Sample records for generations selected implications

  1. Age-related differences in idea generation and selection for propositional language.

    PubMed

    Madden, Daniel L; Sale, Martin V; Robinson, Gail A

    2018-05-21

    Conceptual preparation mechanisms such as novel idea generation and selection from amongst competing alternatives are critical for language production and may contribute to age-related language deficits. This study investigated whether older adults show diminished idea generation and selection abilities, compared to younger adults. Twenty younger (18-35 years) and 20 older (60-80 years) adults completed two novel experimental tasks, an idea generation task and a selection task. Older participants were slower than younger participants overall on both tasks. Importantly, this difference was more pronounced for task conditions with greater demands on generation and selection. Older adults were also significantly reduced on a semantic, but not phonemic, word fluency task. Overall, the older group showed evidence of age-related decline specific to idea generation and selection ability. This has implications for the message formulation stage of propositional language decline in normal aging.

  2. The Next Generation of Science Standards: Implications for Biology Education

    ERIC Educational Resources Information Center

    Bybee, Rodger W.

    2012-01-01

    The release of A Framework for K-12 Science Education: Practices, Crosscutting Concepts, and Core Ideas (NRC, 2012) provides the basis for the next generation of science standards. This article first describes that foundation for the life sciences; it then presents a draft standard for natural selection and evolution. Finally, there is a…

  3. Emerging U.S. Immigrant Geographies: Racial Wages and Migration Selectivity*

    PubMed Central

    Goodwin-White, Jamie

    2014-01-01

    Objective The maturing of the post-1965 children of immigrants and the recent emergence of immigrant settlement outside of traditional locations have implications for understanding immigrant economic incorporation. This analysis examines how changing immigrant geographies will affect the economic prospects of immigrants and a maturing second generation, and addresses sociological and economic perspectives on internal migration and immigrant progress. Methods Using the 2000 5 percent Public Use Microdata Files (PUMS), I employ endogenous switching regression models in analyzing the selectivity of internal migration and state residence patterns to the wages of immigrant, 1.5 generation, and U.S.-born workers. Results Nonwhite immigrant and 1.5-generation workers evade racial wage penalties through migration, but not through residing in emerging immigrant states. Conclusions Understanding the selectivity of internal migration to wages across racialized labor markets is important in assessing new immigrant geographies and prospects for the second generation. PMID:25364059

  4. Hockey-stick steam generator for LMFBR

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

    Hallinan, G.J.; Svedlund, P.E.

    1981-01-01

    This paper presents the criteria and evaluation leading to the selection of the Hockey Stick Steam Generator Concept and subsequent development of that concept for LMFBR application. The selection process and development of the Modular Steam Generator (MSG) is discussed, including the extensive test programs that culminated in the manufacture and test of a 35 MW(t) Steam Generator. The design of the CRBRP Steam Generator is described, emphasizing the current status and a review of the critical structural areas. CRBRP steam generator development tests are evaluated, with a discussion of test objectives and rating of the usefulness of test resultsmore » to the CRBRP prototype design. Manufacturing experience and status of the CRBRP prototype and plant units is covered. The scaleup of the Hockey Stick concept to large commercial plant application is presented, with an evaluation of scaleup limitations, transient effects, and system design implications.« less

  5. Life history traits and phenotypic selection among sunflower crop–wild hybrids and their wild counterpart: implications for crop allele introgression

    PubMed Central

    Kost, Matthew A; Alexander, Helen M; Jason Emry, D; Mercer, Kristin L

    2015-01-01

    Hybridization produces strong evolutionary forces. In hybrid zones, selection can differentially occur on traits and selection intensities may differ among hybrid generations. Understanding these dynamics in crop–wild hybrid zones can clarify crop-like traits likely to introgress into wild populations and the particular hybrid generations through which introgression proceeds. In a field experiment with four crop–wild hybrid Helianthus annuus (sunflower) cross types, we measured growth and life history traits and performed phenotypic selection analysis on early season traits to ascertain the likelihood, and routes, of crop allele introgression into wild sunflower populations. All cross types overwintered, emerged in the spring, and survived until flowering, indicating no early life history barriers to crop allele introgression. While selection indirectly favored earlier seedling emergence and taller early season seedlings, direct selection only favored greater early season leaf length. Further, there was cross type variation in the intensity of selection operating on leaf length. Thus, introgression of multiple early season crop-like traits, due to direct selection for greater early season leaf length, should not be impeded by any cross type and may proceed at different rates among generations. In sum, alleles underlying early season sunflower crop-like traits are likely to introgress into wild sunflower populations. PMID:26029263

  6. Life history traits and phenotypic selection among sunflower crop-wild hybrids and their wild counterpart: implications for crop allele introgression.

    PubMed

    Kost, Matthew A; Alexander, Helen M; Jason Emry, D; Mercer, Kristin L

    2015-06-01

    Hybridization produces strong evolutionary forces. In hybrid zones, selection can differentially occur on traits and selection intensities may differ among hybrid generations. Understanding these dynamics in crop-wild hybrid zones can clarify crop-like traits likely to introgress into wild populations and the particular hybrid generations through which introgression proceeds. In a field experiment with four crop-wild hybrid Helianthus annuus (sunflower) cross types, we measured growth and life history traits and performed phenotypic selection analysis on early season traits to ascertain the likelihood, and routes, of crop allele introgression into wild sunflower populations. All cross types overwintered, emerged in the spring, and survived until flowering, indicating no early life history barriers to crop allele introgression. While selection indirectly favored earlier seedling emergence and taller early season seedlings, direct selection only favored greater early season leaf length. Further, there was cross type variation in the intensity of selection operating on leaf length. Thus, introgression of multiple early season crop-like traits, due to direct selection for greater early season leaf length, should not be impeded by any cross type and may proceed at different rates among generations. In sum, alleles underlying early season sunflower crop-like traits are likely to introgress into wild sunflower populations.

  7. Natural selection stops the evolution of male attractiveness

    PubMed Central

    Hine, Emma; McGuigan, Katrina; Blows, Mark W.

    2011-01-01

    Sexual selection in natural populations acts on highly heritable traits and tends to be relatively strong, implicating sexual selection as a causal agent in many phenotypic radiations. Sexual selection appears to be ineffectual in promoting phenotypic divergence among contemporary natural populations, however, and there is little evidence from artificial selection experiments that sexual fitness can evolve. Here, we demonstrate that a multivariate male trait preferred by Drosophila serrata females can respond to selection and results in the maintenance of male mating success. The response to selection was associated with a gene of major effect increasing in frequency from 12 to 35% in seven generations. No further response to selection, or increase in frequency of the major gene, was observed between generations 7 and 11, indicating an evolutionary limit had been reached. Genetic analyses excluded both depletion of genetic variation and overdominance as causes of the evolutionary limit. Relaxing artificial selection resulted in the loss of 52% of the selection response after a further five generations, demonstrating that the response under artificial sexual selection was opposed by antagonistic natural selection. We conclude that male D. serrata sexually selected traits, and attractiveness to D. serrata females conferred by these traits, were held at an evolutionary limit by the lack of genetic variation that would allow an increase in sexual fitness while simultaneously maintaining nonsexual fitness. Our results suggest that sexual selection is unlikely to cause divergence among natural populations without a concomitant change in natural selection, a conclusion consistent with observational evidence from natural populations. PMID:21321197

  8. Brain-specific enhancers for cell-based therapy

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

    Visel, Axel; Rubenstein, John L.R.; Chen, Ying-Jiun

    Herein are described a set of novel specific human enhancers for specific forebrain cell types used to study and select for human neural progenitor cells. This approach enables the ability to generate interneurons from human ES, iPS and iN cells, making them available for human transplantation and for molecular/cellular analyzes. These approaches are also directly applicable to generating other neuronal cell types, such as cortical and striatal projection neurons, which have implications for many human diseases.

  9. Peptides for Specific Intracellular Delivery and Targeting of Nanoparticles: Implications for Developing Nanoparticle-Mediated Drug Delivery

    DTIC Science & Technology

    2010-01-01

    for selective delivery of therapeutics and imaging agents to the tumour vasculature. Drug Resist. Update 8(6), 381–402 (2005). 89 Smith BR, Cheng Z...component can be realized. Select examples from the literature have already demonstrated the feasibility of generating hybrid NP–peptide constructs in...peptide-mediated delivery of NP-based imaging agents (fluorescence and magnetic resonance), drug-delivery vehicles, therapeutic proteins and nucleic

  10. An experimental demonstration of Fisher's principle: evolution of sexual proportion by natural selection.

    PubMed Central

    Carvalho, A B; Sampaio, M C; Varandas, F R; Klaczko, L B

    1998-01-01

    Most sexually reproducing species have sexual proportions around 1:1. This major biological phenomenon remained unexplained until 1930, when FISHER proposed that it results from a mechanism of natural selection. Here we report the first experimental test of his model that obeys all its assumptions. We used a naturally occurring X-Y meiotic drive system--the sex-ratio trait of Drosophila mediopunctat--to generate female-biased experimental populations. As predicted by FISHER, these populations evolved toward equal sex proportions due to natural selection, by accumulation of autosomal alleles that direct the parental reproductive effort toward the rare sex. Classical Fisherian evolution is a rather slow mechanism: despite a very large amount of genetic variability, the experimental populations evolved from 16% of males to 32% of males in 49 generations and would take 330 generations (29 years) to reach 49%. This slowness has important implications for species potentially endangered by skewed sexual proportions, such as reptiles with temperature sex determination. PMID:9504919

  11. A PET study of word generation in Huntington's disease: effects of lexical competition and verb/noun category.

    PubMed

    Lepron, Evelyne; Péran, Patrice; Cardebat, Dominique; Démonet, Jean-François

    2009-08-01

    Huntington's disease (HD) patients show language production deficits that have been conceptualized as a consequence of executive disorders, e.g. selection deficit between candidate words or switching between word categories. More recently, a deficit of word generation specific to verbs has been reported, which might relate to impaired action representations in HD. We studied the brain correlates of language impairment in HD using H(2)O(15) positron emission tomography (PET). The activation task consisted of generation of semantically appropriate nouns and verbs in dominant (low lexical selection) and selective conditions (high lexical selection). Reaction times were longer and number of errors was higher in 12 non-demented HD than in 17 age-matched controls in all conditions. In both groups, the selective condition yielded longer reaction time and a greater number of errors than the dominant one. PET data revealed that, in control subjects, the left inferior temporal gyrus was involved in the selective condition whereas it was not in HD. Moreover, activity in the anterior cingulate and the inferior frontal gyri was correlated with behavioral performance in control subjects only. In HD, the lack of implication of these regions, already shown to be crucial in lexical selection, might have been partly compensated by the activation in the left supramarginal gyrus (phonological loop activity) and the right inferior frontal gyrus (effortful retrieval processes), which might support accessory language strategies allowing patients to achieve word generation.

  12. Case Problems for Problem-Based Pedagogical Approaches: A Comparative Analysis

    ERIC Educational Resources Information Center

    Dabbagh, Nada; Dass, Susan

    2013-01-01

    A comparative analysis of 51 case problems used in five problem-based pedagogical models was conducted to examine whether there are differences in their characteristics and the implications of such differences on the selection and generation of ill-structured case problems. The five pedagogical models were: situated learning, goal-based scenario,…

  13. Statistical aspects of evolution under natural selection, with implications for the advantage of sexual reproduction.

    PubMed

    Crouch, Daniel J M

    2017-10-27

    The prevalence of sexual reproduction remains mysterious, as it poses clear evolutionary drawbacks compared to reproducing asexually. Several possible explanations exist, with one of the most likely being that finite population size causes linkage disequilibria to randomly generate and impede the progress of natural selection, and that these are eroded by recombination via sexual reproduction. Previous investigations have either analysed this phenomenon in detail for small numbers of loci, or performed population simulations for many loci. Here we present a quantitative genetic model for fitness, based on the Price Equation, in order to examine the theoretical consequences of randomly generated linkage disequilibria when there are many loci. In addition, most previous work has been concerned with the long-term consequences of deleterious linkage disequilibria for population fitness. The expected change in mean fitness between consecutive generations, a measure of short-term evolutionary success, is shown under random environmental influences to be related to the autocovariance in mean fitness between the generations, capturing the effects of stochastic forces such as genetic drift. Interaction between genetic drift and natural selection, due to randomly generated linkage disequilibria, is demonstrated to be one possible source of mean fitness autocovariance. This suggests a possible role for sexual reproduction in reducing the negative effects of genetic drift, thereby improving the short-term efficacy of natural selection. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Recombination within the nonstructural genes of the parvovirus minute virus of mice (MVM) generates functional levels of wild-type NS1, which can be detected in the absence of selective pressure following transfection of nonreplicating plasmids.

    PubMed

    Pearson, J L; Pintel, D J

    2000-03-30

    Recombination within the coding region of the nonstructural genes of minute virus of mice (MVM), which generates functional levels of wild-type NS1, was observed in the absence of selective pressure following cotransfection of nonreplicating plasmids. P38 activity was used as a measure of recombinant NS1 production, which, together with direct detection of recombinant-generated products by RT-PCR, allowed an estimation of recombination efficiency. In addition, we show that very low levels of wild-type NS1 were able to significantly transactivate P38. Given that recombination following cotransfection can generate NS1 at these levels, our observations have implications for the study of parvoviral genetics, the construction of recombinant parvoviral vectors for gene therapy applications, and perhaps other systems using cotransfection of plasmids that share homologous sequences. Copyright 2000 Academic Press.

  15. From what should we protect future generations: germ-line therapy or genetic screening?

    PubMed

    Mallia, Pierre; ten Have, Henk

    2003-01-01

    This paper discusses the issue of whether we have responsibilities to future generations with respect to genetic screening, including for purposes of selective abortion or discard. Future generations have been discussed at length among scholars. The concept of 'Guardian for Future Generations' is tackled and its main criticisms discussed. Whilst germ-line cures, it is argued, can only affect family trees, genetic screening and testing can have wider implications. If asking how this may affect future generations is a legitimate question and since we indeed make retrospective moral judgements, it would be wise to consider that future generations will make the same retrospective judgements on us. Moreover such technologies affect present embryos to which we indeed can be considered to have an obligation.

  16. Insect outbreak shifts the direction of selection from fast to slow growth rates in the long-lived conifer Pinus ponderosa.

    PubMed

    de la Mata, Raul; Hood, Sharon; Sala, Anna

    2017-07-11

    Long generation times limit species' rapid evolution to changing environments. Trees provide critical global ecosystem services, but are under increasing risk of mortality because of climate change-mediated disturbances, such as insect outbreaks. The extent to which disturbance changes the dynamics and strength of selection is unknown, but has important implications on the evolutionary potential of tree populations. Using a 40-y-old Pinus ponderosa genetic experiment, we provide rare evidence of context-dependent fluctuating selection on growth rates over time in a long-lived species. Fast growth was selected at juvenile stages, whereas slow growth was selected at mature stages under strong herbivory caused by a mountain pine beetle ( Dendroctonus ponderosae ) outbreak. Such opposing forces led to no net evolutionary response over time, thus providing a mechanism for the maintenance of genetic diversity on growth rates. Greater survival to mountain pine beetle attack in slow-growing families reflected, in part, a host-based life-history trade-off. Contrary to expectations, genetic effects on tree survival were greatest at the peak of the outbreak and pointed to complex defense responses. Our results suggest that selection forces in tree populations may be more relevant than previously thought, and have implications for tree population responses to future environments and for tree breeding programs.

  17. Direction selectivity in the larval zebrafish tectum is mediated by asymmetric inhibition.

    PubMed

    Grama, Abhinav; Engert, Florian

    2012-01-01

    The extraction of the direction of motion is an important computation performed by many sensory systems and in particular, the mechanism by which direction-selective retinal ganglion cells (DS-RGCs) in the retina acquire their selective properties, has been studied extensively. However, whether DS-RGCs simply relay this information to downstream areas or whether additional and potentially de novo processing occurs in these recipient structures is a matter of great interest. Neurons in the larval zebrafish tectum, the largest retino-recipent area in this animal, show direction-selective (DS) responses to moving visual stimuli but how these properties are acquired is still unknown. In order to study this, we first used two-photon calcium imaging to classify the population responses of tectal cells to bars moving at different speeds and in different directions. Subsequently, we performed in vivo whole cell electrophysiology on these DS tectal neurons and we found that their inhibitory inputs were strongly biased toward the null direction of motion, whereas the excitatory inputs showed little selectivity. In addition, we found that excitatory currents evoked by a stimulus moving in the preferred direction occurred before the inhibitory currents whereas a stimulus moving in the null direction evoked currents in the reverse temporal order. The membrane potential modulations resulting from these currents were enhanced by the spike generation mechanism to generate amplified direction selectivity in the spike output. Thus, our results implicate a local inhibitory circuit in generating direction selectivity in tectal neurons.

  18. Direction selectivity in the larval zebrafish tectum is mediated by asymmetric inhibition

    PubMed Central

    Grama, Abhinav; Engert, Florian

    2012-01-01

    The extraction of the direction of motion is an important computation performed by many sensory systems and in particular, the mechanism by which direction-selective retinal ganglion cells (DS-RGCs) in the retina acquire their selective properties, has been studied extensively. However, whether DS-RGCs simply relay this information to downstream areas or whether additional and potentially de novo processing occurs in these recipient structures is a matter of great interest. Neurons in the larval zebrafish tectum, the largest retino-recipent area in this animal, show direction-selective (DS) responses to moving visual stimuli but how these properties are acquired is still unknown. In order to study this, we first used two-photon calcium imaging to classify the population responses of tectal cells to bars moving at different speeds and in different directions. Subsequently, we performed in vivo whole cell electrophysiology on these DS tectal neurons and we found that their inhibitory inputs were strongly biased toward the null direction of motion, whereas the excitatory inputs showed little selectivity. In addition, we found that excitatory currents evoked by a stimulus moving in the preferred direction occurred before the inhibitory currents whereas a stimulus moving in the null direction evoked currents in the reverse temporal order. The membrane potential modulations resulting from these currents were enhanced by the spike generation mechanism to generate amplified direction selectivity in the spike output. Thus, our results implicate a local inhibitory circuit in generating direction selectivity in tectal neurons. PMID:22969706

  19. Women in Mauritania: The Effects of Drought and Migration on Their Economic Status and Implications for Development Programs.

    ERIC Educational Resources Information Center

    Smale, Melinda

    In order to indicate potential income-generating programs for women, 67 women in the river region and selected sites in the Assaba and the Guidimakha were interviewed in 1980 to illuminate effects of the 1970s-80s drought and male migration on Mauritanian women. Hypotheses were based on the drought causing unprecedented disruption to Mauritanian…

  20. Selectively altering belief formation in the human brain

    PubMed Central

    Sharot, Tali; Kanai, Ryota; Marston, David; Korn, Christoph W.; Rees, Geraint; Dolan, Raymond J.

    2012-01-01

    Humans form beliefs asymmetrically; we tend to discount bad news but embrace good news. This reduced impact of unfavorable information on belief updating may have important societal implications, including the generation of financial market bubbles, ill preparedness in the face of natural disasters, and overly aggressive medical decisions. Here, we selectively improved people’s tendency to incorporate bad news into their beliefs by disrupting the function of the left (but not right) inferior frontal gyrus using transcranial magnetic stimulation, thereby eliminating the engrained “good news/bad news effect.” Our results provide an instance of how selective disruption of regional human brain function paradoxically enhances the ability to incorporate unfavorable information into beliefs of vulnerability. PMID:23011798

  1. Artificial Photosystem I and II: Highly Selective solar fuels and tandem photocatalysis

    NASA Astrophysics Data System (ADS)

    Ding, Yuchen; Castellanos, Ignacio; Cerkovnik, Logan; Nagpal, Prashant

    2014-03-01

    Artificial photosynthesis, or generation of solar fuels from CO2/H2O, can provide an important alternative for rising CO2 emission and renewable energy generation. In our recent work, composite photocatalysts (CPCs) made from widebandgap nanotubes and different QDs were used to mimic Photosystem II (PS680) and I (PS700), respectively. By tuning the redox potentials using the size, composition and energy band alignment of QDs, we demonstrate highly selective (>90%) and efficient production of ethane, ethanol and acetaldehyde as solar fuels with different wavelengths of light. We also show that this selectivity is a result of precise energy band alignments (using cationic/anionic doping of nanotubes, QD size etc.), confirmed using measurements of electronic density of states, and alignment of higher redox potentials with hot-carriers can also lead to hot-carrier photocatalysis. This wavelength-selective CPCs can have important implications for inexpensive production of solar fuels including alkanes, alcohols, aldehydes and hydrogen, and making tandem structures (red, green, blue) with three CPCs, allowing almost full visible spectrum (410 ~ 730nm) utilization with different fuels produced simultaneously.

  2. Assessments of Wind-Energy Potential in Selected Sites from Three Geopolitical Zones in Nigeria: Implications for Renewable/Sustainable Rural Electrification

    PubMed Central

    Okeniyi, Joshua Olusegun; Ohunakin, Olayinka Soledayo; Okeniyi, Elizabeth Toyin

    2015-01-01

    Electricity generation in rural communities is an acute problem militating against socioeconomic well-being of the populace in these communities in developing countries, including Nigeria. In this paper, assessments of wind-energy potential in selected sites from three major geopolitical zones of Nigeria were investigated. For this, daily wind-speed data from Katsina in northern, Warri in southwestern and Calabar in southeastern Nigeria were analysed using the Gumbel and the Weibull probability distributions for assessing wind-energy potential as a renewable/sustainable solution for the country's rural-electrification problems. Results showed that the wind-speed models identified Katsina with higher wind-speed class than both Warri and Calabar that were otherwise identified as low wind-speed sites. However, econometrics of electricity power simulation at different hub heights of low wind-speed turbine systems showed that the cost of electric-power generation in the three study sites was converging to affordable cost per kWh of electric energy from the wind resource at each site. These power simulations identified cost/kWh of electricity generation at Kaduna as €0.0507, at Warri as €0.0774, and at Calabar as €0.0819. These bare positive implications on renewable/sustainable rural electrification in the study sites even as requisite options for promoting utilization of this viable wind-resource energy in the remote communities in the environs of the study sites were suggested. PMID:25879063

  3. Assessments of wind-energy potential in selected sites from three geopolitical zones in Nigeria: implications for renewable/sustainable rural electrification.

    PubMed

    Okeniyi, Joshua Olusegun; Ohunakin, Olayinka Soledayo; Okeniyi, Elizabeth Toyin

    2015-01-01

    Electricity generation in rural communities is an acute problem militating against socioeconomic well-being of the populace in these communities in developing countries, including Nigeria. In this paper, assessments of wind-energy potential in selected sites from three major geopolitical zones of Nigeria were investigated. For this, daily wind-speed data from Katsina in northern, Warri in southwestern and Calabar in southeastern Nigeria were analysed using the Gumbel and the Weibull probability distributions for assessing wind-energy potential as a renewable/sustainable solution for the country's rural-electrification problems. Results showed that the wind-speed models identified Katsina with higher wind-speed class than both Warri and Calabar that were otherwise identified as low wind-speed sites. However, econometrics of electricity power simulation at different hub heights of low wind-speed turbine systems showed that the cost of electric-power generation in the three study sites was converging to affordable cost per kWh of electric energy from the wind resource at each site. These power simulations identified cost/kWh of electricity generation at Kaduna as €0.0507, at Warri as €0.0774, and at Calabar as €0.0819. These bare positive implications on renewable/sustainable rural electrification in the study sites even as requisite options for promoting utilization of this viable wind-resource energy in the remote communities in the environs of the study sites were suggested.

  4. Insect outbreak shifts the direction of selection from fast to slow growth rates in the long-lived conifer Pinus ponderosa

    PubMed Central

    Sala, Anna

    2017-01-01

    Long generation times limit species’ rapid evolution to changing environments. Trees provide critical global ecosystem services, but are under increasing risk of mortality because of climate change-mediated disturbances, such as insect outbreaks. The extent to which disturbance changes the dynamics and strength of selection is unknown, but has important implications on the evolutionary potential of tree populations. Using a 40-y-old Pinus ponderosa genetic experiment, we provide rare evidence of context-dependent fluctuating selection on growth rates over time in a long-lived species. Fast growth was selected at juvenile stages, whereas slow growth was selected at mature stages under strong herbivory caused by a mountain pine beetle (Dendroctonus ponderosae) outbreak. Such opposing forces led to no net evolutionary response over time, thus providing a mechanism for the maintenance of genetic diversity on growth rates. Greater survival to mountain pine beetle attack in slow-growing families reflected, in part, a host-based life-history trade-off. Contrary to expectations, genetic effects on tree survival were greatest at the peak of the outbreak and pointed to complex defense responses. Our results suggest that selection forces in tree populations may be more relevant than previously thought, and have implications for tree population responses to future environments and for tree breeding programs. PMID:28652352

  5. Using Transcranial Direct Current Stimulation to Enhance Creative Cognition: Interactions between Task, Polarity, and Stimulation Site

    PubMed Central

    Weinberger, Adam B.; Green, Adam E.; Chrysikou, Evangelia G.

    2017-01-01

    Creative cognition is frequently described as involving two primary processes, idea generation and idea selection. A growing body of research has used transcranial direct current stimulation (tDCS) to examine the neural mechanisms implicated in each of these processes. This literature has yielded a diverse set of findings that vary depending on the location and type (anodal, cathodal, or both) of electrical stimulation employed, as well as the task’s reliance on idea generation or idea selection. As a result, understanding the interactions between stimulation site, polarity and task demands is required to evaluate the potential of tDCS to enhance creative performance. Here, we review tDCS designs that have elicited reliable and dissociable enhancements for creative cognition. Cathodal stimulation over the left inferior frontotemporal cortex has been associated with improvements on tasks that rely primarily on idea generation, whereas anodal tDCS over left dorsolateral prefrontal cortex (DLPFC) and frontopolar cortex has been shown to augment performance on tasks that impose high demands on creative idea selection. These results highlight the functional selectivity of tDCS for different components of creative thinking and confirm the dissociable contributions of left dorsal and inferior lateral frontotemporal cortex for different creativity tasks. We discuss promising avenues for future research that can advance our understanding of the effectiveness of tDCS as a method to enhance creative cognition. PMID:28559804

  6. Genome-wide analysis of allele frequency change in sunflower crop-wild hybrid populations evolving under natural conditions.

    PubMed

    Corbi, Jonathan; Baack, Eric J; Dechaine, Jennifer M; Seiler, Gerald; Burke, John M

    2018-01-01

    Crop-wild hybridization occurs in numerous plant species and could alter the genetic structure and evolutionary dynamics of wild populations. Studying crop-derived alleles in wild populations is also relevant to assessing/mitigating the risks associated with transgene escape. To date, crop-wild hybridization has generally been examined via short-term studies, typically within a single generation, focusing on few traits or genetic markers. Little is known about patterns of selection on crop-derived alleles over multiple generations, particularly at a genome-wide scale. Here, we documented patterns of natural selection in an experimental crop × wild sunflower population that was allowed to evolve under natural conditions for two generations at two locations. Allele frequencies at a genome-wide collection of SNPs were tracked across generations, and a common garden experiment was conducted to compare trait means between generations. These data allowed us to identify instances of selection on crop-derived alleles/traits and, in concert with QTL mapping results, test for congruence between our genotypic and phenotypic results. We found that natural selection overwhelmingly favours wild alleles and phenotypes. However, crop alleles in certain genomic regions can be favoured, and these changes often occurred in parallel across locations. We did not, however, consistently observe close agreement between our genotypic and phenotypic results. For example, when a trait evolved towards the wild phenotype, wild QTL alleles associated with that trait did not consistently increase in frequency. We discuss these results in the context of crop allele introgression into wild populations and implications for the management of GM crops. © 2017 John Wiley & Sons Ltd.

  7. The neovasculature homing motif NGR: more than meets the eye

    PubMed Central

    Curnis, Flavio; Arap, Wadih; Pasqualini, Renata

    2008-01-01

    A growing body of evidence suggests that peptides containing the Asn-Gly-Arg (NGR) motif can selectively recognize tumor neovasculature and can be used, therefore, for ligand-directed targeted delivery of various drugs and particles to tumors or to other tissues with an angiogenesis component. The neovasculature binding properties of these peptides rely on the interaction with an endothelium-associated form of aminopeptidase N (CD13), an enzyme that has been implicated in angiogenesis and tumor growth. Recent studies have shown that NGR can rapidly convert to isoaspartate-glycine-arginine (isoDGR) by asparagine deamidation, generating αvβ3 ligands capable of affecting endothelial cell functions and tumor growth. This review focuses on structural and functional properties of the NGR motif and its application in drug development for angiogenesis-dependent diseases. Furthermore, we discuss the time-dependent transition of NGR to isoDGR in natural proteins, such as fibronectins, and its potential role of as a “molecular timer” for generating new binding sites for integrins impli-cated in angiogenesis. PMID:18574027

  8. Evaluating Acoustic Emission Signals as an in situ process monitoring technique for Selective Laser Melting (SLM)

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

    Fisher, Karl A.; Candy, Jim V.; Guss, Gabe

    2016-10-14

    In situ real-time monitoring of the Selective Laser Melting (SLM) process has significant implications for the AM community. The ability to adjust the SLM process parameters during a build (in real-time) can save time, money and eliminate expensive material waste. Having a feedback loop in the process would allow the system to potentially ‘fix’ problem regions before a next powder layer is added. In this study we have investigated acoustic emission (AE) phenomena generated during the SLM process, and evaluated the results in terms of a single process parameter, of an in situ process monitoring technique.

  9. Antimicrobial aspects of inflammatory resolution in the mucosa: A role for pro-resolving mediators1

    PubMed Central

    Campbell, Eric L.; Serhan, Charles N.; Colgan, Sean P.

    2011-01-01

    Mucosal surfaces function as selectively permeable barriers between the host and the outside world. Given their close proximity to microbial antigens, mucosal surfaces have evolved sophisticated mechanisms for maintaining homeostasis and preventing excessive acute inflammatory reactions. The role attributed to epithelial cells was historically limited to serving as a selective barrier, in recent years numerous findings implicate an active role of the epithelium with pro-resolving mediators in the maintenance of immunological equilibrium. In this brief review, we highlight new evidence that the epithelium actively contributes to coordination and resolution of inflammation, principally through the generation of anti-inflammatory and pro-resolution lipid mediators. These autacoids, derived from ω-6 and ω-3 polyunsaturated fatty acids, are implicated in the initiation, progression and resolution of acute inflammation and display specific, epithelial-directed actions focused on mucosalhomeostasis. We also summarize present knowledge of mechanisms for resolution via regulation of epithelial-derived antimicrobial peptides in response to pro-resolving lipid mediators. PMID:21934099

  10. Feasibility of pedigree recording and genetic selection in village sheep flocks of smallholder farmers.

    PubMed

    Gizaw, Solomon; Goshme, Shenkute; Getachew, Tesfaye; Haile, Aynalem; Rischkowsky, Barbara; van Arendonk, Johan; Valle-Zárate, Anne; Dessie, Tadelle; Mwai, Ally Okeyo

    2014-06-01

    Pedigree recording and genetic selection in village flocks of smallholder farmers have been deemed infeasible by researchers and development workers. This is mainly due to the difficulty of sire identification under uncontrolled village breeding practices. A cooperative village sheep-breeding scheme was designed to achieve controlled breeding and implemented for Menz sheep of Ethiopia in 2009. In this paper, we evaluated the reliability of pedigree recording in village flocks by comparing genetic parameters estimated from data sets collected in the cooperative village and in a nucleus flock maintained under controlled breeding. Effectiveness of selection in the cooperative village was evaluated based on trends in breeding values over generations. Heritability estimates for 6-month weight recorded in the village and the nucleus flock were very similar. There was an increasing trend over generations in average estimated breeding values for 6-month weight in the village flocks. These results have a number of implications: the pedigree recorded in the village flocks was reliable; genetic parameters, which have so far been estimated based on nucleus data sets, can be estimated based on village recording; and appreciable genetic improvement could be achieved in village sheep selection programs under low-input smallholder farming systems.

  11. Aberrant supplementary motor complex and limbic activity during motor preparation in motor conversion disorder

    PubMed Central

    Voon, V; Brezing, C; Gallea, C; Hallett, M

    2014-01-01

    Background Conversion disorder is characterized by unexplained neurological symptoms presumed related to psychological issues. The main hypotheses to explain conversion paralysis, characterized by a lack of movement, include impairments in either motor intention or disruption of motor execution, and further, that hyperactive self-monitoring, limbic processing or top-down regulation from higher order frontal regions may interfere with motor execution. We have recently shown that conversion disorder with positive abnormal or excessive motor symptoms was associated with greater amygdala activity to arousing stimuli along with greater functional connectivity between the amgydala and supplementary motor area. Here we studied patients with such symptoms focusing on motor initiation. Methods Subjects performed either an internally or externally generated two-button action selection task in a functional MRI study. Results Eleven conversion disorder patients without major depression and 11 age- and gender-matched normal volunteers were assessed. During both internally and externally generated movement, conversion disorder patients relative to normal volunteers had lower left supplementary motor area (SMA) (implicated in motor initiation) and higher right amygdala, left anterior insula and bilateral posterior cingulate activity (implicated in assigning emotional salience). These findings were confirmed in a subgroup analysis of patients with tremor symptoms. During internally versus externally generated action in CD patients, the left SMA had lower functional connectivity with bilateral dorsolateral prefrontal cortices. Conclusion We propose a theory in which previously mapped conversion motor representations may in an arousing context hijack the voluntary action selection system which is both hypoactive and functionally disconnected from prefrontal top-down regulation. PMID:21935985

  12. Aberrant supplementary motor complex and limbic activity during motor preparation in motor conversion disorder.

    PubMed

    Voon, Valerie; Brezing, Christina; Gallea, Cecile; Hallett, Mark

    2011-11-01

    Conversion disorder (CD) is characterized by unexplained neurological symptoms presumed related to psychological issues. The main hypotheses to explain conversion paralysis, characterized by a lack of movement, include impairments in either motor intention or disruption of motor execution, and further, that hyperactive self-monitoring, limbic processing or top-down regulation from higher order frontal regions may interfere with motor execution. We have recently shown that CD with positive abnormal or excessive motor symptoms was associated with greater amygdala activity to arousing stimuli along with greater functional connectivity between the amygdala and supplementary motor area. Here we studied patients with such symptoms focusing on motor initiation. Subjects performed either an internally or externally generated 2-button action selection task in a functional MRI study. Eleven CD patients without major depression and 11 age- and gender-matched normal volunteers were assessed. During both internally and externally generated movement, conversion disorder patients relative to normal volunteers had lower left supplementary motor area (SMA) (implicated in motor initiation) and higher right amygdala, left anterior insula, and bilateral posterior cingulate activity (implicated in assigning emotional salience). These findings were confirmed in a subgroup analysis of patients with tremor symptoms. During internally versus externally generated action in CD patients, the left SMA had lower functional connectivity with bilateral dorsolateral prefrontal cortices. We propose a theory in which previously mapped conversion motor representations may in an arousing context hijack the voluntary action selection system, which is both hypoactive and functionally disconnected from prefrontal top-down regulation. Copyright © 2011 Movement Disorder Society.

  13. MHC class I-associated peptides derive from selective regions of the human genome.

    PubMed

    Pearson, Hillary; Daouda, Tariq; Granados, Diana Paola; Durette, Chantal; Bonneil, Eric; Courcelles, Mathieu; Rodenbrock, Anja; Laverdure, Jean-Philippe; Côté, Caroline; Mader, Sylvie; Lemieux, Sébastien; Thibault, Pierre; Perreault, Claude

    2016-12-01

    MHC class I-associated peptides (MAPs) define the immune self for CD8+ T lymphocytes and are key targets of cancer immunosurveillance. Here, the goals of our work were to determine whether the entire set of protein-coding genes could generate MAPs and whether specific features influence the ability of discrete genes to generate MAPs. Using proteogenomics, we have identified 25,270 MAPs isolated from the B lymphocytes of 18 individuals who collectively expressed 27 high-frequency HLA-A,B allotypes. The entire MAP repertoire presented by these 27 allotypes covered only 10% of the exomic sequences expressed in B lymphocytes. Indeed, 41% of expressed protein-coding genes generated no MAPs, while 59% of genes generated up to 64 MAPs, often derived from adjacent regions and presented by different allotypes. We next identified several features of transcripts and proteins associated with efficient MAP production. From these data, we built a logistic regression model that predicts with good accuracy whether a gene generates MAPs. Our results show preferential selection of MAPs from a limited repertoire of proteins with distinctive features. The notion that the MHC class I immunopeptidome presents only a small fraction of the protein-coding genome for monitoring by the immune system has profound implications in autoimmunity and cancer immunology.

  14. MHC class I–associated peptides derive from selective regions of the human genome

    PubMed Central

    Pearson, Hillary; Granados, Diana Paola; Durette, Chantal; Bonneil, Eric; Courcelles, Mathieu; Rodenbrock, Anja; Laverdure, Jean-Philippe; Côté, Caroline; Thibault, Pierre

    2016-01-01

    MHC class I–associated peptides (MAPs) define the immune self for CD8+ T lymphocytes and are key targets of cancer immunosurveillance. Here, the goals of our work were to determine whether the entire set of protein-coding genes could generate MAPs and whether specific features influence the ability of discrete genes to generate MAPs. Using proteogenomics, we have identified 25,270 MAPs isolated from the B lymphocytes of 18 individuals who collectively expressed 27 high-frequency HLA-A,B allotypes. The entire MAP repertoire presented by these 27 allotypes covered only 10% of the exomic sequences expressed in B lymphocytes. Indeed, 41% of expressed protein-coding genes generated no MAPs, while 59% of genes generated up to 64 MAPs, often derived from adjacent regions and presented by different allotypes. We next identified several features of transcripts and proteins associated with efficient MAP production. From these data, we built a logistic regression model that predicts with good accuracy whether a gene generates MAPs. Our results show preferential selection of MAPs from a limited repertoire of proteins with distinctive features. The notion that the MHC class I immunopeptidome presents only a small fraction of the protein-coding genome for monitoring by the immune system has profound implications in autoimmunity and cancer immunology. PMID:27841757

  15. Use it or lose it: reproductive implications of ecological specialization in a haematophagous ectoparasite.

    PubMed

    Arbiv, A; Khokhlova, I S; Ovadia, O; Novoplansky, A; Krasnov, B R

    2012-06-01

    Using experimentally induced disruptive selection, we tested two hypotheses regarding the evolution of specialization in parasites. The 'trade-off' hypothesis suggests that adaptation to a specific host may come at the expense of a reduced performance when exploiting another host. The alternative 'relaxed selection' hypothesis suggests that the ability to exploit a given host would deteriorate when becoming obsolete. Three replicate populations of a flea Xenopsylla ramesis were maintained on each of two rodent hosts, Meriones crassus and Dipodillus dasyurus, for nine generations. Fleas maintained on a specific host species for a few generations substantially decreased their reproductive performance when transferred to an alternative host species, whereas they generally did not increase their performance on their maintenance host. The results support the 'relaxed selection' hypothesis of the evolution of ecological specialization in haematophagous ectoparasites, while suggesting that trade-offs are unlikely drivers of specialization. Further work is needed to study the extent by which the observed specializations are based on epigenetic or genetic modifications. © 2012 The Authors. Journal of Evolutionary Biology © 2012 European Society For Evolutionary Biology.

  16. Selective methylative homologation: an alternate route to alkane upgrading.

    PubMed

    Bercaw, John E; Hazari, Nilay; Labinger, Jay A; Scott, Valerie J; Sunley, Glenn J

    2008-09-10

    InI3 catalyzes the reaction of branched alkanes with methanol to produce heavier and more highly branched alkanes, which are more valuable fuels. The reaction of 2,3-dimethylbutane with methanol in the presence of InI3 at 180-200 degrees C affords the maximally branched C7 alkane, 2,2,3-trimethylbutane (triptane). With the addition of catalytic amounts of adamantane the selectivity of this transformation can be increased up to 60%. The lighter branched alkanes isobutane and isopentane also react with methanol to generate triptane, while 2-methylpentane is converted into 2,3-dimethylpentane and other more highly branched species. Observations implicate a chain mechanism in which InI3 activates branched alkanes to produce tertiary carbocations which are in equilibrium with olefins. The latter react with a methylating species generated from methanol and InI3 to give the next-higher carbocation, which accepts a hydride from the starting alkane to form the homologated alkane and regenerate the original carbocation. Adamantane functions as a hydride transfer agent and thus helps to minimize competing side reactions, such as isomerization and cracking, that are detrimental to selectivity.

  17. Short-chain fatty acid sensing in rat duodenum

    PubMed Central

    Akiba, Yasutada; Inoue, Takuya; Kaji, Izumi; Higashiyama, Masaaki; Narimatsu, Kazuyuki; Iwamoto, Ken-ichi; Watanabe, Masahiko; Guth, Paul H; Engel, Eli; Kuwahara, Atsukazu; Kaunitz, Jonathan D

    2015-01-01

    Intraduodenal fatty acids (FA) and bacterial overgrowth, which generate short-chain FAs (SCFAs), have been implicated in the generation of functional dyspepsia symptoms. We studied the mechanisms by which luminal SCFA perfusion affects duodenal HCO3− secretion (DBS), a measure of mucosal neurohumoral activation. Free fatty acid receptor (FFAR) 1 (FFA1), which binds long-chain FA (LCFA), and SCFA receptors FFA2 and FFA3 were immunolocalised to duodenal enteroendocrine cells. FFA3 colocalised with glucagon-like peptide (GLP)-1, whereas FFA2 colocalised with 5-HT. Luminal perfusion of the SCFA acetate or propionate increased DBS, enhanced by dipeptidyl peptidase-IV (DPPIV) inhibition, at the same time as increasing GLP-2 portal blood concentrations. Acetate-induced DBS was partially inhibited by monocarboxylate/HCO3− exchanger inhibition without affecting GLP-2 release, implicating acetate absorption in the partial mediation of DBS. A selective FFA2 agonist dose-dependently increased DBS, unaffected by DPPIV inhibition or by cholecystokinin or 5-HT3 receptor antagonists, but was inhibited by atropine and a 5-HT4 antagonist. By contrast, a selective FFA1 agonist increased DBS accompanied by GLP-2 release, enhanced by DPPIV inhibition and inhibited by a GLP-2 receptor antagonist. Activation of FFA1 by LCFA and presumably FFA3 by SCFA increased DBS via GLP-2 release, whereas FFA2 activation stimulated DBS via muscarinic and 5-HT4 receptor activation. SCFA/HCO3− exchange also appears to be present in the duodenum. The presence of duodenal fatty acid sensing receptors that signal hormone release and possibly signal neural activation may be implicated in the pathogenesis of functional dyspepsia. PMID:25433076

  18. Group selections among laboratory populations of Tribolium.

    PubMed

    Wade, M J

    1976-12-01

    Selection at the population level or group selection is defined as genetic change that is brought about or maintained by the differential extinction and/or proliferation of populations. Group selection for both increased and decreased adult population size was carried out among laboratory populations of Tribolium castaneum at 37-day intervals. The effect of individual selection within populations on adult population size was evaluated in an additional control series of populations. The response in the group selection treatments occurred rapidly, within three or four generations, and was large in magnitude, at times differing from the controls by over 200%. This response to selection at the populational level occurred despite strong individual selection which caused a decline in the mean size of the control populations from over 200 adults to near 50 adults in nine 37-day intervals. "Assay" experiments indicated that selective changes in fecundity, developmental time, body weight, and cannibalism rates were responsible in part for the observed treatment differences in adult population size. These findings have implications in terms of speciation in organisms whose range is composed of many partially isolated local populations.

  19. EVOLUTION OF DIVERGENT FEMALE MATING PREFERENCE IN RESPONSE TO EXPERIMENTAL SEXUAL SELECTION

    PubMed Central

    Debelle, Allan; Ritchie, Michael G; Snook, Rhonda R

    2014-01-01

    Sexual selection is predicted to drive the coevolution of mating signals and preferences (mating traits) within populations, and could play a role in speciation if sexual isolation arises due to mating trait divergence between populations. However, few studies have demonstrated that differences in mating traits between populations result from sexual selection alone. Experimental evolution is a promising approach to directly examine the action of sexual selection on mating trait divergence among populations. We manipulated the opportunity for sexual selection (low vs. high) in populations of Drosophila pseudoobscura. Previous studies on these experimental populations have shown that sexual selection manipulation resulted in the divergence between sexual selection treatments of several courtship song parameters, including interpulse interval (IPI) which markedly influences male mating success. Here, we measure female preference for IPI using a playback design to test for preference divergence between the sexual selection treatments after 130 generations of experimental sexual selection. The results suggest that female preference has coevolved with male signal, in opposite directions between the sexual selection treatments, providing direct evidence of the ability of sexual selection to drive the divergent coevolution of mating traits between populations. We discuss the implications in the context sexual selection and speciation. PMID:24931497

  20. Laboratory plasma interactions experiments: Results and implications to future space systems

    NASA Technical Reports Server (NTRS)

    Leung, Philip

    1986-01-01

    The experimental results discussed show the significance of the effects caused by spacecraft plasma interactions, in particular the generation of Electromagnetic Interference. As the experimental results show, the magnitude of the adverse effects induced by Plasma Interactions (PI) will be more significant for spacecraft of the next century. Therefore, research is needed to control possible adverse effects. Several techniques to control the selected PI effects are discussed. Tests, in the form of flight experiments, are needed to validate these proposed ideas.

  1. In silico cancer modeling: is it ready for primetime?

    PubMed Central

    Deisboeck, Thomas S; Zhang, Le; Yoon, Jeongah; Costa, Jose

    2011-01-01

    SUMMARY At the dawn of the era of personalized, systems-driven medicine, computational or in silico modeling and the simulation of disease processes is becoming increasingly important for hypothesis generation and data integration in both experiment and clinics alike. Arguably, this is nowhere more visible than in oncology. To illustrate the field’s vast potential as well as its current limitations we briefly review selected works on modeling malignant brain tumors. Implications for clinical practice, including trial design and outcome prediction are also discussed. PMID:18852721

  2. Hydrological simulations in the Rhine basin.

    PubMed

    van den Hurk, B; Beersma, J; Lenderink, G

    2005-01-01

    Simulations with regional climate models (RCMs), carried out for the Rhine basin, have been analyzed in the context of implications of the possible future discharge of the Rhine river. In a first analysis, the runoff generated by the RCMs is compared to observations, in order to detect the way the RCMs treat anomalies in precipitation in their land surface component. A second analysis is devoted to the frequency distribution of area averaged precipitation, and the impact of selection of various driving global climate models.

  3. A trait-based approach for examining microbial community assembly

    NASA Astrophysics Data System (ADS)

    Prest, T. L.; Nemergut, D.

    2015-12-01

    Microorganisms regulate all of Earth's major biogeochemical cycles and an understanding of how microbial communities assemble is a key part in evaluating controls over many types of ecosystem processes. Rapid advances in technology and bioinformatics have led to a better appreciation for the variation in microbial community structure in time and space. Yet, advances in theory are necessary to make sense of these data and allow us to generate unifying hypotheses about the causes and consequences of patterns in microbial biodiversity and what they mean for ecosystem function. Here, I will present a metaanalysis of microbial community assembly from a variety of successional and post-disturbance systems. Our analysis shows various distinct patterns in community assembly, and the potential importance of nutrients and dispersal in shaping microbial community beta diversity in these systems. We also used a trait-based approach to generate hypotheses about the mechanisms driving patterns of microbial community assembly and the implications for function. Our work reveals the importance of rRNA operon copy number as a community aggregated trait in helping to reconcile differences in community dynamics between distinct types of successional and disturbed systems. Specifically, our results demonstrate that decreases in average copy number can be a common feature of communities across various drivers of ecological succession, supporting a transition from an r-selected to a K-selected community. Importantly, our work supports the scaling of the copy number trait over multiple levels of biological organization, from cells to populations and communities, and has implications for both ecology and evolution. Trait-based approaches are an important next step to generate and test hypotheses about the forces structuring microbial communities and the subsequent consequences for ecosystem function.

  4. Quantitative genetic models of sexual conflict based on interacting phenotypes.

    PubMed

    Moore, Allen J; Pizzari, Tommaso

    2005-05-01

    Evolutionary conflict arises between reproductive partners when alternative reproductive opportunities are available. Sexual conflict can generate sexually antagonistic selection, which mediates sexual selection and intersexual coevolution. However, despite intense interest, the evolutionary implications of sexual conflict remain unresolved. We propose a novel theoretical approach to study the evolution of sexually antagonistic phenotypes based on quantitative genetics and the measure of social selection arising from male-female interactions. We consider the phenotype of one sex as both a genetically influenced evolving trait as well as the (evolving) social environment in which the phenotype of the opposite sex evolves. Several important points emerge from our analysis, including the relationship between direct selection on one sex and indirect effects through selection on the opposite sex. We suggest that the proposed approach may be a valuable tool to complement other theoretical approaches currently used to study sexual conflict. Most importantly, our approach highlights areas where additional empirical data can help clarify the role of sexual conflict in the evolutionary process.

  5. Artificial selection for food colour preferences.

    PubMed

    Cole, Gemma L; Endler, John A

    2015-04-07

    Colour is an important factor in food detection and acquisition by animals using visually based foraging. Colour can be used to identify the suitability of a food source or improve the efficiency of food detection, and can even be linked to mate choice. Food colour preferences are known to exist, but whether these preferences are heritable and how these preferences evolve is unknown. Using the freshwater fish Poecilia reticulata, we artificially selected for chase behaviour towards two different-coloured moving stimuli: red and blue spots. A response to selection was only seen for chase behaviours towards the red, with realized heritabilities ranging from 0.25 to 0.30. Despite intense selection, no significant chase response was recorded for the blue-selected lines. This lack of response may be due to the motion-detection mechanism in the guppy visual system and may have novel implications for the evolvability of responses to colour-related signals. The behavioural response to several colours after five generations of selection suggests that the colour opponency system of the fish may regulate the response to selection. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  6. Artificial selection for food colour preferences

    PubMed Central

    Cole, Gemma L.; Endler, John A.

    2015-01-01

    Colour is an important factor in food detection and acquisition by animals using visually based foraging. Colour can be used to identify the suitability of a food source or improve the efficiency of food detection, and can even be linked to mate choice. Food colour preferences are known to exist, but whether these preferences are heritable and how these preferences evolve is unknown. Using the freshwater fish Poecilia reticulata, we artificially selected for chase behaviour towards two different-coloured moving stimuli: red and blue spots. A response to selection was only seen for chase behaviours towards the red, with realized heritabilities ranging from 0.25 to 0.30. Despite intense selection, no significant chase response was recorded for the blue-selected lines. This lack of response may be due to the motion-detection mechanism in the guppy visual system and may have novel implications for the evolvability of responses to colour-related signals. The behavioural response to several colours after five generations of selection suggests that the colour opponency system of the fish may regulate the response to selection. PMID:25740894

  7. A Review of the Empirical Generations at Work Research: Implications for School Leaders and Future Research

    ERIC Educational Resources Information Center

    Edge, Karen

    2014-01-01

    Most schools currently employ three generations of teachers and leaders: Baby Boomers (1946-65), Generation X (1966-80) and Generation Y (1981-2003). However, the implications for school leaders of multi-generational schools remain relatively unexplored. This paper examines the empirical multi-disciplinary generations at work evidence to identify…

  8. Generator-specific targets of mitochondrial reactive oxygen species.

    PubMed

    Bleier, Lea; Wittig, Ilka; Heide, Heinrich; Steger, Mirco; Brandt, Ulrich; Dröse, Stefan

    2015-01-01

    To understand the role of reactive oxygen species (ROS) in oxidative stress and redox signaling it is necessary to link their site of generation to the oxidative modification of specific targets. Here we have studied the selective modification of protein thiols by mitochondrial ROS that have been implicated as deleterious agents in a number of degenerative diseases and in the process of biological aging, but also as important players in cellular signal transduction. We hypothesized that this bipartite role might be based on different generator sites for "signaling" and "damaging" ROS and a directed release into different mitochondrial compartments. Because two main mitochondrial ROS generators, complex I (NADH:ubiquinone oxidoreductase) and complex III (ubiquinol:cytochrome c oxidoreductase; cytochrome bc1 complex), are known to predominantly release superoxide and the derived hydrogen peroxide (H2O2) into the mitochondrial matrix and the intermembrane space, respectively, we investigated whether these ROS generators selectively oxidize specific protein thiols. We used redox fluorescence difference gel electrophoresis analysis to identify redox-sensitive targets in the mitochondrial proteome of intact rat heart mitochondria. We observed that the modified target proteins were distinctly different when complex I or complex III was employed as the source of ROS. These proteins are potential targets involved in mitochondrial redox signaling and may serve as biomarkers to study the generator-dependent dual role of mitochondrial ROS in redox signaling and oxidative stress. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Paleolithic vs. modern diets--selected pathophysiological implications.

    PubMed

    Eaton, S B; Eaton, S B

    2000-04-01

    The nutritional patterns of Paleolithic humans influenced genetic evolution during the time segment within which defining characteristics of contemporary humans were selected. Our genome can have changed little since the beginnings of agriculture, so, genetically, humans remain Stone Agers--adapted for a Paleolithic dietary regimen. Such diets were based chiefly on wild game, fish and uncultivated plant foods. They provided abundant protein; a fat profile much different from that of affluent Western nations; high fibre; carbohydrate from fruits and vegetables (and some honey) but not from cereals, refined sugars and dairy products; high levels of micronutrients and probably of phytochemicals as well. Differences between contemporary and ancestral diets have many pathophysiological implications. This review addresses phytochemicals and cancer; calcium, physical exertion, bone mineral density and bone structural geometry; dietary protein, potassium, renal acid secretion and urinary calcium loss; and finally sarcopenia, adiposity, insulin receptors and insulin resistance. While not, yet, a basis for formal recommendations, awareness of Paleolithic nutritional patterns should generate novel, testable hypotheses grounded in evolutionary theory and it should dispel complacency regarding currently accepted nutritional tenets.

  10. Psychological empowerment and job satisfaction between Baby Boomer and Generation X nurses.

    PubMed

    Sparks, Amy M

    2012-05-01

    This paper is a report of a study of differences in nurses' generational psychological empowerment and job satisfaction. Generations differ in work styles such as autonomy, work ethics, involvement, views on leadership, and primary views on what constitutes innovation, quality, and service. A secondary analysis was conducted from two data sets resulting in a sample of 451 registered nurses employed at five hospitals in West Virginia. One data set was gathered from a convenience sample and one from a randomly selected sample. Data were collected from 2000 to 2004. Baby Boomer nurses reported higher mean total psychological empowerment scores than Generation X nurses. There were no differences in total job satisfaction scores between the generations. There were significant differences among the generations' psychological empowerment scores. Generational differences related to psychological empowerment could provide insight into inconsistent findings related to nurse job satisfaction. Nurse administrators may consider this evidence when working on strategic plans to motivate and entice Generation X nurses and retain Baby Boomers. Although implications based on this study are tentative, the results indicate the need for administrators to consider the differences between Baby Boomer and Generation X nurses. © 2011 Blackwell Publishing Ltd.

  11. Future directions in personality, occupational and medical selection: myths, misunderstandings, measurement, and suggestions.

    PubMed

    Ferguson, Eamonn; Lievens, Filip

    2017-05-01

    This paper has two objectives: (1) presenting recent advances in personality theory whereby personality traits are conceptualized within a framework that focuses on the dynamic interactions of behaviour, biology, context, and states, and (2) discussing the implications of these developments for measurement and medical selection. We start by presenting evidence that traits are no longer regarded as stable deterministic predictors of behaviour. Instead, traits are found to change across generations, the life span, and in response to environmental contingencies. Thus, there is an urgent need to explore how traits change as function of medical education. Second, drawing on recent theory and research (behavioural reaction norms and the density distribution model) we highlight evidence to show how the expression of trait relevant behaviour is dependent on context, and is distributed with an average (typical behaviour or personality) and a variance (plasticity or adaptability), with traditional personality measure associated with typical responding. Third, we demystify that some traits are better than others showing that so-called "good" traits have a dark-side. Fourth, we show how these developments impact on how personality might be assessed, thereby presenting recent evidence on the use of contextualized personality measures, situational judgment tests, other reports, and implicit measures. Throughout the paper, we outline the key implications of these developments for medical selection practices.

  12. Carbamate resistance in Anopheles albimanus

    PubMed Central

    Ariaratnam, Veluppillai; Georghiou, George P.

    1974-01-01

    Carbamate resistance induced in a field strain of A. albimanus from El Salvador by laboratory selection with propoxur remained fairly stable on relaxation of selection pressure for 12 generations. Studies on cross and multiple resistance showed that this strain was not resistant to the pyrethroids bioresmethrin, bioallethrin, and CRC 11451, although resistance to cismethrin was 2.3-fold. Resistance to 10 carbamates of various structural configurations covered a broad spectrum, being for example >100× to Bay 38799, Ciba 17474, and Ciba 18107, 74.8× to carbaryl, 20.57× to carbanolate, and 2.27× to Stauffer R 15396. The possible causes of the presence or absence of cross resistance and the implications of stability of resistance and cross resistance are discussed. PMID:4549614

  13. Evolution of divergent female mating preference in response to experimental sexual selection.

    PubMed

    Debelle, Allan; Ritchie, Michael G; Snook, Rhonda R

    2014-09-01

    Sexual selection is predicted to drive the coevolution of mating signals and preferences (mating traits) within populations, and could play a role in speciation if sexual isolation arises due to mating trait divergence between populations. However, few studies have demonstrated that differences in mating traits between populations result from sexual selection alone. Experimental evolution is a promising approach to directly examine the action of sexual selection on mating trait divergence among populations. We manipulated the opportunity for sexual selection (low vs. high) in populations of Drosophila pseudoobscura. Previous studies on these experimental populations have shown that sexual selection manipulation resulted in the divergence between sexual selection treatments of several courtship song parameters, including interpulse interval (IPI) which markedly influences male mating success. Here, we measure female preference for IPI using a playback design to test for preference divergence between the sexual selection treatments after 130 generations of experimental sexual selection. The results suggest that female preference has coevolved with male signal, in opposite directions between the sexual selection treatments, providing direct evidence of the ability of sexual selection to drive the divergent coevolution of mating traits between populations. We discuss the implications in the context sexual selection and speciation. © 2014 The Authors. Evolution published by Wiley Periodicals, Inc. on behalf of The Society for the Study of Evolution.

  14. A theory of germinal center B cell selection, division, and exit.

    PubMed

    Meyer-Hermann, Michael; Mohr, Elodie; Pelletier, Nadége; Zhang, Yang; Victora, Gabriel D; Toellner, Kai-Michael

    2012-07-26

    High-affinity antibodies are generated in germinal centers in a process involving mutation and selection of B cells. Information processing in germinal center reactions has been investigated in a number of recent experiments. These have revealed cell migration patterns, asymmetric cell divisions, and cell-cell interaction characteristics, used here to develop a theory of germinal center B cell selection, division, and exit (the LEDA model). According to this model, B cells selected by T follicular helper cells on the basis of successful antigen processing always return to the dark zone for asymmetric division, and acquired antigen is inherited by one daughter cell only. Antigen-retaining B cells differentiate to plasma cells and leave the germinal center through the dark zone. This theory has implications for the functioning of germinal centers because compared to previous models, high-affinity antibodies appear one day earlier and the amount of derived plasma cells is considerably larger. Copyright © 2012 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Social knowledge in children with language impairments: examination of strategies, predicted consequences, and goals in peer conflict situations.

    PubMed

    Timler, Geralyn R

    2008-09-01

    This study investigated social knowledge in school-age children, aged 8-12 years, with and without language impairment (LI and TD groups). A hypothetical peer conflict task was administered to examine the relationship among prosocial responses and parent/teacher ratings of children's social behaviours. Stimuli included 12 hypothetical peer conflict vignettes presented in an open-ended and forced choice condition. The LI group generated (open-ended) and selected (forced choice) fewer prosocial strategies. When asked to predict a friend's reaction to a selected conflict resolution strategy, the LI group predicted fewer positive consequences; however, the proportion of prosocial strategies followed by prediction of a positive peer consequence was similar across groups. Both groups identified more self-interest than relationship goals as the rationale for selected strategies. In the LI group, teacher ratings of children's social skills and problems in peer provocation situations were associated with selection of prosocial strategies. Implications for clinical service providers are discussed.

  16. Isoform-selective chemical inhibition of mDia-mediated actin assembly

    PubMed Central

    Gauvin, Timothy J.; Fukui, Jami; Peterson, Jeffrey R.; Higgs, Henry N.

    2009-01-01

    Formins are potent actin assembly factors. Diaphanous formins, including mDia1, mDia2, and mDia3 in mammals, are implicated in mitosis and cytokinesis but no chemical interactors have been reported. We developed an in vitro screen for inhibitors of actin assembly by mDia1, and identified an inhibitor of mDia1 and mDia2 that does not inhibit mDia3 at the concentrations tested. These results establish the druggability of mDia formins and introduce a first generation inhibitor. PMID:19764708

  17. Rational use of medicines in older adults: Can we do better during clinical development?

    PubMed

    Saeed, M A; Vlasakakis, G; Della Pasqua, O

    2015-05-01

    There is an evidence gap to ensuring safe/effective use of medicines in older adults. Generating clinical data in these patients poses ethical and operational challenges, yielding results that may not be generalizable to the overall population. Modeling and simulation (M&S) is proposed as a basis for assessing the impact of age-related changes and their clinical implications. M&S can be used in conjunction with bridging and extrapolation to ensure the selection of appropriate dose(s)/regimen(s) in this population. © 2015 ASCPT.

  18. Adenosine mimetics as inhibitors of NAD+-dependent histone deacetylases, from kinase to sirtuin inhibition.

    PubMed

    Trapp, Johannes; Jochum, Anne; Meier, Rene; Saunders, Laura; Marshall, Brett; Kunick, Conrad; Verdin, Eric; Goekjian, Peter; Sippl, Wolfgang; Jung, Manfred

    2006-12-14

    NAD+-dependent histone deacetylases, sirtuins, cleave acetyl groups from lysines of histones and other proteins to regulate their activity. Identification of potent selective inhibitors would help to elucidate sirtuin biology and could lead to useful therapeutic agents. NAD+ has an adenosine moiety that is also present in the kinase cofactor ATP. Kinase inhibitors based upon adenosine mimesis may thus also target NAD+-dependent enzymes. We present a systematic approach using adenosine mimics from one cofactor class (kinase inhibitors) as a viable method to generate new lead structures in another cofactor class (sirtuin inhibitors). Our findings have broad implications for medicinal chemistry and specifically for sirtuin inhibitor design. Our results also raise a question as to whether selectivity profiling for kinase inhibitors should be limited to ATP-dependent targets.

  19. Selection for long and short sleep duration in Drosophila melanogaster reveals the complex genetic network underlying natural variation in sleep

    PubMed Central

    2017-01-01

    Why do some individuals need more sleep than others? Forward mutagenesis screens in flies using engineered mutations have established a clear genetic component to sleep duration, revealing mutants that convey very long or short sleep. Whether such extreme long or short sleep could exist in natural populations was unknown. We applied artificial selection for high and low night sleep duration to an outbred population of Drosophila melanogaster for 13 generations. At the end of the selection procedure, night sleep duration diverged by 9.97 hours in the long and short sleeper populations, and 24-hour sleep was reduced to 3.3 hours in the short sleepers. Neither long nor short sleeper lifespan differed appreciably from controls, suggesting little physiological consequences to being an extreme long or short sleeper. Whole genome sequence data from seven generations of selection revealed several hundred thousand changes in allele frequencies at polymorphic loci across the genome. Combining the data from long and short sleeper populations across generations in a logistic regression implicated 126 polymorphisms in 80 candidate genes, and we confirmed three of these genes and a larger genomic region with mutant and chromosomal deficiency tests, respectively. Many of these genes could be connected in a single network based on previously known physical and genetic interactions. Candidate genes have known roles in several classic, highly conserved developmental and signaling pathways—EGFR, Wnt, Hippo, and MAPK. The involvement of highly pleiotropic pathway genes suggests that sleep duration in natural populations can be influenced by a wide variety of biological processes, which may be why the purpose of sleep has been so elusive. PMID:29240764

  20. Selection for long and short sleep duration in Drosophila melanogaster reveals the complex genetic network underlying natural variation in sleep.

    PubMed

    Harbison, Susan T; Serrano Negron, Yazmin L; Hansen, Nancy F; Lobell, Amanda S

    2017-12-01

    Why do some individuals need more sleep than others? Forward mutagenesis screens in flies using engineered mutations have established a clear genetic component to sleep duration, revealing mutants that convey very long or short sleep. Whether such extreme long or short sleep could exist in natural populations was unknown. We applied artificial selection for high and low night sleep duration to an outbred population of Drosophila melanogaster for 13 generations. At the end of the selection procedure, night sleep duration diverged by 9.97 hours in the long and short sleeper populations, and 24-hour sleep was reduced to 3.3 hours in the short sleepers. Neither long nor short sleeper lifespan differed appreciably from controls, suggesting little physiological consequences to being an extreme long or short sleeper. Whole genome sequence data from seven generations of selection revealed several hundred thousand changes in allele frequencies at polymorphic loci across the genome. Combining the data from long and short sleeper populations across generations in a logistic regression implicated 126 polymorphisms in 80 candidate genes, and we confirmed three of these genes and a larger genomic region with mutant and chromosomal deficiency tests, respectively. Many of these genes could be connected in a single network based on previously known physical and genetic interactions. Candidate genes have known roles in several classic, highly conserved developmental and signaling pathways-EGFR, Wnt, Hippo, and MAPK. The involvement of highly pleiotropic pathway genes suggests that sleep duration in natural populations can be influenced by a wide variety of biological processes, which may be why the purpose of sleep has been so elusive.

  1. Determining the biomass fraction of mixed waste fuels: A comparison of existing industry and {sup 14}C-based methodologies

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

    Muir, G.K.P., E-mail: Graham.Muir@glasgow.ac.uk; Hayward, S.; Tripney, B.G.

    2015-01-15

    Highlights: • Compares industry standard and {sup 14}C methods for determining bioenergy content of MSW. • Differences quantified through study at an operational energy from waste plant. • Manual sort and selective dissolution are unreliable measures of feedstock bioenergy. • {sup 14}C methods (esp. AMS) improve precision and reliability of bioenergy determination. • Implications for electricity generators and regulators for award of bio-incentives. - Abstract: {sup 14}C analysis of flue gas by accelerator mass spectrometry (AMS) and liquid scintillation counting (LSC) were used to determine the biomass fraction of mixed waste at an operational energy-from-waste (EfW) plant. Results were convertedmore » to bioenergy (% total) using mathematical algorithms and assessed against existing industry methodologies which involve manual sorting and selective dissolution (SD) of feedstock. Simultaneous determinations using flue gas showed excellent agreement: 44.8 ± 2.7% for AMS and 44.6 ± 12.3% for LSC. Comparable bioenergy results were obtained using a feedstock manual sort procedure (41.4%), whilst a procedure based on selective dissolution of representative waste material is reported as 75.5% (no errors quoted). {sup 14}C techniques present significant advantages in data acquisition, precision and reliability for both electricity generator and industry regulator.« less

  2. Natural gas in the energy industry of the 21st century

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

    Cuttica, J.

    1995-12-31

    This paper provides a gas industry perspective on the impacts of restructuring the natural gas and electric industries. The four main implications discussed are: (1) market trends, (2) strategic positioning, (3) significant market implications, and (4) issues for the future. Market trends discussed include transitioning rate of return to market competition and regulatory impacts. Significant market implications for gas-fired generation identified include limited new generation investment, extension of existing plants, and an opportunity for distributed power generation. 12 tabs.

  3. Sexually antagonistic polymorphism in simultaneous hermaphrodites

    PubMed Central

    Jordan, Crispin Y.; Connallon, Tim

    2015-01-01

    In hermaphrodites, pleiotropic genetic tradeoffs between female and male reproductive functions can lead to sexually antagonistic (SA) selection, where individual alleles have conflicting fitness effects on each sex function. While an extensive theory of SA selection exists for dioecious species, these results have not been generalized to hermaphrodites. We develop population genetic models of SA selection in simultaneous hermaphrodites, and evaluate effects of dominance, selection on each sex function, self-fertilization, and population size, on the maintenance of polymorphism. Under obligate outcrossing, hermaphrodite model predictions converge exactly with those of dioecious populations. Self-fertilization in hermaphrodites generates three points of divergence with dioecious theory. First, opportunities for stable polymorphism decline sharply and become less sensitive to dominance with increased selfing. Second, selfing introduces an asymmetry in the relative importance of selection through male versus female reproductive functions, expands the parameter space favorable for the evolutionary invasion of female-beneficial alleles, and restricts invasion criteria for male-beneficial alleles. Finally, contrary to models of unconditionally beneficial alleles, selfing decreases genetic hitchhiking effects of invading SA alleles, and should therefore decrease these population genetic signals of SA polymorphisms. We discuss implications of SA selection in hermaphrodites, including its potential role in the evolution of “selfing syndromes”. PMID:25311368

  4. Queerin' the PGD clinic : human enhancement and the future of bodily diversity.

    PubMed

    Sparrow, Robert

    2013-06-01

    Disability activists influenced by queer theory and advocates of "human enhancement" have each disputed the idea that what is "normal" is normatively significant, which currently plays a key role in the regulation of pre-implantation genetic diagnosis (PGD). Previously, I have argued that the only way to avoid the implication that parents have strong reasons to select children of one sex (most plausibly, female) over the other is to affirm the moral significance of sexually dimorphic human biological norms. After outlining the logic that generates this conclusion, I investigate the extent to which it might also facilitate an alternative, progressive, opening up of the notion of the normal and of the criteria against which we should evaluate the relative merits of different forms of embodiment. This paper therefore investigates the implications of ideas derived from queer theory for the future of PGD and of PGD for the future of queerness.

  5. DNA adducts of ethylene dibromide: Aspects of formation and mutagenicity

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

    Cmarik, J.L.

    1,2-Dibromoethane (ethylene dibromide, EDB), a potential human carcinogen, undergoes bioactivation by the pathway of glutathione (GSH) conjugation, which generates a reactive intermediate capable of alkylating DNA. The major DNA adduct formed is S-[2-(N[sup 7]-guanyl)ethyl]GSH. This dissertation examined the bioactivation of EDB and the formation of DNA adducts. The selectivity of purified rat and human GSH S-transferases for EDB was examined in vitro. An assay was developed to measure the formation of S,S[prime]-ethylene-bis(GSH). The [alpha] class of the GSH S-transferases was responsible for the majority of EDB-GSH conjugation with both the rat and human enzymes. Human tissue samples for a victimmore » of EDB poisoning were analyzed for S-[2-(N[sup 7]-guanyl)ethyl]GSH utilizing electrochemical detection. No adducts were detected in samples of brain, heart, or kidney. The pattern of alkylation of guanines in fragments of plasmid pBR322 DNA by S-(2-chloroethyl)GSH and related compounds was determined. Alkylation varied approximately ten-fold in intensity and was strongest in runs of guanines. Few differences were observed in the alkylation patterns generated by the different compounds tested. The spectrum of mutations caused by S-(2-chloroethyl)GSH was determined using an M13 bacteriophage forward mutation assay. The majority of mutations (70%) were G:C to A:T transitions. Participation of the N[sup 7]-guanyl adduct in the mutagenic process is strongly implicated. The sequence selectivity of alkylation in the region of M13 sequenced in the mutation assay was determined. Comparison of the sequence selectivity with the mutation spectrum revealed no obligate relationship between the extent of adduct formation and the number of mutations which resulted at different sites. Sequence context appears to exert a strong influence on the processing of lesions. These studies strongly implicate S-[2-(N[sup 7]-guanyl)-ethyl]GSH as a mutagenic lesion formed by EDB.« less

  6. Variation and evolution of male sex combs in Drosophila: nature of selection response and theories of genetic variation for sexual traits.

    PubMed

    Ahuja, Abha; Singh, Rama S

    2008-05-01

    We investigated the genetic architecture of variation in male sex comb bristle number, a rapidly evolving secondary sexual character of Drosophila. Twenty-four generations of divergent artificial selection for sex comb bristle number in a heterogeneous population of Drosophila melanogaster resulted in a significant response that was more pronounced in the direction of low bristle numbers. We observed a strong positive correlated response to selection in the corresponding female transverse bristle row. The correlated response in male abdominal and sternopleural bristle numbers, on the other hand, did not follow the same pattern as sex comb bristle number differences between selection lines. Relaxation-of-selection experiments along with mate choice and fecundity assays using the selection lines developed demonstrated the action of stabilizing selection on sex comb bristle number. Our results show (1) substantial genetic variation underlying sex comb bristle number variation; (2) a weak relationship between the sex comb and developmentally related, non-sex bristle systems; and (3) that sexual selection may be a driving force in sex comb evolution, indicating the potential of sex combs to diversify rapidly during population differentiation and speciation. We discuss the implications of these results for theories of genetic variation in display and nondisplay male sex traits.

  7. Rising Trend of Use of Antidepressants Induced Non- Puerperal Lactation: A Case Report.

    PubMed

    Kukreti, Prerna; Ali, Wazid; Jiloha, R C

    2016-06-01

    Non puerperal lactation or galactorrhea is a well known side effect of antipsychotic drugs but has been infrequently described with the use of antidepressants. In past few decades, there have been emerging trend of isolated case reports of selective serotonin reuptake inhibitors induced non puerperal lactation. We report a case of non puerperal lactation following usage of second generation tricyclic antidepressant, nortriptyline and resolution on withdrawing the drug. Literature review has been done for antidepressant induced galactorrhea to understand the current trends, putative mechanism as different from one implicated for antipsychotics and its clinical utility.

  8. Equal Employment Opportunity and ADA Implications of Screening and Selection.

    ERIC Educational Resources Information Center

    Norton, Steven D.; Hundley, John R.

    1995-01-01

    The process of screening and selecting new employees is viewed as one having discrete steps, each with implications concerning Equal Employment Opportunity and the Americans with Disabilities Act. Several screening and selection methods are examined, with questionnaire forms used by Indiana University, South Bend provided for illustration. Typical…

  9. Investigating Turkish Primary School Students' Interest in Science by Using Their Self-Generated Questions

    NASA Astrophysics Data System (ADS)

    Cakmakci, Gultekin; Sevindik, Hatice; Pektas, Meryem; Uysal, Asli; Kole, Fatma; Kavak, Gamze

    2012-06-01

    This paper reports on an attempt to investigate Turkish primary school students' interest in science by using their self-generated questions. We investigated students' interest in science by analyzing 1704 self-generated science-related questions. Among them, 826 questions were submitted to a popular science magazine called Science and Children. Such a self-selected sample may represent a group of students who have a higher level of motivation to seek sources of information outside their formal education and have more access to resources than the students of low social classes. To overcome this problem, 739 students were asked to write a question that they wanted to learn from a scientist and as a result 878 questions were gathered. Those students were selected from 13 different schools at 9 cities in Turkey. These schools were selected to represent a mixture of socioeconomic areas and also to cover different students' profile. Students' questions were classified into two main categories: the field of interest and the cognitive level of the question. The results point to the popularity of biology, astrophysics, nature of scientific inquiry, technology and physics over other science areas, as well as indicating a difference in interest according to gender, grade level and the setting in which the questions were asked. However, our study suggests that only considering questions submitted to informal learning environments, such as popular science magazines or Ask-A-Scientist Internet sites has limitations and deficiencies. Other methodologies of data collection also need to be considered in designing teaching and school science curriculum to meet students' needs and interest. The findings from our study tend to challenge existing thinking from other studies. Our results show that self-generated questions asked in an informal and a formal setting have different patterns. Some aspects of students' self-generated questions and their implications for policy, science curriculum reform and teaching are discussed in this paper.

  10. Age-related differences in the automatic processing of single letters: implications for selective attention.

    PubMed

    Daffner, Kirk R; Alperin, Brittany R; Mott, Katherine K; Holcomb, Phillip J

    2014-01-22

    Older adults exhibit diminished ability to inhibit the processing of visual stimuli that are supposed to be ignored. The extent to which age-related changes in early visual processing contribute to impairments in selective attention remains to be determined. Here, 103 adults, 18-85 years of age, completed a color selective attention task in which they were asked to attend to a specified color and respond to designated target letters. An optimal approach would be to initially filter according to color and then process letter forms in the attend color to identify targets. An asymmetric N170 ERP component (larger amplitude over left posterior hemisphere sites) was used as a marker of the early automatic processing of letter forms. Young and middle-aged adults did not generate an asymmetric N170 component. In contrast, young-old and old-old adults produced a larger N170 over the left hemisphere. Furthermore, older adults generated a larger N170 to letter than nonletter stimuli over the left, but not right hemisphere. More asymmetric N170 responses predicted greater allocation of late selection resources to target letters in the ignore color, as indexed by P3b amplitude. These results suggest that unlike their younger counterparts, older adults automatically process stimuli as letters early in the selection process, when it would be more efficient to attend to color only. The inability to ignore letters early in the processing stream helps explain the age-related increase in subsequent processing of target letter forms presented in the ignore color.

  11. Recent selective sweeps in North American Drosophila melanogaster show signatures of soft sweeps.

    PubMed

    Garud, Nandita R; Messer, Philipp W; Buzbas, Erkan O; Petrov, Dmitri A

    2015-02-01

    Adaptation from standing genetic variation or recurrent de novo mutation in large populations should commonly generate soft rather than hard selective sweeps. In contrast to a hard selective sweep, in which a single adaptive haplotype rises to high population frequency, in a soft selective sweep multiple adaptive haplotypes sweep through the population simultaneously, producing distinct patterns of genetic variation in the vicinity of the adaptive site. Current statistical methods were expressly designed to detect hard sweeps and most lack power to detect soft sweeps. This is particularly unfortunate for the study of adaptation in species such as Drosophila melanogaster, where all three confirmed cases of recent adaptation resulted in soft selective sweeps and where there is evidence that the effective population size relevant for recent and strong adaptation is large enough to generate soft sweeps even when adaptation requires mutation at a specific single site at a locus. Here, we develop a statistical test based on a measure of haplotype homozygosity (H12) that is capable of detecting both hard and soft sweeps with similar power. We use H12 to identify multiple genomic regions that have undergone recent and strong adaptation in a large population sample of fully sequenced Drosophila melanogaster strains from the Drosophila Genetic Reference Panel (DGRP). Visual inspection of the top 50 candidates reveals that in all cases multiple haplotypes are present at high frequencies, consistent with signatures of soft sweeps. We further develop a second haplotype homozygosity statistic (H2/H1) that, in combination with H12, is capable of differentiating hard from soft sweeps. Surprisingly, we find that the H12 and H2/H1 values for all top 50 peaks are much more easily generated by soft rather than hard sweeps. We discuss the implications of these results for the study of adaptation in Drosophila and in species with large census population sizes.

  12. Comparing millennial and generation X medical students at one medical school.

    PubMed

    Borges, Nicole J; Manuel, R Stephen; Elam, Carol L; Jones, Bonnie J

    2006-06-01

    Two main generational cohorts comprising students enrolled in medical schools today are Generation Xers (born 1965-1980) and Millennial students (born 1981-1999). A subset is Cuspars (born 1975-1980), who share traits with both generations. Population theorists ascribe different personal characteristics, attitudes, and preferences to each group. The authors examined whether selected characteristics describing Generation X and Millennial students were quantifiable using a personality measure. Differences among Generation X, Millennial, and Cuspar medical students were investigated. Eight hundred and nine medical students (399 females and 410 males) who matriculated between 1989-94 and 2001-04 at the Northeastern Ohio Universities College of Medicine completed the 16 Personality Factor Questionnaire (16PF). Differences in responses to the 16PF among the three generations were analyzed using multivariate analysis of variance (MANOVA). Analyses showed significant differences for Generation X versus Millennial students on 10 of the 16 personality factors. Millennial students scored significantly higher than Generation X students on factors including Rule-Consciousness, Emotional Stability, and Perfectionism; Generation X students scored higher than Millennials on Self-Reliance. Millennials also were significantly different from Generation Xers on several other factors. Significant differences were noted among Cuspars, Generation Xers, and Millennials. The 16PF is a useful tool to examine differences among these groups and to help understand the factors that constitute their personalities. Given differences among the generational groups, the authors forecast possible educational implications for medical school academic affairs and student services, and suggest areas for future research.

  13. Population genetics of the cytoplasm and the units of selection on mitochondrial DNA in Drosophila melanogaster

    PubMed Central

    2011-01-01

    Biological variation exists across a nested set of hierarchical levels from nucleotides within genes to populations within species to lineages within the tree of life. How selection acts across this hierarchy is a long-standing question in evolutionary biology. Recent studies have suggested that genome size is influenced largely by the balance of selection, mutation and drift in lineages with different population sizes. Here we use population cage and maternal transmission experiments to identify the relative strength of selection at an individual and cytoplasmic level. No significant trends were observed in the frequency of large (L) and small (S) mtDNAs across 14 generations in population cages. In all replicate cages, new length variants were observed in heteroplasmic states indicating that spontaneous length mutations occurred in these experimental populations. Heteroplasmic flies carrying L genomes were more frequent than those carrying S genomes suggesting an asymmetric mutation dynamic from larger to smaller mtDNAs. Mother-offspring transmission of heteroplasmy showed that the L mtDNA increased in frequency within flies both between and within generations despite sampling drift of the same intensity as occurred in population cages. These results suggest that selection for mtDNA size is stronger at the cytoplasmic than at the organismal level. The fixation of novel mtDNAs within and between species requires a transient intracellular heteroplasmic stage. The balance of population genetic forces at the cytoplasmic and individual levels governs the units of selection on mtDNA, and has implications for evolutionary inference as well as for the effects of mtDNA mutations on fitness, disease and aging. PMID:21538136

  14. Potential of different mechanical and thermal treatments to control off-flavour generation in broccoli puree.

    PubMed

    Koutidou, Maria; Grauwet, Tara; Van Loey, Ann; Acharya, Parag

    2017-02-15

    The aim of this study was scientifically investigate the impact of the sequence of different thermo-mechanical treatments on the volatile profile of differently processed broccoli puree, and to investigate if any relationship persists between detected off-flavour changes and microstructural changes as a function of selected process conditions. Comparison of the headspace GC-MS fingerprinting of the differently processed broccoli purees revealed that an adequate combination of processing steps allows to reduce the level of off-flavour volatiles. Moreover, applying mechanical processing before or after the thermal processing at 90°C determines the pattern of broccoli tissue disruption, resulting into different microstructures and various enzymatic reactions inducing volatile generation. These results may aid the identification of optimal process conditions generating a reduced level of off-flavour in processed broccoli. In this way, broccoli can be incorporated as a food ingredient into mixed food products with limited implications on sensorial consumer acceptance. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. How organisms do the right thing: The attractor hypothesis

    USGS Publications Warehouse

    Emlen, J.M.; Freeman, D.C.; Mills, A.; Graham, J.H.

    1998-01-01

    Neo-Darwinian theory is highly successful at explaining the emergence of adaptive traits over successive generations. However, there are reasons to doubt its efficacy in explaining the observed, impressively detailed adaptive responses of organisms to day-to-day changes in their surroundings. Also, the theory lacks a clear mechanism to account for both plasticity and canalization. In effect, there is a growing sentiment that the neo-Darwinian paradigm is incomplete, that something more than genetic structure, mutation, genetic drift, and the action of natural selection is required to explain organismal behavior. In this paper we extend the view of organisms as complex self-organizing entities by arguing that basic physical laws, coupled with the acquisitive nature of organisms, makes adaptation all but tautological. That is, much adaptation is an unavoidable emergent property of organisms' complexity and, to some a significant degree, occurs quite independently of genomic changes wrought by natural selection. For reasons that will become obvious, we refer to this assertion as the attractor hypothesis. The arguments also clarify the concept of "adaptation." Adaptation across generations, by natural selection, equates to the (game theoretic) maximization of fitness (the success with which one individual produces more individuals), while self-organizing based adaptation, within generations, equates to energetic efficiency and the matching of intake and biosynthesis to need. Finally, we discuss implications of the attractor hypothesis for a wide variety of genetical and physiological phenomena, including genetic architecture, directed mutation, genetic imprinting, paramutation, hormesis, plasticity, optimality theory, genotype-phenotype linkage and puncuated equilibrium, and present suggestions for tests of the hypothesis. ?? 1998 American Institute of Physics.

  16. How organisms do the right thing: The attractor hypothesis

    NASA Astrophysics Data System (ADS)

    Emlen, John M.; Freeman, D. Carl; Mills, April; Graham, John H.

    1998-09-01

    Neo-Darwinian theory is highly successful at explaining the emergence of adaptive traits over successive generations. However, there are reasons to doubt its efficacy in explaining the observed, impressively detailed adaptive responses of organisms to day-to-day changes in their surroundings. Also, the theory lacks a clear mechanism to account for both plasticity and canalization. In effect, there is a growing sentiment that the neo-Darwinian paradigm is incomplete, that something more than genetic structure, mutation, genetic drift, and the action of natural selection is required to explain organismal behavior. In this paper we extend the view of organisms as complex self-organizing entities by arguing that basic physical laws, coupled with the acquisitive nature of organisms, makes adaptation all but tautological. That is, much adaptation is an unavoidable emergent property of organisms' complexity and, to some a significant degree, occurs quite independently of genomic changes wrought by natural selection. For reasons that will become obvious, we refer to this assertion as the attractor hypothesis. The arguments also clarify the concept of "adaptation." Adaptation across generations, by natural selection, equates to the (game theoretic) maximization of fitness (the success with which one individual produces more individuals), while self-organizing based adaptation, within generations, equates to energetic efficiency and the matching of intake and biosynthesis to need. Finally, we discuss implications of the attractor hypothesis for a wide variety of genetical and physiological phenomena, including genetic architecture, directed mutation, genetic imprinting, paramutation, hormesis, plasticity, optimality theory, genotype-phenotype linkage and puncuated equilibrium, and present suggestions for tests of the hypothesis.

  17. Enhanced photocurrent in engineered bacteriorhodopsin monolayer.

    PubMed

    Patil, Amol V; Premaruban, Thenhuan; Berthoumieu, Olivia; Watts, Anthony; Davis, Jason J

    2012-01-12

    The integration of the transmembrane protein bacteriorhodopsin (BR) with man-made electrode surfaces has attracted a great deal of interest for some two decades or more and holds significant promise from the perspective of derived photoresponse or energy capture interfaces. Here we demonstrate that a novel and strategically engineered cysteine site (M163C) can be used to intimately and effectively couple delipidated BR to supporting metallic electrode surfaces. By virtue of the combined effects of the greater surface molecular density afforded by delipidation, and the vicinity of the electrostatic changes associated with proton pumping to the transducing metallic continuum, the resulting films generate a considerably greater photocurrent density on wavelength-selective illumination than previously achievable with monolayers of BR. Given the uniquely photoresponsive, wavelength-selective, and photostable characteristics of this protein, the work has implications for utilization in solar energy capture and photodetector devices.

  18. Emergency management leadership in 2030: Shaping the next generation meta-leader.

    PubMed

    Cwiak, Carol L; Campbell, Ronald; Cassavechia, Matthew G; Haynes, Chuck; Lloyd, Lanita A; Brockway, Neil; Navarini, George O; Piatt, Byron E; Senger, Mary

    The complexities, interdependencies, and ambiguity that face next generation emergency management meta-leaders in an ever-evolving global community heighten the expectation and need for competencies that far exceed those common in practice today and necessitate the ability to move seamlessly through the dimensions of meta-leadership (ie, the person, the situation, and connectivity) while utilizing scientific-based evidence, information, resources, processes, and tools. The objective of this effort was to examine the recently developed next generation emergency management competencies through a meta-leadership lens by juxtaposing the competencies and the meta-leadership model. This resulted in a new framing of the skills and attributes within the meta-leadership model as they are relevant to each competency. Selected trends, drivers, and challenges were used to provide examples within each competency area of the utility of meta-leadership to next generation emergency management practice. This effort also offers training and education implications for next generation emergency management meta-leaders. The examination of the new framing created in this effort is intended to prompt dialog and research within the emergency management practice and academic communities that furthers the practice and study of emergency management.

  19. The ‘Friendship Dynamics of Religion,’ or the ‘Religious Dynamics of Friendship’? A Social Network Analysis of Adolescents Who Attend Small Schools*

    PubMed Central

    Cheadle, Jacob E.; Schwadel, Philip

    2012-01-01

    Longitudinal social network data on adolescents in seven schools are analyzed to reach a new understanding about how the personal and interpersonal social dimensions of adolescent religion intertwine together in small school settings. We primarily address two issues relevant to the sociology of religion and sociology in general: (1) social selection as a source of religious homophily and (2) friend socialization of religion. Analysis results are consistent with Collins’ interaction ritual chain theory, which stresses the social dimensions of religion, since network-religion autocorrelations are relatively substantial in magnitude and both selection and socialization mechanisms play key roles in generating them. Results suggest that socialization plays a stronger role than social selection in four of six religious outcomes, and that more religious youth are more cliquish. Implications for our understanding of the social context of religion, religious homophily, and the ways we model religious influence, as well as limitations and considerations for future research, are discussed. PMID:23017927

  20. Cohesiveness tunes assembly and morphology of FG nucleoporin domain meshworks – Implications for nuclear pore permeability

    PubMed Central

    Eisele, Nico B.; Labokha, Aksana A.; Frey, Steffen; Görlich, Dirk; Richter, Ralf P.

    2013-01-01

    Nuclear pore complexes control the exchange of macromolecules between the cytoplasm and the nucleus. A selective permeability barrier that arises from a supramolecular assembly of intrinsically unfolded nucleoporin domains rich in phenylalanine-glycine dipeptides (FG domains) fills the nuclear pore. There is increasing evidence that selective transport requires cohesive FG domain interactions. To understand the functional roles of cohesive interactions, we studied monolayers of end-grafted FG domains as a bottom-up nanoscale model system of the permeability barrier. Based on detailed physicochemical analysis of the model films and comparison of the data with polymer theory, we propose that cohesiveness is tuned to promote rapid assembly of the permeability barrier and to generate a stable and compact pore-filling meshwork with a small mesh size. Our results highlight the functional importance of weak interactions, typically a few kBT per chain, and contribute important information to understand the mechanism of size-selective transport. PMID:24138862

  1. Implications of sex-specific selection for the genetic basis of disease.

    PubMed

    Morrow, Edward H; Connallon, Tim

    2013-12-01

    Mutation and selection are thought to shape the underlying genetic basis of many common human diseases. However, both processes depend on the context in which they occur, such as environment, genetic background, or sex. Sex has widely known effects on phenotypic expression of genotype, but an analysis of how it influences the evolutionary dynamics of disease-causing variants has not yet been explored. We develop a simple population genetic model of disease susceptibility and evaluate it using a biologically plausible empirically based distribution of fitness effects among contributing mutations. The model predicts that alleles under sex-differential selection, including sexually antagonistic alleles, will disproportionately contribute to genetic variation for disease predisposition, thereby generating substantial sexual dimorphism in the genetic architecture of complex (polygenic) diseases. This is because such alleles evolve into higher population frequencies for a given effect size, relative to alleles experiencing equally strong purifying selection in both sexes. Our results provide a theoretical justification for expecting a sexually dimorphic genetic basis for variation in complex traits such as disease. Moreover, they suggest that such dimorphism is interesting - not merely something to control for - because it reflects the action of natural selection in molding the evolution of common disease phenotypes.

  2. Bidirectional plasticity of pontine pneumotaxic postinspiratory drive: implication for a pontomedullary respiratory central pattern generator.

    PubMed

    Poon, Chi-Sang; Song, Gang

    2014-01-01

    The "pneumotaxic center" in the rostral dorsolateral pons as delineated by Lumsden nine decades ago is known to play an important role in promoting the inspiratory off-switch (IOS) for inspiratory-expiratory phase transition as a fail-safe mechanism for preventing apneusis in the absence of vagal input. Traditionally, the pontine pneumotaxic mechanism has been thought to contribute a tonic descending input that lowers the IOS threshold in medullary respiratory central pattern generator (rCPG) circuits, but otherwise does not constitute part of the rCPG. Recent evidence indicates that descending input from the Kölliker-Fuse nucleus (KFN) within the pneumotaxic center is essential for gating the postinspiratory phase of the three-phase respiratory rhythm to control the IOS in vagotomized animals. A critical question arising is whether such a descending pneumotaxic input from KFN that drives postinspiratory activity is tonic (null hypothesis) or rhythmic with postinspiratory phase modulation (alternative hypothesis). Here, we show that multifarious evidence reported in the literature collectively indicates that the descending pneumotaxic input may exhibit NMDA receptor-dependent short-term plasticity in the form of a biphasic neural differentiator that bidirectionally and phase-selectively modulates postinspiratory phase duration in response to vagal and peripheral chemoreceptor inputs independent of the responses in inspiratory and late-expiratory activities. The phase-selectivity property of the descending pneumotaxic input implicates a population of pontine early-expiratory (postinspiratory/expiratory-decrementing) neurons as the most likely neural correlate of the pneumotaxic mechanism that drives post-I activity, suggesting that the pontine pneumotaxic mechanism may be an integral part of a pontomedullary rCPG that underlies the three-phase respiratory rhythm. © 2014 Elsevier B.V. All rights reserved.

  3. Prevention of dopaminergic neurotoxicity by targeting nitric oxide and peroxynitrite: implications for the prevention of methamphetamine-induced neurotoxic damage.

    PubMed

    Imam, S Z; Islam, F; Itzhak, Y; Slikker, W; Ali, S F

    2000-09-01

    Methamphetamine (METH) is a neurotoxic psychostimulant that produces catecholaminergic brain damage by producing oxidative stress and free radical generation. The role of oxygen and nitrogen radicals is well documented as a cause of METH-induced neurotoxic damage. In this study, we have obtained evidence that METH-induced neurotoxicity is the resultant of interaction between oxygen and nitrogen radicals, and it is mediated by the production of peroxynitrite. We have also assessed the effects of inhibitors of neuronal nitric oxide synthase (nNOS) as well as scavenger of nitric oxide and a peroxynitrite decomposition catalyst. Significant protective effects were observed with the inhibitor of nNOS, 7-nitroindazole (7-NI), as well as by the selective peroxynitrite scavenger or decomposition catalyst, 5,10,15,20-tetrakis(2,4,6-trimethyl-3,5-sulfonatophenyl)porphyrinato iron III (FeTPPS). However, the use of a nitric oxide scavenger, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO), did not provide any significant protection against METH-induced hyperthermia or peroxynitrite generation and the resulting dopaminergic neurotoxicity. In particular, treatment with FeTPPS completely prevented METH-induced hyperthermia, peroxynitrite production, and METH-induced dopaminergic depletion. Together, these data demonstrate that METH-induced dopaminergic neurotoxicity is mediated by the generation of peroxynitrite, which can be selectively protected by nNOS inhibitors or peroxynitrite scavenger or decomposition catalysts.

  4. Preparing for what might happen: An episodic specificity induction impacts the generation of alternative future events.

    PubMed

    Jing, Helen G; Madore, Kevin P; Schacter, Daniel L

    2017-12-01

    A critical adaptive feature of future thinking involves the ability to generate alternative versions of possible future events. However, little is known about the nature of the processes that support this ability. Here we examined whether an episodic specificity induction - brief training in recollecting details of a recent experience that selectively impacts tasks that draw on episodic retrieval - (1) boosts alternative event generation and (2) changes one's initial perceptions of negative future events. In Experiment 1, an episodic specificity induction significantly increased the number of alternative positive outcomes that participants generated to a series of standardized negative events, compared with a control induction not focused on episodic specificity. We also observed larger decreases in the perceived plausibility and negativity of the original events in the specificity condition, where participants generated more alternative outcomes, relative to the control condition. In Experiment 2, we replicated and extended these findings using a series of personalized negative events. Our findings support the idea that episodic memory processes are involved in generating alternative outcomes to anticipated future events, and that boosting the number of alternative outcomes is related to subsequent changes in the perceived plausibility and valence of the original events, which may have implications for psychological well-being. Published by Elsevier B.V.

  5. Ciliary proteins Bbs8 and Ift20 promote planar cell polarity in the cochlea

    PubMed Central

    May-Simera, Helen L.; Petralia, Ronald S.; Montcouquiol, Mireille; Wang, Ya-Xian; Szarama, Katherine B.; Liu, Yun; Lin, Weichun; Deans, Michael R.; Pazour, Gregory J.; Kelley, Matthew W.

    2015-01-01

    Primary cilia have been implicated in the generation of planar cell polarity (PCP). However, variations in the severity of polarity defects in different cilia mutants, coupled with recent demonstrations of non-cilia-related actions of some cilia genes, make it difficult to determine the basis of these polarity defects. To address this issue, we evaluated PCP defects in cochlea from a selection of mice with mutations in cilia-related genes. Results indicated notable PCP defects, including mis-oriented hair cell stereociliary bundles, in Bbs8 and Ift20 single mutants that are more severe than in other cilia gene knockouts. In addition, deletion of either Bbs8 or Ift20 results in disruptions in asymmetric accumulation of the core PCP molecule Vangl2 in cochlear cells, suggesting a role for Bbs8 and/or Ift20, possibly upstream of core PCP asymmetry. Consistent with this, co-immunoprecipitation experiments indicate direct interactions of Bbs8 and Ift20 with Vangl2. We observed localization of Bbs and Ift proteins to filamentous actin as well as microtubules. This could implicate these molecules in selective trafficking of membrane proteins upstream of cytoskeletal reorganization, and identifies new roles for cilia-related proteins in cochlear PCP. PMID:25605782

  6. Maximum spectral demands in the near-fault region

    USGS Publications Warehouse

    Huang, Yin-Nan; Whittaker, Andrew S.; Luco, Nicolas

    2008-01-01

    The Next Generation Attenuation (NGA) relationships for shallow crustal earthquakes in the western United States predict a rotated geometric mean of horizontal spectral demand, termed GMRotI50, and not maximum spectral demand. Differences between strike-normal, strike-parallel, geometric-mean, and maximum spectral demands in the near-fault region are investigated using 147 pairs of records selected from the NGA strong motion database. The selected records are for earthquakes with moment magnitude greater than 6.5 and for closest site-to-fault distance less than 15 km. Ratios of maximum spectral demand to NGA-predicted GMRotI50 for each pair of ground motions are presented. The ratio shows a clear dependence on period and the Somerville directivity parameters. Maximum demands can substantially exceed NGA-predicted GMRotI50 demands in the near-fault region, which has significant implications for seismic design, seismic performance assessment, and the next-generation seismic design maps. Strike-normal spectral demands are a significantly unconservative surrogate for maximum spectral demands for closest distance greater than 3 to 5 km. Scale factors that transform NGA-predicted GMRotI50 to a maximum spectral demand in the near-fault region are proposed.

  7. Maximum spectral demands in the near-fault region

    USGS Publications Warehouse

    Huang, Y.-N.; Whittaker, A.S.; Luco, N.

    2008-01-01

    The Next Generation Attenuation (NGA) relationships for shallow crustal earthquakes in the western United States predict a rotated geometric mean of horizontal spectral demand, termed GMRotI50, and not maximum spectral demand. Differences between strike-normal, strike-parallel, geometric-mean, and maximum spectral demands in the near-fault region are investigated using 147 pairs of records selected from the NGA strong motion database. The selected records are for earthquakes with moment magnitude greater than 6.5 and for closest site-to-fault distance less than 15 km. Ratios of maximum spectral demand to NGA-predicted GMRotI50 for each pair of ground motions are presented. The ratio shows a clear dependence on period and the Somerville directivity parameters. Maximum demands can substantially exceed NGA-predicted GMRotI50 demands in the near-fault region, which has significant implications for seismic design, seismic performance assessment, and the next-generation seismic design maps. Strike-normal spectral demands are a significantly unconservative surrogate for maximum spectral demands for closest distance greater than 3 to 5 km. Scale factors that transform NGA-predicted GMRotI50 to a maximum spectral demand in the near-fault region are proposed. ?? 2008, Earthquake Engineering Research Institute.

  8. Source memory in the rat

    PubMed Central

    Crystal, Jonathon D.; Alford, Wesley T.; Zhou, Wenyi; Hohmann, Andrea G.

    2013-01-01

    Summary Source memory is a representation of the origin (source) of information. When source information is bound together, it makes a memory episodic, allowing us to differentiate one event from another [1, 2]. Here we asked if rats remember the source of encoded information. Rats foraged for distinctive flavors of food that replenished (or failed to replenish) at its recently encountered location according to a source-information rule. To predict replenishment, rats needed to remember where they had encountered a preferred food type (chocolate) with self-generated (walking along a runway encountering chocolate) or experimenter-generated (placement of the rat at the chocolate site by an experimenter) cues. Three lines of evidence implicate the presence of source memory. First, rats selectively adjusted revisits to the chocolate location based on source information, under conditions in which familiarity of events could not produce successful performance. Second, source memory was dissociated from location memory by different decay rates. Third, temporary inactivation of the CA3 region of the hippocampus with lidocaine selectively eliminated source memory, suggesting that source memory is dependent upon an intact hippocampus. Development of an animal model of source memory may be valuable to probe the biological underpinnings of memory disorders marked by impairments in source memory. PMID:23394830

  9. Getting a taste for food waste: a mixed methods ethnographic study into hospital food waste before patient consumption conducted at three New Zealand foodservice facilities.

    PubMed

    Goonan, Sarah; Mirosa, Miranda; Spence, Heather

    2014-01-01

    Foodservice organizations, particularly those in hospitals, are large producers of food waste. To date, research on waste in hospitals has focused primarily on plate waste and the affect of food waste on patient nutrition outcomes. Less focus has been placed on waste generation at the kitchen end of the hospital food system. We used a novel approach to understand reasons for hospital food waste before consumption and offer recommendations on waste minimization within foodservices. A mixed methods ethnographic research approach was adopted. Three New Zealand hospital foodservices were selected as research sites, all of which were contracted to an external foodservice provider. Data collection techniques included document analyses, observations, focus groups with kitchen staff, and one-on-one interviews with managers. Thematic analysis was conducted to generate common themes. Most food waste occurred during service and as a result of overproduction. Attitudes and habits of foodservice personnel were considered influential factors of waste generation. Implications of food waste were perceived differently by different levels of staff. Whereas managers raised discussion from a financial perspective, kitchen staff drew upon social implications. Organizational plans, controls, and use of pre-prepared ingredients assisted in waste minimization. An array of factors influenced waste generation in hospital foodservices. Exploring attitudes and practices of foodservice personnel allowed an understanding of reasons behind hospital food waste and ways in which it could be minimized. This study provides a foundation for further research on sustainable behavior within the wider foodservice sector and dietetics practice. Copyright © 2014 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

  10. A perspective on reagent diversity and non-covalent binding of reactive carbonyl species (RCS) and effector reagents in nonenzymatic glycation (NEG): Mechanistic considerations and implications for future research

    NASA Astrophysics Data System (ADS)

    Rodnick, Kenneth J.; Holman, R. W.; Ropski, Pamela S.; Huang, Mingdong; Swislocki, Arthur L. M.

    2017-06-01

    This perspective focuses on illustrating the underappreciated connections between reactive carbonyl species (RCS), initial binding in the nonenzymatic glycation (NEG) process, and nonenzymatic covalent protein modification (here termed NECPM). While glucose is the central species involved in NEG, recent studies indicate that the initially-bound glucose species in the NEG of human hemoglobin (HbA) and human serum albumin (HSA) are non-RCS ring-closed isomers. The ring-opened glucose, an RCS structure that reacts in the NEG process, is most likely generated from previously-bound ring-closed isomers undergoing concerted acid/base reactions while bound to protein. The generation of the glucose RCS can involve concomitantly-bound physiological species (e.g., inorganic phosphate, water, etc.); here termed effector reagents. Extant NEG schemes do not account for these recent findings. In addition, effector reagent reactions with glucose in the serum and erythrocyte cytosol can generate RCS (e.g., glyoxal, glyceraldehyde, etc.). Recent research has shown that these RCS covalently modify proteins in vivo via NECPM mechanisms. A general scheme that reflects both the reagent and mechanistic diversity that can lead to NEG and NECPM is presented here. A perspective that accounts for the relationships between RCS, NEG, and NECPM can facilitate the understanding of site selectivity, may help explain overall glycation rates, and may have implications for the clinical assessment/control of diabetes mellitus. In view of this perspective, concentrations of ribose, fructose, Pi, bicarbonate, counter ions, and the resulting RCS generated within intracellular and extracellular compartments may be of importance and of clinical relevance. Future research is also proposed.

  11. Ectopic Integration of Transforming DNA Is Rare among Neurospora Transformants Selected for Gene Replacement

    PubMed Central

    Miao, VPW.; Rountree, M. R.; Selker, E. U.

    1995-01-01

    In a variety of organisms, DNA-mediated transformation experiments commonly produce transformants with multiple copies of the transforming DNA, including both selected and unselected molecules. Such ``cotransformants'' are much more common than expected from the individual transformation frequencies, suggesting that subpopulations of cells, or nuclei, are particularly competent for transformation. We found that Neurospora crassa transformants selected for gene replacement at the am gene had not efficiently incorporated additional DNA, suggesting that nuclei that undergo transformation by homologous recombination are not highly competent at integration of DNA by illegitimate recombination. Spheroplasts were treated with DNA fragments homologous to am and with an Escherichia coli hph plasmid. Transformants were initially selected for hph (hygromycin(R)), allowed to conidiate to generate homokaryons and then selected for either Am(-) (gene replacements) or hph. Surprisingly, most am replacement strains were hygromycin(S) (124/140) and carried no extraneous DNA (116/140). Most transformants selected for hph also had ectopic copies of am DNA and/or multiple copies of hph sequences (32/35), generally at multiple sites, confirming that efficient cotransformation could occur. To test the implication that cotransformation involving gene replacement and ectopic integration is rare, we compared the yields of am replacement strains with or without prior selection for hph. The initial selection did not appreciably help (or hinder) recovery of strains with replacements. PMID:7789758

  12. Locus-dependent selection in crop-wild hybrids of lettuce under field conditions and its implication for GM crop development

    PubMed Central

    Hooftman, Danny A P; Flavell, Andrew J; Jansen, Hans; den Nijs, Hans C M; Syed, Naeem H; Sørensen, Anker P; Orozco-ter Wengel, Pablo; van de Wiel, Clemens C M

    2011-01-01

    Gene escape from crops has gained much attention in the last two decades, as transgenes introgressing into wild populations could affect the latter's ecological characteristics. However, different genes have different likelihoods of introgression. The mixture of selective forces provided by natural conditions creates an adaptive mosaic of alleles from both parental species. We investigated segregation patterns after hybridization between lettuce (Lactuca sativa) and its wild relative, L. serriola. Three generations of hybrids (S1, BC1, and BC1S1) were grown in habitats mimicking the wild parent's habitat. As control, we harvested S1 seedlings grown under controlled conditions, providing very limited possibility for selection. We used 89 AFLP loci, as well as more recently developed dominant markers, 115 retrotransposon markers (SSAP), and 28 NBS loci linked to resistance genes. For many loci, allele frequencies were biased in plants exposed to natural field conditions, including over-representation of crop alleles for various loci. Furthermore, Linkage disequilibrium was locally changed, allegedly by selection caused by the natural field conditions, providing ample opportunity for genetic hitchhiking. Our study indicates that when developing genetically modified crops, a judicious selection of insertion sites, based on knowledge of selective (dis)advantages of the surrounding crop genome under field conditions, could diminish transgene persistence. PMID:25568012

  13. Locus-dependent selection in crop-wild hybrids of lettuce under field conditions and its implication for GM crop development.

    PubMed

    Hooftman, Danny A P; Flavell, Andrew J; Jansen, Hans; den Nijs, Hans C M; Syed, Naeem H; Sørensen, Anker P; Orozco-Ter Wengel, Pablo; van de Wiel, Clemens C M

    2011-09-01

    Gene escape from crops has gained much attention in the last two decades, as transgenes introgressing into wild populations could affect the latter's ecological characteristics. However, different genes have different likelihoods of introgression. The mixture of selective forces provided by natural conditions creates an adaptive mosaic of alleles from both parental species. We investigated segregation patterns after hybridization between lettuce (Lactuca sativa) and its wild relative, L. serriola. Three generations of hybrids (S1, BC1, and BC1S1) were grown in habitats mimicking the wild parent's habitat. As control, we harvested S1 seedlings grown under controlled conditions, providing very limited possibility for selection. We used 89 AFLP loci, as well as more recently developed dominant markers, 115 retrotransposon markers (SSAP), and 28 NBS loci linked to resistance genes. For many loci, allele frequencies were biased in plants exposed to natural field conditions, including over-representation of crop alleles for various loci. Furthermore, Linkage disequilibrium was locally changed, allegedly by selection caused by the natural field conditions, providing ample opportunity for genetic hitchhiking. Our study indicates that when developing genetically modified crops, a judicious selection of insertion sites, based on knowledge of selective (dis)advantages of the surrounding crop genome under field conditions, could diminish transgene persistence.

  14. Kin groups and trait groups: population structure and epidemic disease selection.

    PubMed

    Fix, A G

    1984-10-01

    A Monte Carlo simulation based on the population structure of a small-scale human population, the Semai Senoi of Malaysia, has been developed to study the combined effects of group, kin, and individual selection. The population structure resembles D.S. Wilson's structured deme model in that local breeding populations (Semai settlements) are subdivided into trait groups (hamlets) that may be kin-structured and are not themselves demes. Additionally, settlement breeding populations are connected by two-dimensional stepping-stone migration approaching 30% per generation. Group and kin-structured group selection occur among hamlets the survivors of which then disperse to breed within the settlement population. Genetic drift is modeled by the process of hamlet formation; individual selection as a deterministic process, and stepping-stone migration as either random or kin-structured migrant groups. The mechanism for group selection is epidemics of infectious disease that can wipe out small hamlets particularly if most adults become sick and social life collapses. Genetic resistance to a disease is an individual attribute; however, hamlet groups with several resistant adults are less likely to disintegrate and experience high social mortality. A specific human gene, hemoglobin E, which confers resistance to malaria, is studied as an example of the process. The results of the simulations show that high genetic variance among hamlet groups may be generated by moderate degrees of kin-structuring. This strong microdifferentiation provides the potential for group selection. The effect of group selection in this case is rapid increase in gene frequencies among the total set of populations. In fact, group selection in concert with individual selection produced a faster rate of gene frequency increase among a set of 25 populations than the rate within a single unstructured population subject to deterministic individual selection. Such rapid evolution with plausible rates of extinction, individual selection, and migration and a population structure realistic in its general form, has implications for specific human polymorphisms such as hemoglobin variants and for the more general problem of the tempo of evolution as well.

  15. Isolation of Coherent Synchrotron Emission During Relativistic Laser Plasma Interactions

    NASA Astrophysics Data System (ADS)

    Dromey, B.; Rykovanov, S. G.; Lewis, C. L. S.; Zepf, M.

    Coherent Synchrotron Emission (CSE) from relativistic laser plasmas (Pukhov et al., Plas Phys Control Fusion 52:124039, 2010; Dromey et al., Nat Phys 8:804-808, 2012; Dromey et al., New J Phys 15:015025, 2013) has recently been identified as a unique platform for the generation of coherent extreme ultraviolet (XUV) and X-Ray radiation with clear potential for bright attosecond pulse production. Exploiting this potential requires careful selection of interaction geometry, spectral wavelength range and target characteristics to allow the generation of high fidelity single attosecond pulses. In the laboratory the first step on this road is to study the individual mechanisms driving the emission of coherent extreme ultraviolet and X-Ray radiation during laser solid interactions in isolation. Here we show how interactions can be tailored to permit the unambiguous observation of coherent synchrotron emission (CSE) and the implications of this geometry for the resulting harmonic spectrum over the duration of the interaction.

  16. The origin of risk aversion

    PubMed Central

    Zhang, Ruixun; Brennan, Thomas J.; Lo, Andrew W.

    2014-01-01

    Risk aversion is one of the most basic assumptions of economic behavior, but few studies have addressed the question of where risk preferences come from and why they differ from one individual to the next. Here, we propose an evolutionary explanation for the origin of risk aversion. In the context of a simple binary-choice model, we show that risk aversion emerges by natural selection if reproductive risk is systematic (i.e., correlated across individuals in a given generation). In contrast, risk neutrality emerges if reproductive risk is idiosyncratic (i.e., uncorrelated across each given generation). More generally, our framework implies that the degree of risk aversion is determined by the stochastic nature of reproductive rates, and we show that different statistical properties lead to different utility functions. The simplicity and generality of our model suggest that these implications are primitive and cut across species, physiology, and genetic origins. PMID:25453072

  17. Chemotherapy-Induced Nausea and Vomiting Mitigation With Music Interventions
.

    PubMed

    Kiernan, Jason M; Conradi Stark, Jody; Vallerand, April H

    2018-01-01

    Despite three decades of studies examining music interventions as a mitigant of chemotherapy-induced nausea and vomiting (CINV), to date, no systematic review of this literature exists.
. PubMed, Scopus, PsycInfo®, CINAHL®, Cochrane Library, and Google Scholar were searched. Keywords for all databases were music, chemotherapy, and nausea.
. All studies were appraised for methodology and results.
. 10 studies met inclusion criteria for review. Sample sizes were generally small and nonrandomized. Locus of control for music selection was more often with the investigator rather than the participant. Few studies controlled for the emetogenicity of the chemotherapy administered, nor for known patient-specific risk factors for CINV.
. The existing data have been largely generated by nurse scientists, and implications for nursing practice are many, because music interventions are low-cost, easily accessible, and without known adverse effects. However, this specific body of knowledge requires additional substantive inquiry to generate clinically relevant data.

  18. The origin of risk aversion.

    PubMed

    Zhang, Ruixun; Brennan, Thomas J; Lo, Andrew W

    2014-12-16

    Risk aversion is one of the most basic assumptions of economic behavior, but few studies have addressed the question of where risk preferences come from and why they differ from one individual to the next. Here, we propose an evolutionary explanation for the origin of risk aversion. In the context of a simple binary-choice model, we show that risk aversion emerges by natural selection if reproductive risk is systematic (i.e., correlated across individuals in a given generation). In contrast, risk neutrality emerges if reproductive risk is idiosyncratic (i.e., uncorrelated across each given generation). More generally, our framework implies that the degree of risk aversion is determined by the stochastic nature of reproductive rates, and we show that different statistical properties lead to different utility functions. The simplicity and generality of our model suggest that these implications are primitive and cut across species, physiology, and genetic origins.

  19. [Source-monitoring deficits in schizophrenia: review and pharmacotherapeutic implications].

    PubMed

    Juhász, Levente Zsolt; Bartkó, György

    2007-03-01

    The disturbance of source-monitoring is one of the various impairments in cognitive functioning observed in schizophrenic patients. The process of source-monitoring allows individuals to distinguish self generated thoughts and behaviours from those generated by others. The aim of the present study is to review the general psychological definition of source memory and source-monitoring and its neurological basis as well as the models for explanation of source-monitoring deficits. The relationship between source-monitoring-deficits and psychopathological symptoms as well as the effect of antipsychotic treatment on source-monitoring disturbances are introduced. There is evidence suggesting, that a selective source-monitoring deficit is in the occurrence of auditory hallucinations. The disturbance of prospective memory may influence unfavorably the compliance. Administration of antipsychotics in general can improve source-monitoring deficits. The neuropsychiatric perspective provides a more accurate and comprehensive understanding of schizophrenia.

  20. Stochastic dynamics of adaptive trait and neutral marker driven by eco-evolutionary feedbacks.

    PubMed

    Billiard, Sylvain; Ferrière, Régis; Méléard, Sylvie; Tran, Viet Chi

    2015-11-01

    How the neutral diversity is affected by selection and adaptation is investigated in an eco-evolutionary framework. In our model, we study a finite population in continuous time, where each individual is characterized by a trait under selection and a completely linked neutral marker. Population dynamics are driven by births and deaths, mutations at birth, and competition between individuals. Trait values influence ecological processes (demographic events, competition), and competition generates selection on trait variation, thus closing the eco-evolutionary feedback loop. The demographic effects of the trait are also expected to influence the generation and maintenance of neutral variation. We consider a large population limit with rare mutation, under the assumption that the neutral marker mutates faster than the trait under selection. We prove the convergence of the stochastic individual-based process to a new measure-valued diffusive process with jumps that we call Substitution Fleming-Viot Process (SFVP). When restricted to the trait space this process is the Trait Substitution Sequence first introduced by Metz et al. (1996). During the invasion of a favorable mutation, a genetical bottleneck occurs and the marker associated with this favorable mutant is hitchhiked. By rigorously analysing the hitchhiking effect and how the neutral diversity is restored afterwards, we obtain the condition for a time-scale separation; under this condition, we show that the marker distribution is approximated by a Fleming-Viot distribution between two trait substitutions. We discuss the implications of the SFVP for our understanding of the dynamics of neutral variation under eco-evolutionary feedbacks and illustrate the main phenomena with simulations. Our results highlight the joint importance of mutations, ecological parameters, and trait values in the restoration of neutral diversity after a selective sweep.

  1. Low level exposure to inorganic mercury interferes with B cell receptor signaling in transitional type 1 B cells.

    PubMed

    Gill, R; McCabe, M J; Rosenspire, A J

    2017-09-01

    Mercury (Hg) has been implicated as a factor contributing to autoimmune disease in animal models and humans. However the mechanism by which this occurs has remained elusive. Since the discovery of B cells it has been appreciated by immunologists that during the normal course of B cell development, some immature B cells must be generated that produce immunoglobulin reactive to self-antigens (auto-antibodies). However in the course of normal development, the vast majority of immature auto-reactive B cells are prevented from maturing by processes collectively known as tolerance. Autoimmune disease arises when these mechanisms of tolerance are disrupted. In the B cell compartment, it is firmly established that tolerance depends in part upon negative selection of self-reactive immature (transitional type 1) B cells. In these cells negative selection depends upon signals generated by the B Cell Receptor (BCR), in the sense that those T1 B cells who's BCRs most strongly bind to, and so generate the strongest signals to self-antigens are neutralized. In this report we have utilized multicolor phosphoflow cytometry to show that in immature T1 B cells Hg attenuates signal generation by the BCR through mechanisms that may involve Lyn, a key tyrosine kinase in the BCR signal transduction pathway. We suggest that exposure to low, environmentally relevant levels of Hg, disrupts tolerance by interfering with BCR signaling in immature B cells, potentially leading to the appearance of mature auto-reactive B cells which have the ability to contribute to auto-immune disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Genetic diversity of Elaeis oleifera (HBK) Cortes populations using cross species SSRs: implication's for germplasm utilization and conservation.

    PubMed

    Ithnin, Maizura; Teh, Chee-Keng; Ratnam, Wickneswari

    2017-04-19

    The Elaeis oleifera genetic materials were assembled from its center of diversity in South and Central America. These materials are currently being preserved in Malaysia as ex situ living collections. Maintaining such collections is expensive and requires sizable land. Information on the genetic diversity of these collections can help achieve efficient conservation via maintenance of core collection. For this purpose, we have applied fourteen unlinked microsatellite markers to evaluate 532 E. oleifera palms representing 19 populations distributed across Honduras, Costa Rica, Panama and Colombia. In general, the genetic diversity decreased from Costa Rica towards the north (Honduras) and south-east (Colombia). Principle coordinate analysis (PCoA) showed a single cluster indicating low divergence among palms. The phylogenetic tree and STRUCTURE analysis revealed clusters based on country of origin, indicating considerable gene flow among populations within countries. Based on the values of the genetic diversity parameters, some genetically diverse populations could be identified. Further, a total of 34 individual palms that collectively captured maximum allelic diversity with reduced redundancy were also identified. High pairwise genetic differentiation (Fst > 0.250) among populations was evident, particularly between the Colombian populations and those from Honduras, Panama and Costa Rica. Crossing selected palms from highly differentiated populations could generate off-springs that retain more genetic diversity. The results attained are useful for selecting palms and populations for core collection. The selected materials can also be included into crossing scheme to generate offsprings that capture greater genetic diversity for selection gain in the future.

  3. Short-chain fatty acid sensing in rat duodenum.

    PubMed

    Akiba, Yasutada; Inoue, Takuya; Kaji, Izumi; Higashiyama, Masaaki; Narimatsu, Kazuyuki; Iwamoto, Ken-ichi; Watanabe, Masahiko; Guth, Paul H; Engel, Eli; Kuwahara, Atsukazu; Kaunitz, Jonathan D

    2015-02-01

    Luminal lipid in the duodenum modulates gastroduodenal functions via the release of gut hormones and mediators such as cholecystokinin and 5-HT. The effects of luminal short-chain fatty acids (SCFAs) in the foregut are unknown. Free fatty acid receptors (FFARs) for long-chain fatty acids (LCFAs) and SCFAs are expressed in enteroendocrine cells. SCFA receptors, termed FFA2 and FFA3, are expressed in duodenal enterochromaffin cells and L cells, respectively. Activation of LCFA receptor (FFA1) and presumed FFA3 stimulates duodenal HCO3(-) secretion via a glucagon-like peptide (GLP)-2 pathway, whereas FFA2 activation induces HCO3(-) secretion via muscarinic and 5-HT4 receptor activation. The presence of SCFA sensing in the duodenum with GLP-2 and 5-HT signals further supports the hypothesis that luminal SCFA in the foregut may contribute towards the generation of functional symptoms. Intraduodenal fatty acids (FA) and bacterial overgrowth, which generate short-chain FAs (SCFAs), have been implicated in the generation of functional dyspepsia symptoms. We studied the mechanisms by which luminal SCFA perfusion affects duodenal HCO3(-) secretion (DBS), a measure of mucosal neurohumoral activation. Free fatty acid receptor (FFAR) 1 (FFA1), which binds long-chain FA (LCFA), and SCFA receptors FFA2 and FFA3 were immunolocalised to duodenal enteroendocrine cells. FFA3 colocalised with glucagon-like peptide (GLP)-1, whereas FFA2 colocalised with 5-HT. Luminal perfusion of the SCFA acetate or propionate increased DBS, enhanced by dipeptidyl peptidase-IV (DPPIV) inhibition, at the same time as increasing GLP-2 portal blood concentrations. Acetate-induced DBS was partially inhibited by monocarboxylate/HCO3(-) exchanger inhibition without affecting GLP-2 release, implicating acetate absorption in the partial mediation of DBS. A selective FFA2 agonist dose-dependently increased DBS, unaffected by DPPIV inhibition or by cholecystokinin or 5-HT3 receptor antagonists, but was inhibited by atropine and a 5-HT4 antagonist. By contrast, a selective FFA1 agonist increased DBS accompanied by GLP-2 release, enhanced by DPPIV inhibition and inhibited by a GLP-2 receptor antagonist. Activation of FFA1 by LCFA and presumably FFA3 by SCFA increased DBS via GLP-2 release, whereas FFA2 activation stimulated DBS via muscarinic and 5-HT4 receptor activation. SCFA/HCO3(-) exchange also appears to be present in the duodenum. The presence of duodenal fatty acid sensing receptors that signal hormone release and possibly signal neural activation may be implicated in the pathogenesis of functional dyspepsia. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

  4. Putative oncogene Brachyury (T) is essential to specify cell fate but dispensable for notochord progenitor proliferation and EMT.

    PubMed

    Zhu, Jianjian; Kwan, Kin Ming; Mackem, Susan

    2016-04-05

    The transcription factor Brachyury (T) gene is expressed throughout primary mesoderm (primitive streak and notochord) during early embryonic development and has been strongly implicated in the genesis of chordoma, a sarcoma of notochord cell origin. Additionally, T expression has been found in and proposed to play a role in promoting epithelial-mesenchymal transition (EMT) in various other types of human tumors. However, the role of T in normal mammalian notochord development and function is still not well-understood. We have generated an inducible knockdown model to efficiently and selectively deplete T from notochord in mouse embryos. In combination with genetic lineage tracing, we show that T function is essential for maintaining notochord cell fate and function. Progenitors adopt predominantly a neural fate in the absence of T, consistent with an origin from a common chordoneural progenitor. However, T function is dispensable for progenitor cell survival, proliferation, and EMT, which has implications for the therapeutic targeting of T in chordoma and other cancers.

  5. Putative oncogene Brachyury (T) is essential to specify cell fate but dispensable for notochord progenitor proliferation and EMT

    PubMed Central

    Zhu, Jianjian; Kwan, Kin Ming; Mackem, Susan

    2016-01-01

    The transcription factor Brachyury (T) gene is expressed throughout primary mesoderm (primitive streak and notochord) during early embryonic development and has been strongly implicated in the genesis of chordoma, a sarcoma of notochord cell origin. Additionally, T expression has been found in and proposed to play a role in promoting epithelial–mesenchymal transition (EMT) in various other types of human tumors. However, the role of T in normal mammalian notochord development and function is still not well-understood. We have generated an inducible knockdown model to efficiently and selectively deplete T from notochord in mouse embryos. In combination with genetic lineage tracing, we show that T function is essential for maintaining notochord cell fate and function. Progenitors adopt predominantly a neural fate in the absence of T, consistent with an origin from a common chordoneural progenitor. However, T function is dispensable for progenitor cell survival, proliferation, and EMT, which has implications for the therapeutic targeting of T in chordoma and other cancers. PMID:27006501

  6. Praziquantel decreases fecundity in Schistosoma mansoni adult worms that survive treatment: evidence from a laboratory life-history trade-offs selection study.

    PubMed

    Lamberton, Poppy H L; Faust, Christina L; Webster, Joanne P

    2017-06-16

    Mass drug administration of praziquantel is the World Health Organization's endorsed control strategy for schistosomiasis. A decade of annual treatments across sub-Saharan Africa has resulted in significant reductions of infection prevalence and intensity levels, although 'hotspots' remain. Repeated drug treatments place strong selective pressures on parasites, which may affect life-history traits that impact transmission dynamics. Understanding drug treatment responses and the evolution of such traits can help inform on how to minimise the risk of drug resistance developing, maximise sustainable control programme success, and improve diagnostic protocols. We performed a four-generation Schistosoma mansoni praziquantel selection experiment in mice and snails. We used three S. mansoni lines: a praziquantel-resistant isolate (R), a praziquantel-susceptible isolate (S), and a co-infected line (RS), under three treatment regimens: untreated, 25 mg/kg praziquantel, or 50 mg/kg praziquantel. Life-history traits, including parasite adult-worm establishment, survival, reproduction (fecundity), and associated morbidity, were recorded in mice across all four generations. Predictor variables were tested in a series of generalized linear mixed effects models to determine which factors had a significant influence on parasite life-history traits in definitive hosts under different selection regimes. Praziquantel pressure significantly reduced adult-worm burdens across all generations and isolates, including within R-lines. However, previous drug treatment resulted in an increase in adult-worm establishment with increasing generation from P1 to F3. The highest worm numbers were in the co-infected RS line. Praziquantel treatment decreased adult-worm burden, but had a larger negative impact on the mean daily number of miracidia, a proxy for fecundity, across all three parasite isolates. Our predicted cost of resistance was not supported by the traits we measured within the murine host. We did not find evidence for negative adult worm density-dependent effects on fecundity. In contrast, of the adult worms that survived treatment, even low doses of praziquantel significantly reduced adult-worm fecundity. Such reductions in worm fecundity post treatment suggest that egg - based measures of drug efficacy, such as Kato-Katz, may overestimate the short-term effect of praziquantel on adult - worm burdens. These findings have important implications for S. mansoni transmission control, diagnostic protocols, and the potential for undetected selection toward drug resistance.

  7. Vigabatrin therapy implicates neocortical high frequency oscillations in an animal model of infantile spasms.

    PubMed

    Frost, James D; Le, John T; Lee, Chong L; Ballester-Rosado, Carlos; Hrachovy, Richard A; Swann, John W

    2015-10-01

    Abnormal high frequency oscillations (HFOs) in EEG recordings are thought to be reflections of mechanisms responsible for focal seizure generation in the temporal lobe and neocortex. HFOs have also been recorded in patients and animal models of infantile spasms. If HFOs are important contributors to infantile spasms then anticonvulsant drugs that suppress these seizures should decrease the occurrence of HFOs. In experiments reported here, we used long-term video/EEG recordings with digital sampling rates capable of capturing HFOs. We tested the effectiveness of vigabatrin (VGB) in the TTX animal model of infantile spasms. VGB was found to be quite effective in suppressing spasms. In 3 of 5 animals, spasms ceased after a daily two week treatment. In the other 2 rats, spasm frequency dramatically decreased but gradually increased following treatment cessation. In all animals, hypsarrhythmia was abolished by the last treatment day. As VGB suppressed the frequency of spasms, there was a decrease in the intensity of the behavioral spasms and the duration of the ictal EEG event. Analysis showed that there was a burst of high frequency activity at ictal onset, followed by a later burst of HFOs. VGB was found to selectively suppress the late HFOs of ictal complexes. VGB also suppressed abnormal HFOs recorded during the interictal periods. Thus VGB was found to be effective in suppressing both the generation of spasms and hypsarrhythmia in the TTX model. Vigabatrin also appears to preferentially suppress the generation of abnormal HFOs, thus implicating neocortical HFOs in the infantile spasms disease state. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Vigabatrin Therapy Implicates Neocortical High Frequency Oscillations in an Animal Model of Infantile Spasms

    PubMed Central

    Frost, James D.; Le, John T.; Lee, Chong L.; Ballester-Rosado, Carlos; Hrachovy, Richard A.; Swann, John W.

    2015-01-01

    Abnormal high frequency oscillations (HFOs) in EEG recordings are thought to be reflections of mechanisms responsible for focal seizure generation in the temporal lobe and neocortex. HFOs have also been recorded in patients and animal models of infantile spasms. If HFOs are important contributors to infantile spasms then anticonvulsant drugs that suppress these seizures should decrease the occurrence of HFOs. In experiments reported here, we used long-term video/EEG recordings with digital sampling rates capable of capturing HFOs. We tested the effectiveness of vigabatrin (VGB) in the TTX animal model of infantile spasms. VGB was found to be quite effective in suppressing spasms. In 3 of 5 animals, spasms ceased after a daily two week treatment. In the other 2 rats, spasm frequency dramatically decreased but gradually increased following treatment cessation. In all animals, hypsarrhythmia was abolished by the last treatment day. As VGB suppressed the frequency of spasms, there was a decrease in the intensity of the behavioral spasms and the duration of the ictal EEG event. Analysis showed that there was a burst of high frequency activity at ictal onset, followed by a later burst of HFOs. VGB was found to selectively suppress the late HFOs of ictal complexes. VGB also suppressed abnormal HFOs recorded during the interictal periods. Thus VGB was found to be effective in suppressing both the generation of spasms and hypsarrhythmia in the TTX model. Vigabatrin also appears to preferentially suppress the generation of abnormal HFOs, thus implicating neocortical HFOs in the infantile spasms disease state. PMID:26026423

  9. Comprehending 3D Diagrams: Sketching to Support Spatial Reasoning.

    PubMed

    Gagnier, Kristin M; Atit, Kinnari; Ormand, Carol J; Shipley, Thomas F

    2017-10-01

    Science, technology, engineering, and mathematics (STEM) disciplines commonly illustrate 3D relationships in diagrams, yet these are often challenging for students. Failing to understand diagrams can hinder success in STEM because scientific practice requires understanding and creating diagrammatic representations. We explore a new approach to improving student understanding of diagrams that convey 3D relations that is based on students generating their own predictive diagrams. Participants' comprehension of 3D spatial diagrams was measured in a pre- and post-design where students selected the correct 2D slice through 3D geologic block diagrams. Generating sketches that predicated the internal structure of a model led to greater improvement in diagram understanding than visualizing the interior of the model without sketching, or sketching the model without attempting to predict unseen spatial relations. In addition, we found a positive correlation between sketched diagram accuracy and improvement on the diagram comprehension measure. Results suggest that generating a predictive diagram facilitates students' abilities to make inferences about spatial relationships in diagrams. Implications for use of sketching in supporting STEM learning are discussed. Copyright © 2016 Cognitive Science Society, Inc.

  10. Darwin, artificial selection, and poverty.

    PubMed

    Sanchez, Luis

    2010-03-01

    This paper argues that the processes of evolutionary selection are becoming increasingly artificial, a trend that goes against the belief in a purely natural selection process claimed by Darwin's natural selection theory. Artificial selection is mentioned by Darwin, but it was ignored by Social Darwinists, and it is all but absent in neo-Darwinian thinking. This omission results in an underestimation of probable impacts of artificial selection upon assumed evolutionary processes, and has implications for the ideological uses of Darwin's language, particularly in relation to poverty and other social inequalities. The influence of artificial selection on genotypic and phenotypic adaptations arguably represents a substantial shift in the presumed path of evolution, a shift laden with both biological and political implications.

  11. Evidences of local adaptation in quantitative traits in Prosopis alba (Leguminosae).

    PubMed

    Bessega, C; Pometti, C; Ewens, M; Saidman, B O; Vilardi, J C

    2015-02-01

    Signals of selection on quantitative traits can be detected by the comparison between the genetic differentiation of molecular (neutral) markers and quantitative traits, by multivariate extensions of the same model and by the observation of the additive covariance among relatives. We studied, by three different tests, signals of occurrence of selection in Prosopis alba populations over 15 quantitative traits: three economically important life history traits: height, basal diameter and biomass, 11 leaf morphology traits that may be related with heat-tolerance and physiological responses and spine length that is very important from silvicultural purposes. We analyzed 172 G1-generation trees growing in a common garden belonging to 32 open pollinated families from eight sampling sites in Argentina. The multivariate phenotypes differ significantly among origins, and the highest differentiation corresponded to foliar traits. Molecular genetic markers (SSR) exhibited significant differentiation and allowed us to provide convincing evidence that natural selection is responsible for the patterns of morphological differentiation. The heterogeneous selection over phenotypic traits observed suggested different optima in each population and has important implications for gene resource management. The results suggest that the adaptive significance of traits should be considered together with population provenance in breeding program as a crucial point prior to any selecting program, especially in Prosopis where the first steps are under development.

  12. Selective two-photon collagen crosslinking in situ measured by Brillouin microscopy (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Kwok, Sheldon J. J.; Kuznetsov, Ivan A.; Kim, Moonseok; Choi, Myunghwan; Scarcelli, Giuliano; Yun, Seok-Hyun

    2017-02-01

    Two-photon polymerization and crosslinking are commonly used methods for microfabrication of three-dimensional structures with applications spanning from photonic microdevices, drug delivery systems, to cellular scaffolds. However, the use of two-photon processes for precise, internal modification of biological tissues has not yet been reported. One of the major challenges has been a lack of appropriate tools to monitor and characterize crosslinked regions nondestructively. Here, we demonstrate spatially selective two-photon collagen crosslinking (2P-CXL) in intact tissue for the first time. Using riboflavin photosensitizer and femtosecond laser irradiation, we crosslinked a small volume of tissue within animal corneas. Collagen fiber orientations and photobleaching were characterized by second harmonic generation and two-photon fluorescence imaging, respectively. Using confocal Brillouin microscopy, we measured local changes in longitudinal mechanical moduli and visualized the cross-linked pattern without perturbing surrounding non-irradiated regions. 2P-CXL-induced tissue stiffening was comparable to that achieved with conventional one-photon CXL. Our results demonstrate the ability to selectively stiffen biological tissue in situ at high spatial resolution, with broad implications in ophthalmology, laser surgery, and tissue engineering.

  13. The 'friendship dynamics of religion,' or the 'religious dynamics of friendship'? A social network analysis of adolescents who attend small schools.

    PubMed

    Cheadle, Jacob E; Schwadel, Philip

    2012-09-01

    Longitudinal social network data on adolescents in seven schools are analyzed to reach a new understanding about how the personal and interpersonal social dimensions of adolescent religion intertwine together in small school settings. We primarily address two issues relevant to the sociology of religion and sociology in general: (1) social selection as a source of religious homophily and (2) friend socialization of religion. Analysis results are consistent with Collins' interaction ritual chain theory, which stresses the social dimensions of religion, since network-religion autocorrelations are relatively substantial in magnitude and both selection and socialization mechanisms play key roles in generating them. Results suggest that socialization plays a stronger role than social selection in four of six religious outcomes, and that more religious youth are more cliquish. Implications for our understanding of the social context of religion, religious homophily, and the ways we model religious influence, as well as limitations and considerations for future research, are discussed. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Altered selection during language processing in individuals at high risk for psychosis.

    PubMed

    Vargas, T; Snyder, H; Banich, M; Newberry, R; Shankman, Stewart A; Strauss, Gregory P; Mittal, V A

    2018-06-19

    Performance in the executive function (EF) domain has been linked to symptoms and functional outcomes in psychosis. Studies have found that UHR populations have difficulty with verbal fluency, which involves multiple facets of EF. Two potentially implicated EF facets were examined to explore whether these could be dissociated in UHR populations: selection among alternatives (measured by selection costs) and retrieval from semantic memory retrieval (measured by retrieval costs). A total of 45 UHR individuals and 46 healthy controls (HVs) were assessed with a verb generation task. Differences in selection cost (RT difference between high and low selection demand conditions) and retrieval cost (RT difference between high and low retrieval demand conditions) were examined and participants were also assessed for clinical symptoms. The UHR group showed greater selection costs relative to HVs, F (1, 91) = 4.39, p = 0.039. However, there were no group differences on retrieval cost, F (1, 91) = 0.63, p = 0.43. A positive association (r = 0.41) was found between disorganized and negative symptoms and selection costs (but not retrieval costs) in the UHR group. There was no significant association between selection costs and positive symptoms. Increased selection costs may reflect impaired performance in the neural inhibition domain of EF in the UHR population, potentially underlying a mechanistically distinct EF subdomain that affects the group's ability to efficiently select between competing options. Findings suggest that UHR individuals may exhibit impairment in selecting among alternatives, but not in retrieval from semantic memory. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Overtone-based pitch selection in hermit thrush song: unexpected convergence with scale construction in human music.

    PubMed

    Doolittle, Emily L; Gingras, Bruno; Endres, Dominik M; Fitch, W Tecumseh

    2014-11-18

    Many human musical scales, including the diatonic major scale prevalent in Western music, are built partially or entirely from intervals (ratios between adjacent frequencies) corresponding to small-integer proportions drawn from the harmonic series. Scientists have long debated the extent to which principles of scale generation in human music are biologically or culturally determined. Data from animal "song" may provide new insights into this discussion. Here, by examining pitch relationships using both a simple linear regression model and a Bayesian generative model, we show that most songs of the hermit thrush (Catharus guttatus) favor simple frequency ratios derived from the harmonic (or overtone) series. Furthermore, we show that this frequency selection results not from physical constraints governing peripheral production mechanisms but from active selection at a central level. These data provide the most rigorous empirical evidence to date of a bird song that makes use of the same mathematical principles that underlie Western and many non-Western musical scales, demonstrating surprising convergence between human and animal "song cultures." Although there is no evidence that the songs of most bird species follow the overtone series, our findings add to a small but growing body of research showing that a preference for small-integer frequency ratios is not unique to humans. These findings thus have important implications for current debates about the origins of human musical systems and may call for a reevaluation of existing theories of musical consonance based on specific human vocal characteristics.

  16. Sex-ratio control erodes sexual selection, revealing evolutionary feedback from adaptive plasticity.

    PubMed

    Fawcett, Tim W; Kuijper, Bram; Weissing, Franz J; Pen, Ido

    2011-09-20

    Female choice is a powerful selective force, driving the elaboration of conspicuous male ornaments. This process of sexual selection has profound implications for many life-history decisions, including sex allocation. For example, females with attractive partners should produce more sons, because these sons will inherit their father's attractiveness and enjoy high mating success, thereby yielding greater fitness returns than daughters. However, previous research has overlooked the fact that there is a reciprocal feedback from life-history strategies to sexual selection. Here, using a simple mathematical model, we show that if mothers adaptively control offspring sex in relation to their partner's attractiveness, sexual selection is weakened and male ornamentation declines. This weakening occurs because the ability to determine offspring sex reduces the fitness difference between females with attractive and unattractive partners. We use individual-based, evolutionary simulations to show that this result holds under more biologically realistic conditions. Sexual selection and sex allocation thus interact in a dynamic fashion: The evolution of conspicuous male ornaments favors sex-ratio adjustment, but this conditional strategy then undermines the very same process that generated it, eroding sexual selection. We predict that, all else being equal, the most elaborate sexual displays should be seen in species with little or no control over offspring sex. The feedback process we have described points to a more general evolutionary principle, in which a conditional strategy weakens directional selection on another trait by reducing fitness differences.

  17. The complexity of selection at the major primate beta-defensin locus.

    PubMed

    Semple, Colin A M; Maxwell, Alison; Gautier, Philippe; Kilanowski, Fiona M; Eastwood, Hayden; Barran, Perdita E; Dorin, Julia R

    2005-05-18

    We have examined the evolution of the genes at the major human beta-defensin locus and the orthologous loci in a range of other primates and mouse. For the first time these data allow us to examine selective episodes in the more recent evolutionary history of this locus as well as the ancient past. We have used a combination of maximum likelihood based tests and a maximum parsimony based sliding window approach to give a detailed view of the varying modes of selection operating at this locus. We provide evidence for strong positive selection soon after the duplication of these genes within an ancestral mammalian genome. Consequently variable selective pressures have acted on beta-defensin genes in different evolutionary lineages, with episodes both of negative, and more rarely positive selection, during the divergence of primates. Positive selection appears to have been more common in the rodent lineage, accompanying the birth of novel, rodent-specific beta-defensin genes. These observations allow a fuller understanding of the evolution of mammalian innate immunity. In both the rodent and primate lineages, sites in the second exon have been subject to positive selection and by implication are important in functional diversity. A small number of sites in the mature human peptides were found to have undergone repeated episodes of selection in different primate lineages. Particular sites were consistently implicated by multiple methods at positions throughout the mature peptides. These sites are clustered at positions predicted to be important for the specificity of the antimicrobial or chemoattractant properties of beta-defensins. Surprisingly, sites within the prepropeptide region were also implicated as being subject to significant positive selection, suggesting previously unappreciated functional significance for this region. Identification of these putatively functional sites has important implications for our understanding of beta-defensin function and for novel antibiotic design.

  18. Strategies in identifying individuals in a segregant population of common bean and implications of genotype x environment interaction in the success of selection.

    PubMed

    Mendes, M P; Ramalho, M A P; Abreu, A F B

    2012-04-10

    The objective of this study was to compare the BLUP selection method with different selection strategies in F(2:4) and assess the efficiency of this method on the early choice of the best common bean (Phaseolus vulgaris) lines. Fifty-one F(2:4) progenies were produced from a cross between the CVIII8511 x RP-26 lines. A randomized block design was used with 20 replications and one-plant field plots. Character data on plant architecture and grain yield were obtained and then the sum of the standardized variables was estimated for simultaneous selection of both traits. Analysis was carried out by mixed models (BLUP) and the least squares method to compare different selection strategies, like mass selection, stratified mass selection and between and within progeny selection. The progenies selected by BLUP were assessed in advanced generations, always selecting the greatest and smallest sum of the standardized variables. Analyses by the least squares method and BLUP procedure ranked the progenies in the same way. The coincidence of the individuals identified by BLUP and between and within progeny selection was high and of the greatest magnitude when BLUP was compared with mass selection. Although BLUP is the best estimator of genotypic value, its efficiency in the response to long term selection is not different from any of the other methods, because it is also unable to predict the future effect of the progenies x environments interaction. It was inferred that selection success will always depend on the most accurate possible progeny assessment and using alternatives to reduce the progenies x environments interaction effect.

  19. Generation Y Student-Teachers' Motivational Factors: Retention Implications for K-12 Educational Leaders

    ERIC Educational Resources Information Center

    Bontempo, Brian

    2010-01-01

    Generation Y represents a growing number of student-teachers who will impact the future of educational practice, yet little research has been conducted for this demographic group. The purpose of this mixed-method study was to identify motivational factors of neophyte teachers and the retention implications these findings had on Kindergarten…

  20. Shuttle/ISS EMU Failure History and the Impact on Advanced EMU Portable Life Support System (PLSS) Design

    NASA Technical Reports Server (NTRS)

    Campbell, Colin

    2015-01-01

    As the Shuttle/ISS EMU Program exceeds 35 years in duration and is still supporting the needs of the International Space Station (ISS), a critical benefit of such a long running program with thorough documentation of system and component failures is the ability to study and learn from those failures when considering the design of the next generation space suit. Study of the subject failure history leads to changes in the Advanced EMU Portable Life Support System (PLSS) schematic, selected component technologies, as well as the planned manner of ground testing. This paper reviews the Shuttle/ISS EMU failure history and discusses the implications to the AEMU PLSS.

  1. Harnessing dendritic cells in inflammatory skin diseases

    PubMed Central

    Chu, Chung-Ching; Di Meglio, Paola; Nestle, Frank O.

    2011-01-01

    The skin immune system harbors a complex network of dendritic cells (DCs). Recent studies highlight a diverse functional specialization of skin DC subsets. In addition to generating cellular and humoral immunity against pathogens, skin DCs are involved in tolerogenic mechanisms to ensure the maintenance of immune homeostasis, as well as in pathogenesis of chronic inflammation in the skin when excessive immune responses are initiated and unrestrained. Harnessing DCs by directly targeting DC-derived molecules or selectively modulate DC subsets is a convincing strategy to tackle inflammatory skin diseases. In this review we discuss recent advances underlining the functional specialization of skin DCs and discuss the potential implication for future DC-based therapeutic strategies. PMID:21295490

  2. The impact of high- and low-preference stimuli on vocational and academic performances of youths with severe disabilities.

    PubMed

    Graff, Richard B; Gibson, Lenwood; Galiatsatos, G Tracey

    2006-01-01

    Pictorial and tangible paired-stimulus preference assessments were compared with 4 adolescents with developmental disabilities. In the tangible assessment, two stimuli were placed in front of the participant on each trial; in the pictorial assessment, two line drawings were placed in front of the participant on each trial. Approach responses were recorded for each assessment. The assessments generated similar preference hierarchies for all participants. Reinforcer assessments confirmed that response rates were higher when access to high-preference items was available than when low-preference items were available. Implications for assessing preferences and selecting items to be used in training programs are discussed.

  3. 'Knock, and it shall be opened': knocking out and knocking in to reveal mechanisms of disease and novel therapies.

    PubMed

    Hacking, Douglas F

    2008-12-01

    Recent significant advances in molecular biology have generated genetically modified bacteria, yeast, nematodes, fruit flies, and fish. However, it is the genetic modification of mammalian model organisms, particularly the mouse, that has the greatest potential to shed light on human development, physiology and pathology in ways that have significant implications for neonatal and paediatric clinical practice. Here, we review some of the techniques for knocking out (inactivating), mutating and knocking in (inserting) selected genes that are important to neonatology and show how this research will lead both to a better understanding of disease and to novel therapies for infants and children.

  4. Reduced mutation rate in exons due to differential mismatch repair

    PubMed Central

    Mularoni, Loris; Muiños, Ferran; Gonzalez-Perez, Abel; López-Bigas, Núria

    2017-01-01

    While recent studies have revealed higher than anticipated heterogeneity of mutation rate across genomic regions, mutations in exons and introns are assumed to be generated at the same rate. Here we find fewer somatic mutations in exons than expected based on their sequence content, and demonstrate that this is not due to purifying selection. Moreover, we show that it is caused by higher mismatch repair activity in exonic than in intronic regions. Our findings have important implications for our understanding of mutational and DNA repair processes, our knowledge of the evolution of eukaryotic genes, and practical ramifications for the study of the evolution of both tumors and species. PMID:29106418

  5. Responsive Persistence Part II. Practices of Postmodern Therapists.

    PubMed

    Sutherland, Olga; Dienhart, Anna; Turner, Jean

    2013-10-01

    This article, a companion to Part I of this series of articles, discusses how therapists informed by social constructionist and postmodern ideas enact persistence in their work with families. Transcripts and video-recordings of therapy interaction facilitated by selected major champions for three postmodern (collaborative) therapies: Michael White (narrative therapy), Harlene Anderson (collaborative language systems approach), and Bill O'Hanlon (solution-oriented therapy) were examined for persistence practices. The article offers a range of possible ways in which postmodern therapists may enact their influence in facilitating generative and helpful conversations with families and remain responsive to clients' preferences and understandings. Implications for family therapy practice, training, and supervision are discussed. © 2013 American Association for Marriage and Family Therapy.

  6. Shuttle/ISS EMU Failure History and the Impact on Advanced EMU PLSS Design

    NASA Technical Reports Server (NTRS)

    Campbell, Colin

    2011-01-01

    As the Shuttle/ISS EMU Program exceeds 30 years in duration and is still successfully supporting the needs of the International Space Station (ISS), a critical benefit of such a long running program with thorough documentation of system and component failures is the ability to study and learn from those failures when considering the design of the next generation space suit. Study of the subject failure history leads to changes in the Advanced EMU Portable Life Support System (PLSS) schematic, selected component technologies, as well as the planned manner of ground testing. This paper reviews the Shuttle/ISS EMU failure history and discusses the implications to the AEMU PLSS.

  7. Shuttle/ISS EMU Failure History and the Impact on Advanced EMU PLSS Design

    NASA Technical Reports Server (NTRS)

    Campbell, Colin

    2015-01-01

    As the Shuttle/ISS EMU Program exceeds 30 years in duration and is still supporting the needs of the International Space Station (ISS), a critical benefit of such a long running program with thorough documentation of system and component failures is the ability to study and learn from those failures when considering the design of the next generation space suit. Study of the subject failure history leads to changes in the Advanced EMU Portable Life Support System (PLSS) schematic, selected component technologies, as well as the planned manner of ground testing. This paper reviews the Shuttle/ISS EMU failure history and discusses the implications to the AEMU PLSS.

  8. Source memory in the rat.

    PubMed

    Crystal, Jonathon D; Alford, Wesley T; Zhou, Wenyi; Hohmann, Andrea G

    2013-03-04

    Source memory is a representation of the origin (source) of information. When source information is bound together, it makes a memory episodic, allowing us to differentiate one event from another. Here, we asked whether rats remember the source of encoded information. Rats foraged for distinctive flavors of food that replenished (or failed to replenish) at its recently encountered location according to a source-information rule. To predict replenishment, rats needed to remember where they had encountered a preferred food type (chocolate) with self-generated (walking along a runway encountering chocolate) or experimenter-generated (placement of the rat at the chocolate site by an experimenter) cues. Three lines of evidence implicate the presence of source memory. First, rats selectively adjusted revisits to the chocolate location based on source information, under conditions in which familiarity of events could not produce successful performance. Second, source memory was dissociated from location memory by different decay rates. Third, temporary inactivation of the CA3 region of the hippocampus with lidocaine selectively eliminated source memory, suggesting that source memory is dependent upon an intact hippocampus. Development of an animal model of source memory may be valuable to probe the biological underpinnings of memory disorders marked by impairments in source memory. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Saccade Generation by the Frontal Eye Fields in Rhesus Monkeys Is Separable from Visual Detection and Bottom-Up Attention Shift

    PubMed Central

    Lee, Kyoung-Min; Ahn, Kyung-Ha; Keller, Edward L.

    2012-01-01

    The frontal eye fields (FEF), originally identified as an oculomotor cortex, have also been implicated in perceptual functions, such as constructing a visual saliency map and shifting visual attention. Further dissecting the area’s role in the transformation from visual input to oculomotor command has been difficult because of spatial confounding between stimuli and responses and consequently between intermediate cognitive processes, such as attention shift and saccade preparation. Here we developed two tasks in which the visual stimulus and the saccade response were dissociated in space (the extended memory-guided saccade task), and bottom-up attention shift and saccade target selection were independent (the four-alternative delayed saccade task). Reversible inactivation of the FEF in rhesus monkeys disrupted, as expected, contralateral memory-guided saccades, but visual detection was demonstrated to be intact at the same field. Moreover, saccade behavior was impaired when a bottom-up shift of attention was not a prerequisite for saccade target selection, indicating that the inactivation effect was independent of the previously reported dysfunctions in bottom-up attention control. These findings underscore the motor aspect of the area’s functions, especially in situations where saccades are generated by internal cognitive processes, including visual short-term memory and long-term associative memory. PMID:22761923

  10. Saccade generation by the frontal eye fields in rhesus monkeys is separable from visual detection and bottom-up attention shift.

    PubMed

    Lee, Kyoung-Min; Ahn, Kyung-Ha; Keller, Edward L

    2012-01-01

    The frontal eye fields (FEF), originally identified as an oculomotor cortex, have also been implicated in perceptual functions, such as constructing a visual saliency map and shifting visual attention. Further dissecting the area's role in the transformation from visual input to oculomotor command has been difficult because of spatial confounding between stimuli and responses and consequently between intermediate cognitive processes, such as attention shift and saccade preparation. Here we developed two tasks in which the visual stimulus and the saccade response were dissociated in space (the extended memory-guided saccade task), and bottom-up attention shift and saccade target selection were independent (the four-alternative delayed saccade task). Reversible inactivation of the FEF in rhesus monkeys disrupted, as expected, contralateral memory-guided saccades, but visual detection was demonstrated to be intact at the same field. Moreover, saccade behavior was impaired when a bottom-up shift of attention was not a prerequisite for saccade target selection, indicating that the inactivation effect was independent of the previously reported dysfunctions in bottom-up attention control. These findings underscore the motor aspect of the area's functions, especially in situations where saccades are generated by internal cognitive processes, including visual short-term memory and long-term associative memory.

  11. A web-based multicriteria evaluation of spatial trade-offs between environmental and economic implications from hydraulic fracturing in a shale gas region in Ohio.

    PubMed

    Liu, X; Gorsevski, P V; Yacobucci, M M; Onasch, C M

    2016-06-01

    Planning of shale gas infrastructure and drilling sites for hydraulic fracturing has important spatial implications. The evaluation of conflicting and competing objectives requires an explicit consideration of multiple criteria as they have important environmental and economic implications. This study presents a web-based multicriteria spatial decision support system (SDSS) prototype with a flexible and user-friendly interface that could provide educational or decision-making capabilities with respect to hydraulic fracturing site selection in eastern Ohio. One of the main features of this SDSS is to emphasize potential trade-offs between important factors of environmental and economic ramifications from hydraulic fracturing activities using a weighted linear combination (WLC) method. In the prototype, the GIS-enabled analytical components allow spontaneous visualization of available alternatives on maps which provide value-added features for decision support processes and derivation of final decision maps. The SDSS prototype also facilitates nonexpert participation capabilities using a mapping module, decision-making tool, group decision module, and social media sharing tools. The logical flow of successively presented forms and standardized criteria maps is used to generate visualization of trade-off scenarios and alternative solutions tailored to individual user's preferences that are graphed for subsequent decision-making.

  12. In search of the skeletal stem cell: isolation and separation strategies at the macro/micro scale for skeletal regeneration.

    PubMed

    Gothard, David; Tare, Rahul S; Mitchell, Peter D; Dawson, Jonathan I; Oreffo, Richard O C

    2011-04-07

    Skeletal stem cells (SSCs) show great capacity for bone and cartilage repair however, current in vitro cultures are heterogeneous displaying a hierarchy of differentiation potential. SSCs represent the diminutive true multipotent stem cell fraction of bone marrow mononuclear cell (BMMNC) populations. Endeavours to isolate SSCs have generated a multitude of separation methodologies. SSCs were first identified and isolated by their ability to adhere to culture plastic. Once isolated, further separation is achieved via culture in selective or conditioned media (CM). Indeed, preferential SSC growth has been demonstrated through selective in vitro culture conditions. Other approaches have utilised cell morphology (size and shape) as selection criteria. Studies have also targeted SSCs based on their preferential adhesion to specified compounds, individually or in combination, on both macro and microscale platforms. Nevertheless, most of these methods which represent macroscale function with relatively high throughput, yield insufficient purity. Consequently, research has sought to downsize isolation methodologies to the microscale for single cell analysis. The central approach is identification of the requisite cell populations of SSC-specific surface markers that can be targeted for isolation by either positive or negative selection. SELEX and phage display technology provide apt means to sift through substantial numbers of candidate markers. In contrast, single cell analysis is the paramount advantage of microfluidics, a relatively new field for cell biology. Here cells can be separated under continuous or discontinuous flow according to intrinsic phenotypic and physicochemical properties. The combination of macroscale quantity with microscale specificity to generate robust high-throughput (HT) technology for pure SSC sorting, isolation and enrichment offers significant implications therein for skeletal regenerative strategies as a consequence of lab on chip derived methodology.

  13. Parallel evolution of sexual isolation in sticklebacks.

    PubMed

    Boughman, Janette Wenrick; Rundle, Howard D; Schluter, Dolph

    2005-02-01

    Mechanisms of speciation are not well understood, despite decades of study. Recent work has focused on how natural and sexual selection cause sexual isolation. Here, we investigate the roles of divergent natural and sexual selection in the evolution of sexual isolation between sympatric species of threespine sticklebacks. We test the importance of morphological and behavioral traits in conferring sexual isolation and examine to what extent these traits have diverged in parallel between multiple, independently evolved species pairs. We use the patterns of evolution in ecological and mating traits to infer the likely nature of selection on sexual isolation. Strong parallel evolution implicates ecologically based divergent natural and/or sexual selection, whereas arbitrary directionality implicates nonecological sexual selection or drift. In multiple pairs we find that sexual isolation arises in the same way: assortative mating on body size and asymmetric isolation due to male nuptial color. Body size and color have diverged in a strongly parallel manner, similar to ecological traits. The data implicate ecologically based divergent natural and sexual selection as engines of speciation in this group.

  14. Tone signal generator for producing multioperator tone signals using an operator circuit including a waveform generator, a selector and an enveloper

    DOEpatents

    Dong, Qiujie; Jenkins, Michael V.; Bernadas, Salvador R.

    1997-01-01

    A frequency modulation (FM) tone signal generator for generating a FM tone signal is disclosed. The tone signal generator includes a waveform generator having a plurality of wave tables, a selector and an enveloper. The waveform generator furnishes a waveform signal in response to a phase angle address signal. Each wave table stores a different waveform. The selector selects one of the wave tables in response to a plurality of selection signals such that the selected wave table largely provides the waveform signal upon being addressed largely by the phase angle address signal. Selection of the selected wave table varies with each selection signal. The enveloper impresses an envelope signal on the waveform signal. The envelope signal is used as a carrier or modulator for generating the FM tone signal.

  15. A new method for assessing the impact of medial temporal lobe amnesia on the characteristics of generated autobiographical events.

    PubMed

    Lenton-Brym, Ariella; Kurczek, Jake; Rosenbaum, R Shayna; Sheldon, Signy

    2016-05-01

    Constructing autobiographical events involves an initial phase of event selection, in which a memory or imagined future event is initially brought to mind, followed by a phase of elaboration, in which an individual accesses detailed knowledge specific to the event. While considerable research demonstrates the importance of the medial temporal lobes (MTL) in the later phase, its role in initial event selection is unknown. The present study is the first to investigate the role of the MTL in event selection by assessing whether individuals with MTL lesions select qualitatively different events for remembering and imagining than matched control participants. To do so, we created "event captions" that reflected the type of events selected for an autobiographical event narrative task by four individuals with MTL amnesia and control counterparts. Over 450 online raters assessed these event captions on qualitative dimensions known to vary with autobiographical recall (frequency, significance, emotionality, imageability, and uniqueness). Our critical finding was that individuals with MTL amnesia were more prone to select events that were rated as more frequently occurring than healthy control participants. We interpret this finding as evidence that people with impaired episodic memory from MTL damage compensate for their compromised ability to recall detailed information by relying more heavily on semantic memory processes to select generalized events. We discuss the implications for theoretical models of memory and methodological approaches to studying autobiographical memory. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Extrinsic Motivation as Correlates of Work Attitude of the Nigerian Police Force: Implications for Counselling

    ERIC Educational Resources Information Center

    Igun, Sylvester Nosakhare

    2008-01-01

    The study examined Extrinsic motivation as correlates of work attitude of the Nigeria Police Force and its implications for counselling. 300 Police personnel were selected by random sampling technique from six departments that make up police force Headquarters, Abuja. The personnel were selected from each department using simple sampling…

  17. Policy Implications for Using ICTs for Empowerment of Rural Women in Ghana

    ERIC Educational Resources Information Center

    Kwapong, Olivia Adwoa Tiwaah Frimpong

    2008-01-01

    Using rural household survey data collected from 1000 female household heads selected from all the ten administrative regions in Ghana, this paper explored the policy implications for using ICTs for empowerment of rural women. A contingent valuation (CV) method was used to quantitatively estimate the influence of selected socio-economic factors on…

  18. The structural biochemistry of Zucchini implicates it as a nuclease in piRNA biogenesis

    PubMed Central

    Ipsaro, Jonathan J.; Haase, Astrid D.; Knott, Simon R.; Joshua-Tor, Leemor; Hannon, Gregory J.

    2012-01-01

    PIWI-family proteins and their associated small RNAs (piRNAs) act in an evolutionarily conserved innate immune mechanism that provides an essential protection for germ cell genomes against the activity of mobile genetic elements1. piRNA populations comprise a molecular definition of transposons that permits them to be distinguished from host genes and selectively silenced. piRNAs can be generated in two distinct ways. Primary piRNAs emanate from discrete genomic loci, termed piRNA clusters, and appear to be derived from long, single-stranded precursors2. The biogenesis of primary piRNAs involves at least two nucleolytic steps. An unknown enzyme cleaves piRNA cluster transcripts to generate monophosphorylated piRNA 5' ends. piRNA 3' ends are likely formed by exonucleolytic trimming, after a piRNA precursor is loaded into its PIWI partner1,3. Secondary piRNAs arise during the adaptive ping-pong cycle, with their 5' termini being formed by the activity of PIWIs themselves2,4. A number of proteins have been implicated genetically in primary piRNA biogenesis. One of these, Zucchini, is a member of the phospholipase D family of phosphodiesterases, which includes both phospholipases and nucleases5–7. We have produced a dimeric, soluble fragment of the mouse Zucchini homolog (mZuc/PLD6) and have shown that it possesses single strand-specific nuclease activity. A crystal structure of mZuc at 1.75 Å resolution indicates greater architectural similarity to PLD-family nucleases than to phospholipases. Considered together, our data suggest that the Zucchini proteins act in primary piRNA biogenesis as nucleases, perhaps generating the 5' ends of primary piRNAs. PMID:23064227

  19. The Study of Nursing Care project: back to the future for contemporary nursing research?

    PubMed

    Smith, Kylie M; Crookes, Patrick A

    2012-11-01

      To discuss the Study of Nursing Care project, an initiative from the late 1970s in the UK. The article explores the impact of the Study of Nursing Care on nursing research, and considers to what extent it presents a useful model for contemporary nursing research.   It is acknowledged internationally that the nursing academic workforce is ageing and dwindling. Many possible solutions are being debated with all agreeing that the next generation of evidence based nurse leaders is urgently required.   In this article, the authors survey existing workforce schemes, describe the Study of Nursing Care series, published in the 1970s, and draw on interviews and correspondence conducted in 2009 with four of the original Study of Nursing Care research assistants.   The Study of Nursing Care project poses a potential response to academic workforce issues. This article discusses the evolution of the project, its methods and operation and considers its possible implications for contemporary practice. Implications for nursing.  The Study of Nursing Care model demonstrates the clear benefits of fully committed funding, a programmatic approach towards research development, and the importance of selecting the right kind of people for the work, in a national scheme.   The authors argue that although the clinical outcomes it set out to achieve remain elusive, the project produced a cohort of nurse researchers who went on to give important leadership in nursing, including in nursing academia/research. A contemporary version of the Study of Nursing Care has important potential to generate the next generation of nurse researchers, and leaders, into the twenty-first century. © 2012 Blackwell Publishing Ltd.

  20. A general theory of evolution based on energy efficiency: its implications for diseases.

    PubMed

    Yun, Anthony J; Lee, Patrick Y; Doux, John D; Conley, Buford R

    2006-01-01

    We propose a general theory of evolution based on energy efficiency. Life represents an emergent property of energy. The earth receives energy from cosmic sources such as the sun. Biologic life can be characterized by the conversion of available energy into complex systems. Direct energy converters such as photosynthetic microorganisms and plants transform light energy into high-energy phosphate bonds that fuel biochemical work. Indirect converters such as herbivores and carnivores predominantly feed off the food chain supplied by these direct converters. Improving energy efficiency confers competitive advantage in the contest among organisms for energy. We introduce a term, return on energy (ROE), as a measure of energy efficiency. We define ROE as a ratio of the amount of energy acquired by a system to the amount of energy consumed to generate that gain. Life-death cycling represents a tactic to sample the environment for innovations that allow increases in ROE to develop over generations rather than an individual lifespan. However, the variation-selection strategem of Darwinian evolution may define a particular tactic rather than an overarching biological paradigm. A theory of evolution based on competition for energy and driven by improvements in ROE both encompasses prior notions of evolution and portends post-Darwinian mechanisms. Such processes may involve the exchange of non-genetic traits that improve ROE, as exemplified by cognitive adaptations or memes. Under these circumstances, indefinite persistence may become favored over life-death cycling, as increases in ROE may then occur more efficiently within a single lifespan rather than over multiple generations. The key to this transition may involve novel methods to address the promotion of health and cognitive plasticity. We describe the implications of this theory for human diseases.

  1. Tone signal generator for producing multioperator tone signals using an operator circuit including a waveform generator, a selector and an enveloper

    DOEpatents

    Dong, Q.; Jenkins, M.V.; Bernadas, S.R.

    1997-09-09

    A frequency modulation (FM) tone signal generator for generating a FM tone signal is disclosed. The tone signal generator includes a waveform generator having a plurality of wave tables, a selector and an enveloper. The waveform generator furnishes a waveform signal in response to a phase angle address signal. Each wave table stores a different waveform. The selector selects one of the wave tables in response to a plurality of selection signals such that the selected wave table largely provides the waveform signal upon being addressed largely by the phase angle address signal. Selection of the selected wave table varies with each selection signal. The enveloper impresses an envelope signal on the waveform signal. The envelope signal is used as a carrier or modulator for generating the FM tone signal. 17 figs.

  2. Implications of the licensure of a partially efficacious malaria vaccine on evaluating second-generation vaccines.

    PubMed

    Fowkes, Freya J I; Simpson, Julie A; Beeson, James G

    2013-10-30

    Malaria is a leading cause of morbidity and mortality, with approximately 225 million clinical episodes and >1.2 million deaths annually attributed to malaria. Development of a highly efficacious malaria vaccine will offer unparalleled possibilities for disease prevention and remains a key priority for long-term malaria control and elimination. The Malaria Vaccine Technology Roadmap's goal is to 'develop and license a first-generation malaria vaccine that has protective efficacy of more than 50%'. To date, malaria vaccine candidates have only been shown to be partially efficacious (approximately 30% to 60%). However, licensure of a partially effective vaccine will create a number of challenges for the development and progression of new, potentially more efficacious, malaria vaccines in the future. In this opinion piece we discuss the methodological, logistical and ethical issues that may impact on the feasibility and implementation of superiority, non-inferiority and equivalence trials to assess second generation malaria vaccines in the advent of the licensure of a partially efficacious malaria vaccine. Selecting which new malaria vaccines go forward, and defining appropriate methodology for assessment in logistically challenging clinical trials, is crucial. It is imperative that the scientific community considers all the issues and starts planning how second-generation malaria vaccines will advance in the advent of licensure of a partially effective vaccine.

  3. Reappraisal inventiveness: impact of appropriate brain activation during efforts to generate alternative appraisals on the perception of chronic stress in women.

    PubMed

    Perchtold, Corinna M; Fink, Andreas; Rominger, Christian; Weber, Hannelore; de Assunção, Vera Loureiro; Schulter, Günter; Weiss, Elisabeth M; Papousek, Ilona

    2018-03-01

    Previous research indicated that more left-lateralized prefrontal activation during cognitive reappraisal efforts was linked to a greater capacity for generating reappraisals, which is a prerequisite for the effective implementation of cognitive reappraisal in everyday life. The present study examined whether the supposedly appropriate brain activation is relevant in terms of more distal outcomes, i.e., chronic stress perception. Prefrontal EEG alpha asymmetry was recorded while female participants were generating reappraisals for stressful events and was correlated with their self-reported chronic stress levels in everyday life (n = 80). Women showing less left-lateralized brain activity in the ventrolateral prefrontal cortex during cognitive reappraisal efforts reported experiencing more stress in their daily lives. This effect was independent of self-efficacy beliefs in managing negative emotions. These findings underline the practical relevance of individual differences in appropriate brain activation during emotion regulation efforts and the assumedly related basic capacity for the generation of cognitive reappraisals to the feeling of being stressed. Implications include the selection of interventions for the improvement of coping with stress in women in whom the capability for appropriate brain activation during reappraisal efforts may be impaired, e.g., due to depression or old age.

  4. The Diversity of the Pollen Tube Pathway in Plants: Toward an Increasing Control by the Sporophyte

    PubMed Central

    Lora, Jorge; Hormaza, José I.; Herrero, María

    2016-01-01

    Plants, unlike animals, alternate multicellular diploid, and haploid generations in their life cycle. While this is widespread all along the plant kingdom, the size and autonomy of the diploid sporophyte and the haploid gametophyte generations vary along evolution. Vascular plants show an evolutionary trend toward a reduction of the gametophyte, reflected both in size and lifespan, together with an increasing dependence from the sporophyte. This has resulted in an overlooking of the importance of the gametophytic phase in the evolution of higher plants. This reliance on the sporophyte is most notorious along the pollen tube journey, where the male gametophytes have to travel a long way inside the sporophyte to reach the female gametophyte. Along evolution, there is a change in the scenery of the pollen tube pathway that favors pollen competition and selection. This trend, toward apparently making complicated what could be simple, appears to be related to an increasing control of the sporophyte over the gametophyte with implications for understanding plant evolution. PMID:26904071

  5. A metabolomics study delineating geographical location-associated primary metabolic changes in the leaves of growing tobacco plants by GC-MS and CE-MS

    PubMed Central

    Zhao, Yanni; Zhao, Jieyu; Zhao, Chunxia; Zhou, Huina; Li, Yanli; Zhang, Junjie; Li, Lili; Hu, Chunxiu; Li, Wenzheng; Peng, Xiaojun; Lu, Xin; Lin, Fucheng; Xu, Guowang

    2015-01-01

    Ecological conditions and developmental senescence significantly affect the physiological metabolism of plants, yet relatively little is known about the influence of geographical location on dynamic changes in plant leaves during growth. Pseudotargeted gas chromatography-selected ion monitoring-mass spectrometry and capillary electrophoresis-mass spectrometry were used to investigate a time course of the metabolic responses of tobacco leaves to geographical location. Principal component analysis revealed obvious metabolic discrimination between growing districts relative to cultivars. A complex carbon and nitrogen metabolic network was modulated by environmental factors during growth. When the Xuchang and Dali Districts in China were compared, the results indicated that higher rates of photosynthesis, photorespiration and respiration were utilized in Xuchang District to generate the energy and carbon skeletons needed for the biosynthesis of nitrogen-containing metabolites. The increased abundance of defense-associated metabolites generated from the shikimate-phenylpropanoid pathway in Xuchang relative to Dali was implicated in protection against stress. PMID:26549189

  6. Mesenchymal chemotaxis requires selective inactivation of Myosin II at the leading edge via a non-canonical PLCγ/PKCα pathway

    PubMed Central

    Asokan, Sreeja B.; Johnson, Heath E.; Rahman, Anisur; King, Samantha J.; Rotty, Jeremy D.; Lebedeva, Irina P.; Haugh, Jason M.; Bear, James E.

    2014-01-01

    Summary Chemotaxis, migration towards soluble chemical cues, is critical for processes such as wound healing and immune surveillance, and is exhibited by various cell types from rapidly-migrating leukocytes to slow-moving mesenchymal cells. To interrogate the mechanisms involved in mesenchymal chemotaxis, we observed cell migration in microfluidic chambers that generate stable gradients of the chemoattractant PDGF. Surprisingly, we found that pathways implicated in amoeboid chemotaxis, such as PI3K and mTOR signaling, are dispensable for chemotaxis to PDGF. Instead, we find that local inactivation of Myosin IIA, through a non-canonical Ser1/2 phosphorylation of the regulatory light chain, is essential. This site is phosphorylated by PKCα, which is activated by an intracellular gradient of diacylglycerol generated by PLCγ. Using a combination of TIRF imaging and gradients of activators/inhibitors in the microfluidic chambers, we demonstrate that this signaling pathway and subsequent inhibition of Myosin II activity at the leading edge is required for mesenchymal chemotaxis. PMID:25482883

  7. The Adaptation of the Immigrant Second Generation in America: Theoretical Overview and Recent Evidence

    PubMed Central

    Portes, Alejandro; Fernández-Kelly, Patricia; Haller, William

    2013-01-01

    This paper summarises a research program on the new immigrant second generation initiated in the early 1990s and completed in 2006. The four field waves of the Children of Immigrants Longitudinal Study (CILS) are described and the main theoretical models emerging from it are presented and graphically summarised. After considering critical views of this theory, we present the most recent results from this longitudinal research program in the forum of quantitative models predicting downward assimilation in early adulthood and qualitative interviews identifying ways to escape it by disadvantaged children of immigrants. Quantitative results strongly support the predicted effects of exogenous variables identified by segmented assimilation theory and identify the intervening factors during adolescence that mediate their influence on adult outcomes. Qualitative evidence gathered during the last stage of the study points to three factors that can lead to exceptional educational achievement among disadvantaged youths. All three indicate the positive influence of selective acculturation. Implications of these findings for theory and policy are discussed. PMID:23626483

  8. An air pollution modeling study using three surface coverings near the New International Airport of Mexico City.

    PubMed

    Jazcilevich, Arón D; García, Agustín R; Ruiz-Suárez, Luis-Gerardo

    2003-10-01

    The dry lakebed of what once was the lake of Texcoco is the location selected for the New International Airport of Mexico City. This project will generate an important urban development near the airport with regional implications on air quality. Using a prognostic air quality model, the consequences of photochemical air pollution in the metropolitan area of Mexico City resulting from three possible coverings for the areas of the lakebed that are not occupied by the runway and terminal building are investigated. These coverings are desert, grassland, and water and occupy an area of 63 km2. This study is based on a representative high pollution episode. In addition to reducing the emission of primary natural particles, the water covering generates a land-water breeze capable of maintaining enough ventilation to reduce pollutant concentrations over a localized region of the metropolitan area and may enhance the wind speed on the coasts of the proposed lake.

  9. Energy cost of wheel running in house mice: implications for coadaptation of locomotion and energy budgets.

    PubMed

    Koteja, P; Swallow, J G; Carter, P A; Garland, T

    1999-01-01

    Laboratory house mice (Mus domesticus) that had experienced 10 generations of artificial selection for high levels of voluntary wheel running ran about 70% more total revolutions per day than did mice from random-bred control lines. The difference resulted primarily from increased average velocities rather than from increased time spent running. Within all eight lines (four selected, four control), females ran more than males. Average daily running distances ranged from 4.4 km in control males to 11.6 km in selected females. Whole-animal food consumption was statistically indistinguishable in the selected and control lines. However, mice from selected lines averaged approximately 10% smaller in body mass, and mass-adjusted food consumption was 4% higher in selected lines than in controls. The incremental cost of locomotion (grams food/revolution), computed as the partial regression slope of food consumption on revolutions run per day, did not differ between selected and control mice. On a 24-h basis, the total incremental cost of running (covering a distance) amounted to only 4.4% of food consumption in the control lines and 7.5% in the selected ones. However, the daily incremental cost of time active is higher (15.4% and 13.1% of total food consumption in selected and control lines, respectively). If wheel running in the selected lines continues to increase mainly by increases in velocity, then constraints related to energy acquisition are unlikely to be an important factor limiting further selective gain. More generally, our results suggest that, in small mammals, a substantial evolutionary increase in daily movement distances can be achieved by increasing running speed, without remarkable increases in total energy expenditure.

  10. Identification of yeast DNA topoisomerase II mutants resistant to the antitumor drug doxorubicin: implications for the mechanisms of doxorubicin action and cytotoxicity.

    PubMed

    Patel, S; Sprung, A U; Keller, B A; Heaton, V J; Fisher, L M

    1997-10-01

    Doxorubicin is a therapeutically useful anticancer drug that exerts multiple biological effects. Its antitumor and cardiotoxic properties have been ascribed to anthracycline-mediated free radical damage to DNA and membranes. Evidence for this idea comes in part from the selection by doxorubicin from stationary phase yeast cells of mutants (petites) deficient in mitochondrial respiration and therefore defective in free radical generation. However, doxorubicin also binds to DNA topoisomerase II, converting the enzyme into a DNA damaging agent through the trapping of a covalent enzyme-DNA complex termed the 'cleavable complex.' We have used yeast to determine whether stabilization of cleavable complexes plays a role in doxorubicin action and cytotoxicity. A plasmid-borne yeast TOP2 gene was mutagenized with hydroxylamine and used to transform drug-permeable yeast strain JN394t2-4, which carries a temperature-sensitive top2-4 mutation in its chromosomal TOP2 gene. Selection in growth medium at the nonpermissive temperature of 35 degrees in the presence of doxorubicin resulted in the isolation of plasmid-borne top2 mutants specifying functional doxorubicin-resistant DNA topoisomerase II. Single-point changes of Gly748 to Glu or Ala642 to Ser in yeast topoisomerase II, which lie in and adjacent to the CAP-like DNA binding domain, respectively, were identified as responsible for resistance to doxorubicin, implicating these regions in drug action. None of the mutants selected in JN394t2-4, which has a rad52 defect in double-strand DNA break repair, was respiration-deficient. We conclude that topoisomerase II is an intracellular target for doxorubicin and that the genetic background and/or cell proliferation status can determine the relative importance of topoisomerase II- versus free radical-killing.

  11. The GTP-bound and Sumoylated Form of the rab17 Small Molecular Weight GTPase Selectively Binds Syntaxin 2 in Polarized Hepatic WIF-B Cells*

    PubMed Central

    Striz, Anneliese C.; Tuma, Pamela L.

    2016-01-01

    A major focus for our laboratory is identifying the molecules and mechanisms that regulate polarized apical protein sorting in hepatocytes, the major epithelial cells of the liver. These trafficking pathways are regulated, in part, by small molecular weight rab GTPases. We chose to investigate rab17, whose expression is restricted to polarized epithelial cells, is enriched in liver, and has been implicated in regulating basolateral to apical transcytosis. To initiate our studies, we generated three recombinant adenoviruses expressing wild type, constitutively active (GTP bound), or dominant-negative (GDP bound) rab17. Immunoblotting revealed rab17 immunoreactive species at 25 kDa (the predicted rab17 molecular mass) and 40 kDa. We determined that mono-sumoylation of the 25-kDa rab17 is responsible for the shift in molecular mass, and that rab17 prenylation is required for sumoylation. We further determined that sumoylation selectively promotes interactions with syntaxin 2 (but not syntaxins 3 or 4) and that these interactions are nucleotide dependent. Furthermore, a K68R-mutated rab17 led to the redistribution of syntaxin 2 and 5′ nucleotidase from the apical membrane to subapical puncta, whereas multidrug resistance protein 2 distributions were not changed. Together these data are consistent with the proposed role of rab17 in vesicle fusion with the apical plasma membrane and further implicate sumoylation as an important mediator of protein-protein interactions. The selectivity in syntaxin binding and apical protein redistribution further suggests that rab17 and syntaxin 2 mediate fusion of transcytotic vesicles at the apical surface. PMID:26957544

  12. Censoring of self-reactive B cells by follicular dendritic cell-displayed self-antigen

    PubMed Central

    Yau, Irene W.; Cato, Matthew H.; Jellusova, Julia; Hurtado de Mendoza, Tatiana; Brink, Robert; Rickert, Robert C.

    2013-01-01

    In the secondary lymphoid organs, intimate contact with follicular dendritic cells (FDCs) is required for B cell retention and antigen-driven selection during the germinal center response. However, selection of self-reactive B cells by antigen on FDCs has not been addressed. To this end, we generated a mouse model to conditionally express a membrane-bound self-antigen on FDCs, and monitor the fate of developing self-reactive B cells. Here, we show that self-antigen displayed on FDCs mediates effective elimination of self-reactive B cells at the transitional stage. Notwithstanding, some self-reactive B cells persist beyond this checkpoint, showing evidence of antigen experience and intact proximal BCR signaling, but they are short-lived and unable to elicit T cell help. These results implicate FDCs as an important component of peripheral B cell tolerance that prevent the emergence of naïve B cells capable of responding to sequestered self-antigens. PMID:23817432

  13. Dual Targeting of the Chemokine Receptors CXCR4 and ACKR3 with Novel Engineered Chemokines*

    PubMed Central

    Hanes, Melinda S.; Salanga, Catherina L.; Chowdry, Arnab B.; Comerford, Iain; McColl, Shaun R.; Kufareva, Irina; Handel, Tracy M.

    2015-01-01

    The chemokine CXCL12 and its G protein-coupled receptors CXCR4 and ACKR3 are implicated in cancer and inflammatory and autoimmune disorders and are targets of numerous antagonist discovery efforts. Here, we describe a series of novel, high affinity CXCL12-based modulators of CXCR4 and ACKR3 generated by selection of N-terminal CXCL12 phage libraries on live cells expressing the receptors. Twelve of 13 characterized CXCL12 variants are full CXCR4 antagonists, and four have Kd values <5 nm. The new variants also showed high affinity for ACKR3. The variant with the highest affinity for CXCR4, LGGG-CXCL12, showed efficacy in a murine model for multiple sclerosis, demonstrating translational potential. Molecular modeling was used to elucidate the structural basis of binding and antagonism of selected variants and to guide future designs. Together, this work represents an important step toward the development of therapeutics targeting CXCR4 and ACKR3. PMID:26216880

  14. Multigenerational: Households and the School Readiness of Children Born to Unmarried Mothers

    PubMed Central

    Augustine, Jennifer March; Raley, R. Kelly

    2013-01-01

    Following the ongoing increase in nonmarital fertility, policy makers have looked for ways to limit the disadvantages faced by children of unmarried mothers. Recent initiatives included marriage promotion and welfare-to-work programs. Yet policy might also consider the promotion of three generational households. We know little about whether multigenerational households benefit children of unwed mothers, although they are mandated for unmarried teen mothers applying for welfare benefits. Multigenerational households are also becoming increasingly common. Thus, using data from the Panel Study of Income Dynamics (N = 217), this study examines whether grandparent-headed coresidential households benefit preschool-aged children’s school readiness, employing propensity score techniques to account for selection into these households. Findings reveal living with a grandparent is not associated with child outcomes for families that select into such arrangements but is positively associated with reading scores and behavior problems for families with a low propensity to coreside. The implications of these findings for policy are discussed. PMID:23847390

  15. Alteration in the immunochemical dominance of determinants following the chemical modification of ox insulins: implications for the structure of the ox insulin monomer in solution.

    PubMed Central

    Hollins, P J; Nathan, M M

    1979-01-01

    Insulins of differing species, together with chemically modified insulins, were used in cross-reactivity experiments employing selected antisera raised to ox insulin in the Harley guinea-pig. The immunogen had been administered as a water-in-oil emulsion, using H. pertussis vaccine as adjuvant. Antibody was generated by determinants in the C-terminus of the B chain plus the adjacent N-terminus of the A chain, in the central core of the A chain (A8-A14 region) and in its anti-parallel N-terminus of the B chain. From this antibody pool chemically modified ox insulin selected antibody to unaltered determinants. The immunochemical data were compatible with monomeric ox insulin being immunogenic, the immunogen perhaps being recognized by the immune system in the form of the Molecule-II rather than the Molecule-I of the dimer pair (as originally suggested by X-ray crystallographic data). PMID:93526

  16. Sustainable sewerage servicing options for peri-urban areas with failing septic systems.

    PubMed

    Sharma, A K; Tjandraatmadja, G; Grant, A L; Grant, T; Pamminger, F

    2010-01-01

    The provision of water and wastewater services to peri-urban areas faces very different challenges to providing services to cities. Sustainable solutions for such areas are increasingly being sought, in order to solve the environmental and health risks posed by failing septic systems. These solutions should have the capability to reduce potable water demand, provide fit for purpose reuse options, and minimise impacts on the local and global environment. A methodology for the selection of sustainable sewerage servicing systems and technologies is presented in this paper. This paper describes the outcomes of applying this methodology to a case study in rural community near Melbourne, Australia, and describes the economic and environmental implications of various sewerage servicing options. Applying this methodology has found that it is possible to deliver environmental improvements at a lower community cost, by choosing servicing configurations not historically used by urban water utilities. The selected solution is currently being implemented, with the aim being to generate further transferable learnings for the water industry.

  17. Oncogenic Role of SND1 in Development and Progression of Hepatocellular Carcinoma

    PubMed Central

    Jariwala, Nidhi; Rajasekaran, Devaraja; Mendoza, Rachel G.; Shen, Xue-Ning; Siddiq, Ayesha; Akiel, Maaged A.; Robertson, Chadia L.; Subler, Mark A.; Windle, Jolene J.; Fisher, Paul B.; Sanyal, Arun J.; Sarkar, Devanand

    2017-01-01

    SND1, a subunit of the miRNA regulatory complex RISC, has been implicated as an oncogene in hepatocellular carcinoma (HCC). In this study, we show that hepatocyte-specific SND1 transgenic mice (Alb/SND1 mice) develop spontaneous HCC with partial penetrance and exhibit more highly aggressive HCC induced by chemical carcinogenesis. Livers from Alb/SND1 mice exhibited a relative increase in inflammatory markers and spheroid-generating tumor initiating cells (TIC). Mechanistic investigations defined roles for Akt and NF-κB signaling pathways in promoting TIC formation in Alb/SND1 mice. In human xenograft models of subcutaneous or orthotopic HCC, administration of the selective SND1 inhibitor 3′, 5′-deoxythymidine bisphosphate (pdTp) inhibited tumor formation without effects on body weight or liver function. Our work establishes an oncogenic role for SND1 in promoting TIC formation, and highlights pdTp as a highly selective SND1 inhibitor as a candidate therapeutic lead to treat advanced HCC. PMID:28428278

  18. Integrating Renewable Generation into Grid Operations: Four International Experiences

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

    Weimar, Mark R.; Mylrea, Michael E.; Levin, Todd

    International experiences with power sector restructuring and the resultant impacts on bulk power grid operations and planning may provide insight into policy questions for the evolving United States power grid as resource mixes are changing in response to fuel prices, an aging generation fleet and to meet climate goals. Australia, Germany, Japan and the UK were selected to represent a range in the level and attributes of electricity industry liberalization in order to draw comparisons across a variety of regions in the United States such as California, ERCOT, the Southwest Power Pool and the Southeast Reliability Region. The study drawsmore » conclusions through a literature review of the four case study countries with regards to the changing resource mix and the electricity industry sector structure and their impact on grid operations and planning. This paper derives lessons learned and synthesizes implications for the United States based on answers to the above questions and the challenges faced by the four selected countries. Each country was examined to determine the challenges to their bulk power sector based on their changing resource mix, market structure, policies driving the changing resource mix, and policies driving restructuring. Each countries’ approach to solving those changes was examined, as well as how each country’s market structure either exacerbated or mitigated the approaches to solving the challenges to their bulk power grid operations and planning. All countries’ policies encourage renewable energy generation. One significant finding included the low- to zero-marginal cost of intermittent renewables and its potential negative impact on long-term resource adequacy. No dominant solution has emerged although a capacity market was introduced in the UK and is being contemplated in Japan. Germany has proposed the Energy Market 2.0 to encourage flexible generation investment. The grid operator in Australia proposed several approaches to maintaining synchronous generation. Interconnections to other regions provides added opportunities for balancing that would not be available otherwise, and at this point, has allowed for integration of renewables.« less

  19. Evolution of sparsity and modularity in a model of protein allostery

    NASA Astrophysics Data System (ADS)

    Hemery, Mathieu; Rivoire, Olivier

    2015-04-01

    The sequence of a protein is not only constrained by its physical and biochemical properties under current selection, but also by features of its past evolutionary history. Understanding the extent and the form that these evolutionary constraints may take is important to interpret the information in protein sequences. To study this problem, we introduce a simple but physical model of protein evolution where selection targets allostery, the functional coupling of distal sites on protein surfaces. This model shows how the geometrical organization of couplings between amino acids within a protein structure can depend crucially on its evolutionary history. In particular, two scenarios are found to generate a spatial concentration of functional constraints: high mutation rates and fluctuating selective pressures. This second scenario offers a plausible explanation for the high tolerance of natural proteins to mutations and for the spatial organization of their least tolerant amino acids, as revealed by sequence analysis and mutagenesis experiments. It also implies a faculty to adapt to new selective pressures that is consistent with observations. The model illustrates how several independent functional modules may emerge within the same protein structure, depending on the nature of past environmental fluctuations. Our model thus relates the evolutionary history of proteins to the geometry of their functional constraints, with implications for decoding and engineering protein sequences.

  20. Ethnic and Gender Differences in Science Graduation at Selective Colleges with Implications for Admission Policy and College Choice

    ERIC Educational Resources Information Center

    Smyth, Frederick L.; McArdle, John J.

    2004-01-01

    Using Bowen and Bok's data from 23 selective colleges, we fit multilevel logit models to test two hypotheses with implications for affirmative action and group differences in attainment of science, math, or engineering (SME) degrees. Hypothesis 1, that differences in precollege academic preparation will explain later SME graduation disparities,…

  1. Molecular Characterization of Epithelial Ovarian Cancer: Implications for Diagnosis and Treatment.

    PubMed

    Rojas, Veronica; Hirshfield, Kim M; Ganesan, Shridar; Rodriguez-Rodriguez, Lorna

    2016-12-15

    Epithelial ovarian cancer is a highly heterogeneous disease characterized by multiple histological subtypes. Molecular diversity has been shown to occur within specific histological subtypes of epithelial ovarian cancer, between different tumors of an individual patient, as well as within individual tumors. Recent advances in the molecular characterization of epithelial ovarian cancer tumors have provided the basis for a simplified classification scheme in which these cancers are classified as either type I or type II tumors, and these two categories have implications regarding disease pathogenesis and prognosis. Molecular analyses, primarily based on next-generation sequencing, otherwise known as high-throughput sequencing, are allowing for further refinement of ovarian cancer classification, facilitating the elucidation of the site(s) of precursor lesions of high-grade serous ovarian cancer, and providing insight into the processes of clonal selection and evolution that may be associated with development of chemoresistance. Potential therapeutic targets have been identified from recent molecular profiling studies of these tumors, and the effectiveness and safety of a number of specific targeted therapies have been evaluated or are currently being studied for the treatment of women with this disease.

  2. Molecular Characterization of Epithelial Ovarian Cancer: Implications for Diagnosis and Treatment

    PubMed Central

    Rojas, Veronica; Hirshfield, Kim M.; Ganesan, Shridar; Rodriguez-Rodriguez, Lorna

    2016-01-01

    Epithelial ovarian cancer is a highly heterogeneous disease characterized by multiple histological subtypes. Molecular diversity has been shown to occur within specific histological subtypes of epithelial ovarian cancer, between different tumors of an individual patient, as well as within individual tumors. Recent advances in the molecular characterization of epithelial ovarian cancer tumors have provided the basis for a simplified classification scheme in which these cancers are classified as either type I or type II tumors, and these two categories have implications regarding disease pathogenesis and prognosis. Molecular analyses, primarily based on next-generation sequencing, otherwise known as high-throughput sequencing, are allowing for further refinement of ovarian cancer classification, facilitating the elucidation of the site(s) of precursor lesions of high-grade serous ovarian cancer, and providing insight into the processes of clonal selection and evolution that may be associated with development of chemoresistance. Potential therapeutic targets have been identified from recent molecular profiling studies of these tumors, and the effectiveness and safety of a number of specific targeted therapies have been evaluated or are currently being studied for the treatment of women with this disease. PMID:27983698

  3. Brain networks for visual creativity: a functional connectivity study of planning a visual artwork.

    PubMed

    De Pisapia, Nicola; Bacci, Francesca; Parrott, Danielle; Melcher, David

    2016-12-19

    Throughout recorded history, and across cultures, humans have made visual art. In recent years, the neural bases of creativity, including artistic creativity, have become a topic of interest. In this study we investigated the neural bases of the visual creative process with both professional artists and a group of control participants. We tested the idea that creativity (planning an artwork) would influence the functional connectivity between regions involved in the default mode network (DMN), implicated in divergent thinking and generating novel ideas, and the executive control network (EN), implicated in evaluating and selecting ideas. We measured functional connectivity with functional Magnetic Resonance Imaging (fMRI) during three different conditions: rest, visual imagery of the alphabet and planning an artwork to be executed immediately after the scanning session. Consistent with our hypothesis, we found stronger connectivity between areas of the DMN and EN during the creative task, and this difference was enhanced in professional artists. These findings suggest that creativity involves an expert balance of two brain networks typically viewed as being in opposition.

  4. Brain networks for visual creativity: a functional connectivity study of planning a visual artwork

    PubMed Central

    De Pisapia, Nicola; Bacci, Francesca; Parrott, Danielle; Melcher, David

    2016-01-01

    Throughout recorded history, and across cultures, humans have made visual art. In recent years, the neural bases of creativity, including artistic creativity, have become a topic of interest. In this study we investigated the neural bases of the visual creative process with both professional artists and a group of control participants. We tested the idea that creativity (planning an artwork) would influence the functional connectivity between regions involved in the default mode network (DMN), implicated in divergent thinking and generating novel ideas, and the executive control network (EN), implicated in evaluating and selecting ideas. We measured functional connectivity with functional Magnetic Resonance Imaging (fMRI) during three different conditions: rest, visual imagery of the alphabet and planning an artwork to be executed immediately after the scanning session. Consistent with our hypothesis, we found stronger connectivity between areas of the DMN and EN during the creative task, and this difference was enhanced in professional artists. These findings suggest that creativity involves an expert balance of two brain networks typically viewed as being in opposition. PMID:27991592

  5. Signatures of selection in five Italian cattle breeds detected by a 54K SNP panel.

    PubMed

    Mancini, Giordano; Gargani, Maria; Chillemi, Giovanni; Nicolazzi, Ezequiel Luis; Marsan, Paolo Ajmone; Valentini, Alessio; Pariset, Lorraine

    2014-02-01

    In this study we used a medium density panel of SNP markers to perform population genetic analysis in five Italian cattle breeds. The BovineSNP50 BeadChip was used to genotype a total of 2,935 bulls of Piedmontese, Marchigiana, Italian Holstein, Italian Brown and Italian Pezzata Rossa breeds. To determine a genome-wide pattern of positive selection we mapped the F st values against genome location. The highest F st peaks were obtained on BTA6 and BTA13 where some candidate genes are located. We identified selection signatures peculiar of each breed which suggest selection for genes involved in milk or meat traits. The genetic structure was investigated by using a multidimensional scaling of the genetic distance matrix and a Bayesian approach implemented in the STRUCTURE software. The genotyping data showed a clear partitioning of the cattle genetic diversity into distinct breeds if a number of clusters equal to the number of populations were given. Assuming a lower number of clusters beef breeds group together. Both methods showed all five breeds separated in well defined clusters and the Bayesian approach assigned individuals to the breed of origin. The work is of interest not only because it enriches the knowledge on the process of evolution but also because the results generated could have implications for selective breeding programs.

  6. Expression of heavy metal tolerance in pollen and implications for gametophytic selection. [The plants used were clones of Silene dioica and Mimulus guttatus

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

    Searcy, K.B.

    Many genes are expressed in both sporophytic and microgametophytic phases of the angiosperm life cycle. Thus, selection in one phase could modify gene frequency in both phases. An attempt was made to investigate microgametophytic selection in response to toxic concentrations of heavy metals and the effect of this selection upon the resultant sporophyte generation. The plants used were clones of a zinc-tolerant Silene dioica, closely related nontolerant S. alba, and copper tolerant and non-tolerant clones of Mimulus guttatus. First, the expression of metal tolerance in pollen was established by in vitro pollen germination and tube growth, and was found tomore » be associated with the tolerance of the pollen source. Second, to test the extent to which the parallel expression of metal tolerance was determined by the gametophytic genotype, tolerant but segregating clones were grown with and without added metals. Finally, selection was applied during pollen germination, tube growth and fertilization. In Silene, neither the tolerance of the pollen nor the metal content of the styles affected pollen tube growth rate. In Mimulus, pollen from the nontolerant source grew faster, but the metal content of the floral tissue had no significant effect on pollen tube growth rate, and only slightly reduced the fertilization ability of pollen from the nontolerant clone.« less

  7. Nonhomologous Recombination between Defective Poliovirus and Coxsackievirus Genomes Suggests a New Model of Genetic Plasticity for Picornaviruses

    PubMed Central

    Holmblat, Barbara; Jégouic, Sophie; Muslin, Claire; Blondel, Bruno; Joffret, Marie-Line

    2014-01-01

    ABSTRACT Most of the circulating vaccine-derived polioviruses (cVDPVs) implicated in poliomyelitis outbreaks in Madagascar have been shown to be recombinants between the type 2 poliovirus (PV) strain of the oral polio vaccine (Sabin 2) and another species C human enterovirus (HEV-C), such as type 17 coxsackie A virus (CA17) in particular. We studied intertypic genetic exchanges between PV and non-PV HEV-C by developing a recombination model, making it possible to rescue defective type 2 PV RNA genomes with a short deletion at the 3′ end by the cotransfection of cells with defective or infectious CA17 RNAs. We isolated over 200 different PV/CA17 recombinants, using murine cells expressing the human PV receptor (PVR) and selecting viruses with PV capsids. We found some homologous (H) recombinants and, mostly, nonhomologous (NH) recombinants presenting duplications of parental sequences preferentially located in the regions encoding proteins 2A, 2B, and 3A. Short duplications appeared to be stable, whereas longer duplications were excised during passaging in cultured cells or after multiplication in PVR-transgenic mice, generating H recombinants with diverse sites of recombination. This suggests that NH recombination events may be a transient, intermediate step in the generation and selection of the fittest H recombinants. In addition to the classical copy-choice mechanism of recombination thought to generate mostly H recombinants, there may also be a modular mechanism of recombination, involving NH recombinant precursors, shaping the genomes of recombinant enteroviruses and other picornaviruses. PMID:25096874

  8. The complexity of selection at the major primate β-defensin locus

    PubMed Central

    Semple, Colin AM; Maxwell, Alison; Gautier, Philippe; Kilanowski, Fiona M; Eastwood, Hayden; Barran, Perdita E; Dorin, Julia R

    2005-01-01

    Background We have examined the evolution of the genes at the major human β-defensin locus and the orthologous loci in a range of other primates and mouse. For the first time these data allow us to examine selective episodes in the more recent evolutionary history of this locus as well as the ancient past. We have used a combination of maximum likelihood based tests and a maximum parsimony based sliding window approach to give a detailed view of the varying modes of selection operating at this locus. Results We provide evidence for strong positive selection soon after the duplication of these genes within an ancestral mammalian genome. Consequently variable selective pressures have acted on β-defensin genes in different evolutionary lineages, with episodes both of negative, and more rarely positive selection, during the divergence of primates. Positive selection appears to have been more common in the rodent lineage, accompanying the birth of novel, rodent-specific β-defensin genes. These observations allow a fuller understanding of the evolution of mammalian innate immunity. In both the rodent and primate lineages, sites in the second exon have been subject to positive selection and by implication are important in functional diversity. A small number of sites in the mature human peptides were found to have undergone repeated episodes of selection in different primate lineages. Particular sites were consistently implicated by multiple methods at positions throughout the mature peptides. These sites are clustered at positions predicted to be important for the specificity of the antimicrobial or chemoattractant properties of β-defensins. Surprisingly, sites within the prepropeptide region were also implicated as being subject to significant positive selection, suggesting previously unappreciated functional significance for this region. Conclusions Identification of these putatively functional sites has important implications for our understanding of β-defensin function and for novel antibiotic design. PMID:15904491

  9. Analysis of response to 20 generations of selection for body composition in mice: fit to infinitesimal model assumptions

    PubMed Central

    Martinez, Victor; Bünger, Lutz; Hill, William G

    2000-01-01

    Data were analysed from a divergent selection experiment for an indicator of body composition in the mouse, the ratio of gonadal fat pad to body weight (GFPR). Lines were selected for 20 generations for fat (F), lean (L) or were unselected (C), with three replicates of each. Selection was within full-sib families, 16 families per replicate for the first seven generations, eight subsequently. At generation 20, GFPR in the F lines was twice and in the L lines half that of C. A log transformation removed both asymmetry of response and heterogeneity of variance among lines, and so was used throughout. Estimates of genetic variance and heritability (approximately 50%) obtained using REML with an animal model were very similar, whether estimated from the first few generations of selection, or from all 20 generations, or from late generations having fitted pedigree. The estimates were also similar when estimated from selected or control lines. Estimates from REML also agreed with estimates of realised heritability. The results all accord with expectations under the infinitesimal model, despite the four-fold changes in mean. Relaxed selection lines, derived from generation 20, showed little regression in fatness after 40 generations without selection. PMID:14736404

  10. Oral antibodies to human intestinal alkaline phosphatase reduce dietary phytate phosphate bioavailability in the presence of dietary 1α-hydroxycholecalciferol.

    PubMed

    Bobeck, Elizabeth A; Hellestad, Erica M; Helvig, Christian F; Petkovich, P Martin; Cook, Mark E

    2016-03-01

    While it is well established that active vitamin D treatment increases dietary phytate phosphate utilization, the mechanism by which intestinal alkaline phosphatase (IAP) participates in phytate phosphate use is less clear. The ability of human IAP (hIAP) oral antibodies to prevent dietary phytate phosphate utilization in the presence of 1α-hydroxycholecalciferol (1α-(OH) D3) in a chick model was investigated. hIAP specific chicken immunoglobulin Y (IgY) antibodies were generated by inoculating laying hens with 17 synthetic peptides derived from the human IAP amino acid sequence and harvesting egg yolk. Western blot analysis showed all antibodies recognized hIAP and 6 of the 8 antibodies selected showed modest inhibition of hIAP activity in vitro (6 to 33% inhibition). In chicks where dietary phosphate was primarily in the form of phytate, 4 selected hIAP antibodies inhibited 1α-(OH) D3-induced increases in blood phosphate, one of which, generated against selected peptide (MFPMGTPD), was as effective as sevelamer hydrochloride in preventing the 1α-(OH) D3-induced increase in blood phosphate, but ineffective in preventing an increase in body weight gain and bone ash induced by 1α-(OH) D3. These studies demonstrated that orally-delivered antibodies to IAP limit dietary phytate-phosphate utilization in chicks treated with 1α-(OH) D3, and implicate IAP as an important host enzyme in increasing phytate phosphate bioavailability in 1α-(OH) D3 fed chicks. © 2015 Poultry Science Association Inc.

  11. Functional MRI mapping of visual function and selective attention for performance assessment and presurgical planning using conjunctive visual search.

    PubMed

    Parker, Jason G; Zalusky, Eric J; Kirbas, Cemil

    2014-03-01

    Accurate mapping of visual function and selective attention using fMRI is important in the study of human performance as well as in presurgical treatment planning of lesions in or near visual centers of the brain. Conjunctive visual search (CVS) is a useful tool for mapping visual function during fMRI because of its greater activation extent compared with high-capacity parallel search processes. The purpose of this work was to develop and evaluate a CVS that was capable of generating consistent activation in the basic and higher level visual areas of the brain by using a high number of distractors as well as an optimized contrast condition. Images from 10 healthy volunteers were analyzed and brain regions of greatest activation and deactivation were determined using a nonbiased decomposition of the results at the hemisphere, lobe, and gyrus levels. The results were quantified in terms of activation and deactivation extent and mean z-statistic. The proposed CVS was found to generate robust activation of the occipital lobe, as well as regions in the middle frontal gyrus associated with coordinating eye movements and in regions of the insula associated with task-level control and focal attention. As expected, the task demonstrated deactivation patterns commonly implicated in the default-mode network. Further deactivation was noted in the posterior region of the cerebellum, most likely associated with the formation of optimal search strategy. We believe the task will be useful in studies of visual and selective attention in the neuroscience community as well as in mapping visual function in clinical fMRI.

  12. Overtone-based pitch selection in hermit thrush song: Unexpected convergence with scale construction in human music

    PubMed Central

    Doolittle, Emily L.; Gingras, Bruno; Endres, Dominik M.; Fitch, W. Tecumseh

    2014-01-01

    Many human musical scales, including the diatonic major scale prevalent in Western music, are built partially or entirely from intervals (ratios between adjacent frequencies) corresponding to small-integer proportions drawn from the harmonic series. Scientists have long debated the extent to which principles of scale generation in human music are biologically or culturally determined. Data from animal “song” may provide new insights into this discussion. Here, by examining pitch relationships using both a simple linear regression model and a Bayesian generative model, we show that most songs of the hermit thrush (Catharus guttatus) favor simple frequency ratios derived from the harmonic (or overtone) series. Furthermore, we show that this frequency selection results not from physical constraints governing peripheral production mechanisms but from active selection at a central level. These data provide the most rigorous empirical evidence to date of a bird song that makes use of the same mathematical principles that underlie Western and many non-Western musical scales, demonstrating surprising convergence between human and animal “song cultures.” Although there is no evidence that the songs of most bird species follow the overtone series, our findings add to a small but growing body of research showing that a preference for small-integer frequency ratios is not unique to humans. These findings thus have important implications for current debates about the origins of human musical systems and may call for a reevaluation of existing theories of musical consonance based on specific human vocal characteristics. PMID:25368163

  13. Does dynamic stability govern propulsive force generation in human walking?

    PubMed Central

    Browne, Michael G.

    2017-01-01

    Before succumbing to slower speeds, older adults may walk with a diminished push-off to prioritize stability over mobility. However, direct evidence for trade-offs between push-off intensity and balance control in human walking, independent of changes in speed, has remained elusive. As a critical first step, we conducted two experiments to investigate: (i) the independent effects of walking speed and propulsive force (FP) generation on dynamic stability in young adults, and (ii) the extent to which young adults prioritize dynamic stability in selecting their preferred combination of walking speed and FP generation. Subjects walked on a force-measuring treadmill across a range of speeds as well as at constant speeds while modulating their FP according to a visual biofeedback paradigm based on real-time force measurements. In contrast to improvements when walking slower, walking with a diminished push-off worsened dynamic stability by up to 32%. Rather, we find that young adults adopt an FP at their preferred walking speed that maximizes dynamic stability. One implication of these findings is that the onset of a diminished push-off in old age may independently contribute to poorer balance control and precipitate slower walking speeds. PMID:29291129

  14. Does dynamic stability govern propulsive force generation in human walking?

    PubMed

    Browne, Michael G; Franz, Jason R

    2017-11-01

    Before succumbing to slower speeds, older adults may walk with a diminished push-off to prioritize stability over mobility. However, direct evidence for trade-offs between push-off intensity and balance control in human walking, independent of changes in speed, has remained elusive. As a critical first step, we conducted two experiments to investigate: (i) the independent effects of walking speed and propulsive force ( F P ) generation on dynamic stability in young adults, and (ii) the extent to which young adults prioritize dynamic stability in selecting their preferred combination of walking speed and F P generation. Subjects walked on a force-measuring treadmill across a range of speeds as well as at constant speeds while modulating their F P according to a visual biofeedback paradigm based on real-time force measurements. In contrast to improvements when walking slower, walking with a diminished push-off worsened dynamic stability by up to 32%. Rather, we find that young adults adopt an F P at their preferred walking speed that maximizes dynamic stability. One implication of these findings is that the onset of a diminished push-off in old age may independently contribute to poorer balance control and precipitate slower walking speeds.

  15. Demystifying cognitive flexibility: Implications for clinical and developmental neuroscience

    PubMed Central

    Dajani, Dina R.; Uddin, Lucina Q.

    2015-01-01

    Cognitive flexibility, the readiness with which one can selectively switch between mental processes to generate appropriate behavioral responses, develops in a protracted manner and is compromised in several prevalent neurodevelopmental disorders. It is unclear whether cognitive flexibility arises from neural substrates distinct from the executive control network, or from the interplay of nodes within this and other networks. Here we review neuroimaging studies of cognitive flexibility, focusing on set shifting and task switching. We propose that more consistent operationalization and study of cognitive flexibility is required in clinical and developmental neuroscience. We suggest that an important avenue for future research is the characterization of the relationship between neural flexibility and cognitive flexibility in typical and atypical development. PMID:26343956

  16. Changing demographics and state fiscal outlook: the case of sales taxes.

    PubMed

    Mullins, D R; Wallace, S

    1996-04-01

    "Broad-scale demographic changes have implications for state and local finance in terms of the composition of the base of revenue sources and their yields. This article examines the effect of such changes on the potential future yield of consumption-based taxes. The effect of household characteristics and composition on the consumption of selected groups of goods subject to ad valorem retail sales taxes is estimated, generating demographic elasticities of consumption. These elasticities are applied to projected demographic changes in eight states through the year 2000. The results show rather wide variation in expected consumption shifts and potential tax bases across the states, with income growth having the greatest effect...." The geographical focus is on the United States. excerpt

  17. Harnessing dendritic cells in inflammatory skin diseases.

    PubMed

    Chu, Chung-Ching; Di Meglio, Paola; Nestle, Frank O

    2011-02-01

    The skin immune system harbors a complex network of dendritic cells (DCs). Recent studies highlight a diverse functional specialization of skin DC subsets. In addition to generating cellular and humoral immunity against pathogens, skin DCs are involved in tolerogenic mechanisms to ensure the maintenance of immune homeostasis, as well as in pathogenesis of chronic inflammation in the skin when excessive immune responses are initiated and unrestrained. Harnessing DCs by directly targeting DC-derived molecules or selectively modulate DC subsets is a convincing strategy to tackle inflammatory skin diseases. In this review we discuss recent advances underlining the functional specialization of skin DCs and discuss the potential implication for future DC-based therapeutic strategies. Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. Mycobacterial aerosols and respiratory disease.

    PubMed

    Falkinham, Joseph O

    2003-07-01

    Environmental opportunistic mycobacteria, including Mycobacterium avium, M. terrae, and the new species M. immunogenum, have been implicated in outbreaks of hypersensitivity pneumonitis or respiratory problems in a wide variety of settings. One common feature of the outbreaks has been exposure to aerosols. Aerosols have been generated from metalworking fluid during machining and grinding operations as well as from indoor swimming pools, hot tubs, and water-damaged buildings. Environmental opportunistic mycobacteria are present in drinking water, resistant to disinfection, able to provoke inflammatory reactions, and readily aerosolized. In all outbreaks, the water sources of the aerosols were disinfected. Disinfection may select for the predominance and growth of mycobacteria. Therefore, mycobacteria may be responsible, in part, for many outbreaks of hypersensitivity pneumonitis and other respiratory problems in the workplace and home.

  19. The defined-contribution plan: the next generation of healthcare financing.

    PubMed

    Emery, J D

    2001-01-01

    In response to rising health insurance premiums, many purchasers of coverage are evaluating the possibility of implementing defined-contribution health insurance plans. Under a defined-contribution plan, employers or the government pay a specified portion of the premium, and the consumer chooses a plan from a menu of options, paying the balance of the premium based on their plan selection. A shift to a defined-contribution model will have far-reaching implications for consumers, employer and government purchasers, payers, and providers. Providers will face changes in consumption patterns and the need to develop a brand image, market their strengths directly to consumers, educate consumers about their services and pricing, and reconfigure infrastructures to be able to respond efficiently to consumer demands.

  20. Proceedings of the Seventh International Symposium on Methodologies for Intelligent Systems (Poster Session)

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

    Harber, K.S.

    1993-05-01

    This report contains the following papers: Implications in vivid logic; a self-learning bayesian expert system; a natural language generation system for a heterogeneous distributed database system; competence-switching'' managed by intelligent systems; strategy acquisition by an artificial neural network: Experiments in learning to play a stochastic game; viewpoints and selective inheritance in object-oriented modeling; multivariate discretization of continuous attributes for machine learning; utilization of the case-based reasoning method to resolve dynamic problems; formalization of an ontology of ceramic science in CLASSIC; linguistic tools for intelligent systems; an application of rough sets in knowledge synthesis; and a relational model for imprecise queries.more » These papers have been indexed separately.« less

  1. Proceedings of the Seventh International Symposium on Methodologies for Intelligent Systems (Poster Session)

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

    Harber, K.S.

    1993-05-01

    This report contains the following papers: Implications in vivid logic; a self-learning Bayesian Expert System; a natural language generation system for a heterogeneous distributed database system; ``competence-switching`` managed by intelligent systems; strategy acquisition by an artificial neural network: Experiments in learning to play a stochastic game; viewpoints and selective inheritance in object-oriented modeling; multivariate discretization of continuous attributes for machine learning; utilization of the case-based reasoning method to resolve dynamic problems; formalization of an ontology of ceramic science in CLASSIC; linguistic tools for intelligent systems; an application of rough sets in knowledge synthesis; and a relational model for imprecise queries.more » These papers have been indexed separately.« less

  2. FOXP2 Targets Show Evidence of Positive Selection in European Populations

    PubMed Central

    Ayub, Qasim; Yngvadottir, Bryndis; Chen, Yuan; Xue, Yali; Hu, Min; Vernes, Sonja C.; Fisher, Simon E.; Tyler-Smith, Chris

    2013-01-01

    Forkhead box P2 (FOXP2) is a highly conserved transcription factor that has been implicated in human speech and language disorders and plays important roles in the plasticity of the developing brain. The pattern of nucleotide polymorphisms in FOXP2 in modern populations suggests that it has been the target of positive (Darwinian) selection during recent human evolution. In our study, we searched for evidence of selection that might have followed FOXP2 adaptations in modern humans. We examined whether or not putative FOXP2 targets identified by chromatin-immunoprecipitation genomic screening show evidence of positive selection. We developed an algorithm that, for any given gene list, systematically generates matched lists of control genes from the Ensembl database, collates summary statistics for three frequency-spectrum-based neutrality tests from the low-coverage resequencing data of the 1000 Genomes Project, and determines whether these statistics are significantly different between the given gene targets and the set of controls. Overall, there was strong evidence of selection of FOXP2 targets in Europeans, but not in the Han Chinese, Japanese, or Yoruba populations. Significant outliers included several genes linked to cellular movement, reproduction, development, and immune cell trafficking, and 13 of these constituted a significant network associated with cardiac arteriopathy. Strong signals of selection were observed for CNTNAP2 and RBFOX1, key neurally expressed genes that have been consistently identified as direct FOXP2 targets in multiple studies and that have themselves been associated with neurodevelopmental disorders involving language dysfunction. PMID:23602712

  3. HIV cure research: print and online media reporting in Australia.

    PubMed

    Power, Jennifer; Fileborn, Bianca; Dowsett, Gary W; Lucke, Jayne; Brown, Graham; Ellard, Jeanne; Lewin, Sharon R; Tucker, Joseph D; Slavin, Sean; Sugarman, Jeremy; Hill, Sophie

    2017-10-01

    While still in its early stages, recent scientific research towards a cure for HIV has generated widespread media interest. The aim of this paper was to explore the ways in which this research has been represented in Australian print and online media and discuss implications of this. A search of databases from four selected media outlets was conducted to identify published articles that directly discussed HIV cure research. Content analysis was used to explore the discursive framing of HIV cure research and identify the presence or absence of people living with HIV in articles. In total, 95 articles were identified that had been published in print or online between 2007 and 2015. Media reports tended to focus on research breakthroughs or the future potential of HIV cure research, rather than more immediate implications of research findings. While not inaccurate, this focus often implied the field of HIV cure research was more advanced than was generally the case. There was a notable absence of commentary from people living with HIV or community advocates in media reporting. Media reporting may generate unrealistic expectations of HIV cure research. This raises ethical concerns that media reporting may inadvertently contribute to therapeutic or curative misconceptions among potential participants in HIV cure-related trials. To address this, scientists, HIV advocates and people living with HIV will need to work collaboratively to engage with reporters and media outlets to provide more consistent input and guidance into reporting about research towards a cure for HIV.

  4. Footprints of ancient-balanced polymorphisms in genetic variation data from closely related species

    PubMed Central

    Gao, Ziyue; Przeworski, Molly; Sella, Guy

    2015-01-01

    When long-lasting, balancing selection can lead to “trans-species” polymorphisms that are shared by two or more species identical by descent. In such cases, the gene genealogy at the selected site clusters by allele instead of by species, and nearby neutral sites also have unusual genealogies because of linkage. While this scenario is expected to leave discernible footprints in genetic variation data, the specific patterns remain poorly characterized. Motivated by recent findings in primates, we focus on the case of a biallelic polymorphism under ancient balancing selection and derive approximations for summaries of the polymorphism data from two species. Specifically, we characterize the length of the segment that carries most of the footprints, the expected number of shared neutral single nucleotide polymorphisms (SNPs), and the patterns of allelic associations among them. We confirm the accuracy of our approximations by coalescent simulations. We further show that for humans and chimpanzees—more generally, for pairs of species with low genetic diversity levels—these patterns are highly unlikely to be generated by neutral recurrent mutations. We discuss the implications for the design and interpretation of genome scans for ancient balanced polymorphisms in primates and other taxa. PMID:25403856

  5. Identification and Characterization of a Secondary Sodium-Binding Site and the Main Selectivity Determinants in the Human Concentrative Nucleoside Transporter 3.

    PubMed

    Arimany-Nardi, C; Claudio-Montero, A; Viel-Oliva, A; Schmidtke, P; Estarellas, C; Barril, X; Bidon-Chanal, A; Pastor-Anglada, M

    2017-06-05

    The family of concentrative Na + /nucleoside cotransporters in humans is constituted by three subtypes, namely, hCNT1, hCNT2, and hCNT3. Besides their different nucleoside selectivity, hCNT1 and hCNT2 have a Na + /nucleoside stoichiometry of 1:1, while for hCNT3 it is 2:1. This distinct stoichiometry of subtype 3 might hint the existence of a secondary sodium-binding site that is not present in the other two subtypes, but to date their three-dimensional structures remain unknown and the residues implicated in Na + binding are unclear. In this work, we have identified and characterized the Na + binding sites of hCNT3 by combining molecular modeling and mutagenesis studies. A model of the transporter was obtained by homology modeling, and key residues of two sodium-binding sites were identified and verified with a mutagenesis strategy. The structural model explains the altered sodium-binding properties of the hCNT3C602R polymorphic variant and supports previously generated data identifying the determinant residues of nucleoside selectivity, paving the way to understand how drugs can target this plasma membrane transporter.

  6. Genetic selection increases parthenogenesis in Chinese painted quail (Coturnix chinensis).

    PubMed

    Parker, H M; Kiess, A S; Wells, J B; Young, K M; Rowe, D; McDaniel, C D

    2010-07-01

    Parthenogenesis, embryonic development of an unfertilized egg, occurs naturally in turkey, chicken, and quail species. In fact, parthenogenesis in turkeys and chickens can be increased by genetic selection. However, it is unknown if genetic selection for parthenogenesis is effective in quail or if selection for parthenogenesis affects egg production. Therefore, the objectives of this study were to determine if the incidence of parthenogenesis in quail could be increased by genetic selection and if selection for this trait affects egg production. To prevent fertilization, 1,090 females were caged separately from males at 4 wk of age and then caged individually at 6 wk of age to monitor egg production. Eggs were collected daily, labeled, and stored for 0 to 3 d. After 10 d of incubation, 20 unfertilized eggs from each hen were examined for the occurrence of parthenogenesis and embryonic growth. In the parent (P) generation and subsequent generations (1 to 4), hens laying eggs containing parthenogenetic development and males whose sisters or mothers exhibited parthenogenesis were used for breeding. There was a linear increase in the percentage of hens exhibiting parthenogenesis as generation of selection increased. With each successive generation, there was a quadratic response in the percentage of eggs positive for parthenogenesis. When compared with the P generation, parthenogenesis was almost 3 times greater for eggs laid by the fourth generation (4.6 to 12.5%, respectively). Even when only hens exhibiting parthenogenesis were examined, the percentage of eggs demonstrating embryonic development responded quadratically with generation of selection. The embryonic size at 10 d of incubation was greater for each subsequent generation when compared with the P generation. There was a linear decrease in both egg production and the average position of an egg in a clutch as generation of selection increased. In conclusion, genetic selection for parthenogenesis increased the incidence of parthenogenesis and embryonic size but decreased egg production and average position of an egg in a clutch as generations of selection increased.

  7. Supplementation of serum free media with HT is not sufficient to restore growth properties of DHFR-/- cells in fed-batch processes - Implications for designing novel CHO-based expression platforms.

    PubMed

    Florin, Lore; Lipske, Carolin; Becker, Eric; Kaufmann, Hitto

    2011-04-10

    DHFR-deficient CHO cells are the most commonly used host cells in the biopharmaceutical industry and over the years, individual substrains have evolved, some have been engineered with improved properties and platform technologies have been designed around them. Unexpectedly, we have observed that different DHFR-deficient CHO cells show only poor growth in fed-batch cultures even in HT supplemented medium, whereas antibody producer cells derived from these hosts achieved least 2-3 fold higher peak cell densities. Using a set of different expression vectors, we were able to show that this impaired growth performance was not due to the selection procedure possibly favouring fast growing clones, but a direct consequence of DHFR deficiency. Re-introduction of the DHFR gene reproducibly restored the growth phenotype to the level of wild-type CHO cells or even beyond which seemed to be dose-dependent. The requirement for a functional DHFR gene to achieve optimal growth under production conditions has direct implications for cell line generation since it suggests that changing to a selection system other than DHFR would require another CHO host which - especially for transgenic CHO strains and tailor-suited process platforms - this could mean significant investments and potential changes in product quality. In these cases, DHFR engineering of the current CHO-DG44 or DuxB11-based host could be an attractive alternative. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. Characterizing habitat suitability for a central-place forager in a dynamic marine environment.

    PubMed

    Briscoe, Dana K; Fossette, Sabrina; Scales, Kylie L; Hazen, Elliott L; Bograd, Steven J; Maxwell, Sara M; McHuron, Elizabeth A; Robinson, Patrick W; Kuhn, Carey; Costa, Daniel P; Crowder, Larry B; Lewison, Rebecca L

    2018-03-01

    Characterizing habitat suitability for a marine predator requires an understanding of the environmental heterogeneity and variability over the range in which a population moves during a particular life cycle. Female California sea lions ( Zalophus californianus ) are central-place foragers and are particularly constrained while provisioning their young. During this time, habitat selection is a function of prey availability and proximity to the rookery, which has important implications for reproductive and population success. We explore how lactating females may select habitat and respond to environmental variability over broad spatial and temporal scales within the California Current System. We combine near-real-time remotely sensed satellite oceanography, animal tracking data ( n  = 72) from November to February over multiple years (2003-2009) and Generalized Additive Mixed Models (GAMMs) to determine the probability of sea lion occurrence based on environmental covariates. Results indicate that sea lion presence is associated with cool ( <14°C ), productive waters, shallow depths, increased eddy activity, and positive sea-level anomalies. Predictive habitat maps generated from these biophysical associations suggest winter foraging areas are spatially consistent in the nearshore and offshore environments, except during the 2004-2005 winter, which coincided with an El Niño event. Here, we show how a species distribution model can provide broadscale information on the distribution of female California sea lions during an important life history stage and its implications for population dynamics and spatial management.

  9. Implications of the method of capital cost payment on the weighted average cost of capital.

    PubMed Central

    Boles, K E

    1986-01-01

    The author develops a theoretical and mathematical model, based on published financial management literature, to describe the cost of capital structure for health care delivery entities. This model is then used to generate the implications of changing the capital cost reimbursement mechanism from a cost basis to a prospective basis. The implications are that the cost of capital is increased substantially, the use of debt must be restricted, interest rates for borrowed funds will increase, and, initially, firms utilizing debt efficiently under cost-basis reimbursement will be restricted to the generation of funds from equity only under a prospective system. PMID:3525468

  10. Is the Holocaust implicated in posttraumatic growth in second-generation Holocaust survivors? A prospective study.

    PubMed

    Dekel, Sharon; Mandl, Christine; Solomon, Zahava

    2013-08-01

    With the growing interest in posttraumatic growth (PTG), and the ongoing debate on the implications of transgenerational transmission of trauma, this longitudinal study examined PTG among Holocaust survivor offspring following their own exposure to trauma. Using self-report questionnaires, we assessed PTG over time in middle aged (age: M = 53 years) Israeli male combat veterans of the 1973 Yom Kippur War whose parents were (n = 43) and were not (n = 156) second-generation survivors of the Nazi Holocaust at 2 time points: 30 and 35 years following the war (in 2003 and 2008). Posttraumatic stress disorder symptoms and trauma exposure were also assessed in 1991. We hypothesized that second-generation survivors would report more PTG than controls. However, repeated measures design revealed that the second-generation veterans reported less PTG than veterans who were not second generation, which was evident in the PTG domains of relations to others, personal strength, and appreciation of life. Our findings suggest that transmission of trauma from one generation to the next is possibly implicated in the offspring's propensity for growth following subsequent trauma. Future research is warranted to examine the link between transmission of trauma and positive outcomes following trauma. Copyright © 2013 International Society for Traumatic Stress Studies.

  11. Implications of long tails in the distribution of mutant effects

    NASA Astrophysics Data System (ADS)

    Waxman, D.; Feng, J.

    2005-07-01

    Long-tailed distributions possess an infinite variance, yet a finite sample that is drawn from such a distribution has a finite variance. In this work we consider a model of a population subject to mutation, selection and drift. We investigate the implications of a long-tailed distribution of mutant allelic effects on the distribution of genotypic effects in a model with a continuum of allelic effects. While the analysis is confined to asexual populations, it does also have implications for sexual populations. We obtain analytical results for a selectively neutral population as well as one subject to selection. We supplement these analytical results with numerical simulations, to take into account genetic drift. We find that a long-tailed distribution of mutant effects may affect both the equilibrium and the evolutionary adaptive behaviour of a population.

  12. Polypyrimidine Tract Binding Protein Homologs from Arabidopsis Are Key Regulators of Alternative Splicing with Implications in Fundamental Developmental Processes[W

    PubMed Central

    Rühl, Christina; Stauffer, Eva; Kahles, André; Wagner, Gabriele; Drechsel, Gabriele; Rätsch, Gunnar; Wachter, Andreas

    2012-01-01

    Alternative splicing (AS) generates transcript variants by variable exon/intron definition and massively expands transcriptome diversity. Changes in AS patterns have been found to be linked to manifold biological processes, yet fundamental aspects, such as the regulation of AS and its functional implications, largely remain to be addressed. In this work, widespread AS regulation by Arabidopsis thaliana Polypyrimidine tract binding protein homologs (PTBs) was revealed. In total, 452 AS events derived from 307 distinct genes were found to be responsive to the levels of the splicing factors PTB1 and PTB2, which predominantly triggered splicing of regulated introns, inclusion of cassette exons, and usage of upstream 5′ splice sites. By contrast, no major AS regulatory function of the distantly related PTB3 was found. Dependent on their position within the mRNA, PTB-regulated events can both modify the untranslated regions and give rise to alternative protein products. We find that PTB-mediated AS events are connected to diverse biological processes, and the functional implications of selected instances were further elucidated. Specifically, PTB misexpression changes AS of PHYTOCHROME INTERACTING FACTOR6, coinciding with altered rates of abscisic acid–dependent seed germination. Furthermore, AS patterns as well as the expression of key flowering regulators were massively changed in a PTB1/2 level-dependent manner. PMID:23192226

  13. Kinetic Model Facilitates Analysis of Fibrin Generation and Its Modulation by Clotting Factors: Implications for Hemostasis-Enhancing Therapies

    DTIC Science & Technology

    2014-01-01

    facilitates analysis of fibrin generation and its modulation by clotting factors : implications for hemostasis-enhancing therapies† Alexander Y...investigate the ability of fibrinogen and a recently proposed prothrombin complex concentrate composition, PCC-AT (a combination of the clotting factors II...kinetics. Moreover, the model qualitatively predicted the impact of tissue factor and tPA/tenecteplase level variations on the fibrin output. In the

  14. The Proposed U.S.-South Korea Free Trade Agreement (KORUS FTA): Provisions and Implications

    DTIC Science & Technology

    2008-01-22

    alliance as a whole. Differences between the White House and the Democratic leadership in the Congress over the implications of the KORUS FTA have...FTA will generate vigorous debate. Differences over the implications of the KORUS FTA between the White House and the Democratic leadership in the

  15. The challenge of selecting tomorrow's police officers from Generations X and Y.

    PubMed

    McCafferty, Francis L

    2003-01-01

    Demands on police officers in the past 30 years have grown dramatically with the increasing threats to social order and personal security. Selection of police officers has always been difficult, but now with the increasing demand and complexity of police work, along with the candidates applying from Generation X and even Generation Y, the selection process has become more critical. The personal characteristics attributed to Generation X--and in the future, to Generation Y--should be factored into the selection process to ensure that those individuals selected as police officers will be able to cope with what has been described as the impossible mandate of police work in a free society. Background information on the X and Y generations is imperative for psychiatrists working with police departments and other law enforcement agencies. This article will explore these areas and construct a paradigm selection process.

  16. Comparison of Phenotypic Value Changes in Pure Lines of Bombyx mori (Lepidoptera: Bombycidae) During Consecutive Generations Following Initial Selection on Cocoon Weight

    PubMed Central

    Seidavi, Alireza; Goldsmith, Marian R.

    2014-01-01

    Abstract The experiments reported here were conducted to investigate the effect of selection on three quantitative traits, namely cocoon weight, cocoon shell weight, and cocoon shell percentage, during four generations by rearing six pure breeds of domesticated silkworm, Bombyx mori L. (Lepidoptera: Bombycidae) of Chinese and Japanese origin compared with random unselected groups as controls. All stages of rearing and data recording were performed over four rearing periods, with generations 1–3 during successive spring seasons and generation 4 during the autumn season in year 3. Each pure line contained two groups of selected and random (control) groups. Comparisons included the effect of selection methods, pure line, and generation on the phenotypic values. We found strong main effects of pure line, generation, sex, and group and support for nearly all interactions between these main effects for all three response traits. The results indicated that cocoon weight and cocoon shell weight in the selected group were higher than in the control or nonselected group. Both selected and nonselected groups had the lowest cocoon weight, cocoon shell weight, and cocoon shell percentage in the fourth generation when environmental conditions during the autumn season were less favorable than spring. The cocoon weight and cocoon shell weight averages were higher for nonselected groups in the second and third generations, and for the selected group in the first generation due to the direct effect of selection. PMID:25527593

  17. First-generation students' underperformance at university: the impact of the function of selection.

    PubMed

    Jury, Mickaël; Smeding, Annique; Darnon, Céline

    2015-01-01

    According to recent research, university not only has the role to educate and train students, it also has the role to select the best students. We argue that this function of selection disadvantages first-generation students, in comparison with continuing-generation students. Thus, the mere activation of the function of selection should be sufficient to produce achievement differences between first-generation and continuing-generation students in a novel academic task. Furthermore, we propose that when the function of selection is salient, first-generation students would be more vigilant to a cue that may confirm their inferiority, which should explain their underperformance. In the present experiment, participants were asked to complete an arithmetic modular task under two conditions, which either made the function of selection salient or reduced its importance. Participants' vigilance to a threatening cue (i.e., their performance relative to others) was measured through an eye-tracking technique. The results confirmed that first-generation students performed more poorly compared to continuing-generation students only when the function of selection was salient while no differences appeared in the no-selection condition. Regarding vigilance, the results did not confirm our hypothesis; thus, mediation path could not be tested. However, results indicated that at a high level of initial performance, first-generation students looked more often at the threatening cue. In others words, these students seemed more concerned about whether they were performing more poorly than others compared to their continuing-generation counterparts. Some methodological issues are discussed, notably regarding the measure of vigilance.

  18. First-generation students’ underperformance at university: the impact of the function of selection

    PubMed Central

    Jury, Mickaël; Smeding, Annique; Darnon, Céline

    2015-01-01

    According to recent research, university not only has the role to educate and train students, it also has the role to select the best students. We argue that this function of selection disadvantages first-generation students, in comparison with continuing-generation students. Thus, the mere activation of the function of selection should be sufficient to produce achievement differences between first-generation and continuing-generation students in a novel academic task. Furthermore, we propose that when the function of selection is salient, first-generation students would be more vigilant to a cue that may confirm their inferiority, which should explain their underperformance. In the present experiment, participants were asked to complete an arithmetic modular task under two conditions, which either made the function of selection salient or reduced its importance. Participants’ vigilance to a threatening cue (i.e., their performance relative to others) was measured through an eye-tracking technique. The results confirmed that first-generation students performed more poorly compared to continuing-generation students only when the function of selection was salient while no differences appeared in the no-selection condition. Regarding vigilance, the results did not confirm our hypothesis; thus, mediation path could not be tested. However, results indicated that at a high level of initial performance, first-generation students looked more often at the threatening cue. In others words, these students seemed more concerned about whether they were performing more poorly than others compared to their continuing-generation counterparts. Some methodological issues are discussed, notably regarding the measure of vigilance. PMID:26074854

  19. Efficiency of including first-generation information in second-generation ranking and selection: results of computer simulation.

    Treesearch

    T.Z. Ye; K.J.S. Jayawickrama; G.R. Johnson

    2006-01-01

    Using computer simulation, we evaluated the impact of using first-generation information to increase selection efficiency in a second-generation breeding program. Selection efficiency was compared in terms of increase in rank correlation between estimated and true breeding values (i.e., ranking accuracy), reduction in coefficient of variation of correlation...

  20. Characterization of prostaglandin E2 generation through the cyclooxygenase (COX)-2 pathway in human neutrophils

    PubMed Central

    St-Onge, Mireille; Flamand, Nicolas; Biarc, Jordane; Picard, Serge; Bouchard, Line; Dussault, Andrée-Anne; Laflamme, Cynthia; James, Michael J.; Caughey, Gillian E.; Cleland, Leslie G.; Borgeat, Pierre; Pouliot, Marc

    2010-01-01

    In the present study, we characterized the generation of prostaglandin (PG)E2 in human neutrophils. We found that the Ca2+-dependent type IV cytosolic phospholipase A2 (cPLA2) was pivotally involved in the COX-2-mediated generation of PGE2 in response to a calcium ionophore, as determined by the use of selected PLA2 inhibitors. PGE2 biosynthesis elicited by bacterial-derived peptides or by phagocytic stimuli acting on cell surface receptors also showed to be dependent on cPLA2 activity. We then assessed metabolism of unesterified arachidonic acid (AA), and observed that PGE2 production becomes favored over that of LTB4 with higher AA concentrations. Withdrawal of calcium prevented the generation of PGE2 in response to a calcium ionophore but did not affect the up-regulation of COX-2 or its capacity to convert AA, thus limiting its implication at the level of cPLA2 activation. Of the main eicosanoids produced by neutrophils, only LTB4 was able to up-regulate COX-2 expression. Finally, the only PGE synthase isoform found in neutrophils is microsomal PGE synthase-1; it co-localized with COX-2 and its expression appeared mainly constitutive. These results highlight key differences in regulatory processes of the 5-LO and COX pathways, and enhance our knowledge at several levels in the PGE2 biosynthesis in neutrophils. PMID:17643350

  1. Implications of the licensure of a partially efficacious malaria vaccine on evaluating second-generation vaccines

    PubMed Central

    2013-01-01

    Background Malaria is a leading cause of morbidity and mortality, with approximately 225 million clinical episodes and >1.2 million deaths annually attributed to malaria. Development of a highly efficacious malaria vaccine will offer unparalleled possibilities for disease prevention and remains a key priority for long-term malaria control and elimination. Discussion The Malaria Vaccine Technology Roadmap’s goal is to 'develop and license a first-generation malaria vaccine that has protective efficacy of more than 50%’. To date, malaria vaccine candidates have only been shown to be partially efficacious (approximately 30% to 60%). However, licensure of a partially effective vaccine will create a number of challenges for the development and progression of new, potentially more efficacious, malaria vaccines in the future. In this opinion piece we discuss the methodological, logistical and ethical issues that may impact on the feasibility and implementation of superiority, non-inferiority and equivalence trials to assess second generation malaria vaccines in the advent of the licensure of a partially efficacious malaria vaccine. Conclusions Selecting which new malaria vaccines go forward, and defining appropriate methodology for assessment in logistically challenging clinical trials, is crucial. It is imperative that the scientific community considers all the issues and starts planning how second-generation malaria vaccines will advance in the advent of licensure of a partially effective vaccine. PMID:24228861

  2. Selecting team players: Considering the impact of contextual performance and workplace deviance on selection decisions in the National Football League.

    PubMed

    Whiting, Steven W; Maynes, Timothy D

    2016-04-01

    Contextual performance and workplace deviance likely influence team functioning and effectiveness and should therefore be considered when evaluating job candidates for team-based roles. However, obtaining this information is difficult given a lack of reliable sources and the desire of job applicants to present themselves in a favorable light. Thus, it is unknown whether those selecting employees for teams incorporate prior contextual performance and workplace deviance into their evaluations, or whether doing so improves the quality of selection decisions. To address these issues, we examined the impact of prior task performance, contextual performance, and workplace deviance on National Football League (NFL) decision maker (organizational insider) and external expert (organizational outsider) evaluations of college football players in the NFL draft, using a content analysis methodology to generate measures of contextual performance and workplace deviance. Our findings indicate that insiders value contextual performance more than outsiders, which is likely because of differing interests and goals that lead to different levels of motivation and/or ability to acquire information about prior contextual performance. We also propose that prior task performance, contextual performance, and workplace deviance will predict player performance in the NFL. Our results support this prediction for task and contextual performance. In addition, we investigated the quality of insider and outsider judgments using Brunswik's (1952) lens model. Implications of our findings for the team selection, contextual performance, and workplace deviance literatures are discussed. (c) 2016 APA, all rights reserved).

  3. Degeneracy allows for both apparent homogeneity and diversification in populations

    PubMed Central

    Whitacre, James M.; Atamas, Sergei P.

    2013-01-01

    Trait diversity – the substrate for natural selection – is necessary for adaptation through selection, particularly in populations faced with environmental changes that diminish population fitness. In habitats that remain unchanged for many generations, stabilizing selection maximizes exploitation of resources by reducing trait diversity to a narrow optimal range. One might expect that such ostensibly homogeneous populations would have a reduced potential for heritable adaptive responses when faced with fitness-reducing environmental changes. However, field studies have documented populations that, even after long periods of evolutionary stasis, can still rapidly evolve in response to changed environmental conditions. We argue that degeneracy, the ability of diverse population elements to function similarly, can satisfy both the current need to maximize fitness and the future need for diversity. Degenerate ensembles appear functionally redundant in certain environmental contexts and functionally diverse in others. We propose that genetic variation not contributing to the observed range of phenotypes in a current population, also known as cryptic genetic variation (CGV), is a specific case of degeneracy. We argue that CGV, which gradually accumulates in static populations in stable environments, reveals hidden trait differences when environments change. By allowing CGV accumulation, static populations prepare themselves for future rapid adaptations to environmental novelty. A greater appreciation of degeneracy’s role in resolving the inherent tension between current stabilizing selection and future directional selection has implications in conservation biology and may be applied in social and technological systems to maximize current performance while strengthening the potential for future changes. PMID:22910487

  4. Five generations in the nursing workforce: implications for nursing professional development.

    PubMed

    Bell, Julie A

    2013-01-01

    Positive patient outcomes require effective teamwork, communication, and technological literacy. These skills vary among the unprecedented five generations in the nursing workforce, spanning the "Silent Generation" nurses deferring retirement to the newest "iGeneration." Nursing professional development educators must understand generational differences; address communication, information technology, and team-building competencies across generations; and promote integration of learner-centered strategies into professional development activities.

  5. Atmospheric Oxygen Inhibits Growth and Differentiation of Marrow-Derived Mouse Mesenchymal Stem Cells via a p53 Dependent Mechanism: Implications for Long-Term Culture Expansion

    PubMed Central

    Boregowda, Siddaraju; Krishnappa, Veena; Chambers, Jeremy; LoGrasso, Phillip V.; Lai, Wen-Tzu; Ortiz, Luis A.; Phinney, Donald G.

    2013-01-01

    Large scale expansion of human mesenchymal stem cells (MSCs) is routinely performed for clinical therapy. In contrast, developing protocols for large scale expansion of primary mouse MSCs has been more difficult due to unique aspects of rodent biology. Currently, established methods to isolate mouse MSCs select for rapidly dividing subpopulations that emerge from bone marrow cultures following long-term (months) expansion in atmospheric oxygen. Herein, we demonstrate that exposure to atmospheric oxygen rapidly induced p53, TOP2A and BAX expression and mitochondrial ROS generation in primary mouse MSCs resulting in oxidative stress, reduced cell viability and inhibition of cell proliferation. Alternatively, procurement and culture in 5% oxygen supported more prolific expansion of the CD45−ve/CD44+ve cell fraction in marrow, produced increased MSC yields following immuno-depletion, and supported sustained MSC growth resulting in a 2300-fold increase in cumulative cell yield by 4th passage. MSCs cultured in 5% oxygen also exhibited enhanced tri-lineage differentiation. The oxygen-induced stress response was dependent upon p53 since siRNA mediated knockdown of p53 in wild type cells or exposure of p53−/− MSCs to atmospheric oxygen failed to induce ROS generation, reduce viability, or arrest cell growth. These data indicate that long-term culture expansion of mouse MSCs in atmospheric oxygen selects for clones with absent or impaired p53 function, which allows cells to escape oxygen-induced growth inhibition. In contrast, expansion in 5% oxygen generates large numbers of primary mouse MSCs that retain sensitivity to atmospheric oxygen, and therefore a functional p53 protein, even after long-term expansion in vitro. PMID:22367737

  6. Spatial Frequency Selectivity Is Impaired in Dopamine D2 Receptor Knockout Mice

    PubMed Central

    Souza, Bruno Oliveira Ferreira; Abou Rjeili, Mira; Quintana, Clémentine; Beaulieu, Jean M.; Casanova, Christian

    2018-01-01

    Dopamine is a neurotransmitter implicated in several brain functions, including vision. In the present study, we investigated the impacts of the lack of D2 dopamine receptors on the structure and function of the primary visual cortex (V1) of D2-KO mice using optical imaging of intrinsic signals. Retinotopic maps were generated in order to measure anatomo-functional parameters such as V1 shape, cortical magnification factor, scatter, and ocular dominance. Contrast sensitivity and spatial frequency selectivity (SF) functions were computed from responses to drifting gratings. When compared to control mice, none of the parameters of the retinotopic maps were affected by D2 receptor loss of function. While the contrast sensitivity function of D2-KO mice did not differ from their wild-type counterparts, SF selectivity function was significantly affected as the optimal SF and the high cut-off frequency (p < 0.01) were higher in D2-KO than in WT mice. These findings show that the lack of function of D2 dopamine receptors had no influence on cortical structure whereas it had a significant impact on the spatial frequency selectivity and high cut-off. Taken together, our results suggest that D2 receptors play a specific role on the processing of spatial features in early visual cortex while they do not seem to participate in its development. PMID:29379422

  7. Hypothesis-driven physical examination curriculum.

    PubMed

    Allen, Sharon; Olson, Andrew; Menk, Jeremiah; Nixon, James

    2017-12-01

    Medical students traditionally learn physical examination skills as a rote list of manoeuvres. Alternatives like hypothesis-driven physical examination (HDPE) may promote students' understanding of the contribution of physical examination to diagnostic reasoning. We sought to determine whether first-year medical students can effectively learn to perform a physical examination using an HDPE approach, and then tailor the examination to specific clinical scenarios. Medical students traditionally learn physical examination skills as a rote list of manoeuvres CONTEXT: First-year medical students at the University of Minnesota were taught both traditional and HDPE approaches during a required 17-week clinical skills course in their first semester. The end-of-course evaluation assessed HDPE skills: students were assigned one of two cardiopulmonary cases. Each case included two diagnostic hypotheses. During an interaction with a standardised patient, students were asked to select physical examination manoeuvres in order to make a final diagnosis. Items were weighted and selection order was recorded. First-year students with minimal pathophysiology performed well. All students selected the correct diagnosis. Importantly, students varied the order when selecting examination manoeuvres depending on the diagnoses under consideration, demonstrating early clinical decision-making skills. An early introduction to HDPE may reinforce physical examination skills for hypothesis generation and testing, and can foster early clinical decision-making skills. This has important implications for further research in physical examination instruction. © 2016 John Wiley & Sons Ltd and The Association for the Study of Medical Education.

  8. The role of right and left parietal lobes in the conceptual processing of numbers.

    PubMed

    Cappelletti, Marinella; Lee, Hwee Ling; Freeman, Elliot D; Price, Cathy J

    2010-02-01

    Neuropsychological and functional imaging studies have associated the conceptual processing of numbers with bilateral parietal regions (including intraparietal sulcus). However, the processes driving these effects remain unclear because both left and right posterior parietal regions are activated by many other conceptual, perceptual, attention, and response-selection processes. To dissociate parietal activation that is number-selective from parietal activation related to other stimulus or response-selection processes, we used fMRI to compare numbers and object names during exactly the same conceptual and perceptual tasks while factoring out activations correlating with response times. We found that right parietal activation was higher for conceptual decisions on numbers relative to the same tasks on object names, even when response time effects were fully factored out. In contrast, left parietal activation for numbers was equally involved in conceptual processing of object names. We suggest that left parietal activation for numbers reflects a range of processes, including the retrieval of learnt facts that are also involved in conceptual decisions on object names. In contrast, number selectivity in right parietal cortex reflects processes that are more involved in conceptual decisions on numbers than object names. Our results generate a new set of hypotheses that have implications for the design of future behavioral and functional imaging studies of patients with left and right parietal damage.

  9. Polymorphism at a mimicry supergene maintained by opposing frequency-dependent selection pressures.

    PubMed

    Chouteau, Mathieu; Llaurens, Violaine; Piron-Prunier, Florence; Joron, Mathieu

    2017-08-01

    Explaining the maintenance of adaptive diversity within populations is a long-standing goal in evolutionary biology, with important implications for conservation, medicine, and agriculture. Adaptation often leads to the fixation of beneficial alleles, and therefore it erodes local diversity so that understanding the coexistence of multiple adaptive phenotypes requires deciphering the ecological mechanisms that determine their respective benefits. Here, we show how antagonistic frequency-dependent selection (FDS), generated by natural and sexual selection acting on the same trait, maintains mimicry polymorphism in the toxic butterfly Heliconius numata Positive FDS imposed by predators on mimetic signals favors the fixation of the most abundant and best-protected wing-pattern morph, thereby limiting polymorphism. However, by using mate-choice experiments, we reveal disassortative mate preferences of the different wing-pattern morphs. The resulting negative FDS on wing-pattern alleles is consistent with the excess of heterozygote genotypes at the supergene locus controlling wing-pattern variation in natural populations of H. numata The combined effect of positive and negative FDS on visual signals is sufficient to maintain a diversity of morphs displaying accurate mimicry with other local prey, although some of the forms only provide moderate protection against predators. Our findings help understand how alternative adaptive phenotypes can be maintained within populations and emphasize the need to investigate interactions between selective pressures in other cases of puzzling adaptive polymorphism.

  10. Extraordinarily rapid speciation in a marine fish

    PubMed Central

    Momigliano, Paolo; Jokinen, Henri; Fraimout, Antoine; Florin, Ann-Britt; Norkko, Alf; Merilä, Juha

    2017-01-01

    Divergent selection may initiate ecological speciation extremely rapidly. How often and at what pace ecological speciation proceeds to yield strong reproductive isolation is more uncertain. Here, we document a case of extraordinarily rapid speciation associated with ecological selection in the postglacial Baltic Sea. European flounders (Platichthys flesus) in the Baltic exhibit two contrasting reproductive behaviors: pelagic and demersal spawning. Demersal spawning enables flounders to thrive in the low salinity of the Northern Baltic, where eggs cannot achieve neutral buoyancy. We show that demersal and pelagic flounders are a species pair arising from a recent event of speciation. Despite having a parapatric distribution with extensive overlap, the two species are reciprocally monophyletic and show strongly bimodal genotypic clustering and no evidence of contemporary migration, suggesting strong reproductive isolation. Divergence across the genome is weak but shows strong signatures of selection, a pattern suggestive of a recent ecological speciation event. We propose that spawning behavior in Baltic flounders is the trait under ecologically based selection causing reproductive isolation, directly implicating a process of ecological speciation. We evaluated different possible evolutionary scenarios under the approximate Bayesian computation framework and estimate that the speciation process started in allopatry ∼2,400 generations ago, following the colonization of the Baltic by the demersal lineage. This is faster than most known cases of ecological speciation and represents the most rapid event of speciation ever reported for any marine vertebrate. PMID:28533412

  11. Polymorphism at a mimicry supergene maintained by opposing frequency-dependent selection pressures

    PubMed Central

    Chouteau, Mathieu; Llaurens, Violaine; Piron-Prunier, Florence; Joron, Mathieu

    2017-01-01

    Explaining the maintenance of adaptive diversity within populations is a long-standing goal in evolutionary biology, with important implications for conservation, medicine, and agriculture. Adaptation often leads to the fixation of beneficial alleles, and therefore it erodes local diversity so that understanding the coexistence of multiple adaptive phenotypes requires deciphering the ecological mechanisms that determine their respective benefits. Here, we show how antagonistic frequency-dependent selection (FDS), generated by natural and sexual selection acting on the same trait, maintains mimicry polymorphism in the toxic butterfly Heliconius numata. Positive FDS imposed by predators on mimetic signals favors the fixation of the most abundant and best-protected wing-pattern morph, thereby limiting polymorphism. However, by using mate-choice experiments, we reveal disassortative mate preferences of the different wing-pattern morphs. The resulting negative FDS on wing-pattern alleles is consistent with the excess of heterozygote genotypes at the supergene locus controlling wing-pattern variation in natural populations of H. numata. The combined effect of positive and negative FDS on visual signals is sufficient to maintain a diversity of morphs displaying accurate mimicry with other local prey, although some of the forms only provide moderate protection against predators. Our findings help understand how alternative adaptive phenotypes can be maintained within populations and emphasize the need to investigate interactions between selective pressures in other cases of puzzling adaptive polymorphism. PMID:28673971

  12. Using Classification and Regression Trees (CART) and random forests to analyze attrition: Results from two simulations.

    PubMed

    Hayes, Timothy; Usami, Satoshi; Jacobucci, Ross; McArdle, John J

    2015-12-01

    In this article, we describe a recent development in the analysis of attrition: using classification and regression trees (CART) and random forest methods to generate inverse sampling weights. These flexible machine learning techniques have the potential to capture complex nonlinear, interactive selection models, yet to our knowledge, their performance in the missing data analysis context has never been evaluated. To assess the potential benefits of these methods, we compare their performance with commonly employed multiple imputation and complete case techniques in 2 simulations. These initial results suggest that weights computed from pruned CART analyses performed well in terms of both bias and efficiency when compared with other methods. We discuss the implications of these findings for applied researchers. (c) 2015 APA, all rights reserved).

  13. Mycobacterial Aerosols and Respiratory Disease

    PubMed Central

    2003-01-01

    Environmental opportunistic mycobacteria, including Mycobacterium avium, M. terrae, and the new species M. immunogenum, have been implicated in outbreaks of hypersensitivity pneumonitis or respiratory problems in a wide variety of settings. One common feature of the outbreaks has been exposure to aerosols. Aerosols have been generated from metalworking fluid during machining and grinding operations as well as from indoor swimming pools, hot tubs, and water-damaged buildings. Environmental opportunistic mycobacteria are present in drinking water, resistant to disinfection, able to provoke inflammatory reactions, and readily aerosolized. In all outbreaks, the water sources of the aerosols were disinfected. Disinfection may select for the predominance and growth of mycobacteria. Therefore, mycobacteria may be responsible, in part, for many outbreaks of hypersensitivity pneumonitis and other respiratory problems in the workplace and home. PMID:12890314

  14. Using Classification and Regression Trees (CART) and Random Forests to Analyze Attrition: Results From Two Simulations

    PubMed Central

    Hayes, Timothy; Usami, Satoshi; Jacobucci, Ross; McArdle, John J.

    2016-01-01

    In this article, we describe a recent development in the analysis of attrition: using classification and regression trees (CART) and random forest methods to generate inverse sampling weights. These flexible machine learning techniques have the potential to capture complex nonlinear, interactive selection models, yet to our knowledge, their performance in the missing data analysis context has never been evaluated. To assess the potential benefits of these methods, we compare their performance with commonly employed multiple imputation and complete case techniques in 2 simulations. These initial results suggest that weights computed from pruned CART analyses performed well in terms of both bias and efficiency when compared with other methods. We discuss the implications of these findings for applied researchers. PMID:26389526

  15. Challenges and opportunities for improving food quality and nutrition through plant biotechnology.

    PubMed

    Francis, David; Finer, John J; Grotewold, Erich

    2017-04-01

    Plant biotechnology has been around since the advent of humankind, resulting in tremendous improvements in plant cultivation through crop domestication, breeding and selection. The emergence of transgenic approaches involving the introduction of defined DNA sequences into plants by humans has rapidly changed the surface of our planet by further expanding the gene pool used by plant breeders for plant improvement. Transgenic approaches in food plants have raised concerns on the merits, social implications, ecological risks and true benefits of plant biotechnology. The recently acquired ability to precisely edit plant genomes by modifying native genes without introducing new genetic material offers new opportunities to rapidly exploit natural variation, create new variation and incorporate changes with the goal to generate more productive and nutritious plants. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. A Miniaturized Screen of a Schistosoma mansoni Serotonergic G Protein-Coupled Receptor Identifies Novel Classes of Parasite-Selective Inhibitors

    PubMed Central

    Chan, John D.; McCorvy, John D.; Acharya, Sreemoyee; Day, Timothy A.; Roth, Bryan L.; Marchant, Jonathan S.

    2016-01-01

    Schistosomiasis is a tropical parasitic disease afflicting ~200 million people worldwide and current therapy depends on a single drug (praziquantel) which exhibits several non-optimal features. These shortcomings underpin the need for next generation anthelmintics, but the process of validating physiologically relevant targets (‘target selection’) and pharmacologically profiling them is challenging. Remarkably, even though over a quarter of current human therapeutics target rhodopsin-like G protein coupled receptors (GPCRs), no library screen of a flatworm GPCR has yet been reported. Here, we have pharmacologically profiled a schistosome serotonergic GPCR (Sm.5HTR) implicated as a downstream modulator of PZQ efficacy, in a miniaturized screening assay compatible with high content screening. This approach employs a split luciferase based biosensor sensitive to cellular cAMP levels that resolves the proximal kinetics of GPCR modulation in intact cells. Data evidence a divergent pharmacological signature between the parasitic serotonergic receptor and the closest human GPCR homolog (Hs.5HTR7), supporting the feasibility of optimizing parasitic selective pharmacophores. New ligands, and chemical series, with potency and selectivity for Sm.5HTR over Hs.5HTR7 are identified in vitro and validated for in vivo efficacy against schistosomules and adult worms. Sm.5HTR also displayed a property resembling irreversible inactivation, a phenomenon discovered at Hs.5HTR7, which enhances the appeal of this abundantly expressed parasite GPCR as a target for anthelmintic ligand design. Overall, these data underscore the feasibility of profiling flatworm GPCRs in a high throughput screening format competent to resolve different classes of GPCR modulators. Further, these data underscore the promise of Sm.5HTR as a chemotherapeutically vulnerable node for development of next generation anthelmintics. PMID:27187180

  17. Decursin enhances TRAIL‐induced apoptosis through oxidative stress mediated‐ endoplasmic reticulum stress signalling in non‐small cell lung cancers

    PubMed Central

    Kim, Jaekwang; Yun, Miyong; Kim, Eun‐Ok; Jung, Deok‐Beom; Won, Gunho; Kim, Bonglee; Jung, Ji Hoon

    2016-01-01

    Background and Purpose The TNF‐related apoptosis‐inducing ligand (TRAIL) is a promising anticancer agent due to its remarkable ability to selectively kill tumour cells. However, because most tumours exhibit resistance to TRAIL‐induced apoptosis, the development of combination therapies to overcome resistance to TRAIL is required for effective cancer therapy. Experimental Approach Cell viability and possible synergy between the plant pyranocoumarin decursin and TRAIL was measured by MTT assay and calcusyn software. Reactive oxygen species (ROS) and apoptosis were measured using dichlorodihydrofluorescein and annexin/propidium iodide in cell flow cytometry. Changes in protein levels were assessed with Western blotting. Key Results Combining decursin and TRAIL markedly decreased cell viability and increased apoptosis in TRAIL‐resistant non‐small‐cell lung cancer (NSCLC) cell lines. Decursin induced expression of the death receptor 5 (DR5). Inhibition of DR5 attenuated apoptotic cell death in decursin + TRAIL treated NSCLC cell lines. Interestingly, induction of DR5 and CCAAT/enhancer‐binding protein homologues protein by decursin was mediated through selective induction of the pancreatic endoplasmic reticulum kinase (PERK)/activating transcription factor 4 (ATF4) branch of the endoplasmic reticulum stress response pathway. Furthermore, enhancement of PERK/ATF4 signalling by decursin was mediated by ROS generation in NSCLC cell lines, but not in normal human lung cells. Decursin also markedly down‐regulated expression of survivin and Bcl‐xL in TRAIL‐resistant NSCLC cells. Conclusions and Implications ROS generation by decursin selectively activated the PERK/ATF4 axis of the endoplasmic reticulum stress signalling pathway, leading to enhanced TRAIL sensitivity in TRAIL‐resistant NSCLC cell lines, partly via up‐regulation of DR5. PMID:26661339

  18. Stimulant effects of adenosine antagonists on operant behavior: differential actions of selective A2A and A1 antagonists

    PubMed Central

    Randall, Patrick A.; Nunes, Eric J.; Janniere, Simone L.; Stopper, Colin M.; Farrar, Andrew M.; Sager, Thomas N.; Baqi, Younis; Hockemeyer, Jörg; Müller, Christa E.

    2012-01-01

    Rationale Adenosine A2A antagonists can reverse many of the behavioral effects of dopamine antagonists, including actions on instrumental behavior. However, little is known about the effects of selective adenosine antagonists on operant behavior when these drugs are administered alone. Objective The present studies were undertaken to investigate the potential for rate-dependent stimulant effects of both selective and nonselective adenosine antagonists. Methods Six drugs were tested: two nonselective adenosine antagonists (caffeine and theophylline), two adenosine A1 antagonists (DPCPX and CPT), and two adenosine A2A antagonists (istradefylline (KW6002) and MSX-3). Two schedules of reinforcement were employed; a fixed interval 240-s (FI-240 sec) schedule was used to generate low baseline rates of responding and a fixed ratio 20 (FR20) schedule generated high rates. Results Caffeine and theophylline produced rate-dependent effects on lever pressing, increasing responding on the FI-240 sec schedule but decreasing responding on the FR20 schedule. The A2A antagonists MSX-3 and istradefylline increased FI-240 sec lever pressing but did not suppress FR20 lever pressing in the dose range tested. In fact, there was a tendency for istradefylline to increase FR20 responding at a moderate dose. A1 antagonists failed to increase lever pressing rate, but DPCPX decreased FR20 responding at higher doses. Conclusions These results suggest that adenosine A2A antagonists enhance operant response rates, but A1 antagonists do not. The involvement of adenosine A2A receptors in regulating aspects of instrumental response output and behavioral activation may have implications for the treatment of effort-related psychiatric dysfunctions, such as psychomotor slowing and anergia in depression. PMID:21347642

  19. Functional MRI mapping of visual function and selective attention for performance assessment and presurgical planning using conjunctive visual search

    PubMed Central

    Parker, Jason G; Zalusky, Eric J; Kirbas, Cemil

    2014-01-01

    Background Accurate mapping of visual function and selective attention using fMRI is important in the study of human performance as well as in presurgical treatment planning of lesions in or near visual centers of the brain. Conjunctive visual search (CVS) is a useful tool for mapping visual function during fMRI because of its greater activation extent compared with high-capacity parallel search processes. Aims The purpose of this work was to develop and evaluate a CVS that was capable of generating consistent activation in the basic and higher level visual areas of the brain by using a high number of distractors as well as an optimized contrast condition. Materials and methods Images from 10 healthy volunteers were analyzed and brain regions of greatest activation and deactivation were determined using a nonbiased decomposition of the results at the hemisphere, lobe, and gyrus levels. The results were quantified in terms of activation and deactivation extent and mean z-statistic. Results The proposed CVS was found to generate robust activation of the occipital lobe, as well as regions in the middle frontal gyrus associated with coordinating eye movements and in regions of the insula associated with task-level control and focal attention. As expected, the task demonstrated deactivation patterns commonly implicated in the default-mode network. Further deactivation was noted in the posterior region of the cerebellum, most likely associated with the formation of optimal search strategy. Conclusion We believe the task will be useful in studies of visual and selective attention in the neuroscience community as well as in mapping visual function in clinical fMRI. PMID:24683515

  20. Generative model selection using a scalable and size-independent complex network classifier

    NASA Astrophysics Data System (ADS)

    Motallebi, Sadegh; Aliakbary, Sadegh; Habibi, Jafar

    2013-12-01

    Real networks exhibit nontrivial topological features, such as heavy-tailed degree distribution, high clustering, and small-worldness. Researchers have developed several generative models for synthesizing artificial networks that are structurally similar to real networks. An important research problem is to identify the generative model that best fits to a target network. In this paper, we investigate this problem and our goal is to select the model that is able to generate graphs similar to a given network instance. By the means of generating synthetic networks with seven outstanding generative models, we have utilized machine learning methods to develop a decision tree for model selection. Our proposed method, which is named "Generative Model Selection for Complex Networks," outperforms existing methods with respect to accuracy, scalability, and size-independence.

  1. Selective advantage of implementing optimal contributions selection and timescales for the convergence of long-term genetic contributions.

    PubMed

    Howard, David M; Pong-Wong, Ricardo; Knap, Pieter W; Kremer, Valentin D; Woolliams, John A

    2018-05-10

    Optimal contributions selection (OCS) provides animal breeders with a framework for maximising genetic gain for a predefined rate of inbreeding. Simulation studies have indicated that the source of the selective advantage of OCS is derived from breeding decisions being more closely aligned with estimates of Mendelian sampling terms ([Formula: see text]) of selection candidates, rather than estimated breeding values (EBV). This study represents the first attempt to assess the source of the selective advantage provided by OCS using a commercial pig population and by testing three hypotheses: (1) OCS places more emphasis on [Formula: see text] compared to EBV for determining which animals were selected as parents, (2) OCS places more emphasis on [Formula: see text] compared to EBV for determining which of those parents were selected to make a long-term genetic contribution (r), and (3) OCS places more emphasis on [Formula: see text] compared to EBV for determining the magnitude of r. The population studied also provided an opportunity to investigate the convergence of r over time. Selection intensity limited the number of males available for analysis, but females provided some evidence that the selective advantage derived from applying an OCS algorithm resulted from greater weighting being placed on [Formula: see text] during the process of decision-making. Male r were found to converge initially at a faster rate than female r, with approximately 90% convergence achieved within seven generations across both sexes. This study of commercial data provides some support to results from theoretical and simulation studies that the source of selective advantage from OCS comes from [Formula: see text]. The implication that genomic selection (GS) improves estimation of [Formula: see text] should allow for even greater genetic gains for a predefined rate of inbreeding, once the synergistic benefits of combining OCS and GS are realised.

  2. FOXP2 targets show evidence of positive selection in European populations.

    PubMed

    Ayub, Qasim; Yngvadottir, Bryndis; Chen, Yuan; Xue, Yali; Hu, Min; Vernes, Sonja C; Fisher, Simon E; Tyler-Smith, Chris

    2013-05-02

    Forkhead box P2 (FOXP2) is a highly conserved transcription factor that has been implicated in human speech and language disorders and plays important roles in the plasticity of the developing brain. The pattern of nucleotide polymorphisms in FOXP2 in modern populations suggests that it has been the target of positive (Darwinian) selection during recent human evolution. In our study, we searched for evidence of selection that might have followed FOXP2 adaptations in modern humans. We examined whether or not putative FOXP2 targets identified by chromatin-immunoprecipitation genomic screening show evidence of positive selection. We developed an algorithm that, for any given gene list, systematically generates matched lists of control genes from the Ensembl database, collates summary statistics for three frequency-spectrum-based neutrality tests from the low-coverage resequencing data of the 1000 Genomes Project, and determines whether these statistics are significantly different between the given gene targets and the set of controls. Overall, there was strong evidence of selection of FOXP2 targets in Europeans, but not in the Han Chinese, Japanese, or Yoruba populations. Significant outliers included several genes linked to cellular movement, reproduction, development, and immune cell trafficking, and 13 of these constituted a significant network associated with cardiac arteriopathy. Strong signals of selection were observed for CNTNAP2 and RBFOX1, key neurally expressed genes that have been consistently identified as direct FOXP2 targets in multiple studies and that have themselves been associated with neurodevelopmental disorders involving language dysfunction. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  3. Task-specific Aspects of Goal-directed Word Generation Identified via Simultaneous EEG-fMRI.

    PubMed

    Shapira-Lichter, Irit; Klovatch, Ilana; Nathan, Dana; Oren, Noga; Hendler, Talma

    2016-09-01

    Generating words according to a given rule relies on retrieval-related search and postretrieval control processes. Using fMRI, we recently characterized neural patterns of word generation in response to episodic, semantic, and phonemic cues by comparing free recall of wordlists, category fluency, and letter fluency [Shapira-Lichter, I., Oren, N., Jacob, Y., Gruberger, M., & Hendler, T. Portraying the unique contribution of the default mode network to internally driven mnemonic processes. Proceedings of the National Academy of Sciences, U.S.A., 110, 4950-4955, 2013]. Distinct selectivity for each condition was evident, representing discrete aspects of word generation-related memory retrieval. For example, the precuneus, implicated in processing spatiotemporal information, emerged as a key contributor to the episodic condition, which uniquely requires this information. Gamma band is known to play a central role in memory, and increased gamma power has been observed before word generation. Yet, gamma modulation in response to task demands has not been investigated. To capture the task-specific modulation of gamma power, we analyzed the EEG data recorded simultaneously with the aforementioned fMRI, focusing on the activity locked to and immediately preceding word articulation. Transient increases in gamma power were identified in a parietal electrode immediately before episodic and semantic word generation, however, within a different time frame relative to articulation. Gamma increases were followed by an alpha-theta decrease in the episodic condition, a gamma decrease in the semantic condition. This pattern indicates a task-specific modulation of the gamma signal corresponding to the specific demands of each word generation task. The gamma power and fMRI signal from the precuneus were correlated during the episodic condition, implying the existence of a common cognitive construct uniquely required for this task, possibly the reactivation or processing of spatiotemporal information.

  4. A role for adult TLX-positive neural stem cells in learning and behaviour.

    PubMed

    Zhang, Chun-Li; Zou, Yuhua; He, Weimin; Gage, Fred H; Evans, Ronald M

    2008-02-21

    Neurogenesis persists in the adult brain and can be regulated by a plethora of external stimuli, such as learning, memory, exercise, environment and stress. Although newly generated neurons are able to migrate and preferentially incorporate into the neural network, how these cells are molecularly regulated and whether they are required for any normal brain function are unresolved questions. The adult neural stem cell pool is composed of orphan nuclear receptor TLX-positive cells. Here, using genetic approaches in mice, we demonstrate that TLX (also called NR2E1) regulates adult neural stem cell proliferation in a cell-autonomous manner by controlling a defined genetic network implicated in cell proliferation and growth. Consequently, specific removal of TLX from the adult mouse brain through inducible recombination results in a significant reduction of stem cell proliferation and a marked decrement in spatial learning. In contrast, the resulting suppression of adult neurogenesis does not affect contextual fear conditioning, locomotion or diurnal rhythmic activities, indicating a more selective contribution of newly generated neurons to specific cognitive functions.

  5. Nature versus nurture? Consequences of short captivity in early stages.

    PubMed

    Horreo, Jose L; Valiente, America G; Ardura, Alba; Blanco, Aida; Garcia-Gonzalez, Claudia; Garcia-Vazquez, Eva

    2018-01-01

    Biological changes occurring as a consequence of domestication and/or captivity are not still deeply known. In Atlantic salmon (S almo salar ), endangered (Southern Europe) populations are enhanced by supportive breeding, which involves only 6 months of captive rearing following artificial spawning of wild-collected adults. In this work, we assess whether several fitness-correlated life-history traits (migratory behavior, straying rate, age at maturity, and growth) are affected by early exposure to the captive environment within a generation, before reproduction thus before genetic selection. Results showed significant differences in growth and migratory behavior (including straying), associated with this very short period of captivity in natural fish populations, changing even genetic variability (decreased in hatchery-reared adults) and the native population structure within and between rivers of the species. These changes appeared within a single generation, suggesting very short time of captivity is enough for initiating changes normally attributed to domestication. These results may have potential implications for the long-term population stability/viability of species subjected to restoration and enhancement processes and could be also considered for the management of zoo populations.

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

    Bryant, M.; Starkey, A.H.; Dick-Peddie, W.A.

    A brief overview of the present day geothermal applications for hydrothermal electrical generation and direct heat use and their environmental implications is provided. Technologies and environmental impacts are considered at all points on the pathway of development resource exploration; well field, plant and transmission line construction; and plant operation. The technologies for electrical generation-direct, dry steam conversion; separated steam conversion; single-flash conversion, separated-steam/single-flash conversion and binary cycle conversion and the technologies for direct heat use - direct use of geothermal waters, surface heat exhanger, down-the hole heat exchanger and heat pump are described. A summary of the geothermal technologies plannedmore » or in operation within New Mexico geothermal areas is provided. A review of regulations that affect geothermal development and its related environmental impact in New Mexico is presented. The regulatory pathway, both state and federal, of geothermal exploration after the securing of appropriate leases, development, and construction and implementation of a geothermal facility are described. Six categories (Geophysical, Water, Air, Noise, Biota and Socioeconomics) were selected for environmental assessment. The data available is described.« less

  7. Role of Reactive Oxygen Species in Neonatal Pulmonary Vascular Disease

    PubMed Central

    Steinhorn, Robin H.

    2014-01-01

    Abstract Significance: Abnormal lung development in the perinatal period can result in severe neonatal complications, including persistent pulmonary hypertension (PH) of the newborn and bronchopulmonary dysplasia. Reactive oxygen species (ROS) play a substantive role in the development of PH associated with these diseases. ROS impair the normal pulmonary artery (PA) relaxation in response to vasodilators, and ROS are also implicated in pulmonary arterial remodeling, both of which can increase the severity of PH. Recent Advances: PA ROS levels are elevated when endogenous ROS-generating enzymes are activated and/or when endogenous ROS scavengers are inactivated. Animal models have provided valuable insights into ROS generators and scavengers that are dysregulated in different forms of neonatal PH, thus identifying potential therapeutic targets. Critical Issues: General antioxidant therapy has proved ineffective in reversing PH, suggesting that it is necessary to target specific signaling pathways for successful therapy. Future Directions: Development of novel selective pharmacologic inhibitors along with nonantioxidant therapies may improve the treatment outcomes of patients with PH, while further investigation of the underlying mechanisms may enable earlier detection of the disease. Antioxid. Redox Signal. 21, 1926–1942. PMID:24350610

  8. Intrinsic electrophilic properties of nucleosides: Photoelectron spectroscopy of their parent anions

    NASA Astrophysics Data System (ADS)

    Stokes, Sarah T.; Li, Xiang; Grubisic, Andrej; Ko, Yeon Jae; Bowen, Kit H.

    2007-08-01

    The nucleoside parent anions 2'-deoxythymidine-, 2'-deoxycytidine-, 2'-deoxyadenosine-, uridine-, cytidine-, adenosine-, and guanosine- were generated in a novel source, employing a combination of infrared desorption, electron photoemission, and a gas jet expansion. Once mass selected, the anion photoelectron spectrum of each of these was recorded. In the three cases in which comparisons were possible, the vertical detachment energies and likely adiabatic electron affinities extracted from these spectra agreed well with the values calculated both by Richardson et al. [J. Am. Chem. Soc. 126, 4404 (2004)] and by Li et al. [Radiat. Res. 165, 721 (2006)]. Through the combination of our experimental results and their theoretical calculations, several implications emerge. (1) With the possible exception of dG-, the parent anions of nucleosides exist, and they are stable. (2) These nucleoside anions are valence anions, and in most cases the negative charge is closely associated with the nucleobase moiety. (3) The nucleoside parent anions we have generated and studied are the negative ions of canonical, neutral nucleosides, similar to those found in DNA.

  9. Intrinsic electrophilic properties of nucleosides: photoelectron spectroscopy of their parent anions.

    PubMed

    Stokes, Sarah T; Li, Xiang; Grubisic, Andrej; Ko, Yeon Jae; Bowen, Kit H

    2007-08-28

    The nucleoside parent anions 2(')-deoxythymidine(-), 2(')-deoxycytidine(-), 2(')-deoxyadenosine(-), uridine(-), cytidine(-), adenosine(-), and guanosine(-) were generated in a novel source, employing a combination of infrared desorption, electron photoemission, and a gas jet expansion. Once mass selected, the anion photoelectron spectrum of each of these was recorded. In the three cases in which comparisons were possible, the vertical detachment energies and likely adiabatic electron affinities extracted from these spectra agreed well with the values calculated both by Richardson et al. [J. Am. Chem. Soc. 126, 4404 (2004)] and by Li et al. [Radiat. Res. 165, 721 (2006)]. Through the combination of our experimental results and their theoretical calculations, several implications emerge. (1) With the possible exception of dG(-), the parent anions of nucleosides exist, and they are stable. (2) These nucleoside anions are valence anions, and in most cases the negative charge is closely associated with the nucleobase moiety. (3) The nucleoside parent anions we have generated and studied are the negative ions of canonical, neutral nucleosides, similar to those found in DNA.

  10. Ask the experts how to treat individuals with spatial neglect: a survey study.

    PubMed

    Chen, Peii; Pitteri, Marco; Gillen, Glen; Ayyala, Harsha

    2017-07-11

    Spatial neglect (SN) impedes rehabilitation success and leaves long-term consequences. We asked experts to provide their opinions in addressing SN by scenario (ideal vs. reality) and by recovery phase (earliest, acute, subacute, and chronic). Experts were individuals who have assessed or treated patients with SN clinically. This study was conducted using an anonymous survey on the Internet with 189 responders over 3 months. Located in 23 different countries, 127 experts of seven disciplines were included (occupational therapy, physical therapy, nursing, speech and language pathology or therapy, neurology, physical medicine and rehabilitation, and psychology or neuropsychology). Comparing the two scenarios, more treatments were selected in the ideal than in the reality scenario for all recovery phases except for the chronic phase. In both scenarios, (1) more treatments were selected in acute and subacute phases than in earliest or chronic phases, (2) less experienced experts selected diverse treatment options more often, and (3) highly experienced experts were more likely to provide their reasons of treatment selection, suggestions of treatment delivery methods, and other insights. Finally, 83.7% reported obstacles in treating SN. Experts' treatment selections are consistent with current evidence and practice guidelines. Recognizing the limitation of evidence, their opinions may help generate ideas in various topics (e.g., dosing, integrative intervention, and treatment implementation) to be examined in future studies. Implications for Rehabilitation Clinicians with experience in treating people with spatial neglect (i.e., experts as defined in the present study) recognized the limitation of evidence but nonetheless suggested specific treatments by recovery phase. In both the reality and ideal scenarios, experts included visual scanning, active limb activation, and sustained attention training in the top-five selections. Prism adaptation was in the top-five selections in the ideal scenario, while in the reality scenario, it was in the top-five in all phases except for the earliest phase where it was the sixth most selected. They also shared their valuable opinions in when to use which treatment to address spatial neglect and how to deliver certain interventions, which may help to generate ideas in various topics (e.g., dosing, integrative intervention, knowledge dissemination, and treatment implementation) that can be examined in future studies. We suggest that (1) clinicians consider collective expert opinions reported here to enhance their clinical judgment and practices, (2) researchers develop studies focused on treatments with limited evidence but selected here by experts, and (3) funding agencies provide the means to research and implementation projects that will generate rich information for improving practice guidelines and rehabilitation outcomes for patients with spatial neglect. The majority of the experts reported some obstacles in providing treatment for spatial neglect, and time and equipment shortages were the most common barriers, which should be addressed at the system level to determine whether removing those barriers have long-term beneficial impacts on both patients and healthcare systems.

  11. Forward vs. backwards selection for seed orchards and cooperative second-generation breeding in the US Pacific Northwest.

    Treesearch

    R. Johnson; K. Jayawickrama

    2003-01-01

    Gain from various orchard strategies were modeled. The scenario tested 2,000 first-generation open-pollinated families, from which orchards of 20 selections were formed, using either parents, progeny or both. This was followed by a second-generation breeding population in which 200 full-sib families were tested followed by a second-generation orchard of 20 selections....

  12. The importance of information on relatives for the prediction of genomic breeding values and the implications for the makeup of reference data sets in livestock breeding schemes.

    PubMed

    Clark, Samuel A; Hickey, John M; Daetwyler, Hans D; van der Werf, Julius H J

    2012-02-09

    The theory of genomic selection is based on the prediction of the effects of genetic markers in linkage disequilibrium with quantitative trait loci. However, genomic selection also relies on relationships between individuals to accurately predict genetic value. This study aimed to examine the importance of information on relatives versus that of unrelated or more distantly related individuals on the estimation of genomic breeding values. Simulated and real data were used to examine the effects of various degrees of relationship on the accuracy of genomic selection. Genomic Best Linear Unbiased Prediction (gBLUP) was compared to two pedigree based BLUP methods, one with a shallow one generation pedigree and the other with a deep ten generation pedigree. The accuracy of estimated breeding values for different groups of selection candidates that had varying degrees of relationships to a reference data set of 1750 animals was investigated. The gBLUP method predicted breeding values more accurately than BLUP. The most accurate breeding values were estimated using gBLUP for closely related animals. Similarly, the pedigree based BLUP methods were also accurate for closely related animals, however when the pedigree based BLUP methods were used to predict unrelated animals, the accuracy was close to zero. In contrast, gBLUP breeding values, for animals that had no pedigree relationship with animals in the reference data set, allowed substantial accuracy. An animal's relationship to the reference data set is an important factor for the accuracy of genomic predictions. Animals that share a close relationship to the reference data set had the highest accuracy from genomic predictions. However a baseline accuracy that is driven by the reference data set size and the overall population effective population size enables gBLUP to estimate a breeding value for unrelated animals within a population (breed), using information previously ignored by pedigree based BLUP methods.

  13. Spontaneous mirror-symmetry breaking induces inverse energy cascade in 3D active fluids

    PubMed Central

    Słomka, Jonasz; Dunkel, Jörn

    2017-01-01

    Classical turbulence theory assumes that energy transport in a 3D turbulent flow proceeds through a Richardson cascade whereby larger vortices successively decay into smaller ones. By contrast, an additional inverse cascade characterized by vortex growth exists in 2D fluids and gases, with profound implications for meteorological flows and fluid mixing. The possibility of a helicity-driven inverse cascade in 3D fluids had been rejected in the 1970s based on equilibrium-thermodynamic arguments. Recently, however, it was proposed that certain symmetry-breaking processes could potentially trigger a 3D inverse cascade, but no physical system exhibiting this phenomenon has been identified to date. Here, we present analytical and numerical evidence for the existence of an inverse energy cascade in an experimentally validated 3D active fluid model, describing microbial suspension flows that spontaneously break mirror symmetry. We show analytically that self-organized scale selection, a generic feature of many biological and engineered nonequilibrium fluids, can generate parity-violating Beltrami flows. Our simulations further demonstrate how active scale selection controls mirror-symmetry breaking and the emergence of a 3D inverse cascade. PMID:28193853

  14. Leukocyte-inspired biodegradable particles that selectively and avidly adhere to inflamed endothelium in vitro and in vivo

    NASA Astrophysics Data System (ADS)

    Sakhalkar, Harshad S.; Dalal, Milind K.; Salem, Aliasger K.; Ansari, Ramin; Fu, Jie; Kiani, Mohammad F.; Kurjiaka, David T.; Hanes, Justin; Shakesheff, Kevin M.; Goetz, Douglas J.

    2003-12-01

    We exploited leukocyte-endothelial cell adhesion chemistry to generate biodegradable particles that exhibit highly selective accumulation on inflamed endothelium in vitro and in vivo. Leukocyte-endothelial cell adhesive particles exhibit up to 15-fold higher adhesion to inflamed endothelium, relative to noninflamed endothelium, under in vitro flow conditions similar to that present in blood vessels, a 6-fold higher adhesion to cytokine inflamed endothelium relative to non-cytokine-treated endothelium in vivo, and a 10-fold enhancement in adhesion to trauma-induced inflamed endothelium in vivo due to the addition of a targeting ligand. The leukocyte-inspired particles have adhesion efficiencies similar to that of leukocytes and were shown to target each of the major inducible endothelial cell adhesion molecules (E-selectin, P-selectin, vascular cell adhesion molecule 1, and intercellular adhesion molecule 1) that are up-regulated at sites of pathological inflammation. The potential for targeted drug delivery to inflamed endothelium has significant implications for the improved treatment of an array of pathologies, including cardiovascular disease, arthritis, inflammatory bowel disease, and cancer.

  15. Anchoring in Numeric Judgments of Visual Stimuli

    PubMed Central

    Langeborg, Linda; Eriksson, Mårten

    2016-01-01

    This article investigates effects of anchoring in age estimation and estimation of quantities, two tasks which to different extents are based on visual stimuli. The results are compared to anchoring in answers to classic general knowledge questions that rely on semantic knowledge. Cognitive load was manipulated to explore possible differences between domains. Effects of source credibility, manipulated by differing instructions regarding the selection of anchor values (no information regarding anchor selection, information that the anchors are randomly generated or information that the anchors are answers from an expert) on anchoring were also investigated. Effects of anchoring were large for all types of judgments but were not affected by cognitive load or by source credibility in either one of the researched domains. A main effect of cognitive load on quantity estimations and main effects of source credibility in the two visually based domains indicate that the manipulations were efficient. Implications for theoretical explanations of anchoring are discussed. In particular, because anchoring did not interact with cognitive load, the results imply that the process behind anchoring in visual tasks is predominantly automatic and unconscious. PMID:26941684

  16. How Evolution May Work Through Curiosity-Driven Developmental Process.

    PubMed

    Oudeyer, Pierre-Yves; Smith, Linda B

    2016-04-01

    Infants' own activities create and actively select their learning experiences. Here we review recent models of embodied information seeking and curiosity-driven learning and show that these mechanisms have deep implications for development and evolution. We discuss how these mechanisms yield self-organized epigenesis with emergent ordered behavioral and cognitive developmental stages. We describe a robotic experiment that explored the hypothesis that progress in learning, in and for itself, generates intrinsic rewards: The robot learners probabilistically selected experiences according to their potential for reducing uncertainty. In these experiments, curiosity-driven learning led the robot learner to successively discover object affordances and vocal interaction with its peers. We explain how a learning curriculum adapted to the current constraints of the learning system automatically formed, constraining learning and shaping the developmental trajectory. The observed trajectories in the robot experiment share many properties with those in infant development, including a mixture of regularities and diversities in the developmental patterns. Finally, we argue that such emergent developmental structures can guide and constrain evolution, in particular with regard to the origins of language. Copyright © 2016 Cognitive Science Society, Inc.

  17. Evolution of sequence-defined highly functionalized nucleic acid polymers

    NASA Astrophysics Data System (ADS)

    Chen, Zhen; Lichtor, Phillip A.; Berliner, Adrian P.; Chen, Jonathan C.; Liu, David R.

    2018-03-01

    The evolution of sequence-defined synthetic polymers made of building blocks beyond those compatible with polymerase enzymes or the ribosome has the potential to generate new classes of receptors, catalysts and materials. Here we describe a ligase-mediated DNA-templated polymerization and in vitro selection system to evolve highly functionalized nucleic acid polymers (HFNAPs) made from 32 building blocks that contain eight chemically diverse side chains on a DNA backbone. Through iterated cycles of polymer translation, selection and reverse translation, we discovered HFNAPs that bind proprotein convertase subtilisin/kexin type 9 (PCSK9) and interleukin-6, two protein targets implicated in human diseases. Mutation and reselection of an active PCSK9-binding polymer yielded evolved polymers with high affinity (KD = 3 nM). This evolved polymer potently inhibited the binding between PCSK9 and the low-density lipoprotein receptor. Structure-activity relationship studies revealed that specific side chains at defined positions in the polymers are required for binding to their respective targets. Our findings expand the chemical space of evolvable polymers to include densely functionalized nucleic acids with diverse, researcher-defined chemical repertoires.

  18. Evolutionary dynamics of interactions between plants and their enemies: comparison of herbivorous insects and pathogens.

    PubMed

    Wininger, Kerry; Rank, Nathan

    2017-11-01

    Plants colonized land over 400 million years ago. Shortly thereafter, organisms began to consume terrestrial plant tissue as a nutritional resource. Most plant enemies are plant pathogens or herbivores, and they impose natural selection for plants to evolve defenses. These traits generate selection pressures on enemies. Coevolution between terrestrial plants and their enemies is an important element of the evolutionary history of both groups. However, coevolutionary studies of plant-pathogen interactions have tended to focus on different research topics than plant-herbivore interactions. Specifically, studies of plant-pathogen interactions often adopt a "gene-for-gene" conceptual framework. In contrast, studies of plants and herbivores often investigate escalation or elaboration of plant defense and herbivore adaptations to overcome it. The main exceptions to the general pattern are studies that focus on small, sessile herbivores that share many features with plant pathogens, studies that incorporate both herbivores and pathogens into a single investigation, and studies that test aspects of Thompson's geographic mosaic theory for coevolution. We discuss the implications of these findings for future research. © 2017 New York Academy of Sciences.

  19. Extraordinarily Adaptive Properties of the Genetically Encoded Amino Acids

    PubMed Central

    Ilardo, Melissa; Meringer, Markus; Freeland, Stephen; Rasulev, Bakhtiyor; Cleaves II, H. James

    2015-01-01

    Using novel advances in computational chemistry, we demonstrate that the set of 20 genetically encoded amino acids, used nearly universally to construct all coded terrestrial proteins, has been highly influenced by natural selection. We defined an adaptive set of amino acids as one whose members thoroughly cover relevant physico-chemical properties, or “chemistry space.” Using this metric, we compared the encoded amino acid alphabet to random sets of amino acids. These random sets were drawn from a computationally generated compound library containing 1913 alternative amino acids that lie within the molecular weight range of the encoded amino acids. Sets that cover chemistry space better than the genetically encoded alphabet are extremely rare and energetically costly. Further analysis of more adaptive sets reveals common features and anomalies, and we explore their implications for synthetic biology. We present these computations as evidence that the set of 20 amino acids found within the standard genetic code is the result of considerable natural selection. The amino acids used for constructing coded proteins may represent a largely global optimum, such that any aqueous biochemistry would use a very similar set. PMID:25802223

  20. An fMRI study of acupuncture-induced brain activation of aphasia stroke patients.

    PubMed

    Li, Geng; Yang, Edward S

    2011-01-01

    This investigation aims to test the effect of acupuncture on word generation activation (WGA) in post-stroke aphasia patients. Seven vascular aphasia patients and 14 control subjects were studied using functional magnetic resonance imaging (fMRI). Each performed: (1) a word generation (WG) task alone, followed by (2) repeating WG after insertion of acupuncture needles (WGN) into SJ 8 (a language-implicated acupoint), followed by (3) repeating WGN reinforced by electrical stimulation (WGA) of SJ 8, and finally (4) electrical stimulation (ES) of SJ 8 alone. Significant activation was found in the opercular, triangular, or insula during the ES stimulation in patients when comparing each patient to 14 normal controls. For the WG task, significant activation was found in the inferior frontal gyrus when comparing each patient to 14 normal controls. The signal induced by acupuncture was larger than that of the WG task in the left middle frontal gyrus with the comparison of WGA vs. WGN in seven patients. Further, main significant effects in the right insula in patients were observed when comparing seven patients to 14 normal controls. The activation induced by ES stimulation was only found on the left side in controls. This activation was observed on the lesion side of superior and middle frontal gyrus (SMFG) in patients. This study demonstrates for the first time that language-deficit-implicated acupoint stimulation can selectively activate the brain on the lesion side in post-stroke aphasia patients. These results suggest that acupuncture may have therapeutic benefits in post-stroke aphasia patients. Copyright © 2010 Elsevier Ltd. All rights reserved.

  1. Getting with the times: a narrative review of the literature on group decision making in virtual environments and implications for promotions committees.

    PubMed

    Acai, Anita; Sonnadara, Ranil R; O'Neill, Thomas A

    2018-06-01

    Concerns around the time and administrative burden of trainee promotion processes have been reported, making virtual meetings an attractive option for promotions committees in undergraduate and postgraduate medicine. However, whether such meetings can uphold the integrity of decision-making processes has yet to be explored. This narrative review aimed to summarize the literature on decision making in virtual teams, discuss ways to improve the effectiveness of virtual teams, and explore their implications for practice. In August 2017, the Web of Science platform was searched with the terms 'decision making' AND 'virtual teams' for articles published within the last 20 years. The search yielded 336 articles, which was narrowed down to a final set of 188 articles. A subset of these, subjectively deemed to be of high-quality and relevant to the work of promotions committees, was included in this review. Virtual team functioning was explored with respect to team composition and development, idea generation and selection, group memory, and communication. While virtual teams were found to potentially offer a number of key benefits over face-to-face meetings including convenience and scheduling flexibility, inclusion of members at remote sites, and enhanced idea generation and external storage, these benefits must be carefully weighed against potential challenges involving planning and coordination, integration of perspectives, and relational conflict among members, all of which can potentially reduce decision-making quality. Avenues to address these issues and maximize the outcomes of virtual promotions meetings are offered in light of the evidence.

  2. Assessing community values for reducing agricultural emissions to improve water quality and protect coral health in the Great Barrier Reef

    NASA Astrophysics Data System (ADS)

    Rolfe, John; Windle, Jill

    2011-12-01

    Policymakers wanting to increase protection of the Great Barrier Reef from pollutants generated by agriculture need to identify when measures to improve water quality generate benefits to society that outweigh the costs involved. The research reported in this paper makes a contribution in several ways. First, it uses the improved science understanding about the links between management changes and reef health to bring together the analysis of costs and benefits of marginal changes, helping to demonstrate the appropriate way of addressing policy questions relating to reef protection. Second, it uses the scientific relationships to frame a choice experiment to value the benefits of improved reef health, with the results of mixed logit (random parameter) models linking improvements explicitly to changes in "water quality units." Third, the research demonstrates how protection values are consistent across a broader population, with some limited evidence of distance effects. Fourth, the information on marginal costs and benefits that are reported provide policymakers with information to help improve management decisions. The results indicate that while there is potential for water quality improvements to generate net benefits, high cost water quality improvements are generally uneconomic. A major policy implication is that cost thresholds for key pollutants should be set to avoid more expensive water quality proposals being selected.

  3. What do firefighters desire from the next generation of personal protective equipment? Outcomes from an international survey

    PubMed Central

    LEE, Joo-Young; PARK, Joonhee; PARK, Huiju; COCA, Aitor; KIM, Jung-Hyun; TAYLOR, Nigel A.S.; SON, Su-Young; TOCHIHARA, Yutaka

    2015-01-01

    The purpose of this study was to investigate smart features required for the next generation of personal protective equipment (PPE) for firefighters in Australia, Korea, Japan, and the USA. Questionnaire responses were obtained from 167 Australian, 351 Japanese, 413 Korean, and 763 U.S. firefighters (1,611 males and 61 females). Preferences concerning smart features varied among countries, with 27% of Korean and 30% of U.S. firefighters identifying ‘a location monitoring system’ as the most important element. On the other hand, 43% of Japanese firefighters preferred ‘an automatic body cooling system’ while 21% of the Australian firefighters selected equally ‘an automatic body cooling system’ and ‘a wireless communication system’. When asked to rank these elements in descending priority, responses across these countries were very similar with the following items ranked highest: ‘a location monitoring system’, ‘an automatic body cooling system’, ‘a wireless communication system’, and ‘a vision support system’. The least preferred elements were ‘an automatic body warming system’ and ‘a voice recording system’. No preferential relationship was apparent for age, work experience, gender or anthropometric characteristics. These results have implications for the development of the next generation of PPE along with the international standardisation of the smart PPE. PMID:26027710

  4. Sublethal Ciprofloxacin Treatment Leads to Rapid Development of High-Level Ciprofloxacin Resistance during Long-Term Experimental Evolution of Pseudomonas aeruginosa

    PubMed Central

    Jørgensen, Karin Meinike; Wassermann, Tina; Jensen, Peter Østrup; Hengzuang, Wang; Molin, Søren; Høiby, Niels

    2013-01-01

    The dynamics of occurrence and the genetic basis of ciprofloxacin resistance were studied in a long-term evolution experiment (940 generations) in wild-type, reference strain (PAO1) and hypermutable (PAOΔmutS and PAOMY-Mgm) P. aeruginosa populations continuously exposed to sub-MICs (1/4) of ciprofloxacin. A rapid occurrence of ciprofloxacin-resistant mutants (MIC of ≥12 μg/ml, representing 100 times the MIC of the original population) were observed in all ciprofloxacin-exposed lineages of PAOΔmutS and PAOMY-Mgm populations after 100 and 170 generations, respectively, and in one of the PAO1 lineages after 240 generations. The genetic basis of resistance was mutations in gyrA (C248T and G259T) and gyrB (C1397A). Cross-resistance to beta-lactam antibiotics was observed in the bacterial populations that evolved during exposure to sublethal concentrations of ciprofloxacin. Our study shows that mutants with high-level ciprofloxacin resistance are selected in P. aeruginosa bacterial populations exposed to sub-MICs of ciprofloxacin. This can have implications for the long-term persistence of resistant bacteria and spread of antibiotic resistance by exposure of commensal bacterial flora to low antibiotic concentrations. PMID:23774442

  5. A Genetic Algorithm for the Generation of Packetization Masks for Robust Image Communication

    PubMed Central

    Zapata-Quiñones, Katherine; Duran-Faundez, Cristian; Gutiérrez, Gilberto; Lecuire, Vincent; Arredondo-Flores, Christopher; Jara-Lipán, Hugo

    2017-01-01

    Image interleaving has proven to be an effective solution to provide the robustness of image communication systems when resource limitations make reliable protocols unsuitable (e.g., in wireless camera sensor networks); however, the search for optimal interleaving patterns is scarcely tackled in the literature. In 2008, Rombaut et al. presented an interesting approach introducing a packetization mask generator based in Simulated Annealing (SA), including a cost function, which allows assessing the suitability of a packetization pattern, avoiding extensive simulations. In this work, we present a complementary study about the non-trivial problem of generating optimal packetization patterns. We propose a genetic algorithm, as an alternative to the cited work, adopting the mentioned cost function, then comparing it to the SA approach and a torus automorphism interleaver. In addition, we engage the validation of the cost function and provide results attempting to conclude about its implication in the quality of reconstructed images. Several scenarios based on visual sensor networks applications were tested in a computer application. Results in terms of the selected cost function and image quality metric PSNR show that our algorithm presents similar results to the other approaches. Finally, we discuss the obtained results and comment about open research challenges. PMID:28452934

  6. Translational Epidemiology in Psychiatry

    PubMed Central

    Weissman, Myrna M.; Brown, Alan S.; Talati, Ardesheer

    2012-01-01

    Translational research generally refers to the application of knowledge generated by advances in basic sciences research translated into new approaches for diagnosis, prevention, and treatment of disease. This direction is called bench-to-bedside. Psychiatry has similarly emphasized the basic sciences as the starting point of translational research. This article introduces the term translational epidemiology for psychiatry research as a bidirectional concept in which the knowledge generated from the bedside or the population can also be translated to the benches of laboratory science. Epidemiologic studies are primarily observational but can generate representative samples, novel designs, and hypotheses that can be translated into more tractable experimental approaches in the clinical and basic sciences. This bedside-to-bench concept has not been explicated in psychiatry, although there are an increasing number of examples in the research literature. This article describes selected epidemiologic designs, providing examples and opportunities for translational research from community surveys and prospective, birth cohort, and family-based designs. Rapid developments in informatics, emphases on large sample collection for genetic and biomarker studies, and interest in personalized medicine—which requires information on relative and absolute risk factors—make this topic timely. The approach described has implications for providing fresh metaphors to communicate complex issues in interdisciplinary collaborations and for training in epidemiology and other sciences in psychiatry. PMID:21646577

  7. Determining the Effect of Natural Selection on Linked Neutral Divergence across Species

    PubMed Central

    Phung, Tanya N.; Lohmueller, Kirk E.

    2016-01-01

    A major goal in evolutionary biology is to understand how natural selection has shaped patterns of genetic variation across genomes. Studies in a variety of species have shown that neutral genetic diversity (intra-species differences) has been reduced at sites linked to those under direct selection. However, the effect of linked selection on neutral sequence divergence (inter-species differences) remains ambiguous. While empirical studies have reported correlations between divergence and recombination, which is interpreted as evidence for natural selection reducing linked neutral divergence, theory argues otherwise, especially for species that have diverged long ago. Here we address these outstanding issues by examining whether natural selection can affect divergence between both closely and distantly related species. We show that neutral divergence between closely related species (e.g. human-primate) is negatively correlated with functional content and positively correlated with human recombination rate. We also find that neutral divergence between distantly related species (e.g. human-rodent) is negatively correlated with functional content and positively correlated with estimates of background selection from primates. These patterns persist after accounting for the confounding factors of hypermutable CpG sites, GC content, and biased gene conversion. Coalescent models indicate that even when the contribution of ancestral polymorphism to divergence is small, background selection in the ancestral population can still explain a large proportion of the variance in divergence across the genome, generating the observed correlations. Our findings reveal that, contrary to previous intuition, natural selection can indirectly affect linked neutral divergence between both closely and distantly related species. Though we cannot formally exclude the possibility that the direct effects of purifying selection drive some of these patterns, such a scenario would be possible only if more of the genome is under purifying selection than currently believed. Our work has implications for understanding the evolution of genomes and interpreting patterns of genetic variation. PMID:27508305

  8. Determining the Effect of Natural Selection on Linked Neutral Divergence across Species.

    PubMed

    Phung, Tanya N; Huber, Christian D; Lohmueller, Kirk E

    2016-08-01

    A major goal in evolutionary biology is to understand how natural selection has shaped patterns of genetic variation across genomes. Studies in a variety of species have shown that neutral genetic diversity (intra-species differences) has been reduced at sites linked to those under direct selection. However, the effect of linked selection on neutral sequence divergence (inter-species differences) remains ambiguous. While empirical studies have reported correlations between divergence and recombination, which is interpreted as evidence for natural selection reducing linked neutral divergence, theory argues otherwise, especially for species that have diverged long ago. Here we address these outstanding issues by examining whether natural selection can affect divergence between both closely and distantly related species. We show that neutral divergence between closely related species (e.g. human-primate) is negatively correlated with functional content and positively correlated with human recombination rate. We also find that neutral divergence between distantly related species (e.g. human-rodent) is negatively correlated with functional content and positively correlated with estimates of background selection from primates. These patterns persist after accounting for the confounding factors of hypermutable CpG sites, GC content, and biased gene conversion. Coalescent models indicate that even when the contribution of ancestral polymorphism to divergence is small, background selection in the ancestral population can still explain a large proportion of the variance in divergence across the genome, generating the observed correlations. Our findings reveal that, contrary to previous intuition, natural selection can indirectly affect linked neutral divergence between both closely and distantly related species. Though we cannot formally exclude the possibility that the direct effects of purifying selection drive some of these patterns, such a scenario would be possible only if more of the genome is under purifying selection than currently believed. Our work has implications for understanding the evolution of genomes and interpreting patterns of genetic variation.

  9. Generative model selection using a scalable and size-independent complex network classifier

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

    Motallebi, Sadegh, E-mail: motallebi@ce.sharif.edu; Aliakbary, Sadegh, E-mail: aliakbary@ce.sharif.edu; Habibi, Jafar, E-mail: jhabibi@sharif.edu

    2013-12-15

    Real networks exhibit nontrivial topological features, such as heavy-tailed degree distribution, high clustering, and small-worldness. Researchers have developed several generative models for synthesizing artificial networks that are structurally similar to real networks. An important research problem is to identify the generative model that best fits to a target network. In this paper, we investigate this problem and our goal is to select the model that is able to generate graphs similar to a given network instance. By the means of generating synthetic networks with seven outstanding generative models, we have utilized machine learning methods to develop a decision tree formore » model selection. Our proposed method, which is named “Generative Model Selection for Complex Networks,” outperforms existing methods with respect to accuracy, scalability, and size-independence.« less

  10. A perspective on medical school admission research and practice over the last 25 years.

    PubMed

    Kreiter, Clarence D; Axelson, Rick D

    2013-01-01

    Over the last 25 years a large body of research has investigated how best to select applicants to study medicine. Although these studies have inspired little actual change in admission practice, the implications of this research are substantial. Five areas of inquiry are discussed: (1) the interview and related techniques, (2) admission tests, (3) other measures of personal competencies, (4) the decision process, and (5) defining and measuring the criterion. In each of these areas we summarize consequential developments and discuss their implication for improving practice. (1) The traditional interview has been shown to lack both reliability and validity. Alternatives have been developed that display promising measurement characteristics. (2) Admission test scores have been shown to predict academic and clinical performance and are generally the most useful measures obtained about an applicant. (3) Due to the high-stakes nature of the admission decision, it is difficult to support a logical validity argument for the use of personality tests. Although standardized letters of recommendation appear to offer some promise, more research is needed. (4) The methods used to make the selection decision should be responsive to validity research on how best to utilize applicant information. (5) Few resources have been invested in obtaining valid criterion measures. Future research might profitably focus on composite score as a method for generating a measure of a physician's career success. There are a number of social and organization factors that resist evidence-based change. However, research over the last 25 years does present important findings that could be used to improve the admission process.

  11. Explaining geographic gradients in winter selection of landscapes by boreal caribou with implications under global changes in Eastern Canada.

    PubMed

    Beguin, Julien; McIntire, Eliot J B; Fortin, Daniel; Cumming, Steven G; Raulier, Frédéric; Racine, Pierre; Dussault, Claude

    2013-01-01

    Many animal species exhibit broad-scale latitudinal or longitudinal gradients in their response to biotic and abiotic components of their habitat. Although knowing the underlying mechanism of these patterns can be critical to the development of sound measures for the preservation or recovery of endangered species, few studies have yet identified which processes drive the existence of geographical gradients in habitat selection. Using extensive spatial data of broad latitudinal and longitudinal extent, we tested three hypotheses that could explain the presence of geographical gradients in landscape selection of the endangered boreal woodland caribou (Rangifer tarandus caribou) during winter in Eastern Canadian boreal forests: 1) climate-driven selection, which postulates that geographic gradients are surrogates for climatic gradients; 2) road-driven selection, which proposes that boreal caribou adjust their selection for certain habitat classes as a function of proximity to roads; and 3) an additive effect of both roads and climate. Our data strongly supported road-driven selection over climate influences. Thus, direct human alteration of landscapes drives boreal caribou distribution and should likely remain so until the climate changes sufficiently from present conditions. Boreal caribou avoided logged areas two-fold more strongly than burnt areas. Limiting the spread of road networks and accounting for the uneven impact of logging compared to wildfire should therefore be integral parts of any habitat management plan and conservation measures within the range of the endangered boreal caribou. The use of hierarchical spatial models allowed us to explore the distribution of spatially-structured errors in our models, which in turn provided valuable insights for generating alternative hypotheses about processes responsible for boreal caribou distribution.

  12. How nonuniform contact profiles of T cell receptors modulate thymic selection outcomes

    NASA Astrophysics Data System (ADS)

    Chen, Hanrong; Chakraborty, Arup K.; Kardar, Mehran

    2018-03-01

    T cell receptors (TCRs) bind foreign or self-peptides attached to major histocompatibility complex (MHC) molecules, and the strength of this interaction determines T cell activation. Optimizing the ability of T cells to recognize a diversity of foreign peptides yet be tolerant of self-peptides is crucial for the adaptive immune system to properly function. This is achieved by selection of T cells in the thymus, where immature T cells expressing unique, stochastically generated TCRs interact with a large number of self-peptide-MHC; if a TCR does not bind strongly enough to any self-peptide-MHC, or too strongly with at least one self-peptide-MHC, the T cell dies. Past theoretical work cast thymic selection as an extreme value problem and characterized the statistical enrichment or depletion of amino acids in the postselection TCR repertoire, showing how T cells are selected to be able to specifically recognize peptides derived from diverse pathogens yet have limited self-reactivity. Here, we investigate how the diversity of the postselection TCR repertoire is modified when TCRs make nonuniform contacts with peptide-MHC. Specifically, we were motivated by recent experiments showing that amino acids at certain positions of a TCR sequence have large effects on thymic selection outcomes, and crystal structure data that reveal a nonuniform contact profile between a TCR and its peptide-MHC ligand. Using a representative TCR contact profile as an illustration, we show via simulations that the statistical enrichment or depletion of amino acids now varies by position according to the contact profile, and, importantly, it depends on the implementation of nonuniform contacts during thymic selection. We explain these nontrivial results analytically. Our study has implications for understanding the selection forces that shape the functionality of the postselection TCR repertoire.

  13. Positive Selection Underlies Faster-Z Evolution of Gene Expression in Birds

    PubMed Central

    Dean, Rebecca; Harrison, Peter W.; Wright, Alison E.; Zimmer, Fabian; Mank, Judith E.

    2015-01-01

    The elevated rate of evolution for genes on sex chromosomes compared with autosomes (Fast-X or Fast-Z evolution) can result either from positive selection in the heterogametic sex or from nonadaptive consequences of reduced relative effective population size. Recent work in birds suggests that Fast-Z of coding sequence is primarily due to relaxed purifying selection resulting from reduced relative effective population size. However, gene sequence and gene expression are often subject to distinct evolutionary pressures; therefore, we tested for Fast-Z in gene expression using next-generation RNA-sequencing data from multiple avian species. Similar to studies of Fast-Z in coding sequence, we recover clear signatures of Fast-Z in gene expression; however, in contrast to coding sequence, our data indicate that Fast-Z in expression is due to positive selection acting primarily in females. In the soma, where gene expression is highly correlated between the sexes, we detected Fast-Z in both sexes, although at a higher rate in females, suggesting that many positively selected expression changes in females are also expressed in males. In the gonad, where intersexual correlations in expression are much lower, we detected Fast-Z for female gene expression, but crucially, not males. This suggests that a large amount of expression variation is sex-specific in its effects within the gonad. Taken together, our results indicate that Fast-Z evolution of gene expression is the product of positive selection acting on recessive beneficial alleles in the heterogametic sex. More broadly, our analysis suggests that the adaptive potential of Z chromosome gene expression may be much greater than that of gene sequence, results which have important implications for the role of sex chromosomes in speciation and sexual selection. PMID:26067773

  14. Medicinal Cannabis: History, Pharmacology, And Implications for the Acute Care Setting.

    PubMed

    Bridgeman, Mary Barna; Abazia, Daniel T

    2017-03-01

    The authors review the historical use of medicinal cannabis and discuss the agent's pharmacology and pharmacokinetics, select evidence on medicinal uses, and the implications of evolving regulations on the acute care hospital setting.

  15. Does recall of a past music event invoke a reminiscence bump in young adults?

    PubMed

    Schubert, Emery

    2016-08-01

    Many studies of the reminiscence bump (RB) in music invoke memories from different autobiographical times by using stimulus specific prompts (SSPs). This study investigated the utility of a non-SSP paradigm to determine whether the RB would emerge when participants were asked to recall a single memorable musical event from "a time long ago". The presence of a RB in response to music has not been obtained in such a manner for younger participants. Eighty-eight 20-22 year olds reported music episodes that peaked when their autobiographical age was 13-14 years. Self-selected stimuli included a range of musical styles, including classical and non-Western pop forms, such as J-pop and K-pop, as well as generational pop music, such as the Beatles. However, most participants reported pop/rock music that was contemporaneous with encoding age, providing support for the utility of published SSP paradigms using pop music. Implications for and limitations of SSP paradigms are discussed. Participants were also asked to relate the selected musical piece to current musical tastes. Most participants liked the music that they selected, with many continuing to like the music, but most also reported a general broadening of their taste, consistent with developmental literature on open-earedness.

  16. Species-Specific Relationships between Water Transparency and Male Coloration within and between Two Closely Related Lake Victoria Cichlid Species

    PubMed Central

    Castillo Cajas, Ruth F.; Selz, Oliver M.; Ripmeester, Erwin A. P.; Seehausen, Ole; Maan, Martine E.

    2012-01-01

    Environmental variation in signalling conditions affects animal communication traits, with possible consequences for sexual selection and reproductive isolation. Using spectrophotometry, we studied how male coloration within and between populations of two closely related Lake Victoria cichlid species (Pundamilia pundamilia and P. nyererei) covaries with water transparency. Focusing on coloration patches implicated in sexual selection, we predicted that in clear waters, with broad-spectrum light, (1) colours should become more saturated and (2) shift in hue away from the dominant ambient wavelengths, compared to more turbid waters. We found support for these predictions for the red and yellow coloration of P. nyererei but not the blue coloration of P. pundamilia. This may be explained by the species difference in depth distribution, which generates a steeper gradient in visual conditions for P. nyererei compared to P. pundamilia. Alternatively, the importance of male coloration in intraspecific sexual selection may differ between the species. We also found that anal fin spots, that is, the orange spots on male haplochromine anal fins that presumably mimic eggs, covaried with water transparency in a similar way for both species. This is in contrast to the other body regions studied and suggests that, while indeed functioning as signals, these spots may not play a role in species differentiation. PMID:22888462

  17. Mean-field and linear regime approach to magnetic hyperthermia of core-shell nanoparticles: can tiny nanostructures fight cancer?

    NASA Astrophysics Data System (ADS)

    Carrião, Marcus S.; Bakuzis, Andris F.

    2016-04-01

    The phenomenon of heat dissipation by magnetic materials interacting with an alternating magnetic field, known as magnetic hyperthermia, is an emergent and promising therapy for many diseases, mainly cancer. Here, a magnetic hyperthermia model for core-shell nanoparticles is developed. The theoretical calculation, different from previous models, highlights the importance of heterogeneity by identifying the role of surface and core spins on nanoparticle heat generation. We found that the most efficient nanoparticles should be obtained by selecting materials to reduce the surface to core damping factor ratio, increasing the interface exchange parameter and tuning the surface to core anisotropy ratio for each material combination. From our results we propose a novel heat-based hyperthermia strategy with the focus on improving the heating efficiency of small sized nanoparticles instead of larger ones. This approach might have important implications for cancer treatment and could help improving clinical efficacy.The phenomenon of heat dissipation by magnetic materials interacting with an alternating magnetic field, known as magnetic hyperthermia, is an emergent and promising therapy for many diseases, mainly cancer. Here, a magnetic hyperthermia model for core-shell nanoparticles is developed. The theoretical calculation, different from previous models, highlights the importance of heterogeneity by identifying the role of surface and core spins on nanoparticle heat generation. We found that the most efficient nanoparticles should be obtained by selecting materials to reduce the surface to core damping factor ratio, increasing the interface exchange parameter and tuning the surface to core anisotropy ratio for each material combination. From our results we propose a novel heat-based hyperthermia strategy with the focus on improving the heating efficiency of small sized nanoparticles instead of larger ones. This approach might have important implications for cancer treatment and could help improving clinical efficacy. Electronic supplementary information (ESI) available: Unit cells per region calculation; core-shell Hamiltonian; magnetisation description functions; energy argument of Brillouin function; polydisperse models; details of experimental procedure; LRT versus core-shell model; model calculation software; and shell thickness study. See DOI: 10.1039/C5NR09093H

  18. Implications of the New EEOC Guidelines.

    ERIC Educational Resources Information Center

    Dhanens, Thomas P.

    1979-01-01

    In the next few years employers will frequently be confronted with the fact that they cannot rely on undocumented, subjective selection procedures. As long as disparate impact exists in employee selection, employers will be required to validate whatever selection procedures they use. (Author/IRT)

  19. Green marketing, renewables, and free riders: increasing customer demand for a public good

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

    Wiser, R.; Pickle, S.

    1997-09-01

    Retail electricity competition will allow customers to select their own power suppliers and some customers will make purchase decisions based, in part, on their concern for the environment. Green power marketing targets these customers under the assumption that they will pay a premium for ``green`` energy products such as renewable power generation. But renewable energy is not a traditional product because it supplies public goods; for example, a customer supporting renewable energy is unable to capture the environmental benefits that their investment provides to non-participating customers. As with all public goods, there is a risk that few customers will purchasemore » ``green`` power and that many will instead ``free ride`` on others` participation. By free riding, an individual is able to enjoy the benefits of the public good while avoiding payment. This report reviews current green power marketing activities in the electric industry, introduces the extensive academic literature on public goods, free riders, and collective action problems, and explores in detail the implications of this literature for the green marketing of renewable energy. Specifically, the authors highlight the implications of the public goods literature for green power product design and marketing communications strategies. They emphasize four mechanisms that marketers can use to increase customer demand for renewable energy. Though the public goods literature can also contribute insights into the potential rationale for renewable energy policies, they leave most of these implications for future work (see Appendix A for a possible research agenda).« less

  20. Selecting Students for Training in Health Care. A Practical Guide to Improving Selection Procedures. WHO Offset Publication No. 74.

    ERIC Educational Resources Information Center

    Bennett, Mick; Wakeford, Richard

    This guide is intended to help those responsible for choosing health care trainees to develop and improve their selection procedures. Special reference is given to health workers in maternal and child health. Chapter 1 deals with health care policy implications for selection of trainees, the different functions of selection and conflicts that…

  1. Navigating the Interface Between Landscape Genetics and Landscape Genomics.

    PubMed

    Storfer, Andrew; Patton, Austin; Fraik, Alexandra K

    2018-01-01

    As next-generation sequencing data become increasingly available for non-model organisms, a shift has occurred in the focus of studies of the geographic distribution of genetic variation. Whereas landscape genetics studies primarily focus on testing the effects of landscape variables on gene flow and genetic population structure, landscape genomics studies focus on detecting candidate genes under selection that indicate possible local adaptation. Navigating the transition between landscape genomics and landscape genetics can be challenging. The number of molecular markers analyzed has shifted from what used to be a few dozen loci to thousands of loci and even full genomes. Although genome scale data can be separated into sets of neutral loci for analyses of gene flow and population structure and putative loci under selection for inference of local adaptation, there are inherent differences in the questions that are addressed in the two study frameworks. We discuss these differences and their implications for study design, marker choice and downstream analysis methods. Similar to the rapid proliferation of analysis methods in the early development of landscape genetics, new analytical methods for detection of selection in landscape genomics studies are burgeoning. We focus on genome scan methods for detection of selection, and in particular, outlier differentiation methods and genetic-environment association tests because they are the most widely used. Use of genome scan methods requires an understanding of the potential mismatches between the biology of a species and assumptions inherent in analytical methods used, which can lead to high false positive rates of detected loci under selection. Key to choosing appropriate genome scan methods is an understanding of the underlying demographic structure of study populations, and such data can be obtained using neutral loci from the generated genome-wide data or prior knowledge of a species' phylogeographic history. To this end, we summarize recent simulation studies that test the power and accuracy of genome scan methods under a variety of demographic scenarios and sampling designs. We conclude with a discussion of additional considerations for future method development, and a summary of methods that show promise for landscape genomics studies but are not yet widely used.

  2. Navigating the Interface Between Landscape Genetics and Landscape Genomics

    PubMed Central

    Storfer, Andrew; Patton, Austin; Fraik, Alexandra K.

    2018-01-01

    As next-generation sequencing data become increasingly available for non-model organisms, a shift has occurred in the focus of studies of the geographic distribution of genetic variation. Whereas landscape genetics studies primarily focus on testing the effects of landscape variables on gene flow and genetic population structure, landscape genomics studies focus on detecting candidate genes under selection that indicate possible local adaptation. Navigating the transition between landscape genomics and landscape genetics can be challenging. The number of molecular markers analyzed has shifted from what used to be a few dozen loci to thousands of loci and even full genomes. Although genome scale data can be separated into sets of neutral loci for analyses of gene flow and population structure and putative loci under selection for inference of local adaptation, there are inherent differences in the questions that are addressed in the two study frameworks. We discuss these differences and their implications for study design, marker choice and downstream analysis methods. Similar to the rapid proliferation of analysis methods in the early development of landscape genetics, new analytical methods for detection of selection in landscape genomics studies are burgeoning. We focus on genome scan methods for detection of selection, and in particular, outlier differentiation methods and genetic-environment association tests because they are the most widely used. Use of genome scan methods requires an understanding of the potential mismatches between the biology of a species and assumptions inherent in analytical methods used, which can lead to high false positive rates of detected loci under selection. Key to choosing appropriate genome scan methods is an understanding of the underlying demographic structure of study populations, and such data can be obtained using neutral loci from the generated genome-wide data or prior knowledge of a species' phylogeographic history. To this end, we summarize recent simulation studies that test the power and accuracy of genome scan methods under a variety of demographic scenarios and sampling designs. We conclude with a discussion of additional considerations for future method development, and a summary of methods that show promise for landscape genomics studies but are not yet widely used. PMID:29593776

  3. The Always-Connected Generation

    ERIC Educational Resources Information Center

    Bull, Glen

    2010-01-01

    The Pew Internet and American Life project characterizes the millennials--the first generation to come of age in the new millennium--as the first "always-connected" generation. Significant aspects of culture are changing as a result. A changing world where all students are connected all the time has substantial educational implications. Despite…

  4. Engaging a New Generation of Graduates

    ERIC Educational Resources Information Center

    Shaw, Sue; Fairhurst, David

    2008-01-01

    Purpose: The purpose of this paper is to explore the concept of generational difference and reflect on how this might impact on organisational approaches to graduate development. Design/methodology/approach: The paper explores the characteristics of Generation Y graduates and the implications of their entry into the workplace for organisations'…

  5. The Interaction between Generation Status and Sex on Drinking Motives and Behaviors

    ERIC Educational Resources Information Center

    Lewis, Todd; Wahesh, Edward

    2017-01-01

    Participants included 483 undergraduate drinkers who were assessed on drinking motives and alcohol behaviors. Results indicated differences in coping drinking motives and alcohol-related negative consequences between first-generation college students (FGCS) and continuing generation college students (CGCS) status depended on sex. Implications for…

  6. Theoretical study of the coordination behavior of formate and formamidoximate with dioxovanadium( v ) cation: implications for selectivity towards uranyl

    DOE PAGES

    Mehio, Nada; Johnson, J. Casey; Dai, Sheng; ...

    2015-10-28

    Poly(acrylamidoxime)-based fibers bearing random mixtures of carboxylate and amidoxime groups are the most widely utilized materials for extracting uranium from seawater. However, the competition between uranyl (UO 2 2+) and vanadium ions poses a significant challenge to the industrial mining of uranium from seawater using the current generation of adsorbents. To design more selective adsorbents, a detailed understanding of how major competing ions interact with carboxylate and amidoxime ligands is required. In this work, we employ density functional theory (DFT) and wave-function methods to investigate potential binding motifs of the dioxovanadium ion, VO 2 +, with water, formate, and formamidoximatemore » ligands. Employing higher level of theory calculations (CCSD(T)) resolve the existing controversy between the experimental results and previous DFT calculations for the structure of the hydrated VO 2 + ion. Consistent with the EXAFS data, CCSD(T) calculations predict higher stability of the distorted octahedral geometry of VO 2 +(H 2O) 4 compared to the five-coordinate complex with a single water molecule in the second hydration shell, while all seven tested DFT methods yield the reverse stability of the two conformations. Analysis of the relative stabilities of formate-VO 2 + complexes indicates that both monodentate and bidentate forms may coexist in thermodynamic equilibrium in solution, with the equilibrium balance leaning more towards the formation of monodentate species. Investigations of VO 2 + coordination with the formamidoximate anion has revealed the existence of seven possible binding motifs, four of which are within ~ 4.0 kcal/mol of each other. Calculations establish that the most stable binding motif entails the coordination of oxime oxygen and amide nitrogen atoms via a tautomeric rearrangement of amidoxime to imino hydroxylamine. Lastly, the difference in the most stable VO 2 + and UO 2 2+ binding conformation has important implications for the design of more selective UO 2 2+ ligands.« less

  7. Bias Reduction in Quasi-Experiments with Little Selection Theory but Many Covariates

    ERIC Educational Resources Information Center

    Steiner, Peter M.; Cook, Thomas D.; Li, Wei; Clark, M. H.

    2015-01-01

    In observational studies, selection bias will be completely removed only if the selection mechanism is ignorable, namely, all confounders of treatment selection and potential outcomes are reliably measured. Ideally, well-grounded substantive theories about the selection process and outcome-generating model are used to generate the sample of…

  8. The Fumarate Reductase of Bacteroides thetaiotaomicron, unlike That of Escherichia coli, Is Configured so that It Does Not Generate Reactive Oxygen Species

    PubMed Central

    Lu, Zheng

    2017-01-01

    ABSTRACT The impact of oxidative stress upon organismal fitness is most apparent in the phenomenon of obligate anaerobiosis. The root cause may be multifaceted, but the intracellular generation of reactive oxygen species (ROS) likely plays a key role. ROS are formed when redox enzymes accidentally transfer electrons to oxygen rather than to their physiological substrates. In this study, we confirm that the predominant intestinal anaerobe Bacteroides thetaiotaomicron generates intracellular ROS at a very high rate when it is aerated. Fumarate reductase (Frd) is a prominent enzyme in the anaerobic metabolism of many bacteria, including B. thetaiotaomicron, and prior studies of Escherichia coli Frd showed that the enzyme is unusually prone to ROS generation. Surprisingly, in this study biochemical analysis demonstrated that the B. thetaiotaomicron Frd does not react with oxygen at all: neither superoxide nor hydrogen peroxide is formed. Subunit-swapping experiments indicated that this difference does not derive from the flavoprotein subunit at which ROS normally arise. Experiments with the related enzyme succinate dehydrogenase discouraged the hypothesis that heme moieties are responsible. Thus, resistance to oxidation may reflect a shift of electron density away from the flavin moiety toward the iron-sulfur clusters. This study shows that the autoxidizability of a redox enzyme can be suppressed by subtle modifications that do not compromise its physiological function. One implication is that selective pressures might enhance the oxygen tolerance of an organism by manipulating the electronic properties of its redox enzymes so they do not generate ROS. PMID:28049145

  9. Current advances in the generation of human iPS cells: implications in cell-based regenerative medicine.

    PubMed

    Revilla, Ana; González, Clara; Iriondo, Amaia; Fernández, Bárbara; Prieto, Cristina; Marín, Carlos; Liste, Isabel

    2016-11-01

    Over the last few years, the generation of induced pluripotent stem cells (iPSCs) from human somatic cells has proved to be one of the most potentially useful discoveries in regenerative medicine. iPSCs are becoming an invaluable tool to study the pathology of different diseases and for drug screening. However, several limitations still affect the possibility of applying iPS cell-based technology in therapeutic prospects. Most strategies for iPSCs generation are based on gene delivery via retroviral or lentiviral vectors, which integrate into the host's cell genome, causing a remarkable risk of insertional mutagenesis and oncogenic transformation. To avoid such risks, significant advances have been made with non-integrative reprogramming strategies. On the other hand, although many different kinds of somatic cells have been employed to generate iPSCs, there is still no consensus about the ideal type of cell to be reprogrammed. In this review we present the recent advances in the generation of human iPSCs, discussing their advantages and limitations in terms of safety and efficiency. We also present a selection of somatic cell sources, considering their capability to be reprogrammed and tissue accessibility. From a translational medicine perspective, these two topics will provide evidence to elucidate the most suitable combination of reprogramming strategy and cell source to be applied in each human iPSC-based therapy. The wide variety of diseases this technology could treat opens a hopeful future for regenerative medicine. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  10. Activation and connectivity patterns of the presupplementary and dorsal premotor areas during free improvisation of melodies and rhythms.

    PubMed

    de Manzano, Örjan; Ullén, Fredrik

    2012-10-15

    Free, i.e. non-externally cued generation of movement sequences is fundamental to human behavior. We have earlier hypothesized that the dorsal premotor cortex (PMD), which has been consistently implicated in cognitive aspects of planning and selection of spatial motor sequences may be particularly important for the free generation of spatial movement sequences, whereas the pre-supplementary motor area (pre-SMA), which shows increased activation during perception, learning and reproduction of temporal sequences, may contribute more to the generation of temporal structures. Here we test this hypothesis using fMRI and musical improvisation in professional pianists as a model behavior. We employed a 2 × 2 factorial design with the factors Melody (Specified/Improvised) and Rhythm (Specified/Improvised). The main effect analyses partly confirmed our hypothesis: there was a main effect of Melody in the PMD; the pre-SMA was present in the main effect of Rhythm, as predicted, as well as in the main effect of Melody. A psychophysiological interaction analysis of functional connectivity demonstrated that the correlation in activity between the pre-SMA and cerebellum was higher during rhythmic improvisation than during the other conditions. In summary, there were only subtle differences in activity level between the pre-SMA and PMD during improvisation, regardless of condition. Consequently, the free generation of rhythmic and melodic structures, appears to be largely integrated processes but the functional connectivity between premotor areas and other regions may change during free generation in response to sequence-specific spatiotemporal demands. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Protocols for second-generation business satellites systems

    NASA Astrophysics Data System (ADS)

    Evans, B. G.; Coakley, F. P.; El Amin, M. H. M.

    The paper discusses the nature and mix of traffic in business satellite systems and describes the limitations on the protocol imposed by the differing impairments of speech, video, and data. A simple TDMA system protocol is presented which meets the requirements of mixed-service operation. The efficiency of the protocol together with implications for allocation, scheduling and synchronisation are discussed. Future-generation satellites will probably use on-board processing. Some initial work on protocols that make use of on-board processing and the implications for satellite and earth-station equipment are presented.

  12. What Students Want: Generation Y and the Changing Function of the Academic Library

    ERIC Educational Resources Information Center

    Gardner, Susan; Eng, Susanna

    2005-01-01

    This article presents the results of a 2003 undergraduate library user survey as a case study of Generation Y. Survey data support four main traits attributed to Generation Y, which are discussed within the context of library use and satisfaction. Implications for future directions in academic library services based on the new ways Generation Y…

  13. Effects of Problem Scope and Creativity Instructions on Idea Generation and Selection

    ERIC Educational Resources Information Center

    Rietzschel, Eric F.; Nijstad, Bernard A.; Stroebe, Wolfgang

    2014-01-01

    The basic assumption of brainstorming is that increased quantity of ideas results in increased generation as well as selection of creative ideas. Although previous research suggests that idea quantity correlates strongly with the number of good ideas generated, quantity has been found to be unrelated to the quality of selected ideas. This article…

  14. Relation between social information processing and intimate partner violence in dating couples.

    PubMed

    Setchell, Sarah; Fritz, Patti Timmons; Glasgow, Jillian

    2017-07-01

    We used couple-level data to predict physical acts of intimate partner violence (IPV) from self-reported negative emotions and social information-processing (SIP) abilities among 100 dating couples (n = 200; mean age = 21.45 years). Participants read a series of hypothetical conflict situation vignettes and responded to questionnaires to assess negative emotions and various facets of SIP including attributions for partner behavior, generation of response alternatives, and response selection. We conducted a series of negative binomial mixed-model regressions based on the actor-partner interdependence model (APIM; Kenny, Kashy, & Cook, 2006, Dyadic data analysis. New York, NY: Guilford Press). There were significant results for the response generation and negative emotion models. Participants who generated fewer coping response alternatives were at greater risk of victimization (actor effect). Women were at greater risk of victimization if they had partners who generated fewer coping response alternatives (sex by partner interaction effect). Generation of less competent coping response alternatives predicted greater risk of perpetration among men, whereas generation of more competent coping response alternatives predicted greater risk of victimization among women (sex by actor interaction effects). Two significant actor by partner interaction effects were found for the negative emotion models. Participants who reported discrepant levels of negative emotions from their partners were at greatest risk of perpetration. Participants who reported high levels of negative emotions were at greatest risk of victimization if they had partners who reported low levels of negative emotions. This research has implications for researchers and clinicians interested in addressing the problem of IPV. Aggr. Behav. 43:329-341, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  15. Fluorescent probes for real-time measurement of nitric oxide in living cells.

    PubMed

    Li, Huili; Wan, Ajun

    2015-11-07

    Nitric oxide (NO) is an important signaling molecule in biology. Both NO excess and insufficiency have been implicated in numerous physiological and pathological conditions. In order to study the diverse biological roles of NO in cells and tissues, many techniques have been developed for assaying NO. Recently, new generations of fluorescent probes have become indispensible tools for the study of NO biology because of their sensitivity, selectivity, spatiotemporal resolution, and experimental feasibility. Rational application of these probes in the study requires the understanding of the molecular mechanism that the probes are involved in. In this review, we will present an arsenal of fluorescent probes used to detect NO in living cells and animal tissues. We will also discuss the molecular mechanisms, actualities and prospects of fluorescent probes in detecting NO in cell biology.

  16. The protein cofactor allows the sequence of an RNase P ribozyme to diversify by maintaining the catalytically active structure of the enzyme.

    PubMed Central

    Kim, J J; Kilani, A F; Zhan, X; Altman, S; Liu, F

    1997-01-01

    To study the effect proteins have on the catalysis and evolution of RNA enzymes, we simulated evolution of RNase P catalytic M1 RNA in vitro, in the presence and absence of its C5 protein cofactor. In the presence of C5, functional M1 sequence variants (not catalytically active in the absence of C5) were selected in addition to those identical to M1. C5 maintains the catalytically active structure of the variants and allows for an enhanced spectrum of M1 molecules to function in the context of a ribonucleoprotein (RNP) complex. The generation of an RNP enzyme, requiring both RNA and protein components, from a catalytically active RNA molecule has implications for how modern RNP complexes evolved from ancestral RNAs. PMID:9174096

  17. Science Teachers' Thinking About the Nature of Science: A New Methodological Approach to Its Assessment

    NASA Astrophysics Data System (ADS)

    Vázquez-Alonso, Ángel; García-Carmona, Antonio; Manassero-Mas, María Antonia; Bennàssar-Roig, Antoni

    2013-04-01

    This paper describes Spanish science teachers' thinking about issues concerning the nature of science (NOS) and the relationships connecting science, technology, and society (STS). The sample consisted of 774 in-service and pre-service teachers. The participants responded to a selection of items from the Questionnaire of Opinions on Science, Technology & Society in a multiple response model. These data were processed to generate the invariant indices that are used as the bases for subsequent quantitative and qualitative analyses. The overall results reflect moderately informed conceptions, and a detailed analysis by items, categories, and positions reveals a range of positive and negative conceptions about the topics of NOS dealt with in the questionnaire items. The implications of the findings for teaching and teacher training on the themes of NOS are discussed.

  18. The financial implications of employer-sponsored health insurance.

    PubMed

    Natvig, Deborah; Tolbert, Sam

    2005-01-01

    The purpose of this study was to analyze utilization and costs of employer-sponsored health insurance in select businesses in a rural community in South Carolina. The study was conducted under the auspices of the HR Roundtable of the local Chamber of Commerce, composed of human resources directors from the larger area businesses. Twenty one companies were invited to participate and eight submitted information that was sufficiently complete to analyze. The participating companies employed 6,265 people, of which 5,712 were insured. The data represents a total of 13,057 covered lives. Although the findings cannot be generalized to a broader population, the descriptive data was sufficient to generate a discussion about health care issues for this community and for the group to make preliminary recommendations for collaborative work that may affect the costs of health care coverage for this community.

  19. From experimental imaging techniques to virtual embryology.

    PubMed

    Weninger, Wolfgang J; Tassy, Olivier; Darras, Sébastien; Geyer, Stefan H; Thieffry, Denis

    2004-01-01

    Modern embryology increasingly relies on descriptive and functional three dimensional (3D) and four dimensional (4D) analysis of physically, optically, or virtually sectioned specimens. To cope with the technical requirements, new methods for high detailed in vivo imaging, as well as the generation of high resolution digital volume data sets for the accurate visualisation of transgene activity and gene product presence, in the context of embryo morphology, were recently developed and are under construction. These methods profoundly change the scientific applicability, appearance and style of modern embryo representations. In this paper, we present an overview of the emerging techniques to create, visualise and administrate embryo representations (databases, digital data sets, 3-4D embryo reconstructions, models, etc.), and discuss the implications of these new methods on the work of modern embryologists, including, research, teaching, the selection of specific model organisms, and potential collaborators.

  20. Big Bang Tumor Growth and Clonal Evolution.

    PubMed

    Sun, Ruping; Hu, Zheng; Curtis, Christina

    2018-05-01

    The advent and application of next-generation sequencing (NGS) technologies to tumor genomes has reinvigorated efforts to understand clonal evolution. Although tumor progression has traditionally been viewed as a gradual stepwise process, recent studies suggest that evolutionary rates in tumors can be variable with periods of punctuated mutational bursts and relative stasis. For example, Big Bang dynamics have been reported, wherein after transformation, growth occurs in the absence of stringent selection, consistent with effectively neutral evolution. Although first noted in colorectal tumors, effective neutrality may be relatively common. Additionally, punctuated evolution resulting from mutational bursts and cataclysmic genomic alterations have been described. In this review, we contrast these findings with the conventional gradualist view of clonal evolution and describe potential clinical and therapeutic implications of different evolutionary modes and tempos. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

  1. Managing ecotourism visitation in protected areas

    USGS Publications Warehouse

    Marion, J.L.; Farrell, T.A.; Lindberg, Kreg; Wood, Megan Epler; Engeldrum, David

    1998-01-01

    Ecotourism management seeks to integrate and balance several potentially conflicting objectives: protection of natural and cultural resources, provision of recreation opportunities and generation of economic benefits. In the absence of effective planning and management, ecotourism can lead to significant negative impacts on vegetation, soil, water, wildlife, historic resources, cultures, and visitor experiences. This chapter reviews visitor-related natural resource and experience impacts associated with ecotourism within protected areas. The influence of factors that control the nature and extent of impacts are also reviewed, including type and amount of use, the variable resistance and resilience of environmental attributes such as vegetation and soil types, and the role of management in shaping visitation, resources and facilities to support visitation while minimizing associated impacts. Implications for managing the effects of protected area visitation are highlighted, including carrying capacity decision frameworks and selecting management strategies and tactics.

  2. Degeneracy allows for both apparent homogeneity and diversification in populations.

    PubMed

    Whitacre, James M; Atamas, Sergei P

    2012-10-01

    Trait diversity - the substrate for natural selection - is necessary for adaptation through selection, particularly in populations faced with environmental changes that diminish population fitness. In habitats that remain unchanged for many generations, stabilizing selection maximizes exploitation of resources by reducing trait diversity to a narrow optimal range. One might expect that such ostensibly homogeneous populations would have a reduced potential for heritable adaptive responses when faced with fitness-reducing environmental changes. However, field studies have documented populations that, even after long periods of evolutionary stasis, can still rapidly evolve in response to changed environmental conditions. We argue that degeneracy, the ability of diverse population elements to function similarly, can satisfy both the current need to maximize fitness and the future need for diversity. Degenerate ensembles appear functionally redundant in certain environmental contexts and functionally diverse in others. We propose that genetic variation not contributing to the observed range of phenotypes in a current population, also known as cryptic genetic variation (CGV), is a specific case of degeneracy. We argue that CGV, which gradually accumulates in static populations in stable environments, reveals hidden trait differences when environments change. By allowing CGV accumulation, static populations prepare themselves for future rapid adaptations to environmental novelty. A greater appreciation of degeneracy's role in resolving the inherent tension between current stabilizing selection and future directional selection has implications in conservation biology and may be applied in social and technological systems to maximize current performance while strengthening the potential for future changes. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  3. Selection and life history traits of tebufenozide-resistant sugarcane borer (Lepidoptera: Crambidae).

    PubMed

    Akbar, W; Ottea, J A; Beuzelin, J M; Reagan, T E; Huang, F

    2008-12-01

    Varying susceptibility to tebufenozide was recorded in the sugarcane borer, Diatraea saccharalis (F.) (Lepidoptera: Crambidae), collected from Louisiana sugarcane locations with different selection pressures. Results from diet incorporation bioassays with tebufenozide indicated significant increases in LC50 (3.78-fold) and LC90 (7-fold) values for a colony from Duson (DU), an area with higher selection pressure, compared with a colony from Alexandria (ALEX), an area with no selection pressure. Differences were not detected in LC50 values among colonies from areas where use of tebufenozide was discontinued or rotated with other chemistries. Selections with tebufenozide of DU larvae over 12 generations resulted in a highly resistant colony (DU-R) with 27.1- and 83.3-fold increases in LC50 and LC90 values, respectively. Comparison of pupal weight, days to pupation, and emergence after exposure to an equitoxic (LC20) concentration of tebufenozide revealed a decrease in pupal weight (34 and 33% for males and females, respectively), and an increase in days to pupation (47 and 40% for males and females, respectively), and emergence (43 and 33% for males and females, respectively) for the DU-R colony compared with the parent DU colony. Fecundity of DU-R females decreased to 72 eggs per female compared with 180 (DU) and 261 (ALEX). Egg viability of the ALEX and DU colonies was 61 and 56%, respectively, whereas only 27% of eggs laid by females from the DU-R colony hatched. These results are discussed in terms of their practical implications for control of D. saccharalis in Louisiana sugarcane.

  4. Stabilizing selection on sperm number revealed by artificial selection and experimental evolution.

    PubMed

    Cattelan, Silvia; Di Nisio, Andrea; Pilastro, Andrea

    2018-03-01

    Sperm competition is taxonomically widespread in animals and is usually associated with large sperm production, being the number of sperm in the competing pool the prime predictor of fertilization success. Despite the strong postcopulatory selection acting directionally on sperm production, its genetic variance is often very high. This can be explained by trade-offs between sperm production and traits associated with mate acquisition or survival, that may contribute to generate an overall stabilizing selection. To investigate this hypothesis, we first artificially selected male guppies (Poecilia reticulata) for high and low sperm production for three generations, while simultaneously removing sexual selection. Then, we interrupted artificial selection and restored sexual selection. Sperm production responded to divergent selection in one generation, and when we restored sexual selection, both high and low lines converged back to the mean sperm production of the original population within two generations, indicating that sperm number is subject to strong stabilizing total sexual selection (i.e., selection acting simultaneously on all traits associated with reproductive success). We discuss the possible mechanisms responsible for the maintenance of high genetic variability in sperm production despite strong selection acting on it. © 2018 The Author(s). Evolution © 2018 The Society for the Study of Evolution.

  5. Sexually antagonistic selection on genetic variation underlying both male and female same-sex sexual behavior.

    PubMed

    Berger, David; You, Tao; Minano, Maravillas R; Grieshop, Karl; Lind, Martin I; Arnqvist, Göran; Maklakov, Alexei A

    2016-05-13

    Intralocus sexual conflict, arising from selection for different alleles at the same locus in males and females, imposes a constraint on sex-specific adaptation. Intralocus sexual conflict can be alleviated by the evolution of sex-limited genetic architectures and phenotypic expression, but pleiotropic constraints may hinder this process. Here, we explored putative intralocus sexual conflict and genetic (co)variance in a poorly understood behavior with near male-limited expression. Same-sex sexual behaviors (SSBs) generally do not conform to classic evolutionary models of adaptation but are common in male animals and have been hypothesized to result from perception errors and selection for high male mating rates. However, perspectives incorporating sex-specific selection on genes shared by males and females to explain the expression and evolution of SSBs have largely been neglected. We performed two parallel sex-limited artificial selection experiments on SSB in male and female seed beetles, followed by sex-specific assays of locomotor activity and male sex recognition (two traits hypothesized to be functionally related to SSB) and adult reproductive success (allowing us to assess fitness consequences of genetic variance in SSB and its correlated components). Our experiments reveal both shared and sex-limited genetic variance for SSB. Strikingly, genetically correlated responses in locomotor activity and male sex-recognition were associated with sexually antagonistic fitness effects, but these effects differed qualitatively between male and female selection lines, implicating intralocus sexual conflict at both male- and female-specific genetic components underlying SSB. Our study provides experimental support for the hypothesis that widespread pleiotropy generates pervasive intralocus sexual conflict governing the expression of SSBs, suggesting that SSB in one sex can occur due to the expression of genes that carry benefits in the other sex.

  6. Crucial nesting habitat for gunnison sage-grouse: A spatially explicit hierarchical approach

    USGS Publications Warehouse

    Aldridge, Cameron L.; Saher, D.J.; Childers, T.M.; Stahlnecker, K.E.; Bowen, Z.H.

    2012-01-01

    Gunnison sage-grouse (Centrocercus minimus) is a species of special concern and is currently considered a candidate species under Endangered Species Act. Careful management is therefore required to ensure that suitable habitat is maintained, particularly because much of the species' current distribution is faced with exurban development pressures. We assessed hierarchical nest site selection patterns of Gunnison sage-grouse inhabiting the western portion of the Gunnison Basin, Colorado, USA, at multiple spatial scales, using logistic regression-based resource selection functions. Models were selected using Akaike Information Criterion corrected for small sample sizes (AIC c) and predictive surfaces were generated using model averaged relative probabilities. Landscape-scale factors that had the most influence on nest site selection included the proportion of sagebrush cover >5%, mean productivity, and density of 2 wheel-drive roads. The landscape-scale predictive surface captured 97% of known Gunnison sage-grouse nests within the top 5 of 10 prediction bins, implicating 57% of the basin as crucial nesting habitat. Crucial habitat identified by the landscape model was used to define the extent for patch-scale modeling efforts. Patch-scale variables that had the greatest influence on nest site selection were the proportion of big sagebrush cover >10%, distance to residential development, distance to high volume paved roads, and mean productivity. This model accurately predicted independent nest locations. The unique hierarchical structure of our models more accurately captures the nested nature of habitat selection, and allowed for increased discrimination within larger landscapes of suitable habitat. We extrapolated the landscape-scale model to the entire Gunnison Basin because of conservation concerns for this species. We believe this predictive surface is a valuable tool which can be incorporated into land use and conservation planning as well the assessment of future land-use scenarios. ?? 2011 The Wildlife Society.

  7. Selection Signature Analysis Implicates the PC1/PCSK1 Region for Chicken Abdominal Fat Content

    PubMed Central

    Wang, Zhipeng; Zhang, Yuandan; Wang, Shouzhi; Wang, Ning; Ma, Li; Leng, Li; Wang, Shengwen; Wang, Qigui; Wang, Yuxiang; Tang, Zhiquan; Li, Ning; Da, Yang; Li, Hui

    2012-01-01

    We conducted a selection signature analysis using the chicken 60k SNP chip in two chicken lines that had been divergently selected for abdominal fat content (AFC) for 11 generations. The selection signature analysis used multiple signals of selection, including long-range allele frequency differences between the lean and fat lines, long-range heterozygosity changes, linkage disequilibrium, haplotype frequencies, and extended haplotype homozygosity. Multiple signals of selection identified ten signatures on chromosomes 1, 2, 4, 5, 11, 15, 20, 26 and Z. The 0.73 Mb PC1/PCSK1 region of the Z chromosome at 55.43-56.16 Mb was the most heavily selected region. This region had 26 SNP markers and seven genes, Mar-03, SLC12A2, FBN2, ERAP1, CAST, PC1/PCSK1 and ELL2, where PC1/PCSK1 are the chicken/human names for the same gene. The lean and fat lines had two main haplotypes with completely opposite SNP alleles for the 26 SNP markers and were virtually line-specific, and had a recombinant haplotype with nearly equal frequency (0.193 and 0.196) in both lines. Other haplotypes in this region had negligible frequencies. Nine other regions with selection signatures were PAH-IGF1, TRPC4, GJD4-CCNY, NDST4, NOVA1, GALNT9, the ESRP2-GALR1 region with five genes, the SYCP2-CADH4 with six genes, and the TULP1-KIF21B with 14 genes. Genome-wide association analysis showed that nearly all regions with evidence of selection signature had SNP effects with genome-wide significance (P<10–6) on abdominal fat weight and percentage. The results of this study provide specific gene targets for the control of chicken AFC and a potential model of AFC in human obesity. PMID:22792402

  8. Selection signature analysis implicates the PC1/PCSK1 region for chicken abdominal fat content.

    PubMed

    Zhang, Hui; Hu, Xiaoxiang; Wang, Zhipeng; Zhang, Yuandan; Wang, Shouzhi; Wang, Ning; Ma, Li; Leng, Li; Wang, Shengwen; Wang, Qigui; Wang, Yuxiang; Tang, Zhiquan; Li, Ning; Da, Yang; Li, Hui

    2012-01-01

    We conducted a selection signature analysis using the chicken 60k SNP chip in two chicken lines that had been divergently selected for abdominal fat content (AFC) for 11 generations. The selection signature analysis used multiple signals of selection, including long-range allele frequency differences between the lean and fat lines, long-range heterozygosity changes, linkage disequilibrium, haplotype frequencies, and extended haplotype homozygosity. Multiple signals of selection identified ten signatures on chromosomes 1, 2, 4, 5, 11, 15, 20, 26 and Z. The 0.73 Mb PC1/PCSK1 region of the Z chromosome at 55.43-56.16 Mb was the most heavily selected region. This region had 26 SNP markers and seven genes, Mar-03, SLC12A2, FBN2, ERAP1, CAST, PC1/PCSK1 and ELL2, where PC1/PCSK1 are the chicken/human names for the same gene. The lean and fat lines had two main haplotypes with completely opposite SNP alleles for the 26 SNP markers and were virtually line-specific, and had a recombinant haplotype with nearly equal frequency (0.193 and 0.196) in both lines. Other haplotypes in this region had negligible frequencies. Nine other regions with selection signatures were PAH-IGF1, TRPC4, GJD4-CCNY, NDST4, NOVA1, GALNT9, the ESRP2-GALR1 region with five genes, the SYCP2-CADH4 with six genes, and the TULP1-KIF21B with 14 genes. Genome-wide association analysis showed that nearly all regions with evidence of selection signature had SNP effects with genome-wide significance (P<10(-6)) on abdominal fat weight and percentage. The results of this study provide specific gene targets for the control of chicken AFC and a potential model of AFC in human obesity.

  9. Ceramide Is Metabolized to Acylceramide and Stored in Lipid Droplets.

    PubMed

    Senkal, Can E; Salama, Mohamed F; Snider, Ashley J; Allopenna, Janet J; Rana, Nadia A; Koller, Antonius; Hannun, Yusuf A; Obeid, Lina M

    2017-03-07

    In an approach aimed at defining interacting partners of ceramide synthases (CerSs), we found that fatty acyl-CoA synthase ACSL5 interacts with all CerSs. We demonstrate that ACSL5-generated FA-CoA was utilized with de novo ceramide for the generation of acylceramides, poorly studied ceramide metabolites. Functionally, inhibition of ceramide channeling to acylceramide enhanced accumulation of de novo ceramide and resulted in augmentation of ceramide-mediated apoptosis. Mechanistically, we show that acylceramide generation is catalyzed by diacylglycerol acyltransferase 2 (DGAT2) on lipid droplets. In summary, this study identifies a metabolic pathway of acylceramide generation and its sequestration in LDs in cells and in livers of mice on a high-fat diet. The study also implicates this pathway in ceramide-mediated apoptosis, and has implications in co-regulation of triglyceride and sphingolipid metabolisms. Published by Elsevier Inc.

  10. Educating a new generation: teaching baby boomer faculty about millennial students.

    PubMed

    Mangold, Kara

    2007-01-01

    This review examines the impact of generational influences on the faculty-student relationship. Specifically, the baby boomer faculty-millennial learner dyad is explored, as these two generations are most representative of the faculty-student demographic. Teaching and learning preferences are emphasized, and implications and recommendations for nursing faculty are presented.

  11. Supporting and Preparing Future First-Generation College Students in the High School Environment: Implications for School Counselors

    ERIC Educational Resources Information Center

    Bryant, Jill K.; Nicolas, Joanna

    2011-01-01

    This study surveyed college freshmen from two different institutions in order to examine differences between First-Generation College Students and Continuing-Generation College Students. Differences between groups emerged for high school academic preparation, college exploration behaviors, college application behaviors, and college decision-making…

  12. Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations

    PubMed Central

    Telwatte, Sushama; Hearps, Anna C.; Johnson, Adam; Latham, Catherine F.; Moore, Katie; Agius, Paul; Tachedjian, Mary; Sonza, Secondo; Sluis-Cremer, Nicolas; Harrigan, P. Richard; Tachedjian, Gilda

    2015-01-01

    Resistance to combined antiretroviral therapy (cART) in HIV-1-infected individuals is typically due to nonsynonymous mutations that change the protein sequence; however, the selection of synonymous or ‘silent’ mutations in the HIV-1 genome with cART has been reported. These silent K65K and K66K mutations in the HIV-1 reverse transcriptase (RT) occur in over 35% of drug-experienced individuals and are highly associated with the thymidine analog mutations D67N and K70R, which confer decreased susceptibility to most nucleoside and nucleotide RT inhibitors. However, the basis for selection of these silent mutations under selective drug pressure is unknown. Using Illumina next-generation sequencing, we demonstrate that the D67N/K70R substitutions in HIV-1 RT increase indel frequency by 100-fold at RT codons 65–67, consequently impairing viral fitness. Introduction of either K65K or K66K into HIV-1 containing D67N/K70R reversed the error-prone DNA synthesis at codons 65–67 in RT and improved viral replication fitness, but did not impact RT inhibitor drug susceptibility. These data provide new mechanistic insights into the role of silent mutations selected during antiretroviral therapy and have broader implications for the relevance of silent mutations in the evolution and fitness of RNA viruses. PMID:25765644

  13. The neural dynamics of competition resolution for language production in the prefrontal cortex.

    PubMed

    Bourguignon, Nicolas J; Ohashi, Hiroki; Nguyen, Don; Gracco, Vincent L

    2018-03-01

    Previous research suggests a pivotal role of the prefrontal cortex (PFC) in word selection during tasks of confrontation naming (CN) and verb generation (VG), both of which feature varying degrees of competition between candidate responses. However, discrepancies in prefrontal activity have also been reported between the two tasks, in particular more widespread and intense activation in VG extending into (left) ventrolateral PFC, the functional significance of which remains unclear. We propose that these variations reflect differences in competition resolution processes tied to distinct underlying lexico-semantic operations: Although CN involves selecting lexical entries out of limited sets of alternatives, VG requires exploration of possible semantic relations not readily evident from the object itself, requiring prefrontal areas previously shown to be recruited in top-down retrieval of information from lexico-semantic memory. We tested this hypothesis through combined independent component analysis of functional imaging data and information-theoretic measurements of variations in selection competition associated with participants' performance in overt CN and VG tasks. Selection competition during CN engaged the anterior insula and surrounding opercular tissue, while competition during VG recruited additional activity of left ventrolateral PFC. These patterns remained after controlling for participants' speech onset latencies indicative of possible task differences in mental effort. These findings have implications for understanding the neural-computational dynamics of cognitive control in language production and how it relates to the functional architecture of adaptive behavior. © 2017 Wiley Periodicals, Inc.

  14. Natural Selection as an Emergent Process: Instructional Implications

    ERIC Educational Resources Information Center

    Cooper, Robert A.

    2017-01-01

    Student reasoning about cases of natural selection is often plagued by errors that stem from miscategorising selection as a direct, causal process, misunderstanding the role of randomness, and from the intuitive ideas of intentionality, teleology and essentialism. The common thread throughout many of these reasoning errors is a failure to apply…

  15. Renewable Electricity Futures: Exploration of a U.S. Grid with 80% Renewable Electricity

    NASA Astrophysics Data System (ADS)

    Mai, Trieu

    2013-04-01

    Renewable Electricity Futures is an initial investigation of the extent to which renewable energy supply can meet the electricity demands of the contiguous United States over the next several decades. This study explores the implications and challenges of very high renewable electricity generation levels: from 30% up to 90% (focusing on 80%) of all U.S. electricity generation from renewable technologies in 2050. At such high levels of renewable electricity penetration, the unique characteristics of some renewable resources, specifically geographical distribution and variability and un-certainty in output, pose challenges to the operability of the nation's electric system. The study focuses on key technical implications of this environment from a national perspective, exploring whether the U.S. power system can supply electricity to meet customer demand on an hourly basis with high levels of renewable electricity, including variable wind and solar generation. The study also identifies some of the potential economic, environmental, and social implications of deploying and integrating high levels of renewable electricity in the U.S. The full report and associated supporting information is available at: http://www.nrel.gov/analysis/refutures/.

  16. Contrasting burnout, turnover intention, control, value congruence and knowledge sharing between Baby Boomers and Generation X.

    PubMed

    Leiter, Michael P; Jackson, Nicole J; Shaughnessy, Krystelle

    2009-01-01

    This paper examines the contrasting role of work values for nurses from two generations: Baby Boomers and Generation X. Differences among nurses regarding core values pertaining to their work has a potential to influence the quality of their work life. These differences may have implications for their vulnerability to job burnout. The analysis is based upon questionnaire surveys of nurses representing Generation X (n = 255) and Baby Boomers (n = 193) that contrasted their responses on job burnout, areas of work life, knowledge transfer and intention to quit. The analysis identified a greater person/organization value mismatch for Generation X nurses than for Baby Boomer nurses. Their greater value mismatch was associated with a greater susceptibility to burnout and a stronger intention to quit for Generation X nurses. The article notes the influence of Baby Boomer nurses in the structure of work and the application of new knowledge in health care work settings. Implications for recruitment and retention are discussed with a focus on knowledge transfer activities associated with distinct learning styles. Understanding value differences between generations will help nursing managers to develop more responsive work settings for nurses of all ages.

  17. Too Anxious to Speak? The Implications of Current Research into Selective Mutism for Educational Psychology Practice

    ERIC Educational Resources Information Center

    Cleave, Hayley

    2009-01-01

    Selective Mutism is a low incidence disorder but has considerable impact on the school system when it occurs. Over the last decade several research articles have been published which have challenged the understanding of the aetiology of Selective Mutism. Current perceptions about the aetiology of Selective Mutism are considered in order to inform…

  18. Interest in Low-Threshold Employment among People who Inject Illicit Drugs: Implications for Street Disorder

    PubMed Central

    DeBeck, Kora; Wood, Evan; Qi, Jiezhi; Fu, Eric; McArthur, Doug; Montaner, Julio; Kerr, Thomas

    2011-01-01

    Background Income generation opportunities available to people who use illicit drugs have been associated with street disorder. Among a cohort of injection drug users (IDU) we sought to examine street-based income generation practices and willingness to forgo these sources of income if other low-threshold work opportunities were made available. Methods Data were derived from a prospective community recruited cohort of IDU. We assessed the prevalence of engaging in disorderly street-based income generation activities, including sex work, drug dealing, panhandling, and recycling/salvaging/vending. Using multivariate logistic regressions based on Akaike information criterion and the best subset selection procedure, we identified factors associated with disorderly income generation activities, and assessed willingness to forgo these sources of income during the period of November 2008 to July 2009. Results Among our sample of 874 IDU, 418 (48%) reported engaging in a disorderly income generation activity in the previous six months. In multivariate analyses, engaging in disorderly income generation activities was independently associated with high intensity stimulant use, as well as binge drug use, having encounters with police, being a victim of violence, sharing used syringes, and injecting in public areas. Among those engaged in disorderly income generation, 198 (47%) reported a willingness to forgo these income sources if given opportunities for low-threshold employment, with sex workers being most willing to engage in alternative employment. Conclusion Engagement in disorderly street-based income generation activities was associated with high intensity stimulant drug use and various markers of risk. We found that a high proportion of illicit drug users were willing to cease engagement in these activities if they had options for causal low-threshold employment. These findings indicate that there is a high demand for low-threshold employment that may offer important opportunities to reduce drug-related street disorder and associated harms. PMID:21684142

  19. Interest in low-threshold employment among people who inject illicit drugs: implications for street disorder.

    PubMed

    Debeck, Kora; Wood, Evan; Qi, Jiezhi; Fu, Eric; McArthur, Doug; Montaner, Julio; Kerr, Thomas

    2011-09-01

    Income generation opportunities available to people who use illicit drugs have been associated with street disorder. Among a cohort of injection drug users (IDU) we sought to examine street-based income generation practices and willingness to forgo these sources of income if other low-threshold work opportunities were made available. Data were derived from a prospective community recruited cohort of IDU. We assessed the prevalence of engaging in disorderly street-based income generation activities, including sex work, drug dealing, panhandling, and recycling/salvaging/vending. Using multivariate logistic regressions based on Akaike information criterion and the best subset selection procedure, we identified factors associated with disorderly income generation activities, and assessed willingness to forgo these sources of income during the period of November 2008 to July 2009. Among our sample of 874 IDU, 418 (48%) reported engaging in a disorderly income generation activity in the previous six months. In multivariate analyses, engaging in disorderly income generation activities was independently associated with high intensity stimulant use, as well as binge drug use, having encounters with police, being a victim of violence, sharing used syringes, and injecting in public areas. Among those engaged in disorderly income generation, 198 (47%) reported a willingness to forgo these income sources if given opportunities for low-threshold employment, with sex workers being most willing to engage in alternative employment. Engagement in disorderly street-based income generation activities was associated with high intensity stimulant drug use and various markers of risk. We found that a high proportion of illicit drug users were willing to cease engagement in these activities if they had options for causal low-threshold employment. These findings indicate that there is a high demand for low-threshold employment that may offer important opportunities to reduce drug-related street disorder and associated harms. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. Branched glycerol dialkyl glycerol tetraethers in Arctic lake sediments: Sources and implications for paleothermometry at high latitudes

    NASA Astrophysics Data System (ADS)

    Peterse, Francien; Vonk, Jorien E.; Holmes, R. Max; Giosan, Liviu; Zimov, Nikita; Eglinton, Timothy I.

    2014-08-01

    Branched glycerol dialkyl glycerol tetraethers (brGDGTs) are analyzed in different lakes of the Mackenzie (Canadian Arctic) and Kolyma (Siberian Arctic) River basins to evaluate their sources and the implications for brGDGT-based paleothermometry in high-latitude lakes. The comparison of brGDGT distributions and concentrations in the lakes with those in river suspended particulate matter, riverbank sediments, and permafrost material indicates that brGDGTs in Arctic lake sediments have mixed sources. In contrast to global observations, distributional offsets between brGDGTs in Arctic lakes and elsewhere in the catchment are minor, likely due to the extreme seasonality and short window of biological production at high latitudes. Consequently, both soil- and lake-calibrated brGDGT-based temperature proxies return sensible temperature estimates, even though the mean air temperature (MAT) in the Arctic is below the calibration range. The original soil-calibrated MBT-CBT (methylation of branched tetraethers-cyclisation of branched tetraethers) proxy generates MATs similar to those in the studied river basins, whereas using the recently revised MBT'-CBT calibration overestimates MAT. The application of the two global lake calibrations, generating summer air temperatures (SAT) and MAT, respectively, illustrates the influence of seasonality on the production of brGDGTs in lakes, as the latter overestimates actual MAT, whereas the SAT-based lake calibration accounts for this influence and consequently returns more accurate temperatures. Our results in principle support the application of brGDGT-based temperature proxies in high-latitude lakes in order to obtain long-term paleotemperature records for the Arctic, although the calibration and associated transfer function have to be selected with care.

  1. Digital Natives Come to Preschool: Implications for Early Childhood Practice

    ERIC Educational Resources Information Center

    Zevenbergen, Robyn

    2007-01-01

    This article explores the implications of young learners' dispositions towards the use of digital technologies in contemporary early childhood settings. It is proposed that young learners have grown up in very different social conditions from previous generations, mainly through the saturation of digital technologies, in particular computers. This…

  2. The Effects of Toxic Stress during Pregnancy. Science Briefs

    ERIC Educational Resources Information Center

    National Scientific Council on the Developing Child, 2006

    2006-01-01

    "Science Briefs" summarize the findings and implications of a recent study in basic science or clinical research. This Brief summarizes the findings and implications of "Exposure to Repetitive versus Varied Stress during Prenatal Development Generates Two Distinct Enxiogenic and Veuroendocrine Profiles in Adulthood" (H. N. Richardson; E. P.…

  3. A next-generation marker genotyping platform (AmpSeq) in heterozygous crops: A case study for marker assisted selection in grapevine

    USDA-ARS?s Scientific Manuscript database

    Marker assisted selection (MAS) has become widely used in perennial crop breeding programs to accelerate and enhance cultivar development via selection during the juvenile phase and parental selection prior to crossing. Next generation sequencing (NGS) has been widely used for whole genome molecular...

  4. A next-generation marker genotyping platform (AmpSeq) in heterozygous crops: a case study for marker assisted selection in grapevine

    USDA-ARS?s Scientific Manuscript database

    Marker assisted selection (MAS) is often employed in crop breeding programs to accelerate and enhance cultivar development, via selection during the juvenile phase and parental selection prior to crossing. Next generation sequencing (NGS) and its derivative technologies have been used for genome-wid...

  5. Large Variation in the Ratio of Mitochondrial to Nuclear Mutation Rate across Animals: Implications for Genetic Diversity and the Use of Mitochondrial DNA as a Molecular Marker.

    PubMed

    Allio, Remi; Donega, Stefano; Galtier, Nicolas; Nabholz, Benoit

    2017-11-01

    It is commonly assumed that mitochondrial DNA (mtDNA) evolves at a faster rate than nuclear DNA (nuDNA) in animals. This has contributed to the popularity of mtDNA as a molecular marker in evolutionary studies. Analyzing 121 multilocus data sets and four phylogenomic data sets encompassing 4,676 species of animals, we demonstrate that the ratio of mitochondrial over nuclear mutation rate is highly variable among animal taxa. In nonvertebrates, such as insects and arachnids, the ratio of mtDNA over nuDNA mutation rate varies between 2 and 6, whereas it is above 20, on average, in vertebrates such as scaled reptiles and birds. Interestingly, this variation is sufficient to explain the previous report of a similar level of mitochondrial polymorphism, on average, between vertebrates and nonvertebrates, which was originally interpreted as reflecting the effect of pervasive positive selection. Our analysis rather indicates that the among-phyla homogeneity in within-species mtDNA diversity is due to a negative correlation between mtDNA per-generation mutation rate and effective population size, irrespective of the action of natural selection. Finally, we explore the variation in the absolute per-year mutation rate of both mtDNA and nuDNA using a reduced data set for which fossil calibration is available, and discuss the potential determinants of mutation rate variation across genomes and taxa. This study has important implications regarding DNA-based identification methods in predicting that mtDNA barcoding should be less reliable in nonvertebrates than in vertebrates. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. A review of low-level air pollution and adverse effects on human health: implications for epidemiological studies and public policy

    PubMed Central

    Olmo, Neide Regina Simões; do Nascimento Saldiva, Paulo Hilário; Braga, Alfésio Luís Ferreira; Lin, Chin An; de Paula Santos, Ubiratan; Pereira, Luiz Alberto Amador

    2011-01-01

    The aim of this study was to review original scientific articles describing the relationship between atmospheric pollution and damage to human health. We also aimed to determine which of these studies mentioned public policy issues. Original articles relating to atmospheric pollution and human health published between 1995 and 2009 were retrieved from the PubMed database and analyzed. This study included only articles dealing with atmospheric pollutants resulting primarily from vehicle emissions. Three researchers were involved in the final selection of the studies, and the chosen articles were approved by at least two of the three researchers. Of the 84 non-Brazilian studies analyzed, 80 showed an association between atmospheric pollution and adverse effects on human health. Moreover, 66 showed evidence of adverse effects on human health, even at levels below the permitted emission standards. Three studies mentioned public policies aimed at changing emission standards. Similarly, the 29 selected Brazilian studies reported adverse associations with human health, and 27 showed evidence of adverse effects even at levels below the legally permitted emission standards. Of these studies, 16 mentioned public policies aimed at changing emission standards. Based on the Brazilian and non-Brazilian scientific studies that have been conducted, it can be concluded that, even under conditions that are compliant with Brazilian air quality standards, the concentration of atmospheric pollutants in Brazil can negatively affect human health. However, as little discussion of this topic has been generated, this finding demonstrates the need to incorporate epidemiological evidence into decisions regarding legal regulations and to discuss the public policy implications in epidemiological studies. PMID:21655765

  7. Listening to the Voices of Today's Undergraduates: Implications for Teaching and Learning

    ERIC Educational Resources Information Center

    Bowen, Glenn; Burton, Carol; Cooper, Christopher; Cruz, Laura; McFadden, Anna; Reich, Chesney; Wargo, Melissa

    2011-01-01

    The landscape of higher education has changed with the presence of a new generation of college students. Current studies do not carry the voices of the new generation known as the Millennials. This article presents the findings of a qualitative study that explored the learning experiences of Millennial-generation undergraduates at a public…

  8. Is the Heart a Pressure or Flow Generator? Possible Implications and Suggestions for Cardiovascular Pedagogy

    ERIC Educational Resources Information Center

    Mitchell, Jamie R.

    2015-01-01

    In this article, a physiology instructor with primarily a cardiovascular (CV) background has wondered what approach to take, with both novice and senior learners, when it comes to delivering material on the pressure or flow generation of the heart. A debate surrounds the pressure propulsion versus flow generation theories, where some understand…

  9. Generation and development of RNA ligase ribozymes with modular architecture through "design and selection".

    PubMed

    Fujita, Yuki; Ishikawa, Junya; Furuta, Hiroyuki; Ikawa, Yoshiya

    2010-08-26

    In vitro selection with long random RNA libraries has been used as a powerful method to generate novel functional RNAs, although it often requires laborious structural analysis of isolated RNA molecules. Rational RNA design is an attractive alternative to avoid this laborious step, but rational design of catalytic modules is still a challenging task. A hybrid strategy of in vitro selection and rational design has been proposed. With this strategy termed "design and selection," new ribozymes can be generated through installation of catalytic modules onto RNA scaffolds with defined 3D structures. This approach, the concept of which was inspired by the modular architecture of naturally occurring ribozymes, allows prediction of the overall architectures of the resulting ribozymes, and the structural modularity of the resulting ribozymes allows modification of their structures and functions. In this review, we summarize the design, generation, properties, and engineering of four classes of ligase ribozyme generated by design and selection.

  10. Origins of adult pigmentation: diversity in pigment stem cell lineages and implications for pattern evolution

    PubMed Central

    Spiewak, Jessica E.

    2014-01-01

    Summary Teleosts comprise about half of all vertebrate species and exhibit an extraordinary diversity of adult pigment patterns that function in shoaling, camouflage and mate choice and have played important roles in speciation. Here, we review recent studies that have identified several distinct neural crest lineages, with distinct genetic requirements, that give rise to adult pigment cells in fishes. These lineages include post-embryonic, peripheral nerve associated stem cells that generate black melanophores and iridescent iridophores, cells derived directly from embryonic neural crest cells that generate yellow-orange xanthophores, and bipotent stem cells that generate both melanophores and xanthophores. This complexity in adult chromatophore lineages has implications for our understanding of adult traits, melanoma, and the evolutionary diversification of pigment cell lineages and patterns. PMID:25421288

  11. The volatile anesthetic isoflurane induces ecto-5′-nucleotidase (CD73) to protect against renal ischemia and reperfusion injury

    PubMed Central

    Kim, Mihwa; Ham, Ahrom; Kim, Joo Yun; Brown, Kevin M.; D’Agati, Vivette D.; Lee, H. Thomas

    2013-01-01

    The volatile anesthetic isoflurane protects against renal ischemia and reperfusion injury by releasing renal tubular TGF-β1. Since adenosine is a powerful cytoprotective molecule, we tested whether TGF-β1 generated by isoflurane induces renal tubular ecto-5′-nucleotidase (CD73) and adenosine to protect against renal ischemia and reperfusion injury. Isoflurane induced new CD73 synthesis and increased adenosine generation in cultured kidney proximal tubule cells and in mouse kidney. Moreover, a TGF-β1 neutralizing antibody prevented isoflurane-mediated induction of CD73 activity. Mice anesthetized with isoflurane after renal ischemia and reperfusion had significantly reduced plasma creatinine and decreased renal tubular necrosis, neutrophil infiltration and apoptosis compared to pentobarbital-anesthetized mice. Isoflurane failed to protect against renal ischemia and reperfusion injury in CD73 deficient mice, in mice pretreated with a selective CD73 inhibitor or mice treated with an adenosine receptor antagonist. The TGF-β1 neutralizing antibody or the CD73 inhibitor attenuated isoflurane-mediated protection against HK-2 cell apoptosis. Thus, isoflurane causes TGF-β1-dependent induction of renal tubular CD73 and adenosine generation to protect against renal ischemia and reperfusion injury. Modulation of this pathway may have important therapeutic implications to reduce morbidity and mortality arising from ischemic acute kidney injury. PMID:23423261

  12. Specifying the Concept of Future Generations for Addressing Issues Related to High-Level Radioactive Waste.

    PubMed

    Kermisch, Celine

    2016-12-01

    The nuclear community frequently refers to the concept of "future generations" when discussing the management of high-level radioactive waste. However, this notion is generally not defined. In this context, we have to assume a wide definition of the concept of future generations, conceived as people who will live after the contemporary people are dead. This definition embraces thus each generation following ours, without any restriction in time. The aim of this paper is to show that, in the debate about nuclear waste, this broad notion should be further specified and to clarify the related implications for nuclear waste management policies. Therefore, we provide an ethical analysis of different management strategies for high-level waste in the light of two principles, protection of future generations-based on safety and security-and respect for their choice. This analysis shows that high-level waste management options have different ethical impacts across future generations, depending on whether the memory of the waste and its location is lost, or not. We suggest taking this distinction into account by introducing the notions of "close future generations" and "remote future generations", which has important implications on nuclear waste management policies insofar as it stresses that a retrievable disposal has fewer benefits than usually assumed.

  13. First In-Situ Observations of Exospheric Response to CME Impact at Mercury

    NASA Astrophysics Data System (ADS)

    Raines, J. M.; Wallace, K. L.; Sarantos, M.; Jasinksi, J. M.; Tracy, P. J.; Dewey, R. M.; Weberg, M. J.; Slavin, J. A.

    2018-05-01

    We present the first in-situ observations of enhancements to Mercury's He exosphere generated by CME impact. These results have implications for understanding exosphere generation and loss processes, as well space weathering of the planet's surface.

  14. An Assessment Protocol for Selective Mutism: Analogue Assessment Using Parents as Facilitators.

    ERIC Educational Resources Information Center

    Schill, Melissa T.; And Others

    1996-01-01

    Assesses protocol for conducting a functional analysis of maintaining variables for children with selective mutism. A parent was trained in and later applied various behavior strategies designed to increase speech in an eight-year-old girl with selective mutism. Parent and child ratings of treatment were positive. Presents implications for future…

  15. Research on Journalism as Work: Implications for Education. ASHE 1984 Annual Meeting Paper.

    ERIC Educational Resources Information Center

    Lowther, Malcolm A.

    Selected findings drawn from research studies on journalism and work are discussed. The social science research methodologies employed by Herbert J. Gans and Stephen Hess are described with attention to story selection and general reporters and beat reporters. Selected journalistic research in the fields of science, business, and education are…

  16. Comparing Selections of Environmental Variables for Ecological Studies: A Focus on Terrain Attributes.

    PubMed

    Lecours, Vincent; Brown, Craig J; Devillers, Rodolphe; Lucieer, Vanessa L; Edinger, Evan N

    2016-01-01

    Selecting appropriate environmental variables is a key step in ecology. Terrain attributes (e.g. slope, rugosity) are routinely used as abiotic surrogates of species distribution and to produce habitat maps that can be used in decision-making for conservation or management. Selecting appropriate terrain attributes for ecological studies may be a challenging process that can lead users to select a subjective, potentially sub-optimal combination of attributes for their applications. The objective of this paper is to assess the impacts of subjectively selecting terrain attributes for ecological applications by comparing the performance of different combinations of terrain attributes in the production of habitat maps and species distribution models. Seven different selections of terrain attributes, alone or in combination with other environmental variables, were used to map benthic habitats of German Bank (off Nova Scotia, Canada). 29 maps of potential habitats based on unsupervised classifications of biophysical characteristics of German Bank were produced, and 29 species distribution models of sea scallops were generated using MaxEnt. The performances of the 58 maps were quantified and compared to evaluate the effectiveness of the various combinations of environmental variables. One of the combinations of terrain attributes-recommended in a related study and that includes a measure of relative position, slope, two measures of orientation, topographic mean and a measure of rugosity-yielded better results than the other selections for both methodologies, confirming that they together best describe terrain properties. Important differences in performance (up to 47% in accuracy measurement) and spatial outputs (up to 58% in spatial distribution of habitats) highlighted the importance of carefully selecting variables for ecological applications. This paper demonstrates that making a subjective choice of variables may reduce map accuracy and produce maps that do not adequately represent habitats and species distributions, thus having important implications when these maps are used for decision-making.

  17. The negative priming paradigm: An update and implications for selective attention.

    PubMed

    Frings, Christian; Schneider, Katja Kerstin; Fox, Elaine

    2015-12-01

    Negative Priming (NP) is an influential paradigm in cognitive psychology that was originally developed to measure attentional selection. Yet, up to the mid-1990s, a large number of experimental reports questioned whether the NP effect is based on attentional inhibition and/or episodic retrieval processes. In this review, we summarize findings since the mid-1990s and discuss new and old theoretical approaches to Negative Priming. We conclude that more than one process contributes to NP and that future research should analyze the conditions under which a particular process contributes to NP. Moreover, we argue that the paradigm--although it does not measure a single cognitive process alone--is still a useful tool for understanding selection in cognition. In fact, it might be a virtue of the paradigm that several cognitive processes work here together as selection in nonexperimental contexts is surely a multidimensional process. From this perspective, research on NP is relevant for all research fields analyzing selection. We therefore close our review by discussing the implications of the new evidence on NP for theories of selective attention.

  18. The mechanism of sound production in túngara frogs and its role in sexual selection and speciation.

    PubMed

    Ryan, Michael J; Guerra, Mónica A

    2014-10-01

    Sexual communication can evolve in response to sexual selection, and it can also cause behavioral reproductive isolation between populations and thus drive speciation. Anurans are an excellent system to investigate these links between behavior and evolution because we have detailed knowledge of how neural mechanisms generate behavioral preferences for calls and how these preferences then generate selection on call variation. But we know far less about the physical mechanisms of call production, especially how different laryngeal morphologies generate call variation. Here we review studies of a group of species that differ in the presence of a secondary call component that evolved under sexual selection. We discuss how the larynx produces this call component, and how laryngeal morphology generates sexual selection and can contribute to speciation. Copyright © 2014. Published by Elsevier Ltd.

  19. Response to five generations of selection for growth performance traits in rainbow trout (Oncorhynchus mykiss)

    USDA-ARS?s Scientific Manuscript database

    A pedigreed rainbow trout population (~100 families per generation) was selected for five generations to improve growth performance to the standard ~500-gram US market weight and beyond (greater than 1 kg). Body weights (BW) were recorded each generation at 5, 8, 10, and 13 months post-hatch. Selec...

  20. Mentalising and social problem solving in adults with Asperger's syndrome

    PubMed Central

    Channon, Shelley; Crawford, Sarah; Orlowska, Danuta; Parikh, Nimmi; Thoma, Patrizia

    2013-01-01

    Introduction It is well established that autistic spectrum disorder is linked to difficulties with mentalising, but the ways in which this affects everyday behaviour is less well understood. This study explored the nature and extent of difficulties in everyday social functioning in adults with Asperger's syndrome (AS), since increased understanding can enhance the development of more effective intervention strategies. Methods Individuals with AS (n = 21) were compared with healthy control participants (n = 21) on three tests of social cognition: the Mentalistic Interpretation task, which assesses interpretation of sarcasm and actions; the Social Problem Fluency task, which assesses ability to generate problem solutions; and the Social Problem Resolution task, which assesses judgement in selecting problem solutions. Results Comprehension of both sarcastic remarks and actions was impaired in those with AS on the mentalistic interpretation task. Participants with AS showed difficulties in identifying the awkward elements of everyday social scenarios, and they were also impaired in generating problem solutions but not in judging alternative solutions on the social problem fluency and resolution tasks. Conclusions These tasks potentially provide a means of profiling strengths and weaknesses in social processing, which in turn has implications for informing clinical evaluation and training. PMID:23875885

  1. Targeting the hypoxic fraction of tumours using hypoxia-activated prodrugs.

    PubMed

    Phillips, Roger M

    2016-03-01

    The presence of a microenvironment within most tumours containing regions of low oxygen tension or hypoxia has profound biological and therapeutic implications. Tumour hypoxia is known to promote the development of an aggressive phenotype, resistance to both chemotherapy and radiotherapy and is strongly associated with poor clinical outcome. Paradoxically, it is recognised as a high-priority target and one of the therapeutic strategies designed to eradicate hypoxic cells in tumours is a group of compounds known collectively as hypoxia-activated prodrugs (HAPs) or bioreductive drugs. These drugs are inactive prodrugs that require enzymatic activation (typically by 1 or 2 electron oxidoreductases) to generate cytotoxic species with selectivity for hypoxic cells being determined by (1) the ability of oxygen to either reverse or inhibit the activation process and (2) the presence of elevated expression of oxidoreductases in tumours. The concepts underpinning HAP development were established over 40 years ago and have been refined over the years to produce a new generation of HAPs that are under preclinical and clinical development. The purpose of this article is to describe current progress in the development of HAPs focusing on the mechanisms of action, preclinical properties and clinical progress of leading examples.

  2. Population structure and inbreeding from pedigree analysis of purebred dogs.

    PubMed

    Calboli, Federico C F; Sampson, Jeff; Fretwell, Neale; Balding, David J

    2008-05-01

    Dogs are of increasing interest as models for human diseases, and many canine population-association studies are beginning to emerge. The choice of breeds for such studies should be informed by a knowledge of factors such as inbreeding, genetic diversity, and population structure, which are likely to depend on breed-specific selective breeding patterns. To address the lack of such studies we have exploited one of the world's most extensive resources for canine population-genetics studies: the United Kingdom (UK) Kennel Club registration database. We chose 10 representative breeds and analyzed their pedigrees since electronic records were established around 1970, corresponding to about eight generations before present. We find extremely inbred dogs in each breed except the greyhound and estimate an inbreeding effective population size between 40 and 80 for all but 2 breeds. For all but 3 breeds, >90% of unique genetic variants are lost over six generations, indicating a dramatic effect of breeding patterns on genetic diversity. We introduce a novel index Psi for measuring population structure directly from the pedigree and use it to identify subpopulations in several breeds. As well as informing the design of canine population genetics studies, our results have implications for breeding practices to enhance canine welfare.

  3. An objective comparison of commercially-available cavitation meters.

    PubMed

    Sarno, Daniel; Hodnett, Mark; Wang, Lian; Zeqiri, Bajram

    2017-01-01

    With a number of cavitation meters on the market which claim to characterise fields in ultrasonic cleaning baths, this paper provides an objective comparison of a selection of these devices and establishes the extent to which their claims are met. The National Physical Laboratory's multi-frequency ultrasonic reference vessel provided the stable 21.06kHz field, above and below the inertial cavitation threshold, as a test bed for the sensor comparison. Measurements from these devices were evaluated in relation to the known acoustic pressure distribution in the cavitating vessel as a means of identifying the mode of operation of the sensors and to examine the particular indicator of cavitation activity which they deliver. Through the comparison with megahertz filtered acoustic signals generated by inertial cavitation, it was determined that the majority of the cavitation meters used in this study responded to acoustic pressure generated by the direct applied acoustic field and therefore tended to overestimate the occurrence of cavitation within the vessel, giving non-zero responses under conditions when there was known to be no inertial cavitation occurring with the reference vessel. This has implications for interpreting the data they provide in user applications. Copyright © 2016. Published by Elsevier B.V.

  4. Attenuated expression of interferon-β and interferon-λ1 by human alternatively activated macrophages.

    PubMed

    El Fiky, Ashraf; Perreault, Roger; McGinnis, Gwendolyn J; Rabin, Ronald L

    2013-12-01

    Macrophages can be polarized into classically (CAM) or alternatively (AAM) activated macrophages with IFN-γ or IL-4, respectively. CAM are associated with type 1 immune responses and are implicated in autoimmunity; AAM are associated with type 2 responses and are implicated in allergic diseases. An impediment in investigating macrophage biology using primary human monocyte derived macrophages is the wide inter-donor heterogeneity and the limited quantity of cells that survive in vitro polarization. To overcome this impediment, we established a protocol to generate CAM and AAM cultures derived from the THP-1 human promonocytic cell line. In this report, we demonstrate that THP-CAM and -AAM express gene and protein markers that define their primary human monocyte derived counterparts, such as IL-1β, CXCL10, and CXCL11 for CAM, and MRC1, IL-4 and CCL22 for AAM. In addition, we demonstrate that STAT6 is selectively activated in THP-AAM which, upon LPS stimulation, have an attenuated or delayed expression of IFN-β, IFN-λ1, and IFN α/β pathway genes compared to their CAM counterparts. Taken together, these findings may help further investigate human diseases associated with the alternatively activated macrophage phenotype using this reproducible in vitro macrophage model. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

  5. Phosphoinositides and membrane curvature switch the mode of actin polymerization via selective recruitment of toca-1 and Snx9

    PubMed Central

    Gallop, Jennifer L.; Walrant, Astrid; Cantley, Lewis C.; Kirschner, Marc W.

    2013-01-01

    The membrane–cytosol interface is the major locus of control of actin polymerization. At this interface, phosphoinositides act as second messengers to recruit membrane-binding proteins. We show that curved membranes, but not flat ones, can use phosphatidylinositol 3-phosphate [PI(3)P] along with phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] to stimulate actin polymerization. In this case, actin polymerization requires the small GTPase cell cycle division 42 (Cdc42), the nucleation-promoting factor neural Wiskott–Aldrich syndrome protein (N-WASP) and the actin nucleator the actin-related protein (Arp) 2/3 complex. In liposomes containing PI(4,5)P2 as the sole phosphoinositide, actin polymerization requires transducer of Cdc42 activation-1 (toca-1). In the presence of phosphatidylinositol 3-phosphate, polymerization is both more efficient and independent of toca-1. Under these conditions, sorting nexin 9 (Snx9) can be implicated as a specific adaptor that replaces toca-1 to mobilize neural Wiskott–Aldrich syndrome protein and the Arp2/3 complex. This switch in phosphoinositide and adaptor specificity for actin polymerization from membranes has implications for how different types of actin structures are generated at precise times and locations in the cell. PMID:23589871

  6. PINK1/Parkin-mediated mitophagy alleviates chlorpyrifos-induced apoptosis in SH-SY5Y cells.

    PubMed

    Dai, Hongmei; Deng, Yuanying; Zhang, Jie; Han, Hailong; Zhao, Mingyi; Li, Ying; Zhang, Chen; Tian, Jing; Bing, Guoying; Zhao, Lingling

    2015-08-06

    Chlorpyrifos (CPF) is one of the most widely used organophosphorous insecticides. There are links between CPF exposure and neurological disorders. Mitochondrial damage has been implicated to play a key role in CPF-induced neurotoxicity. Mitophagy, the selective autophagic elimination of mitochondria, is an important mitochondrial quality control mechanism. However, the role of mitophagy in CPF-induced neurotoxicity remains unclear. In this study, CPF-caused mitochondrial damage, role and mechanism of mitophagy on CPF-induced neuroapoptosis were extensively studied by using SH-SY5Y cells. We showed that CPF treatment caused mitochondrial fragmentation, excessive ROS generation and mitochondrial depolarization, thus led to cell apoptosis. Moreover, CPF treatment also resulted in increased colocalizaton of mitochondria with LC3, decreased levels of mitochondrial proteins, PINK1 stabilization and mitochondrial accumulation of Parkin. These data suggested that CPF treatment induced PINK1/Parkin-mediated mitophagy in SH-SY5Y cells. Furthermore, knockdown of Parkin dramatically increased CPF-induced neuroapoptosis. On the other hand, overexpression of Parkin markedly alleviated CPF-induced SH-SY5Y cell apoptosis. Together, these findings implicate a protective role of PINK1/Parkin-mediated mitophagy against neuroapoptosis and that enhancing mitophagy provides a potential therapeutic strategy for CPF-induced neurological disorders. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  7. Selection for fertility in mice - the selection plateau and how to overcome it.

    PubMed

    Schüler, L

    1985-04-01

    A long-term experiment for increasing the traits first day litter size (LS1) and litter weight (LW1) was conducted with two populations for 33 generations. The selection plateau was reached in population DU-C (selection and estrus synchronization (h(2) = 0.02±0.01); in population DU-K (selection) the plateau (h(2) = 0.05±0.2) was nearly reached. Selection progress per generation was in LS1 b = 0.11±0.02; b = 0.12±0.04 (1st to 18th generation DU-K, DU-C) and b = 0.10±0.03; b = 0.07±0.05 (19th to 33rd generation, DU-K, DU-C) in LW1 b = 0.16±0.04 g; 0.19±0.07 g (DU-K, DU-C) b = 0.20±0.09 g; 0.001±0.09 g (DU-K, DU-C). Reverse and relaxe selection as well as systematic inbreeding was applied for 10 generations. Reverse selection yielded h(2) = 0.28±0.11 (R-DU-K) and h(2) = 0.17±0.05 (R-DU-C) and showed that there was still additive genetic variance. Relaxe selection did not cause alterations in the selection parameters, whereas inbreeding lead to inbred depressions (b = LS1 = -0.42±0.15; -0.45±0.12; b = LW1 = -1.13±0.20; -0.82±0.18 I-DU-K, I-DU-C). The plateau was based upon the heterozygote advantage. Several methods for overcoming the plateau were applied. A new selective useful variance could be created by crossing the plateau populations (h(2) = 0.14±0.04). A short-term progress in overcoming the plateau (1st to 3rd generation) could be obtained by litter size standardization (LS = 388). Tandem selection (selection for body weight - BW42) as well as crossing of inbred strains were not suitable for overcoming the selection plateau. Altering the environmental conditions as a possibility for overcoming the plateau has been discussed.

  8. Molecular pathway activation - new type of biomarkers for tumor morphology and personalized selection of target drugs.

    PubMed

    Buzdin, Anton; Sorokin, Maxim; Garazha, Andrew; Sekacheva, Marina; Kim, Ella; Zhukov, Nikolay; Wang, Ye; Li, Xinmin; Kar, Souvik; Hartmann, Christian; Samii, Amir; Giese, Alf; Borisov, Nicolas

    2018-06-20

    Anticancer target drugs (ATDs) specifically bind and inhibit molecular targets that play important roles in cancer development and progression, being deeply implicated in intracellular signaling pathways. To date, hundreds of different ATDs were approved for clinical use in the different countries. Compared to previous chemotherapy treatments, ATDs often demonstrate reduced side effects and increased efficiency, but also have higher costs. However, the efficiency of ATDs for the advanced stage tumors is still insufficient. Different ATDs have different mechanisms of action and are effective in different cohorts of patients. Personalized approaches are therefore needed to select the best ATD candidates for the individual patients. In this review, we focus on a new generation of biomarkers - molecular pathway activation - and on their applications for predicting individual tumor response to ATDs. The success in high throughput gene expression profiling and emergence of novel bioinformatic tools reinforced quick development of pathway related field of molecular biomedicine. The ability to quantitatively measure degree of a pathway activation using gene expression data has revolutionized this field and made the corresponding analysis quick, robust and inexpensive. This success was further enhanced by using machine learning algorithms for selection of the best biomarkers. We review here the current progress in translating these studies to clinical oncology and patient-oriented adjustment of cancer therapy. Copyright © 2018. Published by Elsevier Ltd.

  9. Dairy-cattle health in Gyeongnam, Korea.

    PubMed

    Jong, S K; Gong, S K; Chung, H K; Dae, S H

    2001-12-03

    An animal-health monitoring system in the Gyeongnam area was started in 1997 to develop statistically valid data for use in estimating disease frequencies in dairy cattle, and the associated costs. The objectives of this study were to: (1) describe what was done to implement and maintain the system in Gyeongnam; (2) present selected disease frequencies; (3) discuss the epidemiological consideration of what was done and implications for results obtained. Veterinary medical officers (VMOs), comprising professors and graduate students from Gyeongsang National University, faculty of Gyeongnam Livestock Promotion Institute and clinic veterinarians, served as data collectors. After training on current disease and management problems of dairy cattle, interview techniques, sampling methods and data-collection instruments, the VMOs participated in selection of the sample herds and data gathering. Forty (n=40) of 167 dairy herds were selected randomly using a computer-generated list of random numbers and the VMOs visited farms once in a month for 12 months to collect data about management, disease, inventory, production, preventive treatment, financial and other relevant data. Strict data-quality control devices were used. Specific feed-back was developed for the producers and data collectors. The six disorders found most frequently in cows (from the highest to the lowest) were breeding problems, clinical mastitis, birth problems, gastrointestinal problems, metabolic problems and lameness. In young stock, respiratory, multiple system, breeding and gastrointestinal problems were predominant, whereas in calves, gastrointestinal, respiratory and integumental problems predominated.

  10. Determinants of sheep prices in the highlands of northeastern Ethiopia: implication for sheep value chain development.

    PubMed

    Kassa, Beneberu Teferra; Haile, Anteneh Girma; Essa, John Abdu

    2011-12-01

    In order to assess and identify the determinants of sheep price and price variation across time, a time series data were collected from four selected markets in North Shewa, Northeastern Ethiopia on weekly market day basis for a period of 2 years. Data on animal characteristics and purpose of buying were collected on a weekly basis from randomly selected 15-25 animals, and a total of 7,976 transactions were recorded. A general linear model technique was used to identify factors influencing sheep price, and the results showed that sheep price (liveweight sheep price per kilogram taken as a dependent variable) is affected by animal characteristics such as weight, sex, age, condition, season, and color. Most of the markets' purpose for which the animal was purchased did not affect significantly the price per kilogram. This may be due to the similarity of the markets in terms of buyer's purpose. The results suggest that there will be benefit from coordinated fattening, breeding, and marketing programs to take the highest advantage from the preferred animals' characteristics and selected festival markets. Finally, the study recommends for a coordinated action to enhance the benefit generated for all participant actors in the sheep value chain through raising sheep productivity, improving the capacity of sheep producers and agribusiness entrepreneurs to access and use latest knowledge and technologies; and strengthening linkages among actors in the sheep value chain.

  11. Laboratory Anion Chemistry: Implications for the DIBs, and a Potential Formation Mechanism for a Known Interstellar Molecule

    NASA Technical Reports Server (NTRS)

    Eichelberger, B.; Barckholtz, C.; Stepanovic, M.; Bierbaum, V.; Snow, T.

    2002-01-01

    Due to recent interest in molecular anions as possible interstellar species, we have carried out several laboratory studies of anion chemistry. The reactions of the series C(sub n)(sup -); and C(sub n)H(sup -) with H and H2 were studied to address the viability of such species in the diffuse interstellar medium and to address their ability to be carriers of the diffuse interstellar bands (DIBs). These same molecules were also reacted with N and O to show possible heteroatomic products. C(sub m)N(sup - was a particularly stable product from the reaction of C(sub n)(sup -) + N. C3N(sup -) was further reacted with H to study chemistry that could produce HC3N, a known interstellar species. The reactions were done in a flowing afterglow selected ion flow tube apparatus (FA-SIFT). The anions were generated in an electron impact or cold cathode discharge source and the anion of interest was then selected by a quadrupole mass filter. The selected ion was then reacted with the atomic or molecular species in the flow tube and products were detected by another quadrupole. While the C(sub n)(sup -) species do not appear to be viable DIB carriers, their possible presence could provide a mechanism for the formation of known heteroatomic neutral molecules detected in the interstellar medium (ISM).

  12. Effect of directional selection for body size on fluctuating asymmetry in certain morphological traits in Drosophila ananassae.

    PubMed

    Vishalakshi, C; Singh, B N

    2009-06-01

    Variation in the subtle differences between the right and left sides of bilateral characters or fluctuating asymmetry (FA) has been considered as an indicator of an organism's ability to cope with genetic and environmental stresses during development. However, due to inconsistency in the results of empirical studies, the relationship between FA and stress has been the subject of intense debate. In this study, we investigated whether stress caused by artificial bidirectional selection for body size has any effect on the levels of FA of different morphological traits in Drosophila ananassae. The realised heritability (h2) was higher in low-line females and high-line males, which suggests an asymmetrical response to selection for body size. Further, the levels of FA were compared across 10 generations of selection in different selection lines in both sexes for sternopleural bristle number, wing length, wing-to-thorax ratio, sex combtooth number and ovariole number. The levels of FA differed significantly among generations and selection lines but did not change markedly with directional selection. However, the levels of FA were higher in the G10 generation (at the end of selection) than G0 (at the start of selection) but lower than the G5 generation in different selection lines, suggesting that the levels of FA are not affected by the inbreeding generated during the course of selection. Also, the levels of FA in the hybrids of high and low lines were signifi cantly lower than the parental selection lines, suggesting that FA is influenced by hybridisation. These results are discussed in the framework of the literature available on FA and its relationship with stress.

  13. Algorithmic methods to infer the evolutionary trajectories in cancer progression

    PubMed Central

    Graudenzi, Alex; Ramazzotti, Daniele; Sanz-Pamplona, Rebeca; De Sano, Luca; Mauri, Giancarlo; Moreno, Victor; Antoniotti, Marco; Mishra, Bud

    2016-01-01

    The genomic evolution inherent to cancer relates directly to a renewed focus on the voluminous next-generation sequencing data and machine learning for the inference of explanatory models of how the (epi)genomic events are choreographed in cancer initiation and development. However, despite the increasing availability of multiple additional -omics data, this quest has been frustrated by various theoretical and technical hurdles, mostly stemming from the dramatic heterogeneity of the disease. In this paper, we build on our recent work on the “selective advantage” relation among driver mutations in cancer progression and investigate its applicability to the modeling problem at the population level. Here, we introduce PiCnIc (Pipeline for Cancer Inference), a versatile, modular, and customizable pipeline to extract ensemble-level progression models from cross-sectional sequenced cancer genomes. The pipeline has many translational implications because it combines state-of-the-art techniques for sample stratification, driver selection, identification of fitness-equivalent exclusive alterations, and progression model inference. We demonstrate PiCnIc’s ability to reproduce much of the current knowledge on colorectal cancer progression as well as to suggest novel experimentally verifiable hypotheses. PMID:27357673

  14. Modeling phase separation in mixtures of intrinsically-disordered proteins

    NASA Astrophysics Data System (ADS)

    Gu, Chad; Zilman, Anton

    Phase separation in a pure or mixed solution of intrinsically-disordered proteins (IDPs) and its role in various biological processes has generated interest from the theoretical biophysics community. Phase separation of IDPs has been implicated in the formation of membrane-less organelles such as nucleoli, as well as in a mechanism of selectivity in transport through the nuclear pore complex. Based on a lattice model of polymers, we study the phase diagram of IDPs in a mixture and describe the selective exclusion of soluble proteins from the dense-phase IDP aggregates. The model captures the essential behaviour of phase separation by a minimal set of coarse-grained parameters, corresponding to the average monomer-monomer and monomer-protein attraction strength, as well as the protein-to-monomer size ratio. Contrary to the intuition that strong monomer-monomer interaction increases exclusion of soluble proteins from the dense IDP aggregates, our model predicts that the concentration of soluble proteins in the aggregate phase as a function of monomer-monomer attraction is non-monotonic. We corroborate the predictions of the lattice model using Langevin dynamics simulations of grafted polymers in planar and cylindrical geometries, mimicking various in-vivo and in-vitro conditions.

  15. Resveratrol and its oligomers from wine grapes are selective (1)O2 quenchers: mechanistic implication by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry and theoretical calculation.

    PubMed

    Jiang, Li-Yan; He, Shan; Jiang, Ke-Zhi; Sun, Cui-Rong; Pan, Yuan-Jiang

    2010-08-25

    Resveratrol and its oligomers, abundantly present in wine grapes, are believed to be effective phytoalexins for the phenomenon "French paradox" partially by virtue of their powerful antiradical properties. EPR spin-trapping technique was utilized, demonstrating all polyphenols were selective (1)O2 quenchers but not effective (•)OH and O2(•¯) scavengers. On the basis of the HPLC-ESI-MS(2) analysis for the simulated reactions of polyphenols with (1)O2, the molecular weights of the resulting photochemical products were 14 or 28 Da higher than those of their substrates. No fragment C2H2O (42 Da), which was rather distinctive of the resorcinol rings in these cases, had been observed, whereas their MS/MS spectra displayed characteristic neutral fragments including carbon monoxide (CO, 28 Da) and 2-hydroxy[1,4]benzoquinone (C6H4O3, 124 Da). Finally, PM3 semiempirical calculations and HR-FTICR-MS experiments were performed, supporting the assertion that their quenching mechanism involved physical and chemical pathways. Chemical quenching underwent an endoperoxide intermediate form to generate quinones.

  16. In silico modelling of directed evolution: Implications for experimental design and stepwise evolution.

    PubMed

    Wedge, David C; Rowe, William; Kell, Douglas B; Knowles, Joshua

    2009-03-07

    We model the process of directed evolution (DE) in silico using genetic algorithms. Making use of the NK fitness landscape model, we analyse the effects of mutation rate, crossover and selection pressure on the performance of DE. A range of values of K, the epistatic interaction of the landscape, are considered, and high- and low-throughput modes of evolution are compared. Our findings suggest that for runs of or around ten generations' duration-as is typical in DE-there is little difference between the way in which DE needs to be configured in the high- and low-throughput regimes, nor across different degrees of landscape epistasis. In all cases, a high selection pressure (but not an extreme one) combined with a moderately high mutation rate works best, while crossover provides some benefit but only on the less rugged landscapes. These genetic algorithms were also compared with a "model-based approach" from the literature, which uses sequential fixing of the problem parameters based on fitting a linear model. Overall, we find that purely evolutionary techniques fare better than do model-based approaches across all but the smoothest landscapes.

  17. Production of giant marine diatoms and their export at oceanic frontal zones: Implications for Si and C flux from stratified oceans

    NASA Astrophysics Data System (ADS)

    Kemp, A. E. S.; Pearce, R. B.; Grigorov, I.; Rance, J.; Lange, C. B.; Quilty, P.; Salter, I.

    2006-12-01

    From a synthesis of recent oceanic observations and paleo-data it is evident that certain species of giant diatoms including Rhizosolenia spp. Thalassiothrix spp. and Ethmodiscus rex may become concentrated at oceanic frontal zones and subsequently form episodes of mass flux to the sediment. Within the nutrient bearing waters advecting towards frontal boundaries, these species are generally not dominant, but they appear selectively segregated at fronts, and thus may dominate the export flux. Ancient Thalassiothrix diatom mat deposits in the eastern equatorial Pacific and beneath the Polar Front in the Southern Ocean record the highest open ocean sedimentation rates ever documented and represent vast sinks of silica and carbon. Several of the species involved are adapted to a stratified water column and may thrive in Deep Chlorophyll Maxima. Thus in oceanic regions and/or at times prone to enhanced surface water stratification (e.g., during meltwater pulses) they provide a mechanism for generating substantial biomass at depth and its subsequent export with concomitant implications for Si export and C drawdown. This ecology has important implications for ocean biogeochemical models suggesting that more than one diatom "functional type" should be used. In spite of the importance of these giant diatoms for biogeochemical cycling, their large size coupled with the constraints of conventional oceanographic survey schemes and techniques means that they are undersampled. An improved insight into these key species will be an important prerequisite for enhancing our understanding of marine biogeochemical cycling and for assessing the impacts of climate change on ocean export production.

  18. An Epigenetic Perspective on the Midwife Toad Experiments of Paul Kammerer (1880-1926).

    PubMed

    Vargas, Alexander O; Krabichler, Quirin; Guerrero-Bosagna, Carlos

    2017-01-01

    Paul Kammerer was the most outstanding neo-Lamarckian experimentalist of the early 20th century. He reported spectacular results in the midwife toad, including crosses of environmentally modified toads with normal toads, where acquired traits were inherited in Mendelian fashion. Accusations of fraud generated a great scandal, ending with Kammerer's suicide. Controversy reignited in the 1970s, when journalist Arthur Koestler argued against these accusations. Since then, others have argued that Kammerer's results, even if real, were not groundbreaking and could be explained by somatic plasticity, inadvertent selection, or conventional genetics. More recently, epigenetics has uncovered mechanisms by which inheritance can respond directly to environmental change, inviting a reanalysis of Kammerer's descriptions. Previous arguments for mere somatic plasticity have ignored the description of experiments showing heritable germ line modification. Alleged inadvertent selection associated with egg mortality can be discarded, since mortality decreased in a single generation, upon repeated exposures. The challenging implications did not escape the attention of Kammerer's noted contemporary, William Bateson, but he reacted with disbelief, thus encouraging fraud accusations. Nowadays, formerly puzzling phenomena can be explained by epigenetic mechanisms. Importantly, Kammerer described parent-of-origin effects, an effect of parental sex on dominance. Epigenetic mechanisms underlie these effects in genomic imprinting and experiments of transgenerational epigenetic inheritance. In the early 20th century, researchers had no reason to link them with the inheritance of acquired traits. Thus, the parent-of-origin effects in Kammerer's experiments specifically suggest authenticity. Ultimate proof should come from renewed experimentation. To encourage further research, we present a model of possible epigenetic mechanisms. © 2016 Wiley Periodicals, Inc.

  19. Generation of tumour-necrosis-factor-alpha-specific affibody molecules capable of blocking receptor binding in vitro.

    PubMed

    Jonsson, Andreas; Wållberg, Helena; Herne, Nina; Ståhl, Stefan; Frejd, Fredrik Y

    2009-08-17

    Affibody molecules specific for human TNF-alpha (tumour necrosis factor-alpha) were selected by phage-display technology from a library based on the 58-residue Protein A-derived Z domain. TNF-alpha is a proinflammatory cytokine involved in several inflammatory diseases and, to this day, four TNF-alpha-blocking protein pharmaceuticals have been approved for clinical use. The phage selection generated 18 unique cysteine-free affibody sequences of which 12 were chosen, after sequence cluster analysis, for characterization as proteins. Biosensor binding studies of the 12 Escherichia coli-produced and IMAC (immobilized-metal-ion affinity chromatography)-purified affibody molecules revealed three variants that demonstrated the strongest binding to human TNF-alpha. These three affibody molecules were subjected to kinetic binding analysis and also tested for their binding to mouse, rat and pig TNF-alpha. For ZTNF-alpha:185, subnanomolar affinity (KD=0.1-0.5 nM) for human TNF-alpha was demonstrated, as well as significant binding to TNF-alpha from the other species. Furthermore, the binding site was found to overlap with the binding site for the TNF-alpha receptor, since this interaction could be efficiently blocked by the ZTNF-alpha:185 affibody. When investigating six dimeric affibody constructs with different linker lengths, and one trimeric construct, it was found that the inhibition of the TNF-alpha binding to its receptor could be further improved by using dimers with extended linkers and/or a trimeric affibody construct. The potential implication of the results for the future design of affibody-based reagents for the diagnosis of inflammation is discussed.

  20. Decision-Making Theory Applied to Architectural Programming: Some Research Implications.

    ERIC Educational Resources Information Center

    Green, Meg

    The implications of delineating and determining the sequence of programming decisions are shown in the selection of building committee membership. The role relationships of client and architect are discussed in terms of decision-making function. Decision tables are described as aids in problem analysis. Other topics include information and…

  1. The Inequality Implications of Highly Selective Promotion Practices

    ERIC Educational Resources Information Center

    Mete, Cem

    2004-01-01

    Faced with the evident impossibility of providing free or significantly subsidized secondary and higher education to all, many poor and middle income countries choose to educate only those students who are most promising, using public examinations as means of distributing scarce resources. This paper investigates the inequality implications of…

  2. Unsupervised categorization with individuals diagnosed as having moderate traumatic brain injury: Over-selective responding.

    PubMed

    Edwards, Darren J; Wood, Rodger

    2016-01-01

    This study explored over-selectivity (executive dysfunction) using a standard unsupervised categorization task. Over-selectivity has been demonstrated using supervised categorization procedures (where training is given); however, little has been done in the way of unsupervised categorization (without training). A standard unsupervised categorization task was used to assess levels of over-selectivity in a traumatic brain injury (TBI) population. Individuals with TBI were selected from the Tertiary Traumatic Brain Injury Clinic at Swansea University and were asked to categorize two-dimensional items (pictures on cards), into groups that they felt were most intuitive, and without any learning (feedback from experimenter). This was compared against categories made by a control group for the same task. The findings of this study demonstrate that individuals with TBI had deficits for both easy and difficult categorization sets, as indicated by a larger amount of one-dimensional sorting compared to control participants. Deficits were significantly greater for the easy condition. The implications of these findings are discussed in the context of over-selectivity, and the processes that underlie this deficit. Also, the implications for using this procedure as a screening measure for over-selectivity in TBI are discussed.

  3. Selecting Anatomy and Physiology Textbooks for Nursing Students.

    ERIC Educational Resources Information Center

    Harder, Annie K.; Carline, Jan D.

    1988-01-01

    Describes the criteria used for textbook selection or rejection, how the criteria differ depending on the level of students, and how the criteria differ according to the instructor's training. Discusses results and implications for students, instructors, and publishers. (CW)

  4. Comparative transcriptomic analysis of endothelial progenitor cells derived from umbilical cord blood and adult peripheral blood: Implications for the generation of induced pluripotent stem cells.

    PubMed

    Gao, Xiugong; Yourick, Jeffrey J; Sprando, Robert L

    2017-12-01

    Induced pluripotent stem cells (iPSCs) offer the potential to generate tissues with ethnic diversity enabling toxicity testing on selected populations. Recently, it has been reported that endothelial progenitor cells (EPCs) derived from umbilical cord blood (CB) or adult peripheral blood (PB) afford a practical and efficient cellular substrate for iPSC generation. However, differences between EPCs from different blood sources have rarely been studied. In the current study, we derived EPCs from blood mononuclear cells (MNCs) and reprogrammed EPCs into iPSCs. We also explored differences between CB-EPCs and PB-EPCs at the molecular and cellular levels through a combination of transcriptomic analysis and cell biology techniques. EPC colonies in CB-MNCs emerged 5-7days earlier, were 3-fold higher in number, and consistently larger in size than in PB-MNCs. Similarly, iPSC colonies generated from CB-EPCs was 2.5-fold higher in number than from PB-EPCs, indicating CB-EPCs have a higher reprogramming efficiency than PB-EPCs. Transcriptomic analysis using microarrays found a total of 1133 genes differentially expressed in CB-EPCs compared with PB-EPCs, with 675 genes upregulated and 458 downregulated. Several canonical pathways were impacted, among which the human embryonic stem cell pluripotency pathway was of particular interest. The differences in the gene expression pattern between CB-EPCs and PB-EPCs provide a molecular basis for the discrepancies seen in their derivation and reprogramming efficiencies, and highlight the advantages of using CB as the cellular source for the generation of iPSCs and their derivative tissues for ethnic-related toxicological applications. Published by Elsevier B.V.

  5. Weak gravity conjecture as a razor criterium for exotic D-brane instantons

    NASA Astrophysics Data System (ADS)

    Addazi, Andrea

    2017-01-01

    We discuss implications of weak gravity conjecture (WGC) for exotic D-brane instantons. In particular, WGC leads to indirect stringent bounds on non-perturbative superpotentials generated by exotic instantons with many implications for phenomenology: R-parity violating processes, neutrino mass, μ-problem, neutron-antineutron transitions and collider physics.

  6. Filling in the Gaps: Memory Implications for Inferring Missing Content in Graphic Narratives

    ERIC Educational Resources Information Center

    Magliano, Joseph P.; Kopp, Kristopher; Higgs, Karyn; Rapp, David N.

    2017-01-01

    Visual narratives, including graphic novels, illustrated instructions, and picture books, convey event sequences constituting a plot but cannot depict all events that make up the plot. Viewers must generate inferences that fill the gaps between explicitly shown images. This study explored the inferential products and memory implications of…

  7. Innovation for Transformation in Nigeria University Education: Implications for the Production of Critical and Creative Thinkers

    ERIC Educational Resources Information Center

    Onu, V. C.; Eskay, M. K.; Obiyo, N. O.; Igbo, J. N.; Ezeanwu, A. B.

    2012-01-01

    This descriptive survey research studied innovation for transformation in Nigeria university education: implications for the production of critical and creative thinkers. Thus, students' perception of knowledge generation and dissemination by university lecturers were elicited. From a population of registered students in a Nigerian university, 200…

  8. Analysis of ultraviolet exposure effects on the surface properties of epoxy/graphene nanocomposite films on Mylar substrate

    NASA Astrophysics Data System (ADS)

    Clausi, Marialaura; Santonicola, M. Gabriella; Schirone, Luigi; Laurenzi, Susanna

    2017-05-01

    In this paper, we present a study of the effects generated by exposure to UV-C radiation on nanocomposite films made of graphene nanoplatelets dispersed in an epoxy matrix. The nanocomposite films, at different nanoparticle size and concentration, were fabricated on Mylar substrate using the spin coating process. The effects of UV-C irradiation on the surface hydrophobicity and on the electrical properties of the epoxy/graphene films were investigated using contact angle measurements and electrical impedance spectroscopy, respectively. According to our results, the UV-C irradiation selectively degrades the polymer matrix of the nanocomposite films, giving rise to more conductive and hydrophobic layers due to exposure of the graphene component of the composite material. The results presented here have important implications in the design of spacecraft components and structures destined for long-term space missions.

  9. Sources of avoidance motivation: Valence effects from physical effort and mental rotation.

    PubMed

    Morsella, Ezequiel; Feinberg, Giles H; Cigarchi, Sepeedeh; Newton, James W; Williams, Lawrence E

    2011-09-01

    When reaching goals, organisms must simultaneously meet the overarching goal of conserving energy. According to the law of least effort, organisms will select the means associated with the least effort. The mechanisms underlying this bias remain unknown. One hypothesis is that organisms come to avoid situations associated with unnecessary effort by generating a negative valence toward the stimuli associated with such situations. Accordingly, merely using a dysfunctional, 'slow' computer mouse causes participants to dislike ambient neutral images (Study 1). In Study 2, nonsense shapes were liked less when associated with effortful processing (135° of mental rotation) versus easier processing (45° of rotation). Complementing 'fluency' effects found in perceptuo-semantic research, valence emerged from action-related processing in a principled fashion. The findings imply that negative valence associations may underlie avoidance motivations, and have practical implications for educational/workplace contexts in which effort and positive affect are conducive to success.

  10. Personality profiles of Australian anaesthetists.

    PubMed

    Kluger, M T; Laidlaw, T; Khursandi, D S

    1999-06-01

    Identification of personality traits in anaesthetists has potential implications for selection of trainees, assessment of coping strategies during times of stress and may have a role in the analysis of critical incidents. A 24 question postal questionnaire based on the Cattell 16PF inventory was sent to specialist anaesthetists in Australia. One hundred and sixty-seven replies were received (33% response rate). Personality traits did not differ when the anaesthetists were grouped for age, number of years qualified and country of qualification. City practitioners rated themselves more inquisitive than country practitioners did (P = 0.052). Female anaesthetists self-reported they were calm (P = 0.02), patient (P = 0.02) and tolerant (P = 0.02) more often than their male counterparts, whilst more males reported themselves as highly conscientious (P = 0.01). Although some traits were consistent, personality profiles showed significant heterogeneity. Further examination of how personality and coping mechanisms interact may be central to the management of stress and critical incident generation.

  11. Sperm competition and maternal effects differentially influence testis and sperm size in Callosobruchus maculatus.

    PubMed

    Gay, L; Hosken, D J; Vasudev, R; Tregenza, T; Eady, P E

    2009-05-01

    The evolutionary factors affecting testis size are well documented, with sperm competition being of major importance. However, the factors affecting sperm length are not well understood; there are no clear theoretical predictions and the empirical evidence is inconsistent. Recently, maternal effects have been implicated in sperm length variation, a finding that may offer insights into its evolution. We investigated potential proximate and microevolutionary factors influencing testis and sperm size in the bruchid beetle Callosobruchus maculatus using a combined approach of an artificial evolution experiment over 90 generations and an environmental effects study. We found that while polyandry seems to select for larger testes, it had no detectable effect on sperm length. Furthermore, population density, a proximate indicator of sperm competition risk, was not significantly associated with sperm length or testis size variation. However, there were strong maternal effects influencing sperm length.

  12. The yak genome and adaptation to life at high altitude.

    PubMed

    Qiu, Qiang; Zhang, Guojie; Ma, Tao; Qian, Wubin; Wang, Junyi; Ye, Zhiqiang; Cao, Changchang; Hu, Quanjun; Kim, Jaebum; Larkin, Denis M; Auvil, Loretta; Capitanu, Boris; Ma, Jian; Lewin, Harris A; Qian, Xiaoju; Lang, Yongshan; Zhou, Ran; Wang, Lizhong; Wang, Kun; Xia, Jinquan; Liao, Shengguang; Pan, Shengkai; Lu, Xu; Hou, Haolong; Wang, Yan; Zang, Xuetao; Yin, Ye; Ma, Hui; Zhang, Jian; Wang, Zhaofeng; Zhang, Yingmei; Zhang, Dawei; Yonezawa, Takahiro; Hasegawa, Masami; Zhong, Yang; Liu, Wenbin; Zhang, Yan; Huang, Zhiyong; Zhang, Shengxiang; Long, Ruijun; Yang, Huanming; Wang, Jian; Lenstra, Johannes A; Cooper, David N; Wu, Yi; Wang, Jun; Shi, Peng; Wang, Jian; Liu, Jianquan

    2012-07-01

    Domestic yaks (Bos grunniens) provide meat and other necessities for Tibetans living at high altitude on the Qinghai-Tibetan Plateau and in adjacent regions. Comparison between yak and the closely related low-altitude cattle (Bos taurus) is informative in studying animal adaptation to high altitude. Here, we present the draft genome sequence of a female domestic yak generated using Illumina-based technology at 65-fold coverage. Genomic comparisons between yak and cattle identify an expansion in yak of gene families related to sensory perception and energy metabolism, as well as an enrichment of protein domains involved in sensing the extracellular environment and hypoxic stress. Positively selected and rapidly evolving genes in the yak lineage are also found to be significantly enriched in functional categories and pathways related to hypoxia and nutrition metabolism. These findings may have important implications for understanding adaptation to high altitude in other animal species and for hypoxia-related diseases in humans.

  13. Mean-field and linear regime approach to magnetic hyperthermia of core-shell nanoparticles: can tiny nanostructures fight cancer?

    PubMed

    Carrião, Marcus S; Bakuzis, Andris F

    2016-04-21

    The phenomenon of heat dissipation by magnetic materials interacting with an alternating magnetic field, known as magnetic hyperthermia, is an emergent and promising therapy for many diseases, mainly cancer. Here, a magnetic hyperthermia model for core-shell nanoparticles is developed. The theoretical calculation, different from previous models, highlights the importance of heterogeneity by identifying the role of surface and core spins on nanoparticle heat generation. We found that the most efficient nanoparticles should be obtained by selecting materials to reduce the surface to core damping factor ratio, increasing the interface exchange parameter and tuning the surface to core anisotropy ratio for each material combination. From our results we propose a novel heat-based hyperthermia strategy with the focus on improving the heating efficiency of small sized nanoparticles instead of larger ones. This approach might have important implications for cancer treatment and could help improving clinical efficacy.

  14. Ordered shotgun sequencing of a 135 kb Xq25 YAC containing ANT2 and four possible genes, including three confirmed by EST matches.

    PubMed Central

    Chen, C N; Su, Y; Baybayan, P; Siruno, A; Nagaraja, R; Mazzarella, R; Schlessinger, D; Chen, E

    1996-01-01

    Ordered shotgun sequencing (OSS) has been successfully carried out with an Xq25 YAC substrate. yWXD703 DNA was subcloned into lambda phage and sequences of insert ends of the lambda subclones were used to generate a map to select a minimum tiling path of clones to be completely sequenced. The sequence of 135 038 nt contains the entire ANT2 cDNA as well as four other candidates suggested by computer-assisted analyses. One of the putative genes is homologous to a gene implicated in Graves' disease and it, ANT2 and two others are confirmed by EST matches. The results suggest that OSS can be applied to YACs in accord with earlier simulations and further indicate that the sequence of the YAC accurately reflects the sequence of uncloned human DNA. PMID:8918809

  15. Data Reduction and Image Reconstruction Techniques for Non-redundant Masking

    NASA Astrophysics Data System (ADS)

    Sallum, S.; Eisner, J.

    2017-11-01

    The technique of non-redundant masking (NRM) transforms a conventional telescope into an interferometric array. In practice, this provides a much better constrained point-spread function than a filled aperture and thus higher resolution than traditional imaging methods. Here, we describe an NRM data reduction pipeline. We discuss strategies for NRM observations regarding dithering patterns and calibrator selection. We describe relevant image calibrations and use example Large Binocular Telescope data sets to show their effects on the scatter in the Fourier measurements. We also describe the various ways to calculate Fourier quantities, and discuss different calibration strategies. We present the results of image reconstructions from simulated observations where we adjust prior images, weighting schemes, and error bar estimation. We compare two imaging algorithms and discuss implications for reconstructing images from real observations. Finally, we explore how the current state of the art compares to next-generation Extremely Large Telescopes.

  16. Plasticity within stem cell hierarchies in mammalian epithelia.

    PubMed

    Tetteh, Paul W; Farin, Henner F; Clevers, Hans

    2015-02-01

    Tissue homeostasis and regeneration are fueled by resident stem cells that have the capacity to self-renew, and to generate all the differentiated cell types that characterize a particular tissue. Classical models of such cellular hierarchies propose that commitment and differentiation occur unidirectionally, with the arrows 'pointing away' from the stem cell. Recent studies, all based on genetic lineage tracing, describe various strategies employed by epithelial stem cell hierarchies to replace damaged or lost cells. While transdifferentiation from one tissue type into another ('metaplasia') appears to be generally forbidden in nonpathological contexts, plasticity within an individual tissue stem cell hierarchy may be much more common than previously appreciated. In this review, we discuss recent examples of such plasticity in selected mammalian epithelia, highlighting the different modes of regeneration and their implications for our understanding of cellular hierarchy and tissue self-renewal. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Chamber catalogues of optical and fluorescent signatures distinguish bioaerosol classes

    NASA Astrophysics Data System (ADS)

    Hernandez, Mark; Perring, Anne E.; McCabe, Kevin; Kok, Greg; Granger, Gary; Baumgardner, Darrel

    2016-07-01

    Rapid bioaerosol characterization has immediate applications in the military, environmental and public health sectors. Recent technological advances have facilitated single-particle detection of fluorescent aerosol in near real time; this leverages controlled ultraviolet exposures with single or multiple wavelengths, followed by the characterization of associated fluorescence. This type of ultraviolet induced fluorescence has been used to detect airborne microorganisms and their fragments in laboratory studies, and it has been extended to field studies that implicate bioaerosol to compose a substantial fraction of supermicron atmospheric particles. To enhance the information yield that new-generation fluorescence instruments can provide, we report the compilation of a referential aerobiological catalogue including more than 50 pure cultures of common airborne bacteria, fungi and pollens, recovered at water activity equilibrium in a mesoscale chamber (1 m3). This catalogue juxtaposes intrinsic optical properties and select bandwidths of fluorescence emissions, which manifest to clearly distinguish between major classes of airborne microbes and pollens.

  18. Keeping mtDNA in Shape between Generations

    PubMed Central

    Stewart, James B.; Larsson, Nils-Göran

    2014-01-01

    Since the unexpected discovery that mitochondria contain their own distinct DNA molecules, studies of the mitochondrial DNA (mtDNA) have yielded many surprises. In animals, transmission of the mtDNA genome is explicitly non-Mendelian, with a very high number of genome copies being inherited from the mother after a drastic bottleneck. Recent work has begun to uncover the molecular details of this unusual mode of transmission. Many surprising variations in animal mitochondrial biology are known; however, a series of recent studies have identified a core of evolutionarily conserved mechanisms relating to mtDNA inheritance, e.g., mtDNA bottlenecks during germ cell development, selection against specific mtDNA mutation types during maternal transmission, and targeted destruction of sperm mitochondria. In this review, we outline recent literature on the transmission of mtDNA in animals and highlight the implications for human health and ageing. PMID:25299061

  19. Unifying ecology and macroevolution with individual-based theory

    PubMed Central

    Rosindell, James; Harmon, Luke J; Etienne, Rampal S

    2015-01-01

    A contemporary goal in both ecology and evolutionary biology is to develop theory that transcends the boundary between the two disciplines, to understand phenomena that cannot be explained by either field in isolation. This is challenging because macroevolution typically uses lineage-based models, whereas ecology often focuses on individual organisms. Here, we develop a new parsimonious individual-based theory by adding mild selection to the neutral theory of biodiversity. We show that this model generates realistic phylogenies showing a slowdown in diversification and also improves on the ecological predictions of neutral theory by explaining the occurrence of very common species. Moreover, we find the distribution of individual fitness changes over time, with average fitness increasing at a pace that depends positively on community size. Consequently, large communities tend to produce fitter species than smaller communities. These findings have broad implications beyond biodiversity theory, potentially impacting, for example, invasion biology and paleontology. PMID:25818618

  20. Relationships between thermal maturity indices calculated using Arrhenius equation and Lopatin method: implications for petroleum exploration

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

    Wood, D.A.

    1988-02-01

    Thermal maturity can be calculated with time-temperature indices (TTI) based on the Arrhenius equation using kinetics applicable to a range of Types II and III kerogens. These TTIs are compared with TTI calculations based on the Lopatin method and are related theoretically (and empirically via vitrinite reflectance) to the petroleum-generation window. The TTIs for both methods are expressed mathematically as integrals of temperature combined with variable linear heating rates for selected temperature intervals. Heating rates control the thermal-maturation trends of buried sediments. Relative to Arrhenius TTIs, Lopatin TTIs tend to underestimate thermal maturity at high heating rates and overestimate itmore » as low heating rates. Complex burial histories applicable to a range of tectonic environments illustrate the different exploration decisions that might be made on the basis of independent results of these two thermal-maturation models. 15 figures, 8 tables.« less

  1. Attenuated sensitivity to neuroactive steroids in γ-aminobutyrate type A receptor delta subunit knockout mice

    PubMed Central

    Mihalek, Robert M.; Banerjee, Pradeep K.; Korpi, Esa R.; Quinlan, Joseph J.; Firestone, Leonard L.; Mi, Zhi-Ping; Lagenaur, Carl; Tretter, Verena; Sieghart, Werner; Anagnostaras, Stephan G.; Sage, Jennifer R.; Fanselow, Michael S.; Guidotti, Alessandro; Spigelman, Igor; Li, Zhiwei; DeLorey, Timothy M.; Olsen, Richard W.; Homanics, Gregg E.

    1999-01-01

    γ-Aminobutyric acid (GABA) type A receptors mediate fast inhibitory synaptic transmission and have been implicated in responses to sedative/hypnotic agents (including neuroactive steroids), anxiety, and learning and memory. Using gene targeting technology, we generated a strain of mice deficient in the δ subunit of the GABA type A receptors. In vivo testing of various behavioral responses revealed a strikingly selective attenuation of responses to neuroactive steroids, but not to other modulatory drugs. Electrophysiological recordings from hippocampal slices revealed a significantly faster miniature inhibitory postsynaptic current decay time in null mice, with no change in miniature inhibitory postsynaptic current amplitude or frequency. Learning and memory assessed with fear conditioning were normal. These results begin to illuminate the novel contributions of the δ subunit to GABA pharmacology and sedative/hypnotic responses and behavior and provide insights into the physiology of neurosteroids. PMID:10536021

  2. Functional implications of orientation maps in primary visual cortex

    NASA Astrophysics Data System (ADS)

    Koch, Erin; Jin, Jianzhong; Alonso, Jose M.; Zaidi, Qasim

    2016-11-01

    Stimulus orientation in the primary visual cortex of primates and carnivores is mapped as iso-orientation domains radiating from pinwheel centres, where orientation preferences of neighbouring cells change circularly. Whether this orientation map has a function is currently debated, because many mammals, such as rodents, do not have such maps. Here we show that two fundamental properties of visual cortical responses, contrast saturation and cross-orientation suppression, are stronger within cat iso-orientation domains than at pinwheel centres. These differences develop when excitation (not normalization) from neighbouring oriented neurons is applied to different cortical orientation domains and then balanced by inhibition from un-oriented neurons. The functions of the pinwheel mosaic emerge from these local intra-cortical computations: Narrower tuning, greater cross-orientation suppression and higher contrast gain of iso-orientation cells facilitate extraction of object contours from images, whereas broader tuning, greater linearity and less suppression of pinwheel cells generate selectivity for surface patterns and textures.

  3. Parkin and PINK1 function in a vesicular trafficking pathway regulating mitochondrial quality control

    PubMed Central

    McLelland, Gian-Luca; Soubannier, Vincent; Chen, Carol X; McBride, Heidi M; Fon, Edward A

    2014-01-01

    Mitochondrial dysfunction has long been associated with Parkinson's disease (PD). Parkin and PINK1, two genes associated with familial PD, have been implicated in the degradation of depolarized mitochondria via autophagy (mitophagy). Here, we describe the involvement of parkin and PINK1 in a vesicular pathway regulating mitochondrial quality control. This pathway is distinct from canonical mitophagy and is triggered by the generation of oxidative stress from within mitochondria. Wild-type but not PD-linked mutant parkin supports the biogenesis of a population of mitochondria-derived vesicles (MDVs), which bud off mitochondria and contain a specific repertoire of cargo proteins. These MDVs require PINK1 expression and ultimately target to lysosomes for degradation. We hypothesize that loss of this parkin- and PINK1-dependent trafficking mechanism impairs the ability of mitochondria to selectively degrade oxidized and damaged proteins leading, over time, to the mitochondrial dysfunction noted in PD. PMID:24446486

  4. Social inheritance can explain the structure of animal social networks

    PubMed Central

    Ilany, Amiyaal; Akçay, Erol

    2016-01-01

    The social network structure of animal populations has major implications for survival, reproductive success, sexual selection and pathogen transmission of individuals. But as of yet, no general theory of social network structure exists that can explain the diversity of social networks observed in nature, and serve as a null model for detecting species and population-specific factors. Here we propose a simple and generally applicable model of social network structure. We consider the emergence of network structure as a result of social inheritance, in which newborns are likely to bond with maternal contacts, and via forming bonds randomly. We compare model output with data from several species, showing that it can generate networks with properties such as those observed in real social systems. Our model demonstrates that important observed properties of social networks, including heritability of network position or assortative associations, can be understood as consequences of social inheritance. PMID:27352101

  5. Experimental evolution of protozoan traits in response to interspecific competition.

    PubMed

    terHorst, C P

    2011-01-01

    Decades of experiments have demonstrated the ecological effect of competition, but experimental evidence for competitive effects on trait evolution is rare. I measured the evolution of six protozoan traits in response to competitors from the inquiline community of pitcher plants. Replicate populations of Colpoda, a ciliated protozoan, were allowed to evolve in response to intra- and interspecific competition for 20 days (approximately 100 generations), before traits were measured in two common garden environments. Populations that evolved with interspecific competition had smaller cell sizes, produced fewer cysts and had higher population growth rates relative to populations grown in monoculture. The presence of interspecific competitors led to differential lineage sorting, most likely by increasing the strength of selection. These results are the first to demonstrate protozoan evolution in response to competition and may have implications for species coexistence in this system. © 2010 The Author. Journal of Evolutionary Biology © 2010 European Society For Evolutionary Biology.

  6. Cognitive and emotional processes during dreaming: a neuroimaging view.

    PubMed

    Desseilles, Martin; Dang-Vu, Thien Thanh; Sterpenich, Virginie; Schwartz, Sophie

    2011-12-01

    Dream is a state of consciousness characterized by internally-generated sensory, cognitive and emotional experiences occurring during sleep. Dream reports tend to be particularly abundant, with complex, emotional, and perceptually vivid experiences after awakenings from rapid eye movement (REM) sleep. This is why our current knowledge of the cerebral correlates of dreaming, mainly derives from studies of REM sleep. Neuroimaging results show that REM sleep is characterized by a specific pattern of regional brain activity. We demonstrate that this heterogeneous distribution of brain activity during sleep explains many typical features in dreams. Reciprocally, specific dream characteristics suggest the activation of selective brain regions during sleep. Such an integration of neuroimaging data of human sleep, mental imagery, and the content of dreams is critical for current models of dreaming; it also provides neurobiological support for an implication of sleep and dreaming in some important functions such as emotional regulation. Copyright © 2010 Elsevier Inc. All rights reserved.

  7. Parasites as drivers of key processes in aquatic ecosystems: Facts and future directions.

    PubMed

    Sures, B; Nachev, M; Pahl, M; Grabner, D; Selbach, C

    2017-09-01

    Despite the advances in our understanding of the ecological importance of parasites that we have made in recent years, we are still far away from having a complete picture of the ecological implications connected to parasitism. In the present paper we highlight key issues that illustrate (1) important contributions of parasites to biodiversity, (2) their integral role in ecosystems, (3) as well as their ecological effects as keystone species (4) and in biological invasion processes. By using selected examples from aquatic ecosystems we want to provide an insight and generate interest into the topic, and want to show directions for future research in the field of ecological parasitology. This may help to convince more parasitologists and ecologists contributing and advancing our understanding of the complex and fascinating interplay of parasites, hosts and ecosystems. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Effects of environmental sounds on the guessability of animated graphic symbols.

    PubMed

    Harmon, Ashley C; Schlosser, Ralf W; Gygi, Brian; Shane, Howard C; Kong, Ying-Yee; Book, Lorraine; Macduff, Kelly; Hearn, Emilia

    2014-12-01

    Graphic symbols are a necessity for pre-literate children who use aided augmentative and alternative communication (AAC) systems (including non-electronic communication boards and speech generating devices), as well as for mobile technologies using AAC applications. Recently, developers of the Autism Language Program (ALP) Animated Graphics Set have added environmental sounds to animated symbols representing verbs in an attempt to enhance their iconicity. The purpose of this study was to examine the effects of environmental sounds (added to animated graphic symbols representing verbs) in terms of naming. Participants included 46 children with typical development between the ages of 3;0 to 3;11 (years;months). The participants were randomly allocated to a condition of symbols with environmental sounds or a condition without environmental sounds. Results indicated that environmental sounds significantly enhanced the naming accuracy of animated symbols for verbs. Implications in terms of symbol selection, symbol refinement, and future symbol development will be discussed.

  9. Coinfection of Fusobacterium nucleatum and Actinomyces israelii in Mastoiditis Diagnosed by Next-Generation DNA Sequencing

    PubMed Central

    Hoogestraat, Daniel R.; Abbott, April N.; SenGupta, Dhruba J.; Cummings, Lisa A.; Butler-Wu, Susan M.; Stephens, Karen; Cookson, Brad T.; Hoffman, Noah G.

    2014-01-01

    Some bacterial infections involve potentially complex mixtures of species that can now be distinguished using next-generation DNA sequencing. We present a case of mastoiditis where Gram stain, culture, and molecular diagnosis were nondiagnostic or discrepant. Next-generation sequencing implicated coinfection of Fusobacterium nucleatum and Actinomyces israelii, resolving these diagnostic discrepancies. PMID:24574281

  10. The HLA-net GENE[RATE] pipeline for effective HLA data analysis and its application to 145 population samples from Europe and neighbouring areas.

    PubMed

    Nunes, J M; Buhler, S; Roessli, D; Sanchez-Mazas, A

    2014-05-01

    In this review, we present for the first time an integrated version of the Gene[rate] computer tools which have been developed during the last 5 years to analyse human leukocyte antigen (HLA) data in human populations, as well as the results of their application to a large dataset of 145 HLA-typed population samples from Europe and its two neighbouring areas, North Africa and West Asia, now forming part of the Gene[va] database. All these computer tools and genetic data are, from now, publicly available through a newly designed bioinformatics platform, HLA-net, here presented as a main achievement of the HLA-NET scientific programme. The Gene[rate] pipeline offers user-friendly computer tools to estimate allele and haplotype frequencies, to test Hardy-Weinberg equilibrium (HWE), selective neutrality and linkage disequilibrium, to recode HLA data, to convert file formats, to display population frequencies of chosen alleles and haplotypes in selected geographic regions, and to perform genetic comparisons among chosen sets of population samples, including new data provided by the user. Both numerical and graphical outputs are generated, the latter being highly explicit and of publication quality. All these analyses can be performed on the pipeline after scrupulous validation of the population sample's characterisation and HLA typing reporting according to HLA-NET recommendations. The Gene[va] database offers direct access to the HLA-A, -B, -C, -DQA1, -DQB1, -DRB1 and -DPB1 frequencies and summary statistics of 145 population samples having successfully passed these HLA-NET 'filters', and representing three European subregions (South-East, North-East and Central-West Europe) and two neighbouring areas (North Africa, as far as Sudan, and West Asia, as far as South India). The analysis of these data, summarized in this review, shows a substantial genetic variation at the regional level in this continental area. These results have main implications for population genetics, transplantation and epidemiological studies. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. High-power, cladding-pumped all-fiber laser with selective transverse mode generation property.

    PubMed

    Li, Lei; Wang, Meng; Liu, Tong; Leng, Jinyong; Zhou, Pu; Chen, Jinbao

    2017-06-10

    We demonstrate, to the best of our knowledge, the first cladding-pumped all-fiber oscillator configuration with selective transverse mode generation based on a mode-selective fiber Bragg grating pair. Operating in the second-order (LP 11 ) mode, maximum output power of 4.2 W is obtained with slope efficiency of about 38%. This is the highest reported output power of single higher-order transverse mode generation in an all-fiber configuration. The intensity distribution profile and spectral evolution have also been investigated in this paper. Our work suggests the potential of realizing higher power with selective transverse mode operation based on a mode-selective fiber Bragg grating pair.

  12. Implications of high-spatial-resolution thermal infrared (Termoskan) data for Mars landing site selection

    NASA Technical Reports Server (NTRS)

    Betts, Bruce H.

    1994-01-01

    Thermal infrared observations of Mars from spacecraft provide physical information about the upper thermal skin depth of the surface, which is on the order of a few centimeters in depth and thus very significant for lander site selection. The Termoskan instrument onboard the Soviet Phobos '88 spacecraft acquired the highest spatial-resolution thermal infrared data obtained for Mars, ranging in resolution from 300 m to 3 km per pixel. It simultaneously obtained broadband reflected solar flux data. Although the 6 deg N - 30 deg S Termoskan coverage only slightly overlaps the nominal Mars Pathfinder target range, the implications of Termoskan data for that overlap region and the extrapolations that can be made to other regions give important clues for optimal landing site selection.

  13. Maternal Exposure to Childhood Abuse is Associated with Mate Selection: Implications for Autism in Offspring.

    PubMed

    Roberts, Andrea L; Lyall, Kristen; Weisskopf, Marc G

    2017-07-01

    Maternal experience of childhood abuse has been associated with offspring autism. To explore whether familial tendency towards autistic traits-presumably related to genetic predisposition-accounts for this association, we examined whether women who experienced childhood abuse were more likely to select mates with high levels of autistic traits, and whether parental autistic traits accounted for the association of maternal abuse and offspring autism in 209 autism cases and 833 controls. Maternal childhood abuse was strongly associated with high paternal autistic traits (severe abuse, OR = 3.98, 95% CI = 1.26, 8.31). Maternal and paternal autistic traits accounted for 21% of the association between maternal abuse and offspring autism. These results provide evidence that childhood abuse affects mate selection, with implications for offspring health.

  14. Early generation selection results from a two year, six location study

    USDA-ARS?s Scientific Manuscript database

    In potato breeding programs, early generation selections are rarely evaluated in multiple environments because of limited seed quantities. By the time seed quantities are available, few clones remain from the original population. The purpose of this study was to allow multiple locations to select ...

  15. Selective Attention and Control of Action: Comparative Psychology of an Artificial, Evolved Agent and People

    ERIC Educational Resources Information Center

    Ward, Robert; Ward, Ronnie

    2008-01-01

    This study examined the selective attention abilities of a simple, artificial, evolved agent and considered implications of the agent's performance for theories of selective attention and action. The agent processed two targets in continuous time, catching one and then the other. This task required many cognitive operations, including prioritizing…

  16. Unselective Overimitators: The Evolutionary Implications of Children's Indiscriminate Copying of Successful and Prestigious Models

    ERIC Educational Resources Information Center

    Chudek, Maciej; Baron, Andrew S.; Birch, Susan

    2016-01-01

    Children are both shrewd about whom to copy--they selectively learn from certain adults--and overimitators--they copy adults' obviously superfluous actions. Is overimitation also selective? Does selectivity change with age? In two experiments, 161 two- to seven-year-old children saw videos of one adult receiving better payoffs or more bystander…

  17. Selecting for Creativity and Innovation Potential: Implications for Practice in Healthcare Education

    ERIC Educational Resources Information Center

    Patterson, Fiona; Zibarras, Lara Dawn

    2017-01-01

    The ability to innovate is an important requirement in many organisations. Despite this pressing need, few selection systems in healthcare focus on identifying the potential for creativity and innovation and so this area has been vastly under-researched. As a first step towards understanding how we might select for creativity and innovation, this…

  18. The Construct Validity of HPAT-Ireland for the Selection of Medical Students: Unresolved Issues and Future Research Implications

    ERIC Educational Resources Information Center

    Kelly, Maureen E.; O'Flynn, Siun

    2017-01-01

    Aptitude tests are widely used in selection. However, despite certain advantages their use remains controversial. This paper aims to critically appraise five sources of evidence for the construct validity of the Health Professions Admission Test (HPAT)-Ireland, an aptitude test used for selecting undergraduate medical students. The objectives are…

  19. Perceived Indices of Truancy among Selected Adolescents in Oyo Town: Implications for Behavioural Change

    ERIC Educational Resources Information Center

    Adika, Lawrence Olagoke

    2016-01-01

    The study investigated perceived indices of truancy behaviour among selected adolescents in Oyo town. The descriptive survey study had 200 randomly selected adolescents from five secondary schools in Oyo town. A self-designed instrument tagged Adolescent Truancy Scale (ATS) was employed in collecting data for the study and the data was subjected…

  20. Piecing together stakeholder puzzles-puzzling about (opioid substitute treatment---OST) stakeholders and their pieces: a rambling point-of-view.

    PubMed

    Einstein, Stan

    2013-08-01

    This point-of-view presentation explores "stakeholders" and "opioid substitute treatment," their dimensions, selected enabling necessary conditions to operate, or not, implications, and consequences from a range of selected perspectives.

  1. The genetic basis of traits regulating sperm competition and polyandry: can selection favour the evolution of good- and sexy-sperm?

    PubMed

    Evans, Jonathan P; Simmons, Leigh W

    2008-09-01

    The good-sperm and sexy-sperm (GS-SS) hypotheses predict that female multiple mating (polyandry) can fuel sexual selection for heritable male traits that promote success in sperm competition. A major prediction generated by these models, therefore, is that polyandry will benefit females indirectly via their sons' enhanced fertilization success. Furthermore, like classic 'good genes' and 'sexy son' models for the evolution of female preferences, GS-SS processes predict a genetic correlation between genes for female mating frequency (analogous to the female preference) and those for traits influencing fertilization success (the sexually selected traits). We examine the premise for these predictions by exploring the genetic basis of traits thought to influence fertilization success and female mating frequency. We also highlight recent debates that stress the possible genetic constraints to evolution of traits influencing fertilization success via GS-SS processes, including sex-linked inheritance, nonadditive effects, interacting parental genotypes, and trade-offs between integrated ejaculate components. Despite these possible constraints, the available data suggest that male traits involved in sperm competition typically exhibit substantial additive genetic variance and rapid evolutionary responses to selection. Nevertheless, the limited data on the genetic variation in female mating frequency implicate strong genetic maternal effects, including X-linkage, which is inconsistent with GS-SS processes. Although the relative paucity of studies on the genetic basis of polyandry does not allow us to draw firm conclusions about the evolutionary origins of this trait, the emerging pattern of sex linkage in genes for polyandry is more consistent with an evolutionary history of antagonistic selection over mating frequency. We advocate further development of GS-SS theory to take account of the complex evolutionary dynamics imposed by sexual conflict over mating frequency.

  2. Gating transitions in the selectivity filter region of a sodium channel are coupled to the domain IV voltage sensor.

    PubMed

    Capes, Deborah L; Arcisio-Miranda, Manoel; Jarecki, Brian W; French, Robert J; Chanda, Baron

    2012-02-14

    Voltage-dependent ion channels are crucial for generation and propagation of electrical activity in biological systems. The primary mechanism for voltage transduction in these proteins involves the movement of a voltage-sensing domain (D), which opens a gate located on the cytoplasmic side. A distinct conformational change in the selectivity filter near the extracellular side has been implicated in slow inactivation gating, which is important for spike frequency adaptation in neural circuits. However, it remains an open question whether gating transitions in the selectivity filter region are also actuated by voltage sensors. Here, we examine conformational coupling between each of the four voltage sensors and the outer pore of a eukaryotic voltage-dependent sodium channel. The voltage sensors of these sodium channels are not structurally symmetric and exhibit functional specialization. To track the conformational rearrangements of individual voltage-sensing domains, we recorded domain-specific gating pore currents. Our data show that, of the four voltage sensors, only the domain IV voltage sensor is coupled to the conformation of the selectivity filter region of the sodium channel. Trapping the outer pore in a particular conformation with a high-affinity toxin or disulphide crossbridge impedes the return of this voltage sensor to its resting conformation. Our findings directly establish that, in addition to the canonical electromechanical coupling between voltage sensor and inner pore gates of a sodium channel, gating transitions in the selectivity filter region are also coupled to the movement of a voltage sensor. Furthermore, our results also imply that the voltage sensor of domain IV is unique in this linkage and in the ability to initiate slow inactivation in sodium channels.

  3. The response to selection for broad male response to female sex pheromone and its implications for divergence in close-range mating behavior in the European corn borer moth, Ostrinia nubilalis.

    PubMed

    Droney, David C; Musto, Callie J; Mancuso, Katie; Roelofs, Wendell L; Linn, Charles E

    2012-12-01

    Coordinated sexual communication systems, seen in many species of moths, are hypothesized to be under strong stabilizing natural selection. Stabilized communication systems should be resistant to change, but there are examples of species/populations that show great diversification. A possible solution is that it is directional sexual selection on variation in male response that drives evolution. We tested a component of this model by asking whether 'rare' males (ca. 5 % of all males in a population) of the European corn borer moth (ECB), Ostrinia nubilalis, that respond to the sex pheromones of both ECB and a different Ostrinia species (O. furnacalis, the Asian corn borer, ACB), might play an important role in diversification. We specifically tested, via artificial selection, whether this broad male response has an evolvable genetic component. We increased the frequency of broad male response from 5 to 70 % in 19 generations, showing that broad-responding males could be important for the evolution of novel communication systems in ECB. We did not find a broader range of mating acceptance of broad males by females of the base population, however, suggesting that broad response would be unlikely to increase in frequency without the involvement of other factors. However, we found that ECB selection-line females accepted a broader range of courting males, including those of ACB, than did females of the base population. Thus, a genetic correlation exists between broad, long-range response to female sex pheromone and the breadth of female acceptance of males at close range. These results are discussed in the context of evolution of novel communication systems in Ostrinia.

  4. Minimal Pharmacophoric Elements and Fragment Hopping, an Approach Directed at Molecular Diversity and Isozyme Selectivity. Design of Selective Neuronal Nitric Oxide Synthase Inhibitors

    PubMed Central

    Ji, Haitao; Stanton, Benjamin Z.; Igarashi, Jotaro; Li, Huiying; Martásek, Pavel; Roman, Linda J.; Poulos, Thomas L.; Silverman, Richard B.

    2010-01-01

    Fragment hopping, a new fragment-based approach for de novo inhibitor design focusing on ligand diversity and isozyme selectivity, is described. The core of this approach is the derivation of the minimal pharmacophoric element for each pharmacophore. Sites for both ligand binding and isozyme selectivity are considered in deriving the minimal pharmacophoric elements. Five general-purpose libraries are established: the basic fragment library, the bioisostere library, the rules for metabolic stability, the toxicophore library, and the side chain library. These libraries are employed to generate focused fragment libraries to match the minimal pharmacophoric elements for each pharmacophore and then to link the fragment to the desired molecule. This method was successfully applied to neuronal nitric oxide synthase (nNOS), which is implicated in stroke and neurodegenerative diseases. Starting with the nitroarginine-containing dipeptide inhibitors we developed previously, a small organic molecule with a totally different chemical structure was designed, which showed nanomolar nNOS inhibitory potency and more than 1000-fold nNOS selectivity. The crystallographic analysis confirms that the small organic molecule with a constrained conformation can exactly mimic the mode of action of the dipeptide nNOS inhibitors. Therefore, a new peptidomimetic strategy, referred to as fragment hopping, which creates small organic molecules that mimic the biological function of peptides by a pharmacophore-driven strategy for fragment-based de novo design, has been established as a new type of fragment-based inhibitor design. As an open system, the newly established approach efficiently incorporates the concept of early “ADME/Tox” considerations and provides a basic platform for medicinal chemistry-driven efforts. PMID:18321097

  5. Survival ability of Mexican fruit fly males from different strains in presence of the predatory orb-weaving spider Argiope argentata (Araneae: Araneidae).

    PubMed

    Dor, A; Liedo, P

    2018-04-18

    The sterile insect technique (SIT) is a key element for the integrated management of pest populations of the Mexican fruit fly, Anastrepha ludens, in Mexico. Its success depends on the survival of mass-reared sterile males and their ability to mate with wild females. However, colonization and mass-rearing conditions can adversely affect their ability to avoid predators. To test if colony management strategies could contribute to improve field survival abilities of mass-reared flies, we compared the survival of males exposed to the orb-weaver spider Argiope argentata. Males compared originated from three strains with different colonization strategies: (a) a colony started from field-collected wild flies (replacement), (b) a colony started by hybridizing wild males with mass-reared adapted females (hybrid) and (c) a colony started with mass-reared males selected on the basis of their survival ability and mating competitiveness in field cages (selected). Mass-reared males and wild males were used as controls. Males were exposed to spiders under laboratory cage conditions. Overall, wild males showed better survival ability than mass-reared males. Regarding the colonization approach, wild males survived better than a hybrid, replaced and selected males. We conclude that mass-rearing conditions have a strong negative effect on the ability of males to escape spiders. The colonization systems evaluated did not counter this effect. The lower survival of males from the selected colony suggests that the selection over one generation did not contribute to improve males' predator avoidance and escape abilities and probably needs to be modified. Possible explanations for this and implications on colonization and colony management for SIT purpose are discussed.

  6. Can Adults Who Have Recovered from Selective Mutism in Childhood and Adolescence Tell Us Anything about the Nature of the Condition and/or Recovery from It?

    ERIC Educational Resources Information Center

    Omdal, Heidi

    2007-01-01

    The literature on selective mutism provides little information on the child's own perspective. Six adults who had been selectively mute were interviewed about their childhood and adolescence. Data analysis led to identification of five themes, each of which has potentially important implications for teachers. (1) Origins of selective mutism: all…

  7. NGSS and the Next Generation of Science Teachers

    ERIC Educational Resources Information Center

    Bybee, Rodger W.

    2014-01-01

    This article centers on the "Next Generation Science Standards" (NGSS) and their implications for teacher development, particularly at the undergraduate level. After an introduction to NGSS and the influence of standards in the educational system, the article addresses specific educational shifts--interconnecting science and engineering…

  8. The selection of creative ideas after individual idea generation: choosing between creativity and impact.

    PubMed

    Rietzschel, Eric F; Nijstad, Bernard A; Stroebe, Wolfgang

    2010-02-01

    It is commonly assumed that successful innovation depends on creative idea generation: the more ideas are generated, the higher the probability of selecting a very good idea should be. However, research has shown that people do not perform optimally at idea selection and that ideational output may not contribute much to creative idea selection. The present studies aim to explain this phenomenon. We identified the strong tendency of our participants to select feasible and desirable ideas, at the cost of originality, as the main reason for their poor selection performance. Two manipulations of participants' processing of the available ideas (exclusion instructions and quality ratings) had no effect on selection effectiveness. In contrast, explicitly instructing participants to select creative or original ideas did improve selection effectiveness with regard to idea originality, but at the same time decreased participants' satisfaction and the rated effectiveness of chosen ideas. Results are discussed in relation to an effectiveness-originality trade off.

  9. Ablation of SLP-76 signaling after T cell priming generates memory CD4 T cells impaired in steady-state and cytokine-driven homeostasis.

    PubMed

    Bushar, Nicholas D; Corbo, Evann; Schmidt, Michelle; Maltzman, Jonathan S; Farber, Donna L

    2010-01-12

    The intracellular signaling mechanisms regulating the generation and long-term persistence of memory T cells in vivo remain unclear. In this study, we used mouse models with conditional deletion of the key T cell receptor (TCR)-coupled adaptor molecule SH2-domain-containing phosphoprotein of 76 kDa (SLP-76), to analyze signaling mechanisms for memory CD4 T cell generation, maintenance, and homeostasis. We found that ablation of SLP-76 expression after T cell priming did not inhibit generation of phenotypic effector or memory CD4 T cells; however, the resultant SLP-76-deficient memory CD4 T cells could not produce recall cytokines in response to TCR-mediated stimulation and showed decreased persistence in vivo. In addition, SLP-76-deficient memory CD4 T cells exhibited reduced steady-state homeostasis and were impaired in their ability to homeostatically expand in vivo in response to the gamma(c) cytokine IL-7, despite intact proximal signaling through the IL-7R-coupled JAK3/STAT5 pathway. Direct in vivo deletion of SLP-76 in polyclonal memory CD4 T cells likewise led to impaired steady-state homeostasis as well as impaired homeostatic responses to IL-7. Our findings demonstrate a dominant role for SLP-76-dependent TCR signals in regulating turnover and perpetuation of memory CD4 T cells and their responses to homeostatic cytokines, with implications for the selective survival of memory CD4 T cells following pathogen exposure, vaccination, and aging.

  10. Structural alterations by five disease-causing mutations in the low-pH conformation of human dihydrolipoamide dehydrogenase (hLADH) analyzed by molecular dynamics - Implications in functional loss and modulation of reactive oxygen species generation by pathogenic hLADH forms.

    PubMed

    Ambrus, Attila; Mizsei, Reka; Adam-Vizi, Vera

    2015-07-01

    Human dihydrolipoamide dehydrogenase (hLADH) is a flavoenzyme component (E3) of the human alpha-ketoglutarate dehydrogenase complex (α-KGDHc) and few other dehydrogenase complexes. Pathogenic mutations of hLADH cause severe metabolic diseases (atypical forms of E3 deficiency) that often escalate to cardiological or neurological presentations and even premature death; the pathologies are generally accompanied by lactic acidosis. hLADH presents a distinct conformation under acidosis (pH 5.5-6.8) with lower physiological activity and the capacity of generating reactive oxygen species (ROS). It has been shown by our laboratory that selected pathogenic mutations, besides lowering the physiological activity of hLADH, significantly stimulate ROS generation by hLADH, especially at lower pH, which might play a role in the pathogenesis of E3-deficiency in respective cases. Previously, we generated by molecular dynamics (MD) simulation the low-pH hLADH structure and analyzed the structural changes induced in this structure by eight of the pathogenic mutations of hLADH. In the absence of high resolution mutant structures these pieces of information are crucial for the mechanistic investigation of the molecular pathogeneses of the hLADH protein. In the present work we analyzed by molecular dynamics simulation the structural changes induced in the low-pH conformation of hLADH by five pathogenic mutations of hLADH; the structures of these disease-causing mutants of hLADH have never been examined before.

  11. COMPREHENSIVE ANALYSIS OF BIOLOGICALLY RELEVANT ARSENICALS BY PH-SELECTIVE HYDRIDE GENERATION-ATOMIC ABSORPTION SPECTROMETRY

    EPA Science Inventory


    A method based on pH-selective generation and separation of arsines is commonly used for analysis of inorganic, methylated, and dimethylated trivalent and pentavalent arsenicals by hydride generation-atomic absorption spectrometry (HG-AAS). We have optimized this method to pe...

  12. When does a strategy intervention overcome a failure of inhibition? Evidence from two left frontal brain tumour cases.

    PubMed

    Robinson, Gail A; Walker, David G; Biggs, Vivien; Shallice, Tim

    2016-06-01

    Initiation and inhibition of responses are crucial for appropriate behaviour across different settings. Initiation and inhibition difficulties are well documented following frontal damage, although task differences have limited our understanding. The Hayling Sentence Completion Test was designed to assess verbal initiation and inhibition within the same task. This study investigates the ability of two patients with left frontal tumours (KI: high grade glioma; PM: meningioma) to use a strategy to overcome profound suppression failures on the Hayling Test. KI and PM completed the Hayling Test and two experimental tasks. The Selection Investigation assessed verbal initiation on a sentence completion task that varied selection demands (high/low). The Suppression and Strategy Investigation assessed ability to implement four strategies aimed to override a suppression failure and facilitate production of an unconnected word. On the Hayling Test, KI and PM initiated responses to complete high constraint sentences, in contrast to impaired suppression. KI benefitted minimally from strategies to overcome suppression failure although one strategy (object naming) was partially successful. KI's errors revealed fast suppression errors, in contrast to slow no responses, and selection ability was also impaired for verbal initiation. PM, however, implemented each strategy 100% to overcome a suppression failure and had no difficulty completing sentences meaningfully, regardless of selection demands. This first investigation of strategy implementation to overcome profound suppression impairments provides insights into verbal initiation, inhibition, selection and strategy mechanisms, which has implications for neurorehabilitation. Specifically, both patients had profound inhibition deficits but KI also presented with a selection deficit and was unable to implement a strategy. By contrast, PM's selection ability was intact but she was unable to generate, rather than implement, a strategy. We suggest that KI has both fast, uncontrolled semantic output and response inhibition difficulty, whereas PM's difficulty is underpinned by motivational factors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Positive Selection Underlies Faster-Z Evolution of Gene Expression in Birds.

    PubMed

    Dean, Rebecca; Harrison, Peter W; Wright, Alison E; Zimmer, Fabian; Mank, Judith E

    2015-10-01

    The elevated rate of evolution for genes on sex chromosomes compared with autosomes (Fast-X or Fast-Z evolution) can result either from positive selection in the heterogametic sex or from nonadaptive consequences of reduced relative effective population size. Recent work in birds suggests that Fast-Z of coding sequence is primarily due to relaxed purifying selection resulting from reduced relative effective population size. However, gene sequence and gene expression are often subject to distinct evolutionary pressures; therefore, we tested for Fast-Z in gene expression using next-generation RNA-sequencing data from multiple avian species. Similar to studies of Fast-Z in coding sequence, we recover clear signatures of Fast-Z in gene expression; however, in contrast to coding sequence, our data indicate that Fast-Z in expression is due to positive selection acting primarily in females. In the soma, where gene expression is highly correlated between the sexes, we detected Fast-Z in both sexes, although at a higher rate in females, suggesting that many positively selected expression changes in females are also expressed in males. In the gonad, where intersexual correlations in expression are much lower, we detected Fast-Z for female gene expression, but crucially, not males. This suggests that a large amount of expression variation is sex-specific in its effects within the gonad. Taken together, our results indicate that Fast-Z evolution of gene expression is the product of positive selection acting on recessive beneficial alleles in the heterogametic sex. More broadly, our analysis suggests that the adaptive potential of Z chromosome gene expression may be much greater than that of gene sequence, results which have important implications for the role of sex chromosomes in speciation and sexual selection. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  14. An analysis of the determinants of HMO reenrollment behavior: implications for theory and policy.

    PubMed

    Scotti, D J; Bonner, P G; Wiman, A R

    1986-06-01

    Understanding the evaluative criteria used to select a health plan is central to effective marketing of an HMO. The determinant criteria that guide the reenrollment decision are shown to differ from those that drive initial enrollment. The authors' findings suggest several operational and strategic policy implications for HMO management.

  15. Grading A-Level Double Subject Mathematicians and the Implications for Selection.

    ERIC Educational Resources Information Center

    Newbould, Charles A.

    1981-01-01

    Test data were used to compare the grading of two forms of double mathematics: pure and applied math, and regular and advanced math. Results confirm expectations that in the former system, the grading is comparable, and in the latter, it is not necessarily comparable. Implications for student admission are discussed. (MSE)

  16. Designing Critique for Knowledge Integration

    NASA Astrophysics Data System (ADS)

    Sato, Mie Elissa

    Generating explanations is central to science and has the potential to have a powerful impact on students' conceptual understanding in science instruction. However, improving conceptual understanding by generating explanations is a fraught affair: students may struggle with the sense of false clarity that may arise from generating explanations, fail to detect gaps in their understanding, and dismiss salient information that contradict their beliefs. Critiquing explanations has the potential to counteract these pitfalls by exposing students to alternative ideas to contrast with their own. This dissertation seeks to clarify how to design critique in technology-enhanced science instruction to support students in revising their explanations about scientific phenomena, and in doing so, refining their conceptual understanding. Using the Knowledge Integration framework, I revised two technology-enhanced curriculum units, Plate Tectonics and Global Climate Change, in a design partnership between teachers, researchers, and technologists. I conducted a series of studies with sixth-grade students to investigate the conditions under which guided critique of explanations can support revision. The pilot critique study investigated the impact of the revised Plate Tectonics unit on students' understanding of convection, as well as of a preliminary design of critique where students generated and applied their own criteria for what makes a good explanation in science. The guidance study explored how incorporating a complex selection task that features meta-explanatory criteria into critique supports students in distinguishing among different criteria, as well as how students use peer or expert guidance on their initial explanation during revision. The critique study investigated how designing critique with a complex selection task that features plausible alternative ideas and giving guidance on students' critiques support students in distinguishing among a range of relevant ideas and making productive revisions to their initial explanations. These studies clarify how critique can be designed to help students sort through various ideas in their conceptual repertoire, be they ideas about meta-explanatory criteria or science ideas about a specific phenomenon. The study findings illuminate the challenges of guiding students to examine or re-examine the full range of ideas for knowledge integration. Students struggle to identify salient, missing, or normative ideas in their own or another explanation, and to incorporate their insights in a coherent way through revision. The studies demonstrate that embedding complex selection tasks in critique encourages students to consider a broad range of ideas and supports them in making conceptual revisions of their explanations. The results have implications for the design of critique in technology-enhanced science instruction.

  17. Force sensor

    DOEpatents

    Grahn, A.R.

    1993-05-11

    A force sensor and related method for determining force components is described. The force sensor includes a deformable medium having a contact surface against which a force can be applied, a signal generator for generating signals that travel through the deformable medium to the contact surface, a signal receptor for receiving the signal reflected from the contact surface, a generation controller, a reception controller, and a force determination apparatus. The signal generator has one or more signal generation regions for generating the signals. The generation controller selects and activates the signal generation regions. The signal receptor has one or more signal reception regions for receiving signals and for generating detections signals in response thereto. The reception controller selects signal reception regions and detects the detection signals. The force determination apparatus measures signal transit time by timing activation and detection and, optionally, determines force components for selected cross-field intersections. The timer which times by activation and detection can be any means for measuring signal transit time. A cross-field intersection is defined by the overlap of a signal generation region and a signal reception region.

  18. Force sensor

    DOEpatents

    Grahn, Allen R.

    1993-01-01

    A force sensor and related method for determining force components. The force sensor includes a deformable medium having a contact surface against which a force can be applied, a signal generator for generating signals that travel through the deformable medium to the contact surface, a signal receptor for receiving the signal reflected from the contact surface, a generation controller, a reception controller, and a force determination apparatus. The signal generator has one or more signal generation regions for generating the signals. The generation controller selects and activates the signal generation regions. The signal receptor has one or more signal reception regions for receiving signals and for generating detections signals in response thereto. The reception controller selects signal reception regions and detects the detection signals. The force determination apparatus measures signal transit time by timing activation and detection and, optionally, determines force components for selected cross-field intersections. The timer which times by activation and detection can be any means for measuring signal transit time. A cross-field intersection is defined by the overlap of a signal generation region and a signal reception region.

  19. Sensor Selection and Data Validation for Reliable Integrated System Health Management

    NASA Technical Reports Server (NTRS)

    Garg, Sanjay; Melcher, Kevin J.

    2008-01-01

    For new access to space systems with challenging mission requirements, effective implementation of integrated system health management (ISHM) must be available early in the program to support the design of systems that are safe, reliable, highly autonomous. Early ISHM availability is also needed to promote design for affordable operations; increased knowledge of functional health provided by ISHM supports construction of more efficient operations infrastructure. Lack of early ISHM inclusion in the system design process could result in retrofitting health management systems to augment and expand operational and safety requirements; thereby increasing program cost and risk due to increased instrumentation and computational complexity. Having the right sensors generating the required data to perform condition assessment, such as fault detection and isolation, with a high degree of confidence is critical to reliable operation of ISHM. Also, the data being generated by the sensors needs to be qualified to ensure that the assessments made by the ISHM is not based on faulty data. NASA Glenn Research Center has been developing technologies for sensor selection and data validation as part of the FDDR (Fault Detection, Diagnosis, and Response) element of the Upper Stage project of the Ares 1 launch vehicle development. This presentation will provide an overview of the GRC approach to sensor selection and data quality validation and will present recent results from applications that are representative of the complexity of propulsion systems for access to space vehicles. A brief overview of the sensor selection and data quality validation approaches is provided below. The NASA GRC developed Systematic Sensor Selection Strategy (S4) is a model-based procedure for systematically and quantitatively selecting an optimal sensor suite to provide overall health assessment of a host system. S4 can be logically partitioned into three major subdivisions: the knowledge base, the down-select iteration, and the final selection analysis. The knowledge base required for productive use of S4 consists of system design information and heritage experience together with a focus on components with health implications. The sensor suite down-selection is an iterative process for identifying a group of sensors that provide good fault detection and isolation for targeted fault scenarios. In the final selection analysis, a statistical evaluation algorithm provides the final robustness test for each down-selected sensor suite. NASA GRC has developed an approach to sensor data qualification that applies empirical relationships, threshold detection techniques, and Bayesian belief theory to a network of sensors related by physics (i.e., analytical redundancy) in order to identify the failure of a given sensor within the network. This data quality validation approach extends the state-of-the-art, from red-lines and reasonableness checks that flag a sensor after it fails, to include analytical redundancy-based methods that can identify a sensor in the process of failing. The focus of this effort is on understanding the proper application of analytical redundancy-based data qualification methods for onboard use in monitoring Upper Stage sensors.

  20. MARINE LEECH ANTICOAGULANT DIVERSITY AND EVOLUTION.

    PubMed

    Tessler, Michael; Marancik, David; Champagne, Donald; Dove, Alistair; Camus, Alvin; Siddall, Mark E; Kvist, Sebastian

    2018-03-16

    Leeches (Annelida: Hirudinea) possess powerful salivary anticoagulants and, accordingly, are frequently employed in modern, authoritative medicine. Members of the almost exclusively marine family Piscicolidae account for 20% of leech species diversity, and feed on host groups (e.g., sharks) not encountered by their freshwater and terrestrial counterparts. Moreover, some species of Ozobranchidae feed on endangered marine turtles and have been implicated as potential vectors for the tumor-associated turtle herpesvirus. In spite of their ecological importance and unique host associations, there is a distinct paucity of data regarding the salivary transcriptomes of either of these families. Using next generation sequencing, we profiled transcribed, putative anticoagulants and other salivary bioactive compounds that have previously been linked to bloodfeeding from 7 piscicolid species (3 elasmobranch-feeders; 4 non-cartilaginous fish-feeders) and 1 ozobranchid species (2 samples). In total, 149 putative anticoagulants and bioactive loci were discovered in varying constellations throughout the different samples. The putative anticoagulants showed a broad spectrum of described antagonistic pathways, such as inhibition of factor Xa and platelet aggregation, that likely have similar bioactive roles in marine fish and turtles. A transcript with homology to ohanin, originally isolated from king cobras, was found in Cystobranchus vividus but is otherwise unknown from leeches. Estimation of selection pressures for the putative anticoagulants recovered evidence for both positive and purifying selection along several isolated branches in the gene trees and positive selection was also estimated for a few select codons in a variety of marine species. Similarly, phylogenetic analyses of the amino acid sequences for several anticoagulants indicated divergent evolution.

  1. Pedagogical Beliefs in Work-Based Learning: An Analysis and Implications of Teachers' Belief Orientations

    ERIC Educational Resources Information Center

    Abukari, Abdulai

    2014-01-01

    This paper presents findings of a research project that aimed to critically examine the pedagogical beliefs of work-based learning teachers, and their potential implication on practice and expectations of learners and employers. Based on an online tool, qualitative and quantitative (descriptive) data were generated from a purposive sample of some…

  2. Toward an Integral Approach for Evolving Mindsets for Generative Learning and Timely Action in the Midst of Ambiguity

    ERIC Educational Resources Information Center

    Yorks, Lyle; Nicolaides, Aliki

    2013-01-01

    Background/Context: The implications of complexity theory have become a recurring topic in the literatures of a wide range of scholarly and professional fields including adult education. This paper builds on literature calling attention to the educational need for pedagogically addressing the implications of the intensifying complexity in the…

  3. An Exploratory Analysis of a Middle School Science Curriculum: Implications for Students with Learning Disabilities

    ERIC Educational Resources Information Center

    Taylor, Gregory S.; Hord, Casey

    2016-01-01

    An exploratory study of a middle school curriculum directly aligned with the Next Generation Science Standards was conducted with a focus on how the curriculum addresses the instructional needs of students with learning disabilities. A descriptive analysis of a lesson on speed and velocity was conducted and implications discussed for students with…

  4. Implications of Lower Natural Gas Prices for Electric Generators in the Southeast, The

    EIA Publications

    2009-01-01

    This supplement to the Energy Information Administration's (EIA) May 2009 Short-Term Energy Outlook (STEO) focuses on changes in the utilization of coal- and natural-gas-fired generation capacity in the electric utility sector as the differential between delivered fuel prices narrows.

  5. Towards evenly distributed grazing patterns: including social context in sheep management strategies.

    PubMed

    di Virgilio, Agustina; Morales, Juan Manuel

    2016-01-01

    Background. A large proportion of natural grasslands around the world is exposed to overgrazing resulting in land degradation and biodiversity loss. Although there is an increasing effort in the promotion of sustainable livestock management, rangeland degradation still occurs because animals' foraging behaviour is highly selective at different spatial scales. The assessment of the ecological mechanisms modulating the spatial distribution of grazing and how to control it has critical implications for long term conservation of resources and the sustainability of livestock production. Considering the relevance of social interactions on animals' space use patterns, our aim was to explore the potential effects of including animals' social context into management strategies using domestic sheep grazing in rangelands as case study. Methods. We used GPS data from 19 Merino sheep (approximately 10% of the flock) grazing on three different paddocks (with sizes from 80 to 1000 Ha) during a year, to estimate resource selection functions of sheep grazing in flocks of different levels of heterogeneity. We assessed the effects of sheep class (i.e., ewes, wethers, and hoggets), age, body condition and time since release on habitat selection patterns. Results. We found that social rank was reflected on sheep habitat use, where dominant individuals (i.e., reproductive females) used more intensively the most preferred areas and low-ranked (i.e., yearlings) used less preferred areas. Our results showed that when sheep grazed on more heterogeneous flocks, grazing patterns were more evenly distributed at all the paddocks considered in this study. On the other hand, when high-ranked individuals were removed from the flock, low-ranked sheep shifted their selection patterns by increasing the use of the most preferred areas and strongly avoided to use less preferred sites (i.e., a highly selective grazing behaviour). Discussion. Although homogenization and segregation of flocks by classes are common practices to increase flock productivity, we are proposing an alternative that employs behavioural interactions in heterogeneous flocks to generate more evenly distributed grazing patterns. This practice can be combined with other practices such as rotational grazing and guardian dogs (to decrease mortality levels that may be generated by sheep grazing on more risky habitats). This does not imply any modifications of livestock stocking rates and densities or any additional investments for labour and materials. Considering livestock behaviour is critical for the design of sustainable management practices that balance landscape conservation and livestock productivity.

  6. Geographic consistency and variation in conflicting selection generated by pollinators and seed predators.

    PubMed

    Sun, Shi-Guo; Armbruster, W Scott; Huang, Shuang-Quan

    2016-08-01

    Floral traits that attract pollinators may also attract seed predators, which, in turn, may generate conflicting natural selection on such traits. Although such selection trade-offs are expected to vary geographically, few studies have investigated selection mediated by pollinators and seed predators across a geographic mosaic of environments and floral variation. Floral traits were investigated in 14 populations of the bumble-bee-pollinated herb, Pedicularis rex, in which tubular flowers are subtended by cupular bracts holding rain water. To study potentially conflicting selection on floral traits generated by pollinators and florivores, stigmatic pollen loads, initial seed set, pre-dispersal seed predation and final viable seed production were measured in 12-14 populations in the field. Generalized Linear Model (GLM) analyses indicated that the pollen load on stigmas was positively related to the exsertion of the corolla beyond the cupular bracts and size of the lower corolla lip, but so too was the rate of seed predation, creating conflicting selection on both floral traits. A geographic mosaic of selection mediated by seed predators, but not pollinators, was indicated by significant variation in levels of seed predation and the inclusion of two-, three- and four-way interaction terms between population and seed predation in the best model [lowest corrected Akaike Information Criterion (AICc)] explaining final seed production. These results indicate opposing selection in operation: pollinators generated selection for greater floral exsertion beyond the bracts, but seed predators generated selection for reduced exsertion above the protective pools of water, although the strength of the latter varied across populations. © The Author 2016. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  7. Building Language Educators: The Implications of Case-Based Pedagogy Using Practicum-Based Student-Teacher-Generated Cases for Pre-Service Language Teacher Education

    ERIC Educational Resources Information Center

    Cournoyer, Amy Beth

    2014-01-01

    This case study investigated case-based pedagogy using student-teacher-generated cases as an instructional tool in the preparation of 12 pre-service ESL, Bilingual, and Modern Foreign Language teachers enrolled in a Student Teaching Seminar at a post-secondary institution. In the fall methods course, each participant generated a case study based…

  8. Generating global network structures by triad types

    PubMed Central

    Ferligoj, Anuška; Žiberna, Aleš

    2018-01-01

    This paper addresses the question of whether one can generate networks with a given global structure (defined by selected blockmodels, i.e., cohesive, core-periphery, hierarchical, and transitivity), considering only different types of triads. Two methods are used to generate networks: (i) the newly proposed method of relocating links; and (ii) the Monte Carlo Multi Chain algorithm implemented in the ergm package in R. Most of the selected blockmodel types can be generated by considering all types of triads. The selection of only a subset of triads can improve the generated networks’ blockmodel structure. Yet, in the case of a hierarchical blockmodel without complete blocks on the diagonal, additional local structures are needed to achieve the desired global structure of generated networks. This shows that blockmodels can emerge based only on local processes that do not take attributes into account. PMID:29847563

  9. Positive selection on sociobiological traits in invasive fire ants.

    PubMed

    Privman, Eyal; Cohen, Pnina; Cohanim, Amir B; Riba-Grognuz, Oksana; Shoemaker, DeWayne; Keller, Laurent

    2018-06-19

    The fire ant Solenopsis invicta and its close relatives are highly invasive. Enhanced social cooperation may facilitate invasiveness in these and other invasive ant species. We investigated whether invasiveness in Solenopsis fire ants was accompanied by positive selection on sociobiological traits by applying a phylogenomics approach to infer ancient selection, and a population genomics approach to infer recent and ongoing selection in both native and introduced S. invicta populations. A combination of whole-genome sequencing of 40 haploid males and reduced-representation genomic sequencing of 112 diploid workers identified 1,758,116 and 169,682 polymorphic markers, respectively. The resulting high-resolution maps of genomic polymorphism provide high inference power to test for positive selection. Our analyses provide evidence of positive selection on putative ion channel genes, which are implicated in neurological functions, and on vitellogenin, which is a key regulator of development and caste determination. Furthermore, molecular functions implicated in pheromonal signaling have experienced recent positive selection. Genes with signatures of positive selection were significantly more often those over-expressed in workers compared with queens and males, suggesting that worker traits are under stronger selection than queen and male traits. These results provide insights into selection pressures and ongoing adaptation in an invasive social insect and support the hypothesis that sociobiological traits are under more positive selection than traits related to non-social traits in such invasive species. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  10. Pseudorandom number generation using chaotic true orbits of the Bernoulli map

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

    Saito, Asaki, E-mail: saito@fun.ac.jp; Yamaguchi, Akihiro

    We devise a pseudorandom number generator that exactly computes chaotic true orbits of the Bernoulli map on quadratic algebraic integers. Moreover, we describe a way to select the initial points (seeds) for generating multiple pseudorandom binary sequences. This selection method distributes the initial points almost uniformly (equidistantly) in the unit interval, and latter parts of the generated sequences are guaranteed not to coincide. We also demonstrate through statistical testing that the generated sequences possess good randomness properties.

  11. The Influence of Self-Esteem on the Mate Selection Process of African American Females: Implications for Counseling

    ERIC Educational Resources Information Center

    Gibson-Bilton, Joya

    2009-01-01

    The purpose of this study was twofold. First, this study examined the influence of African American females' level of self-esteem on the mate-selection process. Secondly, this study was concerned with the influence of the level of self-esteem of African American females on valuing the mate-selection characteristics of interpersonal skills,…

  12. Using the Delphi Method for Selecting Effective Rehabilitation Practices for Case Study Research: Methods, Challenges, and Solutions and Implications for Future Research

    ERIC Educational Resources Information Center

    Fleming, Allison R.; Boeltzig-Brown, Heike; Foley, Susan M.

    2015-01-01

    Purpose: We describe a modified Delphi method used to select effective state vocational rehabilitation agency practices to prioritize rehabilitation services for individuals with most significant disabilities within the context of Order of Selection, an area where there is little known and published. Specifically, we describe how we applied the…

  13. A Different World: African American, First Generation College Women at a Selective University

    ERIC Educational Resources Information Center

    Johnson, Jennifer Michelle

    2013-01-01

    The purpose of this study was to gain a better understanding of the academic and social experiences of African American, first generation college students attending a selective university. Following interpretive case study methodology, the major research questions guiding this study were: How do African American, first generation college students…

  14. Fate of a mutation in a fluctuating environment

    PubMed Central

    Cvijović, Ivana; Good, Benjamin H.; Jerison, Elizabeth R.; Desai, Michael M.

    2015-01-01

    Natural environments are never truly constant, but the evolutionary implications of temporally varying selection pressures remain poorly understood. Here we investigate how the fate of a new mutation in a fluctuating environment depends on the dynamics of environmental variation and on the selective pressures in each condition. We find that even when a mutation experiences many environmental epochs before fixing or going extinct, its fate is not necessarily determined by its time-averaged selective effect. Instead, environmental variability reduces the efficiency of selection across a broad parameter regime, rendering selection unable to distinguish between mutations that are substantially beneficial and substantially deleterious on average. Temporal fluctuations can also dramatically increase fixation probabilities, often making the details of these fluctuations more important than the average selection pressures acting on each new mutation. For example, mutations that result in a trade-off between conditions but are strongly deleterious on average can nevertheless be more likely to fix than mutations that are always neutral or beneficial. These effects can have important implications for patterns of molecular evolution in variable environments, and they suggest that it may often be difficult for populations to maintain specialist traits, even when their loss leads to a decline in time-averaged fitness. PMID:26305937

  15. Self-motion perception: assessment by computer-generated animations

    NASA Technical Reports Server (NTRS)

    Parker, D. E.; Harm, D. L.; Sandoz, G. R.; Skinner, N. C.

    1998-01-01

    The goal of this research is more precise description of adaptation to sensory rearrangements, including microgravity, by development of improved procedures for assessing spatial orientation perception. Thirty-six subjects reported perceived self-motion following exposure to complex inertial-visual motion. Twelve subjects were assigned to each of 3 perceptual reporting procedures: (a) animation movie selection, (b) written report selection and (c) verbal report generation. The question addressed was: do reports produced by these procedures differ with respect to complexity and reliability? Following repeated (within-day and across-day) exposures to 4 different "motion profiles," subjects either (a) selected movies presented on a laptop computer, or (b) selected written descriptions from a booklet, or (c) generated self-motion verbal descriptions that corresponded most closely with their motion experience. One "complexity" and 2 reliability "scores" were calculated. Contrary to expectations, reliability and complexity scores were essentially equivalent for the animation movie selection and written report selection procedures. Verbal report generation subjects exhibited less complexity than did subjects in the other conditions and their reports were often ambiguous. The results suggest that, when selecting from carefully written descriptions and following appropriate training, people may be better able to describe their self-motion experience with words than is usually believed.

  16. Analysis of drought impacts on electricity production in the Western and Texas interconnections of the United States.

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

    Harto, C. B.; Yan, Y. E.; Demissie, Y. K.

    2012-02-09

    Electricity generation relies heavily on water resources and their availability. To examine the interdependence of energy and water in the electricity context, the impacts of a severe drought to assess the risk posed by drought to electricity generation within the western and Texas interconnections has been examined. The historical drought patterns in the western United States were analyzed, and the risk posed by drought to electricity generation within the region was evaluated. The results of this effort will be used to develop scenarios for medium- and long-term transmission modeling and planning efforts by the Western Electricity Coordination Council (WECC) andmore » the Electric Reliability Council of Texas (ERCOT). The study was performed in response to a request developed by the Western Governors Association in conjunction with the transmission modeling teams at the participating interconnections. It is part of a U.S. Department of Energy-sponsored, national laboratory-led research effort to develop tools related to the interdependency of energy and water as part of a larger interconnection-wide transmission planning project funded under the American Recovery and Reinvestment Act. This study accomplished three main objectives. It provided a thorough literature review of recent studies of drought and the potential implications for electricity generation. It analyzed historical drought patterns in the western United States and used the results to develop three design drought scenarios. Finally, it quantified the risk to electricity generation for each of eight basins for each of the three drought scenarios and considered the implications for transmission planning. Literature on drought impacts on electricity generation describes a number of examples where hydroelectric generation capacity has been limited because of drought but only a few examples of impact on thermoelectric generation. In all documented cases, shortfalls of generation were met by purchasing power from the market, albeit at higher prices. However, sufficient excess generation and transmission must be available for this strategy to work. Although power purchase was the most commonly discussed drought mitigation strategy, a total of 12 response strategies were identified in the literature, falling into four main categories: electricity supply, electricity demand response, alternative water supplies, and water demand response. Three hydrological drought scenarios were developed based on a literature review and historical data analysis. The literature review helped to identify key drought parameters and data on drought frequency and severity. Historical hydrological drought data were analyzed for the western United States to identify potential drought correlations and estimate drought parameters. The first scenario was a West-wide drought occurring in 1977; it represented a severe drought in five of the eight basins in the study area. A second drought scenario was artificially defined by selecting the conditions from the 10th-percentile drought year for each individual basin; this drought was defined in this way to allow more consistent analysis of risk to electricity generation in each basin. The final scenario was based upon the current low-flow hydro modeling scenario defined by WECC, which uses conditions from the year 2001. These scenarios were then used to quantify the risk to electricity generation in each basin. The risk calculations represent a first-order estimate of the maximum amount of electricity generation that might be lost from both hydroelectric and thermoelectric sources under a worst-case scenario. Even with the conservative methodology used, the majority of basins showed a limited amount of risk under most scenarios. The level of risk in these basins is likely to be amenable to mitigation by known strategies, combined with existing reserve generation and transmission capacity. However, the risks to the Pacific Northwest and Texas Basins require further study. The Pacific Northwest is vulnerable because of its heavy reliance on hydroelectric generation. Texas, conversely, is vulnerable because of its heavy dependence on thermoelectric generation, which relies on surface water for cooling, along with the fact that this basin seems to experience more severe drought events on average. Further modeling analysis will be performed in conjunction with the modeling teams at the participating interconnections (WECC and ERCOT) to explore the transmission implications of the drought scenarios in more detail. Given the first-order nature of this analysis, more detailed study of the potential impacts of drought on electricity generation is recommended. Future analyses should attempt to model the potential impacts of drought at the power-plant level, including potential mitigation strategies; include the effects of drought duration; understand the impacts of climate change; and consider economic impacts.« less

  17. Sexual selection and physical attractiveness : Implications for mating dynamics.

    PubMed

    Gangestad, S W

    1993-09-01

    Sexual selection processes have received much attention in recent years, attention reflected in interest in human mate preferences. Among these mate preferences are preferences for physical attractiveness. Preferences in and of themselves, however, do not fully explain the nature of the relationships that individuals attain. A tacit negotiation process underlies relationship formation and maintenance. The notion that preferences for physical attractiveness evolved under parasite-driven "good genes" sexual selection leads to predictions about the nature of trade-offs that individuals make between mates' physical attractiveness and investment potential. These predictions and relevant data are explored, with a primary emphasis on women's preferences for men's qualities. In addition, further implications of trade-offs are examined, most notably (a) the impact of environmental variations on the nature of mating and (b) some effects of trade-offs on infidelity and male attempts to control women.

  18. "I share, therefore I am": personality traits, life satisfaction, and Facebook check-ins.

    PubMed

    Wang, Shaojung Sharon

    2013-12-01

    This study explored whether agreeableness, extraversion, and openness function to influence self-disclosure behavior, which in turn impacts the intensity of checking in on Facebook. A complete path from extraversion to Facebook check-in through self-disclosure and sharing was found. The indirect effect from sharing to check-in intensity through life satisfaction was particularly salient. The central component of check-in is for users to disclose a specific location selectively that has implications on demonstrating their social lives, lifestyles, and tastes, enabling a selective and optimized self-image. Implications on the hyperpersonal model and warranting principle are discussed.

  19. Supplantation versus Generative Models: Implications for Designers of Instructional Text.

    ERIC Educational Resources Information Center

    Smith, Patricia L.

    Two instructional design alternatives are described and discussed: (1) the supplantation model of Ausburn and Ausburn (1978), where learning strategies are built into the instructional materials; and (2) a generative design model, where strategies are "built" into the learner. These contrasting models are proposed as representing the…

  20. The Experiences of the Younger Supervisor: Implications for Organizations

    ERIC Educational Resources Information Center

    Hanson, Lea

    2012-01-01

    With four generations in today's workforce, roles are being redefined to include a growing number of younger supervisor/older subordinate relationships, referred to as the intergenerational dyad. What current and limited literature exists about the intergenerational dyad exclusively addresses the issues of generational workplace differences…

  1. Epigenetic Mechanisms and the Transgenerational Effects of Maternal Care

    PubMed Central

    Champagne, Frances A.

    2009-01-01

    The transmission of traits across generations has typically been attributed to the inheritance by offspring of genomic information from parental generations. However, recent evidence suggests that epigenetic mechanisms are capable of mediating this type of transmission. In the case of maternal care, there is evidence for the behavioral transmission of postpartum behavior from mothers to female offspring. The neuroendocrine and molecular mediators of this transmission have been explored in rats and implicate estrogen-oxytocin interactions and the differential methylation of hypothalamic estrogen receptors. These maternal effects can influence multiple aspects of neurobiology and behavior of offspring and this particular mode of inheritance is dynamic in response to environmental variation. In this review, evidence for the generational transmission of maternal care and the mechanisms underlying this transmission will be discussed as will the implications of this inheritance system for offspring development and for the transmission of environmental information from parents to offspring. PMID:18462782

  2. Implications of a electroweak triplet scalar leptoquark on the ultra-high energy neutrino events at IceCube

    NASA Astrophysics Data System (ADS)

    Mileo, Nicolas; de la Puente, Alejandro; Szynkman, Alejandro

    2016-11-01

    We study the production of scalar leptoquarks at IceCube, in particular, a particle transforming as a triplet under the weak interaction. The existence of electroweak-triplet scalars is highly motivated by models of grand unification and also within radiative seesaw models for neutrino mass generation. In our framework, we extend the Standard Model by a single colored electroweak-triplet scalar leptoquark and analyze its implications on the excess of ultra-high energy neutrino events observed by the IceCube collaboration. We consider only couplings between the leptoquark to first generation of quarks and first and second generations of leptons, and carry out a statistical analysis to determine the parameters that best describe the IceCube data as well as set 95% CL upper bounds. We analyze whether this study is still consistent with most up-to-date LHC data and various low energy observables.

  3. Dopaminergic and Cholinergic Modulations of Visual-Spatial Attention and Working Memory: Insights from Molecular Genetic Research and Implications for Adult Cognitive Development

    ERIC Educational Resources Information Center

    Stormer, Viola S.; Passow, Susanne; Biesenack, Julia; Li, Shu-Chen

    2012-01-01

    Attention and working memory are fundamental for selecting and maintaining behaviorally relevant information. Not only do both processes closely intertwine at the cognitive level, but they implicate similar functional brain circuitries, namely the frontoparietal and the frontostriatal networks, which are innervated by cholinergic and dopaminergic…

  4. Evaluation in the Context of the Government Market Place: Implications for the Evaluation of Research

    ERIC Educational Resources Information Center

    Della-Piana, Connie Kubo; Della-Piana, Gabriel M.

    2007-01-01

    While the current debate in the evaluation community has concentrated on examining and explicating implications of the choice of methods for evaluating federal programs, the authors of this paper address the challenges faced by the government in the selection of funding mechanisms for supporting program evaluation efforts. The choice of funding…

  5. Undergraduate Usage of Mobile Phones and Its Implication of School Application

    ERIC Educational Resources Information Center

    Dania, P. O.; Iwe-Ewenode, J.

    2016-01-01

    The study is a survey research intended to find out undergraduate usage of mobile phones and its implication of school application. The colloquium population is 27,650 at which two hundred and thirty-eight undergraduate students were randomly selected from two universities in the Federal Republic of Nigeria. A questionnaire on "current trends…

  6. Implications of Computer Technology. Harvard University Program on Technology and Society.

    ERIC Educational Resources Information Center

    Taviss, Irene; Burbank, Judith

    Lengthy abstracts of a small number of selected books and articles on the implications of computer technology are presented, preceded by a brief state-of-the-art survey which traces the impact of computers on the structure of economic and political organizations and socio-cultural patterns. A summary statement introduces each of the three abstract…

  7. Investigating Policy Implications for the Abolition of Corporal Punishment in Secondary Schools in Kenya

    ERIC Educational Resources Information Center

    Kindiki, Jonah Nyaga

    2015-01-01

    The main objective of this study is to investigate policy implications for the abolition of corporal punishment in secondary schools in Kenya. Adopting a survey design, using questionnaires, interviews and documentation, a sample of 355 was selected from target population of 3228 teachers, students and parents. The data were analysed thematically.…

  8. Development of next-generation mapping populations: Multi-parent Advanced Generation Inter-Cross (MAGIC) and Marker-Assisted Recurrent Selection (MARS) populations in peanut

    USDA-ARS?s Scientific Manuscript database

    Generation Inter-Cross (MAGIC) and Marker-Assisted Recurrent Selection (MARS) have been proposed and used in many crops to dissect complex traits or QTL. MAGIC allows for dissecting genomic structure, and for improving breeding populations by integrating multiple alleles from different parents. MAR...

  9. Projects, Training, and Strategies for Generating Income: A Selected Annotated Bibliography. Annotated Bibliography #4.

    ERIC Educational Resources Information Center

    Michigan State Univ., East Lansing. Non-Formal Education Information Center.

    A selected annotated bibliography on projects, training, and strategies for generating income, intended for persons actively engaged in non-formal education for development, reflects a growing number of projects on income generation by and for women's groups, and a reliance upon indigenous associations and group action. Documents dating from 1969…

  10. Making Their Way: An Interpretive Case Study of Male First-Generation Students Attending a Highly Selective Liberal Arts College

    ERIC Educational Resources Information Center

    Peltz, Mark R.

    2013-01-01

    This qualitative study focused on the experiences of eight male first-generation college students attending Kenmont College (pseudonym), a highly selective, residential liberal arts college located in the Midwestern United States. While first-generation college students have been studied in various contexts, very little is known about what…

  11. UWB transmitter

    DOEpatents

    Dallum, Gregory E.; Pratt, Garth C.; Haugen, Peter C.; Romero, Carlos E.

    2013-01-15

    An ultra-wideband (UWB) dual impulse transmitter is made up of a trigger edge selection circuit actuated by a single trigger input pulse; a first step recovery diode (SRD) based pulser connected to the trigger edge selection circuit to generate a first impulse output; and a second step recovery diode (SRD) based pulser connected to the trigger edge selection circuit in parallel to the first pulser to generate a second impulse output having a selected delay from the first impulse output.

  12. Word Production Deficits in Schizophrenia

    ERIC Educational Resources Information Center

    Marvel, Cherie L.; Schwartz, Barbara L.; Isaacs, Keren L.

    2004-01-01

    Fronto-cerebellar circuitry is implicated in word production. Data suggest that the cerebellum is involved in word "search," whereas the prefrontal cortex underlies the "selection" of words from among competing alternatives. We explored the role of search and selection processes in word production deficits in schizophrenia patients. In Experiment…

  13. Role of Friction in Materials Selection for Automotive Applications

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

    Blau, Peter Julian

    This is an invited article for a special issue of the ASM International monthly magazine that concerns "Automotive Materials and Applications." The article itself overviews frictional considerations in material selection for automobiles. It discusses implications for energy efficiency (engine friction) and safety (brakes) among other topics.

  14. Pain expressiveness and altruistic behavior: an exploration using agent-based modeling.

    PubMed

    de C Williams, Amanda C; Gallagher, Elizabeth; Fidalgo, Antonio R; Bentley, Peter J

    2016-03-01

    Predictions which invoke evolutionary mechanisms are hard to test. Agent-based modeling in artificial life offers a way to simulate behaviors and interactions in specific physical or social environments over many generations. The outcomes have implications for understanding adaptive value of behaviors in context. Pain-related behavior in animals is communicated to other animals that might protect or help, or might exploit or predate. An agent-based model simulated the effects of displaying or not displaying pain (expresser/nonexpresser strategies) when injured and of helping, ignoring, or exploiting another in pain (altruistic/nonaltruistic/selfish strategies). Agents modeled in MATLAB interacted at random while foraging (gaining energy); random injury interrupted foraging for a fixed time unless help from an altruistic agent, who paid an energy cost, speeded recovery. Environmental and social conditions also varied, and each model ran for 10,000 iterations. Findings were meaningful in that, in general, contingencies that evident from experimental work with a variety of mammals, over a few interactions, were replicated in the agent-based model after selection pressure over many generations. More energy-demanding expression of pain reduced its frequency in successive generations, and increasing injury frequency resulted in fewer expressers and altruists. Allowing exploitation of injured agents decreased expression of pain to near zero, but altruists remained. Decreasing costs or increasing benefits of helping hardly changed its frequency, whereas increasing interaction rate between injured agents and helpers diminished the benefits to both. Agent-based modeling allows simulation of complex behaviors and environmental pressures over evolutionary time.

  15. JAGGED Controls Arabidopsis Petal Growth and Shape by Interacting with a Divergent Polarity Field

    PubMed Central

    Sauret-Güeto, Susanna; Schiessl, Katharina; Bangham, Andrew; Sablowski, Robert; Coen, Enrico

    2013-01-01

    A flowering plant generates many different organs such as leaves, petals, and stamens, each with a particular function and shape. These types of organ are thought to represent variations on a common underlying developmental program. However, it is unclear how this program is modulated under different selective constraints to generate the diversity of forms observed. Here we address this problem by analysing the development of Arabidopsis petals and comparing the results to models of leaf development. We show that petal development involves a divergent polarity field with growth rates perpendicular to local polarity increasing towards the distal end of the petal. The hypothesis is supported by the observed pattern of clones induced at various stages of development and by analysis of polarity markers, which show a divergent pattern. We also show that JAGGED (JAG) has a key role in promoting distal enhancement of growth rates and influences the extent of the divergent polarity field. Furthermore, we reveal links between the polarity field and auxin function: auxin-responsive markers such as DR5 have a broader distribution along the distal petal margin, consistent with the broad distal organiser of polarity, and PETAL LOSS (PTL), which has been implicated in the control of auxin dynamics during petal initiation, is directly repressed by JAG. By comparing these results with those from studies on leaf development, we show how simple modifications of an underlying developmental system may generate distinct forms, providing flexibility for the evolution of different organ functions. PMID:23653565

  16. The anti-inflammatory effects of PGE2 on human lung macrophages are mediated by the EP4 receptor.

    PubMed

    Gill, Sharonjit K; Yao, Yiwen; Kay, Linda J; Bewley, Martin A; Marriott, Helen M; Peachell, Peter T

    2016-11-01

    PGE 2 inhibits cytokine generation from human lung macrophages. However, the EP receptor that mediates this beneficial anti-inflammatory effect of PGE 2 has not been defined. The aim of this study was to identify the EP receptor by which PGE 2 inhibits cytokine generation from human lung macrophages. This was determined by using recently developed EP receptor ligands. The effects of PGE 2 and EP-selective agonists on LPS-induced generation of TNF-α and IL-6 from macrophages were evaluated. The effects of EP 2 -selective (PF-04852946, PF-04418948) and EP 4 -selective (L-161,982, CJ-042794) receptor antagonists on PGE 2 responses were studied. The expression of EP receptor subtypes by human lung macrophages was determined by RT-PCR. PGE 2 inhibited LPS-induced and Streptococcus pneumoniae-induced cytokine generation from human lung macrophages. Analysis of mRNA levels indicated that macrophages expressed EP 2 and EP 4 receptors. L-902,688 (EP 4 receptor-selective agonist) was considerably more potent than butaprost (EP 2 receptor-selective agonist) as an inhibitor of TNF-α generation from macrophages. EP 2 receptor-selective antagonists had marginal effects on the PGE 2 inhibition of TNF-α generation, whereas EP 4 receptor-selective antagonists caused rightward shifts in the PGE 2 concentration-response curves. These studies demonstrate that the EP 4 receptor is the principal receptor that mediates the anti-inflammatory effects of PGE 2 on human lung macrophages. This suggests that EP 4 receptor agonists could be effective anti-inflammatory agents in human lung disease. © 2016 The British Pharmacological Society.

  17. Distractor Modality Can Turn Semantic Interference into Semantic Facilitation in the Picture-Word Interference Task: Implications for Theories of Lexical Access in Speech Production

    ERIC Educational Resources Information Center

    Hantsch, Ansgar; Jescheniak, Jorg D.; Schriefers, Herbert

    2009-01-01

    A number of recent studies have questioned the idea that lexical selection during speech production is a competitive process. One type of evidence against selection by competition is the observation that in the picture-word interference task semantically related distractors may facilitate the naming of a picture, whereas the selection by…

  18. Impact of an energy education software on rural women

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

    George, R.; Yadla, V.L.; Zohruailiani, M.

    1999-07-01

    Renewable energy cooking technologies (RECTs) like solar cookers, biogas units and improved cookstoves are promoted by Government of India to combat fuel wood scarcity and ensure a cleaner environment. The value of an energy education software (EES) to generate awareness about cooking energy scarcity and to achieve scientific empowerment of potential end users of RECTs, needs no emphasis. An attempt was made to assess the impact of an EES that consisted of flip charts--visuals with minimum text on rural women. The major objective of the research endeavor was to measure the difference in the selected attributes, namely, attitude towards biomassmore » generation and biomass conservation (BG-BC), cooking management practices (CMP) and knowledge level (KL) of rural women due to exposure to EES. A descriptive research design coupled with a before and after experimental design was adopted for the study. A sample of rural women from Nani Sherkhi village were exposed to EES through a series of three training sessions with pre and post sessions for group discussions. Data on the selected attributes were gathered in the pre and post training periods using descriptive rating scales with reliability coefficients of 0.80, 0.81 and 0.74 respectively. The computed t values showed significant differences at 0.01 level in the pre and post exposure mean scores on attitude, cooking management practice and knowledge scale. The t values revealed that the gain in score in each of the attributes due to exposure to EES were significant. Further, utility of EES, policy implications and strategies for popularizing it as an aid to reach sustainable development are also discussed in brief in the paper.« less

  19. Problems, Solutions, and Strategies Reported by Users of Transcutaneous Electrical Nerve Stimulation for Chronic Musculoskeletal Pain: Qualitative Exploration Using Patient Interviews.

    PubMed

    Gladwell, Peter William; Badlan, Kathryn; Cramp, Fiona; Palmer, Shea

    2016-07-01

    Transcutaneous electrical nerve stimulation (TENS) could offer a non-drug form of pain relief, but there is no consensus regarding its effectiveness for chronic musculoskeletal pain or chronic low back pain. A recent review of previous trial methods identified significant problems with low treatment fidelity. There is little information available to inform the development of a pragmatic implementation design for a TENS evaluation. The aim of this study was to explore the experiences of patients who were receiving secondary care in a pain clinic and who had expertise in using TENS to manage chronic musculoskeletal pain. These key informants were selected because they had the potential to generate knowledge that could inform research design and clinical practice. A qualitative method using individual semistructured interviews with open questions was selected for its capacity to generate rich data. Semistructured interviews were conducted with 9 patients (6 women, 3 men). Thematic analysis was used as the primary data analysis method, and this analysis was enhanced by a case-level analysis of the context and processes of TENS use of each individual. Data analysis indicated that patients learned to address a range of problems in order to optimize TENS use. Patients may need to personalize the positioning of electrodes and the TENS settings and to readjust them over time. Patients learned to use TENS in a strategic manner, and the outcomes of each strategy varied. The findings indicated that a pragmatic TENS evaluation may need to incorporate a learning phase to allow patients to optimize this complex pattern of TENS usage, and evaluation may need to be sensitive to the outcomes of strategic use. These findings also have implications for clinical practice. © 2016 American Physical Therapy Association.

  20. The Mosaic Ancestry of the Drosophila Genetic Reference Panel and the D. melanogaster Reference Genome Reveals a Network of Epistatic Fitness Interactions.

    PubMed

    Pool, John E

    2015-12-01

    North American populations of Drosophila melanogaster derive from both European and African source populations, but despite their importance for genetic research, patterns of ancestry along their genomes are largely undocumented. Here, I infer geographic ancestry along genomes of the Drosophila Genetic Reference Panel (DGRP) and the D. melanogaster reference genome, which may have implications for reference alignment, association mapping, and population genomic studies in Drosophila. Overall, the proportion of African ancestry was estimated to be 20% for the DGRP and 9% for the reference genome. Combining my estimate of admixture timing with historical records, I provide the first estimate of natural generation time for this species (approximately 15 generations per year). Ancestry levels were found to vary strikingly across the genome, with less African introgression on the X chromosome, in regions of high recombination, and at genes involved in specific processes (e.g., circadian rhythm). An important role for natural selection during the admixture process was further supported by evidence that many unlinked pairs of loci showed a deficiency of Africa-Europe allele combinations between them. Numerous epistatic fitness interactions may therefore exist between African and European genotypes, leading to ongoing selection against incompatible variants. By focusing on hubs in this network of fitness interactions, I identified a set of interacting loci that include genes with roles in sensation and neuropeptide/hormone reception. These findings suggest that admixed D. melanogaster samples could become an important study system for the genetics of early-stage isolation between populations. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  1. Toxicity tests aiming to protect Brazilian aquatic systems: current status and implications for management.

    PubMed

    Martins, Samantha Eslava; Bianchini, Adalto

    2011-07-01

    The current status of toxicological tests performed with Brazilian native species was evaluated through a survey of the scientific data available in the literature. The information gathered was processed and an electronic toxicology database (http://www.inct-ta.furg.br/bd_toxicologico.php) was generated. This database provides valuable information for researchers to select sensitive and tolerant aquatic species to a large variety of aquatic pollutants. Furthermore, the toxicology database allows researchers to select species representative of an ecosystem of interest. Analysis of the toxicology database showed that ecotoxicological assays have significantly improved in Brazil over the last decade, in spite of the still relatively low number of tests performed and the restricted number of native species tested. This is because most of the research is developed in a few laboratories concentrated in certain regions of Brazil, especially in Southern and Southeast regions. Considering the extremely rich biodiversity and the large variety of aquatic ecosystems in Brazil, this finding points to the urgent need for the development of ecotoxicological studies with other groups of aquatic animals, such as insects, foraminifera, cnidarians, worms, amphibians, among others. This would help to derive more realistic water quality criteria (WQC) values, which would better protect the different aquatic ecosystems in Brazil. Finally, the toxicology database generated presents solid and science based information, which can encourage and drive the Environmental Regulatory Agencies in Brazil to derive WQC based on native species. In this context, the present paper discusses the historical evolution of ecotoxicological studies in Brazil, and how they have contributed to the improvement of the Brazilian Federal and Regional regulations for environment.

  2. Cross-species genomics matches driver mutations and cell compartments to model ependymoma

    PubMed Central

    Johnson, Robert A.; Wright, Karen D.; Poppleton, Helen; Mohankumar, Kumarasamypet M.; Finkelstein, David; Pounds, Stanley B.; Rand, Vikki; Leary, Sarah E.S.; White, Elsie; Eden, Christopher; Hogg, Twala; Northcott, Paul; Mack, Stephen; Neale, Geoffrey; Wang, Yong-Dong; Coyle, Beth; Atkinson, Jennifer; DeWire, Mariko; Kranenburg, Tanya A.; Gillespie, Yancey; Allen, Jeffrey C.; Merchant, Thomas; Boop, Fredrick A.; Sanford, Robert. A.; Gajjar, Amar; Ellison, David W.; Taylor, Michael D.; Grundy, Richard G.; Gilbertson, Richard J.

    2010-01-01

    Understanding the biology that underlies histologically similar but molecularly distinct subgroups of cancer has proven difficult since their defining genetic alterations are often numerous, and the cellular origins of most cancers remain unknown1–3. We sought to decipher this heterogeneity by integrating matched genetic alterations and candidate cells of origin to generate accurate disease models. First, we identified subgroups of human ependymoma, a form of neural tumor that arises throughout the central nervous system (CNS). Subgroup specific alterations included amplifications and homozygous deletions of genes not yet implicated in ependymoma. To select cellular compartments most likely to give rise to subgroups of ependymoma, we matched the transcriptomes of human tumors to those of mouse neural stem cells (NSCs), isolated from different regions of the CNS at different developmental stages, with an intact or deleted Ink4a/Arf locus. The transcriptome of human cerebral ependymomas with amplified EPHB2 and deleted INK4A/ARF matched only that of embryonic cerebral Ink4a/Arf−/− NSCs. Remarkably, activation of Ephb2 signaling in these, but not other NSCs, generated the first mouse model of ependymoma, which is highly penetrant and accurately models the histology and transcriptome of one subgroup of human cerebral tumor. Further comparative analysis of matched mouse and human tumors revealed selective deregulation in the expression and copy number of genes that control synaptogenesis, pinpointing disruption of this pathway as a critical event in the production of this ependymoma subgroup. Our data demonstrate the power of cross-species genomics to meticulously match subgroup specific driver mutations with cellular compartments to model and interrogate cancer subgroups. PMID:20639864

  3. Nonlinear Acoustics in Ultrasound Metrology and other Selected Applications.

    PubMed

    Lewin, Peter A

    2010-01-01

    A succinct background explaining why, initially, both the scientific community and industry were skeptical about the existence of the nonlinear (NL) wave propagation in tissue will be given and the design of an adequately wideband piezoelectric polymer hydrophone probe that was eventually used to verify that the 1-5 MHz probing wave then used in diagnostic ultrasound imaging was undergoing nonlinear distortion and generated harmonics in tissue will be discussed. The far-reaching implications of the advent of the piezoelectric PVDF polymer material will be reviewed and the advances in ultrasound metrology prompted by the regulatory agencies such as US Food and Drug Administration (FDA) and International Electrotechnical Commission (IEC) will be presented. These advances include the development of absolute calibration techniques for hydrophones along with the methods of accounting for spatial averaging corrections up to 100 MHz and the development of "point-receiver" hydrophone probes utilizing acousto-optic sensors. Next, selected therapeutic applications of nonlinear ultrasonics (NLU), including lithotripters will be briefly discussed. Also, the use of shock waves as pain relief tool and in abating penicillin resistant bacteria that develop rock hard "biofilm" that can be shattered by the finite amplitude wave will also be mentioned. The growing applications of NLU in cosmetic industry where it is used for redistribution and reduction of fatty tissue within the body will be briefly reviewed, and, finally, selected examples of NLU applications in retail and entertainment industry will also be pointed out.

  4. Membrane-tethered peptides patterned after the TRP domain (TRPducins) selectively inhibit TRPV1 channel activity.

    PubMed

    Valente, Pierluigi; Fernández-Carvajal, Asia; Camprubí-Robles, María; Gomis, Ana; Quirce, Susana; Viana, Félix; Fernández-Ballester, Gregorio; González-Ros, José M; Belmonte, Carlos; Planells-Cases, Rosa; Ferrer-Montiel, Antonio

    2011-05-01

    The transient receptor potential vanilloid 1 (TRPV1) channel is a thermosensory receptor implicated in diverse physiological and pathological processes. The TRP domain, a highly conserved region in the C terminus adjacent to the internal channel gate, is critical for subunit tetramerization and channel gating. Here, we show that cell-penetrating, membrane-anchored peptides patterned after this protein domain are moderate and selective TRPV1 antagonists both in vitro and in vivo, blocking receptor activity in intact rat primary sensory neurons and their peripheral axons with mean decline time of 30 min. The most potent lipopeptide, TRP-p5, blocked all modes of TRPV1 gating with micromolar efficacy (IC(50)<10 μM), without significantly affecting other thermoTRP channels. In contrast, its retrosequence or the corresponding sequences of other TRPV channels did not alter TRPV1 channel activity (IC(50)>100 μM). TRP-p5 did not affect the capsaicin sensitivity of the vanilloid receptor. Our data suggest that TRP-p5 interferes with protein-protein interactions at the level of the TRP domain that are essential for the "conformational" change that leads to gate opening. Therefore, these palmitoylated peptides, which we termed TRPducins, are noncompetitive, voltage-independent, sequence-specific TRPV1 blockers. Our findings indicate that TRPducin-like peptides may embody a novel molecular strategy that can be exploited to generate a selective pharmacological arsenal for the TRP superfamily of ion channels.

  5. Macromolecular Modelling and Docking Simulations for the Discovery of Selective GPER Ligands.

    PubMed

    Rosano, Camillo; Ponassi, Marco; Santolla, Maria Francesca; Pisano, Assunta; Felli, Lamberto; Vivacqua, Adele; Maggiolini, Marcello; Lappano, Rosamaria

    2016-01-01

    Estrogens influence multiple physiological processes and are implicated in many diseases as well. Cellular responses to estrogens are mainly mediated by the estrogen receptors (ER)α and ERβ, which act as ligand-activated transcription factors. Recently, a member of the G protein-coupled receptor (GPCR) superfamily, namely GPER/GPR30, has been identified as a further mediator of estrogen signalling in different pathophysiological conditions, including cancer. Today, computational methods are commonly used in all areas of health science research. Among these methods, virtual ligand screening has become an established technique for hit discovery and optimization. The absence of an established three-dimensional structure of GPER promoted studies of structure-based drug design in order to build reliable molecular models of this receptor. Here, we discuss the results obtained through the structure-based virtual ligand screening for GPER, which allowed the identification and synthesis of different selective agonist and antagonist moieties. These compounds led significant advances in our understanding of the GPER function at the cellular, tissue, and organismal levels. In particular, selective GPER ligands were critical toward the evaluation of the role elicited by this receptor in several pathophysiological conditions, including cancer. Considering that structure-based approaches are fundamental in drug discovery, future research breakthroughs with the aid of computer-aided molecular design and chemo-bioinformatics could generate a new class of drugs that, acting through GPER, would be useful in a variety of diseases as well as in innovative anticancer strategies.

  6. Study Protocol on Intentional Distortion in Personality Assessment: Relationship with Test Format, Culture, and Cognitive Ability.

    PubMed

    Van Geert, Eline; Orhon, Altan; Cioca, Iulia A; Mamede, Rui; Golušin, Slobodan; Hubená, Barbora; Morillo, Daniel

    2016-01-01

    Self-report personality questionnaires, traditionally offered in a graded-scale format, are widely used in high-stakes contexts such as job selection. However, job applicants may intentionally distort their answers when filling in these questionnaires, undermining the validity of the test results. Forced-choice questionnaires are allegedly more resistant to intentional distortion compared to graded-scale questionnaires, but they generate ipsative data. Ipsativity violates the assumptions of classical test theory, distorting the reliability and construct validity of the scales, and producing interdependencies among the scores. This limitation is overcome in the current study by using the recently developed Thurstonian item response theory model. As online testing in job selection contexts is increasing, the focus will be on the impact of intentional distortion on personality questionnaire data collected online. The present study intends to examine the effect of three different variables on intentional distortion: (a) test format (graded-scale versus forced-choice); (b) culture, as data will be collected in three countries differing in their attitudes toward intentional distortion (the United Kingdom, Serbia, and Turkey); and (c) cognitive ability, as a possible predictor of the ability to choose the more desirable responses. Furthermore, we aim to integrate the findings using a comprehensive model of intentional distortion. In the Anticipated Results section, three main aspects are considered: (a) the limitations of the manipulation, theoretical approach, and analyses employed; (b) practical implications for job selection and for personality assessment in a broader sense; and (c) suggestions for further research.

  7. Nonlinear acoustics in ultrasound metrology and other selected applications

    NASA Astrophysics Data System (ADS)

    Lewin, Peter A.

    2010-01-01

    A succinct background explaining why, initially, both the scientific community and industry were skeptical about the existence of the nonlinear (NL) wave propagation in tissue will be given and the design of an adequately wideband piezoelectric polymer hydrophone probe that was eventually used to verify that the 1-5 MHz probing wave then used in diagnostic ultrasound imaging was undergoing nonlinear distortion and generated harmonics in tissue will be discussed. The far-reaching implications of the advent of the piezoelectric PVDF polymer material will be reviewed and the advances in ultrasound metrology prompted by the regulatory agencies such as US Food and Drug Administration (FDA) and International Electrotechnical Commission (IEC) will be presented. These advances include the development of absolute calibration techniques for hydrophones along with the methods of accounting for spatial averaging corrections up to 100 MHz and the development of 'point-receiver' hydrophone probes utilizing acousto-optic sensors. Next, selected therapeutic applications of nonlinear ultrasonics (NLU), including lithotripters will be briefly discussed. Also, the use of shock waves as pain relief tool and in abating penicillin resistant bacteria that develop rock hard 'biofilm' that can be shattered by the finite amplitude wave will also be mentioned. The growing applications of NLU in cosmetic industry where it is used for redistribution and reduction of fatty tissue within the body will be briefly reviewed, and, finally, selected examples of NLU applications in retail and entertainment industry will also be pointed out.

  8. In vitro selection of shape-changing DNA nanostructures capable of binding-induced cargo release.

    PubMed

    Oh, Seung Soo; Plakos, Kory; Xiao, Yi; Eisenstein, Michael; Soh, H Tom

    2013-11-26

    Many biological systems employ allosteric regulatory mechanisms, which offer a powerful means of directly linking a specific binding event to a wide spectrum of molecular functionalities. There is considerable interest in generating synthetic allosteric regulators that can perform useful molecular functions for applications in diagnostics, imaging and targeted therapies, but generating such molecules through either rational design or directed evolution has proven exceptionally challenging. To address this need, we present an in vitro selection strategy for generating conformation-switching DNA nanostructures that selectively release a small-molecule payload in response to binding of a specific trigger molecule. As an exemplar, we have generated a DNA nanostructure that hybridizes with a separate 'cargo strand' containing an abasic site. This abasic site stably sequesters a fluorescent cargo molecule in an inactive state until the DNA nanostructure encounters an ATP trigger molecule. This ATP trigger causes the nanostructure to release the cargo strand, thereby liberating the fluorescent payload and generating a detectable fluorescent readout. Our DNA nanostructure is highly sensitive, with an EC50 of 30 μM, and highly specific, releasing its payload in response to ATP but not to other chemically similar nucleotide triphosphates. We believe that this selection approach could be generalized to generate synthetic nanostructures capable of selective and controlled release of other small-molecule cargos in response to a variety of triggers, for both research and clinical applications.

  9. Demand response, behind-the-meter generation and air quality.

    PubMed

    Zhang, Xiyue; Zhang, K Max

    2015-02-03

    We investigated the implications of behind-the-meter (BTM) generation participating in demand response (DR) programs. Specifically, we evaluated the impacts of NOx emissions from BTM generators enrolled in the New York Independent System Operator (NYISO)'s reliability-based DR programs. Through analyzing the DR program enrollment data, DR event records, ozone air quality monitoring data, and emission characteristics of the generators, we found that the emissions from BTM generators very likely contribute to exceedingly high ozone concentrations in the Northeast Corridor region, and very likely account for a substantial fraction of total NOx emissions from electricity generation. In addition, a companion study showed that the emissions from BTM generators could also form near-source particulate matter (PM) hotspots. The important policy implications are that the absence of up-to-date regulations on BTM generators may offset the current efforts to reduce the emissions from peaking power plants, and that there is a need to quantify the environmental impacts of DR programs in designing sound policies related to demand-side resources. Furthermore, we proposed the concept of "Green" DR resources, referring to those that not only provide power systems reliability services, but also have verifiable environmental benefits or minimal negative environmental impacts. We argue that Green DR resources that are able to maintain resource adequacy and reduce emissions at the same time are key to achieving the cobenefits of power system reliability and protecting public health during periods with peak electricity demand.

  10. Antidepressant-Induced Hyponatremia in Older Adults.

    PubMed

    Viramontes, Terry S; Truong, Havan; Linnebur, Sunny A

    2016-03-01

    To describe the prevalence of hyponatremia in older adults related to antidepressive agents and identify potential alternative options in older adults with a low-baseline serum sodium concentration and/or when a patient has experienced hyponatremia as a result of taking an antidepressant. A PubMed search was conducted on November 10, 2015. Search terms included: antidepressive agents, antidepressive agents second-generation, bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, hyponatremia, milnacipran, mirtazapine, paroxetine, reboxetine, syndrome of inappropriate antidiuretic hormone, sertraline, trazodone, venlafaxine, and vilazodone. Filters included English language. A search of product labeling was also conducted. Out of 363 results, 124 publications were identified and reviewed along with 11 additional references. Publications were chosen based on relevance to the review: case reports of patients 60 years of age or older or clinical investigations of the association between hyponatremia and antidepressants in older adults. Hyponatremia was counted as an adverse effect if an antidepressant was the likely cause of hyponatremia, and hyponatremia was resolved after withdrawal. Antidepressant-induced hyponatremia in older adults is fairly common. Selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, and mirtazapine were implicated in the majority of the case reports and clinical studies evaluating older adults. Bupropion, trazodone, and tricyclic antidepressants were implicated less often in the same literature. Given its unique mechanism of action, bupropion may be the most appropriate antidepressant for older adults at risk for antidepressant-induced hyponatremia.

  11. Edge Effects in Line Intersect Sampling With

    Treesearch

    David L. R. Affleck; Timothy G. Gregoire; Harry T. Valentine

    2005-01-01

    Transects consisting of multiple, connected segments with a prescribed configuration are commonly used in ecological applications of line intersect sampling. The transect configuration has implications for the probability with which population elements are selected and for how the selection probabilities can be modified by the boundary of the tract being sampled. As...

  12. Research Productivity and Its Policy Implications in Higher Education Institutions

    ERIC Educational Resources Information Center

    Quimbo, Maria Ana T.; Sulabo, Evangeline C.

    2014-01-01

    Responding to the Commission on Higher Education's development plan of enhancing research culture among higher education institutions, this study was conducted to analyze the research productivity of selected higher education institutions. It covered five state universities in the Philippines where a total of 377 randomly selected faculty members…

  13. Tailoring the Interview Process for More Effective Personnel Selection.

    ERIC Educational Resources Information Center

    Saville, Anthony

    Structuring the initial teacher employment interview adds validity to selection and appropriately utilizes human resources. Five aspects of an effective interview program include: (1) developing a job analysis plan; (2) reviewing the applications; (3) planning for the interview; (4) the interview instrument; and (5) legal implications. An…

  14. SPECIAL ISSUE DEVOTED TO THE 80TH BIRTHDAY OF S.A. AKHMANOV: Selective generation of a higher harmonic in plasma

    NASA Astrophysics Data System (ADS)

    Kulagin, I. A.; Usmanov, T.

    2009-07-01

    It is shown for the first time that the use of autoionisation states for phase matching leads to the efficient selection of a single harmonic generated in a plateau region in plasma. The selected harmonic frequency can be tuned by changing the relative concentration of plasma components and tuning the fundamental radiation frequency. It is shown that the contrast of the selected harmonic can exceed 104.

  15. Response to selection while maximizing genetic variance in small populations.

    PubMed

    Cervantes, Isabel; Gutiérrez, Juan Pablo; Meuwissen, Theo H E

    2016-09-20

    Rare breeds represent a valuable resource for future market demands. These populations are usually well-adapted, but their low census compromises the genetic diversity and future of these breeds. Since improvement of a breed for commercial traits may also confer higher probabilities of survival for the breed, it is important to achieve good responses to artificial selection. Therefore, efficient genetic management of these populations is essential to ensure that they respond adequately to genetic selection in possible future artificial selection scenarios. Scenarios that maximize the maximum genetic variance in a unique population could be a valuable option. The aim of this work was to study the effect of the maximization of genetic variance to increase selection response and improve the capacity of a population to adapt to a new environment/production system. We simulated a random scenario (A), a full-sib scenario (B), a scenario applying the maximum variance total (MVT) method (C), a MVT scenario with a restriction on increases in average inbreeding (D), a MVT scenario with a restriction on average individual increases in inbreeding (E), and a minimum coancestry scenario (F). Twenty replicates of each scenario were simulated for 100 generations, followed by 10 generations of selection. Effective population size was used to monitor the outcomes of these scenarios. Although the best response to selection was achieved in scenarios B and C, they were discarded because they are unpractical. Scenario A was also discarded because of its low response to selection. Scenario D yielded less response to selection and a smaller effective population size than scenario E, for which response to selection was higher during early generations because of the moderately structured population. In scenario F, response to selection was slightly higher than in Scenario E in the last generations. Application of MVT with a restriction on individual increases in inbreeding resulted in the largest response to selection during early generations, but if inbreeding depression is a concern, a minimum coancestry scenario is then a valuable alternative, in particular for a long-term response to selection.

  16. The Fifth Generation and Training Strategies

    ERIC Educational Resources Information Center

    Ennals, Richard

    2008-01-01

    Fifth Generation computers should not simply be regarded as an enhancement of current computer technology: the intention is that a fresh approach should be taken to computer science and to the use of computers. The argument of this paper is that the fresh approach must encompass education and training, with implications that extend far beyond the…

  17. Cisco Networking Academy: Next-Generation Assessments and Their Implications for K-12 Education

    ERIC Educational Resources Information Center

    Liu, Meredith

    2014-01-01

    To illuminate the possibilities for next-generation assessments in K-12 schools, this case study profiles the Cisco Networking Academy, which creates comprehensive online training curriculum to teach networking skills. Since 1997, the Cisco Networking Academy has served more than five million high school and college students and now delivers…

  18. Fifth Generation Computers: Their Implications for Further Education. An Occasional Paper.

    ERIC Educational Resources Information Center

    Ennals, Richard; Cotterell, Arthur

    Research to develop a fifth generation of computers is underway in several countries. These computers, which will be distinguished by the ability to provide knowledge information processing and respond to natural language commands, will have a profound impact on the labor market and hence on further education. Rather than being a separate…

  19. Using Generational Theory to Rethink Teaching in Higher Education

    ERIC Educational Resources Information Center

    Buskirk-Cohen, Allison A.; Duncan, Tisha A.; Levicoff, Margaret

    2016-01-01

    This paper reviews the literature on emerging adulthood with a focus on the implications of generational theory on teaching and learning in higher education. During the past 15 years, researchers have described personality traits, attitudes, and behaviors of emerging adults. Two very different views have emerged: one that is prosocial, citing…

  20. A Comparison of the Effectiveness of Two Design Methodologies in a Secondary School Setting.

    ERIC Educational Resources Information Center

    Cannizzaro, Brenton; Boughton, Doug

    1998-01-01

    Examines the effectiveness of the analysis-synthesis and generator-conjuncture-analysis models of design education. Concludes that the generator-conjecture-analysis design method produced student design product of a slightly higher standard than the analysis-synthesis design method. Discusses the findings in more detail and considers implications.…

  1. Language Implications for Advertising in International Markets: A Model for Message Content and Message Execution.

    ERIC Educational Resources Information Center

    Beard, John; Yaprak, Attila

    A content analysis model for assessing advertising themes and messages generated primarily for United States markets to overcome barriers in the cultural environment of international markets was developed and tested. The model is based on three primary categories for generating, evaluating, and executing advertisements: rational, emotional, and…

  2. A New Role for Education in Economic Development: Tomorrow's Economy Today.

    ERIC Educational Resources Information Center

    Blakely, Edward J.

    1997-01-01

    Argues the role of education as a wealth-generating and transformative resource for both local and national economies as communities shift from assembly-line to high-tech economies. Discussions include educational policy implications during a shift to high-technology industries, school districts as job generators, and universities as economic…

  3. Enhanced individual selection for selecting fast growing fish: the "PROSPER" method, with application on brown trout (Salmo trutta fario)

    PubMed Central

    Chevassus, Bernard; Quillet, Edwige; Krieg, Francine; Hollebecq, Marie-Gwénola; Mambrini, Muriel; Fauré, André; Labbé, Laurent; Hiseux, Jean-Pierre; Vandeputte, Marc

    2004-01-01

    Growth rate is the main breeding goal of fish breeders, but individual selection has often shown poor responses in fish species. The PROSPER method was developed to overcome possible factors that may contribute to this low success, using (1) a variable base population and high number of breeders (Ne > 100), (2) selection within groups with low non-genetic effects and (3) repeated growth challenges. Using calculations, we show that individual selection within groups, with appropriate management of maternal effects, can be superior to mass selection as soon as the maternal effect ratio exceeds 0.15, when heritability is 0.25. Practically, brown trout were selected on length at the age of one year with the PROSPER method. The genetic gain was evaluated against an unselected control line. After four generations, the mean response per generation in length at one year was 6.2% of the control mean, while the mean correlated response in weight was 21.5% of the control mean per generation. At the 4th generation, selected fish also appeared to be leaner than control fish when compared at the same size, and the response on weight was maximal (≈130% of the control mean) between 386 and 470 days post fertilisation. This high response is promising, however, the key points of the method have to be investigated in more detail. PMID:15496285

  4. Dynamic Dimensionality Selection for Bayesian Classifier Ensembles

    DTIC Science & Technology

    2015-03-19

    learning of weights in an otherwise generatively learned naive Bayes classifier. WANBIA-C is very cometitive to Logistic Regression but much more...classifier, Generative learning, Discriminative learning, Naïve Bayes, Feature selection, Logistic regression , higher order attribute independence 16...discriminative learning of weights in an otherwise generatively learned naive Bayes classifier. WANBIA-C is very cometitive to Logistic Regression but

  5. 40 CFR 761.308 - Sample selection by random number generation on any two-dimensional square grid.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... generation on any two-dimensional square grid. 761.308 Section 761.308 Protection of Environment... § 761.79(b)(3) § 761.308 Sample selection by random number generation on any two-dimensional square grid. (a) Divide the surface area of the non-porous surface into rectangular or square areas having a...

  6. 40 CFR 761.308 - Sample selection by random number generation on any two-dimensional square grid.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... generation on any two-dimensional square grid. 761.308 Section 761.308 Protection of Environment... § 761.79(b)(3) § 761.308 Sample selection by random number generation on any two-dimensional square grid. (a) Divide the surface area of the non-porous surface into rectangular or square areas having a...

  7. 40 CFR 761.308 - Sample selection by random number generation on any two-dimensional square grid.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... generation on any two-dimensional square grid. 761.308 Section 761.308 Protection of Environment... § 761.79(b)(3) § 761.308 Sample selection by random number generation on any two-dimensional square grid. (a) Divide the surface area of the non-porous surface into rectangular or square areas having a...

  8. 40 CFR 761.308 - Sample selection by random number generation on any two-dimensional square grid.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... generation on any two-dimensional square grid. 761.308 Section 761.308 Protection of Environment... § 761.79(b)(3) § 761.308 Sample selection by random number generation on any two-dimensional square grid. (a) Divide the surface area of the non-porous surface into rectangular or square areas having a...

  9. 40 CFR 761.308 - Sample selection by random number generation on any two-dimensional square grid.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... generation on any two-dimensional square grid. 761.308 Section 761.308 Protection of Environment... § 761.79(b)(3) § 761.308 Sample selection by random number generation on any two-dimensional square grid. (a) Divide the surface area of the non-porous surface into rectangular or square areas having a...

  10. Biophysical force regulation in 3D tumor cell invasion

    NASA Astrophysics Data System (ADS)

    Wu, Mingming

    When embedded within 3D extracellular matrices (ECM), animal cells constantly probe and adapt to the ECM locally (at cell length scale) and exert forces and communicate with other cells globally (up to 10 times of cell length). It is now well accepted that mechanical crosstalk between animal cells and their microenvironment critically regulate cell function such as migration, proliferation and differentiation. Disruption of the cell-ECM crosstalk is implicated in a number of pathologic processes including tumor progression and fibrosis. Central to the problem of cell-ECM crosstalk is the physical force that cells generate. By measuring single cell generated force within 3D collagen matrices, we revealed a mechanical crosstalk mechanism between the tumor cells and the ECM. Cells generate sufficient force to stiffen collagen fiber network, and stiffer matrix, in return promotes larger cell force generation. Our work highlights the importance of fibrous nonlinear elasticity in regulating tumor cell-ECM interaction, and results may have implications in the rapid tissue stiffening commonly found in tumor progression and fibrosis. This work is partially supported by NIH Grants R21RR025801 and R21GM103388.

  11. Development of Neural Sensitivity to Face Identity Correlates with Perceptual Discriminability

    PubMed Central

    Barnett, Michael A.; Hartley, Jake; Gomez, Jesse; Stigliani, Anthony; Grill-Spector, Kalanit

    2016-01-01

    Face perception is subserved by a series of face-selective regions in the human ventral stream, which undergo prolonged development from childhood to adulthood. However, it is unknown how neural development of these regions relates to the development of face-perception abilities. Here, we used functional magnetic resonance imaging (fMRI) to measure brain responses of ventral occipitotemporal regions in children (ages, 5–12 years) and adults (ages, 19–34 years) when they viewed faces that parametrically varied in dissimilarity. Since similar faces generate lower responses than dissimilar faces due to fMRI adaptation, this design objectively evaluates neural sensitivity to face identity across development. Additionally, a subset of subjects participated in a behavioral experiment to assess perceptual discriminability of face identity. Our data reveal three main findings: (1) neural sensitivity to face identity increases with age in face-selective but not object-selective regions; (2) the amplitude of responses to faces increases with age in both face-selective and object-selective regions; and (3) perceptual discriminability of face identity is correlated with the neural sensitivity to face identity of face-selective regions. In contrast, perceptual discriminability is not correlated with the amplitude of response in face-selective regions or of responses of object-selective regions. These data suggest that developmental increases in neural sensitivity to face identity in face-selective regions improve perceptual discriminability of faces. Our findings significantly advance the understanding of the neural mechanisms of development of face perception and open new avenues for using fMRI adaptation to study the neural development of high-level visual and cognitive functions more broadly. SIGNIFICANCE STATEMENT Face perception, which is critical for daily social interactions, develops from childhood to adulthood. However, it is unknown what developmental changes in the brain lead to improved performance. Using fMRI in children and adults, we find that from childhood to adulthood, neural sensitivity to changes in face identity increases in face-selective regions. Critically, subjects' perceptual discriminability among faces is linked to neural sensitivity: participants with higher neural sensitivity in face-selective regions demonstrate higher perceptual discriminability. Thus, our results suggest that developmental increases in face-selective regions' sensitivity to face identity improve perceptual discrimination of faces. These findings significantly advance understanding of the neural mechanisms underlying the development of face perception and have important implications for assessing both typical and atypical development. PMID:27798143

  12. Generation of American elm trees with tolerance to Dutch elm disease through controlled crosses and selection

    Treesearch

    James M. Slavicek; Kathleen S. Knight

    2012-01-01

    The goal of our research and development efforts is to generate new and/or improved selections of the American elm (Ulmus americana L.) with tolerance/resistance to Dutch elm disease (DED). The approaches we are taking for this effort include: 1) controlled breeding using known DED -tolerant selections, 2) controlled breeding using DED-tolerant...

  13. Method of generating features optimal to a dataset and classifier

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

    Bruillard, Paul J.; Gosink, Luke J.; Jarman, Kenneth D.

    A method of generating features optimal to a particular dataset and classifier is disclosed. A dataset of messages is inputted and a classifier is selected. An algebra of features is encoded. Computable features that are capable of describing the dataset from the algebra of features are selected. Irredundant features that are optimal for the classifier and the dataset are selected.

  14. Genetic selection for ovulation rate and litter size in rabbits: Estimation of genetic parameters and direct and correlated responses.

    PubMed

    Ziadi, C; Mocé, M L; Laborda, P; Blasco, A; Santacreu, M A

    2013-07-01

    The aim of this work was to estimate direct and correlated responses in survival rates in an experiment of selection for ovulation rate (OR) and litter size (LS) in a line of rabbits (OR_LS). From generation 0 to 6 (first selection period), females were selected only for second gestation OR estimated by laparoscopy. From generation 7 to 13 (second selection period), a 2-stage selection for OR and LS was performed. In stage 1, females having the greatest OR at second gestation were selected. In stage 2, selection was for the greatest average LS of the first 2 parities of the females selected in stage 1. Total selection pressure in females was about 30%. The line had approximately 17 males and 75 females per generation. Traits recorded were OR estimated as the number of corpora lutea in both ovaries, number of implanted embryos (IE) estimated as the number of implantation sites, LS estimated as total number of rabbits born recorded at each parity, embryo survival (ES) estimated as IE/OR, fetal survival (FS) estimated as LS/IE, and prenatal survival (PS) estimated as LS/OR. Data were analyzed using Bayesian methodology. The estimated heritabilities of LS, OR, IE, ES, FS, and PS were 0.07, 0.21, 0.10, 0.07, 0.12, and 0.16, respectively. Direct and correlated responses from this study were estimated in each period of selection as the difference between the average genetic values of last and first generation. In the first selection period, OR increased 1.36 ova, but no correlated response was observed in LS due to a decrease on FS. Correlated responses for IE, ES, FS, and PS in the first selection period were 1.11, 0.00, -0.04, and -0.01, respectively. After 7 generations of 2-stage selection for OR and LS, OR increased 1.0 ova and response in LS was 0.9 kits. Correlated responses for IE, ES, FS, and PS in the second selection period were 1.14, 0.02, 0.02, and 0.07, respectively. Two-stage selection for OR and LS can be a promising procedure to improve LS in rabbits.

  15. Designing Superoxide-Generating Quantum Dots for Selective Light-Activated Nanotherapy

    NASA Astrophysics Data System (ADS)

    Goodman, Samuel M.; Levy, Max; Li, Fei-Fei; Ding, Yuchen; Courtney, Colleen M.; Chowdhury, Partha P.; Erbse, Annette; Chatterjee, Anushree; Nagpal, Prashant

    2018-03-01

    The rapid emergence of superbugs or multi-drug resistant (MDR) organisms has prompted a search for novel antibiotics, beyond traditional small-molecule therapies. Nanotherapeutics are being investigated as alternatives, and recently superoxide-generating quantum dots (QDs) have been shown as important candidates for selective light-activated therapy and potentiating existing antibiotics against MDR superbugs. Their therapeutic action is selective, can be tailored by simply changing their quantum-confined conduction-valence bands and their alignment with different redox half-reactions, and hence their ability to generate specific radical species in biological media. Here, we show the design of superoxide-generating QDs using optimal QD material and size well matched to superoxide redox potential, charged ligands to modulate their uptake in cells and selective redox interventions, and core/shell structures to improve their stability for therapeutic action. We show that cadmium telluride (CdTe) QDs with conduction band position at -0.5V with respect to Normal Hydrogen Electron (NHE) and visible 2.4 eV bandgap generate a large flux of selective superoxide radicals, thereby demonstrating the most effective light-activated therapy. Although the positively charged QDs demonstrate large cellular uptake, they bind indiscriminately to cell surfaces and cause non-selective cell death, while negatively charged and zwitterionic QD ligands reduce the uptake and allow selective therapeutic action via interaction with redox species. The stability of designed QDs in biologically-relevant media increases with the formation of core-shell QD structures, but an appropriate design of core-shell structures is needed to minimize any reduction in charge injection efficiency to adsorbed oxygen molecules (to form superoxide) and maintain similar quantitative generation of tailored redox species, as measured using electron paramagnetic resonance (EPR) spectroscopy and electrochemical impedance spectroscopy. Using these findings, we demonstrate the rational design of QDs as selective therapeutic kills more than 99% of priority class I pathogens, thus providing an effective therapy against MDR superbugs.

  16. Designing Superoxide-Generating Quantum Dots for Selective Light-Activated Nanotherapy.

    PubMed

    Goodman, Samuel M; Levy, Max; Li, Fei-Fei; Ding, Yuchen; Courtney, Colleen M; Chowdhury, Partha P; Erbse, Annette; Chatterjee, Anushree; Nagpal, Prashant

    2018-01-01

    The rapid emergence of superbugs, or multi-drug resistant (MDR) organisms, has prompted a search for novel antibiotics, beyond traditional small-molecule therapies. Nanotherapeutics are being investigated as alternatives, and recently superoxide-generating quantum dots (QDs) have been shown as important candidates for selective light-activated therapy, while also potentiating existing antibiotics against MDR superbugs. Their therapeutic action is selective, can be tailored by simply changing their quantum-confined conduction-valence band (CB-VB) positions and alignment with different redox half-reactions-and hence their ability to generate specific radical species in biological media. Here, we show the design of superoxide-generating QDs using optimal QD material and size well-matched to superoxide redox potential, charged ligands to modulate their uptake in cells and selective redox interventions, and core/shell structures to improve their stability for therapeutic action. We show that cadmium telluride (CdTe) QDs with conduction band (CB) position at -0.5 V with respect to Normal Hydrogen Electron (NHE) and visible 2.4 eV bandgap generate a large flux of selective superoxide radicals, thereby demonstrating the effective light-activated therapy. Although the positively charged QDs demonstrate large cellular uptake, they bind indiscriminately to cell surfaces and cause non-selective cell death, while negatively charged and zwitterionic QD ligands reduce the uptake and allow selective therapeutic action via interaction with redox species. The stability of designed QDs in biologically-relevant media increases with the formation of core-shell QD structures, but an appropriate design of core-shell structures is needed to minimize any reduction in charge injection efficiency to adsorbed oxygen molecules (to form superoxide) and maintain similar quantitative generation of tailored redox species, as measured using electron paramagnetic resonance (EPR) spectroscopy and electrochemical impedance spectroscopy (EIS). Using these findings, we demonstrate the rational design of QDs as selective therapeutic to kill more than 99% of a priority class I pathogen, thus providing an effective therapy against MDR superbugs.

  17. Between-Region Genetic Divergence Reflects the Mode and Tempo of Tumor Evolution

    PubMed Central

    Sun, Ruping; Hu, Zheng; Sottoriva, Andrea; Graham, Trevor A.; Harpak, Arbel; Ma, Zhicheng; Fischer, Jared M.; Shibata, Darryl; Curtis, Christina

    2017-01-01

    Given the implications of tumor dynamics for precision medicine, there is a need to systematically characterize the mode of evolution across diverse solid tumor types. In particular, methods to infer the role of natural selection within established human tumors are lacking. By simulating spatial tumor growth under different evolutionary modes and examining patterns of between-region subclonal genetic divergence from multi-region sequencing (MRS) data, we demonstrate that it is feasible to distinguish tumors driven by strong positive subclonal selection from those evolving neutrally or under weak selection, as the latter fail to dramatically alter subclonal composition. We developed a classifier based on measures of between-region subclonal genetic divergence and projected patient data into model space, revealing different modes of evolution both within and between solid tumor types. Our findings have broad implications for how human tumors progress, accumulate intra-tumor heterogeneity, and ultimately how they may be more effectively treated. PMID:28581503

  18. Abstraction and generalization in statistical learning: implications for the relationship between semantic types and episodic tokens

    PubMed Central

    2017-01-01

    Statistical approaches to emergent knowledge have tended to focus on the process by which experience of individual episodes accumulates into generalizable experience across episodes. However, there is a seemingly opposite, but equally critical, process that such experience affords: the process by which, from a space of types (e.g. onions—a semantic class that develops through exposure to individual episodes involving individual onions), we can perceive or create, on-the-fly, a specific token (a specific onion, perhaps one that is chopped) in the absence of any prior perceptual experience with that specific token. This article reviews a selection of statistical learning studies that lead to the speculation that this process—the generation, on the basis of semantic memory, of a novel episodic representation—is itself an instance of a statistical, in fact associative, process. The article concludes that the same processes that enable statistical abstraction across individual episodes to form semantic memories also enable the generation, from those semantic memories, of representations that correspond to individual tokens, and of novel episodic facts about those tokens. Statistical learning is a window onto these deeper processes that underpin cognition. This article is part of the themed issue ‘New frontiers for statistical learning in the cognitive sciences’. PMID:27872378

  19. Heritable alteration of DNA methylation induced by whole-chromosome aneuploidy in wheat.

    PubMed

    Gao, Lihong; Diarso, Moussa; Zhang, Ai; Zhang, Huakun; Dong, Yuzhu; Liu, Lixia; Lv, Zhenling; Liu, Bao

    2016-01-01

    Aneuploidy causes changes in gene expression and phenotypes in all organisms studied. A previous study in the model plant Arabidopsis thaliana showed that aneuploidy-generated phenotypic changes can be inherited to euploid progenies and implicated an epigenetic underpinning of the heritable variations. Based on an analysis by amplified fragment length polymorphism and methylation-sensitive amplified fragment length polymorphism markers, we found that although genetic changes at the nucleotide sequence level were negligible, extensive changes in cytosine DNA methylation patterns occurred in all studied homeologous group 1 whole-chromosome aneuploid lines of common wheat (Triticum aestivum), with monosomic 1A showing the greatest amount of methylation changes. The changed methylation patterns were inherited by euploid progenies derived from the aneuploid parents. The aneuploidy-induced DNA methylation alterations and their heritability were verified at selected loci by bisulfite sequencing. Our data have provided empirical evidence supporting earlier suggestions that heritability of aneuploidy-generated, but aneuploidy-independent, phenotypic variations may have an epigenetic basis. That at least one type of aneuploidy - monosomic 1A - was able to cause significant epigenetic divergence of the aneuploid plants and their euploid progenies also lends support to recent suggestions that aneuploidy may have played an important and protracted role in polyploid genome evolution. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

  20. Abstraction and generalization in statistical learning: implications for the relationship between semantic types and episodic tokens.

    PubMed

    Altmann, Gerry T M

    2017-01-05

    Statistical approaches to emergent knowledge have tended to focus on the process by which experience of individual episodes accumulates into generalizable experience across episodes. However, there is a seemingly opposite, but equally critical, process that such experience affords: the process by which, from a space of types (e.g. onions-a semantic class that develops through exposure to individual episodes involving individual onions), we can perceive or create, on-the-fly, a specific token (a specific onion, perhaps one that is chopped) in the absence of any prior perceptual experience with that specific token. This article reviews a selection of statistical learning studies that lead to the speculation that this process-the generation, on the basis of semantic memory, of a novel episodic representation-is itself an instance of a statistical, in fact associative, process. The article concludes that the same processes that enable statistical abstraction across individual episodes to form semantic memories also enable the generation, from those semantic memories, of representations that correspond to individual tokens, and of novel episodic facts about those tokens. Statistical learning is a window onto these deeper processes that underpin cognition.This article is part of the themed issue 'New frontiers for statistical learning in the cognitive sciences'. © 2016 The Author(s).

  1. Characterizing fluvial heavy metal pollutions under different rainfall conditions: Implication for aquatic environment protection.

    PubMed

    Zhang, Lixun; Zhao, Bo; Xu, Gang; Guan, Yuntao

    2018-09-01

    Globally, fluvial heavy metal (HM) pollution has recently become an increasingly severe problem. However, few studies have investigated the variational characteristics of fluvial HMs after rain over long periods (≥1 year). The Dakan River in Xili Reservoir watershed (China) was selected as a case study to investigate pollution levels, influencing factors, and sources of HMs under different rainfall conditions during 2015 and 2016. Fluvial HMs showed evident spatiotemporal variations attributable to the coupled effects of pollution generation and rainfall diffusion. Fluvial HM concentrations were significantly associated with rainfall characteristics (e.g., rainfall intensity, rainfall amount, and antecedent dry period) and river flow, which influenced the generation and the transmission of fluvial HMs in various ways. Moreover, this interrelationship depended considerably on the HM type and particle size distribution. Mn, Pb, Cr, and Ni were major contributors to high values of the comprehensive pollution index; therefore, they should be afforded special attention. Additionally, quantitative source apportionment of fluvial HMs was conducted by combining principal component analysis with multiple linear regression and chemical mass balance models to obtain comprehensive source profiles. Finally, an environment-friendly control strategy coupling "source elimination" and "transport barriers" was proposed for aquatic environment protection. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Bioactive compounds produced by gut microbial tannase: implications for colorectal cancer development

    PubMed Central

    López de Felipe, Félix; de las Rivas, Blanca; Muñoz, Rosario

    2014-01-01

    The microorganisms in the human gastrointestinal tract have a profound influence on the transformation of food into metabolites which can impact human health. Gallic acid (GA) and pyrogallol (PG) are bioactive compounds displaying diverse biological properties, including carcinogenic inhibiting activities. However, its concentration in fruits and vegetables is generally low. These metabolites can be also generated as final products of tannin metabolism by microbes endowed with tannase, which opens up the possibility of their anti-cancer potential being increased. Patients with colorectal cancer (CRC) display an imbalanced gut microbiota respect to healthy population. The recent use of next generation sequencing technologies has greatly improved knowledge of the identity of bacterial species that colonize non-tumorous and tumorous tissues of CRC patients. This information provides a unique opportunity to shed light on the role played by gut microorganisms in the different stages of this disease. We here review the recently published gut microbiome associated to CRC patients and highlight tannase as an underlying gene function of bacterial species that selectively colonize tumorous tissues, but not adjacent non-malignant tissues. Given the anti-carcinogenic roles of GA and PG produced by gut tannin-degrading bacteria, we provide an overview of the possible consequences of this intriguing coincidence for CRC development. PMID:25538697

  3. Bioactive compounds produced by gut microbial tannase: implications for colorectal cancer development.

    PubMed

    López de Felipe, Félix; de Las Rivas, Blanca; Muñoz, Rosario

    2014-01-01

    The microorganisms in the human gastrointestinal tract have a profound influence on the transformation of food into metabolites which can impact human health. Gallic acid (GA) and pyrogallol (PG) are bioactive compounds displaying diverse biological properties, including carcinogenic inhibiting activities. However, its concentration in fruits and vegetables is generally low. These metabolites can be also generated as final products of tannin metabolism by microbes endowed with tannase, which opens up the possibility of their anti-cancer potential being increased. Patients with colorectal cancer (CRC) display an imbalanced gut microbiota respect to healthy population. The recent use of next generation sequencing technologies has greatly improved knowledge of the identity of bacterial species that colonize non-tumorous and tumorous tissues of CRC patients. This information provides a unique opportunity to shed light on the role played by gut microorganisms in the different stages of this disease. We here review the recently published gut microbiome associated to CRC patients and highlight tannase as an underlying gene function of bacterial species that selectively colonize tumorous tissues, but not adjacent non-malignant tissues. Given the anti-carcinogenic roles of GA and PG produced by gut tannin-degrading bacteria, we provide an overview of the possible consequences of this intriguing coincidence for CRC development.

  4. The role of internal duplication in the evolution of multi-domain proteins.

    PubMed

    Nacher, J C; Hayashida, M; Akutsu, T

    2010-08-01

    Many proteins consist of several structural domains. These multi-domain proteins have likely been generated by selective genome growth dynamics during evolution to perform new functions as well as to create structures that fold on a biologically feasible time scale. Domain units frequently evolved through a variety of genetic shuffling mechanisms. Here we examine the protein domain statistics of more than 1000 organisms including eukaryotic, archaeal and bacterial species. The analysis extends earlier findings on asymmetric statistical laws for proteome to a wider variety of species. While proteins are composed of a wide range of domains, displaying a power-law decay, the computation of domain families for each protein reveals an exponential distribution, characterizing a protein universe composed of a thin number of unique families. Structural studies in proteomics have shown that domain repeats, or internal duplicated domains, represent a small but significant fraction of genome. In spite of its importance, this observation has been largely overlooked until recently. We model the evolutionary dynamics of proteome and demonstrate that these distinct distributions are in fact rooted in an internal duplication mechanism. This process generates the contemporary protein structural domain universe, determines its reduced thickness, and tames its growth. These findings have important implications, ranging from protein interaction network modeling to evolutionary studies based on fundamental mechanisms governing genome expansion.

  5. Stochastic simulation and analysis of biomolecular reaction networks

    PubMed Central

    Frazier, John M; Chushak, Yaroslav; Foy, Brent

    2009-01-01

    Background In recent years, several stochastic simulation algorithms have been developed to generate Monte Carlo trajectories that describe the time evolution of the behavior of biomolecular reaction networks. However, the effects of various stochastic simulation and data analysis conditions on the observed dynamics of complex biomolecular reaction networks have not recieved much attention. In order to investigate these issues, we employed a a software package developed in out group, called Biomolecular Network Simulator (BNS), to simulate and analyze the behavior of such systems. The behavior of a hypothetical two gene in vitro transcription-translation reaction network is investigated using the Gillespie exact stochastic algorithm to illustrate some of the factors that influence the analysis and interpretation of these data. Results Specific issues affecting the analysis and interpretation of simulation data are investigated, including: (1) the effect of time interval on data presentation and time-weighted averaging of molecule numbers, (2) effect of time averaging interval on reaction rate analysis, (3) effect of number of simulations on precision of model predictions, and (4) implications of stochastic simulations on optimization procedures. Conclusion The two main factors affecting the analysis of stochastic simulations are: (1) the selection of time intervals to compute or average state variables and (2) the number of simulations generated to evaluate the system behavior. PMID:19534796

  6. The role of alternative splicing coupled to nonsense-mediated mRNA decay in human disease.

    PubMed

    da Costa, Paulo J; Menezes, Juliane; Romão, Luísa

    2017-10-01

    Alternative pre-mRNA splicing (AS) affects gene expression as it generates proteome diversity. Nonsense-mediated mRNA decay (NMD) is a surveillance pathway that recognizes and selectively degrades mRNAs carrying premature translation-termination codons (PTCs), preventing the production of truncated proteins that could result in disease. Several studies have also implicated NMD in the regulation of steady-state levels of physiological mRNAs. In addition, it is known that several regulated AS events do not lead to generation of protein products, as they lead to transcripts that carry PTCs and thus, they are committed to NMD. Indeed, an estimated one-third of naturally occurring, alternatively spliced mRNAs is targeted for NMD, being AS coupled to NMD (AS-NMD) an efficient strategy to regulate gene expression. In this review, we will focus on how AS mechanism operates and how can be coupled to NMD to fine-tune gene expression levels. Furthermore, we will demonstrate the physiological significance of the interplay among AS and NMD in human disease, such as cancer and neurological disorders. The understanding of how AS-NMD orchestrates expression of vital genes is of utmost importance for the advance in diagnosis, prognosis and treatment of many human disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Rare phenotypes in the understanding of autoimmunity

    PubMed Central

    Zeissig, Yvonne; Petersen, Britt-Sabina; Franke, Andre; Blumberg, Richard S; Zeissig, Sebastian

    2017-01-01

    The study of rare phenotypes has a long history in the description of autoimmune disorders. First Mendelian syndromes of idiopathic tissue destruction were defined more than 100 years ago and were later revealed to result from immune-mediated reactivity against self. In the past two decades, continuous advances in sequencing technology and particularly the advent of next-generation sequencing have allowed to define the genetic basis of an ever-growing number of Mendelian forms of autoimmunity. This has provided unique insight into the molecular pathways that govern immunological homeostasis and that are indispensable for the prevention of self-reactive immune-mediated tissue damage and ‘horror autotoxicus’. Here we will discuss selected examples of past and recent investigations into rare phenotypes of autoimmunity that have delineated pathways critical for central and peripheral control of the adaptive immune system. We will outline the implications of these findings for rare and common forms of autoimmunity and will discuss the benefits and potential pitfalls of the integration of next-generation sequencing into algorithms for clinical diagnostics. Because of the concise nature of this review, we will focus on syndromes caused by defects in the control of adaptive immunity as innate immune-mediated autoinflammatory disorders have been covered in excellent recent reviews on Mendelian and polygenic forms of autoimmunity. PMID:27562064

  8. Contributions of Volumetrics of the Hippocampus and Thalamus to Verbal Memory in Temporal Lobe Epilepsy Patients

    ERIC Educational Resources Information Center

    Stewart, Christopher C.; Griffith, H. Randall; Okonkwo, Ozioma C.; Martin, Roy C.; Knowlton, Robert K.; Richardson, Elizabeth J.; Hermann, Bruce P.; Seidenberg, Michael

    2009-01-01

    Recent theories have posited that the hippocampus and thalamus serve distinct, yet related, roles in episodic memory. Whereas the hippocampus has been implicated in long-term memory encoding and storage, the thalamus, as a whole, has been implicated in the selection of items for subsequent encoding and the use of retrieval strategies. However,…

  9. A Surveillance and Targeting System for an Unmanned Ground Vehicle

    DTIC Science & Technology

    1990-08-01

    CHARACTERISTICS - SELECTABLE INFRASONIC AND ULTRASONIC FREQUENCY SHIFTING CAPABILITY - SUPER-BINAURAL CONFIGURATION ANGLE AND PICKUP SEPARATION GREATER THAN...HUMAN HEAD - VARIABLE GAIN WITH CLIPPING - INTEGRATABLE INTO TOV OPERATOR HELMET - CONTROL INTERFACE: VOLUME UP/DOWN, SONIC ON/OFF, ULTRA ON/OFF... INFRA ON/OFF, BOOST HI/MED/OFF ----- UGV/TOV ----- ---- AUVS/DAYTON ---- LASER SAFETY IMPLICATIONS IMPLICATIONS FOR DESIGN: - POWER UP SEQUENCE - ABORT

  10. Economic and Technology Forecasts for the 80's: Implications for Careers. Proceedings of the Patterns Conference (Rochester Institute of Technology, May 1979).

    ERIC Educational Resources Information Center

    Nystrom, Dennis; And Others

    Selected technological and research areas that may affect emerging careers and work expectations were discussed in the five seminar presentations contained in this proceedings. In the introductory section, Dennis Nystrom outlines the goals of the conference and suggests possible implications. Sar Levitan, in the keynote address, examines the…

  11. Implications of Biomedical Technology. Harvard University Program on Technology and Society; Research Review Number One.

    ERIC Educational Resources Information Center

    Taviss, Irene, Ed.; Koivumaki, Judith, Ed.

    A small number of books and articles devoted to the social, political, ethical, and legal implications of the biomedical field and technology have been abstracted for this document. A basic criterion for selection was the focus on questions of overall organization and public policy rather than on more specialized concerns. Topics covered include…

  12. Timing and synchrony of births in bighorn sheep: implications for reintroduction and conservation

    USGS Publications Warehouse

    Whiting, Jericho C.; Olson, Daniel D.; Shannon, Justin M.; Bowyer, R. Terry; Klaver, Robert W.; Flinders, Jerran T.

    2012-01-01

    Implications: Consideration should be given to the adjustment of timing and synchrony of births when reintroducing bighorns, especially when animals are released into different ecoregions. Also, biologists should select release sites that are ecologically similar to source areas, thereby reducing potential negative effects of animals adjusting timing and synchrony of births to environmental conditions of restoration areas.

  13. Generating a Simulated Fluid Flow over a Surface Using Anisotropic Diffusion

    NASA Technical Reports Server (NTRS)

    Rodriguez, David L. (Inventor); Sturdza, Peter (Inventor)

    2016-01-01

    A fluid-flow simulation over a computer-generated surface is generated using a diffusion technique. The surface is comprised of a surface mesh of polygons. A boundary-layer fluid property is obtained for a subset of the polygons of the surface mesh. A gradient vector is determined for a selected polygon, the selected polygon belonging to the surface mesh but not one of the subset of polygons. A maximum and minimum diffusion rate is determined along directions determined using the gradient vector corresponding to the selected polygon. A diffusion-path vector is defined between a point in the selected polygon and a neighboring point in a neighboring polygon. An updated fluid property is determined for the selected polygon using a variable diffusion rate, the variable diffusion rate based on the minimum diffusion rate, maximum diffusion rate, and the gradient vector.

  14. The role of frictional stress in misfit dislocation generation

    NASA Technical Reports Server (NTRS)

    Jesser, William A.

    1992-01-01

    An evaluation is undertaken of the implications of the friction and frictionless models of misfit dislocation generation in view of: (1) experimental measurements of the critical thickness above which misfit dislocation generation occurs; and (2) the amount of strain relaxation that occurs as a function of layer thickness, time, and temperature. Some of the frictional force terms that were expected to exhibit a strong temperature dependence are shown to be independent of temperature.

  15. Policy Challenges of Accelerating Technological Change: Security Policy and Strategy Implications of Parallel Scientific Revolutions

    DTIC Science & Technology

    2014-09-01

    generation, exotic storage technologies, smart power grid management, and better power sources for directed-energy weapons (DEW). Accessible partner nation...near term will help to mitigate risks and improve outcomes. 2 Forecasting typically extrapolates predictions based...eventually, diminished national power . Within this context, this paper examines policy, legal, ethical, and strategy implications for DoD from the impact

  16. Development of a hybrid photo-bioreactor and nanoparticle adsorbent system for the removal of CO2, and selected organic and metal co-pollutants.

    PubMed

    Rocha, Andrea A; Wilde, Christian; Hu, Zhenzhong; Nepotchatykh, Oleg; Nazarenko, Yevgen; Ariya, Parisa A

    2017-07-01

    Fossil fuel combustion and many industrial processes generate gaseous emissions that contain a number of toxic organic pollutants and carbon dioxide (CO 2 ) which contribute to climate change and atmospheric pollution. There is a need for green and sustainable solutions to remove air pollutants, as opposed to conventional techniques which can be expensive, consume additional energy and generate further waste. We developed a novel integrated bioreactor combined with recyclable iron oxide nano/micro-particle adsorption interfaces, to remove CO 2, and undesired organic air pollutants using natural particles, while generating oxygen. This semi-continuous bench-scale photo-bioreactor was shown to successfully clean up simulated emission streams of up to 45% CO 2 with a conversion rate of approximately 4% CO 2 per hour, generating a steady supply of oxygen (6mmol/hr), while nanoparticles effectively remove several undesired organic by-products. We also showed algal waste of the bioreactor can be used for mercury remediation. We estimated the potential CO 2 emissions that could be captured from our new method for three industrial cases in which, coal, oil and natural gas were used. With a 30% carbon capture system, the reduction of CO 2 was estimated to decrease by about 420,000, 320,000 and 240,000 metric tonnes, respectively for a typical 500MW power plant. The cost analysis we conducted showed potential to scale-up, and the entire system is recyclable and sustainable. We further discuss the implications of usage of this complete system, or as individual units, that could provide a hybrid option to existing industrial setups. Copyright © 2016. Published by Elsevier B.V.

  17. Directed midbrain and spinal cord neurogenesis from pluripotent stem cells to model development and disease in a dish

    PubMed Central

    Allodi, Ilary; Hedlund, Eva

    2014-01-01

    Induction of specific neuronal fates is restricted in time and space in the developing CNS through integration of extrinsic morphogen signals and intrinsic determinants. Morphogens impose regional characteristics on neural progenitors and establish distinct progenitor domains. Such domains are defined by unique expression patterns of fate determining transcription factors. These processes of neuronal fate specification can be recapitulated in vitro using pluripotent stem cells. In this review, we focus on the generation of dopamine neurons and motor neurons, which are induced at ventral positions of the neural tube through Sonic hedgehog (Shh) signaling, and defined at anteroposterior positions by fibroblast growth factor (Fgf) 8, Wnt1, and retinoic acid (RA). In vitro utilization of these morphogenic signals typically results in the generation of multiple neuronal cell types, which are defined at the intersection of these signals. If the purpose of in vitro neurogenesis is to generate one cell type only, further lineage restriction can be accomplished by forced expression of specific transcription factors in a permissive environment. Alternatively, cell-sorting strategies allow for selection of neuronal progenitors or mature neurons. However, modeling development, disease and prospective therapies in a dish could benefit from structured heterogeneity, where desired neurons are appropriately synaptically connected and thus better reflect the three-dimensional structure of that region. By modulating the extrinsic environment to direct sequential generation of neural progenitors within a domain, followed by self-organization and synaptic establishment, a reductionist model of that brain region could be created. Here we review recent advances in neuronal fate induction in vitro, with a focus on the interplay between cell intrinsic and extrinsic factors, and discuss the implications for studying development and disease in a dish. PMID:24904255

  18. Directed midbrain and spinal cord neurogenesis from pluripotent stem cells to model development and disease in a dish.

    PubMed

    Allodi, Ilary; Hedlund, Eva

    2014-01-01

    Induction of specific neuronal fates is restricted in time and space in the developing CNS through integration of extrinsic morphogen signals and intrinsic determinants. Morphogens impose regional characteristics on neural progenitors and establish distinct progenitor domains. Such domains are defined by unique expression patterns of fate determining transcription factors. These processes of neuronal fate specification can be recapitulated in vitro using pluripotent stem cells. In this review, we focus on the generation of dopamine neurons and motor neurons, which are induced at ventral positions of the neural tube through Sonic hedgehog (Shh) signaling, and defined at anteroposterior positions by fibroblast growth factor (Fgf) 8, Wnt1, and retinoic acid (RA). In vitro utilization of these morphogenic signals typically results in the generation of multiple neuronal cell types, which are defined at the intersection of these signals. If the purpose of in vitro neurogenesis is to generate one cell type only, further lineage restriction can be accomplished by forced expression of specific transcription factors in a permissive environment. Alternatively, cell-sorting strategies allow for selection of neuronal progenitors or mature neurons. However, modeling development, disease and prospective therapies in a dish could benefit from structured heterogeneity, where desired neurons are appropriately synaptically connected and thus better reflect the three-dimensional structure of that region. By modulating the extrinsic environment to direct sequential generation of neural progenitors within a domain, followed by self-organization and synaptic establishment, a reductionist model of that brain region could be created. Here we review recent advances in neuronal fate induction in vitro, with a focus on the interplay between cell intrinsic and extrinsic factors, and discuss the implications for studying development and disease in a dish.

  19. Behavioral variability in an evolutionary theory of behavior dynamics.

    PubMed

    Popa, Andrei; McDowell, J J

    2016-03-01

    McDowell's evolutionary theory of behavior dynamics (McDowell, 2004) instantiates populations of behaviors (abstractly represented by integers) that evolve under the selection pressure of the environment in the form of positive reinforcement. Each generation gives rise to the next via low-level Darwinian processes of selection, recombination, and mutation. The emergent patterns can be analyzed and compared to those produced by biological organisms. The purpose of this project was to explore the effects of high mutation rates on behavioral variability in environments that arranged different reinforcer rates and magnitudes. Behavioral variability increased with the rate of mutation. High reinforcer rates and magnitudes reduced these effects; low reinforcer rates and magnitudes augmented them. These results are in agreement with live-organism research on behavioral variability. Various combinations of mutation rates, reinforcer rates, and reinforcer magnitudes produced similar high-level outcomes (equifinality). These findings suggest that the independent variables that describe an experimental condition interact; that is, they do not influence behavior independently. These conclusions have implications for the interpretation of high levels of variability, mathematical undermatching, and the matching theory. The last part of the discussion centers on a potential biological counterpart for the rate of mutation, namely spontaneous fluctuations in the brain's default mode network. © 2016 Society for the Experimental Analysis of Behavior.

  20. Environment-dependent regulation of spliceosome activity by the LSM2-8 complex in Arabidopsis.

    PubMed

    Carrasco-López, Cristian; Hernández-Verdeja, Tamara; Perea-Resa, Carlos; Abia, David; Catalá, Rafael; Salinas, Julio

    2017-07-07

    Spliceosome activity is tightly regulated to ensure adequate splicing in response to internal and external cues. It has been suggested that core components of the spliceosome, such as the snRNPs, would participate in the control of its activity. The experimental indications supporting this proposition, however, remain scarce, and the operating mechanisms poorly understood. Here, we present genetic and molecular evidence demonstrating that the LSM2-8 complex, the protein moiety of the U6 snRNP, regulates the spliceosome activity in Arabidopsis, and that this regulation is controlled by the environmental conditions. Our results show that the complex ensures the efficiency and accuracy of constitutive and alternative splicing of selected pre-mRNAs, depending on the conditions. Moreover, miss-splicing of most targeted pre-mRNAs leads to the generation of nonsense mediated decay signatures, indicating that the LSM2-8 complex also guarantees adequate levels of the corresponding functional transcripts. Interestingly, the selective role of the complex has relevant physiological implications since it is required for adequate plant adaptation to abiotic stresses. These findings unveil an unanticipated function for the LSM2-8 complex that represents a new layer of posttranscriptional regulation in response to external stimuli in eukaryotes. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

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