducing human-like behaviors. Through a productive plasticity transfer from cortical to nuclear sites, the distributed cerebellar controller showed in both tasks the capability to optimize learning on multiple time-scales, to store motor memory and to effectively adapt to dynamic ranges of stimuli. PMID:25762922

  17. Distributed cerebellar plasticity implements generalized multiple-scale memory components in real-robot sensorimotor tasks.

    PubMed

    Casellato, Claudia; Antonietti, Alberto; Garrido, Jesus A; Ferrigno, Giancarlo; D'Angelo, Egidio; Pedrocchi, Alessandra

    2015-01-01

    The cerebellum plays a crucial role in motor learning and it acts as a predictive controller. Modeling it and embedding it into sensorimotor tasks allows us to create functional links between plasticity mechanisms, neural circuits and behavioral learning. Moreover, if applied to real-time control of a neurorobot, the cerebellar model has to deal with a real noisy and changing environment, thus showing its robustness and effectiveness in learning. A biologically inspired cerebellar model with distributed plasticity, both at cortical and nuclear sites, has been used. Two cerebellum-mediated paradigms have been designed: an associative Pavlovian task and a vestibulo-ocular reflex, with multiple sessions of acquisition and extinction and with different stimuli and perturbation patterns. The cerebellar controller succeeded to generate conditioned responses and finely tuned eye movement compensation, thus reproducing human-like behaviors. Through a productive plasticity transfer from cortical to nuclear sites, the distributed cerebellar controller showed in both tasks the capability to optimize learning on multiple time-scales, to store motor memory and to effectively adapt to dynamic ranges of stimuli.

  18. Cystic Fibrosis Mutation Detection with SPR Biosensor in Real Samples via Multiple Surfaces Binding Method.

    PubMed

    Kayran, Yasin Ugur; Ozkan-Ariksoysal, Dilsat; Topkaya, Seda Nur; Kaymaz, Burcin Tezcanli; Can, Buket Kosova

    2017-01-01

    Surface Plasmon Resonance (SPR) based biosensor system was developed for the detection of Delta F508 (ΔF508del) Cystic Fibrosis (CF) mutation in both synthetic and real samples. In order to provide an effective hybridization between probe and the Polymerase Chain Reaction (PCR) amplicons (target), streptavidin was bound to the surface and biotin-tag probe was sent to the streptavidin-coated surface. For the target preparation, blood samples were collected from the patients who suffer from CF. Following the DNA isolation; samples were amplified with PCR with biotin-tag. Before sending the biotin-tag PCR amplicons onto the modified surface, amplicons were also interacted with the helper oligonucleotides to prevent re-annealing of the denatured DNA strands. This kind of 'multiple surface binding' method helps increasing the sensitivity of the detection. The limit of detection (S/N= 3) was calculated as 12.24 pico-mole/ml for PCR-like synthetic long target sequence and 13x105 molecules for real samples in less than half an hour. Using the both biotin-tag probe and the helper oligonucleotides together, hybridization was achieved much more efficiently than traditional denaturation protocols for real samples and biotinfree hybridization detection. To the best of our knowledge, the procedure described in this study is one of the simplest, rapid and sensitive methods for CF mutation detection with SPR based biosensor system in real samples. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. Genotyping of Brucella melitensis strains from dromedary camels (Camelus dromedarius) from the United Arab Emirates with multiple-locus variable-number tandem repeat analysis.

    PubMed

    Gyuranecz, Miklós; Wernery, Ulli; Kreizinger, Zsuzsa; Juhász, Judit; Felde, Orsolya; Nagy, Péter

    2016-04-15

    Camel brucellosis is a widespread zoonotic disease in camel-rearing countries caused by Brucella melitensis and Brucella abortus. The aim of this study was the first genetic analysis of B. melitensis strains isolated from dromedary camels (Camelus dromedarius) using multiple-locus variable-number tandem repeat analysis (MLVA). MLVA 16 and its MLVA 8 and MLVA11 subsets were used to determine the genotypes of 15 B. melitensis isolates from dromedary camels (11 strains) and other host species (4 strains) from the United Arab Emirates and the results were then compared to B. melitensis MLVA genotypes from other parts of the world. Five, including two novel genotypes were identified with MLVA 8. MLVA 16 further discriminated these five genotypes to ten variants. The eleven camel isolates clustered into four main genetic groups within the East-Mediterranean and African clades and this clustering correlated with the geographic origin of the hosts (United Arab Emirates, Kingdom of Saudi Arabia and Sudan) and the date of their isolation. The camel strains were also genetically related to strains isolated from wild and domestic ruminants from their close habitat or from other parts of the world. Although limited number of strains were analysed, based on our data imported animals from foreign countries, local small ruminants and wildlife species are hypothesized to be the main sources of camel brucellosis in the United Arab Emirates. MLVA was successfully applied to determine the epidemiological links between the different camel B. melitensis infections in the United Arab Emirates and it can be a beneficial tool in future disease control programs.

  20. A new multiple-locus variable-number tandem repeat analysis reveals different clusters for Anaplasma phagocytophilum circulating in domestic and wild ruminants.

    PubMed

    Dugat, Thibaud; Chastagner, Amélie; Lagrée, Anne-Claire; Petit, Elisabeth; Durand, Benoît; Thierry, Simon; Corbière, Fabien; Verheyden, Hélène; Chabanne, Luc; Bailly, Xavier; Leblond, Agnès; Vourc'h, Gwenaël; Boulouis, Henri-Jean; Maillard, Renaud; Haddad, Nadia

    2014-09-16

    Anaplasma phagocytophilum is a tick-borne intragranulocytic alpha-proteobacterium. It is the causative agent of tick-borne fever in ruminants, and of human granulocytic anaplasmosis in humans, two diseases which are becoming increasingly recognized in Europe and the USA. However, while several molecular typing tools have been developed over the last years, few of them are appropriate for in-depth exploration of the epidemiological cycle of this bacterium. Therefore we have developed a Multiple-Locus Variable number tandem repeat (VNTR) Analysis typing technique for A. phagocytophilum. Five VNTRs were selected based on the HZ human-derived strain genome, and were tested on the Webster human-derived strain and on 123 DNA samples: 67 from cattle, 7 from sheep, 15 from roe deer, 4 from red deer, 1 from a reindeer, 2 from horses, 1 from a dog, and 26 from ticks. From these samples, we obtained 84 different profiles, with a diversity index of 0.96 (0.99 for vertebrate samples, i.e. without tick samples). Our technique confirmed that A. phagocytophilum from roe deer or domestic ruminants belong to two different clusters, while A. phagocytophilum from red deer and domestic ruminants locate within the same cluster, questioning the respective roles of roe vs red deer as reservoir hosts for domestic ruminant strains in Europe. As expected, greater diversity was obtained between rather than within cattle herds. Our technique has great potential to provide detailed information on A. phagocytophilum isolates, improving both epidemiological and phylogenic investigations, thereby helping in the development of relevant prevention and control measures.

  1. Diversity of Mycoplasma hominis clinical isolates from Bordeaux, France, as assessed by multiple-locus variable-number tandem repeat analysis

    PubMed Central

    2013-01-01

    Background Mycoplasma hominis is an opportunistic human mycoplasma species that can cause various urogenital infections and, less frequently, extragenital infections. The objective of this work was to study the genetic diversity of this species using a molecular typing method based on multiple-locus variable-number tandem repeat (VNTR) analysis (MLVA). Results The genome content of M. hominis PG21 was analysed for tandem repeats (TRs), and five of the 130 TRs identified were selected for use in an MLVA assay. The method was based on GeneScan analysis of VNTR loci using multiplex PCR with fluorescent dyes and resolution by capillary electrophoresis. This approach was used on a collection of 210 urogenital and extragenital French clinical isolates collected between 1987 and 2009. Forty MLVA types were found. The discriminatory index of our MLVA scheme was 0.924. Using this new typing tool, persistent infection was suggested for six patients and new infection for one patient. Furthermore, mother-to-child transmission was confirmed in the two cases studied. Application of MLVA to a wide range of M. hominis isolates revealed high genotypic diversity and no obvious link between the MLVA type and the isolate year of collection, the patient’s age or sex, the anatomical origin of the isolates or resistance to antibiotics was found. Conclusions Our MLVA scheme highlights the high genetic heterogeneity of the M. hominis species. It seems too discriminatory to be used for large epidemiological studies but has proven its usefulness for molecular studies at the individual level. PMID:23710536

  2. The potato developer (D) locus encodes an R2R3 MYB transcription factor that regulates expression of multiple anthocyanin structural genes in tuber skin.

    PubMed

    Jung, Chun Suk; Griffiths, Helen M; De Jong, Darlene M; Cheng, Shuping; Bodis, Mary; Kim, Tae Sung; De Jong, Walter S

    2009-12-01

    A dominant allele at the D locus (also known as I in diploid potato) is required for the synthesis of red and purple anthocyanin pigments in tuber skin. It has previously been reported that D maps to a region of chromosome 10 that harbors one or more homologs of Petunia an2, an R2R3 MYB transcription factor that coordinately regulates the expression of multiple anthocyanin biosynthetic genes in the floral limb. To test whether D acts similarly in tuber skin, RT-PCR was used to evaluate the expression of flavanone 3-hydroxylase (f3h), dihydroflavonol 4-reductase (dfr) and flavonoid 3',5'-hydroxylase (f3'5'h). All three genes were expressed in the periderm of red- and purple-skinned clones, while dfr and f3'5'h were not expressed, and f3h was only weakly expressed, in white-skinned clones. A potato cDNA clone with similarity to an2 was isolated from an expression library prepared from red tuber skin, and an assay developed to distinguish the two alleles of this gene in a diploid potato clone known to be heterozygous Dd. One allele was observed to cosegregate with pigmented skin in an F(1) population of 136 individuals. This allele was expressed in tuber skin of red- and purple-colored progeny, but not in white tubers, while other parental alleles were not expressed in white or colored tubers. The allele was placed under the control of a doubled 35S promoter and transformed into the light red-colored cultivar Désirée, the white-skinned cultivar Bintje, and two white diploid clones known to lack the functional allele of D. Transformants accumulated pigment in tuber skin, as well as in other tissues, including young foliage, flower petals, and tuber flesh.

  3. Utilizing Rapid Multiple-Locus Variable-Number Tandem-Repeat Analysis Typing To Aid Control of Hospital-Acquired Clostridium difficile Infection: a Multicenter Study

    PubMed Central

    Manzoor, Susan; Marriott, Claire; Parsons, Helen; Waddington, Claire; Gossain, Savita; Szczepura, Ala; Stallard, Nigel; Hawkey, Peter M.

    2012-01-01

    The early identification of outbreaks is crucial for the control of Clostridium difficile infection. This study aimed to determine if the number of hospital-acquired C. difficile infections could be reduced by rapidly typing C. difficile strains using multiple-locus variable-number tandem-repeat analysis (MLVA) compared to typing using PCR ribotyping. A total of 16 hospitals were recruited to the study, and all periods of increased incidence (PIIs) of C. difficile infection were identified. The hospitals were randomized into two study arms, the test and the control, with all isolates typed in the test using MLVA and in the control using PCR ribotyping. Following a PII, each hospital received a structured questionnaire regarding control measures implemented or stopped prior to or following the typing results. During the study period, there were a total of 1,682 hospital-apportioned C. difficile toxin-positive cases, with 868 in the control and 814 in the test, with modeling demonstrating no differences between the two arms. A total of 245 PIIs occurred, involving 785 patients. There was a significant difference in the mean turnaround time between the ribotyping and MLVA typing (13.6 and 5.3 days, respectively [P < 0.001]). The discriminatory ability of MLVA was greater than ribotyping, with 85 outbreaks being confirmed by ribotyping and 62 by MLVA. In the test arm, 40.6% of respondents strongly agreed that the typing result had aided their management of clusters, as opposed to 9.9% in the control. The study demonstrated the utility of rapidly typing C. difficile strains, demonstrating that it aided the management of clusters, enabling effective targeting of infection control resources. PMID:22837319

  4. Identification of a functional variant in the KIF5A-CYP27B1-METTL1-FAM119B locus associated with multiple sclerosis

    PubMed Central

    Alcina, Antonio; Fedetz, Maria; Fernández, Óscar; Saiz, Albert; Izquierdo, Guillermo; Lucas, Miguel; Leyva, Laura; García-León, Juan-Antonio; Abad-Grau, María del Mar; Alloza, Iraide; Antigüedad, Alfredo; Garcia-Barcina, María J; Vandenbroeck, Koen; Varadé, Jezabel; de la Hera, Belén; Arroyo, Rafael; Comabella, Manuel; Montalban, Xavier; Petit-Marty, Natalia; Navarro, Arcadi; Otaegui, David; Olascoaga, Javier; Blanco, Yolanda; Urcelay, Elena; Matesanz, Fuencisla

    2013-01-01

    Background and aim Several studies have highlighted the association of the 12q13.3–12q14.1 region with coeliac disease, type 1 diabetes, rheumatoid arthritis and multiple sclerosis (MS); however, the causal variants underlying diseases are still unclear. The authors sought to identify the functional variant of this region associated with MS. Methods Tag-single nucleotide polymorphism (SNP) analysis of the associated region encoding 15 genes was performed in 2876 MS patients and 2910 healthy Caucasian controls together with expression regulation analyses. Results rs6581155, which tagged 18 variants within a region where 9 genes map, was sufficient to model the association. This SNP was in total linkage disequilibrium (LD) with other polymorphisms that associated with the expression levels of FAM119B, AVIL, TSFM, TSPAN31 and CYP27B1 genes in different expression quantitative trait loci studies. Functional annotations from Encyclopedia of DNA Elements (ENCODE) showed that six out of these rs6581155-tagged-SNPs were located in regions with regulatory potential and only one of them, rs10877013, exhibited allele-dependent (ratio A/G=9.5-fold) and orientation-dependent (forward/reverse=2.7-fold) enhancer activity as determined by luciferase reporter assays. This enhancer is located in a region where a long-range chromatin interaction among the promoters and promoter-enhancer of several genes has been described, possibly affecting their expression simultaneously. Conclusions This study determines a functional variant which alters the enhancer activity of a regulatory element in the locus affecting the expression of several genes and explains the association of the 12q13.3–12q14.1 region with MS. PMID:23160276

  5. Evaluation of multiple-locus variable number of tandem repeats analysis for typing livestock-associated methicillin-resistant Staphylococcus aureus.

    PubMed

    Brandt, Karin M; Mellmann, Alexander; Ballhausen, Britta; Jenke, Christian; van der Wolf, Peter J; Broens, Els M; Becker, Karsten; Köck, Robin

    2013-01-01

    The increasing occurrence of livestock-associated (LA) methicillin-resistant Staphylococcus aureus (MRSA) associated with the clonal complex (CC) 398 within the past years shows the importance of standardized and comparable typing methods for the purposes of molecular surveillance and outbreak detection. Multiple-locus variable number of tandem repeats analysis (MLVA) has recently been described as an alternative and highly discriminative tool for S. aureus. However, until now the applicability of MLVA for the typing of LA-MRSA isolates from different geographic origin has not been investigated in detail. We therefore compared MLVA and S. aureus protein A (spa) typing for characterizing porcine MRSA from distinct Dutch and German farms. Overall, 134 MRSA isolates originating from 21 different pig-farms in the Netherlands and 36 farms in Germany comprising 21 different spa types were subjected to MLVA-typing. Amplification and subsequent automated fragment sizing of the tandem repeat loci on a capillary sequencer differentiated these 134 isolates into 20 distinct MLVA types. Whereas overall MLVA and spa typing showed the same discriminatory power to type LA-MRSA (p = 0.102), MLVA was more discriminatory than spa typing for isolates associated with the prevalent spa types t011 and t034 (Simpson's Index of Diversity 0.564 vs. 0.429, respectively; p<0.001). Although the applied MLVA scheme was not more discriminatory than spa typing in general, it added valuable information to spa typing results for specific spa types (t011, t034) which are highly prevalent in the study area, i.e. Dutch-German border area. Thus, both methods may complement each other to increase the discriminatory power to resolute highly conserved clones such as CC398 (spa types t011, t034) for the detection of outbreaks and molecular surveillance of zoonotic MRSA.

  6. An improved version of the multiple trajectory search for real value multi-objective optimization problems

    NASA Astrophysics Data System (ADS)

    Chen, Chun; Tseng, Lin-Yu

    2014-10-01

    Multi-objective optimization is widely used in science, engineering and business. In this article, an improved version of the multiple trajectory search (MTS) called MTS2 is presented and successfully applied to real-value multi-objective optimization problems. In the first step, MTS2 generates M initial solutions distributed over the solution space. These solutions are called seeds. Some seeds with good objective values are selected as foreground seeds. Then, MTS2 chooses a suitable region search method for each foreground seed according to the landscape of the neighbourhood of the seed. During the search, MTS2 focuses its search on some promising areas specified by the foreground seeds. The performance of MTS2 was examined by applying it to solve the benchmark problems provided by the Competition of Performance Assessment of Constrained/Bound Constrained Multi-Objective Optimization Algorithms held at the 2009 IEEE Congress on Evolutionary Computation.

  7. Real-time terrain storage generation from multiple sensors towards mobile robot operation interface.

    PubMed

    Song, Wei; Cho, Seoungjae; Xi, Yulong; Cho, Kyungeun; Um, Kyhyun

    2014-01-01

    A mobile robot mounted with multiple sensors is used to rapidly collect 3D point clouds and video images so as to allow accurate terrain modeling. In this study, we develop a real-time terrain storage generation and representation system including a nonground point database (PDB), ground mesh database (MDB), and texture database (TDB). A voxel-based flag map is proposed for incrementally registering large-scale point clouds in a terrain model in real time. We quantize the 3D point clouds into 3D grids of the flag map as a comparative table in order to remove the redundant points. We integrate the large-scale 3D point clouds into a nonground PDB and a node-based terrain mesh using the CPU. Subsequently, we program a graphics processing unit (GPU) to generate the TDB by mapping the triangles in the terrain mesh onto the captured video images. Finally, we produce a nonground voxel map and a ground textured mesh as a terrain reconstruction result. Our proposed methods were tested in an outdoor environment. Our results show that the proposed system was able to rapidly generate terrain storage and provide high resolution terrain representation for mobile mapping services and a graphical user interface between remote operators and mobile robots.

  8. Real-Time Terrain Storage Generation from Multiple Sensors towards Mobile Robot Operation Interface

    PubMed Central

    Cho, Seoungjae; Xi, Yulong; Cho, Kyungeun

    2014-01-01

    A mobile robot mounted with multiple sensors is used to rapidly collect 3D point clouds and video images so as to allow accurate terrain modeling. In this study, we develop a real-time terrain storage generation and representation system including a nonground point database (PDB), ground mesh database (MDB), and texture database (TDB). A voxel-based flag map is proposed for incrementally registering large-scale point clouds in a terrain model in real time. We quantize the 3D point clouds into 3D grids of the flag map as a comparative table in order to remove the redundant points. We integrate the large-scale 3D point clouds into a nonground PDB and a node-based terrain mesh using the CPU. Subsequently, we program a graphics processing unit (GPU) to generate the TDB by mapping the triangles in the terrain mesh onto the captured video images. Finally, we produce a nonground voxel map and a ground textured mesh as a terrain reconstruction result. Our proposed methods were tested in an outdoor environment. Our results show that the proposed system was able to rapidly generate terrain storage and provide high resolution terrain representation for mobile mapping services and a graphical user interface between remote operators and mobile robots. PMID:25101321

  9. Real-time qualitative PCR for 57 human adenovirus types from multiple specimen sources.

    PubMed

    Buckwalter, Seanne P; Teo, Rose; Espy, Mark J; Sloan, Lynne M; Smith, Thomas F; Pritt, Bobbi S

    2012-03-01

    Human adenoviruses (HAdVs) are ubiquitous double-stranded DNA viruses that cause a wide array of diseases in humans including pharyngitis, pneumonia, gastroenteritis, hemorrhagic cystitis, and keratoconjunctivitis. They also cause life-threatening opportunistic infections in immunocompromised individuals and are responsible for outbreaks in certain populations. Diagnosis is traditionally by cell culture or antigen detection methods. However, some HAdVs can take up to 4 weeks to isolate, and diarrheagenic types 40 and 41 will not grow in routine cell culture. Therefore, the goal of this study was to design a rapid, real-time PCR assay to detect all known 57 HAdV types from multiple different specimen sources. Primers and fluorescence resonance energy transfer hybridization probes were designed to target a 185-bp region of the penton base gene of HAdV. The analytical sensitivity was determined to be 10 copies/μl for HAdV types showing exact primer/probe homology in specimen matrix. Using whole-virus strains, the analytical sensitivity for representative HAdV types ranged from 10(-1) to 10(3) 50% tissue culture infective dose (TCID(50))/ml. The assay demonstrated 100% sensitivity and 99% specificity. This real-time PCR assay provides a rapid method for the detection of all 57 known HAdV types from respiratory specimens, blood, stool, urine, and ocular swabs.

  10. Gender differences in Greek centenarians. A cross-sectional nation-wide study, examining multiple socio-demographic and personality factors and health locus of control

    PubMed Central

    2011-01-01

    Background Centenarians are exceptional ageing paradigms, offering valuable information on achieving longevity. Although, there are several studies examining different biomedical factors as determinants of longevity in centenarians, little is known about gender differences with respect to personality traits and health locus of control. Methods Nation -wide study carried out in Greece, between 2007 and 2010. Our final sample of analysis consisted of 400 centenarians who reported on sociodemographic, disease-related and personality factors and health locus of control (HLC). Gender differences were investigated by simple nonparametric comparisons. Bivariate correlations between personality factors and internal and external HLC were obtained. Results Women centenarians outnumbered men by a ratio of 1.68 to 1. Significant gender sociodemographic differences were noted, with men reporting less often widowhood, more often centenarian 1st degree relatives and smoking. Higher BMI score was measured in males than females. Concerning personality variables, females were more reward-dependent and adaptable than men, while men were more optimistic than women. No differences were found on health locus of control profile between the genders. Positive correlations between self-directness and spirituality with internal locus of control in men and negative correlations between optimism and external locus of control in women emerged as the main gender disparities in the correlation analyses. Self-directness in men and optimism in women were consistently correlated with the two HLC subscales. Conclusions Gender differences should be incorporated in future basic research and epidemiological studies of longevity. Informed policies on ageing and wellbeing programs should also take into account gender issues to increase efficacy by targeting health locus of control. PMID:22189185

  11. A real-time multiple-cell tracking platform for dielectrophoresis (DEP)-based cellular analysis

    NASA Astrophysics Data System (ADS)

    Prasad, Brinda; Du, Shan; Badawy, Wael; Kaler, Karan V. I. S.

    2005-04-01

    There is an increasing demand from biosciences to develop new and efficient techniques to assist in the preparation and analysis of biological samples such as cells in suspension. A dielectrophoresis (DEP)-based characterization and measurement technique on biological cells opens up a broader perspective for early diagnosis of diseases. An efficient real-time multiple-cell tracking platform coupled with DEP to capture and quantify the dynamics of cell motion and obtain cell viability information is presented. The procedure for tracking a single DEP-levitated Canola plant protoplast, using the motion-based segmentation algorithm hierarchical adaptive merge split mesh-based technique (HAMSM) for cell identification, has been enhanced for identifying and tracking multiple cells. The tracking technique relies on the deformation of mesh topology that is generated according to the movement of biological cells in a sequence of images that allows the simultaneous extraction of the biological cell from the image and the associated motion characteristics. Preliminary tests were conducted with yeast cells and then applied to a cancerous cell line subjected to DEP fields. Characteristics, such as cell count, velocity and size, were individually extracted from the tracked results of the cell sample. Tests were limited to eight yeast cells and two cancer cells. A performance analysis to assess tracking accuracy, computational effort and processing time was also conducted. The tracking technique employed on model intact cells in DEP fields proved to be accurate, reliable and robust.

  12. Multimodal Wireless Sensor Network-Based Ambient Assisted Living in Real Homes with Multiple Residents

    PubMed Central

    Tunca, Can; Alemdar, Hande; Ertan, Halil; Incel, Ozlem Durmaz; Ersoy, Cem

    2014-01-01

    Human activity recognition and behavior monitoring in a home setting using wireless sensor networks (WSNs) provide a great potential for ambient assisted living (AAL) applications, ranging from health and wellbeing monitoring to resource consumption monitoring. However, due to the limitations of the sensor devices, challenges in wireless communication and the challenges in processing large amounts of sensor data in order to recognize complex human activities, WSN-based AAL systems are not effectively integrated in the home environment. Additionally, given the variety of sensor types and activities, selecting the most suitable set of sensors in the deployment is an important task. In order to investigate and propose solutions to such challenges, we introduce a WSN-based multimodal AAL system compatible for homes with multiple residents. Particularly, we focus on the details of the system architecture, including the challenges of sensor selection, deployment, networking and data collection and provide guidelines for the design and deployment of an effective AAL system. We also present the details of the field study we conducted, using the systems deployed in two different real home environments with multiple residents. With these systems, we are able to collect ambient sensor data from multiple homes. This data can be used to assess the wellbeing of the residents and identify deviations from everyday routines, which may be indicators of health problems. Finally, in order to elaborate on the possible applications of the proposed AAL system and to exemplify directions for processing the collected data, we provide the results of several human activity inference experiments, along with examples on how such results could be interpreted. We believe that the experiences shared in this work will contribute towards accelerating the acceptance of WSN-based AAL systems in the home setting. PMID:24887044

  13. Improving resolution of public health surveillance for human Salmonella enterica serovar Typhimurium infection: 3 years of prospective multiple-locus variable-number tandem-repeat analysis (MLVA)

    PubMed Central

    2012-01-01

    Background Prospective typing of Salmonella enterica serovar Typhimurium (STM) by multiple-locus variable-number tandem-repeat analysis (MLVA) can assist in identifying clusters of STM cases that might otherwise have gone unrecognised, as well as sources of sporadic and outbreak cases. This paper describes the dynamics of human STM infection in a prospective study of STM MLVA typing for public health surveillance. Methods During a three-year period between August 2007 and September 2010 all confirmed STM isolates were fingerprinted using MLVA as part of the New South Wales (NSW) state public health surveillance program. Results A total of 4,920 STM isolates were typed and a subset of 4,377 human isolates was included in the analysis. The STM spectrum was dominated by a small number of phage types, including DT170 (44.6% of all isolates), DT135 (13.9%), DT9 (10.8%), DT44 (4.5%) and DT126 (4.5%). There was a difference in the discriminatory power of MLVA types within endemic phage types: Simpson's index of diversity ranged from 0.109 and 0.113 for DTs 9 and 135 to 0.172 and 0.269 for DTs 170 and 44, respectively. 66 distinct STM clusters were observed ranging in size from 5 to 180 cases and in duration from 4 weeks to 25 weeks. 43 clusters had novel MLVA types and 23 represented recurrences of previously recorded MLVA types. The diversity of the STM population remained relatively constant over time. The gradual increase in the number of STM cases during the study was not related to significant changes in the number of clusters or their size. 667 different MLVA types or patterns were observed. Conclusions Prospective MLVA typing of STM allows the detection of community outbreaks and demonstrates the sustained level of STM diversity that accompanies the increasing incidence of human STM infections. The monitoring of novel and persistent MLVA types offers a new benchmark for STM surveillance. A part of this study was presented at the MEEGID × (Molecular Epidemiology

  14. Multi-locus molecular phylogeny and allelic variation in a transcription factor gene suggest the multiple independent origins of kabuli chickpea

    USDA-ARS?s Scientific Manuscript database

    To examine the patterns of molecular diversity in wild crop relatives and the cultivated gene pool of chickpea we genotyped a set of 98 wild annual and 224 cultivated accessions with a 768 feature assay that monitored SNPs in low-copy orthologous loci. Analyses of the resulting multi-locus genotypin...

  15. [Construction and analysis of a monitoring system with remote real-time multiple physiological parameters based on cloud computing].

    PubMed

    Zhu, Lingyun; Li, Lianjie; Meng, Chunyan

    2014-12-01

    There have been problems in the existing multiple physiological parameter real-time monitoring system, such as insufficient server capacity for physiological data storage and analysis so that data consistency can not be guaranteed, poor performance in real-time, and other issues caused by the growing scale of data. We therefore pro posed a new solution which was with multiple physiological parameters and could calculate clustered background data storage and processing based on cloud computing. Through our studies, a batch processing for longitudinal analysis of patients' historical data was introduced. The process included the resource virtualization of IaaS layer for cloud platform, the construction of real-time computing platform of PaaS layer, the reception and analysis of data stream of SaaS layer, and the bottleneck problem of multi-parameter data transmission, etc. The results were to achieve in real-time physiological information transmission, storage and analysis of a large amount of data. The simulation test results showed that the remote multiple physiological parameter monitoring system based on cloud platform had obvious advantages in processing time and load balancing over the traditional server model. This architecture solved the problems including long turnaround time, poor performance of real-time analysis, lack of extensibility and other issues, which exist in the traditional remote medical services. Technical support was provided in order to facilitate a "wearable wireless sensor plus mobile wireless transmission plus cloud computing service" mode moving towards home health monitoring for multiple physiological parameter wireless monitoring.

  16. Specific detection of enteroaggregative hemorrhagic Escherichia coli O104:H4 strains by use of the CRISPR locus as a target for a diagnostic real-time PCR.

    PubMed

    Delannoy, Sabine; Beutin, Lothar; Burgos, Ylanna; Fach, Patrick

    2012-11-01

    In 2011, a large outbreak of an unusual bacterial strain occurred in Europe. This strain was characterized as a hybrid of an enteroaggregative Escherichia coli (EAEC) and a Shiga toxin-producing E. coli (STEC) strain of the serotype O104:H4. Here, we present a single PCR targeting the clustered regularly interspaced short palindromic repeats locus of E. coli O104:H4 (CRISPR(O104:H4)) for specific detection of EAEC STEC O104:H4 strains from different geographical locations and time periods. The specificity of the CRISPR(O104:H4) PCR was investigated using 1,321 E. coli strains, including reference strains for E. coli O serogroups O1 to O186 and flagellar (H) types H1 to H56. The assay was compared for specificity using PCR assays targeting different O104 antigen-encoding genes (wbwC(O104), wzx(O104), and wzy(O104)). The PCR assays reacted with all types of E. coli O104 strains (O104:H2, O104:H4, O104:H7, and O104:H21) and with E. coli O8 and O9 strains carrying the K9 capsular antigen and were therefore not specific for detection of the EAEC STEC O104:H4 type. A single PCR developed for the CRISPR(O104:H4) target was sufficient for specific identification and detection of the 48 tested EAEC STEC O104:H4 strains. The 35 E. coli O104 strains expressing H types other than H4 as well as 8 E. coli strains carrying a K9 capsular antigen tested all negative for the CRISPR(O104:H4) locus. Only 12 (0.94%) of the 1,273 non-O104:H4 E. coli strains (serotypes Ont:H2, O43:H2, O141:H2, and O174:H2) reacted positive in the CRISPR(O104:H4) PCR (99.06% specificity).

  17. Specific Detection of Enteroaggregative Hemorrhagic Escherichia coli O104:H4 Strains by Use of the CRISPR Locus as a Target for a Diagnostic Real-Time PCR

    PubMed Central

    Delannoy, Sabine; Beutin, Lothar; Burgos, Ylanna

    2012-01-01

    In 2011, a large outbreak of an unusual bacterial strain occurred in Europe. This strain was characterized as a hybrid of an enteroaggregative Escherichia coli (EAEC) and a Shiga toxin-producing E. coli (STEC) strain of the serotype O104:H4. Here, we present a single PCR targeting the clustered regularly interspaced short palindromic repeats locus of E. coli O104:H4 (CRISPRO104:H4) for specific detection of EAEC STEC O104:H4 strains from different geographical locations and time periods. The specificity of the CRISPRO104:H4 PCR was investigated using 1,321 E. coli strains, including reference strains for E. coli O serogroups O1 to O186 and flagellar (H) types H1 to H56. The assay was compared for specificity using PCR assays targeting different O104 antigen-encoding genes (wbwCO104, wzxO104, and wzyO104). The PCR assays reacted with all types of E. coli O104 strains (O104:H2, O104:H4, O104:H7, and O104:H21) and with E. coli O8 and O9 strains carrying the K9 capsular antigen and were therefore not specific for detection of the EAEC STEC O104:H4 type. A single PCR developed for the CRISPRO104:H4 target was sufficient for specific identification and detection of the 48 tested EAEC STEC O104:H4 strains. The 35 E. coli O104 strains expressing H types other than H4 as well as 8 E. coli strains carrying a K9 capsular antigen tested all negative for the CRISPRO104:H4 locus. Only 12 (0.94%) of the 1,273 non-O104:H4 E. coli strains (serotypes Ont:H2, O43:H2, O141:H2, and O174:H2) reacted positive in the CRISPRO104:H4 PCR (99.06% specificity). PMID:22895033

  18. Swarming visual sensor network for real-time multiple object tracking

    NASA Astrophysics Data System (ADS)

    Baranov, Yuri P.; Yarishev, Sergey N.; Medvedev, Roman V.

    2016-04-01

    Position control of multiple objects is one of the most actual problems in various technology areas. For example, in construction area this problem is represented as multi-point deformation control of bearing constructions in order to prevent collapse, in mining - deformation control of lining constructions, in rescue operations - potential victims and sources of ignition location, in transport - traffic control and traffic violations detection, in robotics -traffic control for organized group of robots and many other problems in different areas. Usage of stationary devices for solving these problems is inappropriately due to complex and variable geometry of control areas. In these cases self-organized systems of moving visual sensors is the best solution. This paper presents a concept of scalable visual sensor network with swarm architecture for multiple object pose estimation and real-time tracking. In this article recent developments of distributed measuring systems were reviewed with consequent investigation of advantages and disadvantages of existing systems, whereupon theoretical principles of design of swarming visual sensor network (SVSN) were declared. To measure object coordinates in the world coordinate system using TV-camera intrinsic (focal length, pixel size, principal point position, distortion) and extrinsic (rotation matrix, translation vector) calibration parameters were needed to be determined. Robust camera calibration was a too resource-intensive task for using moving camera. In this situation position of the camera is usually estimated using a visual mark with known parameters. All measurements were performed in markcentered coordinate systems. In this article a general adaptive algorithm of coordinate conversion of devices with various intrinsic parameters was developed. Various network topologies were reviewed. Minimum error in objet tracking was realized by finding the shortest path between object of tracking and bearing sensor, which set

  19. High-resolution terrain map from multiple sensor data

    NASA Technical Reports Server (NTRS)

    Kweon, In S.; Kanade, Takeo

    1992-01-01

    The authors present 3-D vision techniques for incrementally building an accurate 3-D representation of rugged terrain using multiple sensors. They have developed the locus method to model the rugged terrain. The locus method exploits sensor geometry to efficiently build a terrain representation from multiple sensor data. The locus method is used to estimate the vehicle position in the digital elevation map (DEM) by matching a sequence of range images with the DEM. Experimental results from large-scale real and synthetic terrains demonstrate the feasibility and power of the 3-D mapping techniques for rugged terrain. In real world experiments, a composite terrain map was built by merging 125 real range images. Using synthetic range images, a composite map of 150 m was produced from 159 images. With the proposed system, mobile robots operating in rugged environments can build accurate terrain models from multiple sensor data.

  20. High-resolution terrain map from multiple sensor data

    NASA Technical Reports Server (NTRS)

    Kweon, In S.; Kanade, Takeo

    1992-01-01

    The authors present 3-D vision techniques for incrementally building an accurate 3-D representation of rugged terrain using multiple sensors. They have developed the locus method to model the rugged terrain. The locus method exploits sensor geometry to efficiently build a terrain representation from multiple sensor data. The locus method is used to estimate the vehicle position in the digital elevation map (DEM) by matching a sequence of range images with the DEM. Experimental results from large-scale real and synthetic terrains demonstrate the feasibility and power of the 3-D mapping techniques for rugged terrain. In real world experiments, a composite terrain map was built by merging 125 real range images. Using synthetic range images, a composite map of 150 m was produced from 159 images. With the proposed system, mobile robots operating in rugged environments can build accurate terrain models from multiple sensor data.

  1. Real-time optical multiple-object recognition and tracking demonstration: A friendly challenge to the digital field

    NASA Technical Reports Server (NTRS)

    Chao, Tien-Hsin; Liu, Hua-Kuang

    1980-01-01

    Researchers demonstrated the first optical multiple object tracking system. The system is capable of simultaneous tracking of multiple objects, each with independent movements in real-time, limited only to the TV frame rate (30 msec). In order to perform a similar tracking operation, a large computer system and very complex software would be needed. Although researchers have demonstrated the tracking of only 3 objects, the system capacity can easily be expanded by 2 orders of magnitude.

  2. Immunochip analyses identify a novel risk locus for primary biliary cirrhosis at 13q14, multiple independent associations at four established risk loci and epistasis between 1p31 and 7q32 risk variants.

    PubMed

    Juran, Brian D; Hirschfield, Gideon M; Invernizzi, Pietro; Atkinson, Elizabeth J; Li, Yafang; Xie, Gang; Kosoy, Roman; Ransom, Michael; Sun, Ye; Bianchi, Ilaria; Schlicht, Erik M; Lleo, Ana; Coltescu, Catalina; Bernuzzi, Francesca; Podda, Mauro; Lammert, Craig; Shigeta, Russell; Chan, Landon L; Balschun, Tobias; Marconi, Maurizio; Cusi, Daniele; Heathcote, E Jenny; Mason, Andrew L; Myers, Robert P; Milkiewicz, Piotr; Odin, Joseph A; Luketic, Velimir A; Bacon, Bruce R; Bodenheimer, Henry C; Liakina, Valentina; Vincent, Catherine; Levy, Cynthia; Franke, Andre; Gregersen, Peter K; Bossa, Fabrizio; Gershwin, M Eric; deAndrade, Mariza; Amos, Christopher I; Lazaridis, Konstantinos N; Seldin, Michael F; Siminovitch, Katherine A

    2012-12-01

    To further characterize the genetic basis of primary biliary cirrhosis (PBC), we genotyped 2426 PBC patients and 5731 unaffected controls from three independent cohorts using a single nucleotide polymorphism (SNP) array (Immunochip) enriched for autoimmune disease risk loci. Meta-analysis of the genotype data sets identified a novel disease-associated locus near the TNFSF11 gene at 13q14, provided evidence for association at six additional immune-related loci not previously implicated in PBC and confirmed associations at 19 of 22 established risk loci. Results of conditional analyses also provided evidence for multiple independent association signals at four risk loci, with haplotype analyses suggesting independent SNP effects at the 2q32 and 16p13 loci, but complex haplotype driven effects at the 3q25 and 6p21 loci. By imputing classical HLA alleles from this data set, four class II alleles independently contributing to the association signal from this region were identified. Imputation of genotypes at the non-HLA loci also provided additional associations, but none with stronger effects than the genotyped variants. An epistatic interaction between the IL12RB2 risk locus at 1p31and the IRF5 risk locus at 7q32 was also identified and suggests a complementary effect of these loci in predisposing to disease. These data expand the repertoire of genes with potential roles in PBC pathogenesis that need to be explored by follow-up biological studies.

  3. Immunochip analyses identify a novel risk locus for primary biliary cirrhosis at 13q14, multiple independent associations at four established risk loci and epistasis between 1p31 and 7q32 risk variants

    PubMed Central

    Juran, Brian D.; Hirschfield, Gideon M.; Invernizzi, Pietro; Atkinson, Elizabeth J.; Li, Yafang; Xie, Gang; Kosoy, Roman; Ransom, Michael; Sun, Ye; Bianchi, Ilaria; Schlicht, Erik M.; Lleo, Ana; Coltescu, Catalina; Bernuzzi, Francesca; Podda, Mauro; Lammert, Craig; Shigeta, Russell; Chan, Landon L.; Balschun, Tobias; Marconi, Maurizio; Cusi, Daniele; Heathcote, E. Jenny; Mason, Andrew L.; Myers, Robert P.; Milkiewicz, Piotr; Odin, Joseph A.; Luketic, Velimir A.; Bacon, Bruce R.; Bodenheimer, Henry C.; Liakina, Valentina; Vincent, Catherine; Levy, Cynthia; Franke, Andre; Gregersen, Peter K.; Bossa, Fabrizio; Gershwin, M. Eric; deAndrade, Mariza; Amos, Christopher I.; Lazaridis, Konstantinos N.; Seldin, Michael F.; Siminovitch, Katherine A.

    2012-01-01

    To further characterize the genetic basis of primary biliary cirrhosis (PBC), we genotyped 2426 PBC patients and 5731 unaffected controls from three independent cohorts using a single nucleotide polymorphism (SNP) array (Immunochip) enriched for autoimmune disease risk loci. Meta-analysis of the genotype data sets identified a novel disease-associated locus near the TNFSF11 gene at 13q14, provided evidence for association at six additional immune-related loci not previously implicated in PBC and confirmed associations at 19 of 22 established risk loci. Results of conditional analyses also provided evidence for multiple independent association signals at four risk loci, with haplotype analyses suggesting independent SNP effects at the 2q32 and 16p13 loci, but complex haplotype driven effects at the 3q25 and 6p21 loci. By imputing classical HLA alleles from this data set, four class II alleles independently contributing to the association signal from this region were identified. Imputation of genotypes at the non-HLA loci also provided additional associations, but none with stronger effects than the genotyped variants. An epistatic interaction between the IL12RB2 risk locus at 1p31and the IRF5 risk locus at 7q32 was also identified and suggests a complementary effect of these loci in predisposing to disease. These data expand the repertoire of genes with potential roles in PBC pathogenesis that need to be explored by follow-up biological studies. PMID:22936693

  4. Real-time multiple objects tracking on Raspberry-Pi-based smart embedded camera

    NASA Astrophysics Data System (ADS)

    Dziri, Aziz; Duranton, Marc; Chapuis, Roland

    2016-07-01

    Multiple-object tracking constitutes a major step in several computer vision applications, such as surveillance, advanced driver assistance systems, and automatic traffic monitoring. Because of the number of cameras used to cover a large area, these applications are constrained by the cost of each node, the power consumption, the robustness of the tracking, the processing time, and the ease of deployment of the system. To meet these challenges, the use of low-power and low-cost embedded vision platforms to achieve reliable tracking becomes essential in networks of cameras. We propose a tracking pipeline that is designed for fixed smart cameras and which can handle occlusions between objects. We show that the proposed pipeline reaches real-time processing on a low-cost embedded smart camera composed of a Raspberry-Pi board and a RaspiCam camera. The tracking quality and the processing speed obtained with the proposed pipeline are evaluated on publicly available datasets and compared to the state-of-the-art methods.

  5. Treatment decisions in multiple sclerosis - insights from real-world observational studies.

    PubMed

    Trojano, Maria; Tintore, Mar; Montalban, Xavier; Hillert, Jan; Kalincik, Tomas; Iaffaldano, Pietro; Spelman, Tim; Sormani, Maria Pia; Butzkueven, Helmut

    2017-02-01

    The complexity of multiple sclerosis (MS) treatment means that doctors and decision-makers need the best available evidence to make the best decisions for patient care. Randomized controlled trials (RCTs) are accepted as the gold standard for assessing the efficacy and safety of any new drug, but conclusions of these trials do not always aid in daily decision-making processes. Indeed, RCTs are usually conducted in ideal conditions, so can measure efficacy only in restricted and unrepresentative populations. In the past decade, a growing number of MS databases and registries have started to produce long-term outcome data from large cohorts of patients with MS treated with disease-modifying therapies in real-world settings. Such observational studies are addressing issues that are otherwise difficult or impossible to study. In this Review, we focus on the most recently published observational studies designed to identify predictors of poor outcome and treatment response or failure, and to evaluate the relative and long-term effectiveness of currently used MS treatments. We also outline the statistical approaches that are most commonly used to reduce bias and limitations in these studies, and the challenges associated with the use of 'big MS data' to facilitate the implementation of personalized medicine in MS.

  6. Use of external cavity quantum cascade laser compliance voltage in real-time trace gas sensing of multiple chemicals

    SciTech Connect

    Phillips, Mark C.; Taubman, Matthew S.; Kriesel, Jason M.

    2015-02-08

    We describe a prototype trace gas sensor designed for real-time detection of multiple chemicals. The sensor uses an external cavity quantum cascade laser (ECQCL) swept over its tuning range of 940-1075 cm-1 (9.30-10.7 µm) at a 10 Hz repetition rate.

  7. Prevalence, antimicrobial resistance and multiple-locus variable-number tandem-repeat analysis profiles of diarrheagenic Escherichia coli isolated from different retail foods.

    PubMed

    Wang, Lili; Nakamura, Hiromi; Kage-Nakadai, Eriko; Hara-Kudo, Yukiko; Nishikawa, Yoshikazu

    2017-03-07

    Diarrheagenic E. coli (DEC) isolates were recovered from local retail markets and the Osaka Municipal Central Wholesale Market in Japan. Retail food samples were collected for analysis in Osaka Japan from 2005 to 2008 and consisted of 32 beef, 28 pork, 20 poultry, 136 fish, 66 fruits and vegetables and 51 ready-to-eat (RTE) food samples. A total of 82 DEC strains were recovered from 64 (19%) food samples with the highest prevalence in poultry (100%, 20/20), followed by pork (54%, 15/28), beef (28%, 9/32), fruits and vegetables (12%, 8/66), fish (6.6%, 9/136) and RTE foods (5.9%, 3/51). Most of the strains belonged to E. coli possessing the enteroaggregative E. coli (EAEC) heat-stable enterotoxin 1 (EAST1) gene (EAST1EC; n=62, P<0.0001) and enteropathogenic E. coli (EPEC; n=16, P<0.01), whereas only 1 strain belonged to Shiga toxin-producing E. coli (STEC), 1 to EAEC and 2 to enterotoxigenic E. coli (ETEC) strains. Of the 82 DEC isolates, 22 O and 13H serogroups were detected, including some specific serogroups (O91, O103, O115, O119, O126, and O157) which have been associated with human diarrheal infections. Phylogenetic group A and B1 were predominant among the DEC isolates. Antimicrobial resistance to tetracycline was most common (49%), followed by nalidixic acid (28%), ampicillin (24%), sulfamethoxazole/trimethoprim (20%), and cephalothin (18%). All isolates were susceptible to aztreonam. Of the resistant strains, 44% (22/50) demonstrated resistance to >3 antimicrobial agents. Isolates resistant to >5 antimicrobials were only found in the meat samples, while isolates from the fruits and vegetables as well as RTE foods showed resistance to only 1 or 2 antimicrobial agents. Sixty one percent of EAST1EC, 56% of EPEC and all of the EAEC and ETEC were resistant to at least 1 antimicrobial agent. Multiple-locus variable-number tandem repeat analysis (MLVA) was used in this study for genotyping of DEC. The 82 isolates collected for this study showed 77 distinct MLVA

  8. Genome-wide quantitative trait locus mapping identifies multiple major loci for brittle rachis and threshability in Tibetan semi-wild wheat (Triticum aestivum ssp. tibetanum Shao).

    PubMed

    Jiang, Yun-Feng; Lan, Xiu-Jin; Luo, Wei; Kong, Xing-Chen; Qi, Peng-Fei; Wang, Ji-Rui; Wei, Yu-Ming; Jiang, Qian-Tao; Liu, Ya-Xi; Peng, Yuan-Ying; Chen, Guo-Yue; Dai, Shou-Fen; Zheng, You-Liang

    2014-01-01

    Tibetan semi-wild wheat (Triticum aestivum ssp. tibetanum Shao) is a semi-wild hexaploid wheat resource that is only naturally distributed in the Qinghai-Tibet Plateau. Brittle rachis and hard threshing are two important characters of Tibetan semi-wild wheat. A whole-genome linkage map of T. aestivum ssp. tibetanum was constructed using a recombinant inbred line population (Q1028×ZM9023) with 186 lines, 564 diversity array technology markers, and 117 simple sequence repeat markers. Phenotypic data on brittle rachis and threshability, as two quantitative traits, were evaluated on the basis of the number of average spike rachis fragments per spike and percent threshability in 2012 and 2013, respectively. Quantitative trait locus (QTL) mapping performed using inclusive composite interval mapping analysis clearly identified four QTLs for brittle rachis and three QTLs for threshability. However, three loci on 2DS, 2DL, and 5AL showed pleiotropism for brittle rachis and threshability; they respectively explained 5.3%, 18.6%, and 18.6% of phenotypic variation for brittle rachis and 17.4%, 13.2%, and 35.2% of phenotypic variation for threshability. A locus on 3DS showed an independent effect on brittle rachis, which explained 38.7% of the phenotypic variation. The loci on 2DS and 3DS probably represented the effect of Tg and Br1, respectively. The locus on 5AL was in very close proximity to the Q gene, but was different from the predicted q in Tibetan semi-wild wheat. To our knowledge, the locus on 2DL has never been reported in common wheat but was prominent in T. aestivum ssp. tibetanum accession Q1028. It remarkably interacted with the locus on 5AL to affect brittle rachis. Several major loci for brittle rachis and threshability were identified in Tibetan semi-wild wheat, improving the understanding of these two characters and suggesting the occurrence of special evolution in Tibetan semi-wild wheat.

  9. A multiple model approach to respiratory motion prediction for real-time IGRT.

    PubMed

    Putra, Devi; Haas, Olivier C L; Mills, John A; Burnham, Keith J

    2008-03-21

    Respiration induces significant movement of tumours in the vicinity of thoracic and abdominal structures. Real-time image-guided radiotherapy (IGRT) aims to adapt radiation delivery to tumour motion during irradiation. One of the main problems for achieving this objective is the presence of time lag between the acquisition of tumour position and the radiation delivery. Such time lag causes significant beam positioning errors and affects the dose coverage. A method to solve this problem is to employ an algorithm that is able to predict future tumour positions from available tumour position measurements. This paper presents a multiple model approach to respiratory-induced tumour motion prediction using the interacting multiple model (IMM) filter. A combination of two models, constant velocity (CV) and constant acceleration (CA), is used to capture respiratory-induced tumour motion. A Kalman filter is designed for each of the local models and the IMM filter is applied to combine the predictions of these Kalman filters for obtaining the predicted tumour position. The IMM filter, likewise the Kalman filter, is a recursive algorithm that is suitable for real-time applications. In addition, this paper proposes a confidence interval (CI) criterion to evaluate the performance of tumour motion prediction algorithms for IGRT. The proposed CI criterion provides a relevant measure for the prediction performance in terms of clinical applications and can be used to specify the margin to accommodate prediction errors. The prediction performance of the IMM filter has been evaluated using 110 traces of 4-minute free-breathing motion collected from 24 lung-cancer patients. The simulation study was carried out for prediction time 0.1-0.6 s with sampling rates 3, 5 and 10 Hz. It was found that the prediction of the IMM filter was consistently better than the prediction of the Kalman filter with the CV or CA model. There was no significant difference of prediction errors for the

  10. Use of Accelerometers to Measure Real-Life Physical Activity in Ambulatory Individuals with Multiple Sclerosis

    PubMed Central

    Fjeldstad, Anette S.; Pardo, Gabriel

    2015-01-01

    Background: Multiple sclerosis (MS) may negatively affect individuals' participation in physical activity (PA). We used accelerometers to determine PA level in individuals with MS with varying degrees of disability as measured by the Expanded Disability Status Scale (EDSS) during regular daily activities. Methods: Participants wore an accelerometer from 8 a.m. to 9 p.m. for 7 consecutive days. Activity counts recorded during this period were analyzed in 1-minute epochs and categorized into one of four PA levels: light, moderate, hard, and very hard. Results: The study cohort comprised 13 patients with MS and 12 controls. There were significant negative correlations for minutes spent in PA and EDSS measures on weekdays (r = −0.61), weekend (r = −0.64), and full week (r = −0.61) and number of steps taken on weekdays (r = −0.56), weekend (r = −0.80), and full-week average (r = −0.68). Significant positive correlations were found for minutes spent in light PA and EDSS score (r = 0.69). Significant negative correlations were found for minutes spent in moderate and hard PA and EDSS score. No significant difference was seen between the MS group and controls on any parameters (P > .05). Conclusions: This study showed that accelerometers can be used to objectively quantify PA levels in individuals with MS with different disability levels. This cohort demonstrated that the amount of PA is inversely proportional to the degree of physical disability. Collected data revealed not only the amount but also the intensity of PA performed in real-life circumstances. PMID:26472942

  11. Multi-camera real-time three-dimensional tracking of multiple flying animals

    PubMed Central

    Straw, Andrew D.; Branson, Kristin; Neumann, Titus R.; Dickinson, Michael H.

    2011-01-01

    Automated tracking of animal movement allows analyses that would not otherwise be possible by providing great quantities of data. The additional capability of tracking in real time—with minimal latency—opens up the experimental possibility of manipulating sensory feedback, thus allowing detailed explorations of the neural basis for control of behaviour. Here, we describe a system capable of tracking the three-dimensional position and body orientation of animals such as flies and birds. The system operates with less than 40 ms latency and can track multiple animals simultaneously. To achieve these results, a multi-target tracking algorithm was developed based on the extended Kalman filter and the nearest neighbour standard filter data association algorithm. In one implementation, an 11-camera system is capable of tracking three flies simultaneously at 60 frames per second using a gigabit network of nine standard Intel Pentium 4 and Core 2 Duo computers. This manuscript presents the rationale and details of the algorithms employed and shows three implementations of the system. An experiment was performed using the tracking system to measure the effect of visual contrast on the flight speed of Drosophila melanogaster. At low contrasts, speed is more variable and faster on average than at high contrasts. Thus, the system is already a useful tool to study the neurobiology and behaviour of freely flying animals. If combined with other techniques, such as ‘virtual reality’-type computer graphics or genetic manipulation, the tracking system would offer a powerful new way to investigate the biology of flying animals. PMID:20630879

  12. Real-time optical path control method that utilizes multiple support vector machines for traffic prediction

    NASA Astrophysics Data System (ADS)

    Kawase, Hiroshi; Mori, Yojiro; Hasegawa, Hiroshi; Sato, Ken-ichi

    2016-02-01

    An effective solution to the continuous Internet traffic expansion is to offload traffic to lower layers such as the L2 or L1 optical layers. One possible approach is to introduce dynamic optical path operations such as adaptive establishment/tear down according to traffic variation. Path operations cannot be done instantaneously; hence, traffic prediction is essential. Conventional prediction techniques need optimal parameter values to be determined in advance by averaging long-term variations from the past. However, this does not allow adaptation to the ever-changing short-term variations expected to be common in future networks. In this paper, we propose a real-time optical path control method based on a machinelearning technique involving support vector machines (SVMs). A SVM learns the most recent traffic characteristics, and so enables better adaptation to temporal traffic variations than conventional techniques. The difficulty lies in determining how to minimize the time gap between optical path operation and buffer management at the originating points of those paths. The gap makes the required learning data set enormous and the learning process costly. To resolve the problem, we propose the adoption of multiple SVMs running in parallel, trained with non-overlapping subsets of the original data set. The maximum value of the outputs of these SVMs will be the estimated number of necessary paths. Numerical experiments prove that our proposed method outperforms a conventional prediction method, the autoregressive moving average method with optimal parameter values determined by Akaike's information criterion, and reduces the packet-loss ratio by up to 98%.

  13. Efficiency of typing unaffected relatives in an affected-sib-pair linkage study with single-locus and multiple tightly linked markers

    SciTech Connect

    Holmans, P.; Clayton, D.

    1995-11-01

    In an affected-sib-pair study, the parents are often unavailable for typing, particularly for diseases of late onset. In many cases, however, it is possible to sample unaffected siblings. It is therefore desirable to assess the contribution of such siblings to the power of such a study. The likelihood ratio introduced by Risch and improved by Holmans was extended to incorporate data from unaffected siblings. Tests based on two likelihoods were considered: the full likelihood of the data, based on the identity-by-descent (IBD) sharing states of the entire sibship, and a pseudolikelihood based on the IBD sharing states of the affected pair only, using the unaffected siblings to infer parental genotypes. The latter approach was found to be more powerful, except when penetrance was high. Typing an unaffected sibling, or just one parent, was found to give only a small increase in power except when the PIC of the marker was low. Even then, typing an unaffected relative increased the overall number of individuals that had to be typed to achieve a given power. If there is no highly informative marker locus in the area under study, it may be possible to {open_quotes}build{close_quotes} one by combining the alleles from two or more neighboring tightly linked loci into haplotypes. Typing two loci gave a sizeable power increase over a single locus, but typing further loci gave much smaller gains. Building haplotypes will introduce phase uncertainties, with the result that such a system will yield less power than will a single locus with the same number of alleles. This power loss was small, however, and did not affect the conclusions regarding the worth of typing unaffected relatives. 14 refs., 2 figs., 11 tabs.

  14. Multiple indices method for real-time tsunami inundation forecast using a dense offshore observation network

    NASA Astrophysics Data System (ADS)

    Yamamoto, N.; Aoi, S.; Hirata, K.; Suzuki, W.; Kunugi, T.; Nakamura, H.

    2015-12-01

    We started to develop a new methodology for real-time tsunami inundation forecast system (Aoi et al., 2015, this meeting) using densely offshore tsunami observations of the Seafloor Observation Network for Earthquakes and Tsunamis (S-net), which is under construction along the Japan Trench (Kanazawa et al., 2012, JpGU; Uehira et al., 2015, IUGG). In our method, the most important concept is involving any type and/or form uncertainties in the tsunami forecast, which cannot be dealt with any of standard linear/nonlinear least square approaches. We first prepare a Tsunami Scenario Bank (TSB), which contains offshore tsunami waveforms at the S-net stations and tsunami inundation information calculated from any possible tsunami source. We then quickly select several acceptable tsunami scenarios that can explain offshore observations by using multiple indices and appropriate thresholds, after a tsunami occurrence. At that time, possible tsunami inundations coupled with selected scenarios are forecasted (Yamamoto et al., 2014, AGU). Currently, we define three indices: correlation coefficient and two variance reductions, whose L2-norm part is normalized either by observations or calculations (Suzuki et al., 2015, JpGU; Yamamoto et al., 2015, IUGG). In this study, we construct the TSB, which contains various tsunami source models prepared for the probabilistic tsunami hazard assessment in the Japan Trench region (Hirata et al., 2014, AGU). To evaluate the propriety of our method, we adopt the fault model based on the 2011 Tohoku earthquake as a pseudo "observation". We also calculate three indices using coastal maximum tsunami height distributions between observation and calculation. We then obtain the correlation between coastal and offshore indices. We notice that the index value of coastal maximum tsunami heights is closer to 1 than the index value of offshore waveforms, i.e., the coastal maximum tsunami height may be predictable within appropriate thresholds defined for

  15. Geographic information systems for real-time environmental sensing at multiple scales

    NASA Astrophysics Data System (ADS)

    Esswein, Samuel Thomas

    The purpose of this investigation was to design, implement, and apply a real-time geographic information system for data intensive water resource research and management. The research presented is part of an ongoing, interdisciplinary research program supporting the development of the Intelligent River ® observation instrument. The objectives of this research were to 1) design and describe software architecture for a streaming environmental sensing information system, 2) implement and evaluate the proposed information system, and 3) apply the information system for monitoring, analysis, and visualization of an urban stormwater improvement project located in the City of Aiken, South Carolina, USA. This research contributes to the fields of software architecture and urban ecohydrology. The first contribution is a formal architectural description of a streaming environmental sensing information system. This research demonstrates the operation of the information system and provides a reference point for future software implementations. Contributions to urban ecohydrology are in three areas. First, a characterization of soil properties for the study region of the City of Aiken, SC is provided. The analysis includes an evaluation of spatial structure for soil hydrologic properties. Findings indicate no detectable structure at the scales explored during the study. The second contribution to ecohydrology comes from a long-term, continuous monitoring program for bioinfiltration basin structures located in the study area. Results include an analysis of soil moisture dynamics based on data collected at multiple depths with high spatial and temporal resolution. A novel metric is introduced to evaluate the long-term performance of bioinfiltration basin structures based on soil moisture observation data. Findings indicate a decrease in basin performance over time for the monitored sites. The third contribution to the field of ecohydrology is the development and application of a

  16. Real-space multiple-scattering theory of XMCD including spin-orbit interaction in scattering process

    NASA Astrophysics Data System (ADS)

    Koide, Akihiro; Niki, Kaori; Sakai, Seiji; Fujikawa, Takashi

    2016-05-01

    The effects of the spin-orbit interaction on surrounding atoms for XMCD spectra are studied by a real-space multiple-scattering theory. The present numerical calculation for Fe K-edge XMCD spectra from BCC iron demonstrates the importance of the spin-orbit interaction on scattering atoms, which has been disregarded in previous works. These effects will be inevitable for K-edge XMCD analyses of light elements surrounded by heavy magnetic atoms.

  17. Variation in the ICAM1–ICAM4–ICAM5 locus is associated with systemic lupus erythematosus susceptibility in multiple ancestries

    PubMed Central

    Kim, Kwangwoo; Brown, Elizabeth E; Choi, Chan-Bum; Alarcón-Riquelme, Marta E; Kelly, Jennifer A; Glenn, Stuart B; Ojwang, Joshua O; Adler, Adam; Lee, Hye-Soon; Boackle, Susan A; Criswell, Lindsey A; Alarcón, Graciela S; Edberg, Jeffrey C; Stevens, Anne M; Jacob, Chaim O; Gilkeson, Gary S; Kamen, Diane L; Tsao, Betty P; Anaya, Juan-Manuel; Guthridge, Joel M; Nath, Swapan K; Richardson, Bruce; Sawalha, Amr H; Kang, Young Mo; Shim, Seung Cheol; Suh, Chang-Hee; Lee, Soo-Kon; Kim, Chang-sik; Merrill, Joan T; Petri, Michelle; Ramsey-Goldman, Rosalind; Vilá, Luis M; Niewold, Timothy B; Martin, Javier; Pons-Estel, Bernardo A; Vyse, Timothy J; Freedman, Barry I; Moser, Kathy L; Gaffney, Patrick M; Williams, Adrienne; Comeau, Mary; Reveille, John D; James, Judith A; Scofield, R Hal; Langefeld, Carl D; Kaufman, Kenneth M; Harley, John B; Kang, Changwon; Kimberly, Robert P; Bae, Sang-Cheol

    2012-01-01

    Objective Systemic lupus erythematosus (SLE; OMIM 152700) is a chronic autoimmune disease for which the aetiology includes genetic and environmental factors. ITGAM, integrin αΜ (complement component 3 receptor 3 subunit) encoding a ligand for intracellular adhesion molecule (ICAM) proteins, is an established SLE susceptibility locus. This study aimed to evaluate the independent and joint effects of genetic variations in the genes that encode ITGAM and ICAM. Methods The authors examined several markers in the ICAM1–ICAM4–ICAM5 locus on chromosome 19p13 and the single ITGAM polymorphism (rs1143679) using a large-scale case–control study of 17 481 unrelated participants from four ancestry populations. The single marker association and gene–gene interaction were analysed for each ancestry, and a meta-analysis across the four ancestries was performed. Results The A-allele of ICAM1–ICAM4–ICAM5 rs3093030, associated with elevated plasma levels of soluble ICAM1, and the A-allele of ITGAM rs1143679 showed the strongest association with increased SLE susceptibility in each of the ancestry populations and the trans-ancestry meta-analysis (ORmeta=1.16, 95% CI 1.11 to 1.22; p=4.88×10−10 and ORmeta=1.67, 95% CI 1.55 to 1.79; p=3.32×10−46, respectively). The effect of the ICAM single-nucleotide polymorphisms (SNPs) was independent of the effect of the ITGAM SNP rs1143679, and carriers of both ICAM rs3093030-AA and ITGAM rs1143679-AA had an OR of 4.08 compared with those with no risk allele in either SNP (95% CI 2.09 to 7.98; p=3.91×10−5). Conclusion These findings are the first to suggest that an ICAM–integrin-mediated pathway contributes to susceptibility to SLE. PMID:22523428

  18. Application of Molecular Typing Results in Source Attribution Models: The Case of Multiple Locus Variable Number Tandem Repeat Analysis (MLVA) of Salmonella Isolates Obtained from Integrated Surveillance in Denmark.

    PubMed

    de Knegt, Leonardo V; Pires, Sara M; Löfström, Charlotta; Sørensen, Gitte; Pedersen, Karl; Torpdahl, Mia; Nielsen, Eva M; Hald, Tine

    2016-03-01

    Salmonella is an important cause of bacterial foodborne infections in Denmark. To identify the main animal-food sources of human salmonellosis, risk managers have relied on a routine application of a microbial subtyping-based source attribution model since 1995. In 2013, multiple locus variable number tandem repeat analysis (MLVA) substituted phage typing as the subtyping method for surveillance of S. Enteritidis and S. Typhimurium isolated from animals, food, and humans in Denmark. The purpose of this study was to develop a modeling approach applying a combination of serovars, MLVA types, and antibiotic resistance profiles for the Salmonella source attribution, and assess the utility of the results for the food safety decisionmakers. Full and simplified MLVA schemes from surveillance data were tested, and model fit and consistency of results were assessed using statistical measures. We conclude that loci schemes STTR5/STTR10/STTR3 for S. Typhimurium and SE9/SE5/SE2/SE1/SE3 for S. Enteritidis can be used in microbial subtyping-based source attribution models. Based on the results, we discuss that an adjustment of the discriminatory level of the subtyping method applied often will be required to fit the purpose of the study and the available data. The issues discussed are also considered highly relevant when applying, e.g., extended multi-locus sequence typing or next-generation sequencing techniques.

  19. Maximizing Multiple Intelligences through Multimedia: A Real Application of Gardner's Theories.

    ERIC Educational Resources Information Center

    Martin, Graham P.; Burnette, Carter

    2000-01-01

    Discusses Howard Gardner's theory of Multiple Intelligences that addresses how students assimilate information and suggests the use of electronic portfolios to allow a broader array of learning styles and increase the effectiveness of activities by addressing more Multiple Intelligences. Explains the use of hypertext and multimedia on a CD-ROM.…

  20. Real-time multiple-parameter tuning of PPF controllers for smart structures by genetic algorithms

    NASA Astrophysics Data System (ADS)

    Kwak, Moon K.; Heo, Seok

    2000-06-01

    This paper is concerned with the real-time automatic tuning of the multi-input multi-output positive position feedback controllers for smart structures by the genetic algorithms. The genetic algorithms have proven its effectiveness in searching optimal design parameters without falling into local minimums thus rendering globally optimal solutions. The previous real-time algorithm that tunes a single control parameter is extended to tune more parameters of the MIMO PPF controller. We employ the MIMO PPF controller since it can enhance the damping value of a target mode without affecting other modes if tuned properly. Hence, the traditional positive position feedback controller can be used in adaptive fashion in real time. The final form of the MIMO PPF controller results in the centralized control, thus it involves many parameters. The bounds of the control parameters are estimated from the theoretical model to guarantee the stability. As in the previous research, the digital MIMO PPF control law is downloaded to the DSP chip and a main program, which runs genetic algorithms in real time, updates the parameters of the controller in real time. The experimental frequency response results show that the MIMO PPF controller tuned by GA gives better performance than the theoretically designed PPF. The time response also shows that the GA tuned MIMO PPF controller can suppress vibrations very well.

  1. Reliable real-time calculation of heart-rate complexity in critically ill patients using multiple noisy waveform sources.

    PubMed

    Liu, Nehemiah T; Cancio, Leopoldo C; Salinas, Jose; Batchinsky, Andriy I

    2014-04-01

    Heart-rate complexity (HRC) has been proposed as a new vital sign for critical care medicine. The purpose of this research was to develop a reliable method for determining HRC continuously in real time in critically ill patients using multiple waveform channels that also compensates for noisy and unreliable data. Using simultaneously acquired electrocardiogram (Leads I, II, V) and arterial blood pressure waveforms sampled at 360 Hz from 250 patients (over 375 h of patient data), we evaluated a new data fusion framework for computing HRC in real time. The framework employs two algorithms as well as signal quality indices. HRC was calculated (via the method of sample entropy), and equivalence tests were then performed. Bland-Altman plots and box plots of differences between mean HRC values were also obtained. Finally, HRC differences were analyzed by paired t tests. The gold standard for obtaining true means was manual verification of R waves and subsequent entropy calculations. Equivalence tests between mean HRC values derived from manually verified sequences and those derived from automatically detected peaks showed that the "Fusion" values were the least statistically different from the gold standard. Furthermore, the fusion of waveform sources produced better error density distributions than those derived from individual waveforms. The data fusion framework was shown to provide in real-time a reliable continuously streamed HRC value, derived from multiple waveforms in the presence of noise and artifacts. This approach will be validated and tested for assessment of HRC in critically ill patients.

  2. Multiple Roles for UV RESISTANCE LOCUS8 in Regulating Gene Expression and Metabolite Accumulation in Arabidopsis under Solar Ultraviolet Radiation1[W][OA

    PubMed Central

    Morales, Luis O.; Brosché, Mikael; Vainonen, Julia; Jenkins, Gareth I.; Wargent, Jason J.; Sipari, Nina; Strid, Åke; Lindfors, Anders V.; Tegelberg, Riitta; Aphalo, Pedro J.

    2013-01-01

    Photomorphogenic responses triggered by low fluence rates of ultraviolet B radiation (UV-B; 280–315 nm) are mediated by the UV-B photoreceptor UV RESISTANCE LOCUS8 (UVR8). Beyond our understanding of the molecular mechanisms of UV-B perception by UVR8, there is still limited information on how the UVR8 pathway functions under natural sunlight. Here, wild-type Arabidopsis (Arabidopsis thaliana) and the uvr8-2 mutant were used in an experiment outdoors where UV-A (315–400 nm) and UV-B irradiances were attenuated using plastic films. Gene expression, PYRIDOXINE BIOSYNTHESIS1 (PDX1) accumulation, and leaf metabolite signatures were analyzed. The results show that UVR8 is required for transcript accumulation of genes involved in UV protection, oxidative stress, hormone signal transduction, and defense against herbivores under solar UV. Under natural UV-A irradiance, UVR8 is likely to interact with UV-A/blue light signaling pathways to moderate UV-B-driven transcript and PDX1 accumulation. UVR8 both positively and negatively affects UV-A-regulated gene expression and metabolite accumulation but is required for the UV-B induction of phenolics. Moreover, UVR8-dependent UV-B acclimation during the early stages of plant development may enhance normal growth under long-term exposure to solar UV. PMID:23250626

  3. Substitution mapping of dth1.1, a flowering-time quantitative trait locus (QTL) associated with transgressive variation in rice, reveals multiple sub-QTL.

    PubMed

    Thomson, Michael J; Edwards, Jeremy D; Septiningsih, Endang M; Harrington, Sandra E; McCouch, Susan R

    2006-04-01

    A quantitative trait locus (QTL), dth1.1, was associated with transgressive variation for days to heading in an advanced backcross population derived from the Oryza sativa variety Jefferson and an accession of the wild rice relative Oryza rufipogon. A series of near-isogenic lines (NILs) containing different O. rufipogon introgressions across the target region were constructed to dissect dth1.1 using substitution mapping. In contrast to the late-flowering O. rufipogon parent, O. rufipogon alleles in the substitution lines caused early flowering under both short- and long-day lengths and provided evidence for at least two distinct sub-QTL: dth1.1a and dth1.1b. Potential candidate genes underlying these sub-QTL include genes with sequence similarity to Arabidopsis GI, FT, SOC1, and EMF1, and Pharbitis nil PNZIP. Evidence from families with nontarget O. rufipogon introgressions in combination with dth1.1 alleles also detected an early flowering QTL on chromosome 4 and a late-flowering QTL on chromosome 6 and provided evidence for additional sub-QTL in the dth1.1 region. The availability of a series of near-isogenic lines with alleles introgressed from a wild relative of rice provides an opportunity to better understand the molecular basis of transgressive variation in a quantitative trait.

  4. Substitution Mapping of dth1.1, a Flowering-Time Quantitative Trait Locus (QTL) Associated With Transgressive Variation in Rice, Reveals Multiple Sub-QTL

    PubMed Central

    Thomson, Michael J.; Edwards, Jeremy D.; Septiningsih, Endang M.; Harrington, Sandra E.; McCouch, Susan R.

    2006-01-01

    A quantitative trait locus (QTL), dth1.1, was associated with transgressive variation for days to heading in an advanced backcross population derived from the Oryza sativa variety Jefferson and an accession of the wild rice relative Oryza rufipogon. A series of near-isogenic lines (NILs) containing different O. rufipogon introgressions across the target region were constructed to dissect dth1.1 using substitution mapping. In contrast to the late-flowering O. rufipogon parent, O. rufipogon alleles in the substitution lines caused early flowering under both short- and long-day lengths and provided evidence for at least two distinct sub-QTL: dth1.1a and dth1.1b. Potential candidate genes underlying these sub-QTL include genes with sequence similarity to Arabidopsis GI, FT, SOC1, and EMF1, and Pharbitis nil PNZIP. Evidence from families with nontarget O. rufipogon introgressions in combination with dth1.1 alleles also detected an early flowering QTL on chromosome 4 and a late-flowering QTL on chromosome 6 and provided evidence for additional sub-QTL in the dth1.1 region. The availability of a series of near-isogenic lines with alleles introgressed from a wild relative of rice provides an opportunity to better understand the molecular basis of transgressive variation in a quantitative trait. PMID:16452146

  5. Detection of Avian bornavirus in multiple tissues of infected psittacine birds using real-time reverse transcription polymerase chain reaction.

    PubMed

    Delnatte, Pauline; Mak, Matthew; Ojkic, Davor; Raghav, Raj; DeLay, Josepha; Smith, Dale A

    2014-03-01

    Avian bornavirus (ABV), the cause of proventricular dilation disease in psittacine birds, has been detected in multiple tissues of infected birds using immunohistochemical staining (IHC) and reverse transcription polymerase chain reaction (RT-PCR). In the current study, real-time RT-PCR, using primers targeting the ABV matrix gene, was used to detect ABV in 146 tissues from 7 ABV-infected psittacine birds. Eighty-six percent of the samples tested positive, with crossing point values ranging from 13.82 to 37.82 and a mean of 22.3. These results were compared to the findings of a previous study using gel-based RT-PCR and IHC on the same samples. The agreement between the 2 RT-PCR techniques was 91%; when tests disagreed it was because samples were negative using gel-based RT-PCR but positive on real-time RT-PCR. Agreement with IHC was 77%; 16 out of 74 samples were negative using IHC but positive on real-time RT-PCR. The results suggest that real-time RT-PCR is a more sensitive technique than gel-based RT-PCR and IHC to detect ABV in tissues. The tissues that were ranked most frequently as having a high amount of viral RNA were proventriculus, kidney, colon, cerebrum, and cerebellum. Skeletal muscle, on the other hand, was found to have a consistently low amount of viral RNA.

  6. Using LabView for real-time monitoring and tracking of multiple biological objects

    NASA Astrophysics Data System (ADS)

    Nikolskyy, Aleksandr I.; Krasilenko, Vladimir G.; Bilynsky, Yosyp Y.; Starovier, Anzhelika

    2017-04-01

    Today real-time studying and tracking of movement dynamics of various biological objects is important and widely researched. Features of objects, conditions of their visualization and model parameters strongly influence the choice of optimal methods and algorithms for a specific task. Therefore, to automate the processes of adaptation of recognition tracking algorithms, several Labview project trackers are considered in the article. Projects allow changing templates for training and retraining the system quickly. They adapt to the speed of objects and statistical characteristics of noise in images. New functions of comparison of images or their features, descriptors and pre-processing methods will be discussed. The experiments carried out to test the trackers on real video files will be presented and analyzed.

  7. Simultaneous multiple target detection in real-time loop-mediated isothermal amplification.

    PubMed

    Tanner, Nathan A; Zhang, Yinhua; Evans, Thomas C

    2012-08-01

    Loop-mediated isothermal amplification (LAMP) is a rapid and reliable sequence-specific isothermal nucleic acid amplification technique. To date, all reported real-time detection methods for LAMP have been restricted to single targets, limiting the utility of this technique. Here, we adapted standard LAMP primers to contain a quencher-fluorophore duplex region that upon strand separation results in a gain of fluorescent signal. This approach permitted the real-time detection of 1-4 target sequences in a single LAMP reaction tube utilizing a standard real-time fluorimeter. The methodology was highly reproducible and sensitive, detecting below 100 copies of human genomic DNA. It was also robust, with a 7-order of magnitude dynamic range of detectable targets. Furthermore, using a new strand-displacing DNA polymerase or its warm-start version, Bst 2.0 or Bst 2.0 WarmStart DNA polymerases, resulted in 50% faster amplification signals than wild-type Bst DNA polymerase, large fragment in this new multiplex LAMP procedure. The coupling of this new multiplex technique with next generation isothermal DNA polymerases should increase the utility of the LAMP method for molecular diagnostics.

  8. Real-time multiple-look synthetic aperture radar processor for spacecraft applications

    NASA Technical Reports Server (NTRS)

    Wu, C.; Tyree, V. C. (Inventor)

    1981-01-01

    A spaceborne synthetic aperture radar (SAR) having pipeline multiple-look data processing is described which makes use of excessive azimuth bandwidth in radar echo signals to produce multiple-looking images. Time multiplexed single-look image lines from an azimuth correlator go through an energy analyzer which analyzes the mean energy in each separate look to determine the radar antenna electric boresight for use in generating the correct reference functions for the production of high quality SAR images. The multiplexed single look image lines also go through a registration delay to produce multi-look images.

  9. Systematic Fine-Mapping of Association with BMI and Type 2 Diabetes at the FTO Locus by Integrating Results from Multiple Ethnic Groups

    PubMed Central

    Chakrawarthy, Sureka; Nguyen, Quang Ngoc; Wen, Wanqing; Yamamoto, Ken; Katsuya, Tomohiro; Kasturiratne, Anuradhani; Pham, Son Thai; Zheng, Wei; Matsushita, Yumi; Kishimoto, Miyako; Do, Loi Doan; Shu, Xiao-Ou; Wickremasinghe, Ananda R.; Kajio, Hiroshi; Kato, Norihiro

    2014-01-01

    Background/Objective The 16q12.2 locus in the first intron of FTO has been robustly associated with body mass index (BMI) and type 2 diabetes in genome-wide association studies (GWAS). To improve the resolution of fine-scale mapping at FTO, we performed a systematic approach consisting of two parts. Methods The first part is to partition the associated variants into linkage disequilibrium (LD) clusters, followed by conditional and haplotype analyses. The second part is to filter the list of potential causal variants through trans-ethnic comparison. Results We first examined the LD relationship between FTO SNPs showing significant association with type 2 diabetes in Japanese GWAS and between those previously reported in European GWAS. We could partition all the assayed or imputed SNPs showing significant association in the target FTO region into 7 LD clusters. Assaying 9 selected SNPs in 4 Asian-descent populations—Japanese, Vietnamese, Sri Lankan and Chinese (n≤26,109 for BMI association and n≤24,079 for type 2 diabetes association), we identified a responsible haplotype tagged by a cluster of SNPs and successfully narrowed the list of potential causal variants to 25 SNPs, which are the smallest in number among the studies conducted to date for FTO. Conclusions Our data support that the power to resolve the causal variants from those in strong LD increases consistently when three distant populations—Europeans, Asians and Africans—are included in the follow-up study. It has to be noted that this fine-mapping approach has the advantage of applicability to the existing GWAS data set in combination with direct genotyping of selected variants. PMID:24978468

  10. Fine scale genetic and physical mapping using interstitial deletion mutants of Lr34 /Yr18: a disease resistance locus effective against multiple pathogens in wheat.

    PubMed

    Spielmeyer, W; Singh, R P; McFadden, H; Wellings, C R; Huerta-Espino, J; Kong, X; Appels, R; Lagudah, E S

    2008-02-01

    The Lr34/Yr18 locus has contributed to durable, non-race specific resistance against leaf rust (Puccinia triticina) and stripe rust (P. striiformis f. sp. tritici) in wheat (Triticum aestivum). Lr34/Yr18 also cosegregates with resistance to powdery mildew (Pm38) and a leaf tip necrosis phenotype (Ltn1). Using a high resolution mapping family from a cross between near-isogenic lines in the "Thatcher" background we demonstrated that Lr34/Yr18 also cosegregated with stem rust resistance in the field. Lr34/Yr18 probably interacts with unlinked genes to provide enhanced stem rust resistance in "Thatcher". In view of the relatively low levels of DNA polymorphism reported in the Lr34/Yr18 region, gamma irradiation of the single chromosome substitution line, Lalbahadur(Parula7D) that carries Lr34/Yr18 was used to generate several mutant lines. Characterisation of the mutants revealed a range of highly informative genotypes, which included variable size deletions and an overlapping set of interstitial deletions. The mutants enabled a large number of wheat EST derived markers to be mapped and define a relatively small physical region on chromosome 7DS that carried Lr34/Yr18. Fine scale genetic mapping confirmed the physical mapping and identified a genetic interval of less than 0.5 cM, which contained Lr34/Yr18. Both rice and Brachypodium genome sequences provided useful information for fine mapping of ESTs in wheat. Gene order was more conserved between wheat and Brachypodium than with rice but these smaller grass genomes did not reveal sequence information that could be used to identify a candidate gene for rust resistance in wheat. We predict that Lr34/Yr18 is located within a large insertion in wheat not found at syntenic positions in Brachypodium and rice.

  11. Coordinate Control of the Locus of Enterocyte Effacement and Enterohemolysin Genes by Multiple Common Virulence Regulators in Enterohemorrhagic Escherichia coli ▿

    PubMed Central

    Iyoda, Sunao; Honda, Naoko; Saitoh, Takehito; Shimuta, Ken; Terajima, Jun; Watanabe, Haruo; Ohnishi, Makoto

    2011-01-01

    The locus of enterocyte effacement (LEE) pathogenicity island is required for the intimate adhesion of enterohemorrhagic Escherichia coli (EHEC) to the intestinal epithelial cells. GrlR and GrlA are LEE-encoded negative and positive regulators, respectively. The interaction of these two regulators is important for controlling the transcription of LEE genes through Ler, a LEE-encoded central activator for the LEE. The GrlR-GrlA regulatory system controls not only LEE but also the expression of the flagellar and enterohemolysin (Ehx) genes in EHEC. Since Ehx levels were markedly induced in a grlR mutant but not in a grlR grlA double mutant and significantly increased by overexpression of GrlA in a ler mutant, GrlA is responsible for this regulation (T. Saitoh et al., J. Bacteriol. 190:4822-4830, 2008). In this study, additional investigations of the regulation of ehx gene expression determined that Ler also acts as an activator for Ehx expression without requiring GrlA function. We recently reported that the LysR-type regulator LrhA positively controls LEE expression (N. Honda et al., Mol. Microbiol. 74:1393-1411, 2009). The hemolytic activity of the lrhA mutant strain of EHEC was lower than that of the wild-type strain, and LrhA markedly induced ehx transcription in an E. coli K-12 strain, suggesting that LrhA also activates the transcription of ehx without GrlA and Ler. Gel mobility shift assays demonstrated that Ler and LrhA directly bind to the regulatory region of ehxC. Together, these results indicate that transcription of ehx is positively regulated by Ler, GrlA, and LrhA, which all act as positive regulators for LEE expression. PMID:21844237

  12. Multiple Sclerosis Risk Allele in CLEC16A Acts as an Expression Quantitative Trait Locus for CLEC16A and SOCS1 in CD4+ T Cells.

    PubMed

    Leikfoss, Ingvild S; Keshari, Pankaj K; Gustavsen, Marte W; Bjølgerud, Anja; Brorson, Ina S; Celius, Elisabeth G; Spurkland, Anne; Bos, Steffan D; Harbo, Hanne F; Berge, Tone

    2015-01-01

    For multiple sclerosis, genome wide association studies and follow up studies have identified susceptibility single nucleotide polymorphisms located in or near CLEC16A at chromosome 16p13.13, encompassing among others CIITA, DEXI and SOCS1 in addition to CLEC16A. These genetic variants are located in intronic or intergenic regions and display strong linkage disequilibrium with each other, complicating the understanding of their functional contribution and the identification of the direct causal variant(s). Previous studies have shown that multiple sclerosis-associated risk variants in CLEC16A act as expression quantitative trait loci for CLEC16A itself in human pancreatic β-cells, for DEXI and SOCS1 in thymic tissue samples, and for DEXI in monocytes and lymphoblastoid cell lines. Since T cells are major players in multiple sclerosis pathogenesis, we have performed expression analyses of the CIITA-DEXI-CLEC16A-SOCS1 gene cluster in CD4+ and CD8+ T cells isolated from multiple sclerosis patients and healthy controls. We observed a higher expression of SOCS1 and CLEC16A in CD4+ T cells in samples homozygous for the risk allele of CLEC16A rs12927355. Pair-wise linear regression analysis revealed high correlation in gene expression in peripheral T cells of CIITA, DEXI, CLEC16A and SOCS1. Our data imply a possible regulatory role for the multiple sclerosis-associated rs12927355 in CLEC16A.

  13. Use of an Automated Multiple-Locus, Variable-Number Tandem Repeat-Based Method for Rapid and High-Throughput Genotyping of Staphylococcus aureus Isolates

    PubMed Central

    Francois, Patrice; Huyghe, Antoine; Charbonnier, Yvan; Bento, Manuela; Herzig, Sébastien; Topolski, Ivan; Fleury, Bénédicte; Lew, Daniel; Vaudaux, Pierre; Harbarth, Stephan; van Leeuwen, Willem; van Belkum, Alex; Blanc, Dominique S.; Pittet, Didier; Schrenzel, Jacques

    2005-01-01

    Fast and reliable genotyping methods that allow real-time epidemiological surveillance would be instrumental to monitoring of the spread of methicillin-resistant Staphylococcus aureus. We describe an automated variable-number tandem repeat-based method for the rapid genotyping of Staphylococcus aureus. Multiplex PCR amplifications with eight primer pairs that target gene regions with variable numbers of tandem repeats were resolved by microcapillary electrophoresis and automatically assessed by cluster analysis. This genotyping technique was evaluated for its discriminatory power and reproducibility with clinical isolates of various origins, including a panel of control strains previously characterized by several typing methods and collections from either long-term carriers or defined nosocomial outbreaks. All steps of this new procedure were developed to ensure a rapid turnaround time and moderate cost. The results obtained suggest that this rapid approach is a valuable tool for the genotyping of S. aureus isolates in real time. PMID:16000459

  14. Real-time segmentation of multiple implanted cylindrical liver markers in kilovoltage and megavoltage x-ray images

    NASA Astrophysics Data System (ADS)

    Fledelius, W.; Worm, E.; Høyer, M.; Grau, C.; Poulsen, P. R.

    2014-06-01

    Gold markers implanted in or near a tumor can be used as x-ray visible landmarks for image based tumor localization. The aim of this study was to develop and demonstrate fast and reliable real-time segmentation of multiple liver tumor markers in intra-treatment kV and MV images and in cone-beam CT (CBCT) projections, for real-time motion management. Thirteen patients treated with conformal stereotactic body radiation therapy in three fractions had 2-3 cylindrical gold markers implanted in the liver prior to treatment. At each fraction, the projection images of a pre-treatment CBCT scan were used for automatic generation of a 3D marker model that consisted of the size, orientation, and estimated 3D trajectory of each marker during the CBCT scan. The 3D marker model was used for real-time template based segmentation in subsequent x-ray images by projecting each marker's 3D shape and likely 3D motion range onto the imager plane. The segmentation was performed in intra-treatment kV images (526 marker traces, 92 097 marker projections) and MV images (88 marker traces, 22 382 marker projections), and in post-treatment CBCT projections (42 CBCT scans, 71 381 marker projections). 227 kV marker traces with low mean contrast-to-noise ratio were excluded as markers were not visible due to MV scatter. Online segmentation times measured for a limited dataset were used for estimating real-time segmentation times for all images. The percentage of detected markers was 94.8% (kV), 96.1% (MV), and 98.6% (CBCT). For the detected markers, the real-time segmentation was erroneous in 0.2-0.31% of the cases. The mean segmentation time per marker was 5.6 ms [2.1-12 ms] (kV), 5.5 ms [1.6-13 ms] (MV), and 6.5 ms [1.8-15 ms] (CBCT). Fast and reliable real-time segmentation of multiple liver tumor markers in intra-treatment kV and MV images and in CBCT projections was demonstrated for a large dataset.

  15. Patterns of disturbance at multiple scales in real and simulated landscapes

    Treesearch

    Giovanni Zurlini; Kurt H. Riitters; Nicola Zaccarelli; Irene Petrosoillo

    2007-01-01

    We describe a framework to characterize and interpret the spatial patterns of disturbances at multiple scales in socio-ecological systems. Domains of scale are defined in pattern metric space and mapped in geographic space, which can help to understand how anthropogenic disturbances might impact biodiversity through habitat modification. The approach identifies typical...

  16. Use of external cavity quantum cascade laser compliance voltage in real-time trace gas sensing of multiple chemicals

    NASA Astrophysics Data System (ADS)

    Phillips, Mark C.; Taubman, Matthew S.; Kriesel, Jason

    2015-01-01

    We describe a prototype trace gas sensor designed for real-time detection of multiple chemicals. The sensor uses an external cavity quantum cascade laser (ECQCL) swept over its tuning range of 940-1075 cm-1 (9.30-10.7 μm) at a 10 Hz repetition rate. The sensor was designed for operation in multiple modes, including gas sensing within a multi-pass Heriott cell and intracavity absorption sensing using the ECQCL compliance voltage. In addition, the ECQCL compliance voltage was used to reduce effects of long-term drifts in the ECQCL output power. The sensor was characterized for noise, drift, and detection of chemicals including ammonia, methanol, ethanol, isopropanol, Freon- 134a, Freon-152a, and diisopropyl methylphosphonate (DIMP). We also present use of the sensor for mobile detection of ammonia downwind of cattle facilities, in which concentrations were recorded at 1-s intervals.

  17. A noninvasive, direct real-time PCR method for sex determination in multiple avian species.

    PubMed

    Brubaker, Jessica L; Karouna-Renier, Natalie K; Chen, Yu; Jenko, Kathryn; Sprague, Daniel T; Henry, Paula F P

    2011-03-01

    Polymerase chain reaction (PCR)-based methods to determine the sex of birds are well established and have seen few modifications since they were first introduced in the 1990s. Although these methods allowed for sex determination in species that were previously difficult to analyse, they were not conducive to high-throughput analysis because of the laboriousness of DNA extraction and gel electrophoresis. We developed a high-throughput real-time PCR-based method for analysis of sex in birds, which uses noninvasive sample collection and avoids DNA extraction and gel electrophoresis.

  18. A noninvasive, direct real-time PCR method for sex determination in multiple avian species

    USGS Publications Warehouse

    Brubaker, Jessica L.; Karouna-Renier, Natalie K.; Chen, Yu; Jenko, Kathryn; Sprague, Daniel T.; Henry, Paula F.P.

    2011-01-01

    Polymerase chain reaction (PCR)-based methods to determine the sex of birds are well established and have seen few modifications since they were first introduced in the 1990s. Although these methods allowed for sex determination in species that were previously difficult to analyse, they were not conducive to high-throughput analysis because of the laboriousness of DNA extraction and gel electrophoresis. We developed a high-throughput real-time PCR-based method for analysis of sex in birds, which uses noninvasive sample collection and avoids DNA extraction and gel electrophoresis.

  19. Identification of Burkholderia pseudomallei and Related Bacteria by Multiple-Locus Sequence Typing-Derived PCR and Real-Time PCR▿

    PubMed Central

    Wattiau, Pierre; Van Hessche, Mieke; Neubauer, Heinrich; Zachariah, Reena; Wernery, Ulrich; Imberechts, Hein

    2007-01-01

    Close relatedness and genomic plasticity characterizing the high-threat pathogens Burkholderia pseudomallei and Burkholderia mallei render the molecular diagnosis of these species hard to guarantee with a maximal confidence level. This article describes fast molecular assays derived from compiled sequences of housekeeping genes determined in more than 1,000 strains. The assays proved to be robust and appropriate for general detection as well as species identification purposes. PMID:17251403

  20. Spectroscopic Axonal Damage of the Right Locus Coeruleus Relates to Selective Attention Impairment in Early Stage Relapsing-Remitting Multiple Sclerosis

    ERIC Educational Resources Information Center

    Gadea, Marien; Martinez-Bisbal, M. Carmen; Marti-Bonmati, Luis; Espert, Raul; Casanova, Bonaventura; Coret, Francisco; Celda, Bernardo

    2004-01-01

    Lower levels of N-acetylaspartate (NAA), a marker of axonal damage, have been found in the normal-appearing white matter (NAWM) of relapsing-remitting multiple sclerosis (RRMS) patients with low physical disability. However, its relation to the clinical status of these patients remains unclear. We explored the association between NAA levels…

  1. Spectroscopic Axonal Damage of the Right Locus Coeruleus Relates to Selective Attention Impairment in Early Stage Relapsing-Remitting Multiple Sclerosis

    ERIC Educational Resources Information Center

    Gadea, Marien; Martinez-Bisbal, M. Carmen; Marti-Bonmati, Luis; Espert, Raul; Casanova, Bonaventura; Coret, Francisco; Celda, Bernardo

    2004-01-01

    Lower levels of N-acetylaspartate (NAA), a marker of axonal damage, have been found in the normal-appearing white matter (NAWM) of relapsing-remitting multiple sclerosis (RRMS) patients with low physical disability. However, its relation to the clinical status of these patients remains unclear. We explored the association between NAA levels…

  2. Incipient multiple fault diagnosis in real time with applications to large-scale systems

    SciTech Connect

    Chung, H.Y.; Bien, Z.; Park, J.H.; Seon, P.H. . Dept. of Electrical Engineering)

    1994-08-01

    By using a modified signed directed graph (SDG) together with the distributed artificial neutral networks and a knowledge-based system, a method of incipient multi-fault diagnosis is presented for large-scale physical systems with complex pipes and instrumentations such as valves, actuators, sensors, and controllers. The proposed method is designed so as to (1) make a real-time incipient fault diagnosis possible for large-scale systems, (2) perform the fault diagnosis not only in the steady-state case but also in the transient case as well by using a concept of fault propagation time, which is newly adopted in the SDG model, (3) provide with highly reliable diagnosis results and explanation capability of faults diagnosed as in an expert system, and (4) diagnose the pipe damage such as leaking, break, or throttling. This method is applied for diagnosis of a pressurizer in the Kori Nuclear Power Plant (NPP) unit 2 in Korea under a transient condition, and its result is reported to show satisfactory performance of the method for the incipient multi-fault diagnosis of such a large-scale system in a real-time manner.

  3. Stone Soup Projects: Using real-time resources and creative partnering to meet multiple needs

    NASA Astrophysics Data System (ADS)

    McLean, S.; Searle, R.; Zala, K.

    2010-12-01

    Ocean Networks Canada oversees the VENUS and NEPTUNE Canada undersea cabled observatories. Its Centre for Enterprise and Engagement communicates the scientific discoveries and technological innovations happening at the two systems. Not surprisingly, funders in ocean science are interested in seeing evidence of increased recruitment of Highly Qualified Personnel into marine science and industry. This demand creates a series of opportunities for inspiring students, ranging from graduate school down to middle school, to pursue studies in chemistry, biology, physics, geology, engineering, and beyond. As the Engagement section is a small operation, we partner with others to produce educational assets incorporating real-time data from VENUS and NEPTUNE Canada observatories that enable frontline educators to create exciting ocean science experiences for students and the public. In one project, the lab component of an entire undergraduate course lets students conduct their own investigations into marine oxygen levels by using VENUS data. In another, Fine Arts graduate and undergraduate students are using high-tech tools to create a series of webisodes that map the principles of Ocean Literacy onto the science themes of VENUS and NEPTUNE Canada. In a third project, we hosted a website for a collaborative expedition to small coastal towns that focused on the marine science happening in the Salish Sea, British Columbia. Our projects and challenges for engaging students and the public with ocean science using real-time and other data offer strategies for outreach and education sections of similar organizations.

  4. Real-Time, Multiple, Pan/Tilt/Zoom, Computer Vision Tracking, and 3D Position Estimating System for Unmanned Aerial System Metrology

    DTIC Science & Technology

    2013-10-18

    2012. 136. Zhang, J., Y. Wang, J. Chen, and K. Xue. “A framework of surveillance system using a PTZ camera,” Computer Science and Information Technology...Real-Time, Multiple, Pan/Tilt/Zoom, Computer Vision Tracking, and 3D Position Estimating System for Small Unmanned Aircraft System Metrology...United States Government. AFIT-ENY-DS-13-D- Real-Time, Multiple, Pan/Tilt/Zoom, Computer Vision Tracking, and 3D Position Estimating System for Small

  5. Performance of a Frequency-Hopped Real-Time Remote Control System in a Multiple Access Scenario

    NASA Astrophysics Data System (ADS)

    Cervantes, Frank

    A recent trend is observed in the context of the radio-controlled aircrafts and automobiles within the hobby grade category and Unmanned Aerial Vehicles (UAV) applications moving to the well-known Industrial, Scientific and Medical (ISM) band. Based on this technological fact, the present thesis evaluates an individual user performance by featuring a multiple-user scenario where several point-to-point co-located real-time Remote Control (RC) applications operate using Frequency Hopping Spread Spectrum (FHSS) as a medium access technique in order to handle interference efficiently. Commercial-off-the-shelf wireless transceivers ready to operate in the ISM band are considered as the operational platform supporting the above-mentioned applications. The impact of channel impairments and of different critical system engineering issues, such as working with real clock oscillators and variable packet duty cycle, are considered. Based on the previous, simulation results allowed us to evaluate the range of variation for those parameters for an acceptable system performance under Multiple Access (MA) environments.

  6. Real-time generation of high-definition resolution digital holograms by using multiple graphic processing units

    NASA Astrophysics Data System (ADS)

    Song, Joongseok; Park, Jungsik; Park, Hanhoon; Park, Jong-Il

    2013-01-01

    We describe and evaluate a practical approach for implementing computer-generated-holography (CGH) using multiple graphic processing units (GPUs). The proposed method can generate high-definition (HD) resolution (1920×1080) digital holograms in real-time. In order to demonstrate the plausibility of our method, some experimental results will be given. First, we discuss the advantage of GPUs for CGH against central processing units (CPUs) by comparing the performance of both. Our results show that use of GPUs can shorten CGH computation time by 2791 times. Then, we discuss the potential of multiple GPUs for generating HD resolution digital holograms in real-time by measuring and analyzing the CGH computational time in accordance with the number of GPUs. Our result shows that the CGH computational time decreases nonlinearly, with a logarithmic-like curve, as the number of GPU increases. Therefore, we can determine the number of GPUs to maximize the efficiency. Consequently, our implementation can generate HD resolution digital holograms at a rate of more than 66 hps (holograms-per-second) using two NVIDIA GTX 590 cards.

  7. Multiple Solutions of Real-time Tsunami Forecasting Using Short-term Inundation Forecasting for Tsunamis Tool

    NASA Astrophysics Data System (ADS)

    Gica, E.

    2016-12-01

    The Short-term Inundation Forecasting for Tsunamis (SIFT) tool, developed by NOAA Center for Tsunami Research (NCTR) at the Pacific Marine Environmental Laboratory (PMEL), is used in forecast operations at the Tsunami Warning Centers in Alaska and Hawaii. The SIFT tool relies on a pre-computed tsunami propagation database, real-time DART buoy data, and an inversion algorithm to define the tsunami source. The tsunami propagation database is composed of 50×100km unit sources, simulated basin-wide for at least 24 hours. Different combinations of unit sources, DART buoys, and length of real-time DART buoy data can generate a wide range of results within the defined tsunami source. For an inexperienced SIFT user, the primary challenge is to determine which solution, among multiple solutions for a single tsunami event, would provide the best forecast in real time. This study investigates how the use of different tsunami sources affects simulated tsunamis at tide gauge locations. Using the tide gauge at Hilo, Hawaii, a total of 50 possible solutions for the 2011 Tohoku tsunami are considered. Maximum tsunami wave amplitude and root mean square error results are used to compare tide gauge data and the simulated tsunami time series. Results of this study will facilitate SIFT users' efforts to determine if the simulated tide gauge tsunami time series from a specific tsunami source solution would be within the range of possible solutions. This study will serve as the basis for investigating more historical tsunami events and tide gauge locations.

  8. A real-time plane-wave decomposition algorithm for characterizing perforated liners damping at multiple mode frequencies.

    PubMed

    Zhao, Dan

    2011-03-01

    Perforated liners with a narrow frequency range are widely used as acoustic dampers to stabilize combustion systems. When the frequency of unstable modes present in the combustion system is within the effective frequency range, the liners can efficiently dissipate acoustic waves. The fraction of the incident waves being absorbed (known as power absorption coefficient) is generally used to characterize the liners damping. To estimate it, plane waves either side of the liners need to be decomposed and characterized. For this, a real-time algorithm is developed. Emphasis is being placed on its ability to online decompose plane waves at multiple mode frequencies. The performance of the algorithm is evaluated first in a numerical model with two unstable modes. It is then experimentally implemented in an acoustically driven pipe system with a lined section attached. The acoustic damping of perforated liners is continuously characterized in real-time. Comparison is then made between the results from the algorithm and those from the short-time fast Fourier transform (FFT)-based techniques, which are typically used in industry. It was found that the real-time algorithm allows faster tracking of the liners damping, even when the forcing frequency was suddenly changed.

  9. Method for Visually Integrating Multiple Data Acquisition Technologies for Real Time and Retrospective Analysis

    NASA Technical Reports Server (NTRS)

    Bogart, Edward H. (Inventor); Pope, Alan T. (Inventor)

    2000-01-01

    A system for display on a single video display terminal of multiple physiological measurements is provided. A subject is monitored by a plurality of instruments which feed data to a computer programmed to receive data, calculate data products such as index of engagement and heart rate, and display the data in a graphical format simultaneously on a single video display terminal. In addition live video representing the view of the subject and the experimental setup may also be integrated into the single data display. The display may be recorded on a standard video tape recorder for retrospective analysis.

  10. Real-life walking impairment in multiple sclerosis: preliminary comparison of four methods for processing accelerometry data.

    PubMed

    Sosnoff, Jacob J; Goldman, Myla D; Motl, Robert W

    2010-07-01

    This study further validates accelerometers as a measure of walking impairment in persons with multiple sclerosis. We examined total movement counts and three novel methods of processing accelerometer data (i.e. standard deviation, approximate entropy and detrended fluctuation analysis) for quantifying real-life walking impairment in this population. A total of 70 individuals with a definite diagnosis of multiple sclerosis completed a battery of patient-rated measures of walking impairment and then wore an ActiGraph accelerometer for 7 days. The data were analyzed using multivariate analysis of variance and bivariate correlation analysis. The results indicated that total daily movement counts and standard deviation of daily movement counts differed between groups of persons with mild, moderate, and severe self-reported disability status and who were independently ambulatory or ambulatory with assistance. Those two metrics for the accelerometer data further demonstrated strong correlations with patient-rated measures of walking impairment. By comparison, there were smaller and often non-significant differences in approximate entropy and detrended fluctuation analysis metrics for the accelerometer data as a function of disability and ambulatory status, and only moderate correlations with patient-rated measures of walking impairment. The results confirm that the metric of total daily movement counts correlates with level of disability, ambulatory status, and patient reports of walking impairment in persons with multiple sclerosis. We further demonstrate that variability, indexed by the standard deviation of daily movement counts, correlates with multiple sclerosis-related disability, ambulatory status, and self-reported walking impairment. Such results provide preliminary evidence that variability in accelerometer counts is not simply noise and may provide important information about multiple sclerosis-related walking impairment.

  11. Image simulation using LOCUS

    SciTech Connect

    Strachan, J.D.; Roberts, J.A.

    1989-09-01

    The LOCUS data base program has been used to simulate images and to solve simple equations. This has been accomplished by making each record (which normally would represent a data entry)represent sequenced or random number pairs.

  12. Real-time video breakup detection for multiple HD video streams on a single GPU

    NASA Astrophysics Data System (ADS)

    Rosner, Jakub; Fassold, Hannes; Winter, Martin; Schallauer, Peter

    2012-06-01

    An important task in film and video preservation is the quality assessment of the content to be archived or reused out of the archive. This task, if done manually, is a straining and time consuming process, so it is highly recommended to automate this process as far as possible. In this paper, we show how to port a previously proposed algorithm for detection of severe analog and digital video distortions (termed "video breakup"), efficiently to NVIDIA GPUs of the Fermi Architecture with CUDA. By parallizing of the algorithm massively in order to take usage of the hundreds of cores on a typical GPU and careful usage of GPU features like atomic functions, texture and shared memory, we achive a speedup of roughly 10-15 when comparing the GPU implementation with an highly optimized, multi-threaded CPU implementation. Thus our GPU algorithm is able to analyze nine Full HD (1920 × 1080) video streams or 40 standard definition (720 × 576) video streams in real-time on a single inexpensive Nvidia Geforce GTX 480 GPU. Additionally, we present the AV-Inspector application for video quality analysis where the video breakup algorithm has been integrated.

  13. Real-Time Radar-Based Tracking and State Estimation of Multiple Non-Conformant Aircraft

    NASA Technical Reports Server (NTRS)

    Cook, Brandon; Arnett, Timothy; Macmann, Owen; Kumar, Manish

    2017-01-01

    In this study, a novel solution for automated tracking of multiple unknown aircraft is proposed. Many current methods use transponders to self-report state information and augment track identification. While conformant aircraft typically report transponder information to alert surrounding aircraft of its state, vehicles may exist in the airspace that are non-compliant and need to be accurately tracked using alternative methods. In this study, a multi-agent tracking solution is presented that solely utilizes primary surveillance radar data to estimate aircraft state information. Main research challenges include state estimation, track management, data association, and establishing persistent track validity. In an effort to realize these challenges, techniques such as Maximum a Posteriori estimation, Kalman filtering, degree of membership data association, and Nearest Neighbor Spanning Tree clustering are implemented for this application.

  14. Double Relapsed and/or Refractory Multiple Myeloma: Clinical Outcomes and Real World Healthcare Costs

    PubMed Central

    Gooding, Sarah; Lau, I-Jun; Sheikh, Mimi; Roberts, Pamela; Wong, Julia; Dickens, Emmy; Bullement, Ash; Elvidge, Jamie; Lee, Dawn; Ramasamy, Karthik

    2015-01-01

    Double relapsed and/or refractory multiple myeloma (DRMM), MM that is relapsed and/or refractory to bortezomib and lenalidomide, carries a poor prognosis. The healthcare costs of DRMM have not previously been reported. We analyzed detailed medical resource utilization (MRU) costs, drug costs and outcomes for 39 UK patients receiving standard DRMM therapy. Median OS in this cohort was 5.6 months. The mean cost of DRMM treatment plus MRU until death was £23,472 [range: £1,411–£90,262], split between drug costs £11,191 and other resource use costs £12,281. The cost per assumed quality-adjusted life year (QALY) during DRMM was £66,983. These data provide a standard of care comparison when evaluating the cost-effectiveness of new drugs in DRMM. PMID:26367874

  15. Combining Multiple Rupture Models in Real-Time for Earthquake Early Warning

    NASA Astrophysics Data System (ADS)

    Minson, S. E.; Wu, S.; Beck, J. L.; Heaton, T. H.

    2015-12-01

    The ShakeAlert earthquake early warning system for the west coast of the United States is designed to combine information from multiple independent earthquake analysis algorithms in order to provide the public with robust predictions of shaking intensity at each user's location before they are affected by strong shaking. The current contributing analyses come from algorithms that determine the origin time, epicenter, and magnitude of an earthquake (On-site, ElarmS, and Virtual Seismologist). A second generation of algorithms will provide seismic line source information (FinDer), as well as geodetically-constrained slip models (BEFORES, GPSlip, G-larmS, G-FAST). These new algorithms will provide more information about the spatial extent of the earthquake rupture and thus improve the quality of the resulting shaking forecasts.Each of the contributing algorithms exploits different features of the observed seismic and geodetic data, and thus each algorithm may perform differently for different data availability and earthquake source characteristics. Thus the ShakeAlert system requires a central mediator, called the Central Decision Module (CDM). The CDM acts to combine disparate earthquake source information into one unified shaking forecast. Here we will present a new design for the CDM that uses a Bayesian framework to combine earthquake reports from multiple analysis algorithms and compares them to observed shaking information in order to both assess the relative plausibility of each earthquake report and to create an improved unified shaking forecast complete with appropriate uncertainties. We will describe how these probabilistic shaking forecasts can be used to provide each user with a personalized decision-making tool that can help decide whether or not to take a protective action (such as opening fire house doors or stopping trains) based on that user's distance to the earthquake, vulnerability to shaking, false alarm tolerance, and time required to act.

  16. Relationships between locus of control and paranormal beliefs.

    PubMed

    Newby, Robert W; Davis, Jessica Boyette

    2004-06-01

    The present study investigated the associations between scores on paranormal beliefs, locus of control, and certain psychological processes such as affect and cognitions as measured by the Linguistic Inquiry and Word Count. Analysis yielded significant correlations between scores on Locus of Control and two subscales of Tobacyk's (1988) Revised Paranormal Beliefs Scale, New Age Philosophy and Traditional Paranormal Beliefs. A step-wise multiple regression analysis indicated that Locus of Control was significantly related to New Age Philosophy. Other correlations were found between Tobacyk's subscales, Locus of Control, and three processes measured by the Linguistic Inquiry and Word Count.

  17. Sequence divergence and loss-of-function phenotypes of S locus F-box brothers genes are consistent with non-self recognition by multiple pollen determinants in self-incompatibility of Japanese pear (Pyrus pyrifolia).

    PubMed

    Kakui, Hiroyuki; Kato, Masaki; Ushijima, Koichiro; Kitaguchi, Miyoko; Kato, Shu; Sassa, Hidenori

    2011-12-01

    The S-RNase-based gametophytic self-incompatibility (SI) of Rosaceae, Solanaceae, and Plantaginaceae is controlled by at least two tightly linked genes located at the complex S locus; the highly polymorphic S-RNase for pistil specificity and the F-box gene (SFB/SLF) for pollen. Self-incompatibility in Prunus (Rosaceae) is considered to represent a 'self recognition by a single factor' system, because loss-of-function of SFB is associated with self-compatibility, and allelic divergence of SFB is high and comparable to that of S-RNase. In contrast, Petunia (Solanaceae) exhibits 'non-self recognition by multiple factors'. However, the distribution of 'self recognition' and 'non-self recognition' SI systems in different taxa is not clear. In addition, in 'non-self recognition' systems, a loss-of-function phenotype of pollen S is unknown. Here we analyze the divergence of SFBB genes, the multiple pollen S candidates, of a rosaceous plant Japanese pear (Pyrus pyrifolia) and show that intrahaplotypic divergence is high and comparable to the allelic diversity of S-RNase while interhaplotypic divergence is very low. Next, we analyzed loss-of-function of the SFBB1 type gene. Genetic analysis showed that pollen with the mutant haplotype S(4sm) lacking SFBB1-S(4) is rejected by pistils with an otherwise compatible S(1) while it is accepted by other non-self pistils. We found that the S(5) haplotype encodes a truncated SFBB1 protein, even though S(5) pollen is accepted normally by pistils with S(1) and other non-self haplotypes. These findings suggest that Japanese pear has a 'non-self recognition by multiple factors' SI system, although it is a species of Rosaceae to which Prunus also belongs.

  18. Near-real Time Monitoring of Global Biomass Burning Emissions from Multiple Geostationary Instruments

    NASA Astrophysics Data System (ADS)

    Zhang, X.; Kondragunta, S.; Ram, J.; Schmidt, C. C.

    2010-12-01

    Biomass burning from wildland fires releases a significant amount of trace gases and aerosols into the atmosphere. These emissions and their long-range transports significantly affect air quality, climate change, and carbon budget. We present the use of fire radiative power (FRP) to derive biomass burning emissions in near-real time. The instantaneous FRP at an interval of 15-30 minutes is retrieved using WF_ABBA_V65 (Wildfire Automated Biomass Burning Algorithm) from a network of geostationary satellites. This network consists of two Geostationary Operation Environmental Satellites (GOES) which are operated by the National Oceanic and Atmospheric Administration(NOAA), the Meteosat Second Generation satellites (MET-09) operated by the European Organization for the Exploitation of Meteorological Satellites (EUMETSAT), and the Multi-functional Transport Satellite (MTSAT-1R) operated by the Japan Meteorological Agency (JMA). The spatial consistence of FRP values retrieved from different geostationary instruments are investigated and compared with MODIS FRP retrievals. Further, the consistency of temporal pattern in instantaneous FRP is simulated because the continuous observations from satellites are impeded by sensor saturation, cloud cover, and background surface effects. The gaps in observations are filled using simulated values which are calculated by combing the observed instantaneous FRP values within a day and a set of representative diurnal patterns of half-hourly FRPs for various ecosystems. Furthermore, the diurnal variation in FRP is applied to quantify emissions of PM2.5 (particulate mass for particles with diameter < 2.5 µm), CH4, CO2, N2O, NH3, NOX, and TNMHC. This algorithm has been applied to produce global biomass emissions with one-day latency since January 2010. Results from the analysis of global patterns in hourly biomass burning emissions for 2009-2010 will be presented.

  19. Simulating on-line dynamic voltages of multiple trains under real operating conditions for AC railways

    SciTech Connect

    Hsi, P.H.; Chen, S.L.; Li, R.J.

    1999-05-01

    The analysis of Railway Power Supplies (RPS) presents a unique type of load flow problem which is characterized by its constant moving loads, dynamically changing load types (constant current/constant power), and its specialized network structure. When multiple trains and the capacitors for power factor correction are also involved, the analysis of this special kind of power system can be very complicated and time consuming which will prevent on-line state analysis from becoming possible. This paper presents a novel and extremely efficient algorithm to solve this special kind of power flow problem with high precision. By first decoupling the Autotransformer (AT) current into 2 equal phasor components and then applying an iteration-based circuit-analysis approach, the RPS power flow problem can be solved in an accurate but extremely efficient manner. An on-line Railway Power-Supply State Analyzer (RPSA) based on this approach is presented in this paper while the extension of using this approach to perform power factor corrector (PFC) simulation is also presented.

  20. Real-time optical multiple object recognition and tracking system and method

    NASA Technical Reports Server (NTRS)

    Chao, Tien-Hsin (Inventor); Liu, Hua-Kuang (Inventor)

    1990-01-01

    System for optically recognizing and tracking a plurality of objects within a field of vision. Laser (46) produces a coherent beam (48). Beam splitter (24) splits the beam into object (26) and reference (28) beams. Beam expanders (50) and collimators (52) transform the beams (26, 28) into coherent collimated light beams (26', 28'). A two-dimensional SLM (54), disposed in the object beam (26'), modulates the object beam with optical information as a function of signals from a first camera (16) which develops X and Y signals reflecting the contents of its field of vision. A hololens (38), positioned in the object beam (26') subsequent to the modulator (54), focuses the object beam at a plurality of focal points (42). A planar transparency-forming film (32), disposed with the focal points on an exposable surface, forms a multiple position interference filter (62) upon exposure of the surface and development processing of the film (32). A reflector (53) directing the reference beam (28') onto the film (32), exposes the surface, with images focused by the hololens (38), to form interference patterns on the surface. There is apparatus (16', 64) for sensing and indicating light passage through respective ones of the positions of the filter (62), whereby recognition of objects corresponding to respective ones of the positions of the filter (62) is affected. For tracking, apparatus (64) focuses light passing through the filter (62) onto a matrix of CCD's in a second camera (16') to form a two-dimensional display of the recognized objects.

  1. Real-Time Localization of Moving Dipole Sources for Tracking Multiple Free-Swimming Weakly Electric Fish.

    PubMed

    Jun, James Jaeyoon; Longtin, André; Maler, Leonard

    2013-01-01

    In order to survive, animals must quickly and accurately locate prey, predators, and conspecifics using the signals they generate. The signal source location can be estimated using multiple detectors and the inverse relationship between the received signal intensity (RSI) and the distance, but difficulty of the source localization increases if there is an additional dependence on the orientation of a signal source. In such cases, the signal source could be approximated as an ideal dipole for simplification. Based on a theoretical model, the RSI can be directly predicted from a known dipole location; but estimating a dipole location from RSIs has no direct analytical solution. Here, we propose an efficient solution to the dipole localization problem by using a lookup table (LUT) to store RSIs predicted by our theoretically derived dipole model at many possible dipole positions and orientations. For a given set of RSIs measured at multiple detectors, our algorithm found a dipole location having the closest matching normalized RSIs from the LUT, and further refined the location at higher resolution. Studying the natural behavior of weakly electric fish (WEF) requires efficiently computing their location and the temporal pattern of their electric signals over extended periods. Our dipole localization method was successfully applied to track single or multiple freely swimming WEF in shallow water in real-time, as each fish could be closely approximated by an ideal current dipole in two dimensions. Our optimized search algorithm found the animal's positions, orientations, and tail-bending angles quickly and accurately under various conditions, without the need for calibrating individual-specific parameters. Our dipole localization method is directly applicable to studying the role of active sensing during spatial navigation, or social interactions between multiple WEF. Furthermore, our method could be extended to other application areas involving dipole source

  2. Real Time Multiplicative Memory Amplification Mediated by Whole-Cell Scaling of Synaptic Response in Key Neurons

    PubMed Central

    Reuveni, Iris; Ghosh, Sourav; Barkai, Edi

    2017-01-01

    Intense spiking response of a memory-pattern is believed to play a crucial role both in normal learning and pathology, where it can create biased behavior. We recently proposed a novel model for memory amplification where the simultaneous two-fold increase of all excitatory (AMPAR-mediated) and inhibitory (GABAAR-mediated) synapses in a sub-group of cells that constitutes a memory-pattern selectively amplifies this memory. Here we confirm the cellular basis of this model by validating its major predictions in four sets of experiments, and demonstrate its induction via a whole-cell transduction mechanism. Subsequently, using theory and simulations, we show that this whole-cell two-fold increase of all inhibitory and excitatory synapses functions as an instantaneous and multiplicative amplifier of the neurons’ spiking. The amplification mechanism acts through multiplication of the net synaptic current, where it scales both the average and the standard deviation of the current. In the excitation-inhibition balance regime, this scaling creates a linear multiplicative amplifier of the cell’s spiking response. Moreover, the direct scaling of the synaptic input enables the amplification of the spiking response to be synchronized with rapid changes in synaptic input, and to be independent of previous spiking activity. These traits enable instantaneous real-time amplification during brief elevations of excitatory synaptic input. Furthermore, the multiplicative nature of the amplifier ensures that the net effect of the amplification is large mainly when the synaptic input is mostly excitatory. When induced on all cells that comprise a memory-pattern, these whole-cell modifications enable a substantial instantaneous amplification of the memory-pattern when the memory is activated. The amplification mechanism is induced by CaMKII dependent phosphorylation that doubles the conductance of all GABAA and AMPA receptors in a subset of neurons. This whole-cell transduction

  3. Real-Time Localization of Moving Dipole Sources for Tracking Multiple Free-Swimming Weakly Electric Fish

    PubMed Central

    Jun, James Jaeyoon; Longtin, André; Maler, Leonard

    2013-01-01

    In order to survive, animals must quickly and accurately locate prey, predators, and conspecifics using the signals they generate. The signal source location can be estimated using multiple detectors and the inverse relationship between the received signal intensity (RSI) and the distance, but difficulty of the source localization increases if there is an additional dependence on the orientation of a signal source. In such cases, the signal source could be approximated as an ideal dipole for simplification. Based on a theoretical model, the RSI can be directly predicted from a known dipole location; but estimating a dipole location from RSIs has no direct analytical solution. Here, we propose an efficient solution to the dipole localization problem by using a lookup table (LUT) to store RSIs predicted by our theoretically derived dipole model at many possible dipole positions and orientations. For a given set of RSIs measured at multiple detectors, our algorithm found a dipole location having the closest matching normalized RSIs from the LUT, and further refined the location at higher resolution. Studying the natural behavior of weakly electric fish (WEF) requires efficiently computing their location and the temporal pattern of their electric signals over extended periods. Our dipole localization method was successfully applied to track single or multiple freely swimming WEF in shallow water in real-time, as each fish could be closely approximated by an ideal current dipole in two dimensions. Our optimized search algorithm found the animal’s positions, orientations, and tail-bending angles quickly and accurately under various conditions, without the need for calibrating individual-specific parameters. Our dipole localization method is directly applicable to studying the role of active sensing during spatial navigation, or social interactions between multiple WEF. Furthermore, our method could be extended to other application areas involving dipole source

  4. Microfluidic platform for real-time signaling analysis of multiple single T cells in parallel.

    PubMed

    Faley, Shannon; Seale, Kevin; Hughey, Jacob; Schaffer, David K; VanCompernolle, Scott; McKinney, Brett; Baudenbacher, Franz; Unutmaz, Derya; Wikswo, John P

    2008-10-01

    Deciphering the signaling pathways that govern stimulation of naïve CD4+ T helper cells by antigen-presenting cells via formation of the immunological synapse is key to a fundamental understanding of the progression of successful adaptive immune response. The study of T cell-APC interactions in vitro is challenging, however, due to the difficulty of tracking individual, non-adherent cell pairs over time. Studying single cell dynamics over time reveals rare, but critical, signaling events that might be averaged out in bulk experiments, but these less common events are undoubtedly important for an integrated understanding of a cellular response to its microenvironment. We describe a novel application of microfluidic technology that overcomes many limitations of conventional cell culture and enables the study of hundreds of passively sequestered hematopoietic cells for extended periods of time. This microfluidic cell trap device consists of 440 18 micromx18 micromx10 microm PDMS, bucket-like structures opposing the direction of flow which serve as corrals for cells as they pass through the cell trap region. Cell viability analysis revealed that more than 70% of naïve CD4+ T cells (TN), held in place using only hydrodynamic forces, subsequently remain viable for 24 hours. Cytosolic calcium transients were successfully induced in TN cells following introduction of chemical, antibody, or cellular forms of stimulation. Statistical analysis of TN cells from a single stimulation experiment reveals the power of this platform to distinguish different calcium response patterns, an ability that might be utilized to characterize T cell signaling states in a given population. Finally, we investigate in real time contact- and non-contact-based interactions between primary T cells and dendritic cells, two main participants in the formation of the immunological synapse. Utilizing the microfluidic traps in a daisy-chain configuration allowed us to observe calcium transients in TN

  5. Real time, high accuracy, relative state estimation for multiple vehicle systems

    NASA Astrophysics Data System (ADS)

    Williamson, Walton Ross

    2000-10-01

    This dissertation presents the development, implementation, and test results from a new instrumentation package for relative navigation between moving vehicles. The instrumentation package on each vehicle is composed of a GPS (Global Positioning System) receiver, an IMU (Inertial Measurement Unit), a wireless communication system, and a modular computer system. The GPS places all vehicles into the same inertial reference frame and provides a common clock allowing synchronization among all instrument packages. The IMU tracks the high frequency motion of the vehicle alleviating the need for a fixed base station. The wireless communication system communicates GPS code and carrier phase measurements and computed state estimates from each vehicle at a rate fast enough to capture the dynamic changes in the vehicles. This data representing both GPS and IMU measurements from each vehicle is fused together on each vehicle to produce position, velocity and attitude estimates relative to the other vehicles. This capability to estimate relative motion without a base station appears unique. Furthermore, the application of fusion algorithms to address this new estimation problem is unique. The use of carrier phase provides very accurate relative measurements. In constructing carrier phase measurement, the integer number of wave lengths between vehicles must be resolved. Although there exist integer resolution schemes, these algorithms are ad hoe. The scheme presented here is based on generating the conditional probability of the hypothesis of each integer given the measurement sequence. This nonlinear filter is an elegant and novel contribution. The entire system is tested in real time in an experiment intended to validate the measurement accuracy. The system built using the algorithms designed in this dissertation is capable of estimating relative range to less than 5 cm. RMS, relative roll and pitch to less than 0.2 degrees RMS, and relative yaw to less than 0.7 degrees RMS

  6. Determining the bistability parameter ranges of artificially induced lac operon using the root locus method.

    PubMed

    Avcu, N; Alyürük, H; Demir, G K; Pekergin, F; Cavas, L; Güzeliş, C

    2015-06-01

    This paper employs the root locus method to conduct a detailed investigation of the parameter regions that ensure bistability in a well-studied gene regulatory network namely, lac operon of Escherichia coli (E. coli). In contrast to previous works, the parametric bistability conditions observed in this study constitute a complete set of necessary and sufficient conditions. These conditions were derived by applying the root locus method to the polynomial equilibrium equation of the lac operon model to determine the parameter values yielding the multiple real roots necessary for bistability. The lac operon model used was defined as an ordinary differential equation system in a state equation form with a rational right hand side, and it was compatible with the Hill and Michaelis-Menten approaches of enzyme kinetics used to describe biochemical reactions that govern lactose metabolism. The developed root locus method can be used to study the steady-state behavior of any type of convergent biological system model based on mass action kinetics. This method provides a solution to the problem of analyzing gene regulatory networks under parameter uncertainties because the root locus method considers the model parameters as variable, rather than fixed. The obtained bistability ranges for the lac operon model parameters have the potential to elucidate the appearance of bistability for E. coli cells in in vivo experiments, and they could also be used to design robust hysteretic switches in synthetic biology.

  7. Real-world outcome and healthcare costs of relapsed or refractory multiple myeloma: A retrospective analysis from the Chinese experience.

    PubMed

    Zhou, Xin; Xia, Jun; Mao, Jingjue; Cheng, Feng; Qian, Xifeng; Guo, Hongfeng

    2016-06-01

    Our aim was to retrospectively investigate the real-world outcome and healthcare costs associated with the treatment of patients with relapsed or refractory multiple myeloma (RRMM) in a Chinese single center. A retrospective study was conducted for 93 patients between January 2008 and December 2013 in a Chinese hematology department. Total monthly costs attributable to each cost component were described across all regimens and for bortezomib-based treatment regimens. Mean total cost per patient-month ($1139.85) varied depending on the sequence of therapy (range: mean $51.63-$6600.96). Drugs and hospital visit were the most and the least consumed resource (65.48% and 2.87%, respectively). Mean total monthly costs were $2071.96 (range: $679.73-$6600.96) and $551.14 (range: $51.63-$1698.59) for patients receiving bortezomib and patients not receiving bortezomib, respectively. Differences between the two groups were significant for drugs; drugs costs were higher for patients treated with bortezomib. Kaplan-Meier curves showed a longer overall survival (mean [median] 31.43 [25] vs. 21.93 [18] months) for patients treated with bortezomib. Real-world costs during treatment of RRMM varied greatly. Total costs during bortezomib-based regimens are significantly higher compared with non-bortezomib regimens. Further multi-center studies are needed to assess the cost-effectiveness of bortezomib for the treatment of RRMM in China.

  8. A kind of multilevel authentication system for multiple-image by modulated real part synthesis and iterative phase multiplexing

    NASA Astrophysics Data System (ADS)

    Pan, Xuemei; Meng, Xiangfeng; Wang, Yurong; Yang, Xiulun; Peng, Xiang; He, Wenqi; Dong, Guoyan; Chen, Hongyi

    2016-04-01

    A kind of multilevel authentication system for multiple-image based on modulated real part synthesis and iterative phase multiplexing in the Fresnel domain is proposed. In the design process of the low-level authentication system, a series of normalized real part information are iteratively generated by phase retrieval algorithm in the Fresnel domain, and the final private keys for different individual low-level certification images can be fabricated by binary amplitude modulation, superposition, synthesis, and sampling; while in the design process of the high-level authentication system, the final private keys for different individual high-level certification images can be generated by iterative phase information encoding and multiplexing. During the high-level authentication, the meaningful certification image can be reconstructed by the inverse Fresnel transform with the corresponding correct private keys, meanwhile, the correlation coefficient is utilized as judgment criterion; while in the low-level authentication, with the help of correct keys, the noise-like image with meaningless information can be recovered, but a remarkable peak output in the nonlinear correlation coefficient can be generated, which is adopted as the criterion to judge whether the low-level authentication is successful or not. Theoretical analysis and numerical simulations both verify the feasibility of the proposed method.

  9. Natalizumab Treatment Reduces Fatigue in Multiple Sclerosis. Results from the TYNERGY Trial; A Study in the Real Life Setting

    PubMed Central

    Svenningsson, Anders; Falk, Eva; Celius, Elisabeth G.; Fuchs, Siegrid; Schreiber, Karen; Berkö, Sara; Sun, Jennifer; Penner, Iris-Katharina; for the TYNERGY trial investigators

    2013-01-01

    Fatigue is a significant symptom in multiple sclerosis (MS) patients. First-generation disease modifying therapies (DMTs) are at best moderately effective to improve fatigue. Observations from small cohorts have indicated that natalizumab, an antibody targeting VLA-4, may reduce MS-related fatigue. The TYNERGY study aimed to further evaluate the effects of natalizumab treatment on MS-related fatigue. In this one-armed clinical trial including 195 MS patients, natalizumab was prescribed in a real-life setting, and a validated questionnaire, the Fatigue Scale for Motor and Cognitive functions (FSMC), was used both before and after 12 months of treatment to evaluate a possible change in the fatigue experienced by the patients. In the treated cohort all measured variables, that is, fatigue score, quality of life, sleepiness, depression, cognition, and disability progression were improved from baseline (all p values<0.0001). Walking speed as measured by the six-minute walk-test also increased at month 12 (p = 0.0016). All patients were aware of the nature of the treatment agent, and of the study outcomes. Conclusion Natalizumab, as used in a real-life setting, might improve MS-related fatigue based on the results from this one-armed un-controlled stud. Also other parameters related to patients' quality of life seemed to improve with natalizumab treatment. Trial Registration ClinicalTrials.gov NCT00884481 PMID:23555589

  10. Staphylococcus aureus from 152 cases of bovine, ovine and caprine mastitis investigated by Multiple-locus variable number of tandem repeat analysis (MLVA).

    PubMed

    Bergonier, Dominique; Sobral, Daniel; Feßler, Andrea T; Jacquet, Eric; Gilbert, Florence B; Schwarz, Stefan; Treilles, Michaël; Bouloc, Philippe; Pourcel, Christine; Vergnaud, Gilles

    2014-10-02

    Staphylococcus aureus is one of the main etiological agents of mastitis in ruminants. In the present retrospective study, we evaluated the potential interest of a previously described automated multiple loci Variable Number of Tandem Repeats (VNTR) Assay (MLVA) comprising 16 loci as a first line tool to investigate the population structure of S. aureus from mastitis. We determined the genetic diversity of S. aureus strains from cases of clinical and subclinical mastitis in dairy cattle (n = 118, of which 16 were methicillin-resistant), sheep (n = 18) and goats (n = 16). The 152 strains could be subdivided into 115 MLVA genotypes (including 14 genotypes for the ovine strains and 15 genotypes for the caprine strains). This corresponds to a discriminatory index (D) value of 0.9936. Comparison with published MLVA data obtained using the same protocol applied to strains from diverse human and animal origins revealed a low number (8.5%) of human-related MLVA genotypes among the present collection. Eighteen percent of the S. aureus mastitis collection belonged to clonal complexes apparently not associated with other pathological conditions. Some of them displayed a relatively low level of diversity in agreement with a restricted ecological niche. These findings provide arguments suggesting that specific S. aureus lineages particularly adapted to ruminant mammary glands have emerged and that MLVA is a convenient tool to provide a broad overview of the population, owing to the availability via internet of databases compiling published MLVA genotypes.

  11. Multiple-locus variable number of tandem repeats analysis of Salmonella enterica serotype paratyphi A from Yuxi and comparison with isolates from the Chinese Medical Culture Collection Center.

    PubMed

    Yao, Yingbo; Cui, Xiaoyan; Chen, Qingshan; Huang, Xinrong; Elmore, Bradley; Pan, Qing; Wang, Shukun; Liu, Jie

    2014-07-01

    The aim of the present study was to genotype Salmonella enterica serotype paratyphi A (SPA) isolated from Yuxi, China, in a multiple-locus variable number of tandem repeats (VNTRs) analysis (MLVA) and to compare them with isolates from the Chinese Medical Culture Collection Center (CMCC). Potential VNTRs were screened from the genomes of ATCC9150 and AKU_12601 using the Tandem Repeats Finder program. Nine VNTRs were established for MLVA typing of 195 SPA isolates from Yuxi and 20 isolates from CMCC. The dendogram for MLVA profiles and minimum spanning tree (MST) were drawn using the categorical coefficient calculated by BioNumerics software. A total of 23 MLVA types were identified in 215 SPA isolates and were grouped into six distinct cluster groups A, B, C, D, E and F. A total of 195 Yuxi SPA isolates were exclusively grouped into cluster C with nine MLVA genotypes. A total of 20 CMCC isolates were grouped in clusters A B, D, E and F with the other 14 MLVA types. The MLVA with nine VNTR loci, which was exploited in the present study, represents a successful strategy for genotyping SPA. Furthermore, the 195 Yuxi isolates appear to be closely related to each other and distinct from the 20 CMCC strains.

  12. Emergence of a multidrug-resistant (ASSuTTm) strain of Salmonella enterica serovar Typhimurium DT120 in England in 2011 and the use of multiple-locus variable-number tandem-repeat analysis in supporting outbreak investigations.

    PubMed

    Paranthaman, Karthikeyan; Haroon, Sophie; Latif, Samia; Vinnyey, Natalie; de Souza, Valerie; Welfare, William; Tahir, Mamoona; Cooke, Edward; Stone, Kirsten; Lane, Chris; Peters, Tansy; Puleston, Richard

    2013-10-01

    In summer 2011, two outbreaks of a unique, multidrug-resistant strain of Salmonella enterica serovar Typhimurium phage type 120 (DT120) occurred mainly in the Midlands, England. The first outbreak occurred among guests attending a wedding in July 2011 ('Wedding outbreak'), followed by a more geographically dispersed outbreak in August and September 2011 ('Midlands outbreak'). Fifty-one cases were confirmed. Detailed epidemiological and environmental health investigations suggested that pork was the most likely source of both outbreaks. All human samples and one pork sample showed the specific multiple-locus variable-number tandem-repeat analysis (MLVA) profile 3-11-12-NA-0211, with at most two loci variations. Trace-back investigations suggested a link to a butcher's shop and a pig farm in the East Midlands. The investigations highlight the utility of molecular analysis (MLVA) in supporting epidemiological investigations of outbreaks caused by S. Typhimurium DT120. Safe handling and cooking of pork by food business operators and consumers are key interventions to prevent future outbreaks.

  13. Multiple-locus variable-number tandem repeat fingerprinting as a method for rapid and cost-effective typing of animal-associated Staphylococcus aureus strains from lineages other than sequence type 398.

    PubMed

    Kosecka-Strojek, Maja; Ilczyszyn, Weronika M; Buda, Aneta; Polakowska, Klaudia; Murzyn, Krzysztof; Panz, Tomasz; Bialecka, Anna; Kasprowicz, Andrzej; Jakubczak, Antoni; Krol, Jaroslaw; Wieliczko, Alina; Wladyka, Benedykt; Miedzobrodzki, Jacek

    2016-12-01

    In veterinary medicine, Staphylococcus aureus is associated with a range of mild to severe infections. The high density of livestock in intensive farming systems increases the risk of disease spread and hampers its control and measures of prevention, making S. aureus one of the most important animal pathogens. Multiple-locus variable-number tandem repeat fingerprinting (MLVF) has been successfully applied to the characterization of livestock-associated meticillin-resistant Staphylococcus aureus (MRSA) ST398 but not to the characterization of a wide range of other animal isolates. The objective of the current study was to examine the effectiveness of MLVF for studying S. aureus strains isolated from households, farms and exotic animals in three regions of Poland. MLVF, random amplification of polymorphic DNA (RAPD), spa typing and diagnostic microarrays were compared to determine the most suitable combination of methods for veterinary purposes. MLVF generated results consistent with host and geographic origins, reflecting population structures with a high concordance to spa typing results. MLVF has been proven to be a rapid, highly discriminatory and cost-effective method suitable for molecular typing in veterinary settings.

  14. Identification of a Novel Risk Locus for Multiple Sclerosis at 13q31.3 by a Pooled Genome-Wide Scan of 500,000 Single Nucleotide Polymorphisms

    PubMed Central

    Camiña-Tato, Montse; Morcillo, Carlos; Lopez, Cristina; Navarro, Arcadi; Rio, Jordi; Montalban, Xavier; Martin, Roland

    2008-01-01

    Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system with an important genetic component and strongest association driven by the HLA genes. We performed a pooling-based genome-wide association study of 500,000 SNPs in order to find new loci associated with the disease. After applying several criteria, 320 SNPs were selected from the microarrays and individually genotyped in a first and independent Spanish Caucasian replication cohort. The 8 most significant SNPs validated in this cohort were also genotyped in a second US Caucasian replication cohort for confirmation. The most significant association was obtained for SNP rs3129934, which neighbors the HLA-DRB/DQA loci and validates our pooling-based strategy. The second strongest association signal was found for SNP rs1327328, which resides in an unannotated region of chromosome 13 but is in linkage disequilibrium with nearby functional elements that may play important roles in disease susceptibility. This region of chromosome 13 has not been previously identified in MS linkage genome screens and represents a novel risk locus for the disease. PMID:18941528

  15. The icmF3 locus is involved in multiple adaptation- and virulence-related characteristics in Pseudomonas aeruginosa PAO1

    PubMed Central

    Lin, Jinshui; Cheng, Juanli; Chen, Keqi; Guo, Chenghao; Zhang, Weipeng; Yang, Xu; Ding, Wei; Ma, Li; Wang, Yao; Shen, Xihui

    2015-01-01

    The type VI secretion system (T6SS) is widely distributed in Gram-negative bacteria. Three separate T6SSs called H1-, H2-, and H3-T6SS have been discovered in Pseudomonas aeruginosa PAO1. Recent studies suggest that, in contrast to the H1-T6SS that targets prokaryotic cells, H2- and H3-T6SS are involved in interactions with both prokaryotic and eukaryotic cells. However, the detailed functions of T6SS components are still uncharacterized. The intracellular multiplication factor (IcmF) protein is conserved in type VI secretion systems (T6SS) of all different bacterial pathogens. Bioinformatic analysis revealed that IcmF3 in P. aeruginosa PAO1 is different from other IcmF homologs and may represent a new branch of these proteins with distinct functions. Herein, we have investigated the function of IcmF3 in this strain. We have shown that deletion of the icmF3 gene in P. aeruginosa PAO1 is associated with pleiotropic phenotypes. The icmF3 mutant has variant colony morphology and an hypergrowth phenotype in iron-limiting medium. Surprisingly, this mutant is also defective for the production of pyoverdine, as well as defects in swimming motility and virulence in a C. elegans worm model. The icmF3 mutant exhibits higher conjugation frequency than the wild type and increased biofilm formation on abiotic surfaces. Additionally, expression of two phenazine biosynthetic loci is increased in the icmF3 mutant, leading to the overproduction of pyocyanin. Finally, the mutant exhibits decreased susceptibility to aminoglycosides such as tobramycin and gentamicin. And the detected phenotypes can be restored completely or partially by trans complementation of wild type icmF3 gene. The pleiotropic effects observed upon icmF3 deletion demonstrate that icmF3 plays critical roles in both pathogenesis and environmental adaptation in P. aeruginosa PAO1. PMID:26484316

  16. The icmF3 locus is involved in multiple adaptation- and virulence-related characteristics in Pseudomonas aeruginosa PAO1.

    PubMed

    Lin, Jinshui; Cheng, Juanli; Chen, Keqi; Guo, Chenghao; Zhang, Weipeng; Yang, Xu; Ding, Wei; Ma, Li; Wang, Yao; Shen, Xihui

    2015-01-01

    The type VI secretion system (T6SS) is widely distributed in Gram-negative bacteria. Three separate T6SSs called H1-, H2-, and H3-T6SS have been discovered in Pseudomonas aeruginosa PAO1. Recent studies suggest that, in contrast to the H1-T6SS that targets prokaryotic cells, H2- and H3-T6SS are involved in interactions with both prokaryotic and eukaryotic cells. However, the detailed functions of T6SS components are still uncharacterized. The intracellular multiplication factor (IcmF) protein is conserved in type VI secretion systems (T6SS) of all different bacterial pathogens. Bioinformatic analysis revealed that IcmF3 in P. aeruginosa PAO1 is different from other IcmF homologs and may represent a new branch of these proteins with distinct functions. Herein, we have investigated the function of IcmF3 in this strain. We have shown that deletion of the icmF3 gene in P. aeruginosa PAO1 is associated with pleiotropic phenotypes. The icmF3 mutant has variant colony morphology and an hypergrowth phenotype in iron-limiting medium. Surprisingly, this mutant is also defective for the production of pyoverdine, as well as defects in swimming motility and virulence in a C. elegans worm model. The icmF3 mutant exhibits higher conjugation frequency than the wild type and increased biofilm formation on abiotic surfaces. Additionally, expression of two phenazine biosynthetic loci is increased in the icmF3 mutant, leading to the overproduction of pyocyanin. Finally, the mutant exhibits decreased susceptibility to aminoglycosides such as tobramycin and gentamicin. And the detected phenotypes can be restored completely or partially by trans complementation of wild type icmF3 gene. The pleiotropic effects observed upon icmF3 deletion demonstrate that icmF3 plays critical roles in both pathogenesis and environmental adaptation in P. aeruginosa PAO1.

  17. Multiple-locus sequence typing analysis of Bacillus cereus and Bacillus thuringiensis reveals separate clustering and a distinct population structure of psychrotrophic strains.

    PubMed

    Sorokin, Alexei; Candelon, Benjamin; Guilloux, Kévin; Galleron, Nathalie; Wackerow-Kouzova, Natalia; Ehrlich, S Dusko; Bourguet, Denis; Sanchis, Vincent

    2006-02-01

    We used multilocus sequence typing (MLST) to characterize phylogenetic relationships for a collection of Bacillus cereus group strains isolated from forest soil in the Paris area during a mild winter. This collection contains multiple strains isolated from the same soil sample and strains isolated from samples from different sites. We characterized 115 strains of this collection and 19 other strains based on the sequences of the clpC, dinB, gdpD, panC, purF, and yhfL loci. The number of alleles ranged from 36 to 53, and a total of 93 allelic profiles or sequence types were distinguished. We identified three major strain clusters-C, T, and W-based on the comparison of individual gene sequences or concatenated sequences. Some less representative clusters and subclusters were also distinguished. Analysis of the MLST data using the concept of clonal complexes led to the identification of two, five, and three such groups in clusters C, T, and W, respectively. Some of the forest isolates were closely related to independently isolated psychrotrophic strains. Systematic testing of the strains of this collection showed that almost all the strains that were able to grow at a low temperature (6 degrees C) belonged to cluster W. Most of these strains, including three independently isolated strains, belong to two clonal complexes and are therefore very closely related genetically. These clonal complexes represent strains corresponding to the previously identified species Bacillus weihenstephanensis. Most of the other strains of our collection, including some from the W cluster, are not psychrotrophic. B. weihenstephanensis (cluster W) strains appear to comprise an effectively sexual population, whereas Bacillus thuringiensis (cluster T) and B. cereus (cluster C) have clonal population structures.

  18. Identification of deletion carriers in hemophilia B: quantitative real-time polymerase chain reaction or multiple ligation probe amplification.

    PubMed

    Casaña, Pilar; Haya, Saturnino; Cid, Ana R; Oltra, Silvestre; Martínez, Francisco; Cabrera, Noelia; Aznar, José A

    2009-03-01

    Gross deletions in the F9 gene are easily detected by routinely sequencing hemophilia B-affected men. Nevertheless, a carrier diagnosis proves difficult as the presence of a normal allele does not recognize the partial or complete loss of the F9 gene and may be challenging if no DNA sample from affected men is available. This work aimed to identify hemophilia carriers in 2 families in which gross deletions of the F9 gene could be expected. The indirect genetic study was not conclusive, and sequencing did not show genetic defects in family 1. A real-time polymerase chain reaction (RT-PCR) assay using SYBR Green revealed the deletion of a copy of exon 8 in 3 women, whereas the multiple ligation-dependent probe amplification (MLPA) assay showed the deletion of a copy of exons 7 and 8 in these 3 women. These studies enabled us not only to rule out a pregnant woman as a carrier but also to confirm a complete deletion of the gene in the patient from family 2 and the heterozygous state of his mother. The advantages that the MLPA method offers are the identification of a multiple exon deletion in the same assay and commonly used technology. The RT-PCR technology used involves standardizing and analyzing each exon independently.

  19. Real-life experience with fampridine (Fampyra®) for patients with multiple sclerosis and gait disorders.

    PubMed

    Fragoso, Yara Dadalti; Adoni, Tarso; Alves-Leon, Soniza Vieira; Apostolos-Pereira, Samira Luisa; Barreira, Amilton Antunes; Brooks, Joseph Bruno Bidin; Claudino, Rinaldo; Correa, Eber Castro; Ferreira, Maria Lucia Brito; Finkelsztejn, Alessandro; Finkelsztejn, Juliana; da Gama, Paulo Diniz; Goncalves, Marcus Vinicius Magno; Guerreiro, Carlos Tostes; da Cunha Matta, Andre Palma; Marques, Vanessa Daccach; Rizo Morales, Rogerio; Parolin, Monica Fiuza Koncke; de Castro Ribeiro, Marlise; Ribeiro, Taysa Alexandrino Gonsalves Jube; Ruocco, Heloisa Helena; Sato, Henry; Scherpenhuijzen, Simone; Siquineli, Fabio; de Carvalho Sousa, Nise Alessandra; Varela, Daniel Lima; Tauil, Carlos Bernardo; Winckler, Thereza Cristina

    2016-06-30

    Fampridine is a broad-spectrum voltage-dependent potassium channel blocker that enhances synaptic transmission. The drug has been shown to be able to ameliorate conduction in demyelinated axons, thereby leading to improved gait in patients with multiple sclerosis (MS). To assess the "real-life" efficacy and safety of fampridine prescribed for gait disorders in MS. This was an observational and prospective study carried out at MS Units participating in the Brazilian Multiple Sclerosis Study Group. Patients with MS and gait disorders were prescribed fampridine (10 mg twice a day), irrespectively of the degree of disability determined by MS. Neurological disability determined by MS was assessed with the expanded disability scale score (EDSS). Outcomes for efficacy and safety of the drug were evaluated by the 25 foot-walk test and by the adverse events of fampridine. The time taken to walk 25 feet decreased by 20% or more in 62 patients (70%). Twenty-five patients were considered to be non-responders to this treatment. Improvement in walking speed was independent of improvement of disability. Mild or moderate adverse events were reported in 8% of patients. Fampridine is an efficient and safe therapeutic option for patients with MS and gait disorders.

  20. Adaptive marker-free registration using a multiple point strategy for real-time and robust endoscope electromagnetic navigation.

    PubMed

    Luo, Xiongbiao; Wan, Ying; He, Xiangjian; Mori, Kensaku

    2015-02-01

    Registration of pre-clinical images to physical space is indispensable for computer-assisted endoscopic interventions in operating rooms. Electromagnetically navigated endoscopic interventions are increasingly performed at current diagnoses and treatments. Such interventions use an electromagnetic tracker with a miniature sensor that is usually attached at an endoscope distal tip to real time track endoscope movements in a pre-clinical image space. Spatial alignment between the electromagnetic tracker (or sensor) and pre-clinical images must be performed to navigate the endoscope to target regions. This paper proposes an adaptive marker-free registration method that uses a multiple point selection strategy. This method seeks to address an assumption that the endoscope is operated along the centerline of an intraluminal organ which is easily violated during interventions. We introduce an adaptive strategy that generates multiple points in terms of sensor measurements and endoscope tip center calibration. From these generated points, we adaptively choose the optimal point, which is the closest to its assigned the centerline of the hollow organ, to perform registration. The experimental results demonstrate that our proposed adaptive strategy significantly reduced the target registration error from 5.32 to 2.59 mm in static phantoms validation, as well as from at least 7.58 mm to 4.71 mm in dynamic phantom validation compared to current available methods.

  1. The Locus analytical framework for indoor localization and tracking applications

    NASA Astrophysics Data System (ADS)

    Segou, Olga E.; Thomopoulos, Stelios C. A.

    2015-05-01

    Obtaining location information can be of paramount importance in the context of pervasive and context-aware computing applications. Many systems have been proposed to date, e.g. GPS that has been proven to offer satisfying results in outdoor areas. The increased effect of large and small scale fading in indoor environments, however, makes localization a challenge. This is particularly reflected in the multitude of different systems that have been proposed in the context of indoor localization (e.g. RADAR, Cricket etc). The performance of such systems is often validated on vastly different test beds and conditions, making performance comparisons difficult and often irrelevant. The Locus analytical framework incorporates algorithms from multiple disciplines such as channel modeling, non-uniform random number generation, computational geometry, localization, tracking and probabilistic modeling etc. in order to provide: (a) fast and accurate signal propagation simulation, (b) fast experimentation with localization and tracking algorithms and (c) an in-depth analysis methodology for estimating the performance limits of any Received Signal Strength localization system. Simulation results for the well-known Fingerprinting and Trilateration algorithms are herein presented and validated with experimental data collected in real conditions using IEEE 802.15.4 ZigBee modules. The analysis shows that the Locus framework accurately predicts the underlying distribution of the localization error and produces further estimates of the system's performance limitations (in a best-case/worst-case scenario basis).

  2. Efficacy and safety of nabiximols (Sativex(®)) on multiple sclerosis spasticity in a real-life Italian monocentric study.

    PubMed

    Ferrè, Laura; Nuara, Arturo; Pavan, Giulia; Radaelli, Marta; Moiola, Lucia; Rodegher, Mariaemma; Colombo, Bruno; Keller Sarmiento, Ignacio Juan; Martinelli, Vittorio; Leocani, Letizia; Martinelli Boneschi, Filippo; Comi, Giancarlo; Esposito, Federica

    2016-02-01

    Multiple sclerosis (MS) patients frequently suffer from limb spasticity and pain despite antispastic treatments. To investigate nabiximols efficacy and safety in a real-world monocentric Italian cohort, the following data were collected at baseline, week 4, 14 and 48: Ambulation Index (AI), 10-min walking test (10MWT), combined Modified Ashworth scale (cMAS), scores at numerical rating scale for spasticity (sNRS) and pain (pNRS). Responder status was defined as a ≥20 % reduction in sNRS after 4 weeks of treatment. 144 MS patients (123 progressive and 21 relapsing-remitting) complaining of moderate-to-severe spasticity (mean sNRS: 7.5) were included: 138 (95.8 %) completed the first month of therapy and were classified as follows-23.2 % were non-responders, 5.1 % were responders but discontinued treatment due to side effects, 71.7 % were responders with a mean 32 % reduction in sNRS (p < 0.001). In responders sNRS further decreased between 4 and 14 weeks (p = 0.03). Similarly, pNRS improvement was seen during the first month and between 4 and 14 weeks (p < 0.001 and p = 0.004, respectively). Moreover, at 4 weeks responders showed a significant (p < 0.05) improvement in cMAS, AI and 10MWT, which was maintained at 14 weeks. At 1-year follow-up, a benefit was still evident on spasticity and painful symptoms with a low drop-out rate. Confusion/ideomotor slowing, fatigue and dizziness were the most frequent side effects; no major adverse events were reported. Shorter disease duration at treatment start was associated with better response. This real-world study confirms nabiximols efficacy and safety in the treatment of MS-related spasticity and pain, which is maintained up to 48 weeks.

  3. Expanding the use of administrative claims databases in conducting clinical real-world evidence studies in multiple sclerosis.

    PubMed

    Capkun, Gorana; Lahoz, Raquel; Verdun, Elisabetta; Song, Xue; Chen, Weston; Korn, Jonathan R; Dahlke, Frank; Freitas, Rita; Fraeman, Kathy; Simeone, Jason; Johnson, Barbara H; Nordstrom, Beth

    2015-05-01

    Administrative claims databases provide a wealth of data for assessing the effect of treatments in clinical practice. Our aim was to propose methodology for real-world studies in multiple sclerosis (MS) using these databases. In three large US administrative claims databases: MarketScan, PharMetrics Plus and Department of Defense (DoD), patients with MS were selected using an algorithm identified in the published literature and refined for accuracy. Algorithms for detecting newly diagnosed ('incident') MS cases were also refined and tested. Methodology based on resource and treatment use was developed to differentiate between relapses with and without hospitalization. When various patient selection criteria were applied to the MarketScan database, an algorithm requiring two MS diagnoses at least 30 days apart was identified as the preferred method of selecting patient cohorts. Attempts to detect incident MS cases were confounded by the limited continuous enrollment of patients in these databases. Relapse detection algorithms identified similar proportions of patients in the MarketScan and PharMetrics Plus databases experiencing relapses with (2% in both databases) and without (15-20%) hospitalization in the 1 year follow-up period, providing findings in the range of those in the published literature. Additional validation of the algorithms proposed here would increase their credibility. The methods suggested in this study offer a good foundation for performing real-world research in MS using administrative claims databases, potentially allowing evidence from different studies to be compared and combined more systematically than in current research practice.

  4. Effective learning strategies for real-time image-guided adaptive control of multiple-source hyperthermia applicators

    PubMed Central

    Cheng, Kung-Shan; Dewhirst, Mark W.; Stauffer, Paul R.; Das, Shiva

    2010-01-01

    Purpose: This paper investigates overall theoretical requirements for reducing the times required for the iterative learning of a real-time image-guided adaptive control routine for multiple-source heat applicators, as used in hyperthermia and thermal ablative therapy for cancer. Methods: Methods for partial reconstruction of the physical system with and without model reduction to find solutions within a clinically practical timeframe were analyzed. A mathematical analysis based on the Fredholm alternative theorem (FAT) was used to compactly analyze the existence and uniqueness of the optimal heating vector under two fundamental situations: (1) noiseless partial reconstruction and (2) noisy partial reconstruction. These results were coupled with a method for further acceleration of the solution using virtual source (VS) model reduction. The matrix approximation theorem (MAT) was used to choose the optimal vectors spanning the reduced-order subspace to reduce the time for system reconstruction and to determine the associated approximation error. Numerical simulations of the adaptive control of hyperthermia using VS were also performed to test the predictions derived from the theoretical analysis. A thigh sarcoma patient model surrounded by a ten-antenna phased-array applicator was retained for this purpose. The impacts of the convective cooling from blood flow and the presence of sudden increase of perfusion in muscle and tumor were also simulated. Results: By FAT, partial system reconstruction directly conducted in the full space of the physical variables such as phases and magnitudes of the heat sources cannot guarantee reconstructing the optimal system to determine the global optimal setting of the heat sources. A remedy for this limitation is to conduct the partial reconstruction within a reduced-order subspace spanned by the first few maximum eigenvectors of the true system matrix. By MAT, this VS subspace is the optimal one when the goal is to maximize the

  5. The IGF2 Locus

    USDA-ARS?s Scientific Manuscript database

    Insulin-like growth factor 2 (IGF2) is a peptide hormone regulating various cellular processes such as proliferation and apoptosis. IGF2 is vital to embryo development. The IGF2 locus covers approximately 150-kb genomic region on human chromosome 11, containing two imprinted genes, IGF2 and H19, sha...

  6. A multiple receiver - multiple transmitter VLF high-order differential analysis evaluation network for near real-time detection and discrimination of seismic-ionospheric precursor phenomena

    NASA Astrophysics Data System (ADS)

    Skeberis, Christos; Zaharis, Zaharias; Xenos, Thomas; Spatalas, Spyridon; Stratakis, Dimitrios; Maggipinto, Tommaso; Biagi, Pier francesco

    2016-04-01

    This study provides an evaluation of the application of high-order differential analysis on VLF signals on a multiple-receiver multiple-transmitter network. This application provides a method for near-real-time detection of disturbances that can be attributed to seismic-ionospheric precursor phenomena and can discriminate disturbances that could be classified as false positives and thus should be attributed to other geomagnetic influences. VLF data acquired in Thessaloniki, Greece (40.59N, 22,78E) Herakleion, Greece (35.31N, 25.10E), Nicosia, Cyprus (35.17N, 33.35E), Italy (42.42N, 13.08E) and transmitted by the VLF station in Tavolara, Italy (ICV station 40.923N, 9.731E) and the station in Keflavik, Iceland (ICE 64.02N, 22.57W) from January 2015 to January 2016 were used for the purpose of this paper. The receivers have been developed by Elettronika Srl and are part of the International Network for Frontier Research on Earthquake Precursors (INFREP). The process applied for this study has been further developed and is based on differential analysis. The signals undergo transformation using an enhanced version of the Hilbert Huang Transform, and relevant spectra are produced. On the product of this process, differential analysis is applied. Finally, the method produces the correlation coefficient of signals that are on the same path over an earthquake epicenter in order to highlight disturbances, and on the opposite can make comparisons with unrelated transmitted signals of different paths to eliminate disturbances that are not localized to the area of interest. This improvement provides a simple method of noise cancellation to signals that would otherwise be considered as false positives. A further evaluation of the method is provided with the presentation and discussion of sample results. The method seems to be a robust tool of analysis of VLF signals and also an automatic detection tool with built-in noise cancellation of outside disturbances.

  7. Three-dimensional reach trajectories as a probe of real-time decision-making between multiple competing targets

    PubMed Central

    Gallivan, Jason P.; Chapman, Craig S.

    2014-01-01

    Though several features of cognitive processing can be inferred from the discrete measurement [e.g., reaction time (RT), accuracy, etc.] of participants' conscious reports (e.g., verbal or key-press responses), it is becoming increasingly clear that a much richer understanding of these features can be captured from continuous measures of rapid, largely non-conscious behaviors like hand or eye movements. Here, using new experimental data, we describe in detail both the approach and analyses implemented in some of our previous studies that have used rapid reaching movements under cases of target uncertainty in order to probe the features, constraints and dynamics of stimulus-related processing in the brain. This work, as well as that of others, shows that when individuals are simultaneously presented with multiple potential targets—only one of which will be cued after reach onset—they produce initial reach trajectories that are spatially biased in accordance with the probabilistic distribution of targets. Such “spatial averaging” effects are consistent with observations from neurophysiological studies showing that neuronal populations in sensorimotor brain structures represent multiple target choices in parallel and they compete for selection. These effects also confirm and help extend computational models aimed at understanding the underlying mechanisms that support action-target selection. We suggest that the use of this simple, yet powerful behavioral paradigm for providing a “real-time” visualization of ongoing cognitive processes occurring at the neural level offers great promise for studying processes related to a wide range of psychological phenomena, such as decision-making and the representation of objects. PMID:25100941

  8. Use of multiple-locus variable-number of tandem repeats analysis (MLVA) to investigate genetic diversity of Salmonella enterica subsp. enterica serovar Typhimurium isolates from human, food, and veterinary sources.

    PubMed

    Mateva, Gergana; Pedersen, Karl; Sørensen, Gitte; Asseva, Galina; Daskalov, Hristo; Petrov, Petar; Kantardjiev, Todor; Alexandar, Irina; Löfström, Charlotta

    2017-08-23

    Salmonella enterica subspecies enterica serovar Typhimurium is the most common zoonotic pathogen in Bulgaria. To allow efficient outbreak investigations and surveillance in the food chain, accurate and discriminatory methods for typing are needed. This study evaluated the use of multiple-locus variable-number of tandem repeats analysis (MLVA) and compared results with antimicrobial resistance (AMR) determinations for 100 S. Typhimurium strains isolated in Bulgaria during 2008-2012 (50 veterinary/food and 50 human isolates). Results showed that isolates were divided into 80 and 34 groups using MLVA and AMR, respectively. Simpson's index of diversity was determined to 0.994 ± 0.003 and 0.945 ± 0.012. The most frequently encountered MLVA profiles were 3-11-9-NA-211 (n = 5); 3-12-9-NA-211 (n = 3); 3-12-11-21-311 (n = 3); 3-17-10-NA-311 (n = 3); 2-20-9-7-212 (n = 3); and 2-23-NA-NA-111 (n = 3). No clustering of isolates related to susceptibility/resistance to antimicrobials, source of isolation, or year of isolation was observed. Some MLVA types were found in both human and veterinary/food isolates, indicating a possible route of transmission. A majority (83%) of the isolates were found to be resistant against at least one antimicrobial and 44% against ≥4 antimicrobials. Further studies are needed to verify MLVA usefulness over a longer period of time and with more isolates, including outbreak strains. © 2017 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

  9. Epidemiological and Phylogenetic Analysis of Spanish Human Brucella melitensis Strains by Multiple-Locus Variable-Number Tandem-Repeat Typing, Hypervariable Octameric Oligonucleotide Fingerprinting, and rpoB Typing▿

    PubMed Central

    Valdezate, Sylvia; Navarro, Ana; Villalón, Pilar; Carrasco, Gema; Saéz-Nieto, Juan A.

    2010-01-01

    The severe morbidity of human brucellosis is one of the main reasons for using molecular typing in the epidemiological surveillance of this worldwide zoonosis. Multiple-locus variable-number repeat analysis (MLVA-16), hypervariable octameric oligonucleotide fingerprinting (HOOF-print), and the differences in the single nucleotide polymorphisms (SNPs) (codons 1249 and 1309) of the DNA-dependent RNA polymerase β subunit (rpoB) were used to type a human Brucella melitensis population (108 strains) collected from throughout Spain over 13 years. Eighty-six MLVA types (discriminatory index, 0.99) were detected, with a wide-ranging genetic similarity coefficient (37.2 to 93.7%). The population clustered into the following groups: American, with genotypes 47 (1 strain), 48 (13 strains), 53 (12 strains), 55 (2 strains), 80 (1 strain), and a new genotype (2 strains), Western Mediterranean, with genotype 51 (9 strains), and Eastern Mediterranean, with genotypes 42 (60 strains), 43 (4 strains), and 63 (4 strains). Two profession-related and two foodborne acquisitions were confirmed. Distributed throughout Spain, Eastern Mediterranean genotype 42 was the most common (55%). The low MLVA-16 allelic polymorphism (genetic similarity range, 75 to 94%) of the genotype 42 strains suggests that they recently evolved from a common ancestor. rpoB typing grouped the strains as rpoB type 1 (1249-ATG/1309-CTG; 28.7%), rpoB type 2 (1249-ATG/1309-CTA; 62.9%), and rpoB type 3 (1249-ATA/1309-CTG; 8.3%). According to the MLVA-16 results, the population clustered by rpoB type. Given the correlation between B. melitensis MLVA groups and rpoB types (American and rpoB type 1, Eastern Mediterranean and rpoB type 2, and Western Mediterranean and rpoB type 3), the rpoB type could be used as an initial marker for the epidemiological surveillance of brucellosis. PMID:20554816

  10. Use of multiple-locus variable-number tandem repeat analysis to evaluate Escherichia coli O157 subtype distribution and transmission dynamics following natural exposure on a closed beef feedlot facility.

    PubMed

    Williams, Michele L; Pearl, David L; Bishop, Katherine E; Lejeune, Jeffrey T

    2013-10-01

    To better understand the epizootiology of Escherichia coli O157:H7 among cattle, all E. coli O157 isolates recovered on a research feedlot during a single feeding period were characterized by multiple-locus variable-number tandem repeat analysis (MLVA). Three distinct MLVA subtypes (A, B, C), accounting for 24%, 15%, and 64% of total isolates, respectively, were identified. Subtypes A and B were isolated at the initiation of sampling, but their prevalence waned and subtype C, first isolated on the third sampling date, became the predominant subtype on the feedlot. Supershedding events, however, occurred with equal frequency for all three MLVA-types. Using a multilevel logistic regression model, we investigated whether the odds of shedding subtype C relative to subtypes A or B were associated with time, diet, or the presence of a penmate shedding high numbers of subtype C. Only time and exposure to an animal shedding MLVA-type C at 10³ colony-forming units or greater in the pen at the time of sampling were significantly associated with increased shedding of subtype C. High-level shedding of those E. coli O157 subtypes better suited for survival in the environment and/or in the host appear to play a significant role in the development of predominant E. coli O157 subtypes. Supershedding events alone are neither required nor sufficient to drive the epidemiology of specific E. coli O157 subtypes. Additional factors are necessary to direct successful on-farm transmission of E. coli O157.

  11. Modelling a real-world buried valley system with vertical non-stationarity using multiple-point statistics

    NASA Astrophysics Data System (ADS)

    He, Xiulan; Sonnenborg, Torben O.; Jørgensen, Flemming; Jensen, Karsten H.

    2017-03-01

    Stationarity has traditionally been a requirement of geostatistical simulations. A common way to deal with non-stationarity is to divide the system into stationary sub-regions and subsequently merge the realizations for each region. Recently, the so-called partition approach that has the flexibility to model non-stationary systems directly was developed for multiple-point statistics simulation (MPS). The objective of this study is to apply the MPS partition method with conventional borehole logs and high-resolution airborne electromagnetic (AEM) data, for simulation of a real-world non-stationary geological system characterized by a network of connected buried valleys that incise deeply into layered Miocene sediments (case study in Denmark). The results show that, based on fragmented information of the formation boundaries, the MPS partition method is able to simulate a non-stationary system including valley structures embedded in a layered Miocene sequence in a single run. Besides, statistical information retrieved from the AEM data improved the simulation of the geology significantly, especially for the deep-seated buried valley sediments where borehole information is sparse.

  12. Collective Influence of Multiple Spreaders Evaluated by Tracing Real Information Flow in Large-Scale Social Networks.

    PubMed

    Teng, Xian; Pei, Sen; Morone, Flaviano; Makse, Hernán A

    2016-10-26

    Identifying the most influential spreaders that maximize information flow is a central question in network theory. Recently, a scalable method called "Collective Influence (CI)" has been put forward through collective influence maximization. In contrast to heuristic methods evaluating nodes' significance separately, CI method inspects the collective influence of multiple spreaders. Despite that CI applies to the influence maximization problem in percolation model, it is still important to examine its efficacy in realistic information spreading. Here, we examine real-world information flow in various social and scientific platforms including American Physical Society, Facebook, Twitter and LiveJournal. Since empirical data cannot be directly mapped to ideal multi-source spreading, we leverage the behavioral patterns of users extracted from data to construct "virtual" information spreading processes. Our results demonstrate that the set of spreaders selected by CI can induce larger scale of information propagation. Moreover, local measures as the number of connections or citations are not necessarily the deterministic factors of nodes' importance in realistic information spreading. This result has significance for rankings scientists in scientific networks like the APS, where the commonly used number of citations can be a poor indicator of the collective influence of authors in the community.

  13. Collective Influence of Multiple Spreaders Evaluated by Tracing Real Information Flow in Large-Scale Social Networks

    NASA Astrophysics Data System (ADS)

    Teng, Xian; Pei, Sen; Morone, Flaviano; Makse, Hernán A.

    2016-10-01

    Identifying the most influential spreaders that maximize information flow is a central question in network theory. Recently, a scalable method called “Collective Influence (CI)” has been put forward through collective influence maximization. In contrast to heuristic methods evaluating nodes’ significance separately, CI method inspects the collective influence of multiple spreaders. Despite that CI applies to the influence maximization problem in percolation model, it is still important to examine its efficacy in realistic information spreading. Here, we examine real-world information flow in various social and scientific platforms including American Physical Society, Facebook, Twitter and LiveJournal. Since empirical data cannot be directly mapped to ideal multi-source spreading, we leverage the behavioral patterns of users extracted from data to construct “virtual” information spreading processes. Our results demonstrate that the set of spreaders selected by CI can induce larger scale of information propagation. Moreover, local measures as the number of connections or citations are not necessarily the deterministic factors of nodes’ importance in realistic information spreading. This result has significance for rankings scientists in scientific networks like the APS, where the commonly used number of citations can be a poor indicator of the collective influence of authors in the community.

  14. Interaction of multiple networks modulated by the working memory training based on real-time fMRI

    NASA Astrophysics Data System (ADS)

    Shen, Jiahui; Zhang, Gaoyan; Zhu, Chaozhe; Yao, Li; Zhao, Xiaojie

    2015-03-01

    Neuroimaging studies of working memory training have identified the alteration of brain activity as well as the regional interactions within the functional networks such as central executive network (CEN) and default mode network (DMN). However, how the interaction within and between these multiple networks is modulated by the training remains unclear. In this paper, we examined the interaction of three training-induced brain networks during working memory training based on real-time functional magnetic resonance imaging (rtfMRI). Thirty subjects assigned to the experimental and control group respectively participated in two times training separated by seven days. Three networks including silence network (SN), CEN and DMN were identified by the training data with the calculated function connections within each network. Structural equation modeling (SEM) approach was used to construct the directional connectivity patterns. The results showed that the causal influences from the percent signal changes of target ROI to the SN were positively changed in both two groups, as well as the causal influence from the SN to CEN was positively changed in experimental group but negatively changed in control group from the SN to DMN. Further correlation analysis of the changes in each network with the behavioral improvements showed that the changes in SN were stronger positively correlated with the behavioral improvement of letter memory task. These findings indicated that the SN was not only a switch between the target ROI and the other networks in the feedback training but also an essential factor to the behavioral improvement.

  15. Collective Influence of Multiple Spreaders Evaluated by Tracing Real Information Flow in Large-Scale Social Networks

    PubMed Central

    Teng, Xian; Pei, Sen; Morone, Flaviano; Makse, Hernán A.

    2016-01-01

    Identifying the most influential spreaders that maximize information flow is a central question in network theory. Recently, a scalable method called “Collective Influence (CI)” has been put forward through collective influence maximization. In contrast to heuristic methods evaluating nodes’ significance separately, CI method inspects the collective influence of multiple spreaders. Despite that CI applies to the influence maximization problem in percolation model, it is still important to examine its efficacy in realistic information spreading. Here, we examine real-world information flow in various social and scientific platforms including American Physical Society, Facebook, Twitter and LiveJournal. Since empirical data cannot be directly mapped to ideal multi-source spreading, we leverage the behavioral patterns of users extracted from data to construct “virtual” information spreading processes. Our results demonstrate that the set of spreaders selected by CI can induce larger scale of information propagation. Moreover, local measures as the number of connections or citations are not necessarily the deterministic factors of nodes’ importance in realistic information spreading. This result has significance for rankings scientists in scientific networks like the APS, where the commonly used number of citations can be a poor indicator of the collective influence of authors in the community. PMID:27782207

  16. Interlaboratory study of DNA extraction from multiple ground samples, multiplex real-time PCR, and multiplex qualitative PCR for individual kernel detection system of genetically modified maize.

    PubMed

    Akiyama, Hiroshi; Sakata, Kozue; Makiyma, Daiki; Nakamura, Kosuke; Teshima, Reiko; Nakashima, Akie; Ogawa, Asako; Yamagishi, Toru; Futo, Satoshi; Oguchi, Taichi; Mano, Junichi; Kitta, Kazumi

    2011-01-01

    In many countries, the labeling of grains, feed, and foodstuff is mandatory if the genetically modified (GM) organism content exceeds a certain level of approved GM varieties. We previously developed an individual kernel detection system consisting of grinding individual kernels, DNA extraction from the individually ground kernels, GM detection using multiplex real-time PCR, and GM event detection using multiplex qualitative PCR to analyze the precise commingling level and varieties of GM maize in real sample grains. We performed the interlaboratory study of the DNA extraction with multiple ground samples, multiplex real-time PCR detection, and multiplex qualitative PCR detection to evaluate its applicability, practicality, and ruggedness for the individual kernel detection system of GM maize. DNA extraction with multiple ground samples, multiplex real-time PCR, and multiplex qualitative PCR were evaluated by five laboratories in Japan, and all results from these laboratories were consistent with the expected results in terms of the commingling level and event analysis. Thus, the DNA extraction with multiple ground samples, multiplex real-time PCR, and multiplex qualitative PCR for the individual kernel detection system is applicable and practicable in a laboratory to regulate the commingling level of GM maize grain for GM samples, including stacked GM maize.

  17. The real-world effectiveness and safety of fingolimod in relapsing-remitting multiple sclerosis patients: An observational study.

    PubMed

    Izquierdo, Guillermo; Damas, Fátima; Páramo, Maria Dolores; Ruiz-Peña, Juan Luis; Navarro, Guillermo

    2017-01-01

    Fingolimod approval was based mainly on two clinical trials, FREEDOMS and TRANSFORMS, which demonstrated the efficacy and safety of fingolimod in patients with multiple sclerosis (MS). We present an observational study that validates these trials findings in a real-world setting, whereby the effectiveness and safety of fingolimod was assessed in Seville's' (Spain) clinical practice. This retrospective study in MS patients assessed effectiveness (relapses, EDSS, gadolinium-enhancing T1 and new/enlarged T2-weighted lesions): total cohort (n = 249) and stratified according to prior treatment (glatiramer acetate/interferon beta-1 [immunomodulator], natalizumab, naïve), gender, basal EDSS score, basal Gd+ lesions, ARR prior to treatment, age at treatment initiation and number of prior treatments. A multivariante model was used to assess the ARR with baseline characteristics. The safety profile (adverse events [AEs]) was also described. Fingolimod reduced the annualized relapse rate (ARR) by 75%, 67% and 85% in the total cohort, patients previously treated with immunomodulatory and naïve patients (p<0.0001 all cases). However, patients previously treated with natalizumab kept a constant ARR. The ARR results and the consequent increase in the proportion of relapse-free patients were independent of the age at treatment initiation, number of prior treatments, gender and basal Gd+ lesions. Although fingolimod was effective regardless the basal EDSS score and ARR prior to fingolimod treatment, better outcomes were observed in patients with basal EDSS score <3 (0.2 vs. 0.4; p = 0.0244) and ARR ≥ 2 prior to fingolimod treatment (p = 0.0338). Only the basal EDSS score was association with ARR in the first 24 months of fingolimod treatment in the multivariante model (p = 0.0439). The cumulative probability of disability progression was 20% (month-24) in the total cohort, and was independent from prior treatment, age at treatment initiation, number of prior treatments, gender

  18. The real-world effectiveness and safety of fingolimod in relapsing-remitting multiple sclerosis patients: An observational study

    PubMed Central

    Damas, Fátima; Páramo, Maria Dolores; Ruiz-Peña, Juan Luis; Navarro, Guillermo

    2017-01-01

    Fingolimod approval was based mainly on two clinical trials, FREEDOMS and TRANSFORMS, which demonstrated the efficacy and safety of fingolimod in patients with multiple sclerosis (MS). We present an observational study that validates these trials findings in a real-world setting, whereby the effectiveness and safety of fingolimod was assessed in Seville’s’ (Spain) clinical practice. This retrospective study in MS patients assessed effectiveness (relapses, EDSS, gadolinium-enhancing T1 and new/enlarged T2-weighted lesions): total cohort (n = 249) and stratified according to prior treatment (glatiramer acetate/interferon beta-1 [immunomodulator], natalizumab, naïve), gender, basal EDSS score, basal Gd+ lesions, ARR prior to treatment, age at treatment initiation and number of prior treatments. A multivariante model was used to assess the ARR with baseline characteristics. The safety profile (adverse events [AEs]) was also described. Fingolimod reduced the annualized relapse rate (ARR) by 75%, 67% and 85% in the total cohort, patients previously treated with immunomodulatory and naïve patients (p<0.0001 all cases). However, patients previously treated with natalizumab kept a constant ARR. The ARR results and the consequent increase in the proportion of relapse-free patients were independent of the age at treatment initiation, number of prior treatments, gender and basal Gd+ lesions. Although fingolimod was effective regardless the basal EDSS score and ARR prior to fingolimod treatment, better outcomes were observed in patients with basal EDSS score <3 (0.2 vs. 0.4; p = 0.0244) and ARR ≥ 2 prior to fingolimod treatment (p = 0.0338). Only the basal EDSS score was association with ARR in the first 24 months of fingolimod treatment in the multivariante model (p = 0.0439). The cumulative probability of disability progression was 20% (month-24) in the total cohort, and was independent from prior treatment, age at treatment initiation, number of prior treatments

  19. [Non-modified magnetic beads coupled with multiple real-time PCR for detection and quantification of mycotoxigenic fungi in paprika samples].

    PubMed

    Jin, Yan; Zhang, Wei-Wei; Wang, Su-Yuan; Ye, Zheng-Mao; Zhang, Li-Shi; Pei, Xiao-Fang

    2015-01-01

    To establish a method for detecting 3 common toxigenic molds (Aspergillus, Penicillium, and Fusarium) based on non-modified magnetic beads coupled with multiple real-time PCR (NMB-multiple qPCR). The primers and genus-specific probes were designed based on the rDNA sequences to develop a multiple real-time PCR using non-modified magnetic bead to enrichment of fungal spores. The sensitivity, specificity and repeatability of this assay were evaluated. The detection limit of this assay for spiked samples was 10(4) CFU/g, demonstrating a 10-fold greater detection sensitivity of this assay than that of real-time PCR. The NMB-multiple qPCR assay also showed good specificity and reproducibility and yielded comparable results with those by traditional colony counting method for spiked samples (P>0.05). NMB-multiple qPCR assay we established allows rapid and sensitive detection of common mycotoxigenic fungi in paprika.

  20. Evaluation of multiple hydraulic models in generating design/near-real time flood inundation extents under various geophysical settings

    NASA Astrophysics Data System (ADS)

    Liu, Z.; Rajib, M. A.; Jafarzadegan, K.; Merwade, V.

    2015-12-01

    Application of land surface/hydrologic models within an operational flood forecasting system can provide probable time of occurrence and magnitude of streamflow at specific locations along a stream. Creating time-varying spatial extent of flood inundation and depth requires the use of a hydraulic or hydrodynamic model. Models differ in representing river geometry and surface roughness which can lead to different output depending on the particular model being used. The result from a single hydraulic model provides just one possible realization of the flood extent without capturing the uncertainty associated with the input or the model parameters. The objective of this study is to compare multiple hydraulic models toward generating ensemble flood inundation extents. Specifically, relative performances of four hydraulic models, including AutoRoute, HEC-RAS, HEC-RAS 2D, and LISFLOOD are evaluated under different geophysical conditions in several locations across the United States. By using streamflow output from the same hydrologic model (SWAT in this case), hydraulic simulations are conducted for three configurations: (i) hindcasting mode by using past observed weather data at daily time scale in which models are being calibrated against USGS streamflow observations, (ii) validation mode using near real-time weather data at sub-daily time scale, and (iii) design mode with extreme streamflow data having specific return periods. Model generated inundation maps for observed flood events both from hindcasting and validation modes are compared with remotely sensed images, whereas the design mode outcomes are compared with corresponding FEMA generated flood hazard maps. The comparisons presented here will give insights on probable model-specific nature of biases and their relative advantages/disadvantages as components of an operational flood forecasting system.

  1. Relation of organizational citizenship behavior and locus of control.

    PubMed

    Turnipseed, David L; Bacon, Calvin M

    2009-12-01

    The relation of organizational citizenship behavior and locus of control was assessed in a sample of 286 college students (52% men; M age = 24 yr.) who worked an average of 26 hr. per week. Measures were Spector's Work Locus of Control Scale and Podsakoff, et al.'s Organization Citizenship Behavior scale. Hierarchical multiple regressions indicated positive association of scores on work locus of control with scores on each of the four tested dimensions of organizational citizenship, as well as total organizational citizenship behavior.

  2. [Multiple-locus variable number tandem repeat analysis of Bordetella pertussis strains collected in the Czech Republic in 1967-2015: spread of a variant adapted to the population with a high vaccination coverage].

    PubMed

    Lžičařová, D; Zavadilová, J; Musílek, M; Jandová, Z; Křížová, P; Fabiánová, K

    To perform multiple-locus variable number tandem repeat analysis (MLVA) of B. pertussis strains from the collection of the National Reference Laboratory for Diphtheria and Pertussis (NRL/DIPE), National Institute of Public Health (NIPH), Prague. The study strains were isolated from clinical specimens collected mostly in the Czech Republic over a nearly 50-year period from 1967 to 2015 (June). The isolates from three periods characterized by different vaccination strategies and trends in pertussis are compared for genetic diversity and distribution of MLVA types (MT). Based on the results obtained, the suitability for use of MLVA in the analysis of epidemic outbreaks of B. pertussis in the Czech Republic is considered. DNA samples extracted from B. pertussis strains included in the present study were examined by MLVA using the standard protocol. Data were processed by means of the eBURST algorithm and the calculation of the Simpson diversity index (DI) was used for the statistical analysis. Data were analyzed as a whole and also separately for strains from the three periods: 1967-1980, 1990-2007, and 2008-2015 (June). Fourteen different MT were detected in the study strains, with three of them not being reported before. The most common MTs were MT27 and MT29. MT29 was predominant in 1967-1980 while MT27 was the most prevalent in 1990-2007 and 2008-2015 (June). The DI was the lowest (0.49) in 2008-2015 (June), and comparably higher DIs were calculated for the two previous periods (i.e. 0.667 for 1967-1980 and 0.654 for 1990-2007). MLVA revealed a decrease in genetic diversity and shifts in MT distribution of B. pertussis strains isolated from clinical specimens in the Czech Republic from 1967 to 2015 (June). These shifts in the Czech Republic can be characterized as a progressive increase in global MTs at the expense of the locally unique ones. The most common MT, similarly to other geographical areas with long-term high vaccination coverage, is MT27. The results of

  3. Real-World Adherence and Persistence to Oral Disease-Modifying Therapies in Multiple Sclerosis Patients Over 1 Year.

    PubMed

    Johnson, Kristen M; Zhou, Huanxue; Lin, Feng; Ko, John J; Herrera, Vivian

    2017-08-01

    Disease-modifying therapies (DMTs) are indicated to reduce relapse rates and slow disease progression for relapsing-remitting multiple sclerosis (MS) patients when taken as prescribed. Nonadherence or non-persistence in the real-world setting can lead to greater risk for negative clinical outcomes. Although previous research has demonstrated greater adherence and persistence to oral DMTs compared with injectable DMTs, comparisons among oral DMTs are lacking. To compare adherence, persistence, and time to discontinuation among MS patients newly prescribed the oral DMTs fingolimod, dimethyl fumarate, or teriflunomide. This retrospective study used MarketScan Commercial and Medicare Supplemental claims databases. MS patients with ≥ 1 claim for specified DMTs from April 1, 2013, to June 30, 2013, were identified. The index drug was defined as the first oral DMT within this period. To capture patients newly initiating index DMTs, patients could not have a claim for their index drugs in the previous 12 months. Baseline characteristics were described for patients in each treatment cohort. Adherence, as measured by medication possession ratio (MPR) and proportion of days covered (PDC); persistence (30-day gap allowed); and time to discontinuation over a 12-month follow-up period were compared across treatment cohorts. Adjusted logistic regression models were used to examine adherence, and Cox regression models estimated risk of discontinuation. 1,498 patients newly initiated oral DMTs and met study inclusion criteria: fingolimod (n = 185), dimethyl fumarate (n = 1,160), and teriflunomide (n = 143). Patients were similar across most baseline characteristics, including region, relapse history, and health care resource utilization. Statistically significant differences were observed across the treatment cohorts for age, gender, previous injectable/infused DMT use, and comorbidities. Adherence and time to discontinuation were adjusted for age, gender, region, previous oral

  4. Longitudinal prevalence and molecular typing of Escherichia coli O157:H7 using multiple-locus variable-number tandem-repeats analysis and pulsed field gel electrophoresis in a range cattle herd in California

    USDA-ARS?s Scientific Manuscript database

    Objectives –(1) Identify the seasonal pattern and risk factors for Escherichia coli O157:H7 in feces in range cattle in California, (2) Determine strain diversity and transition over time using Multi-Locus Variable-Number Tandem Repeat Analysis (MLVA) and Pulsed Field Gel Electrophoresis (PFGE) Samp...

  5. Multiplicity

    DTIC Science & Technology

    1991-04-01

    practice as a "[descent] into that inner circle of the Inferno where the damned endlessly degate multiplicity for sentencing." United States v. Barnard...select the charges to be brought in a particular case"). 19 Brown v. Ohio, 432 U.S. 161, 165 (1977). 20 Whalen v. United States, 445 U.S. at 689. 21...parte Lange, 8-5 U.S. (19 Wall.) 163 (1874). Cf. Brown v. Ohio, 432 U.S. at 165 ("once the legislature has acted courts may not impose more than one

  6. Real-Time Assessment of Fatigue in Patients With Multiple Sclerosis: How Does It Relate to Commonly Used Self-Report Fatigue Questionnaires?

    PubMed

    Heine, Martin; van den Akker, Lizanne Eva; Blikman, Lyan; Hoekstra, Trynke; van Munster, Erik; Verschuren, Olaf; Visser-Meily, Anne; Kwakkel, Gert

    2016-11-01

    (1) To assess real-time patterns of fatigue; (2) to assess the association between a real-time fatigue score and 3 commonly used questionnaires (Checklist Individual Strength [CIS] fatigue subscale, Modified Fatigue Impact Scale (MFIS), and Fatigue Severity Scale [FSS]); and (3) to establish factors that confound the association between the real-time fatigue score and the conventional fatigue questionnaires in patients with multiple sclerosis (MS). Cross-sectional study. MS-specialized outpatient facility. Ambulant patients with MS (N=165) experiencing severe self-reported fatigue. Not applicable. A real-time fatigue score was assessed by sending participants 4 text messages on a particular day (How fatigued do you feel at this moment?; score range, 0-10). Latent class growth mixed modeling was used to determine diurnal patterns of fatigue. Regression analyses were used to assess the association between the mean real-time fatigue score and the CIS fatigue subscale, MFIS, and FSS. Significant associations were tested for candidate confounders (eg, disease severity, work status, sleepiness). Four significantly different fatigue profiles were identified by the real-time fatigue score, namely a stable high (n=79), increasing (n=57), stable low (n=16), and decreasing (n=13). The conventional questionnaires correlated poorly (r<.300) with the real-time fatigue score. The Epworth Sleepiness Scale significantly reduced the regression coefficient between the real-time fatigue score and conventional questionnaires, ranging from 15.4% to 35%. Perceived fatigue showed 4 different diurnal patterns in patients with MS. Severity of sleepiness is an important confounder to take into account in the assessment of fatigue. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  7. Utilization of multiple real-time PCR assays for the diagnosis of Bordetella spp. in clinical specimens.

    PubMed

    Tatti, Kathleen M; Tondella, Maria Lucia

    2013-01-01

    Bordetella pertussis causes an upper respiratory infection in infants, adolescents, and adults. Diagnosis of pertussis, a vaccine-preventable disease, can be difficult, but recent implementation of real-time PCR assays in laboratories has hastened the ability of clinicians to make an accurate diagnosis. In this paper we describe the method of nasopharyngeal specimen collection, extraction of DNA, and real-time PCR assays that will allow the detection and identification of Bordetella spp. in clinical specimens.

  8. Multiplex, Rapid, and Sensitive Isothermal Detection of Nucleic-Acid Sequence by Endonuclease Restriction-Mediated Real-Time Multiple Cross Displacement Amplification.

    PubMed

    Wang, Yi; Wang, Yan; Zhang, Lu; Liu, Dongxin; Luo, Lijuan; Li, Hua; Cao, Xiaolong; Liu, Kai; Xu, Jianguo; Ye, Changyun

    2016-01-01

    We have devised a novel isothermal amplification technology, termed endonuclease restriction-mediated real-time multiple cross displacement amplification (ET-MCDA), which facilitated multiplex, rapid, specific and sensitive detection of nucleic-acid sequences at a constant temperature. The ET-MCDA integrated multiple cross displacement amplification strategy, restriction endonuclease cleavage and real-time fluorescence detection technique. In the ET-MCDA system, the functional cross primer E-CP1 or E-CP2 was constructed by adding a short sequence at the 5' end of CP1 or CP2, respectively, and the new E-CP1 or E-CP2 primer was labeled at the 5' end with a fluorophore and in the middle with a dark quencher. The restriction endonuclease Nb.BsrDI specifically recognized the short sequence and digested the newly synthesized double-stranded terminal sequences (5' end short sequences and their complementary sequences), which released the quenching, resulting on a gain of fluorescence signal. Thus, the ET-MCDA allowed real-time detection of single or multiple targets in only a single reaction, and the positive results were observed in as short as 12 min, detecting down to 3.125 fg of genomic DNA per tube. Moreover, the analytical specificity and the practical application of the ET-MCDA were also successfully evaluated in this study. Here, we provided the details on the novel ET-MCDA technique and expounded the basic ET-MCDA amplification mechanism.

  9. A real case comparison between surface-related multiple elimination and other wave equation-based techniques

    SciTech Connect

    Jugla, F.; Julien, P.; Groot, P.F. de; Verschuur, E.

    1994-12-31

    A new antimultiple software has been developed by E. Verschuur (1991) and industrialized by TNO and TOTAL. This is a surface related multiple elimination technique which uses the seismic data itself to predict and subtract all the multiples related to the free reflecting surface. A benchmark test was performed to compare five contractors wave equation based antimultiples with the new technique. The benchmark has shown that this new technique has effectively attenuated numerous strong peg-leg multiples in the interval of interest (2.0--3.5 sec) where it compares favorably with the other methods results. The water bottom multiples and the deep multiples (below 3.5 sec) have only been slightly attacked. Some tests have shown that the present results can be improved by applying a refined near offsets data interpolation and an XT least squares filtering that ameliorates the adaptative multiple subtraction.

  10. Multiple Linear Regression Analysis of Factors Affecting Real Property Price Index From Case Study Research In Istanbul/Turkey

    NASA Astrophysics Data System (ADS)

    Denli, H. H.; Koc, Z.

    2015-12-01

    Estimation of real properties depending on standards is difficult to apply in time and location. Regression analysis construct mathematical models which describe or explain relationships that may exist between variables. The problem of identifying price differences of properties to obtain a price index can be converted into a regression problem, and standard techniques of regression analysis can be used to estimate the index. Considering regression analysis for real estate valuation, which are presented in real marketing process with its current characteristics and quantifiers, the method will help us to find the effective factors or variables in the formation of the value. In this study, prices of housing for sale in Zeytinburnu, a district in Istanbul, are associated with its characteristics to find a price index, based on information received from a real estate web page. The associated variables used for the analysis are age, size in m2, number of floors having the house, floor number of the estate and number of rooms. The price of the estate represents the dependent variable, whereas the rest are independent variables. Prices from 60 real estates have been used for the analysis. Same price valued locations have been found and plotted on the map and equivalence curves have been drawn identifying the same valued zones as lines.

  11. Combination of real-time PCR and sequencing to detect multiple clinically relevant genetic variations in the lactase gene.

    PubMed

    Brasen, Claus Lohman; Frischknecht, Lone; Ørnskov, Dorthe; Andreasen, Lotte; Madsen, Jonna Skov

    2017-02-01

    Lactase persistence is an autosomal dominant trait commonly distributed in Europe as well as some parts of east Africa and the Arabian Peninsula. Using real-time PCR to detect the -13910C > T variant common in the European population is a reliable analysis although other variants in the probe-binding site may cause errors in analysis. The aim of this study was to determine the prevalence of the variants in a Danish cohort examined for lactose intolerance as well as to improve the real-time PCR analysis for detection of the different variants. We genotyped 3395 routine samples using real-time PCR for the -13910C > T-variant. All consecutive samples identified as -13910CC were sequenced using Sanger Sequencing. Using the SDS software we examined various quality value settings to improve on the genetic analysis. Using real-time PCR resulted in 100% successful genotyping of the -13910C > T variant. By using a quality value of 99% and sequencing the undetermined samples we improved the ability of the assay to identify variants other than -13910C > T. This resulted in a reduction of the diagnostic error rate by a factor of 2.4 while increasing the expenses only 3%. We conclude that using a quality value of 99% in the SDS software significantly improves the diagnostic efficiency of the real-time PCR assay for detecting variants associated to lactase persistence.

  12. Detecting purely epistatic multi-locus interactions by an omnibus permutation test on ensembles of two-locus analyses

    PubMed Central

    Wongseree, Waranyu; Assawamakin, Anunchai; Piroonratana, Theera; Sinsomros, Saravudh; Limwongse, Chanin; Chaiyaratana, Nachol

    2009-01-01

    Background Purely epistatic multi-locus interactions cannot generally be detected via single-locus analysis in case-control studies of complex diseases. Recently, many two-locus and multi-locus analysis techniques have been shown to be promising for the epistasis detection. However, exhaustive multi-locus analysis requires prohibitively large computational efforts when problems involve large-scale or genome-wide data. Furthermore, there is no explicit proof that a combination of multiple two-locus analyses can lead to the correct identification of multi-locus interactions. Results The proposed 2LOmb algorithm performs an omnibus permutation test on ensembles of two-locus analyses. The algorithm consists of four main steps: two-locus analysis, a permutation test, global p-value determination and a progressive search for the best ensemble. 2LOmb is benchmarked against an exhaustive two-locus analysis technique, a set association approach, a correlation-based feature selection (CFS) technique and a tuned ReliefF (TuRF) technique. The simulation results indicate that 2LOmb produces a low false-positive error. Moreover, 2LOmb has the best performance in terms of an ability to identify all causative single nucleotide polymorphisms (SNPs) and a low number of output SNPs in purely epistatic two-, three- and four-locus interaction problems. The interaction models constructed from the 2LOmb outputs via a multifactor dimensionality reduction (MDR) method are also included for the confirmation of epistasis detection. 2LOmb is subsequently applied to a type 2 diabetes mellitus (T2D) data set, which is obtained as a part of the UK genome-wide genetic epidemiology study by the Wellcome Trust Case Control Consortium (WTCCC). After primarily screening for SNPs that locate within or near 372 candidate genes and exhibit no marginal single-locus effects, the T2D data set is reduced to 7,065 SNPs from 370 genes. The 2LOmb search in the reduced T2D data reveals that four intronic SNPs

  13. A cost-effectiveness analysis of real-world treatment for elderly patients with multiple myeloma using a full disease model.

    PubMed

    Blommestein, Hedwig M; Verelst, Silvia G R; de Groot, Saskia; Huijgens, Peter C; Sonneveld, Pieter; Uyl-de Groot, Carin A

    2016-02-01

    To study the impact of novel treatments for elderly (≥66 yr) patients with multiple myeloma (MM) in daily practice by comparing real-world effects [overall survival (OS) and quality-adjusted life years (QALYs)] and costs over time. Also, we calculate cost-effectiveness of treatment sequences commonly prescribed to predict effects and costs if patients had received a different treatment sequence. Real-world data including patient and disease characteristics, treatment information and resource use were collected from 1054 elderly patients with MM. Patients received first-line treatment during 2004-2007 (cohort 1) and 2008-2013 (cohort 2). The two cohorts were compared using a patient-level simulation (PLS) model comprising regression models which used patient and disease characteristics to estimate time to next treatment and death. Effects and costs from cohort 2 were compared to 4 commonly prescribed real-world sequences. Utilisation of novel agents was higher for cohort 2 compared to cohort 1. Modelled average OS for cohort 1 was 38 months (median 25) and total costs €44,200. OS for cohort 2 was 42 months (median 28) and total costs €69,017. The model identified potential OS gains if all patients were to be treated using combinations containing thalidomide, lenalidomide and bortezomib in that particular order. This sequence had, compared to real-world treatment, the most favourable incremental cost-effectiveness ratio, €24,618 per life year gained and €34,875 per QALY. Our patient-level model enabled to study the effects and costs of entire treatment sequences and to compare real-world treatment patterns over time. Increased utilisation of novel agents improved survival and increased costs for real-world patients with MM in the Netherlands. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Bifurcations of the conjugate locus

    NASA Astrophysics Data System (ADS)

    Waters, Thomas

    2017-09-01

    The conjugate locus of a point p in a surface S will have a certain number of cusps. As the point p is moved in the surface the conjugate locus may spontaneously gain or lose cusps. In this paper we explain this 'bifurcation' in terms of the vanishing of higher derivatives of the exponential map; we derive simple equations for these higher derivatives in terms of scalar invariants; we classify the bifurcations of cusps in terms of the local structure of the conjugate locus; and we describe an intuitive picture of the bifurcation as the intersection between certain contours in the tangent plane.

  15. SkyDOT: a publicly accessible variability database, containing multiple sky surveys and real-time data

    SciTech Connect

    Starr, D. L.; Wozniak, P. R.; Vestrand, W. T.

    2002-01-01

    SkyDOT (Sky Database for Objects in Time-Domain) is a Virtual Observatory currently comprised of data from the RAPTOR, ROTSE I, and OGLE I1 survey projects. This makes it a very large time domain database. In addition, the RAPTOR project provides SkyDOT with real-time variability data as well as stereoscopic information. With its web interface, we believe SkyDOT will be a very useful tool for both astronomers, and the public. Our main task has been to construct an efficient relational database containing all existing data, while handling a real-time inflow of data. We also provide a useful web interface allowing easy access to both astronomers and the public. Initially, this server will allow common searches, specific queries, and access to light curves. In the future we will include machine learning classification tools and access to spectral information.

  16. A Simulation Study of Four Real-Time Heuristic Algorithms for Multiple Missile Missile Evasion: A Game Theoretic Approach

    DTIC Science & Technology

    1979-06-01

    4.2.1 The Simulation Paradigm 4-1 4.2.2 The Engagement Scenarios 4-3 4.3 Algorithm Performance 4-3 Chapter 5 5.0 A Game Theoretic Model for Determining...Aircraft Evasion Strategies Against a Multiple Missile Threat 5 -1 5.1 Optimal Evasion Strategies Against Multiple Missiles: Part I - For Criteria with...a Fixed Terminal Time 5 -2 5.1.1 Introduction 5 -2 5.2 An Optimal Evasion Problem with Linear Dynamics and Quadratic Cost on Control 5 -4 5.2.1

  17. Accelerated multiple-pass moving average: a novel algorithm for baseline estimation in CE and its application to baseline correction on real-time bases.

    PubMed

    Solis, Alejandro; Rex, Mathew; Campiglia, Andres D; Sojo, Pedro

    2007-04-01

    We present a novel algorithm for baseline estimation in CE. The new algorithm which we have named as accelerated multiple-pass moving average (AMPMA) is combined to three preexisting low-pass filters, spike-removal, moving average, and multi-pass moving average filter, to achieve real-time baseline correction with commercial instrumentation. The successful performance of AMPMA is demonstrated with simulated and experimental data. Straightforward comparison of experimental data clearly shows the improvement AMPMA provides to the linear fitting, LOD, and accuracy (absolute error) of CE analysis.

  18. Real-time optical monitoring of thin film growth by in situ pyrometry through multiple layers and effective media approximation modeling

    SciTech Connect

    Benedic, F.; Bruno, P.; Pigeat, Ph.

    2007-03-26

    A model combining multiple layer description and effective media approximation is developed for pyrometry in the case of thin film synthesis, in order to estimate the film property evolution along its thickness during the growth process in real time. The model is used to investigate optical properties of polycrystalline diamond film prepared by H{sub 2}/CH{sub 4}/N{sub 2} microwave plasma. It is shown that in the presence of nitrogen, the growth is strongly nonhomogeneous. The deposit, initially composed of large amounts of void and nondiamond phases, evolves rapidly towards highest quality dense film where the diamond phase is predominant.

  19. Strategies for conditional two-locus nonparametric linkage analysis.

    PubMed

    Angquist, Lars; Hössjer, Ola; Groop, Leif

    2008-01-01

    In this article we deal with two-locus nonparametric linkage (NPL) analysis, mainly in the context of conditional analysis. This means that one incorporates single-locus analysis information through conditioning when performing a two-locus analysis. Here we describe different strategies for using this approach. Cox et al. [Nat Genet 1999;21:213-215] implemented this as follows: (i) Calculate the one-locus NPL process over the included genome region(s). (ii) Weight the individual pedigree NPL scores using a weighting function depending on the NPL scores for the corresponding pedigrees at speci fi c conditioning loci. We generalize this by conditioning with respect to the inheritance vector rather than the NPL score and by separating between the case of known (prede fi ned) and unknown (estimated) conditioning loci. In the latter case we choose conditioning locus, or loci, according to prede fi ned criteria. The most general approach results in a random number of selected loci, depending on the results from the previous one-locus analysis. Major topics in this article include discussions on optimal score functions with respect to the noncentrality parameter (NCP), and how to calculate adequate p values and perform power calculations. We also discuss issues related to multiple tests which arise from the two-step procedure with several conditioning loci as well as from the genome-wide tests.

  20. Development of Real Time PCR Using Novel Genomic Target for Detection of Multiple Salmonella Serovars from Milk and Chickens

    USDA-ARS?s Scientific Manuscript database

    Background: A highly sensitive and specific novel genomic and plasmid target-based PCR platform was developed to detect multiple Salmonella serovars (S. Heidelberg, S. Dublin, S. Hadar, S. Kentucky and S. Enteritidis). Through extensive genome mining of protein databases of these serovars and compar...

  1. Precipitation Analysis at Fine Time Scales Using Multiple Satellites: Real-time and Research Products and Applications

    NASA Technical Reports Server (NTRS)

    Adler, Robert; Huffman, George; Bolvin, David; Nelkin, Eric; Curtis, Scott; Pierce, Harold

    2004-01-01

    Quasi-global precipitation analyses at fine time scales (3-hr) are described. TRMM observations (radar and passive microwave) are used to calibrate polar-orbit microwave observations from SSM/I (and other satellites instruments, including AMSR and AMSU) and geosynchronous IR observations. The individual data sets are then merged using a priority order based on quality to form the Multi-satellite Precipitation Analysis (MPA). Raingauge information is used to help constrain the satellite-based estimates over land. The TRMM standard research product (Version 6 3B-42 of the TRMM products) will be available for the entire TRMM period (January 1998-present) in 2004. The real-time version of this merged product has been produced over the past two years and is available on the U.S. TRMM web site (trmm.gsfc.nasa.gov) at 0.25" latitude-longitude resolution over the latitude range from 5O"N-5O0S. Validation of daily totals indicates good results, with limitations noted in mid-latitude winter over land and regions of shallow, orographic precipitation. Various applications of these estimates are described, including: 1) detecting potential floods in near real-time; 2) analyzing Indian Ocean precipitation variations related to the initiation of El Nino; 3) determining characteristics of the African monsoon; and 4) analysis of diurnal variations.

  2. Precipitation Analysis at Fine Time Scales Using Multiple Satellites: Real-time and Research Products and Applications

    NASA Technical Reports Server (NTRS)

    Adler, Robert; Huffman, George; Bolvin, David; Nelkin, Eric; Curtis, Scott; Pierce, Harold

    2004-01-01

    Quasi-global precipitation analyses at fine time scales (3-hr) are described. TRMM observations (radar and passive microwave) are used to calibrate polar-orbit microwave observations from SSM/I (and other satellites instruments, including AMSR and AMSU) and geosynchronous IR observations. The individual data sets are then merged using a priority order based on quality to form the Multi-satellite Precipitation Analysis (MPA). Raingauge information is used to help constrain the satellite-based estimates over land. The TRMM standard research product (Version 6 3B-42 of the TRMM products) will be available for the entire TRMM period (January 1998-present) in 2004. The real-time version of this merged product has been produced over the past two years and is available on the U.S. TRMM web site (trmm.gsfc.nasa.gov) at 0.25" latitude-longitude resolution over the latitude range from 5O"N-5O0S. Validation of daily totals indicates good results, with limitations noted in mid-latitude winter over land and regions of shallow, orographic precipitation. Various applications of these estimates are described, including: 1) detecting potential floods in near real-time; 2) analyzing Indian Ocean precipitation variations related to the initiation of El Nino; 3) determining characteristics of the African monsoon; and 4) analysis of diurnal variations.

  3. Vergence and accommodation to multiple-image-plane stereoscopic displays: 'Real world' responses with practical image-plane separations?

    NASA Astrophysics Data System (ADS)

    MacKenzie, K. J.; Dickson, R. A.; Watt, S. J.

    2011-03-01

    Conventional stereoscopic displays present images on a single focal plane. The resulting mismatch between the stimuli to the eyes' focusing response (accommodation) and to convergence causes fatigue and poor stereo performance. One promising solution is to distribute image intensity across a number of relatively widely spaced image planes - a technique referred to as depth filtering. Previously, we found this elicits accurate, continuous monocular accommodation responses with image-plane separations as large as 1.1 Diopters, suggesting that a relatively small (i.e. practical) number of image planes is sufficient to eliminate vergence-accommodation conflicts over a large range of simulated distances. However, accommodation responses have been found to overshoot systematically when the same stimuli are viewed binocularly. Here, we examined the minimum image-plane spacing required for accurate accommodation to binocular depth-filtered images. We compared accommodation and vergence responses to step changes in depth for depth-filtered stimuli, using image-plane separations of 0.6-1.2 D, and equivalent real stimuli. Accommodation responses to real and depth-filtered stimuli were equivalent for image-plane separations of ~0.6-0.9 D, but inaccurate thereafter. We conclude that depth filtering can be used to precisely match accommodation and vergence demand in a practical stereoscopic display, using a relatively small number of image planes.

  4. Vergence and accommodation to multiple-image-plane stereoscopic displays: ``real world'' responses with practical image-plane separations?

    NASA Astrophysics Data System (ADS)

    MacKenzie, Kevin J.; Dickson, Ruth A.; Watt, Simon J.

    2012-01-01

    Conventional stereoscopic displays present images on a single focal plane. The resulting mismatch between the stimuli to the eyes' focusing response (accommodation) and to convergence causes fatigue and poor stereo performance. One solution is to distribute image intensity across a number of widely spaced image planes--a technique referred to as depth filtering. Previously, we found this elicits accurate, continuous monocular accommodation responses with image-plane separations as large as 1.1 Diopters (D, the reciprocal of distance in meters), suggesting that a small number of image planes could eliminate vergence-accommodation conflicts over a large range of simulated distances. Evidence exists, however, of systematic differences between accommodation responses to binocular and monocular stimuli when the stimulus to accommodation is degraded, or at an incorrect distance. We examined the minimum image-plane spacing required for accurate accommodation to binocular depth-filtered images. We compared accommodation and vergence responses to changes in depth specified by depth filtering, using image-plane separations of 0.6 to 1.2 D, and equivalent real stimuli. Accommodation responses to real and depth-filtered stimuli were equivalent for image-plane separations of ~0.6 to 0.9 D, but differed thereafter. We conclude that depth filtering can be used to precisely match accommodation and vergence demand in a practical stereoscopic display.

  5. Real-time particle monitor calibration factors and PM2.5 emission factors for multiple indoor sources.

    PubMed

    Dacunto, Philip J; Cheng, Kai-Chung; Acevedo-Bolton, Viviana; Jiang, Ruo-Ting; Klepeis, Neil E; Repace, James L; Ott, Wayne R; Hildemann, Lynn M

    2013-08-01

    Indoor sources can greatly contribute to personal exposure to particulate matter less than 2.5 μm in diameter (PM2.5). To accurately assess PM2.5 mass emission factors and concentrations, real-time particle monitors must be calibrated for individual sources. Sixty-six experiments were conducted with a common, real-time laser photometer (TSI SidePak™ Model AM510 Personal Aerosol Monitor) and a filter-based PM2.5 gravimetric sampler to quantify the monitor calibration factors (CFs), and to estimate emission factors for common indoor sources including cigarettes, incense, cooking, candles, and fireplaces. Calibration factors for these indoor sources were all significantly less than the factory-set CF of 1.0, ranging from 0.32 (cigarette smoke) to 0.70 (hamburger). Stick incense had a CF of 0.35, while fireplace emissions ranged from 0.44-0.47. Cooking source CFs ranged from 0.41 (fried bacon) to 0.65-0.70 (fried pork chops, salmon, and hamburger). The CFs of combined sources (e.g., cooking and cigarette emissions mixed) were linear combinations of the CFs of the component sources. The highest PM2.5 emission factors per time period were from burned foods and fireplaces (15-16 mg min(-1)), and the lowest from cooking foods such as pizza and ground beef (0.1-0.2 mg min(-1)).

  6. Fiber-optic probe for noninvasive real-time determination of tissue optical properties at multiple wavelengths.

    PubMed

    Dam, J S; Pedersen, C B; Dalgaard, T; Fabricius, P E; Aruna, P; Andersson-Engels, S

    2001-03-01

    We present a compact, fast, and versatile fiber-optic probe system for real-time determination of tissue optical properties from spatially resolved continuous-wave diffuse reflectance measurements. The system collects one set of reflectance data from six source-detector distances at four arbitrary wavelengths with a maximum overall sampling rate of 100 Hz. Multivariate calibration techniques based on two-dimensional polynomial fitting are employed to extract and display the absorption and reduced scattering coefficients in real-time mode. The four wavelengths of the current configuration are 660, 785, 805, and 974 nm, respectively. Cross-validation tests on a 6 x 7 calibration matrix of Intralipid-dye phantoms showed that the mean prediction error at, e.g., 785 nm was 2.8% for the absorption coefficient and 1.3% for the reduced scattering coefficient. The errors are relative to the range of the optical properties of the phantoms at 785 nm, which were 0-0.3/cm for the absorption coefficient and 6-16/cm for the reduced scattering coefficient. Finally, we also present and discuss results from preliminary skin tissue measurements.

  7. REAL TIME CONTINUOUS MEASUREMENTS OF [CO2] AND δ13C AT MULTIPLE LOCATIONS USING CAVITY ENHANCED LASER ABSORPTION

    NASA Astrophysics Data System (ADS)

    McAlexander, W. I.; Rau, G. H.; Dobeck, L.; Spangler, L.

    2009-12-01

    A commercial instrument (Los Gatos Research, model 908-0003) utilizing Cavity Enhanced Laser Absorption Spectroscopy was deployed in 2009 at the ZERT carbon release site (Bozeman, MT) for real time measurement of above-ground CO2 concentration and isotope ratio (δ13C). An automated switching system sampled 13 different locations in the field, as well as two known references, over an 8 day period. Real-time Keeling plots were constructed showing distinct signatures of soil (-27.0 ‰) and fossil (-56.0 ‰) sources compared to background air (-8.2 ‰). Instrument performance gave 0.2 ‰ precision with only 100 seconds of averaging per inlet. Sequential sampling of the various inlets gave a temporal and physical mapping of the CO2 release plume that is difficult to obtain using more conventional techniques. The figures show the nature and quality of the data from one of the locations. Details concerning instrument performance, systematics, calibration, and data processing will be discussed. Fig1: Time chart of CO2 concentration and isotope ratio δ13C from one of 13 sample inlet locations at ZERT release field, July, 2009. Fig2: Keeling plot of data from Fig1 illustrating the two source mixing of soil (-27 ‰) and fossil (-56 ‰) CO2 with background air.

  8. Molecular genetic analysis of the Phaseolus vulgaris P locus

    USDA-ARS?s Scientific Manuscript database

    Common bean market classes are distinguished by their many seed colors, patterns, and size. At least 23 genes, acting independently or in an epistatic manner, affect the seed coat color and pattern. The P locus which is described as the “ground factor” by Emerson, has multiple alleles and controls a...

  9. A Real-Time High Performance Computation Architecture for Multiple Moving Target Tracking Based on Wide-Area Motion Imagery via Cloud and Graphic Processing Units

    PubMed Central

    Liu, Kui; Wei, Sixiao; Chen, Zhijiang; Jia, Bin; Chen, Genshe; Ling, Haibin; Sheaff, Carolyn; Blasch, Erik

    2017-01-01

    This paper presents the first attempt at combining Cloud with Graphic Processing Units (GPUs) in a complementary manner within the framework of a real-time high performance computation architecture for the application of detecting and tracking multiple moving targets based on Wide Area Motion Imagery (WAMI). More specifically, the GPU and Cloud Moving Target Tracking (GC-MTT) system applied a front-end web based server to perform the interaction with Hadoop and highly parallelized computation functions based on the Compute Unified Device Architecture (CUDA©). The introduced multiple moving target detection and tracking method can be extended to other applications such as pedestrian tracking, group tracking, and Patterns of Life (PoL) analysis. The cloud and GPUs based computing provides an efficient real-time target recognition and tracking approach as compared to methods when the work flow is applied using only central processing units (CPUs). The simultaneous tracking and recognition results demonstrate that a GC-MTT based approach provides drastically improved tracking with low frame rates over realistic conditions. PMID:28208684

  10. Real-world treatment patterns and associated progression-free survival in relapsed/refractory multiple myeloma among US community oncology practices.

    PubMed

    Jagannath, Sundar; Roy, Anuja; Kish, Jonathan; Lunacsek, Orsolya; Globe, Denise; Eaddy, Michael; Kuriakose, Emil T; Willey, Joanne; Butler-Bird, Stephanie; Siegel, David

    2016-07-01

    Evidence supporting optimal treatment sequencing in relapsed/refractory multiple myeloma (RRMM) patients requiring multiple therapy lines is lacking. Using retrospective chart data, this study describes real-world RRMM treatment patterns and related progression-free survival (PFS) in US community oncology clinics. Bortezomib ± a non-immunomodulatory drug (IMiD), lenalidomide ± a non-proteasome inhibitor (PI), bortezomib + an IMiD were the most commonly used regimens in early lines of therapy. Median PFS was similar in 1(st) (11.1 months) and 2(nd) line (10.5) and decreased in lines 3 through 5 (3(rd): 7.9; 4(th): 7.2, 5(th): 5.4). Longest PFS (12.5 months) in first line was with bortezomib + ImiD; longest PFS in second line was with lenalidomide ± a non-PI was (13.2 months). Re-treatment with bortezomib was common; novel agents were reserved for later therapy lines. Overall, the observed PFS associated with real-world treatment sequences were shorter than those reported in clinical trials.

  11. A Real-Time High Performance Computation Architecture for Multiple Moving Target Tracking Based on Wide-Area Motion Imagery via Cloud and Graphic Processing Units.

    PubMed

    Liu, Kui; Wei, Sixiao; Chen, Zhijiang; Jia, Bin; Chen, Genshe; Ling, Haibin; Sheaff, Carolyn; Blasch, Erik

    2017-02-12

    This paper presents the first attempt at combining Cloud with Graphic Processing Units (GPUs) in a complementary manner within the framework of a real-time high performance computation architecture for the application of detecting and tracking multiple moving targets based on Wide Area Motion Imagery (WAMI). More specifically, the GPU and Cloud Moving Target Tracking (GC-MTT) system applied a front-end web based server to perform the interaction with Hadoop and highly parallelized computation functions based on the Compute Unified Device Architecture (CUDA©). The introduced multiple moving target detection and tracking method can be extended to other applications such as pedestrian tracking, group tracking, and Patterns of Life (PoL) analysis. The cloud and GPUs based computing provides an efficient real-time target recognition and tracking approach as compared to methods when the work flow is applied using only central processing units (CPUs). The simultaneous tracking and recognition results demonstrate that a GC-MTT based approach provides drastically improved tracking with low frame rates over realistic conditions.

  12. The clinical impact of thalidomide maintenance after autologous stem cell transplantation in patients with newly diagnosed multiple myeloma in real clinical practice of Korea.

    PubMed

    Lee, Ho Sup; Min, Chang-Ki; Lee, Je-Jung; Kim, Kihyun; Kim, Seok Jin; Yoon, Dok Hyun; Eom, Hyeon-Seok; Lee, Hyewon; Lee, Won Sik; Shin, Ho-Jin; Lee, Ji Hyun; Park, Yong; Jo, Jae-Cheol; Do, Young Rok; Mun, Yeung-Chul; Lee, Mark Hong

    2016-05-01

    In real clinical settings (not clinical trials), thalidomide has been accepted as maintenance therapy to patients with multiple myeloma (MM) because of the cost of drugs, the limitations of medical insurance, etc., in our country (South Korea). The purpose of this study was to evaluate the utility of thalidomide maintenance for improving survival in transplantation-eligible patients with MM in the real clinical field. Differences in survival rates were estimated in patients treated with or without thalidomide maintenance. The 3-year progression-free survival rates (PFS) of patients with and without maintenance, respectively, were 55.4 and 37.2 % (p = 0.005). The 3-year overall survival rates (OS) were 88.0 and 84.0 % (p = 0.105). No difference in 3-year OS after relapse or progression (OS2) was observed between the two groups (50.4 and 55.3 %, p = 0.661). The 3-year PFS of patients with and without maintenance therapy who had shown less than CR after ASCT were 68.4 and 23.3 % (p < 0.001). In conclusion, Thalidomide maintenance therapy showed longer PFS in real clinical practice, and long-term use of thalidomide did not interfere with the efficacy of salvage chemotherapy in patients who experienced progression or relapse after ASCT. In addition, thalidomide maintenance might be also useful for patients who have shown less than CR after ASCT.

  13. Real-time qPCR is a powerful assay to estimate the 171 R/Q alleles at the PrP locus directly in a flock's raw milk: a comparison with the targeted next-generation sequencing.

    PubMed

    Feligini, Maria; Bongioni, Graziella; Brambati, Eva; Amadesi, Alessandra; Cambuli, Caterina; Panelli, Simona; Bonacina, Cesare; Galli, Andrea

    2014-10-01

    The hazard to human health represented by transmissible spongiform encephalopathies in sheep is one of the major reasons for implementing the genetic selection plan to break down prion diseases. The problem is particularly important because of the risk of disease transmission from ewe to lamb via milk or colostrum. In order to establish an active and convenient monitoring of the flocks already undergone genetic selection and thus, indirectly increase consumers' security, the challenge of the work was quantifying the classical scrapie risk in bulk milk. A new quantitative real-time PCR assay for the estimation of the 171 R and Q allelic frequencies in a DNA pool representative of all the lactating ewes present in a flock was optimized and validated "in field". The repeatability range was 3.69-5.27 for R and 4.20-5.75 for Q. The ruggedness of the allele frequencies resulted 4.26 for R and 4.77 for Q. Regarding the validation "in field", none of the considered sources of variability (flock, month, number of genotyped animals and somatic cell count) showed a significant effect on flock and milk at the linear model. The targeted next-generation sequencing was also tested to evaluate its applicability in this context. Results show that the real-time PCR assay could represent a valid tool for the determination of 171 R/Q allele frequencies in bulk milk. The implementation of a service for breeder self-control along the production chain would aim to increase the production of high-security dairy products, while monitoring over time of the effects of genetic selection in the flocks.

  14. Locus-specific view of flax domestication history

    PubMed Central

    Fu, Yong-Bi; Diederichsen, Axel; Allaby, Robin G

    2012-01-01

    Crop domestication has been inferred genetically from neutral markers and increasingly from specific domestication-associated loci. However, some crops are utilized for multiple purposes that may or may not be reflected in a single domestication-associated locus. One such example is cultivated flax (Linum usitatissimum L.), the earliest oil and fiber crop, for which domestication history remains poorly understood. Oil composition of cultivated flax and pale flax (L. bienne Mill.) indicates that the sad2 locus is a candidate domestication locus associated with increased unsaturated fatty acid production in cultivated flax. A phylogenetic analysis of the sad2 locus in 43 pale and 70 cultivated flax accessions established a complex domestication history for flax that has not been observed previously. The analysis supports an early, independent domestication of a primitive flax lineage, in which the loss of seed dispersal through capsular indehiscence was not established, but increased oil content was likely occurred. A subsequent flax domestication process occurred that probably involved multiple domestications and includes lineages that contain oil, fiber, and winter varieties. In agreement with previous studies, oil rather than fiber varieties occupy basal phylogenetic positions. The data support multiple paths of flax domestication for oil-associated traits before selection of the other domestication-associated traits of seed dispersal loss and fiber production. The sad2 locus is less revealing about the origin of winter tolerance. In this case, a single domestication-associated locus is informative about the history of domesticated forms with the associated trait while partially informative on forms less associated with the trait. PMID:22408732

  15. Quantitative and qualitative analyses of under-balcony acoustics with real and simulated arrays of multiple sources

    NASA Astrophysics Data System (ADS)

    Kwon, Youngmin

    The objective of this study was to quantitatively and qualitatively identify the acoustics of the under-balcony areas in music performance halls under realistic conditions that are close to an orchestral performance in consideration of multiple music instrumental sources and their diverse sound propagation patterns. The study executed monaural and binaural impulse response measurements with an array of sixteen directional sources (loudspeakers) for acoustical assessments. Actual measurements in a performance hall as well as computer simulations were conducted for the quantitative assessments. Psycho-acoustical listening tests were conducted for the qualitative assessments using the music signals binaurally recorded in the hall with the same source array. The results obtained from the multiple directional source tests were analyzed by comparing them to those obtained from the tests performed with a single omni-directional source. These two sets of results obtained in the under-balcony area were also compared to those obtained in the main orchestra area. The quantitative results showed that the use of a single source conforming to conventional measurement protocol seems to be competent for measurements of the room acoustical parameters such as EDTmid, RTmid, C80500-2k, IACCE3 and IACCL3. These quantitative measures, however, did not always agree with the results of the qualitative assessments. The primary reason is that, in many other acoustical analysis respects, the acoustical phenomena shown from the multiple source measurements were not similar to those shown from the single source measurements. Remarkable differences were observed in time-domain impulse responses, frequency content, spectral distribution, directional distribution of the early reflections, and in sound energy density over time. Therefore, the room acoustical parameters alone should not be the acoustical representative characterizing a performance hall or a specific area such as the under

  16. The development of online real-time multiple-source moment tensor inversion technique for moderate-to-large earthquakes in Taiwan

    NASA Astrophysics Data System (ADS)

    Yeh, T.; Lee, S.; Ma, K.

    2013-12-01

    The point-source parameters of earthquake with small-to-moderate size (Mw<6.5) had shown can be automatically determined by Real-time Moment Tensor monitoring system (RMT) in Taiwan using pre-calculated grid-based Green's functions database. To resolve the dominant attribute in rupture processes for events involving more complexities (multiple sub-events, variation in focal mechanism...etc), especially those with greater sizes (Mw>6.5), we propose a multiple-source moment tensor inversion technique. Frequency band used in this inversion procedure is magnitude adopted. The number of sub-events increases successively where source locations and time delays are optimized. We evaluate the statistical significance of misfit reduction due to every inclusion of extra sub-event by analyzing the residual of current model with respect to the previous model using less number of sub-events. Process stops when the misfit fails to be reduced significantly by including extra sub-events. We perform several synthetic tests to examine the resolvability and limitation of this approach. Results suggest that locations, time delays, and focal mechanisms can be well resolved even with limited station coverage. Four significant earthquakes, occurred in Taiwan are chosen as case studies, including the 20020331 Mw 7.1 Northeastern earthquake, the 20031210 Chengkung Mw 6.8 earthquake, the 20061226 Mw 7.1 Pingtung earthquake, and the 19990920 Mw 7.6 Chi-Chi earthquake. The multiple-source model yields simple and robust determination of complex seismic source features. Sub-events determined through the proposed technique are also compared with asperities derived in finite-fault models. By taking advantage of real-time determination in overall feature of seismic sources, this approach provides a better assessment in the following hazard mitigation. Alternatively, the space-time relations and focal mechanisms of sub-events can also provide additional constraints in determination of the ruptured

  17. Cognitive functioning correlates of self-esteem and health locus of control in schizophrenia

    PubMed Central

    Wang, Chien-Shu; Wu, Jo Yung-Wei; Chang, Wei-Chung; Chuang, Shu-Ping

    2013-01-01

    Aim The study aimed to investigate the relationship among sociodemographic factors, neurocognitive factors, self-esteem, and health locus of control in patients diagnosed with schizophrenia. We examined the self-esteem, internal health locus of control, and external health locus of control through sociodemographic and neurocognitive factors. Methods Forty-six schizophrenic patients and 31 healthy residents from the community or hospital were recruited as the control group. All subjects participated in the self-esteem questionnaire, health locus of control questionnaire, and a series of neuropychological measures. Results Multiple regression analysis revealed that inhibition of attention and external health locus of control were predictors for self-esteem (r=−0.30, P<0.05; r=0.41, P<0.01); inhibition of attention and external health locus of control were contributors for internal health locus of control (r=−0.43, P<0.01; r=0.61, P<0.001); and education was related to external health locus of control (r=−0.31, P<0.05). Conclusion The current study integrated background characteristics and cognitive function to better understand the impact of self-esteem and health locus of control in schizophrenia. The findings indicated that inhibition of attention, external health locus of control, and education contributed to self-esteem, internal health locus of control and external health locus of control. However, the overall predicted variance accounted for by these predictors was small; thus, further research is necessary to examine imperative variables related with self-esteem and health locus of control in schizophrenia. PMID:24194641

  18. Self-regulating positive emotion networks by feedback of multiple emotional brain states using real-time fMRI.

    PubMed

    Li, Zhonglin; Tong, Li; Wang, Linyuan; Li, Yongli; He, Wenjie; Guan, Min; Yan, Bin

    2016-12-01

    Disordered emotion regulation may affect work efficiency, induce social disharmony, and even cause psychiatric diseases. Despite recent neurocomputing advances, whether positive and negative emotion networks can be voluntarily modulated is still unknown. In the present study, we addressed this question through multivariate voxel pattern analysis and real-time functional MRI neurofeedback (rtfMRI-nf). During a sustained emotion regulation task, participants' emotional states (positive or negative) were given to them as feedback. Participants were able to increase the percentage of positive emotional states, enhancing emotion regulation network activities. Participants showed an improvement on the positive subscale of positive and negative affect scale that came close to significance. Furthermore, the activation of several emotion-related brain regions, including insula, amygdala, anterior cingulate cortex, and dorsomedial prefrontal cortex, was also increased during rtfMRI-nf training. These findings suggest that humans are able to voluntarily modulate positive emotion networks, leading to exciting applications in the treatment of various neurological and psychiatric disorders.

  19. Tension versus ecological zones in a two-locus system.

    PubMed

    Hu, Xin-Sheng

    2005-08-01

    Previous theories show that tension and ecological zones are indistinguishable in terms of gene frequency clines. Here I analytically show that these two types of zones can be distinguished in terms of genetic statistics other than gene frequency. A two-locus cline model is examined with the assumptions of random mating, weak selection, no drift, no mutation, and multiplicative viabilities. The genetic statistics for distinguishing the two types of zones are the deviations of one- or two-locus genotypic frequencies from Hardy-Weinberg equilibrium (HWE) or from random association of gametes (RAG), and the deviations of additive and dominance variances from the values at HWE. These deviations have a discontinuous distribution in space and different extents of interruptions in the ecological zone with a sharp boundary, but exhibit a continuous distribution in the tension zone. Linkage disequilibrium enhances the difference between the deviations from HWE and from RAG for any two-locus genotypic frequency.

  20. [Study on preferred retinal locus].

    PubMed

    Dai, Bing-Fa; Hu, Jian-Min; Xu, Duan-Lian

    2012-03-01

    Preferred retinal locus (PRL) is always found in the age-related macular degeneration and other macular damages in patients with low vision, and it is a very important anatomic position in patients with central vision impairment to achieve the rehabilitation. In recent years, the training of preferred retinal locus (PRL) has become a research hotspot of low vision rehabilitation, it can clearly improve functional vision and quality of life. The authors reviewed relevant literatures, and summarized the definition, position, characteristics, training and clinical implications of the PRL.

  1. Rapid gist perception of meaningful real-life scenes: Exploring individual and gender differences in multiple categorization tasks.

    PubMed

    Vanmarcke, Steven; Wagemans, Johan

    2015-01-01

    In everyday life, we are generally able to dynamically understand and adapt to socially (ir)elevant encounters, and to make appropriate decisions about these. All of this requires an impressive ability to directly filter and obtain the most informative aspects of a complex visual scene. Such rapid gist perception can be assessed in multiple ways. In the ultrafast categorization paradigm developed by Simon Thorpe et al. (1996), participants get a clear categorization task in advance and succeed at detecting the target object of interest (animal) almost perfectly (even with 20 ms exposures). Since this pioneering work, follow-up studies consistently reported population-level reaction time differences on different categorization tasks, indicating a superordinate advantage (animal versus dog) and effects of perceptual similarity (animals versus vehicles) and object category size (natural versus animal versus dog). In this study, we replicated and extended these separate findings by using a systematic collection of different categorization tasks (varying in presentation time, task demands, and stimuli) and focusing on individual differences in terms of e.g., gender and intelligence. In addition to replicating the main findings from the literature, we find subtle, yet consistent gender differences (women faster than men).

  2. A comparison of machine learning methods for classification using simulation with multiple real data examples from mental health studies.

    PubMed

    Khondoker, Mizanur; Dobson, Richard; Skirrow, Caroline; Simmons, Andrew; Stahl, Daniel

    2016-10-01

    Recent literature on the comparison of machine learning methods has raised questions about the neutrality, unbiasedness and utility of many comparative studies. Reporting of results on favourable datasets and sampling error in the estimated performance measures based on single samples are thought to be the major sources of bias in such comparisons. Better performance in one or a few instances does not necessarily imply so on an average or on a population level and simulation studies may be a better alternative for objectively comparing the performances of machine learning algorithms. We compare the classification performance of a number of important and widely used machine learning algorithms, namely the Random Forests (RF), Support Vector Machines (SVM), Linear Discriminant Analysis (LDA) and k-Nearest Neighbour (kNN). Using massively parallel processing on high-performance supercomputers, we compare the generalisation errors at various combinations of levels of several factors: number of features, training sample size, biological variation, experimental variation, effect size, replication and correlation between features. For smaller number of correlated features, number of features not exceeding approximately half the sample size, LDA was found to be the method of choice in terms of average generalisation errors as well as stability (precision) of error estimates. SVM (with RBF kernel) outperforms LDA as well as RF and kNN by a clear margin as the feature set gets larger provided the sample size is not too small (at least 20). The performance of kNN also improves as the number of features grows and outplays that of LDA and RF unless the data variability is too high and/or effect sizes are too small. RF was found to outperform only kNN in some instances where the data are more variable and have smaller effect sizes, in which cases it also provide more stable error estimates than kNN and LDA. Applications to a number of real datasets supported the findings from

  3. Making Quality Improvement Happen in the Real World: Building Capability and Improving Multiple Projects at the Same Time.

    PubMed

    Daniel, Malcolm; Puxty, Alex; Miles, Barbara

    2016-01-01

    Improving work as part of clinical practice is challenging. Plans for improvement are often made, but not followed through. A recent experience of failure in an ICU led to a change in approach. Members of the multi-professional team committed to meet weekly to learn about quality improvement by working on improvement projects. The group selected four topics they wanted to work on. These were: a bundle for patients admitted with septic shock; early (≤4 hours) sedation vacation after admission to ICU to allow titration of sedation to effect; achieving ≥ 20 minutes of mobilisation per day in ventilated patients; and medicines reconciliation. This quality improvement meeting was built into another regular weekly meeting. Initially the meeting ran for 30 minutes; each week some focused quality improvement teaching was provided in addition to talking about each individual project. The team found the meeting useful, they saw the progress they were making but felt the allotted time was too short. After 6 weeks, the initial early results persuaded the team to increase the duration of this meeting to 45 minutes. At the start reliability of each process was low (between 10% and 38%). All four projects achieved their stated process reliability aim. This took between 165 and 334 days for each project. Many tests of change ideas were required to achieve this. We have been able to improve multiple topics in a short period and produce sustainable change. The weekly meeting provided the focus to this improvement work. The teaching and coaching on quality improvement methodology that occurred as part of this meeting helped accelerate our rate of progress. We believe this experience and the learning we have gained will help provide ideas for others who also want to improve healthcare delivery in different settings.

  4. Development of multiple-locus variable-number tandem-repeat analysis for rapid genotyping of Ehrlichia ruminantium and its application to infected Amblyomma variegatum collected in heartwater endemic areas in Uganda.

    PubMed

    Nakao, Ryo; Morrison, Liam J; Zhou, Lijia; Magona, Joseph W; Jongejan, Frans; Sugimoto, Chihiro

    2012-01-01

    The rickettsial bacterium Ehrlichia ruminantium is the causative agent of heartwater, a serious tick-borne disease in ruminants. The genetic diversity of organisms in the field will have implications for cross-protective capacities of any vaccine developed, and for an effective vaccine design strategy proper genotyping and understanding of existing genetic diversity in the field is necessary. We searched for variable-number tandem-repeat (VNTR) loci for use in a multi-locus VNTR analysis (MLVA). Sequencing analysis of 30 potential VNTRs using a panel of 17 reference strains from geographically diverse origins identified 12 VNTRs with allelic profiles differing between strains. Application of MLVA to 38 E. ruminantium-infected Amblyomma variegatum collected from indigenous cattle in 6 different districts of Uganda identified 21 MLVA types. The discriminatory power of MLVA was greater than that of map1 PCR-restriction fragment length polymorphism analysis, with which only 6 genotypes were obtained. The high discriminatory power as well as cost- effective performance of MLVA provide the potential for this technique to be applied in the future with respect to optimizing vaccine trials by identifying local strain diversity, and also raise the possibility of exploring the association between E. ruminantium genotypes and phenotypes such as pathological outcome in the ruminant host.

  5. Real-Time Expression Analysis of Selected Anticarsia gemmatalis multiple nucleopolyhedrovirus Gene Promoters during Infection of Permissive, Semipermissive and Nonpermissive Cell Lines.

    PubMed

    Morgado, Fabricio da Silva; Ardisson-Araújo, Daniel Mendes Pereira; Ribeiro, Bergmann Morais

    2017-06-01

    Baculovirus infection follows a transcriptionally controlled sequence of gene expression that occurs by activation of different viral gene promoter sequences during infection. This sequence of promoter activation may be disrupted by cellular defenses against viral infection, which might interfere with viral progeny formation. In this work, the activity of the ie1, gp64, lef-1, vp39, p6.9 and polh promoters of the Anticarsia gemmatalis multiple nucleopolyhedrovirus was assessed during infection of permissive, semipermissive and nonpermissive cell lines by a novel methodology that detects reporter protein luminescence in real-time. This technique allowed us to characterize in rich detail the AgMNPV promoters in permissive cell lines and revealed differential profiles of expression in cells with limited permissivity that correlate well with limitations in viral DNA replication. Semipermissive and nonpermissive cell lines presented delays and restrictions in late and very late promoter expression. Cells undergoing apoptosis did not inhibit late gene expression; however, viral progeny formation is severely affected. This work demonstrates the application of the real-time luminescence detection methodology and how the promoter expression profile may be used to diagnose cellular permissivity to baculovirus infection.

  6. Real-World Safety and Patient Profile of Fingolimod in Relapsing-Remitting Multiple Sclerosis: A Prospective Analysis in Buenos Aires, Argentina.

    PubMed

    Rojas, Juan Ignacio; Patrucco, Liliana; Miguez, Jimena; Cristiano, Edgardo

    2017-10-02

    The aim was to evaluate fingolimod safety and patient profiles in a real-world setting in Buenos Aires, Argentina. Relapsing-remitting patients with multiple sclerosis who had been prescribed fingolimod and at least 18 months or more of follow-up were included. Demographic, clinical, and safety issues were described during first dose and follow-up. A total of 145 patients were included, 68% female; mean age, 30 ± 10.5 years; mean disease duration, 6.5 ± 3.1 years; mean fingolimod use, 25 ± 13 months. Eleven patients (7.6%) discontinued fingolimod (7 owing to disease activity/4 owing to desire of pregnancy and personal decisions). Forty-two percent of patients experienced adverse events: headache, fatigue, liver enzyme elevation, and lymphopenia were the most commonly found. No serious cardiac event was reported during the first dose. The safety and patient profile of fingolimod in a new real-world setting were consistent with information provided from phase III clinical trials.

  7. Real-Time Expression Analysis of Selected Anticarsia gemmatalis multiple nucleopolyhedrovirus Gene Promoters during Infection of Permissive, Semipermissive and Nonpermissive Cell Lines

    PubMed Central

    Morgado, Fabricio da Silva; Ardisson-Araújo, Daniel Mendes Pereira; Ribeiro, Bergmann Morais

    2017-01-01

    Baculovirus infection follows a transcriptionally controlled sequence of gene expression that occurs by activation of different viral gene promoter sequences during infection. This sequence of promoter activation may be disrupted by cellular defenses against viral infection, which might interfere with viral progeny formation. In this work, the activity of the ie1, gp64, lef-1, vp39, p6.9 and polh promoters of the Anticarsia gemmatalis multiple nucleopolyhedrovirus was assessed during infection of permissive, semipermissive and nonpermissive cell lines by a novel methodology that detects reporter protein luminescence in real-time. This technique allowed us to characterize in rich detail the AgMNPV promoters in permissive cell lines and revealed differential profiles of expression in cells with limited permissivity that correlate well with limitations in viral DNA replication. Semipermissive and nonpermissive cell lines presented delays and restrictions in late and very late promoter expression. Cells undergoing apoptosis did not inhibit late gene expression; however, viral progeny formation is severely affected. This work demonstrates the application of the real-time luminescence detection methodology and how the promoter expression profile may be used to diagnose cellular permissivity to baculovirus infection. PMID:28587184

  8. External locus of control contributes to racial disparities in memory and reasoning training gains in ACTIVE.

    PubMed

    Zahodne, Laura B; Meyer, Oanh L; Choi, Eunhee; Thomas, Michael L; Willis, Sherry L; Marsiske, Michael; Gross, Alden L; Rebok, George W; Parisi, Jeanine M

    2015-09-01

    Racial disparities in cognitive outcomes may be partly explained by differences in locus of control. African Americans report more external locus of control than non-Hispanic Whites, and external locus of control is associated with poorer health and cognition. The aims of this study were to compare cognitive training gains between African American and non-Hispanic White participants in the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) study and determine whether racial differences in training gains are mediated by locus of control. The sample comprised 2,062 (26% African American) adults aged 65 and older who participated in memory, reasoning, or speed training. Latent growth curve models evaluated predictors of 10-year cognitive trajectories separately by training group. Multiple group modeling examined associations between training gains and locus of control across racial groups. Compared to non-Hispanic Whites, African Americans evidenced less improvement in memory and reasoning performance after training. These effects were partially mediated by locus of control, controlling for age, sex, education, health, depression, testing site, and initial cognitive ability. African Americans reported more external locus of control, which was associated with smaller training gains. External locus of control also had a stronger negative association with reasoning training gain for African Americans than for Whites. No racial difference in training gain was identified for speed training. Future intervention research with African Americans should test whether explicitly targeting external locus of control leads to greater cognitive improvement following cognitive training.

  9. External locus of control contributes to racial disparities in memory and reasoning training gains in ACTIVE

    PubMed Central

    Zahodne, Laura B.; Meyer, Oanh L.; Choi, Eunhee; Thomas, Michael L.; Willis, Sherry L.; Marsiske, Michael; Gross, Alden L.; Rebok, George W.; Parisi, Jeanine M.

    2015-01-01

    Racial disparities in cognitive outcomes may be partly explained by differences in locus of control. African Americans report more external locus of control than non-Hispanic Whites, and external locus of control is associated with poorer health and cognition. The aims of this study were to compare cognitive training gains between African American and non-Hispanic White participants in the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) study and determine whether racial differences in training gains are mediated by locus of control. The sample comprised 2,062 (26% African American) adults aged 65 and older who participated in memory, reasoning, or speed training. Latent growth curve models evaluated predictors of 10-year cognitive trajectories separately by training group. Multiple group modeling examined associations between training gains and locus of control across racial groups. Compared to non-Hispanic Whites, African Americans evidenced less improvement in memory and reasoning performance after training. These effects were partially mediated by locus of control, controlling for age, sex, education, health, depression, testing site, and initial cognitive ability. African Americans reported more external locus of control, which was associated with smaller training gains. External locus of control also had a stronger negative association with reasoning training gain for African Americans than for Whites. No racial difference in training gain was identified for speed training. Future intervention research with African Americans should test whether explicitly targeting external locus of control leads to greater cognitive improvement following cognitive training. PMID:26237116

  10. Inside the CBF locus in Poaceae.

    PubMed

    Tondelli, Alessandro; Francia, Enrico; Barabaschi, Delfina; Pasquariello, Marianna; Pecchioni, Nicola

    2011-01-01

    Several molecular evidences have been gathered in Poaceae that point out a central role of the CBF/DREB1 transcription factors in the signal transduction pathways leading to low-temperature tolerance, although to a quite different extent between crops originating from either temperate or tropical climates. A common feature of the CBF/DREB1 genes in Poaceae is their structural organization at the genome level in clusters of tandemly duplicated genes. In temperate cereals such as barley and wheat, expansion of specific multigene phylogenetic clades of CBFs that map at the Frost Resistance-2 locus has been exclusively observed. In addition, copy number variants of CBF genes between frost resistant and frost sensitive genotypes raise the question if multiple copies of the CBF/DREB1s are required to ensure freezing tolerance. On the other hand, in crops of tropical origin such as rice and maize, a smaller or less-responsive CBF regulon may have evolved, and different mechanisms might determine chilling tolerance. In this review, recent advances on the organization and diversity at the CBF cluster locus in the grasses are provided and discussed. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  11. Locus of Control and Delinquency.

    ERIC Educational Resources Information Center

    Parrott, C. A.; Strongman, K. T.

    1984-01-01

    Assessed delinquent and nondelinquent male adolescents (N=43) on locus of control and intellectual achievement responsibilty. Results supported a multidimensional model. There was no difference in expectancy of control for negative academic events between delinquents and nondelinquents. Birth order and delinquency were the most important…

  12. Locus of Control and Socialization.

    ERIC Educational Resources Information Center

    Raine, Adrian; And Others

    1982-01-01

    Predicted that an external locus of control would characterize undersocialization. Tested this hypothesis on a random sample of secondary school children (N=97). Scores from the Child Nowicki-Strickland Internal-External Scale were found to predict undersocialization in the expected direction. Suggested several possible interpretations of this…

  13. Prototype Demonstration of Gamma- Blind Tensioned Metastable Fluid Neutron/Multiplicity/Alpha Detector – Real Time Methods for Advanced Fuel Cycle Applications

    SciTech Connect

    McDeavitt, Sean M.

    2016-12-20

    The content of this report summarizes a multi-year effort to develop prototype detection equipment using the Tensioned Metastable Fluid Detector (TMFD) technology developed by Taleyarkhan [1]. The context of this development effort was to create new methods for evaluating and developing advanced methods for safeguarding nuclear materials along with instrumentation in various stages of the fuel cycle, especially in material balance areas (MBAs) and during reprocessing of used nuclear fuel. One of the challenges related to the implementation of any type of MBA and/or reprocessing technology (e.g., PUREX or UREX) is the real-time quantification and control of the transuranic (TRU) isotopes as they move through the process. Monitoring of higher actinides from their neutron emission (including multiplicity) and alpha signatures during transit in MBAs and in aqueous separations is a critical research area. By providing on-line real-time materials accountability, diversion of the materials becomes much more difficult. The Tensioned Metastable Fluid Detector (TMFD) is a transformational technology that is uniquely capable of both alpha and neutron spectroscopy while being “blind” to the intense gamma field that typically accompanies used fuel – simultaneously with the ability to provide multiplicity information as well [1-3]. The TMFD technology was proven (lab-scale) as part of a 2008 NERI-C program [1-7]. The bulk of this report describes the advancements and demonstrations made in TMFD technology. One final point to present before turning to the TMFD demonstrations is the context for discussing real-time monitoring of SNM. It is useful to review the spectrum of isotopes generated within nuclear fuel during reactor operations. Used nuclear fuel (UNF) from a light water reactor (LWR) contains fission products as well as TRU elements formed through neutron absorption/decay chains. The majority of the fission products are gamma and beta emitters and they represent the

  14. High-risk human papillomavirus infection involving multiple anatomic sites of the female lower genital tract: a multiplex real-time polymerase chain reaction-based study.

    PubMed

    Hui, Yiang; Manna, Pradip; Ou, Joyce J; Kerley, Spencer; Zhang, Cunxian; Sung, C James; Lawrence, W Dwayne; Quddus, M Ruhul

    2015-09-01

    High-risk human papillomavirus infection usually is seen at one anatomic site in an individual. Rarely, infection at multiple anatomic sites of the female lower genital tract in the same individual is encountered either simultaneously and/or at a later date. The current study identifies the various subtypes of high-risk human papillomavirus infection in these scenarios and analyzes the potential significance of these findings. High-risk human papillomavirus infection involving 22 anatomic sites from 7 individuals was identified after institutional review board approval. Residual paraffin-embedded tissue samples were retrieved, and all 15 high-risk human papillomavirus were identified and viral load quantified using multiplex real-time polymerase chain reaction-based method. Multiple high-risk human papillomavirus subtypes were identified in 32% of the samples and as many as 5 different subtypes of high-risk human papillomavirus infection in a single anatomic site. In general, each anatomic site has unique combination of viral subtypes, although one individual showed overlapping subtypes in the vagina, cervix, and vulvar samples. Higher viral load and rare subtypes are more frequent in younger patients and in dysplasia compared with carcinoma. Follow-up ranging from 3 to 84 months revealed persistent high-risk human papillomavirus infection in 60% of cases. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Locus of Control and Interpersonal Attraction.

    ERIC Educational Resources Information Center

    Fagan, M. Michael

    1980-01-01

    The role of locus of control in interpersonal attraction was examined by administering 1) the Nowicki-Strickland Locus of Control Scale and 2) a sociometric test of friendship to 200 eighth graders. (CM)

  16. Locus of Control and Status Attainment.

    ERIC Educational Resources Information Center

    Bensman, Miriam Roza; Haller, Archibald O.

    Utilizing data derived from 277 rural, male respondents initially enrolled in Lenawee County, Michigan high schools, the Rotter's Internal-External Locus of Control Scale was employed to test the hypothesis that locus of control will have interactive rather than additive effects on the process of status attainment. Locus of control was defined as…

  17. Which Sry locus is the hypertensive Y chromosome locus?

    PubMed

    Turner, Monte E; Farkas, Joel; Dunmire, Jeff; Ely, Daniel; Milsted, Amy

    2009-02-01

    The Y chromosome of the spontaneously hypertensive rat (SHR) contains a genetic component that raises blood pressure compared with the Wistar-Kyoto (WKY) Y chromosome. This research tests the Sry gene complex as the hypertensive component of the SHR Y chromosome. The Sry loci were sequenced in 1 strain with a hypertensive Y chromosome (SHR/Akr) and 2 strains with a normotensive Y chromosome (SHR/Crl and WKY/Akr). Both SHR strains have 7 Sry loci, whereas the WKY strain has 6. The 6 loci in common between SHR and WKY strains were identical in the sequence compared (coding region, 392-bp 5' prime flanking, 1200-bp 3' flanking). Both SHR strains have a locus (Sry3) not found in WKY rats, but this locus is different between SHR/Akr and SHR/Crl rats. Six mutations have accumulated in Sry3 between the SHR strains, whereas the other 6 Sry loci are identical. This pattern of an SHR-specific locus and mutation in this locus in SHR/Crl coinciding with the loss of Y chromosome hypertension is an expected pattern if Sry3 is the Y chromosome-hypertensive component. The SHR/y strain showed a significant increase in total Sry expression in the kidney between 4 and 15 weeks of age. There are significant differences in Sry expression between adrenal glands and the kidney (15 to 30 times higher in kidneys) but no significant differences between strains. These results, along with previous studies demonstrating an interaction of Sry with the tyrosine hydroxylase promoter and increased blood pressure with exogenous Sry expression, suggest the Sry loci as the hypertensive component of the SHR Y chromosome.

  18. Digital karyotyping reveals probable target genes at 7q21.3 locus in hepatocellular carcinoma

    PubMed Central

    2011-01-01

    Background Hepatocellular carcinoma (HCC) is a worldwide malignant liver tumor with high incidence in China. Subchromosomal amplifications and deletions accounted for major genomic alterations occurred in HCC. Digital karyotyping was an effective method for analyzing genome-wide chromosomal aberrations at high resolution. Methods A digital karyotyping library of HCC was constructed and 454 Genome Sequencer FLX System (Roche) was applied in large scale sequencing of the library. Digital Karyotyping Data Viewer software was used to analyze genomic amplifications and deletions. Genomic amplifications of genes detected by digital karyotyping were examined by real-time quantitative PCR. The mRNA expression level of these genes in tumorous and paired nontumorous tissues was also detected by real-time quantitative RT-PCR. Results A total of 821,252 genomic tags were obtained from the digital karyotyping library of HCC, with 529,162 tags (64%) mapped to unique loci of human genome. Multiple subchromosomal amplifications and deletions were detected through analyzing the digital karyotyping data, among which the amplification of 7q21.3 drew our special attention. Validation of genes harbored within amplicons at 7q21.3 locus revealed that genomic amplification of SGCE, PEG10, DYNC1I1 and SLC25A13 occurred in 11 (21%), 11 (21%), 11 (21%) and 23 (44%) of the 52 HCC samples respectively. Furthermore, the mRNA expression level of SGCE, PEG10 and DYNC1I1 were significantly up-regulated in tumorous liver tissues compared with corresponding nontumorous counterparts. Conclusions Our results indicated that subchromosomal region of 7q21.3 was amplified in HCC, and SGCE, PEG10 and DYNC1I1 were probable protooncogenes located within the 7q21.3 locus. PMID:21767414

  19. Digital karyotyping reveals probable target genes at 7q21.3 locus in hepatocellular carcinoma.

    PubMed

    Dong, Hui; Zhang, Hongyi; Liang, Jianping; Yan, Huadong; Chen, Yangyi; Shen, Yan; Kong, Yalin; Wang, Shengyue; Zhao, Guoping; Jin, Weirong

    2011-07-19

    Hepatocellular carcinoma (HCC) is a worldwide malignant liver tumor with high incidence in China. Subchromosomal amplifications and deletions accounted for major genomic alterations occurred in HCC. Digital karyotyping was an effective method for analyzing genome-wide chromosomal aberrations at high resolution. A digital karyotyping library of HCC was constructed and 454 Genome Sequencer FLX System (Roche) was applied in large scale sequencing of the library. Digital Karyotyping Data Viewer software was used to analyze genomic amplifications and deletions. Genomic amplifications of genes detected by digital karyotyping were examined by real-time quantitative PCR. The mRNA expression level of these genes in tumorous and paired nontumorous tissues was also detected by real-time quantitative RT-PCR. A total of 821,252 genomic tags were obtained from the digital karyotyping library of HCC, with 529,162 tags (64%) mapped to unique loci of human genome. Multiple subchromosomal amplifications and deletions were detected through analyzing the digital karyotyping data, among which the amplification of 7q21.3 drew our special attention. Validation of genes harbored within amplicons at 7q21.3 locus revealed that genomic amplification of SGCE, PEG10, DYNC1I1 and SLC25A13 occurred in 11 (21%), 11 (21%), 11 (21%) and 23 (44%) of the 52 HCC samples respectively. Furthermore, the mRNA expression level of SGCE, PEG10 and DYNC1I1 were significantly up-regulated in tumorous liver tissues compared with corresponding nontumorous counterparts. Our results indicated that subchromosomal region of 7q21.3 was amplified in HCC, and SGCE, PEG10 and DYNC1I1 were probable protooncogenes located within the 7q21.3 locus.

  20. Development of a rapid, sensitive TaqMan real-time RT-PCR assay for the detection of Rose rosette virus using multiple gene targets.

    PubMed

    Babu, Binoy; Jeyaprakash, Ayyamperumal; Jones, Debra; Schubert, Timothy S; Baker, Carlye; Washburn, Brian K; Miller, Steven H; Poduch, Kristina; Knox, Gary W; Ochoa-Corona, Francisco M; Paret, Mathews L

    2016-09-01

    Rose rosette virus (RRV), belonging to the genus Emaravirus, is a highly destructive pathogen that causes rose rosette disease. The disease is a major concern for the rose industry in the U.S. due to the lack of highly sensitive methods for early detection of RRV. This is critical, as early identification of the infected plants and eradication is necessary in minimizing the risks associated with the spread of the disease. A highly reliable, specific and sensitive detection assay is thus required to test and confirm the presence of RRV in suspected plant samples. In this study a TaqMan real-time reverse transcription-polymerase chain reaction (RT-PCR) assay was developed for the detection of RRV from infected roses, utilizing multiple gene targets. Four pairs of primers and probes; two of them (RRV_2-1 and RRV_2-2) based on the consensus sequences of the glycoprotein gene (RNA2) and the other two (RRV_3-2 and RRV_3-5) based on the nucleocapsid gene (RNA3) were designed. The specificity of the primers and probes was evaluated against other representative viruses infecting roses, belonging to the genera Alfamovirus, Cucumovirus, Ilarvirus, Nepovirus, Tobamovirus, and Tospovirus and one Emaravirus (Wheat mosaic virus). Dilution assays using the in vitro transcripts (spiked with total RNA from healthy plants, and non-spiked) showed that all the primers and probes are highly sensitive in consistently detecting RRV with a detection limit of 1 fg. Testing of the infected plants over a period of time (three times in monthly intervals) indicated high reproducibility, with the primer/probe RRV_3-5 showing 100% positive detection, while RRV_2-1, RRV_2-2 and RRV_3-2 showed 90% positive detection. The developed real-time RT-PCR assay is reliable, highly sensitive, and can be easily used in diagnostic laboratories for testing and confirmation of RRV.

  1. Alemtuzumab in the long-term treatment of relapsing-remitting multiple sclerosis: an update on the clinical trial evidence and data from the real world.

    PubMed

    Ziemssen, Tjalf; Thomas, Katja

    2017-10-01

    Alemtuzumab is a humanized monoclonal antibody approved for the treatment of relapsing-remitting multiple sclerosis (RRMS), given as two annual courses on five consecutive days at baseline and on three consecutive days 12 months later. Here we provide an update on the long-term efficacy and safety of alemtuzumab in RRMS, including real-world experience, and advances in our understanding of its mechanism of action. Recent data from the phase II/III extension study have demonstrated that alemtuzumab reduces relapse rates, disability worsening, and the rate of brain volume loss over the long term, with many patients achieving no evidence of disease activity. In high proportions of patients, preexisting disability remained stable or improved. Alemtuzumab is associated with a consistent safety profile over the long term, with no new safety signals emerging and the overall annual incidence of reported adverse events decreasing after the first year on treatment. Acyclovir prophylaxis reduces herpetic infections, and monitoring has been shown to mitigate the risk of autoimmune adverse events, allowing early detection and overall effective management. Data from clinical practice and ongoing observational studies are providing additional information on the real-world use of alemtuzumab. Recent evidence on the mechanism of action of alemtuzumab indicates that in addition to its previously known effects of inducing depletion and repopulation of T and B lymphocytes, it also results in a relative increase of cells with memory and regulatory phenotypes and a decrease in cells with a proinflammatory signature, and may further promote an immunoregulatory environment through an impact on other innate immune cells (e.g. dendritic cells) that play a role in MS. These effects may allow preservation of innate immunity and immunosurveillance. Together, these lines of evidence help explain the durable clinical efficacy of alemtuzumab, in the absence of continuous treatment, in patients

  2. Rapid and Sensitive Detection of Shigella spp. and Salmonella spp. by Multiple Endonuclease Restriction Real-Time Loop-Mediated Isothermal Amplification Technique

    PubMed Central

    Wang, Yi; Wang, Yan; Luo, Lijuan; Liu, Dongxin; Luo, Xia; Xu, Yanmei; Hu, Shoukui; Niu, Lina; Xu, Jianguo; Ye, Changyun

    2015-01-01

    Shigella and Salmonella are frequently isolated from various food samples and can cause human gastroenteritis. Here, a novel multiple endonuclease restriction real-time loop-mediated isothermal amplification technology (MERT-LAMP) were successfully established and validated for simultaneous detection of Shigella strains and Salmonella strains in only a single reaction. Two sets of MERT-LAMP primers for 2 kinds of pathogens were designed from ipaH gene of Shigella spp. and invA gene of Salmonella spp., respectively. Under the constant condition at 63°C, the positive results were yielded in as short as 12 min with the genomic DNA extracted from the 19 Shigella strains and 14 Salmonella strains, and the target pathogens present in a sample could be simultaneously identified based on distinct fluorescence curves in real-time format. Accordingly, the multiplex detection assay significantly reduced effort, materials and reagents used, and amplification and differentiation were conducted at the same time, obviating the use of postdetection procedures. The analytical sensitivity of MERT-LAMP was found to be 62.5 and 125 fg DNA/reaction with genomic templates of Shigella strains and Salmonella strains, which was consist with normal LAMP assay, and at least 10- and 100-fold more sensitive than that of qPCR and conventional PCR approaches. The limit of detection of MERT-LAMP for Shigella strains and Salmonella strains detection in artificially contaminated milk samples was 5.8 and 6.4 CFU per vessel. In conclusion, the MERT-LAMP methodology described here demonstrated a potential and valuable means for simultaneous screening of Shigella and Salmonella in a wide variety of samples. PMID:26697000

  3. Speaking rate effects on locus equation slope

    PubMed Central

    Berry, Jeff; Weismer, Gary

    2013-01-01

    A locus equation describes a 1st order regression fit to a scatter of vowel steady-state frequency values predicting vowel onset frequency values. Locus equation coefficients are often interpreted as indices of coarticulation. Speaking rate variations with a constant consonant–vowel form are thought to induce changes in the degree of coarticulation. In the current work, the hypothesis that locus slope is a transparent index of coarticulation is examined through the analysis of acoustic samples of large-scale, nearly continuous variations in speaking rate. Following the methodological conventions for locus equation derivation, data pooled across ten vowels yield locus equation slopes that are mostly consistent with the hypothesis that locus equations vary systematically with coarticulation. Comparable analyses between different four-vowel pools reveal variations in the locus slope range and changes in locus slope sensitivity to rate change. Analyses across rate but within vowels are substantially less consistent with the locus hypothesis. Taken together, these findings suggest that the practice of vowel pooling exerts a non-negligible influence on locus outcomes. Results are discussed within the context of articulatory accounts of locus equations and the effects of speaking rate change. PMID:24535890

  4. Speaking rate effects on locus equation slope.

    PubMed

    Berry, Jeff; Weismer, Gary

    2013-11-01

    A locus equation describes a 1st order regression fit to a scatter of vowel steady-state frequency values predicting vowel onset frequency values. Locus equation coefficients are often interpreted as indices of coarticulation. Speaking rate variations with a constant consonant-vowel form are thought to induce changes in the degree of coarticulation. In the current work, the hypothesis that locus slope is a transparent index of coarticulation is examined through the analysis of acoustic samples of large-scale, nearly continuous variations in speaking rate. Following the methodological conventions for locus equation derivation, data pooled across ten vowels yield locus equation slopes that are mostly consistent with the hypothesis that locus equations vary systematically with coarticulation. Comparable analyses between different four-vowel pools reveal variations in the locus slope range and changes in locus slope sensitivity to rate change. Analyses across rate but within vowels are substantially less consistent with the locus hypothesis. Taken together, these findings suggest that the practice of vowel pooling exerts a non-negligible influence on locus outcomes. Results are discussed within the context of articulatory accounts of locus equations and the effects of speaking rate change.

  5. Real-time multiplicity counter

    DOEpatents

    Rowland, Mark S [Alamo, CA; Alvarez, Raymond A [Berkeley, CA

    2010-07-13

    A neutron multi-detector array feeds pulses in parallel to individual inputs that are tied to individual bits in a digital word. Data is collected by loading a word at the individual bit level in parallel. The word is read at regular intervals, all bits simultaneously, to minimize latency. The electronics then pass the word to a number of storage locations for subsequent processing, thereby removing the front-end problem of pulse pileup.

  6. Optimization and evaluation of multiple gating beam delivery in a synchrotron-based proton beam scanning system using a real-time imaging technique.

    PubMed

    Yamada, Takahiro; Miyamoto, Naoki; Matsuura, Taeko; Takao, Seishin; Fujii, Yusuke; Matsuzaki, Yuka; Koyano, Hidenori; Umezawa, Masumi; Nihongi, Hideaki; Shimizu, Shinichi; Shirato, Hiroki; Umegaki, Kikuo

    2016-07-01

    To find the optimum parameter of a new beam control function installed in a synchrotron-based proton therapy system. A function enabling multiple gated irradiation in the flat top phase has been installed in a real-time-image gated proton beam therapy (RGPT) system. This function is realized by a waiting timer that monitors the elapsed time from the last gate-off signal in the flat top phase. The gated irradiation efficiency depends on the timer value, Tw. To find the optimum Tw value, gated irradiation efficiency was evaluated for each configurable Tw value. 271 gate signal data sets from 58 patients were used for the simulation. The highest mean efficiency 0.52 was obtained in TW=0.2s. The irradiation efficiency was approximately 21% higher than at TW=0s, which corresponds to ordinary synchrotron operation. The irradiation efficiency was improved in 154 (57%) of the 271 cases. The irradiation efficiency was reduced in 117 cases because the TW value was insufficient or the function introduced an unutilized wait time for the next gate-on signal in the flat top phase. In the actual treatment of a patient with a hepatic tumor at Tw=0.2s, 4.48GyE irradiation was completed within 250s. In contrast, the treatment time of ordinary synchrotron operation was estimated to be 420s. The results suggest that the multiple gated-irradiation function has potential to improve the gated irradiation efficiency and to reduce the treatment time. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  7. Recurrence risks for Bardet-Biedl syndrome: Implications of locus heterogeneity

    PubMed Central

    Sapp, Julie C.; Nishimura, Darryl; Johnston, Jennifer J.; Stone, Edwin M.; Héon, Elise; Sheffield, Val C.; Biesecker, Leslie G.

    2011-01-01

    Purpose Bardet-Biedl syndrome is a pleiotropic multiple anomaly syndrome inherited in an autosomal recessive pattern. It is now known that this disorder has locus heterogeneity, with causative mutations identified in as many as 14 genes. The aim of this study was to derive locus-specific recurrence risk estimates for family members of a proband affected with BBS. Methods Mutation data from 187 probands affected with BBS were used. The authors counted the relative proportion of families with mutations at each of ten loci and estimated locus-specific carrier rates for mutations using Hardy-Weinberg principles and an aggregate population frequency of 1/100,000 for the phenotype. Locus-specific recurrence risks were calculated for relatives of an affected proband. Results Locus-specific carrier frequencies range from 1/250 to 1/2200, and the risks for an offspring of the sibling of an affected individual range from 1/1,500 to 1/13,000. The estimate of this risk derived under a locus homogeneity model is 1/960. Conclusion Variation of recurrence risks of this magnitude may have implications for genetic counseling of families with affected individuals, in particular about prenatal testing and other reproductive options. Similar analyses to determine locus-specific carrier frequencies for other phenotypes with significant locus heterogeneity may yield similarly relevant results. PMID:20949666

  8. Recurrence risks for Bardet-Biedl syndrome: Implications of locus heterogeneity.

    PubMed

    Sapp, Julie C; Nishimura, Darryl; Johnston, Jennifer J; Stone, Edwin M; Héon, Elise; Sheffield, Val C; Biesecker, Leslie G

    2010-10-01

    Bardet-Biedl syndrome is a pleiotropic multiple anomaly syndrome inherited in an autosomal recessive pattern. It is now known that this disorder has locus heterogeneity, with causative mutations identified in as many as 14 genes. The aim of this study was to derive locus-specific recurrence risk estimates for family members of a proband affected with Bardet-Biedl syndrome. Mutation data from 187 probands affected with Bardet-Biedl syndrome were used. The authors counted the relative proportion of families with mutations at each of 10 loci and estimated locus-specific carrier rates for mutations using Hardy-Weinberg principles and an aggregate population frequency of 1/100,000 for the phenotype. Locus-specific recurrence risks were calculated for relatives of an affected proband. Locus-specific carrier frequencies range from 1/250 to 1/2200, and the risks for an offspring of the sibling of an affected individual range from 1/1,500 to 1/13,000. The estimate of this risk derived under a locus homogeneity model is 1/960. Variation of recurrence risks of this magnitude may have implications for genetic counseling of families with affected individuals, in particular about prenatal testing and other reproductive options. Similar analyses to determine locus-specific carrier frequencies for other phenotypes with significant locus heterogeneity may yield similarly relevant results.

  9. Job Stress and Locus of Control in Teachers: Comparisons between Samples from the United States and Zimbabwe

    ERIC Educational Resources Information Center

    Crothers, Laura M.; Kanyongo, Gibbs Y.; Kolbert, Jered B.; Lipinski, John; Kachmar, Steven P.; Koch, Gary D.

    2010-01-01

    This study examines the relationship between educators' locus of control and job stress using samples from the US and Zimbabwe. Multiple regression analyses are used to identify significant relationships in the US sample between teachers' external locus of control and the severity of the job stress that they experience, coupled with the perceived…

  10. Identification of QTLs for serum lipid levels in a female sib-pair cohort: a novel application to improve the power of two-locus linkage analysis.

    PubMed

    Falchi, Mario; Andrew, Toby; Snieder, Harold; Swaminathan, Ramasamyiyer; Surdulescu, Gabriela L; Spector, Tim D

    2005-10-15

    Using a novel approach for a two-locus model that provides a greatly increased power to detect multiple quantitative trait loci (QTLs) in simulated data, we identified in a sample of 961 female sib-pairs, three genome-wide significant QTLs for apolipoprotein A1 on chromosomes 8p21.1-q13.1 (LOD score 3.71), 9q21.32-33.1 (LOD score 3.28) and 10p15.1-p13 (LOD score 5.51), two for lipoprotein (a) on chromosomes 6q25.2-q27 (LOD score 10.18) and 21q21.1-q21.3 (LOD score 4.57) and two for triglycerides on chromosomes 4q28.3-32.1 (LOD score 3.71) and 5q23.1-q32 (LOD score 3.60). The two-locus ordered-subset analysis has led to the confirmation of known and likely identification of novel regions linked to serum lipid levels that would have otherwise been missed and deserves wider application in linkage analyses of quantitative traits. Given the relative lack of power for the sample sizes commonly used in human genetics linkage studies, minor QTL effects often go undetected and those that are detected will be upwardly biased. We show through simulation that the discrepancy between the real and estimated QTL-effects is often likely to generate an unpredictable source of false-negative errors, using multi-locus models, reducing the power to detect multiple QTLs through oligogenic linkage analysis. The successful simultaneous modelling of the identified QTLs in a multi-locus context helps to eliminate false positives and increases the power to detect linkages, adding compelling evidence that they are likely to be reliable QTLs for these lipid traits.

  11. Multiple heart-cutting two dimensional liquid chromatography mass spectrometry: Towards real time determination of related impurities of bio-pharmaceuticals in salt based separation methods.

    PubMed

    Petersson, Patrik; Haselmann, Kim; Buckenmaier, Stephan

    2016-10-14

    Many of the chromatographic methods used in industry to determine related impurities in bio pharmaceuticals employ salt containing mobile phases. "Salty" mobile phases often provide superior chromatographic performance but are not compatible with mass spectrometry (MS) detection. Peak tracking necessary for method development is therefore often based on peak areas and the chemist's experience/intuition. In addition, MS characterization of impurities usually is done by offline fraction collection, which apart from being time consuming often suffers from poor recovery or the degradation of impurities collected. The recent development of multiple heart-cutting (MHC) two-dimensional liquid chromatography (2D-LC) provides a way to address these problems. This study shows how MHC 2D-LC-MS can be used to obtain almost real time MS data for bovine insulin related impurities present at low level (<0.03%). High quality MS spectra were obtained even for a first dimension using a mobile phase containing high concentrations of sodium, sulphate and phosphate. Thereby MHC 2D-LC-MS offers a possibility to eliminate the guesswork currently associated with peak tracking during method development. Furthermore, in contrast to current characterization methods involving fraction collection, solvent reduction/exchange etc., MS determination is done directly, which markedly shortens the workflow (from days to hours) and reduces the risk for poor recovery and degradation.

  12. In-situ Real-Time Monitoring of Volatile Organic Compound Exposure and Heart Rate Variability for Patients with Multiple Chemical Sensitivity

    PubMed Central

    Mizukoshi, Atsushi; Kumagai, Kazukiyo; Yamamoto, Naomichi; Noguchi, Miyuki; Yoshiuchi, Kazuhiro; Kumano, Hiroaki; Sakabe, Kou; Yanagisawa, Yukio

    2015-01-01

    In-situ real-time monitoring of volatile organic compound (VOC) exposure and heart rate variability (HRV) were conducted for eight multiple chemical sensitivity (MCS) patients using a VOC monitor, a Holter monitor, and a time-activity questionnaire for 24 h to identify the relationship between VOC exposure, biological effects, and subjective symptoms in actual life. The results revealed no significantly different parameters for averaged values such as VOC concentration, HF (high frequency), and LF (low frequency) to HF ratio compared with previous data from healthy subjects (Int. J. Environ. Res. Public Health 2010, 7, 4127–4138). Significant negative correlations for four subjects were observed between HF and amounts of VOC change. These results suggest that some patients show inhibition of parasympathetic activities along with VOC exposure as observed in healthy subjects. Comparing the parameters during subjective symptoms and normal condition, VOC concentration and/or VOC change were high except for one subject. HF values were low for five subjects during subjective symptoms. Examining the time-series data for VOC exposure and HF of each subject showed that the subjective symptoms, VOC exposure, and HF seemed well related in some symptoms. Based on these characteristics, prevention measures of symptoms for each subject may be proposed. PMID:26445055

  13. Real-time electroholography using a multiple-graphics processing unit cluster system with a single spatial light modulator and the InfiniBand network

    NASA Astrophysics Data System (ADS)

    Niwase, Hiroaki; Takada, Naoki; Araki, Hiromitsu; Maeda, Yuki; Fujiwara, Masato; Nakayama, Hirotaka; Kakue, Takashi; Shimobaba, Tomoyoshi; Ito, Tomoyoshi

    2016-09-01

    Parallel calculations of large-pixel-count computer-generated holograms (CGHs) are suitable for multiple-graphics processing unit (multi-GPU) cluster systems. However, it is not easy for a multi-GPU cluster system to accomplish fast CGH calculations when CGH transfers between PCs are required. In these cases, the CGH transfer between the PCs becomes a bottleneck. Usually, this problem occurs only in multi-GPU cluster systems with a single spatial light modulator. To overcome this problem, we propose a simple method using the InfiniBand network. The computational speed of the proposed method using 13 GPUs (NVIDIA GeForce GTX TITAN X) was more than 3000 times faster than that of a CPU (Intel Core i7 4770) when the number of three-dimensional (3-D) object points exceeded 20,480. In practice, we achieved ˜40 tera floating point operations per second (TFLOPS) when the number of 3-D object points exceeded 40,960. Our proposed method was able to reconstruct a real-time movie of a 3-D object comprising 95,949 points.

  14. Direct analysis in real time mass spectrometry combined with single-drop liquid-liquid-liquid microextraction for the rapid analysis of multiple phytohormones in fruit juice.

    PubMed

    Bai, Yu; Zhang, Jialing; Bai, Yu; Liu, Huwei

    2012-06-01

    A rapid, simple, and efficient method for the fast determination of multiple phytohormones was developed in this work, based on single-drop liquid-liquid-liquid microextraction (SD-LLLME) combined with direct analysis in real-time mass spectrometry (DART-MS). Six phytohormones--indole-3-acetic acid (IAA), indole-3-butyric acid (IBA), jasmonic acid (JA), salicylic acid (SA), abscisic acid (ABA), and gibberellin A(3) (GA(3))--were analyzed simultaneously using this method, and the conditions employed for DART-MS and SD-LLLME were optimized systematically. Satisfactory results were obtained in terms of linearity (R (2) values for all phytohormones were 0.991-0.996), sensitivity (limits of detection were 0.65-72 ng/mL), and repeatability (RSD values were 6.9-14%). In addition, the proposed method was applied to determine the endogenous phytohormones in three kinds of fruit juice. Different concentrations of phytohormones were detected with satisfactory recoveries, and the whole analytical procedure took no more than 30 min. Therefore, this combination of SD-LLLME and DART-MS was shown to be a suitable and effective approach for the fast analysis of targets present at trace level concentrations in complex matrices.

  15. Detection of multiple Mycoplasma species in bulk tank milk samples using real-time PCR and conventional culture and comparison of test sensitivities.

    PubMed

    Justice-Allen, A; Trujillo, J; Goodell, G; Wilson, D

    2011-07-01

    The objective of this study was to further validate a SYBR PCR protocol for Mycoplasma spp. by comparing it with standard microbial culture in the detection of Mycoplasma spp. in bulk tank milk samples. Additionally, we identified Mycoplasma spp. present by analysis of PCR-generated amplicons [dissociation (melt) temperature (T(m)), length, and DNA sequence]. The research presented herein tests the hypothesis that the SYBR PCR protocol is as sensitive as conventional culture for the detection of Mycoplasma spp. in bulk tank milk samples. Mycoplasmas cause several important disease syndromes in cattle, including mastitis in dairy cows. The standard diagnostic method at the herd level has been microbial isolation of mycoplasmas on 1 of several specialized media and speciation through biochemical or immunological techniques; repeated sampling schemes are recommended. The development of a real-time SYBR PCR protocol offers advantages in decrease of time to detection, cost, and complexity. The T(m) of the double-stranded DNA generated from the PCR reaction was used to detect the presence of and tentatively identify the species of mycoplasmas other than Mycoplasma bovis. In the SYBR PCR protocol, the presence of multiple species of mycoplasmas is indicated by an atypical dissociation curve. Gel electrophoresis and sequencing of the amplicons was used to confirm the mycoplasma species present when a non-M. bovis organism was detected (T(m) not equal to M. bovis) and used to identify all the mycoplasma species present for the samples with atypical dissociation curves. Mycoplasma bovis was identified in 83% of SYBR PCR mycoplasma-positive bulk tank samples. Another mycoplasma was identified either alone or in addition to M. bovis in 25% of SYBR PCR mycoplasma-positive bulk tank milk samples. Four species of mycoplasma other than M. bovis (Mycoplasma alkalescens, Mycoplasma arginini, Mycoplasma bovigenitalium, and Mycoplasma gateae) were identified in bulk tank milk samples

  16. Near real time monitoring of biomass burning particulate emissions (PM2.5) across contiguous United States using multiple satellite instruments

    NASA Astrophysics Data System (ADS)

    Zhang, Xiaoyang; Kondragunta, Shobha; Schmidt, Christopher; Kogan, Felix

    is less than 20% if the same fuel data are used. The evaluation suggests that the biomass burning emissions derived from multiple satellite data provide realistic spatiotemporal patterns and can be assimilated into air quality models for forecasts in real or near real time.

  17. Bayesian inference of population size history from multiple loci.

    PubMed

    Heled, Joseph; Drummond, Alexei J

    2008-10-23

    Effective population size (Ne) is related to genetic variability and is a basic parameter in many models of population genetics. A number of methods for inferring current and past population sizes from genetic data have been developed since JFC Kingman introduced the n-coalescent in 1982. Here we present the Extended Bayesian Skyline Plot, a non-parametric Bayesian Markov chain Monte Carlo algorithm that extends a previous coalescent-based method in several ways, including the ability to analyze multiple loci. Through extensive simulations we show the accuracy and limitations of inferring population size as a function of the amount of data, including recovering information about evolutionary bottlenecks. We also analyzed two real data sets to demonstrate the behavior of the new method; a single gene Hepatitis C virus data set sampled from Egypt and a 10 locus Drosophila ananassae data set representing 16 different populations. The results demonstrate the essential role of multiple loci in recovering population size dynamics. Multi-locus data from a small number of individuals can precisely recover past bottlenecks in population size which can not be characterized by analysis of a single locus. We also demonstrate that sequence data quality is important because even moderate levels of sequencing errors result in a considerable decrease in estimation accuracy for realistic levels of population genetic variability.

  18. Locus of control, self-control, and family income as predictors of young children's mathematics and science scores.

    PubMed

    Martin, Sue; Meyer, James A; Nelson, Laverne; Baldwin, Vernoice; Ting, Ling; Sterling, Deloris

    2007-04-01

    Locus of control, self-control, and family income were investigated as possible predictors of 138 young children's mathematics and science scores. The children, 60 boys and 78 girls, ranging from 4 to 8 years of age (M = 5.4, SD = 1.3) were administered the Stephens-Delys Reinforcement Contingency Interview Scale, the Self-control Rating Scale, the Comprehensive Mathematics Inventory, and a science test based on the work of D. K. Dickinson. Analysis showed mathematics scores were positively related to income, locus of control, and science scores. Mathematics and science scores were negatively related to lack of self-control. Also, science scores were positively related to locus of control. Multiple regression analysis with mathematics as the dependent variable indicated income had the greatest predictive value followed by self-control and locus of control. The multiple regression model of science was also significant, with locus of control having the greatest influence followed by self-control.

  19. Assessment of cardiac safety during fingolimod treatment initiation in a real-world relapsing multiple sclerosis population: a phase 3b, open-label study.

    PubMed

    Gold, Ralf; Comi, Giancarlo; Palace, Jacqueline; Siever, Arno; Gottschalk, Rebecca; Bijarnia, Mahendra; von Rosenstiel, Philipp; Tomic, Davorka; Kappos, Ludwig

    2014-02-01

    The aim of this study was to evaluate short-term safety and tolerability of fingolimod in a real-world population with relapsing multiple sclerosis, focusing on cardiac safety during treatment initiation. Patients received fingolimod 0.5 mg once daily for four months. Patients excluded from the pivotal studies with certain pre-existing cardiac conditions or baseline cardiac findings (PCCs), and those receiving beta blockers (BBs) and/or calcium channel blockers (CCBs), were eligible. Heart rate (HR) and electrical conduction events were monitored using ambulatory electrocardiography for at least 6 h after the first dose. Of 2,417 enrolled patients, 2,282 (94.4 %) completed the study. Fingolimod initiation was associated with a transient, mostly asymptomatic decrease in HR. Bradycardia adverse events occurred in 0.6 % of patients and were more frequent in individuals receiving BBs/CCBs (3.3 %) than in other patient subgroups (0.5-1.4 %); most events were asymptomatic, and all patients recovered without pharmacological intervention. In the 6 h post-dose, the incidences of Mobitz type I second-degree atrioventricular block (AVB) and 2:1 AVB were higher in patients with PCCs (4.1 and 2.0 %, respectively) than in those without (0.9 and 0.3 %, respectively); at pre-dose screening, patients with PCCs had the same incidence of Mobitz type I second-degree AVB (4.1 %) and a slightly lower incidence of 2:1 AVB (0.7 %) than 6 h post-dose. All recorded conduction abnormalities were asymptomatic. This study adds to the evidence showing that cardiac effects during fingolimod initiation remain consistent with those known from previous, controlled studies, even if patients with PCCs are included.

  20. Discrimination of Aspergillosis, Mucormycosis, Fusariosis, and Scedosporiosis in Formalin-Fixed Paraffin-Embedded Tissue Specimens by Use of Multiple Real-Time Quantitative PCR Assays.

    PubMed

    Salehi, Elham; Hedayati, Mohammad T; Zoll, Jan; Rafati, Haleh; Ghasemi, Maryam; Doroudinia, Atosa; Abastabar, Mahdi; Tolooe, Ali; Snelders, Eveline; van der Lee, Henrich A; Rijs, Antonius J M M; Verweij, Paul E; Seyedmousavi, Seyedmojtaba; Melchers, Willem J G

    2016-11-01

    In a retrospective multicenter study, 102 formalin-fixed paraffin-embedded (FFPE) tissue specimens with histopathology results were tested. Two 4- to 5-μm FFPE tissue sections from each specimen were digested with proteinase K, followed by automated nucleic acid extraction. Multiple real-time quantitative PCR (qPCR) assays targeting the internal transcribed spacer 2 (ITS2) region of ribosomal DNA, using fluorescently labeled primers, was performed to identify clinically important genera and species of Aspergillus, Fusarium, Scedosporium, and the Mucormycetes The molecular identification was correlated with results from histological examination. One of the main findings of our study was the high sensitivity of the automated DNA extraction method, which was estimated to be 94%. The qPCR procedure that was evaluated identified a range of fungal genera/species, including Aspergillus fumigatus, Aspergillus flavus, Aspergillus terreus, Aspergillus niger, Fusarium oxysporum, Fusarium solani, Scedosporium apiospermum, Rhizopus oryzae, Rhizopus microsporus, Mucor spp., and Syncephalastrum Fusarium oxysporum and F. solani DNA was amplified from five specimens from patients initially diagnosed by histopathology as having aspergillosis. Aspergillus flavus, S. apiospermum, and Syncephalastrum were detected from histopathological mucormycosis samples. In addition, examination of four samples from patients suspected of having concomitant aspergillosis and mucormycosis infections resulted in the identification of two A. flavus isolates, one Mucor isolate, and only one sample having both R. oryzae and A. flavus Our results indicate that histopathological features of molds may be easily confused in tissue sections. The qPCR assay used in this study is a reliable tool for the rapid and accurate identification of fungal pathogens to the genus and species levels directly from FFPE tissues. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  1. The evaluation of minimal residual disease in multiple myeloma by fluorescent molecular beacons in real time PCR of IgH gene rearrangements and correlation with flow cytometry.

    PubMed

    Kara, I O; Duman, B B; Afsar, C U

    2013-01-01

    Multiple myeloma (MM) patients relapse after a period of time despite longer disease-free survival due to novel treatment options. In this study we aimed to assess the value of real-time polymerase chain reaction (RT-PCR) for detecting the immunoglobulin heavy chain (IgH) gene rearrangement using allele-specific molecular beacons as fluorescence probes to quantify minimal residual disease (MRD) and also to correlate post-treatment flow cytometric detection of plasma cells' (PCs) expression of CD19, CD38, CD45, CD56 and CD138 in MM. After diagnosis of 17 MM patients, the CDR1, CDR2 and CDR3 regions of the IgH gene were analysed and sequenced to identify IgH's clonal nature. Unique sequences of the clonal IgH rearrangement were used to design specific molecular beacon probes for each MM patient. Examined were also the co-expression of CD19, CD38, CD45, CD56, and CD138 molecules in bone marrow aspirates of patients with MM by flow cytometry. Detection of MRD was positive in 13 (76%) of 17 patients by RT-PCR. The infiltration ratio was significantly correlated with CD138 expression (p=0.009). Significant correlation was also found between RT-PCR detection of MRD and CD138 expression (p=0.006). Nevertheless, no correlation was observed among other surface antigens (CD38, CD45, CD56). Our results indicated that RT-PCR with specific molecular beacons provide a feasible, accurate and reproducible method for the determination of MRD in MM. Flow cytometry detection of CD138 expression may be used as a disease marker in addition to RT-PCR.

  2. The X-linked F cell production locus: Genetic mapping and role in fetal hemoglobin production

    SciTech Connect

    Chang, Y.C.; Smith, K.D.; Moore, R.D.

    1994-09-01

    Postnatal fetal hemoglobin (Hb F) production is confined to a subset of erythocytes termed F-cells. There is a 10-20 fold variation in F-cell production in sickle cell disease (SCD) and normal individuals. Most of the variation in F-cell production has been attributed to a diallelic (High, Low) X-linked gene, the F-cell production (FCP) locus that we recently mapped to Xp22.2-22.3 (LOD=4.56, theta=0.04). Using multiple regression analysis in 262 Jamaican SCD patients we determined the relative contribution of the FCP locus and other variables previously associated with variation in Hb F level (gender, age, beta-globin haplotypes, number of alpha-globin genes and the FCP locus phenotypes). When the FCP locus is in the regression model, the FCP locus alone accounts for approximately 40% of the variation in Hb F level while the contribution of age, alpha-globin gene number, and beta-globin haplotypes was insignificant. When individuals with High FCP allele are removed from the analysis, the beta globin haplotype now contribute to >10% of the Hb F variation. We conclude that the X-linked FCP locus is the major determinant of all known variables in Hb F production. Using 4 highly polymorphic dinucleotide repeat markers that we identified from cosmids in Xp22.2-22.3, have localized the FCP locus to a 1 Mb minimal candidate region between DXS143 and DXS410.

  3. Semiparametric approach to match probability calculations using single locus probes.

    PubMed

    Cao, R; Alemany, J; Cabrero, C; Carracedo, A; Díez, A; Valverde, E

    1996-01-01

    A semiparametric approach to match probability calculations using single locus probes has been developed and compared graphically with other standard methods by a one-sample simulation. The density functions obtained using this method are closer to the real distributions than those obtained by conventional approaches. Our method does not need to establish an arbitrary match threshold, which has been a source of problems in practical applications of standard methods. Moreover, it can be adjusted to any particular conditions by setting the experimental error and correlation of each laboratory. To assess the practical performance of this method we carried out a comparison experiment using a sample of 229 individuals analysed in duplicate.

  4. Social capital, political trust, and health locus of control: a population-based study.

    PubMed

    Lindström, Martin

    2011-02-01

    To investigate the association between political trust in the Riksdag and lack of belief in the possibility to influence one's own health (external locus of control), taking horizontal trust into account. The 2008 public health survey in Skåne is a cross-sectional postal questionnaire study with a 55% participation rate. A random sample of 28,198 persons aged 18-80 years participated. Logistic regression models were used to investigate the associations between political trust in the Riksdag (an aspect of vertical trust) and lack of belief in the possibility to influence one's own health (external locus of control). The multiple regression analyses included age, country of birth, education, and horizontal trust in other people. A 33.7% of all men and 31.8% of all women lack internal locus of control. Low (external) health locus of control is more common in higher age groups, among people born outside Sweden, with lower education, low horizontal trust, low political trust, and no opinion concerning political trust. Respondents with not particularly strong political trust, no political trust at all and no opinion have significantly higher odds ratios of external locus of control throughout the multiple regression analyses. Low political trust in the Riksdag seems to be independently associated with external health locus of control.

  5. Factors Determining Adolescent Locus of Control.

    ERIC Educational Resources Information Center

    Kopera-Frye, Karen F.; And Others

    Previous research has demonstrated an association between locus of control in adolescence and a successful transition to adulthood. Having an external locus of control has been implicated as an important factor in adolescent behaviors such as teenage pregnancy and delinquency, and has been found to be negatively related to school achievement. This…

  6. Enhancing the 'real world' prediction of cardiovascular events and major bleeding with the CHA2DS2-VASc and HAS-BLED scores using multiple biomarkers.

    PubMed

    Roldán, Vanessa; Rivera-Caravaca, José Miguel; Shantsila, Alena; García-Fernández, Amaya; Esteve-Pastor, María Asunción; Vilchez, Juan Antonio; Romera, Marta; Valdés, Mariano; Vicente, Vicente; Marín, Francisco; Lip, Gregory Y H

    2017-09-18

    Atrial fibrillation (AF)-European guidelines suggest the use of biomarkers to stratify patients for stroke and bleeding risks. We investigated if a multibiomarker strategy improved the predictive performance of CHA2DS2-VASc and HAS-BLED in anticoagulated AF patients. We included consecutive patients stabilized for six months on vitamin K antagonists (INRs 2.0-3.0). High sensitivity troponin T, NT-proBNP, interleukin-6, von Willebrand factor concentrations and glomerular filtration rate (eGFR; using MDRD-4 formula) were quantified at baseline. Time in therapeutic range (TTR) was recorded at six months after inclusion. Patients were follow-up during a median of 2375 (IQR 1564-2887) days and all adverse events were recorded. In 1361 patients, adding four blood biomarkers, TTR and MDRD-eGFR, the predictive value of CHA2DS2-VASc increased significantly by c-index (0.63 vs. 0.65; p = .030) and IDI (0.85%; p < .001), but not by NRI (-2.82%; p < .001). The predictive value of HAS-BLED increased up to 1.34% by IDI (p < .001). Nevertheless, the overall predictive value remains modest (c-indexes approximately 0.65) and decision curve analyses found lower net benefit compared with the originals scores. Addition of biomarkers enhanced the predictive value of CHA2DS2-VASc and HAS-BLED, although the overall improvement was modest and the added predictive advantage over original scores was marginal. Key Messages Recent atrial fibrillation (AF)-European guidelines for the first time suggest the use of biomarkers to stratify patients for stroke and bleeding risks, but their usefulness in real world for risk stratification is still questionable. In this cohort study involving 1361 AF patients optimally anticoagulated with vitamin K antagonists, adding high sensitivity troponin T, N-terminal pro-B-type natriuretic peptide, interleukin 6, von Willebrand factor, glomerular filtration rate (by the MDRD-4 formula) and time in therapeutic range, increased the predictive

  7. Greater Real-Life Diagnostic Efficacy of Allergen Molecule-Based Diagnosis for Prescription of Immunotherapy in an Area with Multiple Pollen Exposure.

    PubMed

    Saltabayeva, Ulbosin; Garib, Victoria; Morenko, Marina; Rosenson, Rafail; Ispayeva, Zhanat; Gatauova, Madina; Zulus, Loreta; Karaulov, Alexander; Gastager, Felix; Valenta, Rudolf

    2017-01-01

    Allergen molecule-based diagnosis has been suggested to facilitate the identification of disease-causing allergen sources and the prescription of allergen-specific immunotherapy (AIT). The aim of the current study was to compare allergen molecule-based IgE serology with allergen extract-based skin testing for the identification of the disease-causing allergen sources. The study was conducted in an area where patients are exposed to pollen from multiple sources (trees, grasses, and weeds) at the same time to compare the diagnostic efficiency of the 2 forms of diagnosis. Patients from Astana, Kazakhstan, who suffered from pollen-induced allergy (n = 95) were subjected to skin prick testing (SPT) with a local panel of tree pollen, grass pollen, and weed pollen allergen extracts and IgE antibodies specific for marker allergen molecules (nArt v 1, nArt v 3, rAmb a 1, rPhl p 1, rPhl p 5, rBet v 1) were measured by ImmunoCAP. Direct and indirect costs for diagnosis based on SPT and marker allergen-based IgE serology as well as direct costs for immunotherapy depending on SPT and serological test results were calculated. The costs for SPT-based diagnosis per patient were lower than the costs for allergen molecule-based IgE serology. However, allergen molecule-based serology was more precise in detecting the disease-causing allergen sources. A lower number of immunotherapy treatments (n = 119) was needed according to molecular diagnosis as compared to extract-based diagnosis (n = 275), which considerably reduced the total costs for diagnosis and for a 3-year treatment from EUR 1,112.30 to 521.77 per patient. The results from this real-life study show that SPT is less expensive than allergen molecule-based diagnostic testing, but molecular diagnosis allowed more precise prescription of immunotherapy which substantially reduced treatment costs and combined costs for diagnosis and treatment. © 2017 The Author(s) Published by S. Karger AG, Basel.

  8. Ideal vial size for bortezomib: real-world data on waste and cost reduction in treatment of multiple myeloma in Brazil.

    PubMed

    Clark, Luciana; Castro, Ana Paula; Fortes, Anna Flávia; Santos, Fábio; Clark, Otávio; Engel, Tobias; Pegoretti, Bruna; Teich, Vanessa; Vianna, Denizar; Puty, Fabíola

    2011-01-01

    Single-size vials of drugs may be a source of waste and increase in treatment costs. Bortezomib, indicated for multiple myeloma (MM) treatment, is available in 3.5-mg vials, a quantity higher than the average dose commonly prescribed. This analysis aimed to demonstrate, through real-world data, which would be the optimal vial presentation for bortezomib in Brazil and quantify the reduction in medication waste related to this option. From November 2007 to October 2009 all patients with MM treated with bortezomib were identified via the Evidências database. Analysis of prescribed, dispensed, and wasted doses, their costs and projections of the ideal vial size were performed. Thirty-five patients (mean body surface area of 1.73 m(2)) received 509 infusions in 131 cycles of treatment (average of 3.77 cycles per patient). The average dose prescribed was 2.1 mg per infusion (95% confidence interval [CI] 1.97-2.26) with average waste of 39.5% of the vial content (95% CI 35.35-43.76). The mean waste per patient per day was 1.38 mg (95% CI 1.24-1.52). If a 3-mg vial were available, the average drug waste per patient per day would be 0.88 mg (95% CI 0.74-1.03) or 36.2% less. With a 2.5-mg vial the waste would be 1.05 mg (95% CI 0.81-1.29) or 23.9% less. If two presentations were available (2.5 mg and 0.5 mg), the waste would be 0.52 mg (95% CI 0.4-0.63) or 62.5% less. Considering the price of the different vials to be proportional to the original 3.5-mg vial, the cost would be also reduced by the same rates described above. A simple adjustment in vial size may reduce the waste of bortezomib by 36% to 62% and can also reduce the cost of treatment. Copyright © 2011 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  9. THE LOCUS COERULEUS AND CENTRAL CHEMOSENSITIVITY

    PubMed Central

    Gargaglioni, Luciane H.; Hartzler, Lynn K.; Putnam, Robert W.

    2010-01-01

    The locus coeruleus (LC) lies in the dorsal pons and supplies noradrenergic (NA) input to many regions of the brain, including respiratory control areas. The LC may provide tonic input for basal respiratory drive and is involved in central chemosensitivity since focal acidosis of the region stimulates ventilation and ablation reduces CO2-induced increased ventilation. The output of LC is modulated by both serotonergic and glutamatergic inputs. A large percentage of LC neurons are intrinsically activated by hypercapnia. This percentage and the magnitude of their response are highest in young neonates and decrease dramatically after postnatal day P10. The cellular bases for intrinsic chemosensitivity of LC neurons are comprised of multiple factors, primary among them being reduced extracellular and intracellular pH, which inhibit inwardly rectifying and voltage-gated K+ channels, and activate L-type Ca2+ channels. Activation of KCa channels in LC neurons may limit their ultimate response to hypercapnia. Finally, the LC mediates central chemosensitivity and contains pH-sensitive neurons in amphibians, suggesting that the LC has a long-standing phylogenetic role in respiratory control. PMID:20435170

  10. Methodological implementation of mixed linear models in multi-locus genome-wide association studies.

    PubMed

    Wen, Yang-Jun; Zhang, Hanwen; Ni, Yuan-Li; Huang, Bo; Zhang, Jin; Feng, Jian-Ying; Wang, Shi-Bo; Dunwell, Jim M; Zhang, Yuan-Ming; Wu, Rongling

    2017-02-01

    The mixed linear model has been widely used in genome-wide association studies (GWAS), but its application to multi-locus GWAS analysis has not been explored and assessed. Here, we implemented a fast multi-locus random-SNP-effect EMMA (FASTmrEMMA) model for GWAS. The model is built on random single nucleotide polymorphism (SNP) effects and a new algorithm. This algorithm whitens the covariance matrix of the polygenic matrix K and environmental noise, and specifies the number of nonzero eigenvalues as one. The model first chooses all putative quantitative trait nucleotides (QTNs) with ≤ 0.005 P-values and then includes them in a multi-locus model for true QTN detection. Owing to the multi-locus feature, the Bonferroni correction is replaced by a less stringent selection criterion. Results from analyses of both simulated and real data showed that FASTmrEMMA is more powerful in QTN detection and model fit, has less bias in QTN effect estimation and requires a less running time than existing single- and multi-locus methods, such as empirical Bayes, settlement of mixed linear model under progressively exclusive relationship (SUPER), efficient mixed model association (EMMA), compressed MLM (CMLM) and enriched CMLM (ECMLM). FASTmrEMMA provides an alternative for multi-locus GWAS. © The Author 2017. Published by Oxford University Press.

  11. A novel method of multiple nucleic acid detection: Real-time RT-PCR coupled with probe-melting curve analysis.

    PubMed

    Han, Yang; Hou, Shao-Yang; Ji, Shang-Zhi; Cheng, Juan; Zhang, Meng-Yue; He, Li-Juan; Ye, Xiang-Zhong; Li, Yi-Min; Zhang, Yi-Xuan

    2017-09-04

    A novel method, real-time reverse transcription PCR (real-time RT-PCR) coupled with probe-melting curve analysis, has been established to detect two kinds of samples within one fluorescence channel. Besides a conventional TaqMan probe, this method employs another specially designed melting-probe with a 5' terminus modification which meets the same label with the same fluorescent group. By using an asymmetric PCR method, the melting-probe is able to detect an extra sample in the melting stage effectively while it almost has little influence on the amplification detection. Thus, this method allows the availability of united employment of both amplification stage and melting stage for detecting samples in one reaction. The further demonstration by simultaneous detection of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) in one channel as a model system is presented in this essay. The sensitivity of detection by real-time RT-PCR coupled with probe-melting analysis was proved to be equal to that detected by conventional real-time RT-PCR. Because real-time RT-PCR coupled with probe-melting analysis can double the detection throughputs within one fluorescence channel, it is expected to be a good solution for the problem of low-throughput in current real-time PCR. Copyright © 2017. Published by Elsevier Inc.

  12. Characterization of frequently deleted 6q locus in prostate cancer.

    PubMed

    Sun, Mei; Srikantan, Vasantha; Ma, Lanfeng; Li, Jia; Zhang, Wei; Petrovics, Gyorgy; Makarem, Mazen; Strovel, Jeffrey W; Horrigan, Stephen G; Augustus, Meena; Sesterhenn, Isabell A; Moul, Judd W; Chandrasekharappa, Settara; Zou, Zhiqiang; Srivastava, Shiv

    2006-11-01

    The long arm of chromosome 6 is frequently deleted in diverse human neoplasms. Our previous study showed a minimum deletion region between markers D6S1056 and D6S300 on chromosome 6q in primary prostate cancer (CaP). In this study, we further refined a 200-kb minimal region of deletion (6qTSG1) centered around D6S1013 marker. The 6qTSG1 transcripts contained complex multiple splicing variants with low or absent expression in CaP cells. None of the transcripts identified contained open reading frames that code for a protein in the NCBI database. The expression of 6qTSG transcripts revealed interesting hormonal regulation relevant to CaP biology. Expression of 6q TSG transcript was induced in LNCaP cells that were cultured in charcoal-stripped serum medium suggesting an upregulation of 6qTSG transcript by androgen ablation and cell growth inhibition/apoptosis. Induction of 6qTSG1 expression in response to androgen ablation was abrogated in androgen-independent derivatives of LNCaP cells. In summary, we have defined a candidate CaP suppressor locus on chromosome 6q16.1, and deletions of this locus are frequently associated with prostate tumorigenesis. In the light of emerging role of noncoding RNAs in cancer biology including CaP, future investigations of 6qTSG11 locus is warranted.

  13. Congenic mapping and sequence analysis of the Renin locus

    PubMed Central

    Flister, Michael J.; Hoffman, Matthew J.; Reddy, Prajwal; Jacob, Howard J.; Moreno, Carol

    2013-01-01

    Renin was the first blood pressure (BP) quantitative trait locus (QTL) mapped by linkage analysis in the rat. Subsequent BP linkage and congenic studies capturing different portions of the renin region have returned conflicting results, suggesting that multiple interdependent BP loci may be residing in the chromosome 13 BP QTL that includes Renin. We used SS-13BN congenic strains to map 2 BP loci in the Renin region (chr13:45.2–49.0 Mb). We identified a 1.1 Mb protective Brown Norway (BN) region around Renin (chr13:46.1–47.2 Mb) that significantly decreased BP by 32 mmHg. The Renin protective BP locus was offset by an adjacent hypertensive locus (chr13:47.2–49.0 Mb) that significantly increased BP by 29 mmHg. Sequence analysis of the protective and hypertensive BP loci revealed 1,433 and 2,063 variants between Dahl salt-sensitive/Mcwi (SS) and BN rats, respectively. To further reduce the list of candidate variants, we re-genotyped an overlapping SS-13SR congenic strain (S/renrr) with a previously reported BP phenotype. Sequence comparison between SS, Dahl R (SR), and BN reduced the number of candidate variants in the 2 BP loci by 42% for further study. Combined with previous studies, these data suggest that at least 4 BP loci reside within the 30 cM chromosome 13 BP QTL that includes Renin. PMID:23460292

  14. Longitudinal prevalence and molecular typing of Escherichia coli O157:H7 by use of multiple-locus variable-number tandem-repeat analysis and pulsed-field gel electrophoresis in fecal samples collected from a range-based herd of beef cattle in California.

    PubMed

    Kondo, Sonoko; Hoar, Bruce R; Villanueva, Veronica; Mandrell, Robert E; Atwill, Edward R

    2010-11-01

    To evaluate seasonal patterns and risk factors for Escherichia coli O157:H7 in feces in a beef cattle herd and determine strain diversity and transition in E coli over time by use of multiple-locus variable-number tandem-repeat analysis (MLVA) and pulsed-field gel electrophoresis (PFGE). 456 samples of freshly passed feces collected over a 1-year period from cattle in a range-based cow-calf operation located in the foothills of the Sierra Nevada Mountains in California. E coli O157:H7 was recovered from feces by use of immunomagnetic separation and 2 selective media. Virulence factors were detected via reverse transcriptase-PCR assay. Escherichia coli O157:H7 isolates were subtyped with MLVA and PFGE. Prevalence estimates were calculated and significant risk factors determined. A dendrogram was constructed on the basis of results of MLVA typing. Overall prevalence estimate for E coli O157:H7 was 10.5%, with the prevalence lowest during the winter. Mean temperature during the 30 days before collection of samples was significantly associated with prevalence of E coli O157:H7 in feces. Nineteen MLVA and 12 PFGE types were identified. A seasonal pattern was detected for prevalence of E coli O157:H7 in feces collected from beef cattle in California. Subtyping via MLVA and PFGE revealed a diversity of E coli O157:H7 strains in a cow-calf operation and noteworthy turnover of predominant types. Given the importance of accurately determining sources of contamination in investigations of disease outbreaks in humans, MLVA combined with PFGE should be powerful tools for epidemiologists.

  15. Multiple Locus Variable Number Tandem Repeat Analysis of Francisella tularensis

    DTIC Science & Technology

    2009-10-01

    populations within Canada and worldwide would help to distinguish a natural outbreak from an intentional use situation. This would require a large...Microbiol., 27, 1601–1608. [7] Titball, R. W.; Johansson, A. and Forsman, M. (2003), Will the enigma of Francisella tularensis virulence soon be

  16. Two-stage association study in Chinese Han identifies two independent associations in CCR1/CCR3 locus as candidate for Behçet's disease susceptibility.

    PubMed

    Hou, Shengping; Xiao, Xiang; Li, Fuzhen; Jiang, Zhengxuan; Kijlstra, Aize; Yang, Peizeng

    2012-12-01

    Previous GWAS studies from Turkey suggested a potential risk locus at CCR1/CCR3 for Behçet's disease. However, this locus did not reach the GWAS significance threshold and has not yet been examined in other ethnic populations. The current study aimed to explore whether this locus was associated with Behçet's disease in Chinese Han and the functional role of the identified variants. A two-stage association study was performed in 653 patients and 1,685 controls using the iPLEX system. Real-time PCR was performed to examine the expression level of CCR1 and CCR3 genes. Haplotype analysis was used to construct the haplotype block. Logistic regression analysis was applied to calculate the independence of multiple associations. Bonferroni correction was applied to account for multiple testing. First stage analysis showed that ten SNPs, located in 3'UTR, 5'UTR in CCR1 or 5'UTR in CCR3, were significantly associated with Behçet's disease (P(c) = 0.018 to 1.3 × 10(-3)). The associations of six SNPs within this locus are independent after control for the genetic effect of rs17282391 using logistic regression analysis. Haplotype analysis identified three associated haplotypes: H3 (GTGAC), H6 (CCATTA) and H9 (CGA) (P(c) = 0.04 to 7.79 × 10(-4)). Three SNPs rs13084057, rs13092160 and rs13075270 showed consistent association in replication and combining studies (replication P(c) = 5.31 × 10(-5) to 1.44 × 10(-5); combining P(c) = 2.76 × 10(-7) to 6.50 × 10(-8)). Interestingly, eQTLs database reveals that SNP rs13092160 is eQTLs SNP, suggesting that this SNP is likely to be functional SNP that directly affects gene expression. The expression of CCR1 and CCR3 was increased in individuals with the CT genotype of rs13092160 (P < 0.05). No significant difference was found for the mRNA level of CCR1 and CCR3 between Behçet's patients and controls. These findings strongly indicate CCR1/CCR3 as a novel locus underlying Behçet's disease.

  17. Real Earthquakes, Real Learning

    ERIC Educational Resources Information Center

    Schomburg, Aaron

    2003-01-01

    One teacher took her class on a year long earthquake expedition. The goal was to monitor the occurrences of real earthquakes during the year and mark their locations with push pins on a wall-sized world map in the hallway outside the science room. The purpose of the project was to create a detailed picture of the earthquakes that occurred…

  18. Real Earthquakes, Real Learning

    ERIC Educational Resources Information Center

    Schomburg, Aaron

    2003-01-01

    One teacher took her class on a year long earthquake expedition. The goal was to monitor the occurrences of real earthquakes during the year and mark their locations with push pins on a wall-sized world map in the hallway outside the science room. The purpose of the project was to create a detailed picture of the earthquakes that occurred…

  19. Hierarchical Spatio-Temporal Probabilistic Graphical Model with Multiple Feature Fusion for Binary Facial Attribute Classification in Real-World Face Videos.

    PubMed

    Demirkus, Meltem; Precup, Doina; Clark, James J; Arbel, Tal

    2016-06-01

    Recent literature shows that facial attributes, i.e., contextual facial information, can be beneficial for improving the performance of real-world applications, such as face verification, face recognition, and image search. Examples of face attributes include gender, skin color, facial hair, etc. How to robustly obtain these facial attributes (traits) is still an open problem, especially in the presence of the challenges of real-world environments: non-uniform illumination conditions, arbitrary occlusions, motion blur and background clutter. What makes this problem even more difficult is the enormous variability presented by the same subject, due to arbitrary face scales, head poses, and facial expressions. In this paper, we focus on the problem of facial trait classification in real-world face videos. We have developed a fully automatic hierarchical and probabilistic framework that models the collective set of frame class distributions and feature spatial information over a video sequence. The experiments are conducted on a large real-world face video database that we have collected, labelled and made publicly available. The proposed method is flexible enough to be applied to any facial classification problem. Experiments on a large, real-world video database McGillFaces [1] of 18,000 video frames reveal that the proposed framework outperforms alternative approaches, by up to 16.96 and 10.13%, for the facial attributes of gender and facial hair, respectively.

  20. Internal locus of control and vocational rehabilitation.

    PubMed

    Selander, John; Marnetoft, Sven-Uno; Asell, Malin; Selander, Ulrika; Millet, Patrick

    2008-01-01

    In previous studies, internal locus of control (ILC) has been pointed out as a key factor for return to work after vocational rehabilitation. The aim of the current study was to gain a deeper understanding of the concept of ILC in a Swedish vocational rehabilitation context. The study was based on data from 347 long-term sick-listed clients collected at the onset of vocational rehabilitation. A first bi-variate analysis showed that ILC was positively associated with physical functioning and general health, and negatively associated with bodily pain. The analysis also showed that women, more than men, reported high internal locus of control. After a second multivariate analysis, only bodily pain remained associated. It is concluded that there exist a strong and negative association between bodily pain and internal locus of control. Clients with severe pain often also suffer from low internal locus of control. This should be kept in mind when providing vocational rehabilitation.

  1. Molecular Identification of the Schwannomatosis Locus

    DTIC Science & Technology

    2005-07-01

    AD Award Number: DAMD17-03-1-0445 TITLE: Molecular Identification of the Schwannomatosis Locus PRINCIPAL INVESTIGATOR: Mia M. MacCollin, M.D...NUMBER Molecular Identification of the Schwannomatosis Locus 5b. GRANT NUMBER DAMD17-03-1-0445 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER...can be found on next page. 15. SUBJECT TERMS schwannomatosis, tumor suppressor gene, NF2, molecular genetics 16. SECURITY CLASSIFICATION OF: 17

  2. Isolation and characterization of a FLOWERING LOCUS T homolog from pineapple (Ananas comosus (L.) Merr).

    PubMed

    Lv, LingLing; Duan, Jun; Xie, JiangHui; Wei, ChangBin; Liu, YuGe; Liu, ShengHui; Sun, GuangMing

    2012-09-01

    FLOWERING LOCUS T (FT)-like genes are crucial regulators of flowering in angiosperms. A homolog of FT, designated as AcFT (GenBank ID: HQ343233), was isolated from pineapple cultivar Comte de Paris by reverse transcriptase polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends (RACE). The cDNA sequence of AcFT is 915 bp in length and contains an ORF of 534 bp, which encodes a protein of 177 aa. Molecular weight was 19.9 kDa and isoelectric point was 6.96. The deduced protein sequence of AcFT was 84% and 82% identical to homologs encoded by CgFT in Cymbidium goeringii and OgFT in Oncidium Gower Ramsey respectively. Quantitative real-time PCR (qRT-PCR) analyses showed that the expression of AcFT was high in flesh and none in leaves. qRT-PCR analyses in different stages indicated that the expression of AcFT reached the highest level on 40 d after flower inducing, when the multiple fruit and floral organs were forming. The 35S::AcFT transgenic Arabidopsis plants flowered earlier and had more inflorescences or branches than wild type plants. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. Multiple Influences of Semantic Memory on Sentence Processing: Distinct Effects of Semantic Relatedness on Violations of Real-World Event/State Knowledge and Animacy Selection Restrictions

    PubMed Central

    Paczynski, Martin; Kuperberg, Gina R.

    2012-01-01

    We aimed to determine whether semantic relatedness between an incoming word and its preceding context can override expectations based on two types of stored knowledge: real-world knowledge about the specific events and states conveyed by a verb, and the verb’s broader selection restrictions on the animacy of its argument. We recorded event-related potentials on post-verbal Agent arguments as participants read and made plausibility judgments about passive English sentences. The N400 evoked by incoming animate Agent arguments that violated expectations based on real-world event/state knowledge, was strongly attenuated when they were semantically related to the context. In contrast, semantic relatedness did not modulate the N400 evoked by inanimate Agent arguments that violated the preceding verb’s animacy selection restrictions. These findings suggest that, under these task and experimental conditions, semantic relatedness can facilitate processing of post-verbal animate arguments that violate specific expectations based on real-world event/state knowledge, but only when the semantic features of these arguments match the coarser-grained animacy restrictions of the verb. Animacy selection restriction violations also evoked a P600 effect, which was not modulated by semantic relatedness, suggesting that it was triggered by propositional impossibility. Together, these data indicate that the brain distinguishes between real-world event/state knowledge and animacy-based selection restrictions during online processing. PMID:23284226

  4. Multiple Influences of Semantic Memory on Sentence Processing: Distinct Effects of Semantic Relatedness on Violations of Real-World Event/State Knowledge and Animacy Selection Restrictions.

    PubMed

    Paczynski, Martin; Kuperberg, Gina R

    2012-11-01

    We aimed to determine whether semantic relatedness between an incoming word and its preceding context can override expectations based on two types of stored knowledge: real-world knowledge about the specific events and states conveyed by a verb, and the verb's broader selection restrictions on the animacy of its argument. We recorded event-related potentials on post-verbal Agent arguments as participants read and made plausibility judgments about passive English sentences. The N400 evoked by incoming animate Agent arguments that violated expectations based on real-world event/state knowledge, was strongly attenuated when they were semantically related to the context. In contrast, semantic relatedness did not modulate the N400 evoked by inanimate Agent arguments that violated the preceding verb's animacy selection restrictions. These findings suggest that, under these task and experimental conditions, semantic relatedness can facilitate processing of post-verbal animate arguments that violate specific expectations based on real-world event/state knowledge, but only when the semantic features of these arguments match the coarser-grained animacy restrictions of the verb. Animacy selection restriction violations also evoked a P600 effect, which was not modulated by semantic relatedness, suggesting that it was triggered by propositional impossibility. Together, these data indicate that the brain distinguishes between real-world event/state knowledge and animacy-based selection restrictions during online processing.

  5. Unusual multiple large abscesses of the liver: interest of the radiological features and the real-time PCR to distinguish between bacterial and amebic etiologies.

    PubMed

    Desoubeaux, Guillaume; Chaussade, Hélène; Thellier, Marc; Poussing, Sophie; Bastides, Frédéric; Bailly, Eric; Lanotte, Philippe; Alison, Daniel; Brunereau, Laurent; Bernard, Louis; Chandenier, Jacques

    2014-01-01

    We report a rare case of amebiasis generating 19 large liver abscesses. Such a quantity of abscesses is rare, especially when occurring in a young casual traveler without any immunodeficiency disorders. A possible co-infection was excluded. By contrast, the amebic etiology was confirmed by means of serology and real-time PCR.

  6. Unusual multiple large abscesses of the liver: interest of the radiological features and the real-time PCR to distinguish between bacterial and amebic etiologies

    PubMed Central

    Desoubeaux, Guillaume; Chaussade, Hélène; Thellier, Marc; Poussing, Sophie; Bastides, Frédéric; Bailly, Eric; Lanotte, Philippe; Alison, Daniel; Brunereau, Laurent; Bernard, Louis; Chandenier, Jacques

    2014-01-01

    We report a rare case of amebiasis generating 19 large liver abscesses. Such a quantity of abscesses is rare, especially when occurring in a young casual traveler without any immunodeficiency disorders. A possible co-infection was excluded. By contrast, the amebic etiology was confirmed by means of serology and real-time PCR. PMID:24548161

  7. Multiple Influences of Semantic Memory on Sentence Processing: Distinct Effects of Semantic Relatedness on Violations of Real-World Event/State Knowledge and Animacy Selection Restrictions

    ERIC Educational Resources Information Center

    Paczynski, Martin; Kuperberg, Gina R.

    2012-01-01

    We aimed to determine whether semantic relatedness between an incoming word and its preceding context can override expectations based on two types of stored knowledge: real-world knowledge about the specific events and states conveyed by a verb, and the verb's broader selection restrictions on the animacy of its argument. We recorded event-related…

  8. Analysing the Trait Anxiety and Locus of Control of Undergraduates in Terms of Attachment Styles

    ERIC Educational Resources Information Center

    Dilmac, Bulent; Hamarta, Erdal; Arslan, Coskun

    2009-01-01

    The aim of this research is to analyse the trait anxiety and locus of control of undergraduates in terms of their attachment styles. This research has been conducted in accordance with general screening model. The target population of the research is constituted of 480 undergraduates. Pearson moments multiplication correlation coefficient…

  9. Complex evolution of a highly conserved microsatellite locus in several fish species.

    PubMed

    Liu, J-X; Ely, B

    2009-08-01

    The evolutionary dynamics of a highly conserved microsatellite locus (Dla 11) were studied in several fish species. The data indicated that multiple types of compound microsatellites arose through point mutations that were sometimes followed by expansion of the derived motif. Furthermore, extensive length variation was detected among species in the regions immediately flanking the repeat region.

  10. A monotonicity conjecture for real cubic maps

    SciTech Connect

    Dawson, S.P.; Galeeva, R.; Milnor, J.; Tresser, C.

    1993-12-01

    This will be an outline of work in progress. We study the conjecture that the topological entropy of a real cubic map depends ``monotonely`` on its parameters, in the sense that each locus of constant entropy in parameter space is a connected set. This material will be presented in more detail in a later paper.

  11. Real-World Treatment Patterns, Time to Next Treatment, and Economic Outcomes in Relapsed or Refractory Multiple Myeloma Patients Treated with Pomalidomide or Carfilzomib.

    PubMed

    Chen, Chi-Chang; Parikh, Kejal; Abouzaid, Safiya; Purnomo, Lea; McGuiness, Catherine B; Hussein, Mohamed; Wade, Rolin L

    2017-02-01

    Negligible real-world evidence exists for later line treatment of multiple myeloma (MM) to assist treatment decisions or reimbursement models, such as episode-based payments. To describe the treatment patterns and clinical/economic outcomes when pomalidomide or carfilzomib is used for relapsed/refractory MM. A U.S. claims database was used to identify MM patients with an initial pomalidomide or carfilzomib claim (index date) between February 1, 2013, and February 28, 2015, which was assumed to be relapse therapy. Treatment regimens were defined as all MM chemotherapy observed within 60 days of index. Patients receiving pomalidomide and carfilzomib within 60 days of index were excluded. Time to next treatment (TTNT), a progression proxy, was defined as the addition of a new agent > 60 days from index or as treatment restart following a > 90-day therapy gap. Cost estimations used plan-allowed amounts. Descriptive statistics were used to compare outcomes between treatment groups, and regression models were used to adjust for baseline patient characteristics. There were 454 patients initiating treatment with pomalidomide (n = 264) or carfilzomib (n = 190) during the index period. The most frequent initial regimens for pomalidomide patients included pomalidomide + dexamethasone (47.0%) and pomalidomide alone (33.0%); the most frequent regimens for carfilzomib patients were carfilzomib alone (45.3%) and carfilzomib + dexamethasone (14.7%). The most frequent next line treatment for pomalidomide patients who progressed was the addition of (14.0%) or switch to (15.0%) carfilzomib ± dexamethasone and for carfilzomib patients, the most frequent next line treatment was pomalidomide + dexamethasone (9.3%) and carfilzomib alone or carfilzomib + dexamethasone + cyclophosphamide (6.7% each). The median (95% CI) TTNT for pomalidomide patients was 11.9 (10.7-14.8) compared with 9.4 (7.7-10.0) months for carfilzomib (P = 0.060). For patients followed to progression (pomalidomide: n

  12. A familial venous malformation locus is on chromosome 9p

    SciTech Connect

    Boon, L.M.; Mulliken, J.B.; Vikkula, M.

    1994-09-01

    Venous malformation is the most common vascular malformation affecting 0.2% of the population. Depending upon size and location, these slow-flow lesions may cause pain, anatomic distortion and threaten life. Most venous malformations occur sporadically and present as solitary lesions. For this reason, determining their pathogenic bases has proven elusive. However, venous malformations also occur in several rare syndromes, some of which demonstrate Mendelian inheritance. As a first step towards identifying the pathogenic bases for these lesions, we have mapped a locus for an autosomal dominant disorder in a three generation family that manifests as multiple cutaneous and mucosal venous malformations. This locus lies within a 24.5 cM interval on chromosome 9p, defined by the markers D9S157 and D9S163. A maximum LOD score of 4.11 at {theta} = 0.05 is obtained with several markers within the interval. The interferon gene cluster, which has previously been implicated in angiogenesis, and the multiple tumor suppressor gene, responsible for several types of malignant tumors, also lie within this interval and are potential candidates.

  13. Single locus complementary sex determination in Hymenoptera: an "unintelligent" design?

    PubMed Central

    van Wilgenburg, Ellen; Driessen, Gerard; Beukeboom, Leo W

    2006-01-01

    The haplodiploid sex determining mechanism in Hymenoptera (males are haploid, females are diploid) has played an important role in the evolution of this insect order. In Hymenoptera sex is usually determined by a single locus, heterozygotes are female and hemizygotes are male. Under inbreeding, homozygous diploid and sterile males occur which form a genetic burden for a population. We review life history and genetical traits that may overcome the disadvantages of single locus complementary sex determination (sl-CSD). Behavioural adaptations to avoid matings between relatives include active dispersal from natal patches and mating preferences for non-relatives. In non-social species, temporal and spatial segregation of male and female offspring reduces the burden of sl-CSD. In social species, diploid males are produced at the expense of workers and female reproductives. In some social species, diploid males and diploid male producing queens are killed by workers. Diploid male production may have played a role in the evolution or maintenance of polygyny (multiple queens) and polyandry (multiple mating). Some forms of thelytoky (parthenogenetic female production) increase homozygosity and are therefore incompatible with sl-CSD. We discuss a number of hypothetical adaptations to sl-CSD which should be considered in future studies of this insect order. PMID:16393347

  14. Root locus analysis and design of the adaptation process in active noise control.

    PubMed

    Tabatabaei Ardekani, Iman; Abdulla, Waleed H

    2012-10-01

    This paper applies root locus theory to develop a graphical tool for the analysis and design of adaptive active noise control systems. It is shown that the poles of the adaptation process performed in these systems move on typical trajectories in the z-plane as the adaptation step-size varies. Based on this finding, the dominant root of the adaptation process and its trajectory can be determined. The first contribution of this paper is formulating parameters of the adaptation process root locus. The next contribution is introducing a mechanism for modifying the trajectory of the dominant root in the root locus. This mechanism creates a single open loop zero in the original root locus. It is shown that appropriate localization of this zero can cause the dominant root of the locus to be pushed toward the origin, and thereby the adaptation process becomes faster. The validity of the theoretical findings is confirmed in an experimental setup which is implemented using real-time multi-threading and multi-core processing techniques.

  15. Dynamic Quantitative Trait Locus Analysis of Plant Phenomic Data.

    PubMed

    Li, Zitong; Sillanpää, Mikko J

    2015-12-01

    Advanced platforms have recently become available for automatic and systematic quantification of plant growth and development. These new techniques can efficiently produce multiple measurements of phenotypes over time, and introduce time as an extra dimension to quantitative trait locus (QTL) studies. Functional mapping utilizes a class of statistical models for identifying QTLs associated with the growth characteristics of interest. A major benefit of functional mapping is that it integrates information over multiple timepoints, and therefore could increase the statistical power for QTL detection. We review the current development of computationally efficient functional mapping methods which provide invaluable tools for analyzing large-scale timecourse data that are readily available in our post-genome era. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Use of a Time-of-Flight Camera With an Omek Beckon™ Framework to Analyze, Evaluate and Correct in Real Time the Verticality of Multiple Sclerosis Patients during Exercise

    PubMed Central

    Eguíluz, Gonzalo; García, María Begoña

    2013-01-01

    Any person with Multiple Sclerosis (MS), regardless of the severity of their disability, needs regular physical activity. Poorly performed exercises could aggravate muscle imbalances and worsen the patient’s health. In this paper, we propose a human body verticality detection system using a time-of-flight camera as a tool to detect incorrect postures and improve them in real time. The prototype uses Omek’s Beckon™ Framework to analyze and evaluate the position of patients during exercise. Preliminary results, based on objective questionnaires, indicate an improvement in patients’ evolution through better positions and performance of the exercises. PMID:24192790

  17. Compositional dependence of the local structure of Se{sub x}Te{sub 1-x} alloys: Electron energy-loss spectra, real-space multiple-scattering calculations, and first-principles molecular dynamics

    SciTech Connect

    Katcho, N. A.; Lomba, E.; Urones-Garrote, E.; Otero-Diaz, L. C.; Landa-Canovas, A. R.

    2006-06-01

    In this work we present an investigation on the composition dependence of the local structure in Se{sub x}Te{sub 1-x} crystalline alloys analyzing their experimental energy-loss spectra with the aid of a real-space multiple-scattering modeling approach and first-principles molecular dynamics. The concourse of this latter technique is essential for a proper modeling of the alloy spectra. From our results, it can be inferred that Se{sub x}Te{sub 1-x} alloys exhibit a high degree of substitutional disorder ruling out the existence of fully ordered alternating copolymer chains of Se and Te atoms.

  18. Making the Grid "Smart" Through "Smart" Microgrids: Real-Time Power Management of Microgrids with Multiple Distributed Generation Sources Using Intelligent Control

    SciTech Connect

    Nehrir, M. Hashem

    2016-10-20

    In this Project we collaborated with two DOE National Laboratories, Pacific Northwest National Lab (PNNL) and Lawrence Berkeley National Lab (LBL). Dr. Hammerstrom of PNNL initially supported our project and was on the graduate committee of one of the Ph.D. students (graduated in 2014) who was supported by this project. He is also a committee member of a current graduate student of the PI who was supported by this project in the last two years (August 2014-July 2016). The graduate student is now supported be the Electrical and Computer Engineering (ECE) Department at Montana State University (MSU). Dr. Chris Marney of LBL provided actual load data, and the software WEBOPT developed at LBL for microgrid (MG) design for our project. NEC-Labs America, a private industry, also supported our project, providing expert support and modest financial support. We also used the software “HOMER,” originally developed at the National Renewable Energy Laboratory (NREL) and the most recent version made available to us by HOMER Energy, Inc., for MG (hybrid energy system) unit sizing. We compared the findings from WebOpt and HOMER and designed appropriately sized hybrid systems for our case studies. The objective of the project was to investigate real-time power management strategies for MGs using intelligent control, considering maximum feasible energy sustainability, reliability and efficiency while, minimizing cost and undesired environmental impact (emissions). Through analytic and simulation studies, we evaluated the suitability of several heuristic and artificial-intelligence (AI)-based optimization techniques that had potential for real-time MG power management, including genetic algorithms (GA), ant colony optimization (ACO), particle swarm optimization (PSO), and multi-agent systems (MAS), which is based on the negotiation of smart software-based agents. We found that PSO and MAS, in particular, distributed MAS, were more efficient and better suited for our work. We

  19. Real time simultaneous and proportional control of multiple degrees of freedom from surface EMG: Preliminary results on subjects with limb deficiency.

    PubMed

    Rehbaum, Hubertus; Jiang, Ning; Paredes, Liliana; Amsuess, Sebastian; Graimann, Bernhard; Farina, Dario

    2012-01-01

    We present the real time simultaneous and proportional control of two degrees of freedom (DoF), using surface electromyographic signals from the residual limbs of three subject with limb deficiency. Three subjects could control a virtual object in two dimensions using their residual muscle activities to achieve goal-oriented tasks. The subjects indicated that they found the control intuitive and useful. These results show that such a simultaneous and proportional control paradigm is a promising direction for multi-functional prosthetic control.

  20. Development of a generic system for real-time data access and remote control of multiple in-situ water quality monitoring instruments

    NASA Astrophysics Data System (ADS)

    Wright, S. A.; Bennett, G. E.; Andrews, T.; Melis, T. S.; Topping, D. J.

    2005-05-01

    Currently, in-situ monitoring of water quality parameters (e.g. water temperature, conductivity, turbidity) in the Colorado River ecosystem typically consists of deploying instruments in the river, retrieving them at a later date, downloading the datalogger, then examining the data; an arduous process in the remote settings of Grand Canyon. Under this protocol, data is not available real-time and there is no way to detect problems with the instrumentation until after retrieval. The next obvious stage in the development of in-situ monitoring in Grand Canyon was the advent of one-way telemetry, i.e. streaming data in real-time from the instrument to the office and/or the world-wide-web. This protocol allows for real-time access to data and the identification of instrumentation problems, but still requires a site visit to address instrument malfunctions, i.e. the user does not have the ability to remotely control the instrument. At some field sites, such as the Colorado River in Grand Canyon, site visitation is restricted by remoteness and lack of traditional access routes (i.e. roads). Even at less remote sites, it may still be desirable to have two-way communication with instruments in order to, for example, diagnose and potentially fix instrumentation problems, change sampling parameters to save battery power, etc., without having to visit the site. To this end, the U.S. Geological Survey, Grand Canyon Monitoring and Research Center, is currently developing and testing a high-speed, two-way communication system that allows for real-time data access and remote control of instrumentation. The approach tested relies on internet access and may be especially useful in areas where land-line or cellular connections are unavailable. The system is composed of off-the-shelf products, uses a commercial broadband satellite service, and is designed in a generic way such that any instrument that communicates through RS-232 communication (i.e. a serial port) is compatible with

  1. QualiCOP: real-world effectiveness, tolerability, and quality of life in patients with relapsing-remitting multiple sclerosis treated with glatiramer acetate, treatment-naïve patients, and previously treated patients.

    PubMed

    Ziemssen, Tjalf; Calabrese, Pasquale; Penner, Iris-Katharina; Apfel, Rainer

    2016-04-01

    Treatment of symptoms and signs beyond the expanded disability status scale remains a major target in multiple sclerosis. QualiCOP was an observational, non-interventional, open-label study conducted at 170 sites in Germany. Of the 754 enrolled patients, 96 % had relapsing-remitting multiple sclerosis (MS) and were either disease-modifying therapy naïve (de novo, n = 481) or previously treated (n = 237) with once-daily, subcutaneous 20-mg/mL glatiramer acetate (GA). Assessments of relapse rate, disease progression, overall functioning, quality of life (QoL), cognition, fatigue, and depression were performed over 24 months. GA treatment over 24 months was associated with reduced annual relapse rate for previously treated (from 0.98 to 0.54 relapses) and de novo (from 0.81 to 0.48 relapses) patients. Multiple Sclerosis Functional Composite scores showed slight improvement in both cohorts (all p < 0.01). Paced Auditory Serial Addition Test and Multiple Sclerosis Inventory Cognition scale scores showed robust improvement in cognition among previously treated and de novo cohorts (all p < 0.001). General Depression Scale scores showed significantly reduced depressive symptoms (p < 0.001). Disease severity, fatigue, and QoL were stable over the observational period. These real-world findings suggest that patients with MS show benefit from GA treatment in important QoL parameters beyond standard measures of relapse and disease severity.

  2. Isolation of identical nitrilase genes from multiple bacterial strains and real-time PCR detection of the genes from soils provides evidence of horizontal gene transfer.

    PubMed

    Coffey, Lee; Clarke, Adrienne; Duggan, Patrick; Tambling, Karen; Horgan, Serenia; Dowling, David; O'Reilly, Catherine

    2009-10-01

    Bacterial enzymes capable of nitrile hydrolysis have significant industrial potential. Microbacterium sp. AJ115, Rhodococcus erythropolis AJ270 and AJ300 were isolated from the same location in England and harbour identical nitrile hydratase/amidase gene clusters. Strain AJ270 has been well studied due to its nitrile hydratase and amidase activity. R. erythropolis ITCBP was isolated from Denmark and carries a very similar nitrile hydratase/amidase gene cluster. In this study, an identical nitrilase gene (nit1) was isolated from the four strains, and the nitrilase from strain AJ270 cloned and expressed in Escherichia coli. Analysis of the recombinant nitrilase has shown it to be functional with activity demonstrated towards phenylacetonitrile. A real-time PCR TaqMan assay was developed that allowed nit1 detection directly from soil enrichment cultures without DNA extraction, with nit1 detected in all samples tested. Real-time PCR screening of isolates from these soils resulted in the isolation of nit1 and also very similar nitrilase gene nit2 from a number of Burkholderia sp. The genes nit1 and nit2 have also been detected in many bacteria of different genera but are unstable in these isolates. It is likely that the genes were acquired by horizontal gene transfer and may be wide-spread in the environment.

  3. Real-time capture and reconstruction system with multiple GPUs for a 3D live scene by a generation from 4K IP images to 8K holograms.

    PubMed

    Ichihashi, Yasuyuki; Oi, Ryutaro; Senoh, Takanori; Yamamoto, Kenji; Kurita, Taiichiro

    2012-09-10

    We developed a real-time capture and reconstruction system for three-dimensional (3D) live scenes. In previous research, we used integral photography (IP) to capture 3D images and then generated holograms from the IP images to implement a real-time reconstruction system. In this paper, we use a 4K (3,840 × 2,160) camera to capture IP images and 8K (7,680 × 4,320) liquid crystal display (LCD) panels for the reconstruction of holograms. We investigate two methods for enlarging the 4K images that were captured by integral photography to 8K images. One of the methods increases the number of pixels of each elemental image. The other increases the number of elemental images. In addition, we developed a personal computer (PC) cluster system with graphics processing units (GPUs) for the enlargement of IP images and the generation of holograms from the IP images using fast Fourier transform (FFT). We used the Compute Unified Device Architecture (CUDA) as the development environment for the GPUs. The Fast Fourier transform is performed using the CUFFT (CUDA FFT) library. As a result, we developed an integrated system for performing all processing from the capture to the reconstruction of 3D images by using these components and successfully used this system to reconstruct a 3D live scene at 12 frames per second.

  4. Real-time PCR detection of Fe-type nitrile hydratase genes from environmental isolates suggests horizontal gene transfer between multiple genera.

    PubMed

    Coffey, Lee; Owens, Erica; Tambling, Karen; O'Neill, David; O'Connor, Laura; O'Reilly, Catherine

    2010-11-01

    Nitriles are widespread in the environment as a result of biological and industrial activity. Nitrile hydratases catalyse the hydration of nitriles to the corresponding amide and are often associated with amidases, which catalyze the conversion of amides to the corresponding acids. Nitrile hydratases have potential as biocatalysts in bioremediation and biotransformation applications, and several successful examples demonstrate the advantages. In this work a real-time PCR assay was designed for the detection of Fe-type nitrile hydratase genes from environmental isolates purified from nitrile-enriched soils and seaweeds. Specific PCR primers were also designed for amplification and sequencing of the genes. Identical or highly homologous nitrile hydratase genes were detected from isolates of numerous genera from geographically diverse sites, as were numerous novel genes. The genes were also detected from isolates of genera not previously reported to harbour nitrile hydratases. The results provide further evidence that many bacteria have acquired the genes via horizontal gene transfer. The real-time PCR assay should prove useful in searching for nitrile hydratases that could have novel substrate specificities and therefore potential in industrial applications.

  5. Molecular characterization of the mouse agouti locus.

    PubMed

    Bultman, S J; Michaud, E J; Woychik, R P

    1992-12-24

    The agouti (a) locus acts within the microenvironment of the hair follicle to regulate coat color pigmentation in the mouse. We have characterized a gene encoding a novel 131 amino acid protein that we propose is the one gene associated with the agouti locus. This gene is normally expressed in a manner consistent with a locus function, and, more importantly, its structure and expression are affected by a number of representative alleles in the agouti dominance hierarchy. In addition, we found that the pleiotropic effects associated with the lethal yellow (Ay) mutation, which include pronounced obesity, diabetes, and the development of neoplasms, are accompanied by deregulated overexpression of the agouti gene in numerous tissues of the adult animal.

  6. Accurate molecular dynamics and nuclear quantum effects at low cost by multiple steps in real and imaginary time: Using density functional theory to accelerate wavefunction methods.

    PubMed

    Kapil, V; VandeVondele, J; Ceriotti, M

    2016-02-07

    The development and implementation of increasingly accurate methods for electronic structure calculations mean that, for many atomistic simulation problems, treating light nuclei as classical particles is now one of the most serious approximations. Even though recent developments have significantly reduced the overhead for modeling the quantum nature of the nuclei, the cost is still prohibitive when combined with advanced electronic structure methods. Here we present how multiple time step integrators can be combined with ring-polymer contraction techniques (effectively, multiple time stepping in imaginary time) to reduce virtually to zero the overhead of modelling nuclear quantum effects, while describing inter-atomic forces at high levels of electronic structure theory. This is demonstrated for a combination of MP2 and semi-local DFT applied to the Zundel cation. The approach can be seamlessly combined with other methods to reduce the computational cost of path integral calculations, such as high-order factorizations of the Boltzmann operator or generalized Langevin equation thermostats.

  7. Accurate molecular dynamics and nuclear quantum effects at low cost by multiple steps in real and imaginary time: Using density functional theory to accelerate wavefunction methods

    SciTech Connect

    Kapil, V.; Ceriotti, M.; VandeVondele, J.

    2016-02-07

    The development and implementation of increasingly accurate methods for electronic structure calculations mean that, for many atomistic simulation problems, treating light nuclei as classical particles is now one of the most serious approximations. Even though recent developments have significantly reduced the overhead for modeling the quantum nature of the nuclei, the cost is still prohibitive when combined with advanced electronic structure methods. Here we present how multiple time step integrators can be combined with ring-polymer contraction techniques (effectively, multiple time stepping in imaginary time) to reduce virtually to zero the overhead of modelling nuclear quantum effects, while describing inter-atomic forces at high levels of electronic structure theory. This is demonstrated for a combination of MP2 and semi-local DFT applied to the Zundel cation. The approach can be seamlessly combined with other methods to reduce the computational cost of path integral calculations, such as high-order factorizations of the Boltzmann operator or generalized Langevin equation thermostats.

  8. Accurate molecular dynamics and nuclear quantum effects at low cost by multiple steps in real and imaginary time: Using density functional theory to accelerate wavefunction methods

    NASA Astrophysics Data System (ADS)

    Kapil, V.; VandeVondele, J.; Ceriotti, M.

    2016-02-01

    The development and implementation of increasingly accurate methods for electronic structure calculations mean that, for many atomistic simulation problems, treating light nuclei as classical particles is now one of the most serious approximations. Even though recent developments have significantly reduced the overhead for modeling the quantum nature of the nuclei, the cost is still prohibitive when combined with advanced electronic structure methods. Here we present how multiple time step integrators can be combined with ring-polymer contraction techniques (effectively, multiple time stepping in imaginary time) to reduce virtually to zero the overhead of modelling nuclear quantum effects, while describing inter-atomic forces at high levels of electronic structure theory. This is demonstrated for a combination of MP2 and semi-local DFT applied to the Zundel cation. The approach can be seamlessly combined with other methods to reduce the computational cost of path integral calculations, such as high-order factorizations of the Boltzmann operator or generalized Langevin equation thermostats.

  9. Power Hardware-in-the-Loop Testing of Multiple Photovoltaic Inverters' Volt-Var Control with Real-Time Grid Model

    SciTech Connect

    Chakraborty, Sudipta; Nelson, Austin; Hoke, Anderson

    2016-12-12

    Traditional testing methods fall short in evaluating interactions between multiple smart inverters providing advanced grid support functions due to the fact that such interactions largely depend on their placements on the electric distribution systems with impedances between them. Even though significant concerns have been raised by the utilities on the effects of such interactions, little effort has been made to evaluate them. In this paper, power hardware-in-the-loop (PHIL) based testing was utilized to evaluate autonomous volt-var operations of multiple smart photovoltaic (PV) inverters connected to a simple distribution feeder model. The results provided in this paper show that depending on volt-var control (VVC) parameters and grid parameters, interaction between inverters and between the inverter and the grid is possible in some extreme cases with very high VVC slopes, fast response times and large VVC response delays.

  10. Strain-specific copy number variation in the intelectin locus on the 129 mouse chromosome 1.

    PubMed

    Lu, Zen H; di Domenico, Alex; Wright, Steven H; Knight, Pamela A; Whitelaw, C Bruce A; Pemberton, Alan D

    2011-02-16

    C57BL/6J mice possess a single intelectin (Itln) gene on chromosome 1. The function of intelectins is not well understood, but roles have been postulated in insulin sensitivity, bacterial recognition, intestinal lactoferrin uptake and response to parasites and allergens. In contrast to C57BL/6J mice, there is evidence for expansion of the Itln locus in other strains and at least one additional mouse Itln gene product has been described. The aim of this study was to sequence and characterise the Itln locus in the 129S7 strain, to determine the nature of the chromosomal expansion and to inform possible future gene deletion strategies. Six 129S7 BAC clones were sequenced and assembled to generate 600 kbp of chromosomal sequence, including the entire Itln locus of approximately 500 kbp. The locus contained six distinct Itln genes, two CD244 genes and several Itln- and CD244-related pseudogenes. It was approximately 433 kbp larger than the corresponding C57BL/6J locus. The expansion of the Itln locus appears to have occurred through multiple duplications of a segment consisting of a full-length Itln gene, a CD244 (pseudo)gene and an Itln pseudogene fragment. Strong evidence for tissue-specific distribution of Itln variants was found, indicating that Itln duplication contributes more than a simple gene dosage effect. We have characterised the Itln locus in 129S7 mice to reveal six Itln genes with distinct sequence and expression characteristics. Since C57BL/6J mice possess only a single Itln gene, this is likely to contribute to functional differences between C57BL/6J and other mouse strains.

  11. Strain-specific copy number variation in the intelectin locus on the 129 mouse chromosome 1

    PubMed Central

    2011-01-01

    Background C57BL/6J mice possess a single intelectin (Itln) gene on chromosome 1. The function of intelectins is not well understood, but roles have been postulated in insulin sensitivity, bacterial recognition, intestinal lactoferrin uptake and response to parasites and allergens. In contrast to C57BL/6J mice, there is evidence for expansion of the Itln locus in other strains and at least one additional mouse Itln gene product has been described. The aim of this study was to sequence and characterise the Itln locus in the 129S7 strain, to determine the nature of the chromosomal expansion and to inform possible future gene deletion strategies. Results Six 129S7 BAC clones were sequenced and assembled to generate 600 kbp of chromosomal sequence, including the entire Itln locus of approximately 500 kbp. The locus contained six distinct Itln genes, two CD244 genes and several Itln- and CD244-related pseudogenes. It was approximately 433 kbp larger than the corresponding C57BL/6J locus. The expansion of the Itln locus appears to have occurred through multiple duplications of a segment consisting of a full-length Itln gene, a CD244 (pseudo)gene and an Itln pseudogene fragment. Strong evidence for tissue-specific distribution of Itln variants was found, indicating that Itln duplication contributes more than a simple gene dosage effect. Conclusions We have characterised the Itln locus in 129S7 mice to reveal six Itln genes with distinct sequence and expression characteristics. Since C57BL/6J mice possess only a single Itln gene, this is likely to contribute to functional differences between C57BL/6J and other mouse strains. PMID:21324158

  12. Real-time bronchoscope three-dimensional motion estimation using multiple sensor-driven alignment of CT images and electromagnetic measurements.

    PubMed

    Luo, Xiongbiao; Mori, Kensaku

    2014-09-01

    Bronchoscope three-dimensional motion estimation plays a key role in developing bronchoscopic navigation systems. Currently external tracking devices, particularly electromagnetic trackers with electromagnetic sensors, are increasingly introduced to navigate surgical tools in pre-clinical images. An unavoidable problem, which is to align the electromagnetic tracker to pre-clinical images, must be solved before navigation. This paper proposes a multiple sensor-driven registration method to establish this alignment without using any anatomical fiducials. Although current fiducially free registration methods work well, they limit to the initialization of optimization and manipulating the bronchoscope along the bronchial centerlines, which could be failed easily during clinical interventions. To address these limitations, we utilize measurements of multiple electromagnetic sensors to calculate bronchoscope geometric center positions that are usually closer to the bronchial centerlines than the sensor itself measured positions. We validated our method on a bronchial phantom. The experimental results demonstrate that our idea of using multiple sensors to determine bronchoscope geometric center positions for fiducial-free registration was very effective. Compared to currently available methods in bronchoscope three-dimensional motion estimation, our method reduced fiducial alignment error from at least 6.79 to 4.68-5.26 mm and significantly improved motion estimation or tracking accuracy from at least 5.42 to 3.78-4.53 mm. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

  13. Mapping small-effect and linked quantitative trait loci for complex traits in backcross or DH populations via a multi-locus GWAS methodology

    PubMed Central

    Wang, Shi-Bo; Wen, Yang-Jun; Ren, Wen-Long; Ni, Yuan-Li; Zhang, Jin; Feng, Jian-Ying; Zhang, Yuan-Ming

    2016-01-01

    Composite interval mapping (CIM) is the most widely-used method in linkage analysis. Its main feature is the ability to control genomic background effects via inclusion of co-factors in its genetic model. However, the result often depends on how the co-factors are selected, especially for small-effect and linked quantitative trait loci (QTL). To address this issue, here we proposed a new method under the framework of genome-wide association studies (GWAS). First, a single-locus random-SNP-effect mixed linear model method for GWAS was used to scan each putative QTL on the genome in backcross or doubled haploid populations. Here, controlling background via selecting markers in the CIM was replaced by estimating polygenic variance. Then, all the peaks in the negative logarithm P-value curve were selected as the positions of multiple putative QTL to be included in a multi-locus genetic model, and true QTL were automatically identified by empirical Bayes. This called genome-wide CIM (GCIM). A series of simulated and real datasets was used to validate the new method. As a result, the new method had higher power in QTL detection, greater accuracy in QTL effect estimation, and stronger robustness under various backgrounds as compared with the CIM and empirical Bayes methods. PMID:27435756

  14. Role of a Putative Polysaccharide Locus in Bordetella Biofilm Development▿

    PubMed Central

    Parise, Gina; Mishra, Meenu; Itoh, Yoshikane; Romeo, Tony; Deora, Rajendar

    2007-01-01

    Bordetellae are gram-negative bacteria that colonize the respiratory tracts of animals and humans. We and others have recently shown that these bacteria are capable of living as sessile communities known as biofilms on a number of abiotic surfaces. During the biofilm mode of existence, bacteria produce one or more extracellular polymeric substances that function, in part, to hold the cells together and to a surface. There is little information on either the constituents of the biofilm matrix or the genetic basis of biofilm development by Bordetella spp. By utilizing immunoblot assays and by enzymatic hydrolysis using dispersin B (DspB), a glycosyl hydrolase that specifically cleaves the polysaccharide poly-β-1,6-N-acetyl-d-glucosamine (poly-β-1,6-GlcNAc), we provide evidence for the production of poly-β-1,6-GlcNAc by various Bordetella species (Bordetella bronchiseptica, B. pertussis, and B. parapertussis) and its role in their biofilm development. We have investigated the role of a Bordetella locus, here designated bpsABCD, in biofilm formation. The bps (Bordetella polysaccharide) locus is homologous to several bacterial loci that are required for the production of poly-β-1,6-GlcNAc and have been implicated in bacterial biofilm formation. By utilizing multiple microscopic techniques to analyze biofilm formation under both static and hydrodynamic conditions, we demonstrate that the bps locus, although not essential at the initial stages of biofilm formation, contributes to the stability and the maintenance of the complex architecture of Bordetella biofilms. PMID:17114249

  15. Uptake of environmental toxicants by the locus ceruleus: a potential trigger for neurodegenerative, demyelinating and psychiatric disorders.

    PubMed

    Pamphlett, Roger

    2014-01-01

    Damage to the locus ceruleus, with a subsequent decrease of CNS noradrenaline, occurs in a wide range of neurodegenerative, demyelinating and psychiatric disorders. The cause of the initial locus ceruleus damage remains unknown. Recently, inorganic mercury was found to enter human locus ceruleus neurons selectively. This has led to the formulation of a new hypothesis as to the cause of these disorders. Toxicants enter locus ceruleus neurons selectively, aided by the extensive exposure these neurons have to CNS capillaries, as well as by stressors that upregulate locus ceruleus activity. The resulting noradrenaline dysfunction affects a wide range of CNS cells and can trigger a number of neurodegenerative (Alzheimer's, Parkinson's and motor neuron disease), demyelinating (multiple sclerosis), and psychiatric (major depression and bipolar disorder) conditions. This hypothesis proposes that environmental toxicants entering the locus ceruleus can give rise to a variety of CNS disorders. Proposals are made for experiments to gain further evidence for this hypothesis. If it is shown that toxicants in the locus ceruleus are responsible for these conditions, attempts can be made to prevent the toxicant exposures or to remove the toxicants from the nervous system. Copyright © 2013 The Author. Published by Elsevier Ltd.. All rights reserved.

  16. An autosomal locus that controls chromosome-wide replication timing and mono-allelic expression.

    PubMed

    Stoffregen, Eric P; Donley, Nathan; Stauffer, Daniel; Smith, Leslie; Thayer, Mathew J

    2011-06-15

    Mammalian DNA replication initiates at multiple sites along chromosomes at different times, following a temporal replication program. Homologous alleles typically replicate synchronously; however, mono-allelically expressed genes such as imprinted genes, allelically excluded genes and genes on the female X chromosome replicate asynchronously. We have used a chromosome engineering strategy to identify a human autosomal locus that controls this replication timing program in cis. We show that Cre/loxP-mediated rearrangements at a discrete locus at 6q16.1 result in delayed replication of the entire chromosome. This locus displays asynchronous replication timing that is coordinated with other mono-allelically expressed genes on chromosome 6. Characterization of this locus revealed mono-allelic expression of a large intergenic non-coding RNA, which we have named asynchronous replication and autosomal RNA on chromosome 6, ASAR6. Finally, disruption of this locus results in the activation of the previously silent alleles of linked mono-allelically expressed genes. We previously found that chromosome rearrangements involving eight different autosomes display delayed replication timing, and that cells containing chromosomes with delayed replication timing have a 30-80-fold increase in the rate at which new gross chromosomal rearrangements occurred. Taken together, these observations indicate that human autosomes contain discrete cis-acting loci that control chromosome-wide replication timing, mono-allelic expression and the stability of entire chromosomes.

  17. An autosomal locus that controls chromosome-wide replication timing and mono-allelic expression

    PubMed Central

    Stoffregen, Eric P.; Donley, Nathan; Stauffer, Daniel; Smith, Leslie; Thayer, Mathew J.

    2011-01-01

    Mammalian DNA replication initiates at multiple sites along chromosomes at different times, following a temporal replication program. Homologous alleles typically replicate synchronously; however, mono-allelically expressed genes such as imprinted genes, allelically excluded genes and genes on the female X chromosome replicate asynchronously. We have used a chromosome engineering strategy to identify a human autosomal locus that controls this replication timing program in cis. We show that Cre/loxP-mediated rearrangements at a discrete locus at 6q16.1 result in delayed replication of the entire chromosome. This locus displays asynchronous replication timing that is coordinated with other mono-allelically expressed genes on chromosome 6. Characterization of this locus revealed mono-allelic expression of a large intergenic non-coding RNA, which we have named asynchronous replication and autosomal RNA on chromosome 6, ASAR6. Finally, disruption of this locus results in the activation of the previously silent alleles of linked mono-allelically expressed genes. We previously found that chromosome rearrangements involving eight different autosomes display delayed replication timing, and that cells containing chromosomes with delayed replication timing have a 30–80-fold increase in the rate at which new gross chromosomal rearrangements occurred. Taken together, these observations indicate that human autosomes contain discrete cis-acting loci that control chromosome-wide replication timing, mono-allelic expression and the stability of entire chromosomes. PMID:21459774

  18. Real-world use of pomalidomide and dexamethasone in double refractory multiple myeloma suggests benefit in renal impairment and adverse genetics: a multi-centre UK experience.

    PubMed

    Maciocia, Nicola; Melville, Andrew; Cheesman, Simon; Sharpley, Faye; Ramasamy, Karthik; Streetly, Matthew; Jenner, Matthew; Benjamin, Reuben; Schey, Steve; Maciocia, Paul; Popat, Rakesh; D'sa, Shirley; Rismani, Ali; Cerner, Aviva; Yong, Kwee; Rabin, Neil

    2017-03-01

    Myeloma patients who become refractory to immunomodulatory agents (IMiDs) and bortezomib have poor survival, with limited therapeutic options. Pomalidomide has shown improved survival and good tolerability in this patient cohort in clinical trials, but real world data are scarce. We retrospectively analysed all patients treated with pomalidomide at five UK centres between 2013 and 2016. Of 85 patients identified, 70 had sufficient information for response assessments. Median age was 66 years [40-89], 96·5% were refractory to IMiDs, 72·9% were refractory to both an IMiD and bortezomib and 92·9% were refractory to their last treatment. Of 45 patients with fluorescence in situ hybridization results 64% had adverse risk, 19 patients (22·4%) had an estimated glomerular filtration rate <45 ml/min. Grade ≥3 non-haematological toxicities occurred in 42·4%, and grade ≥3 neutropenia and thrombocytopenia in 38% and 24% respectively, but only 18·8% had dose reductions. The overall response rate was 52·9%. At a median follow-up of 13·2 months, median progression-free survival was 5·2 months [95% confidence interval (CI) 4·150-6·238], and median overall survival was 13·7 months (95% CI 11·775-15·707). No significant difference was seen in response, survival or tolerability by renal function, age or cytogenetic risk. This real-world data support the results seen in published clinical trials.

  19. Combined insulin pump therapy with real-time continuous glucose monitoring significantly improves glycemic control compared to multiple daily injection therapy in pump naïve patients with type 1 diabetes; single center pilot study experience.

    PubMed

    Lee, Scott W; Sweeney, Tom; Clausen, Debbie; Kolbach, Celia; Hassen, Allen; Firek, Anthony; Brinegar, Charles; Petrofsky, Jerrold

    2007-05-01

    This study assessed the safety and clinical effectiveness of the training protocol for initiating insulin pump therapy with real-time continuous glucose monitoring (MiniMed Paradigm REAL-Time System) in a stepwise approach on pump naive subjects with type 1 diabetes compared to a control group who remained on multiple daily injection (MDI) therapy. This was a 15-week treat-to-target pilot study of 16 adult subjects (n = 50% male, age 45.9 +/- 16 years) with type 1 diabetes (duration of diabetes 21.9 +/- 11 years) on MDI therapy with hemoglobin A1c levels at or above 7.5% at baseline. Subjects were randomized to either the study arm (using a combined insulin pump and real-time continuous glucose monitoring system) or the control arm [which continued on MDI therapy with self-monitored blood glucose (SMBG) only]. All subjects dosed insulin according to results of SMBG by finger stick and uploaded data into the CareLink data management software. Significant improvements in glycemic control were observed from baseline in both study groups-study arm: pre-A1c 9.45 +/- 0.55 and post-A1c 7.4 +/- 0.66 (p = 0.00037); control arm: pre-A1c 8.58 +/- 1.30 and post-A1c 7.5 +/-1.01 (p = 0.04). Both arms had no incidence of severe hypoglycemia. In this pilot study, the Paradigm REAL-Time System was initiated safely and effectively in type 1 diabetes patients who were pump naïve using a stepwise educational protocol.

  20. Combined Insulin Pump Therapy with Real-Time Continuous Glucose Monitoring Significantly Improves Glycemic Control Compared to Multiple Daily Injection Therapy in Pump Naïve Patients with Type 1 Diabetes; Single Center Pilot Study Experience

    PubMed Central

    Lee, Scott W.; Sweeney, Tom; Clausen, Debbie; Kolbach, Celia; Hassen, Allen; Firek, Anthony; Brinegar, Charles; Petrofsky, Jerrold

    2007-01-01

    Objectives This study assessed the safety and clinical effectiveness of the training protocol for initiating insulin pump therapy with real-time continuous glucose monitoring (MiniMed Paradigm REAL-Time System) in a stepwise approach on pump naive subjects with type 1 diabetes compared to a control group who remained on multiple daily injection (MDI) therapy. Methods This was a 15-week treat-to-target pilot study of 16 adult subjects (n = 50% male, age 45.9 ± 16 years) with type 1 diabetes (duration of diabetes 21.9 ± 11 years) on MDI therapy with hemoglobin A1c levels at or above 7.5% at baseline. Subjects were randomized to either the study arm (using a combined insulin pump and real-time continuous glucose monitoring system) or the control arm [which continued on MDI therapy with self-monitored blood glucose (SMBG) only]. All subjects dosed insulin according to results of SMBG by finger stick and uploaded data into the CareLink data management software. Results Significant improvements in glycemic control were observed from baseline in both study groups—study arm: pre-A1c 9.45 ± 0.55 and post-A1c 7.4 ± 0.66 (p = 0.00037); control arm: pre-A1c 8.58 ± 1.30 and post-A1c 7.5 ±1.01 (p = 0.04). Both arms had no incidence of severe hypoglycemia. Conclusion In this pilot study, the Paradigm REAL-Time System was initiated safely and effectively in type 1 diabetes patients who were pump naïve using a stepwise educational protocol. PMID:19885096

  1. Mox: a novel modifier of the tomato Xa locus.

    PubMed

    Peterson, P W; Yoder, J I

    1995-01-01

    We have isolated a novel mutation that caused variegated leaf color in a tomato plant which had multiple maize Ac transposable elements and the tomato Xa allele. Xa is a previously characterized semi-dominant mutation that causes tomato leaves to be bright yellow when heterozygous (Xa/xa+). The mutation responsible for the new phenotype was named Mox (Modifier of Xa). The Mox mutation modified the Xa/xa+ yellow leaf phenotype in two ways: it compensated for the Xa allele resulting in a plant with a wildtype green color, and it caused somatic variegation which appeared as white and yellow sectors on the green background. Somatic variegation was visible only if the plant contained both the Mox and Xa loci. Genetic studies indicated that the Mox locus was linked in repulsion to Xa and that the Mox locus was genetically transmitted at a reduced frequency through the male gamete. Molecular characterization of the Ac elements in lines segregating for Mox identified an Ac insertion that appeared to cosegregate with Mox variegation. We propose a model in which the Mox mutation consists of a duplication of the xa+ allele and subsequent Ac-induced breakage of the duplicated region causes variegation.

  2. Intrahaplotype polymorphism at the Brassica S locus.

    PubMed Central

    Miege, C; Ruffio-Châble, V; Schierup, M H; Cabrillac, D; Dumas, C; Gaude, T; Cock, J M

    2001-01-01

    The S locus receptor kinase and the S locus glycoproteins are encoded by genes located at the S locus, which controls the self-incompatibility response in Brassica. In class II self-incompatibility haplotypes, S locus glycoproteins can be encoded by two different genes, SLGA and SLGB. In this study, we analyzed the sequences of these genes in several independently isolated plants, all of which carry the same S haplotype (S(2)). Two groups of S(2) haplotypes could be distinguished depending on whether SRK was associated with SLGA or SLGB. Surprisingly, SRK alleles from the two groups could be distinguished at the sequence level, suggesting that recombination rarely occurs between haplotypes of the two groups. An analysis of the distribution of polymorphisms along the S domain of SRK showed that hypervariable domains I and II tend to be conserved within haplotypes but to be highly variable between haplotypes. This is consistent with these domains playing a role in the determination of haplotype specificity. PMID:11606555

  3. The Preconscious: Locus for Significant Written Compositions.

    ERIC Educational Resources Information Center

    Alley, Alvin D.

    1979-01-01

    The author suggests that the preconscious is the true locus of significant prose because of its greater amount of freedom to gather, compare, and rearrange ideas, and that the ultimate challenge to teachers of composition is to give freedom to their students' preconscious processes. (KC)

  4. Exercise Adherence and Locus of Control.

    ERIC Educational Resources Information Center

    Geshuri, Yosef; Glahn, Ronald

    In 1990, a study was conducted to investigate the relationship between students' locus of control and the extent to which they participated in a voluntary exercise program. First-time participants in the "Shape Up" program offered at the Porterville College Fitness Center during the summer and fall semesters of 1990 were identified through the…

  5. A suppressor locus for MODY3-diabetes

    PubMed Central

    Garcia-Gonzalez, Miguel A.; Carette, Claire; Bagattin, Alessia; Chiral, Magali; Makinistoglu, Munevver Parla; Garbay, Serge; Prévost, Géraldine; Madaras, Cécile; Hérault, Yann; Leibovici, Michel; Pontoglio, Marco

    2016-01-01

    Maturity Onset Diabetes of the Young type 3 (MODY3), linked to mutations in the transcription factor HNF1A, is the most prevalent form of monogenic diabetes mellitus. HNF1alpha-deficiency leads to defective insulin secretion via a molecular mechanism that is still not completely understood. Moreover, in MODY3 patients the severity of insulin secretion can be extremely variable even in the same kindred, indicating that modifier genes may control the onset of the disease. With the use of a mouse model for HNF1alpha-deficiency, we show here that specific genetic backgrounds (C3H and CBA) carry a powerful genetic suppressor of diabetes. A genome scan analysis led to the identification of a major suppressor locus on chromosome 3 (Moda1). Moda1 locus contains 11 genes with non-synonymous SNPs that significantly interacts with other loci on chromosomes 4, 11 and 18. Mechanistically, the absence of HNF1alpha in diabetic-prone (sensitive) strains leads to postnatal defective islets growth that is remarkably restored in resistant strains. Our findings are relevant to human genetics since Moda1 is syntenic with a human locus identified by genome wide association studies of fasting glycemia in patients. Most importantly, our results show that a single genetic locus can completely suppress diabetes in Hnf1a-deficiency. PMID:27667715

  6. Dental Outpatients: Health Locus of Control Correlates.

    ERIC Educational Resources Information Center

    Ludenia, Krista; Donham, Greg W.

    1983-01-01

    Examined relationships among specific personality variables, the Multidimensional Health Locus of Control Scales, and criterion-based ratings by staff dentists with dental outpatients (N=101). Found a consistent relationship between the perception that health is maintained by engaging in health-related behaviors and individual difference measures…

  7. Dental Outpatients: Health Locus of Control Correlates.

    ERIC Educational Resources Information Center

    Ludenia, Krista; Donham, Greg W.

    1983-01-01

    Examined relationships among specific personality variables, the Multidimensional Health Locus of Control Scales, and criterion-based ratings by staff dentists with dental outpatients (N=101). Found a consistent relationship between the perception that health is maintained by engaging in health-related behaviors and individual difference measures…

  8. Multidimensionality of Locus of Control in Females.

    ERIC Educational Resources Information Center

    Kearney, Maureen J.; Kearney, James F.

    The Internal-External (I-E) Locus of Control scale (Rotter, 1966) was administered to 185 male and 185 female university students. The resulting scores were factored, producing two factors for males and four for females. The male factors were the generally-accepted "luck" and "powerful others"; for women, however, the "powerful others" dimension…

  9. Locus of Control, Social Class, and Learning.

    ERIC Educational Resources Information Center

    Vasquez, James A.

    The relationship between locus of control, social class, and learning processes were reviewed by analyzing: (1) externality as a function of socioeconomic status, i.e., the lower the status, the greater the degree of externality; (2) the impact of the early home environment on the child's learning and development; (3) classroom and teacher…

  10. Genome-wide association filtering using a highly locus-specific transmission/disequilibrium test

    PubMed Central

    Medina-Medina, Nuria; Montes-Soldado, Rosana; Moreno-Ortega, José; Matesanz, Fuencisla

    2010-01-01

    Multimarker transmission/disequilibrium tests (TDTs) are powerful association and linkage tests used to perform genome-wide filtering in the search for disease susceptibility loci. In contrast to case/control studies, they have a low rate of false positives for population stratification and admixture. However, the length of a region found in association with a disease is usually very large because of linkage disequilibrium (LD). Here, we define a multimarker proportional TDT (mTDTP) designed to improve locus specificity in complex diseases that has good power compared to the most powerful multimarker TDTs. The test is a simple generalization of a multimarker TDT in which haplotype frequencies are used to weight the effect that each haplotype has on the whole measure. Two concepts underlie the features of the metric: the ‘common disease, common variant’ hypothesis and the decrease in LD with chromosomal distance. Because of this decrease, the frequency of haplotypes in strong LD with common disease variants decreases with increasing distance from the disease susceptibility locus. Thus, our haplotype proportional test has higher locus specificity than common multimarker TDTs that assume a uniform distribution of haplotype probabilities. Because of the common variant hypothesis, risk haplotypes at a given locus are relatively frequent and a metric that weights partial results for each haplotype by its frequency will be as powerful as the most powerful multimarker TDTs. Simulations and real data sets demonstrate that the test has good power compared with the best tests but has remarkably higher locus specificity, so that the association rate decreases at a higher rate with distance from a disease susceptibility or disease protective locus. PMID:20603721

  11. Genome-wide association filtering using a highly locus-specific transmission/disequilibrium test.

    PubMed

    Abad-Grau, María M; Medina-Medina, Nuria; Montes-Soldado, Rosana; Moreno-Ortega, José; Matesanz, Fuencisla

    2010-09-01

    Multimarker transmission/disequilibrium tests (TDTs) are powerful association and linkage tests used to perform genome-wide filtering in the search for disease susceptibility loci. In contrast to case/control studies, they have a low rate of false positives for population stratification and admixture. However, the length of a region found in association with a disease is usually very large because of linkage disequilibrium (LD). Here, we define a multimarker proportional TDT (mTDT ( P )) designed to improve locus specificity in complex diseases that has good power compared to the most powerful multimarker TDTs. The test is a simple generalization of a multimarker TDT in which haplotype frequencies are used to weight the effect that each haplotype has on the whole measure. Two concepts underlie the features of the metric: the 'common disease, common variant' hypothesis and the decrease in LD with chromosomal distance. Because of this decrease, the frequency of haplotypes in strong LD with common disease variants decreases with increasing distance from the disease susceptibility locus. Thus, our haplotype proportional test has higher locus specificity than common multimarker TDTs that assume a uniform distribution of haplotype probabilities. Because of the common variant hypothesis, risk haplotypes at a given locus are relatively frequent and a metric that weights partial results for each haplotype by its frequency will be as powerful as the most powerful multimarker TDTs. Simulations and real data sets demonstrate that the test has good power compared with the best tests but has remarkably higher locus specificity, so that the association rate decreases at a higher rate with distance from a disease susceptibility or disease protective locus.

  12. Who's on first? Tracking in real time the growth of multiple crystalline phases of an organic semiconductor: Tetracene on SiO2.

    PubMed

    Nahm, R K; Engstrom, J R

    2017-02-07

    We have examined the effect of growth rate on the evolution of two polymorphs of thin films of tetracene on SiO2 using synchrotron X-ray radiation and molecular beam techniques. Ex situ X-ray reflectivity shows that tetracene forms two phases on SiO2: a thin-film phase and a bulk phase. We have used in situ, real-time grazing incidence diffraction during growth to reveal the nature of growth concerning these two phases. We observe that there is initially growth of only the thin-film phase, up to a thickness of several monolayers. This is followed by the nucleation of the bulk phase, growth of both phases, and finally growth of only the bulk phase. We find that the deposited thickness when the bulk phase nucleates increases with increasing growth rate. Similarly, we find that the deposited thickness at which the thin-film phase saturates also increases with increasing growth rate. These apparent dependencies on growth rate are actually a consequence of the local coverage, which depends on growth rate, particularly for the former effect. At low growth rates, there is 3D growth resulting from the upward transport of tetracene at island edges, resulting in tall features where molecules escape the influence of the substrate and form into the bulk phase. Increasing the growth rate leads to growth that is more 2D and uniform in coverage, delaying the formation of the bulk phase.

  13. Who's on first? Tracking in real time the growth of multiple crystalline phases of an organic semiconductor: Tetracene on SiO2

    NASA Astrophysics Data System (ADS)

    Nahm, R. K.; Engstrom, J. R.

    2017-02-01

    We have examined the effect of growth rate on the evolution of two polymorphs of thin films of tetracene on SiO2 using synchrotron X-ray radiation and molecular beam techniques. Ex situ X-ray reflectivity shows that tetracene forms two phases on SiO2: a thin-film phase and a bulk phase. We have used in situ, real-time grazing incidence diffraction during growth to reveal the nature of growth concerning these two phases. We observe that there is initially growth of only the thin-film phase, up to a thickness of several monolayers. This is followed by the nucleation of the bulk phase, growth of both phases, and finally growth of only the bulk phase. We find that the deposited thickness when the bulk phase nucleates increases with increasing growth rate. Similarly, we find that the deposited thickness at which the thin-film phase saturates also increases with increasing growth rate. These apparent dependencies on growth rate are actually a consequence of the local coverage, which depends on growth rate, particularly for the former effect. At low growth rates, there is 3D growth resulting from the upward transport of tetracene at island edges, resulting in tall features where molecules escape the influence of the substrate and form into the bulk phase. Increasing the growth rate leads to growth that is more 2D and uniform in coverage, delaying the formation of the bulk phase.

  14. Real Language Meets Real Business

    ERIC Educational Resources Information Center

    Muirhead, Muirhead; Schechter, Sarah

    2016-01-01

    The Real Business Language Challenge was a collaborative pilot project between Coca-Cola Enterprises (CCE) and Routes into Languages East for Year 9 and 10 pupils. It was based on CCE's award-winning Real Business Challenge, part of its highly acclaimed education programme. The Real Business Language Challenge transformed the project into a…

  15. Development and Evaluation of a Real-Time Reverse Transcription-PCR Assay for Quantification of Gamma Interferon mRNA To Diagnose Tuberculosis in Multiple Animal Species▿

    PubMed Central

    Harrington, Noel P.; Surujballi, Om P.; Waters, W. Ray; Prescott, John F.

    2007-01-01

    Tuberculosis of free-ranging and captive wildlife, including species implicated in the maintenance and transmission of Mycobacterium bovis, is a difficult disease to diagnose and control. Historically, diagnosis of tuberculosis has relied largely upon assays of cell-mediated immunity (CMI), such as tuberculin skin testing. This approach, however, is problematic or impractical for use with many wildlife species. Increasingly, in vitro diagnostic tests, including gamma interferon (IFN-γ)-based assays, are replacing or complementing skin testing of cattle and humans. Analogous assays are unavailable for most wildlife because of a lack of species-specific immunological reagents. This report describes the development and validation of a whole-blood assay to quantify antigen-specific IFN-γ mRNA expression by quantitative real-time reverse transcription-PCR. Oligonucleotide primers and probes were designed and tested for reactivity towards several susceptible species of interest with respect to tuberculosis infection. The assay was subsequently optimized to quantify the IFN-γ mRNA expression in elk and red deer (Cervus elaphus) and was evaluated for its ability to detect mycobacterial antigen-specific responses of experimentally tuberculosis-infected animals. The assay was a simple, rapid, and sensitive measure of antigen-specific CMI. The IFN-γ mRNA responses correlated well with IFN-γ protein production and showed performance in determining an animal's infection status superior to that of either lymphocyte proliferation or IFN-γ protein enzyme-linked immunosorbent assay methods. An additional advantage is the ease with which the assay can be modified to reliably quantify IFN-γ expression by using consensus sequences of closely related species or of other species for which IFN-γ sequence information is available. PMID:17942606

  16. Characteristics and sensitivity analysis of multiple-time-resolved source patterns of PM2.5 with real time data using Multilinear Engine 2

    NASA Astrophysics Data System (ADS)

    Peng, Xing; Shi, Guo-Liang; Gao, Jian; Liu, Jia-Yuan; HuangFu, Yan-Qi; Ma, Tong; Wang, Hai-Ting; Zhang, Yue-Chong; Wang, Han; Li, Hui; Ivey, Cesunica E.; Feng, Yin-Chang

    2016-08-01

    With real time resolved data of Particulate matter (PM) and chemical species, understanding the source patterns and chemical characteristics is critical to establish controlling of PM. In this work, PM2.5 and chemical species were measured by corresponding online instruments with 1-h time resolution in Beijing. Multilinear Engine 2 (ME2) model was applied to explore the sources, and four sources (vehicle emission, crustal dust, secondary formation and coal combustion) were identified. To investigate the sensitivity of time resolution on the source contributions and chemical characteristics, ME2 was conducted with four time resolution runs (1-h, 2-h, 4-h, and 8-h). Crustal dust and coal combustion display large variation in the four time resolutions runs, with their contributions ranging from 6.7 to 10.4 μg m-3 and from 6.4 to 12.2 μg m-3, respectively. The contributions of vehicle emission and secondary formation range from 7.5 to 10.5 and from 14.7 to 16.7 μg m-3, respectively. The sensitivity analyses were conducted by principal component analysis-plot (PCA-plot), coefficient of divergence (CD), average absolute error (AAE) and correlation coefficients. For the four time resolution runs, the source contributions and profiles of crustal dust and coal combustion were more unstable than other source categories, possibly due to the lack of key markers of crustal dust and coal combustion (e.g. Si, Al). On the other hand, vehicle emission and crustal dust were more sensitive to time series of source contributions at different time resolutions. Findings in this study can improve our knowledge of source contributions and chemical characteristics at different time solutions.

  17. Automated anatomical labeling of bronchial branches using multiple classifiers and its application to bronchoscopy guidance based on fusion of virtual and real bronchoscopy

    NASA Astrophysics Data System (ADS)

    Ota, Shunsuke; Deguchi, Daisuke; Kitasaka, Takayuki; Mori, Kensaku; Suenaga, Yasuhito; Hasegawa, Yoshinori; Imaizumi, Kazuyoshi; Takabatake, Hirotsugu; Mori, Masaki; Natori, Hiroshi

    2008-03-01

    This paper presents a method for automated anatomical labeling of bronchial branches (ALBB) extracted from 3D CT datasets. The proposed method constructs classifiers that output anatomical names of bronchial branches by employing the machine-learning approach. We also present its application to a bronchoscopy guidance system. Since the bronchus has a complex tree structure, bronchoscopists easily tend to get disoriented and lose the way to a target location. A bronchoscopy guidance system is strongly expected to be developed to assist bronchoscopists. In such guidance system, automated presentation of anatomical names is quite useful information for bronchoscopy. Although several methods for automated ALBB were reported, most of them constructed models taking only variations of branching patterns into account and did not consider those of running directions. Since the running directions of bronchial branches differ greatly in individuals, they could not perform ALBB accurately when running directions of bronchial branches were different from those of models. Our method tries to solve such problems by utilizing the machine-learning approach. Actual procedure consists of three steps: (a) extraction of bronchial tree structures from 3D CT datasets, (b) construction of classifiers using the multi-class AdaBoost technique, and (c) automated classification of bronchial branches by using the constructed classifiers. We applied the proposed method to 51 cases of 3D CT datasets. The constructed classifiers were evaluated by leave-one-out scheme. The experimental results showed that the proposed method could assign correct anatomical names to bronchial branches of 89.1% up to segmental lobe branches. Also, we confirmed that it was quite useful to assist the bronchoscopy by presenting anatomical names of bronchial branches on real bronchoscopic views.

  18. A Locked Nucleic Acid (LNA)-Based Real-Time PCR Assay for the Rapid Detection of Multiple Bacterial Antibiotic Resistance Genes Directly from Positive Blood Culture

    PubMed Central

    Zhu, Lingxiang; Shen, Dingxia; Zhou, Qiming; Li, Zexia; Fang, Xiangdong; Li, Quan-Zhen

    2015-01-01

    Bacterial strains resistant to various antibiotic drugs are frequently encountered in clinical infections, and the rapid identification of drug-resistant strains is highly essential for clinical treatment. We developed a locked nucleic acid (LNA)-based quantitative real-time PCR (LNA-qPCR) method for the rapid detection of 13 antibiotic resistance genes and successfully used it to distinguish drug-resistant bacterial strains from positive blood culture samples. A sequence-specific primer-probe set was designed, and the specificity of the assays was assessed using 27 ATCC bacterial strains and 77 negative blood culture samples. No cross-reaction was identified among bacterial strains and in negative samples, indicating 100% specificity. The sensitivity of the assays was determined by spiking each bacterial strain into negative blood samples, and the detection limit was 1–10 colony forming units (CFU) per reaction. The LNA-qPCR assays were first applied to 72 clinical bacterial isolates for the identification of known drug resistance genes, and the results were verified by the direct sequencing of PCR products. Finally, the LNA-qPCR assays were used for the detection in 47 positive blood culture samples, 19 of which (40.4%) were positive for antibiotic resistance genes, showing 91.5% consistency with phenotypic susceptibility results. In conclusion, LNA-qPCR is a reliable method for the rapid detection of bacterial antibiotic resistance genes and can be used as a supplement to phenotypic susceptibility testing for the early detection of antimicrobial resistance to allow the selection of appropriate antimicrobial treatment and to prevent the spread of resistant isolates. PMID:25775001

  19. Development and evaluation of a real-time reverse transcription-PCR assay for quantification of gamma interferon mRNA to diagnose tuberculosis in multiple animal species.

    PubMed

    Harrington, Noel P; Surujballi, Om P; Waters, W Ray; Prescott, John F

    2007-12-01

    Tuberculosis of free-ranging and captive wildlife, including species implicated in the maintenance and transmission of Mycobacterium bovis, is a difficult disease to diagnose and control. Historically, diagnosis of tuberculosis has relied largely upon assays of cell-mediated immunity (CMI), such as tuberculin skin testing. This approach, however, is problematic or impractical for use with many wildlife species. Increasingly, in vitro diagnostic tests, including gamma interferon (IFN-gamma)-based assays, are replacing or complementing skin testing of cattle and humans. Analogous assays are unavailable for most wildlife because of a lack of species-specific immunological reagents. This report describes the development and validation of a whole-blood assay to quantify antigen-specific IFN-gamma mRNA expression by quantitative real-time reverse transcription-PCR. Oligonucleotide primers and probes were designed and tested for reactivity towards several susceptible species of interest with respect to tuberculosis infection. The assay was subsequently optimized to quantify the IFN-gamma mRNA expression in elk and red deer (Cervus elaphus) and was evaluated for its ability to detect mycobacterial antigen-specific responses of experimentally tuberculosis-infected animals. The assay was a simple, rapid, and sensitive measure of antigen-specific CMI. The IFN-gamma mRNA responses correlated well with IFN-gamma protein production and showed performance in determining an animal's infection status superior to that of either lymphocyte proliferation or IFN-gamma protein enzyme-linked immunosorbent assay methods. An additional advantage is the ease with which the assay can be modified to reliably quantify IFN-gamma expression by using consensus sequences of closely related species or of other species for which IFN-gamma sequence information is available.

  20. A locked nucleic acid (LNA)-based real-time PCR assay for the rapid detection of multiple bacterial antibiotic resistance genes directly from positive blood culture.

    PubMed

    Zhu, Lingxiang; Shen, Dingxia; Zhou, Qiming; Li, Zexia; Fang, Xiangdong; Li, Quan-Zhen

    2015-01-01

    Bacterial strains resistant to various antibiotic drugs are frequently encountered in clinical infections, and the rapid identification of drug-resistant strains is highly essential for clinical treatment. We developed a locked nucleic acid (LNA)-based quantitative real-time PCR (LNA-qPCR) method for the rapid detection of 13 antibiotic resistance genes and successfully used it to distinguish drug-resistant bacterial strains from positive blood culture samples. A sequence-specific primer-probe set was designed, and the specificity of the assays was assessed using 27 ATCC bacterial strains and 77 negative blood culture samples. No cross-reaction was identified among bacterial strains and in negative samples, indicating 100% specificity. The sensitivity of the assays was determined by spiking each bacterial strain into negative blood samples, and the detection limit was 1-10 colony forming units (CFU) per reaction. The LNA-qPCR assays were first applied to 72 clinical bacterial isolates for the identification of known drug resistance genes, and the results were verified by the direct sequencing of PCR products. Finally, the LNA-qPCR assays were used for the detection in 47 positive blood culture samples, 19 of which (40.4%) were positive for antibiotic resistance genes, showing 91.5% consistency with phenotypic susceptibility results. In conclusion, LNA-qPCR is a reliable method for the rapid detection of bacterial antibiotic resistance genes and can be used as a supplement to phenotypic susceptibility testing for the early detection of antimicrobial resistance to allow the selection of appropriate antimicrobial treatment and to prevent the spread of resistant isolates.

  1. Evolution of an expanded sex-determining locus in Volvox.

    PubMed

    Ferris, Patrick; Olson, Bradley J S C; De Hoff, Peter L; Douglass, Stephen; Casero, David; Prochnik, Simon; Geng, Sa; Rai, Rhitu; Grimwood, Jane; Schmutz, Jeremy; Nishii, Ichiro; Hamaji, Takashi; Nozaki, Hisayoshi; Pellegrini, Matteo; Umen, James G

    2010-04-16

    Although dimorphic sexes have evolved repeatedly in multicellular eukaryotes, their origins are unknown. The mating locus (MT) of the sexually dimorphic multicellular green alga Volvox carteri specifies the production of eggs and sperm and has undergone a remarkable expansion and divergence relative to MT from Chlamydomonas reinhardtii, which is a closely related unicellular species that has equal-sized gametes. Transcriptome analysis revealed a rewired gametic expression program for Volvox MT genes relative to Chlamydomonas and identified multiple gender-specific and sex-regulated transcripts. The retinoblastoma tumor suppressor homolog MAT3 is a Volvox MT gene that displays sexually regulated alternative splicing and evidence of gender-specific selection, both of which are indicative of cooption into the sexual cycle. Thus, sex-determining loci affect the evolution of both sex-related and non-sex-related genes.

  2. Evolution of an Expanded Sex Determining Locus in Volvox

    PubMed Central

    Ferris, Patrick; Olson, Bradley J.S.C.; De Hoff, Peter L.; Douglass, Stephen; Diaz-Cano, David Casero; Prochnik, Simon; Geng, Sa; Rai, Rhitu; Grimwood, Jane; Schmutz, Jeremy; Nishii, Ichiro; Hamaji, Takashi; Nozaki, Hisayoshi; Pellegrini, Matteo; Umen, James G.

    2010-01-01

    Although dimorphic sexes have evolved repeatedly in multicellular eukaryotes, their origins are unknown. The mating locus (MT) of the sexually dimorphic multicellular green alga, Volvox carteri, specifies the production of eggs and sperm and has undergone a remarkable expansion and divergence relative to MT from Chlamydomonas reinhardtii, a closely related unicellular species that has equal-sized gametes. Transcriptome analysis revealed a rewired gametic expression program for Volvox MT genes relative to Chlamydomonas, and identified multiple gender-specific and sex-regulated transcripts. The retinoblastoma tumor suppressor homolog MAT3 is a Volvox MT gene that displays sexually regulated alternative splicing and evidence of gender-specific selection, both indicative of cooption into the sexual cycle. Thus, sex-determining loci impact the evolution of both sex-related and non-sex-related genes. PMID:20395508

  3. A strabismus susceptibility locus on chromosome 7p

    PubMed Central

    Parikh, Vaishali; Shugart, Yin Yao; Doheny, Kimberly F.; Zhang, Jie; Li, Lan; Williams, John; Hayden, David; Craig, Brian; Capo, Hilda; Chamblee, Denise; Chen, Cathy; Collins, Mary; Dankner, Stuart; Fiergang, Dean; Guyton, David; Hunter, David; Hutcheon, Marcia; Keys, Marshall; Morrison, Nancy; Munoz, Michelle; Parks, Marshall; Plotsky, David; Protzko, Eugene; Repka, Michael X.; Sarubbi, Maria; Schnall, Bruce; Siatkowski, R. Michael; Traboulsi, Elias; Waeltermann, Joanne; Nathans, Jeremy

    2003-01-01

    Strabismus has been known to have a significant genetic component, but the mode of inheritance and the identity of the relevant genes have been enigmatic. This paper reports linkage analysis of nonsyndromic strabismus. The principal results of this study are: (i) the demonstrated feasibility of identifying and recruiting large families in which multiple members have (or had) strabismus; (ii) the linkage in one large family of a presumptive strabismus susceptibility locus to 7p22.1 with a multipoint logarithm of odds score of 4.51 under a model of recessive inheritance; and (iii) the failure to observe significant linkage to 7p in six other multiplex families, consistent with genetic heterogeneity among families. These findings suggest that it will be possible to localize and ultimately identify strabismus susceptibility genes by linkage analysis and mutation screening of candidate genes. PMID:14519848

  4. Cajal bodies and histone locus bodies in Drosophila and Xenopus.

    PubMed

    Nizami, Z F; Deryusheva, S; Gall, J G

    2010-01-01

    The organization of the cell nucleus into specialized compartments is important for nuclear function. We address the significance of compartmentalization by studying the Cajal body, an evolutionarily conserved nuclear organelle proposed to be involved in such diverse functions as assembly of the spliceosome, assembly of the transcription machinery, and modification of spliceosomal small nuclear RNAs. The Cajal body is typically identified by the presence of coilin, a protein of poorly defined function. Here, we demonstrate that coilin is not a unique Cajal body marker but also occurs in a related yet distinct nuclear organelle known as the histone locus body in both Drosophila and Xenopus. We stress the importance of multiple markers not only for identification of nuclear bodies but also for assessing their functional significance.

  5. The Impact of Locus of Control on Language Achievement

    ERIC Educational Resources Information Center

    Nodoushan, Mohammad Ali Salmani

    2012-01-01

    This study hypothesized that students' loci of control affected their language achievement. 198 (N = 198) EFL students took the Rotter's (1966) locus of control test and were classified as locus-internal (ni = 78), and locus-external (ne = 120). They then took their ordinary courses and at the end of the semester, they were given their exams.…

  6. Cognitive Evaluation Theory, Locus of Control and Positive Verbal Feedback.

    ERIC Educational Resources Information Center

    Lonky, Edward; Reihman, Jacqueline

    This study tests the hypothesis that individual differences in locus of control orientation may mediate elementary school students' responses to positive verbal feedback. A total of 30 kindergarten through fourth grade subjects were assessed for locus of control orientation using the Bialer Children's Locus of Control Questionnaire. To establish a…

  7. Self-Esteem, Locus of Control, and Student Achievement.

    ERIC Educational Resources Information Center

    Sterbin, Allan; Rakow, Ernest

    The direct effects of locus of control and self-esteem on standardized test scores were studied. The relationships among the standardized test scores and measures of locus of control and self-esteem for 12,260 students from the National Education Longitudinal Study 1994 database were examined, using the same definition of locus of control and…

  8. Locus of control and the fundamental dimensions of moods.

    PubMed

    Henson, H N; Chang, E C

    1998-06-01

    The present study examined the association between locus of control and positive and negative moods in 253 college students. Using the PANAS-X, designed by Watson and Clark, individuals scoring high on internal locus of control also scored higher across different dimensions of positive mood. Conversely, individuals scoring high on external locus of control had higher scores across different dimensions of negative mood.

  9. Physics of a magnetic filter for negative ion sources. II. E Multiplication-Sign B drift through the filter in a real geometry

    SciTech Connect

    Boeuf, J. P.; Claustre, J.; Chaudhury, B.; Fubiani, G.

    2012-11-15

    The physics of a magnetic filter under conditions similar to those of the negative ion source for the ITER neutral beam injector is analyzed with the help of a two-dimensional particle-in-cell Monte Carlo Collisions model. A detailed analysis of the different terms of the electron momentum equations shows how diamagnetic and drift currents can be dominant in different regions of the filter. Electron transport through the filter is due to an E Multiplication-Sign B drift current on one side of the chamber induced by the presence of the chamber walls perpendicular to the electron diamagnetic current. The filter design of the ITER negative ion source, which does not allow a closed electron diamagnetic current, induces an asymmetry of the plasma that is analyzed with the particle model. It is shown that electron transport through the filter in this geometry is very different from the transport in an ideal, one-dimensional magnetic filter often considered in the literature and described in detail in the companion paper [Boeuf et al., Phys. Plasmas 19, 113509 (2012)].

  10. A silent allele in the locus D5S818 contained within the PowerPlex®21 PCR Amplification Kit.

    PubMed

    Chen, Ling; Tai, Yunchun; Qiu, Pingming; Du, Weian; Liu, Chao

    2015-11-01

    Three paternity tests cases were found with a single locus mismatch at the locus D5S818 with PowerPlex®21 PCR Amplification Kit (Promega). Forward and reverse primers were redesigned to type the samples again and to evaluate if there were alleles dropped out. The results showed the existence of a silent allele 12 in all the three families, due to a point mutation that changed cytosine to adenine at 90 nucleotides upstream from the 5' end of the AGAT repeat sequences in all the six individuals. A single locus mismatch due to a silent allele may occur in any locus using any kit. Therefore, we recommend using multiple kits to confirm the results in paternity testing cases with mismatches, especially when there is a single locus mismatch with homozygote involved.

  11. Long-Term Data of Efficacy, Safety, and Tolerability in a Real-Life Setting of THC/CBD Oromucosal Spray-Treated Multiple Sclerosis Patients.

    PubMed

    Paolicelli, Damiano; Direnzo, Vita; Manni, Alessia; D'Onghia, Mariangela; Tortorella, Carla; Zoccolella, Stefano; Di Lecce, Valentina; Iaffaldano, Antonio; Trojano, Maria

    2016-07-01

    Delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray was approved as add-on therapy for spasticity in patients with multiple sclerosis (MS). We show our 40-week postmarketing experience regarding efficacy and safety of THC/CBD spray in an Italian cohort of 102 MS patients. Patients were evaluated using the Expanded Disability Status Scale (EDSS) score, the Numerical Rating Scale (NRS) for spasticity, the Ambulation Index (AI), and Timed 25-Foot Walk (T25-FW) at the beginning of treatment and then every 3 months. After 4 weeks, if a clinically significant improvement in spasticity (at least 20% of baseline NRS score) was not seen, administration of the drug was stopped. In our cohort, patients received an average of 6.5 ± 1.6 sprays each day. The mean reduction to the NRS spasticity score was 2.5 ± 1.2 points (P < .0001). Thirty-seven patients (36.2%) discontinued the treatment. The incidence of adverse events (AEs) was 40.2%. Fifty-eight patients (56.9%) were also assessed using the NRS for pain, and 46 patients (45.1%) with bladder dysfunction were assessed for the IPSS (International Prostatic Symptoms Score) score, showing a significant improvement in these scales (P = .011 and P = .001, respectively). In conclusion, treatment with THC/CBD spray appears to be a valid answer to some of the unmet needs in MS patients, such as spasticity and other refractory-to-treatment symptoms. © 2015, The American College of Clinical Pharmacology.

  12. Evaluation of pancreatic cancer cell migration with multiple parameters in vitro by using an optical real-time cell mobility assay device.

    PubMed

    Yamauchi, Akira; Yamamura, Masahiro; Katase, Naoki; Itadani, Masumi; Okada, Naoko; Kobiki, Kayoko; Nakamura, Masafumi; Yamaguchi, Yoshiyuki; Kuribayashi, Futoshi

    2017-03-31

    Migration of cancer cell correlates with distant metastasis and local invasion, which are good targets for cancer treatment. An optically accessible device "TAXIScan" was developed, which provides considerably more information regarding the cellular dynamics and less quantity of samples than do the existing methods. Here, we report the establishment of a system to analyze the nature of pancreatic cancer cells using TAXIScan and we evaluated lysophosphatidic acid (LPA)-elicited pancreatic cell migration. Pancreatic cancer cell lines, BxPC3, PANC-1, AsPC1, and MIAPaCa-2, were analyzed for adhesion as well as migration towards LPA by TAXIScan using parameters such as velocity and directionality or for the number of migrated cells by the Boyden chamber methods. To confirm that the migration was initiated by LPA, the expression of LPA receptors and activation of intracellular signal transductions were examined by quantitative reverse transcriptase polymerase reaction and western blotting. Scaffold coating was necessary for the adhesion of pancreatic cancer cells, and collagen I and Matrigel were found to be good scaffolds. BxPC3 and PANC-1 cells clearly migrated towards the concentration gradient formed by injecting 1 μL LPA, which was abrogated by pre-treatment with LPA inhibitor, Ki16425 (IC50 for the directionality ≈ 1.86 μM). The LPA dependent migration was further confirmed by mRNA and protein expression of LPA receptors as well as phosphorylation of signaling molecules. LPA1 mRNA was highest among the 6 receptors, and LPA1, LPA2 and LPA3 proteins were detected in BxPC3 and PANC-1 cells. Phosphorylation of Akt (Thr308 and Ser473) and p42/44MAPK in BxPC3 and PANC-1 cells was observed after LPA stimulation, which was clearly inhibited by pre-treatment with a compound Ki16425. We established a novel pancreatic cancer cell migration assay system using TAXIScan. This assay device provides multiple information on migrating cells simultaneously, such as their

  13. Genetic variability at the PARK16 locus

    PubMed Central

    Tucci, Arianna; Nalls, Mike A; Houlden, Henry; Revesz, Tamas; Singleton, Andrew B; Wood, Nicholas W; Hardy, John; Paisán-Ruiz, Coro

    2010-01-01

    Parkinson's disease (PD) is a complex neurodegenerative disease which is clinically heterogeneous and pathologically consists of loss of dopaminergic neurons in the substantia nigra and intracytoplasmic neuronal inclusions containing alpha-synuclein aggregations known as Lewy bodies. Although the majority of PD is idiopathic, pathogenic mutations in several mendelian genes have been successfully identified through linkage analyses. To identify susceptibility loci for idiopathic PD, several genome-wide association studies (GWAS) within different populations have recently been conducted in both idiopathic and familial forms of PD. These analyses have confirmed SNCA and MAPT as loci harboring PD susceptibility. In addition, the GWAS identified several other genetic loci suggestively associated with the risk of PD; among these, only one was replicated by two different studies of European and Asian ancestries. Hence, we investigated this novel locus known as PARK16 for coding mutations in a large series of idiopathic pathologically proven PD cases, and also conducted an association study in a case–control cohort from the United Kingdom. An association between a novel RAB7L1 mutation, c.379-12insT, and disease (P-value=0.0325) was identified. Two novel coding variants present only in the PD cohort were also identified within the RAB7L1 (p.K157R) and SLC41A1 (p.A350V) genes. No copy number variation analyses have yet been performed within this recently identified locus. We concluded that, although both coding variants and risk alleles within the PARK16 locus seem to be rare, further molecular analyses within the PARK16 locus and within different populations are required in order to examine its biochemical role in the disease process. PMID:20683486

  14. Molecular Identification of the Schwannomatosis Locus

    DTIC Science & Technology

    2004-07-01

    AD Award Number: DAMD17-03-1-0445 TITLE: Molecular Identification of the Schwannomatosis Locus PRINCIPAL INVESTIGATOR: Mia M. MacCollin, M.D...COVERED (Leave blank) July 2004 Annual (1 Jul 2003 - 30 Jun 2004) 4. TITLE AND SUBTITLE 5. FUNDING NUMBERS Molecular Identification of the Schwannomatosis...linkage and loss of heterozygosity analyses. 3. To determine the molecular mechanism of tumor formation in these patients using complementary molecular

  15. Effectiveness, safety and health-related quality of life of multiple sclerosis patients treated with fingolimod: results from a 12-month, real-world, observational PERFORMS study in the Middle East.

    PubMed

    Achiron, Anat; Aref, Hany; Inshasi, Jihad; Harb, Mohamad; Alroughani, Raed; Bijarnia, Mahendra; Cooke, Kathryn; Yuksel, Ozgur

    2017-08-07

    Evidence on the use of fingolimod in real-world clinical practice and data on patient-reported health-related quality of life (HRQoL) in countries such as the Middle East are sparse. The Prospective Evaluation of Treatment with Fingolimod for Multiple Sclerosis (PERFORMS) study assessed HRQoL and effectiveness and safety of fingolimod in patients with relapsing-remitting multiples sclerosis (RRMS), primarily in Middle Eastern countries. This 12-month, observational, multicentre, prospective, real-world study was conducted in patients with RRMS who initiated fingolimod or another approved disease-modifying treatment (DMT) within 4 weeks before study entry. Patients were enrolled in a 2:1 ratio to obtain more data in fingolimod and parallel in other DMTs cohort by physicians during routine medical care. Key study outcomes included HRQoL assessed using MS International QoL (MusiQoL), MS relapses and disability. Safety was assessed throughout the study period. Due to the observational nature of the study, no neuroimaging assessments were mandated and central reading was not performed. Of 249 enrolled patients, 247 were included in the analysis (fingolimod cohort 172; other DMTs cohort 75). Overall, the mean age of patients was 36.5 years, 64.4% were women and ~90% were Caucasians. At baseline, mean MS duration since diagnosis was 7.2 years in the fingolimod and 4.8 years in the other DMTs cohorts. Overall, mean changes in MusiQoL index scores were -2.1 in the fingolimod cohort and -0.7 in the other DMTs cohort at Month 12, but improvement was not significant vs. baseline in both cohorts. Proportion of relapse-free patients increased significantly during the study vs. 0-12 months before the study in the fingolimod cohort (80.2% vs. 24.4%; p < 0.0001). Proportion of patients free from disability progression was 86.5% in the fingolimod cohort. The incidences of AEs were 59.9% and 50.6% in the fingolimod and other DMTs cohorts, respectively. First-dose monitoring of

  16. Bipolar disorder: evidence for a major locus.

    PubMed

    Spence, M A; Flodman, P L; Sadovnick, A D; Bailey-Wilson, J E; Ameli, H; Remick, R A

    1995-10-09

    Complex segregation analyses were conducted on families of bipolar I and bipolar II probands to delineate the mode of inheritance. The probands were ascertained from consecutive referrals to the Mood Disorder Service, University Hospital, University of British Columbia and diagnosed by DSM-III-R and Research Diagnostic Criteria. Data were available on over 1,500 first-degree relatives of the 186 Caucasian probands. The purpose of the analyses was to determine if, after correcting for age and birth cohort, there was evidence for a single major locus. Five models were fit to the data using the statistical package SAGE: i) dominant, ii) recessive, iii) arbitrary mendelian inheritance, iv) environmental, and v) no major effects. A single dominant, mendelian major locus was the best fitting of these models for the sample of bipolar I and II probands when only bipolar relatives were defined as affected (polygenic inheritance could not be tested). Adding recurrent major depression to the diagnosis "affected" for relatives reduced the evidence for a major locus effect. Our findings support the undertaking of linkage studies and are consistent with the analyses of the National Institutes of Mental Health (NIMH) Collaborative Study data by Rice et al. (Arch Gen Psychiatry 44: 441-447, 1987) and Blangero and Elston (Genet Epidemiol 6:221-227, 1989).

  17. Bipolar disorder: Evidence for a major locus

    SciTech Connect

    Spence, M.A.; Flodman, P.L.; Sadovnick, A.D.; Ameli, H.

    1995-10-09

    Complex segregation analyses were conducted on families of bipolar I and bipolar II probands to delineate the mode of inheritance. The probands were ascertained from consecutive referrals to the Mood Disorder Service, University Hospital, University of British Columbia and diagnosed by DSM-III-R and Research Diagnostic Criteria. Data were available on over 1,500 first-degree relatives of the 186 Caucasian probands. The purpose of the analyses was to determine if, after correcting for age and birth cohort, there was evidence for a single major locus. Five models were fit to the data using the statistical package SAGE: (1) dominant, (2) recessive, (3) arbitrary mendelian inheritance, (4) environmental, and (5) no major effects. A single dominant, mendelian major locus was the best fitting of these models for the sample of bipolar I and II probands when only bipolar relatives were defined as affected (polygenic inheritance could not be tested). Adding recurrent major depression to the diagnosis {open_quotes}affected{close_quotes} for relatives reduced the evidence for a major locus effect. Our findings support the undertaking of linkage studies and are consistent with the analyses of the National Institutes of Mental Health (NIMH) Collaborative Study data by Rice et al. and Blangero and Elston. 39 refs., 4 tabs.

  18. Linked Patient-Reported Outcomes Data From Patients With Multiple Sclerosis Recruited on an Open Internet Platform to Health Care Claims Databases Identifies a Representative Population for Real-Life Data Analysis in Multiple Sclerosis

    PubMed Central

    Ghodge, Bhaskar; Bonzani, Ian C; Korn, Jonathan R; Medin, Jennie; Saraykar, Tanmay; Sengupta, Souvik; Saini, Deepanshu; Olson, Melvin

    2016-01-01

    Background An enormous amount of information relevant to public health is being generated directly by online communities. Objective To explore the feasibility of creating a dataset that links patient-reported outcomes data, from a Web-based survey of US patients with multiple sclerosis (MS) recruited on open Internet platforms, to health care utilization information from health care claims databases. The dataset was generated by linkage analysis to a broader MS population in the United States using both pharmacy and medical claims data sources. Methods US Facebook users with an interest in MS were alerted to a patient-reported survey by targeted advertisements. Eligibility criteria were diagnosis of MS by a specialist (primary progressive, relapsing-remitting, or secondary progressive), ≥12-month history of disease, age 18-65 years, and commercial health insurance. Participants completed a questionnaire including data on demographic and disease characteristics, current and earlier therapies, relapses, disability, health-related quality of life, and employment status and productivity. A unique anonymous profile was generated for each survey respondent. Each anonymous profile was linked to a number of medical and pharmacy claims datasets in the United States. Linkage rates were assessed and survey respondents’ representativeness was evaluated based on differences in the distribution of characteristics between the linked survey population and the general MS population in the claims databases. Results The advertisement was placed on 1,063,973 Facebook users’ pages generating 68,674 clicks, 3719 survey attempts, and 651 successfully completed surveys, of which 440 could be linked to any of the claims databases for 2014 or 2015 (67.6% linkage rate). Overall, no significant differences were found between patients who were linked and not linked for educational status, ethnicity, current or prior disease-modifying therapy (DMT) treatment, or presence of a relapse in

  19. Linked Patient-Reported Outcomes Data From Patients With Multiple Sclerosis Recruited on an Open Internet Platform to Health Care Claims Databases Identifies a Representative Population for Real-Life Data Analysis in Multiple Sclerosis.

    PubMed

    Risson, Valery; Ghodge, Bhaskar; Bonzani, Ian C; Korn, Jonathan R; Medin, Jennie; Saraykar, Tanmay; Sengupta, Souvik; Saini, Deepanshu; Olson, Melvin

    2016-09-22

    An enormous amount of information relevant to public health is being generated directly by online communities. To explore the feasibility of creating a dataset that links patient-reported outcomes data, from a Web-based survey of US patients with multiple sclerosis (MS) recruited on open Internet platforms, to health care utilization information from health care claims databases. The dataset was generated by linkage analysis to a broader MS population in the United States using both pharmacy and medical claims data sources. US Facebook users with an interest in MS were alerted to a patient-reported survey by targeted advertisements. Eligibility criteria were diagnosis of MS by a specialist (primary progressive, relapsing-remitting, or secondary progressive), ≥12-month history of disease, age 18-65 years, and commercial health insurance. Participants completed a questionnaire including data on demographic and disease characteristics, current and earlier therapies, relapses, disability, health-related quality of life, and employment status and productivity. A unique anonymous profile was generated for each survey respondent. Each anonymous profile was linked to a number of medical and pharmacy claims datasets in the United States. Linkage rates were assessed and survey respondents' representativeness was evaluated based on differences in the distribution of characteristics between the linked survey population and the general MS population in the claims databases. The advertisement was placed on 1,063,973 Facebook users' pages generating 68,674 clicks, 3719 survey attempts, and 651 successfully completed surveys, of which 440 could be linked to any of the claims databases for 2014 or 2015 (67.6% linkage rate). Overall, no significant differences were found between patients who were linked and not linked for educational status, ethnicity, current or prior disease-modifying therapy (DMT) treatment, or presence of a relapse in the last 12 months. The frequencies of the

  20. Parallel Loss-of-Function at the RPM1 Bacterial Resistance Locus in Arabidopsis thaliana

    PubMed Central

    Rose, Laura; Atwell, Susanna; Grant, Murray; Holub, Eric B.

    2012-01-01

    Dimorphism at the Resistance to Pseudomonas syringae pv. maculicola 1 (RPM1) locus is well documented in natural populations of Arabidopsis thaliana and has been portrayed as a long-term balanced polymorphism. The haplotype from resistant plants contains the RPM1 gene, which enables these plants to recognize at least two structurally unrelated bacterial effector proteins (AvrB and AvrRpm1) from bacterial crop pathogens. A complete deletion of the RPM1 coding sequence has been interpreted as a single event resulting in susceptibility in these individuals. Consequently, the ability to revert to resistance or for alternative R-gene specificities to evolve at this locus has also been lost in these individuals. Our survey of variation at the RPM1 locus in a large species-wide sample of A. thaliana has revealed four new loss-of-function alleles that contain most of the intervening sequence of the RPM1 open reading frame. Multiple loss-of-function alleles may have originated due to the reported intrinsic cost to plants expressing the RPM1 protein. The frequency and geographic distribution of rpm1 alleles observed in our survey indicate the parallel origin and maintenance of these loss-of-function mutations and reveal a more complex history of natural selection at this locus than previously thought. PMID:23272006

  1. Influence of socioeconomic status on the relationship between locus of control and oral health.

    PubMed

    Acharya, Shashidhar; Pentapati, Kalyana Chakravarthy; Singh, Sweta

    2011-01-01

    The objectives of this study were to assess the relationship between Locus of Control (LoC) and oral health among a group of rural adolescent school children and to examine the influence of socioeconomic status (SES) on the association between health, LoC and oral health status. A total of 318 children 15 years of age from a public and private school formed the study population. The children were administered following the Indian translation of the 18-item Multidimensional Health Locus of Control scale, and subsequently examined for caries and oral hygiene. T tests and correlation analyses showed a significant relationship between higher 'Internal' Locus of Control and dental caries. A hierarchical multiple regression analysis was performed to assess the effect of socioeconomic status on LoC and oral health using three interaction models which showed a statistically significant interaction between 'Internal' LoC and socioeconomic status on caries. Socioeconomic stratum-specific estimates of the relationship between the LoC and caries revealed a positive association between Internal LoC and caries in the middle socioeconomic group. The results demonstrated the relationship between Locus of Control and oral health, and the role of socioeconomic status having a strong bearing on this relationship.

  2. Genetic modifier loci of mouse Mfrp(rd6) identified by quantitative trait locus analysis.

    PubMed

    Won, Jungyeon; Charette, Jeremy R; Philip, Vivek M; Stearns, Timothy M; Zhang, Weidong; Naggert, Jürgen K; Krebs, Mark P; Nishina, Patsy M

    2014-01-01

    The identification of genes that modify pathological ocular phenotypes in mouse models may improve our understanding of disease mechanisms and lead to new treatment strategies. Here, we identify modifier loci affecting photoreceptor cell loss in homozygous Mfrp(rd6) mice, which exhibit a slowly progressive photoreceptor degeneration. A cohort of 63 F2 homozygous Mfrp(rd6) mice from a (B6.C3Ga-Mfrp(rd6)/J × CAST/EiJ) F1 intercross exhibited a variable number of cell bodies in the retinal outer nuclear layer at 20 weeks of age. Mice were genotyped with a panel of single nucleotide polymorphism markers, and genotypes were correlated with phenotype by quantitative trait locus (QTL) analysis to map modifier loci. A genome-wide scan revealed a statistically significant, protective candidate locus on CAST/EiJ Chromosome 1 and suggestive modifier loci on Chromosomes 6 and 11. Multiple regression analysis of a three-QTL model indicated that the modifier loci on Chromosomes 1 and 6 together account for 26% of the observed phenotypic variation, while the modifier locus on Chromosome 11 explains only an additional 4%. Our findings indicate that the severity of the Mfrp(rd6) retinal degenerative phenotype in mice depends on the strain genetic background and that a significant modifier locus on CAST/EiJ Chromosome 1 protects against Mfrp(rd6)-associated photoreceptor loss.

  3. [Self-esteem, resilience, locus of control and suicide risk in nursing students].

    PubMed

    Montes-Hidalgo, Javier; Tomás-Sábado, Joaquín

    2016-01-01

    Assuming that suicide is the result of a series of factors acting cumulatively, the aim of this paper was to study the association of self-esteem, resilience and locus of control with the risk of suicidal behavior in a sample of nursing students. Observational, cross-sectional and correlational study with 186 nursing students who answered a questionnaire that contained, in addition to demographic data, the Spanish forms of Rosenberg self-esteem scale, the brief resilient coping scale, the Plutchik scale of suicide risk and the Rotter's internal-external locus of control scale. The scores of males and females are very similar on all scales except Locus of Control, where a significantly greater tendency of females attributed to external control. 6.4% of students have scores indicating suicide risk. Suicide risk scores correlated negatively and significantly with self-esteem and resilience and positively with locus of control. The multiple linear regression analysis identified self-esteem as the main variable related to suicide risk. The results suggest that students who have low self-esteem, have difficulty in adjusting to adverse situations and tend to the external attribution of the consequences of their actions may have an increased risk of suicidal behavior. Furthermore, the identification of self-esteem as the important factor involved in suicide risk can help in designing prevention programs. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  4. Real Forestry for Real Estate

    ERIC Educational Resources Information Center

    Gagnon, Jennifer; Fisher, Jason

    2013-01-01

    Virginia is poised to see an unprecedented change in forest land ownership. To provide new landowners with information on sustainable forest management, we developed a two-part program, Real Forestry for Real Estate. First, we assembled New Landowner Packets, which contain a variety of sustainable forest management resources. Second, two…

  5. Real Forestry for Real Estate

    ERIC Educational Resources Information Center

    Gagnon, Jennifer; Fisher, Jason

    2013-01-01

    Virginia is poised to see an unprecedented change in forest land ownership. To provide new landowners with information on sustainable forest management, we developed a two-part program, Real Forestry for Real Estate. First, we assembled New Landowner Packets, which contain a variety of sustainable forest management resources. Second, two…

  6. Analysis of HLA-ABC locus-specific transcription in normal tissues.

    PubMed

    García-Ruano, Ana Belén; Méndez, Rosa; Romero, José María; Cabrera, Teresa; Ruiz-Cabello, Francisco; Garrido, Federico

    2010-12-01

    We developed a novel human leukocyte antigen HLA-ABC locus-specific quantitative real-time polymerase chain reaction (PCR) to determine the locus-specific gene expression of HLA-ABC in peripheral blood leukocytes (PBLs, n = 53), colon mucosa (n = 15), and larynx mucosa (n = 15). Laser-assisted tissue microdissection allowed us to study the selected cells without interference from surrounding stroma. We report evidence on the specificity of the technique, describing the HLA-ABC locus-specific gene expression patterns found in the PBLs and two solid tissues studied. PBLs showed a higher gene expression of HLA-B than of HLA-A or HLA-C (p = 4.7 × 10(-10) and p = 1.6 × 10(-6), respectively). In solid tissue, HLA-A and HLA-B gene expressions were similar and HLA-C expression lower. In particular, in larynx mucosa, significant differences were found between HLA-A and HLA-C expressions and between HLA-B and HLA-C expressions (p = 6.5 × 10(-4) and p = 8.1 × 10(-4), respectively). The same differences were observed in colon mucosa, but significance was not reached (p = 0.08 and p = 0.06, respectively). Differences in locus-specific regulation may be related to the control of cytotoxic responses of NK and CD8 positive T cells. Gene expression of HLA-ABC specific locus showed no intra-individual variability, but there was a high inter-individual variability. This may result from differences in the expression of common regulatory factors that control HLA-ABC constitutive expression.

  7. Incorporating Single-Locus Tests into Haplotype Cladistic Analysis in Case-Control Studies

    PubMed Central

    Liu, Jianfeng; Papasian, Chris; Deng, Hong-Wen

    2007-01-01

    In case-control studies, genetic associations for complex diseases may be probed either with single-locus tests or with haplotype-based tests. Although there are different views on the relative merits and preferences of the two test strategies, haplotype-based analyses are generally believed to be more powerful to detect genes with modest effects. However, a main drawback of haplotype-based association tests is the large number of distinct haplotypes, which increases the degrees of freedom for corresponding test statistics and thus reduces the statistical power. To decrease the degrees of freedom and enhance the efficiency and power of haplotype analysis, we propose an improved haplotype clustering method that is based on the haplotype cladistic analysis developed by Durrant et al. In our method, we attempt to combine the strengths of single-locus analysis and haplotype-based analysis into one single test framework. Novel in our method is that we develop a more informative haplotype similarity measurement by using p-values obtained from single-locus association tests to construct a measure of weight, which to some extent incorporates the information of disease outcomes. The weights are then used in computation of similarity measures to construct distance metrics between haplotype pairs in haplotype cladistic analysis. To assess our proposed new method, we performed simulation analyses to compare the relative performances of (1) conventional haplotype-based analysis using original haplotype, (2) single-locus allele-based analysis, (3) original haplotype cladistic analysis (CLADHC) by Durrant et al., and (4) our weighted haplotype cladistic analysis method, under different scenarios. Our weighted cladistic analysis method shows an increased statistical power and robustness, compared with the methods of haplotype cladistic analysis, single-locus test, and the traditional haplotype-based analyses. The real data analyses also show that our proposed method has practical

  8. Credit Card Misuse, Money Attitudes, and Compulsive Buying Behaviors: A Comparison of Internal and External Locus of Control (LOC) Consumers

    ERIC Educational Resources Information Center

    Watson, Stevie

    2009-01-01

    This study examined attitudinal and behavioral differences between internal and external locus of control (LOC) consumers on credit card misuse, the importance of money, and compulsive buying. Using multiple analysis of variance and separate analyses of variance, internal LOC consumers were found to have lower scores on credit card misuse and…

  9. Credit Card Misuse, Money Attitudes, and Compulsive Buying Behaviors: A Comparison of Internal and External Locus of Control (LOC) Consumers

    ERIC Educational Resources Information Center

    Watson, Stevie

    2009-01-01

    This study examined attitudinal and behavioral differences between internal and external locus of control (LOC) consumers on credit card misuse, the importance of money, and compulsive buying. Using multiple analysis of variance and separate analyses of variance, internal LOC consumers were found to have lower scores on credit card misuse and…

  10. Comment on 'On the locus formed by the maximum heights of projectile motion with air resistance'

    NASA Astrophysics Data System (ADS)

    Stewart, Seán M.

    2011-03-01

    We show that a remark made by Hernández-Saldaña in 2010 (Eur. J. Phys. 31 1319) concerning the validity of an expression first presented by us in 2006 (Proc. 17th Biennial Congress of the Australian Institute of Physics Paper 27) for the optimal angle of projection for greatest forward skew in the trajectory of a projectile launched in a linear resisting medium is in error. We also draw attention to an earlier treatment (2006 Int. J. Math. Educ. Sci. Technol. 37 411) of the locus of apexes for such a projectile. When expressed in Cartesian form, the locus can be written in terms of the now familiar, though less common, secondary real branch of the Lambert W function.

  11. GET REAL!

    EPA Science Inventory

    Combined sewer overflow (CSO) is a significant source of pollution in receiving waters. However, implementing a real-time control scheme operates automatic regulators more efficiently to maximize a collection system's storage, treatment, and transport capacities, reducing the vol...

  12. Regulatory organization of the staphylococcal sae locus.

    PubMed

    Adhikari, Rajan P; Novick, Richard P

    2008-03-01

    This paper describes an investigation of the complex internal regulatory circuitry of the staphylococcal sae locus and the impact of modifying this circuitry on the expression of external genes in the sae regulon. The sae locus contains four genes, the saeR and S two-component signalling module (TCS), and saeP and Q, two upstream genes of hitherto unknown function. It is expressed from two promoters, P(A)sae, which transcribes only the TCS, and P(C)sae, which transcribes the entire locus. A bursa aurealis (bursa) transposon insertion in saeP in a derivative of Staphylococcus aureus NCTC 8325 has a profound effect on sae function. It modifies the activity of the TCS, changing the expression of many genes in the sae regulon, even though transcription of the TCS (from P(A)sae) is not interrupted. Moreover, these effects are not due to disruption of saeP since an in-frame deletion in saeP has essentially no phenotype. The phenotype of S. aureus strain Newman is remarkably similar to that of the saeP : : bursa and this similarity is explained by an amino acid substitution in the Newman saeS gene that is predicted to modify profoundly the signalling function of the protein. This concurrence suggests that the saeP : : bursa insertion affects the signalling function of saeS, a suggestion that is supported by the ability of an saeQR clone, but not an saeR clone, to complement the effects of the saeP : : bursa insertion.

  13. A root locus based flutter synthesis procedure

    NASA Technical Reports Server (NTRS)

    Hajela, P.

    1983-01-01

    An efficient generalized constraint is proposed in the context of a nonlinear mathematical programming approach for the minimum weight design of wing structures for flutter considerations. The approach is based on a root locus analysis procedure that is better suited for flutter redesign than the conventionally used V-g method. The proposed flutter constraint does not require an actual computation of the flutter speed, allows prescription of meaningful margins of safety in the optimized design and lends itself to elegant computation of sensitivity information. The approach is implemented and results presented for representative structural models.

  14. Root Locus Algorithms for Programmable Pocket Calculators

    NASA Technical Reports Server (NTRS)

    Wechsler, E. R.

    1983-01-01

    Two algorithms are described which allow the plotting of individual points on a root locus diagram with or without time delay. The development was performed during the design of a continuous phase shifter used in the Baseband Antenna Combiner for the Deep Space Network (DSN). The algorithms, which are expected to be useful in similar DSN efforts, are simple enough to be implemented on a programmable pocket calculator. The coordinates of the open-loop zeros and poles, the gain constant K, and the time delay T are the data inputs.

  15. Interfacial phases in epitaxial growth of Y{sub 2}O{sub 3} on MgO studied via combining electron energy-loss spectroscopy and real-space self-consistent full multiple scattering calculations

    SciTech Connect

    Pailloux, F.; Jublot, M.; Gaboriaud, R.J.; Jaouen, M.; Paumier, F.; Imhoff, D.

    2005-09-15

    Electron energy loss spectroscopy (EELS), high resolution transmission electron microscopy (HRTEM), and electron diffraction were used to investigate Y{sub 2}O{sub 3} thin films epitaxially grown on (001) MgO substrate. In the vicinity of the film/substrate interface, HRTEM experiments evidenced the presence of grains with various crystallographic structures most of them crystallizing in the well-known Ia3 cubic phase. Some other grains, nanometric in size, and only observed in the vicinity of the film/substrate interface, have a different and unknown crystallographic structure. EELS spectra have been acquired close to the Y{sub 2}O{sub 3}/MgO interface, to get a better knowledge of the phases nucleated close to the substrate surface. Spectra exhibiting different fine structures have been recorded and compared to multiple scattering calculations. The Ia3 phase has been detected as constituting the main component of the Y{sub 2}O{sub 3} thin film in agreement with previous observations. It is found that calculations performed in a real space self-consistent full multiple scattering scheme (SC-FMS) and experiments are in pretty good agreement even for small cluster sizes. The second family of spectra has also been compared to calculations performed for monoclinic C2/m yttrium oxide, with a little success. Another approach considering a local oxygen neighboring close to a distorted rock-salt-like structure led to a good match between experimental and calculated spectra. Our results emphasize how powerful is the combination of spectroscopic measurements at nanometer scale, as feasible with EELS and modern microscopes, with ab initio calculations for structure determination at such small scale lengths.

  16. Real-World Use of 3rd Line Therapy for Multiple Myeloma in Austria: An Austrian Myeloma Registry (AMR) Analysis of the Therapeutic Landscape and Clinical Outcomes prior to the Use of Next Generation Myeloma Therapeutics.

    PubMed

    Willenbacher, Ella; Weger, Roman; Rochau, Ursula; Siebert, Uwe; Willenbacher, Wolfgang

    2016-01-01

    Clinical trials demonstrate improving survival in patients with multiple myeloma (MM) after treatment. However, it is unclear whether increased survival translates to a similar benefit in a real world setting. We analyzed the overall survival of 347 multiple myeloma patients in Austria by means of a national registry (AMR), focused on results from 3rd and later lines of therapy. This benchmark was chosen to define a baseline prior to the broad application of upcoming 2nd generation drugs (carfilzomib, pomalidomide). Projected 10 years survival for patients with MM in Austria is estimated to be 56% in patients diagnosed in between the years 2011-2014, 21% in patients with a diagnosis made between 2000-2005, and 39% in those with a diagnosis made between 2006-2010). For the same intervals a significant increase in the use of both bortezomib, lenalidomide and thalidomide-so called IMiDs (from 2005 onwards) and their simultaneous use in combination therapies (from 2010 onwards) could be shown. The use of autologous transplantation (ASCT) remained more or less constant at ~ 35% of patients in the 1st line setting over the whole period, comparing well to international practice patterns, while the use of 2nd line ASCT increased from 5.5% to 18.7% of patients. Patients in 3rd or later line treatment (n = 105), showed that even in relapsed and refractory disease median survival was 27 months with a considerable proportion of long-term survivors (~20%). With the expected emergence of additional active anti-myeloma compounds, we aim to assess survival in patients with relapsed and refractory MM.

  17. Patterns of polymorphism at the self-incompatibility locus in 1,083 Arabidopsis thaliana genomes.

    PubMed

    Tsuchimatsu, Takashi; Goubet, Pauline M; Gallina, Sophie; Holl, Anne-Catherine; Fobis-Loisy, Isabelle; Bergès, Hélène; Marande, William; Prat, Elisa; Meng, Dazhe; Long, Quan; Platzer, Alexander; Nordborg, Magnus; Vekemans, Xavier; Castric, Vincent

    2017-04-04

    Although the transition to selfing in the model plant Arabidopsis thaliana involved the loss of the self-incompatibility (SI) system, it clearly did not occur due to the fixation of a single inactivating mutation at the locus determining the specificities of SI (the S-locus). At least three groups of divergent haplotypes (haplogroups), corresponding to ancient functional S-alleles, have been maintained at this locus, and extensive functional studies have shown that all three carry distinct inactivating mutations. However, the historical process of loss of SI is not well understood, in particular its relation with the last glaciation. Here, we took advantage of recently published genomic re-sequencing data in 1,083 Arabidopsis thaliana accessions that we combined with BAC sequencing to obtain polymorphism information for the whole S-locus region at a species-wide scale. The accessions differed by several major rearrangements including large deletions and inter-haplogroup recombinations, forming a set of haplogroups that are widely distributed throughout the native range and largely overlap geographically. 'Relict' A. thaliana accessions that directly derive from glacial refugia are polymorphic at the S-locus, suggesting that the three haplogroups were already present when glacial refugia from the last Ice Age became isolated. Inter-haplogroup recombinant haplotypes were highly frequent, and detailed analysis of recombination breakpoints suggested multiple independent origins. These findings suggest that the complete loss of SI in A. thaliana involved independent self-compatible mutants that arose prior to the last Ice Age, and experienced further rearrangements during post-glacial colonization.

  18. Impact of locus of control on health message effectiveness.

    PubMed

    Kong, Ying; Shen, Fuyuan

    2011-10-01

    This article examined how individuals' locus of control might moderate the effect of health message frames. An experiment was conducted whereby participants read either individual- or social-responsibility message frames after their locus of control was primed. Results indicated that messages presented in individual-responsibility frames were more persuasive when people were primed with internal locus of control, whereas social-responsibility framed appeals were more persuasive when people were primed with external locus of control. These results were found for individuals in both high and low cognitive load conditions. Theoretical and practical implications of the findings are discussed.

  19. Subcutaneous Interferon β-1a Administration by Electronic Auto-injector is Associated with High Adherence in Patients with Relapsing Remitting Multiple Sclerosis in a Real-life Study

    PubMed Central

    Järvinen, Elina; Multanen, Juha; Atula, Sari

    2017-01-01

    The objective was to investigate adherence measured by an electronic auto-injector device, and self-reported adherence and treatment convenience in subjects with relapsing remitting multiple sclerosis (RRMS), using an electronic auto-injector Rebismart® to self-inject interferon β-1a. Thirty one patients with RRMS using the electronic auto-injector Rebismart® for self-injecting interferon β-1a subcutaneously three times weekly were included in a real-life clinical multicenter study for 24 weeks in Finland. Mean adherence reported by the device and mean self-assessment of adherence were studied. Reasons for missing injections and treatment convenience were assessed. Association between adherence and gender and age were studied. The mean adherence calculated from the device data was 93.5%. The mean self-assessment of adherence was 96.6%. The most common reason for missing an injection was forget-fulness. Adherence (measured by the device) was not changed over time. In the high adherence group there were more females and young patients (<30 years of age). The auto-injector was found to substantially ease the treatment by 90% of the patients. The electronic auto-injector was associated with high adherence to treatment. The device was found to ease the patient’s treatment and it was perceived as easy to use. It is a convenient tool to assess patient’s adherence to treatment. PMID:28286627

  20. Electronic structure of Co-induced magic clusters grown on Si(111)-(7×7) : Scanning tunneling microscopy and spectroscopy and real-space multiple-scattering calculations

    NASA Astrophysics Data System (ADS)

    Zilani, M. A. K.; Xu, H.; Liu, T.; Sun, Y. Y.; Feng, Y. P.; Wang, X.-S.; Wee, A. T. S.

    2006-05-01

    The electronic structure of cobalt-induced magic clusters grown on Si(111)-(7×7) is investigated by scanning tunneling microscopy, scanning tunneling spectroscopy, and real-space multiple-scattering calculations. Topographical images of a half unit cell of Si(111)-(7×7) with the cluster acquired at low bias voltages of ±0.4V show greatly reduced cluster heights; however, the heights of the corner adatoms are unchanged, indicative of the highly localized nature of the charge distribution. Spectroscopic studies of the clusters indicate a band gap of ˜0.8eV , suggesting localized nonmetallic behavior. The opening of such a band gap is suggested to be a stabilizing factor for the observed magic clusters. A 65-atom Co-Si cluster is constructed to calculate the momentum- and element-projected density of states. The calculated result identifies that the intense state below the Fermi level at -1.75V in the experimental spectroscopic curve is primarily due to localized 3d orbitals of Co atoms in the magic clusters.

  1. Subcutaneous Interferon β-1a Administration by Electronic Auto-injector is Associated with High Adherence in Patients with Relapsing Remitting Multiple Sclerosis in a Real-life Study.

    PubMed

    Järvinen, Elina; Multanen, Juha; Atula, Sari

    2017-02-20

    The objective was to investigate adherence measured by an electronic auto-injector device, and self-reported adherence and treatment convenience in subjects with relapsing remitting multiple sclerosis (RRMS), using an electronic auto-injector Rebismart(®) to self-inject interferon β-1a. Thirty one patients with RRMS using the electronic auto-injector Rebismart(®) for self-injecting interferon β-1a subcutaneously three times weekly were included in a real-life clinical multicenter study for 24 weeks in Finland. Mean adherence reported by the device and mean self-assessment of adherence were studied. Reasons for missing injections and treatment convenience were assessed. Association between adherence and gender and age were studied. The mean adherence calculated from the device data was 93.5%. The mean self-assessment of adherence was 96.6%. The most common reason for missing an injection was forget-fulness. Adherence (measured by the device) was not changed over time. In the high adherence group there were more females and young patients (<30 years of age). The auto-injector was found to substantially ease the treatment by 90% of the patients. The electronic auto-injector was associated with high adherence to treatment. The device was found to ease the patient's treatment and it was perceived as easy to use. It is a convenient tool to assess patient's adherence to treatment.

  2. Altered expression of glutamate signaling, growth factor, and glia genes in the locus coeruleus of patients with major depression.

    PubMed

    Bernard, R; Kerman, I A; Thompson, R C; Jones, E G; Bunney, W E; Barchas, J D; Schatzberg, A F; Myers, R M; Akil, H; Watson, S J

    2011-06-01

    Several studies have proposed that brain glutamate signaling abnormalities and glial pathology have a role in the etiology of major depressive disorder (MDD). These conclusions were primarily drawn from post-mortem studies in which forebrain brain regions were examined. The locus coeruleus (LC) is the primary source of extensive noradrenergic innervation of the forebrain and as such exerts a powerful regulatory role over cognitive and affective functions, which are dysregulated in MDD. Furthermore, altered noradrenergic neurotransmission is associated with depressive symptoms and is thought to have a role in the pathophysiology of MDD. In the present study we used laser-capture microdissection (LCM) to selectively harvest LC tissue from post-mortem brains of MDD patients, patients with bipolar disorder (BPD) and from psychiatrically normal subjects. Using microarray technology we examined global patterns of gene expression. Differential mRNA expression of select candidate genes was then interrogated using quantitative real-time PCR (qPCR) and in situ hybridization (ISH). Our findings reveal multiple signaling pathway alterations in the LC of MDD but not BPD subjects. These include glutamate signaling genes, SLC1A2, SLC1A3 and GLUL, growth factor genes FGFR3 and TrkB, and several genes exclusively expressed in astroglia. Our data extend previous findings of altered glutamate, astroglial and growth factor functions in MDD for the first time to the brainstem. These findings indicate that such alterations: (1) are unique to MDD and distinguishable from BPD, and (2) affect multiple brain regions, suggesting a whole-brain dysregulation of such functions.

  3. Job stress and locus of control in teachers: comparisons between samples from the United States and Zimbabwe

    NASA Astrophysics Data System (ADS)

    Crothers, Laura M.; Kanyongo, Gibbs Y.; Kolbert, Jered B.; Lipinski, John; Kachmar, Steven P.; Koch, Gary D.

    2010-12-01

    This study examines the relationship between educators' locus of control and job stress using samples from the US and Zimbabwe. Multiple regression analyses are used to identify significant relationships in the US sample between teachers' external locus of control and the severity of the job stress that they experience, coupled with the perceived degree of organisational support received. However, this relationship between the locus of control and stress indices could not be identified for the Zimbabwean sample. Significant differences between the two samples were noted in terms of educators' perceptions of the frequency of poor organisational support, with the Zimbabwean teachers reporting greater dissatisfaction. To explain these differences, a qualitative approach was utilised to illuminate the contextual stressors that educators face in Zimbabwe. The implications for teacher preparation measures are discussed.

  4. [Hereditary Alzheimer's disease with amyloid angiopathy caused by amyloid precursor protein locus].

    PubMed

    Axer, H; Hüge, S; Wilhelm, C; Axer, M; Kunze, A; Reichenbach, J R; Freesmeyer, M; Kohlhase, J; Sauer, H; Bär, K-J

    2009-01-01

    We report a patient with early-onset autosomal dominant dementia. The CSF showed increased levels of tau protein and decreased amyloid beta (ratio 42:40) typical for Alzheimer's disease. Cerebral MRI revealed vascular lesions and white-matter changes around the posterior horns of the ventricles with only moderate atrophy of the brain. Susceptibility-weighted imaging detected multiple small hemorrhagic changes. Gene analysis revealed amyloid precursor protein (APP) locus duplication as the cause of hereditary Alzheimer's dementia. The co-occurrence of CSF changes typical for Alzheimer's disease and MRI findings of cerebral amyloid angiopathy is remarkable, as it is also described for APP locus duplication. In conjunction with a family history suggestive of hereditary dementia, such a constellation should lead to enhanced gene analysis.

  5. Bivariate genomic analysis identifies a hidden locus associated with bacteria hypersensitive response in Arabidopsis thaliana

    PubMed Central

    Wang, Biao; Li, Zhuocheng; Xu, Weilin; Feng, Xiao; Wan, Qianhui; Zan, Yanjun; Sheng, Sitong; Shen, Xia

    2017-01-01

    Multi-phenotype analysis has drawn increasing attention to high-throughput genomic studies, whereas only a few applications have justified the use of multivariate techniques. We applied a recently developed multi-trait analysis method on a small set of bacteria hypersensitive response phenotypes and identified a single novel locus missed by conventional single-trait genome-wide association studies. The detected locus harbors a minor allele that elevates the risk of leaf collapse response to the injection of avrRpm1-modified Pseudomonas syringae (P = 1.66e-08). Candidate gene AT3G32930 with in the detected region and its co-expressed genes showed significantly reduced expression after P. syringae interference. Our results again emphasize that multi-trait analysis should not be neglected in association studies, as the power of specific multi-trait genotype-phenotype maps might only be tractable when jointly considering multiple phenotypes. PMID:28338080

  6. Pneumocystis murina MSG gene family and the structure of the locus associated with its transcription

    PubMed Central

    Keely, Scott P.; Linke, Michael J.; Cushion, Melanie T.; Stringer, James R.

    2007-01-01

    Analysis of the P. murina MSG gene family and expression-site locus showed that, as in P. carinii, P. murina MSG genes are arranged in head-to-tail tandem arrays located on multiple chromosomes, and that a variety of MSG genes can reside at the unique P. murina expression site. Located between the P. murina expression site and attached MSG gene is a block of 132 basepairs that is also present at the beginning of MSG genes that are not at the expression site. The center of this sequence block resembles the 28 basepair CRJE of P. carinii, but the block of conserved sequence in P. murina is nearly five times longer than in P. carinii, and much shorter than in Pneumocystis wakefieldiae. These data indicate that the P. murina expression-site locus has a distinct structure. PMID:17320432

  7. Allelic association at the D14S43 locus in early onset Alzheimer`s disease

    SciTech Connect

    Brice, A.; Tardieu, S.; Campion, D.; Martinez, M.

    1995-04-24

    The D14S43 marker is closely linked to the major gene for early onset autosomal dominant Alzheimer`s disease on chromosome 14. Allelic frequencies at the D14S43 locus were compared in 113 familial and isolated cases of early onset Alzheimer`s disease (<60 years of age at onset) (EOAD) and 109 unaffected individuals of the same geographic origin. Allele 7 was significantly (P = 0.033) more frequent in type 1 EOAD patients (13.2%), defined by the presence of at least another first degree relative with EOAD, than in controls (4.1%). Since an autosomal dominant gene is probably responsible for type 1 patients, allelic association may reflect linkage disequilibrium at the D14S43 locus. This would mean that some patients share a common ancestral mutation. However, since multiple tests were carried out, this result must be interpreted with caution, and needs confirmation in an independent sample. 16 refs., 2 tabs.

  8. Causes and Consequences of Multi-Locus Imprinting Disturbances in Humans.

    PubMed

    Sanchez-Delgado, Marta; Riccio, Andrea; Eggermann, Thomas; Maher, Eamonn R; Lapunzina, Pablo; Mackay, Deborah; Monk, David

    2016-07-01

    Eight syndromes are associated with the loss of methylation at specific imprinted loci. There has been increasing evidence that these methylation defects in patients are not isolated events occurring at a given disease-associated locus but that some of these patients may have multi-locus imprinting disturbances (MLID) affecting additional imprinted regions. With the recent advances in technology, methylation profiling has revealed that imprinted loci represent only a small fraction of the methylation differences observed between the gametes. To figure out how imprinting anomalies occur at multiple imprinted domains, we have to understand the interplay between DNA methylation and histone modifications in the process of selective imprint protection during pre-implantation reprogramming, which, if disrupted, leads to these complex imprinting disorders (IDs).

  9. Large-scale chromatin remodeling at the immunoglobulin heavy chain locus: a paradigm for multigene regulation.

    PubMed

    Bolland, Daniel J; Wood, Andrew L; Corcoran, Anne E

    2009-01-01

    V(D)J recombination in lymphocytes is the cutting and pasting together of antigen receptor genes in cis to generate the enormous variety of coding sequences required to produce diverse antigen receptor proteins. It is the key role of the adaptive immune response, which must potentially combat millions of different foreign antigens. Most antigen receptor loci have evolved to be extremely large and contain multiple individual V, D and J genes. The immunoglobulin heavy chain (Igh) and immunoglobulin kappa light chain (Igk) loci are the largest multigene loci in the mammalian genome and V(D)J recombination is one of the most complicated genetic processes in the nucleus. The challenge for the appropriate lymphocyte is one of macro-management-to make all of the antigen receptor genes in a particular locus available for recombination at the appropriate developmental time-point. Conversely, these large loci must be kept closed in lymphocytes in which they do not normally recombine, to guard against genomic instability generated by the DNA double strand breaks inherent to the V(D)J recombination process. To manage all of these demanding criteria, V(D)J recombination is regulated at numerous levels. It is restricted to lymphocytes since the Rag genes which control the DNA double-strand break step of recombination are only expressed in these cells. Within the lymphocyte lineage, immunoglobulin recombination is restricted to B-lymphocytes and TCR recombination to T-lymphocytes by regulation of locus accessibility, which occurs at multiple levels. Accessibility of recombination signal sequences (RSSs) flanking individual V, D and J genes at the nucleosomal level is the key micro-management mechanism, which is discussed in greater detail in other chapters. This chapter will explore how the antigen receptor loci are regulated as a whole, focussing on the Igh locus as a paradigm for the mechanisms involved. Numerous recent studies have begun to unravel the complex and

  10. Real Heroes.

    ERIC Educational Resources Information Center

    Denenberg, Dennis

    2001-01-01

    Presents stories taken from the book, "50 American Heroes Every Kid Should Meet," explaining that children need to learn about the value of real-life human accomplishments (versus those of athletes, television personalities, and rock stars). The heroes include Elizabeth Blackwell, first American woman doctor; George C. Marshall,…

  11. Real Heroes.

    ERIC Educational Resources Information Center

    Denenberg, Dennis

    2001-01-01

    Presents stories taken from the book, "50 American Heroes Every Kid Should Meet," explaining that children need to learn about the value of real-life human accomplishments (versus those of athletes, television personalities, and rock stars). The heroes include Elizabeth Blackwell, first American woman doctor; George C. Marshall,…

  12. A novel locus for disseminated superficial actinic porokeratosis maps to chromosome 16q24.1-24.3.

    PubMed

    Luan, Jing; Niu, Zhenmin; Zhang, Jing; Crosby, Meredith E; Zhang, Zhenghua; Chu, Xun; Wang, Zhimin; H