Sample records for specific combining abilities

  1. Relations between basic and specific motor abilities and player quality of young basketball players.

    PubMed

    Marić, Kristijan; Katić, Ratko; Jelicić, Mario

    2013-05-01

    Subjects from 5 first league clubs from Herzegovina were tested with the purpose of determining the relations of basic and specific motor abilities, as well as the effect of specific abilities on player efficiency in young basketball players (cadets). A battery of 12 tests assessing basic motor abilities and 5 specific tests assessing basketball efficiency were used on a sample of 83 basketball players. Two significant canonical correlations, i.e. linear combinations explained the relation between the set of twelve variables of basic motor space and five variables of situational motor abilities. Underlying the first canonical linear combination is the positive effect of the general motor factor, predominantly defined by jumping explosive power, movement speed of the arms, static strength of the arms and coordination, on specific basketball abilities: movement efficiency, the power of the overarm throw, shooting and passing precision, and the skill of handling the ball. The impact of basic motor abilities of precision and balance on specific abilities of passing and shooting precision and ball handling is underlying the second linear combination. The results of regression correlation analysis between the variable set of specific motor abilities and game efficiency have shown that the ability of ball handling has the largest impact on player quality in basketball cadets, followed by shooting precision and passing precision, and the power of the overarm throw.

  2. The utility of covariance of combining ability in plant breeding.

    PubMed

    Arunachalam, V

    1976-11-01

    The definition of covariances of half- and full sibs, and hence that of variances of general and specific combining ability with regard to a quantitative character, is extended to take into account the respective covariances between a pair of characters. The interpretation of the dispersion and correlation matrices of general and specific combining ability is discussed by considering a set of single, three- and four-way crosses, made using diallel and line × tester mating systems in Pennisetum typhoides. The general implications of the concept of covariance of combining ability in plant breeding are discussed.

  3. Combining-Ability Determinations for Incomplete Mating Designs

    Treesearch

    E.B. Snyder

    1975-01-01

    It is shown how general combining ability values (GCA's) from cross-, open-, and self-pollinated progeny can be derived in a single analysis. Breeding values are employed to facilitate explaining genetic models of the expected family means and the derivation of the GCA's. A FORTRAN computer program also includes computation of specific combining ability...

  4. Inheritance in a Diallel Crossing Experiment with Longleaf Pine

    Treesearch

    E. B. Snyder; Gene Namkoong

    1978-01-01

    Seven-year-old progeny from crosses among 13 randomly selected parent trees provided genetic information on 51 growth, form, foliage, branch, bud, and pest resistance traits. Presented are he&abilities, phenotypic and genotypic variances, covariances, General Combining Ability (GCA), Specific Combining Ability (SCA), and environmental. correlations for all measured...

  5. Efficiency of circulant diallels via mixed models in the selection of papaya genotypes resistant to foliar fungal diseases.

    PubMed

    Vivas, M; Silveira, S F; Viana, A P; Amaral, A T; Cardoso, D L; Pereira, M G

    2014-07-02

    Diallel crossing methods provide information regarding the performance of genitors between themselves and their hybrid combinations. However, with a large number of parents, the number of hybrid combinations that can be obtained and evaluated become limited. One option regarding the number of parents involved is the adoption of circulant diallels. However, information is lacking regarding diallel analysis using mixed models. This study aimed to evaluate the efficacy of the method of linear mixed models to estimate, for variable resistance to foliar fungal diseases, components of general and specific combining ability in a circulant table with different s values. Subsequently, 50 diallels were simulated for each s value, and the correlations and estimates of the combining abilities of the different diallel combinations were analyzed. The circulant diallel method using mixed modeling was effective in the classification of genitors regarding their combining abilities relative to the complete diallels. The numbers of crosses in which each genitor(s) will compose the circulant diallel and the estimated heritability affect the combining ability estimates. With three crosses per parent, it is possible to obtain good concordance (correlation above 0.8) between the combining ability estimates.

  6. An Analysis of Content Knowledge and Cognitive Abilities as Factors That Are Associated with Algebra Performance

    ERIC Educational Resources Information Center

    McLean, Tamika Ann

    2017-01-01

    The current study investigated college students' content knowledge and cognitive abilities as factors associated with their algebra performance, and examined how combinations of content knowledge and cognitive abilities related to their algebra performance. Specifically, the investigation examined the content knowledge factors of computational…

  7. Do Interests and Cognitive Abilities Help Explain College Major Choice Equally Well for Women and Men?

    ERIC Educational Resources Information Center

    Passler, Katja; Hell, Benedikt

    2012-01-01

    The present study examines whether vocational interests, measured by Holland's RIASEC model, and objectively assessed cognitive abilities, were useful in discriminating among various major categories for a sample of 1990 German university students. Interests and specific abilities, in combination, significantly discriminated among major categories…

  8. Combining Frequency Doubling Technology Perimetry and Scanning Laser Polarimetry for Glaucoma Detection.

    PubMed

    Mwanza, Jean-Claude; Warren, Joshua L; Hochberg, Jessica T; Budenz, Donald L; Chang, Robert T; Ramulu, Pradeep Y

    2015-01-01

    To determine the ability of frequency doubling technology (FDT) and scanning laser polarimetry with variable corneal compensation (GDx-VCC) to detect glaucoma when used individually and in combination. One hundred ten normal and 114 glaucomatous subjects were tested with FDT C-20-5 screening protocol and the GDx-VCC. The discriminating ability was tested for each device individually and for both devices combined using GDx-NFI, GDx-TSNIT, number of missed points of FDT, and normal or abnormal FDT. Measures of discrimination included sensitivity, specificity, area under the curve (AUC), Akaike's information criterion (AIC), and prediction confidence interval lengths. For detecting glaucoma regardless of severity, the multivariable model resulting from the combination of GDx-TSNIT, number of abnormal points on FDT (NAP-FDT), and the interaction GDx-TSNIT×NAP-FDT (AIC: 88.28, AUC: 0.959, sensitivity: 94.6%, specificity: 89.5%) outperformed the best single-variable model provided by GDx-NFI (AIC: 120.88, AUC: 0.914, sensitivity: 87.8%, specificity: 84.2%). The multivariable model combining GDx-TSNIT, NAP-FDT, and interaction GDx-TSNIT×NAP-FDT consistently provided better discriminating abilities for detecting early, moderate, and severe glaucoma than the best single-variable models. The multivariable model including GDx-TSNIT, NAP-FDT, and the interaction GDx-TSNIT×NAP-FDT provides the best glaucoma prediction compared with all other multivariable and univariable models. Combining the FDT C-20-5 screening protocol and GDx-VCC improves glaucoma detection compared with using GDx or FDT alone.

  9. Examining the Inseparability of Content Knowledge from LSP Reading Ability: An Approach Combining Bifactor-Multidimensional Item Response Theory and Structural Equation Modeling

    ERIC Educational Resources Information Center

    Cai, Yuyang; Kunnan, Antony John

    2018-01-01

    This study examined the separability of domain-general and domain-specific content knowledge from Language for Specific Purposes (LSP) reading ability. A pool of 1,491 nursing students in China participated by responding to a nursing English test and a nursing knowledge test. Primary data analysis involved four steps: (a) conducting a…

  10. Inheritance of Resistance to Sorghum Shoot Fly, Atherigona soccata in Sorghum, Sorghum bicolor (L.) Moench

    PubMed Central

    Mohammed, Riyazaddin; Are, Ashok Kumar; Munghate, Rajendra Sudhakar; Bhavanasi, Ramaiah; Polavarapu, Kavi Kishor B.; Sharma, Hari Chand

    2016-01-01

    Sorghum production is affected by a wide array of biotic constraints, of which sorghum shoot fly, Atherigona soccata is the most important pest, which severely damages the sorghum crop during the seedling stage. Host plant resistance is one of the major components to control sorghum shoot fly, A. soccata. To understand the nature of gene action for inheritance of shoot fly resistance, we evaluated 10 parents, 45 F1's and their reciprocals in replicated trials during the rainy and postrainy seasons. The genotypes ICSV 700, Phule Anuradha, ICSV 25019, PS 35805, IS 2123, IS 2146, and IS 18551 exhibited resistance to shoot fly damage across seasons. Crosses between susceptible parents were preferred for egg laying by the shoot fly females, resulting in a susceptible reaction. ICSV 700, ICSV 25019, PS 35805, IS 2123, IS 2146, and IS 18551 exhibited significant and negative general combining ability (gca) effects for oviposition, deadheart incidence, and overall resistance score. The plant morphological traits associated with expression of resistance/susceptibility to shoot fly damage such as leaf glossiness, plant vigor, and leafsheath pigmentation also showed significant gca effects by these genotypes, suggesting the potential for use as a selection criterion to breed for resistance to shoot fly, A. soccata. ICSV 700, Phule Anuradha, IS 2146 and IS 18551 with significant positive gca effects for trichome density can also be utilized in improving sorghums for shoot fly resistance. The parents involved in hybrids with negative specific combining ability (sca) effects for shoot fly resistance traits can be used in developing sorghum hybrids with adaptation to postrainy season. The significant reciprocal effects of combining abilities for oviposition, leaf glossy score and trichome density suggested the influence of cytoplasmic factors in inheritance of shoot fly resistance. Higher values of variance due to specific combining ability (σ2s), dominance variance (σ2d), and lower predictability ratios than the variance due to general combining ability (σ2g) and additive variance (σ2a) for shoot fly resistance traits indicated the predominance of dominance type of gene action, whereas trichome density, leaf glossy score, and plant vigor score with high σ2g, additive variance, predictability ratio, and the ratio of general combining ability to the specific combining ability showed predominance of additive type of gene action indicating importance of heterosis breeding followed by simple selection in breeding shoot fly-resistant sorghums. Most of the traits exhibited high broadsense heritability, indicating high inheritance of shoot fly resistance traits. PMID:27200020

  11. Combining Frequency Doubling Technology Perimetry and Scanning Laser Polarimetry for Glaucoma Detection

    PubMed Central

    Mwanza, Jean-Claude; Warren, Joshua L.; Hochberg, Jessica T.; Budenz, Donald L.; Chang, Robert T.; Ramulu, Pradeep Y.

    2014-01-01

    Purpose To determine the ability of frequency doubling technology (FDT) and scanning laser polarimetry with variable corneal compensation (GDx-VCC) to detect glaucoma when used individually and in combination. Methods One hundred and ten normal and 114 glaucomatous subjects were tested with FDT C-20-5 screening protocol and the GDx-VCC. The discriminating ability was tested for each device individually and for both devices combined using GDx-NFI, GDx-TSNIT, number of missed points of FDT, and normal or abnormal FDT. Measures of discrimination included sensitivity, specificity, area under the curve (AUC), Akaike’s information criterion (AIC), and prediction confidence interval lengths (PIL). Results For detecting glaucoma regardless of severity, the multivariable model resulting from the combination of GDX-TSNIT, number of abnormal points on FDT (NAP-FDT), and the interaction GDx-TSNIT * NAP-FDT (AIC: 88.28, AUC: 0.959, sensitivity: 94.6%, specificity: 89.5%) outperformed the best single variable model provided by GDx-NFI (AIC: 120.88, AUC: 0.914, sensitivity: 87.8%, specificity: 84.2%). The multivariable model combining GDx-TSNIT, NAPFDT, and interaction GDx-TSNIT*NAP-FDT consistently provided better discriminating abilities for detecting early, moderate and severe glaucoma than the best single variable models. Conclusions The multivariable model including GDx-TSNIT, NAP-FDT, and the interaction GDX-TSNIT * NAP-FDT provides the best glaucoma prediction compared to all other multivariable and univariable models. Combining the FDT C-20-5 screening protocol and GDx-VCC improves glaucoma detection compared to using GDx or FDT alone. PMID:24777046

  12. Combining ability of S3 progenies for key agronomic traits in popcorn: comparison of testers in top-crosses.

    PubMed

    de Lima, V J; do Amaral Junior, A T; Kamphorst, S H; Pena, G F; Leite, J T; Schmitt, K F M; Vittorazzi, C; de Almeida Filho, J E; Mora, F

    2016-12-02

    The successful development of hybrid cultivars depends on the reliability of estimated combining ability of the parent lines. The objectives of this study were to assess the combining ability of partially inbred S 3 families of popcorn derived from the open-pollinated variety UENF 14, via top-crosses with four testers, and to compare the testers for their ability to discriminate the S 3 progenies. The experiment was conducted in the 2015/2016 crop season, in an incomplete-block (Lattice) design with three replications. The following agronomic traits were evaluated: average plant height, grain yield (GY), popping expansion (PE), and expanded popcorn volume per hectare. The top-cross hybrid, originating from the BRS-Angela vs S 3 progeny 10 combination, was indicated as promising, showing high values for specific combining ability for GY and PE. For the S 3 progenies that showed high and positive GCA values for GY and PE, the continuity of the breeding program is recommended, with the advance of self-pollination generations. Fasoulas' differentiation index discriminated the BRS-Angela tester as the most suitable for identifying the superior progenies.

  13. Heterosis and combining ability: a diallel cross of three geographically isolated populations of Pacific abalone Haliotis discus hannai Ino

    NASA Astrophysics Data System (ADS)

    Deng, Yuewen; Liu, Xiao; Zhang, Guofan; Wu, Fucun

    2010-11-01

    We conducted a complete diallel cross among three geographically isolated populations of Pacific abalone Haliotis discus hannai Ino to determine the heterosis and the combining ability of growth traits at the spat stage. The three populations were collected from Qingdao (Q) and Dalian (D) in China, and Miyagi (M) in Japan. We measured the shell length, shell width, and total weight. The magnitude of the general combining ability (GCA) variance was more pronounced than the specific combining ability (SCA) variance, which is evidenced by both the ratio of the genetic component in total variation and the GCA/SCA values. The component variances of GCA and SCA were significant for all three traits ( P<0.05), indicating the importance of additive and non-additive genetic effects in determining the expression of these traits. The reciprocal maternal effects (RE) were also significant for these traits ( P<0.05). Our results suggest that population D was the best general combiner in breeding programs to improve growth traits. The DM cross had the highest heterosis values for all three traits.

  14. Capturing specific abilities as a window into human individuality: the example of face recognition.

    PubMed

    Wilmer, Jeremy B; Germine, Laura; Chabris, Christopher F; Chatterjee, Garga; Gerbasi, Margaret; Nakayama, Ken

    2012-01-01

    Proper characterization of each individual's unique pattern of strengths and weaknesses requires good measures of diverse abilities. Here, we advocate combining our growing understanding of neural and cognitive mechanisms with modern psychometric methods in a renewed effort to capture human individuality through a consideration of specific abilities. We articulate five criteria for the isolation and measurement of specific abilities, then apply these criteria to face recognition. We cleanly dissociate face recognition from more general visual and verbal recognition. This dissociation stretches across ability as well as disability, suggesting that specific developmental face recognition deficits are a special case of a broader specificity that spans the entire spectrum of human face recognition performance. Item-by-item results from 1,471 web-tested participants, included as supplementary information, fuel item analyses, validation, norming, and item response theory (IRT) analyses of our three tests: (a) the widely used Cambridge Face Memory Test (CFMT); (b) an Abstract Art Memory Test (AAMT), and (c) a Verbal Paired-Associates Memory Test (VPMT). The availability of this data set provides a solid foundation for interpreting future scores on these tests. We argue that the allied fields of experimental psychology, cognitive neuroscience, and vision science could fuel the discovery of additional specific abilities to add to face recognition, thereby providing new perspectives on human individuality.

  15. Number-specific and general cognitive markers of preschoolers' math ability profiles.

    PubMed

    Gray, Sarah A; Reeve, Robert A

    2016-07-01

    Different number-specific and general cognitive markers have been claimed to underlie preschoolers' math ability. It is unclear, however, whether similar/different cognitive markers, or combinations of them, are associated with different patterns of emerging math abilities (i.e., different patterns of strength and weakness). To examine this question, 103 preschoolers (40-60 months of age) completed six math tasks (count sequence, object counting, give a number, naming numbers, ordinal relations, and arithmetic), three number-specific markers of math ability (dot enumeration, magnitude comparison, and spontaneous focusing on numerosity), and four general markers (working memory, response inhibition, attention, and vocabulary). A three-step latent profile modeling procedure identified five math ability profiles that differed in their patterns of math strengths and weaknesses; specifically, the profiles were characterized by (a) excellent math ability on all math tasks, (b) good arithmetic ability, (c) good math ability but relatively poor count sequence recitation ability, (d) average ability on all math tasks, and (e) poor ability on all math tasks. After controlling for age, only dot enumeration and spontaneous focusing on numerosity were associated with the math ability profiles, whereas vocabulary was also marginally significant, and these markers were differentially associated with different profiles; that is, different cognitive markers were associated with different patterns of strengths and weaknesses in math abilities. Findings are discussed in terms of their implications for the development of math cognition. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Neural signatures of co-occurring reading and mathematical difficulties.

    PubMed

    Skeide, Michael A; Evans, Tanya M; Mei, Edward Z; Abrams, Daniel A; Menon, Vinod

    2018-06-19

    Impaired abilities in multiple domains is common in children with learning difficulties. Co-occurrence of low reading and mathematical abilities (LRLM) appears in almost every second child with learning difficulties. However, little is known regarding the neural bases of this combination. Leveraging a unique and tightly controlled sample including children with LRLM, isolated low reading ability (LR), and isolated low mathematical ability (LM), we uncover a distinct neural signature in children with co-occurring low reading and mathematical abilities differentiable from LR and LM. Specifically, we show that LRLM is neuroanatomically distinct from both LR and LM based on reduced cortical folding of the right parahippocampal gyrus, a medial temporal lobe region implicated in visual associative learning. LRLM children were further distinguished from LR and LM by patterns of intrinsic functional connectivity between parahippocampal gyrus and brain circuitry underlying reading and numerical quantity processing. Our results critically inform cognitive and neural models of LRLM by implicating aberrations in both domain-specific and domain-general brain regions involved in reading and mathematics. More generally, our results provide the first evidence for distinct multimodal neural signatures associated with LRLM, and suggest that this population displays an independent phenotype of learning difficulty that cannot be explained simply as a combination of isolated low reading and mathematical abilities. © 2018 John Wiley & Sons Ltd.

  17. Combining ability of tropical and temperate inbred lines of popcorn.

    PubMed

    da Silva, V Q R; do Amaral Júnior, A T; Gonçalves, L S A; Freitas Júnior, S P; Candido, L S; Vittorazzi, C; Moterle, L M; Vieira, R A; Scapim, C A

    2010-08-31

    In Brazil, using combining ability of popcorn genotypes to achieve superior hybrids has been unsuccessful because the local genotypes are all members of the same heterotic group. To overcome this constraint, 10 lines (P(1) to P(10)) with different adaptations to tropical or temperate edaphoclimatic environments were used to obtain 45 F(1) hybrids in a complete diallel. These hybrids and three controls were evaluated in two environments in Rio de Janeiro State. Grain yield (GY), popping expansion (PE), plant height (PH), ear height (EH), and days to silking (FL) were evaluated in randomized complete blocks with three replications. Significant differences between genotypes (P

  18. Predicting Children's Reading and Mathematics Achievement from Early Quantitative Knowledge and Domain-General Cognitive Abilities

    PubMed Central

    Chu, Felicia W.; vanMarle, Kristy; Geary, David C.

    2016-01-01

    One hundred children (44 boys) participated in a 3-year longitudinal study of the development of basic quantitative competencies and the relation between these competencies and later mathematics and reading achievement. The children's preliteracy knowledge, intelligence, executive functions, and parental educational background were also assessed. The quantitative tasks assessed a broad range of symbolic and nonsymbolic knowledge and were administered four times across 2 years of preschool. Mathematics achievement was assessed at the end of each of 2 years of preschool, and mathematics and word reading achievement were assessed at the end of kindergarten. Our goals were to determine how domain-general abilities contribute to growth in children's quantitative knowledge and to determine how domain-general and domain-specific abilities contribute to children's preschool mathematics achievement and kindergarten mathematics and reading achievement. We first identified four core quantitative competencies (e.g., knowledge of the cardinal value of number words) that predict later mathematics achievement. The domain-general abilities were then used to predict growth in these competencies across 2 years of preschool, and the combination of domain-general abilities, preliteracy skills, and core quantitative competencies were used to predict mathematics achievement across preschool and mathematics and word reading achievement at the end of kindergarten. Both intelligence and executive functions predicted growth in the four quantitative competencies, especially across the first year of preschool. A combination of domain-general and domain-specific competencies predicted preschoolers' mathematics achievement, with a trend for domain-specific skills to be more strongly related to achievement at the beginning of preschool than at the end of preschool. Preschool preliteracy skills, sensitivity to the relative quantities of collections of objects, and cardinal knowledge predicted reading and mathematics achievement at the end of kindergarten. Preliteracy skills were more strongly related to word reading, whereas sensitivity to relative quantity was more strongly related to mathematics achievement. The overall results indicate that a combination of domain-general and domain-specific abilities contribute to development of children's early mathematics and reading achievement. PMID:27252675

  19. Predicting Children's Reading and Mathematics Achievement from Early Quantitative Knowledge and Domain-General Cognitive Abilities.

    PubMed

    Chu, Felicia W; vanMarle, Kristy; Geary, David C

    2016-01-01

    One hundred children (44 boys) participated in a 3-year longitudinal study of the development of basic quantitative competencies and the relation between these competencies and later mathematics and reading achievement. The children's preliteracy knowledge, intelligence, executive functions, and parental educational background were also assessed. The quantitative tasks assessed a broad range of symbolic and nonsymbolic knowledge and were administered four times across 2 years of preschool. Mathematics achievement was assessed at the end of each of 2 years of preschool, and mathematics and word reading achievement were assessed at the end of kindergarten. Our goals were to determine how domain-general abilities contribute to growth in children's quantitative knowledge and to determine how domain-general and domain-specific abilities contribute to children's preschool mathematics achievement and kindergarten mathematics and reading achievement. We first identified four core quantitative competencies (e.g., knowledge of the cardinal value of number words) that predict later mathematics achievement. The domain-general abilities were then used to predict growth in these competencies across 2 years of preschool, and the combination of domain-general abilities, preliteracy skills, and core quantitative competencies were used to predict mathematics achievement across preschool and mathematics and word reading achievement at the end of kindergarten. Both intelligence and executive functions predicted growth in the four quantitative competencies, especially across the first year of preschool. A combination of domain-general and domain-specific competencies predicted preschoolers' mathematics achievement, with a trend for domain-specific skills to be more strongly related to achievement at the beginning of preschool than at the end of preschool. Preschool preliteracy skills, sensitivity to the relative quantities of collections of objects, and cardinal knowledge predicted reading and mathematics achievement at the end of kindergarten. Preliteracy skills were more strongly related to word reading, whereas sensitivity to relative quantity was more strongly related to mathematics achievement. The overall results indicate that a combination of domain-general and domain-specific abilities contribute to development of children's early mathematics and reading achievement.

  20. Capturing specific abilities as a window into human individuality: The example of face recognition

    PubMed Central

    Wilmer, Jeremy B.; Germine, Laura; Chabris, Christopher F.; Chatterjee, Garga; Gerbasi, Margaret; Nakayama, Ken

    2013-01-01

    Proper characterization of each individual's unique pattern of strengths and weaknesses requires good measures of diverse abilities. Here, we advocate combining our growing understanding of neural and cognitive mechanisms with modern psychometric methods in a renewed effort to capture human individuality through a consideration of specific abilities. We articulate five criteria for the isolation and measurement of specific abilities, then apply these criteria to face recognition. We cleanly dissociate face recognition from more general visual and verbal recognition. This dissociation stretches across ability as well as disability, suggesting that specific developmental face recognition deficits are a special case of a broader specificity that spans the entire spectrum of human face recognition performance. Item-by-item results from 1,471 web-tested participants, included as supplementary information, fuel item analyses, validation, norming, and item response theory (IRT) analyses of our three tests: (a) the widely used Cambridge Face Memory Test (CFMT); (b) an Abstract Art Memory Test (AAMT), and (c) a Verbal Paired-Associates Memory Test (VPMT). The availability of this data set provides a solid foundation for interpreting future scores on these tests. We argue that the allied fields of experimental psychology, cognitive neuroscience, and vision science could fuel the discovery of additional specific abilities to add to face recognition, thereby providing new perspectives on human individuality. PMID:23428079

  1. Combining-ability for cacao (Theobroma cacao L.) yield components under southern Bahia conditions.

    PubMed

    Dias, L A; Kageyama, P Y

    1995-03-01

    The objective of this study was to assess five cacao cultivars (selfs) and 20 hybrids with regard to their general-and specific-combining ability for yield components using method 1, model I, of the diallel analysis system. The selfings and the hybrids were obtained through controlled crossings, tested in the field in a random block design with four replications and plots containing 16 plants. The experiment was set up in the Centro de Pesquisas do Cacau, in Itabuna, Bahia, Brasil, in 1975. The characteristics studied were: the number of healthy and collected fruits per plant (NHFP and NCFP), the weight of humid seeds per plant and per fruit (WHSP and WHSF), and the percentage of diseased fruits per plant (PDFP), for 5 years (1986-1990). The F-test values, highly significant for general combining ability (GCA) and specific combining ability (SCA), demonstrated the existence of variability for both effects. However, the effects of SCA were greater than those of GCA, when compared in terms of the average squared effects. This condition held for the characteristics NHFP, NCFP and WHSP, which shows the relative importance of the non-additive genetic effects over the additive effects. The reciprocal effects did not show significance. Breeding methods which explore the additive portion of genetic variance should be employed for obtaining higher-yielding cacao and high seed weight. For this, the segregant populations should involve cultivars CEPEC 1, SIAL 169 and ICS 1. Combinations involving the cultivar ICS 1 presented the most favorable results for the characteristics WHSP and WHSF, where the hybrid SIAL 169 x ICS 1 and its reciprocal were outstanding.

  2. On the nature and nurture of intelligence and specific cognitive abilities: the more heritable, the more culture dependent.

    PubMed

    Kan, Kees-Jan; Wicherts, Jelte M; Dolan, Conor V; van der Maas, Han L J

    2013-12-01

    To further knowledge concerning the nature and nurture of intelligence, we scrutinized how heritability coefficients vary across specific cognitive abilities both theoretically and empirically. Data from 23 twin studies (combined N = 7,852) showed that (a) in adult samples, culture-loaded subtests tend to demonstrate greater heritability coefficients than do culture-reduced subtests; and (b) in samples of both adults and children, a subtest's proportion of variance shared with general intelligence is a function of its cultural load. These findings require an explanation because they do not follow from mainstream theories of intelligence. The findings are consistent with our hypothesis that heritability coefficients differ across cognitive abilities as a result of differences in the contribution of genotype-environment covariance. The counterintuitive finding that the most heritable abilities are the most culture-dependent abilities sheds a new light on the long-standing nature-nurture debate of intelligence.

  3. Determination of high-strength materials diamond grinding rational modes

    NASA Astrophysics Data System (ADS)

    Arkhipov, P. V.; Lobanov, D. V.; Rychkov, D. A.; Yanyushkin, A. S.

    2018-03-01

    The analysis of methods of high-strength materials abrasive processing is carried out. This method made it possible to determine the necessary directions and prospects for the development of shaping combined methods. The need to use metal bonded diamond abrasive tools in combination with a different kind of energy is noted to improve the processing efficiency and reduce the complexity of operations. The complex of experimental research on revealing the importance of mechanical and electrical components of cutting regimes, on the cutting ability of diamond tools, as well as the need to reduce the specific consumption of an abrasive wheel as one of the important economic indicators of the processing process is performed. It is established that combined diamond grinding with simultaneous continuous correction of the abrasive wheel contributes to an increase in the cutting ability of metal bonded diamond abrasive tools when processing high-strength materials by an average of 30% compared to diamond grinding. Particular recommendations on the designation of technological factors are developed depending on specific production problems.

  4. Intercept Centering and Time Coding in Latent Difference Score Models

    ERIC Educational Resources Information Center

    Grimm, Kevin J.

    2012-01-01

    Latent difference score (LDS) models combine benefits derived from autoregressive and latent growth curve models allowing for time-dependent influences and systematic change. The specification and descriptions of LDS models include an initial level of ability or trait plus an accumulation of changes. A limitation of this specification is that the…

  5. Genetic control of number of flowers and pod set in common bean.

    PubMed

    Martins, E S; Pinto Júnior, R A; Abreu, A F B; Ramalho, M A P

    2017-09-21

    This article aimed to study the genetic control of some flowers and pod set of common bean and to verify if its estimate varies with environmental conditions and gene pool. A complete diallel was used among six lines, but no reciprocal ones. The treatments were evaluated in three harvests/generations - F 2 , F 3 , and F 4 - in 2015/2016, in a randomized complete block design with four replications. The plot consisted of 3 lines with 4 m. In the center line, a receptacle to collect the aborted flowers/pods was placed. The traits considered were the number of flowers/plant (N), the percentage of pod set (V), and the production of grain/plant (W). A joint diallel analysis was performed, and the correlations between N, V, ​​and W were estimated. N was 31.9 on average, and V was 40.4%. The average of Mesoamerican parents, for N and V, was higher than for Andean. Specific combining ability explained most of the variation for N, evidencing predominance of dominance effect. For V, specific combining ability was slightly lower than general combining ability, indicating additive loci and also dominance effects. These two traits were very influenced by environment and should be considered a strategy for greater grain yield stability of common bean.

  6. Sound credit scores and financial decisions despite cognitive aging.

    PubMed

    Li, Ye; Gao, Jie; Enkavi, A Zeynep; Zaval, Lisa; Weber, Elke U; Johnson, Eric J

    2015-01-06

    Age-related deterioration in cognitive ability may compromise the ability of older adults to make major financial decisions. We explore whether knowledge and expertise accumulated from past decisions can offset cognitive decline to maintain decision quality over the life span. Using a unique dataset that combines measures of cognitive ability (fluid intelligence) and of general and domain-specific knowledge (crystallized intelligence), credit report data, and other measures of decision quality, we show that domain-specific knowledge and expertise provide an alternative route for sound financial decisions. That is, cognitive aging does not spell doom for financial decision-making in domains where the decision maker has developed expertise. These results have important implications for public policy and for the design of effective interventions and decision aids.

  7. Breeding maize for resistance to ear rot caused by Fusarium moniliforme.

    PubMed

    Hefny, M; Attaa, S; Bayoumi, T; Ammar, S; El-Bramawy, M

    2012-01-15

    Maize ear rots are among the most important impediments to increased maize production in Egypt. The present research was conducted to estimate combining abilities, heterosis and correlation coefficients for resistance to ear rot disease in seven corn inbred lines and their 21 crosses under field conditions. Results demonstrated that both additive and non-additive gene actions were responsible for the genetic expression of all characters with the preponderance of non-additive actions for days to 50% silking. The parental line L51 was the best combiner for earliness, low infection severity %, high phenols content, short plants and reasonable grain yield, while L101 was good combiner for low ear rot infection only. The cross: L122 x L84, L122 x L101, L51 x L101, L76 x L36, L76 x L84, L36 x L84, L36 x L81 and L36 x L101 which involved one or both parents with good General Combining Ability (GCA) effects expressed useful significant heterosis and Specific Combining Ability (SCA) effects for low infection severity %, high phenol contents, early silking, tall plants and high grain yield. Phenotypic and genotypic correlation coefficients suggest that selection for resistance to ear rot should identify lines with high yielding ability, early silking, tall plants, high phenols content and chitinase activity.

  8. Quantitative genetic analysis of agronomic and morphological traits in sorghum, Sorghum bicolor

    PubMed Central

    Mohammed, Riyazaddin; Are, Ashok K.; Bhavanasi, Ramaiah; Munghate, Rajendra S.; Kavi Kishor, Polavarapu B.; Sharma, Hari C.

    2015-01-01

    The productivity in sorghum is low, owing to various biotic and abiotic constraints. Combining insect resistance with desirable agronomic and morphological traits is important to increase sorghum productivity. Therefore, it is important to understand the variability for various agronomic traits, their heritabilities and nature of gene action to develop appropriate strategies for crop improvement. Therefore, a full diallel set of 10 parents and their 90 crosses including reciprocals were evaluated in replicated trials during the 2013–14 rainy and postrainy seasons. The crosses between the parents with early- and late-flowering flowered early, indicating dominance of earliness for anthesis in the test material used. Association between the shoot fly resistance, morphological, and agronomic traits suggested complex interactions between shoot fly resistance and morphological traits. Significance of the mean sum of squares for GCA (general combining ability) and SCA (specific combining ability) of all the studied traits suggested the importance of both additive and non-additive components in inheritance of these traits. The GCA/SCA, and the predictability ratios indicated predominance of additive gene effects for majority of the traits studied. High broad-sense and narrow-sense heritability estimates were observed for most of the morphological and agronomic traits. The significance of reciprocal combining ability effects for days to 50% flowering, plant height and 100 seed weight, suggested maternal effects for inheritance of these traits. Plant height and grain yield across seasons, days to 50% flowering, inflorescence exsertion, and panicle shape in the postrainy season showed greater specific combining ability variance, indicating the predominance of non-additive type of gene action/epistatic interactions in controlling the expression of these traits. Additive gene action in the rainy season, and dominance in the postrainy season for days to 50% flowering and plant height suggested G X E interactions for these traits. PMID:26579183

  9. Biomotor structures in elite female handball players.

    PubMed

    Katić, Ratko; Cavala, Marijana; Srhoj, Vatromir

    2007-09-01

    In order to identify biomotor structures in elite female handball players, factor structures of morphological characteristics and basic motor abilities of elite female handball players (N = 53) were determined first, followed by determination of relations between the morphological-motor space factors obtained and the set of criterion variables evaluating situation motor abilities in handball. Factor analysis of 14 morphological measures produced three morphological factors, i.e. factor of absolute voluminosity (mesoendomorph), factor of longitudinal skeleton dimensionality, and factor of transverse hand dimensionality. Factor analysis of 15 motor variables yielded five basic motor dimensions, i.e. factor of agility, factor of jumping explosive strength, factor of throwing explosive strength, factor of movement frequency rate, and factor of running explosive strength (sprint). Four significant canonic correlations, i.e. linear combinations, explained the correlation between the set of eight latent variables of the morphological and basic motor space and five variables of situation motoricity. First canonic linear combination is based on the positive effect of the factors of agility/coordination on the ability of fast movement without ball. Second linear combination is based on the effect of jumping explosive strength and transverse hand dimensionality on ball manipulation, throw precision, and speed of movement with ball. Third linear combination is based on the running explosive strength determination by the speed of movement with ball, whereas fourth combination is determined by throwing and jumping explosive strength, and agility on ball pass. The results obtained were consistent with the model of selection in female handball proposed (Srhoj et al., 2006), showing the speed of movement without ball and the ability of ball manipulation to be the predominant specific abilities, as indicated by the first and second linear combination.

  10. Analysis of Defined Combinations of Monoclonal Antibodies in Anthrax Toxin Neutralization Assays and Their Synergistic Action

    PubMed Central

    Ngundi, Miriam M.; Meade, Bruce D.; Little, Stephen F.; Quinn, Conrad P.; Corbett, Cindi R.; Brady, Rebecca A.

    2012-01-01

    Antibodies against the protective antigen (PA) component of anthrax toxin play an important role in protection against disease caused by Bacillus anthracis. In this study, we examined defined combinations of PA-specific monoclonal antibodies for their ability to neutralize anthrax toxin in cell culture assays. We observed additive, synergistic, and antagonistic effects of the antibodies depending on the specific antibody combination examined and the specific assay used. Synergistic toxin-neutralizing antibody interactions were examined in more detail. We found that one mechanism that can lead to antibody synergy is the bridging of PA monomers by one antibody, with resultant bivalent binding of the second antibody. These results may aid in optimal design of new vaccines and antibody therapies against anthrax. PMID:22441391

  11. Genetic Variation and Combining Ability Analysis of Bruising Sensitivity in Agaricus bisporus

    PubMed Central

    Gao, Wei; Baars, Johan J. P.; Dolstra, Oene; Visser, Richard G. F.; Sonnenberg, Anton S. M.

    2013-01-01

    Advanced button mushroom cultivars that are less sensitive to mechanical bruising are required by the mushroom industry, where automated harvesting still cannot be used for the fresh mushroom market. The genetic variation in bruising sensitivity (BS) of Agaricus bisporus was studied through an incomplete set of diallel crosses to get insight in the heritability of BS and the combining ability of the parental lines used and, in this way, to estimate their breeding value. To this end nineteen homokaryotic lines recovered from wild strains and cultivars were inter-crossed in a diallel scheme. Fifty-one successful hybrids were grown under controlled conditions, and the BS of these hybrids was assessed. BS was shown to be a trait with a very high heritability. The results also showed that brown hybrids were generally less sensitive to bruising than white hybrids. The diallel scheme allowed to estimate the general combining ability (GCA) for each homokaryotic parental line and to estimate the specific combining ability (SCA) of each hybrid. The line with the lowest GCA is seen as the most attractive donor for improving resistance to bruising. The line gave rise to hybrids sensitive to bruising having the highest GCA value. The highest negative SCA possibly indicates heterosis effects for resistance to bruising. This study provides a foundation for estimating breeding value of parental lines to further study the genetic factors underlying bruising sensitivity and other quality-related traits, and to select potential parental lines for further heterosis breeding. The approach of studying combining ability in a diallel scheme was used for the first time in button mushroom breeding. PMID:24116171

  12. Sound credit scores and financial decisions despite cognitive aging

    PubMed Central

    Li, Ye; Gao, Jie; Enkavi, A. Zeynep; Zaval, Lisa; Weber, Elke U.; Johnson, Eric J.

    2015-01-01

    Age-related deterioration in cognitive ability may compromise the ability of older adults to make major financial decisions. We explore whether knowledge and expertise accumulated from past decisions can offset cognitive decline to maintain decision quality over the life span. Using a unique dataset that combines measures of cognitive ability (fluid intelligence) and of general and domain-specific knowledge (crystallized intelligence), credit report data, and other measures of decision quality, we show that domain-specific knowledge and expertise provide an alternative route for sound financial decisions. That is, cognitive aging does not spell doom for financial decision-making in domains where the decision maker has developed expertise. These results have important implications for public policy and for the design of effective interventions and decision aids. PMID:25535381

  13. Information Processing in Toddlers: Continuity from Infancy and Persistence of Preterm Deficits

    PubMed Central

    Rose, Susan A.; Feldman, Judith F.; Jankowski, Jeffery J.

    2009-01-01

    The present report assesses information processing in the toddler years (24 and 36 months), using a cohort of preterms (<1750 g) and full-terms initially seen in infancy. The children received a battery of tasks tapping 11 specific abilities from four domains – memory, processing speed, attention, and representational competence. The same battery had been used earlier – at 7 and 12 months. There were four main findings. (1) Preterms showed no ‘catch-up,’ but rather persistent deficits in immediate recognition, recall, encoding speed, and attention. (2) There was significant continuity from infancy through the toddler years for most aspects of information processing. (3) These specific abilities combined additively to account for global cognitive ability, consistent with the componential theory of intelligence. (4) Toddler information processing abilities completely mediated the relative deficits of preterms in general cognitive ability. Thus, although the toddler years have often been characterized as a period of discontinuity and transformation, these results indicate that continuity prevails for information processing abilities over the first three years of life. PMID:20161244

  14. Origins of magic: review of genetic and epigenetic effects.

    PubMed

    Ramagopalan, Sreeram V; Knight, Marian; Ebers, George C; Knight, Julian C

    2007-12-22

    To assess the evidence for a genetic basis to magic. Literature review. Harry Potter novels of J K Rowling. Muggles, witches, wizards, and squibs. Limited. Family and twin studies, magical ability, and specific magical skills. Magic shows strong evidence of heritability, with familial aggregation and concordance in twins. Evidence suggests magical ability to be a quantitative trait. Specific magical skills, notably being able to speak to snakes, predict the future, and change hair colour, all seem heritable. A multilocus model with a dominant gene for magic might exist, controlled epistatically by one or more loci, possibly recessive in nature. Magical enhancers regulating gene expressionmay be involved, combined with mutations at specific genes implicated in speech and hair colour such as FOXP2 and MCR1.

  15. Estimation of diversity and combining abilities in Helianthus annuus L. under water stress and normal conditions.

    PubMed

    Saba, M; Khan, F A; Sadaqat, H A; Rana, I A

    2016-10-24

    Sunflower cannot produce high yields under water-limiting conditions. The aim of the present study was to prevent the impediments on yield and to develop varieties with high-yield potential under water scarce conditions. For achieving this objective, it is necessary to detect parents with desirable traits that mainly depend on the action of genes controlling the trait under improvement, combining ability, and genetic makeup of the parents. Heterosis can also be used to pool the desirable genes from genetically divergent varieties and these divergent parents could be detected by molecular studies. Ten tolerant and five susceptible tester lines were selected, crossed, and tested for genetic diversity using simple sequence repeat primers. We identified two parents (A-10.8 and G-60) that showed maximum (46.7%) genetic dissimilarity. On an average 3.1 alleles per locus were detected for twenty pair of primers. Evaluation of mean values revealed that under stress conditions the mean performances of the genotypes were reduced for all traits under study. Parent A-10.8 was consistent as a good general combiner for achene yield per plant under both non-stress and stress conditions. Line A-10.8 in the hybrid A-10.8 x G-60 proved to be a good combiner as it showed negative specific combining ability (SCA) effects for plant height and internodal length and positive SCA effects for head weight, achene yield per plant, and membrane stability index. Valuable information on gene action, combining ability, and heterosis was generated, which could be used in further breeding programs.

  16. Class-specific effector functions of therapeutic antibodies.

    PubMed

    Pascal, Virginie; Laffleur, Brice; Cogné, Michel

    2012-01-01

    Physiology usually combines polyclonal antibodies of multiple classes in a single humoral response. Beyond their common ability to bind antigens, these various classes of human immunoglobulins carry specific functions which can each serve specific goals. In many cases, the function of a monoclonal therapeutic antibody may thus be modulated according to the class of its constant domains. Depending on the immunoglobulin class, different functional assays will be used in order to evaluate the functional activity of a monoclonal antibody.

  17. Clinical Assessment of Physical Examination Maneuvers for Rotator Cuff Lesions.

    PubMed

    Somerville, Lyndsay E; Willits, Kevin; Johnson, Andrew M; Litchfield, Robert; LeBel, Marie-Eve; Moro, Jaydeep; Bryant, Dianne

    2014-08-01

    Shoulder pain and disability pose a diagnostic challenge for clinicians owing to the numerous causes that exist. Unfortunately, the evidence in support of most clinical tests is weak or absent. To determine the diagnostic validity of physical examination maneuvers for rotator cuff lesions. Cohort study (diagnosis); Level of evidence, 1. Consecutive shoulder patients recruited for this study were referred to 2 tertiary orthopaedic clinics. A surgeon took a thorough history and indicated his or her certainty about each possible diagnosis. A clinician performed the physical examination for diagnoses where uncertainty remained. Arthroscopy was considered the reference standard for patients who underwent surgery, and MRI with arthrogram was considered the reference for patients who did not. The sensitivity, specificity, and likelihood ratios were calculated to investigate whether combinations of the top tests provided stronger predictions of the presence or absence of disease. There were 139 participants. None of the tests were highly sensitive for diagnosing rotator cuff tears or tendinosis. Tests for subscapularis tears were all highly specific. No optimal combination of tests improved the ability to correctly diagnose rotator cuff tears. Closer analysis revealed the internal rotation and lateral rotation lag sign did not improve the ability to diagnose subscapularis or supraspinatus tears, respectively, although the lateral rotation lag sign demonstrated a discriminatory ability for tear size. No test in isolation is sufficient to diagnose a patient with rotator cuff damage. A combination of tests improves the ability to diagnose damage to the rotator cuff. It is recommended that the internal rotation and lateral rotation lag signs be removed from the gamut of physical examination tests for supraspinatus and subscapularis tears. © 2014 The Author(s).

  18. Teaching Bird Identification & Vocabulary with Twitter

    ERIC Educational Resources Information Center

    Hallman, Tyler A.; Robinson, W. Douglas

    2015-01-01

    Species identification is essential to biology, conservation, and management. The ability to focus on specific diagnostic characteristics of a species helps improve the speed and accuracy of identification. Birds are excellent subjects for teaching species identification because, in combination with their different shapes and sizes, their plumages…

  19. A library of programmable DNAzymes that operate in a cellular environment.

    PubMed

    Kahan-Hanum, Maya; Douek, Yehonatan; Adar, Rivka; Shapiro, Ehud

    2013-01-01

    DNAzymes were used as inhibitory agents in a variety of experimental disease settings, such as cancer, viral infections and even HIV. Drugs that become active only upon the presence of preprogrammed abnormal environmental conditions may enable selective molecular therapy by targeting abnormal cells without injuring normal cells. Here we show a novel programmable DNAzyme library composed of variety of Boolean logic gates, including YES, AND, NOT, OR, NAND, ANDNOT, XOR, NOR and 3-input-AND gate, that uses both miRNAs and mRNAs as inputs. Each gate is based on the c-jun cleaving Dz13 DNAzyme and active only in the presence of specific input combinations. The library is modular, supports arbitrary inputs and outputs, cascadable, highly specific and robust. We demonstrate the library's potential diagnostic abilities on miRNA and mRNA combinations in cell lysate and its ability to operate in a cellular environment by using beacon-like c-jun mimicking substrate in living mammalian cells.

  20. A library of programmable DNAzymes that operate in a cellular environment

    PubMed Central

    Kahan-Hanum, Maya; Douek, Yehonatan; Adar, Rivka; Shapiro, Ehud

    2013-01-01

    DNAzymes were used as inhibitory agents in a variety of experimental disease settings, such as cancer, viral infections and even HIV. Drugs that become active only upon the presence of preprogrammed abnormal environmental conditions may enable selective molecular therapy by targeting abnormal cells without injuring normal cells. Here we show a novel programmable DNAzyme library composed of variety of Boolean logic gates, including YES, AND, NOT, OR, NAND, ANDNOT, XOR, NOR and 3-input-AND gate, that uses both miRNAs and mRNAs as inputs. Each gate is based on the c-jun cleaving Dz13 DNAzyme and active only in the presence of specific input combinations. The library is modular, supports arbitrary inputs and outputs, cascadable, highly specific and robust. We demonstrate the library's potential diagnostic abilities on miRNA and mRNA combinations in cell lysate and its ability to operate in a cellular environment by using beacon-like c-jun mimicking substrate in living mammalian cells. PMID:23525068

  1. Usefulness of combining gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging and contrast-enhanced ultrasound for diagnosing the macroscopic classification of small hepatocellular carcinoma.

    PubMed

    Kobayashi, Tomoki; Aikata, Hiroshi; Hatooka, Masahiro; Morio, Kei; Morio, Reona; Kan, Hiromi; Fujino, Hatsue; Fukuhara, Takayuki; Masaki, Keiichi; Ohno, Atsushi; Naeshiro, Noriaki; Nakahara, Takashi; Honda, Yohji; Murakami, Eisuke; Kawaoka, Tomokazu; Tsuge, Masataka; Hiramatsu, Akira; Imamura, Michio; Kawakami, Yoshiiku; Hyogo, Hideyuki; Takahashi, Shoichi; Chayama, Kazuaki

    2015-11-01

    Non-simple nodules in hepatocellular carcinoma (HCC) correlate with poor prognosis. Therefore, we examined the diagnostic ability of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) and contrast-enhanced ultrasound (CEUS) for diagnosing the macroscopic classification of small HCCs. A total of 85 surgically resected nodules (≤30 mm) were analyzed. HCCs were pathologically classified as simple nodular (SN) and non-SN. By evaluating hepatobiliary phase (HBP) of EOB-MRI and Kupffer phase of CEUS, the diagnostic abilities of both modalities to correctly distinguish between SN and non-SN were compared. Forty-six nodules were diagnosed as SN and the remaining 39 nodules as non-SN. The area under the ROC curve (AUROCs, 95% confidence interval) for the diagnosis of non-SN were EOB-MRI, 0.786 (0.682-0.890): CEUS, 0.784 (0.679-0.889), in combination, 0.876 (0.792-0.959). The sensitivity, specificity, and accuracy were 64.1%, 95.7%, and 81.2% in EOB-MRI, 56.4%, 97.8%, and 78.8% in CEUS, and 84.6%, 95.7%, and 90.6% in combination, respectively. High diagnostic ability was obtained when diagnosed in both modalities combined. The sensitivity was especially statistically significant compared to CEUS. Combined diagnosis by EOB-MRI and CEUS can provide high-quality imaging assessment for determining non-SN in small HCCs. • Non-SN has a higher frequency of MVI and intrahepatic metastasis than SN. • Macroscopic classification is useful to choose the treatment strategy for small HCCs. • Diagnostic ability for macroscopic findings of EOB-MRI and CEUS were statistically equal. • The diagnosis of macroscopic findings by individual modality has limitations. • Combined diagnosis of EOB-MRI and CEUS provides high diagnostic ability.

  2. Combining atomic force and fluorescence microscopy for analysis of quantum-dot labeled protein–DNA complexes

    PubMed Central

    Ebenstein, Yuval; Gassman, Natalie; Kim, Soohong; Weiss, Shimon

    2011-01-01

    Atomic force microscopy (AFM) and fluorescence microscopy are widely used for the study of protein-DNA interactions. While AFM excels in its ability to elucidate structural detail and spatial arrangement, it lacks the ability to distinguish between similarly sized objects in a complex system. This information is readily accessible to optical imaging techniques via site-specific fluorescent labels, which enable the direct detection and identification of multiple components simultaneously. Here, we show how the utilization of semiconductor quantum dots (QDs), serving as contrast agents for both AFM topography and fluorescence imaging, facilitates the combination of both imaging techniques, and with the addition of a flow based DNA extension method for sample deposition, results in a powerful tool for the study of protein-DNA complexes. We demonstrate the inherent advantages of this novel combination of techniques by imaging individual RNA polymerases (RNAP) on T7 genomic DNA. PMID:19452448

  3. Predicting Bobsled Pushing Ability from Various Combine Testing Events.

    PubMed

    Tomasevicz, Curtis L; Ransone, Jack W; Bach, Christopher W

    2018-03-12

    The requisite combination of speed, power, and strength necessary for a bobsled push athlete coupled with the difficulty in directly measuring pushing ability makes selecting effective push crews challenging. Current practices by USA Bobsled and Skeleton (USABS) utilize field combine testing to assess and identify specifically selected performance variables in an attempt to best predict push performance abilities. Combine data consisting of 11 physical performance variables were collected from 75 subjects across two winter Olympic qualification years (2009 and 2013). These variables were sprints of 15-, 30-, and 60 m, a flying 30 m sprint, a standing broad jump, a shot toss, squat, power clean, body mass, and dry-land brake and side bobsled pushes. Discriminant Analysis (DA) in addition to Principle Component Analysis (PCA) was used to investigate two cases (Case 1: Olympians vs. non-Olympians; Case 2: National Team vs. non-National Team). Using these 11 variables, DA led to a classification rule that proved capable of identifying Olympians from non-Olympians and National Team members from non-National Team members with 9.33% and 14.67% misclassification rates, respectively. The PCA was used to find similar test variables within the combine that provided redundant or useless data. After eliminating the unnecessary variables, DA on the new combinations showed that 8 (Case 1) and 20 (Case 2) other combinations with fewer performance variables yielded misclassification rates as low as 6.67% and 13.33% respectively. Utilizing fewer performance variables can allow governing bodies in many other sports to create more appropriate combine testing that maximize accuracy, while minimizing irrelevant and redundant strategies.

  4. Tall fescue forage mass in a grass-legume mixture: predicted efficiency of indirect selection

    USDA-ARS?s Scientific Manuscript database

    High fertilizer prices and improved environmental stewardship have increased interest in grass-legume mixed pastures. It has been hypothesized, but not validated, that the ecological combining ability between grasses and legumes can be improved by breeding specifically for mixture performance. Thi...

  5. Reciprocal Genetics: Identifying QTL for General and Specific Combining Abilities in Hybrids Between Multiparental Populations from Two Maize (Zea mays L.) Heterotic Groups.

    PubMed

    Giraud, Héloïse; Bauland, Cyril; Falque, Matthieu; Madur, Delphine; Combes, Valérie; Jamin, Philippe; Monteil, Cécile; Laborde, Jacques; Palaffre, Carine; Gaillard, Antoine; Blanchard, Philippe; Charcosset, Alain; Moreau, Laurence

    2017-11-01

    Several plant and animal species of agricultural importance are commercialized as hybrids to take advantage of the heterosis phenomenon. Understanding the genetic architecture of hybrid performances is therefore of key importance. We developed two multiparental maize ( Zea mays L.) populations, each corresponding to an important heterotic group (dent or flint) and comprised of six connected biparental segregating populations of inbred lines (802 and 822 lines for each group, respectively) issued from four founder lines. Instead of using "testers" to evaluate their hybrid values, segregating lines were crossed according to an incomplete factorial design to produce 951 dent-flint hybrids, evaluated for four biomass production traits in eight environments. QTL detection was carried out for the general-combining-ability (GCA) and specific-combining-ability (SCA) components of hybrid value, considering allelic effects transmitted from each founder line. In total, 42 QTL were detected across traits. We detected mostly QTL affecting GCA, 31% (41% for dry matter yield) of which also had mild effects on SCA. The small impact of dominant effects is consistent with the known differentiation between the dent and flint heterotic groups and the small percentage of hybrid variance due to SCA observed in our design (∼20% for the different traits). Furthermore, most (80%) of GCA QTL were segregating in only one of the two heterotic groups. Relative to tester-based designs, use of hybrids between two multiparental populations appears highly cost efficient to detect QTL in two heterotic groups simultaneously. This presents new prospects for selecting superior hybrid combinations with markers. Copyright © 2017 by the Genetics Society of America.

  6. Spatial and numerical abilities without a complete natural language.

    PubMed

    Hyde, Daniel C; Winkler-Rhoades, Nathan; Lee, Sang-Ah; Izard, Veronique; Shapiro, Kevin A; Spelke, Elizabeth S

    2011-04-01

    We studied the cognitive abilities of a 13-year-old deaf child, deprived of most linguistic input from late infancy, in a battery of tests designed to reveal the nature of numerical and geometrical abilities in the absence of a full linguistic system. Tests revealed widespread proficiency in basic symbolic and non-symbolic numerical computations involving the use of both exact and approximate numbers. Tests of spatial and geometrical abilities revealed an interesting patchwork of age-typical strengths and localized deficits. In particular, the child performed extremely well on navigation tasks involving geometrical or landmark information presented in isolation, but very poorly on otherwise similar tasks that required the combination of the two types of spatial information. Tests of number- and space-specific language revealed proficiency in the use of number words and deficits in the use of spatial terms. This case suggests that a full linguistic system is not necessary to reap the benefits of linguistic vocabulary on basic numerical tasks. Furthermore, it suggests that language plays an important role in the combination of mental representations of space. Copyright © 2010 Elsevier Ltd. All rights reserved.

  7. Accuracy of ultra-wide-field fundus ophthalmoscopy-assisted deep learning, a machine-learning technology, for detecting age-related macular degeneration.

    PubMed

    Matsuba, Shinji; Tabuchi, Hitoshi; Ohsugi, Hideharu; Enno, Hiroki; Ishitobi, Naofumi; Masumoto, Hiroki; Kiuchi, Yoshiaki

    2018-05-09

    To predict exudative age-related macular degeneration (AMD), we combined a deep convolutional neural network (DCNN), a machine-learning algorithm, with Optos, an ultra-wide-field fundus imaging system. First, to evaluate the diagnostic accuracy of DCNN, 364 photographic images (AMD: 137) were amplified and the area under the curve (AUC), sensitivity and specificity were examined. Furthermore, in order to compare the diagnostic abilities between DCNN and six ophthalmologists, we prepared yield 84 sheets comprising 50% of normal and wet-AMD data each, and calculated the correct answer rate, specificity, sensitivity, and response times. DCNN exhibited 100% sensitivity and 97.31% specificity for wet-AMD images, with an average AUC of 99.76%. Moreover, comparing the diagnostic abilities of DCNN versus six ophthalmologists, the average accuracy of the DCNN was 100%. On the other hand, the accuracy of ophthalmologists, determined only by Optos images without a fundus examination, was 81.9%. A combination of DCNN with Optos images is not better than a medical examination; however, it can identify exudative AMD with a high level of accuracy. Our system is considered useful for screening and telemedicine.

  8. Auditory sequence analysis and phonological skill

    PubMed Central

    Grube, Manon; Kumar, Sukhbinder; Cooper, Freya E.; Turton, Stuart; Griffiths, Timothy D.

    2012-01-01

    This work tests the relationship between auditory and phonological skill in a non-selected cohort of 238 school students (age 11) with the specific hypothesis that sound-sequence analysis would be more relevant to phonological skill than the analysis of basic, single sounds. Auditory processing was assessed across the domains of pitch, time and timbre; a combination of six standard tests of literacy and language ability was used to assess phonological skill. A significant correlation between general auditory and phonological skill was demonstrated, plus a significant, specific correlation between measures of phonological skill and the auditory analysis of short sequences in pitch and time. The data support a limited but significant link between auditory and phonological ability with a specific role for sound-sequence analysis, and provide a possible new focus for auditory training strategies to aid language development in early adolescence. PMID:22951739

  9. General and specific combining ability of F1-hybrid sweet sorghum in Thailand

    USDA-ARS?s Scientific Manuscript database

    Sweet sorghum (Sorghum bicolor (L.) Moench) is a promising biofuel crop that accumulates fermentable sugar in the stalk and can be directly fermented as bioethanol. Currently, most of sweet sorghum cultivars are pure lines. However, developing high-yielding hybrids has many advantages. To date there...

  10. Two-Component System RgfA/C Activates the fbsB Gene Encoding Major Fibrinogen-Binding Protein in Highly Virulent CC17 Clone Group B Streptococcus

    PubMed Central

    Safadi, Rim Al; Mereghetti, Laurent; Salloum, Mazen; Lartigue, Marie-Frédérique; Virlogeux-Payant, Isabelle; Quentin, Roland; Rosenau, Agnès

    2011-01-01

    Group B streptococcus (GBS) strains with the highest ability to bind to human fibrinogen belong to the highly invasive clonal complex (CC) 17. To investigate the fibrinogen-binding mechanisms of CC17 strains, we determined the prevalence of fibrinogen-binding genes (fbsA and fbsB), and fbs regulator genes (rogB encoding an fbsA activator, rovS encoding an fbsA repressor and rgf encoding a two-component system [TCS] whose role on fbs genes was not determined yet) in a collection of 134 strains representing the major CCs of the species. We showed that specific gene combinations were related to particular CCs; only CC17 strains contained the fbsA, fbsB, and rgf genes combination. Non polar rgfAC deletion mutants of three CC17 serotype III strains were constructed. They showed a 3.2- to 5.1-fold increase of fbsA transcripts, a 4.8- to 6.7-fold decrease of fbsB transcripts, and a 52% to 68% decreased fibrinogen-binding ability, demonstrating that the RgfA/RgfC TCS inhibits the fbsA gene and activates the fbsB gene. The relative contribution of the two fbs genes in fibrinogen-binding ability was determined by constructing isogenic fbsA, fbsB, deletion mutants of the three CC17 strains. The ability to bind to fibrinogen was reduced by 49% to 57% in ΔfbsA mutants, and by 78% to 80% in ΔfbsB mutants, suggesting that FbsB protein plays a greater role in the fibrinogen-binding ability of CC17 strains. Moreover, the relative transcription level of fbsB gene was 9.2- to 12.7-fold higher than that of fbsA gene for the three wild type strains. Fibrinogen-binding ability could be restored by plasmid-mediated expression of rgfAC, fbsA, and fbsB genes in the corresponding deletion mutants. Thus, our results demonstrate that a specific combination of fbs genes and fbs regulator genes account for the high fibrinogen-binding ability of CC17 strains that may participate to their enhanced invasiveness for neonates as compared to strains of other CCs. PMID:21326613

  11. Exploring genotypic variations for improved oil content and healthy fatty acids composition in rapeseed (Brassica napus L.).

    PubMed

    Ishaq, Muhammad; Razi, Raziuddin; Khan, Sabaz Ali

    2017-04-01

    Development of new genotypes having high oil content and desirable levels of fatty acid compositions is a major objective of rapeseed breeding programmes. In the current study combining ability was determined for oil, protein, glucosinolates and various fatty acids content using 8 × 8 full diallel in rapeseed (Brassica napus). Highly significant genotypic differences were observed for oil, protein, glucosinolates, oleic acid, linolenic acid and erucic acid content. Mean squares due to general combining ability (GCA), specific combining ability (SCA) and reciprocal combining ability (RCA) were highly significant (P ≤ 0.01) for biochemical traits. Parental line AUP-17 for high oil content and low glucosinolates, genotype AUP-2 for high protein and oleic acids, and AUP-18 for low lenolenic and erucic acid were best general combiners. Based on desirable SCA effects, F 1 hybrids AUP-17 × AUP-20; AUP-2 × AUP-8; AUP-7 × AUP-14; AUP-2 × AUP-9; AUP-7 × AUP-14 and AUP-2 × AUP-9 were found superior involving at least one best general combiner. F 1 hybrids AUP-17 × AUP-20 (for oil content); AUP-2 × AUP-8 (for protein content); AUP-7 × AUP-14 (for glucosinolates); AUP-2 × AUP-9 (for oleic acid); AUP-7 × AUP-14 (for linolenic acid) and AUP-2 × AUP-9 (for erucic acid) were found superior involving at least one best general combiner. As reciprocal crosses of AUP-14 with AUP-7 and AUP-8 were superior had low × low and low × high GCA effects for glucosinolates and oleic acid, respectively therefore, these could be exploited in future rapeseed breeding programmes to develop new lines with good quality. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  12. Modelling results for the thermal management sub-system of a combined heat and power (CHP) fuel cell system (FCS)

    NASA Astrophysics Data System (ADS)

    Colella, Whitney G.

    Although the fuel cells research and development community has traditionally focused the majority of its efforts on improving the fuel cell stack's voltage (electrical efficiency), combined heat and power (CHP) fuel cell system (FCSs) may achieve a competitive advantage over conventional generators only if the research and development community refocuses its efforts on cultivating other inherent technical qualities of such systems. Based on an analysis of their use within energy markets, these inherent qualities include (1) an ability to vary their electrical load rapidly, (2) an ability to vary their heat to power ratio during operation, and (3) an ability to deliver their waste heat to a useful thermal sink. This article focuses on the last of three design objectives: effectively capturing heat from a CHP FCS. This article (1) delineates the design specifications for a 6 kWe CHP FCS, (2) analyses four possible cooling loop configurations for this system, and (3) concludes which one of these provides the optimal heat recovery performance.

  13. The Ability of Patient-Symptom Questionnaires to Differentiate PVFMD From Asthma.

    PubMed

    Ye, Jinny; Nouraie, Mehdi; Holguin, Fernando; Gillespie, Amanda I

    2017-05-01

    Goals of the current study were to (1) conduct initial validation of a new Paradoxical Vocal Fold Movement Disorder Screening Questionnaire (PVFMD-SQ); (2) determine if symptom-based questionnaires can discriminate between patients with confirmed PVFMD and those with diagnosed uncontrolled asthma without clinical suspicion for PVFMD; and (3) determine if a new questionnaire with diagnostic specificity could be created from a combination of significant items on previously validated questionnaires. This is a prospective, case-controlled study of patients with PVFMD only and asthma only, who completed five questionnaires: Dyspnea Index, Reflux Symptom Index, Voice Handicap Index-10, Sino-Nasal Questionnaire, and PVFMD-SQ. Factor analysis was completed on the new PVFMD-SQ, and the discrimination ability of selected factors was assessed by receiver operating characteristics curve. The factor with the greatest discriminatory ability was selected to create one diagnostic questionnaire, and scores for each participant were calculated to estimate how well the factor correlated with a PVFMD or asthma diagnosis. Mean scores on all questionnaires were compared to test their discriminatory ability. Patients with PVFMD showed greater voice handicap and reflux symptoms than patients with asthma. A 15-item one-factor questionnaire was developed from the original PVFMD-SQ, with a sensitivity of 89% and specificity of 73% for diagnosing asthma versus PVFMD. The combined questionnaires resulted in four factors, none of which showed discriminatory ability between PVFMD and asthma. This study represents the first time that a patient symptom-based screening tool has shown diagnostic sensitivity to differentiate PVFMD from asthma in a cohort of symptomatic patients. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  14. Combining computer adaptive testing technology with cognitively diagnostic assessment.

    PubMed

    McGlohen, Meghan; Chang, Hua-Hua

    2008-08-01

    A major advantage of computerized adaptive testing (CAT) is that it allows the test to home in on an examinee's ability level in an interactive manner. The aim of the new area of cognitive diagnosis is to provide information about specific content areas in which an examinee needs help. The goal of this study was to combine the benefit of specific feedback from cognitively diagnostic assessment with the advantages of CAT. In this study, three approaches to combining these were investigated: (1) item selection based on the traditional ability level estimate (theta), (2) item selection based on the attribute mastery feedback provided by cognitively diagnostic assessment (alpha), and (3) item selection based on both the traditional ability level estimate (theta) and the attribute mastery feedback provided by cognitively diagnostic assessment (alpha). The results from these three approaches were compared for theta estimation accuracy, attribute mastery estimation accuracy, and item exposure control. The theta- and alpha-based condition outperformed the alpha-based condition regarding theta estimation, attribute mastery pattern estimation, and item exposure control. Both the theta-based condition and the theta- and alpha-based condition performed similarly with regard to theta estimation, attribute mastery estimation, and item exposure control, but the theta- and alpha-based condition has an additional advantage in that it uses the shadow test method, which allows the administrator to incorporate additional constraints in the item selection process, such as content balancing, item type constraints, and so forth, and also to select items on the basis of both the current theta and alpha estimates, which can be built on top of existing 3PL testing programs.

  15. Conservation Abilities, Visuospatial Skills, and Numerosity Processing Speed: Association With Math Achievement and Math Difficulties in Elementary School Children.

    PubMed

    Lambert, Katharina; Spinath, Birgit

    The aim of the present study was to investigate the associations between elementary school children's mathematical achievement and their conservation abilities, visuospatial skills, and numerosity processing speed. We also assessed differences in these abilities between children with different types of learning problems. In Study 1 ( N = 229), we investigated second to fourth graders and in Study 2 ( N = 120), third and fourth graders. Analyses revealed significant contributions of numerosity processing speed and visuospatial skills to math achievement beyond IQ. Conservation abilities were predictive in Study 1 only. Children with math difficulties showed lower visuospatial skills and conservation abilities than children with typical achievement levels and children with reading and/or spelling difficulties, whereas children with combined difficulties explicitly showed low conservation abilities. These findings provide further evidence for the relations between children's math skills and their visuospatial skills, conservation abilities, and processing speed and contribute to the understanding of deficits that are specific to mathematical difficulties.

  16. Recent Advances of Cocktail Chemotherapy by Combination Drug Delivery Systems

    PubMed Central

    Hu, Quanyin; Sun, Wujin; Wang, Chao; Gu, Zhen

    2016-01-01

    Combination chemotherapy is widely exploited for enhanced cancer treatment in clinic. However, the traditional cocktail administration of combination regimens often suffers from varying pharmacokinetics among different drugs. The emergence of nanotechnology offers an unparalleled opportunity for developing advanced combination drug delivery strategies with the ability to encapsulate various drugs simultaneously and unify the pharmacokinetics of each drug. This review surveys the most recent advances in combination delivery of multiple small molecule chemotherapeutics using nanocarriers. The mechanisms underlying combination chemotherapy, including the synergistic, additive and potentiation effects, are also discussed with typical examples. We further highlight the sequential and site-specific co-delivery strategies, which provide new guidelines for development of programmable combination drug delivery systems. Clinical outlook and challenges are also discussed in the end. PMID:26546751

  17. Example-Based Learning: Exploring the Use of Matrices and Problem Variability

    ERIC Educational Resources Information Center

    Hancock-Niemic, Mary A.; Lin, Lijia; Atkinson, Robert K.; Renkl, Alexander; Wittwer, Joerg

    2016-01-01

    The purpose of the study was to investigate the efficacy of using faded worked examples presented in matrices with problem structure variability to enhance learners' ability to recognize the underlying structure of the problems. Specifically, this study compared the effects of matrix-format versus linear-format faded worked examples combined with…

  18. Using general and specific combining ability to further advance strawberry (Fragaria sp.) breeding

    USDA-ARS?s Scientific Manuscript database

    Strawberry is one of the five fruit crops included in the USDA-funded multi-institutionaland trans-disciplinary project, “RosBREED: Enabling Marker-Assisted Breeding in Rosaceae”. A Crop Reference Set (CRS) was developed of 900 genotypes and seedlings from 40 crosses representing the breadth of rele...

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

    Kouzes, R.T.; Piilonen, L.; Schreiber, D.

    Apple microcomputers have been combined with CAMAC to produce data acquisition systems used for a variety of applications at the Princeton Cyclotron Laboratory. Two specific implementations are discussed: a general one or two parameter MCA system and a specific eleven parameter system. A multiplicity of off-line experiments led to the need for these systems having data manipulation and control ability beyond that of low cost systems available commercially. A serial communications port allows for data transfer to the main computer for more complete analysis.

  20. Child Modifiability as a Predictor of Language Abilities in Deaf Children Who Use American Sign Language.

    PubMed

    Mann, Wolfgang; Peña, Elizabeth D; Morgan, Gary

    2015-08-01

    This research explored the use of dynamic assessment (DA) for language-learning abilities in signing deaf children from deaf and hearing families. Thirty-seven deaf children, aged 6 to 11 years, were identified as either stronger (n = 26) or weaker (n = 11) language learners according to teacher or speech-language pathologist report. All children received 2 scripted, mediated learning experience sessions targeting vocabulary knowledge—specifically, the use of semantic categories that were carried out in American Sign Language. Participant responses to learning were measured in terms of an index of child modifiability. This index was determined separately at the end of the 2 individual sessions. It combined ratings reflecting each child's learning abilities and responses to mediation, including social-emotional behavior, cognitive arousal, and cognitive elaboration. Group results showed that modifiability ratings were significantly better for stronger language learners than for weaker language learners. The strongest predictors of language ability were cognitive arousal and cognitive elaboration. Mediator ratings of child modifiability (i.e., combined score of social-emotional factors and cognitive factors) are highly sensitive to language-learning abilities in deaf children who use sign language as their primary mode of communication. This method can be used to design targeted interventions.

  1. Hybrid Operations in Patients with Peripheral Arterial Disease

    PubMed Central

    Murakami, Atsubumi

    2018-01-01

    In this seminar, I would like to discuss the recent hybrid operations in patients with peripheral arterial diseases. Hybrid is generally defined as combinations of different types of things. In the surgical community, it is loosely defined as therapy combining open surgery (OS) and endovascular therapy (EVT). In practice, combination surgery of diseased inflow vessels by EVT and outflow vessels by OS is a typical example, namely, the combination therapy of thromboendarterectomy (TEA) for common femoral artery and EVT (PTA and stenting) for iliac artery in patients with PAD (ilio-femoral lesions). Also, there is the potential of various combinations of OS and EVT for complex lesions. Unfortunately, we do not have specific guidelines for hybrid therapy of PAD, but in clinical practices, justified decision-making for surgical indication is strictly required. I emphasize that the cardiovascular surgeon (or vascular specialist) must have the ability of decision-making for suitable combination therapy of OS and EVT which adheres to existing specific guidelines. (This is a translation of Jpn J Vasc Surg 2017; 26: 275–283.) PMID:29682108

  2. Down-regulation of vitamin D receptor in mammospheres: implications for vitamin D resistance in breast cancer and potential for combination therapy.

    PubMed

    Pervin, Shehla; Hewison, Martin; Braga, Melissa; Tran, Lac; Chun, Rene; Karam, Amer; Chaudhuri, Gautam; Norris, Keith; Singh, Rajan

    2013-01-01

    Vitamin D signaling in mammary cancer stem cells (MCSCs), which are implicated in the initiation and progression of breast cancer, is poorly understood. In this study, we examined vitamin D signaling in mammospheres which are enriched in MCSCs from established breast cancer cell lines. Breast cancer cells positive for aldehyde dehydrogenase (ALDH(+)) had increased ability to form mammospheres compared to ALDH(-) cells. These mammospheres expressed MCSC-specific markers and generated transplantable xenografts in nude mice. Vitamin D receptor (VDR) was significantly down-regulated in mammospheres, as well as in ALDH(+) breast cancer cells. TN aggressive human breast tumors as well as transplantable xenografts obtained from SKBR3 expressed significantly lower levels of VDR but higher levels of CD44 expression. Snail was up-regulated in mammospheres isolated from breast cancer cells. Inhibition of VDR expression by siRNA led to a significant change in key EMT-specific transcription factors and increased the ability of these cells to form mammospheres. On the other hand, over-expression of VDR led to a down-regulation of Snail but increased expression of E-cad and significantly compromised the ability of cells to form mammospheres. Mammospheres were relatively insensitive to treatment with 1,25-dihydroxyvitamin D (1,25D), the active form of vitamin D, compared to more differentiated cancer cells grown in presence of serum. Treatment of H-Ras transformed HMLE(HRas) cells with DETA NONOate, a nitric oxide (NO)-donor led to induction of MAP-kinase phosphatase -1 (MKP-1) and dephosphorylation of ERK1/2 in the mammospheres. Combined treatment of these cells with 1,25D and a low-concentration of DETA NONOate led to a significant decrease in the overall size of mammospheres and reduced tumor volume in nude mice. Our findings therefore, suggest that combination therapy using 1,25D with drugs specifically targeting key survival pathways in MCSCs warrant testing in prospective clinical trial for treatment of aggressive breast cancer.

  3. Both Intrinsic Substrate Preference and Network Context Contribute to Substrate Selection of Classical Tyrosine Phosphatases*

    PubMed Central

    Tinti, Michele; Paoluzi, Serena; Santonico, Elena; Masch, Antonia; Schutkowski, Mike

    2017-01-01

    Reversible tyrosine phosphorylation is a widespread post-translational modification mechanism underlying cell physiology. Thus, understanding the mechanisms responsible for substrate selection by kinases and phosphatases is central to our ability to model signal transduction at a system level. Classical protein-tyrosine phosphatases can exhibit substrate specificity in vivo by combining intrinsic enzymatic specificity with the network of protein-protein interactions, which positions the enzymes in close proximity to their substrates. Here we use a high throughput approach, based on high density phosphopeptide chips, to determine the in vitro substrate preference of 16 members of the protein-tyrosine phosphatase family. This approach helped identify one residue in the substrate binding pocket of the phosphatase domain that confers specificity for phosphopeptides in a specific sequence context. We also present a Bayesian model that combines intrinsic enzymatic specificity and interaction information in the context of the human protein interaction network to infer new phosphatase substrates at the proteome level. PMID:28159843

  4. A DNA aptamer recognising a malaria protein biomarker can function as part of a DNA origami assembly

    PubMed Central

    Godonoga, Maia; Lin, Ting-Yu; Oshima, Azusa; Sumitomo, Koji; Tang, Marco S. L.; Cheung, Yee-Wai; Kinghorn, Andrew B.; Dirkzwager, Roderick M.; Zhou, Cunshan; Kuzuya, Akinori; Tanner, Julian A.; Heddle, Jonathan G.

    2016-01-01

    DNA aptamers have potential for disease diagnosis and as therapeutics, particularly when interfaced with programmable molecular technology. Here we have combined DNA aptamers specific for the malaria biomarker Plasmodium falciparum lactate dehydrogenase (PfLDH) with a DNA origami scaffold. Twelve aptamers that recognise PfLDH were integrated into a rectangular DNA origami and atomic force microscopy demonstrated that the incorporated aptamers preserve their ability to specifically bind target protein. Captured PfLDH retained enzymatic activity and protein-aptamer binding was observed dynamically using high-speed AFM. This work demonstrates the ability of DNA aptamers to recognise a malaria biomarker whilst being integrated within a supramolecular DNA scaffold, opening new possibilities for malaria diagnostic approaches based on DNA nanotechnology. PMID:26891622

  5. The Impact of Three Factors on the Recovery of Item Parameters for the Three-Parameter Logistic Model

    ERIC Educational Resources Information Center

    Kim, Kyung Yong; Lee, Won-Chan

    2017-01-01

    This article provides a detailed description of three factors (specification of the ability distribution, numerical integration, and frame of reference for the item parameter estimates) that might affect the item parameter estimation of the three-parameter logistic model, and compares five item calibration methods, which are combinations of the…

  6. Combining routine morphology, p16(INK4a) immunohistochemistry, and in situ hybridization for the detection of human papillomavirus infection in penile carcinomas: a tissue microarray study using classifier performance analyses.

    PubMed

    Chaux, Alcides; Cubilla, Antonio L; Haffner, Michael C; Lecksell, Kristen L; Sharma, Rajni; Burnett, Arthur L; Netto, George J

    2014-02-01

    Infection by high-risk human papillomavirus (HR-HPV) plays an important role in the pathogenesis of penile cancer in approximately 50% of the patients. The gold standard for human papillomavirus (HPV) detection is the polymerase chain reaction (PCR) assay. However, technical requirements and associated costs preclude the worldwide use of PCR assays on a routine basis. Herein, we evaluated the predictive abilities of tumor morphology, immunohistochemistry for p16(INK4a) expression, and in situ hybridization (ISH) for HR-HPV detection in defining HPV status, as established by PCR. Tissue samples from 48 patients with HPV-positive penile squamous cell carcinoma (SCC) were included in 4 tissue microarrays (TMA). Sensitivities and specificities were as follows: tumor morphology, 70% and 68%; p16(INK4a) immunohistochemistry, 65% and 90%; HR-HPV ISH, 47% and 100%. Regarding combinations of the predictors, the best performance was seen when HR-HPV ISH and p16(INK4a) immunohistochemistry were combined, regardless of the tumor morphology: sensitivity, 88%; specificity, 64%; area under the receiver-operating characteristic (AUC) curve, 0.83. Combinations of tumor morphology with p16(INK4a) immunohistochemistry or with HR-HPV ISH performed similarly well. In penile SCC, both p16(INK4a) immunohistochemistry and ISH for HR-HPV increase the predictive ability of routine morphology in defining HPV status. These tests can be interpreted differentially, depending on the necessity of a higher sensitivity or a higher specificity. For research/screening studies, we recommend combining tumor morphology, p16(INK4a) immunohistochemistry, and HR-HPV ISH. To increase sensitivity, positivity in any of these predictors should be considered as indicative of HPV infection. For routine diagnosis of clinical cases, criteria should be more stringent, and, to achieve the highest specificity in classifying a case as HPV-related, all predictors should be consistently positive. The data generated in the present study could be used in algorithms for defining HPV status in penile carcinomas. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. SENSory re-learning of the UPPer limb after stroke (SENSUPP): study protocol for a pilot randomized controlled trial.

    PubMed

    Carlsson, Håkan; Rosén, Birgitta; Pessah-Rasmussen, Hélène; Björkman, Anders; Brogårdh, Christina

    2018-04-17

    Many stroke survivors suffer from sensory impairments of their affected upper limb (UL). Although such impairments can affect the ability to use the UL in everyday activities, very little attention is paid to sensory impairments in stroke rehabilitation. The purpose of this trial is to investigate if sensory re-learning in combination with task-specific training may prove to be more effective than task-specific training alone to improve sensory function of the hand, dexterity, the ability to use the hand in daily activities, perceived participation, and life satisfaction. This study is a single-blinded pilot randomized controlled trial (RCT) with two treatment arms. The participants will be randomly assigned either to sensory re-learning in combination with task-specific training (sensory group) or to task-specific training only (control group). The training will consist of 2.5 h of group training per session, 2 times per week for 5 weeks. The primary outcome measures to assess sensory function are as follows: Semmes-Weinstein monofilament, Shape/Texture Identification (STI™) test, Fugl-Meyer Assessment-upper extremity (FMA-UE; sensory section), and tactile object identification test. The secondary outcome measures to assess motor function are as follows: Box and Block Test (BBT), mini Sollerman Hand Function Test (mSHFT), Modified Motor Assessment Scale (M-MAS), and Grippit. To assess the ability to use the hand in daily activities, perceived participation, and life satisfaction, the Motor Activity Log (MAL), Canadian Occupational Performance Measure (COPM), Stroke Impact Scale (SIS) participation domain, and Life Satisfaction checklist will be used. Assessments will be performed pre- and post-training and at 3-month follow-up by independent assessors, who are blinded to the participants' group allocation. At the 3-month follow-up, the participants in the sensory group will also be interviewed about their general experience of the training and how effective they perceived the training. The results from this study can add new knowledge about the effectiveness of sensory re-learning in combination with task-specific training on UL functioning after stroke. If the new training approach proves efficient, the results can provide information on how to design a larger RCT in the future in persons with sensory impairments of the UL after stroke. ClinicalTrials.gov, NCT03336749 . Registered on 8 November 2017.

  8. High content reduced graphene oxide reinforced copper with a bioinspired nano-laminated structure and large recoverable deformation ability

    PubMed Central

    Xiong, Ding-Bang; Cao, Mu; Guo, Qiang; Tan, Zhanqiu; Fan, Genlian; Li, Zhiqiang; Zhang, Di

    2016-01-01

    By using CuO/graphene-oxide/CuO sandwich-like nanosheets as the building blocks, bulk nacre-inspired copper matrix nano-laminated composite reinforced by molecular-level dispersed and ordered reduced graphene oxide (rGO) with content as high as ∼45 vol% was fabricated via a combined process of assembly, reduction and consolidation. Thanks to nanoconfinement effect, reinforcing effect, as well as architecture effect, the nanocomposite shows increased specific strength and at least one order of magnitude greater recoverable deformation ability as compared with monolithic Cu matrix. PMID:27647264

  9. The measurement of enhancement in mathematical abilities as a result of joint cognitive trainings in numerical and visual- spatial skills: A preliminary study

    NASA Astrophysics Data System (ADS)

    Agus, M.; Mascia, M. L.; Fastame, M. C.; Melis, V.; Pilloni, M. C.; Penna, M. P.

    2015-02-01

    A body of literature shows the significant role of visual-spatial skills played in the improvement of mathematical skills in the primary school. The main goal of the current study was to investigate the impact of a combined visuo-spatial and mathematical training on the improvement of mathematical skills in 146 second graders of several schools located in Italy. Participants were presented single pencil-and-paper visuo-spatial or mathematical trainings, computerised version of the above mentioned treatments, as well as a combined version of computer-assisted and pencil-and-paper visuo-spatial and mathematical trainings, respectively. Experimental groups were presented with training for 3 months, once a week. All children were treated collectively both in computer-assisted or pencil-and-paper modalities. At pre and post-test all our participants were presented with a battery of objective tests assessing numerical and visuo-spatial abilities. Our results suggest the positive effect of different types of training for the empowerment of visuo-spatial and numerical abilities. Specifically, the combination of computerised and pencil-and-paper versions of visuo-spatial and mathematical trainings are more effective than the single execution of the software or of the pencil-and-paper treatment.

  10. Diallel Analysis and Growth Parameters as Selection Tools for Drought Tolerance in Young Theobroma cacao Plants

    PubMed Central

    dos Santos, Emerson Alves; de Almeida, Alex-Alan Furtado; Ahnert, Dario; Branco, Marcia Christina da Silva; Valle, Raúl René; Baligar, Virupax C.

    2016-01-01

    This study aimed to estimate the combining ability, of T. cacao genotypes preselected for drought tolerance through diallel crosses. The experiment was conducted under greenhouse conditions at the Cacao Research Center (CEPEC), Ilhéus, Bahia, Brazil, in a completely randomized block design, in an experimental arrangement 21 x 2 [21 complete diallel crosses and two water regimes (control and stressed)]. In the control, soil moisture was kept close to field capacity, with predawn leaf water potential (ΨWL) ranging from -0.1 to -0.5 MPa. In the drought regime, the soil moisture was reduced gradually by decreasing the amount of water application until ΨWL reached -2.0 to -2.5 MPa. Significant differences (p < 0.05) were observed for most morphological attributes analyzed regarding progenies, water regime and their interactions. The results of the joint diallel analysis revealed significant effects between general combining ability (GCA) x water regimes and between specific combining ability (SCA) x water regimes. The SCA 6 genetic material showed high general combining ability for growth variables regardless of the water regime. In general, the water deficit influenced the production of biomass in most of the evaluated T. cacao crosses, except for SCA-6 x IMC-67, Catongo x SCA, MOC-01 x Catongo, Catongo x IMC-67 and RB-40 x Catongo. Multivariate analysis showed that stem diameter (CD), total leaf area (TLA), leaf dry biomass (LDB), stem dry biomass (SDB), root dry biomass (RDB), total dry biomass (TDB), root length (RL), root volume (RV), root diameter (RD) <1 mm and 1 <(RD) <2 mm were the most important growth parameters in the separation of T. cacao genotypes in to tolerant and intolerant to soil water deficit. PMID:27504627

  11. Diallel Analysis and Growth Parameters as Selection Tools for Drought Tolerance in Young Theobroma cacao Plants.

    PubMed

    Dos Santos, Emerson Alves; Almeida, Alex-Alan Furtado de; Ahnert, Dario; Branco, Marcia Christina da Silva; Valle, Raúl René; Baligar, Virupax C

    2016-01-01

    This study aimed to estimate the combining ability, of T. cacao genotypes preselected for drought tolerance through diallel crosses. The experiment was conducted under greenhouse conditions at the Cacao Research Center (CEPEC), Ilhéus, Bahia, Brazil, in a completely randomized block design, in an experimental arrangement 21 x 2 [21 complete diallel crosses and two water regimes (control and stressed)]. In the control, soil moisture was kept close to field capacity, with predawn leaf water potential (ΨWL) ranging from -0.1 to -0.5 MPa. In the drought regime, the soil moisture was reduced gradually by decreasing the amount of water application until ΨWL reached -2.0 to -2.5 MPa. Significant differences (p < 0.05) were observed for most morphological attributes analyzed regarding progenies, water regime and their interactions. The results of the joint diallel analysis revealed significant effects between general combining ability (GCA) x water regimes and between specific combining ability (SCA) x water regimes. The SCA 6 genetic material showed high general combining ability for growth variables regardless of the water regime. In general, the water deficit influenced the production of biomass in most of the evaluated T. cacao crosses, except for SCA-6 x IMC-67, Catongo x SCA, MOC-01 x Catongo, Catongo x IMC-67 and RB-40 x Catongo. Multivariate analysis showed that stem diameter (CD), total leaf area (TLA), leaf dry biomass (LDB), stem dry biomass (SDB), root dry biomass (RDB), total dry biomass (TDB), root length (RL), root volume (RV), root diameter (RD) <1 mm and 1 <(RD) <2 mm were the most important growth parameters in the separation of T. cacao genotypes in to tolerant and intolerant to soil water deficit.

  12. Pathogen boosted adoptive cell transfer immunotherapy to treat solid tumors.

    PubMed

    Xin, Gang; Schauder, David M; Jing, Weiqing; Jiang, Aimin; Joshi, Nikhil S; Johnson, Bryon; Cui, Weiguo

    2017-01-24

    Because of insufficient migration and antitumor function of transferred T cells, especially inside the immunosuppressive tumor microenvironment (TME), the efficacy of adoptive cell transfer (ACT) is much curtailed in treating solid tumors. To overcome these challenges, we sought to reenergize ACT (ReACT) with a pathogen-based cancer vaccine. To bridge ACT with a pathogen, we genetically engineered tumor-specific CD8 T cells in vitro with a second T-cell receptor (TCR) that recognizes a bacterial antigen. We then transferred these dual-specific T cells in combination with intratumoral bacteria injection to treat solid tumors in mice. The dual-specific CD8 T cells expanded vigorously, migrated to tumor sites, and robustly eradicated primary tumors. The mice cured from ReACT also developed immunological memory against tumor rechallenge. Mechanistically, we have found that this combined approach reverts the immunosuppressive TME and recruits CD8 T cells with an increased number and killing ability to the tumors.

  13. Predicting risk of trace element pollution from municipal roads using site-specific soil samples and remotely sensed data.

    PubMed

    Reeves, Mari Kathryn; Perdue, Margaret; Munk, Lee Ann; Hagedorn, Birgit

    2018-07-15

    Studies of environmental processes exhibit spatial variation within data sets. The ability to derive predictions of risk from field data is a critical path forward in understanding the data and applying the information to land and resource management. Thanks to recent advances in predictive modeling, open source software, and computing, the power to do this is within grasp. This article provides an example of how we predicted relative trace element pollution risk from roads across a region by combining site specific trace element data in soils with regional land cover and planning information in a predictive model framework. In the Kenai Peninsula of Alaska, we sampled 36 sites (191 soil samples) adjacent to roads for trace elements. We then combined this site specific data with freely-available land cover and urban planning data to derive a predictive model of landscape scale environmental risk. We used six different model algorithms to analyze the dataset, comparing these in terms of their predictive abilities and the variables identified as important. Based on comparable predictive abilities (mean R 2 from 30 to 35% and mean root mean square error from 65 to 68%), we averaged all six model outputs to predict relative levels of trace element deposition in soils-given the road surface, traffic volume, sample distance from the road, land cover category, and impervious surface percentage. Mapped predictions of environmental risk from toxic trace element pollution can show land managers and transportation planners where to prioritize road renewal or maintenance by each road segment's relative environmental and human health risk. Published by Elsevier B.V.

  14. Latest advances in confocal microscopy of skin cancers toward guiding patient care: a Mohs surgeon's review and perspective (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Nehal, Kishwer S.; Rajadhyaksha, Milind

    2016-02-01

    Latest advances in confocal microscopy of skin cancers toward guiding patient care: a Mohs surgeon's review and perspective About 350 publications worldwide have reported the ability of reflectance confocal microscopy (RCM) imaging to detect melanocytic skin lesions in vivo with specificity of 84-88% and sensitivity of 71-92%, and non-melanocytic skin lesions with specificity of 85-97% and sensitivity 100-92%. Lentigo maligna melanoma can be detected with sensitivity of 93% and specificity 82%. While the sensitivity is comparable to that of dermoscopy, the specificity is 2X superior, especially for lightly- and non-pigmented lesions. Dermoscopy combined with RCM imaging is proving to be both highly sensitive and highly specific. Recent studies have reported that the ratio of equivocal (i.e., would have been biopsied) lesions to detected melanomas dropped by ~2X when guided by dermoscopy and RCM imaging, compared to that with dermoscopy alone. Dermoscopy combined with RCM imaging is now being implemented to guide noninvasive diagnosis (to rule out malignancy and biopsy) and to also guide treatment, with promising initial impact: thus far, about 3,000 patients have been saved from biopsies of benign lesions. These are currently under follow-up monitoring. With fluorescence confocal microscopy (FCM) mosaicing, residual basal cell carcinomas can be detected in Mohs surgically excised fresh tissue ex vivo, with sensitivity of 94-97% and specificity 89-94%. FCM mosaicing is now being implemented for guiding Mohs surgery. To date, about 600 Mohs procedures have been performed, guided with mosaicing, and with pathology being performed in parallel to confirm the final outcome. These latest advances demonstrate the promising ability of RCM and FCM to guide patient care.

  15. The Effects of Repeated Testing on Verbal and Nonverbal Ability Assessment.

    ERIC Educational Resources Information Center

    Lewis, Ernest L.; Beggs, Donald L.

    The purpose of this study was to attempt to determine if score gains obtained upon repeated testing with an intelligence test result from a practice effect, from students remembering specific items, or from a combination of both. The verbal and nonverbal batteries of an I.Q. test were administered to 860 sixth graders on three occasions with…

  16. Corporations and the State in the Global Era: The Case of Seaboard Farms and Texas

    ERIC Educational Resources Information Center

    Bonanno, Alessandro; Constance, Douglas H.

    2006-01-01

    Employing the case of the expansion and regulation of hog confined animal feeding operations (CAFO) in Texas combined with the actions of the transnational agri-food corporation Seaboard Farms, Inc., this paper probes the relationship between the state and corporations in the global era. It specifically investigates the ability of the state to…

  17. Inheritance of ozone resistance in tall fescue

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

    Johnston, W.J.; Haaland, R.L.; Dickens, R.

    Ozone is considered the most important air pollutant affecting vegetation. With progressive urbanization, ozone levels have steadily escalated. Reports suggest that ozone tolerance is a highly heritable characteristic and that the selection of resistant plants and breeding for ozone resistance should be possible. This study was undertaken to gain information on the inheritance of ozone resistance in tall fescue (Festuca arundinacea Schreb.).Progenies from a diallel among six tall fescue genotypes of diverse origin were evaluated for ozone resistance in a fumigation-chamber. Sixteen-day-old seedlings were exposed to 0.5 ppm ozone for 3 hours and scored for injury after 3 days. Generalmore » combining ability (GCA) and reciprocal effects were both highly significant; however, GCA constituted a major portion of the genotypic variation. Specific combining ability was not significant. The predominance of additive genetic variance observed indicates that breeding for ozone resistance in this tall fescue population should be possible.« less

  18. Insect immunity shows specificity in protection upon secondary pathogen exposure.

    PubMed

    Sadd, Ben M; Schmid-Hempel, Paul

    2006-06-20

    Immunological memory in vertebrates, conferring lasting specific protection after an initial pathogen exposure, has implications for a broad spectrum of evolutionary, epidemiological, and medical phenomena . However, the existence of specificity in protection upon secondary pathogen exposure in invertebrates remains controversial . To separate this functional phenomenon from a particular mechanism, we refer to it as specific immune priming. We investigate the presence of specific immune priming in workers of the social insect Bombus terrestris. Using three bacterial pathogens, we test whether a prior homologous pathogen exposure gives a benefit in terms of long-term protection against a later challenge, over and above a heterologous combination. With a reciprocally designed initial and second-exposure protocol (i.e., all combinations of bacteria were tested), we demonstrate, even several weeks after the clearance of a first exposure, increased protection and narrow specificity upon secondary exposure. This demonstrates that the invertebrate immune system is functionally capable of unexpectedly specific and durable induced protection. Ultimately, despite general broad differences between vertebrates and invertebrates, the ability of both immune systems to show specificity in protection suggests that their immune defenses have found comparable solutions to similar selective pressures over evolutionary time.

  19. Genomic models with genotype × environment interaction for predicting hybrid performance: an application in maize hybrids.

    PubMed

    Acosta-Pech, Rocío; Crossa, José; de Los Campos, Gustavo; Teyssèdre, Simon; Claustres, Bruno; Pérez-Elizalde, Sergio; Pérez-Rodríguez, Paulino

    2017-07-01

    A new genomic model that incorporates genotype × environment interaction gave increased prediction accuracy of untested hybrid response for traits such as percent starch content, percent dry matter content and silage yield of maize hybrids. The prediction of hybrid performance (HP) is very important in agricultural breeding programs. In plant breeding, multi-environment trials play an important role in the selection of important traits, such as stability across environments, grain yield and pest resistance. Environmental conditions modulate gene expression causing genotype × environment interaction (G × E), such that the estimated genetic correlations of the performance of individual lines across environments summarize the joint action of genes and environmental conditions. This article proposes a genomic statistical model that incorporates G × E for general and specific combining ability for predicting the performance of hybrids in environments. The proposed model can also be applied to any other hybrid species with distinct parental pools. In this study, we evaluated the predictive ability of two HP prediction models using a cross-validation approach applied in extensive maize hybrid data, comprising 2724 hybrids derived from 507 dent lines and 24 flint lines, which were evaluated for three traits in 58 environments over 12 years; analyses were performed for each year. On average, genomic models that include the interaction of general and specific combining ability with environments have greater predictive ability than genomic models without interaction with environments (ranging from 12 to 22%, depending on the trait). We concluded that including G × E in the prediction of untested maize hybrids increases the accuracy of genomic models.

  20. Text as a Supplement to Speech in Young and Older Adults a)

    PubMed Central

    Krull, Vidya; Humes, Larry E.

    2015-01-01

    Objective The purpose of this experiment was to quantify the contribution of visual text to auditory speech recognition in background noise. Specifically, we tested the hypothesis that partially accurate visual text from an automatic speech recognizer could be used successfully to supplement speech understanding in difficult listening conditions in older adults, with normal or impaired hearing. Our working hypotheses were based on what is known regarding audiovisual speech perception in the elderly from speechreading literature. We hypothesized that: 1) combining auditory and visual text information will result in improved recognition accuracy compared to auditory or visual text information alone; 2) benefit from supplementing speech with visual text (auditory and visual enhancement) in young adults will be greater than that in older adults; and 3) individual differences in performance on perceptual measures would be associated with cognitive abilities. Design Fifteen young adults with normal hearing, fifteen older adults with normal hearing, and fifteen older adults with hearing loss participated in this study. All participants completed sentence recognition tasks in auditory-only, text-only, and combined auditory-text conditions. The auditory sentence stimuli were spectrally shaped to restore audibility for the older participants with impaired hearing. All participants also completed various cognitive measures, including measures of working memory, processing speed, verbal comprehension, perceptual and cognitive speed, processing efficiency, inhibition, and the ability to form wholes from parts. Group effects were examined for each of the perceptual and cognitive measures. Audiovisual benefit was calculated relative to performance on auditory-only and visual-text only conditions. Finally, the relationship between perceptual measures and other independent measures were examined using principal-component factor analyses, followed by regression analyses. Results Both young and older adults performed similarly on nine out of ten perceptual measures (auditory, visual, and combined measures). Combining degraded speech with partially correct text from an automatic speech recognizer improved the understanding of speech in both young and older adults, relative to both auditory- and text-only performance. In all subjects, cognition emerged as a key predictor for a general speech-text integration ability. Conclusions These results suggest that neither age nor hearing loss affected the ability of subjects to benefit from text when used to support speech, after ensuring audibility through spectral shaping. These results also suggest that the benefit obtained by supplementing auditory input with partially accurate text is modulated by cognitive ability, specifically lexical and verbal skills. PMID:26458131

  1. Additive-dominance genetic model analyses for late-maturity alpha-amylase activity in a bread wheat factorial crossing population.

    PubMed

    Rasul, Golam; Glover, Karl D; Krishnan, Padmanaban G; Wu, Jixiang; Berzonsky, William A; Ibrahim, Amir M H

    2015-12-01

    Elevated level of late maturity α-amylase activity (LMAA) can result in low falling number scores, reduced grain quality, and downgrade of wheat (Triticum aestivum L.) class. A mating population was developed by crossing parents with different levels of LMAA. The F2 and F3 hybrids and their parents were evaluated for LMAA, and data were analyzed using the R software package 'qgtools' integrated with an additive-dominance genetic model and a mixed linear model approach. Simulated results showed high testing powers for additive and additive × environment variances, and comparatively low powers for dominance and dominance × environment variances. All variance components and their proportions to the phenotypic variance for the parents and hybrids were significant except for the dominance × environment variance. The estimated narrow-sense heritability and broad-sense heritability for LMAA were 14 and 54%, respectively. High significant negative additive effects for parents suggest that spring wheat cultivars 'Lancer' and 'Chester' can serve as good general combiners, and that 'Kinsman' and 'Seri-82' had negative specific combining ability in some hybrids despite of their own significant positive additive effects, suggesting they can be used as parents to reduce LMAA levels. Seri-82 showed very good general combining ability effect when used as a male parent, indicating the importance of reciprocal effects. High significant negative dominance effects and high-parent heterosis for hybrids demonstrated that the specific hybrid combinations; Chester × Kinsman, 'Lerma52' × Lancer, Lerma52 × 'LoSprout' and 'Janz' × Seri-82 could be generated to produce cultivars with significantly reduced LMAA level.

  2. The Relationship between a Linear Combination of Intelligence, Musical Background, Rhythm Ability and Tapping Ability to Typewriting Speed and Accuracy.

    ERIC Educational Resources Information Center

    Fante, Cheryl H.

    This study was conducted in an attempt to identify any predictor or combination of predictors of a beginning typewriting student's success. Variables of intelligence, rhythmic ability, musical background, and tapping ability were combined to study their relationship to typewriting speed and accuracy. A sample of 109 high school students was…

  3. Combining Phage and Yeast Cell Surface Antibody Display to Identify Novel Cell Type-Selective Internalizing Human Monoclonal Antibodies.

    PubMed

    Bidlingmaier, Scott; Su, Yang; Liu, Bin

    2015-01-01

    Using phage antibody display, large libraries can be generated and screened to identify monoclonal antibodies with affinity for target antigens. However, while library size and diversity is an advantage of the phage display method, there is limited ability to quantitatively enrich for specific binding properties such as affinity. One way of overcoming this limitation is to combine the scale of phage display selections with the flexibility and quantitativeness of FACS-based yeast surface display selections. In this chapter we describe protocols for generating yeast surface antibody display libraries using phage antibody display selection outputs as starting material and FACS-based enrichment of target antigen-binding clones from these libraries. These methods should be widely applicable for the identification of monoclonal antibodies with specific binding properties.

  4. Treatment with proteasome inhibitor bortezomib enhances antigen-specific CD8+ T cell-mediated antitumor immunity induced by DNA vaccination

    PubMed Central

    Tseng, Chih Wen; Monie, Archana; Wu, Chao-Yi; Huang, Bruce; Wang, Mei-Cheng; Hung, Chien-Fu; Wu, T.-C.

    2008-01-01

    There is an urgent need to develop new innovative therapies for the control of cancer. Antigen-specific immunotherapy and the employment of proteasome inhibitors have emerged as two potentially plausible approaches for the control of cancer. In the current study, we explored the combination of the DNA vaccine encoding calreticulin (CRT) linked to human papillomavirus type 16 (HPV-16) E7 antigen (CRT/E7) with the proteasome inhibitor; bortezomib for their ability to generate E7-specific immune responses and antitumor effects in vaccinated mice. We found that the combination of treatment with bortezomib and CRT/E7(detox) DNA generated more potent E7-specific CD8+ T cell immune responses and better therapeutic effects against TC-1 tumors in tumor bearing mice compared to monotherapy. Furthermore, we found that treatment with bortezomib led to increased apoptosis of TC-1 tumor cells and could render the TC-1 tumor cells more susceptible to lysis by E7-specific CTLs. Our data has significant implications for future clinical translation. PMID:18542898

  5. Specifications of a continual reassessment method design for phase I trials of combined drugs†

    PubMed Central

    Wages, Nolan A.; Conaway, Mark R.

    2013-01-01

    In studies of combinations of agents in phase I oncology trials, the dose–toxicity relationship may not be monotone for all combinations, in which case the toxicity probabilities follow a partial order. The continual reassessment method for partial orders (PO-CRM) is a design for phase I trials of combinations that leans upon identifying possible complete orders associated with the partial order. This article addresses some practical design considerations not previously undertaken when describing the PO-CRM. We describe an approach in choosing a proper subset of possible orderings, formulated according to the known toxicity relationships within a matrix of combination therapies. Other design issues, such as working model selection and stopping rules, are also discussed. We demonstrate the practical ability of PO-CRM as a phase I design for combinations through its use in a recent trial designed at the University of Virginia Cancer Center. PMID:23729323

  6. Effects of combined electromyostimulation and gymnastics training in prepubertal girls.

    PubMed

    Deley, Gaëlle; Cometti, Carole; Fatnassi, Anaïs; Paizis, Christos; Babault, Nicolas

    2011-02-01

    This study investigated the effects of a 6-week combined electromyostimulation (EMS) and gymnastic training program on muscle strength and vertical jump performance of prepubertal gymnasts. Sixteen young women gymnasts (age 12.4 ± 1.2 yrs) participated in this study, with 8 in the EMS group and the remaining 8 as controls. EMS was conducted on knee extensor muscles for 20 minutes 3 times a week during the first 3 weeks and once a week during the last 3 weeks. Gymnasts from both groups underwent similar gymnastics training 5-6 times a week. Isokinetic torque of the knee extensors was determined at different eccentric and concentric angular velocities ranging from -60 to +240° per second. Jumping ability was evaluated using squat jump (SJ), counter movement jump (CMJ), reactivity test, and 3 gymnastic-specific jumps. After the first 3 weeks of EMS, maximal voluntary torque was increased (+40.0 ± 10.0%, +35.3 ± 11.8%, and +50.6 ± 7.7% for -60, +60, and +240°s⁻¹, respectively; p < 0.05), as well as SJ, reactivity test and specific jump performances (+20.9 ± 8.3%, +20.4 ± 26.2% and +14.9 ± 17.2% respectively; p < 0.05). Six weeks of EMS were necessary to improve the CMJ (+10.1 ± 10.0%, p < 0.05). Improvements in jump ability were still maintained 1 month after the end of the EMS training program. To conclude, these results first demonstrate that in prepubertal gymnasts, a 6-week EMS program, combined with the daily gymnastic training, induced significant increases both in knee extensor muscle strength and nonspecific and some specific jump performances.

  7. Whys and hows of in-house writing

    NASA Technical Reports Server (NTRS)

    Lane, J. C.

    1981-01-01

    The combining of requisite technical knowledge with requisite writing ability is addressed. Considerations in the development of in-house writing courses, in-plant training, are presented and evaluated. Specific problems in past methodology are also detailed. It is suggested that teachers of technical writing should be technical people themselves, preferably with working experience in industry or business; the training provided should be user-oriented, not theory oriented.

  8. Cell-specific targeting by heterobivalent ligands.

    PubMed

    Josan, Jatinder S; Handl, Heather L; Sankaranarayanan, Rajesh; Xu, Liping; Lynch, Ronald M; Vagner, Josef; Mash, Eugene A; Hruby, Victor J; Gillies, Robert J

    2011-07-20

    Current cancer therapies exploit either differential metabolism or targeting to specific individual gene products that are overexpressed in aberrant cells. The work described herein proposes an alternative approach--to specifically target combinations of cell-surface receptors using heteromultivalent ligands ("receptor combination approach"). As a proof-of-concept that functionally unrelated receptors can be noncovalently cross-linked with high avidity and specificity, a series of heterobivalent ligands (htBVLs) were constructed from analogues of the melanocortin peptide ligand ([Nle(4), dPhe(7)]-α-MSH) and the cholecystokinin peptide ligand (CCK-8). Binding of these ligands to cells expressing the human Melanocortin-4 receptor and the Cholecystokinin-2 receptor was analyzed. The MSH(7) and CCK(6) were tethered with linkers of varying rigidity and length, constructed from natural and/or synthetic building blocks. Modeling data suggest that a linker length of 20-50 Å is needed to simultaneously bind these two different G-protein coupled receptors (GPCRs). These ligands exhibited up to 24-fold enhancement in binding affinity to cells that expressed both (bivalent binding), compared to cells with only one (monovalent binding) of the cognate receptors. The htBVLs had up to 50-fold higher affinity than that of a monomeric CCK ligand, i.e., Ac-CCK(6)-NH(2). Cell-surface targeting of these two cell types with labeled heteromultivalent ligand demonstrated high avidity and specificity, thereby validating the receptor combination approach. This ability to noncovalently cross-link heterologous receptors and target individual cells using a receptor combination approach opens up new possibilities for specific cell targeting in vivo for therapy or imaging.

  9. Cell-Specific Targeting by Heterobivalent Ligands

    PubMed Central

    Josan, Jatinder S.; Handl, Heather L.; Sankaranarayanan, Rajesh; Xu, Liping; Lynch, Ronald M.; Vagner, Josef; Mash, Eugene A.; Hruby, Victor J.; Gillies, Robert J.

    2012-01-01

    Current cancer therapies exploit either differential metabolism or targeting to specific individual gene products that are overexpressed in aberrant cells. The work described herein proposes an alternative approach—to specifically target combinations of cell-surface receptors using heteromultivalent ligands (“receptor combination approach”). As a proof-of-concept that functionally unrelated receptors can be noncovalently cross-linked with high avidity and specificity, a series of heterobivalent ligands (htBVLs) were constructed from analogues of the melanocortin peptide ligand ([Nle4, DPhe7]-α-MSH) and the cholecystokinin peptide ligand (CCK-8). Binding of these ligands to cells expressing the human Melanocortin-4 receptor and the Cholecystokinin-2 receptor was analyzed. The MSH(7) and CCK(6) were tethered with linkers of varying rigidity and length, constructed from natural and/or synthetic building blocks. Modeling data suggest that a linker length of 20–50 Å is needed to simultaneously bind these two different G-protein coupled receptors (GPCRs). These ligands exhibited up to 24-fold enhancement in binding affinity to cells that expressed both (bivalent binding), compared to cells with only one (monovalent binding) of the cognate receptors. The htBVLs had up to 50-fold higher affinity than that of a monomeric CCK ligand, i.e., Ac-CCK(6)-NH2. Cell-surface targeting of these two cell types with labeled heteromultivalent ligand demonstrated high avidity and specificity, thereby validating the receptor combination approach. This ability to noncovalently cross-link heterologous receptors and target individual cells using a receptor combination approach opens up new possibilities for specific cell targeting in vivo for therapy or imaging. PMID:21639139

  10. Down-Regulation of Vitamin D Receptor in Mammospheres: Implications for Vitamin D Resistance in Breast Cancer and Potential for Combination Therapy

    PubMed Central

    Pervin, Shehla; Hewison, Martin; Braga, Melissa; Tran, Lac; Chun, Rene; Karam, Amer; Chaudhuri, Gautam; Norris, Keith; Singh, Rajan

    2013-01-01

    Vitamin D signaling in mammary cancer stem cells (MCSCs), which are implicated in the initiation and progression of breast cancer, is poorly understood. In this study, we examined vitamin D signaling in mammospheres which are enriched in MCSCs from established breast cancer cell lines. Breast cancer cells positive for aldehyde dehydrogenase (ALDH+) had increased ability to form mammospheres compared to ALDH− cells. These mammospheres expressed MCSC-specific markers and generated transplantable xenografts in nude mice. Vitamin D receptor (VDR) was significantly down-regulated in mammospheres, as well as in ALDH+ breast cancer cells. TN aggressive human breast tumors as well as transplantable xenografts obtained from SKBR3 expressed significantly lower levels of VDR but higher levels of CD44 expression. Snail was up-regulated in mammospheres isolated from breast cancer cells. Inhibition of VDR expression by siRNA led to a significant change in key EMT-specific transcription factors and increased the ability of these cells to form mammospheres. On the other hand, over-expression of VDR led to a down-regulation of Snail but increased expression of E-cad and significantly compromised the ability of cells to form mammospheres. Mammospheres were relatively insensitive to treatment with 1,25-dihydroxyvitamin D (1,25D), the active form of vitamin D, compared to more differentiated cancer cells grown in presence of serum. Treatment of H-Ras transformed HMLEHRas cells with DETA NONOate, a nitric oxide (NO)-donor led to induction of MAP-kinase phosphatase -1 (MKP-1) and dephosphorylation of ERK1/2 in the mammospheres. Combined treatment of these cells with 1,25D and a low-concentration of DETA NONOate led to a significant decrease in the overall size of mammospheres and reduced tumor volume in nude mice. Our findings therefore, suggest that combination therapy using 1,25D with drugs specifically targeting key survival pathways in MCSCs warrant testing in prospective clinical trial for treatment of aggressive breast cancer. PMID:23341935

  11. A STUDY OF THE COMPETITION OF LECITHIN AND ANTITOXIN FOR CL. WELCHII LECITHINASE

    PubMed Central

    Zamecnik, Paul C.; Lipmann, Fritz

    1947-01-01

    Lecithin has been found to interfere with the combining reaction of Cl. welchii alpha toxin (lecithinase) and its antitoxin. If the lecithinase is first brought into contact with lecithin, and the antitoxin is then added, the antitoxin fails to stop the enzymatic reaction, but gradually decelerates it. If the lecithinase is brought into contact with both lecithin and antitoxin at the same instant, it appears to combine in part with each, and the enzymatic process takes place at a reduced rate, which gradually declines further. If the lecithinase is first brought into contact with antitoxin, before the lecithin is added, the enzymatic reaction is completely inhibited. This ability of lecithin to inhibit the antitoxin-toxin combination cannot be explained adequately as a non-specific coating of the toxin-enzyme by the lecithin. It is rather suggested that lecithin and antitoxin compete specifically for combination with the same regions on the enzyme molecule. Lecithin has similarly been found to interfere with the combination of Crotalus terrificus venom and its antiserum. The above findings provide a partial explanation for the lack of effectiveness of antitoxin when given late in the course of Cl. welchii infection. PMID:19871624

  12. Likelihood ratio-based differentiation of nodular Hashimoto thyroiditis and papillary thyroid carcinoma in patients with sonographically evident diffuse hashimoto thyroiditis: preliminary study.

    PubMed

    Wang, Liang; Xia, Yu; Jiang, Yu-Xin; Dai, Qing; Li, Xiao-Yi

    2012-11-01

    To assess the efficacy of sonography for discriminating nodular Hashimoto thyroiditis from papillary thyroid carcinoma in patients with sonographically evident diffuse Hashimoto thyroiditis. This study included 20 patients with 24 surgically confirmed Hashimoto thyroiditis nodules and 40 patients with 40 papillary thyroid carcinoma nodules; all had sonographically evident diffuse Hashimoto thyroiditis. A retrospective review of the sonograms was performed, and significant benign and malignant sonographic features were selected by univariate and multivariate analyses. The combined likelihood ratio was calculated as the product of each feature's likelihood ratio for papillary thyroid carcinoma. We compared the abilities of the original sonographic features and combined likelihood ratios in diagnosing nodular Hashimoto thyroiditis and papillary thyroid carcinoma by their sensitivity, specificity, and Youden index. The diagnostic capabilities of the sonographic features varied greatly, with Youden indices ranging from 0.175 to 0.700. Compared with single features, combinations of features were unable to improve the Youden indices effectively because the sensitivity and specificity usually changed in opposite directions. For combined likelihood ratios, however, the sensitivity improved greatly without an obvious reduction in specificity, which resulted in the maximum Youden index (0.825). With a combined likelihood ratio greater than 7.00 as the diagnostic criterion for papillary thyroid carcinoma, sensitivity reached 82.5%, whereas specificity remained at 100.0%. With a combined likelihood ratio less than 1.00 for nodular Hashimoto thyroiditis, sensitivity and specificity were 90.0% and 92.5%, respectively. Several sonographic features of nodular Hashimoto thyroiditis and papillary thyroid carcinoma in a background of diffuse Hashimoto thyroiditis were significantly different. The combined likelihood ratio may be superior to original sonographic features for discrimination of nodular Hashimoto thyroiditis from papillary thyroid carcinoma; therefore, it is a promising risk index for thyroid nodules and warrants further investigation.

  13. Iterative weighting of multiblock data in the orthogonal partial least squares framework.

    PubMed

    Boccard, Julien; Rutledge, Douglas N

    2014-02-27

    The integration of multiple data sources has emerged as a pivotal aspect to assess complex systems comprehensively. This new paradigm requires the ability to separate common and redundant from specific and complementary information during the joint analysis of several data blocks. However, inherent problems encountered when analysing single tables are amplified with the generation of multiblock datasets. Finding the relationships between data layers of increasing complexity constitutes therefore a challenging task. In the present work, an algorithm is proposed for the supervised analysis of multiblock data structures. It associates the advantages of interpretability from the orthogonal partial least squares (OPLS) framework and the ability of common component and specific weights analysis (CCSWA) to weight each data table individually in order to grasp its specificities and handle efficiently the different sources of Y-orthogonal variation. Three applications are proposed for illustration purposes. A first example refers to a quantitative structure-activity relationship study aiming to predict the binding affinity of flavonoids toward the P-glycoprotein based on physicochemical properties. A second application concerns the integration of several groups of sensory attributes for overall quality assessment of a series of red wines. A third case study highlights the ability of the method to combine very large heterogeneous data blocks from Omics experiments in systems biology. Results were compared to the reference multiblock partial least squares (MBPLS) method to assess the performance of the proposed algorithm in terms of predictive ability and model interpretability. In all cases, ComDim-OPLS was demonstrated as a relevant data mining strategy for the simultaneous analysis of multiblock structures by accounting for specific variation sources in each dataset and providing a balance between predictive and descriptive purpose. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. A combined positron emission tomography (PET)-electron paramagnetic resonance imaging (EPRI) system: initial evaluation of a prototype scanner

    NASA Astrophysics Data System (ADS)

    Tseytlin, Mark; Stolin, Alexander V.; Guggilapu, Priyaankadevi; Bobko, Andrey A.; Khramtsov, Valery V.; Tseytlin, Oxana; Raylman, Raymond R.

    2018-05-01

    The advent of hybrid scanners, combining complementary modalities, has revolutionized the application of advanced imaging technology to clinical practice and biomedical research. In this project, we investigated the melding of two complementary, functional imaging methods: positron emission tomography (PET) and electron paramagnetic resonance imaging (EPRI). PET radiotracers can provide important information about cellular parameters, such as glucose metabolism. While EPR probes can provide assessment of tissue microenvironment, measuring oxygenation and pH, for example. Therefore, a combined PET/EPRI scanner promises to provide new insights not attainable with current imagers by simultaneous acquisition of multiple components of tissue microenvironments. To explore the simultaneous acquisition of PET and EPR images, a prototype system was created by combining two existing scanners. Specifically, a silicon photomultiplier (SiPM)-based PET scanner ring designed as a portable scanner was combined with an EPRI scanner designed for the imaging of small animals. The ability of the system to obtain simultaneous images was assessed with a small phantom consisting of four cylinders containing both a PET tracer and EPR spin probe. The resulting images demonstrated the ability to obtain contemporaneous PET and EPR images without cross-modality interference. Given the promising results from this initial investigation, the next step in this project is the construction of the next generation pre-clinical PET/EPRI scanner for multi-parametric assessment of physiologically-important parameters of tissue microenvironments.

  15. The Development of Combined Raman Spectroscopy-Optical Coherence Tomography and Application for Skin Cancer Diagnosis

    NASA Astrophysics Data System (ADS)

    Patil, Chetan

    2009-11-01

    Optical spectroscopy and imaging have shown promise for performing rapid, non-invasive disease detection and diagnosis in vivo. Independently, Raman Spectroscopy (RS) has demonstrated the ability to perform diagnosis of epithelial cancers such the cervix with excellent overall classification accuracy due to the inherent biochemical specificity of the technique, however relating features of tissue morphology with techniques such as Raman mapping is clinically impractical due to the weak nature of the scattering phenomena resulting in prohibitively long acquisition times. Optical Coherence Tomography (OCT), on the other hand, has demonstrated the ability to perform real-time, high-resolution, cross-sectional imaging of the microstructural characteristics of disease, but typically lacks molecularly specific information that can assist in classifying pathological lesions. We present the development of a combined Raman Spectroscopy-OCT (RS-OCT) instrument capable of compensating for the limitations of each technique individually and performing both biochemical and microstructural evaluation of tissues. We will include the design and development of benchtop RS-OCT implementations based on independent 785 nm Raman and 1310 nm time-domain OCT system backbones, as well as with a 785nm Raman / 850nm spectral-domain OCT setup employing an integrated detection arm. These systems motivated the ultimate design of a clinical RS-OCT system for application in dermatology. In order to aid in the development of our Raman spectral processing and classification methods, we conducted a simultaneous pilot study in which RS alone was used to measure basal and squamous cell carcinomas. We will present the initial results from our clinical experiences with the combined RS-OCT device, and include a discussion of spectral classification and the ultimate potential of combined RS-OCT for skin cancer diagnosis.

  16. Pathogen boosted adoptive cell transfer immunotherapy to treat solid tumors

    PubMed Central

    Xin, Gang; Schauder, David M.; Jing, Weiqing; Jiang, Aimin; Joshi, Nikhil S.; Johnson, Bryon; Cui, Weiguo

    2017-01-01

    Because of insufficient migration and antitumor function of transferred T cells, especially inside the immunosuppressive tumor microenvironment (TME), the efficacy of adoptive cell transfer (ACT) is much curtailed in treating solid tumors. To overcome these challenges, we sought to reenergize ACT (ReACT) with a pathogen-based cancer vaccine. To bridge ACT with a pathogen, we genetically engineered tumor-specific CD8 T cells in vitro with a second T-cell receptor (TCR) that recognizes a bacterial antigen. We then transferred these dual-specific T cells in combination with intratumoral bacteria injection to treat solid tumors in mice. The dual-specific CD8 T cells expanded vigorously, migrated to tumor sites, and robustly eradicated primary tumors. The mice cured from ReACT also developed immunological memory against tumor rechallenge. Mechanistically, we have found that this combined approach reverts the immunosuppressive TME and recruits CD8 T cells with an increased number and killing ability to the tumors. PMID:28069963

  17. Intestinal Master Transcription Factor CDX2 Controls Chromatin Access for Partner Transcription Factor Binding

    PubMed Central

    Verzi, Michael P.; Shin, Hyunjin; San Roman, Adrianna K.

    2013-01-01

    Tissue-specific gene expression requires modulation of nucleosomes, allowing transcription factors to occupy cis elements that are accessible only in selected tissues. Master transcription factors control cell-specific genes and define cellular identities, but it is unclear if they possess special abilities to regulate cell-specific chromatin and if such abilities might underlie lineage determination and maintenance. One prevailing view is that several transcription factors enable chromatin access in combination. The homeodomain protein CDX2 specifies the embryonic intestinal epithelium, through unknown mechanisms, and partners with transcription factors such as HNF4A in the adult intestine. We examined enhancer chromatin and gene expression following Cdx2 or Hnf4a excision in mouse intestines. HNF4A loss did not affect CDX2 binding or chromatin, whereas CDX2 depletion modified chromatin significantly at CDX2-bound enhancers, disrupted HNF4A occupancy, and abrogated expression of neighboring genes. Thus, CDX2 maintains transcription-permissive chromatin, illustrating a powerful and dominant effect on enhancer configuration in an adult tissue. Similar, hierarchical control of cell-specific chromatin states is probably a general property of master transcription factors. PMID:23129810

  18. Pathways to fraction learning: Numerical abilities mediate the relation between early cognitive competencies and later fraction knowledge.

    PubMed

    Ye, Ai; Resnick, Ilyse; Hansen, Nicole; Rodrigues, Jessica; Rinne, Luke; Jordan, Nancy C

    2016-12-01

    The current study investigated the mediating role of number-related skills in the developmental relationship between early cognitive competencies and later fraction knowledge using structural equation modeling. Fifth-grade numerical skills (i.e., whole number line estimation, non-symbolic proportional reasoning, multiplication, and long division skills) mapped onto two distinct factors: magnitude reasoning and calculation. Controlling for participants' (N=536) demographic characteristics, these two factors fully mediated relationships between third-grade general cognitive competencies (attentive behavior, verbal and nonverbal intellectual abilities, and working memory) and sixth-grade fraction knowledge (concepts and procedures combined). However, specific developmental pathways differed by type of fraction knowledge. Magnitude reasoning ability fully mediated paths from all four cognitive competencies to knowledge of fraction concepts, whereas calculation ability fully mediated paths from attentive behavior and verbal ability to knowledge of fraction procedures (all with medium to large effect sizes). These findings suggest that there are partly overlapping, yet distinct, developmental pathways from cognitive competencies to general fraction knowledge, fraction concepts, and fraction procedures. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. A nucleic acid strand displacement system for the multiplexed detection of tuberculosis-specific mRNA using quantum dots

    NASA Astrophysics Data System (ADS)

    Gliddon, H. D.; Howes, P. D.; Kaforou, M.; Levin, M.; Stevens, M. M.

    2016-05-01

    The development of rapid, robust and high performance point-of-care diagnostics relies on the advancement and combination of various areas of research. We have developed an assay for the detection of multiple mRNA molecules that combines DNA nanotechnology with fluorescent nanomaterials. The core switching mechanism is toehold-mediated strand displacement. We have used fluorescent quantum dots (QDs) as signal transducers in this assay, as they bring many benefits including bright fluorescence and multiplexing abilities. The resulting assay is capable of multiplexed detection of long RNA targets against a high concentration of background non-target RNA, with high sensitivity and specificity and limits of detection in the nanomolar range using only a standard laboratory plate reader. We demonstrate the utility of our QD-based system for the detection of two genes selected from a microarray-derived tuberculosis-specific gene expression signature. Levels of up- and downregulated gene transcripts comprising this signature can be combined to give a disease risk score, making the signature more amenable for use as a diagnostic marker. Our QD-based approach to detect these transcripts could pave the way for novel diagnostic assays for tuberculosis.The development of rapid, robust and high performance point-of-care diagnostics relies on the advancement and combination of various areas of research. We have developed an assay for the detection of multiple mRNA molecules that combines DNA nanotechnology with fluorescent nanomaterials. The core switching mechanism is toehold-mediated strand displacement. We have used fluorescent quantum dots (QDs) as signal transducers in this assay, as they bring many benefits including bright fluorescence and multiplexing abilities. The resulting assay is capable of multiplexed detection of long RNA targets against a high concentration of background non-target RNA, with high sensitivity and specificity and limits of detection in the nanomolar range using only a standard laboratory plate reader. We demonstrate the utility of our QD-based system for the detection of two genes selected from a microarray-derived tuberculosis-specific gene expression signature. Levels of up- and downregulated gene transcripts comprising this signature can be combined to give a disease risk score, making the signature more amenable for use as a diagnostic marker. Our QD-based approach to detect these transcripts could pave the way for novel diagnostic assays for tuberculosis. Electronic supplementary information (ESI) available: Base pair mismatch tuning of CProbes. Binding capacity of the QDs. Theoretical limit of detection (LOD) for the monoplex systems. Kinetics of strand displacement. Kinetics of QProbe-CProbe binding. LOD and saturation point calculations. See DOI: 10.1039/c6nr00484a

  20. Regulation of photosensitisation processes by an RNA aptamer

    NASA Astrophysics Data System (ADS)

    Thoa, Tran Thi Thanh; Minagawa, Noriko; Aigaki, Toshiro; Ito, Yoshihiro; Uzawa, Takanori

    2017-02-01

    One of the most powerful attributes of proteins is their ability to bind to and modulate the chemistry of cofactors and prosthetic groups. Here, we demonstrated the ability of an artificial nucleic acid (an aptamer) to similarly control the functionality of a non-biological element. Specifically, we selected an RNA aptamer that binds tris(bipyridine) ruthenium (II), Ru(bpy)32+, an inorganic complex that has attracted intense interest due to its photoredox chemistry, including its ability to split water by visible light. We found that a newly discovered aptamer strongly and enantioselectively binds Λ-Ru(bpy)32+ (Kd = 65 nM) and, in doing so, selectively suppresses deactivation via energy transfer, thereby elongating the lifetime of its photo-excited state by four-fold. The ability of the aptamer to enhance this important aspect of Ru(bpy)32+ chemistry illustrates a broader point concerning the potential power of combining in vitro-created biomolecules with non-biological reactants to perform enhanced chemical reactions.

  1. Breeding Potential of Introgression Lines Developed from Interspecific Crossing between Upland Cotton (Gossypium hirsutum) and Gossypium barbadense: Heterosis, Combining Ability and Genetic Effects

    PubMed Central

    Li, Xingli; Pei, Wenfeng

    2016-01-01

    Upland cotton (Gossypium hirstum L.), which produces more than 95% of the world natural cotton fibers, has a narrow genetic base which hinders progress in cotton breeding. Introducing germplasm from exotic sources especially from another cultivated tetraploid G. barbadense L. can broaden the genetic base of Upland cotton. However, the breeding potential of introgression lines (ILs) in Upland cotton with G. barbadense germplasm integration has not been well addressed. This study involved six ILs developed from an interspecific crossing and backcrossing between Upland cotton and G. barbadense and represented one of the first studies to investigate breeding potentials of a set of ILs using a full diallel analysis. High mid-parent heterosis was detected in several hybrids between ILs and a commercial cultivar, which also out-yielded the high-yielding cultivar parent in F1, F2 and F3 generations. A further analysis indicated that general ability (GCA) variance was predominant for all the traits, while specific combining ability (SCA) variance was either non-existent or much lower than GCA. The estimated GCA effects and predicted additive effects for parents in each trait were positively correlated (at P<0.01). Furthermore, GCA and additive effects for each trait were also positively correlated among generations (at P<0.05), suggesting that F2 and F3 generations can be used as a proxy to F1 in analyzing combining abilities and estimating genetic parameters. In addition, differences between reciprocal crosses in F1 and F2 were not significant for yield, yield components and fiber quality traits. But maternal effects appeared to be present for seed oil and protein contents in F3. This study identified introgression lines as good general combiners for yield and fiber quality improvement and hybrids with high heterotic vigor in yield, and therefore provided useful information for further utilization of introgression lines in cotton breeding. PMID:26730964

  2. Breeding Potential of Introgression Lines Developed from Interspecific Crossing between Upland Cotton (Gossypium hirsutum) and Gossypium barbadense: Heterosis, Combining Ability and Genetic Effects.

    PubMed

    Zhang, Jinfa; Wu, Man; Yu, Jiwen; Li, Xingli; Pei, Wenfeng

    2016-01-01

    Upland cotton (Gossypium hirstum L.), which produces more than 95% of the world natural cotton fibers, has a narrow genetic base which hinders progress in cotton breeding. Introducing germplasm from exotic sources especially from another cultivated tetraploid G. barbadense L. can broaden the genetic base of Upland cotton. However, the breeding potential of introgression lines (ILs) in Upland cotton with G. barbadense germplasm integration has not been well addressed. This study involved six ILs developed from an interspecific crossing and backcrossing between Upland cotton and G. barbadense and represented one of the first studies to investigate breeding potentials of a set of ILs using a full diallel analysis. High mid-parent heterosis was detected in several hybrids between ILs and a commercial cultivar, which also out-yielded the high-yielding cultivar parent in F1, F2 and F3 generations. A further analysis indicated that general ability (GCA) variance was predominant for all the traits, while specific combining ability (SCA) variance was either non-existent or much lower than GCA. The estimated GCA effects and predicted additive effects for parents in each trait were positively correlated (at P<0.01). Furthermore, GCA and additive effects for each trait were also positively correlated among generations (at P<0.05), suggesting that F2 and F3 generations can be used as a proxy to F1 in analyzing combining abilities and estimating genetic parameters. In addition, differences between reciprocal crosses in F1 and F2 were not significant for yield, yield components and fiber quality traits. But maternal effects appeared to be present for seed oil and protein contents in F3. This study identified introgression lines as good general combiners for yield and fiber quality improvement and hybrids with high heterotic vigor in yield, and therefore provided useful information for further utilization of introgression lines in cotton breeding.

  3. The effects of whole body vibration combined biofeedback postural control training on the balance ability and gait ability in stroke patients.

    PubMed

    Uhm, Yo-Han; Yang, Dae-Jung

    2017-11-01

    [Purpose] The purpose of this study was to examine the effect of biofeedback postural control training using whole body vibration in acute stroke patients on balance and gait ability. [Subjects and Methods] Thirty stroke patients participated in this study and were divided into a group of 10, a group for biofeedback postural control training combined with a whole body vibration, one for biofeedback postural control training combined with an aero-step, and one for biofeedback postural control training. Biorescue was used to measure the limits of stability, balance ability, and Lukotronic was used to measure step length, gait ability. [Results] In the comparison of balance ability and gait ability between the groups for before and after intervention, Group I showed a significant difference in balance ability and gait ability compared to Groups II and III. [Conclusion] This study showed that biofeedback postural control training using whole body vibration is effective for improving balance ability and gait ability in stroke patients.

  4. Comparing the effects of combined numerical and visuo- spatial psychoeducational trainings conducted by curricular teachers and external trainers. Preliminary evidence across kindergarteners.

    NASA Astrophysics Data System (ADS)

    Agus, M.; Mascia, M. L.; Fastame, M. C.; Napoleone, V.; Porru, A. M.; Siddu, F.; Lucangeli, D.; Penna, M. P.

    2016-11-01

    The aim of this study was to verify the efficacy of two pencil-and-paper trainings empowering numerical and visuo-spatial abilities in Italian five-year-old kindergarteners. Specifically, the trainings were respectively carried out by the curricular teacher or by an external trainer. The former received a specific training in order to use the psychoeducational programmes with her pupils, whereas the latter received a specific education about the role of numerical and visuo-spatial abilities for school achievement and she was also trained to use psychoeducational trainings in kindergarten schools. At pre-test and post-test nonverbal functions and numeracy knowledge were assessed through a battery of standardized tests. The results show that both the numerical psychoeducational programme and the visuo-spatial one are useful tools to enhance mathematical achievements in kindergarteners. However, when the trainings were proposed by the external trainer, the efficacy of the psychoeducational programmes was more significant. These outcomes seem to be related both to the expertise and the novelty effect of the external trainer on the classroom.

  5. NOUS: Construction and Querying of Dynamic Knowledge Graphs

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

    Choudhury, Sutanay; Agarwal, Khushbu; Purohit, Sumit

    The ability to construct domain specific knowledge graphs (KG) and perform question-answering or hypothesis generation is a trans- formative capability. Despite their value, automated construction of knowledge graphs remains an expensive technical challenge that is beyond the reach for most enterprises and academic institutions. We propose an end-to-end framework for developing custom knowl- edge graph driven analytics for arbitrary application domains. The uniqueness of our system lies A) in its combination of curated KGs along with knowledge extracted from unstructured text, B) support for advanced trending and explanatory questions on a dynamic KG, and C) the ability to answer queriesmore » where the answer is embedded across multiple data sources.« less

  6. Genetic control and combining ability of agronomic attributes and northern leaf blight-related attributes in popcorn.

    PubMed

    Santos, J S; Amaral Júnior, A T; Vivas, M; Mafra, G S; Pena, G F; Silva, F H L; Guimarães, A G

    2017-09-27

    The present study was conducted to investigate the genetic control and to estimate the general and specific combining abilities of popcorn for agronomic attributes and attributes related to resistance to northern leaf blight (NLB). The 56 hybrids (F 1 and reciprocals), together with the eight parent lines and six controls, were evaluated in two harvests, in a randomized-block design with four replications. Dominance components were more expressive than the additive components for grain yield and expression of resistance, and hybridization was the most suitable option for obtaining resistant and productive genotypes. For grain yield, popping expansion, and resistance to NLB, there was no significance for reciprocal effects, which indicates that the direction in which the cross is performed does not interfere with the hybrid's performance. Then, the superior hybrids recommended for more profitable growth were P8 x L61, L61 x L76, and L61 x L77.

  7. Integrating Soluble Biomarkers and Imaging Technologies in the Identification of Vulnerable Atherosclerotic Patients

    PubMed Central

    Páramo, José A.; Rodríguez JA, José A.; Orbe, Josune

    2006-01-01

    The clinical utility of a biomarker depends on its ability to identify high-risk individuals to optimally manage the patient. A new biomarker would be of clinical value if it is accurate and reliable, provides good sensitivity and specificity, and is available for widespread application. Data are accumulating on the potential clinical utility of integrating imaging technologies and circulating biomarkers for the identification of vulnerable (high-risk) cardiovascular patients. A multi-biomarker strategy consisting of markers of inflammation, hemostasis and thrombosis, proteolysis and oxidative stress, combined with new imaging modalities (optical coherence tomography, virtual histology plus IVUS, PET) can increase our ability to identify such thombosis-prone patients. In an ideal scenario, cardiovascular biomarkers and imaging combined will provide a better diagnostic tool to identify high-risk individuals and also more efficient methods for effective therapies to reduce such cardiovascular risk. However, additional studies are required in order to show that this approach can contribute to improved diagnostic and therapeutic of atherosclerotic disease. PMID:19690647

  8. Integrating soluble biomarkers and imaging technologies in the identification of vulnerable atherosclerotic patients.

    PubMed

    Páramo, José A; Rodríguez Ja, José A; Orbe, Josune

    2007-02-07

    The clinical utility of a biomarker depends on its ability to identify high-risk individuals to optimally manage the patient. A new biomarker would be of clinical value if it is accurate and reliable, provides good sensitivity and specificity, and is available for widespread application. Data are accumulating on the potential clinical utility of integrating imaging technologies and circulating biomarkers for the identification of vulnerable (high-risk) cardiovascular patients. A multi-biomarker strategy consisting of markers of inflammation, hemostasis and thrombosis, proteolysis and oxidative stress, combined with new imaging modalities (optical coherence tomography, virtual histology plus IVUS, PET) can increase our ability to identify such thombosis-prone patients. In an ideal scenario, cardiovascular biomarkers and imaging combined will provide a better diagnostic tool to identify high-risk individuals and also more efficient methods for effective therapies to reduce such cardiovascular risk. However, additional studies are required in order to show that this approach can contribute to improved diagnostic and therapeutic of atherosclerotic disease.

  9. The Predicted Cross Value for Genetic Introgression of Multiple Alleles

    PubMed Central

    Han, Ye; Cameron, John N.; Wang, Lizhi; Beavis, William D.

    2017-01-01

    We consider the plant genetic improvement challenge of introgressing multiple alleles from a homozygous donor to a recipient. First, we frame the project as an algorithmic process that can be mathematically formulated. We then introduce a novel metric for selecting breeding parents that we refer to as the predicted cross value (PCV). Unlike estimated breeding values, which represent predictions of general combining ability, the PCV predicts specific combining ability. The PCV takes estimates of recombination frequencies as an input vector and calculates the probability that a pair of parents will produce a gamete with desirable alleles at all specified loci. We compared the PCV approach with existing estimated-breeding-value approaches in two simulation experiments, in which 7 and 20 desirable alleles were to be introgressed from a donor line into a recipient line. Results suggest that the PCV is more efficient and effective for multi-allelic trait introgression. We also discuss how operations research can be used for other crop genetic improvement projects and suggest several future research directions. PMID:28122824

  10. Analysis of high-order SNP barcodes in mitochondrial D-loop for chronic dialysis susceptibility.

    PubMed

    Yang, Cheng-Hong; Lin, Yu-Da; Chuang, Li-Yeh; Chang, Hsueh-Wei

    2016-10-01

    Positively identifying disease-associated single nucleotide polymorphism (SNP) markers in genome-wide studies entails the complex association analysis of a huge number of SNPs. Such large numbers of SNP barcode (SNP/genotype combinations) continue to pose serious computational challenges, especially for high-dimensional data. We propose a novel exploiting SNP barcode method based on differential evolution, termed IDE (improved differential evolution). IDE uses a "top combination strategy" to improve the ability of differential evolution to explore high-order SNP barcodes in high-dimensional data. We simulate disease data and use real chronic dialysis data to test four global optimization algorithms. In 48 simulated disease models, we show that IDE outperforms existing global optimization algorithms in terms of exploring ability and power to detect the specific SNP/genotype combinations with a maximum difference between cases and controls. In real data, we show that IDE can be used to evaluate the relative effects of each individual SNP on disease susceptibility. IDE generated significant SNP barcode with less computational complexity than the other algorithms, making IDE ideally suited for analysis of high-order SNP barcodes. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Inheritance of downy mildew (Plasmopara viticola) and anthracnose (Sphaceloma ampelinum) resistance in grapevines.

    PubMed

    Poolsawat, O; Mahanil, S; Laosuwan, P; Wongkaew, S; Tharapreuksapong, A; Reisch, B I; Tantasawat, P A

    2013-12-13

    Downy mildew (Plasmopara viticola) and anthracnose (Sphaceloma ampelinum) are two of the major diseases of most grapevine (Vitis vinifera L.) cultivars grown in Thailand. Therefore, breeding grapevines for improved downy mildew and anthracnose resistance is crucial. Factorial crosses were made between three downy mildew and/or anthracnose resistant lines ('NY88.0517.01', 'NY65.0550.04', and 'NY65.0551.05'; male parents) and two or three susceptible cultivars of V. vinifera ('Black Queen', 'Carolina Black Rose', and/or 'Italia'; female parents). F1 hybrid seedlings were evaluated for downy mildew and anthracnose resistance using a detached/excised leaf assay. For both diseases, the general combining ability (GCA) variance among male parents was significant, while the variance of GCA among females and the specific combining ability (SCA) variance were not significant, indicating the prevalence of additive over non-additive gene actions. The estimated narrow sense heritabilities of downy mildew and anthracnose resistance were 55.6 and 79.2%, respectively, suggesting that downy mildew/anthracnose resistance gene(s) were highly heritable. The 'Carolina Black Rose x NY65.0550.04' cross combination is recommended for future use.

  12. Ability of preoperative 3.0-Tesla magnetic resonance imaging to predict the absence of side-specific extracapsular extension of prostate cancer.

    PubMed

    Hara, Tomohiko; Nakanishi, Hiroyuki; Nakagawa, Tohru; Komiyama, Motokiyo; Kawahara, Takashi; Manabe, Tomoko; Miyake, Mototaka; Arai, Eri; Kanai, Yae; Fujimoto, Hiroyuki

    2013-10-01

    Recent studies have shown an improvement in prostate cancer diagnosis with the use of 3.0-Tesla magnetic resonance imaging. We retrospectively assessed the ability of this imaging technique to predict side-specific extracapsular extension of prostate cancer. From October 2007 to August 2011, prostatectomy was carried out in 396 patients after preoperative 3.0-Tesla magnetic resonance imaging. Among these, 132 (primary sample) and 134 patients (validation sample) underwent 12-core prostate biopsy at the National Cancer Center Hospital of Tokyo, Japan, and at other institutions, respectively. In the primary dataset, univariate and multivariate analyses were carried out to predict side-specific extracapsular extension using variables determined preoperatively, including 3.0-Tesla magnetic resonance imaging findings (T2-weighted and diffusion-weighted imaging). A prediction model was then constructed and applied to the validation study sample. Multivariate analysis identified four significant independent predictors (P < 0.05), including a biopsy Gleason score of ≥8, positive 3.0-Tesla diffusion-weighted magnetic resonance imaging findings, ≥2 positive biopsy cores on each side and a maximum percentage of positive cores ≥31% on each side. The negative predictive value was 93.9% in the combination model with these four predictors, meanwhile the positive predictive value was 33.8%. Good reproducibility of these four significant predictors and the combination model was observed in the validation study sample. The side-specific extracapsular extension prediction by the biopsy Gleason score and factors associated with tumor location, including a positive 3.0-Tesla diffusion-weighted magnetic resonance imaging finding, have a high negative predictive value, but a low positive predictive value. © 2013 The Japanese Urological Association.

  13. Immunological responses induced by the combination of phototherapy and immunotherapy in the treatment of metastatic tumors

    NASA Astrophysics Data System (ADS)

    Chen, Wei R.; Naylor, Mark F.; Nordquist, Robert E.; Teague, T. Kent; Liu, Hong

    2008-02-01

    Combination therapy using laser photothermal interaction and immunological stimulation has demonstrated its ability to induce immunological responses. Glycated chitosan (GC), an immunological stimulant, and imiquimod, a new type of immune response modifier (IRM), when used in conjunction with laser phototherapy, have shown to have a great immunological stimulation function. Specifically, imiquimod can help release cytokines from immunocompetent cells, stimulate TH1 lymphocyte responses (CD8+ T-cells), and recruit additional dendritic cells. To study the effects of immunoadjuvnats in combination of laser photo-irradiation, we treated animal tumors with laser-ICG-GC combination and late-stage melanoma patients with laser-ICG-imiquimod combination. At designated times, tumors, blood, and spleens in both treated and untreated animals were colleted for analysis. The major immunological indicators, such as IL-6, IL-12, IFN-gamma, CD4, and CD8 were analyzed. The same immunological analysis was also performed for melanoma patients treated by the laser-imiquimod combination.

  14. Protein recognition by a pattern-generating fluorescent molecular probe.

    PubMed

    Pode, Zohar; Peri-Naor, Ronny; Georgeson, Joseph M; Ilani, Tal; Kiss, Vladimir; Unger, Tamar; Markus, Barak; Barr, Haim M; Motiei, Leila; Margulies, David

    2017-12-01

    Fluorescent molecular probes have become valuable tools in protein research; however, the current methods for using these probes are less suitable for analysing specific populations of proteins in their native environment. In this study, we address this gap by developing a unimolecular fluorescent probe that combines the properties of small-molecule-based probes and cross-reactive sensor arrays (the so-called chemical 'noses/tongues'). On the one hand, the probe can detect different proteins by generating unique identification (ID) patterns, akin to cross-reactive arrays. On the other hand, its unimolecular scaffold and selective binding enable this ID-generating probe to identify combinations of specific protein families within complex mixtures and to discriminate among isoforms in living cells, where macroscopic arrays cannot access. The ability to recycle the molecular device and use it to track several binding interactions simultaneously further demonstrates how this approach could expand the fluorescent toolbox currently used to detect and image proteins.

  15. Protein recognition by a pattern-generating fluorescent molecular probe

    NASA Astrophysics Data System (ADS)

    Pode, Zohar; Peri-Naor, Ronny; Georgeson, Joseph M.; Ilani, Tal; Kiss, Vladimir; Unger, Tamar; Markus, Barak; Barr, Haim M.; Motiei, Leila; Margulies, David

    2017-12-01

    Fluorescent molecular probes have become valuable tools in protein research; however, the current methods for using these probes are less suitable for analysing specific populations of proteins in their native environment. In this study, we address this gap by developing a unimolecular fluorescent probe that combines the properties of small-molecule-based probes and cross-reactive sensor arrays (the so-called chemical 'noses/tongues'). On the one hand, the probe can detect different proteins by generating unique identification (ID) patterns, akin to cross-reactive arrays. On the other hand, its unimolecular scaffold and selective binding enable this ID-generating probe to identify combinations of specific protein families within complex mixtures and to discriminate among isoforms in living cells, where macroscopic arrays cannot access. The ability to recycle the molecular device and use it to track several binding interactions simultaneously further demonstrates how this approach could expand the fluorescent toolbox currently used to detect and image proteins.

  16. Vicarious Neural Processing of Outcomes during Observational Learning

    PubMed Central

    Monfardini, Elisabetta; Gazzola, Valeria; Boussaoud, Driss

    2013-01-01

    Learning what behaviour is appropriate in a specific context by observing the actions of others and their outcomes is a key constituent of human cognition, because it saves time and energy and reduces exposure to potentially dangerous situations. Observational learning of associative rules relies on the ability to map the actions of others onto our own, process outcomes, and combine these sources of information. Here, we combined newly developed experimental tasks and functional magnetic resonance imaging (fMRI) to investigate the neural mechanisms that govern such observational learning. Results show that the neural systems involved in individual trial-and-error learning and in action observation and execution both participate in observational learning. In addition, we identified brain areas that specifically activate for others’ incorrect outcomes during learning in the posterior medial frontal cortex (pMFC), the anterior insula and the posterior superior temporal sulcus (pSTS). PMID:24040104

  17. Boosted Hyperthermia Therapy by Combined AC Magnetic and Photothermal Exposures in Ag/Fe3O4 Nanoflowers.

    PubMed

    Das, R; Rinaldi-Montes, N; Alonso, J; Amghouz, Z; Garaio, E; García, J A; Gorria, P; Blanco, J A; Phan, M H; Srikanth, H

    2016-09-28

    Over the past two decades, magnetic hyperthermia and photothermal therapy are becoming very promising supplementary techniques to well-established cancer treatments such as radiotherapy and chemotherapy. These techniques have dramatically improved their ability to perform controlled treatments, relying on the procedure of delivering nanoscale objects into targeted tumor tissues, which can release therapeutic killing doses of heat either upon AC magnetic field exposure or laser irradiation. Although an intense research effort has been made in recent years to study, separately, magnetic hyperthermia using iron oxide nanoparticles and photothermal therapy based on gold or silver plasmonic nanostructures, the full potential of combining both techniques has not yet been systematically explored. Here we present a proof-of-principle experiment showing that designing multifunctional silver/magnetite (Ag/Fe3O4) nanoflowers acting as dual hyperthermia agents is an efficient route for enhancing their heating ability or specific absorption rate (SAR). Interestingly, the SAR of the nanoflowers is increased by at least 1 order of magnitude under the application of both an external magnetic field of 200 Oe and simultaneous laser irradiation. Furthermore, our results show that the synergistic exploitation of the magnetic and photothermal properties of the nanoflowers reduces the magnetic field and laser intensities that would be required in the case that both external stimuli were applied separately. This constitutes a key step toward optimizing the hyperthermia therapy through a combined multifunctional magnetic and photothermal treatment and improving our understanding of the therapeutic process to specific applications that will entail coordinated efforts in physics, engineering, biology, and medicine.

  18. Face recognition: a model specific ability.

    PubMed

    Wilmer, Jeremy B; Germine, Laura T; Nakayama, Ken

    2014-01-01

    In our everyday lives, we view it as a matter of course that different people are good at different things. It can be surprising, in this context, to learn that most of what is known about cognitive ability variation across individuals concerns the broadest of all cognitive abilities; an ability referred to as general intelligence, general mental ability, or just g. In contrast, our knowledge of specific abilities, those that correlate little with g, is severely constrained. Here, we draw upon our experience investigating an exceptionally specific ability, face recognition, to make the case that many specific abilities could easily have been missed. In making this case, we derive key insights from earlier false starts in the measurement of face recognition's variation across individuals, and we highlight the convergence of factors that enabled the recent discovery that this variation is specific. We propose that the case of face recognition ability illustrates a set of tools and perspectives that could accelerate fruitful work on specific cognitive abilities. By revealing relatively independent dimensions of human ability, such work would enhance our capacity to understand the uniqueness of individual minds.

  19. Appraisal of work ability in relation to job-specific health requirements in ambulance workers.

    PubMed

    van Schaaijk, A; Boschman, J S; Frings-Dresen, M H W; Sluiter, J K

    2017-01-01

    To gain insight into which job-specific health requirements relate to work ability, the following two research questions were formulated: Which job-specific health requirements are associated with the appraisal of work ability in ambulance drivers and paramedics? How are appraisals of physical and mental work ability associated with the appraisal of overall work ability in ambulance drivers and paramedics? Workers Health Surveillance cross-sectional data of 506 ambulance workers (236 drivers and 270 paramedics) were used. The tests for specific job requirements were divided into six categories. Work ability was appraised as overall, physical and mental/emotional. Multiple linear stepwise regression analyses were used to model the associations. Outcomes in 'raised alertness and judgment ability' (R 2  = 0.09), 'job-specific physical abilities' (R 2  = 0.10) and 'emotional peak load' (R 2  = 0.07) significantly explained appraised overall, physical and mental/emotional work ability. Physical and mental/emotional work ability together explained 48.3% of the variance of overall work ability. The explained variance by physical and mental/emotional work ability was almost 4% higher in drivers than in paramedics. Overall work ability was significantly explained by outcomes in 'raised alertness and judgment ability' and 'emotional peak load.' Physical work ability was significantly explained by 'job-specific physical abilities' and 'raised alertness and judgment ability' outcomes, while 'emotional peak load' and 'raised alertness and judgment ability' outcomes significantly explained mental/emotional work ability. Physical and mental/emotional work ability explains the same proportion of variance in overall work ability.

  20. An overview of polyurethane foams in higher specification foam mattresses.

    PubMed

    Soppi, Esa; Lehtiö, Juha; Saarinen, Hannu

    2015-02-01

    Soft polyurethane foams exist in thousands of grades and constitute essential components of hospital mattresses. For pressure ulcer prevention, the ability of foams to control the immersion and envelopment of patients is essential. Higher specification foam mattresses (i.e., foam mattresses that relieve pressure via optimum patient immersion and envelopment while enabling patient position changes) are claimed to be more effective for preventing pressure ulcers than standard mattresses. Foam grade evaluations should include resiliency, density, hardness, indentation force/load deflection, progressive hardness, tensile strength, and elongation along with essential criteria for higher specification foam mattresses. Patient-specific requirements may include optimal control of patient immersion and envelopment. Mattress cover characteristics should include breathability, impermeability to fluids, and fire safety and not affect mattress function. Additional determinations such as hardness are assessed according to the guidelines of the American Society for Testing and Materials and the International Organization for Standardization. At this time, no single foam grade provides an optimal combination of the above key requirements, but the literature suggests a combination of at least 2 foams may create an optimal higher specification foam mattress for pressure ulcer prevention. Future research and the development of product specification accuracy standards are needed to help clinicians make evidence-based decisions about mattress use.

  1. Beyond Fluorescent Proteins: Hybrid and Bioluminescent Indicators for Imaging Neural Activities.

    PubMed

    Wang, Anqi; Feng, Jiesi; Li, Yulong; Zou, Peng

    2018-04-18

    Optical biosensors have been invaluable tools in neuroscience research, as they provide the ability to directly visualize neural activity in real time, with high specificity, and with exceptional spatial and temporal resolution. Notably, a majority of these sensors are based on fluorescent protein scaffolds, which offer the ability to target specific cell types or even subcellular compartments. However, fluorescent proteins are intrinsically bulky tags, often insensitive to the environment, and always require excitation light illumination. To address these limitations, there has been a proliferation of alternative sensor scaffolds developed in recent years, including hybrid sensors that combine the advantages of synthetic fluorophores and genetically encoded protein tags, as well as bioluminescent probes. While still in their early stage of development as compared with fluorescent protein-based sensors, these novel probes have offered complementary solutions to interrogate various aspects of neuronal communication, including transmitter release, changes in membrane potential, and the production of second messengers. In this Review, we discuss these important new developments with a particular focus on design strategies.

  2. Combining bio-electrospraying with gene therapy: a novel biotechnique for the delivery of genetic material via living cells.

    PubMed

    Ward, Eliot; Chan, Emma; Gustafsson, Kenth; Jayasinghe, Suwan N

    2010-05-01

    The investigations reported in this article demonstrate the ability of bio-electrosprays and cell electrospinning to deliver a genetic construct in association with living cells. Previous studies on both bio-electrosprays and cell electrospinning demonstrated great promise for tissue engineering and regenerative biology/medicine. The investigations described herein widen the applicability of these biotechniques by combining gene therapy protocols, resulting in a novel drug delivery methodology previously unexplored. In these studies a human cell line was transduced with recombinant self-inactivating lentiviral particles. These particles incorporated a green fluorescent protein fused to an endosomal targeting construct. This construct encodes a peptide, which can subsequently be detected on the surface of cells by specific T-cells. The transduced cell line was subsequently manipulated in association with either bio-electrospraying or cell electrospinning. Hence this demonstrates (i) the ability to safely handle genetically modified living cells and (ii) the ability to directly form pre-determined architectures bearing living therapeutic cells. This merged technology demonstrates a unique approach for directly forming living therapeutic architectures for controlled and targeted release of experimental cells/genes, as well as medical cell/gene therapeutics for a plethora of biological and medical applications. Hence, such developments could be applied to personalised medicine.

  3. Studies examining the efficacy of ankle foot orthoses should report activity level and mechanical evidence.

    PubMed

    Harlaar, Jaap; Brehm, Merel; Becher, Jules G; Bregman, Daan J J; Buurke, Jaap; Holtkamp, Fred; De Groot, Vincent; Nollet, Frans

    2010-09-01

    Ankle Foot Orthoses (AFOs) to promote walking ability are a common treatment in patients with neurological or muscular diseases. However, guidelines on the prescription of AFOs are currently based on a low level of evidence regarding their efficacy. Recent studies aiming to demonstrate the efficacy of wearing an AFO in respect to walking ability are not always conclusive. In this paper it is argued to recognize two levels of evidence related to the ICF levels. Activity level evidence expresses the gain in walking ability for the patient, while mechanical evidence expresses the correct functioning of the AFO. Used in combination for the purpose of evaluating the efficacy of orthotic treatment, a conjunct improvement at both levels reinforces the treatment algorithm that is used. Conversely, conflicting outcomes will challenge current treatment algorithms and the supposed working mechanism of the AFO. A treatment algorithm must use relevant information as an input, derived from measurements with a high precision. Its result will be a specific AFO that matches the patient's needs, specified by the mechanical characterization of the AFO footwear combination. It is concluded that research on the efficacy of AFOs should use parameters from two levels of evidence, to prove the efficacy of a treatment algorithm, i.e., how to prescribe a well-matched AFO.

  4. Diallel analysis for technological traits in upland cotton.

    PubMed

    Queiroz, D R; Farias, F J C; Cavalcanti, J J V; Carvalho, L P; Neder, D G; Souza, L S S; Farias, F C; Teodoro, P E

    2017-09-21

    Final cotton quality is of great importance, and it depends on intrinsic and extrinsic fiber characteristics. The objective of this study was to estimate general (GCA) and specific (SCA) combining abilities for technological fiber traits among six upland cotton genotypes and their fifteen hybrid combinations, as well as to determine the effective genetic effects in controlling the traits evaluated. In 2015, six cotton genotypes: FM 993, CNPA 04-2080, PSC 355, TAM B 139-17, IAC 26, and TAMCOT-CAMD-E and fifteen hybrid combinations were evaluated at the Experimental Station of Embrapa Algodão, located in Patos, PB, Brazil. The experimental design was a randomized block with three replications. Technological fiber traits evaluated were: length (mm); strength (gf/tex); fineness (Micronaire index); uniformity (%); short fiber index (%), and spinning index. The diallel analysis was carried out according to the methodology proposed by Griffing, using method II and model I. Significant differences were detected between the treatments and combining abilities (GCA and SCA), indicating the variability of the study material. There was a predominance of additive effects for the genetic control of all traits. TAM B 139-17 presented the best GCA estimates for all traits. The best combinations were: FM 993 x TAM B 139-17, CNPA 04-2080 x PSC 355, FM 993 x TAMCOT-CAMD-E, PSC 355 x TAM B 139-17, and TAM B 139-17 x TAMCOT-CAMD-E, by obtaining the best estimates of SCA, with one of the parents having favorable estimates for GCA.

  5. Typical intellectual engagement, Big Five personality traits, approaches to learning and cognitive ability predictors of academic performance.

    PubMed

    Furnham, Adrian; Monsen, Jeremy; Ahmetoglu, Gorkan

    2009-12-01

    Both ability (measured by power tests) and non-ability (measured by preference tests) individual difference measures predict academic school outcomes. These include fluid as well as crystalized intelligence, personality traits, and learning styles. This paper examines the incremental validity of five psychometric tests and the sex and age of pupils to predict their General Certificate in Secondary Education (GCSE) test results. The aim was to determine how much variance ability and non-ability tests can account for in predicting specific GCSE exam scores. The sample comprised 212 British schoolchildren. Of these, 123 were females. Their mean age was 15.8 years (SD 0.98 years). Pupils completed three self-report tests: the Neuroticism-Extroversion-Openness-Five-Factor Inventory (NEO-FFI) which measures the 'Big Five' personality traits, (Costa & McCrae, 1992); the Typical Intellectual Engagement Scale (Goff & Ackerman, 1992) and a measure of learning style, the Study Process Questionnaire (SPQ; Biggs, 1987). They also completed two ability tests: the Wonderlic Personnel Test (Wonderlic, 1992) a short measure of general intelligence and the General Knowledge Test (Irving, Cammock, & Lynn, 2001) a measure of crystallized intelligence. Six months later they took their (10th grade) GCSE exams comprising four 'core' compulsory exams as well as a number of specific elective subjects. Correlational analysis suggested that intelligence was the best predictors of school results. Preference test measures accounted for relatively little variance. Regressions indicated that over 50% of the variance in school exams for English (Literature and Language) and Maths and Science combined could be accounted for by these individual difference factors. Data from less than an hour's worth of testing pupils could predict school exam results 6 months later. These tests could, therefore, be used to reliably inform important decisions about how pupils are taught.

  6. Performance and Metabolic Demand of a New Repeated-Sprint Ability Test in Basketball Players: Does the Number of Changes of Direction Matter?

    PubMed

    Zagatto, Alessandro M; Ardigò, Luca P; Barbieri, Fabio A; Milioni, Fabio; Dello Iacono, Antonio; Camargo, Bruno H F; Padulo, Johnny

    2017-09-01

    Zagatto, AM, Ardigò, LP, Barbieri, FA, Milioni, F, Dello Iacono, A, Camargo, BHF, and Padulo, J. Performance and metabolic demand of a new repeated-sprint ability test in basketball players: does the number of changes of direction matter? J Strength Cond Res 31(9): 2438-2446, 2017-This study compared 2 repeated-sprint ability (RSA) tests in basketball players. Both tests included 10 × 30-m sprints, with the difference that the previously validated test (RSA2COD) featured 2 changes of direction (COD) per sprint, whereas the experimental test (RSA5COD) featured 5 CODs per sprint. Test performances and metabolic demands were specifically assessed in 20 basketball players. First, RSA5COD test-retest reliability was investigated. Then, RSA2COD, RSA5COD sprint times, peak speeds, oxygen uptake (V[Combining Dot Above]O2) and posttest blood lactate concentration [La] were measured. The RSA5COD results showed to be reliable. RSA2COD performance resulted better than the RSA5COD version (p < 0.01), with shorter sprint times and higher peak speeds. Over sprints, the tests did not differ from each other in terms of V[Combining Dot Above]O2 (p > 0.05). Over whole bout, the RSA2COD was more demanding than the RSA5COD, considering overall metabolic power requirement (i.e., VO2-driven + [La]-driven components). Given that RSA5COD (a) mimics real game-play as sprint distance and action change frequency/direction and (b) has the same metabolic expenditure per task completion as metabolic cost, RSA5COD is a valuable option for players and coaches for training basketball-specific agility and assessing bioenergetic demands.

  7. Demand-specific work ability, poor health and working conditions in middle-aged full-time employees.

    PubMed

    Nabe-Nielsen, Kirsten; Thielen, Karsten; Nygaard, Else; Thorsen, Sannie Vester; Diderichsen, Finn

    2014-07-01

    We investigated the prevalence of reduced demand-specific work ability, its association with age, gender, education, poor health, and working conditions, and the interaction between poor health and working conditions regarding reduced demand-specific work ability. We used cross-sectional questionnaire data from 3381 full-time employees responding to questions about vocational education, job demands and social support (working conditions), musculoskeletal pain (MSP) and major depression (MD) (poor health) and seven questions about difficulty managing different job demands (reduced demand-specific work ability). Reduced demand-specific work ability varied from 9% to 19% among the 46-year old and from 11% to 21% among the 56-year old. Age was associated with two, gender with four, and education with all measures of reduced demand-specific work ability. MSP was associated with four and MD was associated with six measures of reduced demand-specific work ability. We found no interaction between working conditions and poor health regarding reduced demand-specific work ability. Copyright © 2014 Elsevier Ltd and The Ergonomics Society. All rights reserved.

  8. Combining chemotherapy with PD-1 blockade in NSCLC.

    PubMed

    Mathew, Matthen; Enzler, Thomas; Shu, Catherine A; Rizvi, Naiyer A

    2018-06-01

    Antitumor immunity relies on the ability of the immune system to recognize tumor cells as foreign and eliminate them. An effective immune response in this setting is due to surveillance of tumor-specific antigens that induce an adaptive immune response resulting in T-cell mediated cytotoxicity. Immune checkpoint inhibitors, specifically those targeting the programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) axis, have demonstrated promising activity in non-small cell lung cancer (NSCLC). However, there remains a crucial need for better treatment strategies for the majority of patients with advanced NSCLC, particularly in the frontline setting. Chemotherapy can increase antigenicity via immunogenic cell death (ICD) of tumor cells as well as also reduce "off target" immunosuppression in the tumor microenvironment (TME). Combining chemotherapy with PD-1 blockade harnesses the potential synergy between these agents and has led to encouraging results in the up-front treatment of NSCLC. In this review, we summarize the preclinical rationale behind these combinations and review recent trial data demonstrating their efficacy. Copyright © 2018. Published by Elsevier Inc.

  9. Tumor-targeting domains for chimeric antigen receptor T cells.

    PubMed

    Bezverbnaya, Ksenia; Mathews, Ashish; Sidhu, Jesse; Helsen, Christopher W; Bramson, Jonathan L

    2017-01-01

    Immunotherapy with chimeric antigen receptor (CAR) T cells has been advancing steadily in clinical trials. Since the ability of engineered T cells to recognize intended tumor-associated targets is crucial for the therapeutic success, antigen-binding domains play an important role in shaping T-cell responses. Single-chain antibody and T-cell receptor fragments, natural ligands, repeat proteins, combinations of the above and universal tag-specific domains have all been used in the antigen-binding moiety of chimeric receptors. Here we outline the advantages and disadvantages of different domains, discuss the concepts of affinity and specificity, and highlight the recent progress of each targeting strategy.

  10. Dynamic, continuous multitasking training leads to task-specific improvements but does not transfer across action selection tasks

    NASA Astrophysics Data System (ADS)

    Bender, Angela D.; Filmer, Hannah L.; Naughtin, Claire K.; Dux, Paul E.

    2017-12-01

    The ability to perform multiple tasks concurrently is an ever-increasing requirement in our information-rich world. Despite this, multitasking typically compromises performance due to the processing limitations associated with cognitive control and decision-making. While intensive dual-task training is known to improve multitasking performance, only limited evidence suggests that training-related performance benefits can transfer to untrained tasks that share overlapping processes. In the real world, however, coordinating and selecting several responses within close temporal proximity will often occur in high-interference environments. Over the last decade, there have been notable reports that training on video action games that require dynamic multitasking in a demanding environment can lead to transfer effects on aspects of cognition such as attention and working memory. Here, we asked whether continuous and dynamic multitasking training extends benefits to tasks that are theoretically related to the trained tasks. To examine this issue, we asked a group of participants to train on a combined continuous visuomotor tracking task and a perceptual discrimination task for six sessions, while an active control group practiced the component tasks in isolation. A battery of tests measuring response selection, response inhibition, and spatial attention was administered before and immediately after training to investigate transfer. Multitasking training resulted in substantial, task-specific gains in dual-task ability, but there was no evidence that these benefits generalized to other action control tasks. The findings suggest that training on a combined visuomotor tracking and discrimination task results in task-specific benefits but provides no additional value for untrained action selection tasks.

  11. Situational leadership: a management system to increase staff satisfaction.

    PubMed

    Zurlinden, J; Bongard, B; Magafas, M

    1990-01-01

    Using the principles of Situational Leadership, nurse managers can deal with people and situations effectively and flexibly--helping to retain nurses on their units. Based on the manager's assessment of the nurse's ability and willingness for a specific task, each nurse falls into one of four readiness quadrants. Each quadrant predicts a corresponding leadership style: telling, selling, participating, or delegating. Nurse managers need to use different combinations of task behavior and relationship behavior for each corresponding leadership style.

  12. Peroxisome Proliferator-Activated Receptor Subtype- and Cell-Type-Specific Activation of Genomic Target Genes upon Adenoviral Transgene Delivery

    PubMed Central

    Nielsen, Ronni; Grøntved, Lars; Stunnenberg, Hendrik G.; Mandrup, Susanne

    2006-01-01

    Investigations of the molecular events involved in activation of genomic target genes by peroxisome proliferator-activated receptors (PPARs) have been hampered by the inability to establish a clean on/off state of the receptor in living cells. Here we show that the combination of adenoviral delivery and chromatin immunoprecipitation (ChIP) is ideal for dissecting these mechanisms. Adenoviral delivery of PPARs leads to a rapid and synchronous expression of the PPAR subtypes, establishment of transcriptional active complexes at genomic loci, and immediate activation of even silent target genes. We demonstrate that PPARγ2 possesses considerable ligand-dependent as well as independent transactivation potential and that agonists increase the occupancy of PPARγ2/retinoid X receptor at PPAR response elements. Intriguingly, by direct comparison of the PPARs (α, γ, and β/δ), we show that the subtypes have very different abilities to gain access to target sites and that in general the genomic occupancy correlates with the ability to activate the corresponding target gene. In addition, the specificity and potency of activation by PPAR subtypes are highly dependent on the cell type. Thus, PPAR subtype-specific activation of genomic target genes involves an intricate interplay between the properties of the subtype- and cell-type-specific settings at the individual target loci. PMID:16847324

  13. Oscillations and patterns in a model of simultaneous CO and C2H2 oxidation and NO(x) reduction in a cross-flow reactor.

    PubMed

    Hadač, Otto; Kohout, Martin; Havlica, Jaromír; Schreiber, Igor

    2015-03-07

    A model describing simultaneous catalytic oxidation of CO and C2H2 and reduction of NOx in a cross-flow tubular reactor is explored with the aim of relating spatiotemporal patterns to specific pathways in the mechanism. For that purpose, a detailed mechanism proposed for three-way catalytic converters is split into two subsystems, (i) simultaneous oxidation of CO and C2H2, and (ii) oxidation of CO combined with NOx reduction. The ability of these two subsystems to display mechanism-specific dynamical effects is studied initially by neglecting transport phenomena and applying stoichiometric network and bifurcation analyses. We obtain inlet temperature - inlet oxygen concentration bifurcation diagrams, where each region possessing specific dynamics - oscillatory, bistable and excitable - is associated with a dominant reaction pathway. Next, the spatiotemporal behaviour due to reaction kinetics combined with transport processes is studied. The observed spatiotemporal patterns include phase waves, travelling fronts, pulse waves and spatiotemporal chaos. Although these types of pattern occur generally when the kinetic scheme possesses autocatalysis, we find that some of their properties depend on the underlying dominant reaction pathway. The relation of patterns to specific reaction pathways is discussed.

  14. Polymer-Mediated Delivery of siRNAs to Hepatocellular Carcinoma: Variables Affecting Specificity and Effectiveness.

    PubMed

    Farra, Rossella; Musiani, Francesco; Perrone, Francesca; Čemažar, Maja; Kamenšek, Urška; Tonon, Federica; Abrami, Michela; Ručigaj, Aleš; Grassi, Mario; Pozzato, Gabriele; Bonazza, Deborah; Zanconati, Fabrizio; Forte, Giancarlo; El Boustani, Maguie; Scarabel, Lucia; Garziera, Marica; Russo Spena, Concetta; De Stefano, Lucia; Salis, Barbara; Toffoli, Giuseppe; Rizzolio, Flavio; Grassi, Gabriele; Dapas, Barbara

    2018-03-28

    Despite the advances in anticancer therapies, their effectiveness for many human tumors is still far from being optimal. Significant improvements in treatment efficacy can come from the enhancement of drug specificity. This goal may be achieved by combining the use of therapeutic molecules with tumor specific effects and delivery carriers with tumor targeting ability. In this regard, nucleic acid-based drug (NABD) and particularly small interfering RNAs (siRNAs), are attractive molecules due to the possibility to be engineered to target specific tumor genes. On the other hand, polymeric-based delivery systems are emerging as versatile carriers to generate tumor-targeted delivery systems. Here we will focus on the most recent findings in the selection of siRNA/polymeric targeted delivery systems for hepatocellular carcinoma (HCC), a human tumor for which currently available therapeutic approaches are poorly effective. In addition, we will discuss the most attracting and, in our opinion, promising siRNA-polymer combinations for HCC in relation to the biological features of HCC tissue. Attention will be also put on the mathematical description of the mechanisms ruling siRNA-carrier delivery, this being an important aspect to improve effectiveness reducing the experimental work.

  15. Balance ability measured with the Berg balance scale: a determinant of fall history in community-dwelling adults with leg amputation.

    PubMed

    Wong, Christopher Kevin; Chen, Christine C; Blackwell, Wren M; Rahal, Rana T; Benoy, Stephany A

    2015-01-01

    Falls are common among adults with leg amputations and associated with balance confidence. But subjective confidence is not equivalent with physical ability. This multivariate analyses of community-dwelling adults with leg amputations examined relationships among individual characteristics, falls, balance ability and balance confidence. Cross-sectional study. Community-dwelling adults with leg amputations recruited from a support group and prosthetic clinic. Subjects provided self-reported medical/fall history, prosthetic functional use, and Activities-specific Balance Confidence (ABC) questionnaire data. Balance ability was assessed with the Berg Balance Scale (BBS). Fall incidence was categorized as any fall (one or more) and recurrent falls (more than one). Multivariate logistic regression analyzed relationships within the two fall categories. Cross tabulations and ANOVA analyzed differences among subcategories. Fifty-four subjects (mean age 56.8) with various etiologies, amputation levels, and balance abilities participated. 53.7% had any fall; 25.9% had recurrent falls. Models for both fall categories correctly classified fall history in > 70% of subjects with combinations of the variables ABC, BBS, body-mass-index, and amputation level. Falls occurred regardless of clinical characteristics. Total BBS and select item scores were independent determinants of fall history. Unlike other balance-impaired populations, adults with leg amputation and better balance ability had greater odds of falling.

  16. A Porphyrin Complex as a Self-Conditioned Electrode Material for High-Performance Energy Storage.

    PubMed

    Gao, Ping; Chen, Zhi; Zhao-Karger, Zhirong; Mueller, Jonathan E; Jung, Christoph; Klyatskaya, Svetlana; Diemant, Thomas; Fuhr, Olaf; Jacob, Timo; Behm, R Jürgen; Ruben, Mario; Fichtner, Maximilian

    2017-08-21

    The novel functionalized porphyrin [5,15-bis(ethynyl)-10,20-diphenylporphinato]copper(II) (CuDEPP) was used as electrodes for rechargeable energy-storage systems with an extraordinary combination of storage capacity, rate capability, and cycling stability. The ability of CuDEPP to serve as an electron donor or acceptor supports various energy-storage applications. Combined with a lithium negative electrode, the CuDEPP electrode exhibited a long cycle life of several thousand cycles and fast charge-discharge rates up to 53 C and a specific energy density of 345 Wh kg -1 at a specific power density of 29 kW kg -1 . Coupled with a graphite cathode, the CuDEPP anode delivered a specific power density of 14 kW kg -1 . Whereas the capacity is in the range of that of ordinary lithium-ion batteries, the CuDEPP electrode has a power density in the range of that of supercapacitors, thus opening a pathway toward new organic electrodes with excellent rate capability and cyclic stability. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Effects of P25 TiO2 Nanoparticles on the Free Radical-Scavenging Ability of Antioxidants upon Their Exposure to Simulated Sunlight.

    PubMed

    Li, Meng; Chong, Yu; Fu, Peter P; Xia, Qingsu; Croley, Timothy R; Lo, Y Martin; Yin, Jun-Jie

    2017-11-15

    Although nanosized ingredients, including TiO 2 nanoparticles (NPs), can be found in a wide range of consumer products, little is known about the effects these particles have on other active compounds in product matrices. These NPs can interact with reactive oxygen species (ROS), potentially disrupting or canceling the benefits expected from antioxidants. We used electron spin resonance spectrometry to assess changes in the antioxidant capacities of six dietary antioxidants (ascorbic acid, α-tocopherol, glutathione, cysteine, epicatechin, and epicatechin gallate) during exposure to P25 TiO 2 and/or simulated sunlight. Specifically, we determined the ability of these antioxidants to scavenge 1-diphenyl-2-picryl-hydrazyl radical, superoxide radical, and hydroxyl radical. Exposure to simulated sunlight alone did not lead to noticeable changes in radical-scavenging abilities; however, in combination with P25 TiO 2 NPs, the scavenging abilities of most antioxidants were weakened. We found glutathione to be the most resistant to treatment with sunlight and NPs among these six antioxidants.

  18. Statistical word learning in children with autism spectrum disorder and specific language impairment.

    PubMed

    Haebig, Eileen; Saffran, Jenny R; Ellis Weismer, Susan

    2017-11-01

    Word learning is an important component of language development that influences child outcomes across multiple domains. Despite the importance of word knowledge, word-learning mechanisms are poorly understood in children with specific language impairment (SLI) and children with autism spectrum disorder (ASD). This study examined underlying mechanisms of word learning, specifically, statistical learning and fast-mapping, in school-aged children with typical and atypical development. Statistical learning was assessed through a word segmentation task and fast-mapping was examined in an object-label association task. We also examined children's ability to map meaning onto newly segmented words in a third task that combined exposure to an artificial language and a fast-mapping task. Children with SLI had poorer performance on the word segmentation and fast-mapping tasks relative to the typically developing and ASD groups, who did not differ from one another. However, when children with SLI were exposed to an artificial language with phonemes used in the subsequent fast-mapping task, they successfully learned more words than in the isolated fast-mapping task. There was some evidence that word segmentation abilities are associated with word learning in school-aged children with typical development and ASD, but not SLI. Follow-up analyses also examined performance in children with ASD who did and did not have a language impairment. Children with ASD with language impairment evidenced intact statistical learning abilities, but subtle weaknesses in fast-mapping abilities. As the Procedural Deficit Hypothesis (PDH) predicts, children with SLI have impairments in statistical learning. However, children with SLI also have impairments in fast-mapping. Nonetheless, they are able to take advantage of additional phonological exposure to boost subsequent word-learning performance. In contrast to the PDH, children with ASD appear to have intact statistical learning, regardless of language status; however, fast-mapping abilities differ according to broader language skills. © 2017 Association for Child and Adolescent Mental Health.

  19. Recall and recognition of verbal paired associates in early Alzheimer's disease.

    PubMed

    Lowndes, G J; Saling, M M; Ames, D; Chiu, E; Gonzalez, L M; Savage, G R

    2008-07-01

    The primary impairment in early Alzheimer's disease (AD) is encoding/consolidation, resulting from medial temporal lobe (MTL) pathology. AD patients perform poorly on cued-recall paired associate learning (PAL) tasks, which assess the ability of the MTLs to encode relational memory. Since encoding and retrieval processes are confounded within performance indexes on cued-recall PAL, its specificity for AD is limited. Recognition paradigms tend to show good specificity for AD, and are well tolerated, but are typically less sensitive than recall tasks. Associate-recognition is a novel PAL task requiring a combination of recall and recognition processes. We administered a verbal associate-recognition test and cued-recall analogue to 22 early AD patients and 55 elderly controls to compare their ability to discriminate these groups. Both paradigms used eight arbitrarily related word pairs (e.g., pool-teeth) with varying degrees of imageability. Associate-recognition was equally effective as the cued-recall analogue in discriminating the groups, and logistic regression demonstrated classification rates by both tasks were equivalent. These preliminary findings provide support for the clinical value of this recognition tool. Conceptually it has potential for greater specificity in informing neuropsychological diagnosis of AD in clinical samples but this requires further empirical support.

  20. Population and High-Risk Group Screening for Glaucoma: The Los Angeles Latino Eye Study

    PubMed Central

    Francis, Brian A.; Vigen, Cheryl; Lai, Mei-Ying; Winarko, Jonathan; Nguyen, Betsy; Azen, Stanley

    2011-01-01

    Purpose. To evaluate the ability of various screening tests, both individually and in combination, to detect glaucoma in the general Latino population and high-risk subgroups. Methods. The Los Angeles Latino Eye Study is a population-based study of eye disease in Latinos 40 years of age and older. Participants (n = 6082) underwent Humphrey visual field testing (HVF), frequency doubling technology (FDT) perimetry, measurement of intraocular pressure (IOP) and central corneal thickness (CCT), and independent assessment of optic nerve vertical cup disc (C/D) ratio. Screening parameters were evaluated for three definitions of glaucoma based on optic disc, visual field, and a combination of both. Analyses were also conducted for high-risk subgroups (family history of glaucoma, diabetes mellitus, and age ≥65 years). Sensitivity, specificity, and receiver operating characteristic curves were calculated for those continuous parameters independently associated with glaucoma. Classification and regression tree (CART) analysis was used to develop a multivariate algorithm for glaucoma screening. Results. Preset cutoffs for screening parameters yielded a generally poor balance of sensitivity and specificity (sensitivity/specificity for IOP ≥21 mm Hg and C/D ≥0.8 was 0.24/0.97 and 0.60/0.98, respectively). Assessment of high-risk subgroups did not improve the sensitivity/specificity of individual screening parameters. A CART analysis using multiple screening parameters—C/D, HVF, and IOP—substantially improved the balance of sensitivity and specificity (sensitivity/specificity 0.92/0.92). Conclusions. No single screening parameter is useful for glaucoma screening. However, a combination of vertical C/D ratio, HVF, and IOP provides the best balance of sensitivity/specificity and is likely to provide the highest yield in glaucoma screening programs. PMID:21245400

  1. Diagnosis of rheumatoid arthritis: multivariate analysis of biomarkers.

    PubMed

    Wild, Norbert; Karl, Johann; Grunert, Veit P; Schmitt, Raluca I; Garczarek, Ursula; Krause, Friedemann; Hasler, Fritz; van Riel, Piet L C M; Bayer, Peter M; Thun, Matthias; Mattey, Derek L; Sharif, Mohammed; Zolg, Werner

    2008-02-01

    To test if a combination of biomarkers can increase the classification power of autoantibodies to cyclic citrullinated peptides (anti-CCP) in the diagnosis of rheumatoid arthritis (RA) depending on the diagnostic situation. Biomarkers were subject to three inclusion/exclusion criteria (discrimination between RA patients and healthy blood donors, ability to identify anti-CCP-negative RA patients, specificity in a panel with major non-rheumatological diseases) before univariate ranking and multivariate analysis was carried out using a modelling panel (n = 906). To enable the evaluation of the classification power in different diagnostic settings the disease controls (n = 542) were weighted according to the admission rates in rheumatology clinics modelling a clinic panel or according to the relative prevalences of musculoskeletal disorders in the general population seen by general practitioners modelling a GP panel. Out of 131 biomarkers considered originally, we evaluated 32 biomarkers in this study, of which only seven passed the three inclusion/exclusion criteria and were combined by multivariate analysis using four different mathematical models. In the modelled clinic panel, anti-CCP was the lead marker with a sensitivity of 75.8% and a specificity of 94.0%. Due to the lack in specificity of the markers other than anti-CCP in this diagnostic setting, any gain in sensitivity by any marker combination is off-set by a corresponding loss in specificity. In the modelled GP panel, the best marker combination of anti-CCP and interleukin (IL)-6 resulted in a sensitivity gain of 7.6% (85.9% vs. 78.3%) at a minor loss in specificity of 1.6% (90.3% vs. 91.9%) compared with anti-CCP as the best single marker. Depending on the composition of the sample panel, anti-CCP alone or anti-CCP in combination with IL-6 has the highest classification power for the diagnosis of established RA.

  2. Population specific biomarkers of human aging: a big data study using South Korean, Canadian and Eastern European patient populations.

    PubMed

    Mamoshina, Polina; Kochetov, Kirill; Putin, Evgeny; Cortese, Franco; Aliper, Alexander; Lee, Won-Suk; Ahn, Sung-Min; Uhn, Lee; Skjodt, Neil; Kovalchuk, Olga; Scheibye-Knudsen, Morten; Zhavoronkov, Alex

    2018-01-11

    Accurate and physiologically meaningful biomarkers for human aging are key to assessing anti-aging therapies. Given ethnic differences in health, diet, lifestyle, behaviour, environmental exposures and even average rate of biological aging, it stands to reason that aging clocks trained on datasets obtained from specific ethnic populations are more likely to account for these potential confounding factors, resulting in an enhanced capacity to predict chronological age and quantify biological age. Here we present a deep learning-based hematological aging clock modeled using the large combined dataset of Canadian, South Korean and Eastern European population blood samples that show increased predictive accuracy in individual populations compared to population-specific hematologic aging clocks. The performance of models was also evaluated on publicly-available samples of the American population from the National Health and Nutrition Examination Survey (NHANES). In addition, we explored the association between age predicted by both population-specific and combined hematological clocks and all-cause mortality. Overall, this study suggests a) the population-specificity of aging patterns and b) hematologic clocks predicts all-cause mortality. Proposed models added to the freely available Aging.AI system allowing improved ability to assess human aging. © The Author(s) 2018. Published by Oxford University Press on behalf of The Gerontological Society of America.

  3. Optically enhanced acoustophoresis

    NASA Astrophysics Data System (ADS)

    McDougall, Craig; O'Mahoney, Paul; McGuinn, Alan; Willoughby, Nicholas A.; Qiu, Yongqiang; Demore, Christine E. M.; MacDonald, Michael P.

    2017-08-01

    Regenerative medicine has the capability to revolutionise many aspects of medical care, but for it to make the step from small scale autologous treatments to larger scale allogeneic approaches, robust and scalable label free cell sorting technologies are needed as part of a cell therapy bioprocessing pipeline. In this proceedings we describe several strategies for addressing the requirements for high throughput without labeling via: dimensional scaling, rare species targeting and sorting from a stable state. These three approaches are demonstrated through a combination of optical and ultrasonic forces. By combining mostly conservative and non-conservative forces from two different modalities it is possible to reduce the influence of flow velocity on sorting efficiency, hence increasing robustness and scalability. One such approach can be termed "optically enhanced acoustophoresis" which combines the ability of acoustics to handle large volumes of analyte with the high specificity of optical sorting.

  4. An executable specification for the message processor in a simple combining network

    NASA Technical Reports Server (NTRS)

    Middleton, David

    1995-01-01

    While the primary function of the network in a parallel computer is to communicate data between processors, it is often useful if the network can also perform rudimentary calculations. That is, some simple processing ability in the network itself, particularly for performing parallel prefix computations, can reduce both the volume of data being communicated and the computational load on the processors proper. Unfortunately, typical implementations of such networks require a large fraction of the hardware budget, and so combining networks are viewed as being impractical. The FFP Machine has such a combining network, and various characteristics of the machine allow a good deal of simplification in the network design. Despite being simple in construction however, the network relies on many subtle details to work correctly. This paper describes an executable model of the network which will serve several purposes. It provides a complete and detailed description of the network which can substantiate its ability to support necessary functions. It provides an environment in which algorithms to be run on the network can be designed and debugged more easily than they would on physical hardware. Finally, it provides the foundation for exploring the design of the message receiving facility which connects the network to the individual processors.

  5. Combination of brain-computer interface training and goal-directed physical therapy in chronic stroke: a case report.

    PubMed

    Broetz, Doris; Braun, Christoph; Weber, Cornelia; Soekadar, Surjo R; Caria, Andrea; Birbaumer, Niels

    2010-09-01

    There is no accepted and efficient rehabilitation strategy to reduce focal impairments for patients with chronic stroke who lack residual movements. A 67-year-old hemiplegic patient with no active finger extension was trained with a brain-computer interface (BCI) combined with a specific daily life-oriented physiotherapy. The BCI used electrical brain activity (EEG) and magnetic brain activity (MEG) to drive an orthosis and a robot affixed to the patient's affected upper extremity, which enabled him to move the paralyzed arm and hand driven by voluntary modulation of micro-rhythm activity. In addition, the patient practiced goal-directed physiotherapy training. Over 1 year, he completed 3 training blocks. Arm motor function, gait capacities (using Fugl-Meyer Assessment, Wolf Motor Function Test, Modified Ashworth Scale, 10-m walk speed, and goal attainment score), and brain reorganization (functional MRI, MEG) were repeatedly assessed. The ability of hand and arm movements as well as speed and safety of gait improved significantly (mean 46.6%). Improvement of motor function was associated with increased micro-oscillations in the ipsilesional motor cortex. This proof-of-principle study suggests that the combination of BCI training with goal-directed, active physical therapy may improve the motor abilities of chronic stroke patients despite apparent initial paralysis.

  6. Exploring pima and upland cross-combinations to identify fusarium oxysporum f. sp. vasinfectum race 4 resistant cottons by combining ability of superior cultivars

    USDA-ARS?s Scientific Manuscript database

    A cotton breeding program strives to identify the best performance cultivars or breeding lines which can be used as parents in crosses. Multi-cross combinations provide the means of performance of each parent and assess the combining ability or productivity of parents through the hybridization proce...

  7. Visual Contrast Sensitivity Improvement by Right Frontal High-Beta Activity Is Mediated by Contrast Gain Mechanisms and Influenced by Fronto-Parietal White Matter Microstructure

    PubMed Central

    Quentin, Romain; Elkin Frankston, Seth; Vernet, Marine; Toba, Monica N.; Bartolomeo, Paolo; Chanes, Lorena; Valero-Cabré, Antoni

    2016-01-01

    Behavioral and electrophysiological studies in humans and non-human primates have correlated frontal high-beta activity with the orienting of endogenous attention and shown the ability of the latter function to modulate visual performance. We here combined rhythmic transcranial magnetic stimulation (TMS) and diffusion imaging to study the relation between frontal oscillatory activity and visual performance, and we associated these phenomena to a specific set of white matter pathways that in humans subtend attentional processes. High-beta rhythmic activity on the right frontal eye field (FEF) was induced with TMS and its causal effects on a contrast sensitivity function were recorded to explore its ability to improve visual detection performance across different stimulus contrast levels. Our results show that frequency-specific activity patterns engaged in the right FEF have the ability to induce a leftward shift of the psychometric function. This increase in visual performance across different levels of stimulus contrast is likely mediated by a contrast gain mechanism. Interestingly, microstructural measures of white matter connectivity suggest a strong implication of right fronto-parietal connectivity linking the FEF and the intraparietal sulcus in propagating high-beta rhythmic signals across brain networks and subtending top-down frontal influences on visual performance. PMID:25899709

  8. Specialization of the Right Intraparietal Sulcus for Processing Mathematics During Development.

    PubMed

    Schel, Margot A; Klingberg, Torkel

    2017-09-01

    Mathematical ability, especially perception of numbers and performance of arithmetics, is known to rely on the activation of intraparietal sulcus (IPS). However, reasoning ability and working memory, 2 highly associated abilities also activate partly overlapping regions. Most studies aimed at localizing mathematical function have used group averages, where individual variability is averaged out, thus confounding the anatomical specificity when localizing cognitive functions. Here, we analyze the functional anatomy of the intraparietal cortex by using individual analysis of subregions of IPS based on how they are structurally connected to frontal, parietal, and occipital cortex. Analysis of cortical thickness showed that the right anterior IPS, defined by its connections to the frontal lobe, was associated with both visuospatial working memory, and mathematics in 6-year-old children. This region specialized during development to be specifically related to mathematics, but not visuospatial working memory in adolescents and adults. This could be an example of interactive specialization, where interacting with the environment in combination with interactions between cortical regions leads from a more general role of right anterior IPS in spatial processing, to a specialization of this region for mathematics. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  9. Decellularized ovine arteries as biomatrix scaffold support endothelial of mesenchymal stem cells.

    PubMed

    Zhang, Wenbo; Huo, Yanhong; Wang, Xinling; Jia, Yingmin; Su, Li; Wang, Caixia; Li, Ying; Yang, Yonghong; Liu, Yuanyuan

    2016-11-01

    The differentiation rate of adipose-derived mesenchymal stem cells (Ad-MSCs) into endothelial cells is always lower under normal condition, which limits further clinical application of Ad-MSCs for angiogenesis regenerative medicine and needs to be enhanced. In the present study, the tissue-specific-derived decellularized ovine arteries matrix (DCS) was used as scaffold to investigate the pro-endothelial differentiation ability of decellularized ovine arteries matrix as well as the underlying mechanisms. The prepared decellularized ovine arteries matrix by the combination of enzymatic and chemical decellularization approaches preserved macroscopic 3D architecture, native composition and ultrastructure of natural ovine arteries. The RT-PCR, histopathological and immunofluorescence assay results suggested that DCS could increase the proliferation ability of MSC. What's more, the DCS could also induce the endothelial differentiation of MSC, which was further enhanced by adding VEGF. Our results showed that natural 3D matrix from decellularized ovine arteries could induce the endothelial differentiation of AD-MSCs alone or with the combination of VEGF. Our results indicated that the decellularized ovine arteries matrix would serve as an efficient culture system for promoting endothelial differentiation of Ad-MSCs.

  10. T LYMPHOCYTES TARGETING NATIVE RECEPTORS

    PubMed Central

    Rooney, Cliona M; Leen, Ann M; Vera, Juan F; Heslop, Helen E

    2013-01-01

    Summary The adoptive transfer of T cells specific for native tumor antigens (TAs) is an increasingly popular cancer treatment option because of the ability of these cells to discriminate between normal and tumor tissues and corresponding lack of short or long-term toxicities. Infusions of antigen-specific CD4+ and CD8+ T cells targeting viral antigens derived from Epstein Barr virus (EBV) induce sustained complete tumor remissions in patients with highly immunogenic tumor’s such as post-transplant lymphoproliferative disease, although resistance occurred when the infused T-cell population had restricted antigen specificity. T cells specific for EBV antigens have also produced complete remissions of EBV-positive nasopharyngeal carcinomas and lymphomas developing in immunocompetent individuals, even though in these patients tumor survival is dependent on their ability to evade T-cell immunity. Adapting this strategy to non-viral tumors is more challenging, as the target antigens expressed are less immunogenic and the tumors lack the potent danger signals that are characteristic of viruses. The goals of current studies are to define conditions that promote expansion of antigen-specific T cells ex vivo and to ensure their in vivo persistence and survival by combining with maneuvers such as lymphodepletion, checkpoint inhibition, cytokine infusions, or genetic manipulations. More pragmatic goals are to streamline manufacturing to facilitate the transition of these therapies to late phase trials and to evaluate closely histocompatibility antigen (HLA)-matched banked antigen-specific T-cells so that T-cell therapies can be made more broadly available. PMID:24329788

  11. The Accuracy of the Physical Examination for the Diagnosis of Midlumbar and Low Lumbar Nerve Root Impingement

    PubMed Central

    Suri, Pradeep; Rainville, James; Katz, Jeffrey N.; Jouve, Cristin; Hartigan, Carol; Limke, Janet; Pena, Enrique; Li, Ling; Swaim, Bryan; Hunter, David J

    2010-01-01

    Study Design Cross-sectional study with prospective recruitment. Objective To determine the accuracy of the physical examination for the diagnosis of midlumbar nerve root impingement (L2, L3, or L4), low lumbar nerve root impingement (L5 or S1) and level-specific lumbar nerve root impingement on magnetic resonance imaging (MRI), using individual tests and combinations of tests. Summary of Background Data The sensitivity and specificity of the physical examination for the localization of nerve root impingement has not been previously studied. Methods Sensitivities, specificities and LRs were calculated for the ability of individual tests and test combinations to predict the presence or absence of nerve root impingement at midlumbar, low lumbar, and specific nerve root levels. Results LRs ≥5.0 indicate moderate to large changes from pre-test probability of nerve root impingement to post-test probability. For the diagnosis of midlumbar impingement, the femoral stretch test (FST), crossed femoral stretch test (CFST), medial ankle pinprick sensation, and patellar reflex testing demonstrated LRs ≥5.0 (LR ∞). LRs ≥5.0 were seen with the combinations of FST and either patellar reflex testing (LR 7.0; 95% CI 2.3–21), or the sit-to-stand test (LR ∞). For the diagnosis of low lumbar impingement, the Achilles reflex test demonstrated a LR ≥5.0 (LR 7.1; CI 0.96–53); test combinations did not increase LRs. For the diagnosis of level-specific impingement, LRs ≥5.0 were seen for anterior thigh sensation at L2 (LR 13; 95% CI 1.8–87); FST at L3 (LR 5.7 ; 95% CI 2.3–4.4); patellar reflex testing (LR 7.7; 95% CI 1.7–35), medial ankle sensation (LR ∞), or CFST (LR 13; 95% CI 1.8–87) at L4; and hip abductor strength at L5(LR 11; 95% CI 1.3–84). Test combinations increased LRs for level-specific root impingement at the L4 level only. Conclusions Individual physical examination tests may provide clinical information which substantially alters the likelihood that midlumbar impingement, low lumbar impingement, or level-specific impingement is present. Test combinations improve diagnostic accuracy for midlumbar impingement. PMID:20543768

  12. How Does Attention Relate to the Ability-Specific and Position-Specific Components of Reasoning Measured by APM?

    ERIC Educational Resources Information Center

    Ren, Xuezhu; Goldhammer, Frank; Moosbrugger, Helfried; Schweizer, Karl

    2012-01-01

    The aim of the present study was to clarify the nature of the ability-specific and position-specific components of Raven's Advanced Progressive Matrices (APM) by relating them to a number of types of attention. The ability-specific component represents the constant part of cognitive performance whereas the position-specific component reflects the…

  13. ITS and trnH-psbA as Efficient DNA Barcodes to Identify Threatened Commercial Woody Angiosperms from Southern Brazilian Atlantic Rainforests

    PubMed Central

    Brotto, Marcelo Leandro

    2015-01-01

    The Araucaria Forests in southern Brazil are part of the Atlantic Rainforest, a key hotspot for global biodiversity. This habitat has experienced extensive losses of vegetation cover due to commercial logging and the intense use of wood resources for construction and furniture manufacturing. The absence of precise taxonomic tools for identifying Araucaria Forest tree species motivated us to test the ability of DNA barcoding to distinguish species exploited for wood resources and its suitability for use as an alternative testing technique for the inspection of illegal timber shipments. We tested three cpDNA regions (matK, trnH-psbA, and rbcL) and nrITS according to criteria determined by The Consortium for the Barcode of Life (CBOL). The efficiency of each marker and selected marker combinations were evaluated for 30 commercially valuable woody species in multiple populations, with a special focus on Lauraceae species. Inter- and intraspecific distances, species discrimination rates, and ability to recover species-specific clusters were evaluated. Among the regions and different combinations, ITS was the most efficient for identifying species based on the ‘best close match’ test; similarly, the trnH-psbA + ITS combination also demonstrated satisfactory results. When combining trnH-psbA + ITS, Maximum Likelihood analysis demonstrated a more resolved topology for internal branches, with 91% of species-specific clusters. DNA barcoding was found to be a practical and rapid method for identifying major threatened woody angiosperms from Araucaria Forests such as Lauraceae species, presenting a high confidence for recognizing members of Ocotea. These molecular tools can assist in screening those botanical families that are most targeted by the timber industry in southern Brazil and detecting certain species protected by Brazilian legislation and could be a useful tool for monitoring wood exploitation. PMID:26630282

  14. ITS and trnH-psbA as Efficient DNA Barcodes to Identify Threatened Commercial Woody Angiosperms from Southern Brazilian Atlantic Rainforests.

    PubMed

    Bolson, Mônica; Smidt, Eric de Camargo; Brotto, Marcelo Leandro; Silva-Pereira, Viviane

    2015-01-01

    The Araucaria Forests in southern Brazil are part of the Atlantic Rainforest, a key hotspot for global biodiversity. This habitat has experienced extensive losses of vegetation cover due to commercial logging and the intense use of wood resources for construction and furniture manufacturing. The absence of precise taxonomic tools for identifying Araucaria Forest tree species motivated us to test the ability of DNA barcoding to distinguish species exploited for wood resources and its suitability for use as an alternative testing technique for the inspection of illegal timber shipments. We tested three cpDNA regions (matK, trnH-psbA, and rbcL) and nrITS according to criteria determined by The Consortium for the Barcode of Life (CBOL). The efficiency of each marker and selected marker combinations were evaluated for 30 commercially valuable woody species in multiple populations, with a special focus on Lauraceae species. Inter- and intraspecific distances, species discrimination rates, and ability to recover species-specific clusters were evaluated. Among the regions and different combinations, ITS was the most efficient for identifying species based on the 'best close match' test; similarly, the trnH-psbA + ITS combination also demonstrated satisfactory results. When combining trnH-psbA + ITS, Maximum Likelihood analysis demonstrated a more resolved topology for internal branches, with 91% of species-specific clusters. DNA barcoding was found to be a practical and rapid method for identifying major threatened woody angiosperms from Araucaria Forests such as Lauraceae species, presenting a high confidence for recognizing members of Ocotea. These molecular tools can assist in screening those botanical families that are most targeted by the timber industry in southern Brazil and detecting certain species protected by Brazilian legislation and could be a useful tool for monitoring wood exploitation.

  15. Specific Changes in Young Soccer Player's Fitness After Traditional Bilateral vs. Unilateral Combined Strength and Plyometric Training

    PubMed Central

    Ramirez-Campillo, Rodrigo; Sanchez-Sanchez, Javier; Gonzalo-Skok, Oliver; Rodríguez-Fernandez, Alejandro; Carretero, Manuel; Nakamura, Fabio Y.

    2018-01-01

    The aim of this study was to compare changes in young soccer player's fitness after traditional bilateral vs. unilateral combined plyometric and strength training. Male athletes were randomly divided in two groups; both received the same training, including strength training for knee extensors and flexors, in addition to horizontal plyometric training drills. The only difference between groups was the mode of drills technique: unilateral (UG; n = 9; age, 17.3 ± 1.1 years) vs. bilateral (TG; n = 9; age, 17.6 ± 0.5 years). One repetition maximum bilateral strength of knee muscle extensors (1RM_KE) and flexors (1RM_KF), change of direction ability (COD), horizontal and vertical jump ability with one (unilateral) and two (bilateral) legs, and limb symmetry index were measured before and after an 8-week in-season intervention period. Some regular soccer drills were replaced by combination of plyometric and strength training drills. Magnitude-based inference statistics were used for between-group and within-group comparisons. Beneficial effects (p < 0.05) in 1RM_KE, COD, and several test of jumping performance were found in both groups in comparison to pre-test values. The limb symmetry index was not affected in either group. The beneficial changes in 1RM_KE (8.1%; p = 0.074) and 1RM_KF (6.7%; p = 0.004), COD (3.1%; p = 0.149), and bilateral jump performance (from 2.7% [p = 0.535] to 10.5% [p = 0.002]) were possible to most likely beneficial in the TG than in the UG. However, unilateral jump performance measures achieved likely to most likely beneficial changes in the UG compared to the TG (from 4.5% [p = 0.090] to 8.6% [p = 0.018]). The improvements in jumping ability were specific to the type of jump performed, with greater improvements in unilateral jump performance in the UG and bilateral jump performance in the TG. Therefore, bilateral strength and plyometric training should be complemented with unilateral drills, in order to maximize adaptations. PMID:29623049

  16. Specific Changes in Young Soccer Player's Fitness After Traditional Bilateral vs. Unilateral Combined Strength and Plyometric Training.

    PubMed

    Ramirez-Campillo, Rodrigo; Sanchez-Sanchez, Javier; Gonzalo-Skok, Oliver; Rodríguez-Fernandez, Alejandro; Carretero, Manuel; Nakamura, Fabio Y

    2018-01-01

    The aim of this study was to compare changes in young soccer player's fitness after traditional bilateral vs. unilateral combined plyometric and strength training. Male athletes were randomly divided in two groups; both received the same training, including strength training for knee extensors and flexors, in addition to horizontal plyometric training drills. The only difference between groups was the mode of drills technique: unilateral (UG; n = 9; age, 17.3 ± 1.1 years) vs. bilateral (TG; n = 9; age, 17.6 ± 0.5 years). One repetition maximum bilateral strength of knee muscle extensors (1RM_KE) and flexors (1RM_KF), change of direction ability (COD), horizontal and vertical jump ability with one (unilateral) and two (bilateral) legs, and limb symmetry index were measured before and after an 8-week in-season intervention period. Some regular soccer drills were replaced by combination of plyometric and strength training drills. Magnitude-based inference statistics were used for between-group and within-group comparisons. Beneficial effects ( p < 0.05) in 1RM_KE, COD, and several test of jumping performance were found in both groups in comparison to pre-test values. The limb symmetry index was not affected in either group. The beneficial changes in 1RM_KE (8.1%; p = 0.074) and 1RM_KF (6.7%; p = 0.004), COD (3.1%; p = 0.149), and bilateral jump performance (from 2.7% [ p = 0.535] to 10.5% [ p = 0.002]) were possible to most likely beneficial in the TG than in the UG. However, unilateral jump performance measures achieved likely to most likely beneficial changes in the UG compared to the TG (from 4.5% [ p = 0.090] to 8.6% [ p = 0.018]). The improvements in jumping ability were specific to the type of jump performed, with greater improvements in unilateral jump performance in the UG and bilateral jump performance in the TG. Therefore, bilateral strength and plyometric training should be complemented with unilateral drills, in order to maximize adaptations.

  17. Using Electroencephalography for Treatment Guidance in Major Depressive Disorder.

    PubMed

    Wade, Elizabeth C; Iosifescu, Dan V

    2016-09-01

    Given the high prevalence of treatment-resistant depression and the long delays in finding effective treatments via trial and error, valid biomarkers of treatment outcome with the ability to guide treatment selection represent one of the most important unmet needs in mood disorders. A large body of research has investigated, for this purpose, biomarkers derived from electroencephalography (EEG), using resting state EEG or evoked potentials. Most studies have focused on specific EEG features (or combinations thereof), whereas more recently machine-learning approaches have been used to define the EEG features with the best predictive abilities without a priori hypotheses. While reviewing these different approaches, we have focused on the predictor characteristics and the quality of the supporting evidence. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  18. Variable steroid receptor responses: Intrinsically disordered AF1 is the key

    PubMed Central

    Simons, S. Stoney; Kumar, Raj

    2013-01-01

    Steroid hormones, acting through their cognate receptor proteins, see widespread clinical applications due to their ability to alter the induction or repression of numerous genes. However, steroid usage is limited by the current inability to control off-target, or non-specific, side-effects. Recent results from three separate areas of research with glucocorticoid and other steroid receptors (cofactor-induced changes in receptor structure, the ability of ligands to alter remote regions of receptor structure, and how cofactor concentration affects both ligand potency and efficacy) indicate that a key element of receptor activity is the intrinsically disordered amino-terminal domain. These results are combined to construct a novel framework within which to logically pursue various approaches that could afford increased selectivity in steroid-based therapies. PMID:23792173

  19. The association between cognition and academic performance in Ugandan children surviving malaria with neurological involvement.

    PubMed

    Bangirana, Paul; Menk, Jeremiah; John, Chandy C; Boivin, Michael J; Hodges, James S

    2013-01-01

    The contribution of different cognitive abilities to academic performance in children surviving cerebral insult can guide the choice of interventions to improve cognitive and academic outcomes. This study's objective was to identify which cognitive abilities are associated with academic performance in children after malaria with neurological involvement. 62 Ugandan children with a history of malaria with neurological involvement were assessed for cognitive ability (working memory, reasoning, learning, visual spatial skills, attention) and academic performance (reading, spelling, arithmetic) three months after the illness. Linear regressions were fit for each academic score with the five cognitive outcomes entered as predictors. Adjusters in the analysis were age, sex, education, nutrition, and home environment. Exploratory factor analysis (EFA) and structural equation models (SEM) were used to determine the nature of the association between cognition and academic performance. Predictive residual sum of squares was used to determine which combination of cognitive scores was needed to predict academic performance. In regressions of a single academic score on all five cognitive outcomes and adjusters, only Working Memory was associated with Reading (coefficient estimate = 0.36, 95% confidence interval = 0.10 to 0.63, p<0.01) and Spelling (0.46, 0.13 to 0.78, p<0.01), Visual Spatial Skills was associated with Arithmetic (0.15, 0.03 to 0.26, p<0.05), and Learning was associated with Reading (0.06, 0.00 to 0.11, p<0.05). One latent cognitive factor was identified using EFA. The SEM found a strong association between this latent cognitive ability and each academic performance measure (P<0.0001). Working memory, visual spatial ability and learning were the best predictors of academic performance. Academic performance is strongly associated with the latent variable labelled "cognitive ability" which captures most of the variation in the individual specific cognitive outcome measures. Working memory, visual spatial skills, and learning together stood out as the best combination to predict academic performance.

  20. Low-thrust Isp sensitivity study

    NASA Technical Reports Server (NTRS)

    Schoenman, L.

    1982-01-01

    A comparison of the cooling requirements and attainable specific impulse performance of engines in the 445 to 4448N thrust class utilizing LOX/RP-1, LOX/Hydrogen and LOX/Methane propellants is presented. The unique design requirements for the regenerative cooling of low-thrust engines operating at high pressures (up to 6894 kPa) were explored analytically by comparing single cooling with the fuel and the oxidizer, and dual cooling with both the fuel and the oxidizer. The effects of coolant channel geometry, chamber length, and contraction ratio on the ability to provide proper cooling were evaluated, as was the resulting specific impulse. The results show that larger contraction ratios and smaller channels are highly desirable for certain propellant combinations.

  1. Emotion differentiation dissected: between-category, within-category, and integral emotion differentiation, and their relation to well-being.

    PubMed

    Erbas, Yasemin; Ceulemans, Eva; Blanke, Elisabeth S; Sels, Laura; Fischer, Agneta; Kuppens, Peter

    2018-04-24

    Emotion differentiation, the ability to describe and label our own emotions in a differentiated and specific manner, has been repeatedly associated with well-being. However, it is unclear exactly what type of differentiation is most strongly related to well-being: the ability to make fine-grained distinctions between emotions that are relatively closely related (e.g. anger and irritation), the ability to make larger distinctions between very distinct emotions (e.g. anger and sadness), or the combination of both. To determine which type of differentiation is most predictive of well-being, we performed a comprehensive meta-analysis across six datasets. We examined the correlations between these three types of differentiation and several indicators of well-being (depression, emotional clarity, and self-esteem). Results showed that individuals differentiated most between very distinct emotions and least between more related emotions, and that an index computed across emotions from both the same and different emotion categories was most strongly associated with well-being indicators.

  2. Immunogenicity of Nontypeable Haemophilus influenzae Outer Membrane Vesicles and Protective Ability in the Chinchilla Model of Otitis Media.

    PubMed

    Winter, Linda E; Barenkamp, Stephen J

    2017-10-01

    Outer membrane vesicles (OMVs) produced by Gram-negative bacteria are enriched in several outer membrane components, including major and minor outer membrane proteins and lipooligosaccharide. We assessed the functional activity of nontypeable Haemophilus influenzae (NTHi) OMV-specific antisera and the protective ability of NTHi OMVs as vaccine antigens in the chinchilla otitis media model. OMVs were purified from three HMW1/HMW2-expressing NTHi strains, two of which were also engineered to overexpress Hia proteins. OMV-specific antisera raised in guinea pigs were assessed for their ability to mediate killing of representative NTHi in an opsonophagocytic assay. The three OMV-specific antisera mediated killing of 18 of 65, 24 of 65, and 30 of 65 unrelated HMW1/HMW2-expressing NTHi strains. Overall, they mediated killing of 39 of 65 HMW1/HMW2-expressing strains. The two Hia-expressing OMV-specific antisera mediated killing of 17 of 25 and 14 of 25 unrelated Hia-expressing NTHi strains. Overall, they mediated killing of 20 of 25 Hia-expressing strains. OMVs from prototype NTHi strain 12 were used to immunize chinchillas and the course of middle ear infection was monitored following intrabullar challenge with the homologous strain. All control animals developed culture-positive otitis media, as did two of three HMW1/HMW2-immunized animals. All OMV-immunized animals, with or without supplemental HMW1/HMW2 immunization, were completely protected against otitis media. NTHi OMVs are the first immunogens examined in this model that provided complete protection with sterile immunity after NTHi strain 12 challenge. These data suggest that NTHi OMVs hold significant potential as components of protective NTHi vaccines, possibly in combination with HMW1/HMW2 proteins. Copyright © 2017 American Society for Microbiology.

  3. Anterior temporal cortex and semantic memory: reconciling findings from neuropsychology and functional imaging.

    PubMed

    Rogers, Timothy T; Hocking, Julia; Noppeney, Uta; Mechelli, Andrea; Gorno-Tempini, Maria Luisa; Patterson, Karalyn; Price, Cathy J

    2006-09-01

    Studies of semantic impairment arising from brain disease suggest that the anterior temporal lobes are critical for semantic abilities in humans; yet activation of these regions is rarely reported in functional imaging studies of healthy controls performing semantic tasks. Here, we combined neuropsychological and PET functional imaging data to show that when healthy subjects identify concepts at a specific level, the regions activated correspond to the site of maximal atrophy in patients with relatively pure semantic impairment. The stimuli were color photographs of common animals or vehicles, and the task was category verification at specific (e.g., robin), intermediate (e.g., bird), or general (e.g., animal) levels. Specific, relative to general, categorization activated the antero-lateral temporal cortices bilaterally, despite matching of these experimental conditions for difficulty. Critically, in patients with atrophy in precisely these areas, the most pronounced deficit was in the retrieval of specific semantic information.

  4. Genetic inheritance of pulp colour and selected traits of cassava (Manihot esculenta Crantz) at early generation selection.

    PubMed

    Nduwumuremyi, Athanase; Melis, Rob; Shanahan, Paul; Theodore, Asiimwe

    2018-06-01

    The early generation selection of cassava quantitative and qualitative traits saves breeding resources as it can shorten breeding schemes. Inheritance analysis provides important breeding information for developing new improved varieties. This study aimed at developing an F1 segregating cassava population and determining mode of gene action of pulp colour and selected traits at early generation selection (F1 seedling and clones). The 15 families exhibited significant (P < 0.05) phenotypic variation between offspring. The general combining ability (GCA) was significant for all traits except cassava brown streak disease on leaves, whereas specific combining ability (SCA) was significant for all evaluated traits. The Garukansubire and Gitamisi genotypes were the best general combiners for improving fresh storage root yield, while G1 and G2 were the best general combiners for improved carotenoid (yellow/orange pulp colour) and delayed physiological postharvest deterioration. The pulp colour had the highest GCA/SCA ratio and percent sum of squares due to GCA. The 15 F1 families exhibited essential genetic diversity for cassava improvement. The expression of most cassava traits was controlled by both additive and non-additive gene action. The study elucidated the role of dominance effects over the additive effects for the evaluated traits. However, the pulp colour was predominantly controlled by additive gene action. This implies the possibility of improving cassava through conventional breeding using recurrent selection for most traits. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  5. Rapid and Sensitive Enumeration of Viable Diluted Cells of Members of the Family Enterobacteriaceae in Freshwater and Drinking Water

    PubMed Central

    Baudart, Julia; Coallier, Josée; Laurent, Patrick; Prévost, Michèle

    2002-01-01

    Water quality assessment involves the specific, sensitive, and rapid detection of bacterial indicators and pathogens in water samples, including viable but nonculturable (VBNC) cells. This work evaluates the specificity and sensitivity of a new method which combines a fluorescent in situ hybridization (FISH) approach with a physiological assay (direct viable count [DVC]) for the direct enumeration, at the single-cell level, of highly diluted viable cells of members of the family Enterobacteriaceae in freshwater and drinking water after membrane filtration. The approach (DVC-FISH) uses a new direct detection device, the laser scanning cytometer (Scan RDI). Combining the DVC-FISH method on a membrane with Scan RDI detection makes it possible to detect as few as one targeted cell in approximately 108 nontargeted cells spread over the membrane. The ability of this new approach to detect and enumerate VBNC enterobacterial cells in freshwater and drinking water distribution systems was investigated and is discussed. PMID:12324357

  6. Pathogen variation and urea influence selection and success of Streptomyces mixtures in biological control.

    PubMed

    Otto-Hanson, L K; Grabau, Z; Rosen, C; Salomon, C E; Kinkel, L L

    2013-01-01

    Success in biological control of plant diseases remains inconsistent in the field. A collection of well-characterized Streptomyces antagonists (n = 19 isolates) was tested for their capacities to inhibit pathogenic Streptomyces scabies (n = 15 isolates). There was significant variation among antagonists in ability to inhibit pathogen isolates and among pathogens in their susceptibility to inhibition. Only one antagonist could inhibit all pathogens, and antagonist-pathogen interactions were highly specific, highlighting the limitations of single-strain inoculum in biological control. However, the collection of pathogens could be inhibited by several combinations of antagonists, suggesting the potential for successful antagonist mixtures. Urea generally increased effectiveness of antagonists at inhibiting pathogens in vitro (increased mean inhibition zones) but its specific effects varied among antagonist-pathogen combinations. In greenhouse trials, urea enhanced the effectiveness of antagonist mixtures relative to individual antagonists in controlling potato scab. Although antagonist mixtures were frequently antagonistic in the absence of urea, all n= 2 and n = 3 antagonist-isolate combinations were synergistic in the presence of urea. This work provides insights into the efficacy of single- versus multiple-strain inocula in biological control and on the potential for nutrients to influence mixture success.

  7. Process characteristics of the combination of laser beam- and gas metal arc welding

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

    Kalla, G.; Neuenhahn, J.; Koerber, C.

    1994-12-31

    In this presentation, experiences regarding the combination of laser beam-and gas metal arc welding are discussed. The combination of both techniques offers the possibility of using the specific advantages include the deep penetration effect and the concentrated heat input. Additionally, the gas metal arc welding (GMAW) process is characterized by several advantages, such as high thermal efficiency and good gap-bridging ability. Beyond these characteristics, the combination leads to additional advantages concerning process, technique, and quality. Improvement of seam quality and properties are of special note. Adaptation of the GMAW parameters reduces the hardness of the seam weld at increasing weldingmore » speed. This is possible by adapting the efficiency of metal deposition and by the suitable choice of wire material composition. Another advantage is an improvement of surface topology. The surface of the weld seam and the connection to the base material are very smooth. This leads to advantages with regard to the fatigue strength of the seam.« less

  8. Tabletop Femtosecond VUV Photoionization and PEPICO Detection of Microreactor Pyrolysis Products.

    PubMed

    Couch, David E; Buckingham, Grant T; Baraban, Joshua H; Porterfield, Jessica P; Wooldridge, Laura A; Ellison, G Barney; Kapteyn, Henry C; Murnane, Margaret M; Peters, William K

    2017-07-20

    We report the combination of tabletop vacuum ultraviolet photoionization with photoion-photoelectron coincidence spectroscopy for sensitive, isomer-specific detection of nascent products from a pyrolysis microreactor. Results on several molecules demonstrate two essential capabilities that are very straightforward to implement: the ability to differentiate isomers and the ability to distinguish thermal products from dissociative ionization. Here, vacuum ultraviolet light is derived from a commercial tabletop femtosecond laser system, allowing data to be collected at 10 kHz; this high repetition rate is critical for coincidence techniques. The photoion-photoelectron coincidence spectrometer uses the momentum of the ion to identify dissociative ionization events and coincidence techniques to provide a photoelectron spectrum specific to each mass, which is used to distinguish different isomers. We have used this spectrometer to detect the pyrolysis products that result from the thermal cracking of acetaldehyde, cyclohexene, and 2-butanol. The photoion-photoelectron spectrometer can detect and identify organic radicals and reactive intermediates that result from pyrolysis. Direct comparison of laboratory and synchrotron data illustrates the advantages and potential of this approach.

  9. The effects of musical training on movement pre-programming and re-programming abilities: an event-related potential investigation.

    PubMed

    Anatürk, Melis; Jentzsch, Ines

    2015-03-01

    Two response precuing experiments were conducted to investigate effects of musical skill level on the ability to pre- and re-programme simple movements. Participants successfully used advance information to prepare forthcoming responses and showed response slowing when precue information was invalid rather than valid. This slowing was, however, only observed for partially invalid but not fully invalid precues. Musicians were generally faster than non-musicians, but no group differences in the efficiency of movement pre-programming or re-programming were observed. Interestingly, only musicians exhibited a significant foreperiod lateralized readiness potential (LRP) when response hand was pre-specified or full advance information was provided. These LRP findings suggest increased effector-specific motor preparation in musicians than non-musicians. However, here the levels of effector-specific preparation did not predict preparatory advantages observed in behaviour. In sum, combining the response precuing and ERP paradigms serves a valuable tool to examine influences of musical training on movement pre- or re-programming processes. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Urban soil exploration through multi-receiver electromagnetic induction and stepped-frequency ground penetrating radar.

    PubMed

    Van De Vijver, Ellen; Van Meirvenne, Marc; Vandenhaute, Laura; Delefortrie, Samuël; De Smedt, Philippe; Saey, Timothy; Seuntjens, Piet

    2015-07-01

    In environmental assessments, the characterization of urban soils relies heavily on invasive investigation, which is often insufficient to capture their full spatial heterogeneity. Non-invasive geophysical techniques enable rapid collection of high-resolution data and provide a cost-effective alternative to investigate soil in a spatially comprehensive way. This paper presents the results of combining multi-receiver electromagnetic induction and stepped-frequency ground penetrating radar to characterize a former garage site contaminated with petroleum hydrocarbons. The sensor combination showed the ability to identify and accurately locate building remains and a high-density soil layer, thus demonstrating the high potential to investigate anthropogenic disturbances of physical nature. In addition, a correspondence was found between an area of lower electrical conductivity and elevated concentrations of petroleum hydrocarbons, suggesting the potential to detect specific chemical disturbances. We conclude that the sensor combination provides valuable information for preliminary assessment of urban soils.

  11. Prospecting of popcorn hybrids for resistance to fall armyworm.

    PubMed

    Crubelati-Mulati, N C S; Scapim, C A; Albuquerque, F A; Amaral Junior, A T; Vivas, M; Rodovalho, M A

    2014-08-26

    The fall armyworm, Spodoptera frugiperda, is the pest that causes the greatest economic losses for both common corn and popcorn crops, and the use of resistant plant genotypes is an important tool for integrated pest management. The goal of the present study was to evaluate the damage caused by S. frugiperda on single-cross popcorn hybrids under field conditions with natural infestation as well as to study the effect of 11 popcorn hybrids on the S. frugiperda life cycle under laboratory conditions. A completely randomized block design with 4 replicates was used for the field experiment, and a completely randomized design with 10 replicates was used for the laboratory experiment. In the field experiment, the damage caused by fall armyworm, grain yield, and popping expansion were quantified, and a diallel analysis was performed to select the best hybrids. For the laboratory experiment, caterpillars were obtained from laboratory cultures kept on an artificial diet and were fed with leaves from the 11 hybrids. Hybrids P7.0 x P9.4, P7.1 x P9.6, P7.2.0 x P9.3, P7.4.0 x P9.1 and P7.4.1 x P9.4 exhibited negative specific combining ability for injury by fall armyworm and positive specific combining ability for yield and popping expansion. In the laboratory experiment, the hybrids influenced the mean larval stage duration, mean larval mass, final larval mass, pupal stage duration, mean pupal mass, and adult longevity.

  12. Working Memory Integration Processes in Benign Childhood Epilepsy with Centrotemporal Spikes.

    PubMed

    Kárpáti, Judit; Donauer, Nándor; Somogyi, Eszter; Kónya, Anikó

    2015-12-01

    Benign epilepsy of childhood with centrotemporal spikes (BECTS) is the most frequent focal epilepsy in children; however, the pattern of affected memory processes remains controversial. Previous studies in BECTS imply deficits in complex working memory tasks, but not in simple modality-specific tasks. We studied working memory processes in children with BECTS by comparing performance in memory binding tasks of different complexities. We compared 17 children with BECTS (aged 6 to 13 years) to 17 healthy children matched for age, sex, and intelligence quotient. We measured spatial and verbal memory components separately and jointly on three single-binding tasks (binding of what and where; what and when; and where and when) and a combined-binding task (integration of what, where, and when). We also evaluated basic visuospatial memory functions with subtests of the Children's Memory Scale, and intellectual abilities with verbal tasks of the Wechsler Intelligence Scale for Children-Fourth Edition and the Raven Progressive Matrices. We found no difference between the BECTS and control groups in single-binding tasks; however, the children with BECTS performed significantly worse on the combined task, which included integration of spatial, verbal, and temporal information. We found no deficits in their intellectual abilities or basic visuospatial memory functions. Children with BECTS may have intact simple maintenance processes of working memory, but difficulty with high-level functions requiring attentional and executive resources. Our findings imply no specific memory dysfunction in BECTS, but suggest difficulties in integrating information within working memory, and possible frontal lobe disturbances.

  13. Chemokines additional to IFN-γ can be used to differentiate among Mycobacterium tuberculosis infection possibilities and provide evidence of an early clearance phenotype.

    PubMed

    Nonghanphithak, Ditthawat; Reechaipichitkul, Wipa; Namwat, Wises; Naranbhai, Vivek; Faksri, Kiatichai

    2017-07-01

    Current diagnostic tests for tuberculosis (TB) remain limited in their ability to discriminate between active TB (ATB) and latent TB infection (LTBI). Early clearance (EC) of TB by individuals exposed to Mycobacterium tuberculosis is a debated phenomenon for which evidence is lacking. We measured and compared secreted chemokines in the plasma fraction from 48 ATB, 38 LTBI, 162 presumed EC and 39 healthy controls (HC) using the QuantiFERON ® -TB Gold In-Tube assay. Single chemokine markers were limited in their ability to discriminate between ATB and LTBI: IFN-γ showed 16.7% sensitivity; CCL2 showed moderate sensitivity (70.8%) and specificity (74.4%); CXCL10 showed high sensitivity (87.5%) and specificity (78.9%). Compared to IFN-γ alone, IFN-γ combined with CXCL10 significantly improved (p < 0.001) the sensitivity and specificity to discriminate between ATB and HC (97.9% sensitivity and 94.9% specificity) and between ATB and LTBI (89.6% sensitivity and 71.1% specificity). Levels of CCL2 were very significantly lower (p < 0.0001) in EC compared to HC groups and hence CCL2 is a useful marker for EC. This study demonstrated the potential application of profiling using multiple chemokines for differentiating among the various M. tuberculosis infection possibilities. We also present evidence to support the EC phenomenon based on the decrease of CCL2 levels. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. 48 CFR 18.107 - AbilityOne specification changes.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... changes. 18.107 Section 18.107 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION... AbilityOne specification changes. Contracting officers are not held to the notification required when changes in AbilityOne specifications or descriptions are required to meet emergency needs. (See 8.712(d...

  15. Enhanced backgrounds in scene rendering with GTSIMS

    NASA Astrophysics Data System (ADS)

    Prussing, Keith F.; Pierson, Oliver; Cordell, Chris; Stewart, John; Nielson, Kevin

    2018-05-01

    A core component to modeling visible and infrared sensor responses is the ability to faithfully recreate background noise and clutter in a synthetic image. Most tracking and detection algorithms use a combination of signal to noise or clutter to noise ratios to determine if a signature is of interest. A primary source of clutter is the background that defines the environment in which a target is placed. Over the past few years, the Electro-Optical Systems Laboratory (EOSL) at the Georgia Tech Research Institute has made significant improvements to its in house simulation framework GTSIMS. First, we have expanded our terrain models to include the effects of terrain orientation on emission and reflection. Second, we have included the ability to model dynamic reflections with full BRDF support. Third, we have added the ability to render physically accurate cirrus clouds. And finally, we have updated the overall rendering procedure to reduce the time necessary to generate a single frame by taking advantage of hardware acceleration. Here, we present the updates to GTSIMS to better predict clutter and noise doe to non-uniform backgrounds. Specifically, we show how the addition of clouds, terrain, and improved non-uniform sky rendering improve our ability to represent clutter during scene generation.

  16. Polyunsaturated fatty acids (PUFAs) for children with specific learning disorders.

    PubMed

    Tan, May Loong; Ho, Jacqueline J; Teh, Keng Hwang

    2016-09-28

    About 5% of school children have a specific learning disorder, defined as unexpected failure to acquire adequate abilities in reading, writing or mathematics that is not a result of reduced intellectual ability, inadequate teaching or social deprivation. Of these events, 80% are reading disorders. Polyunsaturated fatty acids (PUFAs), in particular, omega-3 and omega-6 fatty acids, which normally are abundant in the brain and in the retina, are important for learning. Some children with specific learning disorders have been found to be deficient in these PUFAs, and it is argued that supplementation of PUFAs may help these children improve their learning abilities. 1. To assess effects on learning outcomes of supplementation of polyunsaturated fatty acids (PUFAs) for children with specific learning disorders.2. To determine whether adverse effects of supplementation of PUFAs are reported in these children. In November 2015, we searched CENTRAL, Ovid MEDLINE, Embase, PsycINFO, 10 other databases and two trials registers. We also searched the reference lists of relevant articles. Randomised controlled trials (RCTs) or quasi-RCTs comparing PUFAs with placebo or no treatment in children younger than 18 years with specific learning disabilities, as diagnosed in accordance with the fifth (or earlier) edition of theDiagnostic and Statistical Manual of Mental Disorders (DSM-5), or the 10th (or earlier) revision of the International Classification of Diseases (ICD-10) or equivalent criteria. We included children with coexisting developmental disorders such as attention deficit hyperactivity disorder (ADHD) or autism. Two review authors (MLT and KHT) independently screened the titles and abstracts of articles identified by the search and eliminated all studies that did not meet the inclusion criteria. We contacted study authors to ask for missing information and clarification, when needed. We used the GRADE approach to assess the quality of evidence. Two small studies involving 116 children, mainly boys between 10 and 18 years of age, met the inclusion criteria. One study was conducted in a school setting, the other at a specialised clinic. Both studies used three months of a combination of omega-3 and omega-6 supplements as the intervention compared with placebo. Although both studies had generally low risk of bias, we judged the risk of reporting bias as unclear in one study, and as high in the other study. In addition, one of the studies was funded by industry and reported active company involvement in the study.None of the studies reported data on the primary outcomes of reading, writing, spelling and mathematics scores, as assessed by standardised tests.Evidence of low quality indicates that supplementation of PUFAs did not increase the risk of gastrointestinal disturbances (risk ratio 1.43, 95% confidence interval 0.25 to 8.15; two studies, 116 children). Investigators reported no other adverse effects.Both studies reported attention deficit hyperactivity disorder (ADHD)-related behaviour outcomes. We were unable to combine the results in a meta-analysis because one study reported findings as a continuous outcome, and the other as a dichotomous outcome. No other secondary outcomes were reported.We excluded one study because it used a cointervention (carnosine), and five other studies because they did not provide a robust diagnosis of a specific learning disorder. We identified one ongoing study and found three studies awaiting classification. Evidence is insufficient to permit any conclusions about the effect of PUFAs on the learning abilities of children with specific learning disorders. Well-designed RCTs with clearly defined populations of children with specific learning disorders who have been diagnosed by standardised diagnostic criteria are needed.

  17. Odour maps in the brain of butterflies with divergent host-plant preferences.

    PubMed

    Carlsson, Mikael A; Bisch-Knaden, Sonja; Schäpers, Alexander; Mozuraitis, Raimondas; Hansson, Bill S; Janz, Niklas

    2011-01-01

    Butterflies are believed to use mainly visual cues when searching for food and oviposition sites despite that their olfactory system is morphologically similar to their nocturnal relatives, the moths. The olfactory ability in butterflies has, however, not been thoroughly investigated. Therefore, we performed the first study of odour representation in the primary olfactory centre, the antennal lobes, of butterflies. Host plant range is highly variable within the butterfly family Nymphalidae, with extreme specialists and wide generalists found even among closely related species. Here we measured odour evoked Ca(2+) activity in the antennal lobes of two nymphalid species with diverging host plant preferences, the specialist Aglais urticae and the generalist Polygonia c-album. The butterflies responded with stimulus-specific combinations of activated glomeruli to single plant-related compounds and to extracts of host and non-host plants. In general, responses were similar between the species. However, the specialist A. urticae responded more specifically to its preferred host plant, stinging nettle, than P. c-album. In addition, we found a species-specific difference both in correlation between responses to two common green leaf volatiles and the sensitivity to these compounds. Our results indicate that these butterflies have the ability to detect and to discriminate between different plant-related odorants.

  18. Odour Maps in the Brain of Butterflies with Divergent Host-Plant Preferences

    PubMed Central

    Schäpers, Alexander; Mozuraitis, Raimondas; Hansson, Bill S.; Janz, Niklas

    2011-01-01

    Butterflies are believed to use mainly visual cues when searching for food and oviposition sites despite that their olfactory system is morphologically similar to their nocturnal relatives, the moths. The olfactory ability in butterflies has, however, not been thoroughly investigated. Therefore, we performed the first study of odour representation in the primary olfactory centre, the antennal lobes, of butterflies. Host plant range is highly variable within the butterfly family Nymphalidae, with extreme specialists and wide generalists found even among closely related species. Here we measured odour evoked Ca2+ activity in the antennal lobes of two nymphalid species with diverging host plant preferences, the specialist Aglais urticae and the generalist Polygonia c-album. The butterflies responded with stimulus-specific combinations of activated glomeruli to single plant-related compounds and to extracts of host and non-host plants. In general, responses were similar between the species. However, the specialist A. urticae responded more specifically to its preferred host plant, stinging nettle, than P. c-album. In addition, we found a species-specific difference both in correlation between responses to two common green leaf volatiles and the sensitivity to these compounds. Our results indicate that these butterflies have the ability to detect and to discriminate between different plant-related odorants. PMID:21901154

  19. Who rises to the top? Early indicators.

    PubMed

    Kell, Harrison J; Lubinski, David; Benbow, Camilla P

    2013-05-01

    Youth identified before age 13 (N = 320) as having profound mathematical or verbal reasoning abilities (top 1 in 10,000) were tracked for nearly three decades. Their awards and creative accomplishments by age 38, in combination with specific details about their occupational responsibilities, illuminate the magnitude of their contribution and professional stature. Many have been entrusted with obligations and resources for making critical decisions about individual and organizational well-being. Their leadership positions in business, health care, law, the professoriate, and STEM (science, technology, engineering, and mathematics) suggest that many are outstanding creators of modern culture, constituting a precious human-capital resource. Identifying truly profound human potential, and forecasting differential development within such populations, requires assessing multiple cognitive abilities and using atypical measurement procedures. This study illustrates how ultimate criteria may be aggregated and longitudinally sequenced to validate such measures.

  20. Biotin-Containing Reduced Graphene Oxide-Based Nanosystem as a Multieffect Anticancer Agent: Combining Hyperthermia with Targeted Chemotherapy.

    PubMed

    Mauro, Nicolò; Scialabba, Cinzia; Cavallaro, Gennara; Licciardi, Mariano; Giammona, Gaetano

    2015-09-14

    Among the relevant properties of graphene derivatives, their ability of acting as an energy-converting device so as to produce heat (i.e., thermoablation and hyperthermia) was more recently taken into account for the treatment of solid tumors. In this pioneering study, for the first time, the in vitro RGO-induced hyperthermia was assessed and combined with the stimuli-sensitive anticancer effect of a biotinylated inulin-doxorubicin conjugate (CJ-PEGBT), hence, getting to a nanosystem endowed with synergic anticancer effects and high specificity. CJ-PEGBT was synthesized by linking pentynoic acid and citraconic acid to inulin. The citraconylamide pendants, used as pH reversible spacer, were exploited to further conjugate doxorubicin, whereas the alkyne moiety was orthogonally functionalized with an azido PEG-biotin derivative by copper(II) catalyzed 1,3-dipolar cycloaddition. DSC measures, AFM, and UV spectrophotometry were employed to systematically investigate adsorption of CJ-PEGBT onto RGO and its physicochemical stability in aqueous media, demonstrating that a stable π-staked nanosystem can be obtained. In vitro tests using cancer breast cells (MCF-7) showed the ability of the RGO/CJ-PEGBT of efficiently killing cancer cells both via a selective laser beam thermoablation and hyperthermia-triggered chemotherapy. If compared with the nonbiotinylated nanosystem, including virgin RGO and the free conjugate, RGO/CJ-PEGBT is endowed with a smart combination of properties which warrant potential as an anticancer nanomedicine.

  1. Differential effect of plant lipids on membrane organization: specificities of phytosphingolipids and phytosterols.

    PubMed

    Grosjean, Kevin; Mongrand, Sébastien; Beney, Laurent; Simon-Plas, Françoise; Gerbeau-Pissot, Patricia

    2015-02-27

    The high diversity of the plant lipid mixture raises the question of their respective involvement in the definition of membrane organization. This is particularly the case for plant plasma membrane, which is enriched in specific lipids, such as free and conjugated forms of phytosterols and typical phytosphingolipids, such as glycosylinositolphosphoceramides. This question was here addressed extensively by characterizing the order level of membrane from vesicles prepared using various plant lipid mixtures and labeled with an environment-sensitive probe. Fluorescence spectroscopy experiments showed that among major phytosterols, campesterol exhibits a stronger ability than β-sitosterol and stigmasterol to order model membranes. Multispectral confocal microscopy, allowing spatial analysis of membrane organization, demonstrated accordingly the strong ability of campesterol to promote ordered domain formation and to organize their spatial distribution at the membrane surface. Conjugated sterol forms, alone and in synergy with free sterols, exhibit a striking ability to order membrane. Plant sphingolipids, particularly glycosylinositolphosphoceramides, enhanced the sterol-induced ordering effect, emphasizing the formation and increasing the size of sterol-dependent ordered domains. Altogether, our results support a differential involvement of free and conjugated phytosterols in the formation of ordered domains and suggest that the diversity of plant lipids, allowing various local combinations of lipid species, could be a major contributor to membrane organization in particular through the formation of sphingolipid-sterol interacting domains. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. Activation of multiple chemotherapeutic prodrugs by the natural enzymolome of tumour-localised probiotic bacteria.

    PubMed

    Lehouritis, Panos; Stanton, Michael; McCarthy, Florence O; Jeavons, Matthieu; Tangney, Mark

    2016-01-28

    Some chemotherapeutic drugs (prodrugs) require activation by an enzyme for efficacy. We and others have demonstrated the ability of probiotic bacteria to grow specifically within solid tumours following systemic administration, and we hypothesised that the natural enzymatic activity of these tumour-localised bacteria may be suitable for activation of certain such chemotherapeutic drugs. Several wild-type probiotic bacteria; Escherichia coli Nissle, Bifidobacterium breve, Lactococcus lactis and Lactobacillus species, were screened against a panel of popular prodrugs. All strains were capable of activating at least one prodrug. E. coli Nissle 1917 was selected for further studies because of its ability to activate numerous prodrugs and its resistance to prodrug toxicity. HPLC data confirmed biochemical transformation of prodrugs to their toxic counterparts. Further analysis demonstrated that different enzymes can complement prodrug activation, while simultaneous activation of multiple prodrugs (CB1954, 5-FC, AQ4N and Fludarabine phosphate) by E. coli was confirmed, resulting in significant efficacy improvement. Experiments in mice harbouring murine tumours validated in vitro findings, with significant reduction in tumour growth and increase in survival of mice treated with probiotic bacteria and a combination of prodrugs. These findings demonstrate the ability of probiotic bacteria, without the requirement for genetic modification, to enable high-level activation of multiple prodrugs specifically at the site of action. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Phase II Study of HER-2/neu Intracellular Domain Peptide-Based Vaccine Administered to Stage IV HER2 Positive Breast Cancer Patients Receiving Trastuzumab

    DTIC Science & Technology

    2007-05-01

    the combined approach as well as the immunogenicity of HER2 ICD peptide vaccination. If there is evidence to suggest that the true rate of Grade IV... approach will be evaluated as the ability of the vaccine to elicit HER2 ICD specific T cell immunity, to elicit epitope spreading, and to stimulate...July 2006. Unfortunately, by the time all needed source documents (i.e., imaging, clinical labs, cardiac function tests) were collected, this

  4. Educational games for brain health: revealing their unexplored potential through a neurocognitive approach.

    PubMed

    Fissler, Patrick; Kolassa, Iris-Tatjana; Schrader, Claudia

    2015-01-01

    Educational games link the motivational nature of games with learning of knowledge and skills. Here, we go beyond effects on these learning outcomes. We review two lines of evidence which indicate the currently unexplored potential of educational games to promote brain health: First, gaming with specific neurocognitive demands (e.g., executive control), and second, educational learning experiences (e.g., studying foreign languages) improve brain health markers. These markers include cognitive ability, brain function, and brain structure. As educational games allow the combination of specific neurocognitive demands with educational learning experiences, they seem to be optimally suited for promoting brain health. We propose a neurocognitive approach to reveal this unexplored potential of educational games in future research.

  5. Educational games for brain health: revealing their unexplored potential through a neurocognitive approach

    PubMed Central

    Fissler, Patrick; Kolassa, Iris-Tatjana; Schrader, Claudia

    2015-01-01

    Educational games link the motivational nature of games with learning of knowledge and skills. Here, we go beyond effects on these learning outcomes. We review two lines of evidence which indicate the currently unexplored potential of educational games to promote brain health: First, gaming with specific neurocognitive demands (e.g., executive control), and second, educational learning experiences (e.g., studying foreign languages) improve brain health markers. These markers include cognitive ability, brain function, and brain structure. As educational games allow the combination of specific neurocognitive demands with educational learning experiences, they seem to be optimally suited for promoting brain health. We propose a neurocognitive approach to reveal this unexplored potential of educational games in future research. PMID:26257697

  6. Decalcification and survival of benthic foraminifera under the combined impacts of varying pH and salinity.

    PubMed

    Charrieau, Laurie M; Filipsson, Helena L; Nagai, Yukiko; Kawada, Sachiko; Ljung, Karl; Kritzberg, Emma; Toyofuku, Takashi

    2018-07-01

    Coastal areas display natural large environmental variability such as frequent changes in salinity, pH, and carbonate chemistry. Anthropogenic impacts - especially ocean acidification - increase this variability, which may affect the living conditions of coastal species, particularly, calcifiers. We performed culture experiments on living benthic foraminifera to study the combined effects of lowered pH and salinity on the calcification abilities and survival of the coastal, calcitic species Ammonia sp. and Elphidium crispum. We found that in open ocean conditions (salinity ∼35) and lower pH than usual values for these species, the specimens displayed resistance to shell (test) dissolution for a longer time than in brackish conditions (salinity ∼5 to 20). However, the response was species specific as Ammonia sp. specimens survived longer than E. crispum specimens when placed in the same conditions of salinity and pH. Living, decalcified juveniles of Ammonia sp. were observed and we show that desalination is one cause for the decalcification. Finally, we highlight the ability of foraminifera to survive under Ω calc  < 1, and that high salinity and [Ca 2+ ] as building blocks are crucial for the foraminiferal calcification process. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. A Proposed Neurological Interpretation of Language Evolution.

    PubMed

    Ardila, Alfredo

    2015-01-01

    Since the very beginning of the aphasia history it has been well established that there are two major aphasic syndromes (Wernicke's-type and Broca's-type aphasia); each one of them is related to the disturbance at a specific linguistic level (lexical/semantic and grammatical) and associated with a particular brain damage localization (temporal and frontal-subcortical). It is proposed that three stages in language evolution could be distinguished: (a) primitive communication systems similar to those observed in other animals, including nonhuman primates; (b) initial communication systems using sound combinations (lexicon) but without relationships among the elements (grammar); and (c) advanced communication systems including word-combinations (grammar). It is proposed that grammar probably originated from the internal representation of actions, resulting in the creation of verbs; this is an ability that depends on the so-called Broca's area and related brain networks. It is suggested that grammar is the basic ability for the development of so-called metacognitive executive functions. It is concluded that while the lexical/semantic language system (vocabulary) probably appeared during human evolution long before the contemporary man (Homo sapiens sapiens), the grammatical language historically represents a recent acquisition and is correlated with the development of complex cognition (metacognitive executive functions).

  8. A Proposed Neurological Interpretation of Language Evolution

    PubMed Central

    2015-01-01

    Since the very beginning of the aphasia history it has been well established that there are two major aphasic syndromes (Wernicke's-type and Broca's-type aphasia); each one of them is related to the disturbance at a specific linguistic level (lexical/semantic and grammatical) and associated with a particular brain damage localization (temporal and frontal-subcortical). It is proposed that three stages in language evolution could be distinguished: (a) primitive communication systems similar to those observed in other animals, including nonhuman primates; (b) initial communication systems using sound combinations (lexicon) but without relationships among the elements (grammar); and (c) advanced communication systems including word-combinations (grammar). It is proposed that grammar probably originated from the internal representation of actions, resulting in the creation of verbs; this is an ability that depends on the so-called Broca's area and related brain networks. It is suggested that grammar is the basic ability for the development of so-called metacognitive executive functions. It is concluded that while the lexical/semantic language system (vocabulary) probably appeared during human evolution long before the contemporary man (Homo sapiens sapiens), the grammatical language historically represents a recent acquisition and is correlated with the development of complex cognition (metacognitive executive functions). PMID:26124540

  9. Chemical modification of birch allergen extract leads to a reduction in allergenicity as well as immunogenicity.

    PubMed

    Würtzen, Peter Adler; Lund, Lise; Lund, Gitte; Holm, Jens; Millner, Anders; Henmar, Helene

    2007-01-01

    In Europe, specific immunotherapy is currently conducted with vaccines containing allergen preparations based on intact extracts. In addition to this, chemically modified allergen extracts (allergoids) are used for specific allergy treatment. Reduced allergenicity and thereby reduced risk of side effects in combination with retained ability to activate T cells and induce protective allergen-specific antibody responses has been claimed for allergoids. In the current study, we compared intact allergen extracts and allergoids with respect to allergenicity and immunogenicity. The immunological response to birch allergen extract, alum-adsorbed extract, birch allergoid and alum-adsorbed allergoid was investigated in vitro in human basophil histamine release assay and by stimulation of human allergen-specific T cell lines. In vivo, Bet v 1-specific IgG titers in mice were determined after repetitive immunizations. In all patients tested (n = 8), allergoid stimulations led to reduced histamine release compared to the intact allergen extract. However, the allergoid preparations were not recognized by Bet v 1-specific T cell lines (n = 7), which responded strongly to the intact allergen extract. Mouse immunizations showed a clearly reduced IgG induction by allergoids and a strongly potentiating effect of the alum adjuvant. Optimal IgG titers were obtained after 3 immunizations with intact allergen extracts, while 5 immunizations were needed to obtain maximal response to the allergoid. The reduced histamine release observed for allergoid preparations may be at the expense of immunological efficacy because the chemical modifications lead to a clear reduction in T cell activation and the ability to induce allergen-specific IgG antibody responses. Copyright 2007 S. Karger AG, Basel.

  10. Impaired intervertebral disc development and premature disc degeneration in mice with notochord-specific deletion of CCN2.

    PubMed

    Bedore, Jake; Sha, Wei; McCann, Matthew R; Liu, Shangxi; Leask, Andrew; Séguin, Cheryle A

    2013-10-01

    Currently, our ability to treat intervertebral disc (IVD) degeneration is hampered by an incomplete understanding of disc development and aging. The specific function of matricellular proteins, including CCN2, during these processes remains an enigma. The aim of this study was to determine the tissue-specific localization of CCN proteins and to characterize their role in IVD tissues during embryonic development and age-related degeneration by using a mouse model of notochord-specific CCN2 deletion. Expression of CCN proteins was assessed in IVD tissues from wild-type mice beginning on embryonic day 15.5 to 17 months of age. Given the enrichment of CCN2 in notochord-derived tissues, we generated notochord-specific CCN2-null mice to assess the impact on the IVD structure and extracellular matrix composition. Using a combination of histologic evaluation and magnetic resonance imaging (MRI), IVD health was assessed. Loss of the CCN2 gene in notochord-derived cells disrupted the formation of IVDs in embryonic and newborn mice, resulting in decreased levels of aggrecan and type II collagen and concomitantly increased levels of type I collagen within the nucleus pulposus. CCN2-knockout mice also had altered expression of CCN1 (Cyr61) and CCN3 (Nov). Mirroring its role during early development, notochord-specific CCN2 deletion accelerated age-associated degeneration of IVDs. Using a notochord-specific gene targeting strategy, this study demonstrates that CCN2 expression by nucleus pulposus cells is essential to the regulation of IVD development and age-associated tissue maintenance. The ability of CCN2 to regulate the composition of the intervertebral disc suggests that it may represent an intriguing clinical target for the treatment of disc degeneration. Copyright © 2013 by the American College of Rheumatology.

  11. Advances in combination therapy of lung cancer: Rationales, delivery technologies and dosage regimens.

    PubMed

    Wu, Lan; Leng, Donglei; Cun, Dongmei; Foged, Camilla; Yang, Mingshi

    2017-08-28

    Lung cancer is a complex disease caused by a multitude of genetic and environmental factors. The progression of lung cancer involves dynamic changes in the genome and a complex network of interactions between cancer cells with multiple, distinct cell types that form tumors. Combination therapy using different pharmaceuticals has been proven highly effective due to the ability to affect multiple cellular pathways involved in the disease progression. However, the currently used drug combination designs are primarily based on empirical clinical studies, and little attention has been given to dosage regimens, i.e. how administration routes, onsets, and durations of the combinations influence the therapeutic outcome. This is partly because combination therapy is challenged by distinct physicochemical properties and in vivo pharmacokinetics/pharmacodynamics of the individual pharmaceuticals, including small molecule drugs and biopharmaceuticals, which make the optimization of dosing and administration schedule challenging. This article reviews the recent advances in the design and development of combinations of pharmaceuticals for the treatment of lung cancer. Focus is primarily on rationales for the selection of specific combination therapies for lung cancer treatment, and state of the art of delivery technologies and dosage regimens for the combinations, tested in preclinical and clinical trials. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Learning physics concepts as a function of colloquial language usage

    NASA Astrophysics Data System (ADS)

    Maier, Steven J.

    Data from two sections of college introductory, algebra-based physics courses (n1 = 139, n2 = 91) were collected using three separate instruments to investigate the relationships between reasoning ability, conceptual gain and colloquial language usage. To obtain a measure of reasoning ability, Lawson's Classroom Test of Scientific Reasoning Ability (TSR) was administered once near mid-term for each sample. The Force Concept Inventory (FCI) was administered at the beginning and at the end of the term for pre- and post-test measures. Pre- and post-test data from the Mechanics Language Usage instrument were also collected in conjunction with FCI data collection at the beginning and end of the term. The MLU was developed specifically for this study prior to data collection, and results of a pilot test to establish validity and reliability are reported. T-tests were performed on the data collected to compare the means from each sample. In addition, correlations among the measures were investigated between the samples separately and combined. Results from these investigations served as justification for combining the samples into a single sample of 230 for performing further statistical analyses. The primary objective of this study was to determine if scientific reasoning ability (a function of developmental stage) and conceptual gains in Newtonian mechanics predict students' usages of "force" as measured by the MLU. Regression analyses were performed to evaluate these mediated relationships among TSR and FCI performance as a predictor of MLU performance. Statistically significant correlations and relationships existed among several of the measures, which are discussed at length in the body of the narrative. The findings of this research are that although there exists a discernable relationship between reasoning ability and conceptual change, more work needs to be done to establish improved quantitative measures of the role language usage has in developing understandings of course content.

  13. Relationships between gross- and fine motor functions, cognitive abilities, and self-regulatory aspects of students with physical disabilities.

    PubMed

    Varsamis, Panagiotis; Agaliotis, Ioannis

    2015-12-01

    This article reports research on self-regulatory aspects (i.e., goal-setting, self-efficacy and self-evaluation) of secondary and post-secondary students with congenital motor disabilities, who performed a ball-throwing-at-a-target task. Participants were divided into four subgroups presenting distinct combinations of motor and cognitive abilities (i.e., normal cognitive development and mild physical disabilities, normal cognitive development and severe physical disabilities, mild-to-moderate intellectual disability and mild physical disabilities, and mild-to-moderate intellectual disability and severe physical disabilities). Results showed that students presenting mild motor disabilities exhibited a positive self-concept and self-regulation profile, irrespective of their cognitive functioning. Students with considerable motor disabilities, but without cognitive challenges, presented a negative, though realistic self-concept and self-regulation profile. Finally, students with considerable motor disabilities and mild-to-moderate cognitive disabilities showed a positive, though unrealistic, self-regulation profile. The nature of the diverse relationship of motor and cognitive (dis)abilities to specific self-regulatory aspects are discussed, and important instructional implications are mentioned. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets.

    PubMed

    Lam, Max; Trampush, Joey W; Yu, Jin; Knowles, Emma; Davies, Gail; Liewald, David C; Starr, John M; Djurovic, Srdjan; Melle, Ingrid; Sundet, Kjetil; Christoforou, Andrea; Reinvang, Ivar; DeRosse, Pamela; Lundervold, Astri J; Steen, Vidar M; Espeseth, Thomas; Räikkönen, Katri; Widen, Elisabeth; Palotie, Aarno; Eriksson, Johan G; Giegling, Ina; Konte, Bettina; Roussos, Panos; Giakoumaki, Stella; Burdick, Katherine E; Payton, Antony; Ollier, William; Chiba-Falek, Ornit; Attix, Deborah K; Need, Anna C; Cirulli, Elizabeth T; Voineskos, Aristotle N; Stefanis, Nikos C; Avramopoulos, Dimitrios; Hatzimanolis, Alex; Arking, Dan E; Smyrnis, Nikolaos; Bilder, Robert M; Freimer, Nelson A; Cannon, Tyrone D; London, Edythe; Poldrack, Russell A; Sabb, Fred W; Congdon, Eliza; Conley, Emily Drabant; Scult, Matthew A; Dickinson, Dwight; Straub, Richard E; Donohoe, Gary; Morris, Derek; Corvin, Aiden; Gill, Michael; Hariri, Ahmad R; Weinberger, Daniel R; Pendleton, Neil; Bitsios, Panos; Rujescu, Dan; Lahti, Jari; Le Hellard, Stephanie; Keller, Matthew C; Andreassen, Ole A; Deary, Ian J; Glahn, David C; Malhotra, Anil K; Lencz, Todd

    2017-11-28

    Here, we present a large (n = 107,207) genome-wide association study (GWAS) of general cognitive ability ("g"), further enhanced by combining results with a large-scale GWAS of educational attainment. We identified 70 independent genomic loci associated with general cognitive ability. Results showed significant enrichment for genes causing Mendelian disorders with an intellectual disability phenotype. Competitive pathway analysis implicated the biological processes of neurogenesis and synaptic regulation, as well as the gene targets of two pharmacologic agents: cinnarizine, a T-type calcium channel blocker, and LY97241, a potassium channel inhibitor. Transcriptome-wide and epigenome-wide analysis revealed that the implicated loci were enriched for genes expressed across all brain regions (most strongly in the cerebellum). Enrichment was exclusive to genes expressed in neurons but not oligodendrocytes or astrocytes. Finally, we report genetic correlations between cognitive ability and disparate phenotypes including psychiatric disorders, several autoimmune disorders, longevity, and maternal age at first birth. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  15. Cancer stem cells and drug resistance: the potential of nanomedicine

    PubMed Central

    Vinogradov, Serguei; Wei, Xin

    2012-01-01

    Properties of the small group of cancer cells called tumor-initiating or cancer stem cells (CSCs) involved in drug resistance, metastasis and relapse of cancers can significantly affect tumor therapy. Importantly, tumor drug resistance seems to be closely related to many intrinsic or acquired properties of CSCs, such as quiescence, specific morphology, DNA repair ability and overexpression of antiapoptotic proteins, drug efflux transporters and detoxifying enzymes. The specific microenvironment (niche) and hypoxic stability provide additional protection against anticancer therapy for CSCs. Thus, CSC-focused therapy is destined to form the core of any effective anticancer strategy. Nanomedicine has great potential in the development of CSC-targeting drugs, controlled drug delivery and release, and the design of novel gene-specific drugs and diagnostic modalities. This review is focused on tumor drug resistance-related properties of CSCs and describes current nanomedicine approaches, which could form the basis of novel combination therapies for eliminating metastatic and CSCs. PMID:22471722

  16. Combining functionalised nanoparticles and SERS for the detection of DNA relating to disease.

    PubMed

    Graham, Duncan; Stevenson, Ross; Thompson, David G; Barrett, Lee; Dalton, Colette; Faulds, Karen

    2011-01-01

    DNA functionalised nanoparticle probes offer new opportunities in analyte detection. Ultrasensitive, molecularly specific targeting of analytes is possible through the use of metallic nanoparticles and their ability to generate a surface enhanced Raman scattering (SERS) response. This is leading to a new range of diagnostic clinical probes based on SERS detection. Our approaches have shown how such probes can detect specific DNA sequences by using a biomolecular recognition event to 'turn on' a SERS response through a controlled assembly process of the DNA functionalised nanoparticles. Further, we have prepared DNA aptamer functionalised SERS probes and demonstrated how introduction of a protein target can change the aggregation state of the nanoparticles in a dose-dependant manner. These approaches are being used as methods to detect biomolecules that indicate a specific disease being present with a view to improving disease management.

  17. Biophotonic ring resonator for ultrasensitive detection of DMMP as a simulant for organophosphorus agents.

    PubMed

    Bonnot, Karine; Cuesta-Soto, Francisco; Rodrigo, Manuel; Varriale, Antonio; Sanchez, Nuria; D'Auria, Sabato; Spitzer, Denis; Lopez-Royo, Francisco

    2014-05-20

    Combining photonic integrated circuits with a biologically based sensing approach has the ability to provide a new generation of portable and low-cost sensor devices with a high specificity and sensitivity for a number of applications in environmental monitoring, defense, and homeland security. We report herein on the specific biosensing under continuous air flow of DMMP, which is commonly used as a simulant and a precursor for the synthesis of Sarin. The proposed technology is based on the selective recognition of the targeted DMMP molecule by specifically modified proteins immobilized on photonic structures. The response of the biophotonic structures shows a high stability and accuracy over 3 months, allowing for the detection in diluted air of DMMP at concentration as low as 35 μg/m(3) (6.8 ppb) in less than 15 min. The performance of the developed technology satisfies most current homeland and military security requirements.

  18. Turbine Internal and Film Cooling Modeling For 3D Navier-Stokes Codes

    NASA Technical Reports Server (NTRS)

    DeWitt, Kenneth; Garg Vijay; Ameri, Ali

    2005-01-01

    The aim of this research project is to make use of NASA Glenn on-site computational facilities in order to develop, validate and apply aerodynamic, heat transfer, and turbine cooling models for use in advanced 3D Navier-Stokes Computational Fluid Dynamics (CFD) codes such as the Glenn-" code. Specific areas of effort include: Application of the Glenn-HT code to specific configurations made available under Turbine Based Combined Cycle (TBCC), and Ultra Efficient Engine Technology (UEET) projects. Validating the use of a multi-block code for the time accurate computation of the detailed flow and heat transfer of cooled turbine airfoils. The goal of the current research is to improve the predictive ability of the Glenn-HT code. This will enable one to design more efficient turbine components for both aviation and power generation. The models will be tested against specific configurations provided by NASA Glenn.

  19. Functionally defined white matter reveals segregated pathways in human ventral temporal cortex associated with category-specific processing

    PubMed Central

    Gomez, Jesse; Pestilli, Franco; Witthoft, Nathan; Golarai, Golijeh; Liberman, Alina; Poltoratski, Sonia; Yoon, Jennifer; Grill-Spector, Kalanit

    2014-01-01

    Summary It is unknown if the white matter properties associated with specific visual networks selectively affect category-specific processing. In a novel protocol we combined measurements of white matter structure, functional selectivity, and behavior in the same subjects. We find two parallel white matter pathways along the ventral temporal lobe connecting to either face-selective or place-selective regions. Diffusion properties of portions of these tracts adjacent to face- and place-selective regions of ventral temporal cortex correlate with behavioral performance for face or place processing, respectively. Strikingly, adults with developmental prosopagnosia (face blindness) express an atypical structure-behavior relationship near face-selective cortex, suggesting that white matter atypicalities in this region may have behavioral consequences. These data suggest that examining the interplay between cortical function, anatomical connectivity, and visual behavior is integral to understanding functional networks and their role in producing visual abilities and deficits. PMID:25569351

  20. Recent advances in the construction of antibody-drug conjugates

    NASA Astrophysics Data System (ADS)

    Chudasama, Vijay; Maruani, Antoine; Caddick, Stephen

    2016-02-01

    Antibody-drug conjugates (ADCs) comprise antibodies covalently attached to highly potent drugs using a variety of conjugation technologies. As therapeutics, they combine the exquisite specificity of antibodies, enabling discrimination between healthy and diseased tissue, with the cell-killing ability of cytotoxic drugs. This powerful and exciting class of targeted therapy has shown considerable promise in the treatment of various cancers with two US Food and Drug Administration approved ADCs currently on the market (Adcetris and Kadcyla) and approximately 40 currently undergoing clinical evaluation. However, most of these ADCs exist as heterogeneous mixtures, which can result in a narrow therapeutic window and have major pharmacokinetic implications. In order for ADCs to deliver their full potential, sophisticated site-specific conjugation technologies to connect the drug to the antibody are vital. This Perspective discusses the strategies currently used for the site-specific construction of ADCs and appraises their merits and disadvantages.

  1. A novel dendritic cell-based direct ex vivo assay for detection and enumeration of circulating antigen-specific human T cells.

    PubMed

    Carrio, Roberto; Zhang, Ge; Drake, Donald R; Schanen, Brian C

    2018-05-07

    Although a variety of assays have been used to examine T cell responses in vitro, standardized ex vivo detection of antigen-specific CD4 + T cells from human circulatory PBMCs remains constrained by low-dimensional characterization outputs and the need for polyclonal, mitogen-induced expansion methods to generate detectable response signals. To overcome these limitations, we developed a novel methodology utilizing antigen-pulsed autologous human dendritic target cells in a rapid and sensitive assay to accurately enumerate antigen-specific CD4 + T cell precursor frequency by multiparametric flow cytometry. With this approach, we demonstrate the ability to reproducibly quantitate poly-functional T cell responses following both primary and recall antigenic stimulation. Furthermore, this approach enables more comprehensive phenotypic profiling of circulating antigen-specific CD4 + T cells, providing valuable insights into the pre-existing polarization of antigen-specific T cells in humans. Combined, this approach permits sensitive and detailed ex vivo detection of antigen-specific CD4 + T cells delivering an important tool for advancing vaccine, immune-oncology and other therapeutic studies.

  2. Testing domain general learning in an Australian lizard.

    PubMed

    Qi, Yin; Noble, Daniel W A; Fu, Jinzhong; Whiting, Martin J

    2018-06-02

    A key question in cognition is whether animals that are proficient in a specific cognitive domain (domain specific hypothesis), such as spatial learning, are also proficient in other domains (domain general hypothesis) or whether there is a trade-off. Studies testing among these hypotheses are biased towards mammals and birds. To understand constraints on the evolution of cognition more generally, we need broader taxonomic and phylogenetic coverage. We used Australian eastern water skinks (Eulamprus quoyii) with known spatial learning ability in three additional tasks: an instrumental and two discrimination tasks. Under domain specific learning we predicted that lizards that were good at spatial learning would perform less well in the discrimination tasks. Conversely, we predicted that lizards that did not meet our criterion for spatial learning would likewise perform better in discrimination tasks. Lizards with domain general learning should perform approximately equally well (or poorly) in these tasks. Lizards classified as spatial learners performed no differently to non-spatial learners in both the instrumental and discrimination learning tasks. Nevertheless, lizards were proficient in all tasks. Our results reveal two patterns: domain general learning in spatial learners and domain specific learning in non-spatial learners. We suggest that delineating learning into domain general and domain specific may be overly simplistic and we need to instead focus on individual variation in learning ability, which ultimately, is likely to play a key role in fitness. These results, in combination with previously published work on this species, suggests that this species has behavioral flexibility because they are competent across multiple cognitive domains and are capable of reversal learning.

  3. The Effects of Plyometric Training on Change-of-Direction Ability: A Meta-Analysis.

    PubMed

    Asadi, Abbas; Arazi, Hamid; Young, Warren B; Sáez de Villarreal, Eduardo

    2016-07-01

    To show a clear picture about the possible variables of enhancements of change-of-direction (COD) ability using longitudinal plyometric-training (PT) studies and determine specific factors that influence the training effects. A computerized search was performed, and 24 articles with a total of 46 effect sizes (ESs) in an experimental group and 25 ESs in a control group were reviewed to analyze the role of various factors on the impact of PT on COD performance. The results showed that participants with good fitness levels obtained greater improvements in COD performance (P < .05), and basketball players gained more benefits of PT than other athletes. Also, men obtained COD results similar to those of women after PT. In relation to the variables of PT design, it appears that 7 wk (with 2 sessions/wk) using moderate intensity and 100 jumps per training session with a 72-h rest interval tends to improve COD ability. Performing PT with a combination of different types of plyometric exercises such as drop jumps + vertical jumps + standing long jumps is better than 1 form of exercise. It is apparent that PT can be effective at improving COD ability. The loading parameters are essential for exercise professionals, coaches, and strength and conditioning professionals with regard to the most appropriate dose-response trends to optimize plyometric-induced COD-ability gains.

  4. [Diagnostic value of a combination of biomarkers in patients with sepsis and severe sepsis in emergency department].

    PubMed

    Zhao, Yongzhen; Li, Chunsheng

    2014-03-01

    To determine a combination of biomarkers that assure the diagnosis of sepsis and severe sepsis in patients in emergency department (ED). A total of 652 patients with systemic inflammatory response syndrome (SIRS) were enrolled for this prospective study in the ED of Beijing Chaoyang Hospital of the Capital Medical University between March 2010 and March 2013. Eight biomarkers were determined, including levels of procalcitonin (PCT), interleukin-6 (IL-6), D-dimer, C-reactive protein (CRP), brain natriuretic peptide (BNP), white blood cell count (WBC), percentage of immature neutrophil, and platelet count (PLT). Patients were divided into the sepsis group (452 cases) and non-sepsis group (200 cases) according to the diagnostic criteria of sepsis. Then all these patients were stratified into severe sepsis group (190 cases, including septic shock) and non-severe sepsis group (462 cases) according to the diagnosis of severe sepsis. Logistic regression was performed to identify the independent factors for the diagnosis of sepsis and severe sepsis, and the optimal combination of biomarkers was established. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic ability of the combination and the biomarkers.A total of 652 patients with systemic inflammatory response syndrome (SIRS) were enrolled for this prospective study in the ED of Beijing Chaoyang Hospital of the Capital Medical University between March 2010 and March 2013. Eight biomarkers were determined, including levels of procalcitonin (PCT), interleukin-6 (IL-6), D-dimer, C-reactive protein (CRP), brain natriuretic peptide (BNP), white blood cell count (WBC), percentage of immature neutrophil, and platelet count (PLT). Patients were divided into the sepsis group (452 cases) and non-sepsis group (200 cases) according to the diagnostic criteria of sepsis. Then all these patients were stratified into severe sepsis group (190 cases, including septic shock) and non-severe sepsis group (462 cases) according to the diagnosis of severe sepsis. Logistic regression was performed to identify the independent factors for the diagnosis of sepsis and severe sepsis, and the optimal combination of biomarkers was established. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic ability of the combination and the biomarkers. PCT, IL-6 and D-dimer were independent factors for diagnosis of sepsis and severe sepsis. The area under the ROC curve (AUC) of the combination of three biomarkers was 0.866 for diagnosis of sepsis, and it was higher than the AUC of PCT (0.803), IL-6 (0.770) and D-dimer (0.737) alone, and this new combination showed better sensitivity, specificity, positive predictive (PPV), and negative predictive (NPV) values than that when the three biomarkers was used individually (the results of combination were 81.2%, 81.0%, 90.6%, 56.5%; that of PCT were 75.2%, 80.0%, 89.5%, 58.8%; that of IL-6 were 81.0%, 61.0%, 82.4%, 58.7%; and that of D-dimer were 79.9%, 59.0%, 81.5%, 56.5%, respectively). The AUC of the combination was 0.815 for the diagnosis of severe sepsis and was better than the three biomarkers used alone, which was 0.758 for PCT, 0.740 for IL-6, and 0.704 for D-dimer respectively. Moreover, the sensitivity, specificity, PPV and NPV of the combination were higher than that of the three biomarkers used singularly (the results of combination were 81.6%, 73.6%, 56.0%, 90.6%; that of PCT were 79.5%, 65.0%, 48.2%, 88.5%; that of IL-6 were 65.8%, 70.6%, 47.9%, 83.4%; and that of D-dimer were 60.5%, 73.2%, 48.1%, 81.8%, respectively). The combination of PCT, IL-6 and D-dimer enhances the diagnostic ability for sepsis and severe sepsis.

  5. Sex estimation based on tooth measurements using panoramic radiographs.

    PubMed

    Capitaneanu, Cezar; Willems, Guy; Jacobs, Reinhilde; Fieuws, Steffen; Thevissen, Patrick

    2017-05-01

    Sex determination is an important step in establishing the biological profile of unidentified human remains. The aims of the study were, firstly, to assess the degree of sexual dimorphism in permanent teeth, based on digital tooth measurements performed on panoramic radiographs. Secondly, to identify sex-related tooth position-specific measurements or combinations of such measurements, and to assess their applicability for potential sex determination. Two hundred digital panoramic radiographs (100 males, 100 females; age range 22-34 years) were retrospectively collected from the dental clinic files of the Dentomaxillofacial Radiology Center of the University Hospitals Leuven, Belgium, and imported in image enhancement software. Tooth length- and width-related variables were measured on all teeth in upper and lower left quadrant, and ratios of variables were calculated. Univariate and multivariate analyses were performed to quantify the sex discriminative value of the tooth position-specific variables and their combinations. The mandibular and maxillary canine showed the greatest sexual dimorphism, and tooth length variables had the highest discriminative potential. Compared to single variables, combining variables or ratios of variables did not improve substantially the discrimination between males and females. Considering that the discriminative ability values (area under the curve (AUC)) were not higher than 0.80, it is not advocated to use the currently studied dental variables for accurate sex estimation in forensic practice.

  6. MiR-17 Partly Promotes Hematopoietic Cell Expansion through Augmenting HIF-1α in Osteoblasts

    PubMed Central

    Yang, Yuxia; Ma, Wei; Wu, Dan; Huang, Yu; Li, Hongge; Zou, Junhua; Zhang, Yanju; Feng, Meifu; Luo, Jianyuan

    2013-01-01

    Background Hematopoietic stem cell (HSC) regulation is highly dependent on interactions with the marrow microenvironment, of which osteogenic cells play a crucial role. While evidence is accumulating for an important role of intrinsic miR-17 in regulating HSCs and HPCs, whether miR-17 signaling pathways are also necessary in the cell-extrinsic control of hematopoiesis hereto remains poorly understood. Methodology/Principal Findings Using the immortalized clone with the characteristics of osteoblasts, FBMOB-hTERT, in vitro expansion, long-term culture initiating cell (LTC-IC) and non-obese diabetic/severe combined immunodeficient disease (NOD/SCID) mice repopulating cell (SRC) assay revealed that the ectopic expression of miR-17 partly promoted the ability of FBMOB-hTERT to support human cord blood (CB) CD34+ cell expansion and maintain their multipotency. It also seemed that osteoblastic miR-17 was prone to cause a specific expansion of the erythroid lineage. Conversely, deficient expression of miR-17 partly inhibited the hematopoietic supporting ability of FBMOB-hTERT. We further identified that HIF-1α is responsible for, at least in part, the promoted hematopoietic supporting ability of FBMOB-hTERT caused by miR-17. HIF-1α expression is markedly enhanced in miR-17 overexpressed FBMOB-hTERT upon interaction with CB CD34+ cells compared to other niche associated factors. More interestingly, the specific erythroid lineage expansion of CB CD34+ cells caused by osteoblastic miR-17 was abrogated by HIF-1α knock down. Conclusion/Significance Our data demonstrated that CB CD34+ cell expansion can be partly promoted by osteoblastic miR-17, and in particular, ectopic miR-17 can cause a specific expansion of the erythroid lineage through augmenting HIF-1α in osteoblasts. PMID:23936170

  7. Self-Estimation of Blood Alcohol Concentration: A Review

    PubMed Central

    Aston, Elizabeth R.; Liguori, Anthony

    2013-01-01

    This article reviews the history of blood alcohol concentration (BAC) estimation training, which trains drinkers to discriminate distinct BAC levels and thus avoid excessive alcohol consumption. BAC estimation training typically combines education concerning alcohol metabolism with attention to subjective internal cues associated with specific concentrations. Estimation training was originally conceived as a component of controlled drinking programs. However, dependent drinkers were unsuccessful in BAC estimation, likely due to extreme tolerance. In contrast, moderate drinkers successfully acquired this ability. A subsequent line of research translated laboratory estimation studies to naturalistic settings by studying large samples of drinkers in their preferred drinking environments. Thus far, naturalistic studies have provided mixed results regarding the most effective form of BAC feedback. BAC estimation training is important because it imparts an ability to perceive individualized impairment that may be present below the legal limit for driving. Consequently, the training can be a useful component for moderate drinkers in drunk driving prevention programs. PMID:23380489

  8. Design and experimental validation for direct-drive fault-tolerant permanent-magnet vernier machines.

    PubMed

    Liu, Guohai; Yang, Junqin; Chen, Ming; Chen, Qian

    2014-01-01

    A fault-tolerant permanent-magnet vernier (FT-PMV) machine is designed for direct-drive applications, incorporating the merits of high torque density and high reliability. Based on the so-called magnetic gearing effect, PMV machines have the ability of high torque density by introducing the flux-modulation poles (FMPs). This paper investigates the fault-tolerant characteristic of PMV machines and provides a design method, which is able to not only meet the fault-tolerant requirements but also keep the ability of high torque density. The operation principle of the proposed machine has been analyzed. The design process and optimization are presented specifically, such as the combination of slots and poles, the winding distribution, and the dimensions of PMs and teeth. By using the time-stepping finite element method (TS-FEM), the machine performances are evaluated. Finally, the FT-PMV machine is manufactured, and the experimental results are presented to validate the theoretical analysis.

  9. Makeup your mind: The impact of styling on perceived competence and warmth of female leaders.

    PubMed

    Klatt, Jennifer; Eimler, Sabrina C; Krämer, Nicole C

    2016-01-01

    Women are still underrepresented at the highest management levels. The think-manager-think-male phenomenon suggests that leadership is associated with male rather than female attributes. Although styling has been shown to influence the evaluation of women's leadership abilities, the relevant specific features have been left remarkably unaddressed. In a 2 × 2 × 2 × 2 (skirt/pants, with/without jewelry, loose hair/braid, with/without makeup) between-subjects design, 354 participants evaluated a woman in a photograph. Women with makeup, pants, or with jewelry were rated as more competent than women without makeup, with skirts, or without jewelry. A combination of loose hair and no makeup was perceived as warmest, and women with loose hair were more likely to be hired than those with braids. In sum, even subtle changes in styling have a strong impact on how women's leadership abilities are evaluated.

  10. Simultaneous functional photoacoustic and ultrasonic endoscopy of internal organs in vivo.

    PubMed

    Yang, Joon-Mo; Favazza, Christopher; Chen, Ruimin; Yao, Junjie; Cai, Xin; Maslov, Konstantin; Zhou, Qifa; Shung, K Kirk; Wang, Lihong V

    2012-08-01

    At present, clinicians routinely apply ultrasound endoscopy in a variety of interventional procedures that provide treatment solutions for diseased organs. Ultrasound endoscopy not only produces high-resolution images, but also is safe for clinical use and broadly applicable. However, for soft tissue imaging, its mechanical wave-based image contrast fundamentally limits its ability to provide physiologically specific functional information. By contrast, photoacoustic endoscopy possesses a unique combination of functional optical contrast and high spatial resolution at clinically relevant depths, ideal for imaging soft tissues. With these attributes, photoacoustic endoscopy can overcome the current limitations of ultrasound endoscopy. Moreover, the benefits of photoacoustic imaging do not come at the expense of existing ultrasound functions; photoacoustic endoscopy systems are inherently compatible with ultrasound imaging, thereby enabling multimodality imaging with complementary contrast. Here we present simultaneous photoacoustic and ultrasonic dual-mode endoscopy and show its ability to image internal organs in vivo, thus illustrating its potential clinical application.

  11. Simultaneous functional photoacoustic and ultrasonic endoscopy of internal organs in vivo

    PubMed Central

    Yang, Joon-Mo; Favazza, Christopher; Chen, Ruimin; Yao, Junjie; Cai, Xin; Maslov, Konstantin; Zhou, Qifa; Shung, K. Kirk; Wang, Lihong V.

    2013-01-01

    Presently, clinicians routinely apply ultrasound endoscopy in a variety of interventional procedures which provide treatment solutions for diseased organs. Ultrasound endoscopy not only produces high resolution images, it is also safe for clinical use and broadly applicable. However, for soft tissue imaging, its mechanical wave-based image contrast fundamentally limits its ability to provide physiologically-specific functional information. By contrast, photoacoustic endoscopy possesses a unique combination of functional optical contrast and high spatial resolution at clinically-relevant depths, ideal for soft tissue imaging. With these attributes, photoacoustic endoscopy can overcome the current limitations of ultrasound endoscopy. Moreover, the benefits of photoacoustic imaging do not come at the expense of existing ultrasound functions; photoacoustic endoscopy systems are inherently compatible with ultrasound imaging, enabling multi-modality imaging with complementary contrast. Here, we present simultaneous photoacoustic and ultrasonic dual-mode endoscopy and demonstrate its ability to image internal organs in vivo, illustrating its potential clinical application. PMID:22797808

  12. Detecting aromatic compounds on planetary surfaces using ultraviolet time-resolved fluorescence spectroscopy

    NASA Astrophysics Data System (ADS)

    Eshelman, E.; Daly, M. G.; Slater, G.; Cloutis, E.

    2018-02-01

    Many aromatic organic molecules exhibit strong and characteristic fluorescence when excited with ultraviolet radiation. As laser excitation in the ultraviolet generates both fluorescence and resonantly enhanced Raman scattering of aromatic vibrational modes, combined Raman and fluorescence instruments have been proposed to search for organic compounds on Mars. In this work the time-resolved fluorescence of a suite of 24 compounds composed of 2-5 ringed alternant, non-alternant, and heterocyclic PAHs was measured. Fluorescence instrumentation with similar specifications to a putative flight instrument was capable of observing the fluorescence decay of these compounds with a sub-ns resolution. Incorporating time-resolved capabilities was also found to increase the ability to discriminate between individual PAHs. Incorporating time-resolved fluorescence capabilities into an ultraviolet gated Raman system intended for a rover or lander can increase the ability to detect and characterize PAHs on planetary surfaces.

  13. Isolation and Characterization of Nisin-Resistant Leuconostoc mesenteroides for Use in Cabbage Fermentations

    PubMed Central

    Breidt, F.; Crowley, K. A.; Fleming, H. P.

    1993-01-01

    Leuconostoc mesenteroides strains that are resistant to high levels of nisin (up to 25,000 IU/ml in broth) were isolated. These nisin-resistant mutants were evaluated to determine their potential use as starter culture strains for cabbage fermentations. We found that some L. mesenteroides strains could be adapted to high levels of nisin resistance, while others could not. The nisin resistance trait was found to be stable for at least 35 generations, in the absence of nisin selection, for all mutants tested. The effects of nisin and salt, separately and in combination, on growth kinetics of the nisin-resistant strains were determined. Salt was the most influential factor on the specific growth rates of the mutants, and no synergistic effect between nisin and salt on specific growth rates was observed. The nisin-resistant strains were unimpaired in their ability to rapidly produce normal heterolactic fermentation end products. The use of these L. mesenteroides mutants as starter cultures in combination with nisin may extend the heterolactic phase of cabbage fermentations. PMID:16349090

  14. Approaches for monitoring the release of Pochonia chlamydosporia var. catenulata, a biocontrol agent of root-knot nematodes.

    PubMed

    Atkins, Simon D; Hidalgo-Diaz, Leopoldo; Clark, Ian M; Morton, C Oliver; de Oca, Nivian Montes; Gray, Paul A; Kerry, Brian R

    2003-02-01

    Pochonia chlamydosporia var. catenulata is a potential biocontrol agent against root-knot nematodes. Diagnosis of isolates has relied on morphological identification, and is both time-consuming and difficult. beta-tubulin primers have been developed for the identification of this fungus that were specific enough to distinguish between varieties of the fungus within the same species. Separate primers have been developed for the specific detection of P. chlamydosporia var. catenulata based on ITS sequences, which were able to detect the fungus in soil from various sites in Cuba where the biocontrol agent had been added. When the PCR diagnosis was combined with serial dilution of soil samples on selective medium, colonies were rapidly identified. The fungus was still present, albeit at low densities, in soils inoculated five years previously. The development of a baiting method allowed quick in situ screening of the isolates' ability to infect nematode eggs, and when combined with PCR diagnosis both varieties of the fungus could be detected in infected eggs. RFLP analysis of ITS sequences from P. chlamydosporia provided an extra level of discrimination between isolates.

  15. A Subject-Specific Kinematic Model to Predict Human Motion in Exoskeleton-Assisted Gait.

    PubMed

    Torricelli, Diego; Cortés, Camilo; Lete, Nerea; Bertelsen, Álvaro; Gonzalez-Vargas, Jose E; Del-Ama, Antonio J; Dimbwadyo, Iris; Moreno, Juan C; Florez, Julian; Pons, Jose L

    2018-01-01

    The relative motion between human and exoskeleton is a crucial factor that has remarkable consequences on the efficiency, reliability and safety of human-robot interaction. Unfortunately, its quantitative assessment has been largely overlooked in the literature. Here, we present a methodology that allows predicting the motion of the human joints from the knowledge of the angular motion of the exoskeleton frame. Our method combines a subject-specific skeletal model with a kinematic model of a lower limb exoskeleton (H2, Technaid), imposing specific kinematic constraints between them. To calibrate the model and validate its ability to predict the relative motion in a subject-specific way, we performed experiments on seven healthy subjects during treadmill walking tasks. We demonstrate a prediction accuracy lower than 3.5° globally, and around 1.5° at the hip level, which represent an improvement up to 66% compared to the traditional approach assuming no relative motion between the user and the exoskeleton.

  16. A Subject-Specific Kinematic Model to Predict Human Motion in Exoskeleton-Assisted Gait

    PubMed Central

    Torricelli, Diego; Cortés, Camilo; Lete, Nerea; Bertelsen, Álvaro; Gonzalez-Vargas, Jose E.; del-Ama, Antonio J.; Dimbwadyo, Iris; Moreno, Juan C.; Florez, Julian; Pons, Jose L.

    2018-01-01

    The relative motion between human and exoskeleton is a crucial factor that has remarkable consequences on the efficiency, reliability and safety of human-robot interaction. Unfortunately, its quantitative assessment has been largely overlooked in the literature. Here, we present a methodology that allows predicting the motion of the human joints from the knowledge of the angular motion of the exoskeleton frame. Our method combines a subject-specific skeletal model with a kinematic model of a lower limb exoskeleton (H2, Technaid), imposing specific kinematic constraints between them. To calibrate the model and validate its ability to predict the relative motion in a subject-specific way, we performed experiments on seven healthy subjects during treadmill walking tasks. We demonstrate a prediction accuracy lower than 3.5° globally, and around 1.5° at the hip level, which represent an improvement up to 66% compared to the traditional approach assuming no relative motion between the user and the exoskeleton. PMID:29755336

  17. Characterisation of antibody responses in pigs induced by recombinant oncosphere antigens from Taenia solium.

    PubMed

    Jayashi, César M; Gonzalez, Armando E; Castillo Neyra, Ricardo; Kyngdon, Craig T; Gauci, Charles G; Lightowlers, Marshall W

    2012-12-14

    Recombinant antigens cloned from the oncosphere life cycle stage of the cestode parasite Taenia solium (T. solium) have been proven to be effective as vaccines for protecting pigs against infections with T. solium. Previous studies have defined three different host protective oncosphere antigens, TSOL18, TSOL16 and TSOL45. In this study, we evaluated the potential for combining the antigens TSOL16 and TSOL18 as a practical vaccine. Firstly, in a laboratory trial, we compared the immunogenicity of the combined antigens (TSOL16/18) versus the immunogenicity of the antigens separately. Secondly, in a field trial, we tested the ability of the TSOL16/18 vaccine to induce detectable antibody responses in animals living under environmental stress and traditionally reared in areas where T. solium cysticercosis is endemic; and finally, we characterised the immune response of the study population. Pigs of 8-16 weeks of age were vaccinated with 200 μg each of TSOL16 and TSOL18, plus 5mg of Quil-A. Specific total IgG, IgG(1) and IgG(2) antibody responses induced by TSOL16 and TSOL18 were determined with ELISA. The immunogenicity of both antigens was retained in the combined TSOL16/18 vaccine. The combined vaccine TSOL16/18 induced detectable specific anti-TSOL18 antibody responses in 100% (113/113) and specific anti-TSOL16 in 99% (112/113) of the vaccinated animals measured at 2 weeks following the booster vaccination. From the two IgG antibody subtypes analysed we found there was stronger response to IgG(2). Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Analysis of the state of posttranslational calmodulin methylation in developing pea plants. [Pisum sativum

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

    Oh, Sukheung; Roberts, D.M.

    1990-07-01

    A specific calmodulin-N-methyltransferase was used in a radiometric assay to analyze the degree of methylation of lysine-115 in pea (Pisum sativum) plants. Calmodulin was isolated from dissected segments of developing roots of young etiolated and green pea plants and was tested for its ability to be methylated by incubation with the calmodulin methyltransferase in the presence of ({sup 3}H)methyl-S-adenosylmethionine. By this approach, the presence of unmethylated calmodulins were demonstrated in pea tissues, and the levels of methylation varied depending on the developmental state of the tissue tested. Calmodulin methylation levels were lower in apical root segments of both etiolated andmore » green plants, and in the young lateral roots compared with the mature, differentiated root tissues. The incorporation of methyl groups into these calmodulin samples appears to be specific for position 115 since site-directed mutants of calmodulin with substitutions at this position competitively inhibited methyl group incorporation. The present findings, combined with previous data showing differences in the ability of methylated and unmethylated calmodulins to activate pea NAD kinase raise the possibility that posttranslational methylation of calmodulin could be another mechanism for regulating calmodulin activity.« less

  19. Hormonal and transcriptional profiles highlight common and differential host responses to arbuscular mycorrhizal fungi and the regulation of the oxylipin pathway

    PubMed Central

    López-Ráez, Juan A.; Verhage, Adriaan; Fernández, Iván; García, Juan M.; Azcón-Aguilar, Concepción; Flors, Victor; Pozo, María J.

    2010-01-01

    Arbuscular mycorrhizal (AM) symbioses are mutualistic associations between soil fungi and most vascular plants. The symbiosis significantly affects the host physiology in terms of nutrition and stress resistance. Despite the lack of host range specificity of the interaction, functional diversity between AM fungal species exists. The interaction is finely regulated according to plant and fungal characters, and plant hormones are believed to orchestrate the modifications in the host plant. Using tomato as a model, an integrative analysis of the host response to different mycorrhizal fungi was performed combining multiple hormone determination and transcriptional profiling. Analysis of ethylene-, abscisic acid-, salicylic acid-, and jasmonate-related compounds evidenced common and divergent responses of tomato roots to Glomus mosseae and Glomus intraradices, two fungi differing in their colonization abilities and impact on the host. Both hormonal and transcriptional analyses revealed, among others, regulation of the oxylipin pathway during the AM symbiosis and point to a key regulatory role for jasmonates. In addition, the results suggest that specific responses to particular fungi underlie the differential impact of individual AM fungi on plant physiology, and particularly on its ability to cope with biotic stresses. PMID:20378666

  20. Developmental Change in the Influence of Domain-General Abilities and Domain-Specific Knowledge on Mathematics Achievement: An Eight-Year Longitudinal Study

    PubMed Central

    Geary, David C.; Nicholas, Alan; Li, Yaoran; Sun, Jianguo

    2016-01-01

    The contributions of domain-general abilities and domain-specific knowledge to subsequent mathematics achievement were longitudinally assessed (n = 167) through 8th grade. First grade intelligence and working memory and prior grade reading achievement indexed domain-general effects and domain-specific effects were indexed by prior grade mathematics achievement and mathematical cognition measures of prior grade number knowledge, addition skills, and fraction knowledge. Use of functional data analysis enabled grade-by-grade estimation of overall domain-general and domain-specific effects on subsequent mathematics achievement, the relative importance of individual domain-general and domain-specific variables on this achievement, and linear and non-linear across-grade estimates of these effects. The overall importance of domain-general abilities for subsequent achievement was stable across grades, with working memory emerging as the most important domain-general ability in later grades. The importance of prior mathematical competencies on subsequent mathematics achievement increased across grades, with number knowledge and arithmetic skills critical in all grades and fraction knowledge in later grades. Overall, domain-general abilities were more important than domain-specific knowledge for mathematics learning in early grades but general abilities and domain-specific knowledge were equally important in later grades. PMID:28781382

  1. Shared-environmental contributions to high cognitive ability.

    PubMed

    Kirkpatrick, Robert M; McGue, Matt; Iacono, William G

    2009-07-01

    Using a combined sample of adolescent twins, biological siblings, and adoptive siblings, we estimated and compared the differential shared-environmentality for high cognitive ability and the shared-environmental variance for the full range of ability during adolescence. Estimates obtained via multiple methods were in the neighborhood of 0.20, and suggest a modest effect of the shared environment on both high and full-range ability. We then examined the association of ability with three measures of the family environment in a subsample of adoptive siblings: parental occupational status, parental education, and disruptive life events. Only parental education showed significant (albeit modest) association with ability in both the biological and adoptive samples. We discuss these results in terms of the need for cognitive-development research to combine genetically sensitive designs and modern statistical methods with broad, thorough environmental measurement.

  2. Tracking intracellular uptake and localisation of alkyne tagged fatty acids using Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Jamieson, Lauren E.; Greaves, Jennifer; McLellan, Jayde A.; Munro, Kevin R.; Tomkinson, Nicholas C. O.; Chamberlain, Luke H.; Faulds, Karen; Graham, Duncan

    2018-05-01

    Intracellular uptake, distribution and metabolism of lipids are tightly regulated characteristics in healthy cells. An analytical technique capable of understanding these characteristics with a high level of species specificity in a minimally invasive manner is highly desirable in order to understand better how these become disrupted during disease. In this study, the uptake and distribution of three different alkyne tagged fatty acids in single cells were monitored and compared, highlighting the ability of Raman spectroscopy combined with alkyne tags for better understanding of the fine details with regard to uptake, distribution and metabolism of very chemically specific lipid species. This indicates the promise of using Raman spectroscopy directly with alkyne tagged lipids for cellular studies as opposed to subsequently clicking of a fluorophore onto the alkyne for fluorescence imaging.

  3. The mathematics of a successful deconvolution: a quantitative assessment of mixture-based combinatorial libraries screened against two formylpeptide receptors.

    PubMed

    Santos, Radleigh G; Appel, Jon R; Giulianotti, Marc A; Edwards, Bruce S; Sklar, Larry A; Houghten, Richard A; Pinilla, Clemencia

    2013-05-30

    In the past 20 years, synthetic combinatorial methods have fundamentally advanced the ability to synthesize and screen large numbers of compounds for drug discovery and basic research. Mixture-based libraries and positional scanning deconvolution combine two approaches for the rapid identification of specific scaffolds and active ligands. Here we present a quantitative assessment of the screening of 32 positional scanning libraries in the identification of highly specific and selective ligands for two formylpeptide receptors. We also compare and contrast two mixture-based library approaches using a mathematical model to facilitate the selection of active scaffolds and libraries to be pursued for further evaluation. The flexibility demonstrated in the differently formatted mixture-based libraries allows for their screening in a wide range of assays.

  4. 2'-modified nucleosides for site-specific labeling of oligonucleotides

    NASA Technical Reports Server (NTRS)

    Krider, Elizabeth S.; Miller, Jeremiah E.; Meade, Thomas J.

    2002-01-01

    We report the synthesis of 2'-modified nucleosides designed specifically for incorporating labels into oligonucleotides. Conversion of these nucleosides to phosphoramidite and solid support-bound derivatives proceeds in good yield. Large-scale synthesis of 11-mer oligonucleotides possessing the 2'-modified nucleosides is achieved using these derivatives. Thermal denaturation studies indicate that the presence of 2'-modified nucleosides in 11-mer duplexes has minimal destabilizing effects on the duplex structure when the nucleosides are placed at the duplex termini. The powerful combination of phosphoramidite and support-bound derivatives of 2'-modified nucleosides affords the large-scale preparation of an entirely new class of oligonucleotides. The ability to synthesize oligonucleotides containing label attachment sites at 3', intervening, and 5' locations of a duplex is a significant advance in the development of oligonucleotide conjugates.

  5. Causal Evidence for a Mechanism of Semantic Integration in the Angular Gyrus as Revealed by High-Definition Transcranial Direct Current Stimulation

    PubMed Central

    Peelle, Jonathan E.; Bonner, Michael F.; Grossman, Murray

    2016-01-01

    A defining aspect of human cognition is the ability to integrate conceptual information into complex semantic combinations. For example, we can comprehend “plaid” and “jacket” as individual concepts, but we can also effortlessly combine these concepts to form the semantic representation of “plaid jacket.” Many neuroanatomic models of semantic memory propose that heteromodal cortical hubs integrate distributed semantic features into coherent representations. However, little work has specifically examined these proposed integrative mechanisms and the causal role of these regions in semantic integration. Here, we test the hypothesis that the angular gyrus (AG) is critical for integrating semantic information by applying high-definition transcranial direct current stimulation (tDCS) to an fMRI-guided region-of-interest in the left AG. We found that anodal stimulation to the left AG modulated semantic integration but had no effect on a letter-string control task. Specifically, anodal stimulation to the left AG resulted in faster comprehension of semantically meaningful combinations like “tiny radish” relative to non-meaningful combinations, such as “fast blueberry,” when compared to the effects observed during sham stimulation and stimulation to a right-hemisphere control brain region. Moreover, the size of the effect from brain stimulation correlated with the degree of semantic coherence between the word pairs. These findings demonstrate that the left AG plays a causal role in the integration of lexical-semantic information, and that high-definition tDCS to an associative cortical hub can selectively modulate integrative processes in semantic memory. SIGNIFICANCE STATEMENT A major goal of neuroscience is to understand the neural basis of behaviors that are fundamental to human intelligence. One essential behavior is the ability to integrate conceptual knowledge from semantic memory, allowing us to construct an almost unlimited number of complex concepts from a limited set of basic constituents (e.g., “leaf” and “wet” can be combined into the more complex representation “wet leaf”). Here, we present a novel approach to studying integrative processes in semantic memory by applying focal brain stimulation to a heteromodal cortical hub implicated in semantic processing. Our findings demonstrate a causal role of the left angular gyrus in lexical-semantic integration and provide motivation for novel therapeutic applications in patients with lexical-semantic deficits. PMID:27030767

  6. Causal Evidence for a Mechanism of Semantic Integration in the Angular Gyrus as Revealed by High-Definition Transcranial Direct Current Stimulation.

    PubMed

    Price, Amy Rose; Peelle, Jonathan E; Bonner, Michael F; Grossman, Murray; Hamilton, Roy H

    2016-03-30

    A defining aspect of human cognition is the ability to integrate conceptual information into complex semantic combinations. For example, we can comprehend "plaid" and "jacket" as individual concepts, but we can also effortlessly combine these concepts to form the semantic representation of "plaid jacket." Many neuroanatomic models of semantic memory propose that heteromodal cortical hubs integrate distributed semantic features into coherent representations. However, little work has specifically examined these proposed integrative mechanisms and the causal role of these regions in semantic integration. Here, we test the hypothesis that the angular gyrus (AG) is critical for integrating semantic information by applying high-definition transcranial direct current stimulation (tDCS) to an fMRI-guided region-of-interest in the left AG. We found that anodal stimulation to the left AG modulated semantic integration but had no effect on a letter-string control task. Specifically, anodal stimulation to the left AG resulted in faster comprehension of semantically meaningful combinations like "tiny radish" relative to non-meaningful combinations, such as "fast blueberry," when compared to the effects observed during sham stimulation and stimulation to a right-hemisphere control brain region. Moreover, the size of the effect from brain stimulation correlated with the degree of semantic coherence between the word pairs. These findings demonstrate that the left AG plays a causal role in the integration of lexical-semantic information, and that high-definition tDCS to an associative cortical hub can selectively modulate integrative processes in semantic memory. A major goal of neuroscience is to understand the neural basis of behaviors that are fundamental to human intelligence. One essential behavior is the ability to integrate conceptual knowledge from semantic memory, allowing us to construct an almost unlimited number of complex concepts from a limited set of basic constituents (e.g., "leaf" and "wet" can be combined into the more complex representation "wet leaf"). Here, we present a novel approach to studying integrative processes in semantic memory by applying focal brain stimulation to a heteromodal cortical hub implicated in semantic processing. Our findings demonstrate a causal role of the left angular gyrus in lexical-semantic integration and provide motivation for novel therapeutic applications in patients with lexical-semantic deficits. Copyright © 2016 the authors 0270-6474/16/363829-10$15.00/0.

  7. Identification af explosive power factors as predictors of player quality in young female volleyball players.

    PubMed

    Grgantov, Zoran; Milić, Mirjana; Katić, Ratko

    2013-05-01

    With the purpose of determining the factor structure of explosive power, as well as the influence of each factor on situational efficiency, 56 young female volleyball players were tested using 14 tests for assessing nonspecific and specific explosive power. By factor analysis, 4 significant factors were isolated which explained the total of over 80% of the common variability in young female volleyball players. The first factor was defined as volleyball-specific jumping, the second factor as nonspecific jumping and sprinting, the third factor as throwing explosive power, while the fourth factor was interpreted as volleyball-specific throwing and spiking speed from the ground. Results obtained by regression analysis in the latent space of explosive power indicate that the identified factors are good predictors of player quality in young female volleyball players. The fourth factor defined as throwing and spiking speed from the ground had the largest influence on player quality, followed by volleyball-specific jumping and nonspecific jumping and sprinting, and to a much lesser extent, by throwing explosive power The results obtained in this age group bring to the fore the ability of spiking and serving a ball of high speed, which hinders the opponents from playing those balls in serve reception and field defence. This ability, combined with a high standing vertical jump reach and spike approach vertical jump reach (which is the basis of the 1st varimax factor) enables successful performance of all volleyball elements by which points are won in complex 1 (spike) and complex 2 (serve and block). Even though the 2nd factor (nonspecific jumping and sprinting) has a slightly smaller impact on situational efficiency in young players, this ability provides preconditions i.e. preparation for successful realisation of all volleyball elements, so greater attention must be paid to perfecting it in young female volleyball players.

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

    Mullins, JP; Deufel, CL

    Purpose: Bile duct cancer affects 2–3 thousand people annually in the United States. Radiation therapy has been shown to double median survival, with combined external beam and intraluminal high dose-rate (HDR) brachytherapy being most effective. Endoscopic retrograde cholangiopancreatography (ERCP) biliary HDR, a less-invasive alternative to trans-hepatic brachytherapy, is delivered through a catheter that travels a tortuous path from nose to bile duct, requiring wire drive force and dexterity beyond typical afterloader performance specifications. Thus, specific afterloader quality assurance(QA) is recommended for this procedure. Our aim was to create a device and process for Varisource afterloader clearance QA with objectives thatmore » it be quantitative and can monitor afterloader performance over time, compare performance between two distinct afterloaders and potentially Result in a predictive nomogram for patient-specific clearance. Methods: Based on retrospective reconstruction of 20 ERCP patient anatomies, we designed a phantom to test afterloader ability to drive the source wire along an intended treatment path. The ability of the afterloader to fully extend the intended treatment path is a function of number and diameters of turns. We have determined experimentally that relative position of the turns does not impact performance. Results: Both patient and QA paths involve three common turns/loops: a large turn representing the stomach(10.8cm±2.0cm), an elliptical loop representing the duodenum(7.3cm±1.5cmx4.8cm±0.7cm), and a final turn at the end of the bile duct that may be tight for some patient-specific anatomies and absent in others(3.7cm±0.7cm, where present). Our phantom design uses anatomical average turn diameters for the stomach and duodenum then terminates in a turn of quantitatively selectable diameter. The smallest final turn diameter that an afterloader can pass is recorded as the QA parameter. Conclusion: With this device and QA process, we have the ability to quantitatively evaluate and track our afterloader performance for a technically challenging ERCP brachytherapy procedure.« less

  9. Anthropometric, physiological and performance characteristics of elite team-handball players.

    PubMed

    Chaouachi, Anis; Brughelli, Matt; Levin, Gregory; Boudhina, Nahla Ben Brahim; Cronin, John; Chamari, Karim

    2009-01-15

    The objective of this study was to provide anthropometric, physiological, and performance characteristics of an elite international handball team. Twenty-one elite handball players were tested and categorized according to their playing positions (goalkeepers, backs, pivots, and wings). Testing consisted of anthropometric and physiological measures of height, body mass, percentage body fat and endurance (VO(2max)), performance measures of speed (5, 10, and 30 m), strength (bench press and squat), unilateral and bilateral horizontal jumping ability, and a 5-jump horizontal test. Significant differences were found between player positions for some anthropometric characteristics (height and percentage body fat) but not for the physiological or performance characteristics. Strong correlations were noted between single leg horizontal jumping distances with 5-, 10-, and 30-m sprint times (r = 0.51-0.80; P < 0.01). The best predictors of sprint times were single leg horizontal jumping with the dominant leg and the distance measured for the 5-jump test, which when combined accounted for 72% of the common variance associated with sprint ability. In conclusion, performance abilities between positions in elite team-handball players appear to be very similar. Single leg horizontal jumping distance could be a specific standardized test for predicting sprinting ability in elite handball players.

  10. Attenuated total reflectance-FT-IR spectroscopy for gunshot residue analysis: potential for ammunition determination.

    PubMed

    Bueno, Justin; Sikirzhytski, Vitali; Lednev, Igor K

    2013-08-06

    The ability to link a suspect to a particular shooting incident is a principal task for many forensic investigators. Here, we attempt to achieve this goal by analysis of gunshot residue (GSR) through the use of attenuated total reflectance (ATR) Fourier transform infrared spectroscopy (FT-IR) combined with statistical analysis. The firearm discharge process is analogous to a complex chemical process. Therefore, the products of this process (GSR) will vary based upon numerous factors, including the specific combination of the firearm and ammunition which was discharged. Differentiation of FT-IR data, collected from GSR particles originating from three different firearm-ammunition combinations (0.38 in., 0.40 in., and 9 mm calibers), was achieved using projection to latent structures discriminant analysis (PLS-DA). The technique was cross (leave-one-out), both internally and externally, validated. External validation was achieved via assignment (caliber identification) of unknown FT-IR spectra from unknown GSR particles. The results demonstrate great potential for ATR-FT-IR spectroscopic analysis of GSR for forensic purposes.

  11. A Framework for Distributed Problem Solving

    NASA Astrophysics Data System (ADS)

    Leone, Joseph; Shin, Don G.

    1989-03-01

    This work explores a distributed problem solving (DPS) approach, namely the AM/AG model, to cooperative memory recall. The AM/AG model is a hierarchic social system metaphor for DPS based on the Mintzberg's model of organizations. At the core of the model are information flow mechanisms, named amplification and aggregation. Amplification is a process of expounding a given task, called an agenda, into a set of subtasks with magnified degree of specificity and distributing them to multiple processing units downward in the hierarchy. Aggregation is a process of combining the results reported from multiple processing units into a unified view, called a resolution, and promoting the conclusion upward in the hierarchy. The combination of amplification and aggregation can account for a memory recall process which primarily relies on the ability of making associations between vast amounts of related concepts, sorting out the combined results, and promoting the most plausible ones. The amplification process is discussed in detail. An implementation of the amplification process is presented. The process is illustrated by an example.

  12. Pore Breathing of Metal-Organic Frameworks by Environmental Transmission Electron Microscopy.

    PubMed

    Parent, Lucas R; Pham, C Huy; Patterson, Joseph P; Denny, Michael S; Cohen, Seth M; Gianneschi, Nathan C; Paesani, Francesco

    2017-10-11

    Metal-organic frameworks (MOFs) have emerged as a versatile platform for the rational design of multifunctional materials, combining large specific surface areas with flexible, periodic frameworks that can undergo reversible structural transitions, or "breathing", upon temperature and pressure changes, and through gas adsorption/desorption processes. Although MOF breathing can be inferred from the analysis of adsorption isotherms, direct observation of the structural transitions has been lacking, and the underlying processes of framework reorganization in individual MOF nanocrystals is largely unknown. In this study, we describe the characterization and elucidation of these processes through the combination of in situ environmental transmission electron microscopy (ETEM) and computer simulations. This combined approach enables the direct monitoring of the breathing behavior of individual MIL-53(Cr) nanocrystals upon reversible water adsorption and temperature changes. The ability to characterize structural changes in single nanocrystals and extract lattice level information through in silico correlation provides fundamental insights into the relationship between pore size/shape and host-guest interactions.

  13. Specific Abilities May Increment Psychometric g for High Ability Populations

    DTIC Science & Technology

    2016-04-14

    tend to sort themselves into jobs that are commensurate with their ability level ( McCormick , DeNisi, & Staw, 1979; McCormick , Jeanneret, & Mecham...of Genetic Psychology, 153, 229-230. Specific abilities, g, & high ability populations 14 McCormick , E. J., DeNisi, A. S., & Shaw, J. B... McCormick , E. J., Jeanneret, P. R., & Mecham, R. C. (1972). A study of job characteristics and job dimensions as based on the Position Analysis Questionnaire

  14. Highly Self-Healable 3D Microsupercapacitor with MXene-Graphene Composite Aerogel.

    PubMed

    Yue, Yang; Liu, Nishuang; Ma, Yanan; Wang, Siliang; Liu, Weijie; Luo, Cheng; Zhang, Hang; Cheng, Feng; Rao, Jiangyu; Hu, Xiaokang; Su, Jun; Gao, Yihua

    2018-05-22

    High-performance microsupercapacitors (MSCs) with three-dimensional (3D) structure provide an effective approach to improve the ability of energy storage. Because the electrodes with 3D structure are generally easily destroyed under mechanical deformation in practical applications, we fabricated a self-healable 3D MSC consisting of MXene (Ti 3 C 2 T x )-graphene (reduced graphene oxide, rGO) composite aerogel electrode by wrapping it with a self-healing polyurethane as an outer shell. The MXene-rGO composite aerogel combining large specific surface area of rGO and high conductivity of the MXene can not only prevent the self-restacking of the lamella structure but also resist the poor oxidization of MXene to a degree. The MSC based on a 3D MXene-rGO aerogel delivers a large area specific capacitance of 34.6 mF cm -2 at a scan rate of 1 mV s -1 and an outstanding cycling performance with a capacitance retention up to 91% over 15 000 cycles. The 3D MSC presents an excellent self-healing ability with specific capacitance retention of 81.7% after the fifth healing. The preparation of this self-healable 3D MSC can provide a method for designing and manufacturing next-generation long-life multifunctional electronic devices further to meet the requirements of sustainable development.

  15. First principles studies on the redox ability of (Ga(1-x)Zn(x))N(1-x)O(x) solid solutions and thermal reactions for H2 and O2 production on their surfaces.

    PubMed

    Du, Yaojun A; Chen, Yun-Wen; Kuo, Jer-Lai

    2013-12-07

    The (Ga1-xZnx)N1-xOx solid solution has been emerging as an effective photocatalyst for water splitting utilizing the visible solar spectrum, regarded as a host GaN bulk doped with ZnO impurities. H2 and O2 production occur simultaneously and stoichiometrically on the surface of (Ga1-xZnx)N1-xOx particles. In this work, we characterize the redox ability of (Ga1-xZnx)N1-xOx and find that a solid solution with a ZnO concentration of 0.125 < x < 0.250 is optimal for water splitting. This is consistent with the experimental finding that the maximum photocatalytic activity of (Ga1-xZnx)N1-xOx is achieved at x = 0.13. The thermal reactions of water splitting are modeled on both the GaN and an idealized (Ga1-xZnx)N1-xOx (101[combining macron]0) surface. The computed activation barriers allow us to gain some clues on the efficiency of water splitting on a specific photocatalyst surface. Our results suggest that the non-polar (101[combining macron]0) and polar (0001) surfaces may play different roles in water splitting, i.e., the (101[combining macron]0) surface is responsible for O2 production, while hydroxyl groups could dissociate on the (0001) surface.

  16. Long-lasting improvement following tDCS treatment combined with a training for reading in children and adolescents with dyslexia.

    PubMed

    Costanzo, Floriana; Rossi, Serena; Varuzza, Cristiana; Varvara, Pamela; Vicari, Stefano; Menghini, Deny

    2018-03-14

    Noninvasive brain stimulation transiently modulates reading ability in individuals with dyslexia by facilitating the underactive neural pathways in them. However, its long-term effects have not been determined. This study confirmed the ameliorative effects of multiple sessions of transcranial direct current stimulation (tDCS) combined with a training for reading on the reading abilities of children and adolescents with dyslexia and examined whether they are long-lasting. Twenty-six children and adolescents with dyslexia received 3 20-min sessions per week for 6 weeks (18 sessions) of left anodal/right cathodal tDCS, set to 1 mA, over the parieto-temporal regions, combined with training for reading. The participants were randomly assigned to receive active or sham treatment. Reading measures (text, high- and low-frequency words, non-words) were recorded before and immediately after the treatment and 1 and 6 months later. The long-term tolerability to tDCS was also evaluated. The active group received long-lasting benefits in reading. Specifically, the non-word reading efficiency index improved at every time point, as did the low-frequency word reading efficiency index at 1 and 6 months after the end of the treatment. No differences emerged in the sham group. No long-term adverse effects were documented. This study provides evidence of persistent improvements in reading in children and adolescents with dyslexia, constituting a new rehabilitative approach for the remediation of dyslexia. Copyright © 2018 Elsevier Ltd. All rights reserved.

  17. A gene expression system offering multiple levels of regulation: the Dual Drug Control (DDC) system.

    PubMed

    Sudomoina, Marina; Latypova, Ekaterina; Favorova, Olga O; Golemis, Erica A; Serebriiskii, Ilya G

    2004-04-29

    Whether for cell culture studies of protein function, construction of mouse models to enable in vivo analysis of disease epidemiology, or ultimately gene therapy of human diseases, a critical enabling step is the ability to achieve finely controlled regulation of gene expression. Previous efforts to achieve this goal have explored inducible drug regulation of gene expression, and construction of synthetic promoters based on two-hybrid paradigms, among others. In this report, we describe the combination of dimerizer-regulated two-hybrid and tetracycline regulatory elements in an ordered cascade, placing expression of endpoint reporters under the control of two distinct drugs. In this Dual Drug Control (DDC) system, a first plasmid expresses fusion proteins to DBD and AD, which interact only in the presence of a small molecule dimerizer; a second plasmid encodes a cassette transcriptionally responsive to the first DBD, directing expression of the Tet-OFF protein; and a third plasmid encodes a reporter gene transcriptionally responsive to binding by Tet-OFF. We evaluate the dynamic range and specificity of this system in comparison to other available systems. This study demonstrates the feasibility of combining two discrete drug-regulated expression systems in a temporally sequential cascade, without loss of dynamic range of signal induction. The efficient layering of control levels allowed by this combination of elements provides the potential for the generation of complex control circuitry that may advance ability to regulate gene expression in vivo.

  18. Predicting locations of rare aquatic species’ habitat with a combination of species-specific and assemblage-based models

    USGS Publications Warehouse

    McKenna, James E.; Carlson, Douglas M.; Payne-Wynne, Molly L.

    2013-01-01

    Aim: Rare aquatic species are a substantial component of biodiversity, and their conservation is a major objective of many management plans. However, they are difficult to assess, and their optimal habitats are often poorly known. Methods to effectively predict the likely locations of suitable rare aquatic species habitats are needed. We combine two modelling approaches to predict occurrence and general abundance of several rare fish species. Location: Allegheny watershed of western New York State (USA) Methods: Our method used two empirical neural network modelling approaches (species specific and assemblage based) to predict stream-by-stream occurrence and general abundance of rare darters, based on broad-scale habitat conditions. Species-specific models were developed for longhead darter (Percina macrocephala), spotted darter (Etheostoma maculatum) and variegate darter (Etheostoma variatum) in the Allegheny drainage. An additional model predicted the type of rare darter-containing assemblage expected in each stream reach. Predictions from both models were then combined inclusively and exclusively and compared with additional independent data. Results Example rare darter predictions demonstrate the method's effectiveness. Models performed well (R2 ≥ 0.79), identified where suitable darter habitat was most likely to occur, and predictions matched well to those of collection sites. Additional independent data showed that the most conservative (exclusive) model slightly underestimated the distributions of these rare darters or predictions were displaced by one stream reach, suggesting that new darter habitat types were detected in the later collections. Main conclusions Broad-scale habitat variables can be used to effectively identify rare species' habitats. Combining species-specific and assemblage-based models enhances our ability to make use of the sparse data on rare species and to identify habitat units most likely and least likely to support those species. This hybrid approach may assist managers with the prioritization of habitats to be examined or conserved for rare species.

  19. Printed Spacecraft Separation System

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

    Holmans, Walter; Dehoff, Ryan

    In this project Planetary Systems Corporation proposed utilizing additive manufacturing (3D printing) to manufacture a titanium spacecraft separation system for commercial and US government customers to realize a 90% reduction in the cost and energy. These savings were demonstrated via “printing-in” many of the parts and sub-assemblies into one part, thus greatly reducing the labor associated with design, procurement, assembly and calibration of mechanisms. Planetary Systems Corporation redesigned several of the components of the separation system based on additive manufacturing principles including geometric flexibility and the ability to fabricate complex designs, ability to combine multiple parts of an assembly intomore » a single component, and the ability to optimize design for specific mechanical property targets. Shock absorption was specifically targeted and requirements were established to attenuate damage to the Lightband system from shock of initiation. Planetary Systems Corporation redesigned components based on these requirements and sent the designs to Oak Ridge National Laboratory to be printed. ORNL printed the parts using the Arcam electron beam melting technology based on the desire for the parts to be fabricated from Ti-6Al-4V based on the weight and mechanical performance of the material. A second set of components was fabricated from stainless steel material on the Renishaw laser powder bed technology due to the improved geometric accuracy, surface finish, and wear resistance of the material. Planetary Systems Corporation evaluated these components and determined that 3D printing is potentially a viable method for achieving significant cost and savings metrics.« less

  20. Combination Therapy with a Second-Generation Androgen Receptor Antagonist and a Metastasis Vaccine Improves Survival in a Spontaneous Prostate Cancer Model

    PubMed Central

    Ardiani, Andressa; Farsaci, Benedetto; Rogers, Connie J.; Protter, Andy; Guo, Zhimin; King, Thomas H.; Apelian, David; Hodge, James W.

    2013-01-01

    Purpose Enzalutamide, a second-generation androgen antagonist, was approved by the FDA for castration-resistant prostate cancer (CRPC) treatment. Immunotherapy has been shown to be a promising strategy for prostate cancer. This study is performed to provide data to support the combination of enzalutamide and immunotherapy for CRPC treatment. Experimental Design Male C57BL/6 or TRAMP prostate cancer model mice were exposed to enzalutamide and/or a therapeutic vaccine targeting Twist, an antigen involved in epithelial-to-mesenchymal transition and metastasis. The physiological and immunological effects of enzalutamide were characterized. The generation of Twist-specific immunity by Twist-vaccine was evaluated. Finally, the combination of enzalutamide and Twist-vaccine to improve TRAMP mice overall survival was evaluated. Results Enzalutamide mediated immunogenic modulation in TRAMP-C2 cells. In vivo, enzalutamide mediated reduced genitourinary tissue weight, enlargement of the thymus, and increased levels of T-cell excision circles. Because no changes were seen in T-cell function, as determined by CD4+ T-cell proliferation and Treg functional assays, enzalutamide was determined to be immune inert. Enzalutamide did not diminish the Twist-vaccine’s ability to generate Twist-specific immunity. Twist was confirmed as a valid tumor antigen in TRAMP mice by immunohistochemistry. The combination of enzalutamide and Twist-vaccine resulted in significantly increased overall survival of TRAMP mice compared to other treatment groups (27.5 vs. 10.3 weeks). Notably, the effectiveness of the combination therapy increased with disease stage, i.e., the greatest survival benefit was seen in mice with advanced-stage prostate tumors. Conclusions These data support the combination of enzalutamide and immunotherapy as a promising treatment strategy for CRPC. PMID:24048332

  1. Pleural effusion biomarkers and computed tomography findings in diagnosing malignant pleural mesothelioma: A retrospective study in a single center.

    PubMed

    Otoshi, Takehiro; Kataoka, Yuki; Ikegaki, Shunkichi; Saito, Emiko; Matsumoto, Hirotaka; Kaku, Sawako; Shimada, Masatoshi; Hirabayashi, Masataka

    2017-01-01

    In this study, we aimed to examine the clinical value of the pleural effusion (PE) biomarkers, soluble mesothelin-related peptide (SMRP), cytokeratin 19 fragment (CYFRA 21-1) and carcinoembryonic antigen (CEA), and the utility of combining chest computed tomography (CT) findings with these biomarkers, in diagnosing malignant pleural mesothelioma (MPM). We conducted a retrospective cohort study in a single center. Consecutive patients with undiagnosed pleural effusions who underwent PE analysis between September 2014 and August 2016 were reviewed. This study included 240 patients (32 with MPM and 208 non-MPM). SMRP and the CYFRA 21-1/CEA ratio had a sensitivity and specificity for diagnosing MPM of 56.3% and 86.5%, and 87.5% and 74.0%, respectively. Using receiver operating characteristics (ROC) curve analysis of the ability of these markers to distinguish MPM from all other PE causes, the area under the ROC curve (AUC) for SMRP and the CYFRA 21-1/CEA ratio was 0.804 and 0.874, respectively. The sensitivity and specificity of SMRP combined with the CYFRA 21-1/CEA ratio were 93.8% and 64.9%, respectively. The sensitivity of the combination of SMRP, the CYFRA 21-1/CEA ratio, and the presence of Leung's criteria (a chest CT finding that is suggestive of malignant pleural disease) was 93.8%. In conclusion, the combined PE biomarkers had a high sensitivity for diagnosing MPM, although the addition of chest CT findings did not improve the sensitivity of SMRP combined with the CYFRA 21-1/CEA ratio. Combination of these biomarkers helped to rule out MPM effectively among patients at high risk of suffering MPM and would be valuable especially for old frail patients who have difficulty in undergoing invasive procedures such as thoracoscopy.

  2. Polymer Nanocomposite Film with Metal Rich Surface Prepared by In Situ Single-Step Formation of Palladium Nanoparticles: An Interesting Way to Combine Specific Functional Properties.

    PubMed

    Thompson, David; Kranbuehl, David; Espuche, Eliane

    2016-10-18

    This paper presents a continuous single-step route that permits preparation of a thermostable polymer/metal nanocomposite film and to combine different functional properties in a unique material. More precisely, palladium nanoparticles are in situ generated in a polyimide matrix thanks to a designed curing cycle which is applied to a polyamic acid/metal precursor solution cast on a glass plate. A metal-rich surface layer which is strongly bonded to the bulk film is formed in addition to homogeneously dispersed metal nanoparticles. This specific morphology leads to obtaining an optically reflective film. The metal nanoparticles act as gas diffusion barriers for helium, oxygen, and carbon dioxide; they induce a tortuosity effect which allows dividing the gas permeation coefficients by a factor near to 2 with respect to the neat polyimide matrix. Moreover, the ability of the in situ synthesized palladium nanoparticles to entrap hydrogen is evidenced. The nanocomposite film properties can be modulated as a function of the location of the film metal-rich surface with respect to the hydrogen feed. The synthesized nanocomposite could represent a major interest for a wide variety of applications, from specific coatings for aerospace or automotive industry, to catalysis applications or sensors.

  3. Anxiety is not enough to drive me away: A latent profile analysis on math anxiety and math motivation.

    PubMed

    Wang, Zhe; Shakeshaft, Nicholas; Schofield, Kerry; Malanchini, Margherita

    2018-01-01

    Mathematics anxiety (MA) and mathematics motivation (MM) are important multi-dimensional non-cognitive factors in mathematics learning. While the negative relation between global MA and MM is well replicated, the relations between specific dimensions of MA and MM are largely unexplored. The present study utilized latent profile analysis to explore profiles of various aspects of MA (including learning MA and exam MA) and MM (including importance, self-perceived ability, and interest), to provide a more holistic understanding of the math-specific emotion and motivation experiences. In a sample of 927 high school students (13-21 years old), we found 8 distinct profiles characterized by various combinations of dimensions of MA and MM, revealing the complexity in the math-specific emotion-motivation relation beyond a single negative correlation. Further, these profiles differed on mathematics learning behaviors and mathematics achievement. For example, the highest achieving students reported modest exam MA and high MM, whereas the most engaged students were characterized by a combination of high exam MA and high MM. These results call for the need to move beyond linear relations among global constructs to address the complexity in the emotion-motivation-cognition interplay in mathematics learning, and highlight the importance of customized intervention for these heterogeneous groups.

  4. Anxiety is not enough to drive me away: A latent profile analysis on math anxiety and math motivation

    PubMed Central

    Shakeshaft, Nicholas; Schofield, Kerry; Malanchini, Margherita

    2018-01-01

    Mathematics anxiety (MA) and mathematics motivation (MM) are important multi-dimensional non-cognitive factors in mathematics learning. While the negative relation between global MA and MM is well replicated, the relations between specific dimensions of MA and MM are largely unexplored. The present study utilized latent profile analysis to explore profiles of various aspects of MA (including learning MA and exam MA) and MM (including importance, self-perceived ability, and interest), to provide a more holistic understanding of the math-specific emotion and motivation experiences. In a sample of 927 high school students (13–21 years old), we found 8 distinct profiles characterized by various combinations of dimensions of MA and MM, revealing the complexity in the math-specific emotion-motivation relation beyond a single negative correlation. Further, these profiles differed on mathematics learning behaviors and mathematics achievement. For example, the highest achieving students reported modest exam MA and high MM, whereas the most engaged students were characterized by a combination of high exam MA and high MM. These results call for the need to move beyond linear relations among global constructs to address the complexity in the emotion-motivation-cognition interplay in mathematics learning, and highlight the importance of customized intervention for these heterogeneous groups. PMID:29444137

  5. Evaluation of end-tidal CO2 pressure at the anaerobic threshold for detecting and assessing pulmonary hypertension.

    PubMed

    Higashi, Akifumi; Dohi, Yoshihiro; Yamabe, Sayuri; Kinoshita, Hiroki; Sada, Yoshiharu; Kitagawa, Toshiro; Hidaka, Takayuki; Kurisu, Satoshi; Yamamoto, Hideya; Yasunobu, Yuji; Kihara, Yasuki

    2017-11-01

    Cardiopulmonary exercise testing (CPET) is useful for the evaluation of patients with suspected or confirmed pulmonary hypertension (PH). End-tidal carbon dioxide pressure (PETCO 2 ) during exercise is reduced with elevated pulmonary artery pressure. However, the utility of ventilatory parameters such as CPET for detecting PH remains unclear. We conducted a review in 155 patients who underwent right heart catheterization and CPET. Fifty-nine patients had PH [mean pulmonary arterial pressure (mPAP) ≥25 mmHg]. There was an inverse correlation between PETCO 2 at the anaerobic threshold (AT) and mPAP (r = -0.66; P < 0.01). Multiple regression analysis showed that PETCO 2 at the AT was independently associated with an elevated mPAP (P = 0.04). The sensitivity and specificity of CPET for PH were 80 and 86%, respectively, when the cut-off value identified by receiver operating characteristic curve analysis for PETCO 2 at the AT was ≤34.7 mmHg. A combination of echocardiography and CPET improved the sensitivity in detecting PH without markedly reducing specificity (sensitivity 87%, specificity 85%). Evaluation of PETCO 2 at the AT is useful for estimating pulmonary pressure. A combination of CPET and previous screening algorithms for PH may enhance the diagnostic ability of PH.

  6. Cid1, a Fission Yeast Protein Required for S-M Checkpoint Control when DNA Polymerase δ or ɛ Is Inactivated

    PubMed Central

    Wang, Shao-Win; Toda, Takashi; MacCallum, Robert; Harris, Adrian L.; Norbury, Chris

    2000-01-01

    The S-M checkpoint is an intracellular signaling pathway that ensures that mitosis is not initiated in cells undergoing DNA replication. We identified cid1, a novel fission yeast gene, through its ability when overexpressed to confer specific resistance to a combination of hydroxyurea, which inhibits DNA replication, and caffeine, which overrides the S-M checkpoint. Cid1 overexpression also partially suppressed the hydroxyurea sensitivity characteristic of DNA polymerase δ mutants and mutants defective in the “checkpoint Rad” pathway. Cid1 is a member of a family of putative nucleotidyltransferases including budding yeast Trf4 and Trf5, and mutation of amino acid residues predicted to be essential for this activity resulted in loss of Cid1 function in vivo. Two additional Cid1-like proteins play similar but nonredundant checkpoint-signaling roles in fission yeast. Cells lacking Cid1 were found to be viable but specifically sensitive to the combination of hydroxyurea and caffeine and to be S-M checkpoint defective in the absence of Cds1. Genetic data suggest that Cid1 acts in association with Crb2/Rhp9 and through the checkpoint-signaling kinase Chk1 to inhibit unscheduled mitosis specifically when DNA polymerase δ or ɛ is inhibited. PMID:10757807

  7. Six-month Follow Up of the Injured Trauma Survivor Screen (ITSS): Clinical Implications and Future Directions.

    PubMed

    Hunt, Joshua C; Chesney, Samantha A; Brasel, Karen; deRoon-Cassini, Terri A

    2018-04-17

    The Injured Trauma Survivor Screen (ITSS) has been shown to predict PTSD and depression risk at one-month after traumatic injury. This study explored the ability of the ITSS to predict chronic distress after injury, as well as the impact of combining the ITSS with an additional screening measure. Patients were enrolled following admission to a Level 1 trauma center. Baseline measurements were collected during initial hospitalization, and follow-up measures were collected an average of 6.5 months after injury. Receiver Operating Characteristic (ROC) curve analyses were run to determine predictive accuracy, controlling for participants who had mental health intervention and for those who experienced additional potentially psychologically traumatic events since their injury event. Utilizing a cut score of 2, the ITSS PTSD scale had a sensitivity of 85.42%, specificity 67.35%, NPV 91.9% and PPV 51.4%. The Combined PTSD risk group (risk positive on the baseline ITSS and the PTSD Checklist for the DSM-5) had a sensitivity of 72.92%, specificity 81.63%, NPV 88.2% and PPV 61.6%. Also utilizing a cut score of 2, the ITSS Depression scale had a sensitivity of 72.50%, specificity 70.29%, NPV 91.1% and PPV 37.9%. The 9-item ITSS, which takes approximately five minutes to administer, is a stable screening tool for predicting those most at risk for PTSD and/or depression six-months after admission to a Level 1 trauma center following traumatic injury. The Combined PTSD risk group data provide evidence that symptom evaluation by a psychologist can improve specificity. These results further inform the recommendation of the American College of Surgeons Committee on Trauma regarding PTSD and depression screening in trauma centers. Prognostic study, Level III.

  8. Cognitive factors affecting children's nonsymbolic and symbolic magnitude judgment abilities: A latent profile analysis.

    PubMed

    Chew, Cindy S; Forte, Jason D; Reeve, Robert A

    2016-12-01

    Early math abilities are claimed to be linked to magnitude representation ability. Some claim that nonsymbolic magnitude abilities scaffold the acquisition of symbolic (Arabic number) magnitude abilities and influence math ability. Others claim that symbolic magnitude abilities, and ipso facto math abilities, are independent of nonsymbolic abilities and instead depend on the ability to process number symbols (e.g., 2, 7). Currently, the issue of whether symbolic abilities are or are not related to nonsymbolic abilities, and the cognitive factors associated with nonsymbolic-symbolic relationships, remains unresolved. We suggest that different nonsymbolic-symbolic relationships reside within the general magnitude ability distribution and that different cognitive abilities are likely associated with these different relationships. We further suggest that the different nonsymbolic-symbolic relationships and cognitive abilities in combination differentially predict math abilities. To test these claims, we used latent profile analysis to identify nonsymbolic-symbolic judgment patterns of 124, 5- to 7-year-olds. We also assessed four cognitive factors (visuospatial working memory [VSWM], naming numbers, nonverbal IQ, and basic reaction time [RT]) and two math abilities (number transcoding and single-digit addition abilities). Four nonsymbolic-symbolic ability profiles were identified. Naming numbers, VSWM, and basic RT abilities were differentially associated with the different ability profiles and in combination differentially predicted math abilities. Findings show that different patterns of nonsymbolic-symbolic magnitude abilities can be identified and suggest that an adequate account of math development should specify the inter-relationship between cognitive factors and nonsymbolic-symbolic ability patterns. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Antibody-drug conjugates for cancer therapy: The technological and regulatory challenges of developing drug-biologic hybrids.

    PubMed

    Hamilton, Gregory S

    2015-09-01

    Antibody-drug conjugates (ADCs) are a new class of therapeutic agents that combine the targeting ability of monoclonal antibodies (mAbs) with small molecule drugs. The combination of a mAb targeting a cancer-specific antigen with a cytotoxin has tremendous promise as a new type of targeted cancer therapy. Two ADCs have been approved and many more are in clinical development, suggesting that this new class of drugs is coming to the forefront. Because of their unique nature as biologic-small drug hybrids, ADCs are challenging to develop, from both the scientific and regulatory perspectives. This review discusses both these aspects in current practice, and surveys the current state of the art of ADC drug development. Copyright © 2015 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

  10. Lineage plasticity-mediated therapy resistance in prostate cancer.

    PubMed

    Blee, Alexandra M; Huang, Haojie

    2018-06-12

    Therapy resistance is a significant challenge for prostate cancer treatment in clinic. Although targeted therapies such as androgen deprivation and androgen receptor (AR) inhibition are effective initially, tumor cells eventually evade these strategies through multiple mechanisms. Lineage reprogramming in response to hormone therapy represents a key mechanism that is increasingly observed. The studies in this area have revealed specific combinations of alterations present in adenocarcinomas that provide cells with the ability to transdifferentiate and perpetuate AR-independent tumor growth after androgen-based therapies. Interestingly, several master regulators have been identified that drive plasticity, some of which also play key roles during development and differentiation of the cell lineages in the normal prostate. Thus, further study of each AR-independent tumor type and understanding underlying mechanisms are warranted to develop combinational therapies that combat lineage plasticity in prostate cancer.

  11. Magnetic nanoparticles for targeted therapeutic gene delivery and magnetic-inducing heating on hepatoma

    NASA Astrophysics Data System (ADS)

    Yuan, Chenyan; An, Yanli; Zhang, Jia; Li, Hongbo; Zhang, Hao; Wang, Ling; Zhang, Dongsheng

    2014-08-01

    Gene therapy holds great promise for treating cancers, but their clinical applications are being hampered due to uncontrolled gene delivery and expression. To develop a targeted, safe and efficient tumor therapy system, we constructed a tissue-specific suicide gene delivery system by using magnetic nanoparticles (MNPs) as carriers for the combination of gene therapy and hyperthermia on hepatoma. The suicide gene was hepatoma-targeted and hypoxia-enhanced, and the MNPs possessed the ability to elevate temperature to the effective range for tumor hyperthermia as imposed on an alternating magnetic field (AMF). The tumoricidal effects of targeted gene therapy associated with hyperthermia were evaluated in vitro and in vivo. The experiment demonstrated that hyperthermia combined with a targeted gene therapy system proffer an effective tool for tumor therapy with high selectivity and the synergistic effect of hepatoma suppression.

  12. Morphological and motor characteristics of Croatian first league female football players.

    PubMed

    Jelaska, Petra Mandić; Katić, Ratko; Jelaska, Igor

    2013-05-01

    The aim of this study was to determine the structure of morphological and motor characteristics of Croatian first league female football players and their impact on the estimated quality of the players. According to the goal of the research, a sample consisted of 70 Croatian first league female football players. Participants were measured in 18 tests for assessing morphological characteristics, a set of 12 basic motor abilities tests and a set of 7 tests for assessing football-specific motor abilities. Exploratory factor analysis strategy was applied separately to all measured tests: morphological, basic motor abilities and football specific motor abilities. Factor analysis of morphological tests has shown existence of 3 significant latent dimensions that explain 64% of the total variability. Factors are defined as transverse dimensionality of the skeleton and voluminosity (35%), subcutaneous fat tissue (16%) and longitudinal dimensionality of the skeleton (13%). In the area of basic motor abilities, four factors were extracted. The first factor is responsible for the integration of agility and explosive power of legs, i.e. a factor of movement regulation (agility/lower body explosiveness) (23%), the second one defines muscle tone regulation (15%), the third one defines the frequency of leg movements (12%), while the fourth one is recognized as responsible for the manifestation of basic strength, particularly of basic core strength (19%). Two factors were isolated in the space of football-specific motor abilities: football-specific efficiency (53%) and situational football coordination (27%). Furthermore, by use of factor analysis on extracted latent dimensions (morphological, basic and football specific motor abilities) two higher order factors (explaining 87% of common variability) were extracted. They were named morphological-motor factor (54%) and football-specific motor abilities factor (33%). It is assumed that two extracted higher-order factors fully describe morphological and motor status of first league female football players. Furthermore, the linear regression results in latent space showed that the identified factors are very good predictors of female football players quality (delta = 0.959). In doing so, both specific motor abilities factors and the first factor of basic motor abilities as a factor of general motor efficiency have the greatest impact on player quality, and these factors have been identified as most important predictors of player quality in Croatian women's first league and elite female football players in general. Obtained results provide deep insight into the structure of relations between the morphological, motor and specific motor variables and also indicate the importance of such definition of specific motor abilities. Consequently, results explicitly indicate the necessity of early, continuous, and systematic development of football-specific motor abilities in female football players of high competitive level but also, adjusted, to the younger age categories.

  13. The trigonal prism in coordination chemistry.

    PubMed

    Cremades, Eduard; Echeverría, Jorge; Alvarez, Santiago

    2010-09-10

    Herein we analyze the accessibility of the trigonal-prismatic geometry to metal complexes with different electron configurations, as well as the ability of several hexadentate ligands to favor that coordination polyhedron. Our study combines i) a structural database analysis of the occurrence of the prismatic geometry throughout the transition-metal series, ii) a qualitative molecular orbital analysis of the distortions expected for a trigonal-prismatic geometry, and iii) a computational study of complexes of several transition-metal ions with different hexadentate ligands. Also the tendency of specific electron configurations to present a cis bond-stretch Jahn-Teller distortion is analyzed.

  14. Nanotheranostics: Congo Red/Rutin-MNPs with Enhanced Magnetic Resonance Imaging and H2O2-Responsive Therapy of Alzheimer's Disease in APPswe/PS1dE9 Transgenic Mice.

    PubMed

    Hu, Bingbing; Dai, Fengying; Fan, Zhanming; Ma, Guanghui; Tang, Qunwei; Zhang, Xin

    2015-10-07

    As nanotheranostics, Congo red/Rutin-MNPs combine the abilities of diagnosis and treatment of Alzheimer's disease (AD). The biocompatible nanotheranostics system based on iron oxide magnetic nanoparticles, with ultrasmall size and excellent magnetic properties, can specifically detect amyloid plaques by magnetic resonance imaging, realize targeted delivery of AD therapeutic agents, achieve drug controlled release by H2O2 response, and prevent oxidative stress. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Synthesis of 4′-aminopantetheine and derivatives to probe aminoglycoside N-6′-acetyltransferase

    PubMed Central

    Yan, Xuxu; Akinnusi, T. Olukayode; Larsen, Aaron T.; Auclair, Karine

    2011-01-01

    Summary A convenient synthesis of 4′-aminopantetheine from commercial D-pantethine is reported. The amino group was introduced by reductive amination in order to avoid substitution at a sterically congested position. Derivatives of 4′-aminopantetheine were also prepared to evaluate the effect of O-to-N substitution on inhibitors of the resistance-causing enzyme aminoglycoside N-6′-acetyltransferase. The biological results combined with docking studies indicate that in spite of its reported unusual flexibility and ability to adopt different folds, this enzyme is highly specific for AcCoA. PMID:21225062

  16. Ultrafast electron diffraction optimized for studying structural dynamics in thin films and monolayers

    PubMed Central

    Badali, D. S.; Gengler, R. Y. N.; Miller, R. J. D.

    2016-01-01

    A compact electron source specifically designed for time-resolved diffraction studies of free-standing thin films and monolayers is presented here. The sensitivity to thin samples is achieved by extending the established technique of ultrafast electron diffraction to the “medium” energy regime (1–10 kV). An extremely compact design, in combination with low bunch charges, allows for high quality diffraction in a lensless geometry. The measured and simulated characteristics of the experimental system reveal sub-picosecond temporal resolution, while demonstrating the ability to produce high quality diffraction patterns from atomically thin samples. PMID:27226978

  17. Biomarkers of sepsis and their potential value in diagnosis, prognosis and treatment

    PubMed Central

    Sandquist, Mary; Wong, Hector R

    2015-01-01

    Biomarkers have great potential to improve the diagnosis and treatment of sepsis. The available literature supports the potential utility of sTREM-1, IL-27, suPAR, neutrophil CD64, presepsin, cfDNA and miRNAs as novel diagnostic, prognostic and treatment response biomarkers. The future of sepsis biomarkers lies in extensive validation studies of such novel biomarkers across heterogeneous populations and exploration of their power in combination. Furthermore, the use of a companion diagnostics model may augment the ability of investigators to identify novel sepsis biomarkers and develop specific therapeutic strategies based on biomarker information. PMID:25142036

  18. Targeted Capture and High-Throughput Sequencing Using Molecular Inversion Probes (MIPs).

    PubMed

    Cantsilieris, Stuart; Stessman, Holly A; Shendure, Jay; Eichler, Evan E

    2017-01-01

    Molecular inversion probes (MIPs) in combination with massively parallel DNA sequencing represent a versatile, yet economical tool for targeted sequencing of genomic DNA. Several thousand genomic targets can be selectively captured using long oligonucleotides containing unique targeting arms and universal linkers. The ability to append sequencing adaptors and sample-specific barcodes allows large-scale pooling and subsequent high-throughput sequencing at relatively low cost per sample. Here, we describe a "wet bench" protocol detailing the capture and subsequent sequencing of >2000 genomic targets from 192 samples, representative of a single lane on the Illumina HiSeq 2000 platform.

  19. The Effect of a Combined High-Intensity Plyometric and Speed Training Program on the Running and Jumping Ability of Male Handball Players

    PubMed Central

    Cherif, Monsef; Said, Mohamed; Chaatani, Sana; Nejlaoui, Olfa; Gomri, Daghbaji; Abdallah, Aouidet

    2012-01-01

    Purpose The aim of this study was to investigate the effect of a combined program including sprint repetitions and drop jump training in the same session on male handball players. Methods Twenty-two male handball players aged more than 20 years were assigned into 2 groups: experimental group (n=11) and control group (n=11). Selection was based on variables “axis” and “lines”, goalkeepers were not included. The experimental group was subjected to 2 testing periods (test and retest) separated by 12 weeks of an additional combined plyometric and running speed training program. The control group performed the usual handball training. The testing period comprised, at the first day, a medical checking, anthropometric measurements and an incremental exercise test called yo-yo intermittent recovery test. 2 days later, participants performed the Repeated Sprint Ability test (RSA), and performed the Jumping Performance using 3 different events: Squat jump (SJ), Countermovement jump without (CMJ) and with arms (CMJA), and Drop jump (DJ). At the end of the training period, participants performed again the repeated sprint ability test, and the jumping performance. Results The conventional combined program improved the explosive force ability of handball players in CMJ (P=0.01), CMJA (P=0.01) and DJR (P=0.03). The change was 2.78, 2.42 and 2.62% respectively. No significant changes were noted in performances of the experimental group at the squat jump test and the drop jump with the left leg test. The training intervention also improved the running speed ability of the experimental group (P=0.003). No statistical differences were observed between lines or axes. Conclusion Additional combined training program between sprint repetition and vertical jump in the same training session positively influence the jumping ability and the sprint ability of handball players. PMID:22461962

  20. The effect of a combined high-intensity plyometric and speed training program on the running and jumping ability of male handball players.

    PubMed

    Cherif, Monsef; Said, Mohamed; Chaatani, Sana; Nejlaoui, Olfa; Gomri, Daghbaji; Abdallah, Aouidet

    2012-03-01

    The aim of this study was to investigate the effect of a combined program including sprint repetitions and drop jump training in the same session on male handball players. Twenty-two male handball players aged more than 20 years were assigned into 2 groups: experimental group (n=11) and control group (n=11). Selection was based on variables "axis" and "lines", goalkeepers were not included. The experimental group was subjected to 2 testing periods (test and retest) separated by 12 weeks of an additional combined plyometric and running speed training program. The control group performed the usual handball training. The testing period comprised, at the first day, a medical checking, anthropometric measurements and an incremental exercise test called yo-yo intermittent recovery test. 2 days later, participants performed the Repeated Sprint Ability test (RSA), and performed the Jumping Performance using 3 different events: Squat jump (SJ), Countermovement jump without (CMJ) and with arms (CMJA), and Drop jump (DJ). At the end of the training period, participants performed again the repeated sprint ability test, and the jumping performance. The conventional combined program improved the explosive force ability of handball players in CMJ (P=0.01), CMJA (P=0.01) and DJR (P=0.03). The change was 2.78, 2.42 and 2.62% respectively. No significant changes were noted in performances of the experimental group at the squat jump test and the drop jump with the left leg test. The training intervention also improved the running speed ability of the experimental group (P=0.003). No statistical differences were observed between lines or axes. Additional combined training program between sprint repetition and vertical jump in the same training session positively influence the jumping ability and the sprint ability of handball players.

  1. Specific and Modular Binding Code for Cytosine Recognition in Pumilio/FBF (PUF) RNA-binding Domains

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

    Dong, Shuyun; Wang, Yang; Cassidy-Amstutz, Caleb

    2011-10-28

    Pumilio/fem-3 mRNA-binding factor (PUF) proteins possess a recognition code for bases A, U, and G, allowing designed RNA sequence specificity of their modular Pumilio (PUM) repeats. However, recognition side chains in a PUM repeat for cytosine are unknown. Here we report identification of a cytosine-recognition code by screening random amino acid combinations at conserved RNA recognition positions using a yeast three-hybrid system. This C-recognition code is specific and modular as specificity can be transferred to different positions in the RNA recognition sequence. A crystal structure of a modified PUF domain reveals specific contacts between an arginine side chain and themore » cytosine base. We applied the C-recognition code to design PUF domains that recognize targets with multiple cytosines and to generate engineered splicing factors that modulate alternative splicing. Finally, we identified a divergent yeast PUF protein, Nop9p, that may recognize natural target RNAs with cytosine. This work deepens our understanding of natural PUF protein target recognition and expands the ability to engineer PUF domains to recognize any RNA sequence.« less

  2. Rapid and reliable detection and identification of GM events using multiplex PCR coupled with oligonucleotide microarray.

    PubMed

    Xu, Xiaodan; Li, Yingcong; Zhao, Heng; Wen, Si-yuan; Wang, Sheng-qi; Huang, Jian; Huang, Kun-lun; Luo, Yun-bo

    2005-05-18

    To devise a rapid and reliable method for the detection and identification of genetically modified (GM) events, we developed a multiplex polymerase chain reaction (PCR) coupled with a DNA microarray system simultaneously aiming at many targets in a single reaction. The system included probes for screening gene, species reference gene, specific gene, construct-specific gene, event-specific gene, and internal and negative control genes. 18S rRNA was combined with species reference genes as internal controls to assess the efficiency of all reactions and to eliminate false negatives. Two sets of the multiplex PCR system were used to amplify four and five targets, respectively. Eight different structure genes could be detected and identified simultaneously for Roundup Ready soybean in a single microarray. The microarray specificity was validated by its ability to discriminate two GM maizes Bt176 and Bt11. The advantages of this method are its high specificity and greatly reduced false-positives and -negatives. The multiplex PCR coupled with microarray technology presented here is a rapid and reliable tool for the simultaneous detection of GM organism ingredients.

  3. Estimating drought risk across Europe from reported drought impacts, hazard indicators and vulnerability factors

    NASA Astrophysics Data System (ADS)

    Blauhut, V.; Stahl, K.; Stagge, J. H.; Tallaksen, L. M.; De Stefano, L.; Vogt, J.

    2015-12-01

    Drought is one of the most costly natural hazards in Europe. Due to its complexity, drought risk, the combination of the natural hazard and societal vulnerability, is difficult to define and challenging to detect and predict, as the impacts of drought are very diverse, covering the breadth of socioeconomic and environmental systems. Pan-European maps of drought risk could inform the elaboration of guidelines and policies to address its documented severity and impact across borders. This work (1) tests the capability of commonly applied hazard indicators and vulnerability factors to predict annual drought impact occurrence for different sectors and macro regions in Europe and (2) combines information on past drought impacts, drought hazard indicators, and vulnerability factors into estimates of drought risk at the pan-European scale. This "hybrid approach" bridges the gap between traditional vulnerability assessment and probabilistic impact forecast in a statistical modelling framework. Multivariable logistic regression was applied to predict the likelihood of impact occurrence on an annual basis for particular impact categories and European macro regions. The results indicate sector- and macro region specific sensitivities of hazard indicators, with the Standardised Precipitation Evapotranspiration Index for a twelve month aggregation period (SPEI-12) as the overall best hazard predictor. Vulnerability factors have only limited ability to predict drought impacts as single predictor, with information about landuse and water resources as best vulnerability-based predictors. (3) The application of the "hybrid approach" revealed strong regional (NUTS combo level) and sector specific differences in drought risk across Europe. The majority of best predictor combinations rely on a combination of SPEI for shorter and longer aggregation periods, and a combination of information on landuse and water resources. The added value of integrating regional vulnerability information with drought risk prediction could be proven. Thus, the study contributes to the overall understanding of drivers of drought impacts, current practice of drought indicators selection for specific application, and drought risk assessment.

  4. Estimating drought risk across Europe from reported drought impacts, drought indices, and vulnerability factors

    NASA Astrophysics Data System (ADS)

    Blauhut, Veit; Stahl, Kerstin; Stagge, James Howard; Tallaksen, Lena M.; De Stefano, Lucia; Vogt, Jürgen

    2016-07-01

    Drought is one of the most costly natural hazards in Europe. Due to its complexity, drought risk, meant as the combination of the natural hazard and societal vulnerability, is difficult to define and challenging to detect and predict, as the impacts of drought are very diverse, covering the breadth of socioeconomic and environmental systems. Pan-European maps of drought risk could inform the elaboration of guidelines and policies to address its documented severity and impact across borders. This work tests the capability of commonly applied drought indices and vulnerability factors to predict annual drought impact occurrence for different sectors and macro regions in Europe and combines information on past drought impacts, drought indices, and vulnerability factors into estimates of drought risk at the pan-European scale. This hybrid approach bridges the gap between traditional vulnerability assessment and probabilistic impact prediction in a statistical modelling framework. Multivariable logistic regression was applied to predict the likelihood of impact occurrence on an annual basis for particular impact categories and European macro regions. The results indicate sector- and macro-region-specific sensitivities of drought indices, with the Standardized Precipitation Evapotranspiration Index (SPEI) for a 12-month accumulation period as the overall best hazard predictor. Vulnerability factors have only limited ability to predict drought impacts as single predictors, with information about land use and water resources being the best vulnerability-based predictors. The application of the hybrid approach revealed strong regional and sector-specific differences in drought risk across Europe. The majority of the best predictor combinations rely on a combination of SPEI for shorter and longer accumulation periods, and a combination of information on land use and water resources. The added value of integrating regional vulnerability information with drought risk prediction could be proven. Thus, the study contributes to the overall understanding of drivers of drought impacts, appropriateness of drought indices selection for specific applications, and drought risk assessment.

  5. The Interaction of Temporal and Spectral Acoustic Information with Word Predictability on Speech Intelligibility

    NASA Astrophysics Data System (ADS)

    Shahsavarani, Somayeh Bahar

    High-level, top-down information such as linguistic knowledge is a salient cortical resource that influences speech perception under most listening conditions. But, are all listeners able to exploit these resources for speech facilitation to the same extent? It was found that children with cochlear implants showed different patterns of benefit from contextual information in speech perception compared with their normal-haring peers. Previous studies have discussed the role of non-acoustic factors such as linguistic and cognitive capabilities to account for this discrepancy. Given the fact that the amount of acoustic information encoded and processed by auditory nerves of listeners with cochlear implants differs from normal-hearing listeners and even varies across individuals with cochlear implants, it is important to study the interaction of specific acoustic properties of the speech signal with contextual cues. This relationship has been mostly neglected in previous research. In this dissertation, we aimed to explore how different acoustic dimensions interact to affect listeners' abilities to combine top-down information with bottom-up information in speech perception beyond the known effects of linguistic and cognitive capacities shown previously. Specifically, the present study investigated whether there were any distinct context effects based on the resolution of spectral versus slowly-varying temporal information in perception of spectrally impoverished speech. To that end, two experiments were conducted. In both experiments, a noise-vocoded technique was adopted to generate spectrally-degraded speech to approximate acoustic cues delivered to listeners with cochlear implants. The frequency resolution was manipulated by varying the number of frequency channels. The temporal resolution was manipulated by low-pass filtering of amplitude envelope with varying low-pass cutoff frequencies. The stimuli were presented to normal-hearing native speakers of American English. Our results revealed a significant interaction effect between spectral, temporal, and contextual information in the perception of spectrally-degraded speech. This suggests that specific types and degradation of bottom-up information combine differently to utilize contextual resources. These findings emphasize the importance of taking the listener's specific auditory abilities into consideration while studying context effects. These results also introduce a novel perspective for designing interventions for listeners with cochlear implants or other auditory prostheses.

  6. Effectiveness of functional hand splinting and the cognitive orientation to occupational performance (CO-OP) approach in children with cerebral palsy and brain injury: two randomised controlled trial protocols

    PubMed Central

    2014-01-01

    Background Cerebral palsy (CP) and brain injury (BI) are common conditions that have devastating effects on a child’s ability to use their hands. Hand splinting and task-specific training are two interventions that are often used to address deficits in upper limb skills, both in isolation or concurrently. The aim of this paper is to describe the method to be used to conduct two randomised controlled trials (RCT) investigating (a) the immediate effect of functional hand splints, and (b) the effect of functional hand splints used concurrently with task-specific training compared to functional hand splints alone, and to task-specific training alone in children with CP and BI. The Cognitive Orientation to Occupational Performance (CO-OP) approach will be the task-specific training approach used. Methods/Design Two concurrent trials; a two group, parallel design, RCT with a sample size of 30 participants (15 per group); and a three group, parallel design, assessor blinded, RCT with a sample size of 45 participants (15 per group). Inclusion criteria: age 4-15 years; diagnosis of CP or BI; Manual Abilities Classification System (MACS) level I – IV; hand function goals; impaired hand function; the cognitive, language and behavioural ability to participate in CO-OP. Participants will be randomly allocated to one of 3 groups; (1) functional hand splint only (n=15); (2) functional hand splint combined with task-specific training (n=15); (3) task-specific training only (n=15). Allocation concealment will be achieved using sequentially numbered, sealed opaque envelopes opened by an off-site officer after baseline measures. Treatment will be provided for a period of 2 weeks, with outcome measures taken at baseline, 1 hour after randomisation, 2 weeks and 10 weeks. The functional hand splint will be a wrist cock-up splint (+/- thumb support or supination strap). Task-specific training will involve 10 sessions of CO-OP provided in a group of 2-4 children. Primary outcome measures will be the Canadian Occupational Performance Measure (COPM) and the Goal Attainment Scale (GAS). Analysis will be conducted on an intention-to-treat basis. Discussion This paper outlines the protocol for two randomised controlled trials investigating functional hand splints and CO-OP for children with CP and BI. PMID:25023385

  7. Validation of Yoon's Critical Thinking Disposition Instrument.

    PubMed

    Shin, Hyunsook; Park, Chang Gi; Kim, Hyojin

    2015-12-01

    The lack of reliable and valid evaluation tools targeting Korean nursing students' critical thinking (CT) abilities has been reported as one of the barriers to instructing and evaluating students in undergraduate programs. Yoon's Critical Thinking Disposition (YCTD) instrument was developed for Korean nursing students, but few studies have assessed its validity. This study aimed to validate the YCTD. Specifically, the YCTD was assessed to identify its cross-sectional and longitudinal measurement invariance. This was a validation study in which a cross-sectional and longitudinal (prenursing and postnursing practicum) survey was used to validate the YCTD using 345 nursing students at three universities in Seoul, Korea. The participants' CT abilities were assessed using the YCTD before and after completing an established pediatric nursing practicum. The validity of the YCTD was estimated and then group invariance test using multigroup confirmatory factor analysis was performed to confirm the measurement compatibility of multigroups. A test of the seven-factor model showed that the YCTD demonstrated good construct validity. Multigroup confirmatory factor analysis findings for the measurement invariance suggested that this model structure demonstrated strong invariance between groups (i.e., configural, factor loading, and intercept combined) but weak invariance within a group (i.e., configural and factor loading combined). In general, traditional methods for assessing instrument validity have been less than thorough. In this study, multigroup confirmatory factor analysis using cross-sectional and longitudinal measurement data allowed validation of the YCTD. This study concluded that the YCTD can be used for evaluating Korean nursing students' CT abilities. Copyright © 2015. Published by Elsevier B.V.

  8. SNW1 Is a Critical Regulator of Spatial BMP Activity, Neural Plate Border Formation, and Neural Crest Specification in Vertebrate Embryos

    PubMed Central

    Wu, Mary Y.; Ramel, Marie-Christine; Howell, Michael; Hill, Caroline S.

    2011-01-01

    Bone morphogenetic protein (BMP) gradients provide positional information to direct cell fate specification, such as patterning of the vertebrate ectoderm into neural, neural crest, and epidermal tissues, with precise borders segregating these domains. However, little is known about how BMP activity is regulated spatially and temporally during vertebrate development to contribute to embryonic patterning, and more specifically to neural crest formation. Through a large-scale in vivo functional screen in Xenopus for neural crest fate, we identified an essential regulator of BMP activity, SNW1. SNW1 is a nuclear protein known to regulate gene expression. Using antisense morpholinos to deplete SNW1 protein in both Xenopus and zebrafish embryos, we demonstrate that dorsally expressed SNW1 is required for neural crest specification, and this is independent of mesoderm formation and gastrulation morphogenetic movements. By exploiting a combination of immunostaining for phosphorylated Smad1 in Xenopus embryos and a BMP-dependent reporter transgenic zebrafish line, we show that SNW1 regulates a specific domain of BMP activity in the dorsal ectoderm at the neural plate border at post-gastrula stages. We use double in situ hybridizations and immunofluorescence to show how this domain of BMP activity is spatially positioned relative to the neural crest domain and that of SNW1 expression. Further in vivo and in vitro assays using cell culture and tissue explants allow us to conclude that SNW1 acts upstream of the BMP receptors. Finally, we show that the requirement of SNW1 for neural crest specification is through its ability to regulate BMP activity, as we demonstrate that targeted overexpression of BMP to the neural plate border is sufficient to restore neural crest formation in Xenopus SNW1 morphants. We conclude that through its ability to regulate a specific domain of BMP activity in the vertebrate embryo, SNW1 is a critical regulator of neural plate border formation and thus neural crest specification. PMID:21358802

  9. Combined X-ray and neutron fibre diffraction studies of biological and synthetic polymers

    NASA Astrophysics Data System (ADS)

    Parrot, I. M.; Urban, V.; Gardner, K. H.; Forsyth, V. T.

    2005-08-01

    The fibrous state is a natural one for polymer molecules which tend to assume regular helical conformations rather than the globular structures characteristic of many proteins. Fibre diffraction therefore has broad application to the study of a wide range of biological and synthetic polymers. The purpose of this paper is to illustrate the general scope of the method and in particular to demonstrate the impact of a combined approach involving both X-ray and neutron diffraction methods. While the flux of modern X-ray synchrotron radiation sources allows high quality datasets to be recorded with good resolution within a very short space of time, neutron studies can provide unique information through the ability to locate hydrogen or deuterium atoms that are often difficult or impossible to locate using X-ray methods. Furthermore, neutron fibre diffraction methods can, through the ability to selectively label specific parts of a structure, be used to highlight novel aspects of polymer structure that can not be studied using X-rays. Two examples are given. The first describes X-ray and neutron diffraction studies of conformational transitions in DNA. The second describes structural studies of the synthetic high-performance polymer poly(p-phenylene terephthalamide) (PPTA), known commercially as Kevlar® or Twaron®.

  10. Critical thinking in higher education: The influence of teaching styles and peer collaboration on science and math learning

    NASA Astrophysics Data System (ADS)

    Quitadamo, Ian Joseph

    Many higher education faculty perceive a deficiency in students' ability to reason, evaluate, and make informed judgments, skills that are deemed necessary for academic and job success in science and math. These skills, often collected within a domain called critical thinking (CT), have been studied and are thought to be influenced by teaching styles (the combination of beliefs, behavior, and attitudes used when teaching) and small group collaborative learning (SGCL). However, no existing studies show teaching styles and SGCL cause changes in student CT performance. This study determined how combinations of teaching styles called clusters and peer-facilitated SGCL (a specific form of SGCL) affect changes in undergraduate student CT performance using a quasi-experimental pre-test/post-test research design and valid and reliable CT performance indicators. Quantitative analyses of three teaching style cluster models (Grasha's cluster model, a weighted cluster model, and a student-centered/teacher-centered cluster model) and peer-facilitated SGCL were performed to evaluate their ability to cause measurable changes in student CT skills. Based on results that indicated weighted teaching style clusters and peer-facilitated SGCL are associated with significant changes in student CT, we conclude that teaching styles and peer-facilitated SGCL influence the development of undergraduate CT in higher education science and math.

  11. Bacterial-Mediated Knockdown of Tumor Resistance to an Oncolytic Virus Enhances Therapy

    PubMed Central

    Cronin, Michelle; Le Boeuf, Fabrice; Murphy, Carola; Roy, Dominic G; Falls, Theresa; Bell, John C; Tangney, Mark

    2014-01-01

    Oncolytic viruses (OVs) and bacteria share the property of tumor-selective replication following systemic administration. In the case of nonpathogenic bacteria, tumor selectivity relates to their ability to grow extracellularly within tumor stroma and is therefore ideally suited to restricting the production of bacterially produced therapeutic agents to tumors. We have previously shown the ability of the type 1 interferon antagonist B18R to enhance the replication and spread of vesicular stomatitis virus (VSV) by overcoming related cellular innate immunity. In this study, we utilized nonpathogenic bacteria (E. coli) expressing B18R to facilitate tumor-specific production of B18R, resulting in a microenvironment depleted of bioactive antiviral cytokine, thus “preconditioning” the tumor to enhance subsequent tumor destruction by the OV. Both in vitro and in vivo infection by VSVΔ51 was greatly enhanced by B18R produced from E. coli. Moreover, a significant increase in therapeutic efficacy resulted from intravenous (IV) injection of bacteria to tumor-bearing mice 5 days prior to IV VSVΔ51 administration, as evidenced by a significant reduction in tumor growth and increased survival in mice. Our strategy is the first example where two such diverse microorganisms are rationally combined and demonstrates the feasibility of combining complementary microorganisms to improve therapeutic outcome. PMID:24569832

  12. Two-stage selection in slash pine produces good gains in fusiform rust resistance

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

    Sluder, E.R.

    The best 6 of 21 progeny-tested first-generation slash pine selections were crossed in a half diallel to study inheritance patterns of their superior fusiform rust resistance (5 trees) and height (1 tree). Their six first-test progenies were duplicated and included in the study. These two groups of progenies, along with two commercial check lots, were planted on an Upper Coastal Plain and a Flatwoods site in Georgia. At age 10 yr, the 15 progenies in the half diallel averaged 23% rust-infected compared with 54% for the check lots. First-test progenies averaged 30% infected. For percentage infection, the six parents differedmore » in general combining ability (GCA) (0.01>P>0.001) on both test sites and in specific combining ability (0.05>P>0.01) on one site. GCA variation for height was significant (0.05>P>0.01) on one site. The parent selected for height had the highest breeding value for height at age 10 yr. These results show that resistance to the fusiform rust disease, a serious problem in management of the species, can be improved in slash pine. These 6 parents and their 15 progenies in the half-diallel cross are a good source of rust resistance genes for use in slash pine improvement programs.« less

  13. Characterization of combined cross-linked enzyme aggregates from laccase, versatile peroxidase and glucose oxidase, and their utilization for the elimination of pharmaceuticals.

    PubMed

    Touahar, Imad E; Haroune, Lounès; Ba, Sidy; Bellenger, Jean-Phillipe; Cabana, Hubert

    2014-05-15

    In order to transform a wide range of pharmaceutically active compounds (PhACs), the three oxidative enzymes laccase (Lac) from Trametes versicolor, versatile peroxidase (VP) from Bjerkandera adusta and glucose oxidase (GOD) from Aspergillus niger were concomitantly cross-linked after aggregation, thus, making a combined cross-linked enzyme aggregate (combi-CLEA) that was versatile and involved in an enzymatic cascade reaction. From the initial enzymes about 30% of initial laccase activity was recovered along with 40% for each of VP and GOD. The combi-CLEA showed good results in conditions close to those of real wastewater (neutral pH and medium temperature) as well as a good ability to resist to denaturing conditions such as high temperature (60°C) and low pH (3). Batch experiments were realized to test the free enzyme's ability to degrade, a PhACs cocktail, mainly in a synthetic wastewater containing acetaminophen, naproxen, mefenamic acid, indometacin, diclofenac, ketoprofen, caffeine, diazepam, ciprofloxacin, trimethoprim, fenofibrate and bezafibrate, carbamazepine and its by-product 10-11 epoxy-carbamazepine. High removal was achieved (more than 80%) for the five first compounds. Then, the elimination ability of the combi-CLEA with or without hydrogen peroxide, glucose or manganese sulfate was determined. Globally, our results demonstrated that VP has a wider removal spectrum than Lac. These removal features are enhanced under more specific conditions, whereas the combi-CLEA combined advantages of both VP and laccase. Finally, the elimination of PhACs in a municipal wastewater treatment plant effluent using the combi-CLEA was marginally investigated. Concentrations of most of the selected PhACs were below the limit of quantification (lower than 20 ng/L) except for acetaminophen. Its combi-CLEA-mediated removal reached up to 25%. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Improvement of Speaking Ability through Interrelated Skills

    ERIC Educational Resources Information Center

    Liao, Guoqiang

    2009-01-01

    How to improve students' ability of speaking English? That is the key point we are concerned about. This paper discusses the possibility and necessity of improving students' ability by combining the four skills of speaking, listening, reading and writing.

  15. Motor-cognitive dual-task deficits in individuals with early-mid stage Huntington disease.

    PubMed

    Fritz, Nora E; Hamana, Katy; Kelson, Mark; Rosser, Anne; Busse, Monica; Quinn, Lori

    2016-09-01

    Huntington disease (HD) results in a range of cognitive and motor impairments that progress throughout the disease stages; however, little research has evaluated specific dual-task abilities in this population, and the degree to which they may be related to functional ability. The purpose of this study was to a) examine simple and complex motor-cognitive dual-task performance in individuals with HD, b) determine relationships between dual-task walking ability and disease-specific measures of motor, cognitive and functional ability, and c) examine the relationship of dual-task measures to falls in individuals with HD. Thirty-two individuals with HD were evaluated for simple and complex dual-task ability using the Walking While Talking Test. Demographics and disease-specific measures of motor, cognitive and functional ability were also obtained. Individuals with HD had impairments in simple and complex dual-task ability. Simple dual-task walking was correlated to disease-specific motor scores as well as cognitive performance, but complex dual-task walking was correlated with total functional capacity, as well as a range of cognitive measures. Number of prospective falls was moderately-strongly correlated to dual-task measures. Our results suggest that individuals with HD have impairments in cognitive-motor dual-task ability that are related to disease progression and specifically functional ability. Dual-task measures appear to evaluate a unique construct in individuals with early to mid-stage HD, and may have value in improving the prediction of falls risk in this population. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Effect of Mixing Ability Groups on Ability Levels Attained.

    ERIC Educational Resources Information Center

    de Jong, John H. A. L.

    In 1983, in the Netherlands' highly differentiated school system, two types of curriculum representing different ability levels were combined as a first step towards a more heterogeneous grouping of student abilities. A study of one aspect of the results of this change compared over 1000 samples of English and German second language listening…

  17. Differential item functioning analysis with ordinal logistic regression techniques. DIFdetect and difwithpar.

    PubMed

    Crane, Paul K; Gibbons, Laura E; Jolley, Lance; van Belle, Gerald

    2006-11-01

    We present an ordinal logistic regression model for identification of items with differential item functioning (DIF) and apply this model to a Mini-Mental State Examination (MMSE) dataset. We employ item response theory ability estimation in our models. Three nested ordinal logistic regression models are applied to each item. Model testing begins with examination of the statistical significance of the interaction term between ability and the group indicator, consistent with nonuniform DIF. Then we turn our attention to the coefficient of the ability term in models with and without the group term. If including the group term has a marked effect on that coefficient, we declare that it has uniform DIF. We examined DIF related to language of test administration in addition to self-reported race, Hispanic ethnicity, age, years of education, and sex. We used PARSCALE for IRT analyses and STATA for ordinal logistic regression approaches. We used an iterative technique for adjusting IRT ability estimates on the basis of DIF findings. Five items were found to have DIF related to language. These same items also had DIF related to other covariates. The ordinal logistic regression approach to DIF detection, when combined with IRT ability estimates, provides a reasonable alternative for DIF detection. There appear to be several items with significant DIF related to language of test administration in the MMSE. More attention needs to be paid to the specific criteria used to determine whether an item has DIF, not just the technique used to identify DIF.

  18. Working towards the SDGs: measuring resilience from a practitioner's perspective

    NASA Astrophysics Data System (ADS)

    van Manen, S. M.; Both, M.

    2015-12-01

    The broad universal nature of the SDGs requires integrated approaches across development sectors and action at a variety of scales: from global to local. In humanitarian and development contexts, particularly at the local level, working towards these goals is increasingly approached through the concept of resilience. Resilience is broadly defined as the ability to minimise the impact of, cope with and recover from the consequences of shocks and stresses, both natural and manmade, without compromising long-term prospects. Key in this are the physical resources required and the ability to organise these prior to and during a crisis. However, despite the active debate on the theoretical foundations of resilience there is a comparative lack in the development of measurement approaches. The conceptual diversity of the few existing approaches further illustrates the complexity of operationalising the concept. Here we present a practical method to measure community resilience using a questionnaire composed of a generic set of household-level indicators. Rooted in the sustainable livelihoods approach it considers 6 domains: human, social, natural, economic, physical and political, and evaluates both resources and socio-cognitive factors. It is intended to be combined with more specific intervention-based questionnaires to systematically assess, monitor and evaluate the resilience of a community and the contribution of specific activities to resilience. Its use will be illustrated using a Haiti-based case study. The method presented supports knowledge-based decision making and impact monitoring. Furthermore, the evidence-based way of working contributes to accountability to a range of stakeholders and can be used for resource mobilisation. However, it should be noted that due to its inherent complexity and comprehensive nature there is no method or combination of methods and data types that can fully capture resilience in and across all of its facets, scales and domains.

  19. Drug permeation and metabolism in Mycobacterium tuberculosis: Prioritising local exposure as essential criterion in new TB drug development.

    PubMed

    Tanner, Lloyd; Denti, Paolo; Wiesner, Lubbe; Warner, Digby F

    2018-06-22

    Anti-tuberculosis (TB) drugs possess diverse abilities to penetrate the different host tissues and cell types in which infecting Mycobacterium tuberculosis bacilli are located during active disease. This is important since there is increasing evidence that the respective "lesion-penetrating" properties of the front-line TB drugs appear to correlate well with their specific activity in standard combination therapy. In turn, these observations suggest that rational efforts to discover novel treatment-shortening drugs and drug combinations should incorporate knowledge about the comparative abilities of both existing and experimental anti-TB agents to access bacilli in defined physiological states at different sites of infection, as well as avoid elimination by efflux or inactivation by host or bacterial metabolism. However, while there is a fundamental requirement to understand the mode of action and pharmacological properties of any current or experimental anti-TB agent within the context of the obligate human host, this is complex and, until recently, has been severely limited by the available methodologies and models. Here, we discuss advances in analytical models and technologies which have enabled investigations of drug metabolism and pharmacokinetics (DMPK) for new TB drug development. In particular, we consider the potential to shift the focus of traditional pharmacokinetic-pharmacodynamic analyses away from plasma to a more specific "site of action" drug exposure as an essential criterion for drug development and the design of dosing strategies. Moreover, in summarising approaches to determine DMPK data for the "unit of infection" comprising host macrophage and intracellular bacillus, we evaluate the potential benefits of including these analyses at an early stage in the preclinical drug development algorithm. © 2018 IUBMB Life, 2018. © 2018 International Union of Biochemistry and Molecular Biology.

  20. The Superimposed Deubiquitination Effect of OTULIN and Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Nsp11 Promotes Multiplication of PRRSV.

    PubMed

    Su, Yanxin; Shi, Peidian; Zhang, Lilin; Lu, Dong; Zhao, Chengxue; Li, Ruiqiao; Zhang, Lei; Huang, Jinhai

    2018-05-01

    Linear ubiquitination plays an important role in the regulation of the immune response by regulating nuclear factor κB (NF-κB). The linear ubiquitination-specific deubiquitinase ovarian tumor domain deubiquitinase with linear linkage specificity (OTULIN) can control the immune signaling transduction pathway by restricting the Met1-linked ubiquitination process. In our study, the porcine OTLLIN gene was cloned and deubiquitin functions were detected in a porcine reproductive and respiratory syndrome virus (PRRSV)-infected-cell model. PRRSV infection promotes the expression of the OTULIN gene; in turn, overexpression of OTULIN contributes to PRRSV proliferation. There is negative regulation of innate immunity with OTULIN during viral infection. The cooperative effects of swine OTULIN and PRRSV Nsp11 potentiate the ability to reduce levels of cellular protein ubiquitin associated with innate immunity. Importantly, PRRSV Nsp11 recruits OTULIN through a nonenzymatic combination to enhance its ability to remove linear ubiquitination targeting NEMO, resulting in a superimposed effect that inhibits the production of type I interferons (IFNs). Our report presents a new model of virus utilization of the ubiquitin-protease system in vivo from the perspective of the viral proteins that interact with cell deubiquitination enzymes, providing new ideas for prevention and control of PRRSV. IMPORTANCE Deubiquitination effects of swine OTULIN were identified. The interaction between porcine OTULIN and PRRSV Nsp11 is dependent on the OTU domain. PRRSV Nsp11 recruits OTULIN through a nonenzymatic combination to promote removal of linear ubiquitination targeting NEMO, resulting in a superimposed effect that inhibits the production of type I IFNs. Copyright © 2018 American Society for Microbiology.

  1. Predicting phenotypes of asthma and eczema with machine learning

    PubMed Central

    2014-01-01

    Background There is increasing recognition that asthma and eczema are heterogeneous diseases. We investigated the predictive ability of a spectrum of machine learning methods to disambiguate clinical sub-groups of asthma, wheeze and eczema, using a large heterogeneous set of attributes in an unselected population. The aim was to identify to what extent such heterogeneous information can be combined to reveal specific clinical manifestations. Methods The study population comprised a cross-sectional sample of adults, and included representatives of the general population enriched by subjects with asthma. Linear and non-linear machine learning methods, from logistic regression to random forests, were fit on a large attribute set including demographic, clinical and laboratory features, genetic profiles and environmental exposures. Outcome of interest were asthma, wheeze and eczema encoded by different operational definitions. Model validation was performed via bootstrapping. Results The study population included 554 adults, 42% male, 38% previous or current smokers. Proportion of asthma, wheeze, and eczema diagnoses was 16.7%, 12.3%, and 21.7%, respectively. Models were fit on 223 non-genetic variables plus 215 single nucleotide polymorphisms. In general, non-linear models achieved higher sensitivity and specificity than other methods, especially for asthma and wheeze, less for eczema, with areas under receiver operating characteristic curve of 84%, 76% and 64%, respectively. Our findings confirm that allergen sensitisation and lung function characterise asthma better in combination than separately. The predictive ability of genetic markers alone is limited. For eczema, new predictors such as bio-impedance were discovered. Conclusions More usefully-complex modelling is the key to a better understanding of disease mechanisms and personalised healthcare: further advances are likely with the incorporation of more factors/attributes and longitudinal measures. PMID:25077568

  2. Independent mediation of unconditioned motor behavior by striatal D1 and D2 receptors in rats depleted of dopamine as neonates.

    PubMed

    Bruno, J P; Byrnes, E M; Johnson, B J

    1995-11-01

    The effects of systemic administration of DA receptor antagonists suggest that unconditioned motor behavior in rats depleted of DA as neonates continues to be dependent upon dopaminergic transmission, yet the specific contribution of D1 and D2 receptors to these behaviors has been altered. The purpose of the present study was to determine whether these depletion-induced receptor changes are occurring at the level of striatal DA terminals and their targets. The ability of bilateral intrastriatal injections (0.5 microliter) of DA receptor antagonists to induce motoric deficits was determined in adult rats treated with vehicle or 6-OHDA (100 micrograms, intraventricular) on postnatal day 3. Administration of the D1-like antagonist SCH 23390 (0.5-2.0 micrograms) or the D2-like antagonist clebopride (1.0-4.0 micrograms) induced dose-dependent akinesia, catalepsy, and somatosensory neglect in vehicle-treated controls. In contrast, neither antagonist produced deficits in rats depleted of forebrain DA as neonates. However, combined administration of SCH 23390 + clebopride induced similar akinesia, catalepsy, and somatosensory neglect in both controls and DA depleted animals. Animals depleted of DA were more sensitive than controls to the low doses of this combined D1 + D2 antagonism. These results demonstrate that activation of striatal DA receptors remains necessary for unconditioned motor behavior in rats depleted of DA as neonates. However, the specific contributions of D1- and D2-like receptors to these behaviors differ between intact animals and those depleted of DA as neonates. The ability of endogenous DA acting at either D1 or D2 receptors to support spontaneous motor behavior in rats depleted of DA as neonates may contribute to their relative sparing from parkinsonian deficits.

  3. Memory of occasional events in rats: individual episodic memory profiles, flexibility, and neural substrate.

    PubMed

    Veyrac, Alexandra; Allerborn, Marina; Gros, Alexandra; Michon, Frederic; Raguet, Louise; Kenney, Jana; Godinot, Florette; Thevenet, Marc; Garcia, Samuel; Messaoudi, Belkacem; Laroche, Serge; Ravel, Nadine

    2015-05-13

    In search for the mechanisms underlying complex forms of human memory, such as episodic recollection, a primary challenge is to develop adequate animal models amenable to neurobiological investigation. Here, we proposed a novel framework and paradigm that provides means to quantitatively evaluate the ability of rats to form and recollect a combined knowledge of what happened, where it happened, and when or in which context it happened (referred to as episodic-like memory) after a few specific episodes in situations as close as possible to a paradigm we recently developed to study episodic memory in humans. In this task, rats have to remember two odor-drink associations (what happened) encountered in distinct locations (where it happened) within two different multisensory enriched environments (in which context/occasion it happened), each characterized by a particular combination of odors and places. By analyzing licking behavior on each drinking port, we characterized quantitatively individual recollection profiles and showed that rats are able to incidentally form and recollect an accurate, long-term integrated episodic-like memory that can last ≥ 24 d after limited exposure to the episodes. Placing rats in a contextually challenging recollection situation at recall reveals the ability for flexible use of episodic memory as described in humans. We further report that reversible inactivation of the dorsal hippocampus during recall disrupts the animal's capacity to recollect the complete episodic memory. Cellular imaging of c-Fos and Zif268 brain activation reveals that episodic memory recollection recruits a specific, distributed network of hippocampal-prefrontal cortex structures that correlates with the accuracy of the integrated recollection performance. Copyright © 2015 the authors 0270-6474/15/337575-12$15.00/0.

  4. Independent and combined influence of the components of physical fitness on academic performance in youth.

    PubMed

    Esteban-Cornejo, Irene; Tejero-González, Carlos Ma; Martinez-Gomez, David; del-Campo, Juan; González-Galo, Ana; Padilla-Moledo, Carmen; Sallis, James F; Veiga, Oscar L

    2014-08-01

    To examine the independent and combined associations of the components of physical fitness with academic performance among youths. This cross-sectional study included a total of 2038 youths (989 girls) aged 6-18 years. Cardiorespiratory capacity was measured using the 20-m shuttle run test. Motor ability was assessed with the 4×10-m shuttle run test of speed of movement, agility, and coordination. A muscular strength z-score was computed based on handgrip strength and standing long jump distance. Academic performance was assessed through school records using 4 indicators: Mathematics, Language, an average of Mathematics and Language, and grade point average score. Cardiorespiratory capacity and motor ability were independently associated with all academic variables in youth, even after adjustment for fitness and fatness indicators (all P≤.001), whereas muscular strength was not associated with academic performance independent of the other 2 physical fitness components. In addition, the combined adverse effects of low cardiorespiratory capacity and motor ability on academic performance were observed across the risk groups (P for trend<.001). Cardiorespiratory capacity and motor ability, both independently and combined, may have a beneficial influence on academic performance in youth. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Global, broad, or specific cognitive differences? Using a MIMIC model to examine differences in CHC abilities in children with learning disabilities.

    PubMed

    Niileksela, Christopher R; Reynolds, Matthew R

    2014-01-01

    This study was designed to better understand the relations between learning disabilities and different levels of latent cognitive abilities, including general intelligence (g), broad cognitive abilities, and specific abilities based on the Cattell-Horn-Carroll theory of intelligence (CHC theory). Data from the Differential Ability Scales-Second Edition (DAS-II) were used to create a multiple-indicator multiple cause model to examine the latent mean differences in cognitive abilities between children with and without learning disabilities in reading (LD reading), math (LD math), and reading and writing(LD reading and writing). Statistically significant differences were found in the g factor between the norm group and the LD groups. After controlling for differences in g, the LD reading and LD reading and writing groups showed relatively lower latent processing speed, and the LD math group showed relatively higher latent comprehension-knowledge. There were also some differences in some specific cognitive abilities, including lower scores in spatial relations and numerical facility for the LD math group, and lower scores in visual memory for the LD reading and writing group. These specific mean differences were above and beyond any differences in the latent cognitive factor means.

  6. Antioxidant and Anti-Inflammatory Effects of Selected Natural Compounds Contained in a Dietary Supplement on Two Human Immortalized Keratinocyte Lines

    PubMed Central

    Serini, Simona; Mondella, Nadia; Celleno, Leonardo; Lanza, Paola; Calviello, Gabriella

    2014-01-01

    Several advantages may derive from the use of dietary supplements containing multiple natural antioxidants and/or anti-inflammatory agents. At present, however, there is scarce information on the properties and potential of combined supplements. To fill the gap, the antioxidant and anti-inflammatory activities exerted by a combination of seven natural components (coenzyme Q10, krill oil, lipoic acid, resveratrol, grape seed oil, α-tocopherol, and selenium) contained in a dietary supplement used for the prevention of skin disorders were investigated in vitro. Each component was administered, alone or in combination, to human keratinocytes, and the inhibition of Reactive Oxygen Species production and lipid peroxidation as well as the ability to reduce inflammatory cytokine secretion and to modulate Nuclear Factor-κB pathway was evaluated. The combination exhibited high antioxidant activity and in specific conditions the combination's efficiency was higher than that of the most powerful components administered individually. Moreover, the combination showed remarkable anti-inflammatory properties. It reduced more efficiently than each component the secretion of Monocyte Chemoattractant Protein-1, a crucial cytokine for the development of chronic inflammation in skin, and inhibited Nuclear Factor-κB molecular pathway. Overall, our findings suggest that the combined formulation may have the potential to powerfully inhibit oxidative stress and inflammation at skin level. PMID:25197638

  7. Individual Differences in the Speed of Facial Emotion Recognition Show Little Specificity but Are Strongly Related with General Mental Speed: Psychometric, Neural and Genetic Evidence

    PubMed Central

    Liu, Xinyang; Hildebrandt, Andrea; Recio, Guillermo; Sommer, Werner; Cai, Xinxia; Wilhelm, Oliver

    2017-01-01

    Facial identity and facial expression processing are crucial socio-emotional abilities but seem to show only limited psychometric uniqueness when the processing speed is considered in easy tasks. We applied a comprehensive measurement of processing speed and contrasted performance specificity in socio-emotional, social and non-social stimuli from an individual differences perspective. Performance in a multivariate task battery could be best modeled by a general speed factor and a first-order factor capturing some specific variance due to processing emotional facial expressions. We further tested equivalence of the relationships between speed factors and polymorphisms of dopamine and serotonin transporter genes. Results show that the speed factors are not only psychometrically equivalent but invariant in their relation with the Catechol-O-Methyl-Transferase (COMT) Val158Met polymorphism. However, the 5-HTTLPR/rs25531 serotonin polymorphism was related with the first-order factor of emotion perception speed, suggesting a specific genetic correlate of processing emotions. We further investigated the relationship between several components of event-related brain potentials with psychometric abilities, and tested emotion specific individual differences at the neurophysiological level. Results revealed swifter emotion perception abilities to go along with larger amplitudes of the P100 and the Early Posterior Negativity (EPN), when emotion processing was modeled on its own. However, after partialling out the shared variance of emotion perception speed with general processing speed-related abilities, brain-behavior relationships did not remain specific for emotion. Together, the present results suggest that speed abilities are strongly interrelated but show some specificity for emotion processing speed at the psychometric level. At both genetic and neurophysiological levels, emotion specificity depended on whether general cognition is taken into account or not. These findings keenly suggest that general speed abilities should be taken into account when the study of emotion recognition abilities is targeted in its specificity. PMID:28848411

  8. Combining ability analysis for within-boll yield components in upland cotton (Gossypium hirsutum L.).

    PubMed

    Imran, M; Shakeel, A; Azhar, F M; Farooq, J; Saleem, M F; Saeed, A; Nazeer, W; Riaz, M; Naeem, M; Javaid, A

    2012-08-24

    Cotton is an important cash crop worldwide, accounting for a large percentage of world agricultural exports; however, yield per acre is still poor in many countries, including Pakistan. Diallel mating system was used to identify parents for improving within-boll yield and fiber quality parameters. Combining ability analysis was employed to obtain suitable parents for this purpose. The parental genotypes CP-15/2, NIAB Krishma, CIM-482, MS-39, and S-12 were crossed in complete diallel mating under green house conditions during 2009. The F₀ seed of 20 hybrids and five parents were planted in the field in randomized complete block design with three replications during 2010. There were highly significant differences among all F₁ hybrids and their parents. Specific combining ability (SCA) variance was greater than general combining ability (GCA) variance for bolls per plant (9.987), seeds per boll (0.635), seed density (5.672), lint per seed (4.174), boll size (3.69), seed cotton yield (0.315), and lint percentage (0.470), showing predominance of non-additive genes; while seed volume (3.84) was controlled by additive gene action based on maximum GCA variance. Cultivar MS-39 was found to be the best general combiner for seed volume (0.102), seeds per boll (0.448), and lint per seed (0.038) and its utilization produced valuable hybrids, including MS-39 x NIAB Krishma and MS-39 x S-12. The parental line CIM-482 had high GCA effects for boll size (0.33) and seeds per boll (0.90). It also showed good SCA with S-12 and NIAB Krishma for bolls per plant, with CP- 15/2 for boll size, and with MS-39 for seeds per boll. The hybrids, namely, CP-15/2 x NIAB Krishma, NIAB Krishma x S-12, NIAB Krishma x CIM-482, MS-39 x NIAB Krishma, MS-39 x CP-15/2, and S-12 x MS-39 showed promising results. Correlation analysis revealed that seed cotton yield showed significant positive correlation with bolls per plant, boll size and seeds per boll while it showed negative correlation with lint percentage and lint per seed. Seed volume showed significant negative correlation with seed density. Seeds per boll were positively correlated with boll size and negatively correlated with bolls per plant lint percentage and lint per seed. Similarly, lint per seed exhibited positive correlation with lint percentage and boll size showed significantly negative correlation with bolls per plant. Presence of non-additive genetic effects in traits like bolls per plant, seeds per boll, lint per seed, seed cotton yield, and lint percentage is indicative of later generation selection or heterosis breeding may be adopted. For boll size, seed volume and seed density early generation selection may be followed because of the presence of additive gene action. The parental material used in this study and cross combinations obtained from these parents may be exploited in future breeding endeavors.

  9. The Mathematics of a Successful Deconvolution: A Quantitative Assessment of Mixture-Based Combinatorial Libraries Screened Against Two Formylpeptide Receptors

    PubMed Central

    Santos, Radleigh G.; Appel, Jon R.; Giulianotti, Marc A.; Edwards, Bruce S.; Sklar, Larry A.; Houghten, Richard A.; Pinilla, Clemencia

    2014-01-01

    In the past 20 years, synthetic combinatorial methods have fundamentally advanced the ability to synthesize and screen large numbers of compounds for drug discovery and basic research. Mixture-based libraries and positional scanning deconvolution combine two approaches for the rapid identification of specific scaffolds and active ligands. Here we present a quantitative assessment of the screening of 32 positional scanning libraries in the identification of highly specific and selective ligands for two formylpeptide receptors. We also compare and contrast two mixture-based library approaches using a mathematical model to facilitate the selection of active scaffolds and libraries to be pursued for further evaluation. The flexibility demonstrated in the differently formatted mixture-based libraries allows for their screening in a wide range of assays. PMID:23722730

  10. Attention, motivation, and reading coherence failure: a neuropsychological perspective.

    PubMed

    Wasserman, Theodore

    2012-01-01

    Reading coherence, defined as the ability to create appropriate, meaningful connections between the elements within a specific text itself and between elements within a text and the reader's prior knowledge, is one of the key processes involved in reading comprehension. This article describes reading coherence within the context of a neuropsychological model combining recent research in motivation, attention, and working memory. Specifically, a unique neuropsychologically identifiable form of reading coherence failure arising from the attentional and motivational deficiencies, based in altered frontoventral striatal reward circuits associated with noradrenaline (NA) circuitry, consistent with the delay-aversion model (dual-pathway model) of Sonuga-Barke ( 2003 ) is postulated. This article provides a model for this subset of reading disorders of which etiology is based on the executive support processes for reading and not in the mechanics of actual reading such as decoding and phonetics.

  11. Occupational stress perception and its potential impact on work ability.

    PubMed

    Yong, Mei; Nasterlack, Michael; Pluto, Rolf-Peter; Lang, Stefan; Oberlinner, Christoph

    2013-01-01

    To examine perceived stress across employees with different occupational status, to investigate the impact of stress on work ability and to derive conclusions regarding health promotion activities. A comprehensive survey combining questionnaire and medical examination was offered in one division in BASF Ludwigshafen. Among 867 voluntary participants, 653 returned complete questionnaires. The questions were directed at perception of safety at the workplace, self-rated health status, frequency of stress symptoms, unrealistic job demands, time pressure and maladjustment of work life balance. The outcome of interest was self-estimated health measured by the Work Ability Index (WAI). Occupational stressors were perceived differently across occupational status groups. Frontline operators had more health concerns due to workplace conditions, while professional and managerial staff reported higher frequencies of perceived tension, time pressure, and maladjustment of work life balance. After adjustment for occupational status, demographic and lifestyle factors, perceived stress was associated with a modest to strong decline in WAI scores. While perceived occupational stress had an apparent impact on WAI, and WAI has been demonstrated to be predictive of early retirement, more intensive and employee group-specific stress management interventions are being implemented beyond traditional strategies of routine occupational medical surveillance.

  12. Neural activity during natural viewing of Sesame Street statistically predicts test scores in early childhood.

    PubMed

    Cantlon, Jessica F; Li, Rosa

    2013-01-01

    It is not currently possible to measure the real-world thought process that a child has while observing an actual school lesson. However, if it could be done, children's neural processes would presumably be predictive of what they know. Such neural measures would shed new light on children's real-world thought. Toward that goal, this study examines neural processes that are evoked naturalistically, during educational television viewing. Children and adults all watched the same Sesame Street video during functional magnetic resonance imaging (fMRI). Whole-brain intersubject correlations between the neural timeseries from each child and a group of adults were used to derive maps of "neural maturity" for children. Neural maturity in the intraparietal sulcus (IPS), a region with a known role in basic numerical cognition, predicted children's formal mathematics abilities. In contrast, neural maturity in Broca's area correlated with children's verbal abilities, consistent with prior language research. Our data show that children's neural responses while watching complex real-world stimuli predict their cognitive abilities in a content-specific manner. This more ecologically natural paradigm, combined with the novel measure of "neural maturity," provides a new method for studying real-world mathematics development in the brain.

  13. Inhibition of human dendritic cell activation by hydroethanolic but not lipophilic extracts of turmeric (Curcuma longa).

    PubMed

    Krasovsky, Joseph; Chang, David H; Deng, Gary; Yeung, Simon; Lee, Mavis; Leung, Ping Chung; Cunningham-Rundles, Susanna; Cassileth, Barrie; Dhodapkar, Madhav V

    2009-03-01

    Turmeric has been extensively utilized in Indian and Chinese medicine for its immune-modulatory properties. Dendritic cells (DCs) are antigen-presenting cells specialized to initiate and regulate immunity. The ability of DCs to initiate immunity is linked to their activation status. The effects of turmeric on human DCs have not been studied. Here we show that hydroethanolic (HEE) but not lipophilic "supercritical" extraction (SCE) of turmeric inhibits the activation of human DCs in response to inflammatory cytokines. Treatment of DCs with HEE also inhibits the ability of DCs to stimulate the mixed lymphocyte reaction (MLR). Importantly, the lipophilic fraction does not synergize with the hydroethanolic fraction for the ability of inhibiting DC maturation. Rather, culturing of DCs with the combination of HEE and SCE leads to partial abrogation of the effects of HEE on the MLR initiated by DCs. These data provide a mechanism for the anti-inflammatory properties of turmeric. However, they suggest that these extracts are not synergistic and may contain components with mutually antagonistic effects on human DCs. Harnessing the immune effects of turmeric may benefit from specifically targeting the active fractions.

  14. Inhibition of Human Dendritic Cell Activation by Hydroethanolic But Not Lipophilic Extracts of Turmeric (Curcuma longa)

    PubMed Central

    Krasovsky, Joseph; Chang, David H.; Deng, Gary; Yeung, Simon; Lee, Mavis; Leung, Ping Chung; Cunningham-Rundles, Susanna; Cassileth, Barrie; Dhodapkar, Madhav V.

    2015-01-01

    Turmeric has been extensively utilized in Indian and Chinese medicine for its immune-modulatory properties. Dendritic cells (DCs) are antigen-presenting cells specialized to initiate and regulate immunity. The ability of DCs to initiate immunity is linked to their activation status. The effects of turmeric on human DCs have not been studied. Here we show that hydroethanolic (HEE) but not lipophilic “supercritical” extraction (SCE) of turmeric inhibits the activation of human DCs in response to inflammatory cytokines. Treatment of DCs with HEE also inhibits the ability of DCs to stimulate the mixed lymphocyte reaction (MLR). Importantly, the lipophilic fraction does not synergize with the hydroethanolic fraction for the ability of inhibiting DC maturation. Rather, culturing of DCs with the combination of HEE and SCE leads to partial abrogation of the effects of HEE on the MLR initiated by DCs. These data provide a mechanism for the anti-inflammatory properties of turmeric. However, they suggest that these extracts are not synergistic and may contain components with mutually antagonistic effects on human DCs. Harnessing the immune effects of turmeric may benefit from specifically targeting the active fractions. PMID:19034830

  15. Effects of Different Combinations of Strength, Power, and Plyometric Training on the Physical Performance of Elite Young Soccer Players.

    PubMed

    Kobal, Ronaldo; Loturco, Irineu; Barroso, Renato; Gil, Saulo; Cuniyochi, Rogério; Ugrinowitsch, Carlos; Roschel, Hamilton; Tricoli, Valmor

    2017-06-01

    The combination of strength (ST) and plyometric training (PT) has been shown to be effective for improving sport-specific performance. However, there is no consensus about the most effective way to combine these methods in the same training session to produce greater improvements in neuromuscular performance of soccer players. Thus, the purpose of this study was to compare the effects of different combinations of ST and PT sequences on strength, jump, speed, and agility capacities of elite young soccer players. Twenty-seven soccer players (age: 18.9 ± 0.6 years) participated in an 8-week resistance training program and were divided into 3 groups: complex training (CP) (ST before PT), traditional training (TD) (PT before ST), and contrast training (CT) (ST and PT performed alternately, set by set). The experimental design took place during the competitive period of the season. The ST composed of half-squat exercises performed at 60-80% of 1 repetition maximum (1RM); the PT composed of drop jump exercises executed in a range from 30 to 45 cm. After the experimental period, the maximum dynamic strength (half-squat 1RM) and vertical jump ability (countermovement jump height) increased similarly and significantly in the CP, TD, and CT (48.6, 46.3, and 53% and 13, 14.2, and 14.7%, respectively). Importantly, whereas the TD group presented a significant decrease in sprinting speed in 10 (7%) and 20 m (6%), the other groups did not show this response. Furthermore, no significant alterations were observed in agility performance in any experimental group. In conclusion, in young soccer players, different combinations and sequences of ST and PT sets result in similar performance improvements in muscle strength and jump ability. However, it is suggested that the use of the CP and CT methods is more indicated to maintain/maximize the sprint performance of these athletes.

  16. Do cognitive training strategies improve motor and positive psychological skills development in soccer players? Insights from a systematic review.

    PubMed

    Slimani, Maamer; Bragazzi, Nicola Luigi; Tod, David; Dellal, Alexandre; Hue, Olivier; Cheour, Foued; Taylor, Lee; Chamari, Karim

    2016-12-01

    Soccer players are required to have well-developed physical, technical and cognitive abilities. The present systematic review, adhering to Preferred Reporting Items for Systematic reviews and Meta-Analysis guidelines, examined the effects of cognitive training strategies on motor and positive psychological skills development in soccer performance and identified the potential moderators of the "cognitive training-soccer performance" relationship. Thirteen databases were systematically searched using keywords related to psychological or cognitive training in soccer players. The review is based on 18 studies, employing 584 soccer players aged 7-39 years. Cognitive strategies, particularly imagery, appear to improve sports performance in soccer players. Regarding imagery, the combination of two different types of cognitive imagery training (i.e., cognitive general and cognitive specific) has a positive influence on soccer performance during training, whereas motivational imagery (i.e., motivational general-arousal, motivational general-mastery and motivational specific) enhance competition performance. Younger soccer players employ cognitive general and cognitive specific imagery techniques to a greater extent than older soccer players. Combined cognitive training strategies were more beneficial than a single cognitive strategy relative to motor skills enhancement in elite (particularly midfielders) and amateur (i.e., when practising complex and specific soccer skills in precompetitive period) soccer players. In conclusion, it appears that there are differences in cognitive/psychological training interventions, and their efficacy, according to whether they are directed towards training or competition, and the age, standard and playing position of the players.

  17. Low performance on mathematical tasks in preschoolers: the importance of domain-general and domain-specific abilities.

    PubMed

    Costa, H M; Nicholson, B; Donlan, C; Van Herwegen, J

    2018-04-01

    Different domain-specific and domain-general cognitive precursors play a key role in the development of mathematical abilities. The contribution of these domains to mathematical ability changes during development. Primary school-aged children who show mathematical difficulties form a heterogeneous group, but it is not clear whether this also holds for preschool low achievers (LAs) and how domain-specific and domain-general abilities contribute to mathematical difficulties at a young age. The aim of this study was to explore the cognitive characteristics of a sample of preschool LAs and identify sub-types of LAs. 81 children were identified as LAs from 283 preschoolers aged 3 to 5 years old and were assessed on a number of domain-general and domain-specific tasks. Cluster analysis revealed four subgroups of LAs in mathematics: (1) a weak processing sub-type; (2) a general mathematical LAs sub-type; (3) a mixed abilities sub-type; and (4) a visuo-spatial deficit sub-type. Whilst two of the groups showed specific domain-general difficulties, none showed only domain-specific difficulties. Current findings suggest that preschool LAs constitute a heterogeneous group and stress the importance of domain-general factors for the development of mathematical abilities during the preschool years. © 2018 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

  18. Explosive Welding in the 1990's

    NASA Technical Reports Server (NTRS)

    Lalwaney, N. S.; Linse, V. D.

    1985-01-01

    Explosive bonding is a unique joining process with the serious potential to produce composite materials capable of fulfilling many of the high performance materials capable of fulfilling many of the high performance materials needs of the 1990's. The process has the technological versatility to provide a true high quality metallurgical compatible and incompatible systems. Metals routinely explosively bonded include a wide variety of combinations of reactive and refractory metals, low and high density metals and their alloys, corrosion resistant and high strength alloys, and common steels. The major advantage of the process is its ability to custom design and engineer composites with physical and/or mechanical properties that meet a specific or unusual performance requirement. Explosive bonding offers the designer unique opportunities in materials selection with unique combinations of properties and high integrity bonds that cannot be achieved by any other metal joining process. The process and some applications are discussed.

  19. Reprint of: Combining theory and experiment for X-ray absorption spectroscopy and resonant X-ray scattering characterization of polymers

    DOE PAGES

    Su, Gregory M.; Cordova, Isvar A.; Brady, Michael A.; ...

    2016-11-01

    An improved understanding of fundamental chemistry, electronic structure, morphology, and dynamics in polymers and soft materials requires advanced characterization techniques that are amenable to in situ and operando studies. Soft X-ray methods are especially useful in their ability to non-destructively provide information on specific materials or chemical moieties. Analysis of these experiments, which can be very dependent on X-ray energy and polarization, can quickly become complex. Complementary modeling and predictive capabilities are required to properly probe these critical features. Here in this paper, we present relevant background on this emerging suite of techniques. We focus on how the combination ofmore » theory and experiment has been applied and can be further developed to drive our understanding of how these methods probe relevant chemistry, structure, and dynamics in soft materials.« less

  20. Scanning electron microscopy of cells and tissues under fully hydrated conditions

    PubMed Central

    Thiberge, Stephan; Nechushtan, Amotz; Sprinzak, David; Gileadi, Opher; Behar, Vered; Zik, Ory; Chowers, Yehuda; Michaeli, Shulamit; Schlessinger, Joseph; Moses, Elisha

    2004-01-01

    A capability for scanning electron microscopy of wet biological specimens is presented. A membrane that is transparent to electrons protects the fully hydrated sample from the vacuum. The result is a hybrid technique combining the ease of use and ability to see into cells of optical microscopy with the higher resolution of electron microscopy. The resolution of low-contrast materials is ≈100 nm, whereas in high-contrast materials the resolution can reach 10 nm. Standard immunogold techniques and heavy-metal stains can be applied and viewed in the fluid to improve the contrast. Images present a striking combination of whole-cell morphology with a wealth of internal details. A possibility for direct inspection of tissue slices transpires, imaging only the external layer of cells. Simultaneous imaging with photons excited by the electrons incorporates data on material distribution, indicating a potential for multilabeling and specific scintillating markers. PMID:14988502

  1. Combined Infrared Stereo and Laser Ranging Cloud Measurements from Shuttle Mission STS-85

    NASA Technical Reports Server (NTRS)

    Lancaster, R. S.; Spinhirne, J. D.; Manizade, K. F.

    2004-01-01

    Multiangle remote sensing provides a wealth of information for earth and climate monitoring, such as the ability to measure the height of cloud tops through stereoscopic imaging. As technology advances so do the options for developing spacecraft instrumentation versatile enough to meet the demands associated with multiangle measurements. One such instrument is the infrared spectral imaging radiometer, which flew as part of mission STS-85 of the space shuttle in 1997 and was the first earth- observing radiometer to incorporate an uncooled microbolometer array detector as its image sensor. Specifically, a method for computing cloud-top height with a precision of +/- 620 m from the multispectral stereo measurements acquired during this flight has been developed, and the results are compared with coincident direct laser ranging measurements from the shuttle laser altimeter. Mission STS-85 was the first space flight to combine laser ranging and thermal IR camera systems for cloud remote sensing.

  2. Anti-GD2 mAbs and next-generation mAb-based agents for cancer therapy

    PubMed Central

    Perez Horta, Zulmarie; Goldberg, Jacob L; Sondel, Paul M

    2016-01-01

    Tumor-specific monoclonal antibodies (mAbs) have demonstrated efficacy in the clinic, becoming an important approach for cancer immunotherapy. Due to its limited expression on normal tissue, the GD2 disialogangloside expressed on neuroblastoma cells is an excellent candidate for mAb therapy. In 2015, dinutuximab (an anti-GD2 mAb) was approved by the US FDA and is currently used in a combination immunotherapeutic regimen for the treatment of children with high-risk neuroblastoma. Here, we review the extensive preclinical and clinical development of anti-GD2 mAbs and the different mechanisms by which they mediate tumor cell killing. In addition, we discuss different mAb-based strategies that capitalize on the targeting ability of anti-GD2 mAbs to potentially deliver, as monotherapy, or in combination with other treatments, improved antitumor efficacy. PMID:27485082

  3. Combining reactive sputtering and rapid thermal processing for synthesis and discovery of metal oxynitrides

    DOE PAGES

    Zhou, Lan; Suram, Santosh K.; Becerra-Stasiewicz, Natalie; ...

    2015-05-27

    Recent efforts have demonstrated enhanced tailoring of material functionality with mixed-anion materials, yet exploratory research with mixed-anion chemistries is limited by the sensitivity of these materials to synthesis conditions. In order to synthesize a particular metal oxynitride compound by traditional reactive annealing we require specific, limited ranges of both oxygen and nitrogen chemical potentials in order to establish equilibrium between the solid-state material and a reactive atmosphere. While using Ta-O-N as an example system, we describe a combination of reactive sputter deposition and rapid thermal processing for synthesis of mixed-anion inorganic materials. Heuristic optimization of reactive gas pressures to attainmore » a desired anion stoichiometry is discussed, and the ability of rapid thermal processing to enable amorphous to crystalline transitions without preferential anion loss is demonstrated through the controlled synthesis of nitride, oxide and oxynitride phases.« less

  4. Evaluation of ERTS imagery for mapping and detection of changes of snowcover land and on glaciers

    NASA Technical Reports Server (NTRS)

    Meier, M. F.

    1973-01-01

    The percentage of snowcover area on specific drainage basins was measured from ERTS imagery by video density slicing with a repeatability of 4 percent of the snowcovered area. Data from ERTS images of the melt season snowcover in the Thunder Creek drainage basin in the North Cascades were combined with existing hydrologic and meteorologic observations to enable calculation of the time distribution of the water stored in this mountain snowpack. Similar data could be used for frequent updating of expected inflow to reservoirs. Equivalent snowline altitudes were determined from area measurements. Snowline altitudes were also determined by combining enlarged ERTS images with maps with an accuracy of about 60 m under favorable conditions. Ability to map snowcover or to determine snowline altitude depends primarily on cloud cover and vegetation and secondarily on slope, terrain roughness, sun angle, radiometric fidelity, and amount of spectral information available.

  5. The Consequence of Combined Pain and Stress on Work Ability in Female Laboratory Technicians: A Cross-Sectional Study.

    PubMed

    Jay, Kenneth; Friborg, Maria Kristine; Sjøgaard, Gisela; Jakobsen, Markus Due; Sundstrup, Emil; Brandt, Mikkel; Andersen, Lars Louis

    2015-12-11

    Musculoskeletal pain and stress-related disorders are leading causes of impaired work ability, sickness absences and disability pensions. However, knowledge about the combined detrimental effect of pain and stress on work ability is lacking. This study investigates the association between pain in the neck-shoulders, perceived stress, and work ability. In a cross-sectional survey at a large pharmaceutical company in Denmark 473 female laboratory technicians replied to questions about stress (Perceived Stress Scale), musculoskeletal pain intensity (scale 0-10) of the neck and shoulders, and work ability (Work Ability Index). General linear models tested the association between variables. In the multi-adjusted model, stress (p < 0.001) and pain (p < 0.001) had independent main effects on the work ability index score, and there was no significant stress by pain interaction (p = 0.32). Work ability decreased gradually with both increased stress and pain. Workers with low stress and low pain had the highest Work Ability Index score (44.6 (95% CI 43.9-45.3)) and workers with high stress and high pain had the lowest score (32.7 (95% CI 30.6-34.9)). This cross-sectional study indicates that increased stress and musculoskeletal pain are independently associated with lower work ability in female laboratory technicians.

  6. Rapid Identification of Cell-Specific, Internalizing RNA Aptamers with Bioinformatics Analyses of a Cell-Based Aptamer Selection

    PubMed Central

    Thiel, William H.; Bair, Thomas; Peek, Andrew S.; Liu, Xiuying; Dassie, Justin; Stockdale, Katie R.; Behlke, Mark A.; Miller, Francis J.; Giangrande, Paloma H.

    2012-01-01

    Background The broad applicability of RNA aptamers as cell-specific delivery tools for therapeutic reagents depends on the ability to identify aptamer sequences that selectively access the cytoplasm of distinct cell types. Towards this end, we have developed a novel approach that combines a cell-based selection method (cell-internalization SELEX) with high-throughput sequencing (HTS) and bioinformatics analyses to rapidly identify cell-specific, internalization-competent RNA aptamers. Methodology/Principal Findings We demonstrate the utility of this approach by enriching for RNA aptamers capable of selective internalization into vascular smooth muscle cells (VSMCs). Several rounds of positive (VSMCs) and negative (endothelial cells; ECs) selection were performed to enrich for aptamer sequences that preferentially internalize into VSMCs. To identify candidate RNA aptamer sequences, HTS data from each round of selection were analyzed using bioinformatics methods: (1) metrics of selection enrichment; and (2) pairwise comparisons of sequence and structural similarity, termed edit and tree distance, respectively. Correlation analyses of experimentally validated aptamers or rounds revealed that the best cell-specific, internalizing aptamers are enriched as a result of the negative selection step performed against ECs. Conclusions and Significance We describe a novel approach that combines cell-internalization SELEX with HTS and bioinformatics analysis to identify cell-specific, cell-internalizing RNA aptamers. Our data highlight the importance of performing a pre-clear step against a non-target cell in order to select for cell-specific aptamers. We expect the extended use of this approach to enable the identification of aptamers to a multitude of different cell types, thereby facilitating the broad development of targeted cell therapies. PMID:22962591

  7. A bacteriophage T7 RNA polymerase/promoter system for controlled exclusive expression of specific genes.

    PubMed Central

    Tabor, S; Richardson, C C

    1985-01-01

    The RNA polymerase gene of bacteriophage T7 has been cloned into the plasmid pBR322 under the inducible control of the lambda PL promoter. After induction, T7 RNA polymerase constitutes 20% of the soluble protein of Escherichia coli, a 200-fold increase over levels found in T7-infected cells. The overproduced enzyme has been purified to homogeneity. During extraction the enzyme is sensitive to a specific proteolysis, a reaction that can be prevented by a modification of lysis conditions. The specificity of T7 RNA polymerase for its own promoters, combined with the ability to inhibit selectively the host RNA polymerase with rifampicin, permits the exclusive expression of genes under the control of a T7 RNA polymerase promoter. We describe such a coupled system and its use to express high levels of phage T7 gene 5 protein, a subunit of T7 DNA polymerase. Images PMID:3156376

  8. A high-throughput LC-MS/MS screen for GHRP in equine and human urine, featuring peptide derivatization for improved chromatography.

    PubMed

    Timms, Mark; Hall, Nikki; Levina, Vita; Vine, John; Steel, Rohan

    2014-10-01

    The growth hormone releasing peptides (GHRPs) hexarelin, ipamorelin, alexamorelin, GHRP-1, GHRP-2, GHRP-4, GHRP-5, and GHRP-6 are all synthetic met-enkephalin analogues that include unnatural D-amino acids. They were designed specifically for their ability to stimulate growth hormone release and may serve as performance enhancing drugs. To regulate the use of these peptides within the horse racing industry and by human athletes, a method is presented for the extraction, derivatization, and detection of GHRPs from equine and human urine. This method takes advantage of a highly specific solid-phase extraction combined with a novel derivatization method to improve the chromatography of basic peptides. The method was validated with respect to linearity, repeatability, intermediate precision, specificity, limits of detection, limits of confirmation, ion suppression, and stability. As proof of principle, all eight GHRPs or their metabolites could be detected in urine collected from rats after intravenous administration. Copyright © 2014 John Wiley & Sons, Ltd.

  9. Evaluation of genetic polymorphism among Lactobacillus rhamnosus non-starter Parmigiano Reggiano cheese strains.

    PubMed

    Bove, Claudio Giorgio; De Dea Lindner, Juliano; Lazzi, Camilla; Gatti, Monica; Neviani, Erasmo

    2011-01-05

    Parmigiano Reggiano (PR) is an Italian cooked, long-ripened cheese made with unheated cow's milk and natural whey starter. The microflora is involved in the manufacturing of this cheese, arising from the natural whey starter, the raw milk and the environment. Molecular studies have shown that mesophilic non-starter lactic acid bacteria (NSLAB) are the dominant microflora present during the ripening of PR. In this study, a characterisation of Lactobacillus rhamnosus isolated from a single PR manufacturing and ripening process is reported, using a combination of genotypic fingerprinting techniques (RAPD-PCR and REP-PCR). The intraspecies heterogeneity evidenced for 66 strains is correlated to their abilities to adapt to specific environmental and technological conditions. The detection of biotypes that correlate with specific moments in cheese ripening or differential development throughout this process suggests that these strains may have specific roles closely linked to their peculiar technological properties. Copyright © 2010 Elsevier B.V. All rights reserved.

  10. Integrative genomic mining for enzyme function to enable engineering of a non-natural biosynthetic pathway.

    PubMed

    Mak, Wai Shun; Tran, Stephen; Marcheschi, Ryan; Bertolani, Steve; Thompson, James; Baker, David; Liao, James C; Siegel, Justin B

    2015-11-24

    The ability to biosynthetically produce chemicals beyond what is commonly found in Nature requires the discovery of novel enzyme function. Here we utilize two approaches to discover enzymes that enable specific production of longer-chain (C5-C8) alcohols from sugar. The first approach combines bioinformatics and molecular modelling to mine sequence databases, resulting in a diverse panel of enzymes capable of catalysing the targeted reaction. The median catalytic efficiency of the computationally selected enzymes is 75-fold greater than a panel of naively selected homologues. This integrative genomic mining approach establishes a unique avenue for enzyme function discovery in the rapidly expanding sequence databases. The second approach uses computational enzyme design to reprogramme specificity. Both approaches result in enzymes with >100-fold increase in specificity for the targeted reaction. When enzymes from either approach are integrated in vivo, longer-chain alcohol production increases over 10-fold and represents >95% of the total alcohol products.

  11. Differential requirements of androgen receptor in luminal progenitors during prostate regeneration and tumor initiation

    PubMed Central

    Chua, Chee Wai; Epsi, Nusrat J; Leung, Eva Y; Xuan, Shouhong; Lei, Ming; Li, Bo I; Bergren, Sarah K; Hibshoosh, Hanina; Mitrofanova, Antonina

    2018-01-01

    Master regulatory genes of tissue specification play key roles in stem/progenitor cells and are often important in cancer. In the prostate, androgen receptor (AR) is a master regulator essential for development and tumorigenesis, but its specific functions in prostate stem/progenitor cells have not been elucidated. We have investigated AR function in CARNs (CAstration-Resistant Nkx3.1-expressing cells), a luminal stem/progenitor cell that functions in prostate regeneration. Using genetically--engineered mouse models and novel prostate epithelial cell lines, we find that progenitor properties of CARNs are largely unaffected by AR deletion, apart from decreased proliferation in vivo. Furthermore, AR loss suppresses tumor formation after deletion of the Pten tumor suppressor in CARNs; however, combined Pten deletion and activation of oncogenic Kras in AR-deleted CARNs result in tumors with focal neuroendocrine differentiation. Our findings show that AR modulates specific progenitor properties of CARNs, including their ability to serve as a cell of origin for prostate cancer. PMID:29334357

  12. Systems analysis of arrestin pathway functions.

    PubMed

    Maudsley, Stuart; Siddiqui, Sana; Martin, Bronwen

    2013-01-01

    To fully appreciate the diversity and specificity of complex cellular signaling events, such as arrestin-mediated signaling from G protein-coupled receptor activation, a complex systems-level investigation currently appears to be the best option. A rational combination of transcriptomics, proteomics, and interactomics, all coherently integrated with applied next-generation bioinformatics, is vital for the future understanding of the development, translation, and expression of GPCR-mediated arrestin signaling events in physiological contexts. Through a more nuanced, systems-level appreciation of arrestin-mediated signaling, the creation of arrestin-specific molecular response "signatures" should be made simple and ultimately amenable to drug discovery processes. Arrestin-based signaling paradigms possess important aspects, such as its specific temporal kinetics and ability to strongly affect transcriptional activity, that make it an ideal test bed for next-generation of drug discovery bioinformatic approaches such as multi-parallel dose-response analysis, data texturization, and latent semantic indexing-based natural language data processing and feature extraction. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. CRISPR-Barcoding for Intratumor Genetic Heterogeneity Modeling and Functional Analysis of Oncogenic Driver Mutations.

    PubMed

    Guernet, Alexis; Mungamuri, Sathish Kumar; Cartier, Dorthe; Sachidanandam, Ravi; Jayaprakash, Anitha; Adriouch, Sahil; Vezain, Myriam; Charbonnier, Françoise; Rohkin, Guy; Coutant, Sophie; Yao, Shen; Ainani, Hassan; Alexandre, David; Tournier, Isabelle; Boyer, Olivier; Aaronson, Stuart A; Anouar, Youssef; Grumolato, Luca

    2016-08-04

    Intratumor genetic heterogeneity underlies the ability of tumors to evolve and adapt to different environmental conditions. Using CRISPR/Cas9 technology and specific DNA barcodes, we devised a strategy to recapitulate and trace the emergence of subpopulations of cancer cells containing a mutation of interest. We used this approach to model different mechanisms of lung cancer cell resistance to EGFR inhibitors and to assess effects of combined drug therapies. By overcoming intrinsic limitations of current approaches, CRISPR-barcoding also enables investigation of most types of genetic modifications, including repair of oncogenic driver mutations. Finally, we used highly complex barcodes inserted at a specific genome location as a means of simultaneously tracing the fates of many thousands of genetically labeled cancer cells. CRISPR-barcoding is a straightforward and highly flexible method that should greatly facilitate the functional investigation of specific mutations, in a context that closely mimics the complexity of cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. A framework for understanding grocery purchasing in a low-income urban environment.

    PubMed

    Zachary, Drew A; Palmer, Anne M; Beckham, Sarah W; Surkan, Pamela J

    2013-05-01

    Research demonstrates that food desert environments limit low-income shoppers' ability to purchase healthy foods, thereby increasing their likelihood of diet-related illnesses. We sought to understand how individuals in an urban American food desert make grocery-purchasing decisions, and specifically why unhealthy purchases arise. Analysis is based on ethnographic data from participant observation, 37 in-depth interviews, and three focus groups with low-income, primarily African American shoppers with children. We found participants had detailed knowledge of and preference for healthy foods, but the obligation to consistently provide food for their families required them to apply specific decision criteria which, combined with structural qualities of the supermarket environment, increased unhealthy purchases and decreased healthy purchases. Applying situated cognition theory, we constructed an emic model explaining this widely shared grocery-purchasing decision process and its implications. This context-specific understanding of behavior suggests that multifaceted, system-level approaches to intervention are needed to increase healthy purchasing in food deserts.

  15. Tuning the mind: Exploring the connections between musical ability and executive functions.

    PubMed

    Slevc, L Robert; Davey, Nicholas S; Buschkuehl, Martin; Jaeggi, Susanne M

    2016-07-01

    A growing body of research suggests that musical experience and ability are related to a variety of cognitive abilities, including executive functioning (EF). However, it is not yet clear if these relationships are limited to specific components of EF, limited to auditory tasks, or reflect very general cognitive advantages. This study investigated the existence and generality of the relationship between musical ability and EFs by evaluating the musical experience and ability of a large group of participants and investigating whether this predicts individual differences on three different components of EF - inhibition, updating, and switching - in both auditory and visual modalities. Musical ability predicted better performance on both auditory and visual updating tasks, even when controlling for a variety of potential confounds (age, handedness, bilingualism, and socio-economic status). However, musical ability was not clearly related to inhibitory control and was unrelated to switching performance. These data thus show that cognitive advantages associated with musical ability are not limited to auditory processes, but are limited to specific aspects of EF. This supports a process-specific (but modality-general) relationship between musical ability and non-musical aspects of cognition. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Information Processing from Infancy to 11 Years: Continuities and Prediction of IQ

    PubMed Central

    Rose, Susan A.; Feldman, Judith F.; Jankowski, Jeffery J.; Van Rossem, Ronan

    2012-01-01

    This study provides the first direct evidence of cognitive continuity for multiple specific information processing abilities from infancy and toddlerhood to pre-adolescence, and provides support for the view that infant abilities and form the basis of later childhood abilities. Data from a large sample of children (N = 131) were obtained at five different time points (7, 12, 24, 36 months, and 11 years) for a large battery of tasks representing four cognitive domains (attention, processing speed, memory, and representational competence). Structural equation models of continuity were assessed for each domain, in which it was assumed that infant abilities → toddler abilities → 11-year abilities. Abilities at each age were represented by latent variables, which minimize task-specific variance and measurement error. The model for each domain fit the data. Moreover, abilities from the three age periods predicted global outcome, with infant, toddler, and contemporaneous 11-year measures, respectively, accounting for 12.3%, 18.5%, and 45.2% of the variance in 11-year IQ. These findings strengthen contentions that specific cognitive abilities that can be identified in infancy show long-term continuity and contribute importantly to later cognitive competence. PMID:23162179

  17. The proton pump inhibitor pantoprazole disrupts protein degradation systems and sensitizes cancer cells to death under various stresses.

    PubMed

    Cao, Yu; Chen, Min; Tang, Dehua; Yan, Hongli; Ding, Xiwei; Zhou, Fan; Zhang, Mingming; Xu, Guifang; Zhang, Weijie; Zhang, Shu; Zhuge, Yuzheng; Wang, Lei; Zou, Xiaoping

    2018-05-22

    Proton pump inhibitors (PPIs) play a role in antitumor activity, with studies showing specialized impacts of PPIs on cancer cell apoptosis, metastasis, and autophagy. In this study, we demonstrated that pantoprazole (PPI) increased autophagosomes formation and affected autophagic flux depending on the pH conditions. PPI specifically elevated SQSTM1 protein levels by increasing SQSTM1 transcription via NFE2L2 activation independent of the specific effect of PPI on autophagic flux. Via decreasing proteasome subunits expression, PPI significantly impaired the function of the proteasome, accompanied by the accumulation of undegraded poly-ubiquitinated proteins. Notably, PPI-induced autophagy functioned as a downstream response of proteasome inhibition by PPI, while suppressing protein synthesis abrogated autophagy. Blocking autophagic flux in neutral pH condition or further impairing proteasome function with proteasome inhibitors, significantly aggravated PPI cytotoxicity by worsening protein degradation ability. Interestingly, under conditions of mitochondrial stress, PPI showed significant synergism when combined with Bcl-2 inhibitors. Taken together, these findings provide a new understanding of the impact of PPIs on cancer cells' biological processes and highlight the potential to develop more efficient and effective combination therapies.

  18. Design and implementation of an automated compound management system in support of lead optimization.

    PubMed

    Quintero, Catherine; Kariv, Ilona

    2009-06-01

    To meet the needs of the increasingly rapid and parallelized lead optimization process, a fully integrated local compound storage and liquid handling system was designed and implemented to automate the generation of assay-ready plates directly from newly submitted and cherry-picked compounds. A key feature of the system is the ability to create project- or assay-specific compound-handling methods, which provide flexibility for any combination of plate types, layouts, and plate bar-codes. Project-specific workflows can be created by linking methods for processing new and cherry-picked compounds and control additions to produce a complete compound set for both biological testing and local storage in one uninterrupted workflow. A flexible cherry-pick approach allows for multiple, user-defined strategies to select the most appropriate replicate of a compound for retesting. Examples of custom selection parameters include available volume, compound batch, and number of freeze/thaw cycles. This adaptable and integrated combination of software and hardware provides a basis for reducing cycle time, fully automating compound processing, and ultimately increasing the rate at which accurate, biologically relevant results can be produced for compounds of interest in the lead optimization process.

  19. Physical Therapy Adjuvants to Promote Optimization of Walking Recovery after Stroke

    PubMed Central

    Bowden, Mark G.; Embry, Aaron E.; Gregory, Chris M.

    2011-01-01

    Stroke commonly results in substantial and persistent deficits in locomotor function. The majority of scientific inquiries have focused on singular intervention approaches, with recent attention given to task specific therapies. We propose that measurement should indicate the most critical limiting factor(s) to be addressed and that a combination of adjuvant treatments individualized to target accompanying impairment(s) will result in the greatest improvements in locomotor function. We explore training to improve walking performance by addressing a combination of: (1) walking specific motor control; (2) dynamic balance; (3) cardiorespiratory fitness and (4) muscle strength and put forward a theoretical framework to maximize the functional benefits of these strategies as physical adjuvants. The extent to which any of these impairments contribute to locomotor dysfunction is dependent on the individual and will undoubtedly change throughout the rehabilitation intervention. Thus, the ability to identify and measure the relative contributions of these elements will allow for identification of a primary intervention as well as prescription of additional adjuvant approaches. Importantly, we highlight the need for future studies as appropriate dosing of each of these elements is contingent on improving the capacity to measure each element and to titrate the contribution of each to optimal walking performance. PMID:22013549

  20. Developing a Measure of General Academic Ability: An Application of Maximal Reliability and Optimal Linear Combination to High School Students' Scores

    ERIC Educational Resources Information Center

    Dimitrov, Dimiter M.; Raykov, Tenko; AL-Qataee, Abdullah Ali

    2015-01-01

    This article is concerned with developing a measure of general academic ability (GAA) for high school graduates who apply to colleges, as well as with the identification of optimal weights of the GAA indicators in a linear combination that yields a composite score with maximal reliability and maximal predictive validity, employing the framework of…

  1. Social interaction in type 2 diabetes computer-mediated environments: How inherent features of the channels influence peer-to-peer interaction.

    PubMed

    Lewinski, Allison A; Fisher, Edwin B

    2016-06-01

    Interventions via the internet provide support to individuals managing chronic illness. The purpose of this integrative review was to determine how the features of a computer-mediated environment influence social interactions among individuals with type 2 diabetes. A combination of MeSH and keyword terms, based on the cognates of three broad groupings: social interaction, computer-mediated environments, and chronic illness, was used to search the PubMed, PsychInfo, Sociology Research Database, and Cumulative Index to Nursing and Allied Health Literature databases. Eleven articles met the inclusion criteria. Computer-mediated environments enhance an individual's ability to interact with peers while increasing the convenience of obtaining personalized support. A matrix, focused on social interaction among peers, identified themes across all articles, and five characteristics emerged: (1) the presence of synchronous and asynchronous communication, (2) the ability to connect with similar peers, (3) the presence or absence of a moderator, (4) personalization of feedback regarding individual progress and self-management, and (5) the ability of individuals to maintain choice during participation. Individuals interact with peers to obtain relevant, situation-specific information and knowledge about managing their own care. Computer-mediated environments facilitate the ability of individuals to exchange this information despite temporal or geographical barriers that may be present, thus improving T2D self-management. © The Author(s) 2015.

  2. A cluster randomized control trial to assess the impact of active learning on child activity, attention control, and academic outcomes: The Texas I-CAN trial.

    PubMed

    Bartholomew, John B; Jowers, Esbelle M; Errisuriz, Vanessa L; Vaughn, Sharon; Roberts, Gregory

    2017-10-01

    Active learning is designed to pair physical activity with the teaching of academic content. This has been shown to be a successful strategy to increase physical activity and improve academic performance. The existing designs have confounded academic lessons with physical activity. As a result, it is impossible to determine if the subsequent improvement in academic performance is due to: (1) physical activity, (2) the academic content of the active learning, or (3) the combination of academic material taught through physical activity. The Texas I-CAN project is a 3-arm, cluster randomized control trial in which 28 elementary schools were assigned to either control, math intervention, or spelling intervention. As a result, each intervention condition serves as an unrelated content control for the other arm of the trial, allowing the impact of physical activity to be separated from the content. That is, schools that perform only active math lessons provide a content control for the spelling schools on spelling outcomes. This also calculated direct observations of attention and behavior control following periods of active learning. This design is unique in its ability to separate the impact of physical activity, in general, from the combination of physical activity and specific academic content. This, in combination with the ability to examine both proximal and distal outcomes along with measures of time on task will do much to guide the design of future, school-based interventions. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Human facial neural activities and gesture recognition for machine-interfacing applications.

    PubMed

    Hamedi, M; Salleh, Sh-Hussain; Tan, T S; Ismail, K; Ali, J; Dee-Uam, C; Pavaganun, C; Yupapin, P P

    2011-01-01

    The authors present a new method of recognizing different human facial gestures through their neural activities and muscle movements, which can be used in machine-interfacing applications. Human-machine interface (HMI) technology utilizes human neural activities as input controllers for the machine. Recently, much work has been done on the specific application of facial electromyography (EMG)-based HMI, which have used limited and fixed numbers of facial gestures. In this work, a multipurpose interface is suggested that can support 2-11 control commands that can be applied to various HMI systems. The significance of this work is finding the most accurate facial gestures for any application with a maximum of eleven control commands. Eleven facial gesture EMGs are recorded from ten volunteers. Detected EMGs are passed through a band-pass filter and root mean square features are extracted. Various combinations of gestures with a different number of gestures in each group are made from the existing facial gestures. Finally, all combinations are trained and classified by a Fuzzy c-means classifier. In conclusion, combinations with the highest recognition accuracy in each group are chosen. An average accuracy >90% of chosen combinations proved their ability to be used as command controllers.

  4. Deep Belief Networks Learn Context Dependent Behavior

    PubMed Central

    Raudies, Florian; Zilli, Eric A.; Hasselmo, Michael E.

    2014-01-01

    With the goal of understanding behavioral mechanisms of generalization, we analyzed the ability of neural networks to generalize across context. We modeled a behavioral task where the correct responses to a set of specific sensory stimuli varied systematically across different contexts. The correct response depended on the stimulus (A,B,C,D) and context quadrant (1,2,3,4). The possible 16 stimulus-context combinations were associated with one of two responses (X,Y), one of which was correct for half of the combinations. The correct responses varied symmetrically across contexts. This allowed responses to previously unseen stimuli (probe stimuli) to be generalized from stimuli that had been presented previously. By testing the simulation on two or more stimuli that the network had never seen in a particular context, we could test whether the correct response on the novel stimuli could be generated based on knowledge of the correct responses in other contexts. We tested this generalization capability with a Deep Belief Network (DBN), Multi-Layer Perceptron (MLP) network, and the combination of a DBN with a linear perceptron (LP). Overall, the combination of the DBN and LP had the highest success rate for generalization. PMID:24671178

  5. Insoluble elastin reduces collagen scaffold stiffness, improves viscoelastic properties, and induces a contractile phenotype in smooth muscle cells.

    PubMed

    Ryan, Alan J; O'Brien, Fergal J

    2015-12-01

    Biomaterials with the capacity to innately guide cell behaviour while also displaying suitable mechanical properties remain a challenge in tissue engineering. Our approach to this has been to utilise insoluble elastin in combination with collagen as the basis of a biomimetic scaffold for cardiovascular tissue engineering. Elastin was found to markedly alter the mechanical and biological response of these collagen-based scaffolds. Specifically, during extensive mechanical assessment elastin was found to reduce the specific tensile and compressive moduli of the scaffolds in a concentration dependant manner while having minimal effect on scaffold microarchitecture with both scaffold porosity and pore size still within the ideal ranges for tissue engineering applications. However, the viscoelastic properties were significantly improved with elastin addition with a 3.5-fold decrease in induced creep strain, a 6-fold increase in cyclical strain recovery, and with a four-parameter viscoelastic model confirming the ability of elastin to confer resistance to long term deformation/creep. Furthermore, elastin was found to result in the modulation of SMC phenotype towards a contractile state which was determined via reduced proliferation and significantly enhanced expression of early (α-SMA), mid (calponin), and late stage (SM-MHC) contractile proteins. This allows the ability to utilise extracellular matrix proteins alone to modulate SMC phenotype without any exogenous factors added. Taken together, the ability of elastin to alter the mechanical and biological response of collagen scaffolds has led to the development of a biomimetic biomaterial highly suitable for cardiovascular tissue engineering. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. SVM-based automatic diagnosis method for keratoconus

    NASA Astrophysics Data System (ADS)

    Gao, Yuhong; Wu, Qiang; Li, Jing; Sun, Jiande; Wan, Wenbo

    2017-06-01

    Keratoconus is a progressive cornea disease that can lead to serious myopia and astigmatism, or even to corneal transplantation, if it becomes worse. The early detection of keratoconus is extremely important to know and control its condition. In this paper, we propose an automatic diagnosis algorithm for keratoconus to discriminate the normal eyes and keratoconus ones. We select the parameters obtained by Oculyzer as the feature of cornea, which characterize the cornea both directly and indirectly. In our experiment, 289 normal cases and 128 keratoconus cases are divided into training and test sets respectively. Far better than other kernels, the linear kernel of SVM has sensitivity of 94.94% and specificity of 97.87% with all the parameters training in the model. In single parameter experiment of linear kernel, elevation with 92.03% sensitivity and 98.61% specificity and thickness with 97.28% sensitivity and 97.82% specificity showed their good classification abilities. Combining elevation and thickness of the cornea, the proposed method can reach 97.43% sensitivity and 99.19% specificity. The experiments demonstrate that the proposed automatic diagnosis method is feasible and reliable.

  7. Classification of current anticancer immunotherapies

    PubMed Central

    Vacchelli, Erika; Pedro, José-Manuel Bravo-San; Buqué, Aitziber; Senovilla, Laura; Baracco, Elisa Elena; Bloy, Norma; Castoldi, Francesca; Abastado, Jean-Pierre; Agostinis, Patrizia; Apte, Ron N.; Aranda, Fernando; Ayyoub, Maha; Beckhove, Philipp; Blay, Jean-Yves; Bracci, Laura; Caignard, Anne; Castelli, Chiara; Cavallo, Federica; Celis, Estaban; Cerundolo, Vincenzo; Clayton, Aled; Colombo, Mario P.; Coussens, Lisa; Dhodapkar, Madhav V.; Eggermont, Alexander M.; Fearon, Douglas T.; Fridman, Wolf H.; Fučíková, Jitka; Gabrilovich, Dmitry I.; Galon, Jérôme; Garg, Abhishek; Ghiringhelli, François; Giaccone, Giuseppe; Gilboa, Eli; Gnjatic, Sacha; Hoos, Axel; Hosmalin, Anne; Jäger, Dirk; Kalinski, Pawel; Kärre, Klas; Kepp, Oliver; Kiessling, Rolf; Kirkwood, John M.; Klein, Eva; Knuth, Alexander; Lewis, Claire E.; Liblau, Roland; Lotze, Michael T.; Lugli, Enrico; Mach, Jean-Pierre; Mattei, Fabrizio; Mavilio, Domenico; Melero, Ignacio; Melief, Cornelis J.; Mittendorf, Elizabeth A.; Moretta, Lorenzo; Odunsi, Adekunke; Okada, Hideho; Palucka, Anna Karolina; Peter, Marcus E.; Pienta, Kenneth J.; Porgador, Angel; Prendergast, George C.; Rabinovich, Gabriel A.; Restifo, Nicholas P.; Rizvi, Naiyer; Sautès-Fridman, Catherine; Schreiber, Hans; Seliger, Barbara; Shiku, Hiroshi; Silva-Santos, Bruno; Smyth, Mark J.; Speiser, Daniel E.; Spisek, Radek; Srivastava, Pramod K.; Talmadge, James E.; Tartour, Eric; Van Der Burg, Sjoerd H.; Van Den Eynde, Benoît J.; Vile, Richard; Wagner, Hermann; Weber, Jeffrey S.; Whiteside, Theresa L.; Wolchok, Jedd D.; Zitvogel, Laurence; Zou, Weiping

    2014-01-01

    During the past decades, anticancer immunotherapy has evolved from a promising therapeutic option to a robust clinical reality. Many immunotherapeutic regimens are now approved by the US Food and Drug Administration and the European Medicines Agency for use in cancer patients, and many others are being investigated as standalone therapeutic interventions or combined with conventional treatments in clinical studies. Immunotherapies may be subdivided into “passive” and “active” based on their ability to engage the host immune system against cancer. Since the anticancer activity of most passive immunotherapeutics (including tumor-targeting monoclonal antibodies) also relies on the host immune system, this classification does not properly reflect the complexity of the drug-host-tumor interaction. Alternatively, anticancer immunotherapeutics can be classified according to their antigen specificity. While some immunotherapies specifically target one (or a few) defined tumor-associated antigen(s), others operate in a relatively non-specific manner and boost natural or therapy-elicited anticancer immune responses of unknown and often broad specificity. Here, we propose a critical, integrated classification of anticancer immunotherapies and discuss the clinical relevance of these approaches. PMID:25537519

  8. Transfer factor - hypotheses for its structure and function.

    PubMed

    Shifrine, M; Scibienski, R

    1975-01-01

    Transfer factor (TF) is a dialyzable extract from primed lymphocytes that is able to transfer specific delayed hypersensitivity from one animal to another. On the basis of available data we suggest that TF is a polypeptide with a molecular weight below 15,000 daltons. We hypothesize that TF is the variable light or heavy chain domain of immunoglobulin: such a molecule conforms with the accepted properties of TF and also has the necessary specificity requirements. We also hypothesize that TF is part of a receptor site. beta-2-microglobulin, a molecule that is an integral part of cell surfaces, could be the anchor for TF. beta-2-microglobulin has homologies with the constant portion of immunoglobulin light or heavy chain and thus would combine with the variable domain (TF) to form a complete receptor site for a specific antigen. The properties of TF suggest its mode of action, which is discussed in detail in the text. The biologic advantages of TF is its ability to confer immediate (immunologie specific) protection while the 'normal' immune response develops.

  9. Learning-dependent plasticity with and without training in the human brain.

    PubMed

    Zhang, Jiaxiang; Kourtzi, Zoe

    2010-07-27

    Long-term experience through development and evolution and shorter-term training in adulthood have both been suggested to contribute to the optimization of visual functions that mediate our ability to interpret complex scenes. However, the brain plasticity mechanisms that mediate the detection of objects in cluttered scenes remain largely unknown. Here, we combine behavioral and functional MRI (fMRI) measurements to investigate the human-brain mechanisms that mediate our ability to learn statistical regularities and detect targets in clutter. We show two different routes to visual learning in clutter with discrete brain plasticity signatures. Specifically, opportunistic learning of regularities typical in natural contours (i.e., collinearity) can occur simply through frequent exposure, generalize across untrained stimulus features, and shape processing in occipitotemporal regions implicated in the representation of global forms. In contrast, learning to integrate discontinuities (i.e., elements orthogonal to contour paths) requires task-specific training (bootstrap-based learning), is stimulus-dependent, and enhances processing in intraparietal regions implicated in attention-gated learning. We propose that long-term experience with statistical regularities may facilitate opportunistic learning of collinear contours, whereas learning to integrate discontinuities entails bootstrap-based training for the detection of contours in clutter. These findings provide insights in understanding how long-term experience and short-term training interact to shape the optimization of visual recognition processes.

  10. The social brain: scale-invariant layering of Erdős-Rényi networks in small-scale human societies.

    PubMed

    Harré, Michael S; Prokopenko, Mikhail

    2016-05-01

    The cognitive ability to form social links that can bind individuals together into large cooperative groups for safety and resource sharing was a key development in human evolutionary and social history. The 'social brain hypothesis' argues that the size of these social groups is based on a neurologically constrained capacity for maintaining long-term stable relationships. No model to date has been able to combine a specific socio-cognitive mechanism with the discrete scale invariance observed in ethnographic studies. We show that these properties result in nested layers of self-organizing Erdős-Rényi networks formed by each individual's ability to maintain only a small number of social links. Each set of links plays a specific role in the formation of different social groups. The scale invariance in our model is distinct from previous 'scale-free networks' studied using much larger social groups; here, the scale invariance is in the relationship between group sizes, rather than in the link degree distribution. We also compare our model with a dominance-based hierarchy and conclude that humans were probably egalitarian in hunter-gatherer-like societies, maintaining an average maximum of four or five social links connecting all members in a largest social network of around 132 people. © 2016 The Author(s).

  11. Unique volatolomic signatures of TP53 and KRAS in lung cells

    PubMed Central

    Davies, M P A; Barash, O; Jeries, R; Peled, N; Ilouze, M; Hyde, R; Marcus, M W; Field, J K; Haick, H

    2014-01-01

    Background: Volatile organic compounds (VOCs) are potential biomarkers for cancer detection in breath, but it is unclear if they reflect specific mutations. To test this, we have compared human bronchial epithelial cell (HBEC) cell lines carrying the KRASV12 mutation, knockdown of TP53 or both with parental HBEC cells. Methods: VOC from headspace above cultured cells were collected by passive sampling and analysed by thermal desorption gas chromatography mass spectrometry (TD-GC–MS) or sensor array with discriminant factor analysis (DFA). Results: In TD-GC–MS analysis, individual compounds had limited ability to discriminate between cell lines, but by applying DFA analysis combinations of 20 VOCs successfully discriminated between all cell types (accuracies 80–100%, with leave-one-out cross validation). Sensor array detection DFA demonstrated the ability to discriminate samples based on their cell type for all comparisons with accuracies varying between 77% and 93%. Conclusions: Our results demonstrate that minimal genetic changes in bronchial airway cells lead to detectable differences in levels of specific VOCs identified by TD-GC–MS or of patterns of VOCs identified by sensor array output. From the clinical aspect, these results suggest the possibility of breath analysis for detection of minimal genetic changes for earlier diagnosis or for genetic typing of lung cancers. PMID:25051409

  12. Photoelectric professional students in common universities cultivate way to explore under the background of professional certification

    NASA Astrophysics Data System (ADS)

    Sun, Yan-jun; Wang, Li; Leng, Yan-bing

    2017-08-01

    In view of the engineering education professional certification of specialty construction and the specific requirements of the training system, combining with our school optoelectronic information science and engineering characteristics, analysis of the optoelectronic information science and engineering in our school problems and challenges, to locate the specific professional training objectives. From the service oriented industry demand for talent ability, at the same time, according to the ministry of education professional norms of the development of the photoelectric teaching steering committee, and the professional development and the characteristics of target, to build a set to conform to the goal of cultivating the professional curriculum system. At the same time set up a from fundamental to professional practice teaching system, covers the course experiment, course design, case teaching, comprehensive training, such as graduation design practice. Which implements a whole ability training from the practice of foundation to high-end chain, embodies the training goal emphasize "outstanding practical skills, quality education is distinct culture characteristic. By further speed up the professional construction, professional certification standards to standardize our training process, improved the level of professional training, and improve the comprehensive quality of the graduates and talent of social competitiveness, fostered more professional talents for the country.

  13. Using Genetically Engineered Animal Models in the Postgenomic Era to Understand Gene Function in Alcoholism

    PubMed Central

    Reilly, Matthew T.; Harris, R. Adron; Noronha, Antonio

    2012-01-01

    Over the last 50 years, researchers have made substantial progress in identifying genetic variations that underlie the complex phenotype of alcoholism. Not much is known, however, about how this genetic variation translates into altered biological function. Genetic animal models recapitulating specific characteristics of the human condition have helped elucidate gene function and the genetic basis of disease. In particular, major advances have come from the ability to manipulate genes through a variety of genetic technologies that provide an unprecedented capacity to determine gene function in the living organism and in alcohol-related behaviors. Even newer genetic-engineering technologies have given researchers the ability to control when and where a specific gene or mutation is activated or deleted, allowing investigators to narrow the role of the gene’s function to circumscribed neural pathways and across development. These technologies are important for all areas of neuroscience, and several public and private initiatives are making a new generation of genetic-engineering tools available to the scientific community at large. Finally, high-throughput “next-generation sequencing” technologies are set to rapidly increase knowledge of the genome, epigenome, and transcriptome, which, combined with genetically engineered mouse mutants, will enhance insight into biological function. All of these resources will provide deeper insight into the genetic basis of alcoholism. PMID:23134044

  14. Using genetically engineered animal models in the postgenomic era to understand gene function in alcoholism.

    PubMed

    Reilly, Matthew T; Harris, R Adron; Noronha, Antonio

    2012-01-01

    Over the last 50 years, researchers have made substantial progress in identifying genetic variations that underlie the complex phenotype of alcoholism. Not much is known, however, about how this genetic variation translates into altered biological function. Genetic animal models recapitulating specific characteristics of the human condition have helped elucidate gene function and the genetic basis of disease. In particular, major advances have come from the ability to manipulate genes through a variety of genetic technologies that provide an unprecedented capacity to determine gene function in the living organism and in alcohol-related behaviors. Even newer genetic-engineering technologies have given researchers the ability to control when and where a specific gene or mutation is activated or deleted, allowing investigators to narrow the role of the gene's function to circumscribed neural pathways and across development. These technologies are important for all areas of neuroscience, and several public and private initiatives are making a new generation of genetic-engineering tools available to the scientific community at large. Finally, high-throughput "next-generation sequencing" technologies are set to rapidly increase knowledge of the genome, epigenome, and transcriptome, which, combined with genetically engineered mouse mutants, will enhance insight into biological function. All of these resources will provide deeper insight into the genetic basis of alcoholism.

  15. A pilot study for distinguishing chromophobe renal cell carcinoma and oncocytoma using second harmonic generation imaging and convolutional neural network analysis of collagen fibrillar structure

    NASA Astrophysics Data System (ADS)

    Judd, Nicolas; Smith, Jason; Jain, Manu; Mukherjee, Sushmita; Icaza, Michael; Gallagher, Ryan; Szeligowski, Richard; Wu, Binlin

    2018-02-01

    A clear distinction between oncocytoma and chromophobe renal cell carcinoma (chRCC) is critically important for clinical management of patients. But it may often be difficult to distinguish the two entities based on hematoxylin and eosin (H and E) stained sections alone. In this study, second harmonic generation (SHG) signals which are very specific to collagen were used to image collagen fibril structure. We conduct a pilot study to develop a new diagnostic method based on the analysis of collagen associated with kidney tumors using convolutional neural networks (CNNs). CNNs comprise a type of machine learning process well-suited for drawing information out of images. This study examines a CNN model's ability to differentiate between oncocytoma (benign), and chRCC (malignant) kidney tumor images acquired with second harmonic generation (SHG), which is very specific for collagen matrix. To the best of our knowledge, this is the first study that attempts to distinguish the two entities based on their collagen structure. The model developed from this study demonstrated an overall classification accuracy of 68.7% with a specificity of 66.3% and sensitivity of 74.6%. While these results reflect an ability to classify the kidney tumors better than chance, further studies will be carried out to (a) better realize the tumor classification potential of this method with a larger sample size and (b) combining SHG with two-photon excited intrinsic fluorescence signal to achieve better classification.

  16. Controlling disease and creating disparities: a fundamental cause perspective.

    PubMed

    Phelan, Jo C; Link, Bruce G

    2005-10-01

    The United States and other developed countries experienced enormous improvements in population health during the 20th century. In the context of this dramatic positive change, health disparities by race and socioeconomic status emerged for several potent killers. Any explanation for current health disparities must take these changing patterns into account. Any explanation that ignores large improvements in population health and fails to account for the emergence of disparities for specific diseases is an inadequate explanation of current disparities. We argue that genetic explanations and some prominent social causation explanations are incompatible with these facts. We propose that the theory of "fundamental causes" can account for both vast improvements in population health and the creation of large socioeconomic and racial disparities in mortality for specific causes of death over time. Specifically, we argue that it is our enormously expanded capacity to control disease and death in combination with existing social and economic inequalities that create health disparities by race and socioeconomic status: When we develop the ability to control disease and death, the benefits of this new-found ability are distributed according to resources of knowledge, money, power, prestige, and beneficial social connections. We present data on changing mortality patterns by race and socioeconomic status for two types of diseases: those for which our capacity to prevent death has increased significantly and those for which we remain largely unable to prevent death. Time trends in mortality patterns are consistent with the fundamental cause explanation.

  17. The National Football League (NFL) combine: does normalized data better predict performance in the NFL draft?

    PubMed

    Robbins, Daniel W

    2010-11-01

    The objective of this study was to investigate the predictive ability of National Football League (NFL) combine physical test data to predict draft order over the years 2005-2009. The NFL combine provides a setting in which NFL personnel can evaluate top draft prospects. The predictive ability of combine data in its raw form and when normalized in both a ratio and allometric manner was examined for 17 positions. Data from 8 combine physical performance tests were correlated with draft order to determine the direction and strength of relationship between the various combine measures and draft order. Players invited to the combine and subsequently drafted in the same year (n = 1,155) were included in the study. The primary finding was that performance in the combine physical test battery, whether normalized or not, has little association with draft success. In terms of predicting draft order from outcomes of the 8 tests making up the combine battery, normalized data provided no advantage over raw data. Of the 8 performance measures investigated, straight sprint time and jumping ability seem to hold the most weight with NFL personnel responsible for draft decisions. The NFL should consider revising the combine test battery to reflect the physical characteristics it deems important. It may be that NFL teams are more interested in attributes other than the purely physical traits reflected in the combine test battery. Players with aspirations of entering the NFL may be well advised to develop mental and technical skills in addition to developing the physical characteristics necessary to optimize performance.

  18. Coherent beam combining in atmospheric channels using gated backscatter.

    PubMed

    Naeh, Itay; Katzir, Abraham

    2016-02-01

    This paper introduces the concept of atmospheric channels and describes a possible approach for the coherent beam combining of lasers of an optical phased array (OPA) in a turbulent atmosphere. By using the recently introduced sparse spectrum harmonic augmentation method, a comprehensive simulative investigation was performed and the exceptional properties of the atmospheric channels were numerically demonstrated. Among the interesting properties are the ability to guide light in a confined manner in a refractive channel, the ability to gather different sources to the same channel, and the ability to maintain a constant relative phase within the channel between several sources. The newly introduced guiding properties combined with a suggested method for channel probing and phase measurement by aerosol backscattered radiation allows coherence improvement of the phased array's elements and energy refocusing at the location of the channel in order to increase power in the bucket without feedback from the target. The method relies on the electronic focusing, electronic scanning, and time gating of the OPA, combined with elements of the relative phase measurements.

  19. A gender approach to work ability and its relationship to professional and domestic work hours among nursing personnel.

    PubMed

    Rotenberg, Lúcia; Portela, Luciana Fernandes; Banks, Bahby; Griep, Rosane Harter; Fischer, Frida Marina; Landsbergis, Paul

    2008-09-01

    The association between working hours and work ability was examined in a cross-sectional study of male (N=156) and female (N=1092) nurses in three public hospitals. Working hours were considered in terms of their professional and domestic hours per week and their combined impact; total work load. Logistic regression analysis showed a significant association between total work load and inadequate work ability index (WAI) for females only. Females reported a higher proportion of inadequate WAI, fewer professional work hours but longer domestic work hours. There were no significant differences in total work load by gender. The combination of professional and domestic work hours in females seemed to best explain their lower work ability. The findings suggest that investigations into female well-being need to consider their total work load. Our male sample may have lacked sufficient power to detect a relationship between working hours and work ability.

  20. Compositions and Methods for Inhibiting Gene Expressions

    NASA Technical Reports Server (NTRS)

    Williams, Loren D. (Inventor); Hsiao, Chiaolong (Inventor); Fang, Po-Yu (Inventor); Williams, Justin (Inventor)

    2018-01-01

    A combined packing and assembly method that efficiently packs ribonucleic acid (RNA) into virus like particles (VLPs) has been developed. The VLPs can spontaneously assemble and load RNA in vivo, efficiently packaging specifically designed RNAs at high densities and with high purity. In some embodiments the RNA is capable of interference activity, or is a precursor of a RNA capable of causing interference activity. Compositions and methods for the efficient expression, production and purification of VLP-RNAs are provided. VLP-RNAs can be used for the storage of RNA for long periods, and provide the ability to deliver RNA in stable form that is readily taken up by cells.

  1. Atomic resolution Z-contrast imaging and energy loss spectroscopy of carbon nanotubes and bundles

    NASA Astrophysics Data System (ADS)

    Lupini, A. R.; Chisholm, M. F.; Puretzky, A. A.; Eres, G.; Melechko, A. V.; Schaaff, G.; Lowndes, D. H.; Geohegan, D. B.; Schittenhelm, H.; Pennycook, S. J.; Wang, Y.; Smalley, R. E.

    2002-03-01

    Single-wall carbon nanotubes and bundles were studied by a combination of techniques, including conventional imaging and diffraction, atomic resolution Z-contrast imaging in an aberration corrected STEM and electron energy loss spectroscopy (EELS). EELS is ideally suited for the analysis of carbon based structures because of the ability to distinguish between the different forms, specifically nanotubes, graphite, amorphous carbon and diamond. Numerous attempts were made to synthesize crystals of single walled carbon nanotubes, using both solution and vapor deposition of precursor structures directly onto TEM grids for in-situ annealing. The range of structures produced will be discussed.

  2. T-joints of Ti alloys with hybrid laser-MIG welding: macro-graphic and micro-hardness analyses

    NASA Astrophysics Data System (ADS)

    Spina, R.; Sorgente, D.; Palumbo, G.; Scintilla, L. D.; Brandizzi, M.; Satriano, A. A.; Tricarico, L.

    2012-03-01

    Titanium alloys are characterized by high mechanical properties and elevated corrosion resistance. The combination of laser welding with MIG/GMAW has proven to improve beneficial effects of both processes (keyhole, gap-bridging ability) while limiting their drawbacks (high thermal gradient, low mechanical resistance) In this paper, the hybrid Laser-GMAW welding of Ti-6Al-4V 3-mm thick sheets is investigated using a specific designed trailing shield. The joint geometry was the double fillet welded T-joint. Bead morphologies, microstructures and mechanical properties (micro-hardness) of welds were evaluated and compared to those achieved for the base metals.

  3. Investigating early modern Ottoman consumer culture in the light of Bursa probate inventories.

    PubMed

    Karababa, Eminegül

    2012-01-01

    This study investigates the development of early modern Ottoman consumer culture. In particular, the democratization of consumption, which is a significant indicator of the development of western consumer cultures, is examined in relation to Ottoman society. Sixteenth- and seventeenth-century probate inventories of the town of Bursa combined with literary and official sources are used in order to identify democratization of consumption and the macro conditions shaping this development. Findings demonstrate that commercialization, international trade, urbanization which created a fluid social structure, and the ability of the state to negotiate with guilds were possible contextual specificities which encouraged the democratization of consumption in the Bursa context.

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

    Stavridis, Adamantios; Arun, K. G.; Will, Clifford M.

    Spin induced precessional modulations of gravitational wave signals from supermassive black hole binaries can improve the estimation of luminosity distance to the source by space based gravitational wave missions like the Laser Interferometer Space Antenna (LISA). We study how this impacts the ability of LISA to do cosmology, specifically, to measure the dark energy equation of state (EOS) parameter w. Using the {lambda}CDM model of cosmology, we show that observations of precessing binaries with mass ratio 10 ratio 1 by LISA, combined with a redshift measurement, can improve the determination of w up to an order of magnitude with respectmore » to the nonprecessing case depending on the total mass and the redshift.« less

  5. Discrimination in measures of knowledge monitoring accuracy

    PubMed Central

    Was, Christopher A.

    2014-01-01

    Knowledge monitoring predicts academic outcomes in many contexts. However, measures of knowledge monitoring accuracy are often incomplete. In the current study, a measure of students’ ability to discriminate known from unknown information as a component of knowledge monitoring was considered. Undergraduate students’ knowledge monitoring accuracy was assessed and used to predict final exam scores in a specific course. It was found that gamma, a measure commonly used as the measure of knowledge monitoring accuracy, accounted for a small, but significant amount of variance in academic performance whereas the discrimination and bias indexes combined to account for a greater amount of variance in academic performance. PMID:25339979

  6. Biomimetic High Density Lipoprotein Nanoparticles For Nucleic Acid Delivery

    PubMed Central

    McMahon, Kaylin M.; Mutharasan, R. Kannan; Tripathy, Sushant; Veliceasa, Dorina; Bobeica, Mariana; Shumaker, Dale K.; Luthi, Andrea J.; Helfand, Brian T.; Ardehali, Hossein; Mirkin, Chad A.; Volpert, Olga; Thaxton, C. Shad

    2014-01-01

    We report a gold nanoparticle-templated high density lipoprotein (HDL AuNP) platform for gene therapy which combines lipid-based nucleic acid transfection strategies with HDL biomimicry. For proof-of-concept, HDL AuNPs are shown to adsorb antisense cholesterylated DNA. The conjugates are internalized by human cells, can be tracked within cells using transmission electron microscopy (TEM), and regulate target gene expression. Overall, the ability to directly image the AuNP core within cells, the chemical tailorability of the HDL AuNP platform, and the potential for cell-specific targeting afforded by HDL biomimicry make this platform appealing for nucleic acid delivery. PMID:21319839

  7. Non-"g" Residuals of the SAT and ACT Predict Specific Abilities

    ERIC Educational Resources Information Center

    Coyle, Thomas R.; Purcell, Jason M.; Snyder, Anissa C.; Kochunov, Peter

    2013-01-01

    This research examined whether non-"g" residuals of the SAT and ACT subtests, obtained after removing g, predicted specific abilities. Non-"g" residuals of the verbal and math subtests of the SAT and ACT were correlated with academic (verbal and math) and non-academic abilities (speed and shop), both based on the Armed Services…

  8. Low Performance on Mathematical Tasks in Preschoolers: The Importance of Domain-General and Domain-Specific Abilities

    ERIC Educational Resources Information Center

    Costa, H. M.; Nicholson, B.; Donlan, C.; Van Herwegen, J.

    2018-01-01

    Background: Different domain-specific and domain-general cognitive precursors play a key role in the development of mathematical abilities. The contribution of these domains to mathematical ability changes during development. Primary school-aged children who show mathematical difficulties form a heterogeneous group, but it is not clear whether…

  9. Predicting the impact of mutations on the specific activity of Bacillus thermocatenulatus lipase using a combined approach of docking and molecular dynamics.

    PubMed

    Yukselen, Onur; Timucin, Emel; Sezerman, Ugur

    2016-10-01

    Lipases are important biocatalysts owing to their ability to catalyze diverse reactions with exceptional substrate specificities. A combined docking and molecular dynamics (MD) approach was applied to study the chain-length selectivity of Bacillus thermocatenulatus lipase (BTL2) towards its natural substrates (triacylglycerols). A scoring function including electrostatic, van der Waals (vdW) and desolvation energies along with conformational entropy was developed to predict the impact of mutation. The native BTL2 and its 6 mutants (F17A, V175A, V175F, D176F, T178V and I320F) were experimentally analyzed to determine their specific activities towards tributyrin (C4) or tricaprylin (C8), which were used to test our approach. Our scoring methodology predicted the chain-length selectivity of BTL2 with 85.7% (6/7) accuracy with a positive correlation between the calculated scores and the experimental activity values (r = 0.82, p = 0.0004). Additionally, the impact of mutation on activity was predicted with 75% (9/12) accuracy. The described study represents a fast and reliable approach to accurately predict the effect of mutations on the activity and selectivity of lipases and also of other enzymes. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  10. Design and Experimental Validation for Direct-Drive Fault-Tolerant Permanent-Magnet Vernier Machines

    PubMed Central

    Liu, Guohai; Yang, Junqin; Chen, Ming; Chen, Qian

    2014-01-01

    A fault-tolerant permanent-magnet vernier (FT-PMV) machine is designed for direct-drive applications, incorporating the merits of high torque density and high reliability. Based on the so-called magnetic gearing effect, PMV machines have the ability of high torque density by introducing the flux-modulation poles (FMPs). This paper investigates the fault-tolerant characteristic of PMV machines and provides a design method, which is able to not only meet the fault-tolerant requirements but also keep the ability of high torque density. The operation principle of the proposed machine has been analyzed. The design process and optimization are presented specifically, such as the combination of slots and poles, the winding distribution, and the dimensions of PMs and teeth. By using the time-stepping finite element method (TS-FEM), the machine performances are evaluated. Finally, the FT-PMV machine is manufactured, and the experimental results are presented to validate the theoretical analysis. PMID:25045729

  11. Parkinson’s disease and pesticides: a toxicological perspective

    PubMed Central

    Hatcher, Jaime M.; Pennell, Kurt D.; Miller, Gary W.

    2017-01-01

    Environmental factors have been shown to contribute to the incidence of Parkinson’s disease (PD). Pesticides, which represent one of the primary classes of environmental agents associated with PD, share the common feature of being intentionally released into the environment to control or eliminate pests. Pesticides consist of multiple classes and subclasses of insecticides, herbicides, rodenticides, fungicides, fumigants and others and exhibit a vast array of chemically diverse structures. In this review we examine the evidence regarding the ability of each of the major pesticide subclasses to increase the incidence of PD. We propose that, from a toxicological perspective, it would be beneficial to identify specific subclasses, common structural features and the propensity for widespread human exposure when considering the potential role in PD, rather than using the overly broad term of ‘pesticides’ to describe this diverse group of chemicals. Furthermore, these chemicals and their environmentally relevant combinations should be evaluated for their ability to promote or accelerate PD and not merely for being singular causative agents. PMID:18453001

  12. Accessing and operating agricultural machinery: Advancements in assistive technology for users with impaired mobility.

    PubMed

    Ehlers, Shawn G; Field, William E

    2018-02-14

    This research focused on the advancements made in enabling agricultural workers with impaired mobility to access and operate off-road agricultural machinery. Although not a new concept, technological advancements in remote-controlled lifts, electronic actuators, electric over hydraulic controllers, and various modes of hand controls have advanced significantly, allowing operators with limited mobility to resume a high level of productivity in agricultural-related enterprises. In the United States, approximately 1.7% of the population is living with some form of paralysis or significant mobility impairment. When paired with the 2012 USDA Agriculture Census of 3.2 million farmers, it can be extrapolated that these technologies could impact 54,000 agricultural workers who have encountered disabling injuries or disease, which inhibit their ability to access and operate tractors, combines, and other self-propelled agricultural machines. Advancements in agricultural-specific technologies can allow for many of these individuals to regain the ability to effectively operate machinery once more.

  13. An Effective Hybrid Cuckoo Search Algorithm with Improved Shuffled Frog Leaping Algorithm for 0-1 Knapsack Problems

    PubMed Central

    Wang, Gai-Ge; Feng, Qingjiang; Zhao, Xiang-Jun

    2014-01-01

    An effective hybrid cuckoo search algorithm (CS) with improved shuffled frog-leaping algorithm (ISFLA) is put forward for solving 0-1 knapsack problem. First of all, with the framework of SFLA, an improved frog-leap operator is designed with the effect of the global optimal information on the frog leaping and information exchange between frog individuals combined with genetic mutation with a small probability. Subsequently, in order to improve the convergence speed and enhance the exploitation ability, a novel CS model is proposed with considering the specific advantages of Lévy flights and frog-leap operator. Furthermore, the greedy transform method is used to repair the infeasible solution and optimize the feasible solution. Finally, numerical simulations are carried out on six different types of 0-1 knapsack instances, and the comparative results have shown the effectiveness of the proposed algorithm and its ability to achieve good quality solutions, which outperforms the binary cuckoo search, the binary differential evolution, and the genetic algorithm. PMID:25404940

  14. Using GIS-based methods and lidar data to estimate rooftop solar technical potential in US cities

    NASA Astrophysics Data System (ADS)

    Margolis, Robert; Gagnon, Pieter; Melius, Jennifer; Phillips, Caleb; Elmore, Ryan

    2017-07-01

    We estimate the technical potential of rooftop solar photovoltaics (PV) for select US cities by combining light detection and ranging (lidar) data, a validated analytical method for determining rooftop PV suitability employing geographic information systems, and modeling of PV electricity generation. We find that rooftop PV’s ability to meet estimated city electricity consumption varies widely—from meeting 16% of annual consumption (in Washington, DC) to meeting 88% (in Mission Viejo, CA). Important drivers include average rooftop suitability, household footprint/per-capita roof space, the quality of the solar resource, and the city’s estimated electricity consumption. In addition to city-wide results, we also estimate the ability of aggregations of households to offset their electricity consumption with PV. In a companion article, we will use statistical modeling to extend our results and estimate national rooftop PV technical potential. In addition, our publically available data and methods may help policy makers, utilities, researchers, and others perform customized analyses to meet their specific needs.

  15. Building and Retaining the Career Force: New Procedures for Accessing and Assigning Army Enlisted Personnel: Annual Report 1990 Fiscal Year

    DTIC Science & Technology

    1992-05-01

    researched, valid measure of general cognitive abilities. However, many critical Army tasks appear to require psychomotor and perceptual skills for their...temperament (achievement, discipline, stress toler- ance), psychomotor ability (e.g., eye-hand coordination), and spatial ability to job performance...answered: (1) What combinations of aptitude, temperament, psychomotor ability, and spatial ability, measured at or before entry into the Army, best

  16. Subcortical processing of speech regularities underlies reading and music aptitude in children.

    PubMed

    Strait, Dana L; Hornickel, Jane; Kraus, Nina

    2011-10-17

    Neural sensitivity to acoustic regularities supports fundamental human behaviors such as hearing in noise and reading. Although the failure to encode acoustic regularities in ongoing speech has been associated with language and literacy deficits, how auditory expertise, such as the expertise that is associated with musical skill, relates to the brainstem processing of speech regularities is unknown. An association between musical skill and neural sensitivity to acoustic regularities would not be surprising given the importance of repetition and regularity in music. Here, we aimed to define relationships between the subcortical processing of speech regularities, music aptitude, and reading abilities in children with and without reading impairment. We hypothesized that, in combination with auditory cognitive abilities, neural sensitivity to regularities in ongoing speech provides a common biological mechanism underlying the development of music and reading abilities. We assessed auditory working memory and attention, music aptitude, reading ability, and neural sensitivity to acoustic regularities in 42 school-aged children with a wide range of reading ability. Neural sensitivity to acoustic regularities was assessed by recording brainstem responses to the same speech sound presented in predictable and variable speech streams. Through correlation analyses and structural equation modeling, we reveal that music aptitude and literacy both relate to the extent of subcortical adaptation to regularities in ongoing speech as well as with auditory working memory and attention. Relationships between music and speech processing are specifically driven by performance on a musical rhythm task, underscoring the importance of rhythmic regularity for both language and music. These data indicate common brain mechanisms underlying reading and music abilities that relate to how the nervous system responds to regularities in auditory input. Definition of common biological underpinnings for music and reading supports the usefulness of music for promoting child literacy, with the potential to improve reading remediation.

  17. Microbially assisted phytoremediation approaches for two multi-element contaminated sites.

    PubMed

    Langella, Francesca; Grawunder, Anja; Stark, Romy; Weist, Aileen; Merten, Dirk; Haferburg, Götz; Büchel, Georg; Kothe, Erika

    2014-01-01

    Phytoremediation is an environmental friendly, cost-effective technology for a soft restoration of abandoned mine sites. The grasses Agrostis capillaris, Deschampsia flexuosa and Festuca rubra, and the annual herb Helianthus annuus were combined with microbial consortia in pot experiments on multi-metal polluted substrates collected at a former uranium mine near Ronneburg, Germany, and a historic copper mine in Kopparberg, Sweden, to test for phytoextraction versus phytostabilization abilities. Metal uptake into plant biomass was evaluated to identify optimal plant-microbe combinations for each substrate. Metal bioavailability was found to be plant species and element specific, and influenced by the applied bacterial consortia of 10 strains, each isolated from the same soil to which it was applied. H. annuus showed high extraction capacity for several metals on the German soil independent of inoculation. Our study could also show a significant enhancement of extraction for F. rubra and A. capillaris when combined with the bacterial consortium, although usually grasses are considered metal excluder species. On the Swedish mixed substrate, due to its toxicity, with 30 % bark compost, A. capillaris inoculated with the respective consortium was able to extract multi-metal contaminants.

  18. Differentiation of Organically and Conventionally Grown Tomatoes by Chemometric Analysis of Combined Data from Proton Nuclear Magnetic Resonance and Mid-infrared Spectroscopy and Stable Isotope Analysis.

    PubMed

    Hohmann, Monika; Monakhova, Yulia; Erich, Sarah; Christoph, Norbert; Wachter, Helmut; Holzgrabe, Ulrike

    2015-11-04

    Because the basic suitability of proton nuclear magnetic resonance spectroscopy ((1)H NMR) to differentiate organic versus conventional tomatoes was recently proven, the approach to optimize (1)H NMR classification models (comprising overall 205 authentic tomato samples) by including additional data of isotope ratio mass spectrometry (IRMS, δ(13)C, δ(15)N, and δ(18)O) and mid-infrared (MIR) spectroscopy was assessed. Both individual and combined analytical methods ((1)H NMR + MIR, (1)H NMR + IRMS, MIR + IRMS, and (1)H NMR + MIR + IRMS) were examined using principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), linear discriminant analysis (LDA), and common components and specific weight analysis (ComDim). With regard to classification abilities, fused data of (1)H NMR + MIR + IRMS yielded better validation results (ranging between 95.0 and 100.0%) than individual methods ((1)H NMR, 91.3-100%; MIR, 75.6-91.7%), suggesting that the combined examination of analytical profiles enhances authentication of organically produced tomatoes.

  19. A combination of 19F NMR and surface plasmon resonance for site-specific hit selection and validation of fragment molecules that bind to the ATP-binding site of a kinase.

    PubMed

    Nagatoishi, Satoru; Yamaguchi, Sou; Katoh, Etsuko; Kajita, Keita; Yokotagawa, Takane; Kanai, Satoru; Furuya, Toshio; Tsumoto, Kouhei

    2018-05-01

    19 F NMR has recently emerged as an efficient, sensitive tool for analyzing protein binding to small molecules, and surface plasmon resonance (SPR) is also a popular tool for this purpose. Herein a combination of 19 F NMR and SPR was used to find novel binders to the ATP-binding pocket of MAP kinase extracellular regulated kinase 2 (ERK2) by fragment screening with an original fluorinated-fragment library. The 19 F NMR screening yielded a high primary hit rate of binders to the ERK2 ATP-binding pocket compared with the rate for the SPR screening. Hit compounds were evaluated and categorized according to their ability to bind to different binding sites in the ATP-binding pocket. The binding manner was characterized by using isothermal titration calorimetry and docking simulation. Combining 19 F NMR with other biophysical methods allows the identification of multiple types of hit compounds, thereby increasing opportunities for drug design using preferred fragments. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. The application of hyaluronic acid-derivatized carbon nanotubes in hematoporphyrin monomethyl ether-based photodynamic therapy for in vivo and in vitro cancer treatment

    PubMed Central

    Shi, Jinjin; Ma, Rourou; Wang, Lei; Zhang, Jing; Liu, Ruiyuan; Li, Lulu; Liu, Yan; Hou, Lin; Yu, Xiaoyuan; Gao, Jun; Zhang, Zhenzhong

    2013-01-01

    Carbon nanotubes (CNTs) have shown great potential in both photothermal therapy and drug delivery. In this study, a CNT derivative, hyaluronic acid-derivatized CNTs (HA-CNTs) with high aqueous solubility, neutral pH, and tumor-targeting activity, were synthesized and characterized, and then a new photodynamic therapy agent, hematoporphyrin monomethyl ether (HMME), was adsorbed onto the functionalized CNTs to develop HMME-HA-CNTs. Tumor growth inhibition was investigated both in vivo and in vitro by a combination of photothermal therapy and photodynamic therapy using HMME-HA-CNTs. The ability of HMME-HA-CNT nanoparticles to combine local specific photodynamic therapy with external near-infrared photothermal therapy significantly improved the therapeutic efficacy of cancer treatment. Compared with photodynamic therapy or photothermal therapy alone, the combined treatment demonstrated a synergistic effect, resulting in higher therapeutic efficacy without obvious toxic effects to normal organs. Overall, it was demonstrated that HMME-HA-CNTs could be successfully applied to photodynamic therapy and photothermal therapy simultaneously in future tumor therapy. PMID:23843694

  1. Antibiotic combination efficacy (ACE) networks for a Pseudomonas aeruginosa model

    PubMed Central

    Barbosa, Camilo; Beardmore, Robert; Jansen, Gunther

    2018-01-01

    The spread of antibiotic resistance is always a consequence of evolutionary processes. The consideration of evolution is thus key to the development of sustainable therapy. Two main factors were recently proposed to enhance long-term effectiveness of drug combinations: evolved collateral sensitivities between the drugs in a pair and antagonistic drug interactions. We systematically assessed these factors by performing over 1,600 evolution experiments with the opportunistic nosocomial pathogen Pseudomonas aeruginosa in single- and multidrug environments. Based on the growth dynamics during these experiments, we reconstructed antibiotic combination efficacy (ACE) networks as a new tool for characterizing the ability of the tested drug combinations to constrain bacterial survival as well as drug resistance evolution across time. Subsequent statistical analysis of the influence of the factors on ACE network characteristics revealed that (i) synergistic drug interactions increased the likelihood of bacterial population extinction—irrespective of whether combinations were compared at the same level of inhibition or not—while (ii) the potential for evolved collateral sensitivities between 2 drugs accounted for a reduction in bacterial adaptation rates. In sum, our systematic experimental analysis allowed us to pinpoint 2 complementary determinants of combination efficacy and to identify specific drug pairs with high ACE scores. Our findings can guide attempts to further improve the sustainability of antibiotic therapy by simultaneously reducing pathogen load and resistance evolution. PMID:29708964

  2. Salivary mRNA markers having the potential to detect oral squamous cell carcinoma segregated from oral leukoplakia with dysplasia.

    PubMed

    Michailidou, Evangelia; Tzimagiorgis, Georgios; Chatzopoulou, Fani; Vahtsevanos, Konstantinos; Antoniadis, Konstantinos; Kouidou, Sofia; Markopoulos, Anastasios; Antoniades, Dimitrios

    2016-08-01

    In the current study the presence of extracellular IL-1B, IL-8, OAZ and SAT mRNAs in the saliva was evaluated as a tool in the early detection of oral squamous cell carcinoma. 34 patients with primary oral squamous cell carcinoma stage T1N0M0/T2N0M0, 20 patients with oral leukoplakia and dysplasia (15 patients with mild dysplasia and 5 with severe dysplasia/in situ carcinoma) and 31 matched healthy-control subjects were included in the study. The presence of IL-1B, IL-8, OAZ and SAT mRNA was evaluated in extracellular RNA isolated from saliva samples using sequence-specific primers and real-time RT-PCR. ROC curve analysis was used to estimate the ability of the biomarkers to detect oral squamous cell carcinoma patients. The data reveal that the combination of these four biomarkers provides a good predictive probability of up to 80% (AUC=0.799, p=0.002) for patients with oral squamous cell carcinoma but not patients suffering from oral leukoplakia with dysplasia. Moreover, the combination of only the two biomarkers (SAT and IL-8) also raises a high predictive ability of 75.5% (AUC=0.755, p=0.007) approximately equal to the four biomarkers suggesting the use of the two biomarkers only in the prediction model for oral squamous cell carcinoma patients limiting the economic and health cost in half. SAT and IL-8 mRNAs are present in the saliva in high quality and quantity, with a good discriminatory ability for oral squamous cell carcinoma patients only but not for patients with oral leukoplakia and dysplasia an oral potentially malignant disorder. Copyright © 2016. Published by Elsevier Ltd.

  3. Nicotinamide augments the survival and incidence of apoptosis in glioma cells following photodynamic therapy in vitro

    NASA Astrophysics Data System (ADS)

    Bisland, Stuart K.; Modi, Nayan; Wilson, Brian C.

    2004-10-01

    The ability to customize photodynamic therapy (PDT) parameters with regards to timing and dosing of administered drug and light can be beneficial in determining target specificity and mode of cell death. Sustained, low level PDT or metronomic PDT (mPDT) may afford enhanced apoptotic cell death. This is of particular importance when considering PDT for the treatment of brain tumors as unlike apoptosis, necrotic cell death often leads to inflammation with increased intracranial pressure. The ability, therefore, to 'fine tune' PDT in favour of apoptosis is paramount. We have studied both acute (one time treatment) PDT (aPDT) and mPDT delivery strategies in combination with nicotinamide (NA) in an attempt to maximize the number of tumor cells dieing by apoptosis. Using several different glioma cell lines (9L, U87-MG and CNS-1) we now confirm that NA provides a dose-dependent (0.1-0.5 mM) increase in apoptotic cells following d-aminolevulinic acid-mediated aPDT or mPDT. Furthermore, using the 9L cell line stably transfected with the luciferase gene, NA was shown to delay the depletion of bioluminscence signal in aPDT and mPDT treated cells, inferring that adenosine triphosphate levels are maintained for longer following NA treatment. NA has previously been reported as promoting neuronal and vascular cell survival in normal brain following a number of neurological insults in which reactive oxygen species are implicated including, stroke, Alzheimer's disease and toxin-induced lesions. It is likely that the effects of NA reflect its capacity as an antioxidant as well as its ability to inhibit poly (adenosine diphosphate-ribose) polymerase-mediated depletion of ATP. Our results indicate that NA may prove therapeutically advantageous when used in combination with PDT treatment of brain tumors.

  4. Creativity and working memory capacity in sports: working memory capacity is not a limiting factor in creative decision making amongst skilled performers.

    PubMed

    Furley, Philip; Memmert, Daniel

    2015-01-01

    The goal of the study was to investigate the relationship between domain-general working memory capacity and domain-specific creativity amongst experienced soccer players. We administered the automated operation span task in combination with a domain-specific soccer creativity task to a group of 61 experienced soccer players to address the question whether an athlete's domain-specific creativity is restricted by their domain-general cognitive abilities (i.e., working memory capacity). Given that previous studies have either found a positive correlation, a negative correlation, or no correlation between working memory capacity and creativity, we analyzed the data in an exploratory manner by following recent recommendations to report effect-size estimations and their precision in form of 95% confidence intervals. The pattern of results provided evidence that domain-general working memory capacity is not associated with creativity in a soccer-specific creativity task. This pattern of results suggests that future research and theorizing on the role of working memory in everyday creative performance needs to distinguish between different types of creative performance while also taking the role of domain-specific experience into account.

  5. Creativity and working memory capacity in sports: working memory capacity is not a limiting factor in creative decision making amongst skilled performers

    PubMed Central

    Furley, Philip; Memmert, Daniel

    2015-01-01

    The goal of the study was to investigate the relationship between domain-general working memory capacity and domain-specific creativity amongst experienced soccer players. We administered the automated operation span task in combination with a domain-specific soccer creativity task to a group of 61 experienced soccer players to address the question whether an athlete’s domain-specific creativity is restricted by their domain-general cognitive abilities (i.e., working memory capacity). Given that previous studies have either found a positive correlation, a negative correlation, or no correlation between working memory capacity and creativity, we analyzed the data in an exploratory manner by following recent recommendations to report effect-size estimations and their precision in form of 95% confidence intervals. The pattern of results provided evidence that domain-general working memory capacity is not associated with creativity in a soccer-specific creativity task. This pattern of results suggests that future research and theorizing on the role of working memory in everyday creative performance needs to distinguish between different types of creative performance while also taking the role of domain-specific experience into account. PMID:25713552

  6. Bactericidal Specificity and Resistance Profile of Poly(Quaternary Ammonium) Polymers and Protein-Poly(Quaternary Ammonium) Conjugates.

    PubMed

    Ji, Weihang; Koepsel, Richard R; Murata, Hironobu; Zadan, Sawyer; Campbell, Alan S; Russell, Alan J

    2017-08-14

    Antibacterial polymers are potentially powerful biocides that can destroy bacteria on contact. Debate in the literature has surrounded the mechanism of action of polymeric biocides and the propensity for bacteria to develop resistance to them. There has been particular interest in whether surfaces with covalently coupled polymeric biocides have the same mechanism of action and resistance profile as similar soluble polymeric biocides. We designed and synthesized a series of poly(quaternary ammonium) polymers, with tailorable molecular structures and architectures, to engineer their antibacterial specificity and their ability to delay the development of bacterial resistance. These linear poly(quaternary ammonium) homopolymers and block copolymers, generated using atom transfer radical polymerization, had structure-dependent antibacterial specificity toward Gram positive and negative bacterial species. When single block copolymers contained two polymer segments of differing antibacterial specificity, the polymer combined the specificities of its two components. Nanoparticulate human serum albumin-poly(quaternary ammonium) conjugates of these same polymers, synthesized via "grafting from" atom transfer radical polymerization, were strongly biocidal and also exhibited a marked decrease in the rate of bacterial resistance development relative to linear polymers. These protein-biocide conjugates mimicked the behavior of surface-presented polycationic biocides rather than their nonproteinaceous counterparts.

  7. Highly specific and cost-efficient detection of Salmonella Paratyphi A combining aptamers with single-walled carbon nanotubes.

    PubMed

    Yang, Ming; Peng, Zhihui; Ning, Yi; Chen, Yongzhe; Zhou, Qin; Deng, Le

    2013-05-22

    In this paper, a panel of single-stranded DNA aptamers with high affinity and specificity against Salmonella Paratyphi A was selected from an enriched oligonucleotide pool by a whole-cell-Systematic Evolution of Ligands by Exponential Enrichment (SELEX) procedure, during which four other Salmonella serovars were used as counter-selection targets. It was determined through a fluorescence assay that the selected aptamers had high binding ability and specificity to this pathogen. The dissociation constant of these aptamers were up to nanomolar range, and aptamer Apt22 with the lowest Kd (47 ± 3 nM) was used in cell imaging experiments. To detect this bacteria with high specificity and cost-efficiently, a novel useful detection method was also constructed based on the noncovalent self-assembly of single-walled carbon nanotubes (SWNTs) and DNAzyme-labeled aptamer detection probes. The amounts of target bacteria could be quantified by exploiting chemoluminescence intensity changes at 420 nm and the detection limit of the method was 103 cfu/mL. This study demonstrated the applicability of Salmonella specific aptamers and their potential for use in the detection of Salmonella in food, clinical and environmental samples.

  8. Graphic Abilities in Relation to Mathematical and Scientific Ability in Adolescents

    ERIC Educational Resources Information Center

    Stavridou, Fotini; Kakana, Domna

    2008-01-01

    Background: The study investigated a small range of cognitive abilities, related to visual-spatial intelligence, in adolescents. This specific range of cognitive abilities was termed "graphic abilities" and defined as a range of abilities to visualise and think in three dimensions, originating in the domain of visual-spatial…

  9. Evaluation of self-reported work ability and usefulness of interventions among sick-listed patients.

    PubMed

    Wåhlin, Charlotte; Ekberg, Kerstin; Persson, Jan; Bernfort, Lars; Öberg, Birgitta

    2013-03-01

    To describe the types of intervention offered, to investigate the relationship between the type of intervention given, patient-reported usefulness of interventions and the effect on self-reported work ability in a cohort of sick-listed patients with musculoskeletal disorders (MSD) or mental disorders (MD). A prospective cohort study was performed including 810 newly sick-listed patients (MSD 62 % and MD 38 %). The baseline questionnaire included sociodemographic characteristics and measures of work ability. The 3-month follow-up questionnaire included measures of work ability, type of intervention received, and judgment of usefulness. Twenty-five percent received medical intervention modalities (MI) only, 45 % received a combination of medical and rehabilitative intervention modalities (CRI) and 31 % received work-related interventions combined with medical or rehabilitative intervention modalities (WI). Behavioural treatments were more common for patients with MD compared with MSD and exercise therapy were more common for patients with MSD. The most prevalent workplace interventions were adjustment of work tasks or the work environment. Among patients with MD, WI was found to be useful and improved work ability significantly more compared with only MI or CRI. For patients with MSD, no significant differences in improved work ability were found between interventions. Patients with MD who received a combination of work-related and clinical interventions reported best usefulness and best improvement in work ability. There was no difference in improvements in work ability between rehabilitation methods in the MSD group. There seems to be a gap between scientific evidence and praxis behaviour in the rehabilitation process. Unimodal rehabilitation was widely applied in the early rehabilitation process, a multimodal treatment approach was rare and only one-third received work-related interventions. It remains a challenge to understand who needs what type of intervention.

  10. Problem Solving in the General Mathematics Classroom

    ERIC Educational Resources Information Center

    Troutman, Andria Price; Lichtenberg, Betty Plunkett

    1974-01-01

    Five steps common to different problem solving models are listed. Next, seven specific abilities related to solving problems are discussed and examples given. Sample activities, appropriate to help in developing these specific abilities, are suggested. (LS)

  11. Combination of rapamycin and garlic-derived S-allylmercaptocysteine induces colon cancer cell apoptosis and suppresses tumor growth in xenograft nude mice through autophagy/p62/Nrf2 pathway.

    PubMed

    Li, Siying; Yang, Guang; Zhu, Xiaosong; Cheng, Lin; Sun, Yueyue; Zhao, Zhongxi

    2017-09-01

    The natural plant-derived product S-allylmercapto-cysteine (SAMC) has been studied in cancer therapy as a single and combination chemotherapeutic agent. The present study was employed to verify the combination use of SAMC and rapamycin that is the mTOR inhibitor with anticancer ability but has limited efficacy due to drug resistance, and to explore the underlying mechanisms. We combined rapamycin and SAMC for colorectal cancer treatment in the HCT‑116 cancer cells and a xenograft murine model. The in vivo study was established by xenografting HCT‑116 cells in BALB/c nude mice. It was found that the combination therapy had enhanced tumor-suppressing ability with the upregulation of the Bax/Bcl-2 ratio as a consequence of activated apoptosis, inhibition of autophagic activity and prevention of Akt phosphorylation. The rapamycin and SAMC combination activated antioxidant transcription expressions of Nrf2 and downstream gene NQO1. Concomitantly, autophagosome cargo p62 was downregulated, indicating that the p62 played a negative-regulatory role between Nrf2 and autophagy. Our results show that the combination of SAMC and rapamycin enhanced the anticancer ability, which could be used for the treatment of colorectal cancer. The underling mechanism of autophagy/p62/Nrf2 pathway discovered may provide a new direction for drug development, especially for traditional Chinese medicines.

  12. Surfactant biocatalyst for remediation of recalcitrant organics and heavy metals

    DOEpatents

    Brigmon, Robin L [North Augusta, SC; Story, Sandra [Greenville, SC; Altman, Denis J [Evans, GA; Berry, Christopher J [Aiken, SC

    2011-03-15

    Novel strains of isolated and purified bacteria have been identified which have the ability to degrade petroleum hydrocarbons including a variety of PAHs. Several isolates also exhibit the ability to produce a biosurfactant. The combination of the biosurfactant-producing ability along with the ability to degrade PAHs enhances the efficiency with which PAHs may be degraded. Additionally, the biosurfactant also provides an additional ability to bind heavy metal ions for removal from a soil or aquatic environment.

  13. Surfactant biocatalyst for remediation of recalcitrant organics and heavy metals

    DOEpatents

    Brigmon, Robin L [North Augusta, SC; Story, Sandra [Greenville, SC; Altman, Denis [Evans, GA; Berry, Christopher J [Aiken, SC

    2009-01-06

    Novel strains of isolated and purified bacteria have been identified which have the ability to degrade petroleum hydrocarbons including a variety of PAHs. Several isolates also exhibit the ability to produce a biosurfactant. The combination of the biosurfactant-producing ability along with the ability to degrade PAHs enhances the efficiency with which PAHs may be degraded. Additionally, the biosurfactant also provides an additional ability to bind heavy metal ions for removal from a soil or aquatic environment.

  14. Surfactant biocatalyst for remediation of recalcitrant organics and heavy metals

    DOEpatents

    Brigmon, Robin L [North Augusta, SC; Story, Sandra [Greenville, SC; Altman, Denis J [Evans, GA; Berry, Christopher J [Aiken, SC

    2011-05-03

    Novel strains of isolated and purified bacteria have been identified which have the ability to degrade petroleum hydrocarbons including a variety of PAHs. Several isolates also exhibit the ability to produce a biosurfactant. The combination of the biosurfactant-producing ability along with the ability to degrade PAHs enhances the efficiency with which PAHs may be degraded. Additionally, the biosurfactant also provides an additional ability to bind heavy metal ions for removal from a soil or aquatic environment.

  15. Surfactant biocatalyst for remediation of recalcitrant organics and heavy metals

    DOEpatents

    Brigmon, Robin L [North Augusta, SC; Story, Sandra [Greenville, SC; Altman,; Denis, J [Evans, GA; Berry, Christopher J [Aiken, SC

    2011-03-29

    Novel strains of isolated and purified bacteria have been identified which have the ability to degrade petroleum hydrocarbons including a variety of PAHs. Several isolates also exhibit the ability to produce a biosurfactant. The combination of the biosurfactant-producing ability along with the ability to degrade PAHs enhances the efficiency with which PAHs may be degraded. Additionally, the biosurfactant also provides an additional ability to bind heavy metal ions for removal from a soil or aquatic environment.

  16. Fitting perception in and to cognition.

    PubMed

    Goldstone, Robert L; de Leeuw, Joshua R; Landy, David H

    2015-02-01

    Perceptual modules adapt at evolutionary, lifelong, and moment-to-moment temporal scales to better serve the informational needs of cognizers. Perceptual learning is a powerful way for an individual to become tuned to frequently recurring patterns in its specific local environment that are pertinent to its goals without requiring costly executive control resources to be deployed. Mechanisms like predictive coding, categorical perception, and action-informed vision allow our perceptual systems to interface well with cognition by generating perceptual outputs that are systematically guided by how they will be used. In classic conceptions of perceptual modules, people have access to the modules' outputs but no ability to adjust their internal workings. However, humans routinely and strategically alter their perceptual systems via training regimes that have predictable and specific outcomes. In fact, employing a combination of strategic and automatic devices for adapting perception is one of the most promising approaches to improving cognition. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Heuristic value of eclecticism in theory development: the case of Piagetian-Vygotskian dialogue about proportional reasoning.

    PubMed

    Falcão, Jorge Tarcísio Da Rocha; Hazin, Izabel

    2012-03-01

    Køppe's proposition of four layers in theoretical building are used here in the exploration of a specific case of eclectic combination, the use of Piagetian and Vygotskian general approaches to the analysis of proportional reasoning as a cognitive mathematical ability. It is proposed here that the eclectic consideration of these contributions depends on the consideration of their specificity, in the sense that they highlight different aspects of the phenomenon under scrutiny, and also on the consideration of the coherence between this eclectic convergence and premises in terms of schools of thought under which each contribution is framed. We conclude proposing in accordance to S. Køppe's proposal that eclecticism can be valuable and heuristic in theory development, but this contribution will depend largely on the effort in establishing careful relations between the four layers of theory-building.

  18. Isolation and characterization of an immunosuppressive protein from venom of the pupa-specific endoparasitoid Pteromalus puparum.

    PubMed

    Wu, Ma-li; Ye, Gong-yin; Zhu, Jia-ying; Chen, Xue-xin; Hu, Cui

    2008-10-01

    In hymenopteran parasitoids devoid of symbiotic viruses, venom proteins appear to play a major role in host immune suppression and host regulation. Not much is known about the active components of venom proteins in these parasitoids, especially those that have the functions involved in the suppression of host cellular immunity. Here, we report the isolation and characterization of a venom protein Vn.11 with 24.1 kDa in size from Pteromalus puparum, a pupa-specific endoparasitoid of Pieris rapae. The Vn.11 venom protein is isolated with the combination of ammonium sulfate precipitation and anion exchange chromatography, and its purity is verified using SDS-PAGE analysis. Like crude venom, the Vn.11 venom protein significantly inhibits the spreading behavior and encapsulation ability of host hemocytes in vitro. It is suggested that this protein is an actual component of P. puparum crude venom as host cellular-immune suppressive factor.

  19. Morphologic analysis of the zebrafish digestive system.

    PubMed

    Trotter, Andrew J; Parslow, Adam C; Heath, Joan K

    2009-01-01

    The zebrafish provides an ideal model for the study of vertebrate organogenesis, including the formation of the digestive tract and its associated organs. Despite optical transparency of embryos, the internal position of the developing digestive system and its close juxtaposition with the yolk initially made morphological analysis relatively challenging, particularly during the first 3 d of development. However, methodologies have been successfully developed to address these problems and comprehensive morphologic analysis of the developing digestive system has now been achieved using a combination of light and fluorescence microscope approaches-including confocal analysis-to visualize wholemount and histological preparations of zebrafish embryos. Furthermore, the expanding number of antibodies that cross-react with zebrafish proteins and the generation of tissue-specific transgenic green fluorescent protein reporter lines that mark specific cell and tissue compartments have greatly enhanced our ability to successfully image the developing zebrafish digestive system.

  20. Application of virtual screening and molecular dynamics for the analysis of selectivity of inhibitors of HU proteins targeted to the DNA-recognition site

    NASA Astrophysics Data System (ADS)

    Talyzina, A. A.; Agapova, Yu. K.; Podshivalov, D. D.; Timofeev, V. I.; Sidorov-Biryukov, D. D.; Rakitina, T. V.

    2017-11-01

    DNA-Binding HU proteins are essential for the maintenance of genomic DNA supercoiling and compaction in prokaryotic cells and are promising pharmacological targets for the design of new antibacterial agents. The virtual screening for low-molecular-weight compounds capable of specifically interacting with the DNA-recognition loop of the HU protein from the mycoplasma Spiroplasma melliferum was performed. The ability of the initially selected ligands to form stable complexes with the protein target was assessed by molecular dynamics simulation. One compound, which forms an unstable complex, was eliminated by means of a combination of computational methods, resulting in a decrease in the number of compounds that will pass to the experimental test phase. This approach can be used to solve a wide range of problems related to the search for and validation of low-molecular-weight inhibitors specific for a particular protein target.

  1. Thioaptamer Diagnostic System (TDS)

    NASA Technical Reports Server (NTRS)

    Yang, Xianbin

    2015-01-01

    AM Biotechnologies, LLC, in partnership with Sandia National Laboratories, has developed a diagnostic device that quickly detects sampled biomarkers. The TDS quickly quantifies clinically relevant biomarkers using only microliters of a single sample. The system combines ambient-stable, long shelf-life affinity assays with handheld, microfluidic gel electrophoresis affinity assay quantification technology. The TDS is easy to use, operates in microgravity, and permits simultaneous quantification of 32 biomarkers. In Phase I of the project, the partners demonstrated that a thioaptamer assay used in the microfluidic instrument could quantify a specific biomarker in serum in the low nanomolar range. The team also identified novel affinity agents to bone-specific alkaline phosphatase (BAP) and demonstrated their ability to detect BAP with the microfluidic instrument. In Phase II, AM Biotech expanded the number of ambient affinity agents and demonstrated a TDS prototype. In the long term, the clinical version of the TDS will provide a robust, flight-tested diagnostic capability for space exploration missions.

  2. Evaluation of popcorn germplasm for resistance to Sesamia nonagrioides attack.

    PubMed

    Butrón, A; Sandoya, G; Revilla, P; Ordás, A; Malvar, R A

    2005-10-01

    Popcorn adapted to Spanish conditions could be an interesting and profitable alternative to field corn. However, little is known about breeding popcorn germplasm for adaptation to Spain. Sesamia nonagrioides Lefèvbre is the main insect pest affecting popcorn quality and yield under Spanish growing conditions. The objectives of the study were the search for sources of resistance to S. nonagrioides among popcorn germplasm and to study the genetics of the resistance to S. nonagrioides attack. Eight breeding populations along with a five-inbred line diallel and two popcorn commercial checks were evaluated under S. nonagrioides infestation in 2 yr. Significant differences were found among general combining ability (GCA) effects for days to silking, S. nonagrioides tunnel length, general appearance of the ear, kernel moisture, and yield. Specific combining ability (SCA) effects were found to be significant for yield and ear damage. Therefore, heterotic patterns among popcorn materials should be taken into account to generate new popcorn hybrids that are not only more productive but also have higher kernel quality. Breeding popcorn populations BSP4APC0 and PSPW1C1 could be base germplasms in a breeding program for obtaining parental inbreds of healthy kernel popcorn hybrids. New inbred lines could be generated from the cross BP1 x BP2 that would have improved GCA and SCA effects for S. nonagrioides resistance when crossed to South American inbreds.

  3. Role of HCV Core gene of genotype 1a and 3a and host gene Cox-2 in HCV-induced pathogenesis

    PubMed Central

    2011-01-01

    Background Hepatitis C virus (HCV) Core protein is thought to trigger activation of multiple signaling pathways and play a significant role in the alteration of cellular gene expression responsible for HCV pathogenesis leading to hepatocellular carcinoma (HCC). However, the exact molecular mechanism of HCV genome specific pathogenesis remains unclear. We examined the in vitro effects of HCV Core protein of HCV genotype 3a and 1a on the cellular genes involved in oxidative stress and angiogenesis. We also studied the ability of HCV Core and Cox-2 siRNA either alone or in combination to inhibit viral replication and cell proliferation in HCV serum infected Huh-7 cells. Results Over expression of Core gene of HCV 3a genotype showed stronger effect in regulating RNA and protein levels of Cox-2, iNOS, VEGF, p-Akt as compared to HCV-1a Core in hepatocellular carcinoma cell line Huh-7 accompanied by enhanced PGE2 release and cell proliferation. We also observed higher expression levels of above genes in HCV 3a patient's blood and biopsy samples. Interestingly, the Core and Cox-2-specific siRNAs down regulated the Core 3a-enhanced expression of Cox-2, iNOS, VEGF, p-Akt. Furthermore, the combined siRNA treatment also showed a dramatic reduction in viral titer and expression of these genes in HCV serum-infected Huh-7 cells. Taken together, these results demonstrated a differential response by HCV 3a genotype in HCV-induced pathogenesis, which may be due to Core and host factor Cox-2 individually or in combination. Conclusions Collectively, these studies not only suggest a genotype-specific interaction between key players of HCV pathogenesis but also may represent combined viral and host gene silencing as a potential therapeutic strategy. PMID:21457561

  4. Synaptic correlates of increased cognitive vulnerability with aging: peripheral immune challenge and aging interact to disrupt theta-burst late-phase long-term potentiation in hippocampal area CA1.

    PubMed

    Chapman, Timothy R; Barrientos, Ruth M; Ahrendsen, Jared T; Maier, Steven F; Patterson, Susan L

    2010-06-02

    Variability in cognitive functioning increases markedly with age, as does cognitive vulnerability to physiological and psychological challenges. Exploring the basis of this vulnerability may provide important insights into the mechanisms underlying aging-associated cognitive decline. As we have previously reported, the cognitive abilities of aging (24-month-old) F344 x BN rats are generally good, but are more vulnerable to the consequences of a peripheral immune challenge (an intraperitoneal injection of live Escherichia coli) than those of their younger (3-month-old) counterparts. Four days after the injection, the aging, but not the young rats show profound memory deficits, specific to the consolidation of hippocampus-dependent memory processes. Here, we have extended these observations, using hippocampal slices to examine for the first time the combined effects of aging and a recent infection on several forms of synaptic plasticity. We have found that the specific deficit in long-lasting memory observed in the aged animals after infection is mirrored by a specific deficit in a form of long-lasting synaptic plasticity. The late-phase long-term potentiation induced in area CA1 using theta-burst stimulation is particularly compromised by the combined effects of aging and infection-a deficit that can be ameliorated by intra-cisterna magna administration of the naturally occurring antiinflammatory cytokine IL-1Ra (interleukin-1 receptor antagonist). These data support the idea that the combination of aging and a negative life event such as an infection might produce selective, early-stage failures of synaptic plasticity in the hippocampus, with corresponding selective deficits in memory.

  5. Detection and quantification of Plectosphaerella cucumerina, a potential biological control agent of potato cyst nematodes, by using conventional PCR, real-time PCR, selective media, and baiting.

    PubMed

    Atkins, S D; Clark, I M; Sosnowska, D; Hirsch, P R; Kerry, B R

    2003-08-01

    Potato cyst nematodes (PCN) are serious pests in commercial potato production, causing yield losses valued at approximately $300 million in the European Community. The nematophagous fungus Plectosphaerella cucumerina has demonstrated its potential as a biological control agent against PCN populations by reducing field populations by up to 60% in trials. The use of biological control agents in the field requires the development of specific techniques to monitor the release, population size, spread or decline, and pathogenicity against its host. A range of methods have therefore been developed to monitor P. cucumerina. A species-specific PCR primer set (PcCF1-PcCR1) was designed that was able to detect the presence of P. cucumerina in soil, root, and nematode samples. PCR was combined with a bait method to identify P. cucumerina from infected nematode eggs, confirming the parasitic ability of the fungus. A selective medium was adapted to isolate the fungus from root and soil samples and was used to quantify the fungus from field sites. A second P. cucumerina-specific primer set (PcRTF1-PcRTR1) and a Taqman probe (PcRTP1) were designed for real-time PCR quantification of the fungus and provided a very sensitive means of detecting the fungus from soil. PCR, bait, and culture methods were combined to investigate the presence and abundance of P. cucumerina from two field sites in the United Kingdom where PCN populations were naturally declining. All methods enabled differences in the activity of P. cucumerina to be detected, and the results demonstrated the importance of using a combination of methods to investigate population size and activity of fungi.

  6. A Measure of the Broad Substrate Specificity of Enzymes Based on ‘Duplicate’ Catalytic Residues

    PubMed Central

    Chakraborty, Sandeep; Ásgeirsson, Bjarni; Rao, Basuthkar J.

    2012-01-01

    The ability of an enzyme to select and act upon a specific class of compounds with unerring precision and efficiency is an essential feature of life. Simultaneously, these enzymes often catalyze the reaction of a range of similar substrates of the same class, and also have promiscuous activities on unrelated substrates. Previously, we have established a methodology to quantify promiscuous activities in a wide range of proteins. In the current work, we quantitatively characterize the active site for the ability to catalyze distinct, yet related, substrates (BRASS). A protein with known structure and active site residues provides the framework for computing ‘duplicate’ residues, each of which results in slightly modified replicas of the active site scaffold. Such spatial congruence is supplemented by Finite difference Poisson Boltzmann analysis which filters out electrostatically unfavorable configurations. The congruent configurations are used to compute an index (BrassIndex), which reflects the broad substrate profile of the active site. We identify an acetylhydrolase and a methyltransferase as having the lowest and highest BrassIndex, respectively, from a set of non-homologous proteins extracted from the Catalytic Site Atlas. The acetylhydrolase, a regulatory enzyme, is known to be highly specific for platelet-activating factor. In the methyltransferase (PDB: 1QAM), various combinations of glycine (Gly38/40/42), asparagine (Asn101/11) and glutamic acid (Glu59/36) residues having similar spatial and electrostatic profiles with the specified scaffold (Gly38, Asn101 and Glu59) exemplifies the broad substrate profile such an active site may provide. ‘Duplicate’ residues identified by relaxing the spatial and/or electrostatic constraints can be the target of directed evolution methodologies, like saturation mutagenesis, for modulating the substrate specificity of proteins. PMID:23166637

  7. Development of a multi-electrode array for spinal cord epidural stimulation to facilitate stepping and standing after a complete spinal cord injury in adult rats.

    PubMed

    Gad, Parag; Choe, Jaehoon; Nandra, Mandheerej Singh; Zhong, Hui; Roy, Roland R; Tai, Yu-Chong; Edgerton, V Reggie

    2013-01-21

    Stimulation of the spinal cord has been shown to have great potential for improving function after motor deficits caused by injury or pathological conditions. Using a wide range of animal models, many studies have shown that stimulation applied to the neural networks intrinsic to the spinal cord can result in a dramatic improvement of motor ability, even allowing an animal to step and stand after a complete spinal cord transection. Clinical use of this technology, however, has been slow to develop due to the invasive nature of the implantation procedures, the lack of versatility in conventional stimulation technology, and the difficulty of ascertaining specific sites of stimulation that would provide optimal amelioration of the motor deficits. Moreover, the development of tools available to control precise stimulation chronically via biocompatible electrodes has been limited. In this paper, we outline the development of this technology and its use in the spinal rat model, demonstrating the ability to identify and stimulate specific sites of the spinal cord to produce discrete motor behaviors in spinal rats using this array. We have designed a chronically implantable, rapidly switchable, high-density platinum based multi-electrode array that can be used to stimulate at 1-100 Hz and 1-10 V in both monopolar and bipolar configurations to examine the electrophysiological and behavioral effects of spinal cord epidural stimulation in complete spinal cord transected rats. In this paper, we have demonstrated the effectiveness of using high-resolution stimulation parameters in the context of improving motor recovery after a spinal cord injury. We observed that rats whose hindlimbs were paralyzed can stand and step when specific sets of electrodes of the array are stimulated tonically (40 Hz). Distinct patterns of stepping and standing were produced by stimulation of different combinations of electrodes on the array located at specific spinal cord levels and by specific stimulation parameters, i.e., stimulation frequency and intensity, and cathode/anode orientation. The array also was used to assess functional connectivity between the cord dorsum to interneuronal circuits and specific motor pools via evoked potentials induced at 1 Hz stimulation in the absence of any anesthesia. Therefore the high density electrode array allows high spatial resolution and the ability to selectively activate different neural pathways within the lumbosacral region of the spinal cord to facilitate standing and stepping in adult spinal rats and provides the capability to evoke motor potentials and thus a means for assessing connectivity between sensory circuits and specific motor pools and muscles.

  8. Impact of indoor surface material on perceived air quality.

    PubMed

    Senitkova, I

    2014-03-01

    The material combination impact on perceived indoor air quality for various surface interior materials is presented in this paper. The chemical analysis and sensory assessments identifies health adverse of indoor air pollutants (TVOCs). In this study, emissions and odors from different common indoor surface materials were investigated in glass test chamber under standardized conditions. Chemical measurements (TVOC concentration) and sensory assessments (odor intensity, air acceptability) were done after building materials exposure to standardized conditions. The results of the chemical and sensory assessment of individual materials and their combinations are compared and discussed within the paper. The using possibility of individual material surface sorption ability was investigated. The knowledge of targeted sorption effects can be used in the interior design phase. The results demonstrate the various sorption abilities of various indoor materials as well as the various sorption abilities of the same indoor material in various combinations. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Antibacterial activity and dentin bonding ability of combined use of Clearfil SE Protect and sodium hypochlorite.

    PubMed

    Muratovska, Ilijana; Kitagawa, Haruaki; Hirose, Nanako; Kitagawa, Ranna; Imazato, Satoshi

    2018-02-08

    The aim of this study was to evaluate the antibacterial activity and dentin bonding ability of a commercial self-etch adhesive Clearfil SE Protect (Kuraray Noritake Dental, Tokyo, Japan) in combination with sodium hypochlorite (NaOCl). Agar disc diffusion tests and measurement of minimum inhibitory/bactericidal concentrations (MIC/MBC) against Streptococcus mutans were performed to evaluate antibacterial effects. The mixture solution of 5.25% NaOCl and the primer of Clearfil SE Protect demonstrated less antibacterial activity than primer only. In microtensile bond strength tests using non-carious human molars, pretreatment with 5.25% NaOCl aqueous solution had no influence on the bond strength of Clearfil SE Protect. These results indicate that pretreatment with NaOCl does not influence the bonding ability of Clearfil SE Protect, while their combined use does not enhance cavity disinfecting effects.

  10. Brain White Matter Tract Integrity and Cognitive Abilities in Community-Dwelling Older People: The Lothian Birth Cohort, 1936

    PubMed Central

    2013-01-01

    Objective: The present study investigates associations between brain white matter tract integrity and cognitive abilities in community-dwelling older people (N = 655). We explored two potential confounds of white matter tract−cognition associations in later life: (a) whether the associations between tracts and specific cognitive abilities are accounted for by general cognitive ability (g); and (b) how the presence of atrophy and white matter lesions affect these associations. Method: Tract integrity was determined using quantitative diffusion magnetic resonance imaging tractography (tract-averaged fractional anisotropy [FA]). Using confirmatory factor analysis, we compared first-order and bifactor models to investigate whether specific tract-ability associations were accounted for by g. Results: Significant associations were found between g and FA in bilateral anterior thalamic radiations (r range: .16−.18, p < .01), uncinate (r range: .19−.26, p < .001), arcuate fasciculi (r range: .11−.12, p < .05), and the splenium of corpus callosum (r = .14, p < .01). After controlling for g within the bifactor model, some significant specific cognitive domain associations remained. Results also suggest that the primary effects of controlling for whole brain integrity were on g associations, not specific abilities. Conclusion: Results suggest that g accounts for most of, but not all, the tract−cognition associations in the current data. When controlling for age-related overall brain structural changes, only minor attenuations of the tract−cognition associations were found, and these were primarily with g. In totality, the results highlight the importance of controlling for g when investigating associations between specific cognitive abilities and neuropsychology variables. PMID:23937481

  11. Identifying potential dropouts from college physics classes

    NASA Astrophysics Data System (ADS)

    Wollman, Warren; Lawrenz, Frances

    Hudson and Rottman (1981) established that mathematics ability is probably a secondary factor influencing dropout from college physics courses. Other factors remain to be found for predicting who will drop out or at least have difficulty with the course. When mathematics ability is coupled with general indicators of performance (total GPA and ACT natural science), prediction of performance for those who complete the course is substantially improved. Moreover, discriminant analyses reveal who will have at least some difficulty, but not who will drop out. The problem of isolating specific weaknesses of students who have difficulty persists. Physics achievement appears to depend on mathematics ability only to the extent that students possess the ability to utilize mathematics knowledge for solving physics problems. Identification of the specific aspects of this ability as well as the specific deficiencies leading to dropout should be the object of future research. For the present, interviews might be more revealing than group testing methods.

  12. Pleural effusion biomarkers and computed tomography findings in diagnosing malignant pleural mesothelioma: A retrospective study in a single center

    PubMed Central

    Kataoka, Yuki; Ikegaki, Shunkichi; Saito, Emiko; Matsumoto, Hirotaka; Kaku, Sawako; Shimada, Masatoshi; Hirabayashi, Masataka

    2017-01-01

    In this study, we aimed to examine the clinical value of the pleural effusion (PE) biomarkers, soluble mesothelin-related peptide (SMRP), cytokeratin 19 fragment (CYFRA 21–1) and carcinoembryonic antigen (CEA), and the utility of combining chest computed tomography (CT) findings with these biomarkers, in diagnosing malignant pleural mesothelioma (MPM). We conducted a retrospective cohort study in a single center. Consecutive patients with undiagnosed pleural effusions who underwent PE analysis between September 2014 and August 2016 were reviewed. This study included 240 patients (32 with MPM and 208 non-MPM). SMRP and the CYFRA 21-1/CEA ratio had a sensitivity and specificity for diagnosing MPM of 56.3% and 86.5%, and 87.5% and 74.0%, respectively. Using receiver operating characteristics (ROC) curve analysis of the ability of these markers to distinguish MPM from all other PE causes, the area under the ROC curve (AUC) for SMRP and the CYFRA 21-1/CEA ratio was 0.804 and 0.874, respectively. The sensitivity and specificity of SMRP combined with the CYFRA 21-1/CEA ratio were 93.8% and 64.9%, respectively. The sensitivity of the combination of SMRP, the CYFRA 21-1/CEA ratio, and the presence of Leung’s criteria (a chest CT finding that is suggestive of malignant pleural disease) was 93.8%. In conclusion, the combined PE biomarkers had a high sensitivity for diagnosing MPM, although the addition of chest CT findings did not improve the sensitivity of SMRP combined with the CYFRA 21-1/CEA ratio. Combination of these biomarkers helped to rule out MPM effectively among patients at high risk of suffering MPM and would be valuable especially for old frail patients who have difficulty in undergoing invasive procedures such as thoracoscopy. PMID:28968445

  13. Diagnostic performance of an automated analysis software for the diagnosis of Alzheimer’s dementia with 18F FDG PET

    PubMed Central

    Partovi, Sasan; Yuh, Roger; Pirozzi, Sara; Lu, Ziang; Couturier, Spencer; Grosse, Ulrich; Schluchter, Mark D; Nelson, Aaron; Jones, Robert; O’Donnell, James K; Faulhaber, Peter

    2017-01-01

    The objective of this study was to assess the ability of a quantitative software-aided approach to improve the diagnostic accuracy of 18F FDG PET for Alzheimer’s dementia over visual analysis alone. Twenty normal subjects (M:F-12:8; mean age 80.6 years) and twenty mild AD subjects (M:F-12:8; mean age 70.6 years) with 18F FDG PET scans were obtained from the ADNI database. Three blinded readers interpreted these PET images first using a visual qualitative approach and then using a quantitative software-aided approach. Images were classified on two five-point scales based on normal/abnormal (1-definitely normal; 5-definitely abnormal) and presence of AD (1-definitely not AD; 5-definitely AD). Diagnostic sensitivity, specificity, and accuracy for both approaches were compared based on the aforementioned scales. The sensitivity, specificity, and accuracy for the normal vs. abnormal readings of all readers combined were higher when comparing the software-aided vs. visual approach (sensitivity 0.93 vs. 0.83 P = 0.0466; specificity 0.85 vs. 0.60 P = 0.0005; accuracy 0.89 vs. 0.72 P<0.0001). The specificity and accuracy for absence vs. presence of AD of all readers combined were higher when comparing the software-aided vs. visual approach (specificity 0.90 vs. 0.70 P = 0.0008; accuracy 0.81 vs. 0.72 P = 0.0356). Sensitivities of the software-aided and visual approaches did not differ significantly (0.72 vs. 0.73 P = 0.74). The quantitative software-aided approach appears to improve the performance of 18F FDG PET for the diagnosis of mild AD. It may be helpful for experienced 18F FDG PET readers analyzing challenging cases. PMID:28123864

  14. Improving Reasoning Skills in Secondary History Education by Working Memory Training

    ERIC Educational Resources Information Center

    Ariës, Roel Jacobus; Groot, Wim; van den Brink, Henriette Maassen

    2015-01-01

    Secondary school pupils underachieve in tests in which reasoning abilities are required. Brain-based training of working memory (WM) may improve reasoning abilities. In this study, we use a brain-based training programme based on historical content to enhance reasoning abilities in history courses. In the first experiment, a combined intervention…

  15. Differential Regulation of Cryptic Genetic Variation Shapes the Genetic Interactome Underlying Complex Traits.

    PubMed

    Yadav, Anupama; Dhole, Kaustubh; Sinha, Himanshu

    2016-12-01

    Cryptic genetic variation (CGV) refers to genetic variants whose effects are buffered in most conditions but manifest phenotypically upon specific genetic and environmental perturbations. Despite having a central role in adaptation, contribution of CGV to regulation of quantitative traits is unclear. Instead, a relatively simplistic architecture of additive genetic loci is known to regulate phenotypic variation in most traits. In this paper, we investigate the regulation of CGV and its implication on the genetic architecture of quantitative traits at a genome-wide level. We use a previously published dataset of biparental recombinant population of Saccharomyces cerevisiae phenotyped in 34 diverse environments to perform single locus, two-locus, and covariance mapping. We identify loci that have independent additive effects as well as those which regulate the phenotypic manifestation of other genetic variants (variance QTL). We find that whereas additive genetic variance is predominant, a higher order genetic interaction network regulates variation in certain environments. Despite containing pleiotropic loci, with effects across environments, these genetic networks are highly environment specific. CGV is buffered under most allelic combinations of these networks and perturbed only in rare combinations resulting in high phenotypic variance. The presence of such environment specific genetic networks is the underlying cause of abundant gene–environment interactions. We demonstrate that overlaying identified molecular networks on such genetic networks can identify potential candidate genes and underlying mechanisms regulating phenotypic variation. Such an integrated approach applied to human disease datasets has the potential to improve the ability to predict disease predisposition and identify specific therapeutic targets.

  16. Differential Regulation of Cryptic Genetic Variation Shapes the Genetic Interactome Underlying Complex Traits

    PubMed Central

    Yadav, Anupama; Dhole, Kaustubh

    2016-01-01

    Cryptic genetic variation (CGV) refers to genetic variants whose effects are buffered in most conditions but manifest phenotypically upon specific genetic and environmental perturbations. Despite having a central role in adaptation, contribution of CGV to regulation of quantitative traits is unclear. Instead, a relatively simplistic architecture of additive genetic loci is known to regulate phenotypic variation in most traits. In this paper, we investigate the regulation of CGV and its implication on the genetic architecture of quantitative traits at a genome-wide level. We use a previously published dataset of biparental recombinant population of Saccharomyces cerevisiae phenotyped in 34 diverse environments to perform single locus, two-locus, and covariance mapping. We identify loci that have independent additive effects as well as those which regulate the phenotypic manifestation of other genetic variants (variance QTL). We find that whereas additive genetic variance is predominant, a higher order genetic interaction network regulates variation in certain environments. Despite containing pleiotropic loci, with effects across environments, these genetic networks are highly environment specific. CGV is buffered under most allelic combinations of these networks and perturbed only in rare combinations resulting in high phenotypic variance. The presence of such environment specific genetic networks is the underlying cause of abundant gene–environment interactions. We demonstrate that overlaying identified molecular networks on such genetic networks can identify potential candidate genes and underlying mechanisms regulating phenotypic variation. Such an integrated approach applied to human disease datasets has the potential to improve the ability to predict disease predisposition and identify specific therapeutic targets. PMID:28172852

  17. A Combined Experimental and Computational Approach to Subject-Specific Analysis of Knee Joint Laxity

    PubMed Central

    Harris, Michael D.; Cyr, Adam J.; Ali, Azhar A.; Fitzpatrick, Clare K.; Rullkoetter, Paul J.; Maletsky, Lorin P.; Shelburne, Kevin B.

    2016-01-01

    Modeling complex knee biomechanics is a continual challenge, which has resulted in many models of varying levels of quality, complexity, and validation. Beyond modeling healthy knees, accurately mimicking pathologic knee mechanics, such as after cruciate rupture or meniscectomy, is difficult. Experimental tests of knee laxity can provide important information about ligament engagement and overall contributions to knee stability for development of subject-specific models to accurately simulate knee motion and loading. Our objective was to provide combined experimental tests and finite-element (FE) models of natural knee laxity that are subject-specific, have one-to-one experiment to model calibration, simulate ligament engagement in agreement with literature, and are adaptable for a variety of biomechanical investigations (e.g., cartilage contact, ligament strain, in vivo kinematics). Calibration involved perturbing ligament stiffness, initial ligament strain, and attachment location until model-predicted kinematics and ligament engagement matched experimental reports. Errors between model-predicted and experimental kinematics averaged <2 deg during varus–valgus (VV) rotations, <6 deg during internal–external (IE) rotations, and <3 mm of translation during anterior–posterior (AP) displacements. Engagement of the individual ligaments agreed with literature descriptions. These results demonstrate the ability of our constraint models to be customized for multiple individuals and simultaneously call attention to the need to verify that ligament engagement is in good general agreement with literature. To facilitate further investigations of subject-specific or population based knee joint biomechanics, data collected during the experimental and modeling phases of this study are available for download by the research community. PMID:27306137

  18. Developing combination immunotherapies for type 1 diabetes: recommendations from the ITN–JDRF Type 1 Diabetes Combination Therapy Assessment Group

    PubMed Central

    Matthews, J B; Staeva, T P; Bernstein, P L; Peakman, M; von Herrath, M

    2010-01-01

    Like many other complex human disorders of unknown aetiology, autoimmune-mediated type 1 diabetes may ultimately be controlled via a therapeutic approach that combines multiple agents, each with differing modes of action. The numerous advantages of such a strategy include the ability to minimize toxicities and realize synergies to enhance and prolong efficacy. The recognition that combinations might offer far-reaching benefits, at a time when few single agents have yet proved themselves in well-powered trials, represents a significant challenge to our ability to conceive and implement rational treatment designs. As a first step in this process, the Immune Tolerance Network, in collaboration with the Juvenile Diabetes Research Foundation, convened a Type 1 Diabetes Combination Therapy Assessment Group, the recommendations of which are discussed in this Perspective paper. PMID:20629979

  19. Multiplexed detection of anthrax-related toxin genes.

    PubMed

    Moser, Michael J; Christensen, Deanna R; Norwood, David; Prudent, James R

    2006-02-01

    Simultaneous analysis of three targets in three colors on any real-time polymerase chain reaction (PCR) instrument would increase the flexibility of real-time PCR. For the detection of Bacillus strains that can cause inhalation anthrax-related illness, this ability would be valuable because two plasmids confer virulence, and internal positive controls are needed to monitor the testing in cases lacking target-specific signals. Using a real-time PCR platform called MultiCode-RTx, multiple assays were developed that specifically monitor the presence of Bacillus anthracis-specific virulence plasmid-associated genes. In particular for use on LightCycler-1, two triplex RTx systems demonstrated high sensitivity with limits of detection nearing single-copy levels for both plasmids. Specificity was established using a combination of Ct values and correct amplicon melting temperatures. All reactions were further verified by detection of an internal positive control. For these two triplex RTx assays, the analytical detection limit was one to nine plasmid copy equivalents, 100% analytical specificity with a 95% confidence interval (CI) of 9%, and 100% analytical sensitivity with a CI of 2%. Although further testing using clinical or environmental samples will be required to assess diagnostic sensitivity and specificity, the RTx platform achieves similar results to those of probe-based real-time systems.

  20. The Effect of Salts in Promoting Specific and Competitive Interactions between Zinc Finger Proteins and Metals

    NASA Astrophysics Data System (ADS)

    Li, Gongyu; Yuan, Siming; Zheng, Shihui; Chen, Yuting; Zheng, Zhen; Liu, Yangzhong; Huang, Guangming

    2017-12-01

    Specific protein-metal interactions (PMIs) fulfill essential functions in cells and organic bodies, and activation of these functions in vivo are mostly modulated by the complex environmental factors, including pH value, small biomolecules, and salts. Specifically, the role of salts in promoting specific PMIs and their competition among various metals has remained untapped mainly due to the difficulty to distinguish nonspecific PMIs from specific PMIs by classic spectroscopic techniques. Herein, we report Hofmeister salts differentially promote the specific PMIs by combining nanoelectrospray ionization mass spectrometry and spectroscopic techniques (fluorescence measurement and circular dichroism). Furthermore, to explore the influence of salts in competitive binding between metalloproteins and various metals, we designed a series of competitive experiments and applied to a well-defined model system, the competitive binding of zinc (II) and arsenic (III) to holo-promyelocytic leukemia protein (PML). These experiments not only provided new insights at the molecular scale as complementary to previous NMR and spectroscopic results, but also deduced the relative binding ability between zinc finger proteins and metals at the molecular scale, which avoids the mass spectrometric titration-based determination of binding constants that is frequently affected and often degraded by variable solution conditions including salt contents. [Figure not available: see fulltext.

  1. [Shaping ability of two nickel-titanium rotary systems in simulated S-shaped canals].

    PubMed

    Luo, Hong-xia; Huang, Ding-ming; Zhang, Fu-hua; Tan, Hong; Zhou, Xue-dong

    2008-01-01

    To evaluate the shaping ability of two nickel-titanium rotary systems (ProTaper and Hero642) in simulated S-shaped canals. Thirty simulated S-shaped canals were randomly divided into three groups and prepared by ProTaper, Hero642, ProTaper combined with Hero642 respectively. All the canals were scanned before and after instrumentation, and the amount of material removed in the inner and outer wall and the canal width after instrumentation were measured with a computer image analysis program. There was significant difference in the amount of material removed at the inner side of apical curvature and outer side of apex between ProTaper combined with Hero642 and ProTaper files (P < 0.05) at the same tip size. The inner and outer wall of the canals were evenly prepared by ProTaper combined with Hero642, and the taper of canals were better than those prepared by Hero642. ProTaper combined with Hero 642 had better shaping ability to maintain the original shape and could create good taper canals in the simulated S-shaped canal model.

  2. Diagnostic performance of multi-organ ultrasound with pocket-sized device in the management of acute dyspnea.

    PubMed

    Sforza, Alfonso; Mancusi, Costantino; Carlino, Maria Viviana; Buonauro, Agostino; Barozzi, Marco; Romano, Giuseppe; Serra, Sossio; de Simone, Giovanni

    2017-06-19

    The availability of ultra-miniaturized pocket ultrasound devices (PUD) adds diagnostic power to the clinical examination. Information on accuracy of ultrasound with handheld units in immediate differential diagnosis in emergency department (ED) is poor. The aim of this study is to test the usefulness and accuracy of lung ultrasound (LUS) alone or combined with ultrasound of the heart and inferior vena cava (IVC) using a PUD for the differential diagnosis of acute dyspnea (AD). We included 68 patients presenting to the ED of "Maurizio Bufalini" Hospital in Cesena (Italy) for AD. All patients underwent integrated ultrasound examination (IUE) of lung-heart-IVC, using PUD. The series was divided into patients with dyspnea of cardiac or non-cardiac origin. We used 2 × 2 contingency tables to analyze sensitivity, specificity, positive predictive value and negative predictive value of the three ultrasonic methods and their various combinations for the diagnosis of cardiogenic dyspnea (CD), comparing with the final diagnosis made by an independent emergency physician. LUS alone exhibited a good sensitivity (92.6%) and specificity (80.5%). The highest accuracy (90%) for the diagnosis of CD was obtained with the combination of LUS and one of the other two methods (heart or IVC). The IUE with PUD is a useful extension of the clinical examination, can be readily available at the bedside or in ambulance, requires few minutes and has a reliable diagnostic discriminant ability in the setting of AD.

  3. Cooperativity of HIV-Specific Cytolytic CD4 T Cells and CD8 T Cells in Control of HIV Viremia

    PubMed Central

    Johnson, Susan; Eller, Michael; Teigler, Jeffrey E.; Maloveste, Sebastien M.; Schultz, Bruce T.; Soghoian, Damien Z.; Lu, Richard; Oster, Alexander F.; Chenine, Agnès-Laurence; Alter, Galit; Dittmer, Ulf; Marovich, Mary; Robb, Merlin L.; Michael, Nelson L.; Bolton, Diane

    2015-01-01

    ABSTRACT CD4+ T cells play a pivotal role in the control of chronic viral infections. Recently, nontraditional CD4+ T cell functions beyond helper effects have been described, and a role for cytolytic CD4+ T cells in the control of HIV infection has been suggested. We define here the transcriptional, phenotypic, and functional profiles of HIV-specific cytolytic CD4+ T cells. Fluidigm BioMark and multiparameter flow cytometric analysis of HIV-specific cytolytic CD4+ T cells revealed a distinct transcriptional signature compared to Th1 CD4+ cells but shared similar features with HIV-specific cytolytic CD8+ T cells. Furthermore, HIV-specific cytolytic CD4+ T cells showed comparable killing activity relative to HIV-specific CD8+ T cells and worked cooperatively in the elimination of virally infected cells. Interestingly, we found that cytolytic CD4+ T cells emerge early during acute HIV infection and tightly follow acute viral load trajectory. This emergence was associated to the early viral set point, suggesting an involvement in early control, in spite of CD4 T cell susceptibility to HIV infection. Our data suggest cytolytic CD4+ T cells as an independent subset distinct from Th1 cells that show combined activity with CD8+ T cells in the long-term control of HIV infection. IMPORTANCE The ability of the immune system to control chronic HIV infection is of critical interest to both vaccine design and therapeutic approaches. Much research has focused on the effect of the ability of CD8+ T cells to control the virus, while CD4+ T cells have been overlooked as effectors in HIV control due to the fact that they are preferentially infected. We show here that a subset of HIV-specific CD4+ T cells cooperate in the cytolytic control of HIV replication. Moreover, these cells represent a distinct subset of CD4+ T cells showing significant transcriptional and phenotypic differences compared to HIV-specific Th1 cells but with similarities to CD8+ T cells. These findings are important for our understanding of HIV immunopathology. PMID:25972560

  4. Comprehensive Cross-Clade Characterization of Antibody-Mediated Recognition, Complement-Mediated Lysis, and Cell-Mediated Cytotoxicity of HIV-1 Envelope-Specific Antibodies toward Eradication of the HIV-1 Reservoir.

    PubMed

    Mujib, Shariq; Liu, Jun; Rahman, A K M Nur-Ur; Schwartz, Jordan A; Bonner, Phil; Yue, Feng Yun; Ostrowski, Mario A

    2017-08-15

    Immunotherapy with passive administration of broadly neutralizing HIV-1 envelope-specific antibodies (bnAbs) in the setting of established infection in vivo has yielded mixed results. The contribution of different antibodies toward the direct elimination of infected cells is poorly understood. In this study, we determined the ability of 12 well-characterized anti-HIV-1 neutralizing antibodies to recognize and eliminate primary CD4 T cells infected with HIV-1 belonging to clades A, B, C, and D, via antibody-dependent complement-mediated lysis (ADCML) and antibody-dependent cell-mediated cytotoxicity (ADCC), in vitro We further tested unique combinations of these antibodies to determine the optimal antibody cocktails to be tested in future clinical trials. We report that antibody binding to infected CD4 T cells is highly variable and correlates with ADCML and ADCC processes. Particularly, antibodies targeting the envelope glycan shield (2G12) and V1/V2 site (PG9, PG16, and PGT145) are best at recognizing HIV-1-infected CD4 T cells. However, only PG9 and PG16 and their combinations with other bnAbs sufficiently induced the elimination of HIV-1-infected CD4 T cells by ADCML, ADCC, or both. Notably, CD4 binding site antibodies VRC01, 3BNC117, and NIH45-46 G54W did not exhibit recognition of infected cells and were unable to induce their killing. Future trials geared toward the development of a cure for HIV/AIDS should incorporate V1/V2 antibodies for maximal clearance of infected cells. With the use of only primary immune cells, we conducted a comprehensive cross-clade physiological analysis to aid the direction of antibodies as therapeutics toward the development of a cure for HIV/AIDS. IMPORTANCE Several antibodies capable of neutralizing the majority of circulating HIV-1 strains have been identified to date and have been shown to prevent infection in animal models. However, the use of combinations of such broadly neutralizing antibodies (bnAbs) for the treatment and eradication of HIV-1 in infected humans remains uncertain. In this study, we tested the ability of bnAbs to directly recognize and eliminate primary human CD4 T cells infected with diverse HIV-1 strains representative of the global epidemic by antibody-dependent pathways. We also tested several combinations of bnAbs in our assays in order to maximize the clearance of infected cells. We show that the ability of bnAbs to identify and kill infected cells is highly variable and that only a few of them are able to exert this function. Our data will help guide the formulation of bnAbs to test in future human trials aimed at the development of a cure. Copyright © 2017 American Society for Microbiology.

  5. Differential Effect of Plant Lipids on Membrane Organization

    PubMed Central

    Grosjean, Kevin; Mongrand, Sébastien; Beney, Laurent; Simon-Plas, Françoise; Gerbeau-Pissot, Patricia

    2015-01-01

    The high diversity of the plant lipid mixture raises the question of their respective involvement in the definition of membrane organization. This is particularly the case for plant plasma membrane, which is enriched in specific lipids, such as free and conjugated forms of phytosterols and typical phytosphingolipids, such as glycosylinositolphosphoceramides. This question was here addressed extensively by characterizing the order level of membrane from vesicles prepared using various plant lipid mixtures and labeled with an environment-sensitive probe. Fluorescence spectroscopy experiments showed that among major phytosterols, campesterol exhibits a stronger ability than β-sitosterol and stigmasterol to order model membranes. Multispectral confocal microscopy, allowing spatial analysis of membrane organization, demonstrated accordingly the strong ability of campesterol to promote ordered domain formation and to organize their spatial distribution at the membrane surface. Conjugated sterol forms, alone and in synergy with free sterols, exhibit a striking ability to order membrane. Plant sphingolipids, particularly glycosylinositolphosphoceramides, enhanced the sterol-induced ordering effect, emphasizing the formation and increasing the size of sterol-dependent ordered domains. Altogether, our results support a differential involvement of free and conjugated phytosterols in the formation of ordered domains and suggest that the diversity of plant lipids, allowing various local combinations of lipid species, could be a major contributor to membrane organization in particular through the formation of sphingolipid-sterol interacting domains. PMID:25575593

  6. Engineering anatomically shaped vascularized bone grafts with hASCs and 3D-printed PCL scaffolds.

    PubMed

    Temple, Joshua P; Hutton, Daphne L; Hung, Ben P; Huri, Pinar Yilgor; Cook, Colin A; Kondragunta, Renu; Jia, Xiaofeng; Grayson, Warren L

    2014-12-01

    The treatment of large craniomaxillofacial bone defects is clinically challenging due to the limited availability of transplantable autologous bone grafts and the complex geometry of the bones. The ability to regenerate new bone tissues that faithfully replicate the anatomy would revolutionize treatment options. Advances in the field of bone tissue engineering over the past few decades offer promising new treatment alternatives using biocompatible scaffold materials and autologous cells. This approach combined with recent advances in three-dimensional (3D) printing technologies may soon allow the generation of large, bioartificial bone grafts with custom, patient-specific architecture. In this study, we use a custom-built 3D printer to develop anatomically shaped polycaprolactone (PCL) scaffolds with varying internal porosities. These scaffolds are assessed for their ability to support induction of human adipose-derived stem cells (hASCs) to form vasculature and bone, two essential components of functional bone tissue. The development of functional tissues is assessed in vitro and in vivo. Finally, we demonstrate the ability to print large mandibular and maxillary bone scaffolds that replicate fine details extracted from patient's computed tomography scans. The findings of this study illustrate the capabilities and potential of 3D printed scaffolds to be used for engineering autologous, anatomically shaped, vascularized bone grafts. © 2014 Wiley Periodicals, Inc.

  7. General and Specific Effects on Cattell-Horn-Carroll Broad Ability Composites: Analysis of the Woodcock-Johnson III Normative Update Cattell-Horn-Carroll Factor Clusters across Development

    ERIC Educational Resources Information Center

    Floyd, Randy G.; McGrew, Kevin S.; Barry, Amberly; Rafael, Fawziya; Rogers, Joshua

    2009-01-01

    Many school psychologists focus their interpretation on composite scores from intelligence test batteries designed to measure the broad abilities from the Cattell-Horn-Carroll theory. The purpose of this study was to investigate the general factor loadings and specificity of the broad ability composite scores from one such intelligence test…

  8. Phonological deficits in specific language impairment and developmental dyslexia: towards a multidimensional model

    PubMed Central

    Ramus, Franck; Marshall, Chloe R.; Rosen, Stuart

    2013-01-01

    An on-going debate surrounds the relationship between specific language impairment and developmental dyslexia, in particular with respect to their phonological abilities. Are these distinct disorders? To what extent do they overlap? Which cognitive and linguistic profiles correspond to specific language impairment, dyslexia and comorbid cases? At least three different models have been proposed: the severity model, the additional deficit model and the component model. We address this issue by comparing children with specific language impairment only, those with dyslexia-only, those with specific language impairment and dyslexia and those with no impairment, using a broad test battery of language skills. We find that specific language impairment and dyslexia do not always co-occur, and that some children with specific language impairment do not have a phonological deficit. Using factor analysis, we find that language abilities across the four groups of children have at least three independent sources of variance: one for non-phonological language skills and two for distinct sets of phonological abilities (which we term phonological skills versus phonological representations). Furthermore, children with specific language impairment and dyslexia show partly distinct profiles of phonological deficit along these two dimensions. We conclude that a multiple-component model of language abilities best explains the relationship between specific language impairment and dyslexia and the different profiles of impairment that are observed. PMID:23413264

  9. Contrasting physiological responses to excess heat and irradiance in two tropical savanna sedges

    PubMed Central

    John-Bejai, C.; Farrell, A. D.; Cooper, F. M.; Oatham, M. P.

    2013-01-01

    Tropical hyperseasonal savannas provide a rare example of a tropical climax community dominated by graminoid species. Species living in such savannas are frequently exposed to excess heat and light, in addition to drought and waterlogging, and must possess traits to avoid or tolerate these stress factors. Here we examine the contrasting heat and light stress adaptations of two dominant savanna sedges: Lagenocarpus guianensis, which is restricted to the sheltered forest edge, and Lagenocarpus rigidus, which extends from the forest edge to the open savanna. An ecotone extending from the forest edge to the open savanna was used to assess differences in a range of physiological traits (efficiency of photosystem II, cell membrane thermostability, stomatal conductance, leaf surface reflectance and canopy temperature depression) and a range of leaf functional traits (length : width ratio, specific leaf area and degree of folding). Lagenocarpus guianensis showed significantly less canopy temperature depression than L. rigidus, which may explain why this species was restricted to the forest edge. The range of leaf temperatures measured was within the thermal tolerance of L. guianensis and allowed photosystem II to function normally, at least within the cool forest edge. The ability of L. rigidus to extend into the open savanna was associated with an ability to decouple leaf temperature from ambient temperature combined with enhanced cell membrane thermostability. The high degree of canopy temperature depression seen in L. rigidus was not explained by enhanced stomatal conductance or leaf reflectance, but was consistent with a capacity to increase specific leaf area and reduce leaf length: width ratio in the open savanna. Plasticity in leaf functional traits and in cell membrane thermostability are key factors in the ability of this savanna sedge to survive abiotic stress. PMID:24379971

  10. Predictive ability and efficacy for shortening door-to-balloon time of a new prehospital electrocardiogram-transmission flow chart in patients with ST-elevation myocardial infarction - Results of the CASSIOPEIA study.

    PubMed

    Sakai, Toshiaki; Nishiyama, Osamu; Onodera, Masayuki; Matsuda, Shigekatsu; Wakisawa, Shinobu; Nakamura, Motoyuki; Morino, Yoshihiro; Itoh, Tomonori

    2018-05-24

    The purposes of this study were to create a new flow-chart of prehospital electrocardiography (ECG)-transmission, evaluate its predictive ability for ST-elevation myocardial infarction (STEMI) and shorten door-to-balloon time (DTBT). The new transmission flow-chart was created using symptoms from previous medical records of STEMI patients. A total of 4090 consecutive patients transferred emergently to our hospital were divided into two groups: those in ambulances with an ECG-transmission device with the new flow-chart (ECGT-FC) and those transferred without an ECG-transmission device (non-ECGT) groups. A STEMI group comprising walk-in patients during the same period was used as a control group. The predictive ability of STEMI and the effectiveness of shortening the DTBT by the new flow-chart of ECG-transmission was evaluated. In the ECGT-FC group, the prevalence of STEMI in the ECG-transmission by the new flow-chart were significantly higher than in the non-ECG-transmission patients (6.71% vs. 0.19%; p<0.001). The sensitivity and specificity of the new ECG-transmission flow-chart were 83.3% and 88.1%, respectively. The median DTBT was significantly shortened (p=0.045) and the prevalence of DTBT<90min was significantly higher in the ECGT-FC group (p=0.018) than the other groups. The sensitivity and specificity of the new flow-chart for ECG-transmission were high. The new flow-chart combined with an ECG-transmission device could detect STEMI efficiently and shorten DTBT. Copyright © 2018 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  11. Cognitive ability, academic achievement and academic self-concept: extending the internal/external frame of reference model.

    PubMed

    Chen, Ssu-Kuang; Hwang, Fang-Ming; Yeh, Yu-Chen; Lin, Sunny S J

    2012-06-01

    Marsh's internal/external (I/E) frame of reference model depicts the relationship between achievement and self-concept in specific academic domains. Few efforts have been made to examine concurrent relationships among cognitive ability, achievement, and academic self-concept (ASC) within an I/E model framework. To simultaneously examine the influences of domain-specific cognitive ability and grades on domain self-concept in an extended I/E model, including the indirect effect of domain-specific cognitive ability on domain self-concept via grades. Tenth grade respondents (628 male, 452 female) to a national adolescent survey conducted in Taiwan. Respondents completed surveys designed to measure maths and verbal aptitudes. Data on Maths and Chinese class grades and self-concepts were also collected. Statistically significant and positive path coefficients were found between cognitive ability and self-concept in the same domain (direct effect) and between these two constructs via grades (indirect effect). The cross-domain effects of either ability or grades on ASC were negatively significant. Taiwanese 10th graders tend to evaluate their ASCs based on a mix of ability and achievement, with achievement as a mediator exceeding ability as a predictor. In addition, the cross-domain effects suggest that Taiwanese students are likely to view Maths and verbal abilities and achievements as distinctly different. ©2011 The British Psychological Society.

  12. Heuristics and biases: interactions among numeracy, ability, and reflectiveness predict normative responding

    PubMed Central

    Klaczynski, Paul A.

    2014-01-01

    In Stanovich's (2009a, 2011) dual-process theory, analytic processing occurs in the algorithmic and reflective minds. Thinking dispositions, indexes of reflective mind functioning, are believed to regulate operations at the algorithmic level, indexed by general cognitive ability. General limitations at the algorithmic level impose constraints on, and affect the adequacy of, specific strategies and abilities (e.g., numeracy). In a study of 216 undergraduates, the hypothesis that thinking dispositions and general ability moderate the relationship between numeracy (understanding of mathematical concepts and attention to numerical information) and normative responses on probabilistic heuristics and biases (HB) problems was tested. Although all three individual difference measures predicted normative responses, the numeracy-normative response association depended on thinking dispositions and general ability. Specifically, numeracy directly affected normative responding only at relatively high levels of thinking dispositions and general ability. At low levels of thinking dispositions, neither general ability nor numeric skills related to normative responses. Discussion focuses on the consistency of these findings with the hypothesis that the implementation of specific skills is constrained by limitations at both the reflective level and the algorithmic level, methodological limitations that prohibit definitive conclusions, and alternative explanations. PMID:25071639

  13. Cognitive predictors and age-based adverse impact among business executives.

    PubMed

    Klein, Rachael M; Dilchert, Stephan; Ones, Deniz S; Dages, Kelly D

    2015-09-01

    Age differences on measures of general mental ability and specific cognitive abilities were examined in 2 samples of job applicants to executive positions as well as a mix of executive/nonexecutive positions to determine which predictors might lead to age-based adverse impact in making selection and advancement decisions. Generalizability of the pattern of findings was also investigated in 2 samples from the general adult population. Age was negatively related to general mental ability, with older executives scoring lower than younger executives. For specific ability components, the direction and magnitude of age differences depended on the specific ability in question. Older executives scored higher on verbal ability, a measure most often associated with crystallized intelligence. This finding generalized across samples examined in this study. Also, consistent with findings that fluid abilities decline with age, older executives scored somewhat lower on figural reasoning than younger executives, and much lower on a letter series test of inductive reasoning. Other measures of inductive reasoning, such as Raven's Advanced Progressive Matrices, also showed similar age group mean differences across settings. Implications for employee selection and adverse impact on older job candidates are discussed. (c) 2015 APA, all rights reserved).

  14. Heuristics and biases: interactions among numeracy, ability, and reflectiveness predict normative responding.

    PubMed

    Klaczynski, Paul A

    2014-01-01

    In Stanovich's (2009a, 2011) dual-process theory, analytic processing occurs in the algorithmic and reflective minds. Thinking dispositions, indexes of reflective mind functioning, are believed to regulate operations at the algorithmic level, indexed by general cognitive ability. General limitations at the algorithmic level impose constraints on, and affect the adequacy of, specific strategies and abilities (e.g., numeracy). In a study of 216 undergraduates, the hypothesis that thinking dispositions and general ability moderate the relationship between numeracy (understanding of mathematical concepts and attention to numerical information) and normative responses on probabilistic heuristics and biases (HB) problems was tested. Although all three individual difference measures predicted normative responses, the numeracy-normative response association depended on thinking dispositions and general ability. Specifically, numeracy directly affected normative responding only at relatively high levels of thinking dispositions and general ability. At low levels of thinking dispositions, neither general ability nor numeric skills related to normative responses. Discussion focuses on the consistency of these findings with the hypothesis that the implementation of specific skills is constrained by limitations at both the reflective level and the algorithmic level, methodological limitations that prohibit definitive conclusions, and alternative explanations.

  15. The combining of multiple hemispheric resources in learning-disabled and skilled readers' recall of words: a test of three information-processing models.

    PubMed

    Swanson, H L

    1987-01-01

    Three theoretical models (additive, independence, maximum rule) that characterize and predict the influence of independent hemispheric resources on learning-disabled and skilled readers' simultaneous processing were tested. Predictions related to word recall performance during simultaneous encoding conditions (dichotic listening task) were made from unilateral (dichotic listening task) presentations. The maximum rule model best characterized both ability groups in that simultaneous encoding produced no better recall than unilateral presentations. While the results support the hypothesis that both ability groups use similar processes in the combining of hemispheric resources (i.e., weak/dominant processing), ability group differences do occur in the coordination of such resources.

  16. MnTnBuOE-2-PyP protects normal colorectal fibroblasts from radiation damage and simultaneously enhances radio/chemotherapeutic killing of colorectal cancer cells

    PubMed Central

    Kosmacek, Elizabeth A.; Chatterjee, Arpita; Tong, Qiang; Lin, Chi; Oberley, Rebecca E.

    2016-01-01

    Manganese porphyrins have been shown to be potent radioprotectors in a variety of cancer models. However, the mechanism as to how these porphyrins protect normal tissues from radiation damage still remains largely unknown. In the current study, we determine the effects of the manganese porphyrin, MnTnBuOE-2-PyP, on primary colorectal fibroblasts exposed to irradiation. We found that 2 Gy of radiation enhances the fibroblasts' ability to contract a collagen matrix, increases cell size and promotes cellular senesence. Treating fibroblasts with MnTnBuOE-2-PyP significantly inhibited radiation-induced collagen contraction, preserved cell morphology and also inhibited cellular senescence. We further showed that MnTnBuOE-2-PyP enhanced the overall viability of the fibroblasts following exposure to radiation but did not protect colorectal cancer cell viability. Specifically, MnTnBuOE-2-PyP in combination with irradiation, caused a significant decrease in tumor clonogenicity. Since locally advanced rectal cancers are treated with chemoradiation therapy followed by surgery and non-metastatic anal cancers are treated with chemoradiation therapy, we also investigated the effects of MnTnBuOE-2-PyP in combination with radiation, 5-fluorouracil with and without Mitomycin C. We found that MnTnBuOE-2-PyP in combination with Mitomycin C or 5-fluorouracil further enhances those compounds' ability to suppress tumor cell growth. When MnTnBuOE-2-PyP was combined with the two chemotherapeutics and radiation, we observed the greatest reduction in tumor cell growth. Therefore, these studies indicate that MnTnBuOE-2-PyP could be used as a potent radioprotector for normal tissue, while at the same time enhancing radiation and chemotherapy treatment for rectal and anal cancers. PMID:27119354

  17. MnTnBuOE-2-PyP protects normal colorectal fibroblasts from radiation damage and simultaneously enhances radio/chemotherapeutic killing of colorectal cancer cells.

    PubMed

    Kosmacek, Elizabeth A; Chatterjee, Arpita; Tong, Qiang; Lin, Chi; Oberley-Deegan, Rebecca E

    2016-06-07

    Manganese porphyrins have been shown to be potent radioprotectors in a variety of cancer models. However, the mechanism as to how these porphyrins protect normal tissues from radiation damage still remains largely unknown. In the current study, we determine the effects of the manganese porphyrin, MnTnBuOE-2-PyP, on primary colorectal fibroblasts exposed to irradiation. We found that 2 Gy of radiation enhances the fibroblasts' ability to contract a collagen matrix, increases cell size and promotes cellular senesence. Treating fibroblasts with MnTnBuOE-2-PyP significantly inhibited radiation-induced collagen contraction, preserved cell morphology and also inhibited cellular senescence. We further showed that MnTnBuOE-2-PyP enhanced the overall viability of the fibroblasts following exposure to radiation but did not protect colorectal cancer cell viability. Specifically, MnTnBuOE-2-PyP in combination with irradiation, caused a significant decrease in tumor clonogenicity. Since locally advanced rectal cancers are treated with chemoradiation therapy followed by surgery and non-metastatic anal cancers are treated with chemoradiation therapy, we also investigated the effects of MnTnBuOE-2-PyP in combination with radiation, 5-fluorouracil with and without Mitomycin C. We found that MnTnBuOE-2-PyP in combination with Mitomycin C or 5-fluorouracil further enhances those compounds' ability to suppress tumor cell growth. When MnTnBuOE-2-PyP was combined with the two chemotherapeutics and radiation, we observed the greatest reduction in tumor cell growth. Therefore, these studies indicate that MnTnBuOE-2-PyP could be used as a potent radioprotector for normal tissue, while at the same time enhancing radiation and chemotherapy treatment for rectal and anal cancers.

  18. Five year magnetic tape for unattended satellite tape recorders

    NASA Technical Reports Server (NTRS)

    Benn, G. S. L.; Gutfreund, K.

    1972-01-01

    The development and fabrication of a quantity of long life magnetic tape with properties selected specifically for unattended operation in spacecraft tape recorders was studied. A detailed analytical consideration of various binder systems was undertaken. This included the chemical aspects of the binders, cohesion and adhesion effects, stability and the mechanical and physical properties. The ability to form free films of these polymers and their combination with various oxide loadings and other additives allowed a rapid selection of four polymer candidates for a five year magnetic tape. Samples were evaluated under actual running conditions which included physical, magnetic, and extensive life testing. These sample tapes withstood 50,000 bidirectional tape passes under fairly harsh operating conditions.

  19. Lévy walks

    NASA Astrophysics Data System (ADS)

    Zaburdaev, V.; Denisov, S.; Klafter, J.

    2015-04-01

    Random walk is a fundamental concept with applications ranging from quantum physics to econometrics. Remarkably, one specific model of random walks appears to be ubiquitous across many fields as a tool to analyze transport phenomena in which the dispersal process is faster than dictated by Brownian diffusion. The Lévy-walk model combines two key features, the ability to generate anomalously fast diffusion and a finite velocity of a random walker. Recent results in optics, Hamiltonian chaos, cold atom dynamics, biophysics, and behavioral science demonstrate that this particular type of random walk provides significant insight into complex transport phenomena. This review gives a self-consistent introduction to Lévy walks, surveys their existing applications, including latest advances, and outlines further perspectives.

  20. SWI enhances vein detection using gadolinium in multiple sclerosis

    PubMed Central

    Mazzoni, Lorenzo N; Moretti, Marco; Grammatico, Matteo; Chiti, Stefano; Massacesi, Luca

    2015-01-01

    Susceptibility weighted imaging (SWI) combined with the FLAIR sequence provides the ability to depict in vivo the perivenous location of inflammatory demyelinating lesions – one of the most specific pathologic features of multiple sclerosis (MS). In addition, in MS white matter (WM) lesions, gadolinium-based contrast media (CM) can increase vein signal loss on SWI. This report focuses on two cases of WM inflammatory lesions enhancing on SWI images after CM injection. In these lesions in fact the CM increased the contrast between the parenchyma and the central vein allowing as well, in one of the two cases, the detection of a vein not visible on the same SWI sequence acquired before CM injection. PMID:25815209

  1. Microinterferometric optical phase tomography for measuring small, asymmetric refractive-index differences in the profiles of optical fibers and fiber devices.

    PubMed

    Bachim, Brent L; Gaylord, Thomas K

    2005-01-20

    A new technique, microinterferometric optical phase tomography, is introduced for use in measuring small, asymmetric refractive-index differences in the profiles of optical fibers and fiber devices. The method combines microscopy-based fringe-field interferometry with parallel projection-based computed tomography to characterize fiber index profiles. The theory relating interference measurements to the projection set required for tomographic reconstruction is given, and discrete numerical simulations are presented for three test index profiles that establish the technique's ability to characterize fiber with small, asymmetric index differences. An experimental measurement configuration and specific interferometry and tomography practices employed in the technique are discussed.

  2. The Project TALENT Twin and Sibling Study.

    PubMed

    Prescott, Carol A; Achorn, Deanna Lyter; Kaiser, Ashley; Mitchell, Lindsey; McArdle, John J; Lapham, Susan J

    2013-02-01

    Project TALENT is a US national longitudinal study of about 377,000 individuals born in 1942-1946, first assessed in 1960. Students in about 1,200 schools participated in a 2-day battery covering aptitudes, abilities, interests, and individual and family characteristics (Flanagan, 1962; www.projectTALENT.org). Follow-up assessments 1, 5, and 11 years later assessed educational and occupational outcomes. The sample includes approximately 92,000 siblings from 40,000 families, including 2,500 twin pairs and 1,200 other siblings of twins. Until recently, almost no behavior genetic research has been conducted with the sample. In the original data collection information was not collected with the intent to link family members. Recently, we developed algorithms using names, addresses, birthdates, and information about family structure to link siblings and identify twins. We are testing several methods to determine zygosity, including use of yearbook photographs. In this paper, we summarize the design and measures in Project TALENT, describe the Twin and Sibling sample, and present our twin-sib-classmate model. In most twin and family designs, the 'shared environment' includes factors specific to the family combined with between-family differences associated with macro-level variables such as socioeconomic status. The school-based sampling design used in Project TALENT provides a unique opportunity to partition the shared environment into variation shared by siblings, specific to twins, and associated with school- and community-level factors. The availability of many measured characteristics on the family, schools, and neighborhoods enhances the ability to study the impact of specific factors on behavioral variation.

  3. Xylem vulnerability to cavitation in Pseudotsuga menziesii and Pinus ponderosa from contrasting habitats.

    PubMed

    Stout, Deborah H; Sala, Anna

    2003-01-01

    In the Rocky Mountains, ponderosa pine (Pinus ponderosa (ssp.) ponderosa Dougl. ex P. Laws. & C. Laws) often co-occurs with Douglas-fir (Pseudotsuga menziesii var. glauca (Mayr) Franco). Despite previous reports showing higher shoot vulnerability to water-stress-induced cavitation in ponderosa pine, this species extends into drier habitats than Douglas-fir. We examined: (1) whether roots and shoots of ponderosa pine in riparian and slope habitats are more vulnerable to water-stress-induced cavitation than those of Douglas-fir; (2) whether species-specific differences in vulnerability translate into differences in specific conductivity in the field; and (3) whether the ability of ponderosa pine to extend into drier sites is a result of (a) greater plasticity in hydraulic properties or (b) functional or structural adjustments. Roots and shoots of ponderosa pine were significantly more vulnerable to water-stress-induced cavitation (overall mean cavitation pressure, Psi(50%) +/- SE = -3.11 +/- 0.32 MPa for shoots and -0.99 +/- 0.16 MPa for roots) than those of Douglas-fir (Psi(50%) +/- SE = -4.83 +/- 0.40 MPa for shoots and -2.12 +/- 0.35 MPa for roots). However, shoot specific conductivity did not differ between species in the field. For both species, roots were more vulnerable to cavitation than shoots. Overall, changes in vulnerability from riparian to slope habitats were small for both species. Greater declines in stomatal conductance as the summer proceeded, combined with higher allocation to sapwood and greater sapwood water storage, appeared to contribute to the ability of ponderosa pine to thrive in dry habitats despite relatively high vulnerability to water-stress-induced cavitation.

  4. Identification of limited English proficient patients in clinical care.

    PubMed

    Karliner, Leah S; Napoles-Springer, Anna M; Schillinger, Dean; Bibbins-Domingo, Kirsten; Pérez-Stable, Eliseo J

    2008-10-01

    Standardized means to identify patients likely to benefit from language assistance are needed. To evaluate the accuracy of the U.S. Census English proficiency question (Census-LEP) in predicting patients' ability to communicate effectively in English. We investigated the sensitivity and specificity of the Census-LEP alone or in combination with a question on preferred language for medical care for predicting patient-reported ability to discuss symptoms and understand physician recommendations in English. Three hundred and two patients > 18 who spoke Spanish and/or English recruited from a cardiology clinic and an inpatient general medical-surgical ward in 2004-2005. One hundred ninety-eight (66%) participants reported speaking English less than "very well" and 166 (55%) less than "well"; 157 (52%) preferred receiving their medical care in Spanish. Overall, 135 (45%) were able to discuss symptoms and 143 (48%) to understand physician recommendations in English. The Census-LEP with a high-threshold (less than "very well") had the highest sensitivity for predicting effective communication (100% Discuss; 98.7% Understand), but the lowest specificity (72.6% Discuss; 67.1% Understand). The composite measure of Census-LEP and preferred language for medical care provided a significant increase in specificity (91.9% Discuss; 83.9% Understand), with only a marginal decrease in sensitivity (99.4% Discuss; 96.7% Understand). Using the Census-LEP item with a high-threshold of less than "very well" as a screening question, followed by a language preference for medical care question, is recommended for inclusive and accurate identification of patients likely to benefit from language assistance.

  5. Self Views of African American Youth are Related to the Gender Stereotypes and Academic Attributions of Their Mothers.

    PubMed

    Rowley, Stephanie; Kurtz-Costes, Beth; Rouland, Karmen

    2013-01-01

    We examined relations among African American mothers' ( N = 392) stereotypes about gender differences in mathematics, science, and reading performance, parents' attributions about their children's academic successes and failures, and their seventh and eighth grade children's academic self-views (domain-specific ability attributions and self-concept). Parents' stereotypes about gender differences in abilities were related to their ability attributions for their children's successes and failures within academic domains. Mothers' attributions, in turn, were related to children's attributions, particularly among girls. Mothers' attributions of their children's successes to domain-specific ability were related to the self-concepts of daughters, and failure attributions were related to domain-specific self-concepts of sons. The influences of parents' beliefs on young adolescents' identity beliefs are discussed.

  6. A Longitudinal Field Study Comparing a Multiplicative and an Additive Model of Motivation and Ability. Technical Report No. 11.

    ERIC Educational Resources Information Center

    Barrett, Gerald V.; And Others

    The relative contribution of motivation to ability measures in predicting performance criteria of sales personnel from successive fiscal periods was investigated. In this context, the merits of a multiplicative and additive combination of motivation and ability measures were examined. The relationship between satisfaction and motivation and…

  7. Memory Abilities in Children with Mathematical Difficulties: Comorbid Language Difficulties Matter

    ERIC Educational Resources Information Center

    Reimann, Giselle; Gut, Janine; Frischknecht, Marie-Claire; Grob, Alexander

    2013-01-01

    The present study investigated cognitive abilities in children with difficulties in mathematics only (n = 48, M = 8 years and 5 months), combined mathematical and language difficulty (n = 27, M = 8 years and 1 month) and controls (n = 783, M = 7 years and 11 months). Cognitive abilities were measured with seven subtests, tapping visual perception,…

  8. Developmental Change in the Influence of Domain-General Abilities and Domain-Specific Knowledge on Mathematics Achievement: An Eight-Year Longitudinal Study

    ERIC Educational Resources Information Center

    Geary, David C.; Nicholas, Alan; Li, Yaoran; Sun, Jianguo

    2017-01-01

    The contributions of domain-general abilities and domain-specific knowledge to subsequent mathematics achievement were longitudinally assessed (n = 167) through 8th grade. First grade intelligence and working memory and prior grade reading achievement indexed domain-general effects, and domain-specific effects were indexed by prior grade…

  9. Antibiofilm Activity and Synergistic Inhibition of Staphylococcus aureus Biofilms by Bactericidal Protein P128 in Combination with Antibiotics

    PubMed Central

    Nair, Sandhya; Desai, Srividya; Poonacha, Nethravathi; Vipra, Aradhana

    2016-01-01

    P128 is an antistaphylococcal protein, comprising a cell wall-degrading enzymatic region and a Staphylococcus-specific binding region, which possesses specific and potent bactericidal activity against sensitive and drug-resistant strains of Staphylococcus aureus. To explore P128's ability to kill S. aureus in a range of environments relevant to clinical infection, we investigated the anti-S. aureus activity of P128 alone and in combination with standard-of-care antibiotics on planktonic and biofilm-embedded cells. P128 was found to have potent antibiofilm activity on preformed S. aureus biofilms as detected by CFU reduction and a colorimetric minimum biofilm inhibitory concentration (MBIC) assay. Scanning electron microscopic images of biofilms formed on the surfaces of microtiter plates and on catheters showed that P128 at low concentrations could destroy the biofilm structure and lyse the cells. When it was tested in combination with antibiotics which are known to be poor inhibitors of S. aureus in biofilms, such as vancomycin, gentamicin, ciprofloxacin, linezolid, and daptomycin, P128 showed highly synergistic antibiofilm activity that resulted in much reduced MBIC values for P128 and the individual antibiotics. The synergistic effect was seen for both sensitive and resistant isolates of S. aureus. Additionally, in an in vitro mixed-biofilm model mimicking the wound infection environment, P128 was able to prevent biofilm formation by virtue of its anti-Staphylococcus activity. The potent S. aureus biofilm-inhibiting activity of P128 both alone and in combination with antibiotics is an encouraging sign for the development of P128 for treatment of complicated S. aureus infections involving biofilms. PMID:27671070

  10. Visual detection of multiple genetically modified organisms in a capillary array.

    PubMed

    Shao, Ning; Chen, Jianwei; Hu, Jiaying; Li, Rong; Zhang, Dabing; Guo, Shujuan; Hui, Junhou; Liu, Peng; Yang, Litao; Tao, Sheng-Ce

    2017-01-31

    There is an urgent need for rapid, low-cost multiplex methodologies for the monitoring of genetically modified organisms (GMOs). Here, we report a C[combining low line]apillary A[combining low line]rray-based L[combining low line]oop-mediated isothermal amplification for M[combining low line]ultiplex visual detection of nucleic acids (CALM) platform for the simple and rapid monitoring of GMOs. In CALM, loop-mediated isothermal amplification (LAMP) primer sets are pre-fixed to the inner surface of capillaries. The surface of the capillary array is hydrophobic while the capillaries are hydrophilic, enabling the simultaneous loading and separation of the LAMP reaction mixtures into each capillary by capillary forces. LAMP reactions in the capillaries are then performed in parallel, and the results are visually detected by illumination with a hand-held UV device. Using CALM, we successfully detected seven frequently used transgenic genes/elements and five plant endogenous reference genes with high specificity and sensitivity. Moreover, we found that measurements of real-world blind samples by CALM are consistent with results obtained by independent real-time PCRs. Thus, with an ability to detect multiple nucleic acids in a single easy-to-operate test, we believe that CALM will become a widely applied technology in GMO monitoring.

  11. Prefrontal-hippocampal-fusiform activity during encoding predicts intraindividual differences in free recall ability: an event-related functional-anatomic MRI study.

    PubMed

    Dickerson, B C; Miller, S L; Greve, D N; Dale, A M; Albert, M S; Schacter, D L; Sperling, R A

    2007-01-01

    The ability to spontaneously recall recently learned information is a fundamental mnemonic activity of daily life, but has received little study using functional neuroimaging. We developed a functional MRI (fMRI) paradigm to study regional brain activity during encoding that predicts free recall. In this event-related fMRI study, ten lists of fourteen pictures of common objects were shown to healthy young individuals and regional brain activity during encoding was analyzed based on subsequent free recall performance. Free recall of items was predicted by activity during encoding in hippocampal, fusiform, and inferior prefrontal cortical regions. Within-subject variance in free recall performance for the ten lists was predicted by a linear combination of condition-specific inferior prefrontal, hippocampal, and fusiform activity. Recall performance was better for lists in which prefrontal activity was greater for all items of the list and hippocampal and fusiform activity were greater specifically for items that were recalled from the list. Thus, the activity of medial temporal, fusiform, and prefrontal brain regions during the learning of new information is important for the subsequent free recall of this information. These fronto-temporal brain regions act together as a large-scale memory-related network, the components of which make distinct yet interacting contributions during encoding that predict subsequent successful free recall performance.

  12. Diallel analysis of corn for special use as corn grits: determining the main genetic effects for corn gritting ability.

    PubMed

    Conrado, T V; Scapim, C A; Bignotto, L S; Pinto, R J B; Freitas, I L J; Amaral, A T; Pinheiro, A C

    2014-08-26

    Corn grits are used for various purposes such as flakes, snacks, livestock feed, hominy, extruded products, beer, etc. The grit size proportion varies according to the hybrid, and thus, once the use of the grits is linked to the particle size, determining the genetic effects is essential to develop hybrids for any specific use. For this purpose a complete diallel series of crosses, involving eight parents, was performed near Maringá, PR, Brazil. The objective of this study was to evaluate the general (GCA) and specific (SCA) combining abilities of 28 progeny for selection of hybrids for breeding programs and extraction of inbred lines for hybrid development. The response variables, such as plant height, ear insertion height, crop stand, grain yield, and grits, small grits and bran production, were gauged and appraised for each of the 28 progeny. The trait effects and GCA were significant for all response variables, while for SCA, only grain yield and crop stand showed significance (P < 0.05), according to Griffing (1955) analysis. A significant weak negative partial correlation was found between grain yield and grits conversion. In relation to the hybrid selection for breeding programs, the parent IAC Nelore was highly recommended for recurrent selection and the hybrids IPR 119 x HT 392 and IAC Nelore x HD 332 for the extraction of pure lines for hybrid development.

  13. Prefrontal-Hippocampal-Fusiform Activity During Encoding Predicts Intraindividual Differences in Free Recall Ability: An Event-Related Functional-Anatomic MRI Study

    PubMed Central

    Dickerson, B.C.; Miller, S.L.; Greve, D.N.; Dale, A.M.; Albert, M.S.; Schacter, D.L.; Sperling, R.A.

    2009-01-01

    The ability to spontaneously recall recently learned information is a fundamental mnemonic activity of daily life, but has received little study using functional neuroimaging. We developed a functional MRI (fMRI) paradigm to study regional brain activity during encoding that predicts free recall. In this event-related fMRI study, ten lists of fourteen pictures of common objects were shown to healthy young individuals and regional brain activity during encoding was analyzed based on subsequent free recall performance. Free recall of items was predicted by activity during encoding in hippocampal, fusiform, and inferior prefrontal cortical regions. Within-subject variance in free recall performance for the ten lists was predicted by a linear combination of condition-specific inferior prefrontal, hippocampal, and fusiform activity. Recall performance was better for lists in which pre-frontal activity was greater for all items of the list and hippocampal and fusi-form activity were greater specifically for items that were recalled from the list. Thus, the activity of medial temporal, fusiform, and prefrontal brain regions during the learning of new information is important for the subsequent free recall of this information. These fronto-temporal brain regions act together as a large-scale memory-related network, the components of which make distinct yet interacting contributions during encoding that predict subsequent successful free recall performance. PMID:17604356

  14. Sequencing of oligosaccharides using enzyme array digestion with electrochemical and fluorescent detections

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

    Sun, M.; Lee, C.S.

    1997-12-31

    The objective of this study is to develop a rapid and sensitive method for oligosaccharide sequencing. The oligosaccharides are subjected to the enzyme array digestion with exoglycosidases of known and well-defined specificities. The enzyme array method involves the division of oligosaccharide sample into aliquots, and the incubation of each aliquot with a precisely defined mixture of exoglycosidases. In the enzyme array method, the presence of a specific linkage anywhere in the oligosaccharide is determined by the inability of an enzyme mixture lacking a given enzyme to cleave that linkage ( a stop point) and the ability of the other enzymesmore » to cleave the linkage up to that point. The direct quantification of released monosaccharides from the enzyme array can be achieved by using pulsed amperometric detection (PAD) or by fluorescent derivatization with a fluorophoric agent. The measured monosaccharide concentrations in combination with the enzyme array analysis provide detail characterization of oligosaccharides with their sugar composition, configuration, and linkage information, The released monosaccharides are further quantified by anion exchange chromatography and capillary electrophoresis for the comparison with the results obtained from PAD and fluorescence measurements. Our enzyme array-electrochemical (or fluorescent) detection method does not require any separation procedure and any prior labeling of oligosaccharide and have several practical advantages over the current carbohydrate sequencing techniques including simplicity, speed, and the ability to use small amounts of starting material.« less

  15. Distribution drivers and physiological responses in geothermal bryophyte communities.

    PubMed

    García, Estefanía Llaneza; Rosenstiel, Todd N; Graves, Camille; Shortlidge, Erin E; Eppley, Sarah M

    2016-04-01

    Our ability to explain community structure rests on our ability to define the importance of ecological niches, including realized ecological niches, in shaping communities, but few studies of plant distributions have combined predictive models with physiological measures. Using field surveys and statistical modeling, we predicted distribution drivers in geothermal bryophyte (moss) communities of Lassen Volcanic National Park (California, USA). In the laboratory, we used drying and rewetting experiments to test whether the strong species-specific effects of relative humidity on distributions predicted by the models were correlated with physiological characters. We found that the three most common bryophytes in geothermal communities were significantly affected by three distinct distribution drivers: temperature, light, and relative humidity. Aulacomnium palustre, whose distribution is significantly affected by relative humidity according to our model, and which occurs in high-humidity sites, showed extreme signs of stress after drying and never recovered optimal values of PSII efficiency after rewetting. Campylopus introflexus, whose distribution is not affected by humidity according to our model, was able to maintain optimal values of PSII efficiency for 48 hr at 50% water loss and recovered optimal values of PSII efficiency after rewetting. Our results suggest that species-specific environmental stressors tightly constrain the ecological niches of geothermal bryophytes. Tests of tolerance to drying in two bryophyte species corresponded with model predictions of the comparative importance of relative humidity as distribution drivers for these species. © 2016 Botanical Society of America.

  16. Spatial Abilities of High-School Students in the Perception of Geologic Structures.

    ERIC Educational Resources Information Center

    Kali, Yael; Orion, Nir

    1996-01-01

    Characterizes specific spatial abilities required in geology studies through the examination of the performance of high school students in solving structural geology problems on the geologic spatial ability test (GeoSAT). Concludes that visual penetration ability and the ability to perceive the spatial configuration of the structure are…

  17. A randomized controlled trial of an activity specific exercise program for individuals with Alzheimer disease in long-term care settings.

    PubMed

    Roach, Kathryn E; Tappen, Ruth M; Kirk-Sanchez, Neva; Williams, Christine L; Loewenstein, David

    2011-01-01

    To determine whether an activity specific exercise program could improve ability to perform basic mobility activities in long-term care residents with Alzheimer disease (AD). Randomized, controlled, single-blinded clinical trial. Residents of 7 long-term care facilities. Eighty-two long-term care residents with mild to severe AD. An activity specific exercise program was compared to a walking program and to an attention control. Ability to perform bed mobility and transfers was assessed using the subscales of the Acute Care Index of Function; functional mobility was measured using the 6-Minute Walk test. Subjects receiving the activity specific exercise program improved in ability to perform transfers, whereas subjects in the other 2 groups declined.

  18. Characterization of ginger essential oil/palygorskite composite (GEO-PGS) and its anti-bacteria activity.

    PubMed

    Lei, Hong; Wei, Qiaonian; Wang, Qing; Su, Anxiang; Xue, Mei; Liu, Qin; Hu, Qiuhui

    2017-04-01

    To explore a novel kind of anti-bacterial composite material having the excellent antibacterial ability, stability and specific-targeting capability, palygorskite (PGS) was used as the carrier of ginger essential oil (GEO) and a novel kind of composite GEO-PGS was prepared by ion exchange process. The characterization and the antibacterial activity of GEO-PGS was investigated in this study. Results of FTIR, XPS, XRD,TG analysis and SEM observation demonstrated the combination of GEO and PGS, GEO was absorbed on the surface of PGS, and the content of GEO in the composite was estimated to be 18.66%. Results of minimal inhibitory concentration (MIC) analysis, growth curve and Gram staining analysis of Staphylococci aureus and Escherichia coli exposed to GEO-PGS showed that GEO-PGS had much higher antibacterial activity than GEO, and GEO-PGS had the specific-targeting antibacterial capability. Moreover, GEO-PGS showed the characteristics of thermo-stability, acidity and alkalinity-resistance in exerting its anti-bacteria activity. In conclusion, the novel composite GEO-PGS combined the bacteria-absorbent activity of PGS and the antibacterial activity of GEO, suggesting the great potential application of GEO-PGS as the novel composite substance with high antibacterial activity. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Time-saving impact of an algorithm to identify potential surgical site infections.

    PubMed

    Knepper, B C; Young, H; Jenkins, T C; Price, C S

    2013-10-01

    To develop and validate a partially automated algorithm to identify surgical site infections (SSIs) using commonly available electronic data to reduce manual chart review. Retrospective cohort study of patients undergoing specific surgical procedures over a 4-year period from 2007 through 2010 (algorithm development cohort) or over a 3-month period from January 2011 through March 2011 (algorithm validation cohort). A single academic safety-net hospital in a major metropolitan area. Patients undergoing at least 1 included surgical procedure during the study period. Procedures were identified in the National Healthcare Safety Network; SSIs were identified by manual chart review. Commonly available electronic data, including microbiologic, laboratory, and administrative data, were identified via a clinical data warehouse. Algorithms using combinations of these electronic variables were constructed and assessed for their ability to identify SSIs and reduce chart review. The most efficient algorithm identified in the development cohort combined microbiologic data with postoperative procedure and diagnosis codes. This algorithm resulted in 100% sensitivity and 85% specificity. Time savings from the algorithm was almost 600 person-hours of chart review. The algorithm demonstrated similar sensitivity on application to the validation cohort. A partially automated algorithm to identify potential SSIs was highly sensitive and dramatically reduced the amount of manual chart review required of infection control personnel during SSI surveillance.

  20. Dual recognition unit strategy improves the specificity of the adenosine triphosphate (ATP) aptamer biosensor for cerebral ATP assay.

    PubMed

    Yu, Ping; He, Xiulan; Zhang, Li; Mao, Lanqun

    2015-01-20

    Adenosine triphosphate (ATP) aptamer has been widely used as a recognition unit for biosensor development; however, its relatively poor specificity toward ATP against adenosine-5'-diphosphate (ADP) and adenosine-5'-monophosphate (AMP) essentially limits the application of the biosensors in real systems, especially in the complex cerebral system. In this study, for the first time, we demonstrate a dual recognition unit strategy (DRUS) to construct a highly selective and sensitive ATP biosensor by combining the recognition ability of aptamer toward A nucleobase and of polyimidazolium toward phosphate. The biosensors are constructed by first confining the polyimidazolium onto a gold surface by surface-initiated atom transfer radical polymerization (SI-ATRP), and then the aptamer onto electrode surface by electrostatic self-assembly to form dual-recognition-unit-functionalized electrodes. The constructed biosensor based on DRUS not only shows an ultrahigh sensitivity toward ATP with a detection limit down to the subattomole level but also an ultrahigh selectivity toward ATP without interference from ADP and AMP. The constructed biosensor is used for selective and sensitive sensing of the extracellular ATP in the cerebral system by combining in vivo microdialysis and can be used as a promising neurotechnology to probing cerebral ATP concentration.

  1. The hidden ecological resource of andic soils in mountain ecosystems: evidence from Italy

    NASA Astrophysics Data System (ADS)

    Terribile, Fabio; Iamarino, Michela; Langella, Giuliano; Manna, Piero; Mileti, Florindo Antonio; Vingiani, Simona; Basile, Angelo

    2018-01-01

    Andic soils have unique morphological, physical, and chemical properties that induce both considerable soil fertility and great vulnerability to land degradation. Moreover, they are the most striking mineral soils in terms of large organic C storage and long C residence time. This is especially related to the presence of poorly crystalline clay minerals and metal-humus complexes. Recognition of andic soils is then very important.Here we attempt to show, through a combined analysis of 35 sampling points chosen in accordance to specific physical and vegetation rules, that some andic soils have an utmost ecological importance.More specifically, in Italian non-volcanic mountain ecosystems ( > 600 m a.s.l.) combining low slope (< 21 %) and highly active green biomass (high NDVI values) and in agreement to recent findings, we found the widespread occurrence of andic soils having distinctive physical and hydrological properties including low bulk density and remarkably high water retention. Most importantly, we report a demonstration of the ability of these soils to affect ecosystem functions by analysing their influence on the timescale acceleration of photosynthesis estimated by NDVI measurements.Our results are hoped to be a starting point for better understanding of the ecological importance of andic soils and also possibly to better consider pedological information in C balance calculations.

  2. DigiLens color sequential filtering for microdisplay-based projection applications

    NASA Astrophysics Data System (ADS)

    Sagan, Stephen F.; Smith, Ronald T.; Popovich, Milan M.

    2000-10-01

    Application Specific Integrated Filters (ASIFs), based on a unique holographic polymer dispersed liquid crystal (H-PDLC) material system offering high efficiency, fast switching and low power, are being developed for microdisplay based projection applications. A new photonics technology based H-PDLC materials combined with the ability to be electrically switched on and off offers a new approach to color sequential filtering of a white light source for microdisplay-based front and rear projection display applications. Switchable Bragg gratings created in the PDLC are fundamental building blocks. Combined with the well- defined spectral and angular characteristics of Bragg gratings, these selectable filters can provide a large color gamut and a dynamically adjustable white balance. These switchable Bragg gratings can be reflective or transmissive and in each case can be designed to operate in either additive or subtractive mode. The spectral characteristics of filters made from a stack of these Bragg gratings can be configured for a specific lamp spectrum to give high diffractive efficiency over the broad bandwidths required for an illumination system. When it is necessary to reduce the spectral bandwidth, it is possible to use the properties of reflection Bragg holograms to construct very narrow band high efficiency filters. The basic properties and key benefits of ASIFs in projection displays are reviewed.

  3. [Performance of cognitive brief test in elderly patients with dementia in advanced stage living in an urban community of Lima, Peru].

    PubMed

    Custodio, Nilton; Alva-Diaz, Carlos; Becerra-Becerra, Yahaira; Montesinos, Rosa; Lira, David; Herrera-Pérez, Eder; Castro-Suárez, Sheila; Cuenca-Alfaro, José; Valeriano-Lorenzo, Elizabeth

    2016-01-01

    Evaluate the performance of clock drawing test- Manos versión (PDR-M) and Mini Mental State Examination -Peruvian version (MMSE) to detect dementia in a sample based on urban community of Lima, Peru. This study is a secondary analysis database, observational, analytical and cross-sectional, the gold standard was the clinical and the neuropsychological evaluations together. Performance testing individually and in combination were evaluated.. Data were obtained from prevalence study conducted in 2008 in Cercado de Lima. MMSE performance for evaluation of patients with dementia of any kind showed sensitivity of 64,1%, specificity of 84,1%, PPV of 24.4%, NPV of 96.7%, PLR of 4,03 and NLR of 0,43. PDR-M showed sensitivity of 89,3%, specificity of 98,1%, PPV of 79.3%, NPV of 99.1%, PLR of 47,79 and NLR of 0,11. When both tests were applied, and at least one of them was positive, they showed sensitivity 98.1%, specificity 84.1%, PPV of 33.1%, NPV of 99.8%, PLR of 6,17 and NLR of 0,02. When performing separate analysis of Alzheimer-type dementia and non- Alzheimer dementia, the values of the parameters do not differ substantially from those obtained for dementia of any kind. The combination of MMSE and PDR-M show good discriminative ability to detect moderate and severe dementia in population living in urban community in Lima.

  4. Assessment of a multiple biomarker panel for diagnosis of amyotrophic lateral sclerosis.

    PubMed

    Chen, Xueping; Chen, Yongping; Wei, Qianqian; Ou, Ruwei; Cao, Bei; Zhao, Bi; Shang, Hui-Fang

    2016-09-15

    The aim of the study was to assess a panel of promising biomarkers for their ability to improve diagnosis of sporadic amyotrophic lateral sclerosis (ALS). Forty patients with sporadic ALS and 40 controls with other neurological diseases were evaluated. Levels of phosphorylated neurofilament heavy chain (pNfH), S100-β, cystatin C, and chitotriosidase (CHIT) in cerebrospinal fluid were assayed using two-site solid-phase sandwich ELISA. Patients with sporadic ALS showed higher levels of pNfH and CHIT than controls, but lower levels of cystatin C. Multivariate logistic regression that adjusted for patient age and sex identified significant associations between sporadic ALS and levels of pNfH, CHIT and cystatin C. Levels of pNfH correlated positively with rate of progression and decline based on the Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised. Based on receiver operating curve analysis, a pNfH cut-off of 437 ng/L discriminated patients from controls with a sensitivity of 97.3 % and specificity of 83.8 %. A CHIT cut-off of 1593.779 ng/L discriminated patients from controls with a sensitivity of 83.8 % and specificity of 81.1 %. Combining the two biomarkers gave a sensitivity of 83.8 % and specificity of 91.9 %. Levels of pNfH in cerebrospinal fluid may be a reliable biomarker for diagnosing ALS, and combining this biomarker with levels of CHIT may improve diagnostic accuracy.

  5. The effect of tinnitus specific intracochlear stimulation on speech perception in patients with unilateral or asymmetric hearing loss accompanied with tinnitus and the effect of formal auditory training.

    PubMed

    Arts, Remo A G J; George, Erwin L J; Janssen, Miranda A M L; Griessner, Andreas; Zierhofer, Clemens; Stokroos, Robert J

    2018-06-01

    Previous studies show that intracochlear electrical stimulation independent of environmental sounds appears to suppress tinnitus, even long-term. In order to assess the viability of this potential treatment option it is essential to study the effects of this tinnitus specific electrical stimulation on speech perception. A randomised, prospective crossover design. Ten patients with unilateral or asymmetric hearing loss and severe tinnitus complaints. The audiological effects of standard clinical CI, formal auditory training and tinnitus specific electrical stimulation were investigated. Results show that standard clinical CI in unilateral or asymmetric hearing loss is shown to be beneficial for speech perception in quiet, speech perception in noise and subjective hearing ability. Formal auditory training does not appear to improve speech perception performance. However, CI-related discomfort reduces significantly more rapidly during CI rehabilitation in subjects receiving formal auditory training. Furthermore, tinnitus specific electrical stimulation has neither positive nor negative effects on speech perception. In combination with the findings from previous studies on tinnitus suppression using intracochlear electrical stimulation independent of environmental sounds, the results of this study contribute to the viability of cochlear implantation based on tinnitus complaints.

  6. Searching whole genome sequences for biochemical identification features of emerging and reemerging pathogenic Corynebacterium species.

    PubMed

    Santos, André S; Ramos, Rommel T; Silva, Artur; Hirata, Raphael; Mattos-Guaraldi, Ana L; Meyer, Roberto; Azevedo, Vasco; Felicori, Liza; Pacheco, Luis G C

    2018-05-11

    Biochemical tests are traditionally used for bacterial identification at the species level in clinical microbiology laboratories. While biochemical profiles are generally efficient for the identification of the most important corynebacterial pathogen Corynebacterium diphtheriae, their ability to differentiate between biovars of this bacterium is still controversial. Besides, the unambiguous identification of emerging human pathogenic species of the genus Corynebacterium may be hampered by highly variable biochemical profiles commonly reported for these species, including Corynebacterium striatum, Corynebacterium amycolatum, Corynebacterium minutissimum, and Corynebacterium xerosis. In order to identify the genomic basis contributing for the biochemical variabilities observed in phenotypic identification methods of these bacteria, we combined a comprehensive literature review with a bioinformatics approach based on reconstruction of six specific biochemical reactions/pathways in 33 recently released whole genome sequences. We used data retrieved from curated databases (MetaCyc, PathoSystems Resource Integration Center (PATRIC), The SEED, TransportDB, UniProtKB) associated with homology searches by BLAST and profile Hidden Markov Models (HMMs) to detect enzymes participating in the various pathways and performed ab initio protein structure modeling and molecular docking to confirm specific results. We found a differential distribution among the various strains of genes that code for some important enzymes, such as beta-phosphoglucomutase and fructokinase, and also for individual components of carbohydrate transport systems, including the fructose-specific phosphoenolpyruvate-dependent sugar phosphotransferase (PTS) and the ribose-specific ATP-binging cassette (ABC) transporter. Horizontal gene transfer plays a role in the biochemical variability of the isolates, as some genes needed for sucrose fermentation were seen to be present in genomic islands. Noteworthy, using profile HMMs, we identified an enzyme with putative alpha-1,6-glycosidase activity only in some specific strains of C. diphtheriae and this may aid to understanding of the differential abilities to utilize glycogen and starch between the biovars.

  7. [Effects of Acupuncture Intervention Combined with Rehabilitation on Standing-balance-walking Ability in Stroke Patients].

    PubMed

    Chu, Jia-mei; Bao, Ye-hua; Zhu, Min

    2015-12-01

    To observe the influence of acupuncture stimulation of lateral side of Tianzhu (para-BL 10), electroacupuncture (EA) stimulation of scalp-point Balance Area (MS 14), Motor Area (MS 6) and body acupoints combined with rehabilitation training on standing-balance and walking ability in stroke patients. A total of 145 stroke inpatients were randomly assigned to rehabilitation group (n=48), routine acupuncture group (n=49) and para-BL10 group (n = 48). Patients of the rehabilitation group received balance training and routine rehabilitation training treatment, those of the routine acupuncture group received acupuncture stimulation of scalp-points (MS 14, MS 6), body acupoints, balance training and routine rehabilitation training,and those of the para-BL10 group received acupuncture stimulation of lateral side of BL 10 combined with scalp-points of MS 14 and MS 6 and body acupoints, and balance training and routine rehabilitation training. The treatment was conducted once daily, 5 times per week, 8 weeks altogether. The patients' balancing function, lower-limb motor function and walking ability were assessed using Berg Balance Scale (BBS), Sheikh Trunk Control Ability Scale(STCAS), Fugl-Meyer Assessment Scale (FMAS), and Holden Functional Ambulation Classification (FAC), respectively. After 4 and 8 weeks' treatment, the scores of BBS, STCAS, FMAS and FAC in patients of the rehabilitation, routine acupuncture and para-BL10 groups were significantly increased and 10 meters-walking time obviously reduced in comparison with pre-treatment in the same one group (P<0.01). The effects of acupuncture stimulation of para-BL 10 were considerably better than both rehabilitation and routine acupuncture groups in raising BBS, STCAS, FMAS and FAC scores and in reducing 10 m-walking time (P<0.05). Acupuncture stimulation of lateral side of BL 10 combined with scalp-points has a significant benefit for stroke patients in standing-balance ability and walking ability.

  8. A designed screening study with prespecified combinations of factor settings

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

    Anderson-cook, Christine M; Robinson, Timothy J

    2009-01-01

    In many applications, the experimenter has limited options about what factor combinations can be chosen for a designed study. Consider a screening study for a production process involving five input factors whose levels have been previously established. The goal of the study is to understand the effect of each factor on the response, a variable that is expensive to measure and results in destruction of the part. From an inventory of available parts with known factor values, we wish to identify a best collection of factor combinations with which to estimate the factor effects. Though the observational nature of themore » study cannot establish a causal relationship involving the response and the factors, the study can increase understanding of the underlying process. The study can also help determine where investment should be made to control input factors during production that will maximally influence the response. Because the factor combinations are observational, the chosen model matrix will be nonorthogonal and will not allow independent estimation of factor effects. In this manuscript we borrow principles from design of experiments to suggest an 'optimal' selection of factor combinations. Specifically, we consider precision of model parameter estimates, the issue of replication, and abilities to detect lack of fit and to estimate two-factor interactions. Through an example, we present strategies for selecting a subset of factor combinations that simultaneously balance multiple objectives, conduct a limited sensitivity analysis, and provide practical guidance for implementing our techniques across a variety of quality engineering disciplines.« less

  9. Specific detection of cultivable Helicobacter pylori cells from wastewater treatment plants.

    PubMed

    Moreno, Yolanda; Ferrús, M Antonía

    2012-10-01

    Helicobacter pylori is present in surface water and wastewater, and biofilms in drinking water systems have been reported as possible reservoirs of H. pylori. However, its ability to survive in an infectious state in the environment is hindered because it rapidly loses its cultivability. The aim of this study was to determine the presence of cultivable and therefore viable H. pylori in wastewater treatment plants to understand the role of wastewater in the pathogen's transmission. A modified filter technique was used to obtain a positive H. pylori culture, and specific detection of this pathogen was achieved with FISH and PCR techniques. A total of six positive H. pylori cultures were obtained from the water samples, and molecular techniques positively identified H. pylori in 21 culture-negative samples. The combination of a culturing procedure after sample filtration followed by the application of a molecular method, such as PCR or FISH, provides a specific tool for the detection, identification, and direct visualization of cultivable and therefore viable H. pylori cells from complex mixed communities such as water samples. © 2012 Blackwell Publishing Ltd.

  10. Prostate cancer prediction using the random forest algorithm that takes into account transrectal ultrasound findings, age, and serum levels of prostate-specific antigen.

    PubMed

    Xiao, Li-Hong; Chen, Pei-Ran; Gou, Zhong-Ping; Li, Yong-Zhong; Li, Mei; Xiang, Liang-Cheng; Feng, Ping

    2017-01-01

    The aim of this study is to evaluate the ability of the random forest algorithm that combines data on transrectal ultrasound findings, age, and serum levels of prostate-specific antigen to predict prostate carcinoma. Clinico-demographic data were analyzed for 941 patients with prostate diseases treated at our hospital, including age, serum prostate-specific antigen levels, transrectal ultrasound findings, and pathology diagnosis based on ultrasound-guided needle biopsy of the prostate. These data were compared between patients with and without prostate cancer using the Chi-square test, and then entered into the random forest model to predict diagnosis. Patients with and without prostate cancer differed significantly in age and serum prostate-specific antigen levels (P < 0.001), as well as in all transrectal ultrasound characteristics (P < 0.05) except uneven echo (P = 0.609). The random forest model based on age, prostate-specific antigen and ultrasound predicted prostate cancer with an accuracy of 83.10%, sensitivity of 65.64%, and specificity of 93.83%. Positive predictive value was 86.72%, and negative predictive value was 81.64%. By integrating age, prostate-specific antigen levels and transrectal ultrasound findings, the random forest algorithm shows better diagnostic performance for prostate cancer than either diagnostic indicator on its own. This algorithm may help improve diagnosis of the disease by identifying patients at high risk for biopsy.

  11. Socioeconomic Gradients Predict Individual Differences in Neurocognitive Abilities

    ERIC Educational Resources Information Center

    Noble, Kimberly G.; McCandliss, Bruce D.; Farah, Martha J.

    2007-01-01

    Socioeconomic status (SES) is associated with childhood cognitive achievement. In previous research we found that this association shows neural specificity; specifically we found that groups of low and middle SES children differed disproportionately in perisylvian/language and prefrontal/executive abilities relative to other neurocognitive…

  12. On the specificity of face cognition compared with general cognitive functioning across adult age.

    PubMed

    Hildebrandt, Andrea; Wilhelm, Oliver; Schmiedek, Florian; Herzmann, Grit; Sommer, Werner

    2011-09-01

    Face cognition is considered a specific human ability, clearly differentiable from general cognitive functioning. Its specificity is primarily supported by cognitive-experimental and neuroimaging research, but recently also from an individual differences perspective. However, no comprehensive behavioral data are available, which would allow estimating lifespan changes of the covariance structure of face-cognition abilities and general cognitive functioning as well as age-differences in face cognition after accounting for interindividual variability in general cognition. The present study aimed to fill this gap. In an age-heterogeneous (18-82 years) sample of 448 adults, we found no factorial dedifferentiation between face cognition and general cognition. Age-related differences in face memory were still salient after taking into account changes in general cognitive functioning. Face cognition thus remains a specific human ability compared with general cognition, even until old age. We discuss implications for models of cognitive aging and suggest that it is necessary to include more explicitly special social abilities in those models.

  13. Multimodal discrimination of immune cells using a combination of Raman spectroscopy and digital holographic microscopy

    NASA Astrophysics Data System (ADS)

    McReynolds, Naomi; Cooke, Fiona G. M.; Chen, Mingzhou; Powis, Simon J.; Dholakia, Kishan

    2017-03-01

    The ability to identify and characterise individual cells of the immune system under label-free conditions would be a significant advantage in biomedical and clinical studies where untouched and unmodified cells are required. We present a multi-modal system capable of simultaneously acquiring both single point Raman spectra and digital holographic images of single cells. We use this combined approach to identify and discriminate between immune cell populations CD4+ T cells, B cells and monocytes. We investigate several approaches to interpret the phase images including signal intensity histograms and texture analysis. Both modalities are independently able to discriminate between cell subsets and dual-modality may therefore be used a means for validation. We demonstrate here sensitivities achieved in the range of 86.8% to 100%, and specificities in the range of 85.4% to 100%. Additionally each modality provides information not available from the other providing both a molecular and a morphological signature of each cell.

  14. Stepwise molding, etching, and imprinting to form libraries of nanopatterned substrates.

    PubMed

    Zhao, Zhi; Cai, Yangjun; Liao, Wei-Ssu; Cremer, Paul S

    2013-06-04

    Herein, we describe a novel colloidal lithographic strategy for the stepwise patterning of planar substrates with numerous complex and unique designs. In conjunction with colloidal self-assembly, imprint molding, and capillary force lithography, reactive ion etching was used to create complex libraries of nanoscale features. This combinatorial strategy affords the ability to develop an exponentially increasing number of two-dimensional nanoscale patterns with each sequential step in the process. Specifically, dots, triangles, circles, and lines could be assembled on the surface separately and in combination with each other. Numerous architectures are obtained for the first time with high uniformity and reproducibility. These hexagonal arrays were made from polystyrene and gold features, whereby each surface element could be tuned from the micrometer size scale down to line widths of ~35 nm. The patterned area could be 1 cm(2) or even larger. The techniques described herein can be combined with further steps to make even larger libraries. Moreover, these polymer and metal features may prove useful in optical, sensing, and electronic applications.

  15. Validity of the Cambridge Cognitive Examination-Revised new Executive Function Scores in the diagnosis of dementia: some early findings.

    PubMed

    Heinik, Jeremia; Solomesh, Isaac

    2007-03-01

    The Cambridge Cognitive Examination-Revised introduces 2 new executive items (Ideational Fluency and Visual Reasoning), which separately or combined with 2 executive items in the former version (word list generation and similarities) might constitute an Executive Function Score (EFS). The authors studied the validity of these new EFSs in 51 demented (dementia of the Alzheimer's type, vascular dementia) and nondemented individuals (depressives and normals). The new EFSs were found valid to accurately differentiate between demented and nondemented subjects; however, they were considerably less so when specific diagnoses were considered. Correlations between the variously combined executive scores and the cognitive scales and subscales studied were prevalently low to moderate, and ranged from high and significant to low and nonsignificant when the 4 executive items were correlated to each other. The ability of the executive scores to discriminate demented from nondemented individuals was lower compared with the Cambridge Cognitive Examination-Revised scores. EFS was found internally consistent.

  16. Combining forecast weights: Why and how?

    NASA Astrophysics Data System (ADS)

    Yin, Yip Chee; Kok-Haur, Ng; Hock-Eam, Lim

    2012-09-01

    This paper proposes a procedure called forecast weight averaging which is a specific combination of forecast weights obtained from different methods of constructing forecast weights for the purpose of improving the accuracy of pseudo out of sample forecasting. It is found that under certain specified conditions, forecast weight averaging can lower the mean squared forecast error obtained from model averaging. In addition, we show that in a linear and homoskedastic environment, this superior predictive ability of forecast weight averaging holds true irrespective whether the coefficients are tested by t statistic or z statistic provided the significant level is within the 10% range. By theoretical proofs and simulation study, we have shown that model averaging like, variance model averaging, simple model averaging and standard error model averaging, each produces mean squared forecast error larger than that of forecast weight averaging. Finally, this result also holds true marginally when applied to business and economic empirical data sets, Gross Domestic Product (GDP growth rate), Consumer Price Index (CPI) and Average Lending Rate (ALR) of Malaysia.

  17. Simultaneous acquisition of trajectory and fluorescence lifetime of moving single particles

    NASA Astrophysics Data System (ADS)

    Wu, Qianqian; Qi, Jing; Lin, Danying; Yan, Wei; Hu, Rui; Peng, Xiao; Qu, Junle

    2017-02-01

    Fluorescence lifetime imaging (FLIM) has been a powerful tool in life science because it can reveal the interactions of an excited fluorescent molecule and its environment. The combination with two-photon excitation (TPE) and timecorrelated single photon counting (TCSPC) provides it the ability of optical sectioning, high time resolution and detection efficiency. In previous work, we have introduced a two-dimensional acousto-optic deflector (AOD) into TCSPC-based FLIM to achieve fast and flexible FLIM. In this work, we combined the AOD-FLIM system with a single particle tracking (SPT) setup and algorithm and developed an SPT-FLIM system. Using the system, we acquired the trajectory and fluorescence lifetime of a moving particle simultaneously and reconstructed a life-time-marked pseudocolored trajectory, which might reflect dynamic interaction between the moving particle and its local environment along its motion trail. The results indicated the potential of the technique for studying the interaction between specific moving biological macromolecules and the ambient micro-environment in live cells.

  18. Multisensory Integration and Internal Models for Sensing Gravity Effects in Primates

    PubMed Central

    Lacquaniti, Francesco; La Scaleia, Barbara; Maffei, Vincenzo

    2014-01-01

    Gravity is crucial for spatial perception, postural equilibrium, and movement generation. The vestibular apparatus is the main sensory system involved in monitoring gravity. Hair cells in the vestibular maculae respond to gravitoinertial forces, but they cannot distinguish between linear accelerations and changes of head orientation relative to gravity. The brain deals with this sensory ambiguity (which can cause some lethal airplane accidents) by combining several cues with the otolith signals: angular velocity signals provided by the semicircular canals, proprioceptive signals from muscles and tendons, visceral signals related to gravity, and visual signals. In particular, vision provides both static and dynamic signals about body orientation relative to the vertical, but it poorly discriminates arbitrary accelerations of moving objects. However, we are able to visually detect the specific acceleration of gravity since early infancy. This ability depends on the fact that gravity effects are stored in brain regions which integrate visual, vestibular, and neck proprioceptive signals and combine this information with an internal model of gravity effects. PMID:25061610

  19. Multisensory integration and internal models for sensing gravity effects in primates.

    PubMed

    Lacquaniti, Francesco; Bosco, Gianfranco; Gravano, Silvio; Indovina, Iole; La Scaleia, Barbara; Maffei, Vincenzo; Zago, Myrka

    2014-01-01

    Gravity is crucial for spatial perception, postural equilibrium, and movement generation. The vestibular apparatus is the main sensory system involved in monitoring gravity. Hair cells in the vestibular maculae respond to gravitoinertial forces, but they cannot distinguish between linear accelerations and changes of head orientation relative to gravity. The brain deals with this sensory ambiguity (which can cause some lethal airplane accidents) by combining several cues with the otolith signals: angular velocity signals provided by the semicircular canals, proprioceptive signals from muscles and tendons, visceral signals related to gravity, and visual signals. In particular, vision provides both static and dynamic signals about body orientation relative to the vertical, but it poorly discriminates arbitrary accelerations of moving objects. However, we are able to visually detect the specific acceleration of gravity since early infancy. This ability depends on the fact that gravity effects are stored in brain regions which integrate visual, vestibular, and neck proprioceptive signals and combine this information with an internal model of gravity effects.

  20. Nontraditional roles for certified pharmacy technicians in a pharmaceutical company.

    PubMed

    Fung, Stacey M; Gilmour, Christine; McCracken, David; Shane, Korban; Matsuura, Gary

    2006-01-01

    To describe nontraditional roles for Certified Pharmacy Technicians (CPhTs) within pharmaceutical industry. Drug information department within a large biotechnology/pharmaceutical organization. The Medical Communications department within Genentech uses a skills-mix staffing model in which employees with varying educational and training backgrounds work as a team on meeting the informational needs of consumers and health professionals who contact the company. One position within the department is that of Medical Communications Associate, responsible primarily for managing product inquiries. Medical Communications Associates have degrees in life sciences or an equivalent combination of education and experience, including a minimum of 2 years of related experience in the health care industry. Currently, four of the seven Medical Communications Associates in the department are CPhTs. Not applicable. Ability to recruit CPhTs for Medical Communications Associate positions, and job satisfaction of those hired into these positions. Critical basic skills needed for the Medical Communications Associate position include strong computer literacy, ability to multitask, and ability to work in an environment with frequent interruptions. Strong oral and written communications skills, customer service skills, ability to deal with stressful situations, product-specific knowledge, ability to work on a daily basis with Medical Communications Pharmacists, and knowledge of medical terminology are also important. The skills set of CPhTs matches these requirements, as evidenced by the experiences of the four staff members who have worked in the department for a total of 17 person-years. This nontraditional role for CPhTs can be rewarding and beneficial to all, affording an unique opportunity within the pharmaceutical industry. The skill set and experience of CPhTs can be used in the nontraditional pharmacy practice setting of drug information.

  1. Genotypes Associated with Listeria monocytogenes Isolates Displaying Impaired or Enhanced Tolerances to Cold, Salt, Acid, or Desiccation Stress

    PubMed Central

    Hingston, Patricia; Chen, Jessica; Dhillon, Bhavjinder K.; Laing, Chad; Bertelli, Claire; Gannon, Victor; Tasara, Taurai; Allen, Kevin; Brinkman, Fiona S. L.; Truelstrup Hansen, Lisbeth; Wang, Siyun

    2017-01-01

    The human pathogen Listeria monocytogenes is a large concern in the food industry where its continuous detection in food products has caused a string of recalls in North America and Europe. Most recognized for its ability to grow in foods during refrigerated storage, L. monocytogenes can also tolerate several other food-related stresses with some strains possessing higher levels of tolerances than others. The objective of this study was to use a combination of phenotypic analyses and whole genome sequencing to elucidate potential relationships between L. monocytogenes genotypes and food-related stress tolerance phenotypes. To accomplish this, 166 L. monocytogenes isolates were sequenced and evaluated for their ability to grow in cold (4°C), salt (6% NaCl, 25°C), and acid (pH 5, 25°C) stress conditions as well as survive desiccation (33% RH, 20°C). The results revealed that the stress tolerance of L. monocytogenes is associated with serotype, clonal complex (CC), full length inlA profiles, and the presence of a plasmid which was identified in 55% of isolates. Isolates with full length inlA exhibited significantly (p < 0.001) enhanced cold tolerance relative to those harboring a premature stop codon (PMSC) in this gene. Similarly, isolates possessing a plasmid demonstrated significantly (p = 0.013) enhanced acid tolerance. We also identified nine new L. monocytogenes sequence types, a new inlA PMSC, and several connections between CCs and the presence/absence or variations of specific genetic elements. A whole genome single-nucleotide-variants phylogeny revealed sporadic distribution of tolerant isolates and closely related sensitive and tolerant isolates, highlighting that minor genetic differences can influence the stress tolerance of L. monocytogenes. Specifically, a number of cold and desiccation sensitive isolates contained PMSCs in σB regulator genes (rsbS, rsbU, rsbV). Collectively, the results suggest that knowing the sequence type of an isolate in addition to screening for the presence of full-length inlA and a plasmid, could help food processors and food agency investigators determine why certain isolates might be persisting in a food processing environment. Additionally, increased sequencing of L. monocytogenes isolates in combination with stress tolerance profiling, will enhance the ability to identify genetic elements associated with higher risk strains. PMID:28337186

  2. Accuracy of biochemical markers for predicting nasogastric tube placement in adults--a systematic review of diagnostic studies.

    PubMed

    Fernandez, Ritin S; Chau, Janita Pak-Chun; Thompson, David R; Griffiths, Rhonda; Lo, Hoi-Shan

    2010-08-01

    The objective of this study was to investigate the diagnostic performance of biochemical tests used to determine placement of nasogastric (NG) tubes after insertion in adults. A systematic review of diagnostic studies was undertaken. A literature search of the bibliographic databases and the World Wide Web was performed to locate original diagnostic studies in English or Chinese on biochemical markers for detecting NG tube location. Studies in which one or more different tests were evaluated with a reference standard, and diagnostic values were reported or could be calculated were included. Two reviewers independently checked all abstracts and full text studies for inclusion criteria. Included studies were assessed for their quality using the QUADAS tool. Study features and diagnostic values were extracted from the included studies. Of the 10 studies included in this review, seven investigated the diagnostic accuracy of pH, one investigated the diagnostic accuracy of pH and bilirubin respectively, two a combination of pH and bilirubin and one a combination of pH, pepsin and trypsin levels in identifying NG tube location. All studies used X-rays as the reference standard for comparison. Pooled results demonstrated that a pH of

  3. Self Views of African American Youth are Related to the Gender Stereotypes and Academic Attributions of Their Mothers

    PubMed Central

    Rowley, Stephanie; Kurtz-Costes, Beth; Rouland, Karmen

    2012-01-01

    We examined relations among African American mothers’ (N = 392) stereotypes about gender differences in mathematics, science, and reading performance, parents’ attributions about their children’s academic successes and failures, and their seventh and eighth grade children’s academic self-views (domain-specific ability attributions and self-concept). Parents’ stereotypes about gender differences in abilities were related to their ability attributions for their children’s successes and failures within academic domains. Mothers’ attributions, in turn, were related to children’s attributions, particularly among girls. Mothers’ attributions of their children’s successes to domain-specific ability were related to the self-concepts of daughters, and failure attributions were related to domain-specific self-concepts of sons. The influences of parents’ beliefs on young adolescents’ identity beliefs are discussed. PMID:23878519

  4. Targeted delivery of CRISPR/Cas9 to prostate cancer by modified gRNA using a flexible aptamer-cationic liposome.

    PubMed

    Zhen, Shuai; Takahashi, Yoichiro; Narita, Shunichi; Yang, Yi-Chen; Li, Xu

    2017-02-07

    The potent ability of CRISPR/Cas9 system to inhibit the expression of targeted gene is being exploited as a new class of therapeutics for a variety of diseases. However, the efficient and safe delivery of CRISPR/Cas9 into specific cell populations is still the principal challenge in the clinical development of CRISPR/Cas9 therapeutics. In this study, a flexible aptamer-liposome-CRISPR/Cas9 chimera was designed to combine efficient delivery and increased flexibility. Our chimera incorporated an RNA aptamer that specifically binds prostate cancer cells expressing the prostate-specific membrane antigen as a ligand. Cationic liposomes were linked to aptamers by the post-insertion method and were used to deliver therapeutic CRISPR/Cas9 that target the survival gene, polo-like kinase 1, in tumor cells. We demonstrate that the aptamer-liposome-CRISPR/Cas9 chimeras had a significant cell-type binding specificity and a remarkable gene silencing effect in vitro. Furthermore, silencing promoted a conspicuous regression of prostate cancer in vivo. Importantly, the approach described here provides a universal means of cell type-specific CRISPR/Cas9 delivery, which is a critical goal for the widespread therapeutic applicability of CRISPR/Cas9 or other nucleic acid drugs.

  5. Targeted delivery of CRISPR/Cas9 to prostate cancer by modified gRNA using a flexible aptamer-cationic liposome

    PubMed Central

    Zhen, Shuai; Takahashi, Yoichiro; Narita, Shunichi; Yang, Yi-Chen; Li, Xu

    2017-01-01

    The potent ability of CRISPR/Cas9 system to inhibit the expression of targeted gene is being exploited as a new class of therapeutics for a variety of diseases. However, the efficient and safe delivery of CRISPR/Cas9 into specific cell populations is still the principal challenge in the clinical development of CRISPR/Cas9 therapeutics. In this study, a flexible aptamer-liposome-CRISPR/Cas9 chimera was designed to combine efficient delivery and increased flexibility. Our chimera incorporated an RNA aptamer that specifically binds prostate cancer cells expressing the prostate-specific membrane antigen as a ligand. Cationic liposomes were linked to aptamers by the post-insertion method and were used to deliver therapeutic CRISPR/Cas9 that target the survival gene, polo-like kinase 1, in tumor cells. We demonstrate that the aptamer-liposome-CRISPR/Cas9 chimeras had a significant cell-type binding specificity and a remarkable gene silencing effect in vitro. Furthermore, silencing promoted a conspicuous regression of prostate cancer in vivo. Importantly, the approach described here provides a universal means of cell type–specific CRISPR/Cas9 delivery, which is a critical goal for the widespread therapeutic applicability of CRISPR/Cas9 or other nucleic acid drugs. PMID:28030843

  6. 48 CFR 8.712 - Specification changes.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... the AbilityOne participating nonprofit agency and appropriate central nonprofit agency of any change in specifications or descriptions. In the absence of such written notification, the Ability... concerned at least 90 days prior to the date that any changes in the scope of work or other conditions will...

  7. 48 CFR 8.712 - Specification changes.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... the AbilityOne participating nonprofit agency and appropriate central nonprofit agency of any change in specifications or descriptions. In the absence of such written notification, the Ability... concerned at least 90 days prior to the date that any changes in the scope of work or other conditions will...

  8. 48 CFR 8.712 - Specification changes.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... the AbilityOne participating nonprofit agency and appropriate central nonprofit agency of any change in specifications or descriptions. In the absence of such written notification, the Ability... concerned at least 90 days prior to the date that any changes in the scope of work or other conditions will...

  9. A humanized monoclonal antibody neutralizes yellow fever virus strain 17D-204 in vitro but does not protect a mouse model from disease.

    PubMed

    Calvert, Amanda E; Dixon, Kandice L; Piper, Joseph; Bennett, Susan L; Thibodeaux, Brett A; Barrett, Alan D T; Roehrig, John T; Blair, Carol D

    2016-07-01

    The yellow fever virus (YFV) vaccine 17D-204 is considered safe and effective, yet rare severe adverse events (SAEs), some resulting in death, have been documented following vaccination. Individuals exhibiting post-vaccinal SAEs are ideal candidates for antiviral monoclonal antibody (MAb) therapy; the time until appearance of clinical signs post-exposure is usually short and patients are quickly hospitalized. We previously developed a murine-human chimeric monoclonal antibody (cMAb), 2C9-cIgG, reactive with both virulent YFV and 17D-204, and demonstrated its ability to prevent and treat YF disease in both AG129 mouse and hamster models of infection. To counteract possible selection of 17D-204 variants that escape neutralization by treatment with a single MAb (2C9-cIgG), we developed a second cMAb, 864-cIgG, for use in combination with 2C9-cIgG in post-vaccinal therapy. MAb 864-cIgG recognizes/neutralizes only YFV 17D-204 vaccine substrain and binds to domain III (DIII) of the viral envelope protein, which is different from the YFV type-specific binding site of 2C9-cIgG in DII. Although it neutralized 17D-204 in vitro, administration of 864-cIgG had no protective capacity in the interferon receptor-deficient AG129 mouse model of 17D-204 infection. The data presented here show that although DIII-specific 864-cIgG neutralizes virus infectivity in vitro, it does not have the ability to abrogate disease in vivo. Therefore, combination of 864-cIgG with 2C9-cIgG for treatment of YF vaccination SAEs does not appear to provide an improvement on 2C9-cIgG therapy alone. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. A humanized monoclonal antibody neutralizes yellow fever virus strain 17D-204 in vitro but does not protect a mouse model from disease

    PubMed Central

    Calvert, Amanda E.; Dixon, Kandice L.; Piper, Joseph; Bennett, Susan L.; Thibodeaux, Brett A.; Barrett, Alan D.T.; Roehrig, John T.; Blair, Carol D.

    2016-01-01

    The yellow fever virus (YFV) vaccine 17D-204 is considered safe and effective, yet rare severe adverse events (SAEs), some resulting in death, have been documented following vaccination. Individuals exhibiting post-vaccinal SAEs are ideal candidates for antiviral monoclonal antibody (MAb) therapy; the time until appearance of clinical signs post-exposure is usually short and patients are quickly hospitalized. We previously developed a murine-human chimeric monoclonal antibody (cMAb), 2C9-cIgG, reactive with both virulent YFV and 17D-204, and demonstrated its ability to prevent and treat YF disease in both AG129 mouse and hamster models of infection. To counteract possible selection of 17D-204 variants that escape neutralization by treatment with a single MAb (2C9-cIgG), we developed a second cMAb, 864-cIgG, for use in combination with 2C9-cIgG in post-vaccinal therapy. MAb 864-cIgG recognizes/neutralizes only YFV 17D-204 vaccine substrain and binds to domain III (DIII) of the viral envelope protein, which is different from the YFV type-specific binding site of 2C9-cIgG in DII. Although it neutralized 17D-204 in vitro, administration of 864-cIgG had no protective capacity in the interferon receptor-deficient AG129 mouse model of 17D-204 infection. The data presented here show that although DIII-specific 864-cIgG neutralizes virus infectivity in vitro, it does not have the ability to abrogate disease in vivo. Therefore, combination of 864-cIgG with 2C9-cIgG for treatment of YF vaccination SAEs does not appear to provide an improvement on 2C9-cIgG therapy alone. PMID:27126613

  11. Pilot clinical study for quantitative spectral diagnosis of non-melanoma skin cancer.

    PubMed

    Rajaram, Narasimhan; Reichenberg, Jason S; Migden, Michael R; Nguyen, Tri H; Tunnell, James W

    2010-12-01

    Several research groups have demonstrated the non-invasive diagnostic potential of diffuse optical spectroscopy (DOS) and laser-induced fluorescence (LIF) techniques for early cancer detection. By combining both modalities, one can simultaneously measure quantitative parameters related to the morphology, function and biochemical composition of tissue and use them to diagnose malignancy. The objective of this study was to use a quantitative reflectance/fluorescence spectroscopic technique to determine the optical properties of normal skin and non-melanoma skin cancers and the ability to accurately classify them. An additional goal was to determine the ability of the technique to differentiate non-melanoma skin cancers from normal skin. The study comprised 48 lesions measured from 40 patients scheduled for a biopsy of suspected non-melanoma skin cancers. White light reflectance and laser-induced fluorescence spectra (wavelength range = 350-700 nm) were collected from each suspected lesion and adjacent clinically normal skin using a custom-built, optical fiber-based clinical instrument. After measurement, the skin sites were biopsied and categorized according to histopathology. Using a quantitative model, we extracted various optical parameters from the measured spectra that could be correlated to the physiological state of tissue. Scattering from cancerous lesions was significantly lower than normal skin for every lesion group, whereas absorption parameters were significantly higher. Using numerical cut-offs for our optical parameters, our clinical instrument could classify basal cell carcinomas with a sensitivity and specificity of 94% and 89%, respectively. Similarly, the instrument classified actinic keratoses and squamous cell carcinomas with a sensitivity of 100% and specificity of 50%. The measured optical properties and fluorophore contributions of normal skin and non-melanoma skin cancers are significantly different from each other and correlate well with tissue pathology. A diagnostic algorithm that combines these extracted properties holds promise for the potential non-invasive diagnosis of skin cancer. Copyright © 2010 Wiley-Liss, Inc.

  12. Functional architecture of visual emotion recognition ability: A latent variable approach.

    PubMed

    Lewis, Gary J; Lefevre, Carmen E; Young, Andrew W

    2016-05-01

    Emotion recognition has been a focus of considerable attention for several decades. However, despite this interest, the underlying structure of individual differences in emotion recognition ability has been largely overlooked and thus is poorly understood. For example, limited knowledge exists concerning whether recognition ability for one emotion (e.g., disgust) generalizes to other emotions (e.g., anger, fear). Furthermore, it is unclear whether emotion recognition ability generalizes across modalities, such that those who are good at recognizing emotions from the face, for example, are also good at identifying emotions from nonfacial cues (such as cues conveyed via the body). The primary goal of the current set of studies was to address these questions through establishing the structure of individual differences in visual emotion recognition ability. In three independent samples (Study 1: n = 640; Study 2: n = 389; Study 3: n = 303), we observed that the ability to recognize visually presented emotions is based on different sources of variation: a supramodal emotion-general factor, supramodal emotion-specific factors, and face- and within-modality emotion-specific factors. In addition, we found evidence that general intelligence and alexithymia were associated with supramodal emotion recognition ability. Autism-like traits, empathic concern, and alexithymia were independently associated with face-specific emotion recognition ability. These results (a) provide a platform for further individual differences research on emotion recognition ability, (b) indicate that differentiating levels within the architecture of emotion recognition ability is of high importance, and (c) show that the capacity to understand expressions of emotion in others is linked to broader affective and cognitive processes. (c) 2016 APA, all rights reserved).

  13. Investigation of varying gray scale levels for remote manipulation

    NASA Technical Reports Server (NTRS)

    Bierschwale, John M.; Stuart, Mark A.; Sampaio, Carlos E.

    1991-01-01

    A study was conducted to investigate the effects of variant monitor gray scale levels and workplace illumination levels on operators' ability to discriminate between different colors on a monochrome monitor. It was determined that 8-gray scale viewing resulted in significantly worse discrimination performance compared to 16- and 32-gray scale viewing and that there was only a negligible difference found between 16 and 32 shades of gray. Therefore, it is recommended that monitors used while performing remote manipulation tasks have 16 or above shades of gray since this evaluation has found levels lower than this to be unacceptable for color discrimination task. There was no significant performance difference found between a high and a low workplace illumination condition. Further analysis was conducted to determine which specific combinations of colors can be used in conjunction with each other to ensure errorfree color coding/brightness discrimination performance while viewing a monochrome monitor. It was found that 92 three-color combination and 9 four-color combinations could be used with 100 percent accuracy. The results can help to determine which gray scale levels should be provided on monochrome monitors as well as which colors to use to ensure the maximal performance of remotely-viewed color discrimination/coding tasks.

  14. Advanced algorithms for radiographic material discrimination and inspection system design

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

    Gilbert, Andrew J.; McDonald, Benjamin S.; Deinert, Mark R.

    X-ray and neutron radiography are powerful tools for non-invasively inspecting the interior of objects. Materials can be discriminated by noting how the radiographic signal changes with variations in the input spectrum or inspection mode. However, current methods are limited in their ability to differentiate when multiple materials are present, especially within large and complex objects. With X-ray radiography, the inability to distinguish materials of a similar atomic number is especially problematic. To overcome these critical limitations, we augmented our existing inverse problem framework with two important expansions: 1) adapting the previous methodology for use with multi-modal radiography and energy-integrating detectors,more » and 2) applying the Cramer-Rao lower bound to select an optimal set of inspection modes for a given application a priori. Adding these expanded capabilities to our algorithmic framework with adaptive regularization, we observed improved discrimination between high-Z materials, specifically plutonium and tungsten. The combined system can estimate plutonium mass within our simulated system to within 1%. Three types of inspection modes were modeled: multi-endpoint X-ray radiography alone; in combination with neutron radiography using deuterium-deuterium (DD); or in combination with neutron radiography using deuterium-tritium (DT) sources.« less

  15. Chimeric antigen receptor–engineered T cells as oncolytic virus carriers

    PubMed Central

    VanSeggelen, Heather; Tantalo, Daniela GM; Afsahi, Arya; Hammill, Joanne A; Bramson, Jonathan L

    2015-01-01

    The use of engineered T cells in adoptive transfer therapies has shown significant promise in treating hematological cancers. However, successes treating solid tumors are much less prevalent. Oncolytic viruses (OVs) have the capacity to induce specific lysis of tumor cells and indirectly impact tumor growth via vascular shutdown. These viruses bear natural abilities to associate with lymphocytes upon systemic administration, but therapeutic doses must be very high in order to evade antibodies and other components of the immune system. As T cells readily circulate through the body, using these cells to deliver OVs directly to tumors may provide an ideal combination. Our studies demonstrate that loading chimeric antigen receptor–engineered T cells with low doses of virus does not impact receptor expression or function in either murine or human T cells. Engineered T cells can deposit virus onto a variety of tumor targets, which can enhance the tumoricidal activity of the combination treatment. This concept appears to be broadly applicable, as we observed similar results using murine or human T cells, loaded with either RNA or DNA viruses. Overall, loading of engineered T cells with OVs represents a novel combination therapy that may increase the efficacy of both treatments. PMID:27119109

  16. Stroke rehabilitation using noninvasive cortical stimulation: aphasia.

    PubMed

    Mylius, Veit; Zouari, Hela G; Ayache, Samar S; Farhat, Wassim H; Lefaucheur, Jean-Pascal

    2012-08-01

    Poststroke aphasia results from the lesion of cortical areas involved in the motor production of speech (Broca's aphasia) or in the semantic aspects of language comprehension (Wernicke's aphasia). Such lesions produce an important reorganization of speech/language-specific brain networks due to an imbalance between cortical facilitation and inhibition. In fact, functional recovery is associated with changes in the excitability of the damaged neural structures and their connections. Two main mechanisms are involved in poststroke aphasia recovery: the recruitment of perilesional regions of the left hemisphere in case of small lesion and the acquisition of language processing ability in homotopic areas of the nondominant right hemisphere when left hemispheric language abilities are permanently lost. There is some evidence that noninvasive cortical stimulation, especially when combined with language therapy or other therapeutic approaches, can promote aphasia recovery. Cortical stimulation was mainly used to either increase perilesional excitability or reduce contralesional activity based on the concept of reciprocal inhibition and maladaptive plasticity. However, recent studies also showed some positive effects of the reinforcement of neural activities in the contralateral right hemisphere, based on the potential compensatory role of the nondominant hemisphere in stroke recovery.

  17. Using GIS-based methods and lidar data to estimate rooftop solar technical potential in US cities

    DOE PAGES

    Margolis, Robert; Gagnon, Pieter; Melius, Jennifer; ...

    2017-07-06

    Here, we estimate the technical potential of rooftop solar photovoltaics (PV) for select US cities by combining light detection and ranging (lidar) data, a validated analytical method for determining rooftop PV suitability employing geographic information systems, and modeling of PV electricity generation. We find that rooftop PV's ability to meet estimated city electricity consumption varies widely - from meeting 16% of annual consumption (in Washington, DC) to meeting 88% (in Mission Viejo, CA). Important drivers include average rooftop suitability, household footprint/per-capita roof space, the quality of the solar resource, and the city's estimated electricity consumption. In addition to city-wide results,more » we also estimate the ability of aggregations of households to offset their electricity consumption with PV. In a companion article, we will use statistical modeling to extend our results and estimate national rooftop PV technical potential. In addition, our publically available data and methods may help policy makers, utilities, researchers, and others perform customized analyses to meet their specific needs.« less

  18. The Episodic Memory System: Neurocircuitry and Disorders

    PubMed Central

    Dickerson, Bradford C; Eichenbaum, Howard

    2010-01-01

    The ability to encode and retrieve our daily personal experiences, called episodic memory, is supported by the circuitry of the medial temporal lobe (MTL), including the hippocampus, which interacts extensively with a number of specific distributed cortical and subcortical structures. In both animals and humans, evidence from anatomical, neuropsychological, and physiological studies indicates that cortical components of this system have key functions in several aspects of perception and cognition, whereas the MTL structures mediate the organization and persistence of the network of memories whose details are stored in those cortical areas. Structures within the MTL, and particularly the hippocampus, have distinct functions in combining information from multiple cortical streams, supporting our ability to encode and retrieve details of events that compose episodic memories. Conversely, selective damage in the hippocampus, MTL, and other structures of the large-scale memory system, or deterioration of these areas in several diseases and disorders, compromises episodic memory. A growing body of evidence is converging on a functional organization of the cortical, subcortical, and MTL structures that support the fundamental features of episodic memory in humans and animals. PMID:19776728

  19. Study on Flexural Behaviour of Ternary Blended Reinforced Self Compacting Concrete Beam with Conventional RCC Beam

    NASA Astrophysics Data System (ADS)

    Marshaline Seles, M.; Suryanarayanan, R.; Vivek, S. S.; Dhinakaran, G.

    2017-07-01

    The conventional concrete when used for structures having dense congested reinforcement, the problems such as external compaction and vibration needs special attention. In such case, the self compacting concrete (SCC) which has the properties like flow ability, passing and filling ability would be an obvious answer. All those SCC flow behavior was governed by EFNARC specifications. In present study, the combination type of SCC was prepared by replacing cement with silica fume (SF) and metakaolin (MK) along with optimum dosages of chemical admixtures. From the fresh property test, cube compressive strength and cylinder split tensile strength, optimum ternary mix was obtained. In order to study the flexural behavior, the optimum ternary mix was taken in which beam specimens of size 1200 mm x 100 mm x 200 mm was designed as singly reinforced section according to IS: 456-2000, Limit state method. Finally the comparative experimental analysis was made between conventional RCC and SCC beams of same grade in terms of flexural strength namely yield load & ultimate load, load- deflection curve, crack size and pattern respectively.

  20. Using GIS-based methods and lidar data to estimate rooftop solar technical potential in US cities

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

    Margolis, Robert; Gagnon, Pieter; Melius, Jennifer

    Here, we estimate the technical potential of rooftop solar photovoltaics (PV) for select US cities by combining light detection and ranging (lidar) data, a validated analytical method for determining rooftop PV suitability employing geographic information systems, and modeling of PV electricity generation. We find that rooftop PV's ability to meet estimated city electricity consumption varies widely - from meeting 16% of annual consumption (in Washington, DC) to meeting 88% (in Mission Viejo, CA). Important drivers include average rooftop suitability, household footprint/per-capita roof space, the quality of the solar resource, and the city's estimated electricity consumption. In addition to city-wide results,more » we also estimate the ability of aggregations of households to offset their electricity consumption with PV. In a companion article, we will use statistical modeling to extend our results and estimate national rooftop PV technical potential. In addition, our publically available data and methods may help policy makers, utilities, researchers, and others perform customized analyses to meet their specific needs.« less

  1. Application of Fiber Optic ATR-FTIR Methods for In Situ Characterization of Protein Delivery Systems in Real Time

    PubMed Central

    McFearin, Cathryn L.; Sankaranarayanan, Jagadis; Almutairi, Adah

    2011-01-01

    Real Time Characterization of Protein Delivery Systems A fiber optic coupled ATR-FTIR spectroscopy technique was applied to the study of two different therapeutic delivery systems, acid degradable hydrogels and nanoparticles. Real time exponential release of a model protein, human serum albumin (HSA), was observed from two different polymeric hydrogels formulated with a pH sensitive crosslinker. Spectroscopic examination of nanoparticles formulated with an acid degradable polymer shell and encapsulated HSA exhibited vibrational signatures characteristic of both particle and payload when exposed to lowered pH conditions demonstrating the ability of this methodology to simultaneously measure phenomena arising from a system with a mixture of components. In addition, thorough characterization of these pH sensitive delivery vehicles without encapsulated protein was also accomplished in order to separate the effects of the payload during degradation. By providing in situ, real time detection in combination with the ability to specifically identify different components in a mixture without involved sample preparation and minimal sample disturbance, the versatility and suitability of this type of experiment for research in the pharmaceutical field is demonstrated. PMID:21476582

  2. Nano-Bio Engineered Carbon Dot-Peptide Functionalized Water Dispersible Hyperbranched Polyurethane for Bone Tissue Regeneration.

    PubMed

    Gogoi, Satyabrat; Maji, Somnath; Mishra, Debasish; Devi, K Sanjana P; Maiti, Tapas Kumar; Karak, Niranjan

    2017-03-01

    The present study delves into a combined bio-nano-macromolecular approach for bone tissue engineering. This approach relies on the properties of an ideal scaffold material imbued with all the chemical premises required for fostering cellular growth and differentiation. A tannic acid based water dispersible hyperbranched polyurethane is fabricated with bio-nanohybrids of carbon dot and four different peptides (viz. SVVYGLR, PRGDSGYRGDS, IPP, and CGGKVGKACCVPTKLSPISVLYK) to impart target specific in vivo bone healing ability. This polymeric bio-nanocomposite is blended with 10 wt% of gelatin and examined as a non-invasive delivery vehicle. In vitro assessment of the developed polymeric system reveals good osteoblast adhesion, proliferation, and differentiation. Aided by this panel of peptides, the polymeric bio-nanocomposite exhibits in vivo ectopic bone formation ability. The study on in vivo mineralization and vascularization reveals the occurrence of calcification and blood vessel formation. Thus, the study demonstrates carbon dot/peptide functionalized hyperbranched polyurethane gel for bone tissue engineering application. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Combining ability for yield and fruit quality in the pepper Capsicum annuum.

    PubMed

    do Nascimento, N F F; do Rêgo, E R; Nascimento, M F; Bruckner, C H; Finger, F L; do Rêgo, M M

    2014-04-29

    The objective of this study was to determine the effects of the general and specific combining abilities (GCA and SCA, respectively) of 15 characteristics and to evaluate the most promising crosses and the reciprocal effect between the hybrids of six parents of the Capsicum annuum species. Six parents, belonging to the Horticultural Germplasm Bank of Centro de Ciências Agrárias of Universidade Federal da Paraíba, were crossed in complete diallel manner. The 30 hybrids generated and the parents were then analyzed in a completely randomized design with three replicates. The data were submitted to analysis of variance at 1% probability, and the means were grouped by the Scott-Knott test at 1% probability. The diallel analysis was performed according to the Griffing method, model I and fixed model. Both additive and non-additive effects influenced the hybrids' performance, as indicated by the GCA/SCA ratio. The non-additive effects, epistasis and/or dominance, played a more important role than the additive effects in pedicel length, pericarp thickness, fresh matter, dry matter content, seed yield per fruit, fruit yield per plant, days to fructification, and total soluble solids. The GCA effects were more important than the SCA effects in the fruit weight, fruit length and diameter, placenta length, yield, vitamin C, and titratable acidity characteristics. The results found here clearly show that ornamental pepper varieties can be developed through hybridization in breeding programs with C. annuum.

  4. On the usage of divergence nudging in the DMI nowcasting system

    NASA Astrophysics Data System (ADS)

    Korsholm, Ulrik; Petersen, Claus; Hansen Sass, Bent; Woetmann Nielsen, Niels; Getreuer Jensen, David; Olsen, Bjarke Tobias; Vedel, Henrik

    2014-05-01

    DMI has recently proposed a new method for nudging radar reflectivity CAPPI products into their operational nowcasting system. The system is based on rapid update cycles (with hourly frequency) with the High Resolution Limited Area Model combined with surface and upper air analysis at each initial time. During the first 1.5 hours of a simulation the model dynamical state is nudged in accordance with the CAPPI product after which a free forecast is produced with a forecast length of 12 hours. The nudging method is based on the assumption that precipitation is forced by low level moisture convergence and an enhanced moisture source will lead to convective triggering of the model cloud scheme. If the model under-predicts precipitation before cut-off horizontal low level divergence is nudged towards an estimated value. These pseudo observations are calculated from the CAPPI product by assuming a specific vertical profile of the change in divergence field. The strength of the nudging is proportional to the difference between observed and modelled precipitation. When over-predicting, the low level moisture source is reduced, and in-cloud moisture is nudged towards environmental values. Results have been analysed in terms of the fractions skill score and the ability of the nudging method to position the precipitation cells correctly is discussed. The ability of the model to retain memory of the precipitation systems in the free forecast has also been investigated and examples of combining the nudging method with extrapolated reflectivity fields are also shown.

  5. Prediction of industrial tomato hybrids from agronomic traits and ISSR molecular markers.

    PubMed

    Figueiredo, A S T; Resende, J T V; Faria, M V; Da-Silva, P R; Fagundes, B S; Morales, R G F

    2016-05-13

    Heterosis is a highly relevant phenomenon in plant breeding. This condition is usually established in hybrids derived from crosses of highly divergent parents. The success of a breeder in obtaining heterosis is directly related to the correct identification of genetically contrasting parents. Currently, the diallel cross is the most commonly used methodology to detect contrasting parents; however, it is a time- and cost-consuming procedure. Therefore, new tools capable of performing this task quickly and accurately are required. Thus, the purpose of this study was to estimate the genetic divergence in industrial tomato lines, based on agronomic traits, and to compare with estimates obtained using inter-simple sequence repeat (ISSR) molecular markers. The genetic divergence among 10 industrial tomato lines, based on nine morphological characters and 12 ISSR primers was analyzed. For data analysis, Pearson and Spearman correlation coefficients were calculated between the genetic dissimilarity measures estimated by Mahalanobis distance and Jaccard's coefficient of genetic dissimilarity from the heterosis estimates, combining ability, and means of important traits of industrial tomato. The ISSR markers efficiently detected contrasting parents for hybrid production in tomato. Parent RVTD-08 was indicated as the most divergent, both by molecular and morphological markers, that positively contributed to increased heterosis and by the specific combining ability in the crosses in which it participated. The genetic dissimilarity estimated by ISSR molecular markers aided the identification of the best hybrids of the experiment in terms of total fruit yield, pulp yield, and soluble solids content.

  6. Teaching a Machine to Feel Postoperative Pain: Combining High-Dimensional Clinical Data with Machine Learning Algorithms to Forecast Acute Postoperative Pain

    PubMed Central

    Tighe, Patrick J.; Harle, Christopher A.; Hurley, Robert W.; Aytug, Haldun; Boezaart, Andre P.; Fillingim, Roger B.

    2015-01-01

    Background Given their ability to process highly dimensional datasets with hundreds of variables, machine learning algorithms may offer one solution to the vexing challenge of predicting postoperative pain. Methods Here, we report on the application of machine learning algorithms to predict postoperative pain outcomes in a retrospective cohort of 8071 surgical patients using 796 clinical variables. Five algorithms were compared in terms of their ability to forecast moderate to severe postoperative pain: Least Absolute Shrinkage and Selection Operator (LASSO), gradient-boosted decision tree, support vector machine, neural network, and k-nearest neighbor, with logistic regression included for baseline comparison. Results In forecasting moderate to severe postoperative pain for postoperative day (POD) 1, the LASSO algorithm, using all 796 variables, had the highest accuracy with an area under the receiver-operating curve (ROC) of 0.704. Next, the gradient-boosted decision tree had an ROC of 0.665 and the k-nearest neighbor algorithm had an ROC of 0.643. For POD 3, the LASSO algorithm, using all variables, again had the highest accuracy, with an ROC of 0.727. Logistic regression had a lower ROC of 0.5 for predicting pain outcomes on POD 1 and 3. Conclusions Machine learning algorithms, when combined with complex and heterogeneous data from electronic medical record systems, can forecast acute postoperative pain outcomes with accuracies similar to methods that rely only on variables specifically collected for pain outcome prediction. PMID:26031220

  7. On Quantitative Biomarkers of VNS Therapy Using EEG and ECG Signals.

    PubMed

    Ravan, Maryam; Sabesan, Shivkumar; D'Cruz, O'Neill

    2017-02-01

    The goal of this work is to objectively evaluate the effectiveness of neuromodulation therapies, specifically, Vagus nerve stimulation (VNS) in reducing the severity of seizures in patients with medically refractory epilepsy. Using novel quantitative features obtained from combination of electroencephalographic (EEG) and electrocardiographic (ECG) signals around seizure events in 16 patients who underwent implantation of closed-loop VNS therapy system, namely AspireSR, we evaluated if automated delivery of VNS at the time of seizure onset reduces the severity of seizures by reducing EEG spatial synchronization as well as the duration and magnitude of heart rate increase. Unsupervised classification was subsequently applied to test the discriminative ability and validity of these features to measure responsiveness to VNS therapy. Results of application of this methodology to compare 105 pre-VNS treatment and 107 post-VNS treatment seizures revealed that seizures that were acutely stimulated using VNS had a reduced ictal spread as well as reduced impact on cardiovascular function compared to the ones that occurred prior to any treatment. Furthermore, application of an unsupervised fuzzy-c-mean classifier to evaluate the ability of the combined EEG-ECG based features to classify pre and post-treatment seizures achieved a classification accuracy of 85.85%. These results indicate the importance of timely delivery of VNS to reduce seizure severity and thus help achieve better seizure control for patients with epilepsy. The proposed set of quantitative features could be used as potential biomarkers for predicting long-term response to VNS therapy.

  8. Detecting Signals of Disproportionate Reporting from Singapore's Spontaneous Adverse Event Reporting System: An Application of the Sequential Probability Ratio Test.

    PubMed

    Chan, Cheng Leng; Rudrappa, Sowmya; Ang, Pei San; Li, Shu Chuen; Evans, Stephen J W

    2017-08-01

    The ability to detect safety concerns from spontaneous adverse drug reaction reports in a timely and efficient manner remains important in public health. This paper explores the behaviour of the Sequential Probability Ratio Test (SPRT) and ability to detect signals of disproportionate reporting (SDRs) in the Singapore context. We used SPRT with a combination of two hypothesised relative risks (hRRs) of 2 and 4.1 to detect signals of both common and rare adverse events in our small database. We compared SPRT with other methods in terms of number of signals detected and whether labelled adverse drug reactions were detected or the reaction terms were considered serious. The other methods used were reporting odds ratio (ROR), Bayesian Confidence Propagation Neural Network (BCPNN) and Gamma Poisson Shrinker (GPS). The SPRT produced 2187 signals in common with all methods, 268 unique signals, and 70 signals in common with at least one other method, and did not produce signals in 178 cases where two other methods detected them, and there were 403 signals unique to one of the other methods. In terms of sensitivity, ROR performed better than other methods, but the SPRT method found more new signals. The performances of the methods were similar for negative predictive value and specificity. Using a combination of hRRs for SPRT could be a useful screening tool for regulatory agencies, and more detailed investigation of the medical utility of the system is merited.

  9. Outward Bound...Into the Mainstream of Education.

    ERIC Educational Resources Information Center

    Outward Bound, Inc., Andover, MA.

    Outward Bound schools have instituted advanced courses designed specifically for adults engaged in education and youth work. Benefits for teachers include greater development of capacitites and potentialities, greater confidence in their abilities, and the ability to relate more effectively to others. Some of the specific training elements in an…

  10. Suppressing Irrelevant Information from Working Memory: Evidence for Domain-Specific Deficits in Poor Comprehenders

    ERIC Educational Resources Information Center

    Pimperton, Hannah; Nation, Kate

    2010-01-01

    Previous research has suggested that children with specific reading comprehension deficits (poor comprehenders) show an impaired ability to suppress irrelevant information from working memory, with this deficit detrimentally impacting on their working memory ability, and consequently limiting their reading comprehension performance. However, the…

  11. Thyroid-specific questions on work ability showed known-groups validity among Danes with thyroid diseases.

    PubMed

    Nexo, Mette Andersen; Watt, Torquil; Bonnema, Steen Joop; Hegedüs, Laszlo; Rasmussen, Åse Krogh; Feldt-Rasmussen, Ulla; Bjorner, Jakob Bue

    2015-07-01

    We aimed to identify the best approach to work ability assessment in patients with thyroid disease by evaluating the factor structure, measurement equivalence, known-groups validity, and predictive validity of a broad set of work ability items. Based on the literature and interviews with thyroid patients, 24 work ability items were selected from previous questionnaires, revised, or developed anew. Items were tested among 632 patients with thyroid disease (non-toxic goiter, toxic nodular goiter, Graves' disease (with or without orbitopathy), autoimmune hypothyroidism, and other thyroid diseases), 391 of which had participated in a study 5 years previously. Responses to select items were compared to general population data. We used confirmatory factor analyses for categorical data, logistic regression analyses and tests of differential item function, and head-to-head comparisons of relative validity in distinguishing known groups. Although all work ability items loaded on a common factor, the optimal factor solution included five factors: role physical, role emotional, thyroid-specific limitations, work limitations (without disease attribution), and work performance. The scale on thyroid-specific limitations showed the most power in distinguishing clinical groups and time since diagnosis. A global single item proved useful for comparisons with the general population, and a thyroid-specific item predicted labor market exclusion within the next 5 years (OR 5.0, 95 % CI 2.7-9.1). Items on work limitations with attribution to thyroid disease were most effective in detecting impact on work ability and showed good predictive validity. Generic work ability items remain useful for general population comparisons.

  12. Effects of combined physical and cognitive training on fitness and neuropsychological outcomes in healthy older adults

    PubMed Central

    Desjardins-Crépeau, Laurence; Berryman, Nicolas; Fraser, Sarah A; Vu, Thien Tuong Minh; Kergoat, Marie-Jeanne; Li, Karen ZH; Bosquet, Laurent; Bherer, Louis

    2016-01-01

    Purpose Physical exercise and cognitive training have been shown to enhance cognition among older adults. However, few studies have looked at the potential synergetic effects of combining physical and cognitive training in a single study. Prior trials on combined training have led to interesting yet equivocal results. The aim of this study was to examine the effects of combined physical and cognitive interventions on physical fitness and neuropsychological performance in healthy older adults. Methods Seventy-six participants were randomly assigned to one of four training combinations using a 2×2 factorial design. The physical intervention was a mixed aerobic and resistance training program, and the cognitive intervention was a dual-task (DT) training program. Stretching and toning exercises and computer lessons were used as active control conditions. Physical and cognitive measures were collected pre- and postintervention. Results All groups showed equivalent improvements in measures of functional mobility. The aerobic–strength condition led to larger effect size in lower body strength, independently of cognitive training. All groups showed improved speed of processing and inhibition abilities, but only participants who took part in the DT training, independently of physical training, showed increased task-switching abilities. The level of functional mobility after intervention was significantly associated with task-switching abilities. Conclusion Combined training did not yield synergetic effects. However, DT training did lead to transfer effects on executive performance in neuropsychological tests. Both aerobic-resistance training and stretching-toning exercises can improve functional mobility in older adults. PMID:27698558

  13. Temporally and spatially controllable gene expression and knockout in mouse urothelium.

    PubMed

    Zhou, Haiping; Liu, Yan; He, Feng; Mo, Lan; Sun, Tung-Tien; Wu, Xue-Ru

    2010-08-01

    Urothelium that lines almost the entire urinary tract performs important functions and is prone to assaults by urinary microbials, metabolites, and carcinogens. To improve our understanding of urothelial physiology and disease pathogenesis, we sought to develop two novel transgenic systems, one that would allow inducible and urothelium-specific gene expression, and another that would allow inducible and urothelium-specific knockout. Toward this end, we combined the ability of the mouse uroplakin II promoter (mUPII) to drive urothelium-specific gene expression with a versatile tetracycline-mediated inducible system. We found that, when constructed under the control of mUPII, only a modified, reverse tetracycline trans-activator (rtTA-M2), but not its original version (rtTA), could efficiently trans-activate reporter gene expression in mouse urothelium on doxycycline (Dox) induction. The mUPII/rtTA-M2-inducible system retained its strict urothelial specificity, had no background activity in the absence of Dox, and responded rapidly to Dox administration. Using a reporter gene whose expression was secondarily controlled by histone remodeling, we were able to identify, colocalize with 5-bromo-2-deoxyuridine incorporation, and semiquantify newly divided urothelial cells. Finally, we established that, when combined with a Cre recombinase under the control of the tetracycline operon, the mUPII-driven rtTA-M2 could inducibly inactivate any gene of interest in mouse urothelium. The establishment of these two new transgenic mouse systems enables the manipulation of gene expression and/or inactivation in adult mouse urothelium at any given time, thus minimizing potential compensatory effects due to gene overexpression or loss and allowing more accurate modeling of urothelial diseases than previously reported constitutive systems.

  14. Nursing students' reading and English aptitudes and their relationship to discipline-specific formal writing ability: a descriptive correlational study.

    PubMed

    Newton, Sarah; Moore, Gary

    2010-01-01

    Formal writing assignments are commonly used in nursing education to develop students' critical thinking skills, as well as to enhance their communication abilities. However, writing apprehension is a common phenomenon among nursing students. It has been suggested that reading and English aptitudes are related to formal writing ability, yet neither the reading nor the English aptitudes of undergraduate nursing students have been described in the literature, and the relationships that reading and English aptitude have with formal writing ability have not been explored. The purpose of this descriptive correlational study was to describe writing apprehension and to assess the relationships among reading and English aptitude and discipline-specific formal writing ability among undergraduate nursing students. The study sample consisted of 146 sophomores from one baccalaureate nursing program. The results indicated that both reading and English aptitude were related to students' formal writing ability.

  15. Genetic specificity of face recognition.

    PubMed

    Shakeshaft, Nicholas G; Plomin, Robert

    2015-10-13

    Specific cognitive abilities in diverse domains are typically found to be highly heritable and substantially correlated with general cognitive ability (g), both phenotypically and genetically. Recent twin studies have found the ability to memorize and recognize faces to be an exception, being similarly heritable but phenotypically substantially uncorrelated both with g and with general object recognition. However, the genetic relationships between face recognition and other abilities (the extent to which they share a common genetic etiology) cannot be determined from phenotypic associations. In this, to our knowledge, first study of the genetic associations between face recognition and other domains, 2,000 18- and 19-year-old United Kingdom twins completed tests assessing their face recognition, object recognition, and general cognitive abilities. Results confirmed the substantial heritability of face recognition (61%), and multivariate genetic analyses found that most of this genetic influence is unique and not shared with other cognitive abilities.

  16. Genetic specificity of face recognition

    PubMed Central

    Shakeshaft, Nicholas G.; Plomin, Robert

    2015-01-01

    Specific cognitive abilities in diverse domains are typically found to be highly heritable and substantially correlated with general cognitive ability (g), both phenotypically and genetically. Recent twin studies have found the ability to memorize and recognize faces to be an exception, being similarly heritable but phenotypically substantially uncorrelated both with g and with general object recognition. However, the genetic relationships between face recognition and other abilities (the extent to which they share a common genetic etiology) cannot be determined from phenotypic associations. In this, to our knowledge, first study of the genetic associations between face recognition and other domains, 2,000 18- and 19-year-old United Kingdom twins completed tests assessing their face recognition, object recognition, and general cognitive abilities. Results confirmed the substantial heritability of face recognition (61%), and multivariate genetic analyses found that most of this genetic influence is unique and not shared with other cognitive abilities. PMID:26417086

  17. Network design for quantifying urban CO2 emissions: assessing trade-offs between precision and network density

    NASA Astrophysics Data System (ADS)

    Turner, Alexander J.; Shusterman, Alexis A.; McDonald, Brian C.; Teige, Virginia; Harley, Robert A.; Cohen, Ronald C.

    2016-11-01

    The majority of anthropogenic CO2 emissions are attributable to urban areas. While the emissions from urban electricity generation often occur in locations remote from consumption, many of the other emissions occur within the city limits. Evaluating the effectiveness of strategies for controlling these emissions depends on our ability to observe urban CO2 emissions and attribute them to specific activities. Cost-effective strategies for doing so have yet to be described. Here we characterize the ability of a prototype measurement network, modeled after the Berkeley Atmospheric CO2 Observation Network (BEACO2N) in California's Bay Area, in combination with an inverse model based on the coupled Weather Research and Forecasting/Stochastic Time-Inverted Lagrangian Transport (WRF-STILT) to improve our understanding of urban emissions. The pseudo-measurement network includes 34 sites at roughly 2 km spacing covering an area of roughly 400 km2. The model uses an hourly 1 × 1 km2 emission inventory and 1 × 1 km2 meteorological calculations. We perform an ensemble of Bayesian atmospheric inversions to sample the combined effects of uncertainties of the pseudo-measurements and the model. We vary the estimates of the combined uncertainty of the pseudo-observations and model over a range of 20 to 0.005 ppm and vary the number of sites from 1 to 34. We use these inversions to develop statistical models that estimate the efficacy of the combined model-observing system in reducing uncertainty in CO2 emissions. We examine uncertainty in estimated CO2 fluxes on the urban scale, as well as for sources embedded within the city such as a line source (e.g., a highway) or a point source (e.g., emissions from the stacks of small industrial facilities). Using our inversion framework, we find that a dense network with moderate precision is the preferred setup for estimating area, line, and point sources from a combined uncertainty and cost perspective. The dense network considered here (modeled after the BEACO2N network with an assumed mismatch error of 1 ppm at an hourly temporal resolution) could estimate weekly CO2 emissions from an urban region with less than 5 % error, given our characterization of the combined observation and model uncertainty.

  18. Network design for quantifying urban CO 2 emissions: assessing trade-offs between precision and network density

    DOE PAGES

    Turner, Alexander J.; Shusterman, Alexis A.; McDonald, Brian C.; ...

    2016-11-01

    The majority of anthropogenic CO 2 emissions are attributable to urban areas. While the emissions from urban electricity generation often occur in locations remote from consumption, many of the other emissions occur within the city limits. Evaluating the effectiveness of strategies for controlling these emissions depends on our ability to observe urban CO 2 emissions and attribute them to specific activities. Cost-effective strategies for doing so have yet to be described. Here we characterize the ability of a prototype measurement network, modeled after the Berkeley Atmospheric CO 2 Observation Network (BEACO 2N) in California's Bay Area, in combination with anmore » inverse model based on the coupled Weather Research and Forecasting/Stochastic Time-Inverted Lagrangian Transport (WRF-STILT) to improve our understanding of urban emissions. The pseudo-measurement network includes 34 sites at roughly 2 km spacing covering an area of roughly 400 km 2. The model uses an hourly 1 × 1 km 2 emission inventory and 1 × 1 km 2 meteorological calculations. We perform an ensemble of Bayesian atmospheric inversions to sample the combined effects of uncertainties of the pseudo-measurements and the model. We vary the estimates of the combined uncertainty of the pseudo-observations and model over a range of 20 to 0.005 ppm and vary the number of sites from 1 to 34. We use these inversions to develop statistical models that estimate the efficacy of the combined model–observing system in reducing uncertainty in CO 2 emissions. We examine uncertainty in estimated CO 2 fluxes on the urban scale, as well as for sources embedded within the city such as a line source (e.g., a highway) or a point source (e.g., emissions from the stacks of small industrial facilities). Using our inversion framework, we find that a dense network with moderate precision is the preferred setup for estimating area, line, and point sources from a combined uncertainty and cost perspective. The dense network considered here (modeled after the BEACO 2N network with an assumed mismatch error of 1 ppm at an hourly temporal resolution) could estimate weekly CO 2 emissions from an urban region with less than 5 % error, given our characterization of the combined observation and model uncertainty.« less

  19. Network design for quantifying urban CO 2 emissions: assessing trade-offs between precision and network density

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

    Turner, Alexander J.; Shusterman, Alexis A.; McDonald, Brian C.

    The majority of anthropogenic CO 2 emissions are attributable to urban areas. While the emissions from urban electricity generation often occur in locations remote from consumption, many of the other emissions occur within the city limits. Evaluating the effectiveness of strategies for controlling these emissions depends on our ability to observe urban CO 2 emissions and attribute them to specific activities. Cost-effective strategies for doing so have yet to be described. Here we characterize the ability of a prototype measurement network, modeled after the Berkeley Atmospheric CO 2 Observation Network (BEACO 2N) in California's Bay Area, in combination with anmore » inverse model based on the coupled Weather Research and Forecasting/Stochastic Time-Inverted Lagrangian Transport (WRF-STILT) to improve our understanding of urban emissions. The pseudo-measurement network includes 34 sites at roughly 2 km spacing covering an area of roughly 400 km 2. The model uses an hourly 1 × 1 km 2 emission inventory and 1 × 1 km 2 meteorological calculations. We perform an ensemble of Bayesian atmospheric inversions to sample the combined effects of uncertainties of the pseudo-measurements and the model. We vary the estimates of the combined uncertainty of the pseudo-observations and model over a range of 20 to 0.005 ppm and vary the number of sites from 1 to 34. We use these inversions to develop statistical models that estimate the efficacy of the combined model–observing system in reducing uncertainty in CO 2 emissions. We examine uncertainty in estimated CO 2 fluxes on the urban scale, as well as for sources embedded within the city such as a line source (e.g., a highway) or a point source (e.g., emissions from the stacks of small industrial facilities). Using our inversion framework, we find that a dense network with moderate precision is the preferred setup for estimating area, line, and point sources from a combined uncertainty and cost perspective. The dense network considered here (modeled after the BEACO 2N network with an assumed mismatch error of 1 ppm at an hourly temporal resolution) could estimate weekly CO 2 emissions from an urban region with less than 5 % error, given our characterization of the combined observation and model uncertainty.« less

  20. Combination treatment with docetaxel and histone deacetylase inhibitors downregulates androgen receptor signaling in castration-resistant prostate cancer.

    PubMed

    Park, Sang Eun; Kim, Ha-Gyeong; Kim, Dong Eun; Jung, Yoo Jung; Kim, Yunlim; Jeong, Seong-Yun; Choi, Eun Kyung; Hwang, Jung Jin; Kim, Choung-Soo

    2018-04-01

    Backgrounds Since most patients with castration-resistant prostate cancer (CRPC) develop resistance to its standard therapy docetaxel, many studies have attempted to identify novel combination treatment to meet the large clinical unmet need. In this study, we examined whether histone deacetylase inhibitors (HDACIs) enhanced the effect of docetaxel on AR signaling in CRPC cells harboring AR and its splice variants. Methods HDACIs (vorinostat and CG200745) were tested for their ability to enhance the effects of docetaxel on cell viability and inhibition of AR signaling in CRPC 22Rv1 and VCaP cells by using CellTiter-Glo™ Luminescent cell viability assay, synergy index analysis and Western blotting. The nuclear localization of AR was examined via immunocytochemical staining in 22Rv1 cells and primary tumor cells from a patient with CRPC. Results Combination treatment with HDACIs (vorinostat or CG200745) and docetaxel synergistically inhibited the growth of 22Rv1 and VCaP cells. Consistently, the combination treatment decreased the levels of full-length AR (AR-FL), AR splice variants (AR-Vs), prostate-specific antigen (PSA), and anti-apoptotic Bcl-2 proteins more efficiently compared with docetaxel or vorinostat alone. Moreover, the combination treatment accelerated the acetylation and bundling of tubulin, which significantly inhibited the nuclear accumulation of AR in 22Rv1 cells. The cytoplasmic colocalization of AR-FL and AR-V7 with microtubule bundles increased after combination treatment in primary tumor cells from a patient with CRPC. Conclusions The results suggested that docetaxel, in combination with HDACIs, suppressed the expression and nuclear translocation of AR-FL and AR-Vs and showed synergistic anti-proliferative effect in CRPC cells. This combination therapy may be useful for the treatment of patients with CRPC.

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