WorldWideScience

Sample records for response selection disrupts

  1. Incumbent response to disruptive innovation

    Kaulio, Matti; Thorén, Kent; Rohrbeck, René

    in relation to disruptive change. In relation to technical change the case company has successfully in transferred its technology from one generation to the next during more than 20 years. In relation to business model change the case company has been proactive but not successful in major business model......This article presents a preliminary analysis of a retrospective longitudinal case study of an incumbent, the Swedish-Finnish Telecom operator TeliaSonera AB, with focus on its responses to technical and business model change. Findings nuance the general understanding of Telco’s as passive actors...... changes, however successful in minor business model adaptions. An implication hereof is that the business model concept as such has low predictive power in explaining success and failure and is in the need of an operationalization. In addition, the article discusses the relationship between technological...

  2. Routine Responses to Disruption of Routines

    Guha, Mahua

    2015-01-01

    "Organisational routines" is a widely studied research area. However, there is a dearth of research on disruption of routines. The few studies on disruption of routines discussed problem-solving activities that are carried out in response to disruption. In contrast, this study develops a theory of "solution routines" that are a…

  3. Disruptions, loads, and dynamic response of ITER

    Nelson, B.; Riemer, B.; Sayer, R.; Strickler, D.; Barabaschi, P.; Ioki, K.; Johnson, G.; Shimizu, K.; Williamson, D.

    1995-01-01

    Plasma disruptions and the resulting electromagnetic loads are critical to the design of the vacuum vessel and in-vessel components of the International Thermonuclear Experimental Reactor (ITER). This paper describes the status of plasma disruption simulations and related analysis, including the dynamic response of the vacuum vessel and in-vessel components, stresses and deflections in the vacuum vessel, and reaction loads in the support structures

  4. Selective disruption of the AKAP signaling complexes.

    Kennedy, Eileen J; Scott, John D

    2015-01-01

    Synthesis of the second messenger cAMP activates a variety of signaling pathways critical for all facets of intracellular regulation. Protein kinase A (PKA) is the major cAMP-responsive effector. Where and when this enzyme is activated has profound implications on the cellular role of PKA. A-Kinase Anchoring Proteins (AKAPs) play a critical role in this process by orchestrating spatial and temporal aspects of PKA action. A popular means of evaluating the impact of these anchored signaling events is to biochemically interfere with the PKA-AKAP interface. Hence, peptide disruptors of PKA anchoring are valuable tools in the investigation of local PKA action. This article outlines the development of PKA isoform-selective disruptor peptides, documents the optimization of cell-soluble peptide derivatives, and introduces alternative cell-based approaches that interrogate other aspects of the PKA-AKAP interface.

  5. Emotion disrupts neural activity during selective attention in psychopathy.

    Sadeh, Naomi; Spielberg, Jeffrey M; Heller, Wendy; Herrington, John D; Engels, Anna S; Warren, Stacie L; Crocker, Laura D; Sutton, Bradley P; Miller, Gregory A

    2013-03-01

    Dimensions of psychopathy are theorized to be associated with distinct cognitive and emotional abnormalities that may represent unique neurobiological risk factors for the disorder. This hypothesis was investigated by examining whether the psychopathic personality dimensions of fearless-dominance and impulsive-antisociality moderated neural activity and behavioral responses associated with selective attention and emotional processing during an emotion-word Stroop task in 49 adults. As predicted, the dimensions evidenced divergent selective-attention deficits and sensitivity to emotional distraction. Fearless-dominance was associated with disrupted attentional control to positive words, and activation in right superior frontal gyrus mediated the relationship between fearless-dominance and errors to positive words. In contrast, impulsive-antisociality evidenced increased behavioral interference to both positive and negative words and correlated positively with recruitment of regions associated with motivational salience (amygdala, orbitofrontal cortex, insula), emotion regulation (temporal cortex, superior frontal gyrus) and attentional control (dorsal anterior cingulate cortex). Individuals high on both dimensions had increased recruitment of regions related to attentional control (temporal cortex, rostral anterior cingulate cortex), response preparation (pre-/post-central gyri) and motivational value (orbitofrontal cortex) in response to negative words. These findings provide evidence that the psychopathy dimensions represent dual sets of risk factors characterized by divergent dysfunction in cognitive and affective processes.

  6. Production control and supplier selection under demand disruptions

    Xianzhe Chen

    2010-12-01

    Full Text Available This paper investigates the effects of demand disruptions on production control and supplier selection in a three-echelon supply chain system. The customer demand is modeled as a jump-diffusion process in a continuous-time setting. A two-number production-inventory policy is implemented in the production control model for the manufacturer. The objective is to minimize the long-term average total cost consisting of backlog cost, holding cost, switching cost, and ordering cost. The simulated annealing method is applied to search the optimal critical switching values. Furthermore, an improved analytical hierarchy process (AHP is proposed to select the best supplier, based on quantitative factors such as the optimal long-term total cost obtained through the simulated annealing method under demand disruptions and qualitative factors such as quality and service. Numerical studies are conducted to demonstrate the effects of demand disruptions in the face of various risk scenarios. Managerial insights from simulation results are provided as well. Our approaches can be implemented as the “stress test” for companies in front of various supply chain disruption scenarios.

  7. Improved feature selection based on genetic algorithms for real time disruption prediction on JET

    Ratta, G.A., E-mail: garatta@gateme.unsj.edu.ar [GATEME, Facultad de Ingenieria, Universidad Nacional de San Juan, Avda. San Martin 1109 (O), 5400 San Juan (Argentina); JET EFDA, Culham Science Centre, OX14 3DB Abingdon (United Kingdom); Vega, J. [Asociacion EURATOM/CIEMAT para Fusion, Avda. Complutense, 40, 28040 Madrid (Spain); JET EFDA, Culham Science Centre, OX14 3DB Abingdon (United Kingdom); Murari, A. [Associazione EURATOM-ENEA per la Fusione, Consorzio RFX, 4-35127 Padova (Italy); JET EFDA, Culham Science Centre, OX14 3DB Abingdon (United Kingdom)

    2012-09-15

    Highlights: Black-Right-Pointing-Pointer A new signal selection methodology to improve disruption prediction is reported. Black-Right-Pointing-Pointer The approach is based on Genetic Algorithms. Black-Right-Pointing-Pointer An advanced predictor has been created with the new set of signals. Black-Right-Pointing-Pointer The new system obtains considerably higher prediction rates. - Abstract: The early prediction of disruptions is an important aspect of the research in the field of Tokamak control. A very recent predictor, called 'Advanced Predictor Of Disruptions' (APODIS), developed for the 'Joint European Torus' (JET), implements the real time recognition of incoming disruptions with the best success rate achieved ever and an outstanding stability for long periods following training. In this article, a new methodology to select the set of the signals' parameters in order to maximize the performance of the predictor is reported. The approach is based on 'Genetic Algorithms' (GAs). With the feature selection derived from GAs, a new version of APODIS has been developed. The results are significantly better than the previous version not only in terms of success rates but also in extending the interval before the disruption in which reliable predictions are achieved. Correct disruption predictions with a success rate in excess of 90% have been achieved 200 ms before the time of the disruption. The predictor response is compared with that of JET's Protection System (JPS) and the ADODIS predictor is shown to be far superior. Both systems have been carefully tested with a wide number of discharges to understand their relative merits and the most profitable directions of further improvements.

  8. Improved feature selection based on genetic algorithms for real time disruption prediction on JET

    Rattá, G.A.; Vega, J.; Murari, A.

    2012-01-01

    Highlights: ► A new signal selection methodology to improve disruption prediction is reported. ► The approach is based on Genetic Algorithms. ► An advanced predictor has been created with the new set of signals. ► The new system obtains considerably higher prediction rates. - Abstract: The early prediction of disruptions is an important aspect of the research in the field of Tokamak control. A very recent predictor, called “Advanced Predictor Of Disruptions” (APODIS), developed for the “Joint European Torus” (JET), implements the real time recognition of incoming disruptions with the best success rate achieved ever and an outstanding stability for long periods following training. In this article, a new methodology to select the set of the signals’ parameters in order to maximize the performance of the predictor is reported. The approach is based on “Genetic Algorithms” (GAs). With the feature selection derived from GAs, a new version of APODIS has been developed. The results are significantly better than the previous version not only in terms of success rates but also in extending the interval before the disruption in which reliable predictions are achieved. Correct disruption predictions with a success rate in excess of 90% have been achieved 200 ms before the time of the disruption. The predictor response is compared with that of JET's Protection System (JPS) and the ADODIS predictor is shown to be far superior. Both systems have been carefully tested with a wide number of discharges to understand their relative merits and the most profitable directions of further improvements.

  9. Disruption?

    2016-01-01

    This is a short video on the theme disruption and entrepreneurship. It takes the form of an interview with John Murray......This is a short video on the theme disruption and entrepreneurship. It takes the form of an interview with John Murray...

  10. Endocrine disruption of sexual selection by an estrogenic herbicide in the mealworm beetle (Tenebrio molitor).

    McCallum, Malcolm L; Matlock, Makensey; Treas, Justin; Safi, Barroq; Sanson, Wendy; McCallum, Jamie L

    2013-12-01

    The role that endocrine disruption could play in sexual selection remains relatively untested, and although estrogens occur in insects, little information exists about their biological role in insect reproduction. Atrazine is a commonly applied herbicide that mimics estrogen in vertebrates. Tenebrio molitor were raised from egg to adult under a gradation of environmentally relevant atrazine exposures and a non-treated control. Atrazine was delivered in the drinking water ad libitum. Female T. molitor were provided with a choice between unrelated males raised under three levels of atrazine exposures. Female preference for males demonstrated a non-monotonic inverted U-shaped response to atrazine exposure. There was no significant difference between the control and the high exposure to atrazine. Excluding the control, female preference increased as exposure concentration increased. These results have important repercussions for nonlethal effects of endocrine disruption on populations, their capacity to interfere with sexual selection, and the role of estrogen in pheromone communication among insects.

  11. Digital Dimension Disruption: A National Security Enterprise Response

    2017-12-21

    PRISM 7, NO. 2 FEATURES | 41 Digital Dimension Disruption A National Security Enterprise Response By Charles Rybeck, Lanny Cornwell, and Philip Sagan...1 The slow-motion collapse of parts of the 20th century’s legacy is now accelerating in ways that likely will usher in a monumental realignment of...societal institutions, methods of business, and fundamental ideas about national security. This realignment will , of necessity, change the frameworks

  12. The effects of disruptive and stabilizing selection on body size in Drosophila melanogaster. III. Genetic analysis of two lines with different reactions to disruptive selection with mating of opposite extremes

    Bos, M.; Scharloo, W.

    1974-01-01

    A genetic analysis was made of two lines which when subjected to disruptive selection with compulsary mating of opposite extremes (D−) showed a different response viz. one, D−-1, showing predominantly an increase of environmental variance and possibly interaction variance, the other, D−-2, showing

  13. Structural responses to plasma disruptions in toroidal shells

    Tillack, M.S.; Kazimi, M.S.; Lidsky, L.M.

    1985-01-01

    The induced pressures, stresses and strains in unrestrained axisymmetric toroidal shells are studied to scope the behavior of tokamak first walls during plasma disruptions. The modeling includes a circuit analog representation of the shell to solve for induced currents and pressures, and a separate quasi-static 1-D finite element solution for the mechanical response. This work demonstrates that the stresses in tokamkak first walls due to plasma disruption may be large, but to first order will not cause failure in the bulk structure. However, stress concentrations at structural supports and discontinuities together with resonant effects can result in large enhancements of the stresses, which could contribute to plastic deformation or failure when added to the already large steady state thermal and pressure loading of the first wall

  14. A Peptidomimetic Antibiotic Targets Outer Membrane Proteins and Disrupts Selectively the Outer Membrane in Escherichia coli.

    Urfer, Matthias; Bogdanovic, Jasmina; Lo Monte, Fabio; Moehle, Kerstin; Zerbe, Katja; Omasits, Ulrich; Ahrens, Christian H; Pessi, Gabriella; Eberl, Leo; Robinson, John A

    2016-01-22

    Increasing antibacterial resistance presents a major challenge in antibiotic discovery. One attractive target in Gram-negative bacteria is the unique asymmetric outer membrane (OM), which acts as a permeability barrier that protects the cell from external stresses, such as the presence of antibiotics. We describe a novel β-hairpin macrocyclic peptide JB-95 with potent antimicrobial activity against Escherichia coli. This peptide exhibits no cellular lytic activity, but electron microscopy and fluorescence studies reveal an ability to selectively disrupt the OM but not the inner membrane of E. coli. The selective targeting of the OM probably occurs through interactions of JB-95 with selected β-barrel OM proteins, including BamA and LptD as shown by photolabeling experiments. Membrane proteomic studies reveal rapid depletion of many β-barrel OM proteins from JB-95-treated E. coli, consistent with induction of a membrane stress response and/or direct inhibition of the Bam folding machine. The results suggest that lethal disruption of the OM by JB-95 occurs through a novel mechanism of action at key interaction sites within clusters of β-barrel proteins in the OM. These findings open new avenues for developing antibiotics that specifically target β-barrel proteins and the integrity of the Gram-negative OM. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Nonlinear disruption of ecological interactions in response to nitrogen deposition.

    Ochoa-Hueso, Raúl

    2016-10-01

    Global environmental change (GEC) is affecting species interactions and causing a rapid decline in biodiversity. In this study, I present a new Ecosystem Disruption Index to quantify the impacts of simulated nitrogen (N) deposition (0, 10, 20, and 50 kg N·ha -1 ·yr -1  + 6-7 kg N·ha -1 ·yr -1 background) on abiotic and biotic ecological interactions. This comparative index is based on pairwise linear and quadratic regression matrices. These matrices, calculated at the N treatment level, were constructed using a range of abiotic and biotic ecosystem constituents: soil pH, shrub cover, and the first component of several separate principal component analyses using soil fertility data (total carbon and N) and community data (annual plants, microorganisms, biocrusts, edaphic fauna) for a total of seven ecosystem constituents. Four years of N fertilization in a semiarid shrubland completely disrupted the network of ecological interactions, with a greater proportional increase in ecosystem disruption at low N addition levels. Biotic interactions, particularly those involving microbes, shrubs, and edaphic fauna, were more prone to be lost in response to N, whereas interactions involving soil properties were more resilient. In contrast, edaphic fauna was the only group directly affected by N addition, with mites and collembolans increasing their abundance with up to 20 kg N·ha -1 ·yr -1 and then decreasing, which supports the idea of higher-trophic-level organisms being more sensitive to disturbance due to more complex links with other ecosystem constituents. Future experimental studies evaluating the impacts of N deposition, and possibly other GEC drivers, on biodiversity and biotic and abiotic interactions may be able to explain results more effectively in the context of ecological networks as a key feature of ecosystem sensitivity. © 2016 by the Ecological Society of America.

  16. The long-term evolution of multilocus traits under frequency-dependent disruptive selection

    Van Doorn, G. Sander; Dieckmann, Ulf

    Frequency-dependent disruptive selection is widely recognized as an important source of genetic variation. Its evolutionary consequences have been extensively studied using phenotypic evolutionary models, based on quantitative genetics, game theory, or adaptive dynamics. However, the genetic

  17. The selective disruption of spatial working memory by eye movements.

    Postle, Bradley R; Idzikowski, Christopher; Sala, Sergio Della; Logie, Robert H; Baddeley, Alan D

    2006-01-01

    In the late 1970s/early 1980s, Baddeley and colleagues conducted a series of experiments investigating the role of eye movements in visual working memory. Although only described briefly in a book, these studies have influenced a remarkable number of empirical and theoretical developments in fields ranging from experimental psychology to human neuropsychology to nonhuman primate electrophysiology. This paper presents, in full detail, three critical studies from this series, together with a recently performed study that includes a level of eye movement measurement and control that was not available for the older studies. Together, the results demonstrate several facts about the sensitivity of visuospatial working memory to eye movements. First, it is eye movement control, not movement per se, that produces the disruptive effects. Second, these effects are limited to working memory for locations and do not generalize to visual working memory for shapes. Third, they can be isolated to the storage/maintenance components of working memory (e.g., to the delay period of the delayed-recognition task). These facts have important implications for models of visual working memory.

  18. GAP1, a novel selection and counter-selection marker for multiple gene disruptions in Saccharomyces cerevisiae

    Regenberg, Birgitte; Hansen, J.

    2000-01-01

    the GAP1 gene. This is caused by recombination between two Salmonella typuimurium hisG direct repeats embracing GAP1, and will result in a sub-population of gap1 cells. Such cells are selected on a medium containing D-histidine, and may subsequently be used for a second gene disruption. Hence, multiple...... flanked by short (60 bp) stretches of the gene in question. Through homologous recombination, the cassette will integrate into the target gene, which is thus replaced by GAP1, and mutants are selected for on minimal L-citrulline medium. When propagated under non-selective conditions, some cells will lose...... gene disruptions can be made fast, cheaply and easily in a gap1 strain, with two positive selection steps for each disruption. Copyright (C) 2000 John Wiley & Sons, Ltd....

  19. Selective, retrieval-independent disruption of methamphetamine-associated memory by actin depolymerization.

    Young, Erica J; Aceti, Massimiliano; Griggs, Erica M; Fuchs, Rita A; Zigmond, Zachary; Rumbaugh, Gavin; Miller, Courtney A

    2014-01-15

    Memories associated with drugs of abuse, such as methamphetamine (METH), increase relapse vulnerability to substance use disorder. There is a growing consensus that memory is supported by structural and functional plasticity driven by F-actin polymerization in postsynaptic dendritic spines at excitatory synapses. However, the mechanisms responsible for the long-term maintenance of memories, after consolidation has occurred, are largely unknown. Conditioned place preference (n = 112) and context-induced reinstatement of self-administration (n = 19) were used to assess the role of F-actin polymerization and myosin II, a molecular motor that drives memory-promoting dendritic spine actin polymerization, in the maintenance of METH-associated memories and related structural plasticity. Memories formed through association with METH but not associations with foot shock or food reward were disrupted by a highly-specific actin cycling inhibitor when infused into the amygdala during the postconsolidation maintenance phase. This selective effect of depolymerization on METH-associated memory was immediate, persistent, and did not depend upon retrieval or strength of the association. Inhibition of non-muscle myosin II also resulted in a disruption of METH-associated memory. Thus, drug-associated memories seem to be actively maintained by a unique form of cycling F-actin driven by myosin II. This finding provides a potential therapeutic approach for the selective treatment of unwanted memories associated with psychiatric disorders that is both selective and does not rely on retrieval of the memory. The results further suggest that memory maintenance depends upon the preservation of polymerized actin. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  20. Factors behind response strategies of incumbent firms to disruptive innovation: case of TV broadcasting industry

    Markevičiūtė, Imantė

    2017-01-01

    Disruptive technologies and business models are fundamentally changing the established ‘rules of the game’ in many industries. Thus, finding an adequate response becomes a matter of survival to companies touched by disruptive innovation. The current research is attempting to reveal the factors determining the response strategy of local incumbent TV broadcasters to global disruptive innovation. In order to do so, these research objectives are pursued in order to answer the research question: t...

  1. Disrupting gatekeeping practices: Journalists’ source selection in times of crisis

    van der Meer, Toni G.L.A.; Verhoeven, Piet; Beentjes, Johannes W.J.; Vliegenthart, Rens

    2016-01-01

    As gatekeepers, journalists have the power to select the sources that get a voice in crisis coverage. The aim of this study is to find out how journalists select sources during a crisis. In a survey, journalists were asked how they assess the following sources during an organizational crisis: news agencies, an organization undergoing a crisis, and the general public. The sample consisted of 214 Dutch experienced journalists who at least once covered a crisis. Using structural equation modeling, sources’ likelihood of being included in the news was predicted using five source characteristics: credibility, knowledge, willingness, timeliness, and the relationship with the journalist. Findings indicated that during a crisis, news agencies are most likely to be included in the news, followed by the public, and finally the organization. The significance of the five source characteristics is dependent on source type. For example, to be used in the news, news agencies and organizations should be mainly evaluated as knowledgeable, whereas information from the public should be both credible and timely. In addition, organizations should not be seen as too willing or too eager to communicate. The findings imply that, during a crisis, journalists remain critical gatekeepers; however, they rely mainly on familiar sources. PMID:29278263

  2. Disrupting gatekeeping practices: Journalists' source selection in times of crisis.

    van der Meer, Toni G L A; Verhoeven, Piet; Beentjes, Johannes W J; Vliegenthart, Rens

    2017-10-01

    As gatekeepers, journalists have the power to select the sources that get a voice in crisis coverage. The aim of this study is to find out how journalists select sources during a crisis. In a survey, journalists were asked how they assess the following sources during an organizational crisis: news agencies, an organization undergoing a crisis, and the general public. The sample consisted of 214 Dutch experienced journalists who at least once covered a crisis. Using structural equation modeling, sources' likelihood of being included in the news was predicted using five source characteristics: credibility, knowledge, willingness, timeliness, and the relationship with the journalist. Findings indicated that during a crisis, news agencies are most likely to be included in the news, followed by the public, and finally the organization. The significance of the five source characteristics is dependent on source type. For example, to be used in the news, news agencies and organizations should be mainly evaluated as knowledgeable, whereas information from the public should be both credible and timely. In addition, organizations should not be seen as too willing or too eager to communicate. The findings imply that, during a crisis, journalists remain critical gatekeepers; however, they rely mainly on familiar sources.

  3. Maintenance of a genetic polymorphism with disruptive natural selection in stickleback.

    Marchinko, Kerry B; Matthews, Blake; Arnegard, Matthew E; Rogers, Sean M; Schluter, Dolph

    2014-06-02

    The role of natural selection in the maintenance of genetic variation in wild populations remains a major problem in evolution. The influence of disruptive natural selection on genetic variation is especially interesting because it might lead to the evolution of assortative mating or dominance [1, 2]. In theory, variation can persist at a gene under disruptive natural selection, but the process is little studied and there are few examples [3, 4]. We report a stable polymorphism in the bony armor of threespine stickleback maintained with a deficit of heterozygotes at the major underlying gene, Ectodysplasin (Eda) [5]. The deficit vanishes at the embryo life stage only to re-emerge in adults, indicating that disruptive natural selection, rather than nonrandom mating, is the cause. The mechanism enabling long-term persistence of the polymorphism is unknown, but disruptive selection is predicted to be frequency dependent, favoring homozygous genotypes when they become rare. Further research on the ecological and evolutionary processes affecting individual genes will ultimately lead to a better understanding of the causes of genetic variation in populations. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Shares, gaps and the economy's response to oil disruptions

    Huntington, Hillard G.

    2004-01-01

    Most previous studies have focused on whether oil price shocks cause economic recessions but fewer studies have investigated whether the impact of an oil price shock can be different under alternative economic conditions. Using an international data set of industrialized economies, this paper explores whether an economy relying more on oil or operating closer to full employment may be more vulnerable to an oil disruption. Although the results for oil dependence are ambiguous, the analysis does find a significant relationship between the impacts of an oil shock and how closely the economy is operating to its full-employment level prior to the disruption. (Author)

  5. Social media disruptive change in healthcare : Responses of healthcare providers?

    Smailhodzic, E.; Boonstra, A.; Langley, D.J.

    2016-01-01

    Social media represent specific types of technologies that are end-user driven and end-users are able to drive disruptive change giving little time to organizations to react. With rapid and powerful emergence of social media communities in healthcare, this sector is faced with new and alternative

  6. Social media disruptive change in healthcare : responses of healthcare providers

    Smailhodzic, Edin; Boonstra, Albert; Langley, David

    Social media represent specific types of technologies that are end-user driven and end-users are able to drive disruptive change giving little time to organizations to react. With rapid and powerful emergence of social media communities in healthcare, this sector is faced with new and alternative

  7. Chronic alcohol exposure disrupts top-down control over basal ganglia action selection to produce habits.

    Renteria, Rafael; Baltz, Emily T; Gremel, Christina M

    2018-01-15

    Addiction involves a predominance of habitual control mediated through action selection processes in dorsal striatum. Research has largely focused on neural mechanisms mediating a proposed progression from ventral to dorsal lateral striatal control in addiction. However, over reliance on habit striatal processes may also arise from reduced cortical input to striatum, thereby disrupting executive control over action selection. Here, we identify novel mechanisms through which chronic intermittent ethanol exposure and withdrawal (CIE) disrupts top-down control over goal-directed action selection processes to produce habits. We find CIE results in decreased excitability of orbital frontal cortex (OFC) excitatory circuits supporting goal-directed control, and, strikingly, selectively reduces OFC output to the direct output pathway in dorsal medial striatum. Increasing the activity of OFC circuits restores goal-directed control in CIE-exposed mice. Our findings show habitual control in alcohol dependence can arise through disrupted communication between top-down, goal-directed processes onto basal ganglia pathways controlling action selection.

  8. The evolution of sexes: A specific test of the disruptive selection theory.

    da Silva, Jack

    2018-01-01

    The disruptive selection theory of the evolution of anisogamy posits that the evolution of a larger body or greater organismal complexity selects for a larger zygote, which in turn selects for larger gametes. This may provide the opportunity for one mating type to produce more numerous, small gametes, forcing the other mating type to produce fewer, large gametes. Predictions common to this and related theories have been partially upheld. Here, a prediction specific to the disruptive selection theory is derived from a previously published game-theoretic model that represents the most complete description of the theory. The prediction, that the ratio of macrogamete to microgamete size should be above three for anisogamous species, is supported for the volvocine algae. A fully population genetic implementation of the model, involving mutation, genetic drift, and selection, is used to verify the game-theoretic approach and accurately simulates the evolution of gamete sizes in anisogamous species. This model was extended to include a locus for gamete motility and shows that oogamy should evolve whenever there is costly motility. The classic twofold cost of sex may be derived from the fitness functions of these models, showing that this cost is ultimately due to genetic conflict.

  9. Environmental change disrupts communication and sexual selection in a stickleback population.

    Candolin, Ulrika; Tukiainen, Iina; Bertell, Elina

    2016-04-01

    Environmental change that disrupts communication during mate choice and alters sexual selection could influence population dynamics. Yet little is known about such long-term effects. We investigated experimentally the consequences that disrupted visual communication during mate choice has for the quantity and viability of offspring produced in a threespine stickleback population (Gasterosteus aculeatus). We further related the results to long-term monitoring of population dynamics in the field to determine if changes are apparent under natural conditions. The results show that impaired visual communication because of algal blooms reduces reliability of male visual signals as indicators of offspring survival during their first weeks of life. This relaxes sexual selection but has no effect on the number of offspring hatching, as most males have a high hatching success in turbid water. Despite eutrophication and high turbidity levels that interfere with communication during mate choice, the population has grown during recent decades. Large numbers of offspring hatching, combined with high variation in juvenile fitness, has probably shifted selection to later life history stages and maintained a viable population. Together with reduced cost of sexual selection and ongoing ecosystem changes caused by human activities, this could have promoted population growth. These results point to the complexity of ecosystems and the necessity to consider all influencing factors when attempting to understand impacts of human activities on populations.

  10. Quantitative Evaluation of Tumor Early Response to a Vascular-Disrupting Agent with Dynamic PET.

    Guo, Ning; Zhang, Fan; Zhang, Xiaomeng; Guo, Jinxia; Lang, Lixin; Kiesewetter, Dale O; Niu, Gang; Li, Quanzheng; Chen, Xiaoyuan

    2015-12-01

    The purpose of this study is to evaluate the early response of tumors to a vascular-disrupting agent (VDA) VEGF121/recombinant toxin gelonin (rGel) using dynamic [(18)F]FPPRGD2 positron emission tomography (PET) and kinetic parameter estimation. Two tumor xenograft models: U87MG (highly vascularized) and A549 (moderately vascularized), were selected, and both were randomized into treatment and control groups. Sixty-minute dynamic PET scans with [(18)F]FPPRGD2 that targets to integrin αvβ3 were performed at days 0 (baseline), 1, and 3 since VEGF121/rGel treatment started. Dynamic PET-derived binding potential (BPND) and parametric maps were compared with tumor uptake (%ID/g) and the static PET image at 1 h after the tracer administration. The growth of U87MG tumor was obviously delayed upon VEGF121/rGel treatment. A549 tumor was not responsive to the same treatment. BPND of treated U87MG tumors decreased significantly at day 1 (p dynamic PET with [(18)F]FPPRGD2 shows advantages in distinguishing effective from ineffective treatment during the course of VEGF121/rGel therapy at early stage and is therefore more sensitive in assessing therapy response than static PET.

  11. RNA disruption is associated with response to multiple classes of chemotherapy drugs in tumor cell lines.

    Narendrula, Rashmi; Mispel-Beyer, Kyle; Guo, Baoqing; Parissenti, Amadeo M; Pritzker, Laura B; Pritzker, Ken; Masilamani, Twinkle; Wang, Xiaohui; Lannér, Carita

    2016-02-24

    Cellular stressors and apoptosis-inducing agents have been shown to induce ribosomal RNA (rRNA) degradation in eukaryotic cells. Recently, RNA degradation in vivo was observed in patients with locally advanced breast cancer, where mid-treatment tumor RNA degradation was associated with complete tumor destruction and enhanced patient survival. However, it is not clear how widespread chemotherapy induced "RNA disruption" is, the extent to which it is associated with drug response or what the underlying mechanisms are. Ovarian (A2780, CaOV3) and breast (MDA-MB-231, MCF-7, BT474, SKBR3) cancer cell lines were treated with several cytotoxic chemotherapy drugs and total RNA was isolated. RNA was also prepared from docetaxel resistant A2780DXL and carboplatin resistant A2780CBN cells following drug exposure. Disruption of RNA was analyzed by capillary electrophoresis. Northern blotting was performed using probes complementary to the 28S and 18S rRNA to determine the origins of degradation bands. Apoptosis activation was assessed by flow cytometric monitoring of annexin-V and propidium iodide (PI) binding to cells and by measuring caspase-3 activation. The link between apoptosis and RNA degradation (disruption) was investigated using a caspase-3 inhibitor. All chemotherapy drugs tested were capable of inducing similar RNA disruption patterns. Docetaxel treatment of the resistant A2780DXL cells and carboplatin treatment of the A2780CBN cells did not result in RNA disruption. Northern blotting indicated that two RNA disruption bands were derived from the 3'-end of the 28S rRNA. Annexin-V and PI staining of docetaxel treated cells, along with assessment of caspase-3 activation, showed concurrent initiation of apoptosis and RNA disruption, while inhibition of caspase-3 activity significantly reduced RNA disruption. Supporting the in vivo evidence, our results demonstrate that RNA disruption is induced by multiple chemotherapy agents in cell lines from different tissues and is

  12. Disruption of sphingolipid biosynthesis in hepatocyte nodules: selective proliferative stimulus induced by fumonisin B1

    Westhuizen, Liana van der; Gelderblom, Wentzel C.A.; Shephard, Gordon S.; Swanevelder, Sonja

    2004-01-01

    In order to investigate the role of sphingolipid disruption in the cancer promoting potential of fumonisin B 1 (FB 1 ) in the development of hepatocyte nodules, male Fischer 344 rats were subjected to cancer initiation (FB 1 containing diet or diethylnitrosamine (DEN) by i.p. injection) and promotion (2-acetylaminofluorene with partial hepatectomy, 2-AAF/PH) treatments followed by a secondary FB 1 dietary regimen. Sphinganine (Sa) and sphingosine (So) levels were measured by high performance liquid chromatography in control, surrounding and nodular liver tissues of the rats. The disruption of sphingolipid biosynthesis by the secondary FB 1 treatment in the control rats was significantly (P 1 initiation and 2-AAF/PH promotion. When comparing the groups subjected to the secondary FB 1 treatment, the initiation effected by FB 1 was less (P 1 initiation was marginally increased in the nodules compared to the surrounding liver after 2-AAF/PH promotion and significantly (P 1 treatment. Although, the FB 1 -induced hepatocyte nodules were not resistant to the disruption of sphingolipid biosynthesis, the nodular So levels were increased and might provide a selective growth stimulus possibly induced by bio-active sphingoid intermediates such as sphingosine 1-phosphate (S1P)

  13. Isoform-Selective Disruption of AKAP-Localized PKA Using Hydrocarbon Stapled Peptides

    2015-01-01

    A-kinase anchoring proteins (AKAPs) play an important role in the spatial and temporal regulation of protein kinase A (PKA) by scaffolding critical intracellular signaling complexes. Here we report the design of conformationally constrained peptides that disrupt interactions between PKA and AKAPs in an isoform-selective manner. Peptides derived from the A Kinase Binding (AKB) domain of several AKAPs were chemically modified to contain an all-hydrocarbon staple and target the docking/dimerization domain of PKA-R, thereby occluding AKAP interactions. The peptides are cell-permeable against diverse human cell lines, are highly isoform-selective for PKA-RII, and can effectively inhibit interactions between AKAPs and PKA-RII in intact cells. These peptides can be applied as useful reagents in cell-based studies to selectively disrupt AKAP-localized PKA-RII activity and block AKAP signaling complexes. In summary, the novel hydrocarbon-stapled peptides developed in this study represent a new class of AKAP disruptors to study compartmentalized RII-regulated PKA signaling in cells. PMID:24422448

  14. Disruption of Brewers' yeast by hydrodynamic cavitation: Process variables and their influence on selective release.

    Balasundaram, B; Harrison, S T L

    2006-06-05

    Intracellular products, not secreted from the microbial cell, are released by breaking the cell envelope consisting of cytoplasmic membrane and an outer cell wall. Hydrodynamic cavitation has been reported to cause microbial cell disruption. By manipulating the operating variables involved, a wide range of intensity of cavitation can be achieved resulting in a varying extent of disruption. The effect of the process variables including cavitation number, initial cell concentration of the suspension and the number of passes across the cavitation zone on the release of enzymes from various locations of the Brewers' yeast was studied. The release profile of the enzymes studied include alpha-glucosidase (periplasmic), invertase (cell wall bound), alcohol dehydrogenase (ADH; cytoplasmic) and glucose-6-phosphate dehydrogenase (G6PDH; cytoplasmic). An optimum cavitation number Cv of 0.13 for maximum disruption was observed across the range Cv 0.09-0.99. The optimum cell concentration was found to be 0.5% (w/v, wet wt) when varying over the range 0.1%-5%. The sustained effect of cavitation on the yeast cell wall when re-circulating the suspension across the cavitation zone was found to release the cell wall bound enzyme invertase (86%) to a greater extent than the enzymes from other locations of the cell (e.g. periplasmic alpha-glucosidase at 17%). Localised damage to the cell wall could be observed using transmission electron microscopy (TEM) of cells subjected to less intense cavitation conditions. Absence of the release of cytoplasmic enzymes to a significant extent, absence of micronisation as observed by TEM and presence of a lower number of proteins bands in the culture supernatant on SDS-PAGE analysis following hydrodynamic cavitation compared to disruption by high-pressure homogenisation confirmed the selective release offered by hydrodynamic cavitation. Copyright 2006 Wiley Periodicals, Inc.

  15. How does male–male competition generate negative frequency-dependent selection and disruptive selection during speciation?

    Border, Shana E

    2018-01-01

    Abstract Natural selection has been shown to drive population differentiation and speciation. The role of sexual selection in this process is controversial; however, most of the work has centered on mate choice while the role of male–male competition in speciation is relatively understudied. Here, we outline how male–male competition can be a source of diversifying selection on male competitive phenotypes, and how this can contribute to the evolution of reproductive isolation. We highlight how negative frequency-dependent selection (advantage of rare phenotype arising from stronger male–male competition between similar male phenotypes compared with dissimilar male phenotypes) and disruptive selection (advantage of extreme phenotypes) drives the evolution of diversity in competitive traits such as weapon size, nuptial coloration, or aggressiveness. We underscore that male–male competition interacts with other life-history functions and that variable male competitive phenotypes may represent alternative adaptive options. In addition to competition for mates, aggressive interference competition for ecological resources can exert selection on competitor signals. We call for a better integration of male–male competition with ecological interference competition since both can influence the process of speciation via comparable but distinct mechanisms. Altogether, we present a more comprehensive framework for studying the role of male–male competition in speciation, and emphasize the need for better integration of insights gained from other fields studying the evolutionary, behavioral, and physiological consequences of agonistic interactions. PMID:29492042

  16. RNA disruption is associated with response to multiple classes of chemotherapy drugs in tumor cell lines

    Narendrula, Rashmi; Mispel-Beyer, Kyle; Guo, Baoqing; Parissenti, Amadeo M.; Pritzker, Laura B.; Pritzker, Ken; Masilamani, Twinkle; Wang, Xiaohui; Lannér, Carita

    2016-01-01

    Cellular stressors and apoptosis-inducing agents have been shown to induce ribosomal RNA (rRNA) degradation in eukaryotic cells. Recently, RNA degradation in vivo was observed in patients with locally advanced breast cancer, where mid-treatment tumor RNA degradation was associated with complete tumor destruction and enhanced patient survival. However, it is not clear how widespread chemotherapy induced “RNA disruption” is, the extent to which it is associated with drug response or what the underlying mechanisms are. Ovarian (A2780, CaOV3) and breast (MDA-MB-231, MCF-7, BT474, SKBR3) cancer cell lines were treated with several cytotoxic chemotherapy drugs and total RNA was isolated. RNA was also prepared from docetaxel resistant A2780DXL and carboplatin resistant A2780CBN cells following drug exposure. Disruption of RNA was analyzed by capillary electrophoresis. Northern blotting was performed using probes complementary to the 28S and 18S rRNA to determine the origins of degradation bands. Apoptosis activation was assessed by flow cytometric monitoring of annexin-V and propidium iodide (PI) binding to cells and by measuring caspase-3 activation. The link between apoptosis and RNA degradation (disruption) was investigated using a caspase-3 inhibitor. All chemotherapy drugs tested were capable of inducing similar RNA disruption patterns. Docetaxel treatment of the resistant A2780DXL cells and carboplatin treatment of the A2780CBN cells did not result in RNA disruption. Northern blotting indicated that two RNA disruption bands were derived from the 3’-end of the 28S rRNA. Annexin-V and PI staining of docetaxel treated cells, along with assessment of caspase-3 activation, showed concurrent initiation of apoptosis and RNA disruption, while inhibition of caspase-3 activity significantly reduced RNA disruption. Supporting the in vivo evidence, our results demonstrate that RNA disruption is induced by multiple chemotherapy agents in cell lines from different tissues

  17. Phencyclidine Disrupts the Auditory Steady State Response in Rats.

    Emma Leishman

    Full Text Available The Auditory Steady-State Response (ASSR in the electroencephalogram (EEG is usually reduced in schizophrenia (SZ, particularly to 40 Hz stimulation. The gamma frequency ASSR deficit has been attributed to N-methyl-D-aspartate receptor (NMDAR hypofunction. We tested whether the NMDAR antagonist, phencyclidine (PCP, produced similar ASSR deficits in rats. EEG was recorded from awake rats via intracranial electrodes overlaying the auditory cortex and at the vertex of the skull. ASSRs to click trains were recorded at 10, 20, 30, 40, 50, and 55 Hz and measured by ASSR Mean Power (MP and Phase Locking Factor (PLF. In Experiment 1, the effect of different subcutaneous doses of PCP (1.0, 2.5 and 4.0 mg/kg on the ASSR in 12 rats was assessed. In Experiment 2, ASSRs were compared in PCP treated rats and control rats at baseline, after acute injection (5 mg/kg, following two weeks of subchronic, continuous administration (5 mg/kg/day, and one week after drug cessation. Acute administration of PCP increased PLF and MP at frequencies of stimulation below 50 Hz, and decreased responses at higher frequencies at the auditory cortex site. Acute administration had a less pronounced effect at the vertex site, with a reduction of either PLF or MP observed at frequencies above 20 Hz. Acute effects increased in magnitude with higher doses of PCP. Consistent effects were not observed after subchronic PCP administration. These data indicate that acute administration of PCP, a NMDAR antagonist, produces an increase in ASSR synchrony and power at low frequencies of stimulation and a reduction of high frequency (> 40 Hz ASSR activity in rats. Subchronic, continuous administration of PCP, on the other hand, has little impact on ASSRs. Thus, while ASSRs are highly sensitive to NMDAR antagonists, their translational utility as a cross-species biomarker for NMDAR hypofunction in SZ and other disorders may be dependent on dose and schedule.

  18. Passive sampling of selected endocrine disrupting compounds using polar organic chemical integrative samplers

    Arditsoglou, Anastasia; Voutsa, Dimitra

    2008-01-01

    Two types of polar organic chemical integrative samplers (pharmaceutical POCIS and pesticide POCIS) were examined for their sampling efficiency of selected endocrine disrupting compounds (EDCs). Laboratory-based calibration of POCISs was conducted by exposing them at high and low concentrations of 14 EDCs (4-alkyl-phenols, their ethoxylate oligomers, bisphenol A, selected estrogens and synthetic steroids) for different time periods. The kinetic studies showed an integrative uptake up to 28 days. The sampling rates for the individual compounds were obtained. The use of POCISs could result in an integrative approach to the quality status of the aquatic systems especially in the case of high variation of water concentrations of EDCs. The sampling efficiency of POCISs under various field conditions was assessed after their deployment in different aquatic environments. - Calibration and field performance of polar organic integrative samplers for monitoring EDCs in aquatic environments

  19. RNA Disruption and Drug Response in Breast Cancer Primary Systemic Therapy.

    Pritzker, Kenneth; Pritzker, Laura; Generali, Daniele; Bottini, Alberto; Cappelletti, Maria Rosa; Guo, Baoqing; Parissenti, Amadeo; Trudeau, Maureen

    2015-05-01

    As there is now evidence that switching clinical nonresponders early in primary systemic therapy to alternate treatment regimens can enhance survival in some breast cancer patients, the need for a robust intermediate endpoint that can guide treatment response across all tumor subtypes is urgent. Recently, chemotherapy drugs have been shown to induce a decrease in RNA quality in tumor cells from breast cancer biopsies in some patients at midtherapy, and that this has been associated with subsequent achievement of pathological complete response (pCR). The decrease in RNA quality has been shown to be associated with RNA disruption; aberrant RNA bands visualized by RNA electrophoresis have been associated with subsequent tumor cell death. The objectives of these studies are to show that a new assay based on induction of RNA disruption in tumor cells by chemotherapy can stratify at midtherapy, pCR responders from non-pCR responders irrespective of clinical response and to present early evidence that clinically useful RNA disruption can be detected as early as 14 days after initiation of treatment. RNA disruption in tumor cells was quantified by analysis of the RNA electrophoresis banding pattern and expressed as an RNA disruption index (RDI). To develop the RNA disruption assay (RDA), RDI was correlated with clinical outcome (pCR) from the NCIC-CTG MA.22 breast cancer clinical trial (ClinicalTrials.gov NCT00066443). RDA Zones were established by stratifying patients using RDI values into Zone 1, Zone 2, and Zone 3. Zone 3 included seven out of eight pCR responders, whereas Zone 1 contained no pCR responders. An intermediate zone (Zone 2) was established which contained one pCR. Subsequently, to determine early drug response, RNA disruption was examined by RDI after 14 days exposure to trastuzumab, zoledronic acid, or letrozole + cyclophosphamide ± sorafenib therapy. In MA.22, RDA stratified 23 of 85 patients in Zone 1 as pCR nonresponders, 24 patients in Zone 2, an

  20. Altering the selection capabilities of common cloning vectors via restriction enzyme mediated gene disruption

    2013-01-01

    Background The cloning of gene sequences forms the basis for many molecular biological studies. One important step in the cloning process is the isolation of bacterial transformants carrying vector DNA. This involves a vector-encoded selectable marker gene, which in most cases, confers resistance to an antibiotic. However, there are a number of circumstances in which a different selectable marker is required or may be preferable. Such situations can include restrictions to host strain choice, two phase cloning experiments and mutagenesis experiments, issues that result in additional unnecessary cloning steps, in which the DNA needs to be subcloned into a vector with a suitable selectable marker. Results We have used restriction enzyme mediated gene disruption to modify the selectable marker gene of a given vector by cloning a different selectable marker gene into the original marker present in that vector. Cloning a new selectable marker into a pre-existing marker was found to change the selection phenotype conferred by that vector, which we were able to demonstrate using multiple commonly used vectors and multiple resistance markers. This methodology was also successfully applied not only to cloning vectors, but also to expression vectors while keeping the expression characteristics of the vector unaltered. Conclusions Changing the selectable marker of a given vector has a number of advantages and applications. This rapid and efficient method could be used for co-expression of recombinant proteins, optimisation of two phase cloning procedures, as well as multiple genetic manipulations within the same host strain without the need to remove a pre-existing selectable marker in a previously genetically modified strain. PMID:23497512

  1. Facial EMG responses to dynamic emotional facial expressions in boys with disruptive behavior disorders

    Wied, de M.; Boxtel, van Anton; Zaalberg, R.; Goudena, P.P.; Matthys, W.

    2006-01-01

    Based on the assumption that facial mimicry is a key factor in emotional empathy, and clinical observations that children with disruptive behavior disorders (DBD) are weak empathizers, the present study explored whether DBD boys are less facially responsive to facial expressions of emotions than

  2. A cytochrome P450 monooxygenase commonly used for negative selection in transgenic plants causes growth anomalies by disrupting brassinosteroid signaling

    Manivasagam Sindhu

    2011-04-01

    Full Text Available Abstract Background Cytochrome P450 monooxygenases form a large superfamily of enzymes that catalyze diverse reactions. The P450SU1 gene from the soil bacteria Streptomyces griseolus encodes CYP105A1 which acts on various substrates including sulfonylurea herbicides, vitamin D, coumarins, and based on the work presented here, brassinosteroids. P450SU1 is used as a negative-selection marker in plants because CYP105A1 converts the relatively benign sulfonyl urea pro-herbicide R7402 into a highly phytotoxic product. Consistent with its use for negative selection, transgenic Arabidopsis plants were generated with P450SU1 situated between recognition sequences for FLP recombinase from yeast to select for recombinase-mediated excision. However, unexpected and prominent developmental aberrations resembling those described for mutants defective in brassinosteroid signaling were observed in many of the lines. Results The phenotypes of the most affected lines included severe stunting, leaf curling, darkened leaves characteristic of anthocyanin accumulation, delayed transition to flowering, low pollen and seed yields, and delayed senescence. Phenotype severity correlated with P450SU1 transcript abundance, but not with transcript abundance of other experimental genes, strongly implicating CYP105A1 as responsible for the defects. Germination and seedling growth of transgenic and control lines in the presence and absence of 24-epibrassinolide indicated that CYP105A1 disrupts brassinosteroid signaling, most likely by inactivating brassinosteroids. Conclusions Despite prior use of this gene as a genetic tool, deleterious growth in the absence of R7402 has not been elaborated. We show that this gene can cause aberrant growth by disrupting brassinosteroid signaling and affecting homeostasis.

  3. Electromagnetic loads and structural response of the CIT [Compact Ignition Tokamak] vacuum vessel to plasma disruptions

    Salem, S.L.; Listvinsky, G.; Lee, M.Y.; Bailey, C.

    1987-01-01

    Studies of the electromagnetic loads produced by a variety of plasma disruptions, and the resulting structural effects on the compact Ignition Tokamak (CIT) vacuum vessel (VV), have been performed to help optimize the VV design. A series of stationary and moving plasmas, with disruption rates from 0.7--10.0 MA/ms, have been analyzed using the EMPRES code to compute eddy currents and electromagnetic pressures, and the NASTRAN code to evaluate the structural response of the vacuum vessel. Key factors contributing to the magnitude of EM forces and resulting stresses on the vessel have been found to include disruption rate, and direction and synchronization of plasma motion with the onset of plasma current decay. As a result of these analyses, a number of design changes have been made, and design margins for the present 1.75 meter design have been improved over the original CIT configuration. 1 ref., 10 figs., 4 tabs

  4. The thermal response of the first wall of a fusion reactor blanket to plasma disruptions

    Klippel, H.Th.

    1983-09-01

    Major plasma disruptions in Tokamak power reactors are potentially dangerous because high thermal overloading of the first wall may occur, resulting in melting and evaporation. The present uncertainties of the disruption characteristics, in particular the space and time dependence of the energy deposition, lead to a wide variation in the prospective surface energy loads. The thermal response of a first wall of aluminium, stainless steel and of graphite subjected to disruption energy loads up to 1000 J cm -2 has been analysed including the effects of melting and surface evaporation, vapour recondensation, vapour shielding, and the moving of the surface boundary caused by the evaporation. A special calculation model has been developed for this purpose. The main results are the following: by values of local transient energy depositions over 1500 J cm -2 bare stainless steel walls are damaged severely. Further calculations are needed to estimate the endurance limit of several candidate first wall materials. Applications of coatings on surfaces need special attention. For the reference INTOR disruption (approx. 100 J cm -2 ) evaporation is not significant. The effect of vapour shielding on evaporation has been found to be significant. The effect on melting is less pronounced. In a complete analysis the stability and dynamic behaviour of the melted layer under electromagnetic forces should be included. Also a reliable set of plasma disruption characteristics should be gathered

  5. Selective dentate gyrus disruption causes memory impairment at the early stage of experimental multiple sclerosis.

    Planche, Vincent; Panatier, Aude; Hiba, Bassem; Ducourneau, Eva-Gunnel; Raffard, Gerard; Dubourdieu, Nadège; Maitre, Marlène; Lesté-Lasserre, Thierry; Brochet, Bruno; Dousset, Vincent; Desmedt, Aline; Oliet, Stéphane H; Tourdias, Thomas

    2017-02-01

    Memory impairment is an early and disabling manifestation of multiple sclerosis whose anatomical and biological substrates are still poorly understood. We thus investigated whether memory impairment encountered at the early stage of the disease could be explained by a differential vulnerability of particular hippocampal subfields. By using experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, we identified that early memory impairment was associated with selective alteration of the dentate gyrus as pinpointed in vivo with diffusion-tensor-imaging (DTI). Neuromorphometric analyses and electrophysiological recordings confirmed dendritic degeneration, alteration in glutamatergic synaptic transmission and impaired long-term synaptic potentiation selectively in the dentate gyrus, but not in CA1, together with a more severe pattern of microglial activation in this subfield. Systemic injections of the microglial inhibitor minocycline prevented DTI, morphological, electrophysiological and behavioral impairments in EAE-mice. Furthermore, daily infusions of minocycline specifically within the dentate gyrus were sufficient to prevent memory impairment in EAE-mice while infusions of minocycline within CA1 were inefficient. We conclude that early memory impairment in EAE is due to a selective disruption of the dentate gyrus associated with microglia activation. These results open new pathophysiological, imaging, and therapeutic perspectives for memory impairment in multiple sclerosis. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Estimating uncertainty in multivariate responses to selection.

    Stinchcombe, John R; Simonsen, Anna K; Blows, Mark W

    2014-04-01

    Predicting the responses to natural selection is one of the key goals of evolutionary biology. Two of the challenges in fulfilling this goal have been the realization that many estimates of natural selection might be highly biased by environmentally induced covariances between traits and fitness, and that many estimated responses to selection do not incorporate or report uncertainty in the estimates. Here we describe the application of a framework that blends the merits of the Robertson-Price Identity approach and the multivariate breeder's equation to address these challenges. The approach allows genetic covariance matrices, selection differentials, selection gradients, and responses to selection to be estimated without environmentally induced bias, direct and indirect selection and responses to selection to be distinguished, and if implemented in a Bayesian-MCMC framework, statistically robust estimates of uncertainty on all of these parameters to be made. We illustrate our approach with a worked example of previously published data. More generally, we suggest that applying both the Robertson-Price Identity and the multivariate breeder's equation will facilitate hypothesis testing about natural selection, genetic constraints, and evolutionary responses. © 2013 The Author(s). Evolution © 2013 The Society for the Study of Evolution.

  7. Disruptive selection and bet-hedging in planktonic Foraminifera: Shell morphology as predictor of extinctions

    Manuel F. G. Weinkauf

    2014-10-01

    Full Text Available Extinction is a remarkably difficult phenomenon to study under natural conditions. This is because the outcome of stress exposure and associated fitness reduction is not known until the extinction occurs and it remains unclear whether there is any phenotypic reaction of the exposed population that can be used to predict its fate. Here we take advantage of the fossil record, where the ecological outcome of stress exposure is known. Specifically, we analyze shell morphology of planktonic Foraminifera in sediment samples from the Mediterranean, during an interval preceding local extinctions. In two species representing different plankton habitats, we observe shifts in trait state and decrease in variance in association with non-terminal stress, indicating stabilizing selection. At terminal stress levels, immediately before extinction, we observe increased growth asymmetry and trait variance, indicating disruptive selection and bet-hedging. The pre-extinction populations of both species show a combination of trait states and trait variance distinct from all populations exposed to non-terminal levels of stress. This finding indicates that the phenotypic history of a population may allow the detection of threshold levels of stress, likely to lead to extinction. It is thus an alternative to population dynamics in studying and monitoring natural population ecology.

  8. Feature selection for disruption prediction from scratch in JET by using genetic algorithms and probabilistic predictors

    Pereira, Augusto, E-mail: augusto.pereira@ciemat.es [Laboratorio Nacional de Fusión, CIEMAT, Madrid (Spain); Vega, Jesús; Moreno, Raúl [Laboratorio Nacional de Fusión, CIEMAT, Madrid (Spain); Dormido-Canto, Sebastián [Dpto. Informática y Automática – UNED, Madrid (Spain); Rattá, Giuseppe A. [Laboratorio Nacional de Fusión, CIEMAT, Madrid (Spain); Pavón, Fernando [Dpto. Informática y Automática – UNED, Madrid (Spain)

    2015-10-15

    Recently, a probabilistic classifier has been developed at JET to be used as predictor from scratch. It has been applied to a database of 1237 JET ITER-like wall (ILW) discharges (of which 201 disrupted) with good results: success rate of 94% and false alarm rate of 4.21%. A combinatorial analysis between 14 features to ensure the selection of the best ones to achieve good enough results in terms of success rate and false alarm rate was performed. All possible combinations with a number of features between 2 and 7 were tested and 9893 different predictors were analyzed. An important drawback in this analysis was the time required to compute the results that can be estimated in 1731 h (∼2.4 months). Genetic algorithms (GA) are searching algorithms that simulate the process of natural selection. In this article, the GA and the Venn predictors are combined with the objective not only of finding good enough features within the 14 available ones but also of reducing the computational time requirements. Five different performance metrics as measures of the GA fitness function have been evaluated. The best metric was the measurement called Informedness, with just 6 generations (168 predictors at 29.4 h).

  9. Feature selection for disruption prediction from scratch in JET by using genetic algorithms and probabilistic predictors

    Pereira, Augusto; Vega, Jesús; Moreno, Raúl; Dormido-Canto, Sebastián; Rattá, Giuseppe A.; Pavón, Fernando

    2015-01-01

    Recently, a probabilistic classifier has been developed at JET to be used as predictor from scratch. It has been applied to a database of 1237 JET ITER-like wall (ILW) discharges (of which 201 disrupted) with good results: success rate of 94% and false alarm rate of 4.21%. A combinatorial analysis between 14 features to ensure the selection of the best ones to achieve good enough results in terms of success rate and false alarm rate was performed. All possible combinations with a number of features between 2 and 7 were tested and 9893 different predictors were analyzed. An important drawback in this analysis was the time required to compute the results that can be estimated in 1731 h (∼2.4 months). Genetic algorithms (GA) are searching algorithms that simulate the process of natural selection. In this article, the GA and the Venn predictors are combined with the objective not only of finding good enough features within the 14 available ones but also of reducing the computational time requirements. Five different performance metrics as measures of the GA fitness function have been evaluated. The best metric was the measurement called Informedness, with just 6 generations (168 predictors at 29.4 h).

  10. Unfolded protein response (UPR) signaling regulates arsenic trioxide-mediated macrophage innate immune function disruption

    Srivastava, Ritesh K.; Li, Changzhao; Chaudhary, Sandeep C.; Ballestas, Mary E.; Elmets, Craig A.; Robbins, David J.; Matalon, Sadis; Deshane, Jessy S.; Afaq, Farrukh; Bickers, David R.; Athar, Mohammad

    2013-01-01

    Arsenic exposure is known to disrupt innate immune functions in humans and in experimental animals. In this study, we provide a mechanism by which arsenic trioxide (ATO) disrupts macrophage functions. ATO treatment of murine macrophage cells diminished internalization of FITC-labeled latex beads, impaired clearance of phagocytosed fluorescent bacteria and reduced secretion of pro-inflammatory cytokines. These impairments in macrophage functions are associated with ATO-induced unfolded protein response (UPR) signaling pathway characterized by the enhancement in proteins such as GRP78, p-PERK, p-eIF2α, ATF4 and CHOP. The expression of these proteins is altered both at transcriptional and translational levels. Pretreatment with chemical chaperon, 4-phenylbutyric acid (PBA) attenuated the ATO-induced activation in UPR signaling and afforded protection against ATO-induced disruption of macrophage functions. This treatment also reduced ATO-mediated reactive oxygen species (ROS) generation. Interestingly, treatment with antioxidant N-acetylcysteine (NAC) prior to ATO exposure, not only reduced ROS production and UPR signaling but also improved macrophage functions. These data demonstrate that UPR signaling and ROS generation are interdependent and are involved in the arsenic-induced pathobiology of macrophage. These data also provide a novel strategy to block the ATO-dependent impairment in innate immune responses. - Highlights: • Inorganic arsenic to humans and experimental animals disrupt innate immune responses. • The mechanism underlying arsenic impaired macrophage functions involves UPR signaling. • Chemical chaperon attenuates arsenic-mediated macrophage function impairment. • Antioxidant, NAC blocks impairment in arsenic-treated macrophage functions

  11. Unfolded protein response (UPR) signaling regulates arsenic trioxide-mediated macrophage innate immune function disruption

    Srivastava, Ritesh K.; Li, Changzhao; Chaudhary, Sandeep C. [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States); Ballestas, Mary E. [Department of Pediatrics Infectious Disease, Children' s of Alabama, School of Medicine, University of Alabama at Birmingham, AL (United States); Elmets, Craig A. [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States); Robbins, David J. [Department of Surgery, Molecular Oncology Program, Miller School of Medicine, University of Miami, Miami (United States); Matalon, Sadis [Department of Anesthesiology, University of Alabama at Birmingham, Birmingham, AL (United States); Deshane, Jessy S. [Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL (United States); Afaq, Farrukh [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States); Bickers, David R. [Department of Dermatology, Columbia University Medical Center, New York (United States); Athar, Mohammad, E-mail: mathar@uab.edu [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States)

    2013-11-01

    Arsenic exposure is known to disrupt innate immune functions in humans and in experimental animals. In this study, we provide a mechanism by which arsenic trioxide (ATO) disrupts macrophage functions. ATO treatment of murine macrophage cells diminished internalization of FITC-labeled latex beads, impaired clearance of phagocytosed fluorescent bacteria and reduced secretion of pro-inflammatory cytokines. These impairments in macrophage functions are associated with ATO-induced unfolded protein response (UPR) signaling pathway characterized by the enhancement in proteins such as GRP78, p-PERK, p-eIF2α, ATF4 and CHOP. The expression of these proteins is altered both at transcriptional and translational levels. Pretreatment with chemical chaperon, 4-phenylbutyric acid (PBA) attenuated the ATO-induced activation in UPR signaling and afforded protection against ATO-induced disruption of macrophage functions. This treatment also reduced ATO-mediated reactive oxygen species (ROS) generation. Interestingly, treatment with antioxidant N-acetylcysteine (NAC) prior to ATO exposure, not only reduced ROS production and UPR signaling but also improved macrophage functions. These data demonstrate that UPR signaling and ROS generation are interdependent and are involved in the arsenic-induced pathobiology of macrophage. These data also provide a novel strategy to block the ATO-dependent impairment in innate immune responses. - Highlights: • Inorganic arsenic to humans and experimental animals disrupt innate immune responses. • The mechanism underlying arsenic impaired macrophage functions involves UPR signaling. • Chemical chaperon attenuates arsenic-mediated macrophage function impairment. • Antioxidant, NAC blocks impairment in arsenic-treated macrophage functions.

  12. A high efficiency gene disruption strategy using a positive-negative split selection marker and electroporation for Fusarium oxysporum.

    Liang, Liqin; Li, Jianqiang; Cheng, Lin; Ling, Jian; Luo, Zhongqin; Bai, Miao; Xie, Bingyan

    2014-11-01

    The Fusarium oxysporum species complex consists of fungal pathogens that cause serial vascular wilt disease on more than 100 cultivated species throughout the world. Gene function analysis is rapidly becoming more and more important as the whole-genome sequences of various F. oxysporum strains are being completed. Gene-disruption techniques are a common molecular tool for studying gene function, yet are often a limiting step in gene function identification. In this study we have developed a F. oxysporum high-efficiency gene-disruption strategy based on split-marker homologous recombination cassettes with dual selection and electroporation transformation. The method was efficiently used to delete three RNA-dependent RNA polymerase (RdRP) genes. The gene-disruption cassettes of three genes can be constructed simultaneously within a short time using this technique. The optimal condition for electroporation is 10μF capacitance, 300Ω resistance, 4kV/cm field strength, with 1μg of DNA (gene-disruption cassettes). Under these optimal conditions, we were able to obtain 95 transformants per μg DNA. And after positive-negative selection, the transformants were efficiently screened by PCR, screening efficiency averaged 85%: 90% (RdRP1), 85% (RdRP2) and 77% (RdRP3). This gene-disruption strategy should pave the way for high throughout genetic analysis in F. oxysporum. Copyright © 2014 Elsevier GmbH. All rights reserved.

  13. Using response surface methods to explore and optimize mating disruption of the leafminer Phyllocnistis citrella (Lepidoptera: Gracillariidae.

    Denis S. Willett

    2015-03-01

    Full Text Available The application of synthetic sex pheromones to disrupt mating of agricultural pests can be an effective and environmentally friendly alternative to pesticide applications. Optimizing mating disruption through examination of multiple interrelated variables may contribute to wider adoption in agriculture, especially in situations where pheromone synthesis is expensive. Simulations and field experiments designed to produce response surfaces by varying the distribution and number of pheromone dispensers suggested procedures whereby understanding optimization might be increased over that resulting from more common experiments focusing on one factor at a time. Monte Carlo simulations of a spatially explicit agent-based model resulted in nonlinear disruption profiles with increasing point source density. Field trials conducted in citrus infested by the leafminer Phyllocnistis citrella varied the amount of pheromone applied at each point source and point source density using attractive and non-attractive disruption blends. Trap catch disruption in the field resulted in nonlinear disruption profiles similar to those observed with simulations. Response surfaces showed an interaction between the amount of pheromone applied and the number of point sources for the attractive blend, but not for the non-attractive blend. Disruption surfaces were combined with cost curves to optimize trap catch disruption under real world cost constraints. The methods used here highlight the importance of experiment design for understanding the underlying biological dynamics governing mating disruption and optimizing its implementation.

  14. Disruption of visual awareness during the attentional blink is reflected by selective disruption of late-stage neural processing

    Harris, Joseph A.; McMahon, Alex R.; Woldorff, Marty G.

    2015-01-01

    Any information represented in the brain holds the potential to influence behavior. It is therefore of broad interest to determine the extent and quality of neural processing of stimulus input that occurs with and without awareness. The attentional blink is a useful tool for dissociating neural and behavioral measures of perceptual visual processing across conditions of awareness. The extent of higher-order visual information beyond basic sensory signaling that is processed during the attentional blink remains controversial. To determine what neural processing at the level of visual-object identification occurs in the absence of awareness, electrophysiological responses to images of faces and houses were recorded both within and outside of the attentional blink period during a rapid serial visual presentation (RSVP) stream. Electrophysiological results were sorted according to behavioral performance (correctly identified targets versus missed targets) within these blink and non-blink periods. An early index of face-specific processing (the N170, 140–220 ms post-stimulus) was observed regardless of whether the subject demonstrated awareness of the stimulus, whereas a later face-specific effect with the same topographic distribution (500–700 ms post-stimulus) was only seen for accurate behavioral discrimination of the stimulus content. The present findings suggest a multi-stage process of object-category processing, with only the later phase being associated with explicit visual awareness. PMID:23859644

  15. Disrupting astrocyte–neuron lactate transfer persistently reduces conditioned responses to cocaine

    Boury-Jamot, B

    2015-10-27

    A central problem in the treatment of drug addiction is the high risk of relapse often precipitated by drug-associated cues. The transfer of glycogen-derived lactate from astrocytes to neurons is required for long-term memory. Whereas blockade of drug memory reconsolidation represents a potential therapeutic strategy, the role of astrocyte–neuron lactate transport in long-term conditioning has received little attention. By infusing an inhibitor of glycogen phosphorylase into the basolateral amygdala of rats, we report that disruption of astrocyte-derived lactate not only transiently impaired the acquisition of a cocaine-induced conditioned place preference but also persistently disrupted an established conditioning. The drug memory was rescued by L-Lactate co-administration through a mechanism requiring the synaptic plasticity-related transcription factor Zif268 and extracellular signal-regulated kinase (ERK) signalling pathway but not the brain-derived neurotrophic factor (Bdnf). The long-term amnesia induced by glycogenolysis inhibition and the concomitant decreased expression of phospho-ERK were both restored with L-Lactate co-administration. These findings reveal a critical role for astrocyte-derived lactate in positive memory formation and highlight a novel amygdala-dependent reconsolidation process, whose disruption may offer a novel therapeutic target to reduce the long-lasting conditioned responses to cocaine.

  16. Disrupting astrocyte–neuron lactate transfer persistently reduces conditioned responses to cocaine

    Boury-Jamot, B; Carrard, A; Martin, J L; Halfon, O; Magistretti, Pierre J.; Boutrel, B

    2015-01-01

    A central problem in the treatment of drug addiction is the high risk of relapse often precipitated by drug-associated cues. The transfer of glycogen-derived lactate from astrocytes to neurons is required for long-term memory. Whereas blockade of drug memory reconsolidation represents a potential therapeutic strategy, the role of astrocyte–neuron lactate transport in long-term conditioning has received little attention. By infusing an inhibitor of glycogen phosphorylase into the basolateral amygdala of rats, we report that disruption of astrocyte-derived lactate not only transiently impaired the acquisition of a cocaine-induced conditioned place preference but also persistently disrupted an established conditioning. The drug memory was rescued by L-Lactate co-administration through a mechanism requiring the synaptic plasticity-related transcription factor Zif268 and extracellular signal-regulated kinase (ERK) signalling pathway but not the brain-derived neurotrophic factor (Bdnf). The long-term amnesia induced by glycogenolysis inhibition and the concomitant decreased expression of phospho-ERK were both restored with L-Lactate co-administration. These findings reveal a critical role for astrocyte-derived lactate in positive memory formation and highlight a novel amygdala-dependent reconsolidation process, whose disruption may offer a novel therapeutic target to reduce the long-lasting conditioned responses to cocaine.

  17. Selective production of deacetylated mannosylerythritol lipid, MEL-D, by acetyltransferase disruption mutant of Pseudozyma hubeiensis.

    Konishi, Masaaki; Makino, Motoki

    2018-01-01

    Mannosylerythritol lipids (MELs) are produced by several smut fungi of the Ustilaginaceae family; they are promising microbial biosurfactants and have excellent surface-active and self-assembling properties. Pseudozyma hubeiensis is a candidate for abundant MEL production and produces large amounts of 4-O-[(4'-mono-O-acetyl-2',3'-di-O-alkanoyl)-β-d-mannopyranosyl]-meso-erythritol (MEL-C). An acetyltransferase disruption mutant of P. hubeiensis, SY62-MM36, was obtained to selectively produce deacetylated 4-O-[(2',3'-di-O-alkanoyl)-β-d-mannopyranosyl]-meso-erythritol (MEL-D), and the structures of the products were determined. Lower mobility of major spots of the mutant on silica gel thin-layer chromatography verified its more hydrophilic nature than that of wild-type MEL-A, B, and C. Structural analyses confirmed the product to be MEL-D, which comprises acyl chains of caproic acid (C6:0), capric acid (C10:0), and lauric acid (C12:0). The critical micelle concentration (CMC) and the surface tension (γCMC) of the MEL-D were 2.0 × 10 -5  M and 29.7 mN/m, respectively. SY62-MM36 also produced a minor product that was estimated as triacylated MEL-D. The triacylated MEL-D had a CMC of 3.5 × 10 -5  M and a γCMC of 29.6 mN/m. In water, MEL-D formed a lamella liquid crystal phase over a broad range of concentrations. By fed-batch cultivation, the mutant produced 91.6 ± 6.3 g/L of MEL-D for 7 days. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  18. Mating System Evolution under Strong Pollen Limitation: Evidence of Disruptive Selection through Male and Female Fitness in Clarkia xantiana.

    Briscoe Runquist, Ryan D; Geber, Monica A; Pickett-Leonard, Michael; Moeller, David A

    2017-05-01

    Selection on floral traits in hermaphroditic plants is determined by both male and female reproductive success. However, predictions regarding floral trait and mating system evolution are often based solely on female fitness. Selection via male fitness has the potential to affect the outcomes of floral evolution. In this study, we used paternity analysis to assess individual selfing rates and selection on floral traits via male and female fitness in an experimental population of Clarkia xantiana where pollen limitation of seed set was strong. We detected selection through both female and male fitness with reinforcing or noninterfering patterns of selection through the two sex functions. For female fitness, selection favored reduced herkogamy and protandry, traits that promote increased autonomous selfing. For male fitness, selection on petal area was disruptive, with higher trait values conferring greater pollinator attraction and outcross siring success and smaller trait values leading to higher selfed siring success. Combining both female and male fitness, selection on petal area and protandry was disruptive because intermediate phenotypes were less successful as both males and females. Finally, functional relationships among male and female fertility components indicated that selfing resulted in seed discounting and pollen discounting. Under these functional relationships, the evolutionarily stable selfing rate can be intermediate or predominantly selfing or outcrossing, depending on the segregating load of deleterious mutations.

  19. Sleep deprivation selectively disrupts top-down adaptation to cognitive conflict in the Stroop test.

    Gevers, Wim; Deliens, Gaetane; Hoffmann, Sophie; Notebaert, Wim; Peigneux, Philippe

    2015-12-01

    Sleep deprivation is known to exert detrimental effects on various cognitive domains, including attention, vigilance and working memory. Seemingly at odds with these findings, prior studies repeatedly failed to evidence an impact of prior sleep deprivation on cognitive interference in the Stroop test, a hallmark paradigm in the study of cognitive control abilities. The present study investigated further the effect of sleep deprivation on cognitive control using an adapted version of the Stroop test that allows to segregate top-down (attentional reconfiguration on incongruent items) and bottom-up (facilitated processing after repetitions in responses and/or features of stimuli) components of performance. Participants underwent a regular night of sleep or a night of total sleep deprivation before cognitive testing. Results disclosed that sleep deprivation selectively impairs top-down adaptation mechanisms: cognitive control no longer increased upon detection of response conflict at the preceding trial. In parallel, bottom-up abilities were found unaffected by sleep deprivation: beneficial effects of stimulus and response repetitions persisted. Changes in vigilance states due to sleep deprivation selectively impact on cognitive control in the Stroop test by affecting top-down, but not bottom-up, mechanisms that guide adaptive behaviours. © 2015 European Sleep Research Society.

  20. Fire-mediated disruptive selection can explain the reseeder-resprouter dichotomy in Mediterranean-type vegetation.

    Altwegg, Res; De Klerk, Helen M; Midgley, Guy F

    2015-02-01

    Crown fire is a key selective pressure in Mediterranean-type plant communities. Adaptive responses to fire regimes involve trade-offs between investment for persistence (fire survival and resprouting) and reproduction (fire mortality, fast growth to reproductive maturity, and reseeding) as investments that enhance adult survival lower growth and reproductive rates. Southern hemisphere Mediterranean-type ecosystems are dominated by species with either endogenous regeneration from adult resprouting or fire-triggered seedling recruitment. Specifically, on nutrient-poor soils, these are either resprouting or reseeding life histories, with few intermediate forms, despite the fact that the transition between strategies is evolutionarily labile. How did this strong dichotomy evolve? We address this question by developing a stochastic demographic model to assess determinants of relative fitness of reseeders, resprouters and hypothetical intermediate forms. The model was parameterised using published demographic data from South African protea species and run over various relevant fire regime parameters facets. At intermediate fire return intervals, trade-offs between investment in growth versus fire resilience can cause fitness to peak at either of the extremes of the reseeder-resprouter continuum, especially when assuming realistic non-linear shapes for these trade-offs. Under these circumstances, the fitness landscape exhibits a saddle which could lead to disruptive selection. The fitness gradient between the peaks was shallow, which may explain why this life-history trait is phylogenetically labile. Resprouters had maximum fitness at shorter fire-return intervals than reseeders. The model suggests that a strong dichotomy in fire survival strategy depends on a non-linear trade-off between growth and fire persistence traits.

  1. Enhanced cell disruption strategy in the release of recombinant hepatitis B surface antigen from Pichia pastoris using response surface methodology

    2012-01-01

    Background Cell disruption strategies by high pressure homogenizer for the release of recombinant Hepatitis B surface antigen (HBsAg) from Pichia pastoris expression cells were optimized using response surface methodology (RSM) based on the central composite design (CCD). The factors studied include number of passes, biomass concentration and pulse pressure. Polynomial models were used to correlate the above mentioned factors to project the cell disruption capability and specific protein release of HBsAg from P. pastoris cells. Results The proposed cell disruption strategy consisted of a number of passes set at 20 times, biomass concentration of 7.70 g/L of dry cell weight (DCW) and pulse pressure at 1,029 bar. The optimized cell disruption strategy was shown to increase cell disruption efficiency by 2-fold and 4-fold for specific protein release of HBsAg when compared to glass bead method yielding 75.68% cell disruption rate (CDR) and HBsAg concentration of 29.20 mg/L respectively. Conclusions The model equation generated from RSM on cell disruption of P. pastoris was found adequate to determine the significant factors and its interactions among the process variables and the optimum conditions in releasing HBsAg when validated against a glass bead cell disruption method. The findings from the study can open up a promising strategy for better recovery of HBsAg recombinant protein during downstream processing. PMID:23039947

  2. An analysis of reactor structural response to fuel sodium interaction in a hypothetical core disruptive accident

    Suzuki, K.; Tashiro, M.; Sasanuma, K.; Nagashima, K.

    1976-01-01

    This study shows the effect of constraints around FSI zone on FSI phenomena and deformations of reactor structures. SUGAR-PISCES code system has been developed to evaluate the phenomena of FSI and the response of reactor structure. SUGAR calculates the phenomena of FSI. PISCES, developed by Physics International Company in U.S.A., calculates the dynamic response of reactor structure in two-dimensional, time-dependent finite-difference Lagrangian model. The results show that the peak pressure and energy by FSI and the deformation of reactor structures are about twice in case of FSI zone surrounding by blanket than by coolant. The FSI phenomena highly depend on the reactor structure and the realistic configuration around core must be considered for analyzing hypothetical core disruptive accident. This work was supported by a grant from Power Reactor and Nuclear Fuel Development Corporation. (auth.)

  3. From 'omics to otoliths: responses of an estuarine fish to endocrine disrupting compounds across biological scales.

    Brander, Susanne M; Connon, Richard E; He, Guochun; Hobbs, James A; Smalling, Kelly L; Teh, Swee J; White, J Wilson; Werner, Inge; Denison, Michael S; Cherr, Gary N

    2013-01-01

    Endocrine disrupting chemicals (EDCs) cause physiological abnormalities and population decline in fishes. However, few studies have linked environmental EDC exposures with responses at multiple tiers of the biological hierarchy, including population-level effects. To this end, we undertook a four-tiered investigation in the impacted San Francisco Bay estuary with the Mississippi silverside (Menidia audens), a small pelagic fish. This approach demonstrated links between different EDC sources and fish responses at different levels of biological organization. First we determined that water from a study site primarily impacted by ranch run-off had only estrogenic activity in vitro, while water sampled from a site receiving a combination of urban, limited ranch run-off, and treated wastewater effluent had both estrogenic and androgenic activity. Secondly, at the molecular level we found that fish had higher mRNA levels for estrogen-responsive genes at the site where only estrogenic activity was detected but relatively lower expression levels where both estrogenic and androgenic EDCs were detected. Thirdly, at the organism level, males at the site exposed to both estrogens and androgens had significantly lower mean gonadal somatic indices, significantly higher incidence of severe testicular necrosis and altered somatic growth relative to the site where only estrogens were detected. Finally, at the population level, the sex ratio was significantly skewed towards males at the site with measured androgenic and estrogenic activity. Our results suggest that mixtures of androgenic and estrogenic EDCs have antagonistic and potentially additive effects depending on the biological scale being assessed, and that mixtures containing androgens and estrogens may produce unexpected effects. In summary, evaluating EDC response at multiple tiers is necessary to determine the source of disruption (lowest scale, i.e. cell line) and what the ecological impact will be (largest scale, i

  4. Comparative responses to endocrine disrupting compounds in early life stages of Atlantic salmon, Salmo salar

    Duffy, Tara A.; Iwanowicz, Luke R.; McCormick, Stephen D.

    2014-01-01

    Atlantic salmon (Salmo salar) are endangered anadromous fish that may be exposed to feminizing endocrine disrupting compounds (EDCs) during early development, potentially altering physiological capacities, survival and fitness. To assess differential life stage sensitivity to common EDCs, we carried out short-term (four day) exposures using three doses each of 17α-ethinylestradiol (EE2), 17β-estradiol (E2), and nonylphenol (NP) on four early life stages; embryos, yolk-sac larvae, feeding fry and one year old smolts. Differential response was compared using vitellogenin (Vtg, a precursor egg protein) gene transcription. Smolts were also examined for impacts on plasma Vtg, cortisol, thyroid hormones (T4/T3) and hepatosomatic index (HSI). Compound-related mortality was not observed in any life stage, but Vtg mRNA was elevated in a dose-dependent manner in yolk-sac larvae, fry and smolts but not in embyos. The estrogens EE2 and E2 were consistently stronger inducers of Vtg than NP. Embryos responded significantly to the highest concentration of EE2 only, while older life stages responded to the highest doses of all three compounds, as well as intermediate doses of EE2 and E2. Maximal transcription was greater for fry among the three earliest life stages, suggesting fry may be the most responsive life stage in early development. Smolt plasma Vtg was also significantly increased, and this response was observed at lower doses of each compound than was detected by gene transcription suggesting this is a more sensitive indicator at this life stage. HSI was increased at the highest doses of EE2 and E2 and plasma T3 decreased at the highest dose of EE2. Our results indicate that all life stages after hatching are potentially sensitive to endocrine disruption by estrogenic compounds and that physiological responses were altered over a short window of exposure, indicating the potential for these compounds to impact fish in the wild.

  5. Variables Associated with Disrupted Placement in a Select Sample of Abused and Neglected Children.

    Cooper, Carolyn S.

    1987-01-01

    Examination of the placement history of 172 abused and/or neglected children found that children had a more disrupted foster care placement history if they: (1) had severe behavior problems; (2) were very young when first removed from the natural home; or (3) had drug-addicted and/or alcoholic parents. (Author/DB)

  6. Potential exposure to endocrine disrupting chemicals and selected adverse pregnancy outcomes

    Bengtsson, Jessica; Thygesen, Pernille Søgaard; Kaerlev, Linda

    2017-01-01

    potential occupational exposure to endocrine disrupting chemicals (EDC) of the mother during pregnancy is associated with preterm birth and low birth weight. Methods: Pregnant women referred to an Occupational Health Clinic (OHC) in two Danish regions (Copenhagen or Aarhus) between 1984 and 2010, suspected...

  7. Selective Toll-Like Receptor 4 Antagonists Prevent Acute Blood-Brain Barrier Disruption After Subarachnoid Hemorrhage in Mice.

    Okada, Takeshi; Kawakita, Fumihiro; Nishikawa, Hirofumi; Nakano, Fumi; Liu, Lei; Suzuki, Hidenori

    2018-05-31

    There are no direct evidences showing the linkage between Toll-like receptor 4 (TLR4) and blood-brain barrier (BBB) disruption after subarachnoid hemorrhage (SAH). The purpose of this study was to examine if selective blockage of TLR4 prevents BBB disruption after SAH in mice and if the TLR4 signaling involves mitogen-activated protein kinases (MAPKs). One hundred and fifty-one C57BL/6 male mice underwent sham or endovascular perforation SAH operation, randomly followed by an intracerebroventricular infusion of vehicle or two dosages (117 or 585 ng) of a selective TLR4 antagonist IAXO-102 at 30 min post-operation. The effects were evaluated by survival rates, neurological scores, and brain water content at 24-72 h and immunoglobulin G immunostaining and Western blotting at 24 h post-SAH. IAXO-102 significantly prevented post-SAH neurological impairments, brain edema, and BBB disruption, resulting in improved survival rates. IAXO-102 also significantly suppressed post-SAH activation of a major isoform of MAPK p46 c-Jun N-terminal kinase (JNK) and matrix metalloproteinase-9 as well as periostin induction and preserved tight junction protein zona occludens-1. Another selective TLR4 antagonist TAK-242, which has a different binding site from IAXO-102, also showed similar effects to IAXO-102. This study first provided the evidence that TLR4 signaling is involved in post-SAH acute BBB disruption and that the signaling is mediated at least partly by JNK activation. TLR4-targeted therapy may be promising to reduce post-SAH morbidities and mortalities.

  8. Workplace Disruption following Psychological Trauma: Influence of Incident Severity Level on Organizations' Post-Incident Response Planning and Execution.

    DeFraia, G S

    2016-04-01

    Psychologically traumatic workplace events (known as critical incidents), which occur globally, are increasing in prevalence within the USA. Assisting employers in their response is a growing practice area for occupational medicine, occupational social work, industrial psychology and other occupational health professions. Traumatic workplace events vary greatly in their level of organizational disruption. To explore whether extent of workplace disruption influences organizations' decisions for post-incident response planning and plan execution. Administrative data mining was employed to examine practice data from a workplace trauma response unit in the USA. Bivariate analyses were conducted to test whether scores from an instrument measuring extent of workplace disruption associated with organizational decisions regarding post-incident response. The more severe and disruptive the incident, the more likely organizations planned for and followed through to deliver on-site interventions. Following more severe incidents, organizations were also more likely to deliver group sessions and to complete follow-up consultations to ensure ongoing worker recovery. Increasing occupational health practitioners' knowledge of varying levels of organizational disruption and familiarity with a range of organizational response strategies improves incident assessment, consultation and planning, and ensures interventions delivered are consistent with the level of assistance needed on both worker and organizational levels.

  9. Workplace Disruption following Psychological Trauma: Influence of Incident Severity Level on Organizations' Post-Incident Response Planning and Execution

    GS DeFraia

    2016-04-01

    Full Text Available Background: Psychologically traumatic workplace events (known as critical incidents, which occur globally, are increasing in prevalence within the USA. Assisting employers in their response is a growing practice area for occupational medicine, occupational social work, industrial psychology and other occupational health professions. Traumatic workplace events vary greatly in their level of organizational disruption. Objective: To explore whether extent of workplace disruption influences organizations' decisions for post-incident response planning and plan execution. Methods: Administrative data mining was employed to examine practice data from a workplace trauma response unit in the USA. Bivariate analyses were conducted to test whether scores from an instrument measuring extent of workplace disruption associated with organizational decisions regarding post-incident response. Results: The more severe and disruptive the incident, the more likely organizations planned for and followed through to deliver on-site interventions. Following more severe incidents, organizations were also more likely to deliver group sessions and to complete follow-up consultations to ensure ongoing worker recovery. Conclusion: Increasing occupational health practitioners' knowledge of varying levels of organizational disruption and familiarity with a range of organizational response strategies improves incident assessment, consultation and planning, and ensures interventions delivered are consistent with the level of assistance needed on both worker and organizational levels.

  10. Dim light at night disrupts the short-day response in Siberian hamsters.

    Ikeno, Tomoko; Weil, Zachary M; Nelson, Randy J

    2014-02-01

    Photoperiodic regulation of physiology, morphology, and behavior is crucial for many animals to survive seasonally variable conditions unfavorable for reproduction and survival. The photoperiodic response in mammals is mediated by nocturnal secretion of melatonin under the control of a circadian clock. However, artificial light at night caused by recent urbanization may disrupt the circadian clock, as well as the photoperiodic response by blunting melatonin secretion. Here we examined the effect of dim light at night (dLAN) (5lux of light during the dark phase) on locomotor activity rhythms and short-day regulation of reproduction, body mass, pelage properties, and immune responses of male Siberian hamsters. Short-day animals reduced gonadal and body mass, decreased spermatid nuclei and sperm numbers, molted to a whiter pelage, and increased pelage density compared to long-day animals. However, animals that experienced short days with dLAN did not show these short-day responses. Moreover, short-day specific immune responses were altered in dLAN conditions. The nocturnal activity pattern was blunted in dLAN hamsters, consistent with the observation that dLAN changed expression of the circadian clock gene, Period1. In addition, we demonstrated that expression levels of genes implicated in the photoperiodic response, Mel-1a melatonin receptor, Eyes absent 3, thyroid stimulating hormone receptor, gonadotropin-releasing hormone, and gonadotropin-inhibitory hormone, were higher in dLAN animals than those in short-day animals. These results suggest that dLAN disturbs the circadian clock function and affects the molecular mechanisms of the photoperiodic response. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Comparative responses to endocrine disrupting compounds in early life stages of Atlantic salmon, Salmo salar.

    Duffy, T A; Iwanowicz, L R; McCormick, S D

    2014-07-01

    Atlantic salmon (Salmo salar) are endangered anadromous fish that may be exposed to feminizing endocrine disrupting compounds (EDCs) during early development, potentially altering physiological capacities, survival and fitness. To assess differential life stage sensitivity to common EDCs, we carried out short-term (4 day) exposures using three doses each of 17 α-ethinylestradiol (EE2), 17 β-estradiol (E2), and nonylphenol (NP) on four early life stages; embryos, yolk-sac larvae, feeding fry and 1 year old smolts. Differential response was compared using vitellogenin (Vtg, a precursor egg protein) gene transcription. Smolts were also examined for impacts on plasma Vtg, cortisol, thyroid hormones (T4/T3) and hepatosomatic index (HSI). Compound-related mortality was not observed in any life stage, but Vtg mRNA was elevated in a dose-dependent manner in yolk-sac larvae, fry and smolts but not in embryos. The estrogens EE2 and E2 were consistently stronger inducers of Vtg than NP. Embryos responded significantly to the highest concentration of EE2 only, while older life stages responded to the highest doses of all three compounds, as well as intermediate doses of EE2 and E2. Maximal transcription was greater for fry among the three earliest life stages, suggesting fry may be the most responsive life stage in early development. Smolt plasma Vtg was also significantly increased, and this response was observed at lower doses of each compound than was detected by gene transcription suggesting plasma Vtg is a more sensitive indicator at this life stage. HSI was increased at the highest doses of EE2 and E2, and plasma T3 was decreased at the highest dose of EE2. Our results indicate that all life stages are potentially sensitive to endocrine disruption by estrogenic compounds and that physiological responses were altered over a short window of exposure, indicating the potential for these compounds to impact fish in the wild. Copyright © 2014 Elsevier B.V. All rights

  12. Aminolevulinic acid-photodynamic therapy combined with topically applied vascular disrupting agent vadimezan leads to enhanced antitumor responses.

    Marrero, Allison; Becker, Theresa; Sunar, Ulas; Morgan, Janet; Bellnier, David

    2011-01-01

    The tumor vascular-disrupting agent (VDA) vadimezan (5,6-dimethylxanthenone-4-acetic acid, DMXAA) has been shown to potentiate the antitumor activity of photodynamic therapy (PDT) using systemically administered photosensitizers. Here, we characterized the response of subcutaneous syngeneic Colon26 murine colon adenocarcinoma tumors to PDT using the locally applied photosensitizer precursor aminolevulinic acid (ALA) in combination with a topical formulation of vadimezan. Diffuse correlation spectroscopy (DCS), a noninvasive method for monitoring blood flow, was utilized to determine tumor vascular response to treatment. In addition, correlative CD31-immunohistochemistry to visualize endothelial damage, ELISA to measure induction of tumor necrosis factor-alpha (TNF-α) and tumor weight measurements were also examined in separate animals. In our previous work, DCS revealed a selective decrease in tumor blood flow over time following topical vadimezan. ALA-PDT treatment also induced a decrease in tumor blood flow. The onset of blood flow reduction was rapid in tumors treated with both ALA-PDT and vadimezan. CD31-immunostaining of tumor sections confirmed vascular damage following topical application of vadimezan. Tumor weight measurements revealed enhanced tumor growth inhibition with combination treatment compared with ALA-PDT or vadimezan treatment alone. In conclusion, vadimezan as a topical agent enhances treatment efficacy when combined with ALA-PDT. This combination could be useful in clinical applications. © 2011 The Authors. Photochemistry and Photobiology © 2011 The American Society of Photobiology.

  13. Evidence of cardiac involvement in the fetal inflammatory response syndrome: disruption of gene networks programming cardiac development in nonhuman primates.

    Mitchell, Timothy; MacDonald, James W; Srinouanpranchanh, Sengkeo; Bammler, Theodor K; Merillat, Sean; Boldenow, Erica; Coleman, Michelle; Agnew, Kathy; Baldessari, Audrey; Stencel-Baerenwald, Jennifer E; Tisoncik-Go, Jennifer; Green, Richard R; Gale, Michael J; Rajagopal, Lakshmi; Adams Waldorf, Kristina M

    2018-04-01

    Most early preterm births are associated with intraamniotic infection and inflammation, which can lead to systemic inflammation in the fetus. The fetal inflammatory response syndrome describes elevations in the fetal interleukin-6 level, which is a marker for inflammation and fetal organ injury. An understanding of the effects of inflammation on fetal cardiac development may lead to insight into the fetal origins of adult cardiovascular disease. The purpose of this study was to determine whether the fetal inflammatory response syndrome is associated with disruptions in gene networks that program fetal cardiac development. We obtained fetal cardiac tissue after necropsy from a well-described pregnant nonhuman primate model (pigtail macaque, Macaca nemestrina) of intrauterine infection (n=5) and controls (n=5). Cases with the fetal inflammatory response syndrome (fetal plasma interleukin-6 >11 pg/mL) were induced by either choriodecidual inoculation of a hypervirulent group B streptococcus strain (n=4) or intraamniotic inoculation of Escherichia coli (n=1). RNA and protein were extracted from fetal hearts and profiled by microarray and Luminex (Millipore, Billerica, MA) for cytokine analysis, respectively. Results were validated by quantitative reverse transcriptase polymerase chain reaction. Statistical and bioinformatics analyses included single gene analysis, gene set analysis, Ingenuity Pathway Analysis (Qiagen, Valencia, CA), and Wilcoxon rank sum. Severe fetal inflammation developed in the context of intraamniotic infection and a disseminated bacterial infection in the fetus. Interleukin-6 and -8 in fetal cardiac tissues were elevated significantly in fetal inflammatory response syndrome cases vs controls (P1.5-fold change, P<.05) in the fetal heart (analysis of variance). Altered expression of select genes was validated by quantitative reverse transcriptase polymerase chain reaction that included several with known functions in cardiac injury, morphogenesis

  14. Antarctic Climate Change: Extreme Events Disrupt Plastic Phenotypic Response in Adélie Penguins

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

    2014-01-01

    In the context of predicted alteration of sea ice cover and increased frequency of extreme events, it is especially timely to investigate plasticity within Antarctic species responding to a key environmental aspect of their ecology: sea ice variability. Using 13 years of longitudinal data, we investigated the effect of sea ice concentration (SIC) on the foraging efficiency of Adélie penguins (Pygoscelis adeliae) breeding in the Ross Sea. A ‘natural experiment’ brought by the exceptional presence of giant icebergs during 5 consecutive years provided unprecedented habitat variation for testing the effects of extreme events on the relationship between SIC and foraging efficiency in this sea-ice dependent species. Significant levels of phenotypic plasticity were evident in response to changes in SIC in normal environmental conditions. Maximum foraging efficiency occurred at relatively low SIC, peaking at 6.1% and decreasing with higher SIC. The ‘natural experiment’ uncoupled efficiency levels from SIC variations. Our study suggests that lower summer SIC than currently observed would benefit the foraging performance of Adélie penguins in their southernmost breeding area. Importantly, it also provides evidence that extreme climatic events can disrupt response plasticity in a wild seabird population. This questions the predictive power of relationships built on past observations, when not only the average climatic conditions are changing but the frequency of extreme climatic anomalies is also on the rise. PMID:24489657

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

    Amélie Lescroël

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

  16. Response terminated displays unload selective attention.

    Roper, Zachary J J; Vecera, Shaun P

    2013-01-01

    Perceptual load theory successfully replaced the early vs. late selection debate by appealing to adaptive control over the efficiency of selective attention. Early selection is observed unless perceptual load (p-Load) is sufficiently low to grant attentional "spill-over" to task-irrelevant stimuli. Many studies exploring load theory have used limited display durations that perhaps impose artificial limits on encoding processes. We extended the exposure duration in a classic p-Load task to alleviate temporal encoding demands that may otherwise tax mnemonic consolidation processes. If the load effect arises from perceptual demands alone, then freeing-up available mnemonic resources by extending the exposure duration should have little effect. The results of Experiment 1 falsify this prediction. We observed a reliable flanker effect under high p-Load, response-terminated displays. Next, we orthogonally manipulated exposure duration and task-relevance. Counter-intuitively, we found that the likelihood of observing the flanker effect under high p-Load resides with the duration of the task-relevant array, not the flanker itself. We propose that stimulus and encoding demands interact to produce the load effect. Our account clarifies how task parameters differentially impinge upon cognitive processes to produce attentional "spill-over" by appealing to visual short-term memory as an additional processing bottleneck when stimuli are briefly presented.

  17. Response terminated displays unload selective attention

    Zachary Joseph Jackson Roper

    2013-12-01

    Full Text Available Perceptual load theory successfully replaced the early versus late selection debate by appealing to adaptive control over the efficiency of selective attention. Early selection is observed unless perceptual load (p-Load is sufficiently low to grant attentional ‘spill-over‘ to task-irrelevant stimuli. Many studies exploring load theory have used limited display durations that perhaps impose artificial limits on encoding processes. We extended the exposure duration in a classic p-Load task to alleviate temporal encoding demands that may otherwise tax mnemonic consolidation processes. If the load effect arises from perceptual demands alone, then freeing-up available mnemonic resources by extending the exposure duration should have little effect. The results of Experiment 1 falsify this prediction. We observed a reliable flanker effect under high p-Load, response-terminated displays. Next, we orthogonally manipulated exposure duration and task-relevance. Counter-intuitively, we found that the likelihood of observing the flanker effect under high p-Load resides with the duration of the task-relevant array, not the flanker itself. We propose that stimulus and encoding demands interact to produce the load effect. Our account clarifies how task parameters differentially impinge upon cognitive processes to produce attentional ‘spill-over’ by appealing to visual short-term memory as an additional processing bottleneck when stimuli are briefly presented.

  18. Potential exposure to endocrine disrupting chemicals and selected adverse pregnancy outcomes

    Bengtsson, Jessica; Thygesen, Pernille Søgaard; Kaerlev, Linda

    2017-01-01

    potential occupational exposure to endocrine disrupting chemicals (EDC) of the mother during pregnancy is associated with preterm birth and low birth weight. Methods: Pregnant women referred to an Occupational Health Clinic (OHC) in two Danish regions (Copenhagen or Aarhus) between 1984 and 2010, suspected...... on the suspicion of other exposures than EDC (n = 620), and to a sample of births by all occupationally active women in the same geographical regions (n = 346,544), including 1,077 births of the referred women’s non-referred pregnancies. Results: No indications of reduced birth weight or increased risk of preterm...... birth were found among women potentially exposed to EDC. Women potentially exposed to EDC had children with a higher birth weight compared to the sample of occupationally active women but not compared to other women referred to an OHC. Conclusions: Potential maternal exposure to EDC at Danish workplaces...

  19. Sex-specific hippocampal 5-hydroxymethylcytosine is disrupted in response to acute stress.

    Papale, Ligia A; Li, Sisi; Madrid, Andy; Zhang, Qi; Chen, Li; Chopra, Pankaj; Jin, Peng; Keleş, Sündüz; Alisch, Reid S

    2016-12-01

    Environmental stress is among the most important contributors to increased susceptibility to develop psychiatric disorders. While it is well known that acute environmental stress alters gene expression, the molecular mechanisms underlying these changes remain largely unknown. 5-hydroxymethylcytosine (5hmC) is a novel environmentally sensitive epigenetic modification that is highly enriched in neurons and is associated with active neuronal transcription. Recently, we reported a genome-wide disruption of hippocampal 5hmC in male mice following acute stress that was correlated to altered transcript levels of genes in known stress related pathways. Since sex-specific endocrine mechanisms respond to environmental stimulus by altering the neuronal epigenome, we examined the genome-wide profile of hippocampal 5hmC in female mice following exposure to acute stress and identified 363 differentially hydroxymethylated regions (DhMRs) linked to known (e.g., Nr3c1 and Ntrk2) and potentially novel genes associated with stress response and psychiatric disorders. Integration of hippocampal expression data from the same female mice found stress-related hydroxymethylation correlated to altered transcript levels. Finally, characterization of stress-induced sex-specific 5hmC profiles in the hippocampus revealed 778 sex-specific acute stress-induced DhMRs some of which were correlated to altered transcript levels that produce sex-specific isoforms in response to stress. Together, the alterations in 5hmC presented here provide a possible molecular mechanism for the adaptive sex-specific response to stress that may augment the design of novel therapeutic agents that will have optimal effectiveness in each sex. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Autologous Stem Cell Transplantation Disrupts Adaptive Immune Responses during Rebound Simian/Human Immunodeficiency Virus Viremia.

    Reeves, Daniel B; Peterson, Christopher W; Kiem, Hans-Peter; Schiffer, Joshua T

    2017-07-01

    of stem cell transplantation in a macaque simian/HIV (SHIV) system. Using a mechanistic mathematical model, we found that while primary infection generates an adaptive immune memory response, stem cell transplantation disrupts this learned immunity. The results have implications for HIV cure regimens based on stem cell transplantation. Copyright © 2017 American Society for Microbiology.

  1. Pseudomonas aeruginosa disrupts Caenorhabditis elegans iron homeostasis, causing a hypoxic response and death.

    Kirienko, Natalia V; Kirienko, Daniel R; Larkins-Ford, Jonah; Wählby, Carolina; Ruvkun, Gary; Ausubel, Frederick M

    2013-04-17

    The opportunistic pathogen Pseudomonas aeruginosa causes serious human infections, but effective treatments and the mechanisms mediating pathogenesis remain elusive. Caenorhabditis elegans shares innate immune pathways with humans, making it invaluable to investigate infection. To determine how P. aeruginosa disrupts host biology, we studied how P. aeruginosa kills C. elegans in a liquid-based pathogenesis model. We found that P. aeruginosa-mediated killing does not require quorum-sensing pathways or host colonization. A chemical genetic screen revealed that iron chelators alleviate P. aeruginosa-mediated killing. Consistent with a role for iron in P. aeruginosa pathogenesis, the bacterial siderophore pyoverdin was required for virulence and was sufficient to induce a hypoxic response and death in the absence of bacteria. Loss of the C. elegans hypoxia-inducing factor HIF-1, which regulates iron homeostasis, exacerbated P. aeruginosa pathogenesis, further linking hypoxia and killing. As pyoverdin is indispensable for virulence in mice, pyoverdin-mediated hypoxia is likely to be relevant in human pathogenesis. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Circadian clock genes Per1 and Per2 regulate the response of metabolism-associated transcripts to sleep disruption.

    Jana Husse

    Full Text Available Human and animal studies demonstrate that short sleep or poor sleep quality, e.g. in night shift workers, promote the development of obesity and diabetes. Effects of sleep disruption on glucose homeostasis and liver physiology are well documented. However, changes in adipokine levels after sleep disruption suggest that adipocytes might be another important peripheral target of sleep. Circadian clocks regulate metabolic homeostasis and clock disruption can result in obesity and the metabolic syndrome. The finding that sleep and clock disruption have very similar metabolic effects prompted us to ask whether the circadian clock machinery may mediate the metabolic consequences of sleep disruption. To test this we analyzed energy homeostasis and adipocyte transcriptome regulation in a mouse model of shift work, in which we prevented mice from sleeping during the first six hours of their normal inactive phase for five consecutive days (timed sleep restriction--TSR. We compared the effects of TSR between wild-type and Per1/2 double mutant mice with the prediction that the absence of a circadian clock in Per1/2 mutants would result in a blunted metabolic response to TSR. In wild-types, TSR induces significant transcriptional reprogramming of white adipose tissue, suggestive of increased lipogenesis, together with increased secretion of the adipokine leptin and increased food intake, hallmarks of obesity and associated leptin resistance. Some of these changes persist for at least one week after the end of TSR, indicating that even short episodes of sleep disruption can induce prolonged physiological impairments. In contrast, Per1/2 deficient mice show blunted effects of TSR on food intake, leptin levels and adipose transcription. We conclude that the absence of a functional clock in Per1/2 double mutants protects these mice from TSR-induced metabolic reprogramming, suggesting a role of the circadian timing system in regulating the physiological effects

  3. Response characteristics of selected personnel neutron dosimeters

    McDonald, J.C.; Fix, J.J.; Hadley, R.T.; Holbrook, K.L.; Yoder, R.C.; Roberson, P.L.; Endres, G.W.R.; Nichols, L.L.; Schwartz, R.B.

    1983-09-01

    Performance characteristics of selected personnel neutron dosimeters in current use at Department of Energy (DOE) facilities were determined from their evaluation of neutron dose equivalent received after irradiations with specific neutron sources at either the National Bureau of Standards (NBS) or the Pacific Northwest Laboratory (PNL). The characteristics assessed included: lower detection level, energy response, precision and accuracy. It was found that when all of the laboratories employed a common set of calibrations, the overall accuracy was approximately +-20%, which is within uncertainty expected for these dosimeters. For doses above 80 mrem, the accuracy improved to better than 10% when a common calibration was used. Individual differences found in this study may reflect differences in calibration technique rather than differences in the dose rates of actual calibration standards. Second, at dose rates above 100 mrem, the precision for the best participants was generally below +-10% which is also within expected limits for these types of dosimeters. The poorest results had a standard deviation of about +-25%. At the lowest doses, which were sometimes below the lower detection limit, the precision often approached or exceeded +-100%. Third, the lower level of detection for free field 252 Cf neutrons generally ranged between 20 and 50 mrem. Fourth, the energy dependence study provided a characterization of the response of the dosimeters to neutron energies far from the calibration energy. 11 references, 22 figures, 26 tables

  4. Assessing dose-response relationships for endocrine disrupting chemicals (EDCs): a focus on non-monotonicity.

    Zoeller, R Thomas; Vandenberg, Laura N

    2015-05-15

    The fundamental principle in regulatory toxicology is that all chemicals are toxic and that the severity of effect is proportional to the exposure level. An ancillary assumption is that there are no effects at exposures below the lowest observed adverse effect level (LOAEL), either because no effects exist or because they are not statistically resolvable, implying that they would not be adverse. Chemicals that interfere with hormones violate these principles in two important ways: dose-response relationships can be non-monotonic, which have been reported in hundreds of studies of endocrine disrupting chemicals (EDCs); and effects are often observed below the LOAEL, including all environmental epidemiological studies examining EDCs. In recognition of the importance of this issue, Lagarde et al. have published the first proposal to qualitatively assess non-monotonic dose response (NMDR) relationships for use in risk assessments. Their proposal represents a significant step forward in the evaluation of complex datasets for use in risk assessments. Here, we comment on three elements of the Lagarde proposal that we feel need to be assessed more critically and present our arguments: 1) the use of Klimisch scores to evaluate study quality, 2) the concept of evaluating study quality without topical experts' knowledge and opinions, and 3) the requirement of establishing the biological plausibility of an NMDR before consideration for use in risk assessment. We present evidence-based logical arguments that 1) the use of the Klimisch score should be abandoned for assessing study quality; 2) evaluating study quality requires experts in the specific field; and 3) an understanding of mechanisms should not be required to accept observable, statistically valid phenomena. It is our hope to contribute to the important and ongoing debate about the impact of NMDRs on risk assessment with positive suggestions.

  5. Disruption of sphingolipid biosynthesis in hepatocyte nodules: selective proliferative stimulus induced by fumonisin B{sub 1}

    Westhuizen, Liana van der; Gelderblom, Wentzel C.A.; Shephard, Gordon S; Swanevelder, Sonja

    2004-07-15

    In order to investigate the role of sphingolipid disruption in the cancer promoting potential of fumonisin B{sub 1} (FB{sub 1}) in the development of hepatocyte nodules, male Fischer 344 rats were subjected to cancer initiation (FB{sub 1} containing diet or diethylnitrosamine (DEN) by i.p. injection) and promotion (2-acetylaminofluorene with partial hepatectomy, 2-AAF/PH) treatments followed by a secondary FB{sub 1} dietary regimen. Sphinganine (Sa) and sphingosine (So) levels were measured by high performance liquid chromatography in control, surrounding and nodular liver tissues of the rats. The disruption of sphingolipid biosynthesis by the secondary FB{sub 1} treatment in the control rats was significantly (P<0.05) enhanced by the 2-AAF/PH cancer promotion treatment. The nodular and surrounding Sa levels returned to baseline following FB{sub 1} initiation and 2-AAF/PH promotion. When comparing the groups subjected to the secondary FB{sub 1} treatment, the initiation effected by FB{sub 1} was less (P<0.01) sensitive to the accumulation of Sa in the nodular and surrounding tissues than DEN initiation and the 2-AAF/PH control treatment. In contrast, the So level of FB{sub 1} initiation was marginally increased in the nodules compared to the surrounding liver after 2-AAF/PH promotion and significantly (P<0.05) higher with the secondary FB{sub 1} treatment. Although, the FB{sub 1}-induced hepatocyte nodules were not resistant to the disruption of sphingolipid biosynthesis, the nodular So levels were increased and might provide a selective growth stimulus possibly induced by bio-active sphingoid intermediates such as sphingosine 1-phosphate (S1P)

  6. Adsorption of selected pharmaceuticals and an endocrine disrupting compound by granular activated carbon. 2. Model prediction

    Yu, Z.; Peldszus, S.; Huck, P.M. [University of Waterloo, Waterloo, ON (Canada). NSERC Chair in Water Treatment

    2009-03-01

    The adsorption of two representative pharmaceutically active compounds (PhACs) naproxen and carbamazepine and one endocrine disrupting compound (EDC) nonylphenol was studied in pilot-scale granular activated carbon (GAC) adsorbers using post-sedimentation (PS) water from a full-scale drinking water treatment plant. The GAC adsorbents were coal-based Calgon Filtrasorb 400 and coconut shell-based PICA CTIF TE. Acidic naproxen broke through fastest while nonylphenol was removed best, which was consistent with the degree to which fouling affected compound removals. Model predictions and experimental data were generally in good agreement for all three compounds, which demonstrated the effectiveness and robustness of the pore and surface diffusion model (PSDM) used in combination with the time-variable parameter approach for predicting removals at environmentally relevant concentrations (i.e., ng/L range). Sensitivity analyses suggested that accurate determination of film diffusion coefficients was critical for predicting breakthrough for naproxen and carbamazepine, in particular when high removals are targeted. Model simulations demonstrated that GAC carbon usage rates (CURs) for naproxen were substantially influenced by the empty bed contact time (EBCT) at the investigated conditions. Model-based comparisons between GAC CURs and minimum CURs for powdered activated carbon (PAC) applications suggested that PAC would be most appropriate for achieving 90% removal of naproxen, whereas GAC would be more suitable for nonylphenol. 25 refs., 4 figs., 1 tab.

  7. In vitro screening for endocrine disruptive activity in selected South African harbours and river mouths

    Truter, JC

    2015-12-01

    Full Text Available . Moreover, levels of the female hormone 17ß-(o)estradiol (E2) were determined in all samples, as well as a selection of hydrocarbons in the eThekwini samples. A high proportion of samples collected from eThekwini were oestrogenic, whereas none from Port...

  8. The vascular disrupting agent ZD6126 shows increased antitumor efficacy and enhanced radiation response in large, advanced tumors

    Siemann, Dietmar W.; Rojiani, Amyn M.

    2005-01-01

    Purpose: ZD6126 is a vascular-targeting agent that induces selective effects on the morphology of proliferating and immature endothelial cells by disrupting the tubulin cytoskeleton. The efficacy of ZD6126 was investigated in large vs. small tumors in a variety of animal models. Methods and Materials: Three rodent tumor models (KHT, SCCVII, RIF-1) and three human tumor xenografts (Caki-1, KSY-1, SKBR3) were used. Mice bearing leg tumors ranging in size from 0.1-2.0 g were injected intraperitoneally with a single 150 mg/kg dose of ZD6126. The response was assessed by morphologic and morphometric means as well as an in vivo to in vitro clonogenic cell survival assay. To examine the impact of tumor size on the extent of enhancement of radiation efficacy by ZD6126, KHT sarcomas of three different sizes were irradiated locally with a range of radiation doses, and cell survival was determined. Results: All rodent tumors and human tumor xenografts evaluated showed a strong correlation between increasing tumor size and treatment effect as determined by clonogenic cell survival. Detailed evaluation of KHT sarcomas treated with ZD6126 showed a reduction in patent tumor blood vessels that was ∼20% in small ( 90% in large (>1.0 g) tumors. Histologic assessment revealed that the extent of tumor necrosis after ZD6126 treatment, although minimal in small KHT sarcomas, became more extensive with increasing tumor size. Clonogenic cell survival after ZD6126 exposure showed a decrease in tumor surviving fraction from approximately 3 x 10 -1 to 1 x 10 -4 with increasing tumor size. When combined with radiotherapy, ZD6126 treatment resulted in little enhancement of the antitumor effect of radiation in small (<0.3 g) tumors but marked increases in cell kill in tumors larger than 1.0 g. Conclusions: Because bulky neoplastic disease is typically the most difficult to manage, the present findings provide further support for the continued development of vascular disrupting agents such as

  9. Adsorption of selected endocrine disrupting compounds and pharmaceuticals on activated biochars

    Jung, Chanil [Department of Civil and Environmental Engineering, University of South Carolina, Columbia, SC 29208 (United States); Park, Junyeong [Department of Forest Biomaterials, North Carolina State University, Raleigh, NC 27695 (United States); Lim, Kwang Hun [Department of Chemistry, East Carolina University, Greenville, NC 27858 (United States); Park, Sunkyu [Department of Forest Biomaterials, North Carolina State University, Raleigh, NC 27695 (United States); Heo, Jiyong [Department of Civil and Environmental Engineering, Korea Army Academy at Young-Cheon, PO Box 135-1, Changhari, Gogyeongmeon, Young-cheon 770-849, Gyeongbuk (Korea, Republic of); Her, Namguk [Department of Chemistry and Environmental Sciences, Korea Army Academy at Young-Cheon, PO Box 135-1, Changhari, Gogyeongmeon, Young-cheon 770-849, Gyeongbuk (Korea, Republic of); Oh, Jeill; Yun, Soyoung [Department of Civil and Environmental Engineering, Chung-Ang University, Dongjak-Ku, Seoul 156-756 (Korea, Republic of); Yoon, Yeomin, E-mail: yoony@cec.sc.edu [Department of Civil and Environmental Engineering, University of South Carolina, Columbia, SC 29208 (United States)

    2013-12-15

    Highlights: • Biochars were prepared at different gas environments. • The competitive adsorption among EDCs/PhACs were investigated. • Aromaticity of adsorbent plays a significant role for EDCs/PhACs adsorption. -- Abstract: Chemically activated biochar produced under oxygenated (O-biochar) and oxygen-free (N-biochar) conditions were characterized and the adsorption of endocrine disrupting compounds (EDCs): bisphenol A (BPA), atrazine (ATR), 17 α-ethinylestradiol (EE2), and pharmaceutical active compounds (PhACs); sulfamethoxazole (SMX), carbamazepine (CBM), diclofenac (DCF), ibuprofen (IBP) on both biochars and commercialized powdered activated carbon (PAC) were investigated. Characteristic analysis of adsorbents by solid-state nuclear magnetic resonance (NMR) was conducted to determine better understanding about the EDCs/PhACs adsorption. N-biochar consisted of higher polarity moieties with more alkyl (0–45 ppm), methoxyl (45–63 ppm), O-alkyl (63–108 ppm), and carboxyl carbon (165–187 ppm) content than other adsorbents, while aromaticity of O-biochar was higher than that of N-biochar. O-biochar was composed mostly of aromatic moieties, with low H/C and O/C ratios compared to the highly polarized N-biochar that contained diverse polar functional groups. The higher surface area and pore volume of N-biochar resulted in higher adsorption capacity toward EDCs/PhACs along with atomic-level molecular structural property than O-biochar and PAC. N-biochar had a highest adsorption capacity of all chemicals, suggesting that N-biochar derived from loblolly pine chip is a promising sorbent for agricultural and environmental applications. The adsorption of pH-sensitive dissociable SMX, DCF, IBP, and BPA varied and the order of adsorption capacity was correlated with the hydrophobicity (K{sub ow}) of adsorbates throughout the all adsorbents, whereas adsorption of non-ionizable CBM, ATR, and EE2 in varied pH allowed adsorbents to interact with hydrophobic property

  10. Adsorption of selected endocrine disrupting compounds and pharmaceuticals on activated biochars

    Jung, Chanil; Park, Junyeong; Lim, Kwang Hun; Park, Sunkyu; Heo, Jiyong; Her, Namguk; Oh, Jeill; Yun, Soyoung; Yoon, Yeomin

    2013-01-01

    Highlights: • Biochars were prepared at different gas environments. • The competitive adsorption among EDCs/PhACs were investigated. • Aromaticity of adsorbent plays a significant role for EDCs/PhACs adsorption. -- Abstract: Chemically activated biochar produced under oxygenated (O-biochar) and oxygen-free (N-biochar) conditions were characterized and the adsorption of endocrine disrupting compounds (EDCs): bisphenol A (BPA), atrazine (ATR), 17 α-ethinylestradiol (EE2), and pharmaceutical active compounds (PhACs); sulfamethoxazole (SMX), carbamazepine (CBM), diclofenac (DCF), ibuprofen (IBP) on both biochars and commercialized powdered activated carbon (PAC) were investigated. Characteristic analysis of adsorbents by solid-state nuclear magnetic resonance (NMR) was conducted to determine better understanding about the EDCs/PhACs adsorption. N-biochar consisted of higher polarity moieties with more alkyl (0–45 ppm), methoxyl (45–63 ppm), O-alkyl (63–108 ppm), and carboxyl carbon (165–187 ppm) content than other adsorbents, while aromaticity of O-biochar was higher than that of N-biochar. O-biochar was composed mostly of aromatic moieties, with low H/C and O/C ratios compared to the highly polarized N-biochar that contained diverse polar functional groups. The higher surface area and pore volume of N-biochar resulted in higher adsorption capacity toward EDCs/PhACs along with atomic-level molecular structural property than O-biochar and PAC. N-biochar had a highest adsorption capacity of all chemicals, suggesting that N-biochar derived from loblolly pine chip is a promising sorbent for agricultural and environmental applications. The adsorption of pH-sensitive dissociable SMX, DCF, IBP, and BPA varied and the order of adsorption capacity was correlated with the hydrophobicity (K ow ) of adsorbates throughout the all adsorbents, whereas adsorption of non-ionizable CBM, ATR, and EE2 in varied pH allowed adsorbents to interact with hydrophobic property of

  11. Effect of skin barrier disruption on immune responses to topically applied cross-reacting material, CRM(197), of diphtheria toxin.

    Godefroy, S; Peyre, M; Garcia, N; Muller, S; Sesardic, D; Partidos, C D

    2005-08-01

    The high accessibility of the skin and the presence of immunocompetent cells in the epidermis makes this surface an attractive route for needle-free administration of vaccines. However, the lining of the skin by the stratum corneum is a major obstacle to vaccine delivery. In this study we examined the effect of skin barrier disruption on the immune responses to the cross-reacting material CRM(197), a nontoxic mutant of diphtheria toxin (DTx) that is considered as a vaccine candidate. Application of CRM(197), together with cholera toxin (CT), onto the tape-stripped skin of mice elicited antibody responses that had anti-DTx neutralizing activity. Vaccine delivery onto mildly ablated skin or intact skin did not elicit any detectable anti-CRM(197) antibodies. Mice immunized with CRM(197) alone onto the tape-stripped skin mounted a vigorous antigen-specific proliferative response. In contrast, the induction of cellular immunity after CRM(197) deposition onto mildly ablated or intact skin was adjuvant dependent. Furthermore, epidermal cells were activated and underwent apoptosis that was more pronounced when the stratum corneum was removed by tape stripping. Overall, these findings highlight the potential for transcutaneous delivery of CRM(197) and establish a correlation between the degree of barrier disruption and levels of antigen-specific immune responses. Moreover, these results provide the first evidence that the development of a transcutaneous immunization strategy for diphtheria, based on simple and practical methods to disrupt the skin barrier, is feasible.

  12. Selective bilateral amygdala lesions in rhesus monkeys fail to disrupt object reversal learning.

    Izquierdo, Alicia; Murray, Elisabeth A

    2007-01-31

    Neuropsychological studies in nonhuman primates have led to the view that the amygdala plays an essential role in stimulus-reward association. The main evidence in support of this idea is that bilateral aspirative or radiofrequency lesions of the amygdala yield severe impairments on object reversal learning, a task that assesses the ability to shift choices of objects based on the presence or absence of food reward (i.e., reward contingency). The behavioral effects of different lesion techniques, however, can vary. The present study therefore evaluated the effects of selective, excitotoxic lesions of the amygdala in rhesus monkeys on object reversal learning. For comparison, we tested the same monkeys on a task known to be sensitive to amygdala damage, the reinforcer devaluation task. Contrary to previous results based on less selective lesion techniques, monkeys with complete excitotoxic amygdala lesions performed object reversal learning as quickly as controls. As predicted, however, the same operated monkeys were impaired in making object choices after devaluation of the associated food reinforcer. The results suggest two conclusions. First, the results demonstrate that the amygdala makes a selective contribution to stimulus-reward association; the amygdala is critical for guiding object choices after changes in reward value but not after changes in reward contingency. Second, the results implicate a critical contribution to object reversal learning of structures nearby the amygdala, perhaps the subjacent rhinal cortex.

  13. Disruption, control and coping: responses of and to the person with dementia in hospital.

    Porock, Davina; Clissett, Philip; Harwood, Rowan H; Gladman, John R F

    2015-01-01

    This qualitative study aimed to gain insight into the experience of hospitalisation from the perspectives of the older person with dementia, their family care-giver and other patients sharing the ward (co-patients). Non-participant observation of care on 11 acute hospital wards was supplemented by 39 semi-structured interviews with 35 family care-givers and four co-patients following discharge. Constant comparative analysis produced the core problem facing all those involved: disruption from normal routine meaning that the experience of hospitalisation was disrupted by the presence and behaviour of the person with dementia. Disruption adversely affected the person with dementia, triggering constructive, disengaged, distressed and neutral behaviours. Using Kitwood's model of person-centred care, these behaviours were interpreted as attempts by the person with dementia at gaining a sense of control over the unfamiliar environment and experience. Family care-givers' lives and experiences both inside and outside the hospital were disrupted by the hospitalisation. They too attempted to gain a sense of control over the experience and to give a sense of control to the patient, co-patients and staff. Co-patients experienced disruption from sharing space with the person with dementia and were left feeling vulnerable and sometimes afraid. They too attempted to gain a sense of control over their situation and give some control by helping the person with dementia, the family care-giver and the staff.

  14. An Analysis of Reactor Structural Response to Fuel Sodium Interaction in a Hypothetical Core Disruptive Accident

    Suzuki, K.; Tashiro, M.; Sasanuma, K.; Nagashima, K.

    1976-01-01

    This study shows the effect of constraints around FSI zone on FSI phenomena and deformations of reactor structures. SUGAR-PISCES code system has been developed to evaluate the phenomena of FSI and the response of reactor structure. SUGAR calculates the phenomena of FSI. PISCES, developed by Physics International Company in U.S.A, calculates the dynamic response of reactor structure in two-dimensional, time-dependent finite-difference Lagrangian model. The results show that the peak pressure and energy by FSI and the deformation of reactor structures are about twice in case of FSI zone surrounding by blanket than by coolant. The FSI phenomena highly depend on the reactor structure and the realistic configuration around core must be considered for analyzing hypothetical core disruptive accident. In conclusion: FSI phenomena depend highly on constraints around FSI zone, so that the constraints must be dealt with realistically in analytical models. Although a two-dimensional model is superior to a quasi-two-dimensional model. The former needs long calculation time, so it is very expensive using in parametric study. Therefore, it is desirable that the two-dimensional model is used in the final study of reactor design and the quasi-two-dimensional model is used in parametric study. The blanket affects on the acoustic pressure and the deformations of radial structures, but affects scarcely on the upper vessel deformation. The blanket also affects on the mechanical work largely. The core barrel gives scarcely the effects on pressure in single phase but gives highly the effects on pressure in two-phase and deformation of reactor structures in this study. For studying the more realistic phenomena of FSI in the reactor design, the following works should be needed. (i) Spatial Distribution of FSI Region Spatial and time-dependent distribution of fuel temperature and molten fuel fraction must be taken in realistic simulation of accident condition. To this purpose, the code will

  15. The Missing Response to Selection in the Wild

    Pujol, Benoit; Blanchet, Simon; Charmantier, Anne; Danchin, Etienne; Facon, Benoit; Marrot, Pascal; Roux, Fabrice; Scotti, Ivan; Teplitsky, Céline; Thomson, Caroline E.; Winney, Isabel

    2018-01-01

    Although there are many examples of contemporary directional selection, evidence for responses to selection that match predictions are often missing in quantitative genetic studies of wild populations. This is despite the presence of genetic variation and selection pressures – theoretical prerequisites for the response to selection. This conundrum can be explained by statistical issues with accurate parameter estimation, and by biological mechanisms that interfere with the response to selecti...

  16. Helicobacter pylori Disrupts Host Cell Membranes, Initiating a Repair Response and Cell Proliferation

    Hsueh-Fen Juan

    2012-08-01

    Full Text Available Helicobacter pylori (H. pylori, the human stomach pathogen, lives on the inner surface of the stomach and causes chronic gastritis, peptic ulcer, and gastric cancer. Plasma membrane repair response is a matter of life and death for human cells against physical and biological damage. We here test the hypothesis that H. pylori also causes plasma membrane disruption injury, and that not only a membrane repair response but also a cell proliferation response are thereby activated. Vacuolating cytotoxin A (VacA and cytotoxin-associated gene A (CagA have been considered to be major H. pylori virulence factors. Gastric cancer cells were infected with H. pylori wild type (vacA+/cagA+, single mutant (ΔvacA or ΔcagA or double mutant (ΔvacA/ΔcagA strains and plasma membrane disruption events and consequent activation of membrane repair components monitored. H. pylori disrupts the host cell plasma membrane, allowing localized dye and extracellular Ca2+ influx. Ca2+-triggered members of the annexin family, A1 and A4, translocate, in response to injury, to the plasma membrane, and cell surface expression of an exocytotic maker of repair, LAMP-2, increases. Additional forms of plasma membrane disruption, unrelated to H. pylori exposure, also promote host cell proliferation. We propose that H. pylori activation of a plasma membrane repair is pro-proliferative. This study might therefore provide new insight into potential mechanisms of H. pylori-induced gastric carcinogenesis.

  17. Disruptive Behaviors and Maternal Responsibility: A Complex Portrait of Stigma, Self-Blame, and Other Reactions

    Fernandez, Maria C.; Arcia, Emily

    2004-01-01

    Feelings of stigma and self-blame were studied among 62 Cuban, Dominican, and Puerto Rican mothers of 4- to 10-year-old children with disruptive behaviors. Data were collected and analyzed both qualitatively and quantitatively. Results indicated that 42% blamed themselves for their children's behaviors, and 39% felt stigmatized by others.…

  18. Chronic disruptions of circadian sleep regulation induce specific proinflammatory responses in the rat colon

    Polidarová, Lenka; Houdek, Pavel; Sumová, Alena

    2017-01-01

    Roč. 34, č. 9 (2017), s. 1273-1287 ISSN 0742-0528 R&D Projects: GA ČR(CZ) GA14-07711S Institutional support: RVO:67985823 Keywords : aging * colon * constant light * melatonin * proinflammatory cytokine * Rgs16 * sleep disruption Subject RIV: ED - Physiology OBOR OECD: Physiology (including cytology) Impact factor: 2.562, year: 2016

  19. Pesticide-mediated disruption of spotted wing Drosophila flight response to raspberries

    The disruption of chemical communication between insects and host plants may take place due to an interference with the signal-emitting host plant, or the signal-receiving insect, compromising the signal production and emission, or its reception and processing. Anthropogenic compounds in general, an...

  20. Restricted and disrupted sleep : Effects on autonomic function, neuroendocrine stress systems and stress responsivity

    Meerlo, Peter; Sgoifo, Andrea; Suchecki, Deborah

    2008-01-01

    Frequently disrupted and restricted sleep is a common problem for many people in our modern around-the-clock society. In this context, it is an important question how sleep loss affects the stress systems in our bodies since these systems enable us to deal with everyday challenges. Altered activity

  1. Sleep disruption is related to poor response inhibition in individuals with obsessive-compulsive and repetitive negative thought symptoms.

    Nota, Jacob A; Schubert, Jessica R; Coles, Meredith E

    2016-03-01

    Obsessive-compulsive (OC) symptoms and repetitive negative thinking (RNT) are associated with poor inhibitory control. Sleep disruptions may partially mediate these relations and/or act as a "second hit" to individuals with OC symptoms and RNT. Models including habitual (past month) hours slept and bedtimes were tested. We employed a go/no-go task that allowed us to examine the relation between sleep and inhibition with various task contingencies. Sixty-seven unselected individuals were recruited from the participant pool at a public university. Bias-corrected bootstrap estimates did not show that sleep disruption mediated the relation between OC symptoms and response inhibition nor the relation between RNT and response inhibition. Multiple linear regression analyses found significant interactions between hours slept and OC symptom severity and between RNT and hours slept to predict poor response inhibition. Hours slept significantly negatively predicted commission errors when OC symptoms and RNT levels were relatively heightened but not when OC symptoms and RNT levels were relatively low. These effects were present in blocks where task contingencies were designed to shape a no-go bias. No significant relations were found with habitual bedtimes. The cross-sectional study design precludes testing the temporal precedence of symptoms in the "second hit" model. The unselected sample also limits generalization to clinical samples. These findings support a "second hit" model of interaction between sleep disruption and perseverative thoughts and behaviors. Further research on the mechanisms of the relation between sleep disruption and perseverative thought symptoms (OC and RNT) is warranted. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Disruption, control and coping: responses of and to the person with dementia in hospital.

    Porock, Davina; Clissett, Philip; Harwood, Rowan H.; Gladman, John R.F.

    2015-01-01

    This qualitative study aimed to gain insight into the experience of hospitalisation from the perspectives of the older person with dementia, their family care-giver and other patients sharing the ward (co-patients). Non-participant observation of care on 11 acute hospital wards was supplemented by 39 semi-structured interviews with 35 family care-givers and four co-patients following discharge. Constant comparative analysis produced the core problem facing all those involved: disruption from ...

  3. Physiological response of selected eragrostis species to water ...

    Physiological response of selected eragrostis species to water-deficit stress. ... performing crop variety of Eragrostis tef under this stress, the responses of two varieties, ... Comparative study of closely related plant species might be a better ...

  4. Radiative response on massive noble gas injection for Runaway suppression in disruptive plasmas

    Reiter, Bernhard

    2010-01-01

    The most direct way to avoid the formation of a relativistic electron beam under the influence of an electric field in a highly conducting plasma, is to increase the electron density to a value, where the retarding collisional force balances the accelerating one. In a disruptive tokamak plasma, rapid cooling induces a high electric field, which could easily violate the force balance and push electrons into the relativistic regime. Such relativistic electrons, the so-called runaways, accumulate many MeV's and can cause substantial damage when they hit the wall. This thesis is based on the principle of rapidly fueling the plasma for holding the force balance even under the influence of high electric fields typical for disruptions. The method of injecting high amounts of noble gas particles into the plasma from a close distance is put into practice in the ASDEX Upgrade fusion test facility. In the framework of this thesis, a multi-channel photometer system based on 144 AXUV detectors in a toroidal stereo measurement setup was built. It kept its promise to provide new insights into the transport mechanisms in a disruptive plasma under the influence of strong radiative interaction dynamics between injected matter and the hot plasma.

  5. Over-Selectivity as a Learned Response

    Reed, Phil; Petrina, Neysa; McHugh, Louise

    2011-01-01

    An experiment investigated the effects of different levels of task complexity in pre-training on over-selectivity in a subsequent match-to-sample (MTS) task. Twenty human participants were divided into two groups; exposed either to a 3-element, or a 9-element, compound stimulus as a sample during MTS training. After the completion of training,…

  6. Textbook Evaluation and Selection: A Professional Responsibility.

    Kachaturoff, Grace

    1982-01-01

    Discusses why teachers must help to review and/or select textbooks on a regular basis and how they can participate in this process. A slightly revised edition of the criteria used by the State of Michigan Social Studies Review Steering Committee illustrates critical factors that must be considered in evaluating textbooks. (SR)

  7. Selective disruption of acetylcholine synthesis in subsets of motor neurons: a new model of late-onset motor neuron disease.

    Lecomte, Marie-José; Bertolus, Chloé; Santamaria, Julie; Bauchet, Anne-Laure; Herbin, Marc; Saurini, Françoise; Misawa, Hidemi; Maisonobe, Thierry; Pradat, Pierre-François; Nosten-Bertrand, Marika; Mallet, Jacques; Berrard, Sylvie

    2014-05-01

    Motor neuron diseases are characterized by the selective chronic dysfunction of a subset of motor neurons and the subsequent impairment of neuromuscular function. To reproduce in the mouse these hallmarks of diseases affecting motor neurons, we generated a mouse line in which ~40% of motor neurons in the spinal cord and the brainstem become unable to sustain neuromuscular transmission. These mice were obtained by conditional knockout of the gene encoding choline acetyltransferase (ChAT), the biosynthetic enzyme for acetylcholine. The mutant mice are viable and spontaneously display abnormal phenotypes that worsen with age including hunched back, reduced lifespan, weight loss, as well as striking deficits in muscle strength and motor function. This slowly progressive neuromuscular dysfunction is accompanied by muscle fiber histopathological features characteristic of neurogenic diseases. Unexpectedly, most changes appeared with a 6-month delay relative to the onset of reduction in ChAT levels, suggesting that compensatory mechanisms preserve muscular function for several months and then are overwhelmed. Deterioration of mouse phenotype after ChAT gene disruption is a specific aging process reminiscent of human pathological situations, particularly among survivors of paralytic poliomyelitis. These mutant mice may represent an invaluable tool to determine the sequence of events that follow the loss of function of a motor neuron subset as the disease progresses, and to evaluate therapeutic strategies. They also offer the opportunity to explore fundamental issues of motor neuron biology. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Structural response of a Tokamak first wall under electromagnetic forces caused by a plasma disruption

    Crutzen, Y.R.; Biggio, M.; Farfaletti-Casali, F.; Antonacci, P.; Vitali, R.

    1987-01-01

    The modern computerized techniques of CAD/FEM analysis are extensively applied for the numerical simulation of the electromagnetic-mechanical coupling induced in the last design configuration of NET first wall during a plasma disruption event. A picture of the impact of the electromagnetic forces on the structural behaviour of the outboard DN first wall is presented an an improvement of the FW structural section is proposed. In any case, additional investigations will be performed during the long process of structural behaviour optimization of the first wall reactor components

  9. Immunotoxic destruction of distinct catecholaminergic neuron populations disrupts the reproductive response to glucoprivation in female rats.

    I'Anson, Helen; Sundling, Lois A; Roland, Shannon M; Ritter, Sue

    2003-10-01

    We tested the hypothesis that hindbrain catecholamine (norepinephrine or epinephrine) neurons, in addition to their essential role in glucoprivic feeding, are responsible for suppressing estrous cycles during chronic glucoprivation. Normally cycling female rats were given bilateral injections of the retrogradely transported ribosomal toxin, saporin, conjugated to monoclonal dopamine beta-hydroxylase antibody (DSAP) into the paraventricular nucleus (PVN) of the hypothalamus to selectively destroy norepinephrine and epinephrine neurons projecting to the PVN. Controls were injected with unconjugated saporin. After recovery, we assessed the lesion effects on estrous cyclicity under basal conditions and found that DSAP did not alter estrous cycle length. Subsequently, we examined effects of chronic 2-deoxy-d-glucose-induced glucoprivation on cycle length. After two normal 4- to 5-d cycles, rats were injected with 2-deoxy-d-glucose (200 mg/kg every 6 h for 72 h) beginning 24 h after detection of estrus. Chronic glucoprivation increased cycle length in seven of eight unconjugated saporin rats but in only one of eight DSAP rats. Immunohistochemical results confirmed loss of dopamine beta-hydroxylase immunoreactivity in PVN. Thus, hindbrain catecholamine neurons with projections to the PVN are required for inhibition of reproductive function during chronic glucose deficit but are not required for normal estrous cyclicity when metabolic fuels are in abundance.

  10. Dissociation of face-selective cortical responses by attention.

    Furey, Maura L; Tanskanen, Topi; Beauchamp, Michael S; Avikainen, Sari; Uutela, Kimmo; Hari, Riitta; Haxby, James V

    2006-01-24

    We studied attentional modulation of cortical processing of faces and houses with functional MRI and magnetoencephalography (MEG). MEG detected an early, transient face-selective response. Directing attention to houses in "double-exposure" pictures of superimposed faces and houses strongly suppressed the characteristic, face-selective functional MRI response in the fusiform gyrus. By contrast, attention had no effect on the M170, the early, face-selective response detected with MEG. Late (>190 ms) category-related MEG responses elicited by faces and houses, however, were strongly modulated by attention. These results indicate that hemodynamic and electrophysiological measures of face-selective cortical processing complement each other. The hemodynamic signals reflect primarily late responses that can be modulated by feedback connections. By contrast, the early, face-specific M170 that was not modulated by attention likely reflects a rapid, feed-forward phase of face-selective processing.

  11. Responsive and resilient supply chain network design under operational and disruption risks with delivery lead-time sensitive customers

    Fattahi, Mohammad; Govindan, Kannan; Keyvanshokooh, Esmaeil

    2017-01-01

    We address a multi-period supply chain (SC) network design where demands of customers depend on facilities serving them based on their delivery lead-times. Potential customer demands are stochastic, and facilities’ capacity varies randomly because of possible disruptions. Accordingly, we develop...... a multi-stage stochastic program, and model disruptions’ effect on facilities’ capacity. The SC responsiveness risk is limited and, to obtain a resilient network, both mitigation and contingency strategies are exploited. Computational results on a real-life case study and randomly generated problem...... instances demonstrate the model's applicability, risk-measurement policies’ performance, and the influence of mitigation and contingency strategies on SC's resiliency....

  12. Enhancing the radiation response of tumors but not early or late responding normal tissues using a vascular disrupting agent

    Horsman, Michael R

    2017-01-01

    INTRODUCTION: Vascular disrupting agents (VDAs) damage tumor vasculature and enhance tumor radiation response. In this pre-clinical study, we combined radiation with the leading VDA in clinical development, combretastatin A-4 phosphate (CA4P), and compared the effects seen in tumors and relevant...... normal tissues. MATERIAL AND METHODS: Radiation was applied locally to tissues in CDF1 mice to produce full radiation dose-response curves. CA4P (250 mg/kg) was intraperitoneally (i.p.) injected within 30 minutes after irradiating. Response of 200 mm3 foot implanted C3H mammary carcinomas was assessed......% increase in ventilation rate measured by plethysmography within 9 months). A Chi-squared test was used for statistical comparisons (significance level of p 4P. The radiation...

  13. Selection of a design for response surface

    Ranade, Shruti Sunil; Thiagarajan, Padma

    2017-11-01

    Box-Behnken, Central-Composite, D and I-optimal designs were compared using statistical tools. Experimental trials for all designs were generated. Random uniform responses were simulated for all models. R-square, Akaike and Bayesian Information Criterion for the fitted models were noted. One-way ANOVA and Tukey’s multiple comparison test were performed on these parameters. These models were evaluated based on the number of experimental trials generated in addition to the results of the statistical analyses. D-optimal design generated 12 trials in its model, which was lesser in comparison to both Central Composite and Box-Behnken designs. The R-square values of the fitted models were found to possess a statistically significant difference (P<0.0001). D-optimal design not only had the highest mean R-square value (0.7231), but also possessed the lowest means for both Akaike and Bayesian Information Criterion. The D-optimal design was recommended for generation of response surfaces, based on the assessment of the above parameters.

  14. An Approach to Modeling Complex Socio-Economic Impacts and Responses to Climate Disruption

    Pikas, C. K.; Nix, M.; Ihde, A. G.; Weiss, M.; Simpkins, S.; Fountain, G. H.; Paxton, L. J.

    2011-12-01

    In this paper we describe the application of a proven methodology for modeling the complex social and economic interactions of a system under stress to the issues that are arising and will arise from global climate disruption. There is a long history in the Defense community of using what are known as strategic simulations or "wargames" to model the complex interactions between the environment, people, resources, infrastructure and the economy in a competitive environment. We describe in this paper, work that we have done on understanding how this heritage can be repurposed to help us explore how the complex interplay between climate disruption and our socio/political and economic structures will affect our future. These strategic simulations would be done under the auspices of the GAIA project (http://gaia.jhuapl.edu). While these simulations cannot definitively predict what will happen, they do illuminate non-linear feedbacks between human choices and the environment. These simulations can be focused on the global, regional, or local environment and capture the various actors (governments, agencies, resources, industries, religious/political groups, etc.) that compete to achieve their particular goals. We note that these simulations are not "zero sum" games - there need not be a winner and a loser. They are, however, competitive influence games: they represent the tools that a nation, state, faction or group has at its disposal to influence policy (diplomacy), finances, industry (economy), infrastructure, information, etc to achieve their particular goals. In the simulation, humans play various roles and understand that not everyone shares the same definition of a successful or favorable outcome. Rigorous post-analysis is used to illuminate where decisions were made that enabled or prevented a particular outcome from occurring. In addition, the simulations allow us to investigate how effective "technology injects" can be in achieving a particular, desired end

  15. The Missing Response to Selection in the Wild.

    Pujol, Benoit; Blanchet, Simon; Charmantier, Anne; Danchin, Etienne; Facon, Benoit; Marrot, Pascal; Roux, Fabrice; Scotti, Ivan; Teplitsky, Céline; Thomson, Caroline E; Winney, Isabel

    2018-05-01

    Although there are many examples of contemporary directional selection, evidence for responses to selection that match predictions are often missing in quantitative genetic studies of wild populations. This is despite the presence of genetic variation and selection pressures - theoretical prerequisites for the response to selection. This conundrum can be explained by statistical issues with accurate parameter estimation, and by biological mechanisms that interfere with the response to selection. These biological mechanisms can accelerate or constrain this response. These mechanisms are generally studied independently but might act simultaneously. We therefore integrated these mechanisms to explore their potential combined effect. This has implications for explaining the apparent evolutionary stasis of wild populations and the conservation of wildlife. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. A risk-based evaluation of LMFBR containment response under core disruptive accident conditions

    Hartung, J.; Berk, S.

    1978-01-01

    Probabilistic risk methodology is utilized to evaluate the failure modes and effects of LMFBR containment systems under Core Disruptive Accident (CDA) conditions. First, the potential causes of LMFBR containment failure under CDA conditions are discussed and categorized. Then, a simple scoping-type risk assessment of a reference design is presented to help place these potential causes of failure in perspective. The highest risk containment failure modes are identified for the reference design, and several design and research and development options which appear capable of reducing these risks are discussed. The degree to which large LMFBR containment systems must mitigate the consequences of CDA's to achieve a level of risk (for LMFBR's) comparable to the already very low risk of contemporary LWR's is explored. Based on the results of this evaluation, several suggestions are offered concerning CDA-related design goals and research and development priorities for large LMFBR's. (author)

  17. Western High-Fat Diet Consumption during Adolescence Increases Susceptibility to Traumatic Stress while Selectively Disrupting Hippocampal and Ventricular Volumes

    Kalyan-Masih, Priya; Vega-Torres, Julio David; Haddad, Elizabeth; Rainsbury, Sabrina; Baghchechi, Mohsen

    2016-01-01

    Abstract Psychological trauma and obesity co-occur frequently and have been identified as major risk factors for psychiatric disorders. Surprisingly, preclinical studies examining how obesity disrupts the ability of the brain to cope with psychological trauma are lacking. The objective of this study was to determine whether an obesogenic Western-like high-fat diet (WD) predisposes rats to post-traumatic stress responsivity. Adolescent Lewis rats (postnatal day 28) were fed ad libitum for 8 weeks with either the experimental WD diet (41.4% kcal from fat) or the control diet (16.5% kcal from fat). We modeled psychological trauma by exposing young adult rats to a cat odor threat. The elevated plus maze and the open field test revealed increased psychological trauma-induced anxiety-like behaviors in the rats that consumed the WD when compared with control animals 1 week after undergoing traumatic stress (p < 0.05). Magnetic resonance imaging showed significant hippocampal atrophy (20% reduction) and lateral ventricular enlargement (50% increase) in the animals fed the WD when compared with controls. These volumetric abnormalities were associated with behavioral indices of anxiety, increased leptin and FK506-binding protein 51 (FKBP51) levels, and reduced hippocampal blood vessel density. We found asymmetric structural vulnerabilities to the WD, particularly the ventral and left hippocampus and lateral ventricle. This study highlights how WD consumption during adolescence impacts key substrates implicated in post-traumatic stress disorder. Understanding how consumption of a WD affects the developmental trajectories of the stress neurocircuitry is critical, as stress susceptibility imposes a marked vulnerability to neuropsychiatric disorders. PMID:27844058

  18. PEAK SHIFTS PRODUCED BY CORRELATED RESPONSE TO SELECTION.

    Price, Trevor; Turelli, Michael; Slatkin, Montgomery

    1993-02-01

    Traits may evolve both as a consequence of direct selection and also as a correlated response to selection on other traits. While correlated response may be important for both the production of evolutionary novelty and in the build-up of complex characters, its potential role in peak shifts has been neglected empirically and theoretically. We use a quantitative genetic model to investigate the conditions under which a character, Y, which has two alternative optima, can be dragged from one optimum to the other as a correlated response to selection on a second character, X. High genetic correlations between the two characters make the transition, or peak shift, easier, as does weak selection tending to restore Y to the optimum from which it is being dragged. When selection on Y is very weak, the conditions for a peak shift depend only on the location of the new optimum for X and are independent of the strength of selection moving it there. Thus, if the "adaptive valley" for Y is very shallow, little reduction in mean fitness is needed to produce a shift. If the selection acts strongly to keep Y at its current optimum, very intense directional selection on X, associated with a dramatic drop in mean fitness, is required for a peak shift. When strong selection is required, the conditions for peak shifts driven by correlated response might occur rarely, but still with sufficient frequency on a geological timescale to be evolutionarily important. © 1993 The Society for the Study of Evolution.

  19. Responses of selected biota after biostimulation of a vegetable oil ...

    Responses of selected biota after biostimulation of a vegetable oil spill in the Con Joubert Bird Sanctuary wetland: A pilot study. Mapurunyane C Selala, Paul J Oberholster, Karen AK Surridge, Arno R de Klerk, Anna-Maria Botha ...

  20. Selective response of dopamine in the presence of ascorbic acid ...

    Selective response of dopamine in the presence of ascorbic acid and uric acid at gold nanoparticles and multi-walled carbon nanotubes grafted with ethylene diamine tetraacetic acid modified electrode.

  1. Systematic Analysis of Time-Series Gene Expression Data on Tumor Cell-Selective Apoptotic Responses to HDAC Inhibitors

    Yun-feng Qi

    2014-01-01

    Full Text Available SAHA (suberoylanilide hydroxamic acid or vorinostat is the first nonselective histone deacetylase (HDAC inhibitor approved by the US Food and Drug Administration (FDA. SAHA affects histone acetylation in chromatin and a variety of nonhistone substrates, thus influencing many cellular processes. In particularly, SAHA induces selective apoptosis of tumor cells, although the mechanism is not well understood. A series of microarray experiments was recently conducted to investigate tumor cell-selective proapoptotic transcriptional responses induced by SAHA. Based on that gene expression time series, we propose a novel framework for detailed analysis of the mechanism of tumor cell apoptosis selectively induced by SAHA. Our analyses indicated that SAHA selectively disrupted the DNA damage response, cell cycle, p53 expression, and mitochondrial integrity of tumor samples to induce selective tumor cell apoptosis. Our results suggest a possible regulation network. Our research extends the existing research.

  2. Androgen receptor disruption increases the osteogenic response to mechanical loading in male mice

    Callewaert, F.; Bakker, A.; Schrooten, J.; Van Meerbeek, B.; Verhoeven, G.; Boonen, S.; Vanderschueren, D.

    2010-01-01

    In female mice, estrogen receptor-alpha (ERα) mediates the anabolic response of bone to mechanical loading. Whether ERα plays a similar role in the male skeleton and to what extent androgens and androgen receptor (AR) affect this response in males remain unaddressed. Therefore, we studied the

  3. Prior exposure to interpersonal violence and long-term treatment response for boys with a disruptive behavior disorder.

    Shenk, Chad E; Dorn, Lorah D; Kolko, David J; Rausch, Joseph R; Insana, Salvatore P

    2014-10-01

    Interpersonal violence (IPV) is common in children with a disruptive behavior disorder (DBD) and increases the risk for greater DBD symptom severity, callous-unemotional (CU) traits, and neuroendocrine disruption. Thus, IPV may make it difficult to change symptom trajectories for families receiving DBD interventions given these relationships. The current study examined whether IPV prior to receiving treatment for a DBD predicted trajectories of a variety of associated outcomes, specifically DBD symptoms, CU traits, and cortisol concentrations. Boys with a DBD diagnosis (N = 66; age range = 6-11 years; 54.5% of whom experienced IPV prior to treatment) of either oppositional defiant disorder or conduct disorder participated in a randomized clinical trial and were assessed 3 years following treatment. Multilevel modeling demonstrated that prior IPV predicted smaller rates of change in DBD symptoms, CU traits, and cortisol trajectories, indicating less benefit from intervention. The effect size magnitudes of IPV were large for each outcome (d = 0.88-1.07). These results suggest that IPV is a predictor of the long-term treatment response for boys with a DBD. Including trauma-focused components into existing DBD interventions may be worth testing to improve treatment effectiveness for boys with a prior history of IPV. Copyright © 2014 International Society for Traumatic Stress Studies.

  4. Response of beryllium to severe thermal shocks -simulation of disruption and vertical displacement events in future thermonuclear devices

    Linke, J.; Duwe, R.; Roedig, M.; Schuster, A. [Association Euratom-Forschungszentrum Juelich GmbH (Germany); Merola, M.; Qian, R.H.

    1998-01-01

    Beryllium will play an important role for plasma facing components in next step thermonuclear fusion devices such as ITER. In particular for the first wall beryllium will be used with an armor thickness of several millimeters. However, during plasma instabilities they will experience severe thermal shocks. Here plasma disruptions with deposited energy densities of several ten MJm{sup -2} are the most essential damaging mechanism. However, a signifant fraction of the incident energy will be absorbed by a dense cloud of ablation vapor, hence reducing the effective energy density at the beryllium surface to values in the order of 10 MJm{sup -2}. To investigate the material response to all these plasma instabilities thermal shock tests on small scale test coupons (disruption effects) and on actively cooled divertor modules (VDEs) have been performed in the electron beam test facility JUDITH at ITER relevant surface heat loads. These tests have been performed on different bulk beryllium grades and on plasma sprayed coatings; the influence of pulse duration, power density, and temperature effects has been investigated experimentally. Detailed in-situ diagnostics (for beam characterization, optical pyrometry etc.) and post mortem analyses (profilometry, metallography, optical and electron microscopy) have been applied to quantify the resulting material damage. 1D- and 2D models have developed to verify the experimental results obtained in the electron beam simulation experiments. (J.P.N.)

  5. Mechanical disruption of tumors by iron particles and magnetic field application results in increased anti-tumor immune responses.

    Myriam N Bouchlaka

    Full Text Available The primary tumor represents a potential source of antigens for priming immune responses for disseminated disease. Current means of debulking tumors involves the use of cytoreductive conditioning that impairs immune cells or removal by surgery. We hypothesized that activation of the immune system could occur through the localized release of tumor antigens and induction of tumor death due to physical disruption of tumor architecture and destruction of the primary tumor in situ. This was accomplished by intratumor injection of magneto-rheological fluid (MRF consisting of iron microparticles, in Balb/c mice bearing orthotopic 4T1 breast cancer, followed by local application of a magnetic field resulting in immediate coalescence of the particles, tumor cell death, slower growth of primary tumors as well as decreased tumor progression in distant sites and metastatic spread. This treatment was associated with increased activation of DCs in the draining lymph nodes and recruitment of both DCs and CD8(+T cells to the tumor. The particles remained within the tumor and no toxicities were observed. The immune induction observed was significantly greater compared to cryoablation. Further anti-tumor effects were observed when MRF/magnet therapy was combined with systemic low dose immunotherapy. Thus, mechanical disruption of the primary tumor with MRF/magnetic field application represents a novel means to induce systemic immune activation in cancer.

  6. Medial prefrontal-perirhinal cortical communication is necessary for flexible response selection.

    Hernandez, Abbi R; Reasor, Jordan E; Truckenbrod, Leah M; Lubke, Katelyn N; Johnson, Sarah A; Bizon, Jennifer L; Maurer, Andrew P; Burke, Sara N

    2017-01-01

    The ability to use information from the physical world to update behavioral strategies is critical for survival across species. The prefrontal cortex (PFC) supports behavioral flexibility; however, exactly how this brain structure interacts with sensory association cortical areas to facilitate the adaptation of response selection remains unknown. Given the role of the perirhinal cortex (PER) in higher-order perception and associative memory, the current study evaluated whether PFC-PER circuits are critical for the ability to perform biconditional object discriminations when the rule for selecting the rewarded object shifted depending on the animal's spatial location in a 2-arm maze. Following acquisition to criterion performance on an object-place paired association task, pharmacological blockade of communication between the PFC and PER significantly disrupted performance. Specifically, the PFC-PER disconnection caused rats to regress to a response bias of selecting an object on a particular side regardless of its identity. Importantly, the PFC-PER disconnection did not interfere with the capacity to perform object-only or location-only discriminations, which do not require the animal to update a response rule across trials. These findings are consistent with a critical role for PFC-PER circuits in rule shifting and the effective updating of a response rule across spatial locations. Published by Elsevier Inc.

  7. Disruption of Ethylene Responses by Turnip mosaic virus Mediates Suppression of Plant Defense against the Green Peach Aphid Vector.

    Casteel, Clare L; De Alwis, Manori; Bak, Aurélie; Dong, Haili; Whitham, Steven A; Jander, Georg

    2015-09-01

    Plants employ diverse responses mediated by phytohormones to defend themselves against pathogens and herbivores. Adapted pathogens and herbivores often manipulate these responses to their benefit. Previously, we demonstrated that Turnip mosaic virus (TuMV) infection suppresses callose deposition, an important plant defense induced in response to feeding by its aphid vector, the green peach aphid (Myzus persicae), and increases aphid fecundity compared with uninfected control plants. Further, we determined that production of a single TuMV protein, Nuclear Inclusion a-Protease (NIa-Pro) domain, was responsible for changes in host plant physiology and increased green peach aphid reproduction. To characterize the underlying molecular mechanisms of this phenomenon, we examined the role of three phytohormone signaling pathways, jasmonic acid, salicylic acid, and ethylene (ET), in TuMV-infected Arabidopsis (Arabidopsis thaliana), with or without aphid herbivory. Experiments with Arabidopsis mutants ethylene insensitive2 and ethylene response1, and chemical inhibitors of ET synthesis and perception (aminoethoxyvinyl-glycine and 1-methylcyclopropene, respectively), show that the ET signaling pathway is required for TuMV-mediated suppression of Arabidopsis resistance to the green peach aphid. Additionally, transgenic expression of NIa-Pro in Arabidopsis alters ET responses and suppresses aphid-induced callose formation in an ET-dependent manner. Thus, disruption of ET responses in plants is an additional function of NIa-Pro, a highly conserved potyvirus protein. Virus-induced changes in ET responses may mediate vector-plant interactions more broadly and thus represent a conserved mechanism for increasing transmission by insect vectors across generations. © 2015 American Society of Plant Biologists. All Rights Reserved.

  8. The Neural Basis of Cognitive Control: Response Selection and Inhibition

    Goghari, Vina M.; MacDonald, Angus W., III

    2009-01-01

    The functional neuroanatomy of tasks that recruit different forms of response selection and inhibition has to our knowledge, never been directly addressed in a single fMRI study using similar stimulus-response paradigms where differences between scanning time and sequence, stimuli, and experimenter instructions were minimized. Twelve right-handed…

  9. Planning for Biotarrorism. Behavioral & Mental Health Responses to Weapons of Mass Destruction & Mass Disruption

    Ursano, Robert

    2000-01-01

    .... Community and individual responses to potential bioterrorist events were described. Future approaches to the management and treatment of behavioral and mental health issues following exposure to biological agents and bioterrorism were discussed...

  10. Early disrupted neurovascular coupling and changed event level hemodynamic response function in type 2 diabetes: an fMRI study.

    Duarte, João V; Pereira, João M S; Quendera, Bruno; Raimundo, Miguel; Moreno, Carolina; Gomes, Leonor; Carrilho, Francisco; Castelo-Branco, Miguel

    2015-10-01

    Type 2 diabetes (T2DM) patients develop vascular complications and have increased risk for neurophysiological impairment. Vascular pathophysiology may alter the blood flow regulation in cerebral microvasculature, affecting neurovascular coupling. Reduced fMRI signal can result from decreased neuronal activation or disrupted neurovascular coupling. The uncertainty about pathophysiological mechanisms (neurodegenerative, vascular, or both) underlying brain function impairments remains. In this cross-sectional study, we investigated if the hemodynamic response function (HRF) in lesion-free brains of patients is altered by measuring BOLD (Blood Oxygenation Level-Dependent) response to visual motion stimuli. We used a standard block design to examine the BOLD response and an event-related deconvolution approach. Importantly, the latter allowed for the first time to directly extract the true shape of HRF without any assumption and probe neurovascular coupling, using performance-matched stimuli. We discovered a change in HRF in early stages of diabetes. T2DM patients show significantly different fMRI response profiles. Our visual paradigm therefore demonstrated impaired neurovascular coupling in intact brain tissue. This implies that functional studies in T2DM require the definition of HRF, only achievable with deconvolution in event-related experiments. Further investigation of the mechanisms underlying impaired neurovascular coupling is needed to understand and potentially prevent the progression of brain function decrements in diabetes.

  11. A Randomized Clinical Trial Comparison Between Pivotal Response Treatment (PRT) and Adult-Driven Applied Behavior Analysis (ABA) Intervention on Disruptive Behaviors in Public School Children with Autism.

    Mohammadzaheri, Fereshteh; Koegel, Lynn Kern; Rezaei, Mohammad; Bakhshi, Enayatolah

    2015-09-01

    Children with autism often demonstrate disruptive behaviors during demanding teaching tasks. Language intervention can be particularly difficult as it involves social and communicative areas, which are challenging for this population. The purpose of this study was to compare two intervention conditions, a naturalistic approach, Pivotal Response Treatment (PRT) with an adult-directed ABA approach on disruptive behavior during language intervention in the public schools. A randomized clinical trial design was used with two groups of children, matched according to age, sex and mean length of utterance. The data showed that the children demonstrated significantly lower levels of disruptive behavior during the PRT condition. The results are discussed with respect to antecedent manipulations that may be helpful in reducing disruptive behavior.

  12. Technical Resource Potential of Non-disruptive Residential Demand Response in Denmark

    Mathieu, Johanna; Rasmussen, Theis Bo; Sørensen, Mads

    2014-01-01

    Denmark has one of the most aggressive renewable energy strategies in the world; however, large penetrations of fluctuating renewable energy resources will pose new problems in the Danish power system. Demand response (DR) has the potential to mitigate these problems by providing a new source...

  13. Abnormal stress responsivity in a rodent developmental disruption model of schizophrenia.

    Zimmerman, Eric C; Bellaire, Mark; Ewing, Samuel G; Grace, Anthony A

    2013-10-01

    Although numerous studies have implicated stress in the pathophysiology of schizophrenia, less is known about how the effects of stress interact with genetic, developmental, and/or environmental determinants to promote disease progression. In particular, it has been proposed that in humans, stress exposure in adolescence could combine with a predisposition towards increased stress sensitivity, leading to prodromal symptoms and eventually psychosis. However, the neurobiological substrates for this interaction are not fully characterized. Previous work in our lab has demonstrated that rats born to dams administered with the DNA-methylating agent methylazoxymethanol acetate (MAM) at gestational day 17 exhibit as adults behavioral and anatomical abnormalities consistent with those observed in patients with schizophrenia. Here, we examined behavioral and neuroendocrine responses to stress in the MAM model of schizophrenia. MAM-treated male rats were exposed to acute and repeated footshock stress at prepubertal, peripubteral, and adult ages. Ultrasonic vocalizations (USVs), freezing, and corticosterone responses were quantified. We found that juvenile MAM-treated rats emitted significantly more calls, spent more time vocalizing, emitted calls at a higher rate, and showed more freezing in response to acute footshock stress when compared with their saline (SAL) treated counterparts, and that this difference is not present in older animals. In addition, adolescent MAM-treated animals displayed a blunted HPA axis corticosterone response to acute footshock that did not adapt after 10 days of stress exposure. These data demonstrate abnormal stress responsivity in the MAM model of schizophrenia and suggest that these animals are more sensitive to the effects of stress in youth.

  14. Planning for Bioterrorism. Behavioral & Mental Health Responses to Weapons of Mass Destruction & Mass Disruption

    2000-07-16

    through their franchise , responsibility for war and the support of war rest on the people. Sherman’s opinion was by no means universally shared, as one...Only in the private after action reports did the ugly questions of transportation, food distribution, and military logistics enter the experience. In...weak concentration of sari gas on multiple subway trains as they converged on downtown Tokyo. Now we are talking about a terrorist group, using a

  15. Prenatal exposure to vinclozolin disrupts selective aspects of the gonadotropin-releasing hormone neuronal system of the rabbit

    Wadas, B.C.; Hartshorn, C.A.; Aurand, E.R.; Palmer, J.S.; Roselli, C.E.; Noel, M.L.; Gore, A.C.; Veeramachaneni, D.N.R.; Tobet, S.A.

    2010-01-01

    Developmental exposure to the agricultural fungicide vinclozolin can impair reproductive function in male rabbits and was previously found to decrease the number of immunoreactive-gonadotropin-releasing hormone (ir-GnRH) neurons in the region of the organum vasculosum of the lamina terminalis (OVLT) and rostral preoptic area (rPOA) by postnatal week (PNW) 6. To further examine the disruption of GnRH neurons by fetal vinclozolin exposure, in the current study, pregnant rabbits were dosed orall...

  16. Defective bone formation and anabolic response to exogenous estrogen in mice with targeted disruption of endothelial nitric oxide synthase.

    Armour, K E; Armour, K J; Gallagher, M E; Gödecke, A; Helfrich, M H; Reid, D M; Ralston, S H

    2001-02-01

    Nitric oxide (NO) is a pleiotropic signaling molecule that is produced by bone cells constitutively and in response to diverse stimuli such as proinflammatory cytokines, mechanical strain, and sex hormones. Endothelial nitric oxide synthase (eNOS) is the predominant NOS isoform expressed in bone, but its physiological role in regulating bone metabolism remains unclear. Here we studied various aspects of bone metabolism in female mice with targeted disruption of the eNOS gene. Mice with eNOS deficiency (eNOS KO) had reduced bone mineral density, and cortical thinning when compared with WT controls and histomorphometric analysis of bone revealed profound abnormalities of bone formation, with reduced osteoblast numbers, surfaces and mineral apposition rate. Studies in vitro showed that osteoblasts derived from eNOS KO mice had reduced rates of growth when compared with WT and were less well differentiated as reflected by lower levels of alkaline phosphatase activity. Mice with eNOS deficiency lost bone normally following ovariectomy but exhibited a significantly blunted anabolic response to high dose exogenous estrogen. We conclude that the eNOS pathway plays an essential role in regulating bone mass and bone turnover by modulating osteoblast function.

  17. The impact of shift work induced chronic circadian disruption on IL-6 and TNF-α immune responses

    Spallek Michael

    2010-07-01

    Full Text Available Abstract AIM Sleep disturbances induce proinflammatory immune responses, which might increase cardiovascular disease risk. So far the effects of acute sleep deprivation and chronic sleep illnesses on the immune system have been investigated. The particular impact of shift work induced chronic circadian disruption on specific immune responses has not been addressed so far. Methods Pittsburgh-Sleep-Quality-Index (PSQI questionnaire and blood sampling was performed by 225 shift workers and 137 daytime workers. As possible markers the proinflammatory cytokines IL-6 and TNF-α and lymphocyte cell count were investigated. A medical examination was performed and biometrical data including age, gender, height, weight, waist and hip circumference and smoking habits were collected by a structured interview. Results Shift workers had a significantly higher mean PSQI score than day workers (6.73 vs. 4.66; p Conclusion Shift work induces chronic sleep debt. Our data reveals that chronic sleep debt might not always lead to an activation of the immune system, as we did not observe differences in lymphocyte count or level of IL-6 or TNF-α serum concentration between shift workers and day workers. Therefore chronic sleep restriction might be eased by a long-term compensating immune regulation which (in healthy protects against an overstimulation of proinflammatory immune mechanisms and moderates metabolic changes, as they are known from short-term sleep deprivation or sleep related breathing disorders.

  18. Mahalanobis distance and variable selection to optimize dose response

    Moore, D.H. II; Bennett, D.E.; Wyrobek, A.J.; Kranzler, D.

    1979-01-01

    A battery of statistical techniques are combined to improve detection of low-level dose response. First, Mahalanobis distances are used to classify objects as normal or abnormal. Then the proportion classified abnormal is regressed on dose. Finally, a subset of regressor variables is selected which maximizes the slope of the dose response line. Use of the techniques is illustrated by application to mouse sperm damaged by low doses of x-rays

  19. Artemisinin disrupts androgen responsiveness of human prostate cancer cells by stimulating the 26S proteasome-mediated degradation of the androgen receptor protein.

    Steely, Andrea M; Willoughby, Jamin A; Sundar, Shyam N; Aivaliotis, Vasiliki I; Firestone, Gary L

    2017-10-01

    Androgen receptor (AR) expression and activity is highly linked to the development and progression of prostate cancer and is a target of therapeutic strategies for this disease. We investigated whether the antimalarial drug artemisinin, which is a sesquiterpene lactone isolated from the sweet wormwood plant Artemisia annua, could alter AR expression and responsiveness in cultured human prostate cancer cell lines. Artemisinin treatment induced the 26S proteasome-mediated degradation of the receptor protein, without altering AR transcript levels, in androgen-responsive LNCaP prostate cancer cells or PC-3 prostate cancer cells expressing exogenous wild-type AR. Furthermore, artemisinin stimulated AR ubiquitination and AR receptor interactions with the E3 ubiquitin ligase MDM2 in LNCaP cells. The artemisinin-induced loss of AR protein prevented androgen-responsive cell proliferation and ablated total AR transcriptional activity. The serine/threonine protein kinase AKT-1 was shown to be highly associated with artemisinin-induced proteasome-mediated degradation of AR protein. Artemisinin treatment activated AKT-1 enzymatic activity, enhanced receptor association with AKT-1, and induced AR serine phosphorylation. Treatment of LNCaP cells with the PI3-kinase inhibitor LY294002, which inhibits the PI3-kinase-dependent activation of AKT-1, prevented the artemisinin-induced AR degradation. Furthermore, in transfected receptor-negative PC-3 cells, artemisinin failed to stimulate the degradation of an altered receptor protein (S215A/S792A) with mutations in its two consensus AKT-1 serine phosphorylation sites. Taken together, our results indicate that artemisinin induces the degradation of AR protein and disrupts androgen responsiveness of human prostate cancer cells, suggesting that this natural compound represents a new potential therapeutic molecule that selectively targets AR levels.

  20. A peptide targeting an interaction interface disrupts the dopamine D1-D2 receptor heteromer to block signaling and function in vitro and in vivo: effective selective antagonism

    Hasbi, Ahmed; Perreault, Melissa L.; Shen, Maurice Y. F.; Zhang, Lucia; To, Ryan; Fan, Theresa; Nguyen, Tuan; Ji, Xiaodong; O'Dowd, Brian F.; George, Susan R.

    2014-01-01

    Although the dopamine D1-D2 receptor heteromer has emerging physiological relevance and a postulated role in different neuropsychiatric disorders, such as drug addiction, depression, and schizophrenia, there is a need for pharmacological tools that selectively target such receptor complexes in order to analyze their biological and pathophysiological functions. Since no selective antagonists for the D1-D2 heteromer are available, serial deletions and point mutations were used to precisely identify the amino acids involved in an interaction interface between the receptors, residing within the carboxyl tail of the D1 receptor that interacted with the D2 receptor to form the D1-D2 receptor heteromer. It was determined that D1 receptor carboxyl tail residues 404Glu and 405Glu were critical in mediating the interaction with the D2 receptor. Isolated mutation of these residues in the D1 receptor resulted in the loss of agonist activation of the calcium signaling pathway mediated through the D1-D2 receptor heteromer. The physical interaction between the D1 and D2 receptor could be disrupted, as shown by coimmunoprecipitation and BRET analysis, by a small peptide generated from the D1 receptor sequence that contained these amino acids, leading to a switch in G-protein affinities and loss of calcium signaling, resulting in the inhibition of D1-D2 heteromer function. The use of the D1-D2 heteromer-disrupting peptide in vivo revealed a pathophysiological role for the D1-D2 heteromer in the modulation of behavioral despair. This peptide may represent a novel pharmacological tool with potential therapeutic benefits in depression treatment.—Hasbi, A., Perreault, M. L., Shen, M. Y. F., Zhang, L., To, R., Fan, T., Nguyen, T., Ji, X., O'Dowd, B. F., George, S. R. A peptide targeting an interaction interface disrupts the dopamine D1-D2 receptor heteromer to block signaling and function in vitro and in vivo: effective selective antagonism. PMID:25063849

  1. Microsporidia parasites disrupt the responses to cadmium exposure in a gammarid

    Gismondi, Eric; Rigaud, Thierry; Beisel, Jean-Nicolas; Cossu-Leguille, Carole

    2012-01-01

    Microsporidia parasites are commonly found in amphipods, where they are often asymptomatic, vertically-transmitted and have several effects on host sexuality and behaviour. As amphipods are often used as models in ecotoxicological studies, we investigated the effect of microsporidian infections on energy reserves and defence capacities of Gammarus roeseli under cadmium stress. Only females were infected by two microsporidia parasites: Dictyocoela roeselum or Dictyocoela muelleri. In physiological conditions, microsporidia had no major effect on energy reserves and defence capacities of G. roeseli, while under cadmium exposure, energy reserves and antioxidant defence were weaker in infected females. Moreover, higher malondialdehyde levels detected in infected females revealed that they suffered more cellular damages. Our results suggest that microsporidia may affect gammarid fitness in stressful conditions, when parasitic stress cannot be compensated by the host. Consequently, microsporidia parasites should be a factor necessary to take into account in ecotoxicology studies involving amphipods. - Highlights: ► High prevalence of microsporidian parasites in Gammarus roeseli. ► Microsporidia have no effect on G. roeseli biomarkers in physiological conditions. ► Microsporidia disturb the responses of G. roeseli biomarkers in cadmium stress. ► Microsporidian parasites could be confounding factor in ecotoxicological studies. - The presence of microsporidian parasites increases the toxic effect of cadmium in G. roeseli females.

  2. Cigarette smokers have exaggerated alveolar barrier disruption in response to lipopolysaccharide inhalation.

    Moazed, Farzad; Burnham, Ellen L; Vandivier, R William; O'Kane, Cecilia M; Shyamsundar, Murali; Hamid, Umar; Abbott, Jason; Thickett, David R; Matthay, Michael A; McAuley, Daniel F; Calfee, Carolyn S

    2016-12-01

    Cigarette smoke exposure is associated with an increased risk of the acute respiratory distress syndrome (ARDS); however, the mechanisms underlying this relationship remain largely unknown. To assess pathways of lung injury and inflammation in smokers and non-smokers with and without lipopolysaccharide (LPS) inhalation using established biomarkers. We measured plasma and bronchoalveolar lavage (BAL) biomarkers of inflammation and lung injury in smokers and non-smokers in two distinct cohorts of healthy volunteers, one unstimulated (n=20) and one undergoing 50 μg LPS inhalation (n=30). After LPS inhalation, cigarette smokers had increased alveolar-capillary membrane permeability as measured by BAL total protein, compared with non-smokers (median 274 vs 208 μg/mL, p=0.04). Smokers had exaggerated inflammation compared with non-smokers, with increased BAL interleukin-1β (p=0.002), neutrophils (p=0.02), plasma interleukin-8 (p=0.003), and plasma matrix metalloproteinase-8 (p=0.006). Alveolar epithelial injury after LPS was more severe in smokers than non-smokers, with increased plasma (p=0.04) and decreased BAL (p=0.02) surfactant protein D. Finally, smokers had decreased BAL vascular endothelial growth factor (VEGF) (p<0.0001) with increased soluble VEGF receptor-1 (p=0.0001). Cigarette smoke exposure may predispose to ARDS through an abnormal response to a 'second hit,' with increased alveolar-capillary membrane permeability, exaggerated inflammation, increased epithelial injury and endothelial dysfunction. LPS inhalation may serve as a useful experimental model for evaluation of the acute pulmonary effects of existing and new tobacco products. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  3. Investigating Disruption

    Lundgaard, Stine Schmieg; Rosenstand, Claus Andreas Foss

    This book shares knowledge collected from 2015 and onward within the Consortium for Digital Disruption anchored at Aalborg University (www.dd.aau.dk). Evidenced by this publication, the field of disruptive innovation research has gone through several stages of operationalizing the theory. In recent...... years, researchers are increasingly looking back towards the origins of the theory in attempts to cure it from its most obvious flaws. This is especially true for the use of the theory in making predictions about future disruptions. In order to continue to develop a valuable theory of disruption, we...... find it useful to first review what the theory of disruptive innovation initially was, how it has developed, and where we are now. A cross section of disruptive innovation literature has been reviewed in order to form a general foundation from which we might better understand the changing world...

  4. Stroop interference and the timing of selective response activation.

    Lansbergen, M.M.; Kenemans, J.L.

    2008-01-01

    OBJECTIVE: To examine the exact timing of selective response activation in a manual color-word Stroop task. METHODS: Healthy individuals performed two versions of a manual color-word Stroop task, varying in the probability of incongruent color-words, while EEG was recorded. RESULTS: Stroop

  5. Rural Women\\'s Response To Selected Crop Production ...

    The study centered on rural women's response to selected crop production technologies in Imo State with a view to making policy recommendations. Structured questionnaire and interview schedule were administered through the assistance of extension agents to 258 randomly sampled rural women farmers from the three ...

  6. Systemic lipopolysaccharide administration impairs retrieval of context-object discrimination, but not spatial, memory: Evidence for selective disruption of specific hippocampus-dependent memory functions during acute neuroinflammation.

    Czerniawski, Jennifer; Miyashita, Teiko; Lewandowski, Gail; Guzowski, John F

    2015-02-01

    Neuroinflammation is implicated in impairments in neuronal function and cognition that arise with aging, trauma, and/or disease. Therefore, understanding the underlying basis of the effect of immune system activation on neural function could lead to therapies for treating cognitive decline. Although neuroinflammation is widely thought to preferentially impair hippocampus-dependent memory, data on the effects of cytokines on cognition are mixed. One possible explanation for these inconsistent results is that cytokines may disrupt specific neural processes underlying some forms of memory but not others. In an earlier study, we tested the effect of systemic administration of bacterial lipopolysaccharide (LPS) on retrieval of hippocampus-dependent context memory and neural circuit function in CA3 and CA1 (Czerniawski and Guzowski, 2014). Paralleling impairment in context discrimination memory, we observed changes in neural circuit function consistent with disrupted pattern separation function. In the current study we tested the hypothesis that acute neuroinflammation selectively disrupts memory retrieval in tasks requiring hippocampal pattern separation processes. Male Sprague-Dawley rats given LPS systemically prior to testing exhibited intact performance in tasks that do not require hippocampal pattern separation processes: novel object recognition and spatial memory in the water maze. By contrast, memory retrieval in a task thought to require hippocampal pattern separation, context-object discrimination, was strongly impaired in LPS-treated rats in the absence of any gross effects on exploratory activity or motivation. These data show that LPS administration does not impair memory retrieval in all hippocampus-dependent tasks, and support the hypothesis that acute neuroinflammation impairs context discrimination memory via disruption of pattern separation processes in hippocampus. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Loss of Oca2 disrupts the unfolded protein response and increases resistance to endoplasmic reticulum stress in melanocytes.

    Cheng, Tsing; Orlow, Seth J; Manga, Prashiela

    2013-11-01

    Accumulation of proteins in the endoplasmic reticulum (ER) typically induces stress and initiates the unfolded protein response (UPR) to facilitate recovery. If homeostasis is not restored, apoptosis is induced. However, adaptation to chronic UPR activation can increase resistance to subsequent acute ER stress. We therefore investigated adaptive mechanisms in Oculocutaneous albinism type 2 (Oca2)-null melanocytes where UPR signaling is arrested despite continued tyrosinase accumulation leading to resistance to the chemical ER stressor thapsigargin. Although thapsigargin triggers UPR activation, instead of Perk-mediated phosphorylation of eIF2α, in Oca2-null melanocytes, eIF2α was rapidly dephosphorylated upon treatment. Dephosphorylation was mediated by the Gadd34-PP1α phosphatase complex. Gadd34-complex inhibition blocked eIF2α dephosphorylation and significantly increased Oca2-null melanocyte sensitivity to thapsigargin. Thus, Oca2-null melanocytes adapt to acute ER stress by disruption of pro-apoptotic Perk signaling, which promotes cell survival. This is the first study to demonstrate rapid eIF2α dephosphorylation as an adaptive mechanism to ER stress. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. An Approach to Understanding Complex Socio-Economic Impacts and Responses to Climate Disruption in the Chesapeake Bay Region

    Schaefer, R. K.; Nix, M.; Ihde, A. G.; Paxton, L. J.; Weiss, M.; Simpkins, S.; Fountain, G. H.; APl GAIA Team

    2011-12-01

    In this paper we describe the application of a proven methodology for modeling the complex social and economic interactions of a system under stress to the regional issues that are tied to global climate disruption. Under the auspices of the GAIA project (http://gaia.jhuapl.edu), we have investigated simulating the complex interplay between climate, politics, society, industry, and the environment in the Chesapeake Bay Watershed and associated geographic areas of Maryland, Virginia, and Pennsylvania. This Chesapeake Bay simulation draws on interrelated geophysical and climate models to support decision-making analysis about the Bay. In addition to physical models, however, human activity is also incorporated via input and output calculations. For example, policy implications are modeled in relation to business activities surrounding fishing, farming, industry and manufacturing, land development, and tourism. This approach fosters collaboration among subject matter experts to advance a more complete understanding of the regional impacts of climate change. Simulated interactive competition, in which teams of experts are assigned conflicting objectives in a controlled environment, allow for subject exploration which avoids trivial solutions that neglect the possible responses of affected parties. Results include improved planning, the anticipation of areas of conflict or high risk, and the increased likelihood of developing mutually acceptable solutions.

  9. Multiple bottlenecks in hierarchical control of action sequences: what does "response selection" select in skilled typewriting?

    Yamaguchi, Motonori; Logan, Gordon D; Li, Vanessa

    2013-08-01

    Does response selection select words or letters in skilled typewriting? Typing performance involves hierarchically organized control processes: an outer loop that controls word level processing, and an inner loop that controls letter (or keystroke) level processing. The present study addressed whether response selection occurs in the outer loop or the inner loop by using the psychological refractory period (PRP) paradigm in which Task1 required typing single words and Task2 required vocal responses to tones. The number of letters (string length) in the words was manipulated to discriminate selection of words from selection of keystrokes. In Experiment 1, the PRP effect depended on string length of words in Task1, suggesting that response selection occurs in the inner loop. To assess contributions of the outer loop, the influence of string length was examined in a lexical-decision task that also involves word encoding and lexical access (Experiment 2), or to-be-typed words were preexposed so outer-loop processing could finish before typing started (Experiment 3). Response time for Task2 (RT2) did not depend on string length with lexical decision, and RT2 still depended on string length with typing preexposed strings. These results support the inner-loop locus of the PRP effect. In Experiment 4, typing was performed as Task2, and the effect of string length on typing RT interacted with stimulus onset asynchrony superadditively, implying that another bottleneck also exists in the outer loop. We conclude that there are at least two bottleneck processes in skilled typewriting. 2013 APA, all rights reserved

  10. Listening to the Shepard-Risset glissando: the relationship between emotional response, disruption of equilibrium and personality

    Eveline eVernooij

    2016-03-01

    Full Text Available The endless scale illusion, obtained by cyclically repeating a chromatic scale made up of Shepard tones, has been used in a variety of musical works. Music psychology and neuroscience has been interested in this particular psychoacoustic phenomenon mainly for studying the cognitive processes of pitch perception involved. In the present study, we investigated the emotional states induced by the Shepard-Risset glissando, a variant of the Shepard scale. For this purpose we chose three musical stimuli: a Matlab-generated Shepard Risset glissando, Jean-Claude Risset’s Computer Suite from Little Boy, which presents a Shepard-Risset glissando integrated in the aesthetic context of a composition, and an ordinary orchestral glissando taken from the opening of Iannis Xenakis’ Metastasis. Seventy-three volunteers completed a listening experiment during which they rated their emotional response to these stimuli on a 7-point Likert scale and indicated whether they had experienced a disruption of equilibrium. Personality was also measured with the Five-Factor Model of personality traits.The results show that negative emotions were most strongly evoked during listening to each of the stimuli. We also found that the Shepard-Risset glissando illusion, both within the aesthetic context of a musical composition and on its own, was capable of evoking disruption of equilibrium, frequently leading to the associated feeling of falling. Moreover, generally for the Shepard-Risset glissando illusion, higher negative emotional ratings were given by individuals who had experienced a feeling of disturbance of equilibrium relative to those who had not had this experience. Finally, we found a complex pattern of relationships between personality and the subjective experience of the glissando. Openness to experience correlated positively with positive emotion ratings for the Computer Suite, while agreeableness correlated negatively with positive emotion ratings for the

  11. Listening to the Shepard-Risset Glissando: the Relationship between Emotional Response, Disruption of Equilibrium, and Personality

    Vernooij, Eveline; Orcalli, Angelo; Fabbro, Franco; Crescentini, Cristiano

    2016-01-01

    The endless scale illusion, obtained by cyclically repeating a chromatic scale made up of Shepard tones, has been used in a variety of musical works. Music psychology and neuroscience has been interested in this particular psychoacoustic phenomenon mainly for studying the cognitive processes of pitch perception involved. In the present study, we investigated the emotional states induced by the Shepard-Risset glissando, a variant of the Shepard scale. For this purpose we chose three musical stimuli: a Matlab-generated Shepard Risset glissando, Jean-Claude Risset's Computer Suite from Little Boy, which presents a Shepard-Risset glissando integrated in the aesthetic context of a composition, and an ordinary orchestral glissando taken from the opening of Iannis Xenakis's Metastasis. Seventy-three volunteers completed a listening experiment during which they rated their emotional response to these stimuli on a seven-point Likert scale and indicated whether they had experienced a disruption of equilibrium. Personality was also measured with the Five-Factor Model of personality traits. The results show that negative emotions were most strongly evoked during listening to each of the stimuli. We also found that the Shepard-Risset glissando illusion, both within the aesthetic context of a musical composition and on its own, was capable of evoking disruption of equilibrium, frequently leading to the associated feeling of falling. Moreover, generally for the Shepard-Risset glissando illusion, higher negative emotional ratings were given by individuals who had experienced a feeling of disturbance of equilibrium relative to those who had not had this experience. Finally, we found a complex pattern of relationships between personality and the subjective experience of the glissando. Openness to experience correlated positively with positive emotion ratings for the Computer Suite, while agreeableness correlated negatively with positive emotion ratings for the Matlab stimulus

  12. Listening to the Shepard-Risset Glissando: the Relationship between Emotional Response, Disruption of Equilibrium, and Personality.

    Vernooij, Eveline; Orcalli, Angelo; Fabbro, Franco; Crescentini, Cristiano

    2016-01-01

    The endless scale illusion, obtained by cyclically repeating a chromatic scale made up of Shepard tones, has been used in a variety of musical works. Music psychology and neuroscience has been interested in this particular psychoacoustic phenomenon mainly for studying the cognitive processes of pitch perception involved. In the present study, we investigated the emotional states induced by the Shepard-Risset glissando, a variant of the Shepard scale. For this purpose we chose three musical stimuli: a Matlab-generated Shepard Risset glissando, Jean-Claude Risset's Computer Suite from Little Boy, which presents a Shepard-Risset glissando integrated in the aesthetic context of a composition, and an ordinary orchestral glissando taken from the opening of Iannis Xenakis's Metastasis. Seventy-three volunteers completed a listening experiment during which they rated their emotional response to these stimuli on a seven-point Likert scale and indicated whether they had experienced a disruption of equilibrium. Personality was also measured with the Five-Factor Model of personality traits. The results show that negative emotions were most strongly evoked during listening to each of the stimuli. We also found that the Shepard-Risset glissando illusion, both within the aesthetic context of a musical composition and on its own, was capable of evoking disruption of equilibrium, frequently leading to the associated feeling of falling. Moreover, generally for the Shepard-Risset glissando illusion, higher negative emotional ratings were given by individuals who had experienced a feeling of disturbance of equilibrium relative to those who had not had this experience. Finally, we found a complex pattern of relationships between personality and the subjective experience of the glissando. Openness to experience correlated positively with positive emotion ratings for the Computer Suite, while agreeableness correlated negatively with positive emotion ratings for the Matlab stimulus

  13. Disruption model

    Murray, J.G.; Bronner, G.

    1982-07-01

    Calculations of disruption time and energy dissipation have been obtained by simulating the plasma as an electrical conducting loop that varies in resistivity, current density, major radius. The calculations provide results which are in good agreement with experimental observations. It is believed that this approach allows engineering designs for disruptions to be completed in large tokamaks such as INTOR or FED

  14. Corporate Social Responsability: Selected Theoretical and Empirical Aspects

    Witkowska Janina

    2016-03-01

    Full Text Available The notion of Corporate social responsibility (CSR is still stirring debate over how it should be interpreted, what models of CSR dominate in business practice, and consequences of enterprises’ engagement into socially responsible actions. While business practice demonstrates that companies voluntarily include social and environmental issues into their activities and into their relations with stakeholders, it is hard to determine what intentions motivate them to do so. This paper analyses selected aspects of discussions focused on the notion of CSR and identifies controversies over the standardisation of ethical and social business activities.

  15. Stress responsiveness predicts individual variation in mate selectivity.

    Vitousek, Maren N; Romero, L Michael

    2013-06-15

    Steroid hormones, including glucocorticoids, mediate a variety of behavioral and physiological processes. Circulating hormone concentrations vary substantially within populations, and although hormone titers predict reproductive success in several species, little is known about how individual variation in circulating hormone concentrations is linked with most reproductive behaviors in free-living organisms. Mate choice is an important and often costly component of reproduction that also varies substantially within populations. We examined whether energetically costly mate selection behavior in female Galápagos marine iguanas (Amblyrhynchus cristatus) was associated with individual variation in the concentrations of hormones previously shown to differ between reproductive and non-reproductive females during the breeding season (corticosterone and testosterone). Stress-induced corticosterone levels - which are suppressed in female marine iguanas during reproduction - were individually repeatable throughout the seven-week breeding period. Mate selectivity was strongly predicted by individual variation in stress-induced corticosterone: reproductive females that secreted less corticosterone in response to a standardized stressor assessed more displaying males. Neither baseline corticosterone nor testosterone predicted variation in mate selectivity. Scaled body mass was not significantly associated with mate selectivity, but females that began the breeding period in lower body condition showed a trend towards being less selective about potential mates. These results provide the first evidence that individual variation in the corticosterone stress response is associated with how selective females are in their choice of a mate, an important contributor to fitness in many species. Future research is needed to determine the functional basis of this association, and whether transient acute increases in circulating corticosterone directly mediate mate choice behaviors

  16. Host response to biomaterials the impact of host response on biomaterial selection

    Badylak, Stephen F

    2015-01-01

    Host Response to Biomaterials: The Impact of Host Response on Biomaterial Selection explains the various categories of biomaterials and their significance for clinical applications, focusing on the host response to each biomaterial. It is one of the first books to connect immunology and biomaterials with regard to host response. The text also explores the role of the immune system in host response, and covers the regulatory environment for biomaterials, along with the benefits of synthetic versus natural biomaterials, and the transition from simple to complex biomaterial solutions. Fiel

  17. Dissociating the influence of response selection and task anticipation on corticospinal suppression during response preparation.

    Duque, Julie; Labruna, Ludovica; Cazares, Christian; Ivry, Richard B

    2014-12-01

    Motor behavior requires selecting between potential actions. The role of inhibition in response selection has frequently been examined in tasks in which participants are engaged in some advance preparation prior to the presentation of an imperative signal. Under such conditions, inhibition could be related to processes associated with response selection, or to more general inhibitory processes that are engaged in high states of anticipation. In Experiment 1, we manipulated the degree of anticipatory preparation. Participants performed a choice reaction time task that required choosing between a movement of the left or right index finger, and used transcranial magnetic stimulation (TMS) to elicit motor evoked potentials (MEPs) in the left hand agonist. In high anticipation blocks, a non-informative cue (e.g., fixation marker) preceded the imperative; in low anticipation blocks, there was no cue and participants were required to divide their attention between two tasks to further reduce anticipation. MEPs were substantially reduced before the imperative signal in high anticipation blocks. In contrast, in low anticipation blocks, MEPs remained unchanged before the imperative signal but showed a marked suppression right after the onset of the imperative. This effect occurred regardless of whether the imperative had signalled a left or right hand response. After this initial inhibition, left MEPs increased when the left hand was selected and remained suppressed when the right hand was selected. We obtained similar results in Experiment 2 except that the persistent left MEP suppression when the left hand was not selected was attenuated when the alternative response involved a non-homologous effector (right foot). These results indicate that, even in the absence of an anticipatory period, inhibitory mechanisms are engaged during response selection, possibly to prevent the occurrence of premature and inappropriate responses during a competitive selection process. Copyright

  18. Dissociating the Influence of Response Selection and Task Anticipation on Corticospinal Suppression During Response Preparation

    Duque, Julie; Labruna, Ludovica; Cazares, Christian; Ivry, Richard B.

    2014-01-01

    Motor behavior requires selecting between potential actions. The role of inhibition in response selection has frequently been examined in tasks in which participants are engaged in some advance preparation prior to the presentation of an imperative signal. Under such conditions, inhibition could be related to processes associated with response selection, or to more general inhibitory processes that are engaged in high states of anticipation. In Experiment 1, we manipulated the degree of anticipatory preparation. Participants performed a choice reaction time task that required choosing between a movement of the left or right index finger, and used transcranial magnetic stimulation (TMS) to elicit motor evoked potentials (MEPs) in the left hand agonist. In high anticipation blocks, a non-informative cue (e.g., fixation marker) preceded the imperative; in low anticipation blocks, there was no cue and participants were required to divide their attention between two tasks to further reduce anticipation. MEPs were substantially reduced before the imperative signal in high anticipation blocks. In contrast, in low anticipation blocks, MEPs remained unchanged before the imperative signal but showed a marked suppression right after the onset of the imperative. This effect occurred regardless of whether the imperative had signaled a left or right hand response. After this initial inhibition, left MEPs increased when the left hand was selected and remained suppressed when the right hand was selected. We obtained similar results in Experiment 2 except that the persistent left MEP suppression when the left hand was not selected was attenuated when the alternative response involved a non-homologous effector (right foot). These results indicate that, even in the absence of an anticipatory period, inhibitory mechanisms are engaged during response selection, possibly to prevent the occurrence of premature and inappropriate responses during a competitive selection process. PMID

  19. Ventral tegmental area disruption selectively affects CA1/CA2 but not CA3 place fields during a differential reward working memory task.

    Martig, Adria K; Mizumori, Sheri J Y

    2011-02-01

    Hippocampus (HPC) receives dopaminergic (DA) projections from the ventral tegmental area (VTA) and substantia nigra. These inputs appear to provide a modulatory signal that influences HPC dependent behaviors and place fields. We examined how efferent projections from VTA to HPC influence spatial working memory and place fields when the reward context changes. CA1 and CA3 process environmental context changes differently and VTA preferentially innervates CA1. Given these anatomical data and electrophysiological evidence that implicate DA in reward processing, we predicted that CA1 place fields would respond more strongly to both VTA disruption and changes in the reward context than CA3 place fields. Rats (N = 9) were implanted with infusion cannula targeting VTA and recording tetrodes aimed at HPC. Then they were tested on a differential reward, win-shift working memory task. One recording session consisted of 5 baseline and 5 manipulation trials during which place cells in CA1/CA2 (N = 167) and CA3 (N = 94) were recorded. Prior to manipulation trials rats were infused with either baclofen or saline and then subjected to control or reward conditions during which the learned locations of large and small reward quantities were reversed. VTA disruption resulted in an increase in errors, and in CA1/CA2 place field reorganization. There were no changes in any measures of CA3 place field stability during VTA disruption. Reward manipulations did not affect performance or place field stability in CA1/CA2 or CA3; however, changes in the reward locations "rescued" performance and place field stability in CA1/CA2 when VTA activity was compromised, perhaps by trigging compensatory mechanisms. These data support the hypothesis that VTA contributes to spatial working memory performance perhaps by maintaining place field stability selectively in CA1/CA2. Copyright © 2009 Wiley-Liss, Inc.

  20. Disruptive event analysis: volcanism and igneous intrusion

    Crowe, B.M.

    1979-01-01

    Three basic topics are addressed for the disruptive event analysis: first, the range of disruptive consequences of a radioactive waste repository by volcanic activity; second, the possible reduction of the risk of disruption by volcanic activity through selective siting of a repository; and third, the quantification of the probability of repository disruption by volcanic activity

  1. Gestational treatment with methylazoxymethanol (MAM) that disrupts hippocampal-dependent memory does not alter behavioural response to cocaine.

    Featherstone, Robert E; Burton, Christie L; Coppa-Hopman, Romina; Rizos, Zoë; Sinyard, Judy; Kapur, Shitij; Fletcher, Paul J

    2009-10-01

    Schizophrenia is associated with increased rates of substance abuse that are thought to be the result of changes in cortical and mesolimbic dopamine activity. Previous work has shown that gestational methylazoxymethanol acetate (MAM) treatment induces increased mesolimbic dopamine activity when given around the time of embryonic day 17 (ED17), suggesting that MAM treatment may model some aspects of schizophrenia. Given that increased dopaminergic activity facilitates aspects of drug self-administration and reinstatement of drug seeking, the current experiments sought to assess cocaine self-administration in MAM treated animals. Experiment 1 examined the acquisition of cocaine self-administration in ED17 MAM and saline treated rats using a sub-threshold dose of cocaine. In experiment 2 ED17 MAM and saline treated animals were trained to self-administer cocaine and were then assessed under varying doses of cocaine (dose-response), followed by extinction and drug-induced reinstatement of responding. A subset of these animals was trained on a win-shift radial maze task, designed to detect impairments in hippocampal-dependent memory. In experiment 3, MAM and saline treated animals were assessed on a progressive ratio schedule of cocaine delivery. Finally, in experiment 4 MAM and saline treated animals were assessed on cocaine-induced locomotor activity across a range of doses of cocaine. MAM treatment disrupted performance of the win-shift task but did not alter cocaine self-administration or cocaine-induced locomotion. Implications of these results for the MAM model of schizophrenia are discussed.

  2. Loss of Subcellular Lipid Transport Due to ARV1 Deficiency Disrupts Organelle Homeostasis and Activates the Unfolded Protein Response*

    Shechtman, Caryn F.; Henneberry, Annette L.; Seimon, Tracie A.; Tinkelenberg, Arthur H.; Wilcox, Lisa J.; Lee, Eunjee; Fazlollahi, Mina; Munkacsi, Andrew B.; Bussemaker, Harmen J.; Tabas, Ira; Sturley, Stephen L.

    2011-01-01

    The ARV1-encoded protein mediates sterol transport from the endoplasmic reticulum (ER) to the plasma membrane. Yeast ARV1 mutants accumulate multiple lipids in the ER and are sensitive to pharmacological modulators of both sterol and sphingolipid metabolism. Using fluorescent and electron microscopy, we demonstrate sterol accumulation, subcellular membrane expansion, elevated lipid droplet formation, and vacuolar fragmentation in ARV1 mutants. Motif-based regression analysis of ARV1 deletion transcription profiles indicates activation of Hac1p, an integral component of the unfolded protein response (UPR). Accordingly, we show constitutive splicing of HAC1 transcripts, induction of a UPR reporter, and elevated expression of UPR targets in ARV1 mutants. IRE1, encoding the unfolded protein sensor in the ER lumen, exhibits a lethal genetic interaction with ARV1, indicating a viability requirement for the UPR in cells lacking ARV1. Surprisingly, ARV1 mutants expressing a variant of Ire1p defective in sensing unfolded proteins are viable. Moreover, these strains also exhibit constitutive HAC1 splicing that interacts with DTT-mediated perturbation of protein folding. These data suggest that a component of UPR induction in arv1Δ strains is distinct from protein misfolding. Decreased ARV1 expression in murine macrophages also results in UPR induction, particularly up-regulation of activating transcription factor-4, CHOP (C/EBP homologous protein), and apoptosis. Cholesterol loading or inhibition of cholesterol esterification further elevated CHOP expression in ARV1 knockdown cells. Thus, loss or down-regulation of ARV1 disturbs membrane and lipid homeostasis, resulting in a disruption of ER integrity, one consequence of which is induction of the UPR. PMID:21266578

  3. Ocean Acidification Disrupts Prey Responses to Predator Cues but Not Net Prey Shell Growth in Concholepas concholepas (loco)

    Manríquez, Patricio H.; Jara, María Elisa; Mardones, María Loreto; Navarro, Jorge M.; Torres, Rodrigo; Lardies, Marcos A.; Vargas, Cristian A.; Duarte, Cristian; Widdicombe, Stephen; Salisbury, Joseph; Lagos, Nelson A.

    2013-01-01

    Background Most research on Ocean Acidification (OA) has largely focused on the process of calcification and the physiological trade-offs employed by calcifying organisms to support the building of calcium carbonate structures. However, there is growing evidence that OA can also impact upon other key biological processes such as survival, growth and behaviour. On wave-swept rocky shores the ability of gastropods to self-right after dislodgement, and rapidly return to normal orientation, reduces the risk of predation. Methodology/Principal Findings The impacts of OA on this self-righting behaviour and other important parameters such as growth, survival, shell dissolution and shell deposition in Concholepas concholepas (loco) were investigated under contrasting pCO2 levels. Although no impacts of OA on either growth or net shell calcification were found, the results did show that OA can significantly affect self-righting behaviour during the early ontogeny of this species with significantly faster righting times recorded for individuals of C. concholepas reared under increased average pCO2 concentrations (± SE) (716±12 and 1036±14 µatm CO2) compared to those reared at concentrations equivalent to those presently found in the surface ocean (388±8 µatm CO2). When loco were also exposed to the predatory crab Acanthocyclus hassleri, righting times were again increased by exposure to elevated CO2, although self-righting times were generally twice as fast as those observed in the absence of the crab. Conclusions and Significance These results suggest that self-righting in the early ontogeny of C. concholepas will be positively affected by pCO2 levels expected by the end of the 21st century and beginning of the next one. However, as the rate of self-righting is an adaptive trait evolved to reduce lethal predatory attacks, our result also suggest that OA may disrupt prey responses to predators in nature. PMID:23844231

  4. Ocean acidification disrupts prey responses to predator cues but not net prey shell growth in Concholepas concholepas (loco.

    Patricio H Manríquez

    Full Text Available BACKGROUND: Most research on Ocean Acidification (OA has largely focused on the process of calcification and the physiological trade-offs employed by calcifying organisms to support the building of calcium carbonate structures. However, there is growing evidence that OA can also impact upon other key biological processes such as survival, growth and behaviour. On wave-swept rocky shores the ability of gastropods to self-right after dislodgement, and rapidly return to normal orientation, reduces the risk of predation. METHODOLOGY/PRINCIPAL FINDINGS: The impacts of OA on this self-righting behaviour and other important parameters such as growth, survival, shell dissolution and shell deposition in Concholepas concholepas (loco were investigated under contrasting pCO2 levels. Although no impacts of OA on either growth or net shell calcification were found, the results did show that OA can significantly affect self-righting behaviour during the early ontogeny of this species with significantly faster righting times recorded for individuals of C. concholepas reared under increased average pCO2 concentrations (± SE (716 ± 12 and 1036 ± 14 µatm CO2 compared to those reared at concentrations equivalent to those presently found in the surface ocean (388 ± 8 µatm CO2. When loco were also exposed to the predatory crab Acanthocyclus hassleri, righting times were again increased by exposure to elevated CO2, although self-righting times were generally twice as fast as those observed in the absence of the crab. CONCLUSIONS AND SIGNIFICANCE: These results suggest that self-righting in the early ontogeny of C. concholepas will be positively affected by pCO2 levels expected by the end of the 21st century and beginning of the next one. However, as the rate of self-righting is an adaptive trait evolved to reduce lethal predatory attacks, our result also suggest that OA may disrupt prey responses to predators in nature.

  5. Ocean acidification disrupts prey responses to predator cues but not net prey shell growth in Concholepas concholepas (loco).

    Manríquez, Patricio H; Jara, María Elisa; Mardones, María Loreto; Navarro, Jorge M; Torres, Rodrigo; Lardies, Marcos A; Vargas, Cristian A; Duarte, Cristian; Widdicombe, Stephen; Salisbury, Joseph; Lagos, Nelson A

    2013-01-01

    Most research on Ocean Acidification (OA) has largely focused on the process of calcification and the physiological trade-offs employed by calcifying organisms to support the building of calcium carbonate structures. However, there is growing evidence that OA can also impact upon other key biological processes such as survival, growth and behaviour. On wave-swept rocky shores the ability of gastropods to self-right after dislodgement, and rapidly return to normal orientation, reduces the risk of predation. The impacts of OA on this self-righting behaviour and other important parameters such as growth, survival, shell dissolution and shell deposition in Concholepas concholepas (loco) were investigated under contrasting pCO2 levels. Although no impacts of OA on either growth or net shell calcification were found, the results did show that OA can significantly affect self-righting behaviour during the early ontogeny of this species with significantly faster righting times recorded for individuals of C. concholepas reared under increased average pCO2 concentrations (± SE) (716 ± 12 and 1036 ± 14 µatm CO2) compared to those reared at concentrations equivalent to those presently found in the surface ocean (388 ± 8 µatm CO2). When loco were also exposed to the predatory crab Acanthocyclus hassleri, righting times were again increased by exposure to elevated CO2, although self-righting times were generally twice as fast as those observed in the absence of the crab. These results suggest that self-righting in the early ontogeny of C. concholepas will be positively affected by pCO2 levels expected by the end of the 21st century and beginning of the next one. However, as the rate of self-righting is an adaptive trait evolved to reduce lethal predatory attacks, our result also suggest that OA may disrupt prey responses to predators in nature.

  6. Effects of response-independent stimuli on fixed-interval and fixed-ratio performance of rats: a model for stressful disruption of cyclical eating patterns.

    Reed, Phil

    2011-03-01

    Binge eating is often associated with stress-induced disruption of typical eating patterns. Three experiments were performed with the aim of developing a potential model for this effect by investigating the effect of presenting response-independent stimuli on rats' lever-pressing for food reinforcement during both fixed-interval (FI) and fixed-ratio (FR) schedules of reinforcement. In Experiment 1, a response-independent brief tone (500-ms, 105-dB, broadband, noisy signal, ranging up to 16 kHz, with spectral peaks at 3 and 500 Hz) disrupted the performance on an FI 60-s schedule. Responding with the response-independent tone was more vigorous than in the absence of the tone. This effect was replicated in Experiment 2 using a within-subject design, but no such effect was noted when a light was employed as a disrupter. In Experiment 3, a 500-ms tone, but not a light, had a similar effect on rats' performance on FR schedules. This tone-induced effect may represent a release from response-inhibition produced by an aversive event. The implications of these results for modeling binge eating are discussed.

  7. Disrupted Disclosure

    Krause Hansen, Hans; Uldam, Julie

    appearances become challenged through disruptive disclosures in mediaenvironments characterized by multiple levels of visibility, with companies both observing andbeing observed by civil society groups that criticize them; (c) why and how the mobilization aroundtransparency and ensuing practices...

  8. Family Disruptions

    ... Spread the Word Shop AAP Find a Pediatrician Family Life Medical Home Family Dynamics Adoption & Foster Care ... Life Listen Español Text Size Email Print Share Family Disruptions Page Content Article Body No matter how ...

  9. Short- and long-term temporal changes in soil concentrations of selected endocrine disrupting compounds (EDCs) following single or multiple applications of sewage sludge to pastures

    Rhind, S.M.; Kyle, C.E.; Ruffie, H.; Calmettes, E.; Osprey, M.; Zhang, Z.L.; Hamilton, D.; McKenzie, C.

    2013-01-01

    Temporal changes in soil burdens of selected endocrine disrupting compounds were determined following application to pasture of either sewage sludge or inorganic fertilizer. Soil polycyclic aromatic hydrocarbon and polychlorinated biphenyl concentrations were not altered. Changes in concentrations of diethylhexyl phthalate (DEHP) and PBDEs 47 and 99 differed with season but concentrations remained elevated for more than three weeks after application, when grazing animals are normally excluded from pasture. It is concluded that single applications of sewage sludge can increase soil concentrations of some, but not all classes of EDCs, possibly to concentrations sufficient to exert biological effects when different chemicals act in combination, but patterns of change depend on season and soil temperature. Analysis of soil from pasture subjected to repeated sludge applications, over 13 years, provided preliminary evidence of greater increases in soil burdens of all of the EDC groups measured, including all of the PBDE congeners measured. -- Highlights: •Sewage sludge or inorganic fertilizer was applied to pasture. •Soil PAH and PCB concentrations were not altered by sludge treatment. •Temporal changes in soil phthalate and PBDE differed with season. •Some soil EDC levels were elevated for more than three weeks after application. -- Effects of sewage sludge application to pastures on temporal changes in soil concentrations of endocrine disrupting compounds differ with chemical class and season

  10. Toxicity and disruption of quorum sensing in Aliivibrio fisheri by environmental chemicals: Impacts of selected contaminants and microplastics

    François Gagné

    2017-11-01

    Full Text Available The purpose of this study was to examine the effects of dissolved and particulate compounds on quorum sensing in the marine luminescent bacterium Aliivibrio fisheri. Bacteria were exposed to increasing concentrations of CuSO4 (Cu2+, gadolinium chloride (Gd3+, 20-nm silver nanoparticles (nanoAg and 1-3 μm microplastic polyethylene beads for 250 min. During this period, luminescence measurements were taken at 5-min intervals. Toxicity was first examined by measuring luminescence output at 5-min and 30-min incubation time. Based on the effective concentration that decreases luminescence by 20% (EC20, the compounds were toxic at the following concentrations in decreasing toxicity: Cu2+ (3.2 mg/L < nanoAg (3.4 mg/L, reported < Gd3+ (34 mg/L < microplastics (2.6 g/L. The data revealed that luminescence changed non-linearly over time. In control bacteria, luminescence changed at eight specific major frequencies between 0.04 and 0.27 cycle/min after Fourier transformation of time-dependent luminescence data. The addition of dissolved Cu2+ and Gd3+ eliminated the amplitude changes at these frequencies in a concentration-dependent manner, indicating loss of quorum sensing between bacteria at concentrations below EC20. In the presence of nanoAg and microplastic beads, the decreases in amplitudes were modest but compressed the luminescence profiles, with shorter frequencies appearing at concentrations well below EC20. Thus, loss of communication between bacteria occurs at non-toxic concentrations. In addition, with exposure to a mixture of the above compounds at concentrations that do not produce effects for Gd3+, nanoAg and microplastics, Cu2+ toxicity was significantly enhanced, suggesting synergy. This study revealed for the first time that small microplastic particles and nanoparticles can disrupt quorum sensing in marine bacteria.

  11. Prenatal exposure to vinclozolin disrupts selective aspects of the gonadotropin-releasing hormone neuronal system of the rabbit

    Wadas, B.C.; Hartshorn, C.A.; Aurand, E.R.; Palmer, J.S.; Roselli, C.E.; Noel, M.L.; Gore, A.C.; Veeramachaneni, D.N.R.; Tobet, S.A.

    2010-01-01

    Developmental exposure to the agricultural fungicide vinclozolin can impair reproductive function in male rabbits and was previously found to decrease the number of immunoreactive-gonadotropin-releasing hormone (ir-GnRH) neurons in the region of the organum vasculosum of the lamina terminalis (OVLT) and rostral preoptic area (rPOA) by postnatal week (PNW) 6. To further examine the disruption of GnRH neurons by fetal vinclozolin exposure, in the current study, pregnant rabbits were dosed orally with vinclozolin, flutamide, or carrot paste vehicle for the last two weeks of gestation. Offspring were euthanized at birth (males and females), PNW6 (females), PNW26 (adult males), or PNW30 (adult females) of age. At birth and in adults, brains were sectioned and processed for immunoreactive GnRH. The numbers of immunoreactive GnRH neuronal perikarya were significantly decreased in vinclozolin-treated rabbits at birth and in adult littermates. By contrast, there was an increase in GnRH immunoreactivity in the terminals in the region of the median eminence. Analysis of PNW6 female brains by radioimmunoassay (RIA) revealed a two-fold increase in GnRH peptide content in the mediobasal hypothalamus in vinclozolin-treated rabbits. This finding was complemented by immunofluorescence analyses that showed a 2.8-fold increase in GnRH immunoreactivity in the median eminence of vinclozolin compared to vehicle-treated females at PNW30. However, there was no difference between treatment groups in the measures of reproduction that were evaluated: ejaculation latency, conception rates or litter size. These results indicate that subacute, prenatal vinclozolin treatment is sufficient to create perdurable alterations in the GnRH neuronal network that forms an important input into the reproductive axis. Finally, the effect of vinclozolin on the GnRH neuronal network was not comparable to that of flutamide, suggesting that vinclozolin was not acting through anti-androgenic mechanisms. PMID

  12. Prenatal exposure to vinclozolin disrupts selective aspects of the gonadotrophin-releasing hormone neuronal system of the rabbit.

    Wadas, B C; Hartshorn, C A; Aurand, E R; Palmer, J S; Roselli, C E; Noel, M L; Gore, A C; Veeramachaneni, D N R; Tobet, S A

    2010-06-01

    Developmental exposure to the agricultural fungicide vinclozolin can impair reproductive function in male rabbits and was previously found to decrease the number of immunoreactive-gonadotrophin-releasing hormone (GnRH) neurones in the region of the organum vasculosum of the lamina terminalis and rostral preoptic area by postnatal week (PNW) 6. In the present study, in an aim to further examine the disruption of GnRH neurones by foetal vinclozolin exposure, pregnant rabbits were dosed orally with vinclozolin, flutamide or carrot paste vehicle for the last 2 weeks of gestation. Offspring were euthanised at birth (males and females), PNW 6 (females), PNW 26 (adult males) or PNW 30 (adult females) of age. At birth and in adults, brains were sectioned and processed for immunoreactive GnRH. The numbers of immunoreactive GnRH neuronal perikarya were significantly decreased in vinclozolin-treated rabbits at birth and in adult littermates. By contrast, there was an increase in GnRH immunoreactivity in the terminals in the region of the median eminence. Analysis of PNW 6 female brains by radioimmunoassay revealed a two-fold increase in GnRH peptide content in the mediobasal hypothalamus in vinclozolin-treated rabbits. This finding was complemented by immunofluorescence analyses, which revealed a 2.8-fold increase in GnRH immunoreactivity in the median eminence of vinclozolin compared to vehicle-treated females at PNW 30. However, there was no difference between treatment groups in the measures of reproduction that were evaluated: ejaculation latency, conception rates or litter size. These results indicate that sub-acute, prenatal vinclozolin treatment is sufficient to create perdurable alterations in the GnRH neuronal network that forms an important input into the reproductive axis. Finally, the effect of vinclozolin on the GnRH neuronal network was not comparable to that of flutamide, suggesting that vinclozolin was not acting through anti-androgenic mechanisms.

  13. Digital Disruption

    Rosenstand, Claus Andreas Foss

    det digitale domæne ud over det niveau, der kendetegner den nuværende debat, så præsenteres der ny viden om digital disruption. Som noget nyt udlægges Clayton Christens teori om disruptiv innovation med et særligt fokus på små organisationers mulighed for eksponentiel vækst. Specielt udfoldes...... forholdet mellem disruption og den stadig accelererende digitale udvikling i konturerne til ny teoridannelse om digital disruption. Bogens undertitel ”faretruende og fascinerende forandringer” peger på, at der er behov for en nuanceret debat om digital disruption i modsætning til den tone, der er slået an i...... videre kalder et ”disruption-råd”. Faktisk er rådet skrevet ind i 2016 regeringsgrundlaget for VLK-regeringen. Disruption af organisationer er ikke et nyt fænomen; men hastigheden, hvormed det sker, er stadig accelererende. Årsagen er den globale mega-trend: Digitalisering. Og derfor er specielt digital...

  14. Implementing a finite-state off-normal and fault response system for disruption avoidance in tokamaks

    Eidietis, N. W.; Choi, W.; Hahn, S. H.; Humphreys, D. A.; Sammuli, B. S.; Walker, M. L.

    2018-05-01

    A finite-state off-normal and fault response (ONFR) system is presented that provides the supervisory logic for comprehensive disruption avoidance and machine protection in tokamaks. Robust event handling is critical for ITER and future large tokamaks, where plasma parameters will necessarily approach stability limits and many systems will operate near their engineering limits. Events can be classified as off-normal plasmas events, e.g. neoclassical tearing modes or vertical displacements events, or faults, e.g. coil power supply failures. The ONFR system presented provides four critical features of a robust event handling system: sequential responses to cascading events, event recovery, simultaneous handling of multiple events and actuator prioritization. The finite-state logic is implemented in Matlab®/Stateflow® to allow rapid development and testing in an easily understood graphical format before automated export to the real-time plasma control system code. Experimental demonstrations of the ONFR algorithm on the DIII-D and KSTAR tokamaks are presented. In the most complex demonstration, the ONFR algorithm asynchronously applies ‘catch and subdue’ electron cyclotron current drive (ECCD) injection scheme to suppress a virulent 2/1 neoclassical tearing mode, subsequently shuts down ECCD for machine protection when the plasma becomes over-dense, and enables rotating 3D field entrainment of the ensuing locked mode to allow a safe rampdown, all in the same discharge without user intervention. When multiple ONFR states are active simultaneously and requesting the same actuator (e.g. neutral beam injection or gyrotrons), actuator prioritization is accomplished by sorting the pre-assigned priority values of each active ONFR state and giving complete control of the actuator to the state with highest priority. This early experience makes evident that additional research is required to develop an improved actuator sharing protocol, as well as a methodology to

  15. Genomic selection improves response to selection in resilience by exploiting genotype by environment interactions

    Han Mulder

    2016-10-01

    Full Text Available Genotype by environment interactions (GxE are very common in livestock and hamper genetic improvement. On the other hand, GxE is a source of genetic variation: genetic variation in response to environment, e.g. environmental perturbations such as heat stress or disease. In livestock breeding, there is tendency to ignore GxE because of increased complexity of models for genetic evaluations and lack of accuracy in extreme environments. GxE, however, creates opportunities to increase resilience of animals towards environmental perturbations. The main aim of the paper is to investigate to which extent GxE can be exploited with traditional and genomic selection methods. Furthermore, we investigated the benefit of reaction norm models compared to conventional methods ignoring GxE. The questions were addressed with selection index theory. GxE was modelled according to a linear reaction norm model in which the environmental gradient is the contemporary group mean. Economic values were based on linear and non-linear profit equations.Accuracies of environment-specific (GEBV were highest in intermediate environments and lowest in extreme environments. Reaction norm models had higher accuracies of (GEBV in extreme environments than conventional models ignoring GxE. Genomic selection always resulted in higher response to selection in all environments than sib or progeny testing schemes. The increase in response was with genomic selection between 9% and 140% compared to sib testing and between 11% and 114% compared to progeny testing when the reference population consisted of 1 million animals across all environments. When the aim was to decrease environmental sensitivity, the response in slope of the reaction norm model with genomic selection was between 1.09 and 319 times larger than with sib or progeny testing and in the right direction in contrast to sib and progeny testing that still increased environmental sensitivity. This shows that genomic selection

  16. Selective Disruption of Metabotropic Glutamate Receptor 5-Homer Interactions Mimics Phenotypes of Fragile X Syndrome in Mice.

    Guo, Weirui; Molinaro, Gemma; Collins, Katie A; Hays, Seth A; Paylor, Richard; Worley, Paul F; Szumlinski, Karen K; Huber, Kimberly M

    2016-02-17

    Altered function of the Gq-coupled, Group 1 metabotropic glutamate receptors, specifically mGlu5, is implicated in multiple mouse models of autism and intellectual disability. mGlu5 dysfunction has been most well characterized in the fragile X syndrome mouse model, the Fmr1 knock-out (KO) mouse, where pharmacological and genetic reduction of mGlu5 reverses many phenotypes. mGlu5 is less associated with its scaffolding protein Homer in Fmr1 KO mice, and restoration of mGlu5-Homer interactions by genetic deletion of a short, dominant negative of Homer, H1a, rescues many phenotypes of Fmr1 KO mice. These results suggested that disruption of mGlu5-Homer leads to phenotypes of FXS. To test this idea, we examined mice with a knockin mutation of mGlu5 (F1128R; mGlu5(R/R)) that abrogates binding to Homer. Although FMRP levels were normal, mGlu5(R/R) mice mimicked multiple phenotypes of Fmr1 KO mice, including reduced mGlu5 association with the postsynaptic density, enhanced constitutive mGlu5 signaling to protein synthesis, deficits in agonist-induced translational control, protein synthesis-independent LTD, neocortical hyperexcitability, audiogenic seizures, and altered behaviors, including anxiety and sensorimotor gating. These results reveal new roles for the Homer scaffolds in regulation of mGlu5 function and implicate a specific molecular mechanism in a complex brain disease. Abnormal function of the metabotropic, or Gq-coupled, glutamate receptor 5 (mGlu5) has been implicated in neurodevelopmental disorders, including a genetic cause of intellectual disability and autism called fragile X syndrome. In brains of a mouse model of fragile X, mGlu5 is less associated with its binding partner Homer, a scaffolding protein that regulates mGlu5 localization to synapses and its ability to activate biochemical signaling pathways. Here we show that a mouse expressing a mutant mGlu5 that cannot bind to Homer is sufficient to mimic many of the biochemical, neurophysiological, and

  17. Selective responsiveness: Online public demands and government responsiveness in authoritarian China.

    Su, Zheng; Meng, Tianguang

    2016-09-01

    The widespread use of information and communication technology (ICT) has reshaped the public sphere in the digital era, making online forums a new channel for political participation. Using big data analytics of full records of citizen-government interactions from 2008 to early 2014 on a nationwide political forum, we find that authoritarian China is considerably responsive to citizens' demands with a rapid growth of response rate; however, government responsiveness is highly selective, conditioning on actors' social identities and the policy domains of their online demands. Results from logistic and duration models suggest that requests which made by local citizens, expressed collectively, focused on the single task issue, and are closely related to economic growth are more likely to be responded to. These strategies adopted by Chinese provincial leaders reveal the scope and selectivity of authoritarian responsiveness. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. The Acoustic Startle Response and Disruption of Aiming. 1. Effect of Stimulus Repetition, Intensity, and Intensity Changes

    1989-11-01

    PEST consisting of an approximate one-third oc- procedure described by Taylor and Creelman tave band centered at 800 Hz (cutoffs at 700 (1967...to some extent Taylor, M. M., and Creelman . C. D. (1967). PEST: Efficient estimates on probability functions. Journal of the performance disruption

  19. Politisk disruption

    Tække, Jesper

    2018-01-01

    Dette blogindlæg giver en kort analyse af hvordan de sociale medier ved at give en ny tid har åbnet for den disruption af de politiske processer som især Trump stå som et eksempel på.......Dette blogindlæg giver en kort analyse af hvordan de sociale medier ved at give en ny tid har åbnet for den disruption af de politiske processer som især Trump stå som et eksempel på....

  20. Disrupting Business

    Cox, Geoff; Bazzichelli, Tatiana

    Disruptive Business explores some of the interconnections between art, activism and the business concept of disruptive innovation. With a backdrop of the crisis of financial capitalism, austerity cuts in the cultural sphere, the idea is to focus on potential art strategies in relation to a broken...... economy. In a perverse way, we ask whether this presents new opportunities for cultural producers to achieve more autonomy over their production process. If it is indeed possible, or desirable, what alternative business models emerge? The book is concerned broadly with business as material for reinvention...

  1. Conflicts during response selection affect response programming: reactions toward the source of stimulation.

    Buetti, Simona; Kerzel, Dirk

    2009-06-01

    In the Simon effect, participants make a left or right keypress in response to a nonspatial attribute (e.g., color) that is presented on the left or right. Reaction times (RTs) increase when the response activated by the irrelevant stimulus location and the response retrieved by instruction are in conflict. The authors measured RTs and movement parameters (MPs) of pointing responses in a typical Simon task. Their results show that the trajectories veer toward the imperative stimulus. This bias decreased as RTs increased. The authors suggest that the time course of trajectory deviations reflects the resolution of the response conflict over time. Further, time pressure did not affect the size of the Simon effect in MPs or its time course, but strongly reduced the Simon effect in RTs. In contrast, response selection before the onset of a go signal on the left or right did not affect the Simon effect in RTs, but reduced the Simon effect in MPs and reversed the time course. The authors speculate about independent Simon effects associated with response selection and programming. (c) 2009 APA, all rights reserved.

  2. The Response of RIF-1 Fibrosarcomas to the Vascular-Disrupting Agent ZD6126 Assessed by In Vivo and Ex Vivo1H Magnetic Resonance Spectroscopy

    Basetti Madhu

    2006-07-01

    Full Text Available The response of radiation-induced fibrosarcoma1 (RIF-1 tumors treated with the vascular-disrupting agent (VDA ZD6126 was assessed by in vivo and ex vivo1H magnetic resonance spectroscopy (MRS methods. Tumors treated with 200 mg/kg ZD6126 showed a significant reduction in total choline (tCho in vivo 24 hours after treatment, whereas control tumors showed a significant increase in tCho. This response was investigated further within both ex vivo unprocessed tumor tissues and tumor tissue metabolite extracts. Ex vivo high-resolution magic angle spinning (HRMAS and 1H MRS of metabolite extracts revealed a significant reduction in phosphocholine and glycerophosphocholine in biopsies of ZD6126-treated tumors, confirming in vivo tCho response. ZD6126-induced reduction in choline compounds is consistent with a reduction in cell membrane turnover associated with necrosis and cell death following disruption of the tumor vasculature. In vivo tumor tissue water diffusion and lactate measurements showed no significant changes in response to ZD6126. Spin-spin relaxation times (T2 of water and metabolites also remained unchanged. Noninvasive 1H MRS measurement of tCho in vivo provides a potential biomarker of tumor response to VDAs in RIF-1 tumors.

  3. Adsorption of selected pharmaceuticals and an endocrine disrupting compound by granular activated carbon. 1. Adsorption capacity and kinetics

    Yu, Z.; Peldszus, S.; Huck, P.M. [University of Waterloo, Waterloo, ON (Canada). NSERC Chair in Water Treatment

    2009-03-01

    The adsorption of two representative PhACs (naproxen and carbamazepine) and one EDC (nonylphenol) were evaluated on two granular activated carbons (GAC) namely coal-based Calgon Filtrasorb 400 and coconut shell-based PICA CTIF TE. The primary objective was to investigate preloading effects by natural organic matter (NOM) on adsorption capacity and kinetics under conditions and concentrations (i.e., ng/L) relevant for drinking water treatment. Isotherms demonstrated that all compounds were significantly negatively impacted by NOM fouling. Adsorption capacity reduction was most severe for the acidic naproxen, followed by the neutral carbamazepine and then the more hydrophobic nonylphenol. The GAC with the wider pore size distribution had considerably greater NOM loading, resulting in lower adsorption capacity. Different patterns for the change in Freundlich KF and 1/n with time revealed different competitive mechanisms for the different compounds. Mass transport coefficients determined by short fixed-bed (SFB) tests with virgin and preloaded GAC demonstrated that film diffusion primarily controls mass transfer on virgin and preloaded carbon. Naproxen suffered the greatest deteriorative effect on kinetic parameters due to preloading, followed by carbamazepine, and then nonylphenol. A type of surface NOM/biofilm, which appeared to add an additional mass transfer resistance layer and thus reduce film diffusion, was observed. In addition, electrostatic interactions between NOM/biofilm and the investigated compounds are proposed to contribute to the reduction of film diffusion. A companion paper building on this work describes treatability studies in pilot-scale GAC adsorbers and the effectiveness of a selected fixed-bed model. 32 refs., 3 figs., 2 tabs.

  4. Selection of technical risk responses for efficient contingencies

    Kujawski, Edouard

    2002-02-28

    The primary goal of good project risk management should be to successfully deliver projects for the lowest cost at an acceptable level of risk. This requires the systematic development and implementation of a set of Risk Response Actions (RRA) that achieves the lowest total project cost for a given probability of success while meeting technical performance and schedule. We refer to this set as the ''efficient RRA set''. This work presents a practical and mathematically sound approach for determining the efficient RRA set. It builds on some of Markowitz's portfolio selection principles and introduces several conceptual and modeling differences to properly treat project technical risks. The set of RRAs is treated as whole and not just individual risks. The efficient RRA set is determined based on ''Outcome Cost Vs Probability of Success''. The risks and RRAs are characterized using scenarios, decision trees, and cumulative probability distributions. The analysis provides information that enables decision-makers to select the efficient RRA set that explicitly takes their attitude toward project risk into account. Decision-makers should find it both useful and practical for sound decision-making under uncertainty/risk and efficiently optimizing project success. The computations are readily performed using commercially available Monte Carlo simulation tools. The approach is detailed using a realistic but simplified case of a project with two technical risks.

  5. When Disruptive Approaches Meet Disruptive Technologies: Learning at a Distance.

    Gibson, Chere Campbell

    2000-01-01

    Reviews research on constructivism in learning and selection of learning strategies. Suggests linking constructivism with instructional technologies for continuing medical education in order to "disrupt" reactive, habitual ways of learning and encourage active engagement. (SK)

  6. Disruptions in DIII-D

    Reiman, A.; Taylor, P.; Kellman, A.; LaHaye, R.

    1996-01-01

    We report on the results of a statistical analysis of the DIII-D disruption data base, and on an examination of a selected subset of the shots to determine the likely causes of disruptions. The statistical analysis focuses on the dependence of the disruption rate on key dimensionless parameters. We find that the disruption frequency is high at modest values of the parameters, and that it can be relatively low at operational limits. For example, the disruption frequency in an ITER relevant regime (β N /l i ∼ 2, 3 G > 0.6, where n G is the Greenwald limit) is approximately 23%. For this range of q, the disruption frequency rises only modestly to about 35% at the β limit, consistent with previous observations of a soft β limit for this q regime. For the range 6 95 G G < .9) in all q regimes we have studied. The location of the minimum moves to higher density with increasing q

  7. Selected endocrine disrupting compounds (vinclozolin, flutamide, ketoconazole and dicofol): effects on survival, occurrence of males, growth, molting and reproduction of Daphnia magna.

    Haeba, Maher H; Hilscherová, Klára; Mazurová, Edita; Bláha, Ludek

    2008-05-01

    Pollution-induced endocrine disruption in vertebrates and invertebrates is a worldwide environmental problem, but relatively little is known about effects of endocrine disrupting compounds (EDCs) in planktonic crustaceans (including Daphnia magna). Aims of the present study were to investigate acute 48 h toxicity and sub-chronic (4-6 days) and chronic (21 days) effects of selected EDCs in D. magna. We have investigated both traditional endpoints as well as other parameters such as sex determination, maturation, molting or embryogenesis in order to evaluate the sensitivity and possible use of these endpoints in ecological risk assessment. We have studied effects of four model EDCs (vinclozolin, flutamide, ketoconazole and dicofol) on D. magna using (i) an acute 48 h immobilization assay, (ii) a sub-chronic, 4-6 day assay evaluating development and the sex ratio of neonates, and (iii) a chronic, 21 day assay studying number of neonates, sex of neonates, molting frequency, day of maturation and the growth of maternal organisms. Acute EC50 values in the 48 h immobilization test were as follows (mg/L): dicofol 0.2, ketoconazole 1.5, flutamide 2.7, vinclozolin >3. Short-term, 4-6 day assays with sublethal concentrations showed that the sex ratio in Daphnia was modulated by vinclozolin (decreased number of neonate males at 1 mg/L) and dicofol (increase in males at 0.1 mg/L). Flutamide (up to 1 mg/L) had no effect on the sex of neonates, but inhibited embryonic development at certain stages during chronic assay, resulting in abortions. Ketoconazole had no significant effects on the studied processes up to 1 mg/L. Sex ratio modulations by some chemicals (vinclozolin and dicofol) corresponded to the known action of these compounds in vertebrates (i.e. anti-androgenicity and anti-oestrogenicity, respectively). Our study revealed that some chemicals known to affect steroid-regulated processes in vertebrates can also affect sublethal endpoints (e.g. embryonic sex determination

  8. A Randomized Trial of the Self-Management Training and Regulation Strategy (STARS): A Selective Intervention for Students with Disruptive Behaviors

    Thompson, Aaron M.

    2012-01-01

    To attain academic goals, school personnel must effectively manage 20% of students who engage in the disruptive behaviors that interrupt instruction, create teacher stress, and contribute to poor student outcomes. Without effective strategies, school personnel often respond to disruptive students with ineffective authoritarian tactics,…

  9. Bayesian selective response-adaptive design using the historical control.

    Kim, Mi-Ok; Harun, Nusrat; Liu, Chunyan; Khoury, Jane C; Broderick, Joseph P

    2018-06-13

    High quality historical control data, if incorporated, may reduce sample size, trial cost, and duration. A too optimistic use of the data, however, may result in bias under prior-data conflict. Motivated by well-publicized two-arm comparative trials in stroke, we propose a Bayesian design that both adaptively incorporates historical control data and selectively adapt the treatment allocation ratios within an ongoing trial responsively to the relative treatment effects. The proposed design differs from existing designs that borrow from historical controls. As opposed to reducing the number of subjects assigned to the control arm blindly, this design does so adaptively to the relative treatment effects only if evaluation of cumulated current trial data combined with the historical control suggests the superiority of the intervention arm. We used the effective historical sample size approach to quantify borrowed information on the control arm and modified the treatment allocation rules of the doubly adaptive biased coin design to incorporate the quantity. The modified allocation rules were then implemented under the Bayesian framework with commensurate priors addressing prior-data conflict. Trials were also more frequently concluded earlier in line with the underlying truth, reducing trial cost, and duration and yielded parameter estimates with smaller standard errors. © 2018 The Authors. Statistics in Medicine Published by John Wiley & Sons, Ltd.

  10. Simulating Impacts of Disruptions to Liquid Fuels Infrastructure

    Wilson, Michael [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States). Resilience and Regulatory Effects; Corbet, Thomas F. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States). Policy and Decision Analytics; Baker, Arnold B. [ABB Consulting, Albuquerque, NM (United States); O' Rourke, Julia M. [Univ. of Texas, Austin, TX (United States). Dept. of Mechanical Engineering

    2015-04-01

    This report presents a methodology for estimating the impacts of events that damage or disrupt liquid fuels infrastructure. The impact of a disruption depends on which components of the infrastructure are damaged, the time required for repairs, and the position of the disrupted components in the fuels supply network. Impacts are estimated for seven stressing events in regions of the United States, which were selected to represent a range of disruption types. For most of these events the analysis is carried out using the National Transportation Fuels Model (NTFM) to simulate the system-level liquid fuels sector response. Results are presented for each event, and a brief cross comparison of event simulation results is provided.

  11. Relationship between neural response and adaptation selectivity to form and color: an ERP study

    Ilias eRentzeperis

    2012-04-01

    Full Text Available Adaptation is widely used as a tool for studying selectivity to visual features. In these studies it is usually assumed that the loci of feature selective neural responses and adaptation coincide. We used an adaptation paradigm to investigate the relationship between response and adaptation selectivity in event-related potentials (ERP. ERPs were evoked by the presentation of colored Glass patterns in a form discrimination task. Response selectivities to form and, to some extent, color of the patterns were reflected in the C1 and N1 ERP components. Adaptation selectivity to color was reflected in N1 and was followed by a late (300-500 ms after stimulus onset effect of form adaptation. Thus for form, response and adaptation selectivity were manifested in non-overlapping intervals. These results indicate that adaptation and response selectivity can be associated with different processes. Therefore inferring selectivity from an adaptation paradigm requires analysis of both adaptation and neural response data.

  12. A strong response to selection on mass-independent maximal metabolic rate without a correlated response in basal metabolic rate

    Wone, B W M; Madsen, Per; Donovan, E R

    2015-01-01

    Metabolic rates are correlated with many aspects of ecology, but how selection on different aspects of metabolic rates affects their mutual evolution is poorly understood. Using laboratory mice, we artificially selected for high maximal mass-independent metabolic rate (MMR) without direct selection...... on mass-independent basal metabolic rate (BMR). Then we tested for responses to selection in MMR and correlated responses to selection in BMR. In other lines, we antagonistically selected for mice with a combination of high mass-independent MMR and low mass-independent BMR. All selection protocols...... and data analyses included body mass as a covariate, so effects of selection on the metabolic rates are mass adjusted (that is, independent of effects of body mass). The selection lasted eight generations. Compared with controls, MMR was significantly higher (11.2%) in lines selected for increased MMR...

  13. Category-specific visual responses: an intracranial study comparing gamma, beta, alpha and ERP response selectivity

    Juan R Vidal

    2010-11-01

    Full Text Available The specificity of neural responses to visual objects is a major topic in visual neuroscience. In humans, functional magnetic resonance imaging (fMRI studies have identified several regions of the occipital and temporal lobe that appear specific to faces, letter-strings, scenes, or tools. Direct electrophysiological recordings in the visual cortical areas of epileptic patients have largely confirmed this modular organization, using either single-neuron peri-stimulus time-histogram or intracerebral event-related potentials (iERP. In parallel, a new research stream has emerged using high-frequency gamma-band activity (50-150 Hz (GBR and low-frequency alpha/beta activity (8-24 Hz (ABR to map functional networks in humans. An obvious question is now whether the functional organization of the visual cortex revealed by fMRI, ERP, GBR, and ABR coincide. We used direct intracerebral recordings in 18 epileptic patients to directly compare GBR, ABR, and ERP elicited by the presentation of seven major visual object categories (faces, scenes, houses, consonants, pseudowords, tools, and animals, in relation to previous fMRI studies. Remarkably both GBR and iERP showed strong category-specificity that was in many cases sufficient to infer stimulus object category from the neural response at single-trial level. However, we also found a strong discrepancy between the selectivity of GBR, ABR, and ERP with less than 10% of spatial overlap between sites eliciting the same category-specificity. Overall, we found that selective neural responses to visual objects were broadly distributed in the brain with a prominent spatial cluster located in the posterior temporal cortex. Moreover, the different neural markers (GBR, ABR, and iERP that elicit selectivity towards specific visual object categories present little spatial overlap suggesting that the information content of each marker can uniquely characterize high-level visual information in the brain.

  14. Short-term spatial memory responses in aged Japanese quail selected for divergent adrenocortical stress responsiveness.

    Suhr, C L; Schmidt, J B; Treese, S T; Satterlee, D G

    2010-04-01

    Stress-induced glucocorticoids can dampen learning and spatial memory via neuronal damage to the hippocampus. Cognition losses can be transient (associated with acute stress episodes) or permanent as in aged individuals who show chronic glucocorticoid-induced accelerated brain aging and neurodegeneration (dementia). Thus, chronic versus acute stress effects on spatial memory responses of quail selected for reduced (low stress, LS) or exaggerated (high stress, HS) plasma corticosterone (B) response to brief restraint were assessed. Aged food-motivated male LS and HS quail were tested for 10 min in a feed-baited 8-arm radial arm maze (RAM) 1) at 255 d of age (quail who had experienced lifelong management stressors but who were otherwise never intentionally stressed; that is, chronically stressed birds), 2) on the next day post-acute stressor treatment (5 min of restraint), and 3) on the next day without treatment (acute stress recovery). The RAM tests used the win-shift procedure in which visited arms were not rebaited. Radial arm maze performance was measured by determination of the total number of arm choices made, the number of correct entries made into baited arms out of the first 8 choices, the time required to make a choice, and the number of pellets eaten. Line effects (P LS), and number of pellets eaten (HS RAM testing nor its interaction with line further influenced these variables. Thus, although selection for divergent plasma B responsiveness to an acute stressor was found to be associated with severe impairment of spatial memory in aged male HS compared with LS quail, the observed spatial memory impairments (HS > LS) could not be further altered by acute stressor treatment. Line differences in cognition may reflect lifelong management-induced stress episodes that periodically produce higher plasma B responses in HS than LS quail, which underlie HS quail memory deficits, or other etiologies, or both.

  15. Laser-scanning astrocyte mapping reveals increased glutamate-responsive domain size and disrupted maturation of glutamate uptake following neonatal cortical freeze-lesion

    Mortiz eArmbruster

    2014-09-01

    Full Text Available Astrocytic uptake of glutamate shapes extracellular neurotransmitter dynamics, receptor activation, and synaptogenesis. During development, glutamate transport becomes more robust. How neonatal brain insult affects the functional maturation of glutamate transport remains unanswered. Neonatal brain insult can lead to developmental delays, cognitive losses, and epilepsy; the disruption of glutamate transport is known to cause changes in synaptogenesis, receptor activation, and seizure. Using the neonatal freeze-lesion (FL model, we have investigated how insult affects the maturation of astrocytic glutamate transport. As lesioning occurs on the day of birth, a time when astrocytes are still functionally immature, this model is ideal for identifying changes in astrocyte maturation following insult. Reactive astrocytosis, astrocyte proliferation, and in vitro hyperexcitability are known to occur in this model. To probe astrocyte glutamate transport with better spatial precision we have developed a novel technique, Laser Scanning Astrocyte Mapping (LSAM, which combines glutamate transport current (TC recording from astrocytes with laser scanning glutamate photolysis. LSAM allows us to identify the area from which a single astrocyte can transport glutamate and to quantify spatial heterogeneity in the rate of glutamate clearance kinetics within that domain. Using LSAM, we report that cortical astrocytes have an increased glutamate-responsive area following FL and that TCs have faster decay times in distal, as compared to proximal processes. Furthermore, the developmental shift from GLAST- to GLT-1-dominated clearance is disrupted following FL. These findings introduce a novel method to probe astrocyte glutamate uptake and show that neonatal cortical FL disrupts the functional maturation of cortical astrocytes.

  16. Response to selection and genetic parameters of body and carcass weights in Japanese quail selected for 4-week body weight

    Khaldari, M; Pakdel, A; Yegane, H Mehrabani

    2010-01-01

    , respectively. There was a significant effect of sex, generation, and line (P difference for BW and carcass weights but not for carcass percentage components between sexes (P ... to improve carcass traits. Also, intense selection resulting in high rates of inbreeding might result in decreased response to selection due to inbreeding depression....

  17. Sustainable Disruptions

    Friis, Silje Alberthe Kamille; Kjær, Lykke Bloch

    2016-01-01

    Since 2012 the Sustainable Disruptions (SD) project at the Laboratory for Sustainability at Design School Kolding (DK) has developed and tested a set of design thinking tools, specifically targeting the barriers to economically, socially, and environmentally sustainable business development....... The tools have been applied in practice in collaboration with 11 small and medium sized companies (SMEs). The study investigates these approaches to further understand how design thinking can contribute to sustainable transition in a business context. The study and the findings are relevant to organizations...... invested in the issue of sustainable business development, in particular the leaders and employees of SMEs, but also to design education seeking new ways to consciously handle and teach the complexity inherent in sustainable transformation. Findings indicate that the SD design thinking approach contributes...

  18. Response to selection in finite locus models with nonadditive effects

    Esfandyari, Hadi; Henryon, Mark; Berg, Peer; Thomasen, Jørn Rind; Bijma, Piter; Sørensen, Anders Christian

    2017-01-01

    Under the finite-locus model in the absence of mutation, the additive genetic variation is expected to decrease when directional selection is acting on a population, according to quantitative-genetic theory. However, some theoretical studies of selection suggest that the level of additive

  19. The Role of Emotions in Reinforcement: Response Selection in Humans

    Overskeid, Geir

    2012-01-01

    Historically, researchers have never quite been able to agree as to the role of emotions, if any, when behavior is selected by its consequences. A brief review of findings from several fields suggests that in contingency-shaped behavior, motivating events, often unconscious, seem needed for reinforcement to select behavior. In rule-governed…

  20. Enhanced Therapeutic Potential of Nano-Curcumin Against Subarachnoid Hemorrhage-Induced Blood-Brain Barrier Disruption Through Inhibition of Inflammatory Response and Oxidative Stress.

    Zhang, Zong-Yong; Jiang, Ming; Fang, Jie; Yang, Ming-Feng; Zhang, Shuai; Yin, Yan-Xin; Li, Da-Wei; Mao, Lei-Lei; Fu, Xiao-Yan; Hou, Ya-Jun; Fu, Xiao-Ting; Fan, Cun-Dong; Sun, Bao-Liang

    2017-01-01

    Curcumin and nano-curcumin both exhibit neuroprotective effects in early brain injury (EBI) after experimental subarachnoid hemorrhage (SAH). However, the mechanism that whether curcumin and its nanoparticles affect the blood-brain barrier (BBB) following SAH remains unclear. This study investigated the effect of curcumin and the poly(lactide-co-glycolide) (PLGA)-encapsulated curcumin nanoparticles (Cur-NPs) on BBB disruption and evaluated the possible mechanism underlying BBB dysfunction in EBI using the endovascular perforation rat SAH model. The results indicated that Cur-NPs showed enhanced therapeutic effects than that of curcumin in improving neurological function, reducing brain water content, and Evans blue dye extravasation after SAH. Mechanically, Cur-NPs attenuated BBB dysfunction after SAH by preventing the disruption of tight junction protein (ZO-1, occludin, and claudin-5). Cur-NPs also up-regulated glutamate transporter-1 and attenuated glutamate concentration of cerebrospinal fluid following SAH. Moreover, inhibition of inflammatory response and microglia activation both contributed to Cur-NPs' protective effects. Additionally, Cur-NPs markedly suppressed SAH-mediated oxidative stress and eventually reversed SAH-induced cell apoptosis in rats. Our findings revealed that the strategy of using Cur-NPs could be a promising way in improving neurological function in EBI after experimental rat SAH.

  1. The cis decoy against the estrogen response element suppresses breast cancer cells via target disrupting c-fos not mitogen-activated protein kinase activity.

    Wang, Li Hua; Yang, Xiao Yi; Zhang, Xiaohu; Mihalic, Kelly; Xiao, Weihua; Farrar, William L

    2003-05-01

    Breast cancer, the most common malignancy in women, has been demonstrated to be associated with the steroid hormone estrogen and its receptor (ER), a ligand-activated transcription factor. Therefore, we developed a phosphorothiolate cis-element decoy against the estrogen response element (ERE decoy) to target disruption of ER DNA binding and transcriptional activity. Here, we showed that the ERE decoy potently ablated the 17beta-estrogen-inducible cell proliferation and induced apoptosis of human breast carcinoma cells by functionally affecting expression of c-fos gene and AP-1 luciferase gene reporter activity. Specificity of the decoy was demonstrated by its ability to directly block ER binding to a cis-element probe and transactivation. Moreover, the decoy failed to inhibit ER-mediated mitogen-activated protein kinase signaling pathways and cell growth of ER-negative breast cancer cells. Taken together, these data suggest that estrogen-mediated cell growth of breast cancer cells can be preferentially restricted via targeted disruption of ER at the level of DNA binding by a novel and specific decoy strategy applied to steroid nuclear receptors.

  2. Neonatal overfeeding disrupts pituitary ghrelin signalling in female rats long-term; Implications for the stress response.

    Sominsky, Luba; Ziko, Ilvana; Spencer, Sarah J

    2017-01-01

    The hypothalamic-pituitary-adrenal (HPA) axis responses to psychological stress are exacerbated in adult female but not male rats made obese due to overfeeding in early life. Ghrelin, traditionally known for its role in energy homeostasis, has been recently recognised for its role in coordinating the HPA responses to stress, particularly by acting directly at the anterior pituitary where the growth hormone secretagogue receptor (GHSR), the receptor for acyl ghrelin, is abundantly expressed. We therefore hypothesised that neonatal overfeeding in female rats would compromise pituitary responsiveness to ghrelin, contributing to a hyperactive central stress responsiveness. Unlike in males where hypothalamic ghrelin signalling is compromised by neonatal overfeeding, there was no effect of early life diet on circulating ghrelin or hypothalamic ghrelin signalling in females, indicating hypothalamic feeding and metabolic ghrelin circuitry remains intact. However, neonatal overfeeding did lead to long-term alterations in the pituitary ghrelin system. The neonatally overfed females had increased neonatal and reduced adult expression of GHSR and ghrelin-O-acyl transferase (GOAT) in the pituitary as well as reduced pituitary responsiveness to exogenous acyl ghrelin-induced adrenocorticotropic hormone (ACTH) release in vitro. These data suggest that neonatal overfeeding dysregulates pituitary ghrelin signalling long-term in females, potentially accounting for the hyper-responsive HPA axis in these animals. These findings have implications for how females may respond to stress throughout life, suggesting the way ghrelin modifies the stress response at the level of the pituitary may be less efficient in the neonatally overfed.

  3. Multiplicative Genotype-Environment Interaction as a Cause of Reversed Response to Directional Selection

    Gimelfarb, A.

    1986-01-01

    In experiments with directional selection on a quantitative character a "reversed response" to selection is occasionally observed, when selection of individuals for a higher (lower) value of the character results in a lower (higher) value of the character among their offspring. A sudden change in environments or random drift is often assumed to be responsible for this. It is demonstrated in this paper that these two causes cannot account for the reversed response at least in some of the exper...

  4. More insight into the interplay of response selection and visual attention in dual-tasks: masked visual search and response selection are performed in parallel.

    Reimer, Christina B; Schubert, Torsten

    2017-09-15

    Both response selection and visual attention are limited in capacity. According to the central bottleneck model, the response selection processes of two tasks in a dual-task situation are performed sequentially. In conjunction search, visual attention is required to select the items and to bind their features (e.g., color and form), which results in a serial search process. Search time increases as items are added to the search display (i.e., set size effect). When the search display is masked, visual attention deployment is restricted to a brief period of time and target detection decreases as a function of set size. Here, we investigated whether response selection and visual attention (i.e., feature binding) rely on a common or on distinct capacity limitations. In four dual-task experiments, participants completed an auditory Task 1 and a conjunction search Task 2 that were presented with an experimentally modulated temporal interval between them (Stimulus Onset Asynchrony, SOA). In Experiment 1, Task 1 was a two-choice discrimination task and the conjunction search display was not masked. In Experiment 2, the response selection difficulty in Task 1 was increased to a four-choice discrimination and the search task was the same as in Experiment 1. We applied the locus-of-slack method in both experiments to analyze conjunction search time, that is, we compared the set size effects across SOAs. Similar set size effects across SOAs (i.e., additive effects of SOA and set size) would indicate sequential processing of response selection and visual attention. However, a significantly smaller set size effect at short SOA compared to long SOA (i.e., underadditive interaction of SOA and set size) would indicate parallel processing of response selection and visual attention. In both experiments, we found underadditive interactions of SOA and set size. In Experiments 3 and 4, the conjunction search display in Task 2 was masked. Task 1 was the same as in Experiments 1 and 2

  5. Responses to selection for body weight in descendants of x-irradiated rats

    Gianola, D.; Chapman, A.B.; Rutledge, J.J.

    1979-01-01

    Th effectiveness of selection for high and low body weight at six weeks of age was studied in descendants of x-irradiated (R) and nonirradiated (C) inbred rats. There were two replicates of each of the direction of selection--irradiation treatments. In C lines, there were no consistent responses to selection, probably due to a low level of genetic variability. In R rats, selection was effective only for decreased body weight. The results of this experiment do not suggest the use of irradiation combined with selection as a means of enhancing responses to selection in animals

  6. Confirmation that pulse and continuous peracetic acid administration does not disrupt the acute stress response in rainbow trout

    Gesto, Manuel; Liu, Dibo; Pedersen, Lars-Flemming

    2018-01-01

    . If that is true, PAA would also be a good option from the point of view of fish physiology. However, stronger evidence is needed to confirm that the use of PAA is welfare-friendly to fish. Besides habituation, other hypothetical factors such as desensitization, physiological exhaustion or PAA-mediated endocrine...... response was evaluated by measuring plasma cortisol, plasma glucose, plasma lactate and brain serotonergic activity. All fish were equally able to mount a normal physiological stress response to the secondary stressor independent of previous exposure to PAA. This suggests that the decrease in the cortisol...

  7. Response to family selection and genetic parameters in Japanese quail selected for four week breast weight

    Khaldari, Majid; Yeganeh, Hassan Mehrabani; Pakdel, Abbas

    2011-01-01

    An experiment was conducted to investigate the effect of short-term selection for 4 week breast weight (4wk BRW), and to estimate genetic parameters of body weight, and carcass traits. A selection (S) line and control (C) line was randomly selected from a base population. Data were collected over...... was 0.35±0.06. There were a significant difference for BW, and carcass weights but not for carcass percent components between lines (Pcarcass and leg weights were 0.46, 0.41 and 0.47, and 13.2, 16.2, 4.4 %, respectively....... The genetic correlations of BRW with BW, carcass, leg, and back weights were 0.85, 0.88 and 0.72, respectively. Selection for 4 wk BRW improved feed conversion ratio (FCR) about 0.19 units over the selection period. Inbreeding caused an insignificant decline of the mean of some traits. Results from...

  8. Selection of response criteria for clinical trials of sarcoma treatment.

    Schuetze, Scott M; Baker, Laurence H; Benjamin, Robert S; Canetta, Renzo

    2008-01-01

    Soft tissue sarcomas are a heterogeneous group of malignancies arising from mesenchymal tissues. A large number of new therapies are being evaluated in patients with sarcomas, and consensus criteria defining treatment responses are essential for comparison of results from studies completed by different research groups. The 1979 World Health Organization (WHO) handbook set forth operationally defined criteria for response evaluation in solid tumors that were updated in 2000 with the publication of the Response Evaluation Criteria in Solid Tumors (RECIST). There have been significant advances in tumor imaging, however, that are not reflected in the RECIST. For example, computed tomography (CT) slice thickness has been reduced from 10 mm to < or =2.5 mm, allowing for more reproducible and accurate measurement of smaller lesions. Combination of imaging techniques, such as positron emission tomography with fluorine-18-fluorodeoxyglucose (18FDG-PET) and CT can provide investigators and clinicians with both anatomical and functional information regarding tumors, and there is now a large body of evidence demonstrating the effectiveness of PET/CT and other newer imaging methods for the detection and staging of tumors as well as early determination of responses to therapy. The application of newer imaging methods has the potential to decrease both the sample sizes required for, and duration of, clinical trials by providing an early indication of therapeutic response that is well correlated with clinical outcomes, such as time to tumor progression or overall survival. The results summarized in this review support the conclusion that the RECIST and the WHO criteria for evaluation of response in solid tumors need to be modernized. In addition, there is a current need for prospective trials to compare new response criteria with established endpoints and to validate imaging-based response rates as surrogate endpoints for clinical trials of new agents for sarcoma and other solid

  9. Utilizing Response Time Distributions for Item Selection in CAT

    Fan, Zhewen; Wang, Chun; Chang, Hua-Hua; Douglas, Jeffrey

    2012-01-01

    Traditional methods for item selection in computerized adaptive testing only focus on item information without taking into consideration the time required to answer an item. As a result, some examinees may receive a set of items that take a very long time to finish, and information is not accrued as efficiently as possible. The authors propose two…

  10. Selected endocrine disrupting compounds (vinclozolin, flutamide, ketoconazole and dicofol): Effects on survival, occurrence of males, growth, molting and reproduction of Daphnia magna

    Haeba, M. H.; Hilscherová, Klára; Mazurová, E.; Bláha, Luděk

    2008-01-01

    Roč. 15, č. 3 (2008), s. 222-227 ISSN 0944-1344 Institutional research plan: CEZ:AV0Z60050516 Keywords : Daphnia magna * dicofol * endocrine disruption Subject RIV: EF - Botanics Impact factor: 2.492, year: 2008

  11. Disruption to the development of maternal responsiveness? The impact of prenatal depression on mother-infant interactions.

    Pearson, R M; Melotti, R; Heron, J; Joinson, C; Stein, A; Ramchandani, P G; Evans, J

    2012-12-01

    Both prenatal and postnatal maternal depression are independently associated with an increased risk of adverse infant development. The impact of postnatal depression on infants may be mediated through the effect of depression in reducing maternal responsiveness. However, the mechanisms underlying the effect of prenatal depression are unclear. Using longitudinal data from over 900 mother-infant pairs in a UK birth cohort (ALSPAC), we found that women with high depressive symptom scores during mid pregnancy, but NOT when their infants were 8 months, had a 30% increased risk of low maternal responsiveness when the infant was 12 months compared to women with consistently low depression. This may provide a mechanism to explain the independent association between prenatal depression and poorer infant development. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. Disruption of murine mp29/Syf2/Ntc31 gene results in embryonic lethality with aberrant checkpoint response.

    Chia-Hsin Chen

    Full Text Available Human p29 is a putative component of spliceosomes, but its role in pre-mRNA is elusive. By siRNA knockdown and stable overexpression, we demonstrated that human p29 is involved in DNA damage response and Fanconi anemia pathway in cultured cells. In this study, we generated p29 knockout mice (mp29(GT/GT using the mp29 gene trap embryonic stem cells to study the role of mp29 in DNA damage response in vivo. Interruption of mp29 at both alleles resulted in embryonic lethality. Embryonic abnormality occurred as early as E6.5 in mp29(GT/GT mice accompanied with decreased mRNA levels of α-tubulin and Chk1. The reduction of α-tubulin and Chk1 mRNAs is likely due to an impaired post-transcriptional event. An aberrant G2/M checkpoint was found in mp29 gene trap embryos when exposed to aphidicolin and UV light. This embryonic lethality was rescued by crossing with mp29 transgenic mice. Additionally, the knockdown of zfp29 in zebrafish resulted in embryonic death at 72 hours of development postfertilization (hpf. A lower level of acetylated α-tubulin was also observed in zfp29 morphants. Together, these results illustrate an indispensable role of mp29 in DNA checkpoint response during embryonic development.

  13. Endocrine Disrupting Chemicals (EDCs)

    ... Center Pacientes y Cuidadores Hormones and Health The Endocrine System Hormones Endocrine Disrupting Chemicals (EDCs) Steroid and Hormone ... Hormones and Health › Endocrine Disrupting Chemicals (EDCs) The Endocrine System Hormones Endocrine Disrupting Chemicals (EDCs) EDCs Myth vs. ...

  14. How Do Parameters of Motor Response Influence Selective Inhibition? Evidence from the Stop-Signal Paradigm

    Chien Hui Tang

    2011-05-01

    Full Text Available The ability to selectively inhibit the execution of an action while performing other ones is crucial in humans' multitasking daily life. The current study aims to compare selective inhibition for choice reaction involving two effectors or response directions. We adopted a variation of the stop-signal paradigm to examine how selective inhibition is modulated by the way potential motor responses are combined and inhibited. Experiment 1 investigated selective inhibition under different combinations of effectors, namely “index and middle fingers” versus “hand and foot”. The results showed SSRT of the index finger was longer when the other response option was the foot than the middle finger. Experiment 2 examined how selective inhibition differs between selective stopping of effectors and movement directions, and that for most of the situations SSRT is longer for stopping a response based on its direction than effector. After equating complexity of response mapping between direction and effector conditions in Experiment 2, Experiment 3 still showed that SSRT differs between selecting direction or effectors. To summarize, SSRT varies depending on the way response effectors are paired and selectively stopped. Selective inhibition is thus likely not amodal and may involve different inhibitory mechanisms depending on parameters specifying the motor response.

  15. Experimental Observations on Dynamic Response of Selected Transparent Armor Materials

    2014-07-01

    Monolithic single crystal sapphire plates (100×100× 10 mm), from GT Crystal Systems, Inc., Salem , MA, in crystallographically controlled directions...Future Army Applications (2011) The National Academies Press , Washington, D.C. 5. Graff KF (1991) Wave motion in elastic solids, Dover Publications 6...2004) Visualization of impact damage in ceramics using the edge-on impact technique. Int J Appl Ceram Technol 1 (3):235–242 Fig. 38 Selection of a

  16. Medium-term responses to and changes in fitness with selection for ...

    It was postulated that poor fit of the model in later generations, a lack of genetic variance, mutation, genetic drift and / or natural selection may be causing these discrepancies. The selection responses were accompanied by losses of fitness during certain generations, while in others, the responses disappeared altogether.

  17. Medium-term responses to and changes in fitness with selection for ...

    generations, however, fitness was regained and this was followed by renewed appearance of responses. This pattern of response points to the presence of natural selection, which was corroborated by the differences between the effective and expected selection intensities. It was concluded that the slope of the allometric.

  18. Selecting a Response in Task Switching: Testing a Model of Compound Cue Retrieval

    Schneider, Darryl W.; Logan, Gordon D.

    2009-01-01

    How can a task-appropriate response be selected for an ambiguous target stimulus in task-switching situations? One answer is to use compound cue retrieval, whereby stimuli serve as joint retrieval cues to select a response from long-term memory. In the present study, the authors tested how well a model of compound cue retrieval could account for a…

  19. Regulation of immune responsiveness in vivo by disrupting an early T-cell signaling event using a cell-permeable peptide.

    David M Guimond

    Full Text Available The inducible T cell kinase (ITK regulates type 2 (Th2 cytokines that provide defense against certain parasitic and bacterial infections and are involved in the pathogenesis of lung inflammation such as allergic asthma. Activation of ITK requires the interaction of its SH3 domain with the poly-proline region of its signaling partner, the SH2 domain containing leukocyte phosphoprotein of 76 kilodaltons (SLP-76. The specific disruption of the ITK-SH3/SLP-76 poly-proline interaction in vitro by a cell-permeable competitive inhibitor peptide (R9-QQP interferes with the activation of ITK and the transduction of its cellular functions in T lymphocytes. In the present investigation, we assessed the effects of R9-QQP treatment on the induction of an in vivo immune response as represented by lung inflammation in a murine model of allergic asthma. We found that mice treated with R9-QQP and sensitized and challenged with the surrogate allergen ovalbumin (OVA display significant inhibition of lung inflammation in a peptide-specific manner. Thus, parameters of the allergic response, such as airway hyper-responsiveness, suppression of inflammatory cell infiltration, reduction of bronchial mucus accumulation, and production of relevant cytokines from draining lymph nodes were significantly suppressed. These findings represent the first demonstration of the biological significance of the interaction between ITK and SLP-76 in the induction of an immune response in a whole animal model and specifically underscore the significance of the ITK-SH3 domain interaction with the poly-proline region of SLP-76 in the development of an inflammatory response. Furthermore, the experimental approach of intracellular peptide-mediated inhibition might be applicable to the study of other important intracellular interactions thus providing a paradigm for dissecting signal transduction pathways.

  20. Direct and correlated responses to selection for total weight of lamb ...

    The estimated selection responses indicate that direct selection for TWW would be the most suitable selection criterion for improving reproductive performance in flocks with a high reproduction rate where an increase in the number of lambs would be undesirable. (South African Journal of Animal Science, 2001, 31(2): ...

  1. Accuracy and responses of genomic selection on key traits in apple breeding

    Muranty, Hélène; Troggio, Michela; Sadok, Ben Inès; Rifaï, Al Mehdi; Auwerkerken, Annemarie; Banchi, E.; Velasco, Riccardo; Stevanato, P.; Weg, van de W.E.; Guardo, Di M.; Kumar, S.; Laurens, François; Bink, M.C.A.M.

    2015-01-01

    The application of genomic selection in fruit tree crops is expected to enhance breeding efficiency by increasing prediction accuracy, increasing selection intensity and decreasing generation interval. The objectives of this study were to assess the accuracy of prediction and selection response in

  2. Non-oncogenic Acute Viral Infections Disrupt Anti-cancer Responses and Lead to Accelerated Cancer-Specific Host Death

    Frederick J. Kohlhapp

    2016-10-01

    Full Text Available In light of increased cancer prevalence and cancer-specific deaths in patients with infections, we investigated whether infections alter anti-tumor immune responses. We report that acute influenza infection of the lung promotes distal melanoma growth in the dermis and leads to accelerated cancer-specific host death. Furthermore, we show that during influenza infection, anti-melanoma CD8+ T cells are shunted from the tumor to the infection site, where they express high levels of the inhibitory receptor programmed cell death protein 1 (PD-1. Immunotherapy to block PD-1 reverses this loss of anti-tumor CD8+ T cells from the tumor and decreases infection-induced tumor growth. Our findings show that acute non-oncogenic infection can promote cancer growth, raising concerns regarding acute viral illness sequelae. They also suggest an unexpected role for PD-1 blockade in cancer immunotherapy and provide insight into the immune response when faced with concomitant challenges.

  3. From Digital Disruption to Business Model Scalability

    Nielsen, Christian; Lund, Morten; Thomsen, Peter Poulsen

    2017-01-01

    This article discusses the terms disruption, digital disruption, business models and business model scalability. It illustrates how managers should be using these terms for the benefit of their business by developing business models capable of achieving exponentially increasing returns to scale...... will seldom lead to business model scalability capable of competing with digital disruption(s)....... as a response to digital disruption. A series of case studies illustrate that besides frequent existing messages in the business literature relating to the importance of creating agile businesses, both in growing and declining economies, as well as hard to copy value propositions or value propositions that take...

  4. Disruption of cyclooxygenase-2 prevents downregulation of cortical AQP2 and AQP3 in response to bilateral ureteral obstruction in the mouse

    Nilsson, Line; Madsen, Kirsten Morill; Topcu, Sukru Oguzkan

    2012-01-01

    Bilateral ureteral obstruction (BUO) in rats is associated with increased cyclooxygenase type 2 (COX-2) expression, and selective COX-2 inhibition prevents downregulation of aquaporins (AQPs) in response to BUO. It was hypothesized that a murine model would display similar changes in renal COX-2 ...

  5. Selective Biological Responses of Phagocytes and Lungs to Purified Histones.

    Fattahi, Fatemeh; Grailer, Jamison J; Lu, Hope; Dick, Rachel S; Parlett, Michella; Zetoune, Firas S; Nuñez, Gabriel; Ward, Peter A

    2017-01-01

    Histones invoke strong proinflammatory responses in many different organs and cells. We assessed biological responses to purified or recombinant histones, using human and murine phagocytes and mouse lungs. H1 had the strongest ability in vitro to induce cell swelling independent of requirements for toll-like receptors (TLRs) 2 or 4. These responses were also associated with lactate dehydrogenase release. H3 and H2B were the strongest inducers of [Ca2+]i elevations in phagocytes. Cytokine and chemokine release from mouse and human phagocytes was predominately a function of H2A and H2B. Double TLR2 and TLR4 knockout (KO) mice had dramatically reduced cytokine release induced in macrophages exposed to individual histones. In contrast, macrophages from single TLR-KO mice showed few inhibitory effects on cytokine production. Using the NLRP3 inflammasome protocol, release of mature IL-1β was predominantly a feature of H1. Acute lung injury following the airway delivery of histones suggested that H1, H2A, and H2B were linked to alveolar leak of albumin and the buildup of polymorphonuclear neutrophils as well as the release of chemokines and cytokines into bronchoalveolar fluids. These results demonstrate distinct biological roles for individual histones in the context of inflammation biology and the requirement of both TLR2 and TLR4. © 2017 S. Karger AG, Basel.

  6. Selecting protective gloves for oil spill response and cleanup

    McDermott, H.J.

    1993-01-01

    Oil spill responders and cleanup workers must be provided with gloves that prevent skin contact while permitting them to do their job safely and efficiently. Glove selection is largely based on professional judgment, considering permeation, resistance to puncture and abrasion, and whether the material gets slick when coated with oil. This paper consolidates the most useful information from various studies and presents a selection rationale. In general, we found neoprene, polyvinyl chloride (PVC), and nitrile to be the glove materials of choice for protection in oil spills. The skin toxicity potential for most petroleum materials encountered in a spill is low. Some fresh crudes may contain hydrocarbon molecules that may penetrate the skin and cause some systemic toxicity with high enough exposure. However, as crude weathers, the more volatile hydrocarbons evaporate rapidly, leaving behind the heavier fraction, which often contains polynuclear aromatic (PNA) compounds. Some PNAs have caused skin cancer in animals after prolonged and repeated contact. As a reference, most weathered crude is similar to used motor oil in skin toxicity; prolonged and repeated skin contact should be avoided, but there is no cause for concern if some gets on the skin. The typical skin problems from excessive skin contact are drying and cracking from the defatting action of the oil itself or from the soap or hand cleaners used to remove the oil, and pustules (similar to boils) if the oil plugs the sweat glands in the skin

  7. Hormone response to bidirectional selection on social behavior.

    Amdam, Gro V; Page, Robert E; Fondrk, M Kim; Brent, Colin S

    2010-01-01

    Behavior is a quantitative trait determined by multiple genes. Some of these genes may have effects from early development and onward by influencing hormonal systems that are active during different life-stages leading to complex associations, or suites, of traits. Honey bees (Apis mellifera) have been used extensively in experiments on the genetic and hormonal control of complex social behavior, but the relationships between their early developmental processes and adult behavioral variation are not well understood. Bidirectional selective breeding on social food-storage behavior produced two honey bee strains, each with several sublines, that differ in an associated suite of anatomical, physiological, and behavioral traits found in unselected wild type bees. Using these genotypes, we document strain-specific changes during larval, pupal, and early adult life-stages for the central insect hormones juvenile hormone (JH) and ecdysteroids. Strain differences correlate with variation in female reproductive anatomy (ovary size), which can be influenced by JH during development, and with secretion rates of ecdysteroid from the ovaries of adults. Ovary size was previously assigned to the suite of traits of honey bee food-storage behavior. Our findings support that bidirectional selection on honey bee social behavior acted on pleiotropic gene networks. These networks may bias a bee's adult phenotype by endocrine effects on early developmental processes that regulate variation in reproductive traits. © 2010 Wiley Periodicals, Inc.

  8. Response to selection under controlled environment versus natural selection in diverse regions across Canada

    Red clover is a widely adaptable and productive forage legume species found in most temperate regions of the world. To date, specific selection techniques for identifying genotypes with superior persistence have not been successful in improving the general adaptation and the long-term persistence o...

  9. Food selection criteria for disaster response planning in urban societies.

    Wien, Michelle; Sabaté, Joan

    2015-05-12

    Nutrition professionals that have menu planning and disaster management responsibilities should consider factors that have transcended from ancient to current times, in addition to recognizing societal trends that have led to our current increased vulnerability in the event of a disaster. Hence, we proceeded to develop a set of "Disaster Response Diets" (DRDs) for use in urban societies inclusive of the aforementioned considerations. A three-phase multidimensional approach was used to identify food groups suitable for creating a set of DRDs. Phase One consisted of calculating the percent daily nutrient intake and Drewnowski's naturally nutrient rich (NNR) score for an individual or mean composite for one serving of food from 11 specific food groups. In Phase Two, in addition to nutrient density, the 11 food groups were evaluated and scored based on the following DRD planning criteria: storage and handling properties, preparation ease and, cultural acceptance/individual tolerance. During Phase Three, three DRDs were developed based upon the data retrieved from Phases one and two. In Phase One, the NNR scores ranged from 2.1 for fresh fruits to 28.1 for dry cereals, a higher score indicating a higher nutrient density. During Phase Two, a maximum score of 12 was possible based on appropriateness for a disaster situation. Five plant-based food groups (dry cereals, nuts, dried fruits, grains and legumes) achieved a score ranging between 7 and 12, whereas the five fresh food groups were deemed ineligible due to sanitation and perishability concerns. During Phase Three, three DRDs (milk-inclusive, milk-free and Grab-and-Go) were developed as benchmarks for disaster response planning. Plant-based DRDs are universally acceptable and tolerated across cultures and religions. Therefore, we suggest nutrition professionals consider using a plant-based approach for creating DRDs for public health institutions and organizations.

  10. What Is "Natural"? Consumer Responses to Selected Ingredients.

    Chambers, Edgar; Chambers, Edgar; Castro, Mauricio

    2018-04-23

    Interest in “natural” food has grown enormously over the last decade. Because the United States government has not set a legal definition for the term “natural”, customers have formed their own sensory perceptions and opinions on what constitutes natural. In this study, we examined 20 ingredients to determine what consumers consider to be natural. Using a national database, 630 consumers were sampled (50% male and 50% female) online, and the results were analyzed using percentages and chi-square tests. No ingredient was considered natural by more than 69% of respondents. We found evidence that familiarity may play a major role in consumers’ determination of naturalness. We also found evidence that chemical sounding names and the age of the consumer have an effect on whether an ingredient and potentially a food is considered natural. Interestingly, a preference towards selecting GMO (genetically modified organisms) foods had no significant impact on perceptions of natural.

  11. What Is “Natural”? Consumer Responses to Selected Ingredients

    Edgar Chambers

    2018-04-01

    Full Text Available Interest in “natural” food has grown enormously over the last decade. Because the United States government has not set a legal definition for the term “natural”, customers have formed their own sensory perceptions and opinions on what constitutes natural. In this study, we examined 20 ingredients to determine what consumers consider to be natural. Using a national database, 630 consumers were sampled (50% male and 50% female online, and the results were analyzed using percentages and chi-square tests. No ingredient was considered natural by more than 69% of respondents. We found evidence that familiarity may play a major role in consumers’ determination of naturalness. We also found evidence that chemical sounding names and the age of the consumer have an effect on whether an ingredient and potentially a food is considered natural. Interestingly, a preference towards selecting GMO (genetically modified organisms foods had no significant impact on perceptions of natural.

  12. What Is “Natural”? Consumer Responses to Selected Ingredients

    Chambers, Edgar; Castro, Mauricio

    2018-01-01

    Interest in “natural” food has grown enormously over the last decade. Because the United States government has not set a legal definition for the term “natural”, customers have formed their own sensory perceptions and opinions on what constitutes natural. In this study, we examined 20 ingredients to determine what consumers consider to be natural. Using a national database, 630 consumers were sampled (50% male and 50% female) online, and the results were analyzed using percentages and chi-square tests. No ingredient was considered natural by more than 69% of respondents. We found evidence that familiarity may play a major role in consumers’ determination of naturalness. We also found evidence that chemical sounding names and the age of the consumer have an effect on whether an ingredient and potentially a food is considered natural. Interestingly, a preference towards selecting GMO (genetically modified organisms) foods had no significant impact on perceptions of natural. PMID:29690627

  13. APC selectively mediates response to chemotherapeutic agents in breast cancer

    VanKlompenberg, Monica K.; Bedalov, Claire O.; Soto, Katia Fernandez; Prosperi, Jenifer R.

    2015-01-01

    The Adenomatous Polyposis Coli (APC) tumor suppressor is mutated or hypermethylated in up to 70 % of sporadic breast cancers depending on subtype; however, the effects of APC mutation on tumorigenic properties remain unexplored. Using the Apc Min/+ mouse crossed to the Polyoma middle T antigen (PyMT) transgenic model, we identified enhanced breast tumorigenesis and alterations in genes critical in therapeutic resistance independent of Wnt/β-catenin signaling. Apc mutation changed the tumor histopathology from solid to squamous adenocarcinomas, resembling the highly aggressive human metaplastic breast cancer. Mechanistic studies in tumor-derived cell lines demonstrated that focal adhesion kinase (FAK)/Src/JNK signaling regulated the enhanced proliferation downstream of Apc mutation. Despite this mechanistic information, the role of APC in mediating breast cancer chemotherapeutic resistance is currently unknown. We have examined the effect of Apc loss in MMTV-PyMT mouse breast cancer cells on gene expression changes of ATP-binding cassette transporters and immunofluorescence to determine proliferative and apoptotic response of cells to cisplatin, doxorubicin and paclitaxel. Furthermore we determined the added effect of Src or JNK inhibition by PP2 and SP600125, respectively, on chemotherapeutic response. We also used the Aldefluor assay to measure the population of tumor initiating cells. Lastly, we measured the apoptotic and proliferative response to APC knockdown in MDA-MB-157 human breast cancer cells after chemotherapeutic treatment. Cells obtained from MMTV-PyMT;Apc Min/+ tumors express increased MDR1 (multidrug resistance protein 1), which is augmented by treatment with paclitaxel or doxorubicin. Furthermore MMTV-PyMT;Apc Min/+ cells are more resistant to cisplatin and doxorubicin-induced apoptosis, and show a larger population of ALDH positive cells. In the human metaplastic breast cancer cell line MDA-MB-157, APC knockdown led to paclitaxel and cisplatin

  14. Disruptive Space Technology

    Benson, Jim

    2004-01-01

    In 1997 "The Innovator’s Dilemma" by Clayton M. Christensen became a popular book in the small satellite and launch vehicle communities. But like the weather, every one talks about “Disruptive Technology” but few do anything about it. In the ‘70s and ‘80s, people were looking for “Paradigm Shifts,” and since the resurrection of Donald Rumsfeld, a recent watchword has been “Transformational Technology.” But today’s buzzword is now “Responsive Space Systems.”

  15. Efficient Customer Selection for Sustainable Demand Response in Smart Grids

    Zois, Vasileios; Frincu, Marc; Chelmis, Charalambos; Saeed, Muhammad Rizwan; Prasanna, Viktor K.

    2014-11-03

    Regulating the power consumption to avoid peaks in demand is a common practice. Demand Response(DR) is being used by utility providers to minimize costs or ensure system reliability. Although it has been used extensively there is a shortage of solutions dealing with dynamic DR. Past attempts focus on minimizing the load demand without considering the sustainability of the reduced energy. In this paper an efficient algorithm is presented which solves the problem of dynamic DR scheduling. Data from the USC campus micro grid were used to evaluate the efficiency as well as the robustness of the proposed solution. The targeted energy reduction is achieved with a maximum average approximation error of ≈ 0.7%. Sustainability of the reduced energy is achieved with respect to the optimal available solution providing a maximum average error less than 0.6%. It is also shown that a solution is provided with a low computational cost fulfilling the requirements of dynamic DR.

  16. A role for VEGFR2 activation in endothelial responses caused by barrier disruptive OxPAPC concentrations.

    Anna A Birukova

    Full Text Available Oxidation products of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphatidylcholine (OxPAPC differentially modulate endothelial cell (EC barrier function in a dose-dependent fashion. Vascular endothelial growth factor receptor-2 (VEGFR2 is involved in the OxPAPC-induced EC inflammatory activation. This study examined a role of VEGFR2 in barrier dysfunction caused by high concentrations of OxPAPC and evaluated downstream signaling mechanisms resulting from the effect of OxPAPC in EC from pulmonary and systemic circulation.EC monolayer permeability in human pulmonary artery endothelial cells (HPAEC and human aortic endothelial cells (HAEC was monitored by changes in transendothelial electrical resistance (TER across EC monolayers. Actin cytoskeleton was examined by immunostaining with Texas Red labeled phalloidin. Phosphorylation of myosin light chains (MLC and VE-Cadherin was examined by Western blot and immunofluorescence techniques. The role of VEGFR2 in OxPAPC-induced permeability and cytoskeletal arrangement were determined using siRNA-induced VEGFR2 knockdown.Low OxPAPC concentrations (5-20 µg/ml induced a barrier protective response in both HPAEC and HAEC, while high OxPAPC concentrations (50-100 µg/ml caused a rapid increase in permeability; actin stress fiber formation and increased MLC phosphorylation were observed as early as 30 min after treatment. VEGFR2 knockdown dramatically decreased the amount of MLC phosphorylation and stress fiber formation caused by high OxPAPC concentrations with modest effects on the amount of VE-cadherin phosphorylation at Y(731. We present evidence that activation of Rho is involved in the OxPAPC/VEGFR2 mechanism of EC permeability induced by high OxPAPC concentrations. Knockdown of VEGFR2 did not rescue the early drop in TER but prevented further development of OxPAPC-induced barrier dysfunction.This study shows that VEGFR2 is involved in the delayed phase of EC barrier dysfunction caused by high Ox

  17. Genomic selection improves response to selection in resilience by exploiting genotype by environment interactions

    Mulder, Herman

    2016-01-01

    Genotype by environment interactions (GxE) are very common in livestock and hamper genetic improvement. On the other hand, GxE is a source of genetic variation: genetic variation in response to environment, e.g., environmental perturbations such as heat stress or disease. In livestock breeding,

  18. Response selection difficulty modulates the behavioral impact of rapidly learnt action effects.

    Uta eWolfensteller

    2014-12-01

    Full Text Available It is well established that we can pick up action effect associations when acting in a free-choice intentional mode. However, it is less clear whether and when action effect associations are learnt and actually affect behavior if we are acting in a forced-choice mode, applying a specific stimulus-response (S-R rule. In the present study, we investigated whether response selection difficulty imposed by S-R rules influences the initial rapid learning and the behavioral expression of previously learnt but weakly practiced action effect associations when those are re-activated by effect exposure. Experiment 1 showed that the rapid acquisition of action effect associations is not directly influenced by response selection difficulty. By contrast, the behavioral expression of re-activated action effect associations is prevented when actions are directly activated by highly over-learnt response cues and thus response selection difficulty is low. However, all three experiments showed that if response selection difficulty is sufficiently high during re-activation, the same action effect associations do influence behavior. Experiment 2 and 3 revealed that the effect of response selection difficulty cannot be fully reduced to giving action effects more time to prime an action, but seems to reflect competition during response selection. Finally, the present data suggest that when multiple novel rules are rapidly learnt in succession, which requires a lot of flexibility, action effect associations continue to influence behavior only if response selection difficulty is sufficiently high. Thus, response selection difficulty might modulate the impact of experiencing multiple learning episodes on action effect expression and learning, possibly via inducing different strategies.

  19. Selected physiotherapeutic techniques and immune response in low back pain

    Piotr Gawda

    2017-04-01

    Full Text Available Physiotherapy, as an element of medical rehabilitation, comprises such methods of function improvement as: massage, kinesiotherapy, physical therapy or manual therapy. In this area, medicine offers a wide range of treatment methods, practically at every stage of a patient’s recovery. Physiotherapy is used to enhance quality of life of people with disabilities, chronic diseases or after injuries, but also as a form of prevention of dysfunctions. The aim of the study  is to present the influence of physiotherapy of low back pain on factors of immune response based on literature review. Effectiveness of a given treatment is most easily noticeable in clinical practice. It is usually the patient who evaluates the efficiency of treatment, through experiencing less pain, easier performance of certain actions or overall better functioning in everyday life. Apart from registering the subjective experience of patients, the focus is on finding objective methods of evaluating effectiveness of physiotherapy and on attempts at scientific explanation of noticeable and perceptible influence of rehabilitation treatment. This also applies to the treatment of lumbar-sacral pain. The involvement of many inflammatory mediators such as nitric oxide, interleukins, matrix metalloproteinases, prostaglandin , tumor necrosis factor alpha and a group of cytokines. and a variety of cytokines have already been  identified in the dysfunction of this region.

  20. Macroeconomic implications of population ageing and selected policy responses.

    Bloom, David E; Chatterji, Somnath; Kowal, Paul; Lloyd-Sherlock, Peter; McKee, Martin; Rechel, Bernd; Rosenberg, Larry; Smith, James P

    2015-02-14

    Between now and 2030, every country will experience population ageing-a trend that is both pronounced and historically unprecedented. Over the past six decades, countries of the world had experienced only a slight increase in the share of people aged 60 years and older, from 8% to 10%. But in the next four decades, this group is expected to rise to 22% of the total population-a jump from 800 million to 2 billion people. Evidence suggests that cohorts entering older age now are healthier than previous ones. However, progress has been very uneven, as indicated by the wide gaps in population health (measured by life expectancy) between the worst (Sierra Leone) and best (Japan) performing countries, now standing at a difference of 36 years for life expectancy at birth and 15 years for life expectancy at age 60 years. Population ageing poses challenges for countries' economies, and the health of older populations is of concern. Older people have greater health and long-term care needs than younger people, leading to increased expenditure. They are also less likely to work if they are unhealthy, and could impose an economic burden on families and society. Like everyone else, older people need both physical and economic security, but the burden of providing these securities will be falling on a smaller portion of the population. Pension systems will be stressed and will need reassessment along with retirement policies. Health systems, which have not in the past been oriented toward the myriad health problems and long-term care needs of older people and have not sufficiently emphasised disease prevention, can respond in different ways to the new demographic reality and the associated changes in population health. Along with behavioural adaptations by individuals and businesses, the nature of such policy responses will establish whether population ageing will lead to major macroeconomic difficulties. Copyright © 2015 World Health Organization. Published by Elsevier Ltd

  1. Endocrine disruption effects in male and intersex roach (Rutilus rutilus, L.) from French rivers: An integrative approach based on subcellular to individual responses.

    Geraudie, Perrine; Gerbron, Marie; Minier, Christophe

    2017-09-01

    Among the chemicals found in the aquatic environment, some have been reported to interact with the endocrine system of organisms and have been identified as endocrine disrupting compounds. In this study, we have assessed the biological effects due to environmental estrogenic compounds in adult male roach (Rutilus rutilus). Wild fish were collected in the Seine River, and one of its affluent, the Epte River in Normandy, France and impacts on endocrine and reproductive functions have been assessed. This study provides innovative data on the intersex condition in wild fish that are crucial to understand estrogenic contamination impacts and maintenance of sustainable fish population. The biomarker responses found in fish from contaminated sites included high plasmatic vitellogenin concentrations, altered steroid levels, histopathological and up to 50% intersex fish among the male. However, the overall sex ratio of the roach population indicated sign of feminization with some sites showing only 20% of males. The chemical organic contamination at the different location sites has been characterized by the levels of PAHs, PCBs and phthalates and total estrogenic activity was measured by the YES in vitro assay. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Responses of Hexaplex (Murex) trunculus to selected pollutants

    Romeo, M.; Gharbi-Bouraoui, S.; Gnassia-Barelli, M.; Dellali, M.; Aissa, P.

    2006-01-01

    Cadmium, copper and zinc concentrations (in whole soft body and in tissues) were measured in Hexaplex trunculus collected from the Bizerta lagoon in Tunisia. An evaluation of the biological effects of the most toxic metals (cadmium and copper) and of two organics (carbofuran and lindane), present in the sediments of the Bizerta lagoon, was attempted by measuring biomarkers (acetylcholinesterase: AChE, catalase: CAT and glutathione S-transferase: GST activities) in animals experimentally exposed for 48 or 72 h. The concentration ranges as follows: Zn > Cu > Cd. Copper concentrations are highly variable (8.0 to 235 μg g -1 d.w.) whereas cadmium (range 1.35-4.86 μg g -1 ) and zinc (range 360-1320 μg g -1 ) concentrations are less variable. The digestive gland and the gill take up more metal than the muscle. AChE activity in H. trunculus is decreased by exposure to carbofuran or the mixture carbofuran and cadmium, in the digestive gland and muscle and by copper and by lindane in the digestive gland. AChE is generally inhibited by carbamates but some other compounds may also decrease this activity as observed in this paper. An increase in CAT activity associated with a decrease in GST activity is noted in the muscle of H. trunculus exposed to cadmium, to carbofuran and to the mixture of cadmium and carbofuran, and in the digestive gland of animals exposed to lindane. These pollutants may act upon glutathione and decrease the GST activity that cannot detoxify them and CAT activity has a protective effect. On the contrary, copper increases CAT and GST activities in the digestive gland of exposed gastropods; these enzymes seem to cooperate and play together their role of anti-oxidant enzymes. If H. trunculus is not a bioindicator species for metal concentrations, due to a high variability in metal concentrations, nevertheless the biochemical responses to pollutants (cadmium, copper, carbofuran and lindane) represented by AChE, CAT and GST activities may act as

  3. Conversion of homothallic yeast to heterothallism trough HO gene disruption

    Van Zyl, WH

    1993-04-01

    Full Text Available A simple method was developed for the conversion of homothallic Saccharomyces cerevisiae yeaststrains to heterothallism through HO gene disruption. An integrative ho:: neo disrupted allele was constructed by cloning a dominant selectable marker...

  4. Mapping the brain pathways of traumatic memory: inactivation of protein kinase M zeta in different brain regions disrupts traumatic memory processes and attenuates traumatic stress responses in rats.

    Cohen, Hagit; Kozlovsky, Nitsan; Matar, Michael A; Kaplan, Zeev; Zohar, Joseph

    2010-04-01

    Protein kinase M zeta (PKMzeta), a constitutively active isoform of protein kinase C, has been implicated in protein synthesis-dependent maintenance of long-term potentiation and memory storage in the brain. Recent studies reported that local application of ZIP, a membrane-permeant PKMzeta inhibitor, into the insular cortex (IC) of behaving rats abolished long-term memory of taste associations. This study assessed the long-term effects of local applications of ZIP microinjected immediately (1 h) or 10 days after predator scent stress exposure, in a controlled prospectively designed animal model for PTSD. Four brain structures known to be involved in memory processes and in anxiety were investigated: lateral ventricle (LV), dorsal hippocampus (DH), basolateral amygdala and IC. The outcome measures included behavior in an elevated plus maze and acoustic startle response 7 days after microinjection, and freezing behavior upon exposure to trauma-related cue 8 days after microinjection. Previously acquired/encoded memories associated with the IC were also assessed. Inactivation of PKMzeta in the LV or DH within 1h of exposure effectively reduced PTSD-like behavioral disruption and trauma cue response 8 days later. Inactivation of PKMzeta 10 days after exposure had equivalent effects only when administered in the IC. The effect was demonstrated to be specific for trauma memories, whereas previously acquired data were unaffected by the procedure. Predator scent related memories are located in different brain areas at different times beginning with an initial hippocampus-dependent consolidation process, and are eventually stored in the IC. These bring the IC to the forefront as a potential region of significance in processes related to traumatic stress-induced disorders. 2010 Elsevier B.V. and ECNP. All rights reserved.

  5. Neutrophil Influx and Chemokine Production during the Early Phases of the Antitumor Response to the Vascular Disrupting Agent DMXAA (ASA404

    Liang-Chuan S. Wang

    2009-08-01

    Full Text Available 5,6-Dimethylxanthenone-4-acetic acid (DMXAA acts through tumor vascular disruption and cytokine production and is the first of its class to enter phase 3 trials. We characterized leukocytes and cytokines in murine Colon 38 tumors before and after DMXAA treatment. Tumor mass declined 50% 24 hours after DMXAA administration, but the leukocyte count per gram of tumor increased threefold owing to a large influx of Ly6G+CD11b+F4/80−. cells with the morphology of neutrophils. However, B and T lymphocytes, natural killer cells, and macrophages in the tumor all decreased in numbers. Seven chemokines were substantially induced in the tumor, spleen, and serum 4 hours after DMXAA administration. Using cultured spleen cell subpopulations, CD11b+ cells (largely monocytes and macrophages were shown to be the primary producers of tumor necrosis factor á, interleukin 6 (IL-6, and macrophage inflammatory 1α (MIP-1α. CD49b+ natural killer cells produced IP-10, whereas CD45R+ B lymphocytes produced regulated upon activation normal T cell express sequence. T lymphocytes were not major producers of cytokines in the response to DMXAA. Murine peripheral blood leukocytes (PBLs produced a similar panel of cytokines in culture to that detected in mouse serum after DMXAA treatment. Cytokines in human PBL cultures were subsequently measured with the aim of identifying potential serum markers of the human response to DMXAA. IP-10 (P < .001, monocyte chemoattractant protein 1 (P < .001, and sCD40L (P < .01 were decreased, whereas IL-8 (P < .001 and MIP-1α (P = .03 were increased in DMXAA-treated compared with untreated PBL cultures from a group of 12 donors.

  6. A strong response to selection on mass-independent maximal metabolic rate without a correlated response in basal metabolic rate.

    Wone, B W M; Madsen, P; Donovan, E R; Labocha, M K; Sears, M W; Downs, C J; Sorensen, D A; Hayes, J P

    2015-04-01

    Metabolic rates are correlated with many aspects of ecology, but how selection on different aspects of metabolic rates affects their mutual evolution is poorly understood. Using laboratory mice, we artificially selected for high maximal mass-independent metabolic rate (MMR) without direct selection on mass-independent basal metabolic rate (BMR). Then we tested for responses to selection in MMR and correlated responses to selection in BMR. In other lines, we antagonistically selected for mice with a combination of high mass-independent MMR and low mass-independent BMR. All selection protocols and data analyses included body mass as a covariate, so effects of selection on the metabolic rates are mass adjusted (that is, independent of effects of body mass). The selection lasted eight generations. Compared with controls, MMR was significantly higher (11.2%) in lines selected for increased MMR, and BMR was slightly, but not significantly, higher (2.5%). Compared with controls, MMR was significantly higher (5.3%) in antagonistically selected lines, and BMR was slightly, but not significantly, lower (4.2%). Analysis of breeding values revealed no positive genetic trend for elevated BMR in high-MMR lines. A weak positive genetic correlation was detected between MMR and BMR. That weak positive genetic correlation supports the aerobic capacity model for the evolution of endothermy in the sense that it fails to falsify a key model assumption. Overall, the results suggest that at least in these mice there is significant capacity for independent evolution of metabolic traits. Whether that is true in the ancestral animals that evolved endothermy remains an important but unanswered question.

  7. Network Formation under the Threat of Disruption

    Hoyer, B.

    2013-01-01

    The studies in this thesis are focused on the impact the presence of a network disruptor has on network formation models. In particular, we build two theoretical models to study the effect of network disruption on network formation and test the effect network disruption has on equilibrium selection

  8. Metabolomic analysis of the selection response of Drosophila melanogaster to environmental stress

    Malmendal, Anders; Sørensen, Jesper Givskov; Overgaard, Johannes

    2013-01-01

    -regulated in response to selection for some of the stresses in this study. Overall, the results illustrate that selection markedly alters the metabolite profile and that the coupling between different levels of biological organization indeed is present though not very strong for stress selection at this level......We investigated the global metabolite response to artificial selection for tolerance to stressful conditions such as cold, heat, starvation, and desiccation, and for longevity in Drosophila melanogaster. Our findings were compared to data from other levels of biological organization, including gene...... expression, physiological traits, and organismal stress tolerance phenotype. Overall, we found that selection for environmental stress tolerance changes the metabolomic (1)H NMR fingerprint largely in a similar manner independent of the trait selected for, indicating that experimental evolution led...

  9. Directional Selection for Specific Sheep Cell Antibody Responses Affects Natural Rabbit Agglutinins of Chickens

    Cotter, P.F.; Ayoub, J.; Parmentier, H.K.

    2005-01-01

    Agglutination data from generations 8 through 19 indicate that bidirectional selection for specific SRBC antibody responses was successful in a line cross of ISA × Warren medium heavy layers. After 11 generations titers of the high SRBC selected line (H line) were nearly 1:32,000; those of the low

  10. Prior Cocaine Self-Administration Increases Response-Outcome Encoding That Is Divorced from Actions Selected in Dorsal Lateral Striatum.

    Burton, Amanda C; Bissonette, Gregory B; Zhao, Adam C; Patel, Pooja K; Roesch, Matthew R

    2017-08-09

    Dorsal lateral striatum (DLS) is a highly associative structure that encodes relationships among environmental stimuli, behavioral responses, and predicted outcomes. DLS is known to be disrupted after chronic drug abuse; however, it remains unclear what neural signals in DLS are altered. Current theory suggests that drug use enhances stimulus-response processing at the expense of response-outcome encoding, but this has mostly been tested in simple behavioral tasks. Here, we investigated what neural correlates in DLS are affected by previous cocaine exposure as rats performed a complex reward-guided decision-making task in which predicted reward value was independently manipulated by changing the delay to or size of reward associated with a response direction across a series of trial blocks. After cocaine self-administration, rats exhibited stronger biases toward higher-value reward and firing in DLS more strongly represented action-outcome contingencies independent from actions subsequently taken rather than outcomes predicted by selected actions (chosen-outcome contingencies) and associations between stimuli and actions (stimulus-response contingencies). These results suggest that cocaine self-administration strengthens action-outcome encoding in rats (as opposed to chosen-outcome or stimulus-response encoding), which abnormally biases behavior toward valued reward when there is a choice between two options during reward-guided decision-making. SIGNIFICANCE STATEMENT Current theories suggest that the impaired decision-making observed in individuals who chronically abuse drugs reflects a decrease in goal-directed behaviors and an increase in habitual behaviors governed by neural representations of response-outcome (R-O) and stimulus-response associations, respectively. We examined the impact that prior cocaine self-administration had on firing in dorsal lateral striatum (DLS), a brain area known to be involved in habit formation and affected by drugs of abuse

  11. Stimulation of the subthalamic region facilitates the selection and inhibition of motor responses in Parkinson's disease

    van den Wildenberg, Wery P. M.; van Boxtel, Geert J. M.; van der Molen, Maurits W.; Bosch, D. Andries; Speelman, Johannes D.; Brunia, Cornelis H. M.

    2006-01-01

    The aim of the present study was to specify the involvement of the basal ganglia in motor response selection and response inhibition. Two samples were studied. The first sample consisted of patients diagnosed with Parkinson's disease (PD) who received deep-brain stimulation (DBS) of the subthalamic

  12. Diminished performance on response-selection tasks in type-2 diabetes

    H.A. Keizer; P.C. Groot; J.J. Adam; dr. Lars B. Borghouts

    2003-01-01

    Comparisons of visual perception, response-selection, and response-execution performance were made between Type 2 diabetes mellitus patients and a matched nondiabetic control group. 10 well-controlled male patients with Type 2 diabetes without diabetic complications (M age 58 yr.) and an age and

  13. Root-secreted allelochemical in the noxious weed Phragmites australis deploys a reactive oxygen species response and microtubule assembly disruption to execute rhizotoxicity.

    Rudrappa, Thimmaraju; Bonsall, Justin; Gallagher, John L; Seliskar, Denise M; Bais, Harsh P

    2007-10-01

    Phragmites australis is considered the most invasive plant in marsh and wetland communities in the eastern United States. Although allelopathy has been considered as a possible displacing mechanism in P. australis, there has been minimal success in characterizing the responsible allelochemical. We tested the occurrence of root-derived allelopathy in the invasiveness of P. australis. To this end, root exudates of two P. australis genotypes, BB (native) and P38 (an exotic) were tested for phytotoxicity on different plant species. The treatment of the susceptible plants with P. australis root exudates resulted in acute rhizotoxicity. It is interesting to note that the root exudates of P38 were more effective in causing root death in susceptible plants compared to the native BB exudates. The active ingredient in the P. australis exudates was identified as 3,4,5-trihydroxybenzoic acid (gallic acid). We tested the phytotoxic efficacy of gallic acid on various plant systems, including the model plant Arabidopsis thaliana. Most tested plants succumbed to the gallic acid treatment with the exception of P. australis itself. Mechanistically, gallic acid treatment generated elevated levels of reactive oxygen species (ROS) in the treated plant roots. Furthermore, the triggered ROS mediated the disruption of the root architecture of the susceptible plants by damaging the microtubule assembly. The study also highlights the persistence of the exuded gallic acid in P. australis's rhizosphere and its inhibitory effects against A. thaliana in the soil. In addition, gallic acid demonstrated an inhibitory effect on Spartina alterniflora, one of the salt marsh species it successfully invades.

  14. Monocrotaline pyrrole-induced megalocytosis of lung and breast epithelial cells: Disruption of plasma membrane and Golgi dynamics and an enhanced unfolded protein response

    Mukhopadhyay, Somshuvra; Shah, Mehul; Patel, Kirit; Sehgal, Pravin B.

    2006-01-01

    The pyrrolizidine alkaloid monocrotaline (MCT) initiates pulmonary hypertension by inducing a 'megalocytosis' phenotype in target pulmonary arterial endothelial, smooth muscle and Type II alveolar epithelial cells. In cultured endothelial cells, a single exposure to the pyrrolic derivative of monocrotaline (MCTP) results in large cells with enlarged endoplasmic reticulum (ER) and Golgi and increased vacuoles. However, these cells fail to enter mitosis. Largely based upon data from endothelial cells, we proposed earlier that a disruption of the trafficking and mitosis-sensor functions of the Golgi (the 'Golgi blockade' hypothesis) may represent the subcellular mechanism leading to MCTP-induced megalocytosis. In the present study, we investigated the applicability of the Golgi blockade hypothesis to epithelial cells. MCTP induced marked megalocytosis in cultures of lung A549 and breast MCF-7 cells. This was associated with a change in the distribution of the cis-Golgi scaffolding protein GM130 from a discrete juxtanuclear localization to a circumnuclear distribution consistent with an anterograde block of GM130 trafficking to/through the Golgi. There was also a loss of plasma membrane caveolin-1 and E-cadherin, cortical actin together with a circumnuclear accumulation of clathrin heavy chain (CHC) and α-tubulin. Flotation analyses revealed losses/alterations in the association of caveolin-1, E-cadherin and CHC with raft microdomains. Moreover, megalocytosis was accompanied by an enhanced unfolded protein response (UPR) as evidenced by nuclear translocation of Ire1α and glucose regulated protein 58 (GRP58/ER-60/ERp57) and a circumnuclear accumulation of PERK kinase and protein disulfide isomerase (PDI). These data further support the hypothesis that an MCTP-induced Golgi blockade and enhanced UPR may represent the subcellular mechanism leading to enlargement of ER and Golgi and subsequent megalocytosis

  15. Sexual selection predicts advancement of avian spring migration in response to climate change

    Spottiswoode, Claire N; Tøttrup, Anders P; Coppack, Timothy

    2006-01-01

    Global warming has led to earlier spring arrival of migratory birds, but the extent of this advancement varies greatly among species, and it remains uncertain to what degree these changes are phenotypically plastic responses or microevolutionary adaptations to changing environmental conditions. We...... suggest that sexual selection could help to understand this variation, since early spring arrival of males is favoured by female choice. Climate change could weaken the strength of natural selection opposing sexual selection for early migration, which would predict greatest advancement in species...... in the timing of first-arriving individuals, suggesting that selection has not only acted on protandrous males. These results suggest that sexual selection may have an impact on the responses of organisms to climate change, and knowledge of a species' mating system might help to inform attempts at predicting...

  16. Monitoring-induced disruption in skilled typewriting.

    Snyder, Kristy M; Logan, Gordon D

    2013-10-01

    It is often disruptive to attend to the details of one's expert performance. The current work presents four experiments that utilized a monitor to report protocol to evaluate the sufficiency of three accounts of monitoring-induced disruption. The inhibition hypothesis states that disruption results from costs associated with preparing to withhold inappropriate responses. The dual-task hypothesis states that disruption results from maintaining monitored information in working memory. The implicit-explicit hypothesis states that disruption results from explicitly monitoring details of performance that are normally implicit. The findings suggest that all three hypotheses are sufficient to produce disruption, but inhibition and dual-task costs are not necessary. Experiment 1 showed that monitoring to report was disruptive even when there was no requirement to inhibit. Experiment 2 showed that maintaining information in working memory caused some disruption but much less than monitoring to report. Experiment 4 showed that monitoring to inhibit was more disruptive than monitoring to report, suggesting that monitoring is more disruptive when it is combined with other task requirements, such as inhibition. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  17. Selective laser melting of Ni-rich NiTi: selection of process parameters and the superelastic response

    Shayesteh Moghaddam, Narges; Saedi, Soheil; Amerinatanzi, Amirhesam; Saghaian, Ehsan; Jahadakbar, Ahmadreza; Karaca, Haluk; Elahinia, Mohammad

    2018-03-01

    Material and mechanical properties of NiTi shape memory alloys strongly depend on the fabrication process parameters and the resulting microstructure. In selective laser melting, the combination of parameters such as laser power, scanning speed, and hatch spacing determine the microstructural defects, grain size and texture. Therefore, processing parameters can be adjusted to tailor the microstructure and mechanical response of the alloy. In this work, NiTi samples were fabricated using Ni50.8Ti (at.%) powder via SLM PXM by Phenix/3D Systems and the effects of processing parameters were systematically studied. The relationship between the processing parameters and superelastic properties were investigated thoroughly. It will be shown that energy density is not the only parameter that governs the material response. It will be shown that hatch spacing is the dominant factor to tailor the superelastic response. It will be revealed that with the selection of right process parameters, perfect superelasticity with recoverable strains of up to 5.6% can be observed in the as-fabricated condition.

  18. Sex differences in immune responses: Hormonal effects, antagonistic selection, and evolutionary consequences.

    Roved, Jacob; Westerdahl, Helena; Hasselquist, Dennis

    2017-02-01

    Males and females differ in both parasite load and the strength of immune responses and these effects have been verified in humans and other vertebrates. Sex hormones act as important modulators of immune responses; the male sex hormone testosterone is generally immunosuppressive while the female sex hormone estrogen tends to be immunoenhancing. Different sets of T-helper cells (Th) have important roles in adaptive immunity, e.g. Th1 cells trigger type 1 responses which are primarily cell-mediated, and Th2 cells trigger type 2 responses which are primarily humoral responses. In our review of the literature, we find that estrogen and progesterone enhance type 2 and suppress type 1 responses in females, whereas testosterone suppresses type 2 responses and shows an inconsistent pattern for type 1 responses in males. When we combine these patterns of generally immunosuppressive and immunoenhancing effects of the sex hormones, our results imply that the sex differences in immune responses should be particularly strong in immune functions associated with type 2 responses, and less pronounced with type 1 responses. In general the hormone-mediated sex differences in immune responses may lead to genetic sexual conflicts on immunity. Thus, we propose the novel hypothesis that sexually antagonistic selection may act on immune genes shared by the sexes, and that the strength of this sexually antagonistic selection should be stronger for type 2- as compared with type 1-associated immune genes. Finally, we put the consequences of sex hormone-induced effects on immune responses into behavioral and ecological contexts, considering social mating system, sexual selection, geographical distribution of hosts, and parasite abundance. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Assessment of skin barrier function and biochemical changes of ex vivo human skin in response to physical and chemical barrier disruption.

    Döge, Nadine; Avetisyan, Araks; Hadam, Sabrina; Pfannes, Eva Katharina Barbosa; Rancan, Fiorenza; Blume-Peytavi, Ulrike; Vogt, Annika

    2017-07-01

    Topical dermatotherapy is intended to be used on diseased skin. Novel drug delivery systems even address differences between intact and diseased skin underlining the need for pre-clinical assessment of different states of barrier disruption. Herein, we studied how short-term incubation in culture media compared to incubation in humidified chambers affects human skin barrier function and viability. On both models we assessed different types and intensities of physical and chemical barrier disruption methods with regard to structural integrity, biophysical parameters and cytokine levels. Tissue degeneration and proliferative activity limited the use of tissue cultures to 48h. Viability is better preserved in cultured tissue. Tape-stripping (50×TS) and 4h sodium lauryl sulfate (SLS) pre-treatment were identified as highly reproducible and effective procedures for barrier disruption. Transepidermal water loss (TEWL) values reproducibly increased with the intensity of disruption while sebum content and skin surface pH were of limited value. Interleukin (IL)-6/8 and various chemokines and proteases were increased in tape-stripped skin which was more pronounced in SLS-treated skin tissue extracts. Thus, albeit limited to 48h, cultured full-thickness skin maintained several barrier characteristics and responded to different intensities of barrier disruption. Potentially, these models can be used to assess pre-clinically the efficacy and penetration of anti-inflammatory compounds. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Genetic and Genomic Response to Selection for Food Consumption in Drosophila melanogaster

    Garlapow, Megan E.; Everett, Logan J.; Zhou, Shanshan; Gearhart, Alexander W.; Fay, Kairsten A.; Huang, Wen; Morozova, Tatiana V.; Arya, Gunjan H.; Turlapati, Lavanya; Armour, Genevieve St.; Hussain, Yasmeen N.; McAdams, Sarah E.; Fochler, Sophia; Mackay, Trudy F. C.

    2016-01-01

    Food consumption is an essential component of animal fitness; however, excessive food intake in humans increases risk for many diseases. The roles of neuroendocrine feedback loops, food sensing modalities, and physiological state in regulating food intake are well understood, but not the genetic basis underlying variation in food consumption. Here, we applied ten generations of artificial selection for high and low food consumption in replicate populations of Drosophila melanogaster. The phenotypic response to selection was highly asymmetric, with significant responses only for increased food consumption and minimal correlated responses in body mass and composition. We assessed the molecular correlates of selection responses by DNA and RNA sequencing of the selection lines. The high and low selection lines had variants with significantly divergent allele frequencies within or near 2,081 genes and 3,526 differentially expressed genes in one or both sexes. A total of 519 genes were both genetically divergent and differentially expressed between the divergent selection lines. We performed functional analyses of the effects of RNAi suppression of gene expression and induced mutations for 27 of these candidate genes that have human orthologs and the strongest statistical support, and confirmed that 25 (93%) affected the mean and/or variance of food consumption. PMID:27704301

  1. Phenotypic selection in natural populations: what limits directional selection?

    Kingsolver, Joel G; Diamond, Sarah E

    2011-03-01

    Studies of phenotypic selection document directional selection in many natural populations. What factors reduce total directional selection and the cumulative evolutionary responses to selection? We combine two data sets for phenotypic selection, representing more than 4,600 distinct estimates of selection from 143 studies, to evaluate the potential roles of fitness trade-offs, indirect (correlated) selection, temporally varying selection, and stabilizing selection for reducing net directional selection and cumulative responses to selection. We detected little evidence that trade-offs among different fitness components reduced total directional selection in most study systems. Comparisons of selection gradients and selection differentials suggest that correlated selection frequently reduced total selection on size but not on other types of traits. The direction of selection on a trait often changes over time in many temporally replicated studies, but these fluctuations have limited impact in reducing cumulative directional selection in most study systems. Analyses of quadratic selection gradients indicated stabilizing selection on body size in at least some studies but provided little evidence that stabilizing selection is more common than disruptive selection for most traits or study systems. Our analyses provide little evidence that fitness trade-offs, correlated selection, or stabilizing selection strongly constrains the directional selection reported for most quantitative traits.

  2. Transient response of nonideal ion-selective microchannel-nanochannel devices

    Leibowitz, Neta; Schiffbauer, Jarrod; Park, Sinwook; Yossifon, Gilad

    2018-04-01

    We report evidence of variation in ion selectivity of a fabricated microchannel-nanochannel device resulting in the appearance of a distinct local maximum in the overlimiting chronopotentiometric response. In this system consisting of shallow microchannels joined by a nanochannel, viscous shear at the microchannel walls suppresses the electro-osmotic instability and prevents any associated contribution to the nonmonotonic response. Thus, this response is primarily electrodiffusive. Numerical simulations indicate that concentration polarization develops not only within the microchannel but also within the nanochannel itself, with a local voltage maximum in the chronopotentiometric response correlated with interfacial depletion and having the classic i-2 Sands time dependence. Furthermore, the occurrence of the local maxima is correlated with the change in selectivity due to internal concentration polarization. Understanding the transient nonideal permselective response is essential for obtaining fundamental insight and for optimizing efficient operation of practical fabricated nanofluidic and membrane devices.

  3. Evidence for selection in response to radiation exposure: Pinus sylvestris in the Chernobyl exclusion zone

    Kuchma, Oleksandra; Finkeldey, Reiner

    2011-01-01

    Changes of genetic structures due to viability selection are likely to occur in populations exposed to rapidly and extremely changing environmental conditions after catastrophic events. However, very little is known about the extent of selective responses and in particular the proportion of the genome involved in putatively adaptive reactions for non-model plants. We used amplified fragment length polymorphisms (AFLPs) in order to investigate genetic differences between pine (Pinus sylvestris) trees which were partially exposed to extreme environmental conditions. Genetic variation patterns of pines exposed to high radiation in the Chernobyl exclusion zone with or without phenotypic stress symptoms were compared to control trees with a similar origin. Six percent of the investigated loci (15 of 222 loci) were identified as candidates for selective responses. Moderate differentiation was observed between groups of trees showing either weak or strong phenotypic responses to high radiation levels. - Highlights: → Genetic variation patterns of pines exposed to high radiation were investigated. → Pines with or without phenotypic stress symptoms were compared to control trees. → AFLP markers were used to reveal evidences of selection processes. → 15 of 222 loci are identified as candidates for selective responses. → Moderate differentiation is observed between irradiated and control trees. - Genetic responses to the exposure of trees to radiation in the Chernobyl zone may involve adaptive changes at a comparatively large part of the genome.

  4. Disruption studies on ASDEX upgrade

    Pautasso, G.; Egorov, S.; Finken, K.H.

    2003-01-01

    Disruptions generate large thermal and mechanical stresses on the tokamak components and are occasionally responsible for damages to the machine. For a future reactor disruptions have a significant impact on the design since all loading conditions must be analyzed in accordance with stricter design criteria (due to safety or difficult maintenance). Therefore the uncertainties affecting the predicted stresses must be reduced as much as possible with a more comprehensive set of measurements and analyses in this generation of experimental machines, and avoidance/predictive methods must be developed further. Disruption studies on ASDEX Upgrade are focused on these subjects, namely on: (1) understanding the physical mechanisms leading to this phenomenon in order to learn to avoid it or to predict its occurrence and to mitigate its effects; (2) analyzing the effects of disruptions on the machine to determine the functional dependence of the thermal and mechanical loads upon the discharge parameters. This allows, firstly, to dimension or reinforce the machine components to withstand these loads and, secondly, to extrapolate them to tokamaks still in the design phase; (3) learning to mitigate the consequence of disruptions, i.e. thermal loads, mechanical forces and runaways with injection of impurity pellets or gas. This paper is focused on most recent results concerning points, i.e. on the analysis of the degree of asymmetry of the forces and on the use of impurity puff for mitigation

  5. Categorization difficulty modulates the mediated route for response selection in task switching.

    Schneider, Darryl W

    2017-12-22

    Conflict during response selection in task switching is indicated by the response congruency effect: worse performance for incongruent targets (requiring different responses across tasks) than for congruent targets (requiring the same response). The effect can be explained by dual-task processing in a mediated route for response selection, whereby targets are categorized with respect to both tasks. In the present study, the author tested predictions for the modulation of response congruency effects by categorization difficulty derived from a relative-speed-of-processing hypothesis. Categorization difficulty was manipulated for the relevant and irrelevant task dimensions in a novel spatial task-switching paradigm that involved judging the locations of target dots in a grid, without repetition of dot configurations. Response congruency effects were observed and they varied systematically with categorization difficulty (e.g., being larger when irrelevant categorization was easy than when it was hard). These results are consistent with the relative-speed-of-processing hypothesis and suggest that task-switching models that implement variations of the mediated route for response selection need to address the time course of categorization.

  6. Testing for a genetic response to sexual selection in a wild Drosophila population.

    Gosden, T P; Thomson, J R; Blows, M W; Schaul, A; Chenoweth, S F

    2016-06-01

    In accordance with the consensus that sexual selection is responsible for the rapid evolution of display traits on macroevolutionary scales, microevolutionary studies suggest sexual selection is a widespread and often strong form of directional selection in nature. However, empirical evidence for the contemporary evolution of sexually selected traits via sexual rather than natural selection remains weak. In this study, we used a novel application of quantitative genetic breeding designs to test for a genetic response to sexual selection on eight chemical display traits from a field population of the fly, Drosophila serrata. Using our quantitative genetic approach, we were able to detect a genetically based difference in means between groups of males descended from fathers who had either successfully sired offspring or were randomly collected from the same wild population for one of these display traits, the diene (Z,Z)-5,9-C27 : 2 . Our experimental results, in combination with previous laboratory studies on this system, suggest that both natural and sexual selection may be influencing the evolutionary trajectories of these traits in nature, limiting the capacity for a contemporary evolutionary response. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

  7. Direct and indirect selection responses for seed yield and its components in

    rasoul dehghan

    2017-06-01

    Full Text Available Breeding based on selection indices is an effective method for improving complex traits such as yield. To assess the efficiency of different selection method, 83 exotic along with 17 Iranian safflower genotypes were evaluated at the research farm of Isfahan University of Technology using 10×10 simple lattice design with three replications in 2011. In this study, the selection indices of Smith-Hazel and Pesek-Baker were determined based on the number of capitulum per plant, number of seeds per capitulum and 1000-seed weight. Also response to selection and relative selection efficiency were estimated for traits under study and seed yield. The highest estimated selection efficiency for genetic improvement of seed yield was obtained via selection for number of capitulum per plant. Therefore, this trait can be used as an appropriate selection criterion for improvement of seed yield. The results showed that seed yield was highly correlated with each of these indices and the estimated efficiency of indirect selection via these indices was relatively high. Thus, it seems that these selection indices can be effectively used for seed yield improvement. Results of present study showed that the efficiency of Smith-Hazel indices for simultaneous improvement of number of capitulum per plant, number of seeds per capitulum and 1000-seed weight was higher than that of Pesek-Baker index.

  8. Transcriptional analysis of porcine intestinal mucosa infected with Salmonella Typhimurium revealed a massive inflammatory response and disruption of bile acid absorption in ileum

    Uribe, Juber Herrera; Collado-Romero, Melania; Zaldívar-López, Sara

    2016-01-01

    -regulated genes of the FXR pathway (e.g., NR1H4, FABP6, APOA1, SLC10A2), indicating disruption of the bile acid absorption in ileum. This result was confirmed by decreased high-density lipoprotein cholesterol in serum of infected pigs. Ileal inflammatory gene expression changes peaked at 2 dpi and tended...

  9. Site quality in Appalachian hardwoods: the biological and economic response under selection silviculture

    Orris D. McCauley; George R., Jr. Trimble

    1975-01-01

    The relative or percentage value response after 12 years of selective cutting practices on low- and high-quality sites in Appalachian hardwoods amounted to a 119-percent increase on the low-quality site and 145 percent on the high-quality site. The absolute value or actual dollar response, on the other hand, showed that the low-quality site increased in value only $76/...

  10. Variance components and selection response for feather-pecking behavior in laying hens.

    Su, G; Kjaer, J B; Sørensen, P

    2005-01-01

    Variance components and selection response for feather pecking behavior were studied by analyzing the data from a divergent selection experiment. An investigation indicated that a Box-Cox transformation with power lambda = -0.2 made the data approximately normally distributed and gave the best fit for the model. Variance components and selection response were estimated using Bayesian analysis with Gibbs sampling technique. The total variation was rather large for the investigated traits in both the low feather-pecking line (LP) and the high feather-pecking line (HP). Based on the mean of marginal posterior distribution, in the Box-Cox transformed scale, heritability for number of feather pecking bouts (FP bouts) was 0.174 in line LP and 0.139 in line HP. For number of feather-pecking pecks (FP pecks), heritability was 0.139 in line LP and 0.105 in line HP. No full-sib group effect and observation pen effect were found in the 2 traits. After 4 generations of selection, the total response for number of FP bouts in the transformed scale was 58 and 74% of the mean of the first generation in line LP and line HP, respectively. The total response for number of FP pecks was 47 and 46% of the mean of the first generation in line LP and line HP, respectively. The variance components and the realized selection response together suggest that genetic selection can be effective in minimizing FP behavior. This would be expected to reduce one of the major welfare problems in laying hens.

  11. Simulated selection responses for breeding programs including resistance and resilience to parasites in Creole goats.

    Gunia, M; Phocas, F; Gourdine, J-L; Bijma, P; Mandonnet, N

    2013-02-01

    The Creole goat is a local breed used for meat production in Guadeloupe (French West Indies). As in other tropical countries, improvement of parasite resistance is needed. In this study, we compared predicted selection responses for alternative breeding programs with or without parasite resistance and resilience traits. The overall breeding goal included traits for production, reproduction, and parasite resilience and resistance to ensure a balanced selection outcome. The production traits were BW and dressing percentage (DP). The reproduction trait was fertility (FER), which was the number of doe kiddings per mating. The resistance trait was worm fecal egg count (FEC), which is a measurement of the number of gastro-intestinal parasite eggs found in the feces. The resilience trait was the packed cell volume (PCV), which is a measurement of the volume of red blood cells in the blood. Dressing percentage, BW, and FEC were measured at 11 mo of age, which is the mating or selling age. Fertility and PCV were measured on females at each kidding period. The breeding program accounting for the overall breeding goal and a selection index including all traits gave annual selection responses of 800 g for BW, 3.75% for FER, 0.08% for DP, -0.005 ln(eggs/g) for FEC, and 0.28% for PCV. The expected selection responses for BW and DP in this breeding program were reduced by 2% and 6%, respectively, compared with a breeding program not accounting for FEC and PCV. The overall breeding program, proposed for the Creole breed, offers the best breeding strategy in terms of expected selection responses, making it possible to improve all traits together. It offers a good balance between production and adaptation traits and may present some interest for the selection of other goat breeds in the tropics.

  12. Tree regeneration response to the group selection method in southern Indiana

    Dale R. Weigel; George R. Parker

    1997-01-01

    Tree regeneration response following the use of the group selection method was studied within 36 group openings on the Naval Surface Warfare Center, Crane Division in south central Indiana. Two different aspects and three time periods since cutting were examined. The objectives were to determine whether aspect, age, species group, location within the opening, or their...

  13. Blindness and Selective Mutism: One Student's Response to Voice-Output Devices

    Holley, Mary; Johnson, Ashli; Herzberg, Tina

    2014-01-01

    This case study was designed to measure the response of one student with blindness and selective mutism to the intervention of voice-output devices across two years and two different teachers in two instructional settings. Before the introduction of the voice output devices, the student did not choose to communicate using spoken language or…

  14. The effect of size-selective samplers (cyclones) on XRD response

    Pretorius, CJ

    2011-07-01

    Full Text Available The study evaluated five size-selective samplers used in the South African mining industry to determine how their performance affects the X-ray powder diffraction (XRD) response when respirable dust samples are analysed for quartz using direct...

  15. Simulated selection responses for breeding programs including resistance and resilience to parasites in Creole goats

    Gunia, M.; Phocas, F.; Gourdine, J.L.; Bijma, P.; Mandonnet, N.

    2013-01-01

    The Creole goat is a local breed used for meat production in Guadeloupe (French West Indies). As in other tropical countries, improvement of parasite resistance is needed. In this study, we compared predicted selection responses for alternative breeding programs with or without parasites resistance

  16. The effects of testosterone on immune function in quail selected for divergent plasma corticosterone response.

    Roberts, Mark L; Buchanan, Katherine L; Evans, Matthew R; Marin, Raul H; Satterlee, Daniel G

    2009-10-01

    The immunocompetence handicap hypothesis (ICHH) suggests that the male sex hormone testosterone has a dual effect; it controls the development and expression of male sexually selected signals, and it suppresses the immune system. Therefore only high quality males are able to fully express secondary sexual traits because only they can tolerate the immunosuppressive qualities of testosterone. A modified version of the ICHH suggests that testosterone causes immunosuppression indirectly by increasing the stress hormone corticosterone (CORT). Lines of Japanese quail (Coturnix japonica) selected for divergent responses in levels of plasma CORT were used to test these hypotheses. Within each CORT response line (as well as in a control stock) we manipulated levels of testosterone in castrated quail by treatment with zero (sham), low or high testosterone implants, before testing the birds' humoral immunity and phytohaemagglutinin (PHA)-induced immune response, as well as body condition. The PHA-induced response was not significantly affected by CORT selected line, testosterone treatment or their interaction. There was, however, a significant effect of CORT line on humoral immunity in that the control birds exhibited the greatest antibody production, but there was no significant effect of testosterone manipulation on humoral immunity. The males in the sham implant treatment group had significantly greater mass than the males in the high testosterone group, suggesting a negative effect of high testosterone on general body condition. We discuss these results in the context of current hypotheses in the field of sexual selection.

  17. Advertising to Italian English Bilinguals in Australia: Attitudes and Response to Language Selection

    Santello, Marco

    2015-01-01

    This article explores attitudes and response to language selection in advertising targeting Italian bilinguals who belong to a defined speech community. The research builds upon (i) research on multilingual advertising by investigating its attitudinal correlates, and (ii) studies on advertising to bilinguals through the verification of the…

  18. Dissociating action-effect activation and effect-based response selection.

    Schwarz, Katharina A; Pfister, Roland; Wirth, Robert; Kunde, Wilfried

    2018-05-25

    Anticipated action effects have been shown to govern action selection and initiation, as described in ideomotor theory, and they have also been demonstrated to determine crosstalk between different tasks in multitasking studies. Such effect-based crosstalk was observed not only in a forward manner (with a first task influencing performance in a following second task) but also in a backward manner (the second task influencing the preceding first task), suggesting that action effect codes can become activated prior to a capacity-limited processing stage often denoted as response selection. The process of effect-based response production, by contrast, has been proposed to be capacity-limited. These observations jointly suggest that effect code activation can occur independently of effect-based response production, though this theoretical implication has not been tested directly at present. We tested this hypothesis by employing a dual-task set-up in which we manipulated the ease of effect-based response production (via response-effect compatibility) in an experimental design that allows for observing forward and backward crosstalk. We observed robust crosstalk effects and response-effect compatibility effects alike, but no interaction between both effects. These results indicate that effect activation can occur in parallel for several tasks, independently of effect-based response production, which is confined to one task at a time. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Internal disruption in tokamaks

    Kuvshinov, B.N.; Savrukhin, P.V.

    1990-01-01

    A review of results of experimental and theoretical investigations of internal disruption in tokamaks is given. Specific features of various types of saw-tooth oscillations are described and their classification is performed. Theoretical models of the process of development of internal disruption instability are discussed. Effect of internal disruption on parameters of plasma, confined in tokamak, is considered. Scalings of period and amplitude of saw-tooth oscillations, as well as version radius are presented. Different methods for stabilizing instability of internal disruption are described

  20. Internal disruptions in tokamaks

    Kuvshinov, B.N.; Savrukhin, P.V.

    1990-01-01

    Experimental and theoretical studies of the phenomenon of internal disruptions in tokamaks are reviewed. A classification scheme is introduced and the features of different types of sawtooth oscillations are described. A theoretical model for the development of the internal disruption instability is discussed. The effect of internal disruptions on the parameters of plasma confined in tokamaks is discussed. Scaling laws for the period and amplitude of sawtooth oscillations, as well as for the inversion radius, are presented. Different methods of stabilizing the internal disruption instability are described

  1. Action video games and improved attentional control: Disentangling selection- and response-based processes.

    Chisholm, Joseph D; Kingstone, Alan

    2015-10-01

    Research has demonstrated that experience with action video games is associated with improvements in a host of cognitive tasks. Evidence from paradigms that assess aspects of attention has suggested that action video game players (AVGPs) possess greater control over the allocation of attentional resources than do non-video-game players (NVGPs). Using a compound search task that teased apart selection- and response-based processes (Duncan, 1985), we required participants to perform an oculomotor capture task in which they made saccades to a uniquely colored target (selection-based process) and then produced a manual directional response based on information within the target (response-based process). We replicated the finding that AVGPs are less susceptible to attentional distraction and, critically, revealed that AVGPs outperform NVGPs on both selection-based and response-based processes. These results not only are consistent with the improved-attentional-control account of AVGP benefits, but they suggest that the benefit of action video game playing extends across the full breadth of attention-mediated stimulus-response processes that impact human performance.

  2. Skin-safe photothermal therapy enabled by responsive release of acid-activated membrane-disruptive polymer from polydopamine nanoparticle upon very low laser irradiation.

    Zhu, Rui; Gao, Feng; Piao, Ji-Gang; Yang, Lihua

    2017-07-25

    How to ablate tumor without damaging skin is a challenge for photothermal therapy. We, herein, report skin-safe photothermal cancer therapy provided by the responsive release of acid-activated hemolytic polymer (aHLP) from the photothermal polydopamine (PDA) nanoparticle upon irradiation at very low dosage. Upon skin-permissible irradiation (via an 850 nm laser irradiation at the power density of 0.4 W cm -2 ), the nanoparticle aHLP-PDA generates sufficient localized-heat to bring about mild hyperthermia treatment and consequently, responsively sheds off the aHLP polymer from its PDA nanocore; this leads to selective cytotoxicity to cancer cells under the acidic conditions of the extracellular microenvironment of tumor. As a result, our aHLP-PDA nanoparticle upon irradiation at a low dosage effectively inhibits tumor growth without damaging skin, as demonstrated using animal models. Effective in mitigating the otherwise inevitable skin damage in tumor photothermal therapy, the nanosystem reported herein offers an efficient pathway towards skin-safe photothermal therapy.

  3. The human auditory brainstem response to running speech reveals a subcortical mechanism for selective attention.

    Forte, Antonio Elia; Etard, Octave; Reichenbach, Tobias

    2017-10-10

    Humans excel at selectively listening to a target speaker in background noise such as competing voices. While the encoding of speech in the auditory cortex is modulated by selective attention, it remains debated whether such modulation occurs already in subcortical auditory structures. Investigating the contribution of the human brainstem to attention has, in particular, been hindered by the tiny amplitude of the brainstem response. Its measurement normally requires a large number of repetitions of the same short sound stimuli, which may lead to a loss of attention and to neural adaptation. Here we develop a mathematical method to measure the auditory brainstem response to running speech, an acoustic stimulus that does not repeat and that has a high ecological validity. We employ this method to assess the brainstem's activity when a subject listens to one of two competing speakers, and show that the brainstem response is consistently modulated by attention.

  4. Development and evaluation of a tool for retrospective exposure assessment of selected endocrine disrupting chemicals and EMF in the car manufacturing industry.

    Mester, Birte; Schmeisser, Nils; Lünzmann, Hauke; Pohlabeln, Hermann; Langner, Ingo; Behrens, Thomas; Ahrens, Wolfgang

    2011-08-01

    A system for retrospective occupational exposure assessment combining the efficiency of a job exposure matrix (JEM) and the precision of a subsequent individual expert exposure assessment (IEEA) was developed. All steps of the exposure assessment were performed by an interdisciplinary expert panel in the context of a case-control study on male germ cell cancer nested in the car manufacturing industries. An industry-specific JEM was developed and automatic exposure estimation was performed based on this JEM. A subsample of exposure ratings was done by IEEA to identify determinants of disagreement between the JEM and the individual review. Possible determinants were analyzed by calculating odds ratios (ORs) of disagreement between ratings with regard to different dimensions (e.g. high versus low intensity of exposure). Disagreement in ≥20% of the sampled exposure ratings with a statistically significant OR was chosen as a threshold for inclusion of the exposure ratings into a final IEEA. The most important determinants of disagreement between JEM and individual review were working outside of the production line (disagreement 80%), low probability of exposure (disagreement 25%), and exposure depending on specific activities like usage of specific lacquers (disagreement 32%) for jobs within the production line. These determinants were the selection criteria of exposure ratings for the subsequent final IEEA. Combining a JEM and a subsequent final IEEA for a selected subset of exposure ratings is a feasible and labor-saving approach for exposure assessment in large occupational epidemiological studies.

  5. Evolution of boldness and life-history in response to selective harvesting

    Andersen, Ken Haste; Marty, Lise; Arlinghaus, Robert

    2018-01-01

    Whether intensive harvesting alters the behavioral repertoire of exploited fishes is currently unknown, but plausible. We extend a fish life-history model to account for boldness as a personality trait that affects foraging intensity, which affects energy intake and risk from predation and fishing...... gear. We systematically investigate life-history and behavioral trait evolution along the boldness–timidity axis in response to the full range of common selectivity and exploitation patterns in fisheries. In agreement with previous studies, we find that any type of harvesting selects for fast life...... histories and that merely elevated, yet unselective, fishing mortality favors boldness. We also find that timid-selective fishing (which can be expected in species targeted by active gear types) selects for increased boldness. By contrast, increased timidity is predicted when fishing targets bolder...

  6. Plasma membrane disruption: repair, prevention, adaptation

    McNeil, Paul L.; Steinhardt, Richard A.

    2003-01-01

    Many metazoan cells inhabit mechanically stressful environments and, consequently, their plasma membranes are frequently disrupted. Survival requires that the cell rapidly repair or reseal the disruption. Rapid resealing is an active and complex structural modification that employs endomembrane as its primary building block, and cytoskeletal and membrane fusion proteins as its catalysts. Endomembrane is delivered to the damaged plasma membrane through exocytosis, a ubiquitous Ca2+-triggered response to disruption. Tissue and cell level architecture prevent disruptions from occurring, either by shielding cells from damaging levels of force, or, when this is not possible, by promoting safe force transmission through the plasma membrane via protein-based cables and linkages. Prevention of disruption also can be a dynamic cell or tissue level adaptation triggered when a damaging level of mechanical stress is imposed. Disease results from failure of either the preventive or resealing mechanisms.

  7. Technical Note: Response measurement for select radiation detectors in magnetic fields

    Reynolds, M., E-mail: michaelreynolds@ualberta.net [Department of Oncology, Medical Physics Division, University of Alberta, 11560 University Avenue, Edmonton, Alberta T6G 1Z2 (Canada); Fallone, B. G. [Department of Medical Physics, Cross Cancer Institute, 11560 University Avenue, Edmonton, Alberta T6G 1Z2, Canada and Departments of Oncology and Physics, University of Alberta, 11560 University Avenue, Edmonton, Alberta T6G 1Z2 (Canada); Rathee, S. [Department of Medical Physics, Cross Cancer Institute, 11560 University Avenue, Edmonton, Alberta T6G 1Z2, Canada and Department of Oncology, Medical Physics Division,University of Alberta, 11560 University Avenue, Edmonton, Alberta T6G 1Z2 (Canada)

    2015-06-15

    Purpose: Dose response to applied magnetic fields for ion chambers and solid state detectors has been investigated previously for the anticipated use in linear accelerator–magnetic resonance devices. In this investigation, the authors present the measured response of selected radiation detectors when the magnetic field is applied in the same direction as the radiation beam, i.e., a longitudinal magnetic field, to verify previous simulation only data. Methods: The dose response of a PR06C ion chamber, PTW60003 diamond detector, and IBA PFD diode detector is measured in a longitudinal magnetic field. The detectors are irradiated with buildup caps and their long axes either parallel or perpendicular to the incident photon beam. In each case, the magnetic field dose response is reported as the ratio of detector signals with to that without an applied longitudinal magnetic field. The magnetic field dose response for each unique orientation as a function of magnetic field strength was then compared to the previous simulation only studies. Results: The measured dose response of each detector in longitudinal magnetic fields shows no discernable response up to near 0.21 T. This result was expected and matches the previously published simulation only results, showing no appreciable dose response with magnetic field. Conclusions: Low field longitudinal magnetic fields have been shown to have little or no effect on the dose response of the detectors investigated and further lend credibility to previous simulation only studies.

  8. Transcranial magnetic stimulation changes response selectivity of neurons in the visual cortex

    Kim, Taekjun; Allen, Elena A.; Pasley, Brian N.; Freeman, Ralph D.

    2015-01-01

    Background Transcranial magnetic stimulation (TMS) is used to selectively alter neuronal activity of specific regions in the cerebral cortex. TMS is reported to induce either transient disruption or enhancement of different neural functions. However, its effects on tuning properties of sensory neurons have not been studied quantitatively. Objective/Hypothesis Here, we use specific TMS application parameters to determine how they may alter tuning characteristics (orientation, spatial frequency, and contrast sensitivity) of single neurons in the cat’s visual cortex. Methods Single unit spikes were recorded with tungsten microelectrodes from the visual cortex of anesthetized and paralyzed cats (12 males). Repetitive TMS (4Hz, 4sec) was delivered with a 70mm figure-8 coil. We quantified basic tuning parameters of individual neurons for each pre- and post-TMS condition. The statistical significance of changes for each tuning parameter between the two conditions was evaluated with a Wilcoxon signed-rank test. Results We generally find long-lasting suppression which persists well beyond the stimulation period. Pre- and post-TMS orientation tuning curves show constant peak values. However, strong suppression at non-preferred orientations tends to narrow the widths of tuning curves. Spatial frequency tuning exhibits an asymmetric change in overall shape, which results in an emphasis on higher frequencies. Contrast tuning curves show nonlinear changes consistent with a gain control mechanism. Conclusions These findings suggest that TMS causes extended interruption of the balance between sub-cortical and intra-cortical inputs. PMID:25862599

  9. High-capacity thermo-responsive magnetic molecularly imprinted polymers for selective extraction of curcuminoids.

    You, Qingping; Zhang, Yuping; Zhang, Qingwen; Guo, Junfang; Huang, Weihua; Shi, Shuyun; Chen, Xiaoqin

    2014-08-08

    Thermo-responsive magnetic molecularly imprinted polymers (TMMIPs) for selective recognition of curcuminoids with high capacity and selectivity have firstly been developed. The resulting TMMIPs were characterized by TEM, FT-IR, TGA, VSM and UV, which indicated that TMMIPs showed thermo-responsiveness [lower critical solution temperature (LCST) at 33.71°C] and rapid magnetic separation (5s). The polymerization, adsorption and release conditions were optimized in detail to obtain the highest binding capacity, selectivity and release ratio. We found that the adopted thermo-responsive monomer [N-isopropylacrylamide (NIPAm)] could be considered not only as inert polymer backbone for thermo-responsiveness but also as functional co-monomers combination with basic monomer (4-VP) for more specific binding sites when ethanol was added in binding solution. The maximum adsorption capacity with highest selectivity of curcumin was 440.3μg/g (1.93 times that on MMIPs with no thermosensitivity) at 45°C (above LCST) in 20% (v/v) ethanol solution on shrunk TMMIPs, and the maximum release proportion was about 98% at 20°C (below LCST) in methanol-acetic acid (9/1, v/v) solution on swelled TMMIPs. The adsorption process between curcumin and TMMIPs followed Langumuir adsorption isotherm and pseudo-first-order reaction kinetics. The prepared TMMIPs also showed high reproducibility (RSD<6% for batch-to-batch evaluation) and stability (only 7% decrease after five cycles). Subsequently, the TMMIPs were successfully applied for selective extraction of curcuminoids from complex natural product, Curcuma longa. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Effect of preweaning nutritional management on yearling weight response in an open-herd selection program.

    Hough, J D; Benyshek, L L

    1988-10-01

    Records on 276 progeny were collected in the final 2 yr (1984 and 1985) of an 8-yr Hereford cattle selection project. Selection was practiced using the top sires from the American Hereford Association's National Cattle Evaluation based on yearling weight expected progeny difference. An unselected control line was maintained to monitor environmental change. One-half of each line was creep-fed during the preweaning period for the last 2 yr to evaluate genotype x environment interactions. Direct response to yearling weight selection averaged 28 +/- 8 kg. Correlated response to selection amounted to .057 +/- .028 kg/d in preweaning ADG, 14 +/- 6 kg in weaning weight, .085 +/- .033 kg/d in postweaning ADG, 4.6 +/- 1.5 cm in yearling hip height and 11.2 +/- 3.0 cm2 in yearling pelvic area. Yearling fat thickness and scrotal circumference were not significantly affected by selection. Significant effects of creep feeding were observed for yearling weight (15 +/- 3 kg), preweaning ADG (.067 +/- .012 kg/d), weaning weight (13 +/- 2 kg), yearling hip height (1.2 +/- .5 cm) and yearling fat thickness (.07 +/- .03 cm). Postweaning ADG, yearling pelvic area and yearling scrotal circumference were not affected by creep feeding. No significant genetic group x creep feeding effects were found for any of the traits analyzed, indicating calves genetically superior for growth did not gain any additional advantage from creep feeding.

  11. Disruptions in JET

    Wesson, J.A.; Gill, R.D.; Hugon, M.

    1989-01-01

    In JET, both high density and low-q operation are limited by disruptions. The density limit disruptions are caused initially by impurity radiation. This causes a contraction of the plasma temperature profile and leads to an MHD unstable configuration. There is evidence of magnetic island formation resulting in minor disruptions. After several minor disruptions, a major disruption with a rapid energy quench occurs. This event takes place in two stages. In the first stage there is a loss of energy from the central region. In the second stage there is a more rapid drop to a very low temperature, apparently due to a dramatic increase in impurity radiation. The final current decay takes place in the resulting cold plasma. During the growth of the MHD instability the initially rotating mode is brought to rest. This mode locking is believed to be due to an electromagnetic interaction with the vacuum vessel and external magnetic field asymmetries. The low-q disruptions are remarkable for the precision with which they occur at q ψ = 2. These disruptions do not have extended precursors or minor disruptions. The instability grows and locks rapidly. The energy quench and current decay are generally similar to those of the density limit. (author). 43 refs, 35 figs, 3 tabs

  12. Selective attention modulates human auditory brainstem responses: relative contributions of frequency and spatial cues.

    Alexandre Lehmann

    Full Text Available Selective attention is the mechanism that allows focusing one's attention on a particular stimulus while filtering out a range of other stimuli, for instance, on a single conversation in a noisy room. Attending to one sound source rather than another changes activity in the human auditory cortex, but it is unclear whether attention to different acoustic features, such as voice pitch and speaker location, modulates subcortical activity. Studies using a dichotic listening paradigm indicated that auditory brainstem processing may be modulated by the direction of attention. We investigated whether endogenous selective attention to one of two speech signals affects amplitude and phase locking in auditory brainstem responses when the signals were either discriminable by frequency content alone, or by frequency content and spatial location. Frequency-following responses to the speech sounds were significantly modulated in both conditions. The modulation was specific to the task-relevant frequency band. The effect was stronger when both frequency and spatial information were available. Patterns of response were variable between participants, and were correlated with psychophysical discriminability of the stimuli, suggesting that the modulation was biologically relevant. Our results demonstrate that auditory brainstem responses are susceptible to efferent modulation related to behavioral goals. Furthermore they suggest that mechanisms of selective attention actively shape activity at early subcortical processing stages according to task relevance and based on frequency and spatial cues.

  13. Disrupting Ethnography through Rhizoanalysis

    Diana Masny

    2014-10-01

    Full Text Available This article interrogates principles of ethnography in education proposed by Mills and Morton: raw tellings, analytic pattern, vignette and empathy. This article adopts a position that is uncomfortable, unconventional and interesting. It involves a deterritorialization/ rupture of ethnography in education in order to reterritorialize a different concept: rhizoanalysis, a way to position theory and data that is multilayered, complex and messy. Rhizoanalysis, the main focus of this article is not a method. It is an approach to research conditioned by a reality in which Deleuze and Guattari disrupt representation, interpretation and subjectivity. In this article, Multiple Literacies Theory, a theoretical and practical framework, becomes a lens to examine a rhizomatic study of a Korean family recently arrived to Australia and attending English as a second language classes. Observations and interviews recorded the daily lives of the family. The vignettes were selected by reading data intensively and immanently through a process of palpation, an innovative approach to educational research. Rhizoanalysis proposes to abandon the given and invent different ways of thinking about and doing research and what might happen when reading data differently, intensively and immanently, through Multiple Literacies Theory. Rhizoanalysis, a game-changer in the way research can be conducted, affords a different lens to tackle issues in education through research.

  14. Mutating the Conserved Q-loop Glutamine 1291 Selectively Disrupts Adenylate Kinase-dependent Channel Gating of the ATP-binding Cassette (ABC) Adenylate Kinase Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) and Reduces Channel Function in Primary Human Airway Epithelia.

    Dong, Qian; Ernst, Sarah E; Ostedgaard, Lynda S; Shah, Viral S; Ver Heul, Amanda R; Welsh, Michael J; Randak, Christoph O

    2015-05-29

    The ATP-binding cassette (ABC) transporter cystic fibrosis transmembrane conductance regulator (CFTR) and two other non-membrane-bound ABC proteins, Rad50 and a structural maintenance of chromosome (SMC) protein, exhibit adenylate kinase activity in the presence of physiologic concentrations of ATP and AMP or ADP (ATP + AMP ⇆ 2 ADP). The crystal structure of the nucleotide-binding domain of an SMC protein in complex with the adenylate kinase bisubstrate inhibitor P(1),P(5)-di(adenosine-5') pentaphosphate (Ap5A) suggests that AMP binds to the conserved Q-loop glutamine during the adenylate kinase reaction. Therefore, we hypothesized that mutating the corresponding residue in CFTR, Gln-1291, selectively disrupts adenylate kinase-dependent channel gating at physiologic nucleotide concentrations. We found that substituting Gln-1291 with bulky side-chain amino acids abolished the effects of Ap5A, AMP, and adenosine 5'-monophosphoramidate on CFTR channel function. 8-Azidoadenosine 5'-monophosphate photolabeling of the AMP-binding site and adenylate kinase activity were disrupted in Q1291F CFTR. The Gln-1291 mutations did not alter the potency of ATP at stimulating current or ATP-dependent gating when ATP was the only nucleotide present. However, when physiologic concentrations of ADP and AMP were added, adenylate kinase-deficient Q1291F channels opened significantly less than wild type. Consistent with this result, we found that Q1291F CFTR displayed significantly reduced Cl(-) channel function in well differentiated primary human airway epithelia. These results indicate that a highly conserved residue of an ABC transporter plays an important role in adenylate kinase-dependent CFTR gating. Furthermore, the results suggest that adenylate kinase activity is important for normal CFTR channel function in airway epithelia. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Selective Preference of Parallel DNA Triplexes Is Due to the Disruption of Hoogsteen Hydrogen Bonds Caused by the Severe Nonisostericity between the G*GC and T*AT Triplets.

    Gunaseelan Goldsmith

    Full Text Available Implications of DNA, RNA and RNA.DNA hybrid triplexes in diverse biological functions, diseases and therapeutic applications call for a thorough understanding of their structure-function relationships. Despite exhaustive studies mechanistic rationale for the discriminatory preference of parallel DNA triplexes with G*GC & T*AT triplets still remains elusive. Here, we show that the highest nonisostericity between the G*GC & T*AT triplets imposes extensive stereochemical rearrangements contributing to context dependent triplex destabilisation through selective disruption of Hoogsteen scheme of hydrogen bonds. MD simulations of nineteen DNA triplexes with an assortment of sequence milieu reveal for the first time fresh insights into the nature and extent of destabilization from a single (non-overlapping, double (overlapping and multiple pairs of nonisosteric base triplets (NIBTs. It is found that a solitary pair of NIBTs, feasible either at a G*GC/T*AT or T*AT/G*GC triplex junction, does not impinge significantly on triplex stability. But two overlapping pairs of NIBTs resulting from either a T*AT or a G*GC interruption disrupt Hoogsteen pair to a noncanonical mismatch destabilizing the triplex by ~10 to 14 kcal/mol, implying that their frequent incidence in multiples, especially, in short sequences could even hinder triplex formation. The results provide (i an unambiguous and generalised mechanistic rationale for the discriminatory trait of parallel triplexes, including those studied experimentally (ii clarity for the prevalence of antiparallel triplexes and (iii comprehensive perspectives on the sequence dependent influence of nonisosteric base triplets useful in the rational design of TFO's against potential triplex target sites.

  16. Plasma turbulence. Structure formation, selection rule, dynamic response and dynamics transport

    Ito, Sanae I.

    2010-01-01

    The five-year project of Grant-in-Aid for Specially Promoted Research entitled general research on the structure formation and selection rule in plasma turbulence had brought many outcomes. Based on these outcomes, the Grant-in-Aid for Scientific Research (S) program entitled general research on dynamic response and dynamic transport in plasma turbulence has started. In the present paper, the state-of-the-art of the research activities on the structure formation, selection rule and dynamics in plasma turbulence are reviewed with reference to outcomes of these projects. (author)

  17. Integration of laser trapping for continuous and selective monitoring of photothermal response of a single microparticle.

    Vasudevan, Srivathsan; Chen, George C K; Ahluwalia, Balpreet Singh

    2008-12-01

    Photothermal response (PTR) is an established pump and probe technique for real-time sensing of biological assays. Continuous and selective PTR monitoring is difficult owing to the Brownian motion changing the relative position of the target with respect to the beams. Integration of laser trapping with PTR is proposed as a solution. The proposed method is verified on red polystyrene microparticles. PTR is continuously monitored for 30 min. Results show that the mean relaxation time variation of the acquired signals is less than 5%. The proposed method is then applied to human red blood cells for continuous and selective PTR.

  18. Disruptions in Tokamaks

    Bondeson, A.

    1987-01-01

    This paper discusses major and minor disruptions in Tokamaks. A number of models and numerical simulations of disruptions based on resistive MHD are reviewed. A discussion is given of how disruptive current profiles are correlated with the experimentally known operational limits in density and current. It is argued that the q a =2 limit is connected with stabilization of the m=2/n=1 tearing mode for a approx.< 2.7 by resistive walls and mode rotation. Experimental and theoretical observations indicate that major disruptions usually occur in at least two phases, first a 'predisruption', or loss of confinement in the region 1 < q < 2, leaving the q approx.= 1 region almost unaffected, followed by a final disruption of the central part, interpreted here as a toroidal n = 1 external kink mode. (author)

  19. Effects of prolonged running in the heat and cool environments on selected physiological parameters and salivary lysozyme responses

    Nur S. Ibrahim

    2017-12-01

    Conclusion: This study found similar lysozyme responses between both hot and cool trials. Thus, room/ambient temperature did not affect lysozyme responses among recreational athletes. Nevertheless, the selected physiological parameters were significantly affected by room temperature.

  20. Inferring the Mode of Selection from the Transient Response to Demographic Perturbations

    Balick, Daniel; Do, Ron; Reich, David; Sunyaev, Shamil

    2014-03-01

    Despite substantial recent progress in theoretical population genetics, most models work under the assumption of a constant population size. Deviations from fixed population sizes are ubiquitous in natural populations, many of which experience population bottlenecks and re-expansions. The non-equilibrium dynamics introduced by a large perturbation in population size are generally viewed as a confounding factor. In the present work, we take advantage of the transient response to a population bottleneck to infer features of the mode of selection and the distribution of selective effects. We develop an analytic framework and a corresponding statistical test that qualitatively differentiates between alleles under additive and those under recessive or more general epistatic selection. This statistic can be used to bound the joint distribution of selective effects and dominance effects in any diploid sexual organism. We apply this technique to human population genetic data, and severely restrict the space of allowed selective coefficients in humans. Additionally, one can test a set of functionally or medically relevant alleles for the primary mode of selection, or determine the local regional variation in dominance coefficients along the genome.

  1. Motivational changes in response to blocked goals and foreshortened time: testing alternatives to socioemotional selectivity theory.

    Fung, Helene H; Carstensen, Laura L

    2004-03-01

    Socioemotional selectivity theory contends that when people perceive time as limited, they prioritize emotionally meaningful goals. Although empirical support for the theory has been found in several studies, 2 alternative explanations for the pattern of findings remain: (a) emotional goals are pursued by default because nonemotional goals are blocked, and (b) emotional goals are pursued in search of emotional support rather than emotional meaning. This study tested these alternatives by examining social goals in response to blocked goals and foreshortened time. Findings reveal distinct motivational patterns, as reflected in social preferences and self-reported social goals, in response to the 2 types of constraints.

  2. Dynamic selection of ship responses for estimation of on-site directional wave spectra

    Andersen, Ingrid Marie Vincent; Storhaug, Gaute

    2012-01-01

    -estimate of the wave spectrum is suggested. The selection method needs to be robust for what reason a parameterised uni-directional, two-parameter wave spectrum is treated. The parameters included are the zero up-crossing period, the significant wave height and the main wave direction relative to the ship’s heading...... with the best overall agreement are selected for the actual estimation of the directional wave spectrum. The transfer functions for the ship responses can be determined using different computational methods such as striptheory, 3D panel codes, closed form expressions or model tests. The uncertainty associated......Knowledge of the wave environment in which a ship is operating is crucial for most on-board decision support systems. Previous research has shown that the directional wave spectrum can be estimated by the use of measured global ship responses and a set of transfer functions determined...

  3. Gene Disruption in Scedosporium aurantiacum: Proof of Concept with the Disruption of SODC Gene Encoding a Cytosolic Cu,Zn-Superoxide Dismutase.

    Pateau, Victoire; Razafimandimby, Bienvenue; Vandeputte, Patrick; Thornton, Christopher R; Guillemette, Thomas; Bouchara, Jean-Philippe; Giraud, Sandrine

    2018-02-01

    Scedosporium species are opportunistic pathogens responsible for a large variety of infections in humans. An increasing occurrence was observed in patients with underlying conditions such as immunosuppression or cystic fibrosis. Indeed, the genus Scedosporium ranks the second among the filamentous fungi colonizing the respiratory tracts of the CF patients. To date, there is very scarce information on the pathogenic mechanisms, at least in part because of the limited genetic tools available. In the present study, we successfully developed an efficient transformation and targeted gene disruption approach on the species Scedosporium aurantiacum. The disruption cassette was constructed using double-joint PCR procedure, and resistance to hygromycin B as the selection marker. This proof of concept was performed on the functional gene SODC encoding the Cu,Zn-superoxide dismutase. Disruption of the SODC gene improved susceptibility of the fungus to oxidative stress. This technical advance should open new research areas and help to better understand the biology of Scedosporium species.

  4. Sympathoadrenal, cardiovascular and blood gas responses to highly selective mu and delta opioid peptides.

    Kiritsy-Roy, J A; Marson, L; Van Loon, G R

    1989-12-01

    The relative importance of mu and delta opioid receptors in brain regulation of sympathoadrenal, cardiovascular and respiratory function was investigated using highly selective mu and delta opioid peptide analogs. Groups of conscious rats received i.c.v. injections of either the mu-selective agonist, [D-Ala2, MePhe4, Gly-ol5]enkephalin (DAMGO) or the delta-selective agonist, [D-Pen2, D-Pen5]enkephalin (DPDPE). Blood pressure and heart rate were recorded continuously via a chronic catheter in the carotid artery, and arterial blood samples were taken at intervals through the same catheter for determination of blood pH, pCO2, pO2 and plasma catecholamine concentrations. Both DAMGO and DPDPE increased plasma catecholamine levels and blood pressure in a dose-related manner. The slopes of the dose-response lines were parallel, but the delta compound was about 250 times less potent than DAMGO. Only the highest dose of 5 nmol of DAMGO caused a significant bradycardia, mediated by parasympathetic (vagal) activation. DAMGO and DPDPE also induced dose-dependent acidosis, with DAMGO again being much more potent than DPDPE. The effects of both DAMGO and DPDPE on plasma catecholamines, blood pressure and blood gases were antagonized by a mu-selective dose of naloxone (0.4 mg/kg i.a.). Intracerebroventricular administration of the delta-selective antagonist, ICI 174,864, only partially attenuated sympathoadrenal and blood gas responses to DAMGO or DPDPE. The pressor responses to DAMGO or DPDPE were resistant to antagonism by ICI 174,864. These results indicate that brain opioid receptors regulating autonomic outflow, cardiovascular and respiratory function are mainly of the mu type, although a delta opioid system may contribute to sympathoadrenal and respiratory effects of opioids.

  5. Female responses to experimental removal of sexual selection components in Drosophila melanogaster

    Innocenti, Paolo; Flis, Ilona; Morrow, Edward H.

    2014-01-01

    Background Despite the common assumption that multiple mating should in general be favored in males, but not in females, to date there is no consensus on the general impact of multiple mating on female fitness. Notably, very little is known about the genetic and physiological features underlying the female response to sexual selection pressures. By combining an experimental evolution approach with genomic techniques, we investigated the effects of single and multiple matings on female fecundi...

  6. The response to selection in Glycoside Hydrolase Family 13 structures: A comparative quantitative genetics approach.

    Jose Sergio Hleap

    Full Text Available The Glycoside Hydrolase Family 13 (GH13 is both evolutionarily diverse and relevant to many industrial applications. Its members hydrolyze starch into smaller carbohydrates and members of the family have been bioengineered to improve catalytic function under industrial environments. We introduce a framework to analyze the response to selection of GH13 protein structures given some phylogenetic and simulated dynamic information. We find that the TIM-barrel (a conserved protein fold consisting of eight α-helices and eight parallel β-strands that alternate along the peptide backbone, common to all amylases is not selectable since it is under purifying selection. We also show a method to rank important residues with higher inferred response to selection. These residues can be altered to effect change in properties. In this work, we define fitness as inferred thermodynamic stability. We show that under the developed framework, residues 112Y, 122K, 124D, 125W, and 126P are good candidates to increase the stability of the truncated α-amylase protein from Geobacillus thermoleovorans (PDB code: 4E2O; α-1,4-glucan-4-glucanohydrolase; EC 3.2.1.1. Overall, this paper demonstrates the feasibility of a framework for the analysis of protein structures for any other fitness landscape.

  7. Influence of nonionic surfactants on the potentiometric response of hydrogen ion-selective polymeric membrane electrodes.

    Espadas-Torre, C; Bakker, E; Barker, S; Meyerhoff, M E

    1996-05-01

    The influence of poly(ethylene oxide)-based nonionic surfactants (i.e., Triton X-100 and Brij 35) in the sample phase on the response properties of hydrogen ion-selective polymeric membrane electrodes containing mobile (lipophilic amines) or covalently bound (aminated-poly-(vinyl chloride)) hydrogen ion carriers is reported. In the presence of these nonionic surfactants, membrane electrode response toward interfering cation activity (e.g., Na+) in the sample phase is increased substantially and the pH measuring range shortened. The degree of cation interference for pH measurements is shown to correlate with the basicity of the hydrogen ion carrier doped within the membrane phase. The observed deterioration in selectivity arises from the partitioning of the surfactant into the membrane and concomitant extraction of metal cations by the surfactants in the organic phase. The effect of nonionic surfactants on pH electrodes prepared with aminated-PVC membranes is shown to be more complex, with additional large shifts in EMF values apparently arising from multidentate interactions between the surfactant molecules and the polymeric amine in the membrane, leading to a change in the apparent pKa values for the amine sites. The effects induced by nonionic surfactants on the EMF response function of hydrogen ion-selective polymeric membrane electrodes are modeled, and experimental results are shown to correlate well with theoretical predictions.

  8. Artificial Selection Response due to Polygenic Adaptation from a Multilocus, Multiallelic Genetic Architecture.

    Zan, Yanjun; Sheng, Zheya; Lillie, Mette; Rönnegård, Lars; Honaker, Christa F; Siegel, Paul B; Carlborg, Örjan

    2017-10-01

    The ability of a population to adapt to changes in their living conditions, whether in nature or captivity, often depends on polymorphisms in multiple genes across the genome. In-depth studies of such polygenic adaptations are difficult in natural populations, but can be approached using the resources provided by artificial selection experiments. Here, we dissect the genetic mechanisms involved in long-term selection responses of the Virginia chicken lines, populations that after 40 generations of divergent selection for 56-day body weight display a 9-fold difference in the selected trait. In the F15 generation of an intercross between the divergent lines, 20 loci explained >60% of the additive genetic variance for the selected trait. We focused particularly on fine-mapping seven major QTL that replicated in this population and found that only two fine-mapped to single, bi-allelic loci; the other five contained linked loci, multiple alleles or were epistatic. This detailed dissection of the polygenic adaptations in the Virginia lines provides a deeper understanding of the range of different genome-wide mechanisms that have been involved in these long-term selection responses. The results illustrate that the genetic architecture of a highly polygenic trait can involve a broad range of genetic mechanisms, and that this can be the case even in a small population bred from founders with limited genetic diversity. © 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.

  9. Understanding disruptions in tokamaksa)

    Zakharov, Leonid E.; Galkin, Sergei A.; Gerasimov, Sergei N.; contributors, JET-EFDA

    2012-05-01

    This paper describes progress achieved since 2007 in understanding disruptions in tokamaks, when the effect of plasma current sharing with the wall was introduced into theory. As a result, the toroidal asymmetry of the plasma current measurements during vertical disruption event (VDE) on the Joint European Torus was explained. A new kind of plasma equilibria and mode coupling was introduced into theory, which can explain the duration of the external kink 1/1 mode during VDE. The paper presents first results of numerical simulations using a free boundary plasma model, relevant to disruptions.

  10. Numerical study of the mode selection in response spectrum analysis-condensed version

    Ng, D.S.

    1986-01-01

    For quality assurance of the dynamic response spectrum analysis, the Nuclear Regulatory Commission (NRC) recommends retaining all modes below the cutoff frequency at which the spectral acceleration (S/sub a/) returns to the peak zero period acceleration (ZPA). It also suggests that modes accounting for at least 90 percent of the structural masses be included in the analysis. A simple frame-type structure is generated as a baseline frame. Then groups of oscillators representing substructure are added onto the frame to study substructure behavior. A base case is established for each frame by including the specific number of modes used. The tests are conducted by incrementing the number of modes in the response spectrum analyses starting with one mode. The structural response of each modal increment is compared with the base case to identify the efficiency of mode selection method. All three methods are then applied to the MFTF-B Axicell Vacuum Vessel. The responses in critical components of the vessel, such as hangers and foundations, will be analyzed to confirm the accuracy of the selected method

  11. ZnO-carbon nanofibers for stable, high response, and selective H2S sensors.

    Zhang, Jitao; Zhu, Zijian; Chen, Changmiao; Chen, Zhi; Cai, Mengqiu; Qu, Baihua; Wang, Taihong; Zhang, Ming

    2018-07-06

    Hydrogen sulfide (H 2 S), as a typical atmospheric pollutant, is neurotoxic and flammable even at a very low concentration. In this study, we design stable H 2 S sensors based on ZnO-carbon nanofibers. Nanofibers with 30.34 wt% carbon are prepared by a facial electrospinning route followed by an annealing treatment. The resulting H 2 S sensors show excellent selectivity and response compared to the pure ZnO nanofiber H 2 S sensors, particularly the response in the range of 102-50 ppm of H 2 S. Besides, they exhibited a nearly constant response of approximately 40-20 ppm of H 2 S over 60 days. The superior performance of these H 2 S sensors can be attributed to the protection of carbon, which ensures the high stability of ZnO, and oxygen vacancies that improve the response and selectivity of H 2 S. The good performance of ZnO-carbon H 2 S sensors suggests that composites with oxygen vacancies prepared by a facial electrospinning route may provide a new research strategy in the field of gas sensors, photocatalysts, and semiconductor devices.

  12. Engineering the temporal response of photoconductive photodetectors via selective introduction of surface trap states.

    Konstantatos, Gerasimos; Levina, Larissa; Fischer, Armin; Sargent, Edward H

    2008-05-01

    Photoconductive photodetectors fabricated using simple solution-processing have recently been shown to exhibit high gains (>1000) and outstanding sensitivities ( D* > 10(13) Jones). One ostensible disadvantage of exploiting photoconductive gain is that the temporal response is limited by the release of carriers from trap states. Here we show that it is possible to introduce specific chemical species onto the surfaces of colloidal quantum dots to produce only a single, desired trap state having a carefully selected lifetime. In this way we demonstrate a device that exhibits an attractive photoconductive gain (>10) combined with a response time ( approximately 25 ms) useful in imaging. We achieve this by preserving a single surface species, lead sulfite, while eliminating lead sulfate and lead carboxylate. In doing so we preserve the outstanding sensitivity of these devices, achieving a specific detectivity of 10(12) Jones in the visible, while generating a temporal response suited to imaging applications.

  13. Using the Animal Model to Accelerate Response to Selection in a Self-Pollinating Crop

    Cowling, Wallace A.; Stefanova, Katia T.; Beeck, Cameron P.; Nelson, Matthew N.; Hargreaves, Bonnie L. W.; Sass, Olaf; Gilmour, Arthur R.; Siddique, Kadambot H. M.

    2015-01-01

    We used the animal model in S0 (F1) recurrent selection in a self-pollinating crop including, for the first time, phenotypic and relationship records from self progeny, in addition to cross progeny, in the pedigree. We tested the model in Pisum sativum, the autogamous annual species used by Mendel to demonstrate the particulate nature of inheritance. Resistance to ascochyta blight (Didymella pinodes complex) in segregating S0 cross progeny was assessed by best linear unbiased prediction over two cycles of selection. Genotypic concurrence across cycles was provided by pure-line ancestors. From cycle 1, 102/959 S0 plants were selected, and their S1 self progeny were intercrossed and selfed to produce 430 S0 and 575 S2 individuals that were evaluated in cycle 2. The analysis was improved by including all genetic relationships (with crossing and selfing in the pedigree), additive and nonadditive genetic covariances between cycles, fixed effects (cycles and spatial linear trends), and other random effects. Narrow-sense heritability for ascochyta blight resistance was 0.305 and 0.352 in cycles 1 and 2, respectively, calculated from variance components in the full model. The fitted correlation of predicted breeding values across cycles was 0.82. Average accuracy of predicted breeding values was 0.851 for S2 progeny of S1 parent plants and 0.805 for S0 progeny tested in cycle 2, and 0.878 for S1 parent plants for which no records were available. The forecasted response to selection was 11.2% in the next cycle with 20% S0 selection proportion. This is the first application of the animal model to cyclic selection in heterozygous populations of selfing plants. The method can be used in genomic selection, and for traits measured on S0-derived bulks such as grain yield. PMID:25943522

  14. Effect of feature-selective attention on neuronal responses in macaque area MT

    Chen, X.; Hoffmann, K.-P.; Albright, T. D.

    2012-01-01

    Attention influences visual processing in striate and extrastriate cortex, which has been extensively studied for spatial-, object-, and feature-based attention. Most studies exploring neural signatures of feature-based attention have trained animals to attend to an object identified by a certain feature and ignore objects/displays identified by a different feature. Little is known about the effects of feature-selective attention, where subjects attend to one stimulus feature domain (e.g., color) of an object while features from different domains (e.g., direction of motion) of the same object are ignored. To study this type of feature-selective attention in area MT in the middle temporal sulcus, we trained macaque monkeys to either attend to and report the direction of motion of a moving sine wave grating (a feature for which MT neurons display strong selectivity) or attend to and report its color (a feature for which MT neurons have very limited selectivity). We hypothesized that neurons would upregulate their firing rate during attend-direction conditions compared with attend-color conditions. We found that feature-selective attention significantly affected 22% of MT neurons. Contrary to our hypothesis, these neurons did not necessarily increase firing rate when animals attended to direction of motion but fell into one of two classes. In one class, attention to color increased the gain of stimulus-induced responses compared with attend-direction conditions. The other class displayed the opposite effects. Feature-selective activity modulations occurred earlier in neurons modulated by attention to color compared with neurons modulated by attention to motion direction. Thus feature-selective attention influences neuronal processing in macaque area MT but often exhibited a mismatch between the preferred stimulus dimension (direction of motion) and the preferred attention dimension (attention to color). PMID:22170961

  15. Best-Response Distributed Subchannel Selection for Minimizing Interference in Femtocell Networks}

    Somsak Kittipiyakul

    2015-08-01

    Full Text Available We study a distributed channel allocation problem of non-cooperative OFDMA femtocells in two-tiered macro-femto networks. The objective is to maximize the total capacity of uplink macro users and femto users. We assume a time-slotted system, a time-invariant channel model (no fading, each user knows the signal-to-interference-plus-noise ratio (SINR of all channels, and the channel selection happens only at the beginning of each time-slot. We study the performance of a best-response strategy where each user chooses to transmit in the highest-SINR channel. For simplicity, we focus on the homogeneous 3-link, 2-channel case and show that if all users update their actions every time-slot (i.e., all users make simultaneous moves, an oscillation can occur and result in the worst performance. To avoid the oscillation and achieve the highest total capacity, while still assuming no coordination among the users, we propose a stochastic best-response algorithm, where each user updates its channel selection with a selection probability p. We use a Markov chain to analyze the average capacity performance and use simulation results to confirm our analysis and also provide performance of other homogeneous cases with more number of links and channels. It is shown that the highest total capacity can be achieved when the selection probability p is very small. This stochastic best response with small p in effect provides a sequential move mechanism which requires no coordination.

  16. Neural-net disruption predictor in JT-60U

    Yoshino, R.

    2003-01-01

    The prediction of major disruptions caused by the density limit, the plasma current ramp-down with high internal inductance l i , the low density locked mode and the β-limit has been investigated in JT-60U. The concept of 'stability level', newly proposed in this paper to predict the occurrence of a major disruption, is calculated from nine input parameters every 2 ms by the neural network and the start of a major disruption is predicted when the stability level decreases to a certain level, the 'alarm level'. The neural network is trained in two steps. It is first trained with 12 disruptive and six non-disruptive shots (total of 8011 data points). Second, the target output data for 12 disruptive shots are modified and the network is trained again with additional data points generated by the operator. The 'neural-net disruption predictor' obtained has been tested for 300 disruptive shots (128 945 data points) and 1008 non-disruptive shots (982 800 data points) selected from nine years of operation (1991-1999) of JT-60U. Major disruptions except for those caused by the -limit have been predicted with a prediction success rate of 97-98% at 10 ms prior to the disruption and higher than 90% at 30 ms prior to the disruption while the false alarm rate is 2.1% for non-disruptive shots. This prediction performance has been confirmed for 120 disruptive shots (56 163 data points), caused by the density limit, as well as 1032 non-disruptive shots (1004 611 data points) in the last four years of operation (1999-2002) of JT-60U. A careful selection of the input parameters supplied to the network and the newly developed two-step training of the network have reduced the false alarm rate resulting in a considerable improvement of the prediction success rate. (author)

  17. Disruptive Mood Dysregulation Disorder

    ... Application Process Managing Grants Clinical Research Training Small Business Research Labs at NIMH Labs at NIMH Home Research ... Chat on Disruptive Mood Dysregulation Disorder (Archived Transcript) Research and ... Journal Articles: References and abstracts from MEDLINE/PubMed (National ...

  18. Disruption Rose Tinted II

    Livingstone, Andrew

    2009-01-01

    'Disruption - Rose Tinted II' continues to engage narratives of historical English china as previously explored in the work 'Rose Tinted'. This work engages the sleepy rural idyll which is overlaid with visual contemporary social commentary.

  19. Digital disruption ?syndromes.

    Sullivan, Clair; Staib, Andrew

    2017-05-18

    The digital transformation of hospitals in Australia is occurring rapidly in order to facilitate innovation and improve efficiency. Rapid transformation can cause temporary disruption of hospital workflows and staff as processes are adapted to the new digital workflows. The aim of this paper is to outline various types of digital disruption and some strategies for effective management. A large tertiary university hospital recently underwent a rapid, successful roll-out of an integrated electronic medical record (EMR). We observed this transformation and propose several digital disruption "syndromes" to assist with understanding and management during digital transformation: digital deceleration, digital transparency, digital hypervigilance, data discordance, digital churn and post-digital 'depression'. These 'syndromes' are defined and discussed in detail. Successful management of this temporary digital disruption is important to ensure a successful transition to a digital platform. What is known about this topic? Digital disruption is defined as the changes facilitated by digital technologies that occur at a pace and magnitude that disrupt established ways of value creation, social interactions, doing business and more generally our thinking. Increasing numbers of Australian hospitals are implementing digital solutions to replace traditional paper-based systems for patient care in order to create opportunities for improved care and efficiencies. Such large scale change has the potential to create transient disruption to workflows and staff. Managing this temporary disruption effectively is an important factor in the successful implementation of an EMR. What does this paper add? A large tertiary university hospital recently underwent a successful rapid roll-out of an integrated electronic medical record (EMR) to become Australia's largest digital hospital over a 3-week period. We observed and assisted with the management of several cultural, behavioural and

  20. Search and Disrupt

    Ørding Olsen, Anders

    . However, incumbent sources engaged in capability reconfiguration to accommodate disruption improve search efforts in disruptive technologies. The paper concludes that the value of external sources is contingent on more than their knowledge. Specifically, interdependence of sources in search gives rise...... to influence from individual strategic interests on the outcomes. More generally, this points to the need for understanding the two-way influence of sources, rather than viewing external search as one-way knowledge accessing....

  1. Disruptive technologies in higher education

    Michael Flavin

    2012-08-01

    Full Text Available This paper analyses the role of “disruptive” innovative technologies in higher education. In this country and elsewhere, Higher Education Institutions (HEIs have invested significant sums in learning technologies, with Virtual Learning Environments (VLEs being more or less universal, but these technologies have not been universally adopted and used by students and staff. Instead, other technologies not owned or controlled by HEIs are widely used to support learning and teaching. According to Christensen's theory of Disruptive Innovation, these disruptive technologies are not designed explicitly to support learning and teaching in higher education, but have educational potential. This study uses Activity Theory and Expansive Learning to analyse data regarding the impact of disruptive technologies. The data were obtained through a questionnaire survey about awareness and use of technologies, and through observation and interviews, exploring participants’ actual practice. The survey answers tended to endorse Disruptive Innovation theory, with participants establishing meanings for technologies through their use of them, rather than in keeping with a designer's intentions. Observation revealed that learners use a narrow range of technologies to support learning, but with a tendency to use resources other than those supplied by their HEIs. Interviews showed that participants use simple and convenient technologies to support their learning and teaching. This study identifies a contradiction between learning technologies made available by HEIs, and technologies used in practice. There is no evidence to suggest that a wide range of technologies is being used to support learning and teaching. Instead, a small range of technologies is being used for a wide range of tasks. Students and lecturers are not dependent on their HEIs to support learning and teaching. Instead, they self-select technologies, with use weighted towards established brands. The

  2. An organizational assessment of disruptive clinician behavior: findings and implications.

    Walrath, Jo M; Dang, Deborah; Nyberg, Dorothy

    2013-01-01

    This study investigated registered nurses' (RNs) and physicians' (MD) experiences with disruptive behavior, triggers, responses, and impacts on clinicians, patients, and the organization. Using the Disruptive Clinician Behavior Survey for Hospital Settings, it was found that RNs experienced a significantly higher frequency of disruptive behaviors and triggers than MDs; MDs (45% of 295) and RNs (37% of 689) reported that their peer's disruptive behavior affected them most negatively. The most frequently occurring trigger was pressure from high census, volume, and patient flow; 189 incidences of harm to patients as a result of disruptive behavior were reported. Findings provide organizational leaders with evidence to customize interventions to strengthen the culture of safety.

  3. Indomethacin causes prostaglandin D(2)-like and eotaxin-like selective responses in eosinophils and basophils.

    Stubbs, Victoria E L; Schratl, Petra; Hartnell, Adele; Williams, Timothy J; Peskar, Bernhard A; Heinemann, Akos; Sabroe, Ian

    2002-07-19

    We investigated the actions of a panel of nonsteroidal anti-inflammatory drugs on eosinophils, basophils, neutrophils, and monocytes. Indomethacin alone was a potent and selective inducer of eosinophil and basophil shape change. In eosinophils, indomethacin induced chemotaxis, CD11b up-regulation, respiratory burst, and L-selectin shedding but did not cause up-regulation of CD63 expression. Pretreatment of eosinophils with indomethacin also enhanced subsequent eosinophil shape change induced by eotaxin, although treatment with higher concentrations of indomethacin resulted in a decrease in the expression of the major eosinophil chemokine receptor, CCR3. Indomethacin activities and cell selectivity closely resembled those of prostaglandin D(2) (PGD(2)). Eosinophil shape change in response to eotaxin was inhibited by pertussis toxin, but indomethacin- and PGD(2)-induced shape change responses were not. Treatment of eosinophils with specific inhibitors of phospholipase C (U-73122), phosphatidylinositol 3-kinase (LY-294002), and p38 mitogen-activated protein kinase (SB-202190) revealed roles for these pathways in indomethacin signaling. Indomethacin and its analogues may therefore provide a structural basis from which selective PGD(2) receptor small molecule antagonists may be designed and which may have utility in the treatment of allergic inflammatory disease.

  4. Gender based disruptive selection maintains body size ...

    2014-07-04

    Jul 4, 2014 ... life (Roff 1992), perhaps a belief strengthened due to its ... tionary time scale. Hence, if 'bigger is .... (RM)'. Freshly emerged adults were paired with the self- ..... Pitnick S and Garcia-Gonzalez F 2002 Harm to females increases.

  5. Evolution in response to social selection: the importance of interactive effects of traits on fitness.

    Westneat, David F

    2012-03-01

    Social interactions have a powerful effect on the evolutionary process. Recent attempts to synthesize models of social selection with equations for indirect genetic effects (McGlothlin et al. 2010) provide a broad theoretical base from which to study selection and evolutionary response in the context of social interactions. However, this framework concludes that social selection will lead to evolution only if the traits carried by social partners are nonrandomly associated. I suggest this conclusion is incomplete, and that traits that do not covary between social partners can nevertheless lead to evolution via interactive effects on fitness. Such effects occur when there are functional interactions between traits, and as an example I use the interplay in water striders (Gerridae) between grasping appendages carried by males and spines by females. Functional interactive effects between traits can be incorporated into both the equations for social selection and the general model of social evolution proposed by McGlothlin et al. These expanded equations would accommodate adaptive coevolution in social interactions, integrate the quantitative genetic approach to social evolution with game theoretical approaches, and stimulate some new questions about the process of social evolution. © 2011 The Author. Evolution© 2011 The Society for the Study of Evolution.

  6. Host-selective toxins of Pyrenophora tritici-repentis induce common responses associated with host susceptibility.

    Iovanna Pandelova

    Full Text Available Pyrenophora tritici-repentis (Ptr, a necrotrophic fungus and the causal agent of tan spot of wheat, produces one or a combination of host-selective toxins (HSTs necessary for disease development. The two most studied toxins produced by Ptr, Ptr ToxA (ToxA and Ptr ToxB (ToxB, are proteins that cause necrotic or chlorotic symptoms respectively. Investigation of host responses induced by HSTs provides better insight into the nature of the host susceptibility. Microarray analysis of ToxA has provided evidence that it can elicit responses similar to those associated with defense. In order to evaluate whether there are consistent host responses associated with susceptibility, a similar analysis of ToxB-induced changes in the same sensitive cultivar was conducted. Comparative analysis of ToxA- and ToxB-induced transcriptional changes showed that similar groups of genes encoding WRKY transcription factors, RLKs, PRs, components of the phenylpropanoid and jasmonic acid pathways are activated. ROS accumulation and photosystem dysfunction proved to be common mechanism-of-action for these toxins. Despite similarities in defense responses, transcriptional and biochemical responses as well as symptom development occur more rapidly for ToxA compared to ToxB, which could be explained by differences in perception as well as by differences in activation of a specific process, for example, ethylene biosynthesis in ToxA treatment. Results of this study suggest that perception of HSTs will result in activation of defense responses as part of a susceptible interaction and further supports the hypothesis that necrotrophic fungi exploit defense responses in order to induce cell death.

  7. Angular and dose dependence of CR-39 neutron response for shape-selected tracks

    Tam, N C; Lakosi, L

    1999-01-01

    A shape selection method corresponding to an energy discrimination was used to eliminate unwanted events disturbing evaluation of CR-39 detectors in detecting tracks induced by particles both of perpendicular and oblique incidence. The angular dependence of the response was examined, detecting fast neutrons from sup 2 sup 5 sup 2 Cf with shape selection technique at various angles and distances. Also, the CR-39 track detectors with the sup 2 sup 5 sup 2 Cf source were exposed to high gamma-intensity of a sup 6 sup 0 Co irradiation facility in the range 0.1 to 4.5 kGy, similar to the exposures inside spent fuel assemblies. Using the two functions the lower limit of burnup could be determined by the method.

  8. Disruption prediction at JET

    Milani, F.

    1998-12-01

    The sudden loss of the plasma magnetic confinement, known as disruption, is one of the major issue in a nuclear fusion machine as JET (Joint European Torus). Disruptions pose very serious problems to the safety of the machine. The energy stored in the plasma is released to the machine structure in few milliseconds resulting in forces that at JET reach several Mega Newtons. The problem is even more severe in the nuclear fusion power station where the forces are in the order of one hundred Mega Newtons. The events that occur during a disruption are still not well understood even if some mechanisms that can lead to a disruption have been identified and can be used to predict them. Unfortunately it is always a combination of these events that generates a disruption and therefore it is not possible to use simple algorithms to predict it. This thesis analyses the possibility of using neural network algorithms to predict plasma disruptions in real time. This involves the determination of plasma parameters every few milliseconds. A plasma boundary reconstruction algorithm, XLOC, has been developed in collaboration with Dr. D. O'Brien and Dr. J. Ellis capable of determining the plasma wall/distance every 2 milliseconds. The XLOC output has been used to develop a multilayer perceptron network to determine plasma parameters as l i and q ψ with which a machine operational space has been experimentally defined. If the limits of this operational space are breached the disruption probability increases considerably. Another approach for prediction disruptions is to use neural network classification methods to define the JET operational space. Two methods have been studied. The first method uses a multilayer perceptron network with softmax activation function for the output layer. This method can be used for classifying the input patterns in various classes. In this case the plasma input patterns have been divided between disrupting and safe patterns, giving the possibility of

  9. Highly selective and rapidly responsive fluorescent probe for hydrogen sulfide detection in wine.

    Wang, Hao; Wang, Jialin; Yang, Shaoxiang; Tian, Hongyu; Liu, Yongguo; Sun, Baoguo

    2018-08-15

    A new fluorescent probe 6-(2, 4-dinitrophenoxy)-2-naphthonitrile (probe 1) was designed and synthesized for the selective detection of hydrogen sulfide (H 2 S). The addition of H 2 S to a solution of probe 1 resulted in a marked fluorescence turn-on alongside a visual color change from colorless to light yellow. Importantly, this distinct color response indicated that probe 1 could be used as a visual sensor for H 2 S. Moreover, probe 1 was successfully used as a signal tool to determine the H 2 S levels in beer and red wine. Copyright © 2018 Elsevier Ltd. All rights reserved.

  10. Selection of the optimum combination of responses for Wave Buoy Analogy - An approach based on local sensitivity analysis

    Montazeri, Najmeh; Nielsen, Ulrik Dam; Jensen, Jørgen Juncher

    2016-01-01

    One method to estimate the wave spectrum onboard ships is to use measured ship responses. In this method, known also as Wave Buoy Analogy, amongst various responses that are available from sensor measurements, a couple of responses (at least three) are usually utilized. Selec-tion of the best com...

  11. Microanalysis on selected video clips with focus on communicative response in music therapy

    Ridder, Hanne Mette Ochsner

    2007-01-01

    This chapter describes a five-step procedure for video analysis where the topic of investigation is the communicative response of clients in music therapy. In this microanalysis procedure only very short video clips are used, and in order to select these clips an overview of each music therapy...... session is obtained with the help of a session-graph that is a systematic way of collecting video observations from one music therapy session and combining the data in one figure. The systematic procedures do not demand sophisticated computer equipment; only standard programmes such as Excel and a media...... player. They are based on individual music therapy work with a population who are difficult to engage in joint activities and who show little response (e.g. persons suffering from severe dementia). The video analysis tools might be relevant to other groups of clients where it is important to form a clear...

  12. Effect of dietary restriction on immune response of laboratory mice divergently selected for basal metabolic rate.

    Książek, Aneta; Konarzewski, Marek

    2012-01-01

    To study whether dietary restriction (DR; 70% of ad lib. feeding)-elicited immunosuppression results from the trade-off between the costs of mounting an immune response and the metabolic costs of maintenance, we subjected mice from two divergent lines selected for high basal metabolic rate (H-BMR) and low BMR (L-BMR) to 4 wk of DR and then challenged them with keyhole limpet hemocyanin (KLH) antigen. Those line types differ genetically with respect to BMR and to the mass of metabolically expensive internal organs, which are larger in H-BMR mice. In mice of both line types, DR resulted in a significant reduction of body mass, an immune response, and the downsizing of spleen, lymph nodes, thymus, heart, and kidneys but not small intestines. DR resulted in a greater reduction of the spleen and lymph nodes in mice of the H-BMR line type, whereas the thymus was more affected in L-BMR line type. In contrast, immunization resulted in an increase of liver mass in DR mice of both line types. A comparison of the results of current and earlier studies on the same mouse line types suggests that metabolic trade-offs involving the costs of an immune response are more apparent when animals are forced to increase energy demands (e.g., by cold exposure) compared to when energy demands are decreased through DR. Our findings also suggest that divelrgent selection on BMR resulted in between-line-type differences in T-cell- and B-cell-mediated types of an immune response. More generally, our results indicate that production of a wide repertoire of antibodies is not correlated with high BMR.

  13. Selective vibration sensing: a new concept for activity-sensing rate-responsive pacing.

    Lau, C P; Stott, J R; Toff, W D; Zetlein, M B; Ward, D E; Camm, A J

    1988-09-01

    A clinically available model of an activity-sensing, rate-responsive pacemaker (Activitrax, Medtronic) utilizes body vibration during exercise as an indicator of the need for a rate increase. Although having the advantage of rapid onset of rate response, this system lacks specificity and the rate response does not closely correlate with the level of exertion. In addition, this pacemaker is susceptible to the effects of extraneous vibration. In this study involving 20 normal subjects fitted with an external Activitrax pacemaker, the rate responses to a variety of exercises were studied and were compared with the corresponding sinus rates. The vibration generated at the level of the pacemaker was also measured by accelerometers in three axes. Only a fair correlation (r = 0.51) was achieved between the pacemaker rate and the sinus rate. The total root mean square value of acceleration in either the anteroposterior or the vertical axes was found to have a better correlation (r = 0.8). As the main accelerations during physical activities were in the lower frequency range (0.1-4 Hz), a low-pass filter was used to reduce the influence of extraneous vibration. Selective sensing of the acceleration level may be usefully implemented in an algorithm for activity pacing.

  14. Postprandial glucose response to selected tropical fruits in normal glucose-tolerant Nigerians.

    Edo, A; Eregie, A; Adediran, O; Ohwovoriole, A; Ebengho, S

    2011-01-01

    The glycemic response to commonly eaten fruits in Nigeria has not been reported. Therefore, this study assessed the plasma glucose response to selected fruits in Nigeria. Ten normal glucose-tolerant subjects randomly consumed 50 g carbohydrate portions of three fruits: banana (Musa paradisiaca), pineapple (Ananus comosus), and pawpaw (Carica papaya), and a 50-g glucose load at 1-week intervals. Blood samples were collected in the fasting state and half-hourly over a 2-h period post-ingestion of the fruits or glucose. The samples were analyzed for plasma glucose concentrations. Plasma glucose responses were assessed by the peak plasma glucose concentration, maximum increase in plasma glucose, 2-h postprandial plasma glucose level, and incremental area under the glucose curve and glycemic index (GI). The results showed that the blood glucose response to these three fruits was similar in terms of their incremental areas under the glucose curve, maximum increase in plasma glucose, and glycemic indices (GIs). The 2-h postprandial plasma glucose level of banana was significantly higher than that of pineapple, P < 0.025. The mean ± SEM GI values were as follows: pawpaw; 86 ± 26.8%; banana, 75.1 ± 21.8%; pineapple, 64.5 ± 11.3%. The GI of glucose is taken as 100. The GI of pineapple was significantly lower than that of glucose (P < 0.05). Banana, pawpaw, and pineapple produced a similar postprandial glucose response. Measured portions of these fruits may be used as fruit exchanges with pineapple having the most favorable glycemic response.

  15. Selective adsorption of oppositely charged PNIPAAM on halloysite surfaces: a route to thermo-responsive nanocarriers.

    Cavallaro, Giuseppe; Lazzara, Giuseppe; Lisuzzo, Lorenzo; Milioto, Stefana; Parisi, Filippo

    2018-05-17

    Halloysite nanotubes were functionalized with stimuli-responsive macromolecules to generate smart nanohybrids. Poly(N-isopropylacrylamide)-co-methacrylic acid (PNIPAAM-co-MA) was selectively adsorbed into halloysite lumen by exploiting electrostatic interactions. Amine-terminated PNIPAAM polymer was also investigated that selectively interacts with the outer surface of the nanotubes. The adsorption site has a profound effect on the thermodynamic behavior and therefore temperature responsive features of the hybrid material. The drug release kinetics was investigated by using Diclofenac as a non-steroidal anti-inflammatory drug model. The release kinetics depends on the nanoarchitecture of the PNIPAAM/Halloysite based material. In particular, diclofenac release was slowed down above the LCST for PNIPAAM-co-MA/Halloysite. Opposite trends occurred for Halloysite functionalized with PNIPAAM at the outer surface. This work represents a further step toward the opportunity to extend and control the delivery conditions of active species, which represent a key point in technological applications. © 2018 IOP Publishing Ltd.

  16. Nutrient Content and Nutritional Water Productivity of Selected Grain Legumes in Response to Production Environment.

    Chibarabada, Tendai Polite; Modi, Albert Thembinkosi; Mabhaudhi, Tafadzwanashe

    2017-10-26

    There is a need to incorporate nutrition into aspects of crop and water productivity to tackle food and nutrition insecurity (FNS). The study determined the nutritional water productivity (NWP) of selected major (groundnut, dry bean) and indigenous (bambara groundnut and cowpea) grain legumes in response to water regimes and environments. Field trials were conducted during 2015/16 and 2016/17 at three sites in KwaZulu-Natal, South Africa (Ukulinga, Fountainhill and Umbumbulu). Yield and evapotranspiration (ET) data were collected. Grain was analysed for protein, fat, Ca, Fe and Zn nutrient content (NC). Yield, ET and NC were then used to compute NWP. Overall, the major legumes performed better than the indigenous grain legumes. Groundnut had the highest NWP fat . Groundnut and dry bean had the highest NWP protein . For NWP Fe, Zn and Ca , dry bean and cowpea were more productive. Yield instability caused fluctuations in NWP. Water treatments were not significant ( p > 0.05). While there is scope to improve NWP under rainfed conditions, a lack of crop improvement currently limits the potential of indigenous grain legumes. This provides an initial insight on the nutrient content and NWP of a limited number of selected grain legumes in response to the production environment. There is a need for follow-up research to include cowpea data. Future studies should provide more experimental data and explore effects of additional factors such as management practices (fertiliser levels and plant density), climate and edaphic factors on nutrient content and NWP of crops.

  17. The disruption management model.

    McAlister, James

    2011-10-01

    Within all organisations, business continuity disruptions present a set of dilemmas that managers may not have dealt with before in their normal daily duties. The disruption management model provides a simple but effective management tool to enable crisis management teams to stay focused on recovery in the midst of a business continuity incident. The model has four chronological primary headlines, which steer the team through a quick-time crisis decision-making process. The procedure facilitates timely, systematic, rationalised and justified decisions, which can withstand post-event scrutiny. The disruption management model has been thoroughly tested within an emergency services environment and is proven to significantly support clear and concise decision making in a business continuity context.

  18. Emerging and Disruptive Technologies.

    Kricka, Larry J

    2016-08-01

    Several emerging or disruptive technologies can be identified that might, at some point in the future, displace established laboratory medicine technologies and practices. These include increased automation in the form of robots, 3-D printing, technology convergence (e.g., plug-in glucose meters for smart phones), new point-of-care technologies (e.g., contact lenses with sensors, digital and wireless enabled pregnancy tests) and testing locations (e.g., Retail Health Clinics, new at-home testing formats), new types of specimens (e.g., cell free DNA), big biology/data (e.g., million genome projects), and new regulations (e.g., for laboratory developed tests). In addition, there are many emerging technologies (e.g., planar arrays, mass spectrometry) that might find even broader application in the future and therefore also disrupt current practice. One interesting source of disruptive technology may prove to be the Qualcomm Tricorder XPrize, currently in its final stages.

  19. Sustainable Disruption Management

    Vaaben, Bo Valdemar

    The world we live in is globalized. Goods are seldom made in the place where they are used or consumed, and we do increasingly travel to other countries for either business or pleasure. In our everyday lives we rely on well-functioning global transportations systems to continue the standard...... in the same way, when operation is disrupted. Never the less, we may recall that the Suez Canal was closed due to riots in Egypt, that the fuel price was impacted by threats of closing of the Strait of Hormuz, and we do from time to time hear about acts of piracy outside the coast of Somalia. All...... papers combining disruption management and flight planning through an integrated optimization approach. An additional contribution of the thesis is to show how flexible flight speeds can be used to improve recovery from disruptions, while at the same time allowing an airline to trade off fuel costs...

  20. Perceptions of similarity and response to selected comparison targets in type 2 diabetes.

    Arigo, Danielle; Smyth, Joshua M; Suls, Jerry M

    2015-01-01

    Social comparisons (i.e. self-evaluations relative to others) may affect motivation for diabetes self-care behaviours. Comparisons can have either positive or negative effects, but it is not clear what differentiates these responses. This study tested the effect of a patient's perceived similarity to a comparison target on motivation for self-care. Individuals with type 2 diabetes (n = 180, MA1c = 7.59%) selected to read one of four brief descriptions of a patient with diabetes. Participants rated their motivation for self-care behaviours prior and subsequent to reading and reported the extent to which they focused on similarities between the self and the selected patient while reading. Perceived similarity moderated the effect of selection on motivation for self-care (p = .01, η2 = .06). Increased motivation was observed if participants focused on similarities with patients 'doing better' (i.e. high coping effectiveness/low symptom severity) and decreased motivation if they focused on similarities with patients 'doing worse' (low coping effectiveness/high symptom severity). Providing social comparison information in diabetes management (and perhaps other chronic diseases) may improve motivation for self-care among some patients. A subset of patients, however, may benefit from guidance to focus on similarities with certain targets.

  1. Objective Model Selection for Identifying the Human Feedforward Response in Manual Control.

    Drop, Frank M; Pool, Daan M; van Paassen, Marinus Rene M; Mulder, Max; Bulthoff, Heinrich H

    2018-01-01

    Realistic manual control tasks typically involve predictable target signals and random disturbances. The human controller (HC) is hypothesized to use a feedforward control strategy for target-following, in addition to feedback control for disturbance-rejection. Little is known about human feedforward control, partly because common system identification methods have difficulty in identifying whether, and (if so) how, the HC applies a feedforward strategy. In this paper, an identification procedure is presented that aims at an objective model selection for identifying the human feedforward response, using linear time-invariant autoregressive with exogenous input models. A new model selection criterion is proposed to decide on the model order (number of parameters) and the presence of feedforward in addition to feedback. For a range of typical control tasks, it is shown by means of Monte Carlo computer simulations that the classical Bayesian information criterion (BIC) leads to selecting models that contain a feedforward path from data generated by a pure feedback model: "false-positive" feedforward detection. To eliminate these false-positives, the modified BIC includes an additional penalty on model complexity. The appropriate weighting is found through computer simulations with a hypothesized HC model prior to performing a tracking experiment. Experimental human-in-the-loop data will be considered in future work. With appropriate weighting, the method correctly identifies the HC dynamics in a wide range of control tasks, without false-positive results.

  2. Application of drug selective electrode in the drug release study of pH-responsive microgels.

    Tan, Jeremy P K; Tam, Kam C

    2007-03-12

    The colloidal phenomenon of soft particles is becoming an important field of research due to the growing interest in using polymeric system in drug delivery. Previous studies have focused on techniques that require intermediate process step such as dialysis or centrifugation, which introduces additional errors in obtaining the diffusion kinetic data. In this study, a drug selective electrode was used to directly measure the concentration of procaine hydrochloride (PrHy) released from methacrylic acid-ethyl acrylate (MAA-EA) microgel, thereby eliminating the intermediate process step. PrHy selective membrane constructed using a modified poly (vinyl chloride) (PVC) membrane and poly (ethylene-co-vinyl acetate-co-carbon monoxide) as plasticizer exhibited excellent reproducibility and stability. The response was reproducible at pH of between 3 to 8.5 and the selectivity coefficients against various organic and inorganic cations were evaluated. Drug release was conducted using the drug electrode under different pHs and the release rate increased with pH. The release behavior of the system under different pH exhibited obvious gradient release characteristics.

  3. Non-ignorable missingness item response theory models for choice effects in examinee-selected items.

    Liu, Chen-Wei; Wang, Wen-Chung

    2017-11-01

    Examinee-selected item (ESI) design, in which examinees are required to respond to a fixed number of items in a given set, always yields incomplete data (i.e., when only the selected items are answered, data are missing for the others) that are likely non-ignorable in likelihood inference. Standard item response theory (IRT) models become infeasible when ESI data are missing not at random (MNAR). To solve this problem, the authors propose a two-dimensional IRT model that posits one unidimensional IRT model for observed data and another for nominal selection patterns. The two latent variables are assumed to follow a bivariate normal distribution. In this study, the mirt freeware package was adopted to estimate parameters. The authors conduct an experiment to demonstrate that ESI data are often non-ignorable and to determine how to apply the new model to the data collected. Two follow-up simulation studies are conducted to assess the parameter recovery of the new model and the consequences for parameter estimation of ignoring MNAR data. The results of the two simulation studies indicate good parameter recovery of the new model and poor parameter recovery when non-ignorable missing data were mistakenly treated as ignorable. © 2017 The British Psychological Society.

  4. An ILP based Algorithm for Optimal Customer Selection for Demand Response in SmartGrids

    Kuppannagari, Sanmukh R. [Univ. of Southern California, Los Angeles, CA (United States); Kannan, Rajgopal [Louisiana State Univ., Baton Rouge, LA (United States); Prasanna, Viktor K. [Univ. of Southern California, Los Angeles, CA (United States)

    2015-12-07

    Demand Response (DR) events are initiated by utilities during peak demand periods to curtail consumption. They ensure system reliability and minimize the utility’s expenditure. Selection of the right customers and strategies is critical for a DR event. An effective DR scheduling algorithm minimizes the curtailment error which is the absolute difference between the achieved curtailment value and the target. State-of-the-art heuristics exist for customer selection, however their curtailment errors are unbounded and can be as high as 70%. In this work, we develop an Integer Linear Programming (ILP) formulation for optimally selecting customers and curtailment strategies that minimize the curtailment error during DR events in SmartGrids. We perform experiments on real world data obtained from the University of Southern California’s SmartGrid and show that our algorithm achieves near exact curtailment values with errors in the range of 10-7 to 10-5, which are within the range of numerical errors. We compare our results against the state-of-the-art heuristic being deployed in practice in the USC SmartGrid. We show that for the same set of available customer strategy pairs our algorithm performs 103 to 107 times better in terms of the curtailment errors incurred.

  5. Bayesian estimation of direct and correlated responses to selection on linear or ratio expressions of feed efficiency in pigs

    Shirali, Mahmoud; Varley, Patrick Francis; Jensen, Just

    2018-01-01

    meat percentage (LMP) along with the derived traits of RFI and FCR; and (3) deriving Bayesian estimates of direct and correlated responses to selection on RFI, FCR, ADG, ADFI, and LMP. Response to selection was defined as the difference in additive genetic mean of the selected top individuals, expected......, respectively. Selection against RFIG showed a direct response of − 0.16 kg/d and correlated responses of − 0.16 kg/kg for FCR and − 0.15 kg/d for ADFI, with no effect on other production traits. Selection against FCR resulted in a direct response of − 0.17 kg/kg and correlated responses of − 0.14 kg/d for RFIG......, − 0.18 kg/d for ADFI, and 0.98% for LMP. Conclusions: The Bayesian methodology developed here enables prediction of breeding values for FCR and RFI from a single multi-variate model. In addition, we derived posterior distributions of direct and correlated responses to selection. Genetic parameter...

  6. Treatment of Osteomyelitis: A Case for Disruption of the Affected Adjacent Periosteum.

    Hudson, John W; Daly, Austin P; Foster, Michael

    2017-10-01

    To evaluate the response of mandibular osteomyelitis treated by surgical decortication with disruption of the affected adjacent periosteum in concert with long-term targeted antibiotic therapy. The hypothesis is that, by removing the buccal cortical plate and disrupting the hypertrophically inflamed adjacent periosteum, the medullary bone will be brought in contact with bleeding tissue and circulating immunologic factors and antibiotics, which will promote definitive resolution. A retrospective review was conducted of 7 patient charts with associated radiographs from November 2010 to August 2016 treated by the first author at the University of Tennessee Medical Center (Knoxville, TN). Patients with chronic suppurative or nonsuppurative osteomyelitis of the mandible without condylar involvement or pathologic fracture were selected and treated with decortication with periosteal disruption in combination with long-term targeted antibiotic therapy. Seven patients (3 women and 4 men; mean age, 60 yr) underwent decortication with periosteal disruption of the affected area and received at least 6 weeks of targeted intravenous antibiotics. Computed tomography was performed preoperatively and a repeat study was performed after completion of antibiotics. In each case, post-treatment imaging showed definitive resolution after treatment with decortication in concert with disruption of the inflamed hypertrophic periosteum and intravenous antibiotics. Debridement of the infected cortical bone with restoration of the blood supply through disruption of the adjacent periosteum provided definitive resolution of mandibular osteomyelitis in the 7 patients treated. The hypothesis is that disruption of the affected adjacent periosteum reintroduces an immune-mediated response in concert with improved antibiotic delivery to and penetrance of the diseased mandible, aiding in definitive resolution. Decortication with periosteal disruption allows for preservation of the inferior alveolar

  7. Evolution of the metabolome in response to selection for increased immunity in populations of Drosophila melanogaster.

    Gogna, Navdeep; Sharma, Rakesh; Gupta, Vanika; Dorai, Kavita; Prasad, N G

    2017-01-01

    We used NMR-based metabolomics to test two hypotheses-(i) there will be evolved differences in the metabolome of selected and control populations even under un-infected conditions and (ii) post infection, the metabolomes of the selected and control populations will respond differently. We selected replicate populations of Drosophila melanogaster for increased survivorship (I) against a gram-negative pathogen. We subjected the selected (I) and their control populations (S) to three different treatments: (1) infected with heat-killed bacteria (i), (2) sham infected (s), and (3) untreated (u). We performed 1D and 2D NMR experiments to identify the metabolic differences. Multivariate analysis of the metabolic profiles of the untreated (Iu and Su) flies yielded higher concentrations of lipids, organic acids, sugars, amino acids, NAD and AMP in the Iu treatment as compared to the Su treatment, showing that even in the absence of infection, the metabolome of the I and S regimes was different. In the S and I regimes, post infection/injury, concentration of metabolites directly or indirectly associated with energy related pathways (lipids, organic acids, sugars) declined while the concentration of metabolites that are probably associated with immune response (amino acids) increased. However, in most cases, the I regime flies had a higher concentration of such metabolites even under un-infected conditions. The change in the metabolite concentration upon infection/injury was not always comparable between I and S regimes (in case of lactate, alanine, leucine, lysine, threonine) indicating that the I and S regimes had evolved to respond differentially to infection and to injury.

  8. HERITABILITY AND RESPONSE TO SELECTION FOR GROWTH IN THE F1 GENERATION OF CRAYFISH Procambarus acanthophorus

    Carlos Perez Rostro

    2012-11-01

    Full Text Available The crayfish Procambarus (A. acanthophorus is a crustacean relevant for regional fisheries in Veracruz, Mexico, with ideal aquaculture characteristics, except for its small size. Thus, a study was conducted with the aim to evaluate the response to selection in the first generation (F1 and heritability (h2 of the crayfish. A group of 2135 organisms with average weight (±S.D. 4.1 ± 1.79 g were captured from the wild (G0, and 10 % (i = 1,755 of the population was selected with the highest body weight by gender: 140 females (5.62 ± 1.97 g and 48 males (6.02 ± 1.9 g, forming the progenitors of the selection line (LS. The control line (LC was formed from a batch obtained at random. Thirty full-sib families were obtained per line (F1, and cultured individually for five months in a recirculation system with mechanical and biological filtration under laboratory conditions and supplied with food twice a day (Camaronina 35 % protein. Monthly heritability (h2 in broad sense was estimated using a full-sib design, based on the components of variance (ANOVA REML method and the growth was compared between lines in the F1. The mean h2's for weight after five months of culture were 0.27±0.11 for LC and 0.34±0.12 for LS, being the LS in F1 9.6 % heavier than the LC, with 84 and 88 % survival at the end of the study. It is possible to implement a breeding program based on selection for species growth.

  9. Integrated watershed-scale response to climate change for selected basins across the United States

    Markstrom, Steven L.; Hay, Lauren E.; Ward-Garrison, D. Christian; Risley, John C.; Battaglin, William A.; Bjerklie, David M.; Chase, Katherine J.; Christiansen, Daniel E.; Dudley, Robert W.; Hunt, Randall J.; Koczot, Kathryn M.; Mastin, Mark C.; Regan, R. Steven; Viger, Roland J.; Vining, Kevin C.; Walker, John F.

    2012-01-01

    A study by the U.S. Geological Survey (USGS) evaluated the hydrologic response to different projected carbon emission scenarios of the 21st century using a hydrologic simulation model. This study involved five major steps: (1) setup, calibrate and evaluated the Precipitation Runoff Modeling System (PRMS) model in 14 basins across the United States by local USGS personnel; (2) acquire selected simulated carbon emission scenarios from the World Climate Research Programme's Coupled Model Intercomparison Project; (3) statistical downscaling of these scenarios to create PRMS input files which reflect the future climatic conditions of these scenarios; (4) generate PRMS projections for the carbon emission scenarios for the 14 basins; and (5) analyze the modeled hydrologic response. This report presents an overview of this study, details of the methodology, results from the 14 basin simulations, and interpretation of these results. A key finding is that the hydrological response of the different geographical regions of the United States to potential climate change may be different, depending on the dominant physical processes of that particular region. Also considered is the tremendous amount of uncertainty present in the carbon emission scenarios and how this uncertainty propagates through the hydrologic simulations.

  10. Acoustic stimulation can induce a selective neural network response mediated by piezoelectric nanoparticles

    Rojas, Camilo; Tedesco, Mariateresa; Massobrio, Paolo; Marino, Attilio; Ciofani, Gianni; Martinoia, Sergio; Raiteri, Roberto

    2018-06-01

    Objective. We aim to develop a novel non-invasive or minimally invasive method for neural stimulation to be applied in the study and treatment of brain (dys)functions and neurological disorders. Approach. We investigate the electrophysiological response of in vitro neuronal networks when subjected to low-intensity pulsed acoustic stimulation, mediated by piezoelectric nanoparticles adsorbed on the neuronal membrane. Main results. We show that the presence of piezoelectric barium titanate nanoparticles induces, in a reproducible way, an increase in network activity when excited by stationary ultrasound waves in the MHz regime. Such a response can be fully recovered when switching the ultrasound pulse off, depending on the generated pressure field amplitude, whilst it is insensitive to the duration of the ultrasound pulse in the range 0.5 s–1.5 s. We demonstrate that the presence of piezoelectric nanoparticles is necessary, and when applying the same acoustic stimulation to neuronal cultures without nanoparticles or with non-piezoelectric nanoparticles with the same size distribution, no network response is observed. Significance. We believe that our results open up an extremely interesting approach when coupled with suitable functionalization strategies of the nanoparticles in order to address specific neurons and/or brain areas and applied in vivo, thus enabling remote, non-invasive, and highly selective modulation of the activity of neuronal subpopulations of the central nervous system of mammalians.

  11. Maternal inflammation induces immune activation of fetal microglia and leads to disrupted microglia immune responses, behavior, and learning performance in adulthood.

    Schaafsma, Wandert; Basterra, Laura Bozal; Jacobs, Sabrina; Brouwer, Nieske; Meerlo, Peter; Schaafsma, Anne; Boddeke, Erik W G M; Eggen, Bart J L

    2017-10-01

    Maternal inflammation during pregnancy can have detrimental effects on embryonic development that persist during adulthood. However, the underlying mechanisms and insights in the responsible cell types are still largely unknown. Here we report the effect of maternal inflammation on fetal microglia, the innate immune cells of the central nervous system (CNS). In mice, a challenge with LPS during late gestation stages (days 15-16-17) induced a pro-inflammatory response in fetal microglia. Adult whole brain microglia of mice that were exposed to LPS during embryonic development displayed a persistent reduction in pro-inflammatory activation in response to a re-challenge with LPS. In contrast, hippocampal microglia of these mice displayed an increased inflammatory response to an LPS re-challenge. In addition, a reduced expression of brain-derived neurotrophic factor (BDNF) was observed in hippocampal microglia of LPS-offspring. Microglia-derived BDNF has been shown to be important for learning and memory processes. In line with these observations, behavioral- and learning tasks with mice that were exposed to maternal inflammation revealed reduced home cage activity, reduced anxiety and reduced learning performance in a T-maze. These data show that exposure to maternal inflammation during late gestation results in long term changes in microglia responsiveness during adulthood, which is different in nature in hippocampus compared to total brain microglia. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Age-related slowing of response selection and production in a visual choice reaction time task

    David L Woods

    2015-04-01

    Full Text Available Aging is associated with delayed processing in choice reaction time (CRT tasks, but the processing stages most impacted by aging have not been clearly identified. Here, we analyzed CRT latencies in a computerized serial visual feature-conjunction task. Participants responded to a target letter (probability 40% by pressing one mouse button, and responded to distractor letters differing either in color, shape, or both features from the target (probabilities 20% each, by pressing the other mouse button. Stimuli were presented randomly to the left and right visual fields and stimulus onset asynchronies (SOAs were adaptively reduced following correct responses using a staircase procedure. In Experiment 1, we tested 1466 participants who ranged in age from 18 to 65 years. CRT latencies increased significantly with age (r = 0.47, 2.80 ms/year. Central processing time (CPT, isolated by subtracting simple reaction times (obtained in a companion experiment performed on the same day from CRT latencies, accounted for more than 80% of age-related CRT slowing, with most of the remaining increase in latency due to slowed motor responses. Participants were faster and more accurate when the stimulus location was spatially compatible with the mouse button used for responding, and this effect increased slightly with age. Participants took longer to respond to distractors with target color or shape than to distractors with no target features. However, the additional time needed to discriminate the more target-like distractors did not increase with age. In Experiment 2, we replicated the findings of Experiment 1 in a second population of 178 participants (ages 18-82 years. CRT latencies did not differ significantly in the two experiments, and similar effects of age, distractor similarity, and stimulus-response spatial compatibility were found. The results suggest that the age-related slowing in visual CRT latencies is largely due to delays in response selection and

  13. Selection for increased desiccation resistance in Drosophila melanogaster: Additive genetic control and correlated responses for other stresses

    Hoffmann, A.A.; Parsons, P.A.

    1989-01-01

    Previously we found that Drosophila melanogaster lines selected for increased desiccation resistance have lowered metabolic rate and behavioral activity levels, and show correlated responses for resistance to starvation and a toxic ethanol level. These results were consistent with a prediction that increased resistance to many environmental stresses may be genetically correlated because of a reduction in metabolic energy expenditure. Here we present experiments on the genetic basis of the selection response and extend the study of correlated responses to other stresses. The response to selection was not sex-specific and involved X-linked and autosomal genes acting additively. Activity differences contributed little to differences in desiccation resistance between selected and control lines. Selected lines had lower metabolic rates than controls in darkness when activity was inhibited. Adults from selected lines showed increased resistance to a heat shock, 60 Co-gamma-radiation, and acute ethanol and acetic acid stress. The desiccation, ethanol and starvation resistance of isofemale lines set up from the F2s of a cross between one of the selected and one of the control lines were correlated. Selected and control lines did not differ in ether-extractable lipid content or in resistance to acetone, ether or a cold shock

  14. Reversed Procrastination by Focal Disruption of Medial Frontal Cortex.

    Jha, Ashwani; Diehl, Beate; Scott, Catherine; McEvoy, Andrew W; Nachev, Parashkev

    2016-11-07

    An enduring puzzle in the neuroscience of voluntary action is the origin of the remarkably wide dispersion of the reaction time distribution, an interval far greater than is explained by synaptic or signal transductive noise [1, 2]. That we are able to change our planned actions-a key criterion of volition [3]-so close to the time of their onset implies decision-making must reach deep into the execution of action itself [4-6]. It has been influentially suggested the reaction time distribution therefore reflects deliberate neural procrastination [7], giving alternative response tendencies sufficient time for fair competition in pursuing a decision threshold that determines which one is behaviorally manifest: a race model, where action selection and execution are closely interrelated [8-11]. Although the medial frontal cortex exhibits a sensitivity to reaction time on functional imaging that is consistent with such a mechanism [12-14], direct evidence from disruptive studies has hitherto been lacking. If movement-generating and movement-delaying neural substrates are closely co-localized here, a large-scale lesion will inevitably mask any acceleration, for the movement itself could be disrupted. Circumventing this problem, here we observed focal intracranial electrical disruption of the medial frontal wall in the context of the pre-surgical evaluation of two patients with epilepsy temporarily reversing such hypothesized procrastination. Effector-specific behavioral acceleration, time-locked to the period of electrical disruption, occurred exclusively at a specific locus at the ventral border of the pre-supplementary motor area. A cardinal prediction of race models of voluntary action is thereby substantiated in the human brain. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Comparison of Portfolio Selection and Performance: Shari’ah-Compliant and Socially Responsible Investment Portfolios

    Mehmet Asutay

    2015-04-01

    Full Text Available This study examines the effect of Islamic screening criteria on Shari’ah-compliant portfolio selection and performance compared to Socially Responsible Investment (SRI portfolio. Each portfolio constructed from 15 stocks based on FTSE 100 using data from year 1997. Mean-variance portfolio optimization is employed with some financial ratios added as constraints for the Shari’ah portfolio. Annual expected return of each portfolio from 2008 to 2013 is used to calculate Sharpe’s ratio, Treynor ratio and Jensen’s alpha as the performance measurement tools. Macroeconomic variables are assessed using ordinary least square to examine whether they influence the portfolios’ expected returns or not. The result finds that Shari’ah portfolio has a better performance than SRI from year 2008 to 2010 shown by higher value of the measurement tools. However, from 2011 to 2013, SRI portfolio has better performance than Shari’ah portfolio. 

  16. Endocrine Disrupting Contaminants—Beyond the Dogma

    Guillette, Louis J.

    2006-01-01

    Descriptions of endocrine disruption have largely been associated with wildlife and driven by observations documenting estrogenic, androgenic, antiandrogenic, and antithyroid actions. These actions, in response to exposure to ecologically relevant concentrations of various environmental contaminants, have now been established in numerous vertebrate species. However, many potential mechanisms and endocrine actions have not been studied. For example, the DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane] metabolite, p,p′-DDE [1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene] is known to disrupt prostaglandin synthesis in the uterus of birds, providing part of the explanation for DDT-induced egg shell thinning. Few studies have examined prostaglandin synthesis as a target for endocrine disruption, yet these hormones are active in reproduction, immune responses, and cardiovascular physiology. Future studies must broaden the basic science approach to endocrine disruption, thereby expanding the mechanisms and endocrine end points examined. This goal should be accomplished even if the primary influence and funding continue to emphasize a narrower approach based on regulatory needs. Without this broader approach, research into endocrine disruption will become dominated by a narrow dogma, focusing on a few end points and mechanisms. PMID:16818240

  17. Statistical analysis of JET disruptions

    Tanga, A.; Johnson, M.F.

    1991-07-01

    In the operation of JET and of any tokamak many discharges are terminated by a major disruption. The disruptive termination of a discharge is usually an unwanted event which may cause damage to the structure of the vessel. In a reactor disruptions are potentially a very serious problem, hence the importance of studying them and devising methods to avoid disruptions. Statistical information has been collected about the disruptions which have occurred at JET over a long span of operations. The analysis is focused on the operational aspects of the disruptions rather than on the underlining physics. (Author)

  18. Maternal and ambient environmental effects of light on germination in Plantago lanceolata: correlated responses to selection on leaf length

    Hinsberg, A. van

    1998-01-01

    1. Seeds from artificial selection lines were exposed to different maternal and ambient conditions, simulating sunlight and vegetation shade. 2. Lines selected for longer leaves also produced larger seeds, indicating a positive genetic correlation between leaf length and seed size. 3. Light conditions during maturation had no large effect on seed size. 4. Seed germination was reduced by a low ratio of red to far-red light (R/FR ratio) in the ambient environment. 5. Seeds maturated under simulated vegetation shade germinated less readily and were more inhibited by a low ambient R/FR ratio than seeds maturated under full sunlight or R/FR-neutral shade. Thus, low R/FR-ratios in the maternal and ambient environment operated synergistically. 6. Large genotypic variation in the germination responses to both maternal and ambient light conditions was found among and within selection lines, indicating that such responses might have the potential to evolve in response to natural selection. 7. Artificial selection for leaf length had affected seed germination characteristics but correlated responses and thus genetic correlations largely depended on light conditions in the selective environment. Selection for longer leaves under a low R/FR ratio increased seed dormancy and plasticity of germination in response to the R/FR ratio. However, in the opposite selective environment selection for longer leaves reduced seed dormancy and plasticity to the R/FR ratio. It is argued that leaf length and seed germination characteristics are somehow linked by shared physiological mechanisms, which may facilitate concerted changes in shade avoidance responses

  19. Effect of selective phosphodiesterase inhibitors on the rat eosinophil chemotactic response in vitro

    Alves Alessandra C

    1997-01-01

    Full Text Available In the present study, we have performed a comparative analysis of the effect of selective inhibitors of phosphodiesterase (PDE type III, IV and V on eosinophil chemotaxis triggered by platelet activating factor (PAF and leukotriene B4 (LTB4 in vitro. The effect of the analogues N6-2'-O-dibutyryladenosine 3':5' cyclic monophosphate (Bt2 cyclic AMP and N2-2'-O- dibutyrylguanosine 3':5' cyclic monophosphate (Bt2 cyclic GMP has also been determined. The eosinophils were obtained from the peritoneal cavity of naive Wistar rats and purified in discontinuous Percoll gradients to 85-95% purity. We observed that pre-incubation of eosinophils with the PDE type IV inhibitor rolipram suppressed the chemotactic response triggered by PAF and LTB4, in association with an increase in the intracellular levels of cyclic AMP. In contrast, neither zaprinast (type V inhibitor nor type III inhibitors milrinone and SK&F 94836 affected the eosinophil migration. Only at the highest concentration tested did the analogue Bt2 cyclic AMP suppress the eosinophil chemotaxis, under conditions where Bt2 cyclic GMP was ineffective. We have concluded that inhibition of PDE IV, but not PDE III or V, was able to block the eosinophil chemotaxis in vitro, suggesting that the suppressive activity of selective PDE IV inhibitors on tissue eosinophil accumulation may, at least, be partially dependent on their ability to directly inhibit the eosinophil migration.

  20. Practical guidelines to select and scale earthquake records for nonlinear response history analysis of structures

    Kalkan, Erol; Chopra, Anil K.

    2010-01-01

    Earthquake engineering practice is increasingly using nonlinear response history analysis (RHA) to demonstrate performance of structures. This rigorous method of analysis requires selection and scaling of ground motions appropriate to design hazard levels. Presented herein is a modal-pushover-based scaling (MPS) method to scale ground motions for use in nonlinear RHA of buildings and bridges. In the MPS method, the ground motions are scaled to match (to a specified tolerance) a target value of the inelastic deformation of the first-'mode' inelastic single-degree-of-freedom (SDF) system whose properties are determined by first-'mode' pushover analysis. Appropriate for first-?mode? dominated structures, this approach is extended for structures with significant contributions of higher modes by considering elastic deformation of second-'mode' SDF system in selecting a subset of the scaled ground motions. Based on results presented for two bridges, covering single- and multi-span 'ordinary standard' bridge types, and six buildings, covering low-, mid-, and tall building types in California, the accuracy and efficiency of the MPS procedure are established and its superiority over the ASCE/SEI 7-05 scaling procedure is demonstrated.

  1. Selective microrobot control using a thermally responsive microclamper for microparticle manipulation

    Go, Gwangjun; Choi, Hyunchul; Ko, Seong Young; Park, Jong-Oh; Park, Sukho; Jeong, Semi

    2016-01-01

    Microparticle manipulation using a microrobot in an enclosed environment, such as a lab-on-a-chip, has been actively studied because an electromagnetic actuated microrobot can have accurate motility and wireless controllability. In most studies on electromagnetic actuated microrobots, only a single microrobot has been used to manipulate cells or microparticles. However, the use of a single microrobot can pose several limitations when performing multiple roles in microparticle manipulation. To overcome the limitations associated with using a single microrobot, we propose a new method for the control of multiple microrobots. Multiple microrobots can be controlled independently by an electromagnetic actuation system and multiple microclampers combined with microheaters. To select a specific microrobot among multiple microrobots, we propose a microclamper composed of a clamper structure using thermally responsive hydrogel and a microheater for controlling the microclamper. A fundamental test of the proposed microparticle manipulation system is performed by selecting a specific microrobot among multiple microrobots. Through the independent locomotion of multiple microrobots with U- and V-shaped tips, heterogeneous microparticle manipulation is demonstrated in the creation of a two-dimensional structure. In the future, our proposed multiple-microrobot system can be applied to tasks that are difficult to perform using a single microrobot, such as cell manipulation, cargo delivery, tissue assembly, and cloning. (paper)

  2. Distributed BOLD-response in association cortex vector state space predicts reaction time during selective attention.

    Musso, Francesco; Konrad, Andreas; Vucurevic, Goran; Schäffner, Cornelius; Friedrich, Britta; Frech, Peter; Stoeter, Peter; Winterer, Georg

    2006-02-15

    Human cortical information processing is thought to be dominated by distributed activity in vector state space (Churchland, P.S., Sejnowski, T.J., 1992. The Computational Brain. MIT Press, Cambridge.). In principle, it should be possible to quantify distributed brain activation with independent component analysis (ICA) through vector-based decomposition, i.e., through a separation of a mixture of sources. Using event-related functional magnetic resonance imaging (fMRI) during a selective attention-requiring task (visual oddball), we explored how the number of independent components within activated cortical areas is related to reaction time. Prior to ICA, the activated cortical areas were determined on the basis of a General linear model (GLM) voxel-by-voxel analysis of the target stimuli (checkerboard reversal). Two activated cortical areas (temporoparietal cortex, medial prefrontal cortex) were further investigated as these cortical regions are known to be the sites of simultaneously active electromagnetic generators which give rise to the compound event-related potential P300 during oddball task conditions. We found that the number of independent components more strongly predicted reaction time than the overall level of "activation" (GLM BOLD-response) in the left temporoparietal area whereas in the medial prefrontal cortex both ICA and GLM predicted reaction time equally well. Comparable correlations were not seen when principle components were used instead of independent components. These results indicate that the number of independently activated components, i.e., a high level of cortical activation complexity in cortical vector state space, may index particularly efficient information processing during selective attention-requiring tasks. To our best knowledge, this is the first report describing a potential relationship between neuronal generators of cognitive processes, the associated electrophysiological evidence for the existence of distributed networks

  3. BET protein function is required for inflammation: Brd2 genetic disruption and BET inhibitor JQ1 impair mouse macrophage inflammatory responses1

    Belkina, Anna C.; Nikolajczyk, Barbara S.; Denis, Gerald V.

    2013-01-01

    Histone acetylation regulates activation and repression of multiple inflammatory genes known to play critical roles in chronic inflammatory diseases. However, proteins responsible for translating the histone acetylation code into an orchestrated pro-inflammatory cytokine response remain poorly characterized. Bromodomain extra terminal (BET) proteins are “readers” of histone acetylation marks with demonstrated roles in gene transcription, but the ability of BET proteins to coordinate the response of inflammatory cytokine genes through translation of histone marks is unknown. We hypothesize that members of the BET family of dual bromodomain-containing transcriptional regulators directly control inflammatory genes. We examined the genetic model of brd2 lo mice, a BET protein hypomorph, to show that Brd2 is essential for pro-inflammatory cytokine production in macrophages. Studies that utilize siRNA knockdown and a small molecule inhibitor of BET protein binding, JQ1, independently demonstrate BET proteins are critical for macrophage inflammatory responses. Furthermore, we show that Brd2 and Brd4 physically associate with the promoters of inflammatory cytokine genes in macrophages. This association is absent in the presence of BET inhibition by JQ1. Finally, we demonstrate that JQ1 ablates cytokine production in vitro and blunts the “cytokine storm” in endotoxemic mice by reducing levels of IL-6 and TNF-α while rescuing mice from LPS-induced death. We propose that targeting BET proteins with small molecule inhibitors will benefit hyper-inflammatory conditions associated with high levels of cytokine production. PMID:23420887

  4. BET protein function is required for inflammation: Brd2 genetic disruption and BET inhibitor JQ1 impair mouse macrophage inflammatory responses.

    Belkina, Anna C; Nikolajczyk, Barbara S; Denis, Gerald V

    2013-04-01

    Histone acetylation regulates activation and repression of multiple inflammatory genes known to play critical roles in chronic inflammatory diseases. However, proteins responsible for translating the histone acetylation code into an orchestrated proinflammatory cytokine response remain poorly characterized. Bromodomain and extraterminal (BET) proteins are "readers" of histone acetylation marks, with demonstrated roles in gene transcription, but the ability of BET proteins to coordinate the response of inflammatory cytokine genes through translation of histone marks is unknown. We hypothesize that members of the BET family of dual bromodomain-containing transcriptional regulators directly control inflammatory genes. We examined the genetic model of brd2 lo mice, a BET protein hypomorph, to show that Brd2 is essential for proinflammatory cytokine production in macrophages. Studies that use small interfering RNA knockdown and a small-molecule inhibitor of BET protein binding, JQ1, independently demonstrate BET proteins are critical for macrophage inflammatory responses. Furthermore, we show that Brd2 and Brd4 physically associate with the promoters of inflammatory cytokine genes in macrophages. This association is absent in the presence of BET inhibition by JQ1. Finally, we demonstrate that JQ1 ablates cytokine production in vitro and blunts the "cytokine storm" in endotoxemic mice by reducing levels of IL-6 and TNF-α while rescuing mice from LPS-induced death. We propose that targeting BET proteins with small-molecule inhibitors will benefit hyperinflammatory conditions associated with high levels of cytokine production.

  5. Maternal inflammation induces immune activation of fetal microglia and leads to disrupted microglia immune responses, behavior, and learning performance in adulthood

    Schaafsma, Wandert; Basterra, Laura Bozal; Jacobs, Sabrina; Brouwer, Nieske; Meerlo, Peter; Schaafsma, Anne; Boddeke, Erik W. G. M.; Eggen, Bart J. L.

    2017-01-01

    Maternal inflammation during pregnancy can have detrimental effects on embryonic development that persist during adulthood. However, the underlying mechanisms and insights in the responsible cell types are still largely unknown. Here we report the effect of maternal inflammation on fetal microglia,

  6. Analysis of recent fuel-disruption experiments

    Kramer, J.M.; Kraft, T.E.; DiMelfi, R.J.; Fenske, G.R.; Gruber, E.E.

    1982-01-01

    Recent USDOE-sponsored DEH, FGR, and TREAT F series fuel-disruption experiments are analyzed with existing analytical models. The experiments are interpreted and the results used to evaluate the models. Calculations are presented using the FRAS3 fission-gas-behavior code and the DiMelfi-Deitrich fuel-response model

  7. An analysis of recent fuel disruption experiments

    Kramer, J.M.; Kraft, T.E.; Dimelfi, R.J.; Fenske, G.R.; Gruber, E.E.

    1982-01-01

    Recent USDOE-Sponsored DEH, FGR, and TREAT F series fuel disruption experiments are analyzed with existing analytical models. The experiments are interpreted and the results used to evaluate the models. Calculations are presented using the FRAS3 fission gas behavior code and the DiMelfi-Deitrich fuel response model

  8. Anxiety-related biases in visual orienting and spatial motor response selection independently assessed by a probe-classification task

    Schrooten, M.G.S.; Smulders, F.T.Y.; Mogg, K.; Bradley, B.P.

    2012-01-01

    This dot-probe study assessed anxiety-related biases in visual attentional orienting and spatial motor response selection (motor attention) in high- and low-trait-anxious adults, and whether anxiety-related biases depend on response speed. Emotional-neutral word pairs appeared for 14 or 500 ms, with

  9. Energy flow during disruptions in JET

    Paley, J.I.; Andrew, P.; Cowley, S.C.; Fundamenski, W.; Huber, A.

    2005-01-01

    Disruptions place severe limitations on the materials selected for plasma facing components in fusion devices. In a disruption, the plasma stored thermal and magnetic energy is dissipated leading to predicted power loadings in the current quench of up to 10 MW m -2 in JET. In the thermal quench very high power loads of up to 10 G Wm -2 would be expected if all the power flowed to the steady state strike points, however this is not observed. In this paper the energy balance associated with both events is investigated. The magnetic energy is found to balance well with radiated energy. Circumstantial evidence for limiter interaction during the thermal quench of plasmas in divertor configuration is presented and a possible mechanism for limiter interaction in disruptions resulting from the collapse of an internal transport barrier is discussed

  10. Concurrent deployment of visual attention and response selection bottleneck in a dual-task: Electrophysiological and behavioural evidence.

    Reimer, Christina B; Strobach, Tilo; Schubert, Torsten

    2017-12-01

    Visual attention and response selection are limited in capacity. Here, we investigated whether visual attention requires the same bottleneck mechanism as response selection in a dual-task of the psychological refractory period (PRP) paradigm. The dual-task consisted of an auditory two-choice discrimination Task 1 and a conjunction search Task 2, which were presented at variable temporal intervals (stimulus onset asynchrony, SOA). In conjunction search, visual attention is required to select items and to bind their features resulting in a serial search process around the items in the search display (i.e., set size). We measured the reaction time of the visual search task (RT2) and the N2pc, an event-related potential (ERP), which reflects lateralized visual attention processes. If the response selection processes in Task 1 influence the visual attention processes in Task 2, N2pc latency and amplitude would be delayed and attenuated at short SOA compared to long SOA. The results, however, showed that latency and amplitude were independent of SOA, indicating that visual attention was concurrently deployed to response selection. Moreover, the RT2 analysis revealed an underadditive interaction of SOA and set size. We concluded that visual attention does not require the same bottleneck mechanism as response selection in dual-tasks.

  11. Bayesian dose selection design for a binary outcome using restricted response adaptive randomization.

    Meinzer, Caitlyn; Martin, Renee; Suarez, Jose I

    2017-09-08

    In phase II trials, the most efficacious dose is usually not known. Moreover, given limited resources, it is difficult to robustly identify a dose while also testing for a signal of efficacy that would support a phase III trial. Recent designs have sought to be more efficient by exploring multiple doses through the use of adaptive strategies. However, the added flexibility may potentially increase the risk of making incorrect assumptions and reduce the total amount of information available across the dose range as a function of imbalanced sample size. To balance these challenges, a novel placebo-controlled design is presented in which a restricted Bayesian response adaptive randomization (RAR) is used to allocate a majority of subjects to the optimal dose of active drug, defined as the dose with the lowest probability of poor outcome. However, the allocation between subjects who receive active drug or placebo is held constant to retain the maximum possible power for a hypothesis test of overall efficacy comparing the optimal dose to placebo. The design properties and optimization of the design are presented in the context of a phase II trial for subarachnoid hemorrhage. For a fixed total sample size, a trade-off exists between the ability to select the optimal dose and the probability of rejecting the null hypothesis. This relationship is modified by the allocation ratio between active and control subjects, the choice of RAR algorithm, and the number of subjects allocated to an initial fixed allocation period. While a responsive RAR algorithm improves the ability to select the correct dose, there is an increased risk of assigning more subjects to a worse arm as a function of ephemeral trends in the data. A subarachnoid treatment trial is used to illustrate how this design can be customized for specific objectives and available data. Bayesian adaptive designs are a flexible approach to addressing multiple questions surrounding the optimal dose for treatment efficacy

  12. Development of a high-throughput microscale cell disruption platform for Pichia pastoris in rapid bioprocess design.

    Bláha, Benjamin A F; Morris, Stephen A; Ogonah, Olotu W; Maucourant, Sophie; Crescente, Vincenzo; Rosenberg, William; Mukhopadhyay, Tarit K

    2018-01-01

    The time and cost benefits of miniaturized fermentation platforms can only be gained by employing complementary techniques facilitating high-throughput at small sample volumes. Microbial cell disruption is a major bottleneck in experimental throughput and is often restricted to large processing volumes. Moreover, for rigid yeast species, such as Pichia pastoris, no effective high-throughput disruption methods exist. The development of an automated, miniaturized, high-throughput, noncontact, scalable platform based on adaptive focused acoustics (AFA) to disrupt P. pastoris and recover intracellular heterologous protein is described. Augmented modes of AFA were established by investigating vessel designs and a novel enzymatic pretreatment step. Three different modes of AFA were studied and compared to the performance high-pressure homogenization. For each of these modes of cell disruption, response models were developed to account for five different performance criteria. Using multiple responses not only demonstrated that different operating parameters are required for different response optima, with highest product purity requiring suboptimal values for other criteria, but also allowed for AFA-based methods to mimic large-scale homogenization processes. These results demonstrate that AFA-mediated cell disruption can be used for a wide range of applications including buffer development, strain selection, fermentation process development, and whole bioprocess integration. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 34:130-140, 2018. © 2017 American Institute of Chemical Engineers.

  13. Disruptive event analysis: volcanism and igneous intrusion

    Crowe, B.M.

    1980-08-01

    An evaluation is made of the disruptive effects of volcanic activity with respect to long term isolation of radioactive waste through deep geologic storage. Three major questions are considered. First, what is the range of disruption effects of a radioactive waste repository by volcanic activity. Second, is it possible, by selective siting of a repository, to reduce the risk of disruption by future volcanic activity. And third, can the probability of repository disruption by volcanic activity be quantified. The main variables involved in the evaluation of the consequences of repository disruption by volcanic activity are the geometry of the magma-repository intersection (partly controlled by depth of burial) and the nature of volcanism. Potential radionuclide dispersal by volcanic transport within the biosphere ranges in distance from several kilometers to global. Risk from the most catastrophic types of eruptions can be reduced by careful site selection to maximize lag time prior to the onset of activity. Certain areas or volcanic provinces within the western United States have been sites of significant volcanism and should be avoided as potential sites for a radioactive waste repository. Examples of projection of future sites of active volcanism are discussed for three areas of the western United States. Probability calculations require two types of data: a numerical rate or frequency of volcanic activity and a numerical evaluation of the areal extent of volcanic disruption for a designated region. The former is clearly beyond the current state of art in volcanology. The latter can be approximated with a reasonable degree of satisfaction. In this report, simplified probability calculations are attempted for areas of past volcanic activity

  14. Emerging and Disruptive Technologies

    Kricka, Larry J.

    2016-01-01

    Several emerging or disruptive technologies can be identified that might, at some point in the future, displace established laboratory medicine technologies and practices. These include increased automation in the form of robots, 3-D printing, technology convergence (e.g., plug-in glucose meters for smart phones), new point-of-care technologies (e.g., contact lenses with sensors, digital and wireless enabled pregnancy tests) and testing locations (e.g., Retail Health Clinics, new at-home test...

  15. Energetics of LMFBR core disruptive accidents

    Marchaterre, J.F.

    1979-01-01

    In general, in the design of fast reactor systems, containment design margins are specified by investigating the response of the containment to core disruptive accidents. The results of these analyses are then translated into criteria which the designers must meet. Currently, uniform and agreed upon criteria are lacking, and in this time while they are being developed, the designer should be aware of the considerations which go into the particular criteria he must work with, and participate in their development. This paper gives an overview of the current state of the art in assessing core disruptive accidents and the design implications of this process. (orig.)

  16. Manufacturing doubt about endocrine disrupter science

    Bergman, Åke; Becher, Georg; Blumberg, Bruce

    2015-01-01

    We present a detailed response to the critique of "State of the Science of Endocrine Disrupting Chemicals 2012" (UNEP/WHO, 2013) by financial stakeholders, authored by Lamb et al. (2014). Lamb et al.'s claim that UNEP/WHO (2013) does not provide a balanced perspective on endocrine disruption......) report is not particularly erudite and that their critique is not intended to be convincing to the scientific community, but to confuse the scientific data. Consequently, it promotes misinterpretation of the UNEP/WHO (2013) report by non-specialists, bureaucrats, politicians and other decision makers...

  17. Spatiotemporal variations in estrogenicity, hormones, and endocrine-disrupting compounds in influents and effluents of selected wastewater-treatment plants and receiving streams in New York, 2008-09

    Baldigo, Barry P.; Phillips, Patrick J.; Ernst, Anne G.; Gray, James L.; Hemming, Jocelyn D.C.

    2014-01-01

    Endocrine-disrupting compounds (EDCs) in wastewater effluents have been linked to changes in sex ratios, intersex (in males), behavioral modifications, and developmental abnormalities in aquatic organisms. Yet efforts to identify and regulate specific EDCs in complex mixtures are problematic because little is known about the estrogen activity (estrogenicity) levels of many common and emerging contaminants. The potential effects of EDCs on the water quality and health of biota in streams of the New York City water supply is especially worrisome because more than 150 wastewater-treatment plants (WWTPs) are permitted to discharge effluents into surface waters and groundwaters of watersheds that provide potable water to more than 9 million people. In 2008, the U.S. Geological Survey (USGS), the New York State Department of Environmental Conservation (NYSDEC), New York State Department of Health (NYSDOH), and New York City Department of Environmental Protection (NYCDEP) began a pilot study to increase the understanding of estrogenicity and EDCs in effluents and receiving streams mainly in southeastern New York. The primary goals of this study were to document and assess the spatial and temporal variability of estrogenicity levels; the effectiveness of various treatment-plant types to remove estrogenicity; the concentrations of hormones, EDCs, and pharmaceuticals, personal care products (PPCPs); and the relations between estrogenicity and concentrations of hormones, EDCs, and PPCPs. The levels of estrogenicity and selected hormones, non-hormone EDCs, and PPCPs were characterized in samples collected seasonally in effluents from 7 WWTPs, once or twice in effluents from 34 WWTPs, and once in influents to 6 WWTPs. Estrogenicity was quantified, as estradiol equivalents, using both the biological e-screen assay and a chemical model. Results generally show that (1) estrogenicity levels in effluents varied spatially and seasonally, (2) a wide range of known and unknown EDCs

  18. Fuel disruption mechanisms determined in-pile in the ACRR

    Wright, S.A.; Fischer, E.A.

    1984-09-01

    Over thirty in-pile experiments were performed to investigate fuel disruption behavior for LMFBR loss of flow (LOF) accidents. These experiments reproduced the heating transients for a variety of accidents ranging from slow LOF accidents to rapid LOF-driven-TOP accidents. In all experiments the timing and mode of the fuel disruption were observed with a high speed camera, enabling detailed comparisons with a fuel pin code, SANDPIN. This code transient intra- and inter-granular fission gas behavior to predict the macroscopic fuel behavior, such as fission gas induced swelling and frothing, cracking and breakup of solid fuel, and fuel vapor pressure driven dispersal. This report reviews the different modes of fuel disruption as seen in the experiments and then describes the mechanism responsible for the disruption. An analysis is presented that describes a set of conditions specifying the mode of fuel disruption and the heating conditions required to produce the disruption. The heating conditions are described in terms of heating rate (K/s), temperature gradient, and fuel temperature. A fuel disruption map is presented which plots heating rate as a function of fuel temperature to illustrate the different criteria for disruption. Although this approach to describing fuel disruption oversimplifies the fission gas processes modeled by SANDPIN, it does illustrate the criteria used to determine which fuel disruption mechanism is dominant and on what major fission gas parameters it depends

  19. Disrupting the Industry with Play

    Lund, Henrik Hautop

    2016-01-01

    or two ago. This is significantly disrupting the industry in several market sectors. This paper describes the components of the playware and embodied artificial intelligence research that has led to disruption in the industrial robotics sector, and which points to the next disruption of the health care...

  20. Wound Disruption Following Colorectal Operations.

    Moghadamyeghaneh, Zhobin; Hanna, Mark H; Carmichael, Joseph C; Mills, Steven; Pigazzi, Alessio; Nguyen, Ninh T; Stamos, Michael J

    2015-12-01

    Postoperative wound disruption is associated with high morbidity and mortality. We sought to identify the risk factors and outcomes of wound disruption following colorectal resection. The American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database was used to examine the clinical data of patients who underwent colorectal resection from 2005 to 2013. Multivariate regression analysis was performed to identify risk factors of wound disruption. We sampled a total of 164,297 patients who underwent colorectal resection. Of these, 2073 (1.3 %) had wound disruption. Patients with wound disruption had significantly higher mortality (5.1 vs. 1.9 %, AOR: 1.46, P = 0.01). The highest risk of wound disruption was seen in patients with wound infection (4.8 vs. 0.9 %, AOR: 4.11, P disruption such as chronic steroid use (AOR: 1.71, P disruption compared to open surgery (AOR: 0.61, P disruption occurs in 1.3 % of colorectal resections, and it correlates with mortality of patients. Wound infection is the strongest predictor of wound disruption. Chronic steroid use, obesity, severe COPD, prolonged operation, non-elective admission, and serum albumin level are strongly associated with wound disruption. Utilization of the laparoscopic approach may decrease the risk of wound disruption when possible.

  1. The Impact of Varied Discrimination Parameters on Mixed-Format Item Response Theory Model Selection

    Whittaker, Tiffany A.; Chang, Wanchen; Dodd, Barbara G.

    2013-01-01

    Whittaker, Chang, and Dodd compared the performance of model selection criteria when selecting among mixed-format IRT models and found that the criteria did not perform adequately when selecting the more parameterized models. It was suggested by M. S. Johnson that the problems when selecting the more parameterized models may be because of the low…

  2. Physiological and perceptual responses of sedentary women while walking at a self-selected pace

    Tatiane Hallage

    2007-06-01

    Full Text Available The purpose of this study was to investigate the physiological and perceptual responses of sedentary women while walking at a self-selected pace. The sample was made up of forty-one women with a median age of 32.6 ± 8.6 years. Subjects underwent an incremental test until exhaustion on a treadmill in order to determine their maximum physiological and perceptual responses. The subjects then a 20-minute walking test at their self-selected pace to determine physiological and perceptual responses. Descriptive analysis was in the form of measures of central tendency, variability and relative frequency. Mean exercise intensity during the walking bout was 57.3 ± 12.1% of peak oxygen consumption (VO2peak and 74.4 ± 9.3% of peak heart rate (HRpeak, corresponding to 88.4 ± 19.8% and 85.6 ± 21.6% of the fi gures obtained at ventilatory threshold (VT, respectively. Nevertheless, the rating of perceived effort (RPE and affective valence (AV during the walking session returned mean values of 11.9 ± 2.1 and 2.4 ± 2.0, which correspond to 100.7 ± 20.0% and 96.0 ± 2.0% of the fi gures obtained at VT, respectively. In conclusion, the exercise intensity that was self-selected by this group of sedentary women meets current recommendations for moderate intensity exercise and was associated with increased pleasure.RESUMO O objetivo desse estudo foi verifi car os parâmetros fi siológicos e perceptivos durante a realização de caminhada de intensidade preferida por mulheres adultas, previamente sedentárias. Foram investigados 41 sujeitos (idade 32,6 ± 8,6 anos, os quais realizaram, inicialmente, um teste de esteira incremental até a exaustão para a determinação de respostas fi siológicas e perceptivas máximas e, posteriormente, um teste de caminhada em esteira por 20 minutos em uma intensidade auto-selecionada, no qual parâmetros fi siológicos e perceptivos foram obtidos. Medidas de tendência central e variabilidade foram empregadas para a an

  3. Long-term response to genomic selection: effects of estimation method and reference population structure for different genetic architectures.

    Bastiaansen, John W M; Coster, Albart; Calus, Mario P L; van Arendonk, Johan A M; Bovenhuis, Henk

    2012-01-24

    Genomic selection has become an important tool in the genetic improvement of animals and plants. The objective of this study was to investigate the impacts of breeding value estimation method, reference population structure, and trait genetic architecture, on long-term response to genomic selection without updating marker effects. Three methods were used to estimate genomic breeding values: a BLUP method with relationships estimated from genome-wide markers (GBLUP), a Bayesian method, and a partial least squares regression method (PLSR). A shallow (individuals from one generation) or deep reference population (individuals from five generations) was used with each method. The effects of the different selection approaches were compared under four different genetic architectures for the trait under selection. Selection was based on one of the three genomic breeding values, on pedigree BLUP breeding values, or performed at random. Selection continued for ten generations. Differences in long-term selection response were small. For a genetic architecture with a very small number of three to four quantitative trait loci (QTL), the Bayesian method achieved a response that was 0.05 to 0.1 genetic standard deviation higher than other methods in generation 10. For genetic architectures with approximately 30 to 300 QTL, PLSR (shallow reference) or GBLUP (deep reference) had an average advantage of 0.2 genetic standard deviation over the Bayesian method in generation 10. GBLUP resulted in 0.6% and 0.9% less inbreeding than PLSR and BM and on average a one third smaller reduction of genetic variance. Responses in early generations were greater with the shallow reference population while long-term response was not affected by reference population structure. The ranking of estimation methods was different with than without selection. Under selection, applying GBLUP led to lower inbreeding and a smaller reduction of genetic variance while a similar response to selection was

  4. Cereal Crop Proteomics: Systemic Analysis of Crop Drought Stress Responses Towards Marker-Assisted Selection Breeding

    Arindam Ghatak

    2017-06-01

    Full Text Available Sustainable crop production is the major challenge in the current global climate change scenario. Drought stress is one of the most critical abiotic factors which negatively impact crop productivity. In recent years, knowledge about molecular regulation has been generated to understand drought stress responses. For example, information obtained by transcriptome analysis has enhanced our knowledge and facilitated the identification of candidate genes which can be utilized for plant breeding. On the other hand, it becomes more and more evident that the translational and post-translational machinery plays a major role in stress adaptation, especially for immediate molecular processes during stress adaptation. Therefore, it is essential to measure protein levels and post-translational protein modifications to reveal information about stress inducible signal perception and transduction, translational activity and induced protein levels. This information cannot be revealed by genomic or transcriptomic analysis. Eventually, these processes will provide more direct insight into stress perception then genetic markers and might build a complementary basis for future marker-assisted selection of drought resistance. In this review, we survey the role of proteomic studies to illustrate their applications in crop stress adaptation analysis with respect to productivity. Cereal crops such as wheat, rice, maize, barley, sorghum and pearl millet are discussed in detail. We provide a comprehensive and comparative overview of all detected protein changes involved in drought stress in these crops and have summarized existing knowledge into a proposed scheme of drought response. Based on a recent proteome study of pearl millet under drought stress we compare our findings with wheat proteomes and another recent study which defined genetic marker in pearl millet.

  5. Wetland survey of selected areas in the K-24 Site Area of responsibility

    Rosensteel, B.A.; Awl, D.J. [JAYCOR, Environmental Division, Oak Ridge, TN (United States)

    1995-07-01

    In accordance with DOE Regulations for Compliance with Floodplain/Wetlands Environmental Review Requirements, wetland surveys were conducted in selected areas within the K-25 Area of Responsibility during the summer of 1994. These areas are Mitchell Branch, Poplar Creek, the K-770 OU, Duct Island Peninsula, the Powerhouse area, and the K-25 South Corner. Previously surveyed areas included in this report are the main plant area of the K-25 Site, the K-901 OU, the AVLIS site, and the K-25 South Site. Wetland determinations were based on the USACE methodology. Forty-four separate wetland areas, ranging in size from 0.13 to 4.23 ha, were identified. Wetlands were identified in all of the areas surveyed with the exception of the interior of the Duct Island Peninsula and the main plant area of the K-25 Site. Wetlands perform functions such as floodflow alteration, sediment stabilization, sediment and toxicant retention, nutrient transformation, production export, and support of aquatic species and wildlife diversity and abundance. The forested, scrub-shrub, and emergent wetlands identified in the K-25 area perform some or all of these functions to varying degrees.

  6. Thermal and Mechanical Buckling and Postbuckling Responses of Selected Curved Composite Panels

    Breivik, Nicole L.; Hyer, Michael W.; Starnes, James H., Jr.

    1998-01-01

    The results of an experimental and numerical study of the buckling and postbuckling responses of selected unstiffened curved composite panels subjected to mechanical end shortening and a uniform temperature increase are presented. The uniform temperature increase induces thermal stresses in the panel when the axial displacement is constrained. An apparatus for testing curved panels at elevated temperature is described, numerical results generated by using a geometrically nonlinear finite element analysis code are presented. Several analytical modeling refinements that provide more accurate representation of the actual experimental conditions, and the relative contribution of each refinement, are discussed. Experimental results and numerical predictions are presented and compared for three loading conditions including mechanical end shortening alone, heating the panels to 250 F followed by mechanical end shortening, and heating the panels to 400 F. Changes in the coefficients of thermal expansion were observed as temperature was increased above 330 F. The effects of these changes on the experimental results are discussed for temperatures up to 400 F.

  7. Phosphorene as a Superior Gas Sensor: Selective Adsorption and Distinct I-V Response.

    Kou, Liangzhi; Frauenheim, Thomas; Chen, Changfeng

    2014-08-07

    Recent reports on the fabrication of phosphorene, that is, mono- or few-layer black phosphorus, have raised exciting prospects of an outstanding two-dimensional (2D) material that exhibits excellent properties for nanodevice applications. Here, we study by first-principles calculations the adsorption of CO, CO2, NH3, NO, and NO2 gas molecules on a monolayer phosphorene. Our results predict superior sensing performance of phosphorene that rivals or even surpasses that of other 2D materials such as graphene and MoS2. We determine the optimal adsorption positions of these molecules on the phosphorene and identify molecular doping, that is, charge transfer between the molecules and phosphorene, as the driving mechanism for the high adsorption strength. We further calculated the current-voltage (I-V) relation using the nonequilibrium Green's function (NEGF) formalism. The transport features show large (1-2 orders of magnitude) anisotropy along different (armchair or zigzag) directions, which is consistent with the anisotropic electronic band structure of phosphorene. Remarkably, the I-V relation exhibits distinct responses with a marked change of the I-V relation along either the armchair or the zigzag directions depending on the type of molecules. Such selectivity and sensitivity to adsorption makes phosphorene a superior gas sensor that promises wide-ranging applications.

  8. Wetland survey of selected areas in the K-24 Site Area of responsibility

    Rosensteel, B.A.; Awl, D.J.

    1995-07-01

    In accordance with DOE Regulations for Compliance with Floodplain/Wetlands Environmental Review Requirements, wetland surveys were conducted in selected areas within the K-25 Area of Responsibility during the summer of 1994. These areas are Mitchell Branch, Poplar Creek, the K-770 OU, Duct Island Peninsula, the Powerhouse area, and the K-25 South Corner. Previously surveyed areas included in this report are the main plant area of the K-25 Site, the K-901 OU, the AVLIS site, and the K-25 South Site. Wetland determinations were based on the USACE methodology. Forty-four separate wetland areas, ranging in size from 0.13 to 4.23 ha, were identified. Wetlands were identified in all of the areas surveyed with the exception of the interior of the Duct Island Peninsula and the main plant area of the K-25 Site. Wetlands perform functions such as floodflow alteration, sediment stabilization, sediment and toxicant retention, nutrient transformation, production export, and support of aquatic species and wildlife diversity and abundance. The forested, scrub-shrub, and emergent wetlands identified in the K-25 area perform some or all of these functions to varying degrees

  9. Metabolic Discrimination of Select List Agents by Monitoring Cellular Responses in a Multianalyte Microphysiometer

    John Wikswo

    2009-03-01

    Full Text Available Harnessing the potential of cells as complex biosensors promises the potential to create sensitive and selective detectors for discrimination of biodefense agents. Here we present toxin detection and suggest discrimination using cells in a multianalyte microphysiometer (MMP that is capable of simultaneously measuring flux changes in four extracellular analytes (acidification rate, glucose uptake, oxygen uptake, and lactate production in real-time. Differential short-term cellular responses were observed between botulinum neurotoxin A and ricin toxin with neuroblastoma cells, alamethicin and anthrax protective antigen with RAW macrophages, and cholera toxin, muscarine, 2,4-dinitro-phenol, and NaF with CHO cells. These results and the post exposure dynamics and metabolic recovery observed in each case suggest the usefulness of cell-based detectors to discriminate between specific analytes and classes of compounds in a complex matrix, and furthermore to make metabolic inferences on the cellular effects of the agents. This may be particularly valuable for classifying unknown toxins.

  10. Disruption - Access cards service

    2014-01-01

    We would like to inform you that between 10 November and 15 December 2014, the access cards service in Building 55 will be disrupted, as the GS Department has decided to improve the facilities for users of this building. During the work, you will find the registration, biometric registration and dosimeter exchange services on the second floor of Building 55 and the vehicle sticker service on the ground floor along with the access cards service. We thank you for your understanding and apologise for any inconvenience caused.

  11. An Estrogen-Responsive Module in the Ventromedial Hypothalamus Selectively Drives Sex-Specific Activity in Females

    Stephanie M. Correa

    2015-01-01

    Full Text Available Estrogen-receptor alpha (ERα neurons in the ventrolateral region of the ventromedial hypothalamus (VMHVL control an array of sex-specific responses to maximize reproductive success. In females, these VMHVL neurons are believed to coordinate metabolism and reproduction. However, it remains unknown whether specific neuronal populations control distinct components of this physiological repertoire. Here, we identify a subset of ERα VMHVL neurons that promotes hormone-dependent female locomotion. Activating Nkx2-1-expressing VMHVL neurons via pharmacogenetics elicits a female-specific burst of spontaneous movement, which requires ERα and Tac1 signaling. Disrupting the development of Nkx2-1+ VMHVL neurons results in female-specific obesity, inactivity, and loss of VMHVL neurons coexpressing ERα and Tac1. Unexpectedly, two responses controlled by ERα+ neurons, fertility and brown adipose tissue thermogenesis, are unaffected. We conclude that a dedicated subset of VMHVL neurons marked by ERα, NKX2-1, and Tac1 regulates estrogen-dependent fluctuations in physical activity and constitutes one of several neuroendocrine modules that drive sex-specific responses.

  12. Disruptions in the TFTR tokamak

    Janos, A.; Fredrickson, E.D.; McGuire, K.; Batha, S.H.; Bell, M.G.; Bitter, M.; Budny, R.; Bush, C.E.; Efthimion, P.C.; Hawryluk, R.J.; Hill, K.W.; Hosea, J.; Jobes, F.C.; Johnson, D.W.; Levinton, F.; Mansfield, D.; Meade, D.; Medley, S.S.; Monticello, D.; Mueller, D.; Nagayama, Y.; Owens, D.K.; Park, H.; Park, W.; Post, D.E.; Schivell, J.; Strachan, J.D.; Taylor, G.; Ulrickson, M.; Goeler, S. von; Wilfrid, E.; Wong, K.L.; Yamada, M.; Young, K.M.; Zarnstorff, M.C.; Zweben, S.J.; Drake, J.F.; Kleva, R.G.; Fleischmann, H.H.

    1993-03-01

    For a successful reactor, it will be useful to predict the occurrence of disruptions and to understand disruption effects including how a plasma disrupts onto the wall and how reproducibly it does so. Studies of disruptions on TFTR at both high-β pol and high-density have shown that, in both types, a fast growing m/n=1/1 mode plays an important role. In highdensity disruptions, a newly observed fast m/n = 1/1 mode occurs early in the thermal decay phase. For the first time in TFTR q-profile measurements just prior to disruptions have been made. Experimental studies of heat deposition patterns on the first wall of TFTR due to disruptions have provided information on MHD phenomena prior to or during the disruption, how the energy is released to the wall, and the reproducibility of the heat loads from disruptions. This information is important in the design of future devices such as ITER. Several new processes of runaway electron generation are theoretically suggested and their application to TFTR and ITER is considered, together with a preliminary assessment of x-ray data from runaways generated during disruptions

  13. Selection for stress responsiveness and slaughter stress affect flesh quality in pan-size rainbow trout, Oncorhynchus mykiss

    Lefevre, Florence; Cos, Isabelle; Pottinger, Tom G.; Bugeon, Jérôme

    2016-01-01

    The control of slaughter stress is of importance with regard to both fish welfare and flesh quality. Muscle characteristics and instrumentally measured quality parameters were determined in rainbow trout lines selected for high-responsiveness (HR) or low-responsiveness (LR) of plasma cortisol to an acute confinement stressor. Measurements were made in both unstressed and stressed fish (a 15 min period of confinement before slaughter) from both lines. Compared to LR fish, HR fish were smaller,...

  14. Extreme Hypoxic Conditions Induce Selective Molecular Responses and Metabolic Reset in Detached Apple Fruit

    Cukrov, Dubravka; Zermiani, Monica; Brizzolara, Stefano; Cestaro, Alessandro; Licausi, Francesco; Luchinat, Claudio; Santucci, Claudio; Tenori, Leonardo; Van Veen, Hans; Zuccolo, Andrea; Ruperti, Benedetto; Tonutti, Pietro

    2016-01-01

    The ripening physiology of detached fruit is altered by low oxygen conditions with profound effects on quality parameters. To study hypoxia-related processes and regulatory mechanisms, apple (Malus domestica, cv Granny Smith) fruit, harvested at commercial ripening, were kept at 1°C under normoxic (control) and hypoxic (0.4 and 0.8 kPa oxygen) conditions for up to 60 days. NMR analyses of cortex tissue identified eight metabolites showing significantly different accumulations between samples, with ethanol and alanine displaying the most pronounced difference between hypoxic and normoxic treatments. A rapid up-regulation of alcohol dehydrogenase and pyruvate-related metabolism (lactate dehydrogenase, pyruvate decarboxylase, alanine aminotransferase) gene expression was detected under both hypoxic conditions with a more pronounced effect induced by the lowest (0.4 kPa) oxygen concentration. Both hypoxic conditions negatively affected ACC synthase and ACC oxidase transcript accumulation. Analysis of RNA-seq data of samples collected after 24 days of hypoxic treatment identified more than 1000 genes differentially expressed when comparing 0.4 vs. 0.8 kPa oxygen concentration samples. Genes involved in cell-wall, minor and major CHO, amino acid and secondary metabolisms, fermentation and glycolysis as well as genes involved in transport, defense responses, and oxidation-reduction appeared to be selectively affected by treatments. The lowest oxygen concentration induced a higher expression of transcription factors belonging to AUX/IAA, WRKY, HB, Zinc-finger families, while MADS box family genes were more expressed when apples were kept under 0.8 kPa oxygen. Out of the eight group VII ERF members present in apple genome, two genes showed a rapid up-regulation under hypoxia, and western blot analysis showed that apple MdRAP2.12 proteins were differentially accumulated in normoxic and hypoxic samples, with the highest level reached under 0.4 kPa oxygen. These data suggest

  15. Short- and long-term health consequences of sleep disruption.

    Medic, Goran; Wille, Micheline; Hemels, Michiel Eh

    2017-01-01

    Sleep plays a vital role in brain function and systemic physiology across many body systems. Problems with sleep are widely prevalent and include deficits in quantity and quality of sleep; sleep problems that impact the continuity of sleep are collectively referred to as sleep disruptions. Numerous factors contribute to sleep disruption, ranging from lifestyle and environmental factors to sleep disorders and other medical conditions. Sleep disruptions have substantial adverse short- and long-term health consequences. A literature search was conducted to provide a nonsystematic review of these health consequences (this review was designed to be nonsystematic to better focus on the topics of interest due to the myriad parameters affected by sleep). Sleep disruption is associated with increased activity of the sympathetic nervous system and hypothalamic-pituitary-adrenal axis, metabolic effects, changes in circadian rhythms, and proinflammatory responses. In otherwise healthy adults, short-term consequences of sleep disruption include increased stress responsivity, somatic pain, reduced quality of life, emotional distress and mood disorders, and cognitive, memory, and performance deficits. For adolescents, psychosocial health, school performance, and risk-taking behaviors are impacted by sleep disruption. Behavioral problems and cognitive functioning are associated with sleep disruption in children. Long-term consequences of sleep disruption in otherwise healthy individuals include hypertension, dyslipidemia, cardiovascular disease, weight-related issues, metabolic syndrome, type 2 diabetes mellitus, and colorectal cancer. All-cause mortality is also increased in men with sleep disturbances. For those with underlying medical conditions, sleep disruption may diminish the health-related quality of life of children and adolescents and may worsen the severity of common gastrointestinal disorders. As a result of the potential consequences of sleep disruption, health care

  16. Long-term air pollution exposure is associated with neuroinflammation, an altered innate immune response, disruption of the blood-brain barrier, ultrafine particulate deposition, and accumulation of amyloid beta-42 and alpha-synuclein in children and young adults.

    Calderón-Garcidueñas, Lilian; Solt, Anna C; Henríquez-Roldán, Carlos; Torres-Jardón, Ricardo; Nuse, Bryan; Herritt, Lou; Villarreal-Calderón, Rafael; Osnaya, Norma; Stone, Ida; García, Raquel; Brooks, Diane M; González-Maciel, Angelica; Reynoso-Robles, Rafael; Delgado-Chávez, Ricardo; Reed, William

    2008-02-01

    Air pollution is a serious environmental problem. We investigated whether residency in cities with high air pollution is associated with neuroinflammation/neurodegeneration in healthy children and young adults who died suddenly. We measured mRNA cyclooxygenase-2, interleukin-1beta, and CD14 in target brain regions from low (n = 12) or highly exposed residents (n = 35) aged 25.1 +/- 1.5 years. Upregulation of cyclooxygenase-2, interleukin-1beta, and CD14 in olfactory bulb, frontal cortex, substantia nigrae and vagus nerves; disruption of the blood-brain barrier; endothelial activation, oxidative stress, and inflammatory cell trafficking were seen in highly exposed subjects. Amyloid beta42 (Abeta42) immunoreactivity was observed in 58.8% of apolipoprotein E (APOE) 3/3 < 25 y, and 100% of the APOE 4 subjects, whereas alpha-synuclein was seen in 23.5% of < 25 y subjects. Particulate material (PM) was seen in olfactory bulb neurons, and PM < 100 nm were observed in intraluminal erythrocytes from lung, frontal, and trigeminal ganglia capillaries. Exposure to air pollution causes neuroinflammation, an altered brain innate immune response, and accumulation of Abeta42 and alpha-synuclein starting in childhood. Exposure to air pollution should be considered a risk factor for Alzheimer's and Parkinson's diseases, and carriers of the APOE 4 allele could have a higher risk of developing Alzheimer's disease if they reside in a polluted environment.

  17. Cell disruption for microalgae biorefineries.

    Günerken, E; D'Hondt, E; Eppink, M H M; Garcia-Gonzalez, L; Elst, K; Wijffels, R H

    2015-01-01

    Microalgae are a potential source for various valuable chemicals for commercial applications ranging from nutraceuticals to fuels. Objective in a biorefinery is to utilize biomass ingredients efficiently similarly to petroleum refineries in which oil is fractionated in fuels and a variety of products with higher value. Downstream processes in microalgae biorefineries consist of different steps whereof cell disruption is the most crucial part. To maintain the functionality of algae biochemicals during cell disruption while obtaining high disruption yields is an important challenge. Despite this need, studies on mild disruption of microalgae cells are limited. This review article focuses on the evaluation of conventional and emerging cell disruption technologies, and a comparison thereof with respect to their potential for the future microalgae biorefineries. The discussed techniques are bead milling, high pressure homogenization, high speed homogenization, ultrasonication, microwave treatment, pulsed electric field treatment, non-mechanical cell disruption and some emerging technologies. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Endocrine Disrupting Chemicals and Disease Susceptibility

    Schug, Thaddeus T.; Janesick, Amanda; Blumberg, Bruce; Heindel, Jerrold J.

    2011-01-01

    Environmental chemicals have significant impacts on biological systems. Chemical exposures during early stages of development can disrupt normal patterns of development and thus dramatically alter disease susceptibility later in life. Endocrine disrupting chemicals (EDCs) interfere with the body's endocrine system and produce adverse developmental, reproductive, neurological, cardiovascular, metabolic and immune effects in humans. A wide range of substances, both natural and man-made, are thought to cause endocrine disruption, including pharmaceuticals, dioxin and dioxin-like compounds, polychlorinated biphenyls, DDT and other pesticides, and components of plastics such as bisphenol A (BPA) and phthalates. EDCs are found in many everyday products– including plastic bottles, metal food cans, detergents, flame retardants, food additives, toys, cosmetics, and pesticides. EDCs interfere with the synthesis, secretion, transport, activity, or elimination of natural hormones. This interference can block or mimic hormone action, causing a wide range of effects. This review focuses on the mechanisms and modes of action by which EDCs alter hormone signaling. It also includes brief overviews of select disease endpoints associated with endocrine disruption. PMID:21899826

  19. Comparison of immune response to lipopolysaccharide of rabbit does selected for litter size at weaning or founded for reproductive longevity

    Ferrian, S; Blas, E; Larsen, Torben

    2013-01-01

    To evaluate differences in maternal lines to the immune response of reproductive rabbit does, a total of 64 animals of two different lines: (1) founded for hyper-longevity and litter size criteria (LP) and (2) selected for litter size at weaning (V) were used. Females were subjected to three diff...

  20. Using response-time constraints in item selection to control for differential speededness in computerized adaptive testing

    van der Linden, Willem J.; Scrams, David J.; Schnipke, Deborah L.

    2003-01-01

    This paper proposes an item selection algorithm that can be used to neutralize the effect of time limits in computer adaptive testing. The method is based on a statistical model for the response-time distributions of the test takers on the items in the pool that is updated each time a new item has

  1. Estimating host genetic effects on susceptibility and infectivity to infectious diseases and their contribution to response to selection

    Anche, M.T.

    2016-01-01

    Mahlet Teka Anche. (2016). Estimating host genetic effects on susceptibility and infectivity to infectious diseases and their contribution to response to selection. PhD thesis, Wageningen University, the Netherlands

    Genetic approaches aiming to reduce the prevalence of an infection in a

  2. Changes in dopamine levels and locomotor activity in response to selection on virgin lifespan in Drosophila melanogaster

    Vermeulen, C.J.; Cremers, T.I.F.H.; Westerink, B.H.C.; van de Zande, L.; Bijlsma, R.

    Among various other mechanisms, genetic differences in the production of reactive oxygen species are thought to underlie genetic variation for longevity. Here we report on possible changes in ROS production related processes in response to selection for divergent virgin lifespan in Drosophila. The

  3. Overview of core disruptive accidents

    Marchaterre, J.F.

    1977-01-01

    An overview of the analysis of core-disruptive accidents is given. These analyses are for the purpose of understanding and predicting fast reactor behavior in severe low probability accident conditions, to establish the consequences of such conditions and to provide a basis for evaluating consequence limiting design features. The methods are used to analyze core-disruptive accidents from initiating event to complete core disruption, the effects of the accident on reactor structures and the resulting radiological consequences are described

  4. Habitat quality influences population distribution, individual space use and functional responses in habitat selection by a large herbivore.

    Bjørneraas, Kari; Herfindal, Ivar; Solberg, Erling Johan; Sæther, Bernt-Erik; van Moorter, Bram; Rolandsen, Christer Moe

    2012-01-01

    Identifying factors shaping variation in resource selection is central for our understanding of the behaviour and distribution of animals. We examined summer habitat selection and space use by 108 Global Positioning System (GPS)-collared moose in Norway in relation to sex, reproductive status, habitat quality, and availability. Moose selected habitat types based on a combination of forage quality and availability of suitable habitat types. Selection of protective cover was strongest for reproducing females, likely reflecting the need to protect young. Males showed strong selection for habitat types with high quality forage, possibly due to higher energy requirements. Selection for preferred habitat types providing food and cover was a positive function of their availability within home ranges (i.e. not proportional use) indicating functional response in habitat selection. This relationship was not found for unproductive habitat types. Moreover, home ranges with high cover of unproductive habitat types were larger, and smaller home ranges contained higher proportions of the most preferred habitat type. The distribution of moose within the study area was partly related to the distribution of different habitat types. Our study shows how distribution and availability of habitat types providing cover and high-quality food shape ungulate habitat selection and space use.

  5. Disrupted Refugee Family Life

    Shapiro, Ditte Krogh

    2017-01-01

    Fleeing civil war involves managing life threatening events and multiple disruptions of everyday life. The theoretical potentials of analysing the recreation of everyday family life among Syrian refugees in Denmark is explored based on conceptualizations that emphasize the collective agency...... of family members in social historical contexts. Studying the multiple perspectives of family members shows how social support conceptualized as care practises is conflictual in the changing everyday family practices that are transformed by policy. The purpose of studying how families manage to flee civil...... war and struggle to recreate an everyday life in exile is to contribute with contextualization and expansion of mainstream understandings of family life, suffering, and resilience in refugee family trajectories in multiple contexts....

  6. Disruptive Technology: An Uncertain Future

    2005-05-21

    Technology that overturns market -- Military - Technology that causes a fundamental change in force structure, basing, and capability balance * Disruptive Technologies may arise from systems or enabling technology.

  7. Major disruption process in tokamak

    Kurita, Gen-ichi; Azumi, Masafumi; Tuda, Takashi; Takizuka, Tomonori; Tsunematsu, Toshihide; Tokuda, Shinji; Itoh, Kimitaka; Takeda, Tatsuoki

    1981-11-01

    The major disruption in a cylindrical tokamak is investigated by using the multi-helicity code, and the destabilization of the 3/2 mode by the mode coupling with the 2/1 mode is confirmed. The evolution of the magnetic field topology caused by the major disruption is studied in detail. The effect of the internal disruption on the 2/1 magnetic island width is also studied. The 2/1 magnetic island is not enhanced by the flattening of the q-profile due to the internal disruption. (author)

  8. Award of Construction Contracts: Public Institutions' Authority to Select the Lowest Responsible Bidder.

    Cole, Elsa Kircher; Goldblatt, Steven M.

    1989-01-01

    The article describes the responsibilities of public colleges and universities to award construction contracts to the lowest responsible bidder; discusses the purpose of bid statutes; and lists the factors institutions should consider in determining a bidder's responsibility. Also covered are the standard of review and due process rights of the…

  9. Divided attention disrupts perceptual encoding during speech recognition.

    Mattys, Sven L; Palmer, Shekeila D

    2015-03-01

    Performing a secondary task while listening to speech has a detrimental effect on speech processing, but the locus of the disruption within the speech system is poorly understood. Recent research has shown that cognitive load imposed by a concurrent visual task increases dependency on lexical knowledge during speech processing, but it does not affect lexical activation per se. This suggests that "lexical drift" under cognitive load occurs either as a post-lexical bias at the decisional level or as a secondary consequence of reduced perceptual sensitivity. This study aimed to adjudicate between these alternatives using a forced-choice task that required listeners to identify noise-degraded spoken words with or without the addition of a concurrent visual task. Adding cognitive load increased the likelihood that listeners would select a word acoustically similar to the target even though its frequency was lower than that of the target. Thus, there was no evidence that cognitive load led to a high-frequency response bias. Rather, cognitive load seems to disrupt sublexical encoding, possibly by impairing perceptual acuity at the auditory periphery.

  10. Chemotherapy disrupts learning, neurogenesis and theta activity in the adult brain.

    Nokia, Miriam S; Anderson, Megan L; Shors, Tracey J

    2012-12-01

    Chemotherapy, especially if prolonged, disrupts attention, working memory and speed of processing in humans. Most cancer drugs that cross the blood-brain barrier also decrease adult neurogenesis. Because new neurons are generated in the hippocampus, this decrease may contribute to the deficits in working memory and related thought processes. The neurophysiological mechanisms that underlie these deficits are generally unknown. A possible mediator is hippocampal oscillatory activity within the theta range (3-12 Hz). Theta activity predicts and promotes efficient learning in healthy animals and humans. Here, we hypothesised that chemotherapy disrupts learning via decreases in hippocampal adult neurogenesis and theta activity. Temozolomide was administered to adult male Sprague-Dawley rats in a cyclic manner for several weeks. Treatment was followed by training with different types of eyeblink classical conditioning, a form of associative learning. Chemotherapy reduced both neurogenesis and endogenous theta activity, as well as disrupted learning and related theta-band responses to the conditioned stimulus. The detrimental effects of temozolomide only occurred after several weeks of treatment, and only on a task that requires the association of events across a temporal gap and not during training with temporally overlapping stimuli. Chemotherapy did not disrupt the memory for previously learned associations, a memory independent of (new neurons in) the hippocampus. In conclusion, prolonged systemic chemotherapy is associated with a decrease in hippocampal adult neurogenesis and theta activity that may explain the selective deficits in processes of learning that describe the 'chemobrain'. © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  11. Direct and correlated responses to selection for total weight of lamb ...

    Unknown

    productivity and that each of these components can be used as a selection criterion, as each has a direct impact on total ewe ... of lamb weaned per ewe joined is more efficient than selection for number of lambs born, number of lambs weaned or weaning ... The estimated grazing capacity is 5.5 ha per small stock unit.

  12. Systematic differences in the response of genetic variation to pedigree and genome-based selection methods

    Heidaritabar, M.; Vereijken, A.; Muir, W.M.; Meuwissen, T.H.E.; Cheng, H.; Megens, H.J.W.C.; Groenen, M.; Bastiaansen, J.W.M.

    2014-01-01

    Genomic selection (GS) is a DNA-based method of selecting for quantitative traits in animal and plant breeding, and offers a potentially superior alternative to traditional breeding methods that rely on pedigree and phenotype information. Using a 60¿K SNP chip with markers spaced throughout the

  13. Tumor RNA disruption predicts survival benefit from breast cancer chemotherapy.

    Parissenti, Amadeo M; Guo, Baoqing; Pritzker, Laura B; Pritzker, Kenneth P H; Wang, Xiaohui; Zhu, Mu; Shepherd, Lois E; Trudeau, Maureen E

    2015-08-01

    In a prior substudy of the CAN-NCIC-MA.22 clinical trial (ClinicalTrials.gov identifier NCT00066443), we observed that neoadjuvant chemotherapy reduced tumor RNA integrity in breast cancer patients, a phenomenon we term "RNA disruption." The purpose of the current study was to assess in the full patient cohort the relationship between mid-treatment tumor RNA disruption and both pCR post-treatment and, subsequently, disease-free survival (DFS) up to 108 months post-treatment. To meet these objectives, we developed the RNA disruption assay (RDA) to quantify RNA disruption and stratify it into 3 response zones of clinical importance. Zone 1 is a level of RNA disruption inadequate for pathologic complete response (pCR); Zone 2 is an intermediate level, while Zone 3 has high RNA disruption. The same RNA disruption cut points developed for pCR response were then utilized for DFS. Tumor RDA identified >fourfold more chemotherapy non-responders than did clinical response by calipers. pCR responders were clustered in RDA Zone 3, irrespective of tumor subtype. DFS was about 2-fold greater for patients with tumors in Zone 3 compared to Zone 1 patients. Kaplan-Meier survival curves corroborated these findings that high tumor RNA disruption was associated with increased DFS. DFS values for patients in zone 3 that did not achieve a pCR were similar to that of pCR recipients across tumor subtypes, including patients with hormone receptor positive tumors that seldom achieve a pCR. RDA appears superior to pCR as a chemotherapy response biomarker, supporting the prospect of its use in response-guided chemotherapy.

  14. The effects of stress and sex on selection, genetic covariance, and the evolutionary response.

    Holman, L; Jacomb, F

    2017-10-01

    The capacity of a population to adapt to selection (evolvability) depends on whether the structure of genetic variation permits the evolution of fitter trait combinations. Selection, genetic variance and genetic covariance can change under environmental stress, and males and females are not genetically independent, yet the combined effects of stress and dioecy on evolvability are not well understood. Here, we estimate selection, genetic (co)variance and evolvability in both sexes of Tribolium castaneum flour beetles under stressful and benign conditions, using a half-sib breeding design. Although stress uncovered substantial latent heritability, stress also affected genetic covariance, such that evolvability remained low under stress. Sexual selection on males and natural selection on females favoured a similar phenotype, and there was positive intersex genetic covariance. Consequently, sexual selection on males augmented adaptation in females, and intralocus sexual conflict was weak or absent. This study highlights that increased heritability does not necessarily increase evolvability, suggests that selection can deplete genetic variance for multivariate trait combinations with strong effects on fitness, and tests the recent hypothesis that sexual conflict is weaker in stressful or novel environments. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

  15. Systematic differences in the response of genetic variation to pedigree and genome-based selection methods.

    Heidaritabar, M; Vereijken, A; Muir, W M; Meuwissen, T; Cheng, H; Megens, H-J; Groenen, M A M; Bastiaansen, J W M

    2014-12-01

    Genomic selection (GS) is a DNA-based method of selecting for quantitative traits in animal and plant breeding, and offers a potentially superior alternative to traditional breeding methods that rely on pedigree and phenotype information. Using a 60 K SNP chip with markers spaced throughout the entire chicken genome, we compared the impact of GS and traditional BLUP (best linear unbiased prediction) selection methods applied side-by-side in three different lines of egg-laying chickens. Differences were demonstrated between methods, both at the level and genomic distribution of allele frequency changes. In all three lines, the average allele frequency changes were larger with GS, 0.056 0.064 and 0.066, compared with BLUP, 0.044, 0.045 and 0.036 for lines B1, B2 and W1, respectively. With BLUP, 35 selected regions (empirical P selected regions were identified. Empirical thresholds for local allele frequency changes were determined from gene dropping, and differed considerably between GS (0.167-0.198) and BLUP (0.105-0.126). Between lines, the genomic regions with large changes in allele frequencies showed limited overlap. Our results show that GS applies selection pressure much more locally than BLUP, resulting in larger allele frequency changes. With these results, novel insights into the nature of selection on quantitative traits have been gained and important questions regarding the long-term impact of GS are raised. The rapid changes to a part of the genetic architecture, while another part may not be selected, at least in the short term, require careful consideration, especially when selection occurs before phenotypes are observed.

  16. Selective CD28 Antagonist Blunts Memory Immune Responses and Promotes Long-Term Control of Skin Inflammation in Nonhuman Primates.

    Poirier, Nicolas; Chevalier, Melanie; Mary, Caroline; Hervouet, Jeremy; Minault, David; Baker, Paul; Ville, Simon; Le Bas-Bernardet, Stephanie; Dilek, Nahzli; Belarif, Lyssia; Cassagnau, Elisabeth; Scobie, Linda; Blancho, Gilles; Vanhove, Bernard

    2016-01-01

    Novel therapies that specifically target activation and expansion of pathogenic immune cell subsets responsible for autoimmune attacks are needed to confer long-term remission. Pathogenic cells in autoimmunity include memory T lymphocytes that are long-lived and present rapid recall effector functions with reduced activation requirements. Whereas the CD28 costimulation pathway predominantly controls priming of naive T cells and hence generation of adaptive memory cells, the roles of CD28 costimulation on established memory T lymphocytes and the recall of memory responses remain controversial. In contrast to CD80/86 antagonists (CTLA4-Ig), selective CD28 antagonists blunt T cell costimulation while sparing CTLA-4 and PD-L1-dependent coinhibitory signals. Using a new selective CD28 antagonist, we showed that Ag-specific reactivation of human memory T lymphocytes was prevented. Selective CD28 blockade controlled both cellular and humoral memory recall in nonhuman primates and induced long-term Ag-specific unresponsiveness in a memory T cell-mediated inflammatory skin model. No modification of memory T lymphocytes subsets or numbers was observed in the periphery, and importantly no significant reactivation of quiescent viruses was noticed. These findings indicate that pathogenic memory T cell responses are controlled by both CD28 and CTLA-4/PD-L1 cosignals in vivo and that selectively targeting CD28 would help to promote remission of autoimmune diseases and control chronic inflammation. Copyright © 2015 by The American Association of Immunologists, Inc.

  17. Synergistic Disruption of External Male Sex Organ Development by a Mixture of Four Antiandrogens

    Christiansen, Sofie; Scholze, Martin; Dalgaard, Majken

    2009-01-01

    : Strikingly, the effect of combined exposure to the selected chemicals on malformations of external sex organs was synergistic, and the observed responses were greater than would be predicted from the toxicities of the individual chemicals. In relation to other hallmarks of disrupted male sexual development......, and a pharmaceutical, finasteride, on landmarks of male sexual development in the rat, including changes in anogenital distance, retained nipples, sex organ weights and malformations of genitalia. These chemicals were chosen because they disrupt androgen action according to differing mechanisms of action. Results...... in male offspring. Conclusions: Since unhindered androgen action is essential for human male development in foetal life, these findings are highly relevant to human risk assessment. Evaluations that ignore the possibility of combination effects may lead to considerable underestimations of risks associated...

  18. Long-term responses to selection for parameters of the allometric ...

    lrene Animal Production Institute, Private Bag X2, lrene, 1675 Republic of South Africa .... infertility, the two best males and females from each family were selected as ..... mical adaptations of heavy-bodied chicks to intermittent feeding. I.

  19. Immunological characteristics and response to lipopolysaccharide of mouse lines selectively bred with natural and acquired immunities.

    Narahara, Hiroki; Sakai, Eri; Katayama, Masafumi; Ohtomo, Yukiko; Yamamoto, Kanako; Takemoto, Miki; Aso, Hisashi; Ohwada, Shyuichi; Mohri, Yasuaki; Nishimori, Katsuhiko; Isogai, Emiko; Yamaguchi, Takahiro; Fukuda, Tomokazu

    2012-05-01

    Genetic improvement of resistance to infectious diseases is a challenging goal in animal breeding. Infection resistance involves multiple immunological characteristics, including natural and acquired immunity. In the present study, we developed an experimental model based on genetic selection, to improve immunological phenotypes. We selectively established three mouse lines based on phagocytic activity, antibody production and the combination of these two phenotypes. We analyzed the immunological characteristics of these lines using a lipopolysaccharide (LPS), which is one of the main components of Gram-negative bacteria. An intense immunological reaction was induced in each of the three mouse lines. Severe loss of body weight and liver damage were observed, and a high level of cytokine messenger RNA was detected in the liver tissue. The mouse line established using a combination of the two selection standards showed unique characteristics relative to the mouse lines selected on the basis of a single phenotype. Our results indicate that genetic selection and breeding is effective, even for immunological phenotypes with a relatively low heritability. Thus, it may be possible to improve resistance to infectious diseases by means of genetic selection. © 2011 The Authors. Animal Science Journal © 2011 Japanese Society of Animal Science.

  20. Correlated responses in tissue weights measured in vivo by computer tomography in Dorset Down sheep selected for lean tissue growth

    Nsoso, S.J.; Young, M.J.; Beatson, P.R.

    2003-01-01

    The aim of this study was to estimate correlated responses in lean, fat and bone weights in vivo in Dorset Down sheep selected for lean tissue growth. Over the period 1986-1992 inclusive, the lean tissue growth line had been selected using two economic indices for an increased aggregate breeding value incorporating predicted lean and fat weights with positive and negative economic weightings, respectively. The control line was selected for no change in lean tissue growth each year. Animals were born and run on pasture all year round. X-ray computer tomography was used to estimate the weights of lean, fat and bone in vivo in the 1994-born sheep, aged 265-274 days and selected randomly into 12 rams and 12 ewes from the selected line and 10 rams and 9 ewes from the control line. The lean tissue growth line had significantly greater responses in lean weight (+0.65 + 0.10 kg) and lean percentage (+1.19 + 0.17%) and significantly lesser fat weight (-0.36 + 0.08 kg) and fat percentage (-1.88 + 0.20%) compared to the control line. There was a significant increase in bone weight (+0.27 + 0.03 kg) and bone percentage (+0.69 + 0.09%) in the lean tissue growth line compared to the control line. Responses differed significantly between sexes of the lean tissue growth line, rams having a greater response in weight of lean (+1.22 + 0.20 vs. +0.08 + 0.22 kg) and bone (+0.45 + 0.06 vs. +0.09 + 0.07 kg), and a lesser response in weight of fat (-0.03 + 0.15 vs. -0.70 + 0.16 kg) than the ewes. Selection led to significant changes in lean (increase) and fat weights (decrease), and bone weight increased. Although responses in the lean tissue growth line differed significantly between sexes, there were confounding factors due to differences in management and lack of comparison at equal stage of development. Therefore, to assess real genetic differences further studies should be conducted taking these factors into consideration

  1. Abnormal responses of ejection fraction to exercise, in healthy subjects, caused by region-of-interest selection

    Sorenson, S.G.; Caldwell, J.; Ritchie, J.; Hamilton, G.

    1981-01-01

    We performed serial exercise equilibrium radionuclide angiography in eight normal subjects with each subject executing three tests: control, after nitroglycerin, and after propranolol. The left-ventricular ejection fraction (EF) was calculated by two methods: (a) fixed region-of-interest (FROI) using a single end-diastolic ROI, and (b) variable region-of-interest (VROI) where an end-diastolic and end-systolic region of interest were used. Abnormal maximal EF responses occurred in five of eight subjects during control using FROI but in zero of eight employing VROI (p < 0.05). After nitroglycerin, three of eight subjects had abnormal responses by FROI, but zero of eight were abnormal by VROI (p < 0.05). After propranolol, blunted EF responses occurred in three of seven by both methods. Falsely abnormal EF responses to exercise RNA may occur due to the method of region-of-interest selection in normal subjects with normal or high ejection fractions

  2. Dynamics of habitat selection in birds: adaptive response to nest predation depends on multiple factors.

    Devries, J H; Clark, R G; Armstrong, L M

    2018-05-01

    According to theory, habitat selection by organisms should reflect underlying habitat-specific fitness consequences and, in birds, reproductive success has a strong impact on population growth in many species. Understanding processes affecting habitat selection also is critically important for guiding conservation initiatives. Northern pintails (Anas acuta) are migratory, temperate-nesting birds that breed in greatest concentrations in the prairies of North America and their population remains below conservation goals. Habitat loss and changing land use practices may have decoupled formerly reliable fitness cues with respect to nest habitat choices. We used data from 62 waterfowl nesting study sites across prairie Canada (1997-2009) to examine nest survival, a primary fitness metric, at multiple scales, in combination with estimates of habitat selection (i.e., nests versus random points), to test for evidence of adaptive habitat choices. We used the same habitat covariates in both analyses. Pintail nest survival varied with nest initiation date, nest habitat, pintail breeding pair density, landscape composition and annual moisture. Selection of nesting habitat reflected patterns in nest survival in some cases, indicating adaptive selection, but strength of habitat selection varied seasonally and depended on population density and landscape composition. Adaptive selection was most evident late in the breeding season, at low breeding densities and in cropland-dominated landscapes. Strikingly, at high breeding density, habitat choice appears to become maladaptive relative to nest predation. At larger spatial scales, the relative availability of habitats with low versus high nest survival, and changing land use practices, may limit the reproductive potential of pintails.

  3. Twenty-three generations of mice bidirectionally selected for open-field thigmotaxis: selection response and repeated exposure to the open field.

    Leppänen, Pia K; Ravaja, N; Ewalds-Kvist, S B M

    2006-03-01

    We examined: (a) the response to bidirectional selection for open-field (OF) thigmotaxis in mice for 23 generations and (b) the effects of repeated exposure (during 5 days) on different OF behaviors in the selectively bred high OF thigmotaxis (HOFT) and low OF thigmotaxis (LOFT) mice. A total of 2049 mice were used in the study. Prior to the testing in the selection experiment, the mice were exposed to the OF apparatus for approximately 2 min on each of 4 consecutive days. Thus, the selection was based on the scores registered on the 5th day after the four habituation periods. The HOFT mice were more thigmotactic than the LOFT mice in almost each generation. The HOFT mice also tended to rear less than the LOFT mice, which was explained by the inverse relationship between emotionality and exploratory tendencies. The lines did not generally differ in ambulation. Sex differences were found in thigmotaxis, ambulation, and rearing. In the repeated exposure experiment, the development of nine different OF behaviors across the 5 days of testing was addressed. Both lines ambulated, explored, and reared most on the 1st, 4th, and 5th days. Grooming and radial latency decreased and thigmotaxis increased linearly across the testing days. Line differences were found in ambulation, exploration, grooming, and rearing, while sex differences were manifested in ambulation and exploration. The line difference in thigmotaxis was evident only on the 5th day. Temporal changes were partially at variance with the general assumptions. OF thigmotaxis was found to be a powerful characteristic for producing two diverging lines of mice.

  4. Geographical gradients in selection can reveal genetic constraints for evolutionary responses to ocean acidification.

    Gaitán-Espitia, Juan Diego; Marshall, Dustin; Dupont, Sam; Bacigalupe, Leonardo D; Bodrossy, Levente; Hobday, Alistair J

    2017-02-01

    Geographical gradients in selection can shape different genetic architectures in natural populations, reflecting potential genetic constraints for adaptive evolution under climate change. Investigation of natural pH/pCO 2 variation in upwelling regions reveals different spatio-temporal patterns of natural selection, generating genetic and phenotypic clines in populations, and potentially leading to local adaptation, relevant to understanding effects of ocean acidification (OA). Strong directional selection, associated with intense and continuous upwellings, may have depleted genetic variation in populations within these upwelling regions, favouring increased tolerances to low pH but with an associated cost in other traits. In contrast, diversifying or weak directional selection in populations with seasonal upwellings or outside major upwelling regions may have resulted in higher genetic variances and the lack of genetic correlations among traits. Testing this hypothesis in geographical regions with similar environmental conditions to those predicted under climate change will build insights into how selection may act in the future and how populations may respond to stressors such as OA. © 2017 The Author(s).

  5. Concentration-mortality responses of Myzus persicae and natural enemies to selected insecticides.

    Bacci, Leandro; Rosado, Jander F; Picanço, Marcelo C; Pereira, Eliseu J G; Silva, Gerson A; Martins, Júlio C

    2012-01-01

    The toxicity of six insecticides was determined for the peach-potato aphid, Myzus persicae (Hemiptera: Aphididae), and some of its natural enemies - the predatory beetles Cycloneda sanguinea (Coccinellidae) and Acanthinus sp. (Anthicidae), and the wasp parasitoid Diaeretiella rapae (Aphidiidae). Natural enemies from these groups are important natural biological control agents in a number of agroecosystems, and insecticides potentially safe to these non-target organisms should be identified using standardized tests. Thus, concentration-mortality bioassays were carried out with both the aphid and its natural enemies to assess the toxicity and selectivity of acephate, deltamethrin, dimethoate, methamidophos, methyl parathion, and pirimicarb. The latter insecticide was highly selective to all natural enemies tested, and its LC(90) for M. persicae was 14-fold lower than the field rate recommended for control of the aphid in brassica crops. Methyl parathion also showed selectivity to C. sanguinea and Acanthinus sp., but not to D. rapae. Acephate was the least potent insecticide against M. persicae and was equally or more toxic to the natural enemies relative to the aphid. Pirimicarb and methyl parathion were efficient against M. persicae and selective in favor of two of the natural enemies tested. Acanthinus sp. and C. sanguinea were more tolerant to the insecticides than was the parasitoid D. rapae. This study shows that there are selective insecticides that may be compatible with conservation of natural enemies in brassica crops, which is important practical information to improve integrated pest management systems in these crops.

  6. Erosion of melt layers developed during a plasma disruption

    Hassanein, A.; Konkashbaev, A.; Konkashbaev, I.

    1995-01-01

    Material erosion of plasma-facing components during a tokamak disruption is a serious problem that limits reactor operation and economical reactor lifetime. In particular, metallic low-Z components such as Be will be subjected to severe melting during disruptions and edge localized modes (ELMs). Loss of the developed melt layer will critically shorten the lifetime of these components, severely contaminate the plasma, and seriously inhibit successful and reliable operation of the reactor. In this study mechanisms responsible for melt-layer loss during a disruption are modeled and evaluated. Implications of melt-layer loss on the performance of metallic facing components in the reactor environment are discussed. (orig.)

  7. Erosion of melt layers developed during a plasma disruption

    Hassanein, A.; Konkashbaev, A.; Konkashbaev, I.

    1994-08-01

    Material erosion of plasma-facing components during a tokamak disruption is a serious problem that limits reactor operation and economical reactor lifetime. In particular, metallic low-Z components such as Be will be subjected to severe melting during disruptions and edge localized models (ELMs). Loss of the developed melt layer will critically shorten the lifetime of these components, severely contaminate the plasma, and seriously inhibit successful and reliable operation of the reactor. In this study mechanisms responsible for melt-layer loss during a disruption are modeled and evaluated. Implications of melt-layer loss on the performance of metallic facing components in the reactor environment are discussed

  8. Comprehensive model for disruption erosion in a reactor environment

    Hassanein, A.; Konkashbaev, I.

    1995-01-01

    A comprehensive disruption erosion model which takes into account the interplay of major physical processes during plasma-material interaction has been developed. The model integrates with sufficient detail and in a self-consistent way, material thermal evolution response, plasma-vapor interaction physics, vapor hydrodynamics and radiation transport in order to realistically simulate the effects of a plasma disruption on plasma-facing components. Candidate materials such as beryllium and carbon have been analyzed. The dependence of the net erosion rate on disruption physics and various parameters was analyzed and is discussed. ((orig.))

  9. Tokamak plasma current disruption infrared control system

    Kugel, H.W.; Ulrickson, M.

    1987-01-01

    This patent describes a device for magnetically confining a plasma driven by a plasma current and contained within a toroidal vacuum chamber, the device having an inner toroidal limiter on an inside wall of the vacuum chamber and an arrangement for the rapid prediction and control in real time of a major plasma disruption. The arrangement is described which includes: scanning means sensitive to infrared radiation emanating from within the vacuum chamber, the infrared radiation indicating the temperature along a vertical profile of the inner toroidal limiter. The scanning means is arranged to observe the infrared radiation and to produce in response thereto an electrical scanning output signal representative of a time scan of temperature along the vertical profile; detection means for analyzing the scanning output signal to detect a first peaked temperature excursion occurring along the profile of the inner toroidal limiter, and to produce a detection output signal in repsonse thereto, the detection output signal indicating a real time prediction of a subsequent major plasma disruption; and plasma current reduction means for reducing the plasma current driving the plasma, in response to the detection output signal and in anticipation of a subsequent major plasma disruption

  10. Multimodal Microvascular Imaging Reveals that Selective Inhibition of Class I PI3K Is Sufficient to Induce an Antivascular Response

    Deepak Sampath

    2013-07-01

    Full Text Available The phosphatidylinositol 3-kinase (PI3K pathway is a central mediator of vascular endothelial growth factor (VEGF-driven angiogenesis. The discovery of small molecule inhibitors that selectively target PI3K or PI3K and mammalian target of rapamycin (mTOR provides an opportunity to pharmacologically determine the contribution of these key signaling nodes in VEGF-A-driven tumor angiogenesis in vivo. This study used an array of microvascular imaging techniques to monitor the antivascular effects of selective class I PI3K, mTOR, or dual PI3K/ mTOR inhibitors in colorectal and prostate cancer xenograft models. Micro-computed tomography (micro-CT angiography, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI, vessel size index (VSI MRI, and DCE ultrasound (DCE-U/S were employed to quantitatively evaluate the vascular (structural and physiological response to these inhibitors. GDC-0980, a dual PI3K/mTOR inhibitor, was found to reduce micro-CT angiography vascular density, while VSI MRI demonstrated a significant reduction in vessel density and an increase in mean vessel size, consistent with a loss of small functional vessels and a substantial antivascular response. DCE-MRI showed that GDC-0980 produces a strong functional response by decreasing the vascular permeability/perfusion-related parameter, Ktrans. Interestingly, comparable antivascular effects were observed for both GDC-980 and GNE-490 (a selective class I PI3K inhibitor. In addition, mTOR-selective inhibitors did not affect vascular density, suggesting that PI3K inhibition is sufficient to generate structural changes, characteristic of a robust antivascular response. This study supports the use of noninvasive microvascular imaging techniques (DCE-MRI, VSI MRI, DCE-U/S as pharmacodynamic assays to quantitatively measure the activity of PI3K and dual PI3K/mTOR inhibitors in vivo.

  11. Short-term responses to selection for parameters of the allometric ...

    The allometric-autoregressive model describes growth accurately and is useful in the characterization of growth responses. ... of value in genetic studies and some of its parameters ..... (1990) appear to be fair estimates of the heritabilities of.

  12. Characterization of HIV-Specific CD4+T Cell Responses against Peptides Selected with Broad Population and Pathogen Coverage

    Buggert, Marcus; Norstrom, Melissa M.; Czarnecki, Chris

    2012-01-01

    for the identification of HIV-specific CD4+ T cells targeting broadly reactive epitopes in populations with diverse ethnic background stems from the vast genomic variation of HIV and the diversity of the host cellular immune system. Here, we describe a novel epitope selection strategy, PopCover, that aims to resolve...... this challenge, and identify a set of potential HLA class II-restricted HIV epitopes that in concert will provide optimal viral and host coverage. Using this selection strategy, we identified 64 putative epitopes (peptides) located in the Gag, Nef, Env, Pol and Tat protein regions of HIV. In total, 73...... II-restricted epitopes. All together, selection strategies, such as PopCover, might with success be used for the evaluation of antigen-specific CD4+ T cell responses and design of future vaccines....

  13. Human place and response learning: navigation strategy selection, pupil size and gaze behavior.

    de Condappa, Olivier; Wiener, Jan M

    2016-01-01

    In this study, we examined the cognitive processes and ocular behavior associated with on-going navigation strategy choice using a route learning paradigm that distinguishes between three different wayfinding strategies: an allocentric place strategy, and the egocentric associative cue and beacon response strategies. Participants approached intersections of a known route from a variety of directions, and were asked to indicate the direction in which the original route continued. Their responses in a subset of these test trials allowed the assessment of strategy choice over the course of six experimental blocks. The behavioral data revealed an initial maladaptive bias for a beacon response strategy, with shifts in favor of the optimal configuration place strategy occurring over the course of the experiment. Response time analysis suggests that the configuration strategy relied on spatial transformations applied to a viewpoint-dependent spatial representation, rather than direct access to an allocentric representation. Furthermore, pupillary measures reflected the employment of place and response strategies throughout the experiment, with increasing use of the more cognitively demanding configuration strategy associated with increases in pupil dilation. During test trials in which known intersections were approached from different directions, visual attention was directed to the landmark encoded during learning as well as the intended movement direction. Interestingly, the encoded landmark did not differ between the three navigation strategies, which is discussed in the context of initial strategy choice and the parallel acquisition of place and response knowledge.

  14. Thigmotaxis Mediates Trail Odour Disruption.

    Stringer, Lloyd D; Corn, Joshua E; Sik Roh, Hyun; Jiménez-Pérez, Alfredo; Manning, Lee-Anne M; Harper, Aimee R; Suckling, David M

    2017-05-10

    Disruption of foraging using oversupply of ant trail pheromones is a novel pest management application under investigation. It presents an opportunity to investigate the interaction of sensory modalities by removal of one of the modes. Superficially similar to sex pheromone-based mating disruption in moths, ant trail pheromone disruption lacks an equivalent mechanistic understanding of how the ants respond to an oversupply of their trail pheromone. Since significant compromise of one sensory modality essential for trail following (chemotaxis) has been demonstrated, we hypothesised that other sensory modalities such as thigmotaxis could act to reduce the impact on olfactory disruption of foraging behaviour. To test this, we provided a physical stimulus of thread to aid trailing by Argentine ants otherwise under disruptive pheromone concentrations. Trail following success was higher using a physical cue. While trail integrity reduced under continuous over-supply of trail pheromone delivered directly on the thread, provision of a physical cue in the form of thread slightly improved trail following and mediated trail disruption from high concentrations upwind. Our results indicate that ants are able to use physical structures to reduce but not eliminate the effects of trail pheromone disruption.

  15. Sleep disruption in chronic rhinosinusitis.

    Mahdavinia, Mahboobeh; Schleimer, Robert P; Keshavarzian, Ali

    2017-05-01

    Chronic rhinosinusitis (CRS) is a common disease of the upper airways and paranasal sinuses with a marked decline in quality of life (QOL). CRS patients suffer from sleep disruption at a significantly higher proportion (60 to 75%) than in the general population (8-18 %). Sleep disruption in CRS causes decreased QOL and is linked to poor functional outcomes such as impaired cognitive function and depression. Areas covered: A systematic PubMed/Medline search was done to assess the results of studies that have investigated sleep and sleep disturbances in CRS. Expert commentary: These studies reported sleep disruption in most CRS patients. The main risk factors for sleep disruption in CRS include allergic rhinitis, smoking, and high SNOT-22 total scores. The literature is inconsistent with regard to the prevalence of sleep-related disordered breathing (e.g. obstructive sleep apnea) in CRS patients. Although nasal obstruction is linked to sleep disruption, the extent of sleep disruption in CRS seems to expand beyond that expected from physical blockage of the upper airways alone. Despite the high prevalence of sleep disruption in CRS, and its detrimental effects on QOL, the literature contains a paucity of studies that have investigated the mechanisms underlying this major problem in CRS.

  16. Genetic evolution, plasticity, and bet-hedging as adaptive responses to temporally autocorrelated fluctuating selection: A quantitative genetic model.

    Tufto, Jarle

    2015-08-01

    Adaptive responses to autocorrelated environmental fluctuations through evolution in mean reaction norm elevation and slope and an independent component of the phenotypic variance are analyzed using a quantitative genetic model. Analytic approximations expressing the mutual dependencies between all three response modes are derived and solved for the joint evolutionary outcome. Both genetic evolution in reaction norm elevation and plasticity are favored by slow temporal fluctuations, with plasticity, in the absence of microenvironmental variability, being the dominant evolutionary outcome for reasonable parameter values. For fast fluctuations, tracking of the optimal phenotype through genetic evolution and plasticity is limited. If residual fluctuations in the optimal phenotype are large and stabilizing selection is strong, selection then acts to increase the phenotypic variance (bet-hedging adaptive). Otherwise, canalizing selection occurs. If the phenotypic variance increases with plasticity through the effect of microenvironmental variability, this shifts the joint evolutionary balance away from plasticity in favor of genetic evolution. If microenvironmental deviations experienced by each individual at the time of development and selection are correlated, however, more plasticity evolves. The adaptive significance of evolutionary fluctuations in plasticity and the phenotypic variance, transient evolution, and the validity of the analytic approximations are investigated using simulations. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

  17. Does selective logging stress tropical forest invertebrates? Using fat stores to examine sublethal responses in dung beetles.

    França, Filipe; Barlow, Jos; Araújo, Bárbara; Louzada, Julio

    2016-12-01

    The increased global demand for tropical timber has driven vast expanses of tropical forests to be selectively logged worldwide. While logging impacts on wildlife are predicted to change species distribution and abundance, the underlying physiological responses are poorly understood. Although there is a growing consensus that selective logging impacts on natural populations start with individual stress-induced sublethal responses, this literature is dominated by investigations conducted with vertebrates from temperate zones. Moreover, the sublethal effects of human-induced forest disturbance on tropical invertebrates have never been examined. To help address this knowledge gap, we examined the body fat content and relative abundance of three dung beetle species (Coleoptera: Scarabaeinae) with minimum abundance of 40 individuals within each examined treatment level. These were sampled across 34 plots in a before-after control-impact design (BACI) in a timber concession area of the Brazilian Amazon. For the first time, we present evidence of logging-induced physiological stress responses in tropical invertebrates. Selective logging increased the individual levels of fat storage and reduced the relative abundance of two dung beetle species. Given this qualitative similarity, we support the measurement of body fat content as reliable biomarker to assess stress-induced sublethal effects on dung beetles. Understanding how environmental modification impacts the wildlife has never been more important. Our novel approach provides new insights into the mechanisms through which forest disturbances impose population-level impacts on tropical invertebrates.

  18. Plasma disruption modeling and simulation

    Hassanein, A.

    1994-01-01

    Disruptions in tokamak reactors are considered a limiting factor to successful operation and reliable design. The behavior of plasma-facing components during a disruption is critical to the overall integrity of the reactor. Erosion of plasma facing-material (PFM) surfaces due to thermal energy dump during the disruption can severely limit the lifetime of these components and thus diminish the economic feasibility of the reactor. A comprehensive understanding of the interplay of various physical processes during a disruption is essential for determining component lifetime and potentially improving the performance of such components. There are three principal stages in modeling the behavior of PFM during a disruption. Initially, the incident plasma particles will deposit their energy directly on the PFM surface, heating it to a very high temperature where ablation occurs. Models for plasma-material interactions have been developed and used to predict material thermal evolution during the disruption. Within a few microseconds after the start of the disruption, enough material is vaporized to intercept most of the incoming plasma particles. Models for plasma-vapor interactions are necessary to predict vapor cloud expansion and hydrodynamics. Continuous heating of the vapor cloud above the material surface by the incident plasma particles will excite, ionize, and cause vapor atoms to emit thermal radiation. Accurate models for radiation transport in the vapor are essential for calculating the net radiated flux to the material surface which determines the final erosion thickness and consequently component lifetime. A comprehensive model that takes into account various stages of plasma-material interaction has been developed and used to predict erosion rates during reactor disruption, as well during induced disruption in laboratory experiments

  19. The Effect of Conceptual Advancement in Jazz Music Selections and Jazz Experience on Musicians' Aesthetic Response

    Coggiola, John C.

    2004-01-01

    This study is an investigation of what musicians consider to be their aesthetic experience with jazz music selections that vary in level of conceptual advancement (melodic complexity during improvised solos). Music major participants (N = 128) were assigned to either the jazz musician (n = 64) or nonjazz musician (n = 64) group. Data were gathered…

  20. Optimizing the Use of Response Times for Item Selection in Computerized Adaptive Testing

    Choe, Edison M.; Kern, Justin L.; Chang, Hua-Hua

    2018-01-01

    Despite common operationalization, measurement efficiency of computerized adaptive testing should not only be assessed in terms of the number of items administered but also the time it takes to complete the test. To this end, a recent study introduced a novel item selection criterion that maximizes Fisher information per unit of expected response…

  1. Response to Comment on "Positive Selection of Tyrosine Loss in Metazoan Evolution"

    Tan, Chris Soon Heng; Schoof, Erwin; Creixell, Pau

    2011-01-01

    Su et al. claim guanine-cytosine (GC) content variation can largely explain the observed tyrosine frequency variation, independent of adaptive evolution of cell-signaling complexity. We found that GC content variation, in the absence of selection for amino acid changes, can only maximally account...

  2. The effects of social stress and cortisol responses on the preconscious selective attention to social threat

    Roelofs, K.; Bakvis, P.; Hermans, E.J.; Pelt, J. van; Honk, E.J. van

    2007-01-01

    The purpose of the present study was to investigate the effects of social stress and stress-induced cortisol on the preconscious selective attention to social threat. Twenty healthy participants were administered a masked emotional Stroop task (comparing color-naming latencies for angry, neutral and

  3. The effects of social stress and cortisol responses on the preconscious selective attention to social threat.

    Roelofs, K.; Bakvis, P.; Hermans, E.J.; Pelt, J. van; Honk, E.J. van

    2007-01-01

    The purpose of the present study was to investigate the effects of social stress and stress-induced cortisol on the preconscious selective attention to social threat. Twenty healthy participants were administered a masked emotional Stroop task (comparing color-naming latencies for angry, neutral and

  4. A Common Capacity Limitation for Response and Item Selection in Working Memory

    Janczyk, Markus

    2017-01-01

    Successful completion of any cognitive task requires selecting a particular action and the object the action is applied to. Oberauer (2009) suggested a working memory (WM) model comprising a declarative and a procedural part with analogous structures. One important assumption of this model is that both parts work independently of each other, and…

  5. Addressing the selective role of distinct prefrontal areas in response suppression: A study with brain tumor patients.

    Arbula, Sandra; Pacella, Valentina; De Pellegrin, Serena; Rossetto, Marta; Denaro, Luca; D'Avella, Domenico; Della Puppa, Alessandro; Vallesi, Antonino

    2017-06-01

    The diverging evidence for functional localization of response inhibition within the prefrontal cortex might be justified by the still unclear involvement of other intrinsically related cognitive processes like response selection and sustained attention. In this study, the main aim was to understand whether inhibitory impairments, previously found in patients with both left and right frontal lesions, could be better accounted for by assessing these potentially related cognitive processes. We tested 37 brain tumor patients with left prefrontal, right prefrontal and non-prefrontal lesions and a healthy control group on Go/No-Go and Foreperiod tasks. In both types of tasks inhibitory impairments are likely to cause false alarms, although additionally the former task requires response selection and the latter target detection abilities. Irrespective of the task context, patients with right prefrontal damage showed frequent Go and target omissions, probably due to sustained attention lapses. Left prefrontal patients, on the other hand, showed both Go and target omissions and high false alarm rates to No-Go and warning stimuli, suggesting a decisional rather than an inhibitory impairment. An exploratory whole-brain voxel-based lesion-symptom mapping analysis confirmed the association of left ventrolateral and dorsolateral prefrontal lesions with target discrimination failure, and right ventrolateral and medial prefrontal lesions with target detection failure. Results from this study show how left and right prefrontal areas, which previous research has linked to response inhibition, underlie broader cognitive control processes, particularly involved in response selection and target detection. Based on these findings, we suggest that successful inhibitory control relies on more than one functionally distinct process which, if assessed appropriately, might help us to better understand inhibitory impairments across different pathologies. Copyright © 2017 The Authors

  6. Can we disrupt the sensing of honey bees by the bee parasite Varroa destructor?

    Eliash, Nurit; Singh, Nitin Kumar; Kamer, Yosef; Pinnelli, Govardhana Reddy; Plettner, Erika; Soroker, Victoria

    2014-01-01

    The ectoparasitic mite, Varroa destructor, is considered to be one of the most significant threats to apiculture around the world. Chemical cues are known to play a significant role in the host-finding behavior of Varroa. The mites distinguish between bees from different task groups, and prefer nurses over foragers. We examined the possibility of disrupting the Varroa--honey bee interaction by targeting the mite's olfactory system. In particular, we examined the effect of volatile compounds, ethers of cis 5-(2'-hydroxyethyl) cyclopent-2-en-1-ol or of dihydroquinone, resorcinol or catechol. We tested the effect of these compounds on the Varroa chemosensory organ by electrophysiology and on behavior in a choice bioassay. The electrophysiological studies were conducted on the isolated foreleg. In the behavioral bioassay, the mite's preference between a nurse and a forager bee was evaluated. We found that in the presence of some compounds, the response of the Varroa chemosensory organ to honey bee headspace volatiles significantly decreased. This effect was dose dependent and, for some of the compounds, long lasting (>1 min). Furthermore, disruption of the Varroa volatile detection was accompanied by a reversal of the mite's preference from a nurse to a forager bee. Long-term inhibition of the electrophysiological responses of mites to the tested compounds was a good predictor for an alteration in the mite's host preference. These data indicate the potential of the selected compounds to disrupt the Varroa--honey bee associations, thus opening new avenues for Varroa control.

  7. Investigation of the impact of seed record selection on structural response

    Houston, Thomas W.; Mertz, Greg E.; Costantino, Michael C.; Costantino, Carl J.

    2010-01-01

    Time history records are typically used to define the seismic demand for criteria structures for which soil structure interaction (SSI) analyses are often required. Criteria for the development of time histories is provided in ASCE 43-05. The time histories are based on a close fit of 5% damped target response spectra. Recent experience has demonstrated that for cases where the transfer functions associated with the structural response are narrow, the ASCE 43 criteria can under-predict peak spectral responses in the structure by as much as 70% in some frequency ranges. One potential solution for this issue is to reinstate requirements for matching target response spectra for multiple damping levels to ASCE 43 criteria. However, recent probabilistic seismic hazard analyses (PSHA) do not generally contain spectra for multiple damping levels. This paper proposes an approach to generate target spectra at multiple damping levels, given the 5% damped target spectrum provided by the PSHA, utilizing catalogs of recorded earthquakes. The process of fitting time histories to multiple damped spectra is effective in correcting deficiencies observed in the computed structural response when time histories meeting the ASCE 43 fitting criteria are used.

  8. Positive selection in the chromosome 16 VKORC1 genomic region has contributed to the variability of anticoagulant response in humans.

    Blandine Patillon

    Full Text Available VKORC1 (vitamin K epoxide reductase complex subunit 1, 16p11.2 is the main genetic determinant of human response to oral anticoagulants of antivitamin K type (AVK. This gene was recently suggested to be a putative target of positive selection in East Asian populations. In this study, we genotyped the HGDP-CEPH Panel for six VKORC1 SNPs and downloaded chromosome 16 genotypes from the HGDP-CEPH database in order to characterize the geographic distribution of footprints of positive selection within and around this locus. A unique VKORC1 haplotype carrying the promoter mutation associated with AVK sensitivity showed especially high frequencies in all the 17 HGDP-CEPH East Asian population samples. VKORC1 and 24 neighboring genes were found to lie in a 505 kb region of strong linkage disequilibrium in these populations. Patterns of allele frequency differentiation and haplotype structure suggest that this genomic region has been submitted to a near complete selective sweep in all East Asian populations and only in this geographic area. The most extreme scores of the different selection tests are found within a smaller 45 kb region that contains VKORC1 and three other genes (BCKDK, MYST1 (KAT8, and PRSS8 with different functions. Because of the strong linkage disequilibrium, it is not possible to determine if VKORC1 or one of the three other genes is the target of this strong positive selection that could explain present-day differences among human populations in AVK dose requirement. Our results show that the extended region surrounding a presumable single target of positive selection should be analyzed for genetic variation in a wide range of genetically diverse populations in order to account for other neighboring and confounding selective events and the hitchhiking effect.

  9. Symposium on disruptive instabilities at Garching

    Lackner, K.

    1979-01-01

    The phenomenon of disruptive instabilities was investigated with a special care at the IPP at Garching. After lectures and panel sessions it appears suitable, to subdivide the disruptive phenomena into four classes: 1. The internal disruption (the socalled saw-tooth oscillators). 2. the socalled reconnection disruptions. 3. The large disruptions. 4. The small disruptions. The four appearance forms of the phenomena are briefly explained. (GG) [de

  10. Resveratrol Attenuates Exercise-Induced Adaptive Responses in Rats Selectively Bred for Low Running Performance

    Hart, Nikolett; Sarga, Linda; Csende, Zsolt; Koch, Lauren G.; Britton, Steven L.; Davies, Kelvin J.A.; Radak, Zsolt

    2013-01-01

    Low capacity runner (LCR) rats have been developed by divergent artificial selection for treadmill endurance capacity to explore an aerobic biology-disease connection. The beneficial effects of resveratrol supplementation have been demonstrated in endurance running. In this study it was examined whether 12 weeks of treadmill exercise training and/or resveratrol can retrieve the low running performance of the LCR and impact mitochondrial biogenesis and quality control. Resveratrol regressed ru...

  11. Leader-Follower Effects in Resource Dilemmas: The Roles of Leadership Selection and Social Responsibility

    Cremer, David de; Dijk, Eric van

    2008-01-01

    Abstract Previous research on the allocation of scarce resources shows that when people are assigned labels of leader or follower in their group, leaders allocate more of the scarce resources to themselves than followers do. In three laboratory studies, we examine the idea that how people are selected for the leader role (i.e. election or appointment) determines whether leaders take more or equal shares (relative to followers) from a common resource. In a first experiment, we show ...

  12. Contrasting taxonomic and functional responses of a tropical tree community to selective logging

    Baraloto, C.; Hérault, B.; Paine, C. E. T.; Massot, H.; Blanc, L.; Bonal, D.; Molino, Jean-François; Nicolini, E. A.; Sabatier, Daniel

    2012-01-01

    1. Considerable debate surrounds the extent to which tropical forests can be managed for resource extraction while conserving biodiversity and ecosystem properties, which depend on functional composition. Here we evaluate the compatibility of these aims by examining the effects of logging on taxonomic and functional diversity and composition in a tropical forest. 2. Twenty years after selective logging, we inventoried 4140 stems regenerating in logging gaps and adjacent undisturbed areas, and...

  13. Potential Response to Selection of HSP70 as a Component of Innate Immunity in the Abalone Haliotis rufescens

    Brokordt, Katherina B.; González, Roxana C.; Farías, William J.; Winkler, Federico M.

    2015-01-01

    Assessing components of the immune system may reflect disease resistance. In some invertebrates, heat shock proteins (HSPs) are immune effectors and have been described as potent activators of the innate immune response. Several diseases have become a threat to abalone farming worldwide; therefore, increasing disease resistance is considered to be a long-term goal for breeding programs. A trait will respond to selection only if it is determined partially by additive genetic variation. The aim of this study was to estimate the heritability (h 2) and the additive genetic coefficient of variation (CV A) of HSP70 as a component of innate immunity of the abalone Haliotis rufescens, in order to assess its potential response to selection. These genetic components were estimated for the variations in the intracellular (in haemocytes) and extracellular (serum) protein levels of HSP70 in response to an immunostimulant agent in 60 full-sib families of H. rufescens. Levels of HSP70 were measured twice in the same individuals, first when they were young and again when they were pre-harvest adults, to estimate the repeatability (R), the h 2 and the potential response to selection of these traits at these life stages. High HSP70 levels were observed in abalones subjected to immunostimulation in both the intracellular and extracellular haemolymph fractions. This is the first time that changes in serum levels of HSP70 have been reported in response to an immune challenge in molluscs. HSP70 levels in both fractions and at both ages showed low h 2 and R, with values that were not significantly different from zero. However, HSP70 induced levels had a CV A of 13.3–16.2% in young adults and of 2.7–8.1% in pre-harvest adults. Thus, despite its low h 2, HSP70 synthesis in response to an immune challenge in red abalone has the potential to evolve through selection because of its large phenotypic variation and the presence of additive genetic variance, especially in young animals. PMID

  14. Potential Response to Selection of HSP70 as a Component of Innate Immunity in the Abalone Haliotis rufescens.

    Katherina B Brokordt

    Full Text Available Assessing components of the immune system may reflect disease resistance. In some invertebrates, heat shock proteins (HSPs are immune effectors and have been described as potent activators of the innate immune response. Several diseases have become a threat to abalone farming worldwide; therefore, increasing disease resistance is considered to be a long-term goal for breeding programs. A trait will respond to selection only if it is determined partially by additive genetic variation. The aim of this study was to estimate the heritability (h2 and the additive genetic coefficient of variation (CVA of HSP70 as a component of innate immunity of the abalone Haliotis rufescens, in order to assess its potential response to selection. These genetic components were estimated for the variations in the intracellular (in haemocytes and extracellular (serum protein levels of HSP70 in response to an immunostimulant agent in 60 full-sib families of H. rufescens. Levels of HSP70 were measured twice in the same individuals, first when they were young and again when they were pre-harvest adults, to estimate the repeatability (R, the h2 and the potential response to selection of these traits at these life stages. High HSP70 levels were observed in abalones subjected to immunostimulation in both the intracellular and extracellular haemolymph fractions. This is the first time that changes in serum levels of HSP70 have been reported in response to an immune challenge in molluscs. HSP70 levels in both fractions and at both ages showed low h2 and R, with values that were not significantly different from zero. However, HSP70 induced levels had a CVA of 13.3-16.2% in young adults and of 2.7-8.1% in pre-harvest adults. Thus, despite its low h2, HSP70 synthesis in response to an immune challenge in red abalone has the potential to evolve through selection because of its large phenotypic variation and the presence of additive genetic variance, especially in young animals.

  15. The response of natural enemies to selective insecticides applied to soybean.

    Varenhorst, A J; O'Neal, M E

    2012-12-01

    Natural enemies of the invasive pest Aphis glycines Matsumura can prevent its establishment and population growth. However, current A. glycines management practices include the application of broad-spectrum insecticides that affect pests and natural enemies that are present in the field at the time of application. An alternative is the use of selective insecticides that affect the targeted pest species, although having a reduced impact on the natural enemies. We tested the effects of esfenvalerate, spirotetramat, imidacloprid, and a combination of spirotetramat and imidacloprid on the natural enemies in soybean during the 2009 and 2010 field season. The natural enemy community that was tested differed significantly between 2009 and 2010 (F = 87.41; df = 1, 598; P natural enemy in 2009 was Harmonia axyridis (Pallas) (56.0%) and in 2010 was Orius insidiosus (Say) (41.0%). During 2009, the abundance of natural enemies did not vary between the broad-spectrum and selective insecticides; however, the abundance of natural enemies was reduced by all insecticide treatments when compared with the untreated control. In 2010, the selective insecticide imidacloprid had more natural enemies than the broad-spectrum insecticide. Although we did not observe a difference in the abundance of the total natural enemy community in 2009, we did observe more H. axyridis in plots treated with spirotetramat. In 2010, we observed more O. insidiosus in plots treated with imidacloprid. We suggest a couple of mechanisms to explain how the varying insecticides have different impacts on separate components of the natural enemy community.

  16. Correlated effects of selection for immunity in White Leghorn chicken lines on natural antibodies and specific antibody responses to KLH and M. butyricum

    Minozzi, G.; Parmentier, H.K.; Mignon-Grasteau, S.; Nieuwland, M.G.B.; Bed'hom, B.; Gourichon, D.; Minvielle, F.; Pinard-van der Laan, M.H.

    2008-01-01

    Background - The effect of selection for three general immune response traits on primary antibody responses (Ab) to Mycobacterium butyricum or keyhole limpet hemocyanin (KLH) was studied in four experimental lines of White Leghorn chicken. Birds underwent 12 generations of selection for one of three

  17. Evolution of floral display in Eichhornia paniculata (Pontederiaceae): direct and correlated responses to selection on flower size and number.

    Worley, A C; Barrett, S C

    2000-10-01

    Trade-offs between flower size and number seem likely to influence the evolution of floral display and are an important assumption of several theoretical models. We assessed floral trade-offs by imposing two generations of selection on flower size and number in a greenhouse population of bee-pollinated Eichhornia paniculata. We established a control line and two replicate selection lines of 100 plants each for large flowers (S+), small flowers (S-), and many flowers per inflorescence (N+). We compared realized heritabilities and genetic correlations with estimates based on restricted-maximum-likelihood (REML) analysis of pedigrees. Responses to selection confirmed REML heritability estimates (flower size, h2 = 0.48; daily flower number, h2 = 0.10; total flower number, h2 = 0.23). Differences in nectar, pollen, and ovule production between S+ and S- lines supported an overall divergence in investment per flower. Both realized and REML estimates of the genetic correlation between daily and total flower number were r = 1.0. However, correlated responses to selection were inconsistent in their support of a trade-off. In both S- lines, correlated increases in flower number indicated a genetic correlation of r = -0.6 between flower size and number. In contrast, correlated responses in N+ and S+ lines were not significant, although flower size decreased in one N+ line. In addition, REML estimates of genetic correlations between flower size and number were positive, and did not differ from zero when variation in leaf area and age at first flowering were taken into account. These results likely reflect the combined effects of variation in genes controlling the resources available for flowering and genes with opposing effects on flower size and number. Our results suggest that the short-term evolution of floral display is not necessarily constrained by trade-offs between flower size and number, as is often assumed.

  18. A Network Disruption Modeling Tool

    Leinart, James

    1998-01-01

    Given that network disruption has been identified as a military objective and C2-attack has been identified as the mechanism to accomplish this objective, a target set must be acquired and priorities...

  19. Dietary diversity, feeding selectivity, and responses to fruit scarcity of two sympatric Bornean primates (Hylobates albibarbis and Presbytis rubicunda rubida.

    Dena J Clink

    Full Text Available Effectively characterizing primate diets is fundamental to understanding primate behavior, ecology and morphology. Examining temporal variation in a species' diet, as well as comparing the responses of different species to variation in resource availability, can enhance understanding of the evolution of morphology and socioecology. In this study, we use feeding data collected over five years to describe the diets of two sympatric Southeast Asian primate species of similar body size: white-bearded gibbons (Hylobates albibarbis and red leaf monkeys (Presbytis rubicunda rubida, in Gunung Palung National Park, West Kalimantan, Indonesia. Long-term data sets are especially important for characterizing primate diets in Southeast Asia, where the forests exhibit supra-annual mast fruiting events. We found that gibbons were mainly frugivorous, with fruit and figs comprising 70% of their 145 independent feeding observations, whereas leaf monkeys ate a substantial amount of seeds (26%, fruits and figs (26.5% and leaves (30%, n = 219 independent feeding observations. Leaf monkeys consumed a higher number of plant genera, and this was due mostly to the non-frugivorous portion of their diet. To investigate resource selection by these primates we utilized two different approaches: the Manly Selectivity Ratio, which did not take into account temporal variation of resource availability, and a model selection framework which did incorporate temporal variation. Both species selected figs (Ficus more than predicted based on their availability under the Manly Selectivity Ratio. Model selection allowed us to determine how these primates alter the proportion of leaves, flowers, seeds, figs and fruit in their diets in response to variation in fruit availability. When fruits were scarce, both gibbons and leaf monkeys incorporated more leaves and figs into their diets, indicating that these two food classes are fallback foods for these primates. We discuss how different

  20. Community emergency response to nuclear power plant accidents: A selected and partially annotated bibliography

    Youngen, G.

    1988-10-01

    The role of responding to emergencies at nuclear power plants is often considered the responsibility of the personnel onsite. This is true for most, if not all, of the incidents that may happen during the course of the plant's operating lifetime. There is however, the possibility of a major accident occurring at anytime. Major nuclear accidents at Chernobyl and Three Mile Island have taught their respective countries and communities a significant lesson in local emergency preparedness and response. Through these accidents, the rest of the world can also learn a great deal about planning, preparing and responding to the emergencies unique to nuclear power. This bibliography contains books, journal articles, conference papers and government reports on emergency response to nuclear power plant accidents. It does not contain citations for ''onsite'' response or planning, nor does it cover the areas of radiation releases from transportation accidents. The compiler has attempted to bring together a sampling of the world's collective written experience on dealing with nuclear reactor accidents on the sate, local and community levels. Since the accidents at Three Mile Island and Chernobyl, that written experience has grown enormously

  1. Community emergency response to nuclear power plant accidents: A selected and partially annotated bibliography

    Youngen, G.

    1988-10-01

    The role of responding to emergencies at nuclear power plants is often considered the responsibility of the personnel onsite. This is true for most, if not all, of the incidents that may happen during the course of the plant`s operating lifetime. There is however, the possibility of a major accident occurring at anytime. Major nuclear accidents at Chernobyl and Three Mile Island have taught their respective countries and communities a significant lesson in local emergency preparedness and response. Through these accidents, the rest of the world can also learn a great deal about planning, preparing and responding to the emergencies unique to nuclear power. This bibliography contains books, journal articles, conference papers and government reports on emergency response to nuclear power plant accidents. It does not contain citations for ``onsite`` response or planning, nor does it cover the areas of radiation releases from transportation accidents. The compiler has attempted to bring together a sampling of the world`s collective written experience on dealing with nuclear reactor accidents on the sate, local and community levels. Since the accidents at Three Mile Island and Chernobyl, that written experience has grown enormously.

  2. Charged pion electroproduction, a selective probe of nuclear spin isospin responses

    Chanfray, G.; Delorme, J.

    1983-05-01

    We study the reaction of pion electroproduction on nuclei in the quasi-elastic region. We show that detection of the pion in the direction of the virtual photon permits the separation of the spin longitudinal and transverse responses through a Rosenbluth plot. Emphasis is also put on consistency between medium effects and gauge invariance

  3. Precision metabolic engineering: The design of responsive, selective, and controllable metabolic systems.

    McNerney, Monica P; Watstein, Daniel M; Styczynski, Mark P

    2015-09-01

    Metabolic engineering is generally focused on static optimization of cells to maximize production of a desired product, though recently dynamic metabolic engineering has explored how metabolic programs can be varied over time to improve titer. However, these are not the only types of applications where metabolic engineering could make a significant impact. Here, we discuss a new conceptual framework, termed "precision metabolic engineering," involving the design and engineering of systems that make different products in response to different signals. Rather than focusing on maximizing titer, these types of applications typically have three hallmarks: sensing signals that determine the desired metabolic target, completely directing metabolic flux in response to those signals, and producing sharp responses at specific signal thresholds. In this review, we will first discuss and provide examples of precision metabolic engineering. We will then discuss each of these hallmarks and identify which existing metabolic engineering methods can be applied to accomplish those tasks, as well as some of their shortcomings. Ultimately, precise control of metabolic systems has the potential to enable a host of new metabolic engineering and synthetic biology applications for any problem where flexibility of response to an external signal could be useful. Copyright © 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  4. Selective Acquiescence, Creative Commitment and Strategic Conformity: Situated National Policy Responses to Bologna

    Sin, Cristina; Saunders, Murray

    2014-01-01

    The non-binding nature of the Bologna Declaration and loose policy-making and implementation through the open method of coordination (OMC) have led to varied national responses to the Bologna Process. The OMC has allowed countries room for manoeuvre to interpret Bologna policy and attach different degrees of importance to it. Looking at the…

  5. Acute Exposure of College Basketball Players to Moderate Altitude: Selected Physiological Responses.

    Noble, Bruce J.; Maresh, Carl M.

    1979-01-01

    In general, basketball players with moderately high aerobic power who reside at an altitude of 1,000 m do not display the hypoxic response to an altitude of 2,200 m expected of sea level residents and aerobically trained athletes. (JD)

  6. Relation between derived-band auditory brainstem response latencies and behavioral frequency selectivity

    Strelcyk, Olaf; Christoforidis, Dimitrios; Dau, Torsten

    2009-01-01

    response times. For the same listeners, auditory-filter bandwidths at 2 kHz were estimated using a behavioral notched-noise masking paradigm. Generally, shorter derived-band latencies were observed for the HI than for the NH listeners. Only at low click sensation levels, prolonged latencies were obtained...

  7. The Effects of an Environmental Studies Course on Selected Variables Related To Environmentally Responsible Behavior.

    Smith-Sebasto, N. J.

    1995-01-01

    Reports that students completing an environmental studies course displayed significant gains when compared with students not completing such a course. These gains were made in acquiring a more internally-oriented locus of control of reinforcement for environmentally responsible behavior, a higher perception of their knowledge of and skill in using…

  8. Attention as Inference: Selection Is Probabilistic; Responses Are All-or-None Samples

    Vul, Edward; Hanus, Deborah; Kanwisher, Nancy

    2009-01-01

    Theories of probabilistic cognition postulate that internal representations are made up of multiple simultaneously held hypotheses, each with its own probability of being correct (henceforth, "probability distributions"). However, subjects make discrete responses and report the phenomenal contents of their mind to be all-or-none states rather than…

  9. Selection on feather pecking affects response to novelty and foraging behaviour in laying hens

    Haas, de E.N.; Nielsen, B.; Rodenburg, T.B.; Buitenhuis, A.J.

    2010-01-01

    Feather pecking (FP) is a major welfare problem in laying hens, influenced by multiple factors. FP is thought to be redirected foraging behaviour, however fearful birds are also known to be more sensitive to develop FP. The relationship between fear-responses, foraging and FP is not well understood,

  10. Comparative analysis of response to selection with three insecticides in the dengue mosquito Aedes aegypti using mRNA sequencing.

    David, Jean-Philippe; Faucon, Frédéric; Chandor-Proust, Alexia; Poupardin, Rodolphe; Riaz, Muhammad Asam; Bonin, Aurélie; Navratil, Vincent; Reynaud, Stéphane

    2014-03-05

    selection strongly affected the polymorphism of several transcripts encoding cytochrome P450 monooxygenases likely involved in insecticide biodegradation. The present study confirmed the power of RNA-seq for identifying concomitantly quantitative and qualitative transcriptome changes associated with insecticide resistance in mosquitoes. Our results suggest that transcriptome modifications can be selected rapidly by insecticides and affect multiple biological functions. Previously neglected by molecular screenings, polymorphism variations of detoxification enzymes may play an important role in the adaptive response of mosquitoes to insecticides.

  11. Glucocorticoid receptor gene inactivation in dopamine-innervated areas selectively decreases behavioral responses to amphetamine

    Parnaudeau, Sébastien; Dongelmans, Marie-louise; Turiault, Marc; Ambroggi, Frédéric; Delbes, Anne-Sophie; Cansell, Céline; Luquet, Serge; Piazza, Pier-Vincenzo; Tronche, François; Barik, Jacques

    2014-01-01

    The meso-cortico-limbic system, via dopamine release, encodes the rewarding and reinforcing properties of natural rewards. It is also activated in response to abused substances and is believed to support drug-related behaviors. Dysfunctions of this system lead to several psychiatric conditions including feeding disorders and drug addiction. These disorders are also largely influenced by environmental factors and in particular stress exposure. Stressors activate the corticotrope axis ultimately leading to glucocorticoid hormone (GCs) release. GCs bind the glucocorticoid receptor (GR) a transcription factor ubiquitously expressed including within the meso-cortico-limbic tract. While GR within dopamine-innervated areas drives cocaine's behavioral responses, its implication in responses to other psychostimulants such as amphetamine has never been clearly established. Moreover, while extensive work has been made to uncover the role of this receptor in addicted behaviors, its contribution to the rewarding and reinforcing properties of food has yet to be investigated. Using mouse models carrying GR gene inactivation in either dopamine neurons or in dopamine-innervated areas, we found that GR in dopamine responsive neurons is essential to properly build amphetamine-induced conditioned place preference and locomotor sensitization. c-Fos quantification in the nucleus accumbens further confirmed defective neuronal activation following amphetamine injection. These diminished neuronal and behavioral responses to amphetamine may involve alterations in glutamate transmission as suggested by the decreased MK801-elicited hyperlocomotion and by the hyporeactivity to glutamate of a subpopulation of medium spiny neurons. In contrast, GR inactivation did not affect rewarding and reinforcing properties of food suggesting that responding for natural reward under basal conditions is preserved in these mice. PMID:24574986

  12. In Vitro Cytotoxicity and Adaptive Stress Responses to Selected Haloacetic Acid and Halobenzoquinone Water Disinfection Byproducts.

    Procházka, Erik; Escher, Beate I; Plewa, Michael J; Leusch, Frederic D L

    2015-10-19

    The process of disinfecting drinking water inadvertently leads to the formation of numerous disinfection byproducts (DBPs). Some of these are mutagenic, genotoxic, teratogenic, and cytotoxic, as well as potentially carcinogenic both in vivo and in vitro. We investigated the in vitro biological activity of five DBPs: three monohaloacetic acids (monoHAAs) [chloroacetic acid (CAA), bromoacetic acid (BAA), and iodoacetic acid (IAA)] and two novel halobenzoquinones (HBQs) [2,6-dichloro-p-benzoquinone (DCBQ) and 2,6-dibromo-p-benzoquinone]. We focused particularly on cytotoxicity and induction of two adaptive stress response pathways: the oxidative stress responsive Nrf2/ARE and DNA-damage responsive p53 pathways. All five DBPs were cytotoxic to the Caco-2 cell line after a 4 h exposure, and all DBPs induced both of the adaptive stress response pathways, Nrf2/ARE and p53, in the micromolar range, as measured by two β-lactamase-based reporter gene assays. The decreasing order of potency for all three endpoints for the five DBPs was IAA ∼ BAA > DCBQ ∼ DBBQ > CAA. Induction of oxidative stress was previously proposed to be the molecular initiating event (MIE) for both classes of DBPs. However, comparing the levels of activation of the two pathways uncovered that the Nrf2/ARE pathway was the more sensitive endpoint for HAAs, whereas the p53 pathway was more sensitive in the case of HBQs. Therefore, the DNA damage-responsive p53 pathway may be an important piece of information to fill in a gap in the adverse outcome pathway framework for the assessment of HBQs. Finally, we cautiously compared the potential risk of the two novel HBQs using a benchmarking approach to that of the well-studied CAA, which suggested that their relative risk may be lower than that of BAA and IAA.

  13. Glucocorticoid receptor gene inactivation in dopamine-innervated areas selectively decreases behavioral responses to amphetamine

    Sebastien eParnaudeau

    2014-02-01

    Full Text Available The meso-cortico-limbic system, via dopamine release, encodes the rewarding and reinforcing properties of natural rewards. It is also activated in response to abused substances and is believed to support drug-related behaviors. Dysfunctions of this system lead to several psychiatric conditions including feeding disorders and drug addiction. These disorders are also largely influenced by environmental factors and in particular stress exposure. Stressors activate the corticotrope axis ultimately leading to glucocorticoid hormone (GCs release. GCs bind the glucocorticoid receptor (GR a transcription factor ubiquitously expressed including within the meso-cortico-limbic tract. While the GR within dopamine-innervated areas drives cocaine’s behavioral responses, its implication in responses to other psychostimulants such as amphetamine has never been clearly established. Moreover, while extensive work has been made to uncover the role of this receptor in addicted behaviors, its contribution to the rewarding and reinforcing properties of food has yet to be investigated. Using mouse models carrying GR gene inactivation in either dopamine neurons or in dopamine-innervated areas, we found that GR in dopamine responsive neurones is essential to properly build amphetamine-induced conditioned place preference and locomotor sensitization. c-Fos quantification in the nucleus accumbens further confirmed defective neuronal activation following amphetamine injection. These diminished neuronal and behavioral responses to amphetamine may involve alterations in glutamate transmission as suggested by the decreased MK801-elicited hyperlocomotion and by the hyporeactivity to glutamate of a subpopulation of medium spiny neurons. In contrast, GR inactivation did not affect rewarding and reinforcing properties of food suggesting that responding for natural reward under basal conditions is preserved in these mice.

  14. DISRUPTIVE TECHNOLOGIES: AN EXPANDED VIEW

    JAMES M. UTTERBACK; HAPPY J. ACEE

    2005-01-01

    The term "disruptive technology" as coined by Christensen (1997, The Innovator's Dilemma; How New Technologies Cause Great Firms to Fail. Harvard Business School Press) refers to a new technology having lower cost and performance measured by traditional criteria, but having higher ancillary performance. Christensen finds that disruptive technologies may enter and expand emerging market niches, improving with time and ultimately attacking established products in their traditional markets. This...

  15. A randomized trial on mineralocorticoid receptor blockade in men: effects on stress responses, selective attention, and memory.

    Cornelisse, Sandra; Joëls, Marian; Smeets, Tom

    2011-12-01

    Corticosteroids, released in high amounts after stress, exert their effects via two different receptors in the brain: glucocorticoid receptors (GRs) and mineralocorticoid receptors (MRs). GRs have a role in normalizing stress-induced effects and promoting consolidation, while MRs are thought to be important in determining the threshold for activation of the hypothalamic-pituitary-adrenal (HPA) axis. We investigated the effects of MR blockade on HPA axis responses to stress and stress-induced changes in cognitive function. In a double-blind, placebo-controlled study, 64 healthy young men received 400 mg of the MR antagonist spironolactone or placebo. After 1.5 h, they were exposed to either a Trier Social Stress Test or a non-stressful control task. Responses to stress were evaluated by hormonal, subjective, and physiological measurements. Afterwards, selective attention, working memory, and long-term memory performance were assessed. Spironolactone increased basal salivary cortisol levels as well as cortisol levels in response to stress. Furthermore, spironolactone significantly impaired selective attention, but only in the control group. The stress group receiving spironolactone showed impaired working memory performance. By contrast, long-term memory was enhanced in this group. These data support a role of MRs in the regulation of the HPA axis under basal conditions as well as in response to stress. The increased availability of cortisol after spironolactone treatment implies enhanced GR activation, which, in combination with MR blockade, presumably resulted in a decreased MR/GR activation ratio. This condition influences both selective attention and performance in various memory tasks.

  16. Disrupting Mating Behavior of Diaphorina citri (Liviidae).

    Lujo, S; Hartman, E; Norton, K; Pregmon, E A; Rohde, B B; Mankin, R W

    2016-12-01

    Severe economic damage from citrus greening disease, caused by 'Candidatus Liberibacter asiaticus' bacteria, has stimulated development of methods to reduce mating and reproduction in populations of its insect vector, Diaphorina citri (Hemiptera: Liviidae). Male D. citri find mating partners by walking on host plants, intermittently producing vibrational calls that stimulate duetting replies by receptive females. The replies provide orientational feedback, assisting the search process. To test a hypothesis that D. citri mating can be disrupted using vibrational signals that compete with and/or mask female replies, courtship bioassays were conducted in citrus trees with or without interference from female reply mimics produced by a vibrating buzzer. Statistically significant reductions occurred in the rates and proportions of mating when the buzzer produced reply mimics within 0.4 s after male courtship calls compared with undisturbed controls. Observations of courtship behaviors in the two bioassays revealed activity patterns that likely contributed to the reductions. In both disruption and control tests, males reciprocated frequently between structural bifurcations and other transition points where signal amplitudes changed. Males in the disruption bioassay had to select among vibrational signals combined from the buzzer and the female at each transition point. They often turned towards the buzzer instead of the female. There was a statistically significant reduction in the proportion of males mating if they contacted the buzzer, possibly due to its higher vibration amplitude and duration in comparison with female replies. Potential applications of D. citri mating disruption technology in citrus groves are discussed. Published by Oxford University Press on behalf of Entomological Society of America 2016. This work is written by US Government employees and is in the public domain in the US.

  17. Quick profile-reorganization driven by helical field perturbation for suppressing tokamak major disruptions

    Yamazaki, K.; Kawahata, K.; Ando, R.

    1986-09-01

    Disruptive behavior of magnetic field configuration leading to tokamak major disruption is found to be controlled by a mild ''mini-disruption'' which is induced by the compact external modular multipole-field coils with m = 3/n = 2 dominant helical field component in the JIPP T-IIU tokamak. This mini-disruption ergodizes the m = 2/n = 1 magnetic island quickly but mildly and then prevents the profile of electron temperature from flattening. This quick profile-reorganization is effective to avoid the two-step disruption (pre- and major disuptions) responsible for the chatastrophic current termination. (author)

  18. Improvements in disruption prediction at ASDEX Upgrade

    Aledda, R., E-mail: raffaele.aledda@diee.unica.it; Cannas, B., E-mail: cannas@diee.unica.it; Fanni, A., E-mail: fanni@diee.unica.it; Pau, A., E-mail: alessandro.pau@diee.unica.it; Sias, G., E-mail: giuliana.sias@diee.unica.it

    2015-10-15

    Highlights: • A disruption prediction system for AUG, based on a logistic model, is designed. • The length of the disruptive phase is set for each disruption in the training set. • The model is tested on dataset different from that used during the training phase. • The generalization capability and the aging of the model have been tested. • The predictor performance is compared with the locked mode detector. - Abstract: In large-scale tokamaks disruptions have the potential to create serious damage to the facility. Hence disruptions must be avoided, but, when a disruption is unavoidable, minimizing its severity is mandatory. A reliable detection of a disruptive event is required to trigger proper mitigation actions. To this purpose machine learning methods have been widely studied to design disruption prediction systems at ASDEX Upgrade. The training phase of the proposed approaches is based on the availability of disrupted and non-disrupted discharges. In literature disruptive configurations were assumed appearing into the last 45 ms of each disruption. Even if the achieved results in terms of correct predictions were good, it has to be highlighted that the choice of such a fixed temporal window might have limited the prediction performance. In fact, it generates confusing information in cases of disruptions with disruptive phase different from 45 ms. The assessment of a specific disruptive phase for each disruptive discharge represents a relevant issue in understanding the disruptive events. In this paper, the Mahalanobis distance is applied to define a specific disruptive phase for each disruption, and a logistic regressor has been trained as disruption predictor. The results show that enhancements on the achieved performance on disruption prediction are possible by defining a specific disruptive phase for each disruption.

  19. Improvements in disruption prediction at ASDEX Upgrade

    Aledda, R.; Cannas, B.; Fanni, A.; Pau, A.; Sias, G.

    2015-01-01

    Highlights: • A disruption prediction system for AUG, based on a logistic model, is designed. • The length of the disruptive phase is set for each disruption in the training set. • The model is tested on dataset different from that used during the training phase. • The generalization capability and the aging of the model have been tested. • The predictor performance is compared with the locked mode detector. - Abstract: In large-scale tokamaks disruptions have the potential to create serious damage to the facility. Hence disruptions must be avoided, but, when a disruption is unavoidable, minimizing its severity is mandatory. A reliable detection of a disruptive event is required to trigger proper mitigation actions. To this purpose machine learning methods have been widely studied to design disruption prediction systems at ASDEX Upgrade. The training phase of the proposed approaches is based on the availability of disrupted and non-disrupted discharges. In literature disruptive configurations were assumed appearing into the last 45 ms of each disruption. Even if the achieved results in terms of correct predictions were good, it has to be highlighted that the choice of such a fixed temporal window might have limited the prediction performance. In fact, it generates confusing information in cases of disruptions with disruptive phase different from 45 ms. The assessment of a specific disruptive phase for each disruptive discharge represents a relevant issue in understanding the disruptive events. In this paper, the Mahalanobis distance is applied to define a specific disruptive phase for each disruption, and a logistic regressor has been trained as disruption predictor. The results show that enhancements on the achieved performance on disruption prediction are possible by defining a specific disruptive phase for each disruption.

  20. Visual object agnosia is associated with a breakdown of object-selective responses in the lateral occipital cortex.

    Ptak, Radek; Lazeyras, François; Di Pietro, Marie; Schnider, Armin; Simon, Stéphane R

    2014-07-01

    Patients with visual object agnosia fail to recognize the identity of visually presented objects despite preserved semantic knowledge. Object agnosia may result from damage to visual cortex lying close to or overlapping with the lateral occipital complex (LOC), a brain region that exhibits selectivity to the shape of visually presented objects. Despite this anatomical overlap the relationship between shape processing in the LOC and shape representations in object agnosia is unknown. We studied a patient with object agnosia following isolated damage to the left occipito-temporal cortex overlapping with the LOC. The patient showed intact processing of object structure, yet often made identification errors that were mainly based on the global visual similarity between objects. Using functional Magnetic Resonance Imaging (fMRI) we found that the damaged as well as the contralateral, structurally intact right LOC failed to show any object-selective fMRI activity, though the latter retained selectivity for faces. Thus, unilateral damage to the left LOC led to a bilateral breakdown of neural responses to a specific stimulus class (objects and artefacts) while preserving the response to a different stimulus class (faces). These findings indicate that representations of structure necessary for the identification of objects crucially rely on bilateral, distributed coding of shape features. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Planarians in toxicology. Responses of asexual Dugesia dorotocephala to selected metals

    Kapu, M.M.; Schaeffer, D.J. (Univ. of Illinois, Urbana (United States))

    1991-08-01

    The planarian Dugesia dorotocephala is a freshwater invertebrate found in unpolluted flowing surface waters. Planarians have a sensitive nervous system with synapses and true brain and evidence these in a variety of social and response behaviors. The inclusion of planarians in a screening battery would provide improved sensitivity in detecting toxicity because planarians commonly respond to lower levels of contamination than do other species. Numerous toxicity test have been conducted to determine the acute and chronic effects of toxicants to provide data necessary for the development of water quality criteria. The appropriateness of Illinois water quality standards for metals was investigated using a 1-hr behavioral test based on the responses of the planarian D. dorotocephala. One possible difficulty with water quality standards for metals is that the standard for each metal is usually established without regard to the effects of other metals present in the receiving water.

  2. Neuronal Activation in the Medulla Oblongata during Selective Elicitation of the Laryngeal Adductor Response

    Ambalavanar, Ranjinidevi; Tanaka, Yasumasa; Selbie, W. Scott; Ludlow, Christy L.

    2008-01-01

    Swallow and cough are complex motor patterns elicited by rapid and intense electrical stimulation of the internal branch of the superior laryngeal nerve (ISLN). The laryngeal adductor response (LAR) includes only a laryngeal response, is elicited by single stimuli to the ISLN, and is thought to represent the brain stem pathway involved in laryngospasm. To identify which regions in the medulla are activated during elicitation of the LAR alone, single electrical stimuli were presented once every 2 s to the ISLN. Two groups of 5 cats each were studied; an experimental group with unilateral ISLN stimulation at 0.5 Hz and a surgical control group. Three additional cats were studied to evaluate whether other oral, pharyngeal or respiratory muscles were activated during ISLN stimulation eliciting LAR. We quantified up to 22 sections for each of 14 structures in the medulla to determine if regions had increased Fos-like immunoreactive neurons in the experimental group. Significant increases (p medulla. PMID:15212423

  3. Thermotolerant yeasts selected by adaptive evolution express heat stress response at 30ºC

    Caspeta, Luis; Chen, Yun; Nielsen, Jens

    2016-01-01

    to grow at increased temperature, activated a constitutive heat stress response when grown at the optimal ancestral temperature, and that this is associated with a reduced growth rate. This preventive response was perfected by additional transcriptional changes activated when the cultivation temperature...... is increased. Remarkably, the sum of global transcriptional changes activated in the thermotolerant strains when transferred from the optimal to the high temperature, corresponded, in magnitude and direction, to the global changes observed in the ancestral strain exposed to the same transition....... This demonstrates robustness of the yeast transcriptional program when exposed to heat, and that the thermotolerant strains streamlined their path to rapidly and optimally reach post-stress transcriptional and metabolic levels. Thus, long-term adaptation to heat improved yeasts ability to rapidly adapt to increased...

  4. Saccade frequency response to visual cues during gait in Parkinson's disease: the selective role of attention.

    Stuart, Samuel; Lord, Sue; Galna, Brook; Rochester, Lynn

    2018-04-01

    Gait impairment is a core feature of Parkinson's disease (PD) with implications for falls risk. Visual cues improve gait in PD, but the underlying mechanisms are unclear. Evidence suggests that attention and vision play an important role; however, the relative contribution from each is unclear. Measurement of visual exploration (specifically saccade frequency) during gait allows for real-time measurement of attention and vision. Understanding how visual cues influence visual exploration may allow inferences of the underlying mechanisms to response which could help to develop effective therapeutics. This study aimed to examine saccade frequency during gait in response to a visual cue in PD and older adults and investigate the roles of attention and vision in visual cue response in PD. A mobile eye-tracker measured saccade frequency during gait in 55 people with PD and 32 age-matched controls. Participants walked in a straight line with and without a visual cue (50 cm transverse lines) presented under single task and dual-task (concurrent digit span recall). Saccade frequency was reduced when walking in PD compared to controls; however, visual cues ameliorated saccadic deficit. Visual cues significantly increased saccade frequency in both PD and controls under both single task and dual-task. Attention rather than visual function was central to saccade frequency and gait response to visual cues in PD. In conclusion, this study highlights the impact of visual cues on visual exploration when walking and the important role of attention in PD. Understanding these complex features will help inform intervention development. © 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  5. Behavioral and electroantennogram responses of plum curculio, Conotrachelus nenuphar, to selected noxious plant extracts and insecticides.

    Gӧkçe, A; Stelinski, L L; Nortman, D R; Bryan, W W; Whalon, M E

    2014-01-01

    Behavioral and electroantennogram responses of plum curculio, Conotrachelus nenuphar (Herbst) (Coleoptera: Curculionidae), adults were tested for several methanolic plant extracts and organically approved insecticides. Plant extracts were evaluated for their potential as antifeedants or oviposition deterrents. These extract responses were also compared to those elicited by the non-neurotoxic, organic irritant-insecticide kaolin clay. Both sexes of plum curculio exhibited antennal response as measured by electroantennogram, which ranged from 0.2 to 1.1 mV, to plant extracts and the organic irritant/insecticide, with the greatest response to the extract of rough cocklebur, Xanthium strumarium L. (1.1 mV). No choice tests were conducted to compare feeding and oviposition by plum curculio on untreated apples or on apples treated with one of the extracts or the insecticide. The insecticide pyrethrum and extracts of X. strumarium and greater burdock, Arctium lappa L., significantly reduced feeding. Also, pyrethrum, A. lappa, Humulus lupulus L. (common hop), X. strumarium, and Verbascum songaricum Schrenk extracts completely inhibited egg deposition. In no-choice assays, the effects of kaolin clay with incorporated plant extracts on plum curculio feeding and oviposition were monitored as complementary tests. A. lappa-kaolin, H. lupulus-kaolin, and X. strumarium-kaolin mixtures significantly reduced the feeding of plum curculio compared to the control or kaolin clay alone. Each of the plant extract-kaolin mixtures evaluated, with the exception of Bifora radians Bieberstein (wild bishop), completely inhibited plum curculio oviposition as compared to controls. This is an open access paper. We use the Creative Commons Attribution 3.0 license that permits unrestricted use, provided that the paper is properly attributed.

  6. CORPORATE SOCIAL RESPONSIBILITY (CSR) IN THEORY AND IN PRACTICE. SELECTED ISSUES

    Wolska, Grażyna

    2017-01-01

    The increased interest in creating socially responsible business model results from various reasons. The most important ones include: recently frequently acceptable need to apply the so-called sustainable development concept, need for civil society development, increased clarity of business activity and its consequences, including elimination of corruption and unethical behaviour in business and implementation of good practices in relations with a wide group of stakeholders. The study aims at...

  7. The Physiological Response of Soybean Genotypes to VAM Inoculation on Selected Drought Stress Levels

    HAPSOH

    2006-06-01

    Full Text Available Present research was aimed to study physiological changes of soybean which were inoculated with vesicular arbuscular mycorrhizal fungi (VAM. Glomus etunicatum was exposed to moderate and severe drought condition. Symbiotic association with VAM improved adaptability as it was shown by the increasing leaf proline content. The MLG 3474 and Sindoro are the more tolerant genotypes while the responses of plant to VAM on improving the adaptability to drought were larger on Lokon.

  8. Cloned, CD117 selected human amniotic fluid stem cells are capable of modulating the immune response.

    Emily C Moorefield

    Full Text Available Amniotic fluid stem (AFS cells are broadly multipotent, can be expanded extensively in culture, are not tumorigenic and can be readily cryopreserved for cell banking. Mesenchymal stem cells (MSC show immunomodulatory activity and secrete a wide spectrum of cytokines and chemokines that suppress inflammatory responses, block mixed lymphocyte reactions (MLR and other immune reactions, and have proven therapeutic against conditions such as graft-versus-host disease. AFS cells resemble MSCs in many respects including surface marker expression and differentiation potential. We therefore hypothesized that AFS cells may exhibit similar immunomodulatory capabilities. We present data to demonstrate that direct contact with AFS cells inhibits lymphocyte activation. In addition, we show that cell-free supernatants derived from AFS cells primed with total blood monocytes or IL-1β, a cytokine released by monocytes and essential in mediation of the inflammatory response, also inhibited lymphocyte activation. Further investigation of AFS cell-free supernatants by protein array revealed secretion of multiple factors in common with MSCs that are known to be involved in immune regulation including growth related oncogene (GRO and monocyte chemotactic protein (MCP family members as well as interleukin-6 (IL-6. AFS cells activated by PBMCs released several additional cytokines as compared to BM-MSCs, including macrophage inflammatory protein-3α (MIP-3α, MIP-1α and Activin. AFS cells also released higher levels of MCP-1 and lower levels of MCP-2 compared to BM-MSCs in response to IL-1β activation. This suggests that there may be some AFS-specific mechanisms of inhibition of lymphocyte activation. Our results indicate that AFS cells are able to suppress inflammatory responses in vitro and that soluble factors are an essential component in the communication between lymphocytes and AFS cells. Their extensive self-renewal capacity, possibility for banking and

  9. Corporate social responsibility approaches and implementation in selected fast food restaurants

    Emma E. Montalbo

    2015-08-01

    Full Text Available This study sought to determine Corporate Social Responsibility approaches and implementation in Fast Food Restaurants in Batangas City, Philippines. The researchers employed a descriptive design and quantitative method in the analysis of data with the questionnaire as the main instrument. Five (5 restaurant- participants were purposively chosen from the total population of 15. Results showed that CSR related mission/vision is clearly not embedded in the institutional websites of fast food restaurants while personal relation/social proximity approach is highly evident. Also, factors in the implementation of corporate social responsibility in relation to philanthropic behavior, shows a significant behavioral change from the statistical result such as moderately evident. CSR approaches and implementation are highly evident that clearly proves the responsible behavior of local fast food restaurants. Institutional integration of CSR in the company’s mission/vision statements, structure, decisions, activities, communication, practices stated appears to be beneficial in light of new corporate-state-market-society relationship.

  10. Antioxidant activity of seedling growth in selected soybean genotypes (Glycine max (L.) Merrill) responses of submergence

    Damanik, R. I.; Marbun, P.; Sihombing, L.

    2016-08-01

    In order to better understand the physiological and biochemical responses relating to direct seeding establishment in soybeans, the plant growth rate and antioxidative defense responses of seedlings in seven Indonesian soybean genotypes (Anjasmoro, Detam-1, Detam-2, Dieng, Grobogan, Tanggamus, and Willis) at different submergence periods (4, and 8 days) were examined. Twelve-day old seedlings were hydroponically grown in limited oxygen conditions. The results showed that the chlorophyll content in soybean seedlings was reduced beginning as early as 4 d under submerged condition, except for Detam-1, Detam-2, and Grobogan genotypes. The dry weight and protein concentration of seedlings were significantly higher at control condition (0 d) than those in submerged condition. The activities of superoxide dismutase (SOD) increased linearly until 8 d submerged for all genotypes. On the other hand, our results showed that catalase (CAT) and ascorbate peroxidase (APX) activities did not work together, meaning that CAT is activated and APX deactivated, or vice versa, in response to submergence conditions, except for Grobogan and Tanggamus genotypes which had an effect on both CAT and APX activities. Submergence stress led to a significant increase in glutathione reductase (GR) together with APX activity for Detam-2 and Dieng genotypes at 8 d submerged.

  11. Selected topics in the quantum theory of solids: collective excitations and linear response

    Balakrishnan, V.

    1977-08-01

    This report is based on the lecture notes of a course given at the Department of Physics, Indian Institute of Technology, Madras, during the period January-April 1976 for M.Sc. students. The emphasis is on the concept of elementary excitations in many-body systems, and on the technique of linear response theory. Various topics are covered in 7 sections. The second section following the introductory section is on 'second quantization' and includes discussion on creation and destruction operators, multiparticle states, time-dependent operators etc. Section 3 deals with the 'electron gas' and includes discussion on non-interacting Fermi gas, Coulomb interaction and exchange energy, the two-electron correlation function etc. Section 4 deals with the dielectric response analysis of the electron gas and includes discussion on Coulomb interaction in terms of density fluctuations, self-consistent field dielectric function etc. In section 5 the 'linear response theory' is explained. The Liouville operator, Boltzmann's superposition integral, dispersion relations etc. are explained. Quasiparticles and plasmous are discussed in the Section 6. Section 7 deals with 'lattice dynamics and phonons'. In the last section 8, spin waves are explained. The Heisenberg exchange hamiltonian, Green Function for noninteracting magnons etc. are discussed. (author)

  12. Helping reasoners succeed in the Wason selection task: when executive learning discourages heuristic response but does not necessarily encourage logic.

    Sandrine Rossi

    Full Text Available Reasoners make systematic logical errors by giving heuristic responses that reflect deviations from the logical norm. Influential studies have suggested first that our reasoning is often biased because we minimize cognitive effort to surpass a cognitive conflict between heuristic response from system 1 and analytic response from system 2 thinking. Additionally, cognitive control processes might be necessary to inhibit system 1 responses to activate a system 2 response. Previous studies have shown a significant effect of executive learning (EL on adults who have transferred knowledge acquired on the Wason selection task (WST to another isomorphic task, the rule falsification task (RFT. The original paradigm consisted of teaching participants to inhibit a classical matching heuristic that sufficed the first problem and led to significant EL transfer on the second problem. Interestingly, the reasoning tasks differed in inhibiting-heuristic metacognitive cost. Success on the WST requires half-suppression of the matching elements. In contrast, the RFT necessitates a global rejection of the matching elements for a correct answer. Therefore, metacognitive learning difficulty most likely differs depending on whether one uses the first or second task during the learning phase. We aimed to investigate this difficulty and various matching-bias inhibition effects in a new (reversed paradigm. In this case, the transfer effect from the RFT to the WST could be more difficult because the reasoner learns to reject all matching elements in the first task. We observed that the EL leads to a significant reduction in matching selections on the WST without increasing logical performances. Interestingly, the acquired metacognitive knowledge was too "strictly" transferred and discouraged matching rather than encouraging logic. This finding underlines the complexity of learning transfer and adds new evidence to the pedagogy of reasoning.

  13. Helping reasoners succeed in the Wason selection task: when executive learning discourages heuristic response but does not necessarily encourage logic.

    Rossi, Sandrine; Cassotti, Mathieu; Moutier, Sylvain; Delcroix, Nicolas; Houdé, Olivier

    2015-01-01

    Reasoners make systematic logical errors by giving heuristic responses that reflect deviations from the logical norm. Influential studies have suggested first that our reasoning is often biased because we minimize cognitive effort to surpass a cognitive conflict between heuristic response from system 1 and analytic response from system 2 thinking. Additionally, cognitive control processes might be necessary to inhibit system 1 responses to activate a system 2 response. Previous studies have shown a significant effect of executive learning (EL) on adults who have transferred knowledge acquired on the Wason selection task (WST) to another isomorphic task, the rule falsification task (RFT). The original paradigm consisted of teaching participants to inhibit a classical matching heuristic that sufficed the first problem and led to significant EL transfer on the second problem. Interestingly, the reasoning tasks differed in inhibiting-heuristic metacognitive cost. Success on the WST requires half-suppression of the matching elements. In contrast, the RFT necessitates a global rejection of the matching elements for a correct answer. Therefore, metacognitive learning difficulty most likely differs depending on whether one uses the first or second task during the learning phase. We aimed to investigate this difficulty and various matching-bias inhibition effects in a new (reversed) paradigm. In this case, the transfer effect from the RFT to the WST could be more difficult because the reasoner learns to reject all matching elements in the first task. We observed that the EL leads to a significant reduction in matching selections on the WST without increasing logical performances. Interestingly, the acquired metacognitive knowledge was too "strictly" transferred and discouraged matching rather than encouraging logic. This finding underlines the complexity of learning transfer and adds new evidence to the pedagogy of reasoning.

  14. Functional characterization of the modified melanocortin peptides responsible for ligand selectivity at the human melanocortin receptors.

    Chen, Min; Georgeson, Keith E; Harmon, Carroll M; Haskell-Luevano, Carrie; Yang, Yingkui

    2006-11-01

    The melanocortin system plays an important role in energy homeostasis as well as skin pigmentation, steroidogenesis and exocrine gland function. In this study, we examined eight Ac-His-Phe-Arg-Trp-NH(2) tetrapeptides that were modified at the Phe position and pharmacologically characterized their activities at the human MCR wild-types and their mutants. Our results indicate that at the hMC1R, all D stereochemical modified residues at the Phe position of peptides increase cAMP production in a dose-dependent manner. At the hMC3R, the DPhe peptide dose dependently increases cAMP production but all other three tetrapeptides were not. At the hMC4R, both the DPhe and DNal(1') peptides induce cAMP production. However, both DTyr and DNal(2') were not able to induce cAMP production. Further studies indicated that at the hMC1R M128L mutant receptor, the all D-configured tetrapeptides reduce their potencies as compared to that of hMC1R wild-type. However, at the hMC3R and hMC4R L165M and L133M mutant receptors, the DNal(2') and DTyr tetrapeptides possess agonist activity. These findings indicate that DPhe in tetrapeptide plays an important role in ligand selectivity and specific residue TM3 of the melanocortin receptors is crucial for ligand selectivity.

  15. Responses to cholinergic agonists of rats selectively bred for differential sensitivity to ethanol.

    de Fiebre, C M; Romm, E; Collins, J T; Draski, L J; Deitrich, R A; Collins, A C

    1991-03-01

    Alcoholics are almost invariably heavy users of tobacco. Both alcoholism and smoking appear to be influenced by genetic factors but it is not known whether the same or different genes regulate the abuse of ethanol and nicotine. Recent studies have demonstrated that the long-sleep (LS) and short-sleep (SS) mouse lines, which were selectively bred for differences in ethanol-induced anesthesia ("sleep-time"), also differ in several effects of nicotine and the muscarinic agonist, oxotremorine. In order to determine whether or not these differences are due to chance, the relative sensitivities of rat lines which were selectively bred for differences in ethanol-induced sleep-time were determined. The high alcohol sensitivity (HAS) rat line was more sensitive to the locomotor and body temperature depressant effects of nicotine than was the low alcohol sensitivity (LAS) rat line. The control line (CAS) was intermediate in sensitivity. The rat lines did not differ in sensitivity to oxotremorine's hypothermia-producing effects. The numbers and affinities of two classes of brain nicotinic receptors were measured in eight brain regions. No differences among the rat lines were detected. These results suggest that ethanol elicits some of its depressant actions via an effect on brain nicotinic systems, but the differences in sensitivity to ethanol and nicotine are probably not due to differences in the number of brain nicotinic receptors. Perhaps this interaction explains the high correlation between alcoholism and smoking in humans.

  16. Biochemical biomarker responses to pollution in selected sentinel organisms across the Eastern Mediterranean and the Black Sea.

    Tsangaris, Catherine; Moschino, Vanessa; Strogyloudi, Evangelia; Coatu, Valentina; Ramšak, Andreja; Alhaija, Rana Abu; Carvalho, Susana; Felline, Serena; Kosyan, Alisa; Lazarou, Yiota; Hatzianestis, Ioannis; Oros, Andra; Tiganus, Daniela

    2016-01-01

    Pollution effects were assessed by means of biochemical biomarkers (catalase, glutathione S-transferase and acetylcholinesterase activities, and metallothioneins content) in five species at selected coastal sites across the Eastern Mediterranean and the Black Sea. The mussel Mytilus galloprovincialis, a well-established sentinel species, was investigated in the Adriatic Sea, Aegean Sea, and Black Sea. The mussel Brachidontes pharaonis and the striped red mullet Mullus surmuletus were used in the Levantine Sea where M. galloprovincialis is not present. The white seabream Diplodus sargus sargus and the gastropod Rapana venosa were additionally sampled in the Adriatic and the Black Sea, respectively. Mussels showed catalase, glutathione S-transferase, and acetylcholinesterase responses to pollution in most geographical areas while the response of metallothioneins was restricted to a few sites. R. venosa showed marked responses of catalase and metallothioneins whereas both fish species did not generally exhibit variations in biomarker values among sites. The approach based on the reference deviation concept using the "Integrated Biological Responses version 2" index was useful for the interpretation of overall biomarker responses.

  17. First- and Second-Line Targeted Systemic Therapy in Hepatocellular Carcinoma—An Update on Patient Selection and Response Evaluation

    Johann von Felden

    2016-11-01

    Full Text Available Advanced hepatocellular carcinoma (HCC with vascular invasion and/or extrahepatic spread and preserved liver function, according to stage C of the Barcelona Clinic Liver Cancer (BCLC classification, has a dismal prognosis. The multi-targeted tyrosine-kinase receptor inhibitor (TKI sorafenib is the only proven active substance in systemic HCC therapy for first-line treatment. In this review, we summarize current aspects in patient selection and management of side effects, and provide an update on response evaluation during first-line sorafenib therapy. Since second-line treatment options have been improved with the successful completion of the RESORCE trial, demonstrating a survival benefit for second-line treatment with the TKI regorafenib, response monitoring during first-line therapy will be critical to deliver optimal systemic therapy in HCC. To this regard, specific side effects, in particular worsening of arterial hypertension and diarrhea, might suggest treatment response during first-line sorafenib therapy; however, clear predictive clinical markers, as well as laboratory test or serum markers, are not established. Assessment of radiologic response according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST is helpful to identify patients who do not benefit from sorafenib treatment.

  18. Biochemical biomarker responses to pollution in selected sentinel organisms across the Eastern Mediterranean and the Black Sea

    Tsangaris, Catherine

    2015-09-23

    Pollution effects were assessed by means of biochemical biomarkers (catalase, glutathione S-transferase and acetylcholinesterase activities, and metallothioneins content) in five species at selected coastal sites across the Eastern Mediterranean and the Black Sea. The mussel Mytilus galloprovincialis, a well-established sentinel species, was investigated in the Adriatic Sea, Aegean Sea, and Black Sea. The mussel Brachidontes pharaonis and the striped red mullet Mullus surmuletus were used in the Levantine Sea where M. galloprovincialis is not present. The white seabream Diplodus sargus sargus and the gastropod Rapana venosa were additionally sampled in the Adriatic and the Black Sea, respectively. Mussels showed catalase, glutathione S-transferase, and acetylcholinesterase responses to pollution in most geographical areas while the response of metallothioneins was restricted to a few sites. R. venosa showed marked responses of catalase and metallothioneins whereas both fish species did not generally exhibit variations in biomarker values among sites. The approach based on the reference deviation concept using the “Integrated Biological Responses version 2” index was useful for the interpretation of overall biomarker responses.

  19. Biochemical biomarker responses to pollution in selected sentinel organisms across the Eastern Mediterranean and the Black Sea

    Tsangaris, Catherine; Moschino, Vanessa; Strogyloudi, Evangelia; Coatu, Valentina; Ramšak, Andreja; Abu Alhaija, Rana; Carvalho, Susana; Felline, Serena; Kosyan, Alisa; Lazarou, Yiota; Hatzianestis, Ioannis; Oros, Andra; Tiganus, Daniela

    2015-01-01

    Pollution effects were assessed by means of biochemical biomarkers (catalase, glutathione S-transferase and acetylcholinesterase activities, and metallothioneins content) in five species at selected coastal sites across the Eastern Mediterranean and the Black Sea. The mussel Mytilus galloprovincialis, a well-established sentinel species, was investigated in the Adriatic Sea, Aegean Sea, and Black Sea. The mussel Brachidontes pharaonis and the striped red mullet Mullus surmuletus were used in the Levantine Sea where M. galloprovincialis is not present. The white seabream Diplodus sargus sargus and the gastropod Rapana venosa were additionally sampled in the Adriatic and the Black Sea, respectively. Mussels showed catalase, glutathione S-transferase, and acetylcholinesterase responses to pollution in most geographical areas while the response of metallothioneins was restricted to a few sites. R. venosa showed marked responses of catalase and metallothioneins whereas both fish species did not generally exhibit variations in biomarker values among sites. The approach based on the reference deviation concept using the “Integrated Biological Responses version 2” index was useful for the interpretation of overall biomarker responses.

  20. Circadian Disruption Changes Gut Microbiome Taxa and Functional Gene Composition.

    Deaver, Jessica A; Eum, Sung Y; Toborek, Michal

    2018-01-01

    Disrupted circadian rhythms and alterations of the gut microbiome composition were proposed to affect host health. Therefore, the aim of this research was to identify whether these events are connected and if circadian rhythm disruption by abnormal light-dark (LD) cycles affects microbial community gene expression and host vulnerability to intestinal dysfunction. Mice were subjected to either a 4-week period of constant 24-h light or of normal 12-h LD cycles. Stool samples were collected at the beginning and after the circadian rhythm disruption. A metatranscriptomic analysis revealed an increase in Ruminococcus torques , a bacterial species known to decrease gut barrier integrity, and a decrease in Lactobacillus johnsonii , a bacterium that helps maintain the intestinal epithelial cell layer, after circadian rhythm disruption. In addition, genes involved in pathways promoting host beneficial immune responses were downregulated, while genes involved in the synthesis and transportation of the endotoxin lipopolysaccharide were upregulated in mice with disrupted circadian cycles. Importantly, these mice were also more prone to dysfunction of the intestinal barrier. These results further elucidate the impact of light-cycle disruption on the gut microbiome and its connection with increased incidence of disease in response to circadian rhythm disturbances.